tbuckley/cabot-search huggingface dataset:
How T Cells Earn the Follicular Rite of Passage
Authors: Carola G. Vinuesa, Jason G. Cyster
Journal: Immunity (2011)

The discovery that Bcl-6 was the transcriptional regulator of follicular helper T (Tfh) cells completed the recognition of this population as an effector subset specialized in the provision of help to B cells. Improved reagents and recent models that allow tracking of Bcl-6-expressing T cells have revealed that the decision to become a Tfh cell occurs soon after T cells are primed by dendritic cells and start dividing, before interaction with B cells. The latter are important for sustaining Bcl-6 expression. Bcl-6 coordinates a signaling program that changes expression or function of multiple guidance receptors, leading to Tfh cell localization within germinal centers. This program is not unique to CD4(+) helper T cells; FoxP3(+) regulatory T cells and NKT cells co-opt the follicular differentiation pathway to enter the follicle and become specialized follicular cells. This review will focus on recent insights into the early events that determine Tfh cell differentiation.
A Prospective Study of Plasma Selenium Levels and Prostate Cancer Risk
Authors: Haojie Li, Meir J Stampfer, Edward L Giovannucci, J Steven Morris, Walter C Willett, J Michael Gaziano, Jing Ma
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Epidemiologic studies suggest that low selenium levels are associated with an increased incidence of prostate cancer, although results are conflicting. We examined the association between pre-diagnostic plasma selenium levels and risk of prostate cancer in men enrolled in the Physicians' Health Study. Methods: Using plasma samples obtained in 1982 from healthy men enrolled in the study, we conducted a nested case–control study among 586 men diagnosed with prostate cancer during 13 years of follow-up and 577 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of prostate cancer in pre- (before October 1990) and post- (after October 1990) prostate-specific antigen (PSA) screening eras were calculated using multivariable logistic regression. Results: Pre-diagnostic plasma selenium levels were inversely associated with risk of advanced prostate cancer (5th versus 1st quintile OR = 0.52, 95% CI = 0.28 to 0.98; Ptrend = .05), even among men diagnosed after 1990 (5th versus 1st quintile OR = 0.39, 95% CI = 0.16 to 0.97). The inverse association with prostate cancer risk was observed only for case subjects with elevated baseline PSA levels (PSA >4 ng/mL, 5th versus 1st quintile OR = 0.49, 95% CI = 0.28 to 0.86; Ptrend = .002). These inverse associations were observed in both pre- and post-PSA eras. Conclusions: The inverse association between baseline plasma selenium levels and risk of advanced prostate cancer, even among men diagnosed during the post-PSA era, suggests that higher levels of selenium may slow prostate cancer tumor progression. Ongoing randomized trials of selenium supplements may help to further evaluate this issue.
Reverse Ventricular Remodeling Reduces Ischemic Mitral Regurgitation
Authors: Judy Hung, J. Luis Guerrero, Mark D. Handschumacher, Gregory Supple, Suzanne Sullivan, Robert A. Levine
Journal: Circulation (2002)

