bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular smooth muscle–derived tissue factor is critical for arterial thrombosis after ferric chloride–induced injury
Authors: Wang Li , Miller Christine , Swarthout Robert F. , Rao Mohan , Mackman Nigel , Taubman Mark B. 
Published: October 2008

Abstract
Tissue factor (TF) initiates coagulation, regulates hemostasis, and plays a critical role in mediating arterial thrombosis. TF is up-regulated in vascular smooth muscle cells (VSMCs) in atherosclerosis and arterial injury. To examine the biologic role of VSMC-derived TF, we crossed TFflox/flox mice with SM22αCre+/− mice. TF mRNA and activity were decreased in the aortic media of TF-deficient mice by 96% and 94.8%, respectively. There were no differences in TF activity measured in plasma or concentrated microparticles. TF-deficient mice were generated with the expected frequency, showed no evidence of bleeding or increased mortality, and had similar activated partial thromboplastin and tail vein bleeding times. Thrombus-mediated flow reduction in response to ferric chloride injury of the carotid arteries was significantly attenuated in VSMC-specific TF-deficient. Stable occlusion was seen in 11 of 12 wild-type mice, but in only 6 of 16 VSMC-specific TF-deficient mice (P = .001). These data suggest that VSMC-derived TF is critical in a macrovascular model of arterial thrombosis. This mouse model should be valuable in determining the contribution of VSMC-derived TF in other TF-mediated phenomena, such as restenosis.
The monovalent cation leak in overhydrated stomatocytic red blood cells results from amino acid substitutions in the Rh-associated glycoprotein
Authors: Bruce Lesley J. , Guizouarn Hélène , Burton Nicholas M. , Gabillat Nicole , Poole Joyce , Flatt Joanna F. , Brady R. Leo , Borgese Franck , Delaunay Jean , Stewart Gordon W. 
Published: October 2008

AbstractOverhydrated hereditary stomatocytosis (OHSt) is a rare dominantly inherited hemolytic anemia characterized by a profuse membrane leak to monovalent cations. Here, we show that OHSt red cell membranes contain slightly reduced amounts of Rh-associated glycoprotein (RhAG), a putative gas channel protein. DNA analysis revealed that the OHSt patients have 1 of 2 heterozygous mutations (t182g, t194c) in RHAG that lead to substitutions of 2 highly conserved amino acids (Ile61Arg, Phe65Ser). Unexpectedly, expression of wild-type RhAG in Xenopus laevis oocytes induced a monovalent cation leak; expression of the mutant RhAG proteins induced a leak about 6 times greater than that in wild type. RhAG belongs to the ammonium transporter family of proteins that form pore-like structures. We have modeled RhAG on the homologous Nitrosomonas europaea Rh50 protein and shown that these mutations are likely to lead to an opening of the pore. Although the function of RhAG remains controversial, this first report of functional RhAG mutations supports a role for RhAG as a cation pore.
Incomplete T-cell receptor–β peptides target the mitochondrion and induce apoptosis
Authors: Shani Nir , Rubin-Lifshitz Hila , Peretz-Cohen Yifat , Shkolnik Ketty , Shinder Vera , Cohen-Sfady Michal , Shav-Tal Yaron , Barda-Saad Mira , Zipori Dov 
Published: October 2008

AbstractThe default pathway of cell-surface T-cell receptor (TCR) complex formation, and the subsequent transport to the membrane, is thought to entail endoplasmic reticulum (ER) localization followed by proteasome degradation of the unassembled chains. We show herein an alternative pathway: short, incomplete peptide versions of TCRβ naturally occur in the thymus. Such peptides, which have minimally lost the leader sequence or have been massively truncated, leaving only the very C terminus intact, are sorted preferentially to the mitochondrion. As a consequence of the mitochondrial localization, apoptotic cell death is induced. Structure function analysis showed that both the specific localization and induction of apoptosis depend on the transmembrane domain (TMD) and associated residues at the COOH-terminus of TCR. Truncated forms of TCR, such as the short peptides that we detected in the thymus, may be products of protein degradation within thymocytes. Alternatively, they may occur through the translation of truncated mRNAs resulting from unfruitful rearrangement or from germline transcription. It is proposed that mitochondria serve as a subcellular sequestration site for incomplete TCR molecules.
IL-17 contributes to CD4-mediated graft-versus-host disease
Authors: Kappel Lucy W. , Goldberg Gabrielle L. , King Christopher G. , Suh David Y. , Smith Odette M. , Ligh Cassandra , Holland Amanda M. , Grubin Jeremy , Mark Nicholas M. , Liu Chen , Iwakura Yoichiro , Heller Glenn , van den Brink Marcel R. M. 
Published: October 2008

