pmid
stringlengths 7
8
| title
stringlengths 29
245
| abstract
stringlengths 1
2.89k
| revised_title
stringlengths 29
251
| revised_abstract
stringlengths 1
2.97k
| all_entity_list
listlengths 2
58
| head_gene_entity
dict | tail_diease_entity
dict | label
stringclasses 2
values |
|---|---|---|---|---|---|---|---|---|
10091612 | Variations in the monoamine oxidase B (MAOB) gene are associated with Parkinson's disease. | The monoamine oxidase B gene (MAOB; Xp15.21-4) is a candidate gene for Parkinson's disease (PD) given its role in dopamine metabolism and its possible role in the activation of neurotoxins. The association of MAOB polymorphisms (a [GT] repeat allelic variation in intron 2 and an A-G transition in intron 13) with Parkinson's disease (PD) was studied in an Australian cohort of 204 (male:female ratio 1.60) people with PD and 285 (male:female ratio 1.64) age- and gender-matched control subjects. Genomic DNA was extracted from venous blood and polymerase chain reaction was used to amplify the appropriate regions of the MAOB gene. The length of each (GT) repeat sequence was determined by 5% polyacrylamide denaturing gel electrophoresis and a DNA fragment analyzer, while the G-A genotype was determined using 2% agarose gel electrophoresis. The G-A polymorphism showed no association with PD (odds ratio [OR] = 0.80; p = 0.51; 95% confidence interval [CI] = 0.42-1.53). There was a significant difference in allele frequencies of the (GT) repeat allelic variation between patients and control subjects (chi2 = 20.09; p<0.01). After statistical adjustment for potential confounders using a logistic regression analysis, the (GT) repeat alleles > or =188 base pairs in the intron 2 marker of the MAOB gene were significantly associated with PD (OR = 4.60; p<0.00005; 95% CI = 1.97-10.77). The 186 base pair allele was also significantly associated with PD (OR = 1.85; p = 0.048; 95% CI = 1.01-3.42). The GT repeat in intron 2 of the MAOB gene is a powerful marker for PD in this large Australian cohort. | Variations in the /"monoamine oxidase B"/ (/"MAOB"/) gene are associated with /"Parkinson's disease"/. | The /"monoamine oxidase B"/ gene (/"MAOB"/; Xp15.21-4) is a candidate gene for /"Parkinson's disease"/ (/"PD"/) given its role in dopamine metabolism and its possible role in the activation of neurotoxins. The association of /"MAOB"/ polymorphisms (a [GT] repeat allelic variation in intron 2 and an A-G transition in intron 13) with /"Parkinson's disease"/ (/"PD"/) was studied in an Australian cohort of 204 (male:female ratio 1.60) people with /"PD"/ and 285 (male:female ratio 1.64) age- and gender-matched control subjects. Genomic DNA was extracted from venous blood and polymerase chain reaction was used to amplify the appropriate regions of the /"MAOB"/ gene. The length of each (GT) repeat sequence was determined by 5% polyacrylamide denaturing gel electrophoresis and a DNA fragment analyzer, while the G-A genotype was determined using 2% agarose gel electrophoresis. The G-A polymorphism showed no association with /"PD"/ (odds ratio [OR] = 0.80; p = 0.51; 95% confidence interval [CI] = 0.42-1.53). There was a significant difference in allele frequencies of the (GT) repeat allelic variation between patients and control subjects (chi2 = 20.09; p<0.01). After statistical adjustment for potential confounders using a logistic regression analysis, the (GT) repeat alleles > or =188 base pairs in the intron 2 marker of the /"MAOB"/ gene were significantly associated with /"PD"/ (OR = 4.60; p<0.00005; 95% CI = 1.97-10.77). The 186 base pair allele was also significantly associated with /"PD"/ (OR = 1.85; p = 0.048; 95% CI = 1.01-3.42). The GT repeat in intron 2 of the /"MAOB"/ gene is a powerful marker for /"PD"/ in this large Australian cohort. | [
{
"begin_idx": "70",
"end_idx": "89",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "Parkinson's disease"
},
{
"begin_idx": "162",
"end_idx": "181",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "Parkinson's disease"
},
{
"begin_idx": "183",
"end_idx": "185",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "405",
"end_idx": "424",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "Parkinson's disease"
},
{
"begin_idx": "426",
"end_idx": "428",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "510",
"end_idx": "512",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "984",
"end_idx": "986",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "1434",
"end_idx": "1436",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "1546",
"end_idx": "1548",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "1661",
"end_idx": "1663",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "323",
"end_idx": "325",
"entity_id": "D013915",
"entity_type": "Disease",
"text_name": "GT"
},
{
"begin_idx": "744",
"end_idx": "746",
"entity_id": "D013915",
"entity_type": "Disease",
"text_name": "GT"
},
{
"begin_idx": "1130",
"end_idx": "1132",
"entity_id": "D013915",
"entity_type": "Disease",
"text_name": "GT"
},
{
"begin_idx": "1319",
"end_idx": "1321",
"entity_id": "D013915",
"entity_type": "Disease",
"text_name": "GT"
},
{
"begin_idx": "1597",
"end_idx": "1599",
"entity_id": "D013915",
"entity_type": "Disease",
"text_name": "GT"
},
{
"begin_idx": "18",
"end_idx": "37",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "monoamine oxidase B"
},
{
"begin_idx": "39",
"end_idx": "43",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "MAOB"
},
{
"begin_idx": "95",
"end_idx": "114",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "monoamine oxidase B"
},
{
"begin_idx": "121",
"end_idx": "125",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "MAOB"
},
{
"begin_idx": "300",
"end_idx": "304",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "MAOB"
},
{
"begin_idx": "713",
"end_idx": "717",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "MAOB"
},
{
"begin_idx": "1389",
"end_idx": "1393",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "MAOB"
},
{
"begin_idx": "1626",
"end_idx": "1630",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "MAOB"
}
] | {
"begin_idx": "18",
"end_idx": "37",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "monoamine oxidase B"
} | {
"begin_idx": "70",
"end_idx": "89",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "Parkinson's disease"
} | Yes |
10091612 | Variations in the monoamine oxidase B (MAOB) gene are associated with Parkinson's disease. | The monoamine oxidase B gene (MAOB; Xp15.21-4) is a candidate gene for Parkinson's disease (PD) given its role in dopamine metabolism and its possible role in the activation of neurotoxins. The association of MAOB polymorphisms (a [GT] repeat allelic variation in intron 2 and an A-G transition in intron 13) with Parkinson's disease (PD) was studied in an Australian cohort of 204 (male:female ratio 1.60) people with PD and 285 (male:female ratio 1.64) age- and gender-matched control subjects. Genomic DNA was extracted from venous blood and polymerase chain reaction was used to amplify the appropriate regions of the MAOB gene. The length of each (GT) repeat sequence was determined by 5% polyacrylamide denaturing gel electrophoresis and a DNA fragment analyzer, while the G-A genotype was determined using 2% agarose gel electrophoresis. The G-A polymorphism showed no association with PD (odds ratio [OR] = 0.80; p = 0.51; 95% confidence interval [CI] = 0.42-1.53). There was a significant difference in allele frequencies of the (GT) repeat allelic variation between patients and control subjects (chi2 = 20.09; p<0.01). After statistical adjustment for potential confounders using a logistic regression analysis, the (GT) repeat alleles > or =188 base pairs in the intron 2 marker of the MAOB gene were significantly associated with PD (OR = 4.60; p<0.00005; 95% CI = 1.97-10.77). The 186 base pair allele was also significantly associated with PD (OR = 1.85; p = 0.048; 95% CI = 1.01-3.42). The GT repeat in intron 2 of the MAOB gene is a powerful marker for PD in this large Australian cohort. | Variations in the /"monoamine oxidase B"/ (/"MAOB"/) gene are associated with Parkinson's disease. | The /"monoamine oxidase B"/ gene (/"MAOB"/; Xp15.21-4) is a candidate gene for Parkinson's disease (PD) given its role in dopamine metabolism and its possible role in the activation of neurotoxins. The association of /"MAOB"/ polymorphisms (a [/"GT"/] repeat allelic variation in intron 2 and an A-G transition in intron 13) with Parkinson's disease (PD) was studied in an Australian cohort of 204 (male:female ratio 1.60) people with PD and 285 (male:female ratio 1.64) age- and gender-matched control subjects. Genomic DNA was extracted from venous blood and polymerase chain reaction was used to amplify the appropriate regions of the /"MAOB"/ gene. The length of each (/"GT"/) repeat sequence was determined by 5% polyacrylamide denaturing gel electrophoresis and a DNA fragment analyzer, while the G-A genotype was determined using 2% agarose gel electrophoresis. The G-A polymorphism showed no association with PD (odds ratio [OR] = 0.80; p = 0.51; 95% confidence interval [CI] = 0.42-1.53). There was a significant difference in allele frequencies of the (/"GT"/) repeat allelic variation between patients and control subjects (chi2 = 20.09; p<0.01). After statistical adjustment for potential confounders using a logistic regression analysis, the (/"GT"/) repeat alleles > or =188 base pairs in the intron 2 marker of the /"MAOB"/ gene were significantly associated with PD (OR = 4.60; p<0.00005; 95% CI = 1.97-10.77). The 186 base pair allele was also significantly associated with PD (OR = 1.85; p = 0.048; 95% CI = 1.01-3.42). The /"GT"/ repeat in intron 2 of the /"MAOB"/ gene is a powerful marker for PD in this large Australian cohort. | [
{
"begin_idx": "70",
"end_idx": "89",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "Parkinson's disease"
},
{
"begin_idx": "162",
"end_idx": "181",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "Parkinson's disease"
},
{
"begin_idx": "183",
"end_idx": "185",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "405",
"end_idx": "424",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "Parkinson's disease"
},
{
"begin_idx": "426",
"end_idx": "428",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "510",
"end_idx": "512",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "984",
"end_idx": "986",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "1434",
"end_idx": "1436",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "1546",
"end_idx": "1548",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "1661",
"end_idx": "1663",
"entity_id": "D010300",
"entity_type": "Disease",
"text_name": "PD"
},
{
"begin_idx": "323",
"end_idx": "325",
"entity_id": "D013915",
"entity_type": "Disease",
"text_name": "GT"
},
{
"begin_idx": "744",
"end_idx": "746",
"entity_id": "D013915",
"entity_type": "Disease",
"text_name": "GT"
},
{
"begin_idx": "1130",
"end_idx": "1132",
"entity_id": "D013915",
"entity_type": "Disease",
"text_name": "GT"
},
{
"begin_idx": "1319",
"end_idx": "1321",
"entity_id": "D013915",
"entity_type": "Disease",
"text_name": "GT"
},
{
"begin_idx": "1597",
"end_idx": "1599",
"entity_id": "D013915",
"entity_type": "Disease",
"text_name": "GT"
},
{
"begin_idx": "18",
"end_idx": "37",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "monoamine oxidase B"
},
{
"begin_idx": "39",
"end_idx": "43",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "MAOB"
},
{
"begin_idx": "95",
"end_idx": "114",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "monoamine oxidase B"
},
{
"begin_idx": "121",
"end_idx": "125",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "MAOB"
},
{
"begin_idx": "300",
"end_idx": "304",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "MAOB"
},
{
"begin_idx": "713",
"end_idx": "717",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "MAOB"
},
{
"begin_idx": "1389",
"end_idx": "1393",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "MAOB"
},
{
"begin_idx": "1626",
"end_idx": "1630",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "MAOB"
}
] | {
"begin_idx": "121",
"end_idx": "125",
"entity_id": "4129",
"entity_type": "Gene",
"text_name": "MAOB"
} | {
"begin_idx": "1319",
"end_idx": "1321",
"entity_id": "D013915",
"entity_type": "Disease",
"text_name": "GT"
} | No |
10094550 | Identification of a 5' splice site mutation in the RPGR gene in a family with X-linked retinitis pigmentosa (RP3). | We have identified a novel RPGR gene mutation in a large Dutch family with X-linked retinitis pigmentosa (RP3). In affected members, a G-->T transversion was found at position +1 of the 5' splice site of intron 5 of the RPGR (retinitis pigmentosa GTPase regulator) gene. Analysis of this mutation at the RNA level showed cryptic splicing upstream of the mutation in exon 5 leading to a frameshift and downstream termination codon. Identification of the causative mutation in this family has facilitated the detection of females at risk of having an affected son. | Identification of a 5' splice site mutation in the /"RPGR"/ gene in a family with X-linked retinitis pigmentosa (/"RP3"/). | We have identified a novel /"RPGR"/ gene mutation in a large Dutch family with X-linked retinitis pigmentosa (/"RP3"/). In affected members, a G-->T transversion was found at position +1 of the 5' splice site of intron 5 of the /"RPGR"/ (/"retinitis pigmentosa"/ GTPase regulator) gene. Analysis of this mutation at the RNA level showed cryptic splicing upstream of the mutation in exon 5 leading to a frameshift and downstream termination codon. Identification of the causative mutation in this family has facilitated the detection of females at risk of having an affected son. | [
{
"begin_idx": "78",
"end_idx": "107",
"entity_id": "C564481",
"entity_type": "Disease",
"text_name": "X-linked retinitis pigmentosa"
},
{
"begin_idx": "190",
"end_idx": "219",
"entity_id": "C564481",
"entity_type": "Disease",
"text_name": "X-linked retinitis pigmentosa"
},
{
"begin_idx": "341",
"end_idx": "361",
"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "retinitis pigmentosa"
},
{
"begin_idx": "51",
"end_idx": "55",
"entity_id": "6103",
"entity_type": "Gene",
"text_name": "RPGR"
},
{
"begin_idx": "109",
"end_idx": "112",
"entity_id": "6103",
"entity_type": "Gene",
"text_name": "RP3"
},
{
"begin_idx": "142",
"end_idx": "146",
"entity_id": "6103",
"entity_type": "Gene",
"text_name": "RPGR"
},
{
"begin_idx": "221",
"end_idx": "224",
"entity_id": "6103",
"entity_type": "Gene",
"text_name": "RP3"
},
{
"begin_idx": "335",
"end_idx": "339",
"entity_id": "6103",
"entity_type": "Gene",
"text_name": "RPGR"
}
] | {
"begin_idx": "51",
"end_idx": "55",
"entity_id": "6103",
"entity_type": "Gene",
"text_name": "RPGR"
} | {
"begin_idx": "341",
"end_idx": "361",
"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "retinitis pigmentosa"
} | Yes |
10094550 | Identification of a 5' splice site mutation in the RPGR gene in a family with X-linked retinitis pigmentosa (RP3). | We have identified a novel RPGR gene mutation in a large Dutch family with X-linked retinitis pigmentosa (RP3). In affected members, a G-->T transversion was found at position +1 of the 5' splice site of intron 5 of the RPGR (retinitis pigmentosa GTPase regulator) gene. Analysis of this mutation at the RNA level showed cryptic splicing upstream of the mutation in exon 5 leading to a frameshift and downstream termination codon. Identification of the causative mutation in this family has facilitated the detection of females at risk of having an affected son. | Identification of a 5' splice site mutation in the /"RPGR"/ gene in a family with /"X-linked retinitis pigmentosa"/ (/"RP3"/). | We have identified a novel /"RPGR"/ gene mutation in a large Dutch family with /"X-linked retinitis pigmentosa"/ (/"RP3"/). In affected members, a G-->T transversion was found at position +1 of the 5' splice site of intron 5 of the /"RPGR"/ (retinitis pigmentosa GTPase regulator) gene. Analysis of this mutation at the RNA level showed cryptic splicing upstream of the mutation in exon 5 leading to a frameshift and downstream termination codon. Identification of the causative mutation in this family has facilitated the detection of females at risk of having an affected son. | [
{
"begin_idx": "78",
"end_idx": "107",
"entity_id": "C564481",
"entity_type": "Disease",
"text_name": "X-linked retinitis pigmentosa"
},
{
"begin_idx": "190",
"end_idx": "219",
"entity_id": "C564481",
"entity_type": "Disease",
"text_name": "X-linked retinitis pigmentosa"
},
{
"begin_idx": "341",
"end_idx": "361",
"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "retinitis pigmentosa"
},
{
"begin_idx": "51",
"end_idx": "55",
"entity_id": "6103",
"entity_type": "Gene",
"text_name": "RPGR"
},
{
"begin_idx": "109",
"end_idx": "112",
"entity_id": "6103",
"entity_type": "Gene",
"text_name": "RP3"
},
{
"begin_idx": "142",
"end_idx": "146",
"entity_id": "6103",
"entity_type": "Gene",
"text_name": "RPGR"
},
{
"begin_idx": "221",
"end_idx": "224",
"entity_id": "6103",
"entity_type": "Gene",
"text_name": "RP3"
},
{
"begin_idx": "335",
"end_idx": "339",
"entity_id": "6103",
"entity_type": "Gene",
"text_name": "RPGR"
}
] | {
"begin_idx": "221",
"end_idx": "224",
"entity_id": "6103",
"entity_type": "Gene",
"text_name": "RP3"
} | {
"begin_idx": "190",
"end_idx": "219",
"entity_id": "C564481",
"entity_type": "Disease",
"text_name": "X-linked retinitis pigmentosa"
} | No |
10200057 | Two novel mutations in exon 11 of the PAH gene (V1163del TG and P362T) associated with classic phenylketonuira and mild phenylketonuria. Mutations in brief no. 143. Online. | PKU is one of the commonest genetic disease in man, affecting 1/10,000 individuals. It presents a wide phenotypical spectrum, from classic PKU to moderate Hyperpheylalaninemia depending on the residual enzymatic activity. Two novel mutations 1163/1164delTG and P362T in exon 11 have been detected during the mutational screening of the PAH gene in 84 families. 1163/1164delTC can be confused with V388M if the mutational screening is performed with BsaAI restriction enzyme, this mutation in heterozigosis presents a moderate phenotype. P362T mutation in heterozigosis with V388M shows a classical PKU phenotype. We report here two new mutations in exon 11 of the PAH gene (GenBank U49897), V1163delTG and P362T (using cDNA sequence), detected during the analysis of 57 PKU and 36 HPA patients belonging to 84 unrelated families detected under a neonatal screening program performed in Catalonia. | Two novel mutations in exon 11 of the /"PAH"/ gene (V1163del TG and P362T) associated with classic phenylketonuira and mild /"phenylketonuria"/. Mutations in brief no. 143. Online. | /"PKU"/ is one of the commonest genetic disease in man, affecting 1/10,000 individuals. It presents a wide phenotypical spectrum, from classic /"PKU"/ to moderate Hyperpheylalaninemia depending on the residual enzymatic activity. Two novel mutations 1163/1164delTG and P362T in exon 11 have been detected during the mutational screening of the /"PAH"/ gene in 84 families. 1163/1164delTC can be confused with V388M if the mutational screening is performed with BsaAI restriction enzyme, this mutation in heterozigosis presents a moderate phenotype. P362T mutation in heterozigosis with V388M shows a classical /"PKU"/ phenotype. We report here two new mutations in exon 11 of the /"PAH"/ gene (GenBank U49897), V1163delTG and P362T (using cDNA sequence), detected during the analysis of 57 /"PKU"/ and 36 /"HPA"/ patients belonging to 84 unrelated families detected under a neonatal screening program performed in Catalonia. | [
{
"begin_idx": "120",
"end_idx": "135",
"entity_id": "D010661",
"entity_type": "Disease",
"text_name": "phenylketonuria"
},
{
"begin_idx": "173",
"end_idx": "176",
"entity_id": "D010661",
"entity_type": "Disease",
"text_name": "PKU"
},
{
"begin_idx": "312",
"end_idx": "315",
"entity_id": "D010661",
"entity_type": "Disease",
"text_name": "PKU"
},
{
"begin_idx": "771",
"end_idx": "774",
"entity_id": "D010661",
"entity_type": "Disease",
"text_name": "PKU"
},
{
"begin_idx": "943",
"end_idx": "946",
"entity_id": "D010661",
"entity_type": "Disease",
"text_name": "PKU"
},
{
"begin_idx": "954",
"end_idx": "957",
"entity_id": "D010661",
"entity_type": "Disease",
"text_name": "HPA"
},
{
"begin_idx": "201",
"end_idx": "216",
"entity_id": "D030342",
"entity_type": "Disease",
"text_name": "genetic disease"
},
{
"begin_idx": "38",
"end_idx": "41",
"entity_id": "5053",
"entity_type": "Gene",
"text_name": "PAH"
},
{
"begin_idx": "509",
"end_idx": "512",
"entity_id": "5053",
"entity_type": "Gene",
"text_name": "PAH"
},
{
"begin_idx": "837",
"end_idx": "840",
"entity_id": "5053",
"entity_type": "Gene",
"text_name": "PAH"
}
] | {
"begin_idx": "38",
"end_idx": "41",
"entity_id": "5053",
"entity_type": "Gene",
"text_name": "PAH"
} | {
"begin_idx": "120",
"end_idx": "135",
"entity_id": "D010661",
"entity_type": "Disease",
"text_name": "phenylketonuria"
} | Yes |
10200057 | Two novel mutations in exon 11 of the PAH gene (V1163del TG and P362T) associated with classic phenylketonuira and mild phenylketonuria. Mutations in brief no. 143. Online. | PKU is one of the commonest genetic disease in man, affecting 1/10,000 individuals. It presents a wide phenotypical spectrum, from classic PKU to moderate Hyperpheylalaninemia depending on the residual enzymatic activity. Two novel mutations 1163/1164delTG and P362T in exon 11 have been detected during the mutational screening of the PAH gene in 84 families. 1163/1164delTC can be confused with V388M if the mutational screening is performed with BsaAI restriction enzyme, this mutation in heterozigosis presents a moderate phenotype. P362T mutation in heterozigosis with V388M shows a classical PKU phenotype. We report here two new mutations in exon 11 of the PAH gene (GenBank U49897), V1163delTG and P362T (using cDNA sequence), detected during the analysis of 57 PKU and 36 HPA patients belonging to 84 unrelated families detected under a neonatal screening program performed in Catalonia. | Two novel mutations in exon 11 of the /"PAH"/ gene (V1163del TG and P362T) associated with classic phenylketonuira and mild phenylketonuria. Mutations in brief no. 143. Online. | PKU is one of the commonest /"genetic disease"/ in man, affecting 1/10,000 individuals. It presents a wide phenotypical spectrum, from classic PKU to moderate Hyperpheylalaninemia depending on the residual enzymatic activity. Two novel mutations 1163/1164delTG and P362T in exon 11 have been detected during the mutational screening of the /"PAH"/ gene in 84 families. 1163/1164delTC can be confused with V388M if the mutational screening is performed with BsaAI restriction enzyme, this mutation in heterozigosis presents a moderate phenotype. P362T mutation in heterozigosis with V388M shows a classical PKU phenotype. We report here two new mutations in exon 11 of the /"PAH"/ gene (GenBank U49897), V1163delTG and P362T (using cDNA sequence), detected during the analysis of 57 PKU and 36 HPA patients belonging to 84 unrelated families detected under a neonatal screening program performed in Catalonia. | [
{
"begin_idx": "120",
"end_idx": "135",
"entity_id": "D010661",
"entity_type": "Disease",
"text_name": "phenylketonuria"
},
{
"begin_idx": "173",
"end_idx": "176",
"entity_id": "D010661",
