bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of ADAMTS13 secretion and specific activity by a combination of common amino acid polymorphisms and a missense mutation
Authors: Plaimauer Barbara , Fuhrmann Jakob , Mohr Gabriele , Wernhart Waltraud , Bruno Katharina , Ferrari Silvia , Konetschny Christian , Antoine Gerhard , Rieger Manfred , Scheiflinger Friedrich 
Published: September 2005

Abstract
Sequence analysis of the ADAMTS13 locus of 2 patients with hereditary thrombotic thrombocytopenic purpura (TTP) revealed the homozygous presence of 4 single nucleotide polymorphisms (SNPs) (R7W, Q448E, P618A, A732V) and a rare missense mutation (R1336W). Analysis of the individual effect of any amino acid exchanges showed that several sequence variations can interact with each other, thereby altering the phenotype of ADAMTS13 deficiency. Introduction of polymorphisms R7W, Q448E, and A732V had no or only minor effects on ADAMTS13 secretion. In contrast, P618A, R1336W, and the A732V-P618A combination strongly reduced ADAMTS13-specific activity and antigen levels. Surprisingly, R7W and Q448E were positive modifiers of ADAMTS13 secretion in the context of P618A and A732V but neither could rescue the severely reduced specific activity conferred by P618A. However, in the context of R1336W, polymorphisms R7W and Q448E enhanced the detrimental effect of the missense mutation and led to undetectable enzyme activity. We show that dependent on the sequence context, the same polymorphisms might be either positive or negative modifiers of gene expression. Our results might therefore be widely relevant to understanding the influence of polymorphisms on the phenotypic expression of complex diseases.
Initial depletion of regulatory T cells: the missing solution to preserve the immune functions of T lymphocytes designed for cell therapy
Authors: Mesel-Lemoine Mariana , Cherai Mustapha , Le Gouvello Sabine , Guillot Maude , Leclercq Virginie , Klatzmann David , Thomas-Vaslin Véronique , Lemoine François M. 
Published: September 2005

Abstract
We investigated the causes of the altered functionality of T cells cultured under conditions designed for cell and gene therapy and the strategies to prevent their defects. We first showed that human T cells cultured for 6 days with anti-CD3 ± anti-CD28 antibodies and interleukin-2 presented a 50% decrease of their proliferative responses to allogeneic or recall antigens. Similarly, day-6 cultured murine T cells completely lost their capacity to reject allogeneic skin grafts and to provoke graft-versus-host disease (GVHD) when infused into irradiated semi-allogeneic mice. Interestingly, injection of higher amounts of cultured T cells restored GVHD induction. Moreover, depletion of CD25+ cells prior to T-cell cultures can prevent these deficiencies both in mice and humans. Therefore, we demonstrated that culture conditions used for T-cell therapy preferentially activated and expanded regulatory T cells (Treg's). Thus, we showed that dividing cells sorted from T-cell cultures strongly suppressed the proliferation of autologous T cells in response to allogeneic stimulation. An increased detection of Foxp3 at mRNA and protein levels in the cultures confirmed the Treg expansion. Overall, we demonstrate that T-cell cultures promote Treg expansion over effector T cells, leading to deleterious immune functions, and that this imbalance can be prevented by an initial depletion of CD25+ cells.
Loss of Sp1 function via inhibitory phosphorylation in antifolate-resistant human leukemia cells with down-regulation of the reduced folate carrier
Authors: Stark Michal , Assaraf Yehuda G. 
Published: September 2005