AbstractCD4+ interleukin-17 (IL-17)+ T cells (Th17 cells) have been implicated in allograft rejection of solid organs and several autoimmune diseases. However, the functional role of Th17 cells in the development of acute graft-versus-host disease (GVHD) has not been well-characterized. We detected significant numbers of alloreactive CD4+ donor T cells expressing IL-17, IL-17F, or IL-22 in the lymphoid organs of recipients of an allogeneic bone marrow transplant. We found no differences in GVHD mortality or graft-versus-tumor (GVT) activity between wild type (WT) and IL-17−/− T-cell recipients. However, upon transfer of murine IL-17−/− CD4+ T cells in an allogeneic BMT model, GVHD development was significantly delayed behind recipients of WT CD4+ T cells, yet overall GVHD mortality was unaffected. Moreover, recipients of IL-17−/− CD4+ T cells had significantly fewer Th1 cells during the early stages of GVHD. Furthermore, we observed a decrease in the number of IFN-γ–secreting macrophages and granulocytes and decreased production of proinflammatory cytokines (interferon [IFN]-γ, IL-4, and IL-6) in recipients of IL-17−/− CD4+ T cells. We conclude that IL-17 is dispensable for GVHD and GVT activity by whole T cells, but contributes to the early development of CD4-mediated GVHD by promoting production of proinflammatory cytokines.
Copy number variations (CNVs) identified in Korean individuals
Authors: Kang Tae-Wook , Jeon Yeo-Jin , Jang Eunsu , Kim Hee-Jin , Kim Jeong-Hwan , Park Jong-Lyul , Lee Siwoo , Kim Yong Sung , Kim Jong Yeol , Kim Seon-Young 
Published: October 2008

Abstract

Background
Copy number variations (CNVs) are deletions, insertions, duplications, and more complex variations ranging from 1 kb to sub-microscopic sizes. Recent advances in array technologies have enabled researchers to identify a number of CNVs from normal individuals. However, the identification of new CNVs has not yet reached saturation, and more CNVs from diverse populations remain to be discovered.

Results
We identified 65 copy number variation regions (CNVRs) in 116 normal Korean individuals by analyzing Affymetrix 250 K Nsp whole-genome SNP data. Ten of these CNVRs were novel and not present in the Database of Genomic Variants (DGV). To increase the specificity of CNV detection, three algorithms, CNAG, dChip and GEMCA, were applied to the data set, and only those regions recognized at least by two algorithms were identified as CNVs. Most CNVRs identified in the Korean population were rare (<1%), occurring just once among the 116 individuals. When CNVs from the Korean population were compared with CNVs from the three HapMap ethnic groups, African, European, and Asian; our Korean population showed the highest degree of overlap with the Asian population, as expected. However, the overlap was less than 40%, implying that more CNVs remain to be discovered from the Asian population as well as from other populations. Genes in the novel CNVRs from the Korean population were enriched for genes involved in regulation and development processes.

Conclusion
CNVs are recently-recognized structural variations among individuals, and more CNVs need to be identified from diverse populations. Until now, CNVs from Asian populations have been studied less than those from European or American populations. In this regard, our study of CNVs from the Korean population will contribute to the full cataloguing of structural variation among diverse human populations.
Role of cytochrome P450 in drug interactions
Authors: Bibi Zakia 
Published: October 2008

AbstractDrug-drug interactions have become an important issue in health care. It is now realized that many drug-drug interactions can be explained by alterations in the metabolic enzymes that are present in the liver and other extra-hepatic tissues. Many of the major pharmacokinetic interactions between drugs are due to hepatic cytochrome P450 (P450 or CYP) enzymes being affected by previous administration of other drugs. After coadministration, some drugs act as potent enzyme inducers, whereas others are inhibitors. However, reports of enzyme inhibition are very much more common. Understanding these mechanisms of enzyme inhibition or induction is extremely important in order to give appropriate multiple-drug therapies. In future, it may help to identify individuals at greatest risk of drug interactions and adverse events.
Vitamin D deficiency in undifferentiated connective tissue disease
Authors: Zold Eva , Szodoray Peter , Gaal Janos , Kappelmayer János , Csathy Laszlo , Gyimesi Edit , Zeher Margit , Szegedi Gyula , Bodolay Edit 
Published: October 2008

Abstract
Introduction
Both experimental and clinical data provide evidence that vitamin D is one of those important environmental factors that can increase the prevalence of certain autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, insulin-dependent diabetes mellitus, and inflammatory bowel disease. The aim of the present study was to investigate the prevalence of vitamin D insufficiency in patients with undifferentiated connective tissue disease (UCTD).

