tbuckley/cabot-search huggingface dataset:
Cardiovascular Risk Factors Are Differently Associated with Urinary Albumin Excretion in Men and Women
Authors: Jacobien C. Verhave, Hans L. Hillege, Johannes G. M. Burgerhof, Gerjan Navis, Dick de Zeeuw, Paul E. de Jong
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Cardiovascular morbidity and mortality is not equally distributed among genders, men being more affected than women. It is not clear whether this is only related to a higher prevalence of the cardiovascular risk factors or to a similar prevalence of the risk factors as in women but a greater vascular susceptibility to these risk factors in men. This was tested by studying the association between various cardiovascular risk factors and urinary albumin excretion (UAE) in a large cohort of male and female subjects. While the prevalence of smoking and hypercholesterolemia was comparable between the genders, obesity was more common in women, and diabetes and hypertension were more frequent in men. The prevalence of microalbuminuria was about twofold higher in men. Interestingly, for a given level of any risk factor, UAE was higher in men than in women. On multivariate analysis with UAE as the dependent variable, an interaction with gender was found for the risk factors age, body mass index, and plasma glucose. Thus, for a higher age, body mass index, and glucose, the UAE is significantly increased in men when compared with women. It is concluded that gender differences exist in the association between cardiovascular risk factors and UAE. This is consistent with a larger vascular susceptibility to these risk factors in men as compared with women. E-mail: [email protected]
Tamoxifen Stimulates the Growth of Cyclin D1–Overexpressing Breast Cancer Cells by Promoting the Activation of Signal Transducer and Activator of Transcription 3
Authors: Yuki Ishii, Samuel Waxman, Doris Germain
Journal: Cancer Research (2008)

Abstract De novo or acquired resistance to tamoxifen is a major clinical challenge for the management of estrogen receptor (ER)–positive breast cancers. Although cyclin D1 overexpression is associated with a better outcome for breast cancer patients, its overexpression is also linked to tamoxifen resistance. We previously reported that the beneficial effect of cyclin D1 correlates with its ability to repress the antiapoptotic transcription factor signal transducer and activator of transcription 3 (STAT3). In contrast, molecular pathways linking overexpression of cyclin D1 to tamoxifen resistance have not been established. In the current study, the effect of tamoxifen on the growth of genetically matched high or low cyclin D1–expressing breast cancer cells was characterized and the interactions between cyclin D1, ER, and STAT3 in response to tamoxifen treatment were determined. We show that repression of STAT3 by cyclin D1 inhibits cell growth on Matrigel and in tumors in vivo; however, treatment with tamoxifen abolishes cyclin D1–mediated repression of STAT3 and growth suppression. We show that tamoxifen induces a redistribution of cyclin D1 from STAT3 to the ER, which results in the activation of both STAT3 and the ER. These results offer a molecular mechanism for the dual effect of cyclin D1 overexpression in breast cancer and support the notion that the level of cyclin D1 expression and activated STAT3 are important markers to predict response to tamoxifen treatment. [Cancer Res 2008;68(3):852–60]
A GREM1 Gene Variant Associates with Diabetic Nephropathy
Authors: Amy Jayne McKnight, Christopher C. Patterson, Kerry A. Pettigrew, David A. Savage, Jill Kilner, Madeline Murphy, Denise Sadlier, Alexander P. Maxwell
Journal: Journal of the American Society of Nephrology (2010)

Gremlin, a cell growth and differentiation factor, promotes the development of diabetic nephropathy in animal models, but whether GREM1 gene variants associate with diabetic nephropathy is unknown. We comprehensively screened the 5' upstream region (including the predicted promoter), all exons, intron-exon boundaries, complete untranslated regions, and the 3' region downstream of the GREM1 gene. We identified 31 unique variants, including 24 with a minor allele frequency exceeding 5%, and 9 haplotype-tagging single nucleotide polymorphisms (htSNPs). We selected one additional variant that we predicted to alter transcription factor binding. We genotyped 709 individuals with type 1 diabetes of whom 267 had nephropathy (cases) and 442 had no evidence of kidney disease (controls). Three individual SNPs significantly associated with nephropathy at the 5% level, and two remained significant after adjustment for multiple testing. Subsequently, we genotyped a replicate population comprising 597 cases and 502 controls: this population supported an association with one of the SNPs (rs1129456; P = 0.0003). Combined analysis, adjusted for recruitment center (n = 8), suggested that the T allele conferred greater odds of nephropathy (OR 1.69; 95% CI 1.36 to 2.11). In summary, the GREM1 variant rs1129456 associates with diabetic nephropathy, perhaps explaining some of the genetic susceptibility to this condition.
Voting Competence and Mental Illness
Authors: MORRIS M. KLEIN, SAUL A. GROSSMAN
Journal: American Journal of Psychiatry (1971)

