bluuebunny/crossref_metadata_2025_split huggingface dataset:
DR_SEQAN: a PC/Windows-based software to evaluate drug resistance using human immunodeficiency virus type 1 genotypes
Authors: Garriga César , Menéndez-Arias Luis 
Published: March 2006

AbstractBackgroundGenotypic assays based on DNA sequencing of part or the whole reverse transcriptase (RT)- and protease (PR)-coding regions of the human immunodeficiency virus type 1 (HIV-1) genome have become part of the routine clinical management of HIV-infected individuals. However, the results are difficult to interpret due to complex interactions between mutations found in viral genes.ResultsDR_SEQAN is a tool to analyze RT and PR sequences. The program output includes a list containing all of the amino acid changes found in the query sequence in comparison with the sequence of a wild-type HIV-1 strain. Translation of codons containing nucleotide mixtures can result in potential ambiguities or heterogeneities in the amino acid sequence. The program identifies all possible combinations of 2 or 3 amino acids that derive from translation of triplets containing nucleotide mixtures. In addition, when ambiguities affect codons relevant for drug resistance, DR_SEQAN allows the user to select the appropriate mutation to be considered by the program's drug resistance interpretation algorithm. Resistance is predicted using a rule-based algorithm, whose efficiency and accuracy has been tested with a large set of drug susceptibility data. Drug resistance predictions given by DR_SEQAN were consistent with phenotypic data and coherent with predictions provided by other publicly available algorithms. In addition, the program output provides two tables showing published drug susceptibility data and references for mutations and combinations of mutations found in the analyzed sequence. These data are retrieved from an integrated relational database, implemented in Microsoft Access, which includes two sets of non-redundant core tables (one for combinations of mutations in the PR and the other for combinations in the RT).ConclusionDR_SEQAN is an easy to use off-line application that provides expert advice on HIV genotypic resistance interpretation. It is coded in Visual Basic for use in PC/Windows-based platforms. The program is freely available under the General Public License. The program (including the integrated database), documentation and a sample sequence can be downloaded fromhttp://www2.cbm.uam.es:8080/lmenendez/DR_SEQAN.zip
Multilevel analysis of systolic blood pressure and ACE gene I/D polymorphism in 438 Swedish families – a public health perspective
Authors: Merlo Juan , Bengtsson-Boström Kristina , Lindblad Ulf , Råstam Lennart , Melander Olle 
Published: March 2006

Abstract

Background
Individuals belonging to the same family share a number of genetic as well as environmental circumstances that may condition a common SBP level. Among the genetic factors, the angiotensin converting enzyme (ACE) gene I/D polymorphism appears as a possible candidate as it might influence both SBP and the pharmacological effect of ACE inhibitors. We aimed to combine genetic epidemiology with public health ideas concerning life-course and multilevel epidemiology in order to understand the role of familial factors regarding individual SBP.

Methods
We applied multilevel regression analysis on 1926 individuals nested within 438 families from South Sweden. Modelling familial SBP variance as a function of age and use of ACE inhibitors we calculates a variance partition coefficient and the proportional change in familial SBP variance attributable to differences in ACE gene I/D polymorphism

Results
Our results suggest the existence of genetic or environmental circumstances that produce a considerable familial clustering of SBP, especially among individuals using ACE-inhibitors. However, ACE gene I/D polymorphism seems to play a minor role in this context. In addition, familial factors – genetic, environmental or their interaction – shape SBP among non-users of ACE inhibitors but their effect is expressed later in the life-course.

Conclusion
Strategies directed to prevent hypertension should be launched in younger rather than in older ages and both prevention of hypertension and its treatment with ACE inhibitors should be focused on families rather than on individuals.
A study of 82 extended HLA haplotypes in HFE-C282Y homozygous hemochromatosis subjects: relationship to the genetic control of CD8+ T-lymphocyte numbers and severity of iron overload
Authors: Cruz Eugénia , Vieira Jorge , Almeida Susana , Lacerda Rosa , Gartner Andrea , Cardoso Carla S , Alves Helena , Porto Graça 
Published: March 2006