Background— In ischemic mitral regurgitation (MR), mitral leaflet closure is restricted by ventricular remodeling with displacement of the papillary muscles (PMs). Therapy is uncertain because ring annuloplasty does not alleviate PM displacement. We tested the hypothesis that echo-guided PM repositioning using an external device can reduce MR without compromising left ventricular (LV) function. Methods and Results— We studied 10 sheep with ischemic MR produced by circumflex ligation with inferior infarction, 6 acutely and 4 eight weeks after myocardial infarction (MI). A Dacron patch containing an inflatable balloon was placed over the PMs and adjusted under echo guidance to reverse LV remodeling and reposition the infarcted PM. 3D echo assessed mitral valve geometric changes. In 7 sheep, sonomicrometry and Millar catheters assessed changes in end-systolic and end-diastolic pressure-volume relationships, and microspheres were injected to assess coronary flow. Moderate MR after MI resolved with patch application alone (n=3) or echo-guided balloon inflation, which repositioned the infarcted PM, decreasing the PM tethering distance from 31.1±2.5 mm after MI to 26.8±1.8 with patch ( P &lt;0.01; baseline=25.5±1.5). LV contractility was unchanged (end-systolic slope=3.4±1.6 mm Hg/mL with patch versus 2.8±1.6 after MI). Although there was a nonsignificant trend for a mild increase in stiffness constant (0.07±0.05 mL −1 versus 0.05±0.03 after MI, P =0.06), LV end-diastolic pressure was unchanged as MR resolved. Coronary flow to noninfarcted regions was not reduced. Conclusions— An external device that repositions the PMs can reduce ischemic MR without compromising LV function. This relatively simple technique can be applied under echo guidance in the beating heart.
The Study Team for Early Life Asthma Research (STELAR) consortium ‘Asthma e-lab’: team science bringing data, methods and investigators together
Authors: Adnan Custovic, John Ainsworth, Hasan Arshad, Christopher Bishop, Iain Buchan, Paul Cullinan, Graham Devereux, John Henderson, John Holloway, Graham Roberts, Steve Turner, Ashley Woodcock, Angela Simpson
Journal: Thorax (2015)

We created Asthma e-Lab, a secure web-based research environment to support consistent recording, description and sharing of data, computational/statistical methods and emerging findings across the five UK birth cohorts. The e-Lab serves as a data repository for our unified dataset and provides the computational resources and a scientific social network to support collaborative research. All activities are transparent, and emerging findings are shared via the e-Lab, linked to explanations of analytical methods, thus enabling knowledge transfer. eLab facilitates the iterative interdisciplinary dialogue between clinicians, statisticians, computer scientists, mathematicians, geneticists and basic scientists, capturing collective thought behind the interpretations of findings.
Cognitive Function and Army Rejection Rate in Young Adult Male Offspring of Women With Diabetes
Authors: Gunnar Lauge Nielsen, Claus Dethlefsen, Henrik Toft Sørensen, Jan Fog Pedersen, Lars Molsted-Pedersen
Journal: Diabetes Care (2007)

While maternal diabetes is a known risk factor for perinatal complications, there is little data on long-term intellectual outcome in offspring. We compare the rejection rate and cognitive functioning of military conscripts according to maternal diabetes status during pregnancy.We identified a cohort of Danish male offspring of diabetic mothers born between 1976 and 1984 and followed this cohort together with population-based control subjects to military conscription. The main outcome was army rejection rate and cognitive function measured with a validated intelligence test.The army rejection rate was 52.5% among 282 men whose mothers had diabetes during pregnancy and 45.4% among 870 control subjects (risk difference 7.3 [95% CI 0.6-14.0]). Mean cognitive scores were 41.4 units (95% CI 40.2-42.6) in diabetes-exposed conscripts and 42.7 units (42.0-43.4) in control subjects. Stratification by gestational age, Apgar score, and White's class (A-F) did not change the associations. In a subgroup analysis using available data on A1C levels during pregnancy, this variable was inversely associated with cognitive functioning. In men with maternal A1C <7%, cognitive scores were identical to those in control subjects.The slightly higher army rejection rate in men with maternal diabetes indicates higher morbidity. The identical cognitive functioning in cases of well-controlled maternal diabetes compared with that in control subjects is reassuring, but the negative association between A1C and cognitive score highlights the importance of striving for optimal metabolic control in diabetic women who are or plan to become pregnant.
Coordinated epithelial NHE3 inhibition and barrier dysfunction are required for TNF-mediated diarrhea in vivo
Authors: D. R. Clayburgh, M. W. Musch, M. Leitges, Y.-X. Fu, J. R. Turner
Journal: Journal of Clinical Investigation (2006)

