bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absence of mutations in NR2E1 and SNX3in five patients with MMEP (microcephaly, microphthalmia, ectrodactyly, and prognathism) and related phenotypes
Authors: Kumar Ravinesh A , Everman David B , Morgan Chad T , Slavotinek Anne , Schwartz Charles E , Simpson Elizabeth M 
Published: August 2007

Abstract

Background
A disruption of sorting nexin 3 (SNX3) on 6q21 was previously reported in a patient with MMEP (microcephaly, microphthalmia, ectrodactyly, and prognathism) and t(6;13)(q21;q12) but no SNX3 mutations were identified in another sporadic case of MMEP, suggesting involvement of another gene. In this work, SNX3 was sequenced in three patients not previously studied for this gene. In addition, we test the hypothesis that mutations in the neighbouring gene NR2E1 may underlie MMEP and related phenotypes.

Methods
Mutation screening was performed in five patients: the t(6;13)(q21;q12) MMEP patient, three additional patients with possible MMEP or a related phenotype, and one patient with oligodactyly, ulnar aplasia, and a t(6;7)(q21;q31.2) translocation. We used sequencing to exclude SNX3 coding mutations in three patients not previously studied for this gene. To test the hypothesis that mutations in NR2E1 may contribute to MMEP or related phenotypes, we sequenced the entire coding region, complete 5' and 3' untranslated regions, consensus splice-sites, and evolutionarily conserved regions including core and proximal promoter in all five patients. Two-hundred and fifty control subjects were genotyped for any candidate mutation.

Results
We did not detect any synonymous nor nonsynonymous coding mutations of NR2E1 or SNX3. In one patient with possible MMEP, we identified a candidate regulatory mutation that has been reported previously in a patient with microcephaly but was not found in 250 control subjects examined here.

Conclusion
Our results do not support involvement of coding mutations in NR2E1 or SNX3 in MMEP or related phenotypes; however, we cannot exclude the possibility that regulatory NR2E1 or SNX3 mutations or deletions at this locus may underlie abnormal human cortical development in some patients.
Subarachnoid hemorrhage: tests of association with apolipoprotein E and elastin genes
Authors: Kaushal Ritesh , Woo Daniel , Pal Prodipto , Haverbusch Mary , Xi Huifeng , Moomaw Charles , Sekar Padmini , Kissela Brett , Kleindorfer Dawn , Flaherty Matthew , Sauerbeck Laura , Chakraborty Ranajit , Broderick Joseph , Deka Ranjan 
Published: August 2007

Abstract

Background
Apolipoprotein E (APOE) and elastin (ELN) are plausible candidate genes involved in the pathogenesis of stroke. We tested for association of variants in APOE and ELN with subarachnoid hemorrhage (SAH) in a population-based study. We genotyped 12 single nucleotide polymorphisms (SNPs) on APOE and 10 SNPs on ELN in a sample of 309 Caucasian individuals, of whom 107 are SAH cases and 202 are age-, race-, and gender-matched controls from the Greater Cincinnati/Northern Kentucky region. Associations were tested at genotype, allele, and haplotype levels. A genomic control analysis was performed to check for spurious associations resulting from population substructure.

Results
At the APOE locus, no individual SNP was associated with SAH after correction for multiple comparisons. Haplotype analysis revealed significant association of the major haplotype (Hap1) in APOE with SAH (p = 0.001). The association stemmed from both the 5' promoter and the 3' region of the APOE gene. APOE ε2 and ε 4 were not significantly associated with SAH. No association was observed for ELN at genotype, allele, or haplotype level and our study failed to confirm previous reports of ELN association with aneurysmal SAH.

Conclusion
This study suggests a role of the APOE gene in the etiology of aneurysmal SAH.
Predictors of health-related quality of life in type II diabetic patients in Greece
Authors: Papadopoulos Angelos A , Kontodimopoulos Nick , Frydas Aristidis , Ikonomakis Emmanuel , Niakas Dimitris 
Published: August 2007

Abstract

Background
Diabetes Mellitus (DM) is a major cause of morbidity and mortality affecting millions of people worldwide, while placing a noteworthy strain on public health funding. The aim of this study was to assess health-related quality of life (HRQOL) of Greek Type II DM patients and to identify significant predictors of the disease in this patient population.