AbstractBackgroundIt has been recently demonstrated that CD8+ T-lymphocyte numbers are genetically transmitted in association with the MHC class I region. The present study was designed with the objective of narrowing the region associated with the setting of CD8+ T-lymphocyte numbers in a population of C282Y homozygous hemochromatosis subjects, in whom a high prevalence of abnormally low CD8+ T-lymphocyte counts has been described.MethodsThe study includes 43 C282Y homozygous subjects fully characterized both phenotypically and genotypically. Clinical characterization includes measurements of iron parameters at diagnosis (transferrin saturation and serum ferritin), total body iron stores and T-cell immunophenotyping determined by flow cytometry. Genetic characterization includes HLA class I alleles (A, B and C) and four additional microsatellite markers (D6S265, D6S2222, D6S105 and D6S2239) spanning 5 Megabases in the 6p21.3 region.ResultsEighty-two extended C282Y carrying haplotypes were defined. Single-locus analysis revealed that the HLA-A region was associated with CD8+ T-cell numbers. Multivariate analysis showed that the combinations of the most common HLA-A alleles (HLA-A*03, -A*02 and -A*01) were associated with significantly lower numbers of CD8+ T-lymphocytes (0.30 ± 0.14 × 106/ml), in comparison with subjects carrying only one copy of those alleles (0.46 ± 0.19 × 106/ml) and subjects without any copy of those alleles (0.79 ± 0.15 × 106/ml;p= 0.0001). No differences were observed in CD8+ T-cell counts among control subjects carrying the same combinations of HLA-A alleles (0.47 ± 0.14; 0.45 ± 0.21 and 0.41 ± 0.17 × 106/ml, respectively), therefore not supporting a direct effect of HLA specificity but rather an indirect association with a locus close to HLA-A. Multivariate analysis showed that the combination of the most common HLA-A alleles also have an impact on the clinical expression of HH in terms of iron stores, in males(p= 0.0009).ConclusionThe present study provides evidence supporting an inextricable link between extended HLA haplotypes, CD8+ T-lymphocyte numbers and severity of iron overload in hereditary hemochromatosis(HH). It gives additional information to better define a candidate region involved in the regulation of CD8+ T-lymphocyte numbers. A new evolutionary hypothesis concerning the inheritance of the phenotype of low CD8+ T-lymphocyte numbers associated with particular ancestral HLA haplotypes carrying the C282Y mutation and its implication on the clinical heterogeneity of HH is discussed.
Breakpoint Associated with a novel 2.3 Mb deletion in the VCFS region of 22q11 and the role of Alu (SINE) in recurring microdeletions
Authors: Uddin Raihan K , Zhang Yang , Siu Victoria Mok , Fan Yao-Shan , O'Reilly Richard L , Rao Jay , Singh Shiva M 
Published: March 2006

Abstract

Background
Chromosome 22q11.2 region is highly susceptible to rearrangement, specifically deletions that give rise to a variety of genomic disorders including velocardiofacial or DiGeorge syndrome. Individuals with this 22q11 microdeletion syndrome are at a greatly increased risk to develop schizophrenia.

Methods
Genotype analysis was carried out on the DNA from a patient with the 22q11 microdeletion using genetic markers and custom primer sets to define the deletion. Bioinformatic analysis was performed for molecular characterization of the deletion breakpoint sequences in this patient.

Results
This 22q11 deletion patient was established to have a novel 2.3 Mb deletion with a proximal breakpoint located between genetic markers RH48663 and RH48348 and a distal breakpoint between markers D22S1138 and SHGC-145314. Molecular characterization of the sequences at the breakpoints revealed a 270 bp shared sequence of the breakpoint regions (SSBR) common to both ends that share >90% sequence similarity to each other and also to short interspersed nuclear elements/Alu elements.

Conclusion
This Alu sequence like SSBR is commonly in the proximity of all known deletion breakpoints of 22q11 region and also in the low copy repeat regions (LCRs). This sequence may represent a preferred sequence in the breakpoint regions or LCRs for intra-chromosomal homologous recombination mechanisms resulting in common 22q11 deletion.
On the Wegener granulomatosis associated region on chromosome 6p21.3
Authors: Szyld Paweł , Jagiello Peter , Csernok Elena , Gross Wolfgang L , Epplen Joerg T 
Published: March 2006

