bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of mediator and cytokine release from dispersed nasal polyp cells by mizolastine
Authors: Carayol N. , Crampette L. , Mainprice B. , Ben‐Soussen Paul , Verrecchia M. , Bousquet J. , Lebel B. 
Published: March 2003

Background Mizolastine is a potent and selective H1‐receptor antagonist with antiallergic properties; in in‐vitro animal models, mizolastine was shown to inhibit 5‐lipoxygenase activity and to decrease the release of leukotrienes (LT) and tumor necrosis factor‐α (TNF‐α). This study investigated the effects of three concentrations of mizolastine (0.1, 1.0, 10 µM) on the release of LT (LTB4 and LTC4/D4) and prostaglandin D2 (PGD2) after stimulation by anti‐IgE, and on the spontaneous release of cytokines (TNF‐α and granulocyte/macrophage‐colony‐stimulating factor [GM‐CSF]), from dispersed cells obtained from surgically resected nasal polyps of patients with nasal polyposis.Methods Cells from nasal polyps were obtained using enzymatic dispersion. For experiments involving the measurement of LT and PGD2, the cells were preincubated with mizolastine or its dissolution vehicle for 20 min prior to challenge with 10 µg/ml ε‐chain specific anti‐IgE for 45 min at 37°C; for the cytokine release, cells were incubated with mizolastine or its dissolution vehicle for 24 h. LT and PGD2 were measured by enzyme immunoassay (EIA) and cytokines by enzyme‐linked immunosorbent assay (ELISA) using commercially available kits.Results Mizolastine inhibited significantly and in a dose‐dependent manner the release of LTB4 and TNF‐α at all concentrations, LTC4/D4 at 10 µM, and GM‐CSF from 1 µM; no effect was observed on the release of PGD2.Conclusion Mizolastine inhibits the release of LT, TNF‐α and GM‐CSF in this in vitro model, which mimics closely the inflammatory cells of allergic rhinitis.
Phthalic anhydride allergy: development and characterization of optimized hapten–carrier conjugates for improved diagnosis
Authors: Pakarinen M. , Koivuluhta M. , Kalkkinen N. , Keskinen H. , Nordman H. , Estlander T. , Tupasela O. , Jolanki R. , Lauerma A. I. , Pfäffli P. , Alenius H. 
Published: March 2003

Background: At present the diagnosis of IgE‐mediated hypersensitivity to phthalic anhydride (PA) is based on conjugates that are not characterized or standardized. The aim of this study was to develop optimized and molecularly characterized PA conjugates that can be used to improve the diagnosis of PA‐allergy.Methods: The PA conjugates were synthesized and the number of haptens bound on a carrier protein was estimated by matrix‐assisted laser desorption/ionization time of light (MALDI‐TOF) mass spectrometry. The ability of conjugates to bind IgE and IgG antibodies was measured by enzyme‐linked immunosorbent assay (ELISA). Reactivity of the conjugates in vivo was evaluated by skin prick testing.Results: The most active IgE‐binding conjugates had a PA : HSA molar ratio of 80 : 1. In the optimal conjugates the average numbers of PA haptens per carrier molecule of human serum albumin (HSA) were 14–16. In ELISA, all 13 patients and none of the 20 controls had IgE antibodies to optimized PA conjugate. The sensitivity and specificity of the ELISA was comparable to commercial CAP RAST. PA conjugates elicited positive test results in skin prick testing showing that conjugates are immunologically active also in vivo.Conclusions: These results indicate that optimized and molecularly characterized PA–HSA conjugates can be used both in vitro and in vivo assays to improve the diagnosis of PA allergy.
Nasal mucosal histamine reactivity among young students and teachers, having no or prolonged exposure to a deteriorated indoor climate
Authors: Rudblad S. , Andersson K. , Bodin L. , Stridh G. , Juto J. E. 
Published: March 2003