Acute T cell–mediated diarrhea is associated with increased mucosal expression of proinflammatory cytokines, including the TNF superfamily members TNF and LIGHT. While we have previously shown that epithelial barrier dysfunction induced by myosin light chain kinase (MLCK) is required for the development of diarrhea, MLCK inhibition does not completely restore water absorption. In contrast, although TNF-neutralizing antibodies completely restore water absorption after systemic T cell activation, barrier function is only partially corrected. This suggests that, while barrier dysfunction is critical, other processes must be involved in T cell–mediated diarrhea. To define these processes in vivo, we asked whether individual cytokines might regulate different events in T cell–mediated diarrhea. Both TNF and LIGHT caused MLCK-dependent barrier dysfunction. However, while TNF caused diarrhea, LIGHT enhanced intestinal water absorption. Moreover, TNF, but not LIGHT, inhibited Na+ absorption due to TNF-induced internalization of the brush border Na+/H+ exchanger NHE3. LIGHT did not cause NHE3 internalization. PKCα activation by TNF was responsible for NHE3 internalization, and pharmacological or genetic PKCα inhibition prevented NHE3 internalization, Na+ malabsorption, and diarrhea despite continued barrier dysfunction. These data demonstrate the necessity of coordinated Na+ malabsorption and barrier dysfunction in TNF-induced diarrhea and provide insight into mechanisms of intestinal water transport.
A nemaline myopathy mutation in α-tropomyosin causes defective regulation of striated muscle force production
Authors: Daniel E. Michele, Faris P. Albayya, Joseph M. Metzger
Journal: Journal of Clinical Investigation (1999)

Nemaline myopathy (NM) is a rare autosomal dominant skeletal muscle myopathy characterized by severe muscle weakness and the subsequent appearance of nemaline rods within the muscle fibers. Recently, a missense mutation inTPM3, which encodes the slow skeletal α-tropomyosin (αTm), was linked to NM in a large kindred with an autosomal-dominant, childhood-onset form of the disease. We used adenoviral gene transfer to fully differentiated rat adult myocytes in vitro to determine the effects of NM mutant human αTm expression on striated muscle sarcomeric structure and contractile function. The mutant αTm was expressed and incorporated correctly into sarcomeres of adult muscle cells. The primary defect caused by expression of the mutant αTm was a decrease in the sensitivity of contraction to activating Ca2+, which could help explain the hypotonia seen in NM. Interestingly, NM mutant αTm expression did not directly result in nemaline rod formation, which suggests that rod formation is secondary to contractile dysfunction and that load-dependent processes are likely involved in nemaline rod formation in vivo.
Primary prophylaxis with nadolol in cirrhotic patients: Doppler patterns of splanchnic hemodynamics in good and poor responders
Authors: Annalisa Berzigotti, Maria Francesca Rinaldi, Donatella Magalotti, Maria Cristina Morelli, Paola Zappoli, Pietro Andreone, Cristina Rossi, Marco Zoli
Journal: Journal of Hepatology (2005)
Phrenic neuropathy: A missed issue in chronic obstructive pulmonary disease
Authors: Gihan Younis El-tantawi, Mohamed Imam, Tamer Morsi
Journal: European Respiratory Journal (2012)

Diaphragmatic weakness in chronic obstructive pulmonary disease (COPD) is ascribed to hyperinflation-induced diaphragm shortening as well as impairment in cellular and subcellular structures.1 Although phrenic neuropathy is known to cause diaphragmatic weakness,2 phrenic neuropathy was not previously considered in COPD patients.  Objective: This work aimed at assessing phrenic nerve conduction in COPD patients and its relation to radiographic hyperinflation and pulmonary function.  Methods: Twenty COPD patients were evaluated. Radiographic measures of hyperinflation included diaphragmatic angle of depression (DAOD), lung height, lung width, heart size, and diaphragm level. Flow volume loop parameters were obtained from all patients. Phrenic nerves were transcutaneously stimulated in the neck and diaphragmatic potentials were recorded at xiphoid process and ipsilateral 7th intercostal space. Fifteen healthy subjects were enrolled as controls.  Results: terminal latency of diaphragmatic potential was significantly prolonged in patients compared to controls (P=0.006 & 0.005 for right and left sides). Phrenic neuropathy was found in 9 patients (45%). Electrophysiological measures of phrenic neuropathy correlated with DAOD on lateral chest film (r=-0.75, P=0.02) as well as with lung height (r=0.67, P=0.003); however they did not correlate with the flow volume loop data.  Conclusion: Phrenic neuropathy is an appreciated finding in COPD patients. Diaphragmatic descend secondary to hyperinflation would induce stretch neuropathy of the phrenic nerve that can negatively affect diaphragmatic function.  1- Ottenheijm CA et al. Am J Respir Crit Care Med. 2007;175(12):1233-40  2- Wilcox PG, Pardy RL. Lung 1989;167:323-41.
Gastric intestinal metaplasia as detected by a monoclonal antibody is highly associated with gastric adenocarcinoma
Authors: Z K Mirza
Journal: Gut (2003)