Does mental illness render a person incompetent to vote? Two studies highlight the similarity of voting behavior between patients hospitalized in a community state hospital and citizens living in the community. The results of the studies appear to dispel any need to maintain separate laws that govern the voting rights of citizens who are hospitalized for mental illness.
Vitamin E restores endothelium dependent vasodilatation in cholesterol fed rabbits: in vivo measurements by photoplethysmography
Authors: T. O Klemsdal, T. L G Andersson, J. Matz, G. A A Ferns, K. Gjesdal, E. E Anggard
Journal: Cardiovascular Research (1994)

Objective: Pulse curve plethysmography was used to examine the effect of vitamin E on endothelium dependent and independent vasodilatation in unanaesthetised cholesterol fed rabbits in vivo. The height of the dicrotic notch was used as an index of general arterial vasodilatation. Methods: Twenty eight rabbits were divided into three study groups; a control group (group 1, n = 8), a group fed 1% cholesterol (group 2, n = 10), and a group fed 1% cholesterol with the addition of 0.2% vitamin E after four weeks (group 3, n= 10). After six weeks on diet the vasodilator responses to acetylcholine and glyceryl trinitrate were measured by photoplethysmography of the rabbit ear. Recordings were made during light sedation at baseline and during infusion of acetylcholine (1.5, 3.0, 6.0, and 12 μg·min−1) and glyceryl trinitrate (3.75, 7.5, and 15.0 μg·min−1). In a second set of experiments with control fed rabbits (n = 5), acetylcholine infusions were given before and after infusion of L-nitro-arginine (15 mg). Results: The relative height of the dicrotic notch (which predominantly indicates arterial tone in the larger vessels) was reduced by acetylcholine in a dose dependent manner, but in cholesterol fed rabbits (group 2) this response was significantly decreased. Rabbits receiving concomitant dietary vitamin E responded in a similar manner to controls. The difference was most prominent using acetylcholine at a dose of 3.0 μg·min−1, where the mean change from baseline was 11(SEM 4)% in group 2, compared to 31(6)% in group 1 (p = 0.01), and to 26(5)% in group 3 (p = 0.02). Similar differences between the groups were observed for the increase in heart rate during acetylcholine infusions. In contrast, the responses to glyceryl trinitrate were similar in all groups. After infusions of L-nitro-arginine, the responses to acetylcholine were blunted. Conclusions: Supplementation with vitamin E restored the otherwise reduced vascular response to acetylcholine in cholesterol fed rabbits. Analysis of photoplethysmographic pulse curves is a simle non-invasive method of evaluating arterial vasodilator effects. However, the nature of the measured dilator response needs to be characterised further. Cardiovascular Research 1994;28:1397-1402
Long-Term Balancing Selection at the West Nile Virus Resistance Gene, Oas1b, Maintains Transspecific Polymorphisms in the House Mouse
Authors: W. Ferguson, S. Dvora, J. Gallo, A. Orth, S. Boissinot
Journal: Molecular Biology and Evolution (2008)

Oligoadenylate synthetases (OASs) are interferon-inducible enzymes that participate in the first line of defense against a wide range of viral infection.Recent studies have determined that Oas1b, a member of the OAS gene family in the house mouse (Mus musculus), provides specific protection against flavivirus infection (e.g., West Nile virus, dengue fever virus, and yellow fever virus).We characterized the nucleotide sequence variation in coding and noncoding regions of the Oas1b gene for a large number of wild-derived strains of M. musculus and related species.Our sequence analyses determined that this gene is one of the most polymorphic genes ever described in any mammal.The level of variation in noncoding regions of Oas1b is an order of magnitude higher than the level reported for other regions of the mouse genome and is significantly different from the level of intraspecific variation expected under neutrality.Furthermore, a phylogenetic analysis of intronic sequences demonstrated that Oas1b alleles are ancient and that their divergence predates several speciation events, resulting in transspecific polymorphisms.The amino acid sequence of Oas1b is also extremely variable, with 1 out of 7 amino acid positions being polymorphic within M. musculus.Oas1b alleles are comparatively more divergent at synonymous positions than most autosomal genes and the ratio of nonsynonymous to synonymous substitution is remarkably high, suggesting that positive selection has been acting on Oas1b.The ancestry of Oas1b polymorphisms and the high level of amino acid polymorphisms strongly suggest that the allelic variation at Oas1b has been maintained in mouse populations by long-term balancing selection.
Falling neonatal autopsy rates
Authors: T Y. Khong
Journal: BMJ (2002)