Methods
The sample (N = 229, 52.8% female, 70.0 years mean age) lived in a rural community of Lesvos, an island in the northeast of the Aegean Archipelagos. The generic SF-36 instrument, administered by trainee physicians, was used to measure HRQOL. Scale scores were compared with non-parametric Mann-Whitney and Kruskal-Wallis tests and multivariate stepwise linear regression analyses were used to investigate the effect of sociodemographic and diabetes-related variables on HRQOL.

Results
The most important predictors of impaired HRQOL were female gender, diabetic complications, non-diabetic comorbidity and years with diabetes. Older age, lower education, being unmarried, obesity, hypertension and hyperlipidaemia were also associated with impaired HRQOL in at least one SF-36 subscale. Multivariate regression analyses produced models explaining significant portions of the variance in SF-36 subscales, especially physical functioning (R2 = 42%), and also showed that diabetes-related indicators were more important disease predictors, compared to sociodemographic variables.

Conclusion
The findings could have implications for health promotion in rural medical practice in Greece. In order to preserve a good HRQOL, it is obviously important to prevent diabetes complications and properly manage concomitant chronic diseases. Furthermore, the gender difference is interesting and requires further elucidation. Modifying screening methods and medical interventions or formulating educational programs for the local population appear to be steps in the correct direction.
Using system dynamics for collaborative design: a case study
Authors: Elf Marie , Putilova Mariya , von Koch Lena , Öhrn Kerstin 
Published: August 2007

Abstract
Background
In order to facilitate the collaborative design, system dynamics (SD) with a group modelling approach was used in the early stages of planning a new stroke unit. During six workshops a SD model was created in a multiprofessional group.

Aim
To explore to which extent and how the use of system dynamics contributed to the collaborative design process.

Method
A case study was conducted using several data sources.

Results
SD supported a collaborative design, by facilitating an explicit description of stroke care process, a dialogue and a joint understanding. The construction of the model obliged the group to conceptualise the stroke care and experimentation with the model gave the opportunity to reflect on care.

Conclusion
SD facilitated the collaborative design process and should be integrated in the early stages of the design process as a quality improvement tool.
Primary T-cells from human CD4/CCR5-transgenic rats support all early steps of HIV-1 replication including integration, but display impaired viral gene expression
Authors: Goffinet Christine , Michel Nico , Allespach Ina , Tervo Hanna-Mari , Hermann Volker , Kräusslich Hans-Georg , Greene Warner C , Keppler Oliver T 
Published: August 2007

Abstract

Background

In vivo studies on HIV-1 pathogenesis and testing of antiviral strategies have been hampered by the lack of an immunocompetent small animal model that is highly susceptible to HIV-1 infection. Since native rodents are non-permissive, we developed transgenic rats that selectively express the HIV-1 receptor complex, hCD4 and hCCR5, on relevant target cells. These animals display a transient low-level plasma viremia after HIV-1YU-2 infection, demonstrating HIV-1 susceptibility in vivo. However, unlike macrophages, primary CD4 T-cells from double-transgenic animals fail to support viral spread ex vivo. To identify quantitative limitations or absolute blocks in this rodent species, we quantitatively assessed the efficiency of key steps in the early phase of the viral replication cycle in a side-by-side comparison in infected cell lines and primary T-cells from hCD4/hCCR5-transgenic rats and human donors.

Results
Levels of virus entry, HIV-1 cDNA synthesis, nuclear import, and integration into the host genome were shown to be remarkably similar in cell lines and, where technically accessible, in primary T-cells from both species. In contrast, a profound impairment at the level of early HIV gene expression was disclosed at the single-cell level in primary rat T-cells and most other rat-derived cells. Macrophages were a notable exception, possibly reflecting the unique transcriptional milieu in this evolutionarily conserved target cell of all lentiviruses. Importantly, transient trans-complementation by ex vivo nucleofection with the Tat-interacting protein Cyclin T1 of human origin markedly elevated HIV gene expression in primary rat T-cells.