Methods
Plasma 25(OH)D3 levels in 161 UCTD patients were measured in both summer and winter periods. Autoantibody profiles (antinuclear antibody, anti-U1-ribonucleoprotein, anti-SSA, anti-SSB, anti-Jo1, anti-Scl70, anti-double-stranded DNA, anti-centromere, anti-cardiolipin, rheumatoid factor, and anti-cyclic citrullinated peptide) and clinical symptoms of the patients were assessed.

Results
Plasma levels of 25(OH)D3 in UCTD patients were significantly lower compared with controls in both summer and winter periods (UCTD summer: 33 ± 13.4 ng/mL versus control: 39.9 ± 11.7 ng/mL, P = 0.01; UCTD winter: 27.8 ± 12.48 ng/mL versus control: 37.8 ± 12.3 ng/mL, P = 0.0001). The presence of dermatological symptoms (photosensitivity, erythema, and chronic discoid rash) and pleuritis was associated with low levels of vitamin D. During the average follow-up period of 2.3 years, 35 out of 161 patients (21.7%) with UCTD further developed into well-established connective tissue disease (CTD). Patients who progressed into CTDs had lower vitamin D levels than those who remained in the UCTD stage (vitamin D levels: CTD: 14.7 ± 6.45 ng/mL versus UCTD: 33.0 ± 13.4 ng/mL, P = 0.0001).

Conclusions
In patients with UCTD, a seasonal variance in levels of 25(OH)D3 was identified and showed that these levels were significantly lower than in controls during the corresponding seasons. Our results suggest that vitamin D deficiency in UCTD patients may play a role in the subsequent progression into well-defined CTDs.
IGF1 as predictor of all cause mortality and cardiovascular disease in an elderly population
Authors: Andreassen Mikkel , Raymond Ilan , Kistorp Caroline , Hildebrandt Per , Faber Jens , Kristensen Lars Østergaard 
Published: October 2008

BackgroundIGF1 is believed to influence ageing and development of cardiovascular disease (CVD) through complex mechanisms. Reduced IGF1 levels might be causally associated with conditions accompanying ageing including development of CVD. However, in animal models reduced GH–IGF1 signalling increases lifespan. Reduced IGF1 activity might also be associated with longevity in humans.ObjectiveThe objective was to investigate if plasma IGF1 levels were associated with all cause mortality, and the development of chronic heart failure (CHF) and a major CV event.Patients and designA population based study of 642 individuals, aged 50–89 years. Development of CHF was evaluated in 576 individuals with normal systolic function assessed by echocardiography and without the history of CHF or myocardial infarction. Development of the first major CV event was evaluated in 504 individuals with normal systolic function and without prevalent CVD. Outcomes were ascertained after 5 years using hospital discharge diagnoses.ResultsAdjustment for risk factors IGF1 values in the fourth quartile versus values below the fourth quartile was associated with increased mortality (n=103), hazard ratio (HR) 1.52 (95% confidence interval (CI) 1.01–2.28;P=0.044). IGF1 in the fourth quartile was also independently associated with risk of development of CHF (n=19), HR 5.02 (95% CI 2.00–12.64;P=0.001) but showed no association with the overall incidence of major CV events (n=58), HR 1.05 (95% CI 0.59–1.90;P=0.861).ConclusionsHigh IGF1 levels were independently associated with increased all cause mortality and risk of development of CHF, whereas no relation with the overall incidence of CVD was observed.
Cerebral Hemodynamic Changes During Intensive Care of Preterm Infants
Authors: Limperopoulos Catherine , Gauvreau Kimberlee K. , O'Leary Heather , Moore Marianne , Bassan Haim , Eichenwald Eric C. , Soul Janet S. , Ringer Steven A. , Di Salvo Donald N. , du Plessis Adré J. 
Published: October 2008