AbstractThe reduced folate carrier (RFC) is the dominant influx transporter for antifolates. A major mechanism of antifolate resistance is loss of RFC (SLC19A1) gene expression due to decreased GC-box-dependent transcription. However, despite the poor GC-box binding in multiple antifolate-resistant cell lines, normal Sp1 levels were retained. Here we explored the post-translational modifications that may disrupt Sp1 function. Phospho-affinity purification of nuclear proteins revealed that resistant cells contained approximately 8-fold more phosphorylated Sp1 than parental cells; treatment of nuclear proteins from these cells with alkaline phosphatase restored GC-box binding. As protein kinase A phosphorylates Sp1, resistant cells were treated with various cAMP-reactive agents, revealing no apparent effect on GC-box binding except for the general phosphodiesterase inhibitor IBMX. As cGMP levels also may be affected by IBMX, resistant cells were treated with 8-pCPT-cGMP, resulting in the complete restoration of GC-box binding, luciferase reporter activity, and RFC mRNA levels. This restoration was abolished in the presence of the protein phosphatase 2A inhibitor (PP2A) okadaic acid. Importantly, whereas resistant cells showed multiple phosphorylated Sp1 forms barely detectable in parental cells, treatment with 8-pCPT-cGMP resulted in their elimination; this disappearance, however, was prevented by the copresence of okadaic acid. These findings provide the first evidence that loss of RFC gene expression in antifolate-resistant cells is associated with an inhibitory Sp1 phosphorylation that can be eliminated by a cGMP-dependent activation of PP2A. (Blood. 2006;107:708-715)
Laterally transferred elements and high pressure adaptation in Photobacterium profundum strains
Authors: Campanaro Stefano , Vezzi Alessandro , Vitulo Nicola , Lauro Federico M , D'Angelo Michela , Simonato Francesca , Cestaro Alessandro , Malacrida Giorgio , Bertoloni Giulio , Valle Giorgio , Bartlett Douglas H 
Published: September 2005

Abstract

Background
Oceans cover approximately 70% of the Earth's surface with an average depth of 3800 m and a pressure of 38 MPa, thus a large part of the biosphere is occupied by high pressure environments. Piezophilic (pressure-loving) organisms are adapted to deep-sea life and grow optimally at pressures higher than 0.1 MPa. To better understand high pressure adaptation from a genomic point of view three different Photobacterium profundum strains were compared. Using the sequenced piezophile P. profundum strain SS9 as a reference, microarray technology was used to identify the genomic regions missing in two other strains: a pressure adapted strain (named DSJ4) and a pressure-sensitive strain (named 3TCK). Finally, the transcriptome of SS9 grown under different pressure (28 MPa; 45 MPa) and temperature (4°C; 16°C) conditions was analyzed taking into consideration the differentially expressed genes belonging to the flexible gene pool.

Results
These studies indicated the presence of a large flexible gene pool in SS9 characterized by various horizontally acquired elements. This was verified by extensive analysis of GC content, codon usage and genomic signature of the SS9 genome. 171 open reading frames (ORFs) were found to be specifically absent or highly divergent in the piezosensitive strain, but present in the two piezophilic strains. Among these genes, six were found to also be up-regulated by high pressure.

Conclusion
These data provide information on horizontal gene flow in the deep sea, provide additional details of P. profundum genome expression patterns and suggest genes which could perform critical functions for abyssal survival, including perhaps high pressure growth.
Comparative analyses of six solanaceous transcriptomes reveal a high degree of sequence conservation and species-specific transcripts
Authors: Rensink Willem Albert , Lee Yuandan , Liu Jia , Iobst Stacy , Ouyang Shu , Buell C Robin 
Published: September 2005

Abstract

Background
The Solanaceae is a family of closely related species with diverse phenotypes that have been exploited for agronomic purposes. Previous studies involving a small number of genes suggested sequence conservation across the Solanaceae. The availability of large collections of Expressed Sequence Tags (ESTs) for the Solanaceae now provides the opportunity to assess sequence conservation and divergence on a genomic scale.

Results
All available ESTs and Expressed Transcripts (ETs), 449,224 sequences for six Solanaceae species (potato, tomato, pepper, petunia, tobacco and Nicotiana benthamiana), were clustered and assembled into gene indices. Examination of gene ontologies revealed that the transcripts within the gene indices encode a similar suite of biological processes. Although the ESTs and ETs were derived from a variety of tissues, 55–81% of the sequences had significant similarity at the nucleotide level with sequences among the six species. Putative orthologs could be identified for 28–58% of the sequences. This high degree of sequence conservation was supported by expression profiling using heterologous hybridizations to potato cDNA arrays that showed similar expression patterns in mature leaves for all six solanaceous species. 16–19% of the transcripts within the six Solanaceae gene indices did not have matches among Solanaceae, Arabidopsis, rice or 21 other plant gene indices.