Conclusion
This is the first study that has quantitatively determined the efficiency of consecutive steps in the HIV-1 replication cycle in infected primary HIV target cells from a candidate transgenic small animal and compared it to human cells. Unlike cells derived from mice or rabbits, rat cells complete all of the early steps in the HIV-1 replication cycle, including provirus integration in vivo, with high efficiency. A deficiency in gene expression was disclosed at the single cell level and could be counteracted by the human pTEFb transcription complex factor Cyclin T1. Collectively, these results provide the basis for the advancement of this transgenic rat model through strategies aimed at boosting HIV-1 gene expression in primary rat CD4 T-cells, including human Cyclin T1 transgenesis.
Pathophysiology of ageing, longevity and age related diseases
Authors: Bürkle Alexander , Caselli Graziella , Franceschi Claudio , Mariani Erminia , Sansoni Paolo , Santoni Angela , Vecchio Giancarlo , Witkowski Jacek M , Caruso Calogero 
Published: August 2007

Abstract
On April 18, 2007 an international meeting on Pathophysiology of Ageing, Longevity and Age-Related Diseases was held in Palermo, Italy. Several interesting topics on Cancer, Immunosenescence, Age-related inflammatory diseases and longevity were discussed. In this report we summarize the most important issues. However, ageing must be considered an unavoidable end point of the life history of each individual, nevertheless the increasing knowledge on ageing mechanisms, allows envisaging many different strategies to cope with, and delay it. So, a better understanding of pathophysiology of ageing and age-related disease is essential for giving everybody a reasonable chance for living a long and enjoyable final part of the life.
Evolution of naturally occurring 5'non-coding region variants of Hepatitis C virus in human populations of the South American region
Authors: Moratorio Gonzalo , Martínez Mariela , Gutiérrez María F , González Katiuska , Colina Rodney , López-Tort Fernando , López Lilia , Recarey Ricardo , Schijman Alejandro G , Moreno María P , García-Aguirre Laura , Manascero Aura R , Cristina Juan 
Published: August 2007

Abstract

Background
Hepatitis C virus (HCV) has been the subject of intense research and clinical investigation as its major role in human disease has emerged. Previous and recent studies have suggested a diversification of type 1 HCV in the South American region. The degree of genetic variation among HCV strains circulating in Bolivia and Colombia is currently unknown. In order to get insight into these matters, we performed a phylogenetic analysis of HCV 5' non-coding region (5'NCR) sequences from strains isolated in Bolivia, Colombia and Uruguay, as well as available comparable sequences of HCV strains isolated in South America.

Methods
Phylogenetic tree analysis was performed using the neighbor-joining method under a matrix of genetic distances established under the Kimura-two parameter model. Signature pattern analysis, which identifies particular sites in nucleic acid alignments of variable sequences that are distinctly representative relative to a background set, was performed using the method of Korber & Myers, as implemented in the VESPA program. Prediction of RNA secondary structures was done by the method of Zuker & Turner, as implemented in the mfold program.

Results
Phylogenetic tree analysis of HCV strains isolated in the South American region revealed the presence of a distinct genetic lineage inside genotype 1. Signature pattern analysis revealed that the presence of this lineage is consistent with the presence of a sequence signature in the 5'NCR of HCV strains isolated in South America. Comparisons of these results with the ones found for Europe or North America revealed that this sequence signature is characteristic of the South American region.

Conclusion
Phylogentic analysis revealed the presence of a sequence signature in the 5'NCR of type 1 HCV strains isolated in South America. This signature is frequent enough in type 1 HCV populations circulating South America to be detected in a phylogenetic tree analysis as a distinct type 1 sub-population. The coexistence of distinct type 1 HCV subpopulations is consistent with quasispecies dynamics, and suggests that multiple coexisting subpopulations may allow the virus to adapt to its human host populations.
Is untargeted educational outreach visiting delivered by pharmaceutical advisers effective in primary care? A pragmatic randomized controlled trial
Authors: Eccles Martin P , Steen Ian N , Whitty Paula M , Hall Lesley 
Published: August 2007

Abstract

Background
There is increasing evidence that clinical guidelines can lead to improvements in clinical care. However, they are not self-implementing. While educational outreach visits may improve prescribing behaviour, the effectiveness of routine delivery of these visits by existing pharmaceutical advisers is unknown.