Background: In a study performed in the spring of 1995, we found a significantly greater nasal mucosal histamine reactivity among teachers, who had worked for several years in a recently renovated moisture‐damaged school, than in those in a control school. In the present study we investigated the students who begun their high‐school studies at both schools in the autumn of 1995 and compared them with the teachers as regards mucosal reactivity, atopy and symptoms.Methods: Twenty‐eight teachers in the target school, 18 teachers in the control school and 45 students from each school underwent a nasal histamine provocation test and a skin‐prick test. They also answered a standardized questionnaire.Results: The teachers in both schools had more marked nasal mucosal histamine reactivity at the lowest provocation concentrations than the students. The histamine provocation curve of the target school teachers had consistently higher values than that of the students (P = 0.0001), but its slope and shape were similar (P = 0.15), while the slope of the provocation curve of the control school teachers was flatter. However, there was only a borderline significance in this respect compared to the students (P = 0.07). Teachers with a dry and crusty appearance of the nasal mucosa on anterior rhinoscopy reacted more strongly to histamine provocation than those without this finding (P = 0.0004). There was a significantly higher frequency of skin‐prick test positivity (SPT+) among the students (P = 0.03). There were no significant differences in nasal mucosal histamine reactivity between atopic and non‐atopic subjects out of pollen season.Conclusions: Teachers had a significantly greater mucosal histamine reactivity than the students, whereas the latter had a significantly higher frequency of atopy. These results are compatible with an age‐related pattern of mucosal reactivity. A crusty appearance of the nasal mucosa seems to predispose to an increase in histamine reactivity. There were no significant differences according to histamine reactivity between atopic and non‐atopic subjects.
The influence of a residual group in low‐molecular‐weight allergoids of Artemisia vulgaris pollen on their allergenicity, IgE‐ and IgG‐binding properties
Authors: Ćirković T. , Gavrović‐Jankulović M. , Prišić S. , Jankov R. M. , Burazer L. , Vučković O. , Šporčić Z. , Paranos S. 
Published: March 2003

Background: Reaction of ε‐amino groups of lysine with potassium cyanate, maleic, or succinic anhydride leads to allergoids of low molecular weight. No study has been performed to compare their properties and investigate the influence of a residual group on allergenicity and human IgE‐ and IgG‐binding of these derivatives.Methods: Allergoids of a pollen extract of Artemisia vulgaris were obtained by means of potassium cyanate, and succinic and maleic anhydride. Biochemical properties were investigated by determination of amino groups, enzyme activity, isoelectric focusing IEF and SDS–PAGE. IgE‐ and IgG‐binding was determined using immunoblots and ELISA inhibition. Allergenicity was investigated by skin prick tests (SPT) on a group of 52 patients, of which 6 were control subjects, 30 were patients with no previous immunotherapy (IT), and 16 were patients undergoing immunotherapy.Results: The same degree of amino‐group modification (more than 85%), residual enzyme activity (less then 15%), IEF, and SDS–PAGE pattern were noted. In the immunoblots of IgE‐binding, there was more pronounced reduction in the succinyl and maleyl derivatives than in the carbamyl one. IgG‐binding was less affected by carbamylation than by acid anhydride modification. The SPT showed that the succinylated derivative had the most reduced allergenicity (98% showed a reduced wheal diameter when tested with the succinyl derivative, 87% with the maleyl allergoid, and 83% with the carbamyl allergoid). The most significant difference among allergoids could be seen in the group of patients with high skin reactivity (83% of patients showed no reaction to the succinyl derivative when compared to the value of 28% for the carbamyl derivative or 22% for the maleyl derivative).Conclusions: According to our results, all three modification procedures yielded allergoids with a similar extent of modification. No single biochemical parameter investigated in the study could predict the degree of reduced allergenicity in vivo. The most reduced allergenicity was seen in the succinyl derivative while the preservation of IgG binding epitopes was of the highest degree for the carbamyl derivative.
Pets in the home and the development of pet allergy in adulthood. The Copenhagen Allergy Study
Authors: Linneberg A. , Nielsen N. H. , Madsen F. , Frølund L. , Dirksen A. , Jørgensen T. 
Published: March 2003

Background: The aim of the study was to investigate the association between exposure to cat and dog in the home and the development (incidence) of IgE sensitization to cat and dog.Methods: Participants in a population‐based study of 15–69‐year‐olds in 1990 were invited to a follow‐up in 1998. Serum IgE antibodies against common inhalant allergens was assessed in 734 subjects (participation rate 69.0%) on two occasions 8 years apart. Information about current or previous keeping of cats and dogs in the home was obtained in a questionnaire at baseline.Results: A cat in the home currently was significantly associated with the development of IgE sentisization to cat (adjusted odds ratio 8.4, 95% confidence interval (CI) 1.7–42.7). Moreover, an atopic predisposition in terms of IgE sensitization to allergens other than cat at baseline was an independent risk factor for the development of IgE sensitization to cat. A dog in the home was not significantly associated with the development of IgE sensitization to dog.Conclusions: In this adult population, exposure to a cat in the home increased the risk of developing IgE sensitization to cat. More prospective data are needed on this issue.
RMRP gene sequence analysis confirms a cartilage‐hair hypoplasia variant with only skeletal manifestations and reveals a high density of single‐nucleotide polymorphisms
Authors: Bonafé L , Schmitt K , Eich G , Giedion A , Superti‐Furga A 
Published: March 2003