Conclusion
Results from this genome scale analysis confirmed a high level of sequence conservation at the nucleotide level of the coding sequence among Solanaceae. Additionally, the results indicated that part of the Solanaceae transcriptome is likely to be unique for each species.
Modeling repeated ordinal responses using a family of power transformations: application to neonatal hypothermia data
Authors: Zayeri Farid , Kazemnejad Anoshirvan , Khanafshar Navid , Nayeri Fatemeh 
Published: September 2005

AbstractBackgroundFor analyzing a repeated ordinal response, it is common to use a multivariate cumulative logit model. This model may fit poorly, especially when a nonsymmetric response is available. In these cases, alternative strategies should be utilized.MethodsIn this paper, we present a family of power transformations for the cumulative probabilities to model asymmetric departures from the random-intercept cumulative logit model. To illustrate this method, we analyze the data from an epidemiologic study to identify risk factors of hypothermia among newly born infants in some referral university hospitals in Tehran, Iran.ResultsFor hypothermia data, using this family of transformations and comparing the goodness-of-fit statistics showed that a model with the cumulative complementary log-log link gives us a better fit compared to a model with the cumulative logit link.ConclusionIn some areas, using the ordinary cumulative logit link function does not lead to the best fit. So, other link functions should be evaluated to discover the best transformation for the cumulative probabilities.
Avoidance as a strategy of (not) coping: qualitative interviews with carers of Huntington's Disease patients
Authors: Lowit Alison , van Teijlingen Edwin R 
Published: September 2005

Abstract

Background
Since Huntington's Disease (HD) is a familial disease with an average onset in the mid-thirties, one might expect that spousal carers are concerned with providing care for off-spring who may turn out to be affected.

Methods
This study involved ten face-to-face interviews with carers of spouses affected by HD in Northeast Scotland. Carers were recruited through two channels: a genetic clinic and the Scottish Huntington's Association (SHA). Interviews were conducted in carers' own homes. A thematic analysis of the transcripts was conducted.

Results
Although carers did worry about their children, they did not envisage being involved in their care. Many avoided talking about the disease, both within and outwith their family; this may have greatly reduced the level of support provided by family members. Conversely, avoidance was often accompanied by symptom-spotting. For example, several people had given up driving, before they were incapable of doing so. The explanation appears to be that they avoided getting into situations in which HD may express itself.
Support meetings seem to be valued amongst patients with other serious diseases and their carers, however, although all participants had had contact with the SHA, only one regularly attended meetings. It was felt that seeing others with HD provided a constant reminder of the possible effect of HD on the wider family, which seemed to outweigh the benefit of attending. Overall, the analysis highlighted 'avoidance' as a key theme.

Conclusion
Many denied symptoms of HD in their spouses, pre-diagnosis. All had pretended at some point that it was not happening, through ignoring early signs and 'obvious' symptoms. Some partners had refused to go to the doctor until it was no longer possible to deny symptoms. Formal health and social care seemed to play a very small role compared to informal care arrangements.
Primary angiitis of the central nervous system presenting with subacute and fatal course of disease: a case report
Authors: Lukas Carsten , Keyvani Kathy , Börnke Christian 
Published: September 2005

Abstract

Background
Primary angiitis of the central nervous system is an idiopathic disorder characterized by vasculitis within the dural confines. The clinical presentation shows a wide variation and the course and the duration of disease are heterogeneous. This rare but treatable disease provides a diagnostic challenge owing to the lack of pathognomonic tests and the necessity of a histological confirmation.

Case presentation
A 28-year-old patient presenting with headache and fluctuating signs of encephalopathy was treated on the assumption of viral meningoencephalitis. The course of the disease led to his death 10 days after hospital admission. Postmortem examination revealed primary angiitis of the central nervous system.