Methods
Within a pragmatic randomized controlled trial, involving all general practices in two primary care trusts (PCTs), routine methods were used to distribute guidelines for the choice of antidepressants for the management of depression. Intervention practices were offered two visits (most accepted only one) by their PCT pharmaceutical adviser who had been trained in the techniques of outreach visiting. Intervention practices were visited regardless of whether they had prior problems with prescribing ('untargeted' visits). The intervention was evaluated using level three prescribing analysis and cost (PACT) data for antidepressant drugs for the six months during which the intervention was delivered and the subsequent twelve months.

Results
Across the 72 study practices there was no significant impact of the intervention on usage of any group of antidepressant drugs.

Conclusion
The routine use of untargeted educational outreach visiting delivered by existing pharmaceutical advisers may not be a worthwhile strategy.

Trial registration
ClinicalTrials.gov NCT00393536
Giant hepatocellular adenoma as cause of severe abdominal pain: a case report
Authors: Sandonato Luigi , Cipolla Calogero , Graceffa Giuseppa , Bartolotta Tommaso V. , Li Petri Sergio , Ciacio Oriana , Cannizzaro Fabio , Latteri Mario A. 
Published: August 2007

Abstract
The authors describe the case of a large hepatocellular adenoma diagnosed in a 30-year old woman who came to us complaining of acute pain in the upper abdominal quadrants. The patient had been taking an oral contraceptive pill for the last ten years. We present the clinical features, the diagnostic work-up and the treatment prescribed.
Diurnal secretion of growth hormone, cortisol, and dehydroepiandrosterone in pre- and perimenopausal women with active rheumatoid arthritis: a pilot case-control study
Authors: Blackman Marc R , Muniyappa Ranganath , Wilson Mildred , Moquin Barbara E , Baldwin Howard L , Wong Kelli A , Snyder Christopher , Magalnick Michael , Alli Shaan , Reynolds James , Steinberg Seth M , Goldbach-Mansky Raphaela 
Published: August 2007

AbstractRheumatoid arthritis (RA) is associated with neuroendocrine and immunologic dysfunction leading to rheumatoid cachexia. Although excess proinflammatory cytokines can decrease somatotropic axis activity, little is known about the effects of RA on growth hormone/insulin-like growth factor-1 (GH/IGF-I) axis function. We tested the hypothesis that patients with active RA exhibit decreased GH/IGF-I axis activity. To do so, we conducted a pilot case-control study at a clinical research center in 7 pre- and perimenopausal women with active RA and 10 age- and body mass index-matched healthy women. Participants underwent blood sampling every 20 minutes for 24 hours (8 a.m. to 8 a.m.), and sera were assayed for GH, cortisol, and dehydroepiandrosterone (DHEA). Sera obtained after overnight fasting were assayed for IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-3, C-reactive protein (CRP), interleukin-6 (IL-6), glucose, insulin, and lipids. Body composition and bone mineral density were evaluated by DEXA (dual emission x-ray absorptiometry) scans. In patients with RA, mean disease duration was 7.6 ± 6.8 years, and erythrocyte sedimentation rate, CRP, and IL-6 were elevated. GH half-life was shorter than in control subjects (p = 0.0037), with no other significant group differences in GH deconvolution parameters or approximate entropy scores. IGF-I (p = 0.05) and IGFBP-3 (p = 0.058) were lower, whereas IGFBP-1 tended to be higher (p = 0.066), in patients with RA, with nonsignificantly increased 24-hour total GH production rates. There were no significant group differences in cortisol or DHEA secretion. Lean body mass was lower in patients with RA (p = 0.019), particularly in the legs (p = 0.01). Women with active RA exhibit a trend toward GH insensitivity and relatively diminished diurnal cortisol and DHEA secretion for their state of inflammation. Whether these changes contribute to rheumatoid cachexia remains to be determined.Trial registration numberNCT00034060.
Characterization of a negative transcriptional element in the BRCA1 promoter
Authors: MacDonald Gwen , Stramwasser Melissa , Mueller Christopher R 
Published: August 2007

Abstract
Introduction
Decreased transcription of the BRCA1 gene has previously been observed to occur in sporadic breast tumours, making elucidation of the mechanisms regulating the expression of this gene important for our understanding of the etiology of the disease.

Methods
Transcriptional elements involved in the regulation of the BRCA1 promoter were analysed by co-transfection experiments into the human MCF-7 and T-47D breast cancer cell lines.