AbstractBackgroundWegener granulomatosis (WG) belongs to the heterogeneous group of systemic vasculitides. The multifactorial pathophysiology of WG is supposedly caused by yet unknown environmental influence(s) on the basis of genetic predisposition. The presence of anti-neutrophil cytoplasmic antibodies (ANCA) in the plasma of patients and genetic involvement of the human leukocyte antigen system reflect an autoimmune background of the disease. Strong associations were revealed with WG by markers located in the major histocompatibility complex class II (MHC II) region in the vicinity of human leukocyte antigen (HLA)-DPB1and theretinoid X receptor B(RXRB) loci. In order to define the involvement of the 6p21.3 region in WG in more detail this previous population-based association study was expanded here to the respective 3.6 megabase encompassing this region on chromosome 6. TheRXRBgene was analysed as well as a splice-site variation of thebutyrophilin-like(BTNL2) gene which is also located within the respective region. The latter polymorphism has been evaluated here as it appears as a HLA independent susceptibility factor in another granulomatous disorder, sarcoidosis.Methods150–180 German WG patients and a corresponding cohort of healthy controls (n = 100–261) were used in a two-step study. A panel of 94 microsatellites was designed for the initial step using a DNA pooling approach. Markers with significantly differing allele frequencies between patient and control pools were individually genotyped. TheRXRBgene was analysed for single strand conformation polymorphisms (SSCP) and restriction fragment length polymorphisms (RFLP). The splice-site polymorphism in theBTNL2gene was also investigated by RFLP analysis.ResultsA previously investigated microsatellite (#1.0.3.7, Santa Cruz genome browser (UCSC) May 2004 Freeze localisation: chr6:31257596-34999883), which was used as a positive control, remained associated throughout the whole two-step approach. Yet, no additional evidence for association of other microsatellite markers was found in the entire investigated region. Analysis of theRXRBgene located in the WG associated region revealed associations of two variations (rs10548957 pallelic= 0.02 and rs6531 pallelic= 5.20 × 10-5, OR = 1.88). Several alleles of markers located betweenHLA-DPB1, SNP rs6531 and microsatellite 1.0.3.7 showed linkage disequilibrium withr2values exceeding 0.10. Significant differences were not demonstrable for the sarcoidosis associated splice-site variation (rs2076530 pallelic= 0.80) in our WG cohort.ConclusionSince a microsatellite flanking theRXRBgene and two intragenic polymorphisms are associated significantly with WG on chromosome 6p21.3, further investigations should be focussed on extensive fine-mapping in this region by densely mapping with additional markers such as SNPs. This strategy may reveal even deeper insights into the genetic contributions of the respective region for the pathogenesis of WG.
The effect of bisphosphonates on gene expression: GAPDH as a housekeeping or a new target gene?
Authors: Valenti Maria Teresa , Bertoldo Francesco , Dalle Carbonare Luca , Azzarello Giuseppe , Zenari Sonia , Zanatta Mirko , Balducci Elena , Vinante Orazio , Cascio Vincenzo Lo 
Published: March 2006

Abstract

Background
RT-PCR has been widely used for the analysis of gene expression in many systems, including tumor samples. GAPDH (Glyceraldehyde-3-phosphate dehydrogenase) has been frequently considered as a constitutive housekeeping gene and used to normalize changes in specific gene expression. However, GAPDH has been shown to be up-regulated in many cancers and down-regulated by chemotherapic drugs. Bisphosphonates, potent inhibitors of bone resorption, have recently shown a direct and indirect antitumor effect in vitro and in animal models. They exert their effects mainly by inhibiting the mevalonate pathway but also by modulating the expression of many genes not only in osteoclasts but also in cancer cells.

Methods
We evaluated GAPDH gene expression by real time RT PCR in breast (MCF-7 and T47D) and prostate (PC3 and DU-145) cancer cell lines treated with amino and non-amino bisphosphonates.

Results
Our results showed that amino-bisphosphonates significantly decrease in a dose-dependent manner the expression of GAPDH gene.

Conclusion
Therefore, GAPDH is inaccurate to normalize mRNA levels in studies investigating the effect of bisphosphonates on gene expression and it should be avoided. On the other hand, this gene could be considered a potential target to observe the effects of bisphosphonates on cancer cells.
Results of radiation therapy combined with nedaplatin (cis-diammine-glycoplatinum) and 5-Fluorouracil for postoperative locoregional recurrent esophageal cancer
Authors: Jingu Keiichi , Nemoto Kenji , Matsushita Haruo , Takahashi Chiaki , Ogawa Yoshihiro , Sugawara Toshiyuki , Nakata Eiko , Takai Yoshihiro , Yamada Shogo 
Published: March 2006

Abstract

Background
Although the effectiveness of radiotherapy with concurrent administration of several anti-tumor drugs for postoperative recurrent esophageal cancer has been demonstrated, the results are not satisfactory. The purpose of the present study was to evaluate the effectiveness and safety of radiotherapy combined with nedaplatin and 5-FU for postoperative locoregional (excluding hematogenous metastasis) recurrent esophageal cancer.