Mutations in the RMRP gene that codes for an RNA subunit of the MRP RNAse complex are the cause of cartilage‐hair hypoplasia (CHH; MIM 250250). We tested the hypothesis that recessive metaphyseal dysplasia without hypotrichosis (M1M 250460), a disorder presenting with short stature and metaphyseal dysplasia similar to CHH, but lacking hair anomalies, immunodeficiency and other extra skeletal features, might be allelic to CHH. We identified four mutation‐carrying alleles segregating with the skeletal phenotype in two unrelated boys and their parents. One allele carried the common Finnish mutation +70A → G; the remaining three carried +195C → T, +238C → T, and dupAAGCTGAGGACG at −2. Sequencing 120 alleles from a control group revealed an unusually high density of single‐nucleotide polymorphisms in and around the RMRP gene: the biological significance of this finding is unclear.We conclude that recessive metaphyseal dysplasia without hypotrichosis is a variant of CHH, manifesting only as short stature and metaphyseal dysplasia. Precise diagnosis of this form of metaphyseal dysplasia is not without importance because of recessive inheritance with corresponding recurrence risk, as well as because of potential complications such as anaemia, susceptibility to infections and the increased likelihood of developing cancer. The short stature and metaphyseal changes associated with cone‐shaped epiphyses of the hands should raise the diagnostic possibility of a CHH‐related disorder that can then be confirmed by mutation analysis.
Gene conversion (655G splicing mutation) and the founder effect (Gln318Stop) contribute to the most frequent severe point mutations in congenital adrenal hyperplasia (21‐hydroxylase deficiency) in the Spanish population
Authors: Ezquieta B , Cueva E , Oyarzábal M , Oliver A , Varela J M , Jariego C 
Published: March 2003

This study addresses the contributions of gene conversion and a founder effect to the distribution of the two most frequent severe point mutations of the 21‐hydroxylase (21OH) gene causing congenital adrenal hyperplasia: the 655G splicing mutation at intron 2, and Gln318Stop in a Spanish population. Direct and indirect analyses of segregated mutant and normal 21OH genes in 200 Spanish families (classic and nonclassic 21OH deficiency) were performed. Both mechanisms were found to contribute to different degrees to the defective investigated alleles. The 655G splicing mutation (62 alleles, 15.5%) seemed to be almost exclusively related to recent conversion events, whereas Gln318Stop (33 alleles, 8.3%) is more likely to be due to the dissemination of remotely generated mutant alleles. Other severe defective alleles, 8 bp‐deletion (13 alleles, 3.3%), 306insT (5 alleles, 1.3%), and gene deletions (43 alleles, 11%), as well as the mild mutation Val281Leu (120 alleles, 30%), also appear to be strongly associated with particular D6S273 alleles.Although gene conversion contributes to the generation of severe 21OH alleles, the high frequency of some severe mutations in different geographic areas is consistent with a founder effect.
SCA8 in the Spanish population including one homozygous patient
Authors: Tazón B , Badenas C , Jiménez L , Muñoz E , Milà M 
Published: March 2003

Controversial data have been reported about SCA8 since its description in 1999. The most accepted hypothesis is that CTG expansions within the CTA/CTG combined repeat expansion in the SCA8 locus causes SCA8. It is inherited as a dominant trait with reduced penetrance. The present study, reports the first data regarding SCA8 in the Spanish population and the clinical findings in patients carrying expanded alleles, including one homozygous patient. Two hundred and forty‐six individuals from the Spanish population,including controls (149) and ataxic patients (97), were studied. DNA was extracted from blood samples using standard methods. Amplification of the CTA/CTG 3′untranslated region was achieved by PCR using primers SCA8‐F3 and SCA8‐R4 and conditions described previously. Neurological revaluation was done in individuals carrying the expanded allele. We detected five unrelated expanded alleles corresponding to three affected patients (one of them homozygous) and one healthy individual. SCA8 represents 4% of the total dominant spinocerebellar ataxias studied in our group (Spanish population) (three index patients out of 75 dominant ataxic independent nucleus). The patient that resulted homozygous for the expansion is a 25‐year‐old man with a clinical picture of progressive ataxia and dysarthria that began at the age of 12. On neurological examination, he showed ataxia, slight dysarthria and nystagmus to the extreme lateral gaze. A cranial MRI showed global atrophy of cerebellum but the brainstem was spared. Family history showed the presence of ataxia in his grandfather and father. His mother is healthy at the age of 52 and a molecular study of SCA8 reveals one allele that could be considered as premutated. She has no ataxia antecedents in her family. Our results provide additional information about the SCA8 expansion, within the Spanish population. These results are in agreement with the hypothesis of the CTG expansion in the SCA8 locus being responsible for the SCA8 ataxia showing reduced penetrance. Besides homozygous status, advancing age at onset (as previously described for other SCAs) supports this idea.
Genetic origins in a South American clefting population
Authors: Vieira AR , Karras JC , Orioli IM , Castilla EE , Murray JC 
Published: March 2003