"entity_type": "Disease",
"text_name": "PKU"
},
{
"begin_idx": "312",
"end_idx": "315",
"entity_id": "D010661",
"entity_type": "Disease",
"text_name": "PKU"
},
{
"begin_idx": "771",
"end_idx": "774",
"entity_id": "D010661",
"entity_type": "Disease",
"text_name": "PKU"
},
{
"begin_idx": "943",
"end_idx": "946",
"entity_id": "D010661",
"entity_type": "Disease",
"text_name": "PKU"
},
{
"begin_idx": "954",
"end_idx": "957",
"entity_id": "D010661",
"entity_type": "Disease",
"text_name": "HPA"
},
{
"begin_idx": "201",
"end_idx": "216",
"entity_id": "D030342",
"entity_type": "Disease",
"text_name": "genetic disease"
},
{
"begin_idx": "38",
"end_idx": "41",
"entity_id": "5053",
"entity_type": "Gene",
"text_name": "PAH"
},
{
"begin_idx": "509",
"end_idx": "512",
"entity_id": "5053",
"entity_type": "Gene",
"text_name": "PAH"
},
{
"begin_idx": "837",
"end_idx": "840",
"entity_id": "5053",
"entity_type": "Gene",
"text_name": "PAH"
}
] | {
"begin_idx": "38",
"end_idx": "41",
"entity_id": "5053",
"entity_type": "Gene",
"text_name": "PAH"
} | {
"begin_idx": "201",
"end_idx": "216",
"entity_id": "D030342",
"entity_type": "Disease",
"text_name": "genetic disease"
} | No |
10213916 | Urocortin and inflammation: confounding effects of hypotension on measures of inflammation. | Urocortin, a newly isolated 40-amino-acid mammalian peptide homologous to corticotropin-releasing hormone (CRH), activates both CRH type 1 and 2 receptors, but may be an endogenous ligand for CRH receptor type 2. Urocortin given systemically inhibited heat-induced paw edema in the rat, and was therefore ascribed anti-inflammatory properties. We examined the effects of urocortin in the carrageenin-induced subcutaneous inflammation model. Rats were treated with urocortin 200 (n = 6) or 20 nmol/kg (n = 6); inflammatory exudates were reduced by approximately 30% compared to controls (n = 7) at both doses. However, since subcutaneous urocortin has been shown to reduce arterial blood pressure, we tested the hypothesis that its antiedema and antiextravasatory effects were secondary to arterial hypotension. Therefore, we examined the parallel effects of urocortin- and hydralazine-induced hypotension on acute inflammation induced by carrageenin in the rat. Rats were treated with subcutaneous carrageenin and control injections (n = 8), carrageenin and urocortin (20 nmol/kg, n = 9), or carrageenin and intraperitoneal hydralazine (10 mg/kg, n = 8). Mean arterial blood pressure was measured hourly for 7 h in 12 animals, and after 2 h, the nadir of treatment, in a further 13 animals. Rats were then sacrificed, and the inflammatory exudate volume and leukocyte count were measured. Mean exudate volumes were reduced from 4.8 +/- 0.5 ml (controls) to 2.4 +/- 0.3 ml (p = 0.004) and 2.9 +/- 0.6 ml (p = 0.007) in urocortin- and hydralazine-treated animals, respectively. Urocortin and hydralazine both produced a significant fall in blood pressure compared to controls, with mean arterial pressure 2 h after carrageenin injection falling to 51.0 +/- 4.1 (p < 0.001) and 34.6 +/- 4.6 (p < 0.001) vs. 92.9 +/- 3.7 mm Hg in controls, respectively. A significant positive correlation was noted between blood pressure and inflammatory exudate volume (r = 0. 52, p = 0.007). As both hydralazine and urocortin lowered blood pressure and inflammatory exudate volume, we suggest that the anti-inflammatory effects of urocortin and related neuropeptides may be nonspecific, acting through hypotension rather than through direct anti-inflammatory mechanisms. The use of inflammatory models which rely on extravasation may be inappropriate for the study of substances that produce hypotension. | /"Urocortin"/ and /"inflammation"/: confounding effects of hypotension on measures of /"inflammation"/. | /"Urocortin"/, a newly isolated 40-amino-acid mammalian peptide homologous to corticotropin-releasing hormone (CRH), activates both CRH type 1 and 2 receptors, but may be an endogenous ligand for CRH receptor type 2. /"Urocortin"/ given systemically inhibited heat-induced paw edema in the rat, and was therefore ascribed anti-inflammatory properties. We examined the effects of /"urocortin"/ in the carrageenin-induced subcutaneous /"inflammation"/ model. Rats were treated with /"urocortin"/ 200 (n = 6) or 20 nmol/kg (n = 6); inflammatory exudates were reduced by approximately 30% compared to controls (n = 7) at both doses. However, since subcutaneous /"urocortin"/ has been shown to reduce arterial blood pressure, we tested the hypothesis that its antiedema and antiextravasatory effects were secondary to arterial hypotension. Therefore, we examined the parallel effects of /"urocortin"/- and hydralazine-induced hypotension on acute /"inflammation"/ induced by carrageenin in the rat. Rats were treated with subcutaneous carrageenin and control injections (n = 8), carrageenin and /"urocortin"/ (20 nmol/kg, n = 9), or carrageenin and intraperitoneal hydralazine (10 mg/kg, n = 8). Mean arterial blood pressure was measured hourly for 7 h in 12 animals, and after 2 h, the nadir of treatment, in a further 13 animals. Rats were then sacrificed, and the inflammatory exudate volume and leukocyte count were measured. Mean exudate volumes were reduced from 4.8 +/- 0.5 ml (controls) to 2.4 +/- 0.3 ml (p = 0.004) and 2.9 +/- 0.6 ml (p = 0.007) in /"urocortin"/- and hydralazine-treated animals, respectively. /"Urocortin"/ and hydralazine both produced a significant fall in blood pressure compared to controls, with mean arterial pressure 2 h after carrageenin injection falling to 51.0 +/- 4.1 (p < 0.001) and 34.6 +/- 4.6 (p < 0.001) vs. 92.9 +/- 3.7 mm Hg in controls, respectively. A significant positive correlation was noted between blood pressure and inflammatory exudate volume (r = 0. 52, p = 0.007). As both hydralazine and /"urocortin"/ lowered blood pressure and inflammatory exudate volume, we suggest that the anti-inflammatory effects of /"urocortin"/ and related neuropeptides may be nonspecific, acting through hypotension rather than through direct anti-inflammatory mechanisms. The use of inflammatory models which rely on extravasation may be inappropriate for the study of substances that produce hypotension. | [
{
"begin_idx": "361",
"end_idx": "366",
"entity_id": "D004487",
"entity_type": "Disease",
"text_name": "edema"
},
{
"begin_idx": "51",
"end_idx": "62",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "890",
"end_idx": "901",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "985",
"end_idx": "996",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "1722",
"end_idx": "1744",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "fall in blood pressure"
},
{
"begin_idx": "2276",
"end_idx": "2287",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "2466",
"end_idx": "2477",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "14",
"end_idx": "26",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "78",
"end_idx": "90",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "513",
"end_idx": "525",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "1006",
"end_idx": "1018",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "166",
"end_idx": "197",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "corticotropin-releasing hormone"
},
{
"begin_idx": "199",
"end_idx": "202",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "CRH"
},
{
"begin_idx": "220",
"end_idx": "223",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "CRH"
},
{
"begin_idx": "284",
"end_idx": "287",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "CRH"
},
{
"begin_idx": "0",
"end_idx": "9",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "92",
"end_idx": "101",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "305",
"end_idx": "314",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "463",
"end_idx": "472",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "556",
"end_idx": "565",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "729",
"end_idx": "738",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "950",
"end_idx": "959",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "1150",
"end_idx": "1159",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "1610",
"end_idx": "1619",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "1668",
"end_idx": "1677",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "2090",
"end_idx": "2099",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "2205",
"end_idx": "2214",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
}
] | {
"begin_idx": "0",
"end_idx": "9",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
} | {
"begin_idx": "14",
"end_idx": "26",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
} | Yes |
10213916 | Urocortin and inflammation: confounding effects of hypotension on measures of inflammation. | Urocortin, a newly isolated 40-amino-acid mammalian peptide homologous to corticotropin-releasing hormone (CRH), activates both CRH type 1 and 2 receptors, but may be an endogenous ligand for CRH receptor type 2. Urocortin given systemically inhibited heat-induced paw edema in the rat, and was therefore ascribed anti-inflammatory properties. We examined the effects of urocortin in the carrageenin-induced subcutaneous inflammation model. Rats were treated with urocortin 200 (n = 6) or 20 nmol/kg (n = 6); inflammatory exudates were reduced by approximately 30% compared to controls (n = 7) at both doses. However, since subcutaneous urocortin has been shown to reduce arterial blood pressure, we tested the hypothesis that its antiedema and antiextravasatory effects were secondary to arterial hypotension. Therefore, we examined the parallel effects of urocortin- and hydralazine-induced hypotension on acute inflammation induced by carrageenin in the rat. Rats were treated with subcutaneous carrageenin and control injections (n = 8), carrageenin and urocortin (20 nmol/kg, n = 9), or carrageenin and intraperitoneal hydralazine (10 mg/kg, n = 8). Mean arterial blood pressure was measured hourly for 7 h in 12 animals, and after 2 h, the nadir of treatment, in a further 13 animals. Rats were then sacrificed, and the inflammatory exudate volume and leukocyte count were measured. Mean exudate volumes were reduced from 4.8 +/- 0.5 ml (controls) to 2.4 +/- 0.3 ml (p = 0.004) and 2.9 +/- 0.6 ml (p = 0.007) in urocortin- and hydralazine-treated animals, respectively. Urocortin and hydralazine both produced a significant fall in blood pressure compared to controls, with mean arterial pressure 2 h after carrageenin injection falling to 51.0 +/- 4.1 (p < 0.001) and 34.6 +/- 4.6 (p < 0.001) vs. 92.9 +/- 3.7 mm Hg in controls, respectively. A significant positive correlation was noted between blood pressure and inflammatory exudate volume (r = 0. 52, p = 0.007). As both hydralazine and urocortin lowered blood pressure and inflammatory exudate volume, we suggest that the anti-inflammatory effects of urocortin and related neuropeptides may be nonspecific, acting through hypotension rather than through direct anti-inflammatory mechanisms. The use of inflammatory models which rely on extravasation may be inappropriate for the study of substances that produce hypotension. | /"Urocortin"/ and inflammation: confounding effects of /"hypotension"/ on measures of inflammation. | /"Urocortin"/, a newly isolated 40-amino-acid mammalian peptide homologous to corticotropin-releasing hormone (CRH), activates both CRH type 1 and 2 receptors, but may be an endogenous ligand for CRH receptor type 2. /"Urocortin"/ given systemically inhibited heat-induced paw edema in the rat, and was therefore ascribed anti-inflammatory properties. We examined the effects of /"urocortin"/ in the carrageenin-induced subcutaneous inflammation model. Rats were treated with /"urocortin"/ 200 (n = 6) or 20 nmol/kg (n = 6); inflammatory exudates were reduced by approximately 30% compared to controls (n = 7) at both doses. However, since subcutaneous /"urocortin"/ has been shown to reduce arterial blood pressure, we tested the hypothesis that its antiedema and antiextravasatory effects were secondary to arterial /"hypotension"/. Therefore, we examined the parallel effects of /"urocortin"/- and hydralazine-induced /"hypotension"/ on acute inflammation induced by carrageenin in the rat. Rats were treated with subcutaneous carrageenin and control injections (n = 8), carrageenin and /"urocortin"/ (20 nmol/kg, n = 9), or carrageenin and intraperitoneal hydralazine (10 mg/kg, n = 8). Mean arterial blood pressure was measured hourly for 7 h in 12 animals, and after 2 h, the nadir of treatment, in a further 13 animals. Rats were then sacrificed, and the inflammatory exudate volume and leukocyte count were measured. Mean exudate volumes were reduced from 4.8 +/- 0.5 ml (controls) to 2.4 +/- 0.3 ml (p = 0.004) and 2.9 +/- 0.6 ml (p = 0.007) in /"urocortin"/- and hydralazine-treated animals, respectively. /"Urocortin"/ and hydralazine both produced a significant /"fall in blood pressure"/ compared to controls, with mean arterial pressure 2 h after carrageenin injection falling to 51.0 +/- 4.1 (p < 0.001) and 34.6 +/- 4.6 (p < 0.001) vs. 92.9 +/- 3.7 mm Hg in controls, respectively. A significant positive correlation was noted between blood pressure and inflammatory exudate volume (r = 0. 52, p = 0.007). As both hydralazine and /"urocortin"/ lowered blood pressure and inflammatory exudate volume, we suggest that the anti-inflammatory effects of /"urocortin"/ and related neuropeptides may be nonspecific, acting through /"hypotension"/ rather than through direct anti-inflammatory mechanisms. The use of inflammatory models which rely on extravasation may be inappropriate for the study of substances that produce /"hypotension"/. | [
{
"begin_idx": "361",
"end_idx": "366",
"entity_id": "D004487",
"entity_type": "Disease",
"text_name": "edema"
},
{
"begin_idx": "51",
"end_idx": "62",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "890",
"end_idx": "901",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "985",
"end_idx": "996",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "1722",
"end_idx": "1744",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "fall in blood pressure"
},
{
"begin_idx": "2276",
"end_idx": "2287",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "2466",
"end_idx": "2477",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "14",
"end_idx": "26",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "78",
"end_idx": "90",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "513",
"end_idx": "525",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "1006",
"end_idx": "1018",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "166",
"end_idx": "197",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "corticotropin-releasing hormone"
},
{
"begin_idx": "199",
"end_idx": "202",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "CRH"
},
{
"begin_idx": "220",
"end_idx": "223",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "CRH"
},
{
"begin_idx": "284",
"end_idx": "287",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "CRH"
},
{
"begin_idx": "0",
"end_idx": "9",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "92",
"end_idx": "101",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "305",
"end_idx": "314",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "463",
"end_idx": "472",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "556",
"end_idx": "565",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "729",
"end_idx": "738",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "950",
"end_idx": "959",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "1150",
"end_idx": "1159",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "1610",
"end_idx": "1619",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "1668",
"end_idx": "1677",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "2090",
"end_idx": "2099",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "2205",
"end_idx": "2214",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
}
] | {
"begin_idx": "0",
"end_idx": "9",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
} | {
"begin_idx": "1722",
"end_idx": "1744",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "fall in blood pressure"
} | Yes |
10213916 | Urocortin and inflammation: confounding effects of hypotension on measures of inflammation. | Urocortin, a newly isolated 40-amino-acid mammalian peptide homologous to corticotropin-releasing hormone (CRH), activates both CRH type 1 and 2 receptors, but may be an endogenous ligand for CRH receptor type 2. Urocortin given systemically inhibited heat-induced paw edema in the rat, and was therefore ascribed anti-inflammatory properties. We examined the effects of urocortin in the carrageenin-induced subcutaneous inflammation model. Rats were treated with urocortin 200 (n = 6) or 20 nmol/kg (n = 6); inflammatory exudates were reduced by approximately 30% compared to controls (n = 7) at both doses. However, since subcutaneous urocortin has been shown to reduce arterial blood pressure, we tested the hypothesis that its antiedema and antiextravasatory effects were secondary to arterial hypotension. Therefore, we examined the parallel effects of urocortin- and hydralazine-induced hypotension on acute inflammation induced by carrageenin in the rat. Rats were treated with subcutaneous carrageenin and control injections (n = 8), carrageenin and urocortin (20 nmol/kg, n = 9), or carrageenin and intraperitoneal hydralazine (10 mg/kg, n = 8). Mean arterial blood pressure was measured hourly for 7 h in 12 animals, and after 2 h, the nadir of treatment, in a further 13 animals. Rats were then sacrificed, and the inflammatory exudate volume and leukocyte count were measured. Mean exudate volumes were reduced from 4.8 +/- 0.5 ml (controls) to 2.4 +/- 0.3 ml (p = 0.004) and 2.9 +/- 0.6 ml (p = 0.007) in urocortin- and hydralazine-treated animals, respectively. Urocortin and hydralazine both produced a significant fall in blood pressure compared to controls, with mean arterial pressure 2 h after carrageenin injection falling to 51.0 +/- 4.1 (p < 0.001) and 34.6 +/- 4.6 (p < 0.001) vs. 92.9 +/- 3.7 mm Hg in controls, respectively. A significant positive correlation was noted between blood pressure and inflammatory exudate volume (r = 0. 52, p = 0.007). As both hydralazine and urocortin lowered blood pressure and inflammatory exudate volume, we suggest that the anti-inflammatory effects of urocortin and related neuropeptides may be nonspecific, acting through hypotension rather than through direct anti-inflammatory mechanisms. The use of inflammatory models which rely on extravasation may be inappropriate for the study of substances that produce hypotension. | Urocortin and /"inflammation"/: confounding effects of hypotension on measures of /"inflammation"/. | Urocortin, a newly isolated 40-amino-acid mammalian peptide homologous to /"corticotropin-releasing hormone"/ (/"CRH"/), activates both /"CRH"/ type 1 and 2 receptors, but may be an endogenous ligand for /"CRH"/ receptor type 2. Urocortin given systemically inhibited heat-induced paw edema in the rat, and was therefore ascribed anti-inflammatory properties. We examined the effects of urocortin in the carrageenin-induced subcutaneous /"inflammation"/ model. Rats were treated with urocortin 200 (n = 6) or 20 nmol/kg (n = 6); inflammatory exudates were reduced by approximately 30% compared to controls (n = 7) at both doses. However, since subcutaneous urocortin has been shown to reduce arterial blood pressure, we tested the hypothesis that its antiedema and antiextravasatory effects were secondary to arterial hypotension. Therefore, we examined the parallel effects of urocortin- and hydralazine-induced hypotension on acute /"inflammation"/ induced by carrageenin in the rat. Rats were treated with subcutaneous carrageenin and control injections (n = 8), carrageenin and urocortin (20 nmol/kg, n = 9), or carrageenin and intraperitoneal hydralazine (10 mg/kg, n = 8). Mean arterial blood pressure was measured hourly for 7 h in 12 animals, and after 2 h, the nadir of treatment, in a further 13 animals. Rats were then sacrificed, and the inflammatory exudate volume and leukocyte count were measured. Mean exudate volumes were reduced from 4.8 +/- 0.5 ml (controls) to 2.4 +/- 0.3 ml (p = 0.004) and 2.9 +/- 0.6 ml (p = 0.007) in urocortin- and hydralazine-treated animals, respectively. Urocortin and hydralazine both produced a significant fall in blood pressure compared to controls, with mean arterial pressure 2 h after carrageenin injection falling to 51.0 +/- 4.1 (p < 0.001) and 34.6 +/- 4.6 (p < 0.001) vs. 92.9 +/- 3.7 mm Hg in controls, respectively. A significant positive correlation was noted between blood pressure and inflammatory exudate volume (r = 0. 52, p = 0.007). As both hydralazine and urocortin lowered blood pressure and inflammatory exudate volume, we suggest that the anti-inflammatory effects of urocortin and related neuropeptides may be nonspecific, acting through hypotension rather than through direct anti-inflammatory mechanisms. The use of inflammatory models which rely on extravasation may be inappropriate for the study of substances that produce hypotension. | [
{
"begin_idx": "361",
"end_idx": "366",
"entity_id": "D004487",
"entity_type": "Disease",
"text_name": "edema"
},
{
"begin_idx": "51",
"end_idx": "62",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "890",
"end_idx": "901",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "985",
"end_idx": "996",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "1722",
"end_idx": "1744",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "fall in blood pressure"
},
{
"begin_idx": "2276",
"end_idx": "2287",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "2466",
"end_idx": "2477",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "14",
"end_idx": "26",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "78",
"end_idx": "90",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "513",
"end_idx": "525",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "1006",
"end_idx": "1018",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "166",
"end_idx": "197",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "corticotropin-releasing hormone"
},
{
"begin_idx": "199",
"end_idx": "202",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "CRH"
},
{
"begin_idx": "220",
"end_idx": "223",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "CRH"
},
{
"begin_idx": "284",
"end_idx": "287",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "CRH"
},
{
"begin_idx": "0",
"end_idx": "9",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "92",
"end_idx": "101",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "305",
"end_idx": "314",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "463",
"end_idx": "472",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "556",
"end_idx": "565",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "729",
"end_idx": "738",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "950",
"end_idx": "959",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "1150",
"end_idx": "1159",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "1610",
"end_idx": "1619",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "1668",
"end_idx": "1677",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "2090",