Methods
In June 2000, we started a phase II study on treatment of postoperative locoregional recurrent esophageal cancer with radiotherapy (60 Gy/30 fr/6 weeks) combined with chemotherapy consisting of two cycles of nedaplatin (70 mg/m2/2 h) and 5-FU (500 mg/m2/24 h for 5 days).
The primary endpoint of the present study was overall survival rate, and the second endpoints were irradiated-field control rate, tumor response and toxicity.

Results
A total of 30 patients were included in this study. The 1-year and 3-year overall survival rates were 60.6% and 56.3%, respectively, with a median survival period of 39.0 months, and the 1-year and 3-year irradiated-field control rates were 86.4% and 72%, respectively. Complete response and partial response were observed in 13.3% and 60.0% of the patients, respectively. Grade 3 or higher leukocytopenia and thrombocytopenia were observed in 30% and 3.3% of the patients, respectively, but renal toxicity of grade 3 or higher was not observed. The regimen was completed in 76.7% of the patients.
In univariate analysis, the difference between survival rate in preradiotherapy performance status, recurrent pattern (worse for patients with anastomotic recurrence) and age (worse for younger patients) were statistically significant.

Conclusion
Radiotherapy combined with nedaplatin and 5-FU is a safe and effective salvage treatment for postoperative locoregional recurrent esophageal cancer.
Fibroblast-derived MT1-MMP promotes tumor progression in vitro and in vivo
Authors: Zhang Wenyue , Matrisian Lynn M , Holmbeck Kenn , Vick Catherine C , Rosenthal Eben L 
Published: March 2006

Abstract

Background
Identification of fibroblast derived factors in tumor progression has the potential to provide novel molecular targets for modulating tumor cell growth and metastasis. Multiple matrix metalloproteases (MMPs) are expressed by both mesenchymal and epithelial cells within head and neck squamous cell carcinomas (HNSCCs), but the relative importance of these enzymes and the cell source is the subject of controversy.

Methods
The invasive potential of HNSCC tumor cells were assessed in vitro atop type I collagen gels in coculture with wild-type (WT), MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts. A floor of mouth mouse model of HNSCC was used to assess in vivo growth after co-injection of FaDu tumor cells with MMP null fibroblasts.

Results
Here we report changes in tumor phenotype when FaDu HNSCCs cells are cocultured with WT, MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts in vitro and in vivo. WT, MMP-2 null and MMP-9 null fibroblasts, but not MT1-MMP null fibroblasts, spontaneously invaded into type I collagen gels. WT fibroblasts stimulated FaDu tumor cell invasion in coculture. This invasive phenotype was unaffected by combination with MMP-9 null fibroblasts, reduced with MMP-2 null fibroblasts (50%) and abrogated in MT1-MMP null fibroblasts. Co-injection of FaDu tumor cells with fibroblasts in an orthotopic oral cavity SCID mouse model demonstrated a reduction of tumor volume using MMP-9 and MMP-2 null fibroblasts (48% and 49%, respectively) compared to WT fibroblasts. Consistent with in vitro studies, MT1-MMP null fibroblasts when co-injected with FaDu cells resulted in a 90% reduction in tumor volume compared to FaDu cells injected with WT fibroblasts.

Conclusion
These data suggest a role for fibroblast-derived MMP-2 and MT1-MMP in HNSCC tumor invasion in vitro and tumor growth in vivo.
PPARγ-independent induction of growth arrest and apoptosis in prostate and bladder carcinoma
Authors: Chaffer Christine L , Thomas David M , Thompson Erik W , Williams Elizabeth D 
Published: March 2006

Abstract

Background
Although PPARγ antagonists have shown considerable pre-clinical efficacy, recent studies suggest PPARγ ligands induce PPARγ-independent effects. There is a need to better define such effects to permit rational utilization of these agents.

Methods
We have studied the effects of a range of endogenous and synthetic PPARγ ligands on proliferation, growth arrest (FACS analysis) and apoptosis (caspase-3/7 activation and DNA fragmentation) in multiple prostate carcinoma cell lines (DU145, PC-3 and LNCaP) and in a series of cell lines modelling metastatic transitional cell carcinoma of the bladder (TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2).

Results
15-deoxy-prostaglandin J2 (15dPGJ2), troglitazone (TGZ) and to a lesser extent ciglitazone exhibited inhibitory effects on cell number; the selective PPARγ antagonist GW9662 did not reverse these effects. Rosiglitazone and pioglitazone had no effect on proliferation. In addition, TGZ induced G0/G1 growth arrest whilst 15dPGJ2 induced apoptosis.