Vieira AR, Karras JC, Orioli IM, Castilla EE, Murray JC. Genetic origins in a South American clefting population.  Clin Genet 2002: 62: 458–463. © Blackwell Munksgaard, 2002It has been proposed that susceptibility to clefting in South America is related to Amerindian ancestry, where clefting is present at a higher frequency than in the other admixed populations (Caucasian and African) that make up the diverse racial mix of current South Americans. To clarify the genetic origins and establish a method for genetic mapping, mitochondrial DNA variation and Y‐chromosome markers were studied in a South American population affected with clefting. Two‐hundred and seventeen subjects and matched controls were selected through the Latin‐American Collaborative Study of Congenital Malformations (ECLAMC). The case group showed a higher frequency of Native American haplogroups and a lower frequency of African haplogroups (p < 0.00001). In addition, the case group showed a much higher frequency of the specific native American haplogroup D than the control group (p < 0.00001). For the Y‐chromosome markers, the case group showed a lower frequency of the African‐specific marker, YAP (p = 0.002), and a higher frequency of the Native American‐specific marker, DYS199 (p < 0.00001). Even though differences were found in the frequencies of the markers studied, the contribution of each founder population was similar for both groups. Results suggest a strong Native American maternal contribution and a strong Caucasian (Spanish and Portuguese) paternal contribution to the population studied. The implications of this finding include the possibility of using admixture mapping approaches to this population.
Influence of hyperglycemia and hyperuricemia on long‐term transplant survival in kidney transplant recipients
Authors: Gerhardt U , Große Hüttmann M , Hohage H 
Published: March 2003

Long‐term prognosis in kidney transplant recipients depends on multiple factors. The purpose of this study was to quantify the influence of hyperuricemia and hyperglycemia (elements of the so‐called ‘syndrome X’, i.e., a combination of metabolic disorders like hyperuricemia, diabetes mellitus, hyperlipidemia, and hypertension) on organ function in 350 kidney transplant recipients who had received 375 kidney transplants up to 1990 and in whom sex, age of recipient and donor, nephrologic disease, duration of dialysis, human leukocyte antigen (HLA) classification, and duration of transplant ischemia had been well matched. We found the influence of hyperuricemia on graft survival to be statistically significant (p≤0.05), while a statistically significant correlation between hyperglycemia and graft survival could not be detected in the present study. The transplant survival rates 2, 4, and 5 yr post‐kidney‐transplantation were 96.7, 80.7, and 78.7 in normogylcemic patients vs. 96.9, 85, and 82.7% in hyperglycemic (>100 mg/dL) kidney transplant recipients (p>0.05). Transplant survival in hyperuricemic patients (male,> 8 mg/dL; female,> 6.2 mg/dL) 2, 4, and 5 yr post‐transplantation was significantly reduced (92.2, 70.6, and 68.8% vs. 98.1, 85.6, and 83.3%), as compared to normouricemic recipients. A combined presence of both hyperuricemia and hyperglycemia probably influencing the prognosis post‐kidney‐transplantation failed to reach the level of statistical significance. We found a significant correlation between age of recipients and plasma glucose (p≤0.01) and between serum uric acid concentrations and diuretic therapy (p≤0.05) and gender (p≤0.05).In conclusion, hyperuricemia after kidney transplantation seems to reduce graft survival, whereas an influence of the carbohydrate metabolism has to be denied.
Chronic cyclosporin nephropathy: long‐term effects of cyclosporin on renal allografts
Authors: Takeda Asami , Uchida Kazuharu , Haba Toshihito , Tominaga Yoshihiro , Katayama Akio , Yoshida Atsuhiro , Oikawa Tadashi , Morozumi Kunio 
Published: March 2003