<h3>Abstract</h3> Reading literature (e.g., an entire book) is an enriching experience that qualitatively differs from reading a single sentence; however, the brain dynamics of such context-dependent memory remains unclear. This study aimed to elucidate mnemonic neural dynamics during natural reading of literature by performing electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI). Brain activities of human participants recruited on campus were correlated with their subsequent memory, which was quantified by semantic correlation between the read text and reports subsequently written by them based on state of the art natural language processing procedures. The results of the EEG data analysis showed a significant positive relationship between subsequent memory and fixation-related EEG. Sentence-length and paragraph-length mnemonic processes were associated with N1-P2 and P3 fixation-related potential (FRP) components and fixation-related theta-band (4-8 Hz) EEG power, respectively. In contrast, the results of fMRI analysis showed a significant negative relationship between subsequent memory and blood-oxygenation-level dependent (BOLD) activation. Sentence-length and paragraph-length mnemonic processes were associated with networks of regions forming part of the salience network and the default mode network (DMN), respectively. Taken together with the EEG results, these memory-related deactivations in the salience network and the DMN were thought to reflect the reading of sentences characterized by low mnemonic load and the suppression of task-irreverent thoughts, respectively. It was suggested that the context-dependent mnemonic process during literature reading requires large-scale network deactivation, which might reflect coordination of a range of voluntary processes during reading. <b>Significance statement</b> Context-dependent memory encoding during natural reading of literature was evaluated using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) based on a subsequent memory paradigm. Subsequent memory was quantified by semantic correlation between the read text and reports subsequently written by the participants, based on a recent natural language processing procedure. Our results demonstrated a positive correlation between subsequent memory and fixation-related EEG and a negative correlation with fMRI activity. Sentence-length and paragraph-length processes were associated with regions belonging to the salience network and the default mode network, respectively. This is the first demonstration that memory encoding during literature reading is associated with large-scale network deactivations, which might reflect the coordination of a range of voluntary processes during reading.
Comment on: Khurana et al. The Diagnosis of Neonatal Diabetes in a Mother at 25 Years of Age. Diabetes Care 2012;35:e59
Authors: Ali J. Chakera, Sarah E. Flanagan, Sian Ellard, Andrew T. Hattersley
Journal: Diabetes Care (2013)

We read with interest the observation by Khurana et al. (1) regarding the speculative treatment of their case of neonatal diabetes (ND) pending molecular genetic confirmation. The authors report the successful trial of a sulfonylurea in a baby diagnosed with diabetes on day 2 of life in whom an activating KCNJ11 mutation was subsequently identified. Khurana et al. suggest a controlled trial of sulfonylurea in patients with ND if genetic testing is not feasible.

We would not agree with this suggested management plan for two reasons: Firstly, not all patients with ND will respond to treatment with a sulfonylurea, and secondly, the result of genetic testing for ND can be available …
Role of Toll-like receptor 2 (TLR2) in neutrophil activation: GM-CSF enhances TLR2 expression and TLR2-mediated interleukin 8 responses in neutrophils
Authors: Evelyn A. Kurt-Jones, Leisa Mandell, Constance Whitney, Alison Padgett, Kerri Gosselin, Peter E. Newburger, Robert W. Finberg
Journal: Blood (2002)
Chemotherapy for management of localised high-grade gastric B-cell lymphoma: how much is necessary?
Authors: M. Raderer, A. Chott, J. Drach, C. Montalban, B. Dragosics, U. Jäger, A. Püspök, C. Österreicher, C.C. Zielinski
Journal: Annals of Oncology (2002)
THE CELL BIOLOGY OF THE BLOOD-BRAIN BARRIER
Authors: L. L. Rubin, J. M. Staddon
Journal: Annual Review of Neuroscience (1999)