"end_idx": "2099",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "2205",
"end_idx": "2214",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
}
] | {
"begin_idx": "166",
"end_idx": "197",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "corticotropin-releasing hormone"
} | {
"begin_idx": "513",
"end_idx": "525",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
} | No |
10213916 | Urocortin and inflammation: confounding effects of hypotension on measures of inflammation. | Urocortin, a newly isolated 40-amino-acid mammalian peptide homologous to corticotropin-releasing hormone (CRH), activates both CRH type 1 and 2 receptors, but may be an endogenous ligand for CRH receptor type 2. Urocortin given systemically inhibited heat-induced paw edema in the rat, and was therefore ascribed anti-inflammatory properties. We examined the effects of urocortin in the carrageenin-induced subcutaneous inflammation model. Rats were treated with urocortin 200 (n = 6) or 20 nmol/kg (n = 6); inflammatory exudates were reduced by approximately 30% compared to controls (n = 7) at both doses. However, since subcutaneous urocortin has been shown to reduce arterial blood pressure, we tested the hypothesis that its antiedema and antiextravasatory effects were secondary to arterial hypotension. Therefore, we examined the parallel effects of urocortin- and hydralazine-induced hypotension on acute inflammation induced by carrageenin in the rat. Rats were treated with subcutaneous carrageenin and control injections (n = 8), carrageenin and urocortin (20 nmol/kg, n = 9), or carrageenin and intraperitoneal hydralazine (10 mg/kg, n = 8). Mean arterial blood pressure was measured hourly for 7 h in 12 animals, and after 2 h, the nadir of treatment, in a further 13 animals. Rats were then sacrificed, and the inflammatory exudate volume and leukocyte count were measured. Mean exudate volumes were reduced from 4.8 +/- 0.5 ml (controls) to 2.4 +/- 0.3 ml (p = 0.004) and 2.9 +/- 0.6 ml (p = 0.007) in urocortin- and hydralazine-treated animals, respectively. Urocortin and hydralazine both produced a significant fall in blood pressure compared to controls, with mean arterial pressure 2 h after carrageenin injection falling to 51.0 +/- 4.1 (p < 0.001) and 34.6 +/- 4.6 (p < 0.001) vs. 92.9 +/- 3.7 mm Hg in controls, respectively. A significant positive correlation was noted between blood pressure and inflammatory exudate volume (r = 0. 52, p = 0.007). As both hydralazine and urocortin lowered blood pressure and inflammatory exudate volume, we suggest that the anti-inflammatory effects of urocortin and related neuropeptides may be nonspecific, acting through hypotension rather than through direct anti-inflammatory mechanisms. The use of inflammatory models which rely on extravasation may be inappropriate for the study of substances that produce hypotension. | Urocortin and /"inflammation"/: confounding effects of hypotension on measures of /"inflammation"/. | Urocortin, a newly isolated 40-amino-acid mammalian peptide homologous to /"corticotropin-releasing hormone"/ (/"CRH"/), activates both /"CRH"/ type 1 and 2 receptors, but may be an endogenous ligand for /"CRH"/ receptor type 2. Urocortin given systemically inhibited heat-induced paw edema in the rat, and was therefore ascribed anti-inflammatory properties. We examined the effects of urocortin in the carrageenin-induced subcutaneous /"inflammation"/ model. Rats were treated with urocortin 200 (n = 6) or 20 nmol/kg (n = 6); inflammatory exudates were reduced by approximately 30% compared to controls (n = 7) at both doses. However, since subcutaneous urocortin has been shown to reduce arterial blood pressure, we tested the hypothesis that its antiedema and antiextravasatory effects were secondary to arterial hypotension. Therefore, we examined the parallel effects of urocortin- and hydralazine-induced hypotension on acute /"inflammation"/ induced by carrageenin in the rat. Rats were treated with subcutaneous carrageenin and control injections (n = 8), carrageenin and urocortin (20 nmol/kg, n = 9), or carrageenin and intraperitoneal hydralazine (10 mg/kg, n = 8). Mean arterial blood pressure was measured hourly for 7 h in 12 animals, and after 2 h, the nadir of treatment, in a further 13 animals. Rats were then sacrificed, and the inflammatory exudate volume and leukocyte count were measured. Mean exudate volumes were reduced from 4.8 +/- 0.5 ml (controls) to 2.4 +/- 0.3 ml (p = 0.004) and 2.9 +/- 0.6 ml (p = 0.007) in urocortin- and hydralazine-treated animals, respectively. Urocortin and hydralazine both produced a significant fall in blood pressure compared to controls, with mean arterial pressure 2 h after carrageenin injection falling to 51.0 +/- 4.1 (p < 0.001) and 34.6 +/- 4.6 (p < 0.001) vs. 92.9 +/- 3.7 mm Hg in controls, respectively. A significant positive correlation was noted between blood pressure and inflammatory exudate volume (r = 0. 52, p = 0.007). As both hydralazine and urocortin lowered blood pressure and inflammatory exudate volume, we suggest that the anti-inflammatory effects of urocortin and related neuropeptides may be nonspecific, acting through hypotension rather than through direct anti-inflammatory mechanisms. The use of inflammatory models which rely on extravasation may be inappropriate for the study of substances that produce hypotension. | [
{
"begin_idx": "361",
"end_idx": "366",
"entity_id": "D004487",
"entity_type": "Disease",
"text_name": "edema"
},
{
"begin_idx": "51",
"end_idx": "62",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "890",
"end_idx": "901",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "985",
"end_idx": "996",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "1722",
"end_idx": "1744",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "fall in blood pressure"
},
{
"begin_idx": "2276",
"end_idx": "2287",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "2466",
"end_idx": "2477",
"entity_id": "D007022",
"entity_type": "Disease",
"text_name": "hypotension"
},
{
"begin_idx": "14",
"end_idx": "26",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "78",
"end_idx": "90",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "513",
"end_idx": "525",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "1006",
"end_idx": "1018",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
},
{
"begin_idx": "166",
"end_idx": "197",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "corticotropin-releasing hormone"
},
{
"begin_idx": "199",
"end_idx": "202",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "CRH"
},
{
"begin_idx": "220",
"end_idx": "223",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "CRH"
},
{
"begin_idx": "284",
"end_idx": "287",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "CRH"
},
{
"begin_idx": "0",
"end_idx": "9",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "92",
"end_idx": "101",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "305",
"end_idx": "314",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "463",
"end_idx": "472",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "556",
"end_idx": "565",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "729",
"end_idx": "738",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "950",
"end_idx": "959",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "1150",
"end_idx": "1159",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "1610",
"end_idx": "1619",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "1668",
"end_idx": "1677",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "Urocortin"
},
{
"begin_idx": "2090",
"end_idx": "2099",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
},
{
"begin_idx": "2205",
"end_idx": "2214",
"entity_id": "7349",
"entity_type": "Gene",
"text_name": "urocortin"
}
] | {
"begin_idx": "220",
"end_idx": "223",
"entity_id": "1392",
"entity_type": "Gene",
"text_name": "CRH"
} | {
"begin_idx": "14",
"end_idx": "26",
"entity_id": "D007249",
"entity_type": "Disease",
"text_name": "inflammation"
} | No |
10234503 | Mutational analysis of PAX6: 16 novel mutations including 5 missense mutations with a mild aniridia phenotype. | Mutations in the developmental control gene PAX6 have been shown to be the genetic cause of aniridia, which is a severe panocular eye disease characterised by iris hypoplasia. The inheritance is autosomal dominant with high penetrance but variable expressivity. Here we describe a mutational analysis of 27 Danish patients using a dideoxy fingerprinting method, which identified PAX6 mutations in 18 individuals with aniridia. A thorough phenotype description was made for the 18 patients. A total of 19 mutations, of which 16 were novel, are described. Among these were five missense mutations which tended to be associated with a milder aniridia phenotype, and in fact one of them seemed to be non-penetrant. Four of the five missense mutations were located in the paired domain. We also describe a third alternative spliced PAX6 isoform in which two of the four missense mutations would be spliced out. Our observations support the concept of dosage effects of PAX6 mutations as well as presenting evidence for variable expressivity and gonadal mosaicism. | Mutational analysis of /"PAX6"/: 16 novel mutations including 5 missense mutations with a mild /"aniridia"/ phenotype. | Mutations in the developmental control gene /"PAX6"/ have been shown to be the genetic cause of /"aniridia"/, which is a severe panocular eye disease characterised by iris hypoplasia. The inheritance is autosomal dominant with high penetrance but variable expressivity. Here we describe a mutational analysis of 27 Danish patients using a dideoxy fingerprinting method, which identified /"PAX6"/ mutations in 18 individuals with /"aniridia"/. A thorough phenotype description was made for the 18 patients. A total of 19 mutations, of which 16 were novel, are described. Among these were five missense mutations which tended to be associated with a milder /"aniridia"/ phenotype, and in fact one of them seemed to be non-penetrant. Four of the five missense mutations were located in the paired domain. We also describe a third alternative spliced /"PAX6"/ isoform in which two of the four missense mutations would be spliced out. Our observations support the concept of dosage effects of /"PAX6"/ mutations as well as presenting evidence for variable expressivity and gonadal mosaicism. | [
{
"begin_idx": "231",
"end_idx": "252",
"entity_id": "D005128",
"entity_type": "Disease",
"text_name": "panocular eye disease"
},
{
"begin_idx": "270",
"end_idx": "285",
"entity_id": "D007499",
"entity_type": "Disease",
"text_name": "iris hypoplasia"
},
{
"begin_idx": "91",
"end_idx": "99",
"entity_id": "D015783",
"entity_type": "Disease",
"text_name": "aniridia"
},
{
"begin_idx": "203",
"end_idx": "211",
"entity_id": "D015783",
"entity_type": "Disease",
"text_name": "aniridia"
},
{
"begin_idx": "528",
"end_idx": "536",
"entity_id": "D015783",
"entity_type": "Disease",
"text_name": "aniridia"
},
{
"begin_idx": "750",
"end_idx": "758",
"entity_id": "D015783",
"entity_type": "Disease",
"text_name": "aniridia"
},
{
"begin_idx": "23",
"end_idx": "27",
"entity_id": "5080",
"entity_type": "Gene",
"text_name": "PAX6"
},
{
"begin_idx": "155",
"end_idx": "159",
"entity_id": "5080",
"entity_type": "Gene",
"text_name": "PAX6"
},
{
"begin_idx": "490",
"end_idx": "494",
"entity_id": "5080",
"entity_type": "Gene",
"text_name": "PAX6"
},
{
"begin_idx": "938",
"end_idx": "942",
"entity_id": "5080",
"entity_type": "Gene",
"text_name": "PAX6"
},
{
"begin_idx": "1075",
"end_idx": "1079",
"entity_id": "5080",
"entity_type": "Gene",
"text_name": "PAX6"
}
] | {
"begin_idx": "23",
"end_idx": "27",
"entity_id": "5080",
"entity_type": "Gene",
"text_name": "PAX6"
} | {
"begin_idx": "91",
"end_idx": "99",
"entity_id": "D015783",
"entity_type": "Disease",
"text_name": "aniridia"
} | Yes |
10234503 | Mutational analysis of PAX6: 16 novel mutations including 5 missense mutations with a mild aniridia phenotype. | Mutations in the developmental control gene PAX6 have been shown to be the genetic cause of aniridia, which is a severe panocular eye disease characterised by iris hypoplasia. The inheritance is autosomal dominant with high penetrance but variable expressivity. Here we describe a mutational analysis of 27 Danish patients using a dideoxy fingerprinting method, which identified PAX6 mutations in 18 individuals with aniridia. A thorough phenotype description was made for the 18 patients. A total of 19 mutations, of which 16 were novel, are described. Among these were five missense mutations which tended to be associated with a milder aniridia phenotype, and in fact one of them seemed to be non-penetrant. Four of the five missense mutations were located in the paired domain. We also describe a third alternative spliced PAX6 isoform in which two of the four missense mutations would be spliced out. Our observations support the concept of dosage effects of PAX6 mutations as well as presenting evidence for variable expressivity and gonadal mosaicism. | Mutational analysis of /"PAX6"/: 16 novel mutations including 5 missense mutations with a mild aniridia phenotype. | Mutations in the developmental control gene /"PAX6"/ have been shown to be the genetic cause of aniridia, which is a severe panocular eye disease characterised by /"iris hypoplasia"/. The inheritance is autosomal dominant with high penetrance but variable expressivity. Here we describe a mutational analysis of 27 Danish patients using a dideoxy fingerprinting method, which identified /"PAX6"/ mutations in 18 individuals with aniridia. A thorough phenotype description was made for the 18 patients. A total of 19 mutations, of which 16 were novel, are described. Among these were five missense mutations which tended to be associated with a milder aniridia phenotype, and in fact one of them seemed to be non-penetrant. Four of the five missense mutations were located in the paired domain. We also describe a third alternative spliced /"PAX6"/ isoform in which two of the four missense mutations would be spliced out. Our observations support the concept of dosage effects of /"PAX6"/ mutations as well as presenting evidence for variable expressivity and gonadal mosaicism. | [
{
"begin_idx": "231",
"end_idx": "252",
"entity_id": "D005128",
"entity_type": "Disease",
"text_name": "panocular eye disease"
},
{
"begin_idx": "270",
"end_idx": "285",
"entity_id": "D007499",
"entity_type": "Disease",
"text_name": "iris hypoplasia"
},
{
"begin_idx": "91",
"end_idx": "99",
"entity_id": "D015783",
"entity_type": "Disease",
"text_name": "aniridia"
},
{
"begin_idx": "203",
"end_idx": "211",
"entity_id": "D015783",
"entity_type": "Disease",
"text_name": "aniridia"
},
{
"begin_idx": "528",
"end_idx": "536",
"entity_id": "D015783",
"entity_type": "Disease",
"text_name": "aniridia"
},
{
"begin_idx": "750",
"end_idx": "758",
"entity_id": "D015783",
"entity_type": "Disease",
"text_name": "aniridia"
},
{
"begin_idx": "23",
"end_idx": "27",
"entity_id": "5080",
"entity_type": "Gene",
"text_name": "PAX6"
},
{
"begin_idx": "155",
"end_idx": "159",
"entity_id": "5080",
"entity_type": "Gene",
"text_name": "PAX6"
},
{
"begin_idx": "490",
"end_idx": "494",
"entity_id": "5080",
"entity_type": "Gene",
"text_name": "PAX6"
},
{
"begin_idx": "938",
"end_idx": "942",
"entity_id": "5080",
"entity_type": "Gene",
"text_name": "PAX6"
},
{
"begin_idx": "1075",
"end_idx": "1079",
"entity_id": "5080",
"entity_type": "Gene",
"text_name": "PAX6"
}
] | {
"begin_idx": "1075",
"end_idx": "1079",
"entity_id": "5080",
"entity_type": "Gene",
"text_name": "PAX6"
} | {
"begin_idx": "270",
"end_idx": "285",
"entity_id": "D007499",
"entity_type": "Disease",
"text_name": "iris hypoplasia"
} | No |
10318961 | Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. | Delta9-Tetrahydrocannabinol (Delta9-THC), the major psychoactive ingredient in preparations of Cannabis sativa (marijuana, hashish), elicits central nervous system (CNS) responses, including cognitive alterations and euphoria. These responses account for the abuse potential of cannabis, while other effects such as analgesia suggest potential medicinal applications. To study the role of the major known target of cannabinoids in the CNS, the CB1 cannabinoid receptor, we have produced a mouse strain with a disrupted CB1 gene. CB1 knockout mice appeared healthy and fertile, but they had a significantly increased mortality rate. They also displayed reduced locomotor activity, increased ring catalepsy, and hypoalgesia in hotplate and formalin tests. Delta9-THC-induced ring-catalepsy, hypomobility, and hypothermia were completely absent in CB1 mutant mice. In contrast, we still found Delta9-THC-induced analgesia in the tail-flick test and other behavioral (licking of the abdomen) and physiological (diarrhea) responses after Delta9-THC administration. Thus, most, but not all, CNS effects of Delta9-THC are mediated by the CB1 receptor. | Increased mortality, hypoactivity, and hypoalgesia in cannabinoid /"CB1"/ receptor knockout mice. | Delta9-Tetrahydrocannabinol (Delta9-THC), the major psychoactive ingredient in preparations of Cannabis sativa (marijuana, hashish), elicits central nervous system (CNS) responses, including cognitive alterations and euphoria. These responses account for the abuse potential of cannabis, while other effects such as analgesia suggest potential medicinal applications. To study the role of the major known target of cannabinoids in the CNS, the /"CB1"/ cannabinoid receptor, we have produced a mouse strain with a disrupted /"CB1"/ gene. /"CB1"/ knockout mice appeared healthy and fertile, but they had a significantly increased mortality rate. They also displayed reduced locomotor activity, increased ring /"catalepsy"/, and hypoalgesia in hotplate and formalin tests. Delta9-THC-induced ring-/"catalepsy"/, hypomobility, and hypothermia were completely absent in /"CB1"/ mutant mice. In contrast, we still found Delta9-THC-induced analgesia in the tail-flick test and other behavioral (licking of the abdomen) and physiological (diarrhea) responses after Delta9-THC administration. Thus, most, but not all, CNS effects of Delta9-THC are mediated by the /"CB1"/ receptor. | [
{
"begin_idx": "410",
"end_idx": "419",
"entity_id": "D000699",
"entity_type": "Disease",
"text_name": "analgesia"
},
{
"begin_idx": "1003",
"end_idx": "1012",
"entity_id": "D000699",
"entity_type": "Disease",
"text_name": "analgesia"
},
{
"begin_idx": "746",
"end_idx": "772",
"entity_id": "D001523",
"entity_type": "Disease",
"text_name": "reduced locomotor activity"
},
{
"begin_idx": "372",
"end_idx": "380",
"entity_id": "D002189",
"entity_type": "Disease",
"text_name": "cannabis"
},
{
"begin_idx": "789",
"end_idx": "798",
"entity_id": "D002375",
"entity_type": "Disease",
"text_name": "catalepsy"
},
{
"begin_idx": "872",
"end_idx": "881",
"entity_id": "D002375",
"entity_type": "Disease",
"text_name": "catalepsy"
},
{
"begin_idx": "1101",
"end_idx": "1109",
"entity_id": "D003967",
"entity_type": "Disease",
"text_name": "diarrhea"
},
{
"begin_idx": "901",
"end_idx": "912",
"entity_id": "D007035",
"entity_type": "Disease",
"text_name": "hypothermia"
},
{
"begin_idx": "21",
"end_idx": "33",
"entity_id": "D020018",
"entity_type": "Disease",
"text_name": "hypoactivity"
},
{
"begin_idx": "66",
"end_idx": "69",
"entity_id": "1268",
"entity_type": "Gene",
"text_name": "CB1"
},
{
"begin_idx": "538",
"end_idx": "541",
"entity_id": "1268",
"entity_type": "Gene",
"text_name": "CB1"
},
{
"begin_idx": "613",
"end_idx": "616",
"entity_id": "1268",
"entity_type": "Gene",
"text_name": "CB1"
},
{
"begin_idx": "623",
"end_idx": "626",
"entity_id": "1268",
"entity_type": "Gene",
"text_name": "CB1"
},
{
"begin_idx": "939",
"end_idx": "942",
"entity_id": "1268",
"entity_type": "Gene",
"text_name": "CB1"
},
{
"begin_idx": "1225",
"end_idx": "1228",
"entity_id": "1268",
"entity_type": "Gene",
"text_name": "CB1"
}
] | {
"begin_idx": "66",
"end_idx": "69",
"entity_id": "1268",
"entity_type": "Gene",
"text_name": "CB1"
} | {
"begin_idx": "789",
"end_idx": "798",
"entity_id": "D002375",
"entity_type": "Disease",
"text_name": "catalepsy"
} | Yes |
10318961 | Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. | Delta9-Tetrahydrocannabinol (Delta9-THC), the major psychoactive ingredient in preparations of Cannabis sativa (marijuana, hashish), elicits central nervous system (CNS) responses, including cognitive alterations and euphoria. These responses account for the abuse potential of cannabis, while other effects such as analgesia suggest potential medicinal applications. To study the role of the major known target of cannabinoids in the CNS, the CB1 cannabinoid receptor, we have produced a mouse strain with a disrupted CB1 gene. CB1 knockout mice appeared healthy and fertile, but they had a significantly increased mortality rate. They also displayed reduced locomotor activity, increased ring catalepsy, and hypoalgesia in hotplate and formalin tests. Delta9-THC-induced ring-catalepsy, hypomobility, and hypothermia were completely absent in CB1 mutant mice. In contrast, we still found Delta9-THC-induced analgesia in the tail-flick test and other behavioral (licking of the abdomen) and physiological (diarrhea) responses after Delta9-THC administration. Thus, most, but not all, CNS effects of Delta9-THC are mediated by the CB1 receptor. | Increased mortality, hypoactivity, and hypoalgesia in cannabinoid /"CB1"/ receptor knockout mice. | Delta9-Tetrahydrocannabinol (Delta9-THC), the major psychoactive ingredient in preparations of Cannabis sativa (marijuana, hashish), elicits central nervous system (CNS) responses, including cognitive alterations and euphoria. These responses account for the abuse potential of cannabis, while other effects such as /"analgesia"/ suggest potential medicinal applications. To study the role of the major known target of cannabinoids in the CNS, the /"CB1"/ cannabinoid receptor, we have produced a mouse strain with a disrupted /"CB1"/ gene. /"CB1"/ knockout mice appeared healthy and fertile, but they had a significantly increased mortality rate. They also displayed reduced locomotor activity, increased ring catalepsy, and hypoalgesia in hotplate and formalin tests. Delta9-THC-induced ring-catalepsy, hypomobility, and hypothermia were completely absent in /"CB1"/ mutant mice. In contrast, we still found Delta9-THC-induced /"analgesia"/ in the tail-flick test and other behavioral (licking of the abdomen) and physiological (diarrhea) responses after Delta9-THC administration. Thus, most, but not all, CNS effects of Delta9-THC are mediated by the /"CB1"/ receptor. | [
{
"begin_idx": "410",
"end_idx": "419",
"entity_id": "D000699",
"entity_type": "Disease",
"text_name": "analgesia"
},
{
"begin_idx": "1003",
"end_idx": "1012",
"entity_id": "D000699",
"entity_type": "Disease",
"text_name": "analgesia"
},
{
"begin_idx": "746",
"end_idx": "772",
"entity_id": "D001523",
"entity_type": "Disease",
"text_name": "reduced locomotor activity"
},
{
"begin_idx": "372",
"end_idx": "380",
"entity_id": "D002189",
"entity_type": "Disease",
"text_name": "cannabis"
},
{
"begin_idx": "789",
"end_idx": "798",
"entity_id": "D002375",
"entity_type": "Disease",
"text_name": "catalepsy"
},
{
"begin_idx": "872",
"end_idx": "881",
"entity_id": "D002375",