Takeda A, Uchida K, Haba T, Tominaga Y, Katayama A, Yoshida A, Oikawa T, Morozumi K. Chronic cyclosporin nephropathy: long‐term effects of cyclosporin on renal allografts. Clin Transplantation 2001: 15 (Supplement 5): 22–29. ©Munksgaard, 2001.Cyclosporin (CSA) has significantly reduced both incidence and severity of acute rejection, and brought excellent graft survival rates. Chronic CSA nephrotoxicity seems to be the second most important diagnosis responsible for the late graft failure. CSA‐associated arteriolopathy (CAA) is well known as a characteristic lesion of chronic CSA nephrotoxicity by graft biopsies. There are few reports on the long‐term outcome of renal transplant patients with biopsy‐proven chronic CSA nephrotoxicity after diagnosis of CAA. We conducted two studies, the long‐term outcome of the patients with CAA, and the FGS lesion related to CAA. Seventy‐four CAA patients continued on CSA therapy after diagnosis of CAA were classified into two groups by outcome of the graft after follow‐up: the functioning graft group (n=30) and the graft‐loss group (n=44). There was no significant difference in severity of CAA grade between the functioning and graft‐loss groups. Concomitant lesion of chronic rejection but not severity of CAA was the most important risk factor of graft loss for CAA patients in our study. Of a total of 54 recipients with FGS lesion, 32 patients (59%) were diagnosed as CAA‐associated glomerulopathy (CAG) accompanied with severe CAA. Eighteen of 32 CAG patients lost their grafts after follow‐up. Their serum creatinine level at biopsy was higher than that of the functioning group; however, there was no significant difference in daily proteinuria at biopsy between two groups. We have tried to reduce CSA dosage to maintain lower blood levels than the usual optimal target levels, but did not discontinue CSA after diagnosis of severe CAA and FGS lesion. In 15 isolated pure CAG patients, those with increasing daily proteinuria exceeding 2 g lost their graft function even after reducing CSA administration. The change in daily proteinuria seems to be a useful indicator for late graft loss in the patients of FGS lesion with severe CAA. CAA is not specific for chronic CSA nephrotoxicity, and FGS lesion is also a non‐specific lesion often developed in renal allografts. Our study revealed clinicopathological characteristics of chronic CSA nephrotoxicity. Isolated chronic CSA arteriolopathy of severe degree has a fairly good prognosis under controlled CSA therapy. FGS lesion accompanied by CAA is considered as a new concept of CAG, and increasing proteinuria in patients with CAG is a good indicator for poor outcome. These results will contribute towards an appropriate therapeutic plan for renal transplant patients undergoing long‐term CSA treatment.
The influence of successful prophylactic drug treatment on cognitive dysfunction in bipolar disorders
Authors: Wolf Thomas , Müller‐Oerlinghausen Bruno 
Published: March 2003

Background:
Cognitive variables such as negative self‐evaluations have been discussed as vulnerability factors for depressive syndromes. In the context of bipolar disorders dysfunctional cognitive structures have received little interest as these patients seem to be less disturbed during the euthymic interval than patients with major depression.
Methods:
In the present study, the self‐esteem of remitted patients with DSM‐III‐R diagnosis of major depression (n=20), bipolar disorder (n=20) and healthy controls (n=20) was measured with the Frankfurt Self‐concept Scale (FSKN).
Results:
1) Statistical analysis by analysis of variance (ANOVA) showed no significant differences as to age, sex, etc. between the psychiatric groups. The clinical groups showed lower self‐esteem ratings in comparison to healthy controls. 2) Four groups (T1–T4) of remitted patients with bipolar disorders (20 in each group) were successfully maintained on mood stabilizers (lithium or carbamazepine) and classified by the duration of their episode‐free period. T1 included those who were episode‐free for only the week before discharge from hospital. T2 were symptom‐free for <30 months. T3 were episode‐free for >30 months and <60 months. T4 were episode‐free for >60 months. The comparison of their FSKN self‐esteem ratings by ANOVA suggests that self‐esteem improves during successful prophylactic treatment. A posteriori contrasts indicate a normalized self‐esteem after a bipolar episode‐free period of at least 47 months.
Conclusions:
Dysfunctional cognitions can be demonstrated in unipolar as well as in bipolar patients. Successful episode‐preventive medication with mood stabilizers seems to counteract lowered self‐esteem. Adjunctive cognitive therapy might help to optimize the long‐term course of bipolar disorder.