Conclusion
Primary angiitis of the central nervous system should always be taken into consideration when suspected infectious inflammation of the central nervous system does not respond to treatment adequately. In order to confirm the diagnosis with the consequence of a modified therapy angiography and combined leptomeningeal and brain biopsy should be considered immediately.
AIDS knowledge and attitudes in a Turkish population: an epidemiological study
Authors: Ayranci Unal 
Published: September 2005

Abstract

Background
The aim of this study was to investigate and present some pertinent comments concerning Acquired Immunodeficiency Syndrome (AIDS) knowledge, attitudes and misconceptions among the general population in a city of west Turkey. This study was deemed important and relevant due to the increasing importance of AIDS in Turkey and the other countries.

Methods
Using a multistage area sampling method, a random sample of individuals aged 11–83 years, living in 65 different quarters in the city of Eskisehir, Turkey during September, October and November 2004 were interviewed.

Results
In all, 1048 respondents completed the survey. In most items, respondents displayed a fairly good to excellent degree of knowledge about HIV/AIDS. Individuals with higher degrees of education indicated more correct responses in all items relating to knowledge of HIV/AIDS.
In general, the respondents' attitudes towards AIDS and people with AIDS were found to be tolerant and positive, with one answer choice showing that the majority of the respondents agreed with the statement that those with HIV/AIDS must be supported, treated and helped (90.7%). Moreover, the proportions of the respondents' misconceptions were found to be significantly low for all the items. However, nearly one fourth of the respondents agreed with the misconceptions 'AIDS is a punishment by God' and 'One is not infected with HIV/AIDS if engaged in sport and well nourished'.

Conclusion
In general HIV/AIDS related knowledge was high and people showed positive attitudes. However, people continue to hold misconceptions about AIDS and these need to be addressed by health education programs targeting those at higher risk.
Non-obstructive azoospermia and maturation arrest with complex translocation 46,XY t(9;13;14)(p22;q21.2;p13) is consistent with the Luciani-Guo hypothesis of latent aberrant autosomal regions and infertility
Authors: Sills Eric Scott , Kim Joseph Jinsuk , Witt Michael A , Palermo Gianpiero D 
Published: September 2005

Abstract

Objective
To describe clinical and histological features observed in the setting of an unusual complex translocation involving three autosomes (9, 13, and 14) identified in an otherwise healthy male referred for infertility consultation.

Materials and methods
The patient was age 30 and no family history was available (adopted). Total azoospermia was confirmed on multiple semen analyses. Peripheral karyotype showed a 46,XY t(9;13;14)(p22:q21.2;p13) genotype; no Y-chromosome microdeletions were identified. Cystic fibrosis screening was negative. Bilateral testis biopsy revealed uniform maturation arrest and peritubular fibrosis.

Results
Formal genetic counseling was obtained and the extant literature reviewed with the couple. Given the low probability of obtaining sperm on testicular biopsy, as well as the high risk of any retrieved sperm having an unbalanced genetic rearrangement, the couple elected to proceed with fertility treatment using anonymous donor sperm for insemination.

Conclusion
Although genes mapped to the Y-chromosome have been established as critical to normal testicular development and spermatogenesis, certain autosomal genes are now also recognized as important in these processes. Here we present clinical evidence to support the Luciani-Guo hypothesis (first advanced in 1984 and refined in 2002), which predicts severe spermatogenic impairment with aberrations involving chromosomes 9, 13, and/or 14, independent of Y-chromosome status. Additional study including fluorescent in situ hybridization and molecular analysis of specific chromosomal regions is needed to characterize more fully the contribution(s) of these autosomes to male testicular development and spermatogenesis.
Platypnea-orthodeoxia associated with a fenestrated atrial septal aneurysm: Case Report
Authors: van Gaal William J , Joseph Majo , Jones Elizabeth , Matalanis George , Horrigan Mark 
Published: September 2005

Abstract

Background
Platypnea-orthodeoxia describes the condition of combined dyspnea and hypoxia respectively, whilst in the upright position, which improves in the recumbent position.