"entity_type": "Disease",
"text_name": "catalepsy"
},
{
"begin_idx": "1101",
"end_idx": "1109",
"entity_id": "D003967",
"entity_type": "Disease",
"text_name": "diarrhea"
},
{
"begin_idx": "901",
"end_idx": "912",
"entity_id": "D007035",
"entity_type": "Disease",
"text_name": "hypothermia"
},
{
"begin_idx": "21",
"end_idx": "33",
"entity_id": "D020018",
"entity_type": "Disease",
"text_name": "hypoactivity"
},
{
"begin_idx": "66",
"end_idx": "69",
"entity_id": "1268",
"entity_type": "Gene",
"text_name": "CB1"
},
{
"begin_idx": "538",
"end_idx": "541",
"entity_id": "1268",
"entity_type": "Gene",
"text_name": "CB1"
},
{
"begin_idx": "613",
"end_idx": "616",
"entity_id": "1268",
"entity_type": "Gene",
"text_name": "CB1"
},
{
"begin_idx": "623",
"end_idx": "626",
"entity_id": "1268",
"entity_type": "Gene",
"text_name": "CB1"
},
{
"begin_idx": "939",
"end_idx": "942",
"entity_id": "1268",
"entity_type": "Gene",
"text_name": "CB1"
},
{
"begin_idx": "1225",
"end_idx": "1228",
"entity_id": "1268",
"entity_type": "Gene",
"text_name": "CB1"
}
] | {
"begin_idx": "939",
"end_idx": "942",
"entity_id": "1268",
"entity_type": "Gene",
"text_name": "CB1"
} | {
"begin_idx": "1003",
"end_idx": "1012",
"entity_id": "D000699",
"entity_type": "Disease",
"text_name": "analgesia"
} | No |
10433910 | Goosecoid acts cell autonomously in mesenchyme-derived tissues during craniofacial development. | Mice homozygous for a targeted deletion of the homeobox gene Goosecoid (Gsc) have multiple craniofacial defects. To understand the mechanisms responsible for these defects, the behavior of Gsc-null cells was examined in morula aggregation chimeras. In these chimeras, Gsc-null cells were marked with beta-galactosidase (beta-gal) activity using the ROSA26 lacZ allele. In addition, mice with a lacZ gene that had been introduced into the Gsc locus were used as a guide to visualize the location of Gsc-expressing cells. In Gsc-null<->wild-type chimeras, tissues that would normally not express Gsc were composed of both Gsc-null and wild-type cells that were well mixed, reflecting the overall genotypic composition of the chimeras. However, craniofacial tissues that would normally express Gsc were essentially devoid of Gsc-null cells. Furthermore, the nasal capsules and mandibles of the chimeras had defects similar to Gsc-null mice that varied in severity depending upon the proportion of Gsc-null cells. These results combined with the analysis of Gsc-null mice suggest that Gsc functions cell autonomously in mesenchyme-derived tissues of the head. A developmental analysis of the tympanic ring bone, a bone that is always absent in Gsc-null mice because of defects at the cell condensation stage, showed that Gsc-null cells had the capacity to form the tympanic ring condensation in the presence of wild-type cells. However, analysis of the tympanic ring bones of 18.5 d.p.c. chimeras suggests that Gsc-null cells were not maintained. The participation of Gsc-null cells in the tympanic ring condensation of chimeras may be an epigenetic phenomenon that results in a local environment in which more precursor cells are present. Thus, the skeletal defects observed in Gsc-null mice may reflect a regional reduction of precursor cells during embryonic development. | /"Goosecoid"/ acts cell autonomously in mesenchyme-derived tissues during craniofacial development. | Mice homozygous for a targeted deletion of the homeobox gene /"Goosecoid"/ (/"Gsc"/) have multiple /"craniofacial defects"/. To understand the mechanisms responsible for these defects, the behavior of /"Gsc"/-null cells was examined in morula aggregation chimeras. In these chimeras, /"Gsc"/-null cells were marked with beta-galactosidase (beta-gal) activity using the ROSA26 lacZ allele. In addition, mice with a lacZ gene that had been introduced into the /"Gsc"/ locus were used as a guide to visualize the location of /"Gsc"/-expressing cells. In /"Gsc"/-null<->wild-type chimeras, tissues that would normally not express /"Gsc"/ were composed of both /"Gsc"/-null and wild-type cells that were well mixed, reflecting the overall genotypic composition of the chimeras. However, craniofacial tissues that would normally express /"Gsc"/ were essentially devoid of /"Gsc"/-null cells. Furthermore, the nasal capsules and mandibles of the chimeras had defects similar to /"Gsc"/-null mice that varied in severity depending upon the proportion of /"Gsc"/-null cells. These results combined with the analysis of /"Gsc"/-null mice suggest that /"Gsc"/ functions cell autonomously in mesenchyme-derived tissues of the head. A developmental analysis of the tympanic ring bone, a bone that is always absent in /"Gsc"/-null mice because of defects at the cell condensation stage, showed that /"Gsc"/-null cells had the capacity to form the tympanic ring condensation in the presence of wild-type cells. However, analysis of the tympanic ring bones of 18.5 d.p.c. chimeras suggests that /"Gsc"/-null cells were not maintained. The participation of /"Gsc"/-null cells in the tympanic ring condensation of chimeras may be an epigenetic phenomenon that results in a local environment in which more precursor cells are present. Thus, the skeletal defects observed in /"Gsc"/-null mice may reflect a regional reduction of precursor cells during embryonic development. | [
{
"begin_idx": "396",
"end_idx": "414",
"entity_id": "D016537",
"entity_type": "Disease",
"text_name": "beta-galactosidase"
},
{
"begin_idx": "416",
"end_idx": "424",
"entity_id": "D016537",
"entity_type": "Disease",
"text_name": "beta-gal"
},
{
"begin_idx": "187",
"end_idx": "207",
"entity_id": "D019465",
"entity_type": "Disease",
"text_name": "craniofacial defects"
},
{
"begin_idx": "0",
"end_idx": "9",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Goosecoid"
},
{
"begin_idx": "157",
"end_idx": "166",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Goosecoid"
},
{
"begin_idx": "168",
"end_idx": "171",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "285",
"end_idx": "288",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "364",
"end_idx": "367",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "534",
"end_idx": "537",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "594",
"end_idx": "597",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "619",
"end_idx": "622",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "690",
"end_idx": "693",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "716",
"end_idx": "719",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "887",
"end_idx": "890",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "918",
"end_idx": "921",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1019",
"end_idx": "1022",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1090",
"end_idx": "1093",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1150",
"end_idx": "1153",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1177",
"end_idx": "1180",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1336",
"end_idx": "1339",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1413",
"end_idx": "1416",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1603",
"end_idx": "1606",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1660",
"end_idx": "1663",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1871",
"end_idx": "1874",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "445",
"end_idx": "451",
"entity_id": "14910",
"entity_type": "Gene",
"text_name": "ROSA26"
}
] | {
"begin_idx": "0",
"end_idx": "9",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Goosecoid"
} | {
"begin_idx": "187",
"end_idx": "207",
"entity_id": "D019465",
"entity_type": "Disease",
"text_name": "craniofacial defects"
} | Yes |
10433910 | Goosecoid acts cell autonomously in mesenchyme-derived tissues during craniofacial development. | Mice homozygous for a targeted deletion of the homeobox gene Goosecoid (Gsc) have multiple craniofacial defects. To understand the mechanisms responsible for these defects, the behavior of Gsc-null cells was examined in morula aggregation chimeras. In these chimeras, Gsc-null cells were marked with beta-galactosidase (beta-gal) activity using the ROSA26 lacZ allele. In addition, mice with a lacZ gene that had been introduced into the Gsc locus were used as a guide to visualize the location of Gsc-expressing cells. In Gsc-null<->wild-type chimeras, tissues that would normally not express Gsc were composed of both Gsc-null and wild-type cells that were well mixed, reflecting the overall genotypic composition of the chimeras. However, craniofacial tissues that would normally express Gsc were essentially devoid of Gsc-null cells. Furthermore, the nasal capsules and mandibles of the chimeras had defects similar to Gsc-null mice that varied in severity depending upon the proportion of Gsc-null cells. These results combined with the analysis of Gsc-null mice suggest that Gsc functions cell autonomously in mesenchyme-derived tissues of the head. A developmental analysis of the tympanic ring bone, a bone that is always absent in Gsc-null mice because of defects at the cell condensation stage, showed that Gsc-null cells had the capacity to form the tympanic ring condensation in the presence of wild-type cells. However, analysis of the tympanic ring bones of 18.5 d.p.c. chimeras suggests that Gsc-null cells were not maintained. The participation of Gsc-null cells in the tympanic ring condensation of chimeras may be an epigenetic phenomenon that results in a local environment in which more precursor cells are present. Thus, the skeletal defects observed in Gsc-null mice may reflect a regional reduction of precursor cells during embryonic development. | /"Goosecoid"/ acts cell autonomously in mesenchyme-derived tissues during craniofacial development. | Mice homozygous for a targeted deletion of the homeobox gene /"Goosecoid"/ (/"Gsc"/) have multiple craniofacial defects. To understand the mechanisms responsible for these defects, the behavior of /"Gsc"/-null cells was examined in morula aggregation chimeras. In these chimeras, /"Gsc"/-null cells were marked with /"beta-galactosidase"/ (/"beta-gal"/) activity using the ROSA26 lacZ allele. In addition, mice with a lacZ gene that had been introduced into the /"Gsc"/ locus were used as a guide to visualize the location of /"Gsc"/-expressing cells. In /"Gsc"/-null<->wild-type chimeras, tissues that would normally not express /"Gsc"/ were composed of both /"Gsc"/-null and wild-type cells that were well mixed, reflecting the overall genotypic composition of the chimeras. However, craniofacial tissues that would normally express /"Gsc"/ were essentially devoid of /"Gsc"/-null cells. Furthermore, the nasal capsules and mandibles of the chimeras had defects similar to /"Gsc"/-null mice that varied in severity depending upon the proportion of /"Gsc"/-null cells. These results combined with the analysis of /"Gsc"/-null mice suggest that /"Gsc"/ functions cell autonomously in mesenchyme-derived tissues of the head. A developmental analysis of the tympanic ring bone, a bone that is always absent in /"Gsc"/-null mice because of defects at the cell condensation stage, showed that /"Gsc"/-null cells had the capacity to form the tympanic ring condensation in the presence of wild-type cells. However, analysis of the tympanic ring bones of 18.5 d.p.c. chimeras suggests that /"Gsc"/-null cells were not maintained. The participation of /"Gsc"/-null cells in the tympanic ring condensation of chimeras may be an epigenetic phenomenon that results in a local environment in which more precursor cells are present. Thus, the skeletal defects observed in /"Gsc"/-null mice may reflect a regional reduction of precursor cells during embryonic development. | [
{
"begin_idx": "396",
"end_idx": "414",
"entity_id": "D016537",
"entity_type": "Disease",
"text_name": "beta-galactosidase"
},
{
"begin_idx": "416",
"end_idx": "424",
"entity_id": "D016537",
"entity_type": "Disease",
"text_name": "beta-gal"
},
{
"begin_idx": "187",
"end_idx": "207",
"entity_id": "D019465",
"entity_type": "Disease",
"text_name": "craniofacial defects"
},
{
"begin_idx": "0",
"end_idx": "9",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Goosecoid"
},
{
"begin_idx": "157",
"end_idx": "166",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Goosecoid"
},
{
"begin_idx": "168",
"end_idx": "171",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "285",
"end_idx": "288",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "364",
"end_idx": "367",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "534",
"end_idx": "537",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "594",
"end_idx": "597",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "619",
"end_idx": "622",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "690",
"end_idx": "693",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "716",
"end_idx": "719",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "887",
"end_idx": "890",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "918",
"end_idx": "921",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1019",
"end_idx": "1022",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1090",
"end_idx": "1093",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1150",
"end_idx": "1153",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1177",
"end_idx": "1180",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1336",
"end_idx": "1339",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1413",
"end_idx": "1416",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1603",
"end_idx": "1606",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1660",
"end_idx": "1663",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "1871",
"end_idx": "1874",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
},
{
"begin_idx": "445",
"end_idx": "451",
"entity_id": "14910",
"entity_type": "Gene",
"text_name": "ROSA26"
}
] | {
"begin_idx": "594",
"end_idx": "597",
"entity_id": "145258",
"entity_type": "Gene",
"text_name": "Gsc"
} | {
"begin_idx": "396",
"end_idx": "414",
"entity_id": "D016537",
"entity_type": "Disease",
"text_name": "beta-galactosidase"
} | No |
10459349 | Allelic loss of the NF1 gene in NF1-associated plexiform neurofibromas. | Neurofibromatosis 1 (NF1) is an autosomal dominant disorder with a complex variety of clinical symptoms. Genetic alteration of the NF1 gene on 17q11.2 is the disease. Neurofibromas of the peripheral nervous system are one main manifestation. A variant of neurofibroma is the plexiform neurofibroma which can be found in about 30% of NF1-patients, often causing severe clinical symptoms. In this study, we examined 14 such tumors from 10 NF1-patients for allele loss of the NF1 gene (LOH: loss of heterozygosity) using four intragenic polymorphic markers. Loss of heterozygosity was found in eight tumors from five patients, and suspected in one additional tumor from another patient. This finding suggests that loss of the second allele, and thus inactivation of both alleles of the NF1 gene, is associated with the development of plexiform neurofibromas. The 14 plexiform neufibromas were also examined for mutation in the TP53 gene by screening exons 5 through 8 using temperature gradient gel electrophoresis. No mutation was found in any of the tumors. | Allelic loss of the /"NF1"/ gene in /"NF1"/-associated plexiform neurofibromas. | /"Neurofibromatosis 1"/ (/"NF1"/) is an autosomal dominant disorder with a complex variety of clinical symptoms. Genetic alteration of the /"NF1"/ gene on 17q11.2 is the disease. Neurofibromas of the peripheral nervous system are one main manifestation. A variant of /"neurofibroma"/ is the plexiform neurofibroma which can be found in about 30% of /"NF1"/-patients, often causing severe clinical symptoms. In this study, we examined 14 such tumors from 10 /"NF1"/-patients for allele loss of the /"NF1"/ gene (LOH: loss of heterozygosity) using four intragenic polymorphic markers. Loss of heterozygosity was found in eight tumors from five patients, and suspected in one additional tumor from another patient. This finding suggests that loss of the second allele, and thus inactivation of both alleles of the /"NF1"/ gene, is associated with the development of plexiform neurofibromas. The 14 plexiform neufibromas were also examined for mutation in the TP53 gene by screening exons 5 through 8 using temperature gradient gel electrophoresis. No mutation was found in any of the tumors. | [
{
"begin_idx": "494",
"end_idx": "500",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "tumors"
},
{
"begin_idx": "669",
"end_idx": "675",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "tumors"
},
{
"begin_idx": "728",
"end_idx": "733",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "tumor"
},
{
"begin_idx": "1121",
"end_idx": "1127",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "tumors"
},
{
"begin_idx": "327",
"end_idx": "339",
"entity_id": "D009455",
"entity_type": "Disease",
"text_name": "neurofibroma"
},
{
"begin_idx": "239",
"end_idx": "285",
"entity_id": "D010523",
"entity_type": "Disease",
"text_name": "Neurofibromas of the peripheral nervous system"
},
{
"begin_idx": "47",
"end_idx": "70",
"entity_id": "D018318",
"entity_type": "Disease",
"text_name": "plexiform neurofibromas"
},
{
"begin_idx": "347",
"end_idx": "369",
"entity_id": "D018318",
"entity_type": "Disease",
"text_name": "plexiform neurofibroma"
},
{
"begin_idx": "903",
"end_idx": "926",
"entity_id": "D018318",
"entity_type": "Disease",
"text_name": "plexiform neurofibromas"
},
{
"begin_idx": "104",
"end_idx": "131",
"entity_id": "D030342",
"entity_type": "Disease",
"text_name": "autosomal dominant disorder"
},
{
"begin_idx": "20",
"end_idx": "23",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "32",
"end_idx": "35",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "72",
"end_idx": "91",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "Neurofibromatosis 1"
},
{
"begin_idx": "93",
"end_idx": "96",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "203",
"end_idx": "206",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "405",
"end_idx": "408",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "509",
"end_idx": "512",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "545",
"end_idx": "548",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "855",
"end_idx": "858",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "996",
"end_idx": "1000",
"entity_id": "7157",
"entity_type": "Gene",
"text_name": "TP53"
}
] | {
"begin_idx": "72",
"end_idx": "91",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "Neurofibromatosis 1"
} | {
"begin_idx": "327",
"end_idx": "339",
"entity_id": "D009455",
"entity_type": "Disease",
"text_name": "neurofibroma"
} | Yes |
10459349 | Allelic loss of the NF1 gene in NF1-associated plexiform neurofibromas. | Neurofibromatosis 1 (NF1) is an autosomal dominant disorder with a complex variety of clinical symptoms. Genetic alteration of the NF1 gene on 17q11.2 is the disease. Neurofibromas of the peripheral nervous system are one main manifestation. A variant of neurofibroma is the plexiform neurofibroma which can be found in about 30% of NF1-patients, often causing severe clinical symptoms. In this study, we examined 14 such tumors from 10 NF1-patients for allele loss of the NF1 gene (LOH: loss of heterozygosity) using four intragenic polymorphic markers. Loss of heterozygosity was found in eight tumors from five patients, and suspected in one additional tumor from another patient. This finding suggests that loss of the second allele, and thus inactivation of both alleles of the NF1 gene, is associated with the development of plexiform neurofibromas. The 14 plexiform neufibromas were also examined for mutation in the TP53 gene by screening exons 5 through 8 using temperature gradient gel electrophoresis. No mutation was found in any of the tumors. | Allelic loss of the /"NF1"/ gene in /"NF1"/-associated plexiform neurofibromas. | /"Neurofibromatosis 1"/ (/"NF1"/) is an autosomal dominant disorder with a complex variety of clinical symptoms. Genetic alteration of the /"NF1"/ gene on 17q11.2 is the disease. Neurofibromas of the peripheral nervous system are one main manifestation. A variant of neurofibroma is the plexiform neurofibroma which can be found in about 30% of /"NF1"/-patients, often causing severe clinical symptoms. In this study, we examined 14 such /"tumors"/ from 10 /"NF1"/-patients for allele loss of the /"NF1"/ gene (LOH: loss of heterozygosity) using four intragenic polymorphic markers. Loss of heterozygosity was found in eight /"tumors"/ from five patients, and suspected in one additional /"tumor"/ from another patient. This finding suggests that loss of the second allele, and thus inactivation of both alleles of the /"NF1"/ gene, is associated with the development of plexiform neurofibromas. The 14 plexiform neufibromas were also examined for mutation in the TP53 gene by screening exons 5 through 8 using temperature gradient gel electrophoresis. No mutation was found in any of the /"tumors"/. | [
{
"begin_idx": "494",
"end_idx": "500",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "tumors"
},
{
"begin_idx": "669",
"end_idx": "675",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "tumors"
},
{
"begin_idx": "728",
"end_idx": "733",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "tumor"
},
{
"begin_idx": "1121",
"end_idx": "1127",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "tumors"
},
{
"begin_idx": "327",
"end_idx": "339",
"entity_id": "D009455",
"entity_type": "Disease",
"text_name": "neurofibroma"
},
{
"begin_idx": "239",
"end_idx": "285",
"entity_id": "D010523",
"entity_type": "Disease",
"text_name": "Neurofibromas of the peripheral nervous system"
},
{
"begin_idx": "47",
"end_idx": "70",
"entity_id": "D018318",
"entity_type": "Disease",
"text_name": "plexiform neurofibromas"
},
{
"begin_idx": "347",
"end_idx": "369",
"entity_id": "D018318",
"entity_type": "Disease",
"text_name": "plexiform neurofibroma"
},
{
"begin_idx": "903",
"end_idx": "926",
"entity_id": "D018318",
"entity_type": "Disease",
"text_name": "plexiform neurofibromas"
},
{
"begin_idx": "104",
"end_idx": "131",
"entity_id": "D030342",
"entity_type": "Disease",
"text_name": "autosomal dominant disorder"
},
{
"begin_idx": "20",
"end_idx": "23",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "32",
"end_idx": "35",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "72",
"end_idx": "91",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "Neurofibromatosis 1"
},
{
"begin_idx": "93",
"end_idx": "96",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "203",
"end_idx": "206",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "405",
"end_idx": "408",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "509",
"end_idx": "512",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "545",
"end_idx": "548",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "855",
"end_idx": "858",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
},
{
"begin_idx": "996",
"end_idx": "1000",
"entity_id": "7157",
"entity_type": "Gene",
"text_name": "TP53"
}
] | {
"begin_idx": "509",
"end_idx": "512",
"entity_id": "4763",
"entity_type": "Gene",
"text_name": "NF1"
} | {
"begin_idx": "494",
"end_idx": "500",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "tumors"