OBJECTIVES. The objectives of this study were to examine the circulatory changes experienced by the immature systemic and cerebral circulations during routine events in the critical care of preterm infants and to identify clinical factors that are associated with greater hemodynamic-oxygenation changes during these events.METHODS. We studied 82 infants who weighed &lt;1500 g at birth and required intensive care management and continuous blood pressure monitoring from an umbilical arterial catheter. Continuous recording of cerebral and systemic hemodynamic and oxygenation changes was performed. We studied 6 distinct types of caregiving events during 10-minute epochs: (1) quiet baseline periods; (2) minor manipulation; (3) diaper changes; (4) endotracheal tube suctioning; (5) endotracheal tube repositioning; and (6) complex events. Each event was matched with a preceding baseline. We examined the effect of specific clinical factors and cranial ultrasound abnormalities on the systemic and cerebral hemodynamic oxygenation changes that were associated with the various event types.RESULTS. There were highly significant differences in hemodynamics and oxygenation between events overall and baseline epochs. The magnitude of these circulatory changes was greatest during endotracheal tube repositioning and complex caregiving events. Lower gestational age, higher illness severity, chorioamnionitis, low Apgar scores, and need for pressor-inotropes all were associated with circulatory changes of significantly lower magnitude. Cerebral hemodynamic changes were associated with early parenchymal ultrasound abnormalities.CONCLUSIONS. Routine caregiving procedures in critically ill preterm infants are associated with major circulatory fluctuations that are clinically underappreciated and underdetected by current bedside monitoring. Our data underscore the importance of continuous cerebral hemodynamic monitoring in critically ill preterm infants.
Diabetes Medication Satisfaction Tool
Authors: Anderson Roger T. , Girman Cynthia J. , Pawaskar Manjiri D. , Camacho Fabian T. , Calles Jorge , Kelly William S. , DeMuro Carla , Balkrishnan Rajesh 
Published: October 2008

OBJECTIVE—To develop and test a patient questionnaire on treatment satisfaction with diabetes regimens.
RESEARCH DESIGN AND METHODS—Survey items were developed from community clinic focus groups, pretested in patients with diabetes, and examined in two samples of treated patients.
RESULTS—Sixteen items performed well in assessing treatment experiences: ease and convenience, lifestyle burdens, well-being, and medical control. Construct validity was supported by associations (P &lt; 0.05) with treatment complexity, self-rated glucose control, health worries, and A1C. Internal consistency ranged from 0.89 to 0.95.
CONCLUSIONS—The Diabetes Medication Satisfaction Tool offers a comprehensive assessment of patient acceptability, with diabetes therapy useful for individualizing therapeutic decision making.
Clinical Heterogeneity in Patients With FOXP3 Mutations Presenting With Permanent Neonatal Diabetes
Authors: Rubio-Cabezas Oscar , Minton Jayne A.L. , Caswell Richard , Shield Julian P. , Deiss Dorothee , Sumnik Zdenek , Cayssials Amely , Herr Mathias , Loew Anja , Lewis Vaughan , Ellard Sian , Hattersley Andrew T. 
Published: October 2008

OBJECTIVE—Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is caused by FOXP3 mutations. We aimed to determine the prevalence, genetics, and clinical phenotype of FOXP3 mutations in a large cohort with permanent neonatal diabetes (PNDM).
RESEARCH DESIGN AND METHODS—The 11 coding exons and the polyadenylation region of FOXP3 were sequenced in 26 male subjects with diabetes diagnosed before 6 months of age in whom common genetic causes of PNDM had been excluded. Ten subjects had at least one additional immune-related disorder, and the remaining 16 had isolated diabetes.
RESULTS—We identified four hemizygous FOXP3 mutations in 6 of 10 patients with associated immune-related disorders and in 0 of 16 patients with isolated diabetes (P = 0.002). Three patients with two novel mutations (R337Q and P339A) and the previously reported L76QfsX53 developed classic IPEX syndrome and died within the first 13 months. The novel mutation V408M was found in three patients from two unrelated families and had a mild phenotype with hypothyroidism and autoimmune enteropathy (n = 2) or nephrotic syndrome (n = 1) and survival to 12–15 years.
CONCLUSIONS—FOXP3 mutations result in ∼4% of cases of male patients with permanent diabetes diagnosed before 6 months. Patients not only have classic IPEX syndrome but, unexpectedly, may have a more benign phenotype. FOXP3 sequencing should be performed in any male patient with the diagnosis of diabetes in the first 6 months who develops other possible autoimmune-associated conditions, even in the absence of full IPEX syndrome.
Clinical and Behavioral Correlates of Achieving and Maintaining Glycemic Targets in an Underserved Population With Type 2 Diabetes
Authors: Ruelas Valerie , Roybal G. Michael , Lu Yang , Goldman Dana , Peters Anne 
Published: October 2008