Results
We have identified a repressor element, referred to as the UP site, within the proximal BRCA1 promoter whose inactivation results in increased promoter activity. An E2F recognition element, previously suggested to mediate repression via E2F-6, is adjacent to the UP site and its inactivation also leads to increased BRCA1 expression. These two elements appear to form a composite repressor element whose combined effect is additive. The UP element is composed of two sequences, one of which binds the ubiquitously expressed ets family transcription factor GABP alpha/beta. This site is distinct from a previously identified GABP alpha/beta site, the RIBS element, though the RIBS site appears to be necessary for derepression of the promoter via mutations in the UP site. Knockdown of GABP alpha using an shRNA vector confirms that this protein is important for the function of both the RIBS and UP sites.

Conclusion
The identification of a repressor element in the BRCA1 promoter brings a new level of complexity to the regulation of BRCA1 expression. The elements characterized here may play a normal role in the integration of a variety of signals, including two different growth related pathways, and it is possible that loss of the ability to derepress the BRCA1 promoter during critical periods may contribute to breast transformation.
Air-pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells
Authors: Gong Ke Wei , Zhao Wei , Li Ning , Barajas Berenice , Kleinman Michael , Sioutas Constantinos , Horvath Steve , Lusis Aldons J , Nel Andre , Araujo Jesus A 
Published: August 2007

Abstract
Background
Ambient air pollution is associated with increased cardiovascular morbidity and mortality. We have found that exposure to ambient ultrafine particulate matter, highly enriched in redox cycling organic chemicals, promotes atherosclerosis in mice. We hypothesize that these pro-oxidative chemicals could synergize with oxidized lipid components generated in low-density lipoprotein particles to enhance vascular inflammation and atherosclerosis.

Results
We have used human microvascular endothelial cells (HMEC) to study the combined effects of a model air pollutant, diesel exhaust particles (DEP), and oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (ox-PAPC) on genome-wide gene expression. We treated the cells in triplicate wells with an organic DEP extract, ox-PAPC at various concentrations, or combinations of both for 4 hours. Gene-expression profiling showed that both the DEP extract and ox-PAPC co-regulated a large number of genes. Using network analysis to identify coexpressed gene modules, we found three modules that were most highly enriched in genes that were differentially regulated by the stimuli. These modules were also enriched in synergistically co-regulated genes and pathways relevant to vascular inflammation. We validated this synergy in vivo by demonstrating that hypercholesterolemic mice exposed to ambient ultrafine particles exhibited significant upregulation of the module genes in the liver.

Conclusion
Diesel exhaust particles and oxidized phospholipids synergistically affect the expression profile of several gene modules that correspond to pathways relevant to vascular inflammatory processes such as atherosclerosis.
Violating the splicing rules: TG dinucleotides function as alternative 3' splice sites in U2-dependent introns
Authors: Szafranski Karol , Schindler Stefanie , Taudien Stefan , Hiller Michael , Huse Klaus , Jahn Niels , Schreiber Stefan , Backofen Rolf , Platzer Matthias 
Published: August 2007

Abstract
Background
Despite some degeneracy of sequence signals that govern splicing of eukaryotic pre-mRNAs, it is an accepted rule that U2-dependent introns exhibit the 3' terminal dinucleotide AG. Intrigued by anecdotal evidence for functional non-AG 3' splice sites, we carried out a human genome-wide screen.

Results
We identified TG dinucleotides functioning as alternative 3' splice sites in 36 human genes. The TG-derived splice variants were experimentally validated with a success rate of 92%. Interestingly, ratios of alternative splice variants are tissue-specific for several introns. TG splice sites and their flanking intron sequences are substantially conserved between orthologous vertebrate genes, even between human and frog, indicating functional relevance. Remarkably, TG splice sites are exclusively found as alternative 3' splice sites, never as the sole 3' splice site for an intron, and we observed a distance constraint for TG-AG splice site tandems.

Conclusion
Since TGs splice sites are exclusively found as alternative 3' splice sites, the U2 spliceosome apparently accomplishes perfect specificity for 3' AGs at an early splicing step, but may choose 3' TGs during later steps. Given the tiny fraction of TG 3' splice sites compared to the vast amount of non-viable TGs, cis-acting sequence signals must significantly contribute to splice site definition. Thus, we consider TG-AG 3' splice site tandems as promising subjects for studies on the mechanisms of 3' splice site selection.