} | No |
10488956 | The genotype interactions of methylenetetrahydrofolate reductase and renin-angiotensin system genes are associated with myocardial infarction. | We analyzed the evolution with age of the frequencies of the I/D polymorphism of the angiotensin I-converting enzyme (ACE), a1166c of the angiotensin II AT1 receptor (AT1R), M235T of the angiotensinogen (AGT) and A225V of their methylenetetrahydrofolate reductase (MTHFR) gene in a healthy (H) population and the subsequent comparison to age- and sex-matched groups of myocardial infarction (MI) subjects. A total of 472 H subjects were divided into three groups < 30, 30-55 and > 55 years old and 277 individuals with MI into two groups 30-55 and > 55 years old. The evolution with age showed that the AGT M allele (P < 0.001) and the MTHFR V allele (P < 0.05) frequency decreased with age in H men. The comparison between healthy and MI groups showed that the MM genotype frequency increased in MI men > 55 years (OR =4.16; 95% CI; 1.72-10.1) The cc genotype showed a similar behaviour (OR = 3.96; 95% CI; 1.21-12.9). In men, all the combinations with MM genotype presented a high risk, with OR values between 1.10 and 7.22. In women, the cc genotype increased in the MI > 55 group (OR = 6.66; 95% CI; 2.02-21.9). All the combinations with the cc genotype showed OR values between 1.71 and 13.3. The MM genotype in men and cc genotype in men and women, are independent risk factors for MI. We propose that the study of the allele frequency evolution in an H population at different ages is essential to determine risk factors for MI in case-control studies, since data from isolated age-matched groups can be misinterpreted. | The genotype interactions of /"methylenetetrahydrofolate reductase"/ and renin-angiotensin system genes are associated with /"myocardial infarction"/. | We analyzed the evolution with age of the frequencies of the I/D polymorphism of the angiotensin I-converting enzyme (ACE), a1166c of the angiotensin II AT1 receptor (AT1R), M235T of the angiotensinogen (AGT) and A225V of their /"methylenetetrahydrofolate reductase"/ (/"MTHFR"/) gene in a healthy (H) population and the subsequent comparison to age- and sex-matched groups of /"myocardial infarction"/ (/"MI"/) subjects. A total of 472 H subjects were divided into three groups < 30, 30-55 and > 55 years old and 277 individuals with /"MI"/ into two groups 30-55 and > 55 years old. The evolution with age showed that the AGT M allele (P < 0.001) and the /"MTHFR"/ V allele (P < 0.05) frequency decreased with age in H men. The comparison between healthy and /"MI"/ groups showed that the MM genotype frequency increased in /"MI"/ men > 55 years (OR =4.16; 95% CI; 1.72-10.1) The cc genotype showed a similar behaviour (OR = 3.96; 95% CI; 1.21-12.9). In men, all the combinations with MM genotype presented a high risk, with OR values between 1.10 and 7.22. In women, the cc genotype increased in the /"MI"/ > 55 group (OR = 6.66; 95% CI; 2.02-21.9). All the combinations with the cc genotype showed OR values between 1.71 and 13.3. The MM genotype in men and cc genotype in men and women, are independent risk factors for /"MI"/. We propose that the study of the allele frequency evolution in an H population at different ages is essential to determine risk factors for /"MI"/ in case-control studies, since data from isolated age-matched groups can be misinterpreted. | [
{
"begin_idx": "120",
"end_idx": "141",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "myocardial infarction"
},
{
"begin_idx": "512",
"end_idx": "533",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "myocardial infarction"
},
{
"begin_idx": "535",
"end_idx": "537",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "MI"
},
{
"begin_idx": "662",
"end_idx": "664",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "MI"
},
{
"begin_idx": "879",
"end_idx": "881",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "MI"
},
{
"begin_idx": "940",
"end_idx": "942",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "MI"
},
{
"begin_idx": "1213",
"end_idx": "1215",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "MI"
},
{
"begin_idx": "1431",
"end_idx": "1433",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "MI"
},
{
"begin_idx": "1575",
"end_idx": "1577",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "MI"
},
{
"begin_idx": "228",
"end_idx": "259",
"entity_id": "1636",
"entity_type": "Gene",
"text_name": "angiotensin I-converting enzyme"
},
{
"begin_idx": "261",
"end_idx": "264",
"entity_id": "1636",
"entity_type": "Gene",
"text_name": "ACE"
},
{
"begin_idx": "330",
"end_idx": "345",
"entity_id": "183",
"entity_type": "Gene",
"text_name": "angiotensinogen"
},
{
"begin_idx": "310",
"end_idx": "314",
"entity_id": "185",
"entity_type": "Gene",
"text_name": "AT1R"
},
{
"begin_idx": "29",
"end_idx": "64",
"entity_id": "4524",
"entity_type": "Gene",
"text_name": "methylenetetrahydrofolate reductase"
},
{
"begin_idx": "371",
"end_idx": "406",
"entity_id": "4524",
"entity_type": "Gene",
"text_name": "methylenetetrahydrofolate reductase"
},
{
"begin_idx": "408",
"end_idx": "413",
"entity_id": "4524",
"entity_type": "Gene",
"text_name": "MTHFR"
},
{
"begin_idx": "779",
"end_idx": "784",
"entity_id": "4524",
"entity_type": "Gene",
"text_name": "MTHFR"
}
] | {
"begin_idx": "29",
"end_idx": "64",
"entity_id": "4524",
"entity_type": "Gene",
"text_name": "methylenetetrahydrofolate reductase"
} | {
"begin_idx": "120",
"end_idx": "141",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "myocardial infarction"
} | Yes |
10488956 | The genotype interactions of methylenetetrahydrofolate reductase and renin-angiotensin system genes are associated with myocardial infarction. | We analyzed the evolution with age of the frequencies of the I/D polymorphism of the angiotensin I-converting enzyme (ACE), a1166c of the angiotensin II AT1 receptor (AT1R), M235T of the angiotensinogen (AGT) and A225V of their methylenetetrahydrofolate reductase (MTHFR) gene in a healthy (H) population and the subsequent comparison to age- and sex-matched groups of myocardial infarction (MI) subjects. A total of 472 H subjects were divided into three groups < 30, 30-55 and > 55 years old and 277 individuals with MI into two groups 30-55 and > 55 years old. The evolution with age showed that the AGT M allele (P < 0.001) and the MTHFR V allele (P < 0.05) frequency decreased with age in H men. The comparison between healthy and MI groups showed that the MM genotype frequency increased in MI men > 55 years (OR =4.16; 95% CI; 1.72-10.1) The cc genotype showed a similar behaviour (OR = 3.96; 95% CI; 1.21-12.9). In men, all the combinations with MM genotype presented a high risk, with OR values between 1.10 and 7.22. In women, the cc genotype increased in the MI > 55 group (OR = 6.66; 95% CI; 2.02-21.9). All the combinations with the cc genotype showed OR values between 1.71 and 13.3. The MM genotype in men and cc genotype in men and women, are independent risk factors for MI. We propose that the study of the allele frequency evolution in an H population at different ages is essential to determine risk factors for MI in case-control studies, since data from isolated age-matched groups can be misinterpreted. | The genotype interactions of methylenetetrahydrofolate reductase and renin-angiotensin system genes are associated with /"myocardial infarction"/. | We analyzed the evolution with age of the frequencies of the I/D polymorphism of the angiotensin I-converting enzyme (ACE), a1166c of the angiotensin II AT1 receptor (/"AT1R"/), M235T of the angiotensinogen (AGT) and A225V of their methylenetetrahydrofolate reductase (MTHFR) gene in a healthy (H) population and the subsequent comparison to age- and sex-matched groups of /"myocardial infarction"/ (/"MI"/) subjects. A total of 472 H subjects were divided into three groups < 30, 30-55 and > 55 years old and 277 individuals with /"MI"/ into two groups 30-55 and > 55 years old. The evolution with age showed that the AGT M allele (P < 0.001) and the MTHFR V allele (P < 0.05) frequency decreased with age in H men. The comparison between healthy and /"MI"/ groups showed that the MM genotype frequency increased in /"MI"/ men > 55 years (OR =4.16; 95% CI; 1.72-10.1) The cc genotype showed a similar behaviour (OR = 3.96; 95% CI; 1.21-12.9). In men, all the combinations with MM genotype presented a high risk, with OR values between 1.10 and 7.22. In women, the cc genotype increased in the /"MI"/ > 55 group (OR = 6.66; 95% CI; 2.02-21.9). All the combinations with the cc genotype showed OR values between 1.71 and 13.3. The MM genotype in men and cc genotype in men and women, are independent risk factors for /"MI"/. We propose that the study of the allele frequency evolution in an H population at different ages is essential to determine risk factors for /"MI"/ in case-control studies, since data from isolated age-matched groups can be misinterpreted. | [
{
"begin_idx": "120",
"end_idx": "141",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "myocardial infarction"
},
{
"begin_idx": "512",
"end_idx": "533",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "myocardial infarction"
},
{
"begin_idx": "535",
"end_idx": "537",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "MI"
},
{
"begin_idx": "662",
"end_idx": "664",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "MI"
},
{
"begin_idx": "879",
"end_idx": "881",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "MI"
},
{
"begin_idx": "940",
"end_idx": "942",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "MI"
},
{
"begin_idx": "1213",
"end_idx": "1215",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "MI"
},
{
"begin_idx": "1431",
"end_idx": "1433",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "MI"
},
{
"begin_idx": "1575",
"end_idx": "1577",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "MI"
},
{
"begin_idx": "228",
"end_idx": "259",
"entity_id": "1636",
"entity_type": "Gene",
"text_name": "angiotensin I-converting enzyme"
},
{
"begin_idx": "261",
"end_idx": "264",
"entity_id": "1636",
"entity_type": "Gene",
"text_name": "ACE"
},
{
"begin_idx": "330",
"end_idx": "345",
"entity_id": "183",
"entity_type": "Gene",
"text_name": "angiotensinogen"
},
{
"begin_idx": "310",
"end_idx": "314",
"entity_id": "185",
"entity_type": "Gene",
"text_name": "AT1R"
},
{
"begin_idx": "29",
"end_idx": "64",
"entity_id": "4524",
"entity_type": "Gene",
"text_name": "methylenetetrahydrofolate reductase"
},
{
"begin_idx": "371",
"end_idx": "406",
"entity_id": "4524",
"entity_type": "Gene",
"text_name": "methylenetetrahydrofolate reductase"
},
{
"begin_idx": "408",
"end_idx": "413",
"entity_id": "4524",
"entity_type": "Gene",
"text_name": "MTHFR"
},
{
"begin_idx": "779",
"end_idx": "784",
"entity_id": "4524",
"entity_type": "Gene",
"text_name": "MTHFR"
}
] | {
"begin_idx": "310",
"end_idx": "314",
"entity_id": "185",
"entity_type": "Gene",
"text_name": "AT1R"
} | {
"begin_idx": "1213",
"end_idx": "1215",
"entity_id": "D009203",
"entity_type": "Disease",
"text_name": "MI"
} | No |
10508521 | Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12). | Retinitis pigmentosa (RP) comprises a clinically and genetically heterogeneous group of diseases that afflicts approximately 1.5 million people worldwide. Affected individuals suffer from a progressive degeneration of the photoreceptors, eventually resulting in severe visual impairment. To isolate candidate genes for chorioretinal diseases, we cloned cDNAs specifically or preferentially expressed in the human retina and the retinal pigment epithelium (RPE) through a novel suppression subtractive hybridization (SSH) method. One of these cDNAs (RET3C11) mapped to chromosome 1q31-q32.1, a region harbouring a gene involved in a severe form of autosomal recessive RP characterized by a typical preservation of the para-arteriolar RPE (RP12; ref. 3). The full-length cDNA encodes an extracellular protein with 19 EGF-like domains, 3 laminin A G-like domains and a C-type lectin domain. This protein is homologous to the Drosophila melanogaster protein crumbs (CRB), and denoted CRB1 (crumbs homologue 1). In ten unrelated RP patients with preserved para-arteriolar RPE, we identified a homozygous AluY insertion disrupting the ORF, five homozygous missense mutations and four compound heterozygous mutations in CRB1. The similarity to CRB suggests a role for CRB1 in cell-cell interaction and possibly in the maintenance of cell polarity in the retina. The distinct RPE abnormalities observed in RP12 patients suggest that CRB1 mutations trigger a novel mechanism of photoreceptor degeneration. | Mutations in a human homologue of Drosophila crumbs cause /"retinitis pigmentosa"/ (/"RP12"/). | /"Retinitis pigmentosa"/ (/"RP"/) comprises a clinically and genetically heterogeneous group of diseases that afflicts approximately 1.5 million people worldwide. Affected individuals suffer from a progressive degeneration of the photoreceptors, eventually resulting in severe visual impairment. To isolate candidate genes for chorioretinal diseases, we cloned cDNAs specifically or preferentially expressed in the human retina and the retinal pigment epithelium (RPE) through a novel suppression subtractive hybridization (SSH) method. One of these cDNAs (RET3C11) mapped to chromosome 1q31-q32.1, a region harbouring a gene involved in a severe form of /"autosomal recessive RP"/ characterized by a typical preservation of the para-arteriolar RPE (/"RP12"/; ref. 3). The full-length cDNA encodes an extracellular protein with 19 EGF-like domains, 3 laminin A G-like domains and a C-type lectin domain. This protein is homologous to the Drosophila melanogaster protein crumbs (CRB), and denoted /"CRB1"/ (crumbs homologue 1). In ten unrelated /"RP"/ patients with preserved para-arteriolar RPE, we identified a homozygous AluY insertion disrupting the ORF, five homozygous missense mutations and four compound heterozygous mutations in /"CRB1"/. The similarity to CRB suggests a role for /"CRB1"/ in cell-cell interaction and possibly in the maintenance of cell polarity in the retina. The distinct RPE abnormalities observed in /"RP12"/ patients suggest that /"CRB1"/ mutations trigger a novel mechanism of photoreceptor degeneration. | [
{
"begin_idx": "80",
"end_idx": "84",
"entity_id": "C563999",
"entity_type": "Disease",
"text_name": "RP12"
},
{
"begin_idx": "825",
"end_idx": "829",
"entity_id": "C563999",
"entity_type": "Disease",
"text_name": "RP12"
},
{
"begin_idx": "1485",
"end_idx": "1489",
"entity_id": "C563999",
"entity_type": "Disease",
"text_name": "RP12"
},
{
"begin_idx": "406",
"end_idx": "428",
"entity_id": "D002825",
"entity_type": "Disease",
"text_name": "chorioretinal diseases"
},
{
"begin_idx": "1556",
"end_idx": "1582",
"entity_id": "D009410",
"entity_type": "Disease",
"text_name": "photoreceptor degeneration"
},
{
"begin_idx": "58",
"end_idx": "78",
"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "retinitis pigmentosa"
},
{
"begin_idx": "87",
"end_idx": "107",
"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "Retinitis pigmentosa"
},
{
"begin_idx": "109",
"end_idx": "111",
"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "RP"
},
{
"begin_idx": "734",
"end_idx": "756",
"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "autosomal recessive RP"
},
{
"begin_idx": "1111",
"end_idx": "1113",
"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "RP"
},
{
"begin_idx": "356",
"end_idx": "373",
"entity_id": "D014786",
"entity_type": "Disease",
"text_name": "visual impairment"
},
{
"begin_idx": "80",
"end_idx": "84",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "RP12"
},
{
"begin_idx": "825",
"end_idx": "829",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "RP12"
},
{
"begin_idx": "1067",
"end_idx": "1071",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "CRB1"
},
{
"begin_idx": "1300",
"end_idx": "1304",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "CRB1"
},
{
"begin_idx": "1348",
"end_idx": "1352",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "CRB1"
},
{
"begin_idx": "1485",
"end_idx": "1489",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "RP12"
},
{
"begin_idx": "1512",
"end_idx": "1516",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "CRB1"
}
] | {
"begin_idx": "80",
"end_idx": "84",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "RP12"
} | {
"begin_idx": "734",
"end_idx": "756",
"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "autosomal recessive RP"
} | Yes |
10508521 | Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12). | Retinitis pigmentosa (RP) comprises a clinically and genetically heterogeneous group of diseases that afflicts approximately 1.5 million people worldwide. Affected individuals suffer from a progressive degeneration of the photoreceptors, eventually resulting in severe visual impairment. To isolate candidate genes for chorioretinal diseases, we cloned cDNAs specifically or preferentially expressed in the human retina and the retinal pigment epithelium (RPE) through a novel suppression subtractive hybridization (SSH) method. One of these cDNAs (RET3C11) mapped to chromosome 1q31-q32.1, a region harbouring a gene involved in a severe form of autosomal recessive RP characterized by a typical preservation of the para-arteriolar RPE (RP12; ref. 3). The full-length cDNA encodes an extracellular protein with 19 EGF-like domains, 3 laminin A G-like domains and a C-type lectin domain. This protein is homologous to the Drosophila melanogaster protein crumbs (CRB), and denoted CRB1 (crumbs homologue 1). In ten unrelated RP patients with preserved para-arteriolar RPE, we identified a homozygous AluY insertion disrupting the ORF, five homozygous missense mutations and four compound heterozygous mutations in CRB1. The similarity to CRB suggests a role for CRB1 in cell-cell interaction and possibly in the maintenance of cell polarity in the retina. The distinct RPE abnormalities observed in RP12 patients suggest that CRB1 mutations trigger a novel mechanism of photoreceptor degeneration. | Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (/"RP12"/12"/). | Retinitis pigmentosa (RP) comprises a clinically and genetically heterogeneous group of diseases that afflicts approximately 1.5 million people worldwide. Affected individuals suffer from a progressive degeneration of the photoreceptors, eventually resulting in severe visual impairment. To isolate candidate genes for chorioretinal diseases, we cloned cDNAs specifically or preferentially expressed in the human retina and the retinal pigment epithelium (RPE) through a novel suppression subtractive hybridization (SSH) method. One of these cDNAs (RET3C11) mapped to chromosome 1q31-q32.1, a region harbouring a gene involved in a severe form of autosomal recessive RP characterized by a typical preservation of the para-arteriolar RPE (/"RP12"/12"/; ref. 3). The full-length cDNA encodes an extracellular protein with 19 EGF-like domains, 3 laminin A G-like domains and a C-type lectin domain. This protein is homologous to the Drosophila melanogaster protein crumbs (CRB), and denoted /"CRB1"/ (crumbs homologue 1). In ten unrelated RP patients with preserved para-arteriolar RPE, we identified a homozygous AluY insertion disrupting the ORF, five homozygous missense mutations and four compound heterozygous mutations in /"CRB1"/. The similarity to CRB suggests a role for /"CRB1"/ in cell-cell interaction and possibly in the maintenance of cell polarity in the retina. The distinct RPE abnormalities observed in /"RP12"/12"/ patients suggest that /"CRB1"/ mutations trigger a novel mechanism of photoreceptor degeneration. | [
{
"begin_idx": "80",
"end_idx": "84",
"entity_id": "C563999",
"entity_type": "Disease",
"text_name": "RP12"
},
{
"begin_idx": "825",
"end_idx": "829",
"entity_id": "C563999",
"entity_type": "Disease",
"text_name": "RP12"
},
{
"begin_idx": "1485",
"end_idx": "1489",
"entity_id": "C563999",
"entity_type": "Disease",
"text_name": "RP12"
},
{
"begin_idx": "406",
"end_idx": "428",
"entity_id": "D002825",
"entity_type": "Disease",
"text_name": "chorioretinal diseases"
},
{
"begin_idx": "1556",
"end_idx": "1582",
"entity_id": "D009410",
"entity_type": "Disease",
"text_name": "photoreceptor degeneration"
},
{
"begin_idx": "58",
"end_idx": "78",
"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "retinitis pigmentosa"
},
{
"begin_idx": "87",
"end_idx": "107",
"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "Retinitis pigmentosa"
},
{
"begin_idx": "109",
"end_idx": "111",
"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "RP"
},
{
"begin_idx": "734",
"end_idx": "756",
"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "autosomal recessive RP"
},
{
"begin_idx": "1111",
"end_idx": "1113",
"entity_id": "D012174",
"entity_type": "Disease",
"text_name": "RP"
},
{
"begin_idx": "356",
"end_idx": "373",
"entity_id": "D014786",
"entity_type": "Disease",
"text_name": "visual impairment"
},
{
"begin_idx": "80",
"end_idx": "84",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "RP12"
},
{
"begin_idx": "825",
"end_idx": "829",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "RP12"
},
{
"begin_idx": "1067",
"end_idx": "1071",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "CRB1"
},
{
"begin_idx": "1300",
"end_idx": "1304",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "CRB1"
},
{
"begin_idx": "1348",
"end_idx": "1352",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "CRB1"
},
{
"begin_idx": "1485",
"end_idx": "1489",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "RP12"
},
{
"begin_idx": "1512",
"end_idx": "1516",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "CRB1"
}
] | {
"begin_idx": "1300",
"end_idx": "1304",
"entity_id": "23418",
"entity_type": "Gene",
"text_name": "CRB1"
} | {
"begin_idx": "825",
"end_idx": "829",
"entity_id": "C563999",
"entity_type": "Disease",
"text_name": "RP12"
} | No |
10527839 | Association between an alpha(2) macroglobulin DNA polymorphism and late-onset Alzheimer's disease. | An association between a five-base-pair deletion/insertion DNA polymorphism at the alpha(2) macroglobulin gene (A2M) and late-onset Alzheimer's disease (LOAD) has been recently described. We developed a PCR assay to analyze this polymorphism in 190 LOAD patients (older than 65 years) and 400 controls from Spain. Controls were stratified into three groups: <65 years (n = 200), 65 to 80 years (n = 100), and 81 years or older (n = 100). We found a significantly higher frequency of carriers of the D allele in patients older than 81 years compared to controls older than 81 years (p = 0.0012). In addition, the frequency of the D allele was significantly lower in controls older than 81 years compared to controls younger than 65 (p = 0.048). Our work suggests that the D allele confers an age-dependent increased risk to develop late-onset Alzheimer's disease. | Association between an /"alpha(2) macroglobulin"/ DNA polymorphism and /"late-onset Alzheimer's disease"/. | An association between a five-base-pair deletion/insertion DNA polymorphism at the /"alpha(2) macroglobulin"/ gene (/"A2M"/) and /"late-onset Alzheimer's disease"/ (/"LOAD"/) has been recently described. We developed a PCR assay to analyze this polymorphism in 190 /"LOAD"/ patients (older than 65 years) and 400 controls from Spain. Controls were stratified into three groups: <65 years (n = 200), 65 to 80 years (n = 100), and 81 years or older (n = 100). We found a significantly higher frequency of carriers of the D allele in patients older than 81 years compared to controls older than 81 years (p = 0.0012). In addition, the frequency of the D allele was significantly lower in controls older than 81 years compared to controls younger than 65 (p = 0.048). Our work suggests that the D allele confers an age-dependent increased risk to develop /"late-onset Alzheimer's disease"/. | [