OBJECTIVE—In an underserved Latino area, we established a disease-management program and proved its effectiveness. However, many patients still remained above target. This study was designed to evaluate which factors are associated with reaching program goals.
RESEARCH DESIGN AND METHODS—This was a randomized, prospective, observational study in which patients enrolled in our program were followed for 2 years with outcomes, measures, and questionnaires assessed at baseline and at 6, 12, and 24 months.
RESULTS—Overall, A1C fell by 1%. Adherence to medication was the strongest predictor of reaching the target A1C of &lt;8%; baseline A1C was also predictive. Knowledge scores increased in those who reached target, but the measures of self-efficacy and empowerment did not change for either group.
CONCLUSIONS—Diabetes management is effective in a lower-income Latino population. However, adherence was suboptimal even when medications were provided on-site for free. Further research into barriers associated with medication adherence is needed.
Metabolic Syndrome and All-Cause and Cardiovascular Mortality in an Italian Elderly Population
Authors: Zambon Sabina , Zanoni Silvia , Romanato Giovanna , Chiara Corti Maria , Noale Marianna , Sartori Leonardo , Musacchio Estella , Baggio Giovannella , Crepaldi Gaetano , Manzato Enzo 
Published: October 2008

OBJECTIVE—The purpose of this study was to explore the association of metabolic syndrome and each of its components with all-cause and cardiovascular mortality in a general Italian elderly population.
RESEARCH DESIGN AND METHODS—Metabolic syndrome, diagnosed by National Cholesterol Education Program Adult Treatment Panel III criteria, all-cause mortality, and cardiovascular mortality, was evaluated in 2,910 subjects aged ≥65 years of the Progetto Veneto Anziani (Pro.V.A.) Study during a mean follow-up time of 4.4 years.
RESULTS—After multivariable adjustment, metabolic syndrome was associated with increased all-cause mortality in all subjects (hazard ratio 1.41 [95% CI 1.16–1.72], P = 0.001), among men (1.42 [1.06–1.89], P = 0.017), and among women (1.47 [1.13–1.91], P = 0.004). High glucose in all subjects (1.27 [1.02–1.59], P = 0.037) and in women (1.61 [1.16–2.24], P = 0.005) and low HDL cholesterol in women (1.48 [1.08–2.02], P = 0.014) were predictors of all-cause mortality, even independently of the interactions of different metabolic syndrome components. After multivariable adjustment, metabolic syndrome was also associated with increased cardiovascular mortality in all subjects (1.60 [1.17–2.19], P = 0.003), among men (1.66 [1.00–2.76], P = 0.051), and among women (1.60 [1.06–2.33], P = 0.025). High glucose (2.17 [1.28–3.68], P = 0.004) and low HDL cholesterol (1.78 [1.07–2.95], P = 0.026) among women predicted higher cardiovascular mortality.
CONCLUSIONS—In this general Italian elderly population, among metabolic syndrome components, all-cause mortality is better predicted by high glucose in all subjects and in women and by low HDL cholesterol in women, whereas cardiovascular mortality is better predicted by high glucose and low HDL cholesterol in women.
Factors Associated With Intensification of Oral Diabetes Medications in Primary Care Provider-Patient Dyads: A Cohort Study
Authors: Bolen Shari Danielle , Bricker Eric , Samuels T. Alafia , Yeh Hsin-Chieh , Marinopoulos Spyridon S. , McGuire Maura , Abuid Marcela , Brancati Frederick L. 
Published: October 2008

OBJECTIVE—Although suboptimal glycemic control is known to be common in diabetic adults, few studies have evaluated factors at the level of the physician-patient encounter. Our objective was to identify novel visit-based factors associated with intensification of oral diabetes medications in diabetic adults.
RESEARCH DESIGN AND METHODS—We conducted a nonconcurrent prospective cohort study of 121 patients with type 2 diabetes and hyperglycemia (A1C ≥8%) enrolled in an academically affiliated managed-care program. Over a 24-month interval (1999–2001), we identified 574 hyperglycemic visits. We measured treatment intensification and factors associated with intensification at each visit.
RESULTS—Provider-patient dyads intensified oral diabetes treatment in only 128 (22%) of 574 hyperglycemic visits. As expected, worse glycemia was an important predictor of intensification. Treatment was more likely to be intensified for patients with visits that were “routine” (odds ratio [OR] 2.55 [95% CI 1.49–4.38]), for patients taking two or more oral diabetes drugs (2.82 [1.74–4.56]), or for patients with longer intervals between visits (OR per 30 days 1.05 [1.00–1.10]). In contrast, patients with less recent A1C measurements (OR &gt;30 days before the visit 0.53 [0.34–0.85]), patients with a higher number of prior visits (OR per prior visit 0.94 [0.88–1.00]), and African American patients (0.59 [0.35–1.00]) were less likely to have treatment intensified.
CONCLUSIONS—Failure to intensify oral diabetes treatment is common in diabetes care. Quality improvement measures in type 2 diabetes should focus on overcoming inertia, improving continuity of care, and reducing racial disparities.