The blood-brain barrier (BBB) is formed by brain capillary endothelial cells (ECs). In the late embryonic and early postnatal period, these cells respond to inducing factors found in the brain environment by adopting a set of defined characteristics, including high-electrical-resistance tight junctions. Although the factors have not been identified definitively, a great deal of information about brain ECs has been obtained, especially recently. This review concentrates on a cell biological analysis of the BBB, with an emphasis on regulation of the specialized intercellular junctions. The development of these junctions seems to depend on two primary processes: the appearance of high levels of the tight junction protein occludin and intracellular signaling processes that control the state of phosphorylation of junctional proteins. Recent studies have revealed that the BBB can be modulated in an ongoing way to respond to environmental stimuli.
Platelet factor 4 limits Th17 differentiation and cardiac allograft rejection
Authors: Guanfang Shi, David J. Field, Kyung-ae Ko, Sara Ture, Kalyan Srivastava, Scott Levy, M. Anna Kowalska, Mortimer Poncz, Deborah J. Fowell, Craig N. Morrell
Journal: Journal of Clinical Investigation (2014)

Th cells are the major effector cells in transplant rejection and can be divided into Th1, Th2, Th17, and Treg subsets. Th differentiation is controlled by transcription factor expression, which is driven by positive and negative cytokine and chemokine stimuli at the time of T cell activation. Here we discovered that chemokine platelet factor 4 (PF4) is a negative regulator of Th17 differentiation. PF4-deficient and platelet-deficient mice had exaggerated immune responses to cardiac transplantation, including increased numbers of infiltrating Th17 cells and increased plasma IL-17. Although PF4 has been described as a platelet-specific molecule, we found that activated T cells also express PF4. Furthermore, bone marrow transplantation experiments revealed that T cell-derived PF4 contributes to a restriction in Th17 differentiation. Taken together, the results of this study demonstrate that PF4 is a key regulator of Th cell development that is necessary to limit Th17 differentiation. These data likely will impact our understanding of platelet-dependent regulation of T cell development, which is important in many diseases, in addition to transplantation.
Antiarrhythmics After Ablation of Atrial Fibrillation (5A Study)
Authors: Jean-François Roux, Erica Zado, David J. Callans, Fermin Garcia, David Lin, Francis E. Marchlinski, Rupa Bala, Sanjay Dixit, Michael Riley, Andrea M. Russo, Mathew D. Hutchinson, Joshua Cooper, Ralph Verdino, Vickas Patel, Parijat S. Joy, Edward P. Gerstenfeld
Journal: Circulation (2009)

Atrial arrhythmias are common early after atrial fibrillation (AF) ablation. We hypothesized that empirical antiarrhythmic drug (AAD) therapy for 6 weeks after AF ablation would reduce the occurrence of atrial arrhythmias.We randomized consecutive patients with paroxysmal AF undergoing ablation to empirical antiarrhythmic therapy (AAD group) or no antiarrhythmic therapy (no-AAD group) for the first 6 weeks after ablation. In the no-AAD group, only atrioventricular nodal blocking agents were prescribed. All patients wore a transtelephonic monitor for 4 weeks after discharge and were reevaluated at 6 weeks. The primary end point of the study was a composite of (1) atrial arrhythmias lasting more than 24 hours; (2) atrial arrhythmias associated with severe symptoms requiring hospital admission, cardioversion, or initiation/change of antiarrhythmic drug therapy; and (3) intolerance to antiarrhythmic agent requiring drug cessation. Of 110 enrolled patients (age 55+/-9 years, 71% male), 53 were randomized to AAD and 57 to no-AAD. There was no difference in baseline characteristics between groups. During the 6 weeks after ablation, fewer patients reached the primary end point in the AAD compared with the no-AAD group (19% versus 42%; P=0.005). There remained fewer events in the AAD group (13% versus 28%; P=0.05) when only end points of AF >24 hours, arrhythmia-related hospitalization, or electrical cardioversion were compared.AAD treatment during the first 6 weeks after AF ablation is well tolerated and reduces the incidence of clinically significant atrial arrhythmias and need for cardioversion/hospitalization for arrhythmia management.
Summary of the Second Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II)
Authors: Scott M. Grundy
Journal: JAMA (1993)