{
"begin_idx": "67",
"end_idx": "97",
"entity_id": "D000544",
"entity_type": "Disease",
"text_name": "late-onset Alzheimer's disease"
},
{
"begin_idx": "220",
"end_idx": "250",
"entity_id": "D000544",
"entity_type": "Disease",
"text_name": "late-onset Alzheimer's disease"
},
{
"begin_idx": "252",
"end_idx": "256",
"entity_id": "D000544",
"entity_type": "Disease",
"text_name": "LOAD"
},
{
"begin_idx": "348",
"end_idx": "352",
"entity_id": "D000544",
"entity_type": "Disease",
"text_name": "LOAD"
},
{
"begin_idx": "930",
"end_idx": "960",
"entity_id": "D000544",
"entity_type": "Disease",
"text_name": "late-onset Alzheimer's disease"
},
{
"begin_idx": "23",
"end_idx": "45",
"entity_id": "2",
"entity_type": "Gene",
"text_name": "alpha(2) macroglobulin"
},
{
"begin_idx": "182",
"end_idx": "204",
"entity_id": "2",
"entity_type": "Gene",
"text_name": "alpha(2) macroglobulin"
},
{
"begin_idx": "211",
"end_idx": "214",
"entity_id": "2",
"entity_type": "Gene",
"text_name": "A2M"
}
] | {
"begin_idx": "23",
"end_idx": "45",
"entity_id": "2",
"entity_type": "Gene",
"text_name": "alpha(2) macroglobulin"
} | {
"begin_idx": "67",
"end_idx": "97",
"entity_id": "D000544",
"entity_type": "Disease",
"text_name": "late-onset Alzheimer's disease"
} | Yes |
10532948 | Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent. | The Brugada syndrome is a major cause of sudden death, particularly among young men of Southeast Asian and Japanese origin. The syndrome is characterized electrocardiographically by an ST-segment elevation in V1 through V3 and a rapid polymorphic ventricular tachycardia that can degenerate into ventricular fibrillation. Our group recently linked the disease to mutations in SCN5A, the gene encoding for the alpha subunit of the cardiac sodium channel. When heterologously expressed in frog oocytes, electrophysiological data recorded from the Thr1620Met missense mutant failed to adequately explain the electrocardiographic phenotype. Therefore, we sought to further characterize the electrophysiology of this mutant. We hypothesized that at more physiological temperatures, the missense mutation may change the gating of the sodium channel such that the net outward current is dramatically augmented during the early phases of the right ventricular action potential. In the present study, we test this hypothesis by expressing Thr1620Met in a mammalian cell line, using the patch-clamp technique to study the currents at 32 degrees C. Our results indicate that Thr1620Met current decay kinetics are faster when compared with the wild type at 32 degrees C. Recovery from inactivation was slower for Thr1620Met at 32 degrees C, and steady-state activation was significantly shifted. Our findings explain the features of the ECG of Brugada patients, illustrate for the first time a cardiac sodium channel mutation of which the arrhythmogenicity is revealed only at temperatures approaching the physiological range, and suggest that some patients may be more at risk during febrile states. | Ionic mechanisms responsible for the electrocardiographic phenotype of the /"Brugada syndrome"/ are temperature dependent. | The /"Brugada syndrome"/ is a major cause of sudden death, particularly among young men of Southeast Asian and Japanese origin. The syndrome is characterized electrocardiographically by an ST-segment elevation in V1 through V3 and a rapid polymorphic ventricular tachycardia that can degenerate into ventricular fibrillation. Our group recently linked the disease to mutations in /"SCN5A"/, the gene encoding for the alpha subunit of the cardiac sodium channel. When heterologously expressed in frog oocytes, electrophysiological data recorded from the Thr1620Met missense mutant failed to adequately explain the electrocardiographic phenotype. Therefore, we sought to further characterize the electrophysiology of this mutant. We hypothesized that at more physiological temperatures, the missense mutation may change the gating of the sodium channel such that the net outward current is dramatically augmented during the early phases of the right ventricular action potential. In the present study, we test this hypothesis by expressing Thr1620Met in a mammalian cell line, using the patch-clamp technique to study the currents at 32 degrees C. Our results indicate that Thr1620Met current decay kinetics are faster when compared with the wild type at 32 degrees C. Recovery from inactivation was slower for Thr1620Met at 32 degrees C, and steady-state activation was significantly shifted. Our findings explain the features of the ECG of Brugada patients, illustrate for the first time a cardiac sodium channel mutation of which the arrhythmogenicity is revealed only at temperatures approaching the physiological range, and suggest that some patients may be more at risk during febrile states. | [
{
"begin_idx": "160",
"end_idx": "172",
"entity_id": "D003645",
"entity_type": "Disease",
"text_name": "sudden death"
},
{
"begin_idx": "415",
"end_idx": "439",
"entity_id": "D014693",
"entity_type": "Disease",
"text_name": "ventricular fibrillation"
},
{
"begin_idx": "366",
"end_idx": "389",
"entity_id": "D017180",
"entity_type": "Disease",
"text_name": "ventricular tachycardia"
},
{
"begin_idx": "75",
"end_idx": "91",
"entity_id": "D053840",
"entity_type": "Disease",
"text_name": "Brugada syndrome"
},
{
"begin_idx": "123",
"end_idx": "139",
"entity_id": "D053840",
"entity_type": "Disease",
"text_name": "Brugada syndrome"
},
{
"begin_idx": "495",
"end_idx": "500",
"entity_id": "6331",
"entity_type": "Gene",
"text_name": "SCN5A"
}
] | {
"begin_idx": "495",
"end_idx": "500",
"entity_id": "6331",
"entity_type": "Gene",
"text_name": "SCN5A"
} | {
"begin_idx": "75",
"end_idx": "91",
"entity_id": "D053840",
"entity_type": "Disease",
"text_name": "Brugada syndrome"
} | Yes |
10532948 | Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent. | The Brugada syndrome is a major cause of sudden death, particularly among young men of Southeast Asian and Japanese origin. The syndrome is characterized electrocardiographically by an ST-segment elevation in V1 through V3 and a rapid polymorphic ventricular tachycardia that can degenerate into ventricular fibrillation. Our group recently linked the disease to mutations in SCN5A, the gene encoding for the alpha subunit of the cardiac sodium channel. When heterologously expressed in frog oocytes, electrophysiological data recorded from the Thr1620Met missense mutant failed to adequately explain the electrocardiographic phenotype. Therefore, we sought to further characterize the electrophysiology of this mutant. We hypothesized that at more physiological temperatures, the missense mutation may change the gating of the sodium channel such that the net outward current is dramatically augmented during the early phases of the right ventricular action potential. In the present study, we test this hypothesis by expressing Thr1620Met in a mammalian cell line, using the patch-clamp technique to study the currents at 32 degrees C. Our results indicate that Thr1620Met current decay kinetics are faster when compared with the wild type at 32 degrees C. Recovery from inactivation was slower for Thr1620Met at 32 degrees C, and steady-state activation was significantly shifted. Our findings explain the features of the ECG of Brugada patients, illustrate for the first time a cardiac sodium channel mutation of which the arrhythmogenicity is revealed only at temperatures approaching the physiological range, and suggest that some patients may be more at risk during febrile states. | Ionic mechanisms responsible for the electrocardiographic phenotype of the Brugada syndrome are temperature dependent. | The Brugada syndrome is a major cause of sudden death, particularly among young men of Southeast Asian and Japanese origin. The syndrome is characterized electrocardiographically by an ST-segment elevation in V1 through V3 and a rapid polymorphic /"ventricular tachycardia"/ that can degenerate into ventricular fibrillation. Our group recently linked the disease to mutations in /"SCN5A"/, the gene encoding for the alpha subunit of the cardiac sodium channel. When heterologously expressed in frog oocytes, electrophysiological data recorded from the Thr1620Met missense mutant failed to adequately explain the electrocardiographic phenotype. Therefore, we sought to further characterize the electrophysiology of this mutant. We hypothesized that at more physiological temperatures, the missense mutation may change the gating of the sodium channel such that the net outward current is dramatically augmented during the early phases of the right ventricular action potential. In the present study, we test this hypothesis by expressing Thr1620Met in a mammalian cell line, using the patch-clamp technique to study the currents at 32 degrees C. Our results indicate that Thr1620Met current decay kinetics are faster when compared with the wild type at 32 degrees C. Recovery from inactivation was slower for Thr1620Met at 32 degrees C, and steady-state activation was significantly shifted. Our findings explain the features of the ECG of Brugada patients, illustrate for the first time a cardiac sodium channel mutation of which the arrhythmogenicity is revealed only at temperatures approaching the physiological range, and suggest that some patients may be more at risk during febrile states. | [
{
"begin_idx": "160",
"end_idx": "172",
"entity_id": "D003645",
"entity_type": "Disease",
"text_name": "sudden death"
},
{
"begin_idx": "415",
"end_idx": "439",
"entity_id": "D014693",
"entity_type": "Disease",
"text_name": "ventricular fibrillation"
},
{
"begin_idx": "366",
"end_idx": "389",
"entity_id": "D017180",
"entity_type": "Disease",
"text_name": "ventricular tachycardia"
},
{
"begin_idx": "75",
"end_idx": "91",
"entity_id": "D053840",
"entity_type": "Disease",
"text_name": "Brugada syndrome"
},
{
"begin_idx": "123",
"end_idx": "139",
"entity_id": "D053840",
"entity_type": "Disease",
"text_name": "Brugada syndrome"
},
{
"begin_idx": "495",
"end_idx": "500",
"entity_id": "6331",
"entity_type": "Gene",
"text_name": "SCN5A"
}
] | {
"begin_idx": "495",
"end_idx": "500",
"entity_id": "6331",
"entity_type": "Gene",
"text_name": "SCN5A"
} | {
"begin_idx": "366",
"end_idx": "389",
"entity_id": "D017180",
"entity_type": "Disease",
"text_name": "ventricular tachycardia"
} | No |
10533957 | Lipolysis is an important determinant of isoproterenol-induced myocardial necrosis. | The cardiotoxic effect of isoproterenol (ISO) is associated with, and possibly due to, calcium overload. Prior work suggests that calcium entry into cardiac myocytes after ISO administration occurs in two phases: an early rapid phase, followed by a slow phase beginning about 1 hour after ISO injection, leading to a peak myocardial calcium level after about 4 hours. We have tested the relationship of these phases to myocardial necrosis (MN) by determining the time after ISO administration at which the commitment to MN occurs. This was done by administration of propranolol at various times before and after ISO. In addition, since ISO induces lipolysis, and lipids can be toxic, experiments were conducted to determine if adrenergically-activated lipolysis could play a significant role in ISO-MN. We found that propranolol protected the myocardium equally well when administered anytime within 2 hours of ISO injection, but had no effect when given 4 hours after ISO. This showed that metabolic events taking place more than two hours after ISO injection are required for ISO-MN. As expected from prior work, there was a small and consistent amount of propranolol-resistant ISO-MN. Lipolysis, assessed by measuring serum glycerol levels, increased to tenfold above base line at one hour after ISO administration and returned to near basal levels at 4 hours. Potentiation of lipolysis by intravenous injections of phospholipase A2 (PLA2) or lipoprotein lipase (LPL) to rats treated with ISO substantially augmented MN. Propranolol completely blocked the increase in necrosis produced by PLA2 when given with ISO. Lipases induced only minimal necrosis in the absence of ISO. Administration of adenosine (an anti-lipolytic agent), oxfenicine (an inhibitor of mitochondrial palmitoyl carnitine transferase), or vitamin C (an anti-oxidant) resulted in a 55-60% reduction in MN. These results suggest that critical necrosis-determining events occur between 2 and 4 hours after ISO administration and imply a relationship between ISO-induced lipolysis, calcium influx, and ISO-MN. We hypothesize that importance of lipolysis as a determinant of ISO-MN is related to the generation of free fatty acids, their oxidized/metabolic products, or direct damage to plasma membrane. | Lipolysis is an important determinant of isoproterenol-induced myocardial necrosis. | The cardiotoxic effect of isoproterenol (ISO) is associated with, and possibly due to, calcium overload. Prior work suggests that calcium entry into cardiac myocytes after ISO administration occurs in two phases: an early rapid phase, followed by a slow phase beginning about 1 hour after ISO injection, leading to a peak myocardial calcium level after about 4 hours. We have tested the relationship of these phases to myocardial necrosis (MN) by determining the time after ISO administration at which the commitment to MN occurs. This was done by administration of propranolol at various times before and after ISO. In addition, since ISO induces lipolysis, and lipids can be toxic, experiments were conducted to determine if adrenergically-activated lipolysis could play a significant role in ISO-MN. We found that propranolol protected the myocardium equally well when administered anytime within 2 hours of ISO injection, but had no effect when given 4 hours after ISO. This showed that metabolic events taking place more than two hours after ISO injection are required for ISO-MN. As expected from prior work, there was a small and consistent amount of propranolol-resistant ISO-MN. Lipolysis, assessed by measuring serum glycerol levels, increased to tenfold above base line at one hour after ISO administration and returned to near basal levels at 4 hours. Potentiation of lipolysis by intravenous injections of phospholipase A2 (PLA2) or /"lipoprotein lipase"/ (/"LPL"/) to rats treated with ISO substantially augmented MN. Propranolol completely blocked the increase in /"necrosis"/ produced by PLA2 when given with ISO. Lipases induced only minimal /"necrosis"/ in the absence of ISO. Administration of adenosine (an anti-lipolytic agent), oxfenicine (an inhibitor of mitochondrial palmitoyl carnitine transferase), or vitamin C (an anti-oxidant) resulted in a 55-60% reduction in MN. These results suggest that critical /"necrosis"/-determining events occur between 2 and 4 hours after ISO administration and imply a relationship between ISO-induced lipolysis, calcium influx, and ISO-MN. We hypothesize that importance of lipolysis as a determinant of ISO-MN is related to the generation of free fatty acids, their oxidized/metabolic products, or direct damage to plasma membrane. | [
{
"begin_idx": "63",
"end_idx": "82",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "myocardial necrosis"
},
{
"begin_idx": "503",
"end_idx": "522",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "myocardial necrosis"
},
{
"begin_idx": "524",
"end_idx": "526",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "604",
"end_idx": "606",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "883",
"end_idx": "885",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1166",
"end_idx": "1168",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1268",
"end_idx": "1270",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1604",
"end_idx": "1606",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1959",
"end_idx": "1961",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "2160",
"end_idx": "2162",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "2232",
"end_idx": "2234",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1655",
"end_idx": "1663",
"entity_id": "D009336",
"entity_type": "Disease",
"text_name": "necrosis"
},
{
"begin_idx": "1731",
"end_idx": "1739",
"entity_id": "D009336",
"entity_type": "Disease",
"text_name": "necrosis"
},
{
"begin_idx": "1999",
"end_idx": "2007",
"entity_id": "D009336",
"entity_type": "Disease",
"text_name": "necrosis"
},
{
"begin_idx": "88",
"end_idx": "99",
"entity_id": "D066126",
"entity_type": "Disease",
"text_name": "cardiotoxic"
},
{
"begin_idx": "1530",
"end_idx": "1548",
"entity_id": "4023",
"entity_type": "Gene",
"text_name": "lipoprotein lipase"
},
{
"begin_idx": "1550",
"end_idx": "1553",
"entity_id": "4023",
"entity_type": "Gene",
"text_name": "LPL"
}
] | {
"begin_idx": "1530",
"end_idx": "1548",
"entity_id": "4023",
"entity_type": "Gene",
"text_name": "lipoprotein lipase"
} | {
"begin_idx": "1655",
"end_idx": "1663",
"entity_id": "D009336",
"entity_type": "Disease",
"text_name": "necrosis"
} | Yes |
10533957 | Lipolysis is an important determinant of isoproterenol-induced myocardial necrosis. | The cardiotoxic effect of isoproterenol (ISO) is associated with, and possibly due to, calcium overload. Prior work suggests that calcium entry into cardiac myocytes after ISO administration occurs in two phases: an early rapid phase, followed by a slow phase beginning about 1 hour after ISO injection, leading to a peak myocardial calcium level after about 4 hours. We have tested the relationship of these phases to myocardial necrosis (MN) by determining the time after ISO administration at which the commitment to MN occurs. This was done by administration of propranolol at various times before and after ISO. In addition, since ISO induces lipolysis, and lipids can be toxic, experiments were conducted to determine if adrenergically-activated lipolysis could play a significant role in ISO-MN. We found that propranolol protected the myocardium equally well when administered anytime within 2 hours of ISO injection, but had no effect when given 4 hours after ISO. This showed that metabolic events taking place more than two hours after ISO injection are required for ISO-MN. As expected from prior work, there was a small and consistent amount of propranolol-resistant ISO-MN. Lipolysis, assessed by measuring serum glycerol levels, increased to tenfold above base line at one hour after ISO administration and returned to near basal levels at 4 hours. Potentiation of lipolysis by intravenous injections of phospholipase A2 (PLA2) or lipoprotein lipase (LPL) to rats treated with ISO substantially augmented MN. Propranolol completely blocked the increase in necrosis produced by PLA2 when given with ISO. Lipases induced only minimal necrosis in the absence of ISO. Administration of adenosine (an anti-lipolytic agent), oxfenicine (an inhibitor of mitochondrial palmitoyl carnitine transferase), or vitamin C (an anti-oxidant) resulted in a 55-60% reduction in MN. These results suggest that critical necrosis-determining events occur between 2 and 4 hours after ISO administration and imply a relationship between ISO-induced lipolysis, calcium influx, and ISO-MN. We hypothesize that importance of lipolysis as a determinant of ISO-MN is related to the generation of free fatty acids, their oxidized/metabolic products, or direct damage to plasma membrane. | Lipolysis is an important determinant of isoproterenol-induced /"myocardial necrosis"/. | The cardiotoxic effect of isoproterenol (ISO) is associated with, and possibly due to, calcium overload. Prior work suggests that calcium entry into cardiac myocytes after ISO administration occurs in two phases: an early rapid phase, followed by a slow phase beginning about 1 hour after ISO injection, leading to a peak myocardial calcium level after about 4 hours. We have tested the relationship of these phases to /"myocardial necrosis"/ (/"MN"/) by determining the time after ISO administration at which the commitment to /"MN"/ occurs. This was done by administration of propranolol at various times before and after ISO. In addition, since ISO induces lipolysis, and lipids can be toxic, experiments were conducted to determine if adrenergically-activated lipolysis could play a significant role in ISO-/"MN"/. We found that propranolol protected the myocardium equally well when administered anytime within 2 hours of ISO injection, but had no effect when given 4 hours after ISO. This showed that metabolic events taking place more than two hours after ISO injection are required for ISO-/"MN"/. As expected from prior work, there was a small and consistent amount of propranolol-resistant ISO-/"MN"/. Lipolysis, assessed by measuring serum glycerol levels, increased to tenfold above base line at one hour after ISO administration and returned to near basal levels at 4 hours. Potentiation of lipolysis by intravenous injections of phospholipase A2 (PLA2) or /"lipoprotein lipase"/ (/"LPL"/) to rats treated with ISO substantially augmented /"MN"/. Propranolol completely blocked the increase in necrosis produced by PLA2 when given with ISO. Lipases induced only minimal necrosis in the absence of ISO. Administration of adenosine (an anti-lipolytic agent), oxfenicine (an inhibitor of mitochondrial palmitoyl carnitine transferase), or vitamin C (an anti-oxidant) resulted in a 55-60% reduction in /"MN"/. These results suggest that critical necrosis-determining events occur between 2 and 4 hours after ISO administration and imply a relationship between ISO-induced lipolysis, calcium influx, and ISO-/"MN"/. We hypothesize that importance of lipolysis as a determinant of ISO-/"MN"/ is related to the generation of free fatty acids, their oxidized/metabolic products, or direct damage to plasma membrane. | [
{
"begin_idx": "63",
"end_idx": "82",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "myocardial necrosis"
},
{
"begin_idx": "503",
"end_idx": "522",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "myocardial necrosis"
},
{
"begin_idx": "524",
"end_idx": "526",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "604",
"end_idx": "606",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "883",
"end_idx": "885",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1166",
"end_idx": "1168",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1268",
"end_idx": "1270",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1604",
"end_idx": "1606",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1959",
"end_idx": "1961",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "2160",
"end_idx": "2162",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "2232",
"end_idx": "2234",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1655",
"end_idx": "1663",
"entity_id": "D009336",
"entity_type": "Disease",
"text_name": "necrosis"
},
{
"begin_idx": "1731",
"end_idx": "1739",