Case Report
We present a case of platypnea-orthodeoxia due to a fenestrated atrial septal defect associated with an atrial septal aneurysm. Due to the fenestrated nature of the atrial septal defect, surgical rather than percutaneous correction was performed.

Conclusion
A high index of suspicion is required to diagnose the syndrome of platypnea-orthodeoxia. Careful echocardiographic evaluation is required to identify the syndrome, and to determine suitability for percutaneous repair.
Gender differences in perceived environmental correlates of physical activity
Authors: Bengoechea Enrique Garcia , Spence John C , McGannon Kerry R 
Published: September 2005

AbstractBackgroundLimited research has been conducted on gender differences in perceived environmental correlates of physical activity (PA). The purpose of this study was to explore the potential role of gender in the link between perceived environment and PA.MethodsUsing a telephone-administered survey, data was collected on leisure time physical activity (LTPA), perceptions of the neighbourhood environment, and self-efficacy in a representative sample of 1209 adults from the province of Alberta, Canada. LTPA was regressed on ten measures of perceived neighbourhood environment and self-efficacy in a series of logistic regressions.ResultsWomen were more likely than men to perceive their neighbourhood as unsafe to go for walks at night (χ2= 67.46, p < 0.001) and to report seeing people being active in their neighbourhood (χ2= 6.73, p < 0.01). Conversely, women were less likely to perceive easy access to places for PA (χ2= 11.50, p < 0.01) and availability of places to buy things within easy walking distance from home (χ2= 4.30, p < 0.05). Adjusting for age, education, income, and place of residence, access to places for PA (OR = 2.49) and interesting things to look at in the neighbourhood (OR = 1.94), were associated with higher levels of LTPA in men. Access to places for PA (OR = 2.63) and reporting seeing people being active (OR = 1.50) were associated with increased LTPA among women. After controlling for sociodemographic variables and self-efficacy, the presence of shops and places to buy things within easy walking distance from home (OR = 1.73), interesting things to look at in the neighbourhood (OR = 1.65), and access to places for PA (OR = 1.82) were associated with higher levels of LTPA in men. Among women, no significant relationships were observed between perceived environment and LTPA after adjusting for self-efficacy.ConclusionThe results provide additional support for the use of models in which gender is treated as a potential moderator of the link between the perceived environment and PA. Further, the results suggest the possibility of differential interventions to increase PA based on factors associated with gender.
Ruboxistaurin, a Protein Kinase C β Inhibitor, as an Emerging Treatment for Diabetes Microvascular Complications
Authors: Joy Scott V , Scates Ann C , Bearelly Srilaxmi , Dar Moahad , Taulien Christina A , Goebel Jason A , Cooney Michael J 
Published: September 2005

OBJECTIVE: To review current clinical data regarding the pharmacologic actions of ruboxistaurin (LY333531) mesylate, an inhibitor of protein kinase C (PKC) β, and its role to potentially reduce the development and/or the progression of diabetic microvascular complications. DATA SOURCES: Primary literature was obtained via a MEDLINE search (1966–August 2004) and through review of pertinent abstracts and presentations at major medical meetings. STUDY SELECTION AND DATA EXTRACTION: Literature relevant to PKC physiology, the pharmacokinetics of ruboxistaurin, and data evaluating the use of ruboxistaurin in treating diabetic microvascular complications in human and relevant animal models was reviewed. DATA SYNTHESIS: PKC is part of a group of intracellular signaling molecules activated in response to various specific hormonal, neuronal, and growth factor stimuli. Hyperglycemia leads to PKC β 1 and 2 isoform activation, which experimentally has been shown to contribute to the development and progression of diabetic microvascular complications (retinopathy, nephropathy, neuropathy) through various biochemical mechanisms. Animal and/or human studies using ruboxistaurin mesylate, a novel, highly selective inhibitor of PKC β, have shown delay in the progression and, in some cases, reversal of diabetic retinopathy, nephropathy, and neuropathy. CONCLUSIONS: Ruboxistaurin mesylate, by inhibiting excessive activation of certain PKC isoforms, has the potential to reduce the burden of microvascular complications for patients with diabetes.