THE SECOND report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II, or ATP II) presents the National Cholesterol Education Program's updated recommendations for cholesterol management. It is similar to the first in general outline, and the fundamental approach to treatment of high blood cholesterol is comparable. This report continues to identify low-density lipoproteins (LDL) as the primary target of cholesterol-lowering therapy. As in the first report, the second report emphasizes the role of the clinical approach in primary prevention of coronary heart disease (CHD). Dietary therapy remains the first line of treatment of high blood cholesterol, and drug therapy is reserved for patients who are considered to be at high risk for CHD. However, the second report contains new features that distinguish it from the first. These include the following:   Increased emphasis on   See also pp 3002 and 3009.
Constitutive Activation of Stat3 Signaling Confers Resistance to Apoptosis in Human U266 Myeloma Cells
Authors: Robyn Catlett-Falcone, Terry H Landowski, Marc M Oshiro, James Turkson, Alexander Levitzki, Rocco Savino, Gennaro Ciliberto, Lynn Moscinski, Jose Luis Fernández-Luna, Gabriel Nuñez, William S Dalton, Richard Jove
Journal: Immunity (1999)
Reduced selection leads to accelerated gene loss in Shigella
Authors: Ruth Hershberg, Hua Tang, Dmitri A Petrov
Journal: Genome biology (2007)

Abstract Background Obligate pathogenic bacteria lose more genes relative to facultative pathogens, which, in turn, lose more genes than free-living bacteria. It was suggested that the increased gene loss in obligate pathogens may be due to a reduction in the effectiveness of purifying selection. Less attention has been given to the causes of increased gene loss in facultative pathogens. Results We examined in detail the rate of gene loss in two groups of facultative pathogenic bacteria: pathogenic Escherichia coli , and Shigella . We show that Shigella strains are losing genes at an accelerated rate relative to pathogenic E. coli . We demonstrate that a genome-wide reduction in the effectiveness of selection contributes to the observed increase in the rate of gene loss in Shigella . Conclusion When compared with their closely related pathogenic E. coli relatives, the more niche-limited Shigella strains appear to be losing genes at a significantly accelerated rate. A genome-wide reduction in the effectiveness of purifying selection plays a role in creating this observed difference. Our results demonstrate that differences in the effectiveness of selection contribute to differences in rate of gene loss in facultative pathogenic bacteria. We discuss how the lifestyle and pathogenicity of Shigella may alter the effectiveness of selection, thus influencing the rate of gene loss.
Chest Computed Tomography Scores Are Predictive of Survival in Patients with Cystic Fibrosis Awaiting Lung Transplantation
Authors: Martine Loeve, Wim C. J. Hop, Marleen de Bruijne, Peter T. W. van Hal, Phil Robinson, Moira L. Aitken, Jonathan D. Dodd, Harm A. W. M. Tiddens
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Up to one-third of patients with cystic fibrosis (CF) awaiting lung transplantation (LTX) die while waiting. Inclusion of computed tomography (CT) scores may improve survival prediction models such as the lung allocation score (LAS).This study investigated the association between CT and survival in patients with CF screened for LTX.Clinical data and chest CTs of 411 patients with CF screened for LTX between 1990 and 2005 were collected from 17 centers. CTs were scored with the Severe Advanced Lung Disease (SALD) four-category scoring system, including the components infection/inflammation (INF), air trapping/hypoperfusion (AT), normal/hyperperfusion (NOR), and bulla/cysts (BUL). The volume of each component was computed using semiautomated software. Survival analysis included Kaplan-Meier curves and Cox regression models.Three hundred and sixty-six (186 males) of 411 patients entered the waiting list (median age, 23 yr; range, 5-58 yr). Subsequently, 67 of 366 (18%) died while waiting, 263 of 366 (72%) underwent LTX, and 36 of 366 (10%) were awaiting LTX at the census date. INF and LAS were significantly associated with waiting list mortality in univariate analyses. The multivariate Cox model including INF and LAS grouped in tertiles, and comparing tertiles 2 and 3 with tertile 1, showed waiting list mortality hazard ratios of 1.62 (95% confidence interval [95% CI], 0.78-3.36; P = 0.19) and 2.65 (95% CI, 1.35-5.20; P = 0.005) for INF, and 1.42 (95% CI, 0.63-3.24; P = 0.40), and 2.32 (95% CI, 1.17-4.60; P = 0.016) for LAS, respectively. These results indicated that INF and LAS had significant, independent predictive value for survival.CT score INF correlates with survival, and adds to the predictive value of LAS.