"entity_id": "D009336",
"entity_type": "Disease",
"text_name": "necrosis"
},
{
"begin_idx": "1999",
"end_idx": "2007",
"entity_id": "D009336",
"entity_type": "Disease",
"text_name": "necrosis"
},
{
"begin_idx": "88",
"end_idx": "99",
"entity_id": "D066126",
"entity_type": "Disease",
"text_name": "cardiotoxic"
},
{
"begin_idx": "1530",
"end_idx": "1548",
"entity_id": "4023",
"entity_type": "Gene",
"text_name": "lipoprotein lipase"
},
{
"begin_idx": "1550",
"end_idx": "1553",
"entity_id": "4023",
"entity_type": "Gene",
"text_name": "LPL"
}
] | {
"begin_idx": "1530",
"end_idx": "1548",
"entity_id": "4023",
"entity_type": "Gene",
"text_name": "lipoprotein lipase"
} | {
"begin_idx": "63",
"end_idx": "82",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "myocardial necrosis"
} | Yes |
10533957 | Lipolysis is an important determinant of isoproterenol-induced myocardial necrosis. | The cardiotoxic effect of isoproterenol (ISO) is associated with, and possibly due to, calcium overload. Prior work suggests that calcium entry into cardiac myocytes after ISO administration occurs in two phases: an early rapid phase, followed by a slow phase beginning about 1 hour after ISO injection, leading to a peak myocardial calcium level after about 4 hours. We have tested the relationship of these phases to myocardial necrosis (MN) by determining the time after ISO administration at which the commitment to MN occurs. This was done by administration of propranolol at various times before and after ISO. In addition, since ISO induces lipolysis, and lipids can be toxic, experiments were conducted to determine if adrenergically-activated lipolysis could play a significant role in ISO-MN. We found that propranolol protected the myocardium equally well when administered anytime within 2 hours of ISO injection, but had no effect when given 4 hours after ISO. This showed that metabolic events taking place more than two hours after ISO injection are required for ISO-MN. As expected from prior work, there was a small and consistent amount of propranolol-resistant ISO-MN. Lipolysis, assessed by measuring serum glycerol levels, increased to tenfold above base line at one hour after ISO administration and returned to near basal levels at 4 hours. Potentiation of lipolysis by intravenous injections of phospholipase A2 (PLA2) or lipoprotein lipase (LPL) to rats treated with ISO substantially augmented MN. Propranolol completely blocked the increase in necrosis produced by PLA2 when given with ISO. Lipases induced only minimal necrosis in the absence of ISO. Administration of adenosine (an anti-lipolytic agent), oxfenicine (an inhibitor of mitochondrial palmitoyl carnitine transferase), or vitamin C (an anti-oxidant) resulted in a 55-60% reduction in MN. These results suggest that critical necrosis-determining events occur between 2 and 4 hours after ISO administration and imply a relationship between ISO-induced lipolysis, calcium influx, and ISO-MN. We hypothesize that importance of lipolysis as a determinant of ISO-MN is related to the generation of free fatty acids, their oxidized/metabolic products, or direct damage to plasma membrane. | Lipolysis is an important determinant of isoproterenol-induced myocardial necrosis. | The /"cardiotoxic"/ effect of isoproterenol (ISO) is associated with, and possibly due to, calcium overload. Prior work suggests that calcium entry into cardiac myocytes after ISO administration occurs in two phases: an early rapid phase, followed by a slow phase beginning about 1 hour after ISO injection, leading to a peak myocardial calcium level after about 4 hours. We have tested the relationship of these phases to myocardial necrosis (MN) by determining the time after ISO administration at which the commitment to MN occurs. This was done by administration of propranolol at various times before and after ISO. In addition, since ISO induces lipolysis, and lipids can be toxic, experiments were conducted to determine if adrenergically-activated lipolysis could play a significant role in ISO-MN. We found that propranolol protected the myocardium equally well when administered anytime within 2 hours of ISO injection, but had no effect when given 4 hours after ISO. This showed that metabolic events taking place more than two hours after ISO injection are required for ISO-MN. As expected from prior work, there was a small and consistent amount of propranolol-resistant ISO-MN. Lipolysis, assessed by measuring serum glycerol levels, increased to tenfold above base line at one hour after ISO administration and returned to near basal levels at 4 hours. Potentiation of lipolysis by intravenous injections of phospholipase A2 (PLA2) or /"lipoprotein lipase"/ (/"LPL"/) to rats treated with ISO substantially augmented MN. Propranolol completely blocked the increase in necrosis produced by PLA2 when given with ISO. Lipases induced only minimal necrosis in the absence of ISO. Administration of adenosine (an anti-lipolytic agent), oxfenicine (an inhibitor of mitochondrial palmitoyl carnitine transferase), or vitamin C (an anti-oxidant) resulted in a 55-60% reduction in MN. These results suggest that critical necrosis-determining events occur between 2 and 4 hours after ISO administration and imply a relationship between ISO-induced lipolysis, calcium influx, and ISO-MN. We hypothesize that importance of lipolysis as a determinant of ISO-MN is related to the generation of free fatty acids, their oxidized/metabolic products, or direct damage to plasma membrane. | [
{
"begin_idx": "63",
"end_idx": "82",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "myocardial necrosis"
},
{
"begin_idx": "503",
"end_idx": "522",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "myocardial necrosis"
},
{
"begin_idx": "524",
"end_idx": "526",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "604",
"end_idx": "606",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "883",
"end_idx": "885",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1166",
"end_idx": "1168",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1268",
"end_idx": "1270",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1604",
"end_idx": "1606",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1959",
"end_idx": "1961",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "2160",
"end_idx": "2162",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "2232",
"end_idx": "2234",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1655",
"end_idx": "1663",
"entity_id": "D009336",
"entity_type": "Disease",
"text_name": "necrosis"
},
{
"begin_idx": "1731",
"end_idx": "1739",
"entity_id": "D009336",
"entity_type": "Disease",
"text_name": "necrosis"
},
{
"begin_idx": "1999",
"end_idx": "2007",
"entity_id": "D009336",
"entity_type": "Disease",
"text_name": "necrosis"
},
{
"begin_idx": "88",
"end_idx": "99",
"entity_id": "D066126",
"entity_type": "Disease",
"text_name": "cardiotoxic"
},
{
"begin_idx": "1530",
"end_idx": "1548",
"entity_id": "4023",
"entity_type": "Gene",
"text_name": "lipoprotein lipase"
},
{
"begin_idx": "1550",
"end_idx": "1553",
"entity_id": "4023",
"entity_type": "Gene",
"text_name": "LPL"
}
] | {
"begin_idx": "1530",
"end_idx": "1548",
"entity_id": "4023",
"entity_type": "Gene",
"text_name": "lipoprotein lipase"
} | {
"begin_idx": "88",
"end_idx": "99",
"entity_id": "D066126",
"entity_type": "Disease",
"text_name": "cardiotoxic"
} | No |
10533957 | Lipolysis is an important determinant of isoproterenol-induced myocardial necrosis. | The cardiotoxic effect of isoproterenol (ISO) is associated with, and possibly due to, calcium overload. Prior work suggests that calcium entry into cardiac myocytes after ISO administration occurs in two phases: an early rapid phase, followed by a slow phase beginning about 1 hour after ISO injection, leading to a peak myocardial calcium level after about 4 hours. We have tested the relationship of these phases to myocardial necrosis (MN) by determining the time after ISO administration at which the commitment to MN occurs. This was done by administration of propranolol at various times before and after ISO. In addition, since ISO induces lipolysis, and lipids can be toxic, experiments were conducted to determine if adrenergically-activated lipolysis could play a significant role in ISO-MN. We found that propranolol protected the myocardium equally well when administered anytime within 2 hours of ISO injection, but had no effect when given 4 hours after ISO. This showed that metabolic events taking place more than two hours after ISO injection are required for ISO-MN. As expected from prior work, there was a small and consistent amount of propranolol-resistant ISO-MN. Lipolysis, assessed by measuring serum glycerol levels, increased to tenfold above base line at one hour after ISO administration and returned to near basal levels at 4 hours. Potentiation of lipolysis by intravenous injections of phospholipase A2 (PLA2) or lipoprotein lipase (LPL) to rats treated with ISO substantially augmented MN. Propranolol completely blocked the increase in necrosis produced by PLA2 when given with ISO. Lipases induced only minimal necrosis in the absence of ISO. Administration of adenosine (an anti-lipolytic agent), oxfenicine (an inhibitor of mitochondrial palmitoyl carnitine transferase), or vitamin C (an anti-oxidant) resulted in a 55-60% reduction in MN. These results suggest that critical necrosis-determining events occur between 2 and 4 hours after ISO administration and imply a relationship between ISO-induced lipolysis, calcium influx, and ISO-MN. We hypothesize that importance of lipolysis as a determinant of ISO-MN is related to the generation of free fatty acids, their oxidized/metabolic products, or direct damage to plasma membrane. | Lipolysis is an important determinant of isoproterenol-induced myocardial necrosis. | The /"cardiotoxic"/ effect of isoproterenol (ISO) is associated with, and possibly due to, calcium overload. Prior work suggests that calcium entry into cardiac myocytes after ISO administration occurs in two phases: an early rapid phase, followed by a slow phase beginning about 1 hour after ISO injection, leading to a peak myocardial calcium level after about 4 hours. We have tested the relationship of these phases to myocardial necrosis (MN) by determining the time after ISO administration at which the commitment to MN occurs. This was done by administration of propranolol at various times before and after ISO. In addition, since ISO induces lipolysis, and lipids can be toxic, experiments were conducted to determine if adrenergically-activated lipolysis could play a significant role in ISO-MN. We found that propranolol protected the myocardium equally well when administered anytime within 2 hours of ISO injection, but had no effect when given 4 hours after ISO. This showed that metabolic events taking place more than two hours after ISO injection are required for ISO-MN. As expected from prior work, there was a small and consistent amount of propranolol-resistant ISO-MN. Lipolysis, assessed by measuring serum glycerol levels, increased to tenfold above base line at one hour after ISO administration and returned to near basal levels at 4 hours. Potentiation of lipolysis by intravenous injections of phospholipase A2 (PLA2) or /"lipoprotein lipase"/ (/"LPL"/) to rats treated with ISO substantially augmented MN. Propranolol completely blocked the increase in necrosis produced by PLA2 when given with ISO. Lipases induced only minimal necrosis in the absence of ISO. Administration of adenosine (an anti-lipolytic agent), oxfenicine (an inhibitor of mitochondrial palmitoyl carnitine transferase), or vitamin C (an anti-oxidant) resulted in a 55-60% reduction in MN. These results suggest that critical necrosis-determining events occur between 2 and 4 hours after ISO administration and imply a relationship between ISO-induced lipolysis, calcium influx, and ISO-MN. We hypothesize that importance of lipolysis as a determinant of ISO-MN is related to the generation of free fatty acids, their oxidized/metabolic products, or direct damage to plasma membrane. | [
{
"begin_idx": "63",
"end_idx": "82",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "myocardial necrosis"
},
{
"begin_idx": "503",
"end_idx": "522",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "myocardial necrosis"
},
{
"begin_idx": "524",
"end_idx": "526",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "604",
"end_idx": "606",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "883",
"end_idx": "885",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1166",
"end_idx": "1168",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1268",
"end_idx": "1270",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1604",
"end_idx": "1606",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1959",
"end_idx": "1961",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "2160",
"end_idx": "2162",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "2232",
"end_idx": "2234",
"entity_id": "D009202",
"entity_type": "Disease",
"text_name": "MN"
},
{
"begin_idx": "1655",
"end_idx": "1663",
"entity_id": "D009336",
"entity_type": "Disease",
"text_name": "necrosis"
},
{
"begin_idx": "1731",
"end_idx": "1739",
"entity_id": "D009336",
"entity_type": "Disease",
"text_name": "necrosis"
},
{
"begin_idx": "1999",
"end_idx": "2007",
"entity_id": "D009336",
"entity_type": "Disease",
"text_name": "necrosis"
},
{
"begin_idx": "88",
"end_idx": "99",
"entity_id": "D066126",
"entity_type": "Disease",
"text_name": "cardiotoxic"
},
{
"begin_idx": "1530",
"end_idx": "1548",
"entity_id": "4023",
"entity_type": "Gene",
"text_name": "lipoprotein lipase"
},
{
"begin_idx": "1550",
"end_idx": "1553",
"entity_id": "4023",
"entity_type": "Gene",
"text_name": "LPL"
}
] | {
"begin_idx": "1550",
"end_idx": "1553",
"entity_id": "4023",
"entity_type": "Gene",
"text_name": "LPL"
} | {
"begin_idx": "88",
"end_idx": "99",
"entity_id": "D066126",
"entity_type": "Disease",
"text_name": "cardiotoxic"
} | No |
10541293 | Aberrant splicing in the PKD2 gene as a cause of polycystic kidney disease. | It is estimated that approximately 15% of families with autosomal dominant polycystic kidney disease (ADPKD) have mutations in PKD2. Identification of these mutations is central to identifying functionally important regions of gene and to understanding the mechanisms underlying the pathogenesis of the disorder. The current study describes mutations in six type 2 ADPKD families. Two single base substitution mutations discovered in the ORF in exon 14 constitute the most COOH-terminal pathogenic variants described to date. One of these mutations is a nonsense change and the other encodes an apparent missense variant. Reverse transcription-PCR from patient lymphoblast RNA showed that, in addition, both mutations resulted in out-of-frame splice variants by activating cryptic splice sites via different mechanisms. The apparent missense variant produced such a strong splicing signal that the processed transcript from the mutant chromosome did not contain any of the normally spliced, missense product. A third mutation, a nonconservative missense change effecting a negatively charged residue in the third transmembrane span, is likely pathogenic and defines a highly conserved residue consistent with a potential channel subunit function for polycystin-2. The remaining three mutations included two frame shifts resulting from deletion of one or two bases in exons 6 and 10, respectively, and a nonsense mutation due to a single base substitution in exon 4. The study also defined a novel intragenic polymorphism in exon 1 that will be useful in analyzing "second hits" in PKD2. Finally, the study demonstrates that there are reduced levels of normal polycystin-2 protein in lymphoblast lines from PKD2-affected individuals and that truncated mutant polycystin-2 cannot be detected in patient lymphoblasts, suggesting that the latter may be unstable in at least some tissues. The mutations described will serve as critical reagents for future functional studies in PKD2. | Aberrant splicing in the /"PKD2"/D2"/ gene as a cause of polycystic kidney disease. | It is estimated that approximately 15% of families with autosomal dominant polycystic kidney disease (ADPKD) have mutations in /"PKD2"/D2"/. Identification of these mutations is central to identifying functionally important regions of gene and to understanding the mechanisms underlying the pathogenesis of the disorder. The current study describes mutations in six type 2 ADPKD families. Two single base substitution mutations discovered in the ORF in exon 14 constitute the most COOH-terminal pathogenic variants described to date. One of these mutations is a nonsense change and the other encodes an apparent missense variant. Reverse transcription-PCR from patient lymphoblast RNA showed that, in addition, both mutations resulted in out-of-frame splice variants by activating cryptic splice sites via different mechanisms. The apparent missense variant produced such a strong splicing signal that the processed transcript from the mutant chromosome did not contain any of the normally spliced, missense product. A third mutation, a nonconservative missense change effecting a negatively charged residue in the third transmembrane span, is likely pathogenic and defines a highly conserved residue consistent with a potential channel subunit function for polycystin-2. The remaining three mutations included two frame shifts resulting from deletion of one or two bases in exons 6 and 10, respectively, and a nonsense mutation due to a single base substitution in exon 4. The study also defined a novel intragenic polymorphism in exon 1 that will be useful in analyzing "second hits" in /"PKD2"/D2"/. Finally, the study demonstrates that there are reduced levels of normal polycystin-2 protein in lymphoblast lines from /"PKD2"/D2"/-affected individuals and that truncated mutant polycystin-2 cannot be detected in patient lymphoblasts, suggesting that the latter may be unstable in at least some tissues. The mutations described will serve as critical reagents for future functional studies in /"PKD2"/D2"/. | [
{
"begin_idx": "49",
"end_idx": "74",
"entity_id": "D007674",
"entity_type": "Disease",
"text_name": "polycystic kidney disease"
},
{
"begin_idx": "132",
"end_idx": "176",
"entity_id": "D007674",
"entity_type": "Disease",
"text_name": "autosomal dominant polycystic kidney disease"
},
{
"begin_idx": "178",
"end_idx": "183",
"entity_id": "D007674",
"entity_type": "Disease",
"text_name": "ADPKD"
},
{
"begin_idx": "441",
"end_idx": "446",
"entity_id": "D007674",
"entity_type": "Disease",
"text_name": "ADPKD"
},
{
"begin_idx": "25",
"end_idx": "29",
"entity_id": "D016891",
"entity_type": "Disease",
"text_name": "PKD2"
},
{
"begin_idx": "203",
"end_idx": "207",
"entity_id": "D016891",
"entity_type": "Disease",
"text_name": "PKD2"
},
{
"begin_idx": "1657",
"end_idx": "1661",
"entity_id": "D016891",
"entity_type": "Disease",
"text_name": "PKD2"
},
{
"begin_idx": "1782",
"end_idx": "1786",
"entity_id": "D016891",
"entity_type": "Disease",
"text_name": "PKD2"
},
{
"begin_idx": "2049",
"end_idx": "2053",
"entity_id": "D016891",
"entity_type": "Disease",
"text_name": "PKD2"
},
{
"begin_idx": "25",
"end_idx": "29",
"entity_id": "5311",
"entity_type": "Gene",
"text_name": "PKD2"
},
{
"begin_idx": "203",
"end_idx": "207",
"entity_id": "5311",
"entity_type": "Gene",
"text_name": "PKD2"
},
{
"begin_idx": "1657",
"end_idx": "1661",
"entity_id": "5311",
"entity_type": "Gene",
"text_name": "PKD2"
},
{
"begin_idx": "1782",
"end_idx": "1786",
"entity_id": "5311",
"entity_type": "Gene",
"text_name": "PKD2"
},
{
"begin_idx": "2049",
"end_idx": "2053",
"entity_id": "5311",
"entity_type": "Gene",
"text_name": "PKD2"
}
] | {
"begin_idx": "25",
"end_idx": "29",
"entity_id": "5311",
"entity_type": "Gene",
"text_name": "PKD2"
} | {
"begin_idx": "25",
"end_idx": "29",
"entity_id": "D016891",
"entity_type": "Disease",
"text_name": "PKD2"
} | Yes |
10541293 | Aberrant splicing in the PKD2 gene as a cause of polycystic kidney disease. | It is estimated that approximately 15% of families with autosomal dominant polycystic kidney disease (ADPKD) have mutations in PKD2. Identification of these mutations is central to identifying functionally important regions of gene and to understanding the mechanisms underlying the pathogenesis of the disorder. The current study describes mutations in six type 2 ADPKD families. Two single base substitution mutations discovered in the ORF in exon 14 constitute the most COOH-terminal pathogenic variants described to date. One of these mutations is a nonsense change and the other encodes an apparent missense variant. Reverse transcription-PCR from patient lymphoblast RNA showed that, in addition, both mutations resulted in out-of-frame splice variants by activating cryptic splice sites via different mechanisms. The apparent missense variant produced such a strong splicing signal that the processed transcript from the mutant chromosome did not contain any of the normally spliced, missense product. A third mutation, a nonconservative missense change effecting a negatively charged residue in the third transmembrane span, is likely pathogenic and defines a highly conserved residue consistent with a potential channel subunit function for polycystin-2. The remaining three mutations included two frame shifts resulting from deletion of one or two bases in exons 6 and 10, respectively, and a nonsense mutation due to a single base substitution in exon 4. The study also defined a novel intragenic polymorphism in exon 1 that will be useful in analyzing "second hits" in PKD2. Finally, the study demonstrates that there are reduced levels of normal polycystin-2 protein in lymphoblast lines from PKD2-affected individuals and that truncated mutant polycystin-2 cannot be detected in patient lymphoblasts, suggesting that the latter may be unstable in at least some tissues. The mutations described will serve as critical reagents for future functional studies in PKD2. | Aberrant splicing in the /"PKD2"/ gene as a cause of /"polycystic kidney disease"/. | It is estimated that approximately 15% of families with /"autosomal dominant polycystic kidney disease"/ (/"ADPKD"/) have mutations in /"PKD2"/. Identification of these mutations is central to identifying functionally important regions of gene and to understanding the mechanisms underlying the pathogenesis of the disorder. The current study describes mutations in six type 2 /"ADPKD"/ families. Two single base substitution mutations discovered in the ORF in exon 14 constitute the most COOH-terminal pathogenic variants described to date. One of these mutations is a nonsense change and the other encodes an apparent missense variant. Reverse transcription-PCR from patient lymphoblast RNA showed that, in addition, both mutations resulted in out-of-frame splice variants by activating cryptic splice sites via different mechanisms. The apparent missense variant produced such a strong splicing signal that the processed transcript from the mutant chromosome did not contain any of the normally spliced, missense product. A third mutation, a nonconservative missense change effecting a negatively charged residue in the third transmembrane span, is likely pathogenic and defines a highly conserved residue consistent with a potential channel subunit function for polycystin-2. The remaining three mutations included two frame shifts resulting from deletion of one or two bases in exons 6 and 10, respectively, and a nonsense mutation due to a single base substitution in exon 4. The study also defined a novel intragenic polymorphism in exon 1 that will be useful in analyzing "second hits" in /"PKD2"/. Finally, the study demonstrates that there are reduced levels of normal polycystin-2 protein in lymphoblast lines from /"PKD2"/-affected individuals and that truncated mutant polycystin-2 cannot be detected in patient lymphoblasts, suggesting that the latter may be unstable in at least some tissues. The mutations described will serve as critical reagents for future functional studies in /"PKD2"/. | [