Conclusion
Troglitazone and 15dPGJ2 inhibit growth of prostate and bladder carcinoma cell lines through different mechanisms and the effects of both agents are PPARγ-independent.
Perceptions of eye health in schools in Pakistan
Authors: Ahmad Khabir , Khan Mohammad Aman , Khan Mohammad Daud , Qureshi Mohammad Babar , Chaudhry Tanveer Anjum , Gilbert Clare 
Published: March 2006

AbstractBackgroundResearch exploring children's and their teachers' perceptions of eye health is lacking. This paper reports for the first time on perceptions of primary schoolchildren and their teachers of healthy and diseased eyes, things that keep eyes healthy and damage them, and what actions to be taken in case of an eye injury.MethodsUsingdraw and write technique, 160 boys and girls (9–12 years old) attending four primary schools in Abbottabad district, northern Pakistan, were invited to draw pictures in response to a set of semi-structured questions and then label them. Sixteen teachers who were currently teaching the selected students were interviewed one-on-one.ResultsAnalysis of text accompanying 800 drawings and of the interview scripts revealed that most children and teachers perceived healthy eyes to be those which could see well, and diseased eyes to be those which have redness, watering, dirty discharge, pain, and itching; or those which have "weak eyesight" and blindness. Among things that students and teachers thought damage the eyes included sun, television, and sharp pointed objects, particularly pencils. Teachers noted that children with eye problems "have difficulty seeing the blackboard well", "screw up their eyes", and "hold their books too close".ConclusionWe conclude that schoolchildren and their teachers had a good knowledge of eye health, but many of them had serious misconceptions e.g., use of kohl, medicines and eye drops keeps eyes healthy. Kohl is an important source of lead and can reduce children's intelligence even at low blood levels. Health education in schools must take into account children's existing knowledge of and misconceptions about various aspects of eye health. Such steps if taken could improve the relevance of eye health education to schoolchildren.
Management of neonatal hyperbilirubinemia: Pediatricians' practices and educational needs
Authors: Petrova Anna , Mehta Rajeev , Birchwood Gillian , Ostfeld Barbara , Hegyi Thomas 
Published: March 2006

AbstractBackgroundEarly detection and treatment of neonatal hyperbilirubinemia is important in the prevention of bilirubin-induced encephalopathy. In this study, we evaluated the New Jersey pediatricians' practices and beliefs regarding the management of neonatal hyperbilirubinemia and their compliance with the recommendations made by the American Academy of Pediatrics (AAP) in 1994.MethodsA survey questionnaire was mailed to a random sample of 800 pediatricians selected from a list of 1623 New Jersey Fellows of the AAP initially in October 2003 and then in February 2004 for the non-respondents. In addition to the physicians' demographic characteristics, the questionnaire addressed various aspects of neonatal hyperbilirubinemia management including the diagnosis, treatment, and follow up as well as the pediatricians' beliefs regarding the significance of risk factors in the development of severe hyperbilirubinemia.ResultsThe adjusted response rate of 49.1% (n = 356) was calculated from the 725 eligible respondents. Overall, the practicing pediatricians reported high utilization (77.9%) of the cephalocaudal progression of jaundice and low utilization (16.1%) of transcutaneous bilirubinometry for the quantification of the severity of jaundice. Most of the respondents (87.4%) identified jaundice as an indicator for serum bilirubin (TSB) testing prior to the neonate's discharge from hospital, whereas post-discharge, only 57.7% felt that a TSB was indicated (P < 0.01). If the neonate's age was under 72 hours, less than one-third of the respondents reported initiation of phototherapy at TSB levels lower than the treatment parameters recommended by the AAP in 1994, whereas if the infant was more than 72 hours old, almost 60% were initiating phototherapy at TSB lower than the 1994 AAP guidelines. Most respondents did not regard neonatal jaundice noted after discharge and gestational ages 37–38 weeks as being significant in the development of severe hyperbilirubinemia. However, the majority did recognize the importance of jaundice presenting within the first 24 hours and Rh/ABO incompatibility.ConclusionThe pediatricians' practices regarding the low utilization of laboratory diagnosis for the quantification of jaundice after discharge and underestimation of risk factors that contribute to the development of severe hyperbilirubinemia are associated with initiation of phototherapy at lower than AAP recommended treatment parameters and recognition of neonatal hyperbilirubinemia as an important public health concern.