{
"begin_idx": "49",
"end_idx": "74",
"entity_id": "D007674",
"entity_type": "Disease",
"text_name": "polycystic kidney disease"
},
{
"begin_idx": "132",
"end_idx": "176",
"entity_id": "D007674",
"entity_type": "Disease",
"text_name": "autosomal dominant polycystic kidney disease"
},
{
"begin_idx": "178",
"end_idx": "183",
"entity_id": "D007674",
"entity_type": "Disease",
"text_name": "ADPKD"
},
{
"begin_idx": "441",
"end_idx": "446",
"entity_id": "D007674",
"entity_type": "Disease",
"text_name": "ADPKD"
},
{
"begin_idx": "25",
"end_idx": "29",
"entity_id": "D016891",
"entity_type": "Disease",
"text_name": "PKD2"
},
{
"begin_idx": "203",
"end_idx": "207",
"entity_id": "D016891",
"entity_type": "Disease",
"text_name": "PKD2"
},
{
"begin_idx": "1657",
"end_idx": "1661",
"entity_id": "D016891",
"entity_type": "Disease",
"text_name": "PKD2"
},
{
"begin_idx": "1782",
"end_idx": "1786",
"entity_id": "D016891",
"entity_type": "Disease",
"text_name": "PKD2"
},
{
"begin_idx": "2049",
"end_idx": "2053",
"entity_id": "D016891",
"entity_type": "Disease",
"text_name": "PKD2"
},
{
"begin_idx": "25",
"end_idx": "29",
"entity_id": "5311",
"entity_type": "Gene",
"text_name": "PKD2"
},
{
"begin_idx": "203",
"end_idx": "207",
"entity_id": "5311",
"entity_type": "Gene",
"text_name": "PKD2"
},
{
"begin_idx": "1657",
"end_idx": "1661",
"entity_id": "5311",
"entity_type": "Gene",
"text_name": "PKD2"
},
{
"begin_idx": "1782",
"end_idx": "1786",
"entity_id": "5311",
"entity_type": "Gene",
"text_name": "PKD2"
},
{
"begin_idx": "2049",
"end_idx": "2053",
"entity_id": "5311",
"entity_type": "Gene",
"text_name": "PKD2"
}
] | {
"begin_idx": "203",
"end_idx": "207",
"entity_id": "5311",
"entity_type": "Gene",
"text_name": "PKD2"
} | {
"begin_idx": "441",
"end_idx": "446",
"entity_id": "D007674",
"entity_type": "Disease",
"text_name": "ADPKD"
} | No |
10619808 | Association between plasma CC16 levels, the A38G polymorphism, and asthma. | The effect of the A38G polymorphism on Clara cell secretory protein (CC16) gene expression and asthma was investigated by measuring plasma CC16 levels in 100 asthmatic and nonasthmatic children. Restriction digestion determined the A38G genotype and plasma CC16 levels were analyzed using a sensitive latex immunoassay. Asthmatics had lower mean plasma CC16 levels adjusted for age and gender (7.96 microg/L; 95% confidence interval [CI] = 6.79 to 9.31) than nonasthmatic subjects (9.98 microg/L; 95% CI = 8.83 to 11.26) (p = 0. 006). Similarly adjusted, mean plasma CC16 levels were also lower in 38A/38A (6.79 microg/L; 95% CI = 4.56 to 9.02) than 38G/38G subjects (10.01 microg/L; 95% CI = 7.90 to 12.12; p = 0.003). The odds ratio for asthma diagnosis of 38A/38A subjects was 4.78 (95% CI = 1.08 to 21.18; p = 0.04) compared with 38G/38G subjects. However, this was reduced when corrected from plasma CC16 level, suggesting that the odds of asthma was largely mediated through altered plasma CC16 levels. The 38A sequence was associated with reduced plasma CC16 levels and individuals with lower plasma CC16 levels were more likely to have asthma. This provides further evidence for a significant role of the CC16 gene, 38A allele in the development of asthma. | Association between plasma /"CC16"/ levels, the A38G polymorphism, and /"asthma"/. | The effect of the A38G polymorphism on Clara cell secretory protein (/"CC16"/) gene expression and /"asthma"/ was investigated by measuring plasma /"CC16"/ levels in 100 asthmatic and nonasthmatic children. Restriction digestion determined the A38G genotype and plasma /"CC16"/ levels were analyzed using a sensitive latex immunoassay. Asthmatics had lower mean plasma /"CC16"/ levels adjusted for age and gender (7.96 microg/L; 95% confidence interval [CI] = 6.79 to 9.31) than nonasthmatic subjects (9.98 microg/L; 95% CI = 8.83 to 11.26) (p = 0. 006). Similarly adjusted, mean plasma /"CC16"/ levels were also lower in 38A/38A (6.79 microg/L; 95% CI = 4.56 to 9.02) than 38G/38G subjects (10.01 microg/L; 95% CI = 7.90 to 12.12; p = 0.003). The odds ratio for /"asthma"/ diagnosis of 38A/38A subjects was 4.78 (95% CI = 1.08 to 21.18; p = 0.04) compared with 38G/38G subjects. However, this was reduced when corrected from plasma /"CC16"/ level, suggesting that the odds of /"asthma"/ was largely mediated through altered plasma /"CC16"/ levels. The 38A sequence was associated with reduced plasma /"CC16"/ levels and individuals with lower plasma /"CC16"/ levels were more likely to have /"asthma"/. This provides further evidence for a significant role of the /"CC16"/ gene, 38A allele in the development of /"asthma"/. | [
{
"begin_idx": "67",
"end_idx": "73",
"entity_id": "D001249",
"entity_type": "Disease",
"text_name": "asthma"
},
{
"begin_idx": "170",
"end_idx": "176",
"entity_id": "D001249",
"entity_type": "Disease",
"text_name": "asthma"
},
{
"begin_idx": "814",
"end_idx": "820",
"entity_id": "D001249",
"entity_type": "Disease",
"text_name": "asthma"
},
{
"begin_idx": "1020",
"end_idx": "1026",
"entity_id": "D001249",
"entity_type": "Disease",
"text_name": "asthma"
},
{
"begin_idx": "1219",
"end_idx": "1225",
"entity_id": "D001249",
"entity_type": "Disease",
"text_name": "asthma"
},
{
"begin_idx": "1332",
"end_idx": "1338",
"entity_id": "D001249",
"entity_type": "Disease",
"text_name": "asthma"
},
{
"begin_idx": "27",
"end_idx": "31",
"entity_id": "7356",
"entity_type": "Gene",
"text_name": "CC16"
},
{
"begin_idx": "144",
"end_idx": "148",
"entity_id": "7356",
"entity_type": "Gene",
"text_name": "CC16"
},
{
"begin_idx": "214",
"end_idx": "218",
"entity_id": "7356",
"entity_type": "Gene",
"text_name": "CC16"
},
{
"begin_idx": "332",
"end_idx": "336",
"entity_id": "7356",
"entity_type": "Gene",
"text_name": "CC16"
},
{
"begin_idx": "428",
"end_idx": "432",
"entity_id": "7356",
"entity_type": "Gene",
"text_name": "CC16"
},
{
"begin_idx": "642",
"end_idx": "646",
"entity_id": "7356",
"entity_type": "Gene",
"text_name": "CC16"
},
{
"begin_idx": "980",
"end_idx": "984",
"entity_id": "7356",
"entity_type": "Gene",
"text_name": "CC16"
},
{
"begin_idx": "1071",
"end_idx": "1075",
"entity_id": "7356",
"entity_type": "Gene",
"text_name": "CC16"
},
{
"begin_idx": "1136",
"end_idx": "1140",
"entity_id": "7356",
"entity_type": "Gene",
"text_name": "CC16"
},
{
"begin_idx": "1182",
"end_idx": "1186",
"entity_id": "7356",
"entity_type": "Gene",
"text_name": "CC16"
},
{
"begin_idx": "1288",
"end_idx": "1292",
"entity_id": "7356",
"entity_type": "Gene",
"text_name": "CC16"
}
] | {
"begin_idx": "27",
"end_idx": "31",
"entity_id": "7356",
"entity_type": "Gene",
"text_name": "CC16"
} | {
"begin_idx": "67",
"end_idx": "73",
"entity_id": "D001249",
"entity_type": "Disease",
"text_name": "asthma"
} | Yes |
10670188 | [The C1166 allele of the AT1R gene associated with ACE DD phenotype increases the risk for deep venous thrombosis]. | [The C1166 allele of the /"AT1R"/ gene associated with ACE DD phenotype increases the risk for /"deep venous thrombosis"/]. | [
{
"begin_idx": "55",
"end_idx": "57",
"entity_id": "C536170",
"entity_type": "Disease",
"text_name": "DD"
},
{
"begin_idx": "91",
"end_idx": "113",
"entity_id": "D020246",
"entity_type": "Disease",
"text_name": "deep venous thrombosis"
},
{
"begin_idx": "51",
"end_idx": "54",
"entity_id": "1636",
"entity_type": "Gene",
"text_name": "ACE"
},
{
"begin_idx": "25",
"end_idx": "29",
"entity_id": "185",
"entity_type": "Gene",
"text_name": "AT1R"
}
] | {
"begin_idx": "25",
"end_idx": "29",
"entity_id": "185",
"entity_type": "Gene",
"text_name": "AT1R"
} | {
"begin_idx": "91",
"end_idx": "113",
"entity_id": "D020246",
"entity_type": "Disease",
"text_name": "deep venous thrombosis"
} | Yes |
||
10670188 | [The C1166 allele of the AT1R gene associated with ACE DD phenotype increases the risk for deep venous thrombosis]. | [The C1166 allele of the AT1R gene associated with /"ACE"/ /"DD"/ phenotype increases the risk for deep venous thrombosis]. | [
{
"begin_idx": "55",
"end_idx": "57",
"entity_id": "C536170",
"entity_type": "Disease",
"text_name": "DD"
},
{
"begin_idx": "91",
"end_idx": "113",
"entity_id": "D020246",
"entity_type": "Disease",
"text_name": "deep venous thrombosis"
},
{
"begin_idx": "51",
"end_idx": "54",
"entity_id": "1636",
"entity_type": "Gene",
"text_name": "ACE"
},
{
"begin_idx": "25",
"end_idx": "29",
"entity_id": "185",
"entity_type": "Gene",
"text_name": "AT1R"
}
] | {
"begin_idx": "51",
"end_idx": "54",
"entity_id": "1636",
"entity_type": "Gene",
"text_name": "ACE"
} | {
"begin_idx": "55",
"end_idx": "57",
"entity_id": "C536170",
"entity_type": "Disease",
"text_name": "DD"
} | No |
||
10680585 | Orphanin FQ/nociceptin inhibits morphine withdrawal. | The influence of orphanin FQ/nociceptin (OFQ/N) on the morphine-withdrawal symptom was investigated. Withdrawal syndrome was induced in the morphine-dependent rats by an intraperitoneal (i.p.) injection of 2 mg/kg naloxone hydrochloride--an opioid receptors antagonist. Wet-dog shakes were used as a measure of the abstinence syndrome. Intraventricular injections of OFQ/N (5-20 microg/animal) caused significant inhibition of the withdrawal signs at doses between 15-20 microg, in the morphine-dependent rats. OFQ/N alone did not change behavior of the morphine-dependent animals. The obtained results indicate that OFQ/N can inhibit the morphine withdrawal symptoms induced by naloxone. | /"Orphanin FQ"///"nociceptin"/ inhibits morphine withdrawal. | The influence of /"orphanin FQ"///"nociceptin"/ (OFQ/N) on the morphine-withdrawal symptom was investigated. /"Withdrawal syndrome"/ was induced in the morphine-dependent rats by an intraperitoneal (i.p.) injection of 2 mg/kg naloxone hydrochloride--an opioid receptors antagonist. Wet-dog shakes were used as a measure of the abstinence syndrome. Intraventricular injections of OFQ/N (5-20 microg/animal) caused significant inhibition of the withdrawal signs at doses between 15-20 microg, in the morphine-dependent rats. OFQ/N alone did not change behavior of the morphine-dependent animals. The obtained results indicate that OFQ/N can inhibit the morphine withdrawal symptoms induced by naloxone. | [
{
"begin_idx": "368",
"end_idx": "387",
"entity_id": "D009357",
"entity_type": "Disease",
"text_name": "abstinence syndrome"
},
{
"begin_idx": "154",
"end_idx": "173",
"entity_id": "D013375",
"entity_type": "Disease",
"text_name": "Withdrawal syndrome"
},
{
"begin_idx": "0",
"end_idx": "11",
"entity_id": "5368",
"entity_type": "Gene",
"text_name": "Orphanin FQ"
},
{
"begin_idx": "12",
"end_idx": "22",
"entity_id": "5368",
"entity_type": "Gene",
"text_name": "nociceptin"
},
{
"begin_idx": "70",
"end_idx": "81",
"entity_id": "5368",
"entity_type": "Gene",
"text_name": "orphanin FQ"
},
{
"begin_idx": "82",
"end_idx": "92",
"entity_id": "5368",
"entity_type": "Gene",
"text_name": "nociceptin"
}
] | {
"begin_idx": "0",
"end_idx": "11",
"entity_id": "5368",
"entity_type": "Gene",
"text_name": "Orphanin FQ"
} | {
"begin_idx": "154",
"end_idx": "173",
"entity_id": "D013375",
"entity_type": "Disease",
"text_name": "Withdrawal syndrome"
} | Yes |
10680585 | Orphanin FQ/nociceptin inhibits morphine withdrawal. | The influence of orphanin FQ/nociceptin (OFQ/N) on the morphine-withdrawal symptom was investigated. Withdrawal syndrome was induced in the morphine-dependent rats by an intraperitoneal (i.p.) injection of 2 mg/kg naloxone hydrochloride--an opioid receptors antagonist. Wet-dog shakes were used as a measure of the abstinence syndrome. Intraventricular injections of OFQ/N (5-20 microg/animal) caused significant inhibition of the withdrawal signs at doses between 15-20 microg, in the morphine-dependent rats. OFQ/N alone did not change behavior of the morphine-dependent animals. The obtained results indicate that OFQ/N can inhibit the morphine withdrawal symptoms induced by naloxone. | /"Orphanin FQ"///"nociceptin"/ inhibits morphine withdrawal. | The influence of /"orphanin FQ"///"nociceptin"/ (OFQ/N) on the morphine-withdrawal symptom was investigated. Withdrawal syndrome was induced in the morphine-dependent rats by an intraperitoneal (i.p.) injection of 2 mg/kg naloxone hydrochloride--an opioid receptors antagonist. Wet-dog shakes were used as a measure of the /"abstinence syndrome"/. Intraventricular injections of OFQ/N (5-20 microg/animal) caused significant inhibition of the withdrawal signs at doses between 15-20 microg, in the morphine-dependent rats. OFQ/N alone did not change behavior of the morphine-dependent animals. The obtained results indicate that OFQ/N can inhibit the morphine withdrawal symptoms induced by naloxone. | [
{
"begin_idx": "368",
"end_idx": "387",
"entity_id": "D009357",
"entity_type": "Disease",
"text_name": "abstinence syndrome"
},
{
"begin_idx": "154",
"end_idx": "173",
"entity_id": "D013375",
"entity_type": "Disease",
"text_name": "Withdrawal syndrome"
},
{
"begin_idx": "0",
"end_idx": "11",
"entity_id": "5368",
"entity_type": "Gene",
"text_name": "Orphanin FQ"
},
{
"begin_idx": "12",
"end_idx": "22",
"entity_id": "5368",
"entity_type": "Gene",
"text_name": "nociceptin"
},
{
"begin_idx": "70",
"end_idx": "81",
"entity_id": "5368",
"entity_type": "Gene",
"text_name": "orphanin FQ"
},
{
"begin_idx": "82",
"end_idx": "92",
"entity_id": "5368",
"entity_type": "Gene",
"text_name": "nociceptin"
}
] | {
"begin_idx": "12",
"end_idx": "22",
"entity_id": "5368",
"entity_type": "Gene",
"text_name": "nociceptin"
} | {
"begin_idx": "368",
"end_idx": "387",
"entity_id": "D009357",
"entity_type": "Disease",
"text_name": "abstinence syndrome"
} | No |
10702401 | Association of EWS-FLI1 type 1 fusion with lower proliferative rate in Ewing's sarcoma. | The Ewing's sarcoma (ES) family of tumors, including peripheral neuroectodermal tumor (PNET), is defined genetically by specific chromosomal translocations resulting in fusion of the EWS gene with a member of the ETS family of transcription factors, either FLI1 (90-95%) or ERG (5-10%). A second level of molecular genetic heterogeneity stems from the variation in the location of the translocation breakpoints, resulting in the inclusion of different combinations of exons from EWS and FLI1 (or ERG) in the fusion products. The most common type of EWS-FLI1 fusion transcript, type 1, is associated with a favorable prognosis and appears to encode a functionally weaker transactivator, compared to other fusion types. We sought to determine whether the observed covariation of structure, function, and clinical course correlates with tumor cell kinetic parameters such as proliferative rate and apoptosis, and with expression of the receptor for insulin-like growth factor I (IGF-1R). In a group of 86 ES/PNET with defined EWS-ETS fusions (45 EWS-FLI1 type 1, 27 EWS-FLI1 non-type 1, 14 EWS-ERG), we assessed proliferation rate by immunostaining for Ki-67 using MIB1 antibody (n = 85), apoptosis by TUNEL assay (n = 66), and IGF-1R expression by immunostaining with antibody 1H7 (n = 78). Ki-67 proliferative index was lower in tumors with EWS-FLI1 type 1 than those with non-type 1 EWS-FLI1, whether analyzed as a continuous (P = 0.049) or categorical (P = 0.047) variable. Logistic regression analysis suggests that this association was secondary to the association of type 1 EWS-FLI1 and lower IGF-1R expression (P = 0.04). Comparing EWS-FLI1 to EWS-ERG cases, Ki-67 proliferative index was higher in the latter (P = 0.01, Mann-Whitney test; P = 0.02, Fisher's exact test), but there was no significant difference in IGF-1R. TUNEL results showed no significant differences between groups. Our results suggest that clinical and functional differences between alternative forms of EWS-FLI1 are paralleled by differences in proliferative rate, possibly mediated by differential regulation of the IGF-1R pathway. | Association of EWS-/"FLI1"/ type 1 fusion with lower proliferative rate in /"Ewing's sarcoma"/. | The /"Ewing's sarcoma"/ (/"ES"/) family of tumors, including peripheral neuroectodermal tumor (PNET), is defined genetically by specific chromosomal translocations resulting in fusion of the EWS gene with a member of the ETS family of transcription factors, either /"FLI1"/ (90-95%) or ERG (5-10%). A second level of molecular genetic heterogeneity stems from the variation in the location of the translocation breakpoints, resulting in the inclusion of different combinations of exons from EWS and /"FLI1"/ (or ERG) in the fusion products. The most common type of EWS-/"FLI1"/ fusion transcript, type 1, is associated with a favorable prognosis and appears to encode a functionally weaker transactivator, compared to other fusion types. We sought to determine whether the observed covariation of structure, function, and clinical course correlates with tumor cell kinetic parameters such as proliferative rate and apoptosis, and with expression of the receptor for insulin-like growth factor I (IGF-1R). In a group of 86 /"ES"//PNET with defined EWS-ETS fusions (45 EWS-/"FLI1"/ type 1, 27 EWS-/"FLI1"/ non-type 1, 14 EWS-ERG), we assessed proliferation rate by immunostaining for Ki-67 using MIB1 antibody (n = 85), apoptosis by TUNEL assay (n = 66), and IGF-1R expression by immunostaining with antibody 1H7 (n = 78). Ki-67 proliferative index was lower in tumors with EWS-/"FLI1"/ type 1 than those with non-type 1 EWS-/"FLI1"/, whether analyzed as a continuous (P = 0.049) or categorical (P = 0.047) variable. Logistic regression analysis suggests that this association was secondary to the association of /"type 1 EWS-FLI1"/ and lower IGF-1R expression (P = 0.04). Comparing EWS-/"FLI1"/ to EWS-ERG cases, Ki-67 proliferative index was higher in the latter (P = 0.01, Mann-Whitney test; P = 0.02, Fisher's exact test), but there was no significant difference in IGF-1R. TUNEL results showed no significant differences between groups. Our results suggest that clinical and functional differences between alternative forms of EWS-/"FLI1"/ are paralleled by differences in proliferative rate, possibly mediated by differential regulation of the IGF-1R pathway. | [
{
"begin_idx": "123",
"end_idx": "129",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "tumors"
},
{
"begin_idx": "922",
"end_idx": "927",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "tumor"
},
{
"begin_idx": "1416",
"end_idx": "1422",
"entity_id": "D009369",
"entity_type": "Disease",
"text_name": "tumors"
},
{
"begin_idx": "71",
"end_idx": "86",
"entity_id": "D012512",
"entity_type": "Disease",
"text_name": "Ewing's sarcoma"
},
{
"begin_idx": "92",
"end_idx": "107",
"entity_id": "D012512",
"entity_type": "Disease",
"text_name": "Ewing's sarcoma"
},
{
"begin_idx": "109",
"end_idx": "111",
"entity_id": "D012512",
"entity_type": "Disease",
"text_name": "ES"
},
{
"begin_idx": "1090",
"end_idx": "1092",
"entity_id": "D012512",
"entity_type": "Disease",
"text_name": "ES"
},
{
"begin_idx": "152",
"end_idx": "173",
"entity_id": "D017599",
"entity_type": "Disease",
"text_name": "neuroectodermal tumor"
},
{
"begin_idx": "15",
"end_idx": "18",
"entity_id": "2130",
"entity_type": "Gene",
"text_name": "EWS"
},
{
"begin_idx": "271",
"end_idx": "274",
"entity_id": "2130",
"entity_type": "Gene",
"text_name": "EWS"
},
{
"begin_idx": "567",
"end_idx": "570",
"entity_id": "2130",
"entity_type": "Gene",
"text_name": "EWS"
},
{
"begin_idx": "637",
"end_idx": "640",
"entity_id": "2130",
"entity_type": "Gene",
"text_name": "EWS"
},
{
"begin_idx": "1111",
"end_idx": "1114",
"entity_id": "2130",
"entity_type": "Gene",
"text_name": "EWS"
},
{
"begin_idx": "1131",
"end_idx": "1134",
"entity_id": "2130",
"entity_type": "Gene",
"text_name": "EWS"
},
{
"begin_idx": "1151",
"end_idx": "1154",
"entity_id": "2130",
"entity_type": "Gene",
"text_name": "EWS"
},
{
"begin_idx": "1175",
"end_idx": "1178",
"entity_id": "2130",
"entity_type": "Gene",
"text_name": "EWS"
},
{
"begin_idx": "1428",
"end_idx": "1431",
"entity_id": "2130",
"entity_type": "Gene",
"text_name": "EWS"
},
{
"begin_idx": "1471",
"end_idx": "1474",
"entity_id": "2130",
"entity_type": "Gene",
"text_name": "EWS"
},
{
"begin_idx": "1725",
"end_idx": "1728",
"entity_id": "2130",
"entity_type": "Gene",
"text_name": "EWS"
},
{
"begin_idx": "1737",
"end_idx": "1740",
"entity_id": "2130",
"entity_type": "Gene",
"text_name": "EWS"
},
{
"begin_idx": "2070",
"end_idx": "2073",
"entity_id": "2130",
"entity_type": "Gene",
"text_name": "EWS"
},
{
"begin_idx": "19",
"end_idx": "23",
"entity_id": "2313",
"entity_type": "Gene",
"text_name": "FLI1"
},
{
"begin_idx": "345",
"end_idx": "349",
"entity_id": "2313",
"entity_type": "Gene",
"text_name": "FLI1"
},
{
"begin_idx": "575",
"end_idx": "579",
"entity_id": "2313",
"entity_type": "Gene",
"text_name": "FLI1"
},
{
"begin_idx": "641",
"end_idx": "645",
"entity_id": "2313",
"entity_type": "Gene",
"text_name": "FLI1"
},
{
"begin_idx": "1135",
"end_idx": "1139",
"entity_id": "2313",
"entity_type": "Gene",
"text_name": "FLI1"
},
{
"begin_idx": "1155",
"end_idx": "1159",
"entity_id": "2313",
"entity_type": "Gene",
"text_name": "FLI1"
},
{
"begin_idx": "1432",
"end_idx": "1436",
"entity_id": "2313",
"entity_type": "Gene",
"text_name": "FLI1"
},
{
"begin_idx": "1475",
"end_idx": "1479",
"entity_id": "2313",
"entity_type": "Gene",
"text_name": "FLI1"
},
{
"begin_idx": "1659",
"end_idx": "1674",
"entity_id": "2313",
"entity_type": "Gene",
"text_name": "type 1 EWS-FLI1"
},
{
"begin_idx": "1729",
"end_idx": "1733",
"entity_id": "2313",
"entity_type": "Gene",
"text_name": "FLI1"
},
{
"begin_idx": "2074",
"end_idx": "2078",
"entity_id": "2313",
"entity_type": "Gene",
"text_name": "FLI1"
},
{
"begin_idx": "1064",
"end_idx": "1071",
"entity_id": "3480",
"entity_type": "Gene",
"text_name": "IGF-1R)"
},
{
"begin_idx": "1313",
"end_idx": "1319",
"entity_id": "3480",
"entity_type": "Gene",
"text_name": "IGF-1R"
},
{
"begin_idx": "1685",
"end_idx": "1691",
"entity_id": "3480",
"entity_type": "Gene",
"text_name": "IGF-1R"
},
{
"begin_idx": "1908",
"end_idx": "1914",
"entity_id": "3480",
"entity_type": "Gene",
"text_name": "IGF-1R"
},
{
"begin_idx": "2184",
"end_idx": "2190",
"entity_id": "3480",
"entity_type": "Gene",
"text_name": "IGF-1R"
},
{
"begin_idx": "1250",
"end_idx": "1254",
"entity_id": "57534",
"entity_type": "Gene",
"text_name": "MIB1"
}
] | {
"begin_idx": "1659",
"end_idx": "1674",
"entity_id": "2313",
"entity_type": "Gene",
"text_name": "type 1 EWS-FLI1"
} | {
"begin_idx": "71",
"end_idx": "86",
"entity_id": "D012512",
"entity_type": "Disease",
"text_name": "Ewing's sarcoma"
} | Yes |
End of preview. Expand
in Dataset Viewer.
README.md exists but content is empty.
Use the Edit dataset card button to edit it.
- Downloads last month
- 0