Some forms of gastric intestinal metaplasia (GIM) may be precancerous but the cellular phenotype that predisposes to gastric carcinogenesis is not well characterised. Mucin staining, as a means of differentiating GIM, is difficult. A monoclonal antibody, mAb Das-1 (initially called 7E(12)H(12)), whose staining is phenotypically specific to colon epithelium, was used to investigate this issue.Using mAb Das-1, by a sensitive immunoperoxidase assay, we examined histologically confirmed GIM specimens from two countries, the USA and Japan. A total of 150 patients comprised three groups: group A, GIM (fields away from the cancer area) from patients with gastric carcinoma (n=60); group B, GIM with chronic gastritis (without gastric carcinoma) (n=72); and group C, chronic gastritis without GIM (n=18).Fifty six of 60 (93%) patients with GIM (both goblet and non-goblet metaplastic cells) from group A reacted intensely with mAb Das-1. Cancer areas from the same 56 patients also reacted. In contrast, 25/72 (35%) samples of GIM from patients in group B reacted with mAb Das-1 (group A v B, p<0.0001). None of the samples from group C reacted with the mAb.Reactivity of mAb Das-1 is clinically useful to simplify and differentiate the phenotypes of GIM. The colonic phenotype of GIM, as identified by mAb Das-1, is strongly associated with gastric carcinoma.
Dermoscopy of dermatofibrosarcoma protuberans: a study of 15 cases
Authors: J. Bernard, N. Poulalhon, G. Argenziano, S. Debarbieux, S. Dalle, L. Thomas
Journal: British Journal of Dermatology (2013)

Dermatofibrosarcoma protuberans (DFSP) is a rare malignant cutaneous tumour of which diagnosis is often delayed because of the lack of early clinical clues.To describe the main dermoscopic features of DFSP.We performed dermoscopic examination in 15 unselected, consecutive cases of biopsy-proven DFSP. Firstly, six dermoscopic features were identified collegially, then all cases were reviewed separately by six experienced dermoscopists. In a given lesion, features recognized only by all dermoscopists were taken into account.The median number of dermoscopic features was four per lesion. The following dermoscopic features were found: delicate pigmented network (87%), vessels (80%), structureless light brown areas (73%), shiny white streaks (67%), pink background coloration (67%) and structureless hypo- or depigmented areas (60%). When detected, vessels were of arborizing type in 11 of 12 cases, and presented as either unfocused only, or both unfocused and focused.This first study of the dermoscopic spectrum of DFSP identifies six dermoscopic features (often associated in a multicomponent pattern) and a peculiar vascular pattern. Whether dermoscopy can help to identify suspected DFSP remains to be established by further studies.
Depression and cognitive impairment following recovery from thrombotic thrombocytopenic purpura
Authors: Bowie Han, Evaren E. Page, Lauren M. Stewart, Cassandra C. Deford, James G. Scott, Lauren H. Schwartz, Jedidiah J. Perdue, Deirdra R. Terrell, Sara K. Vesely, James N. George
Journal: American Journal of Hematology (2015)

After recovery from an acute episode of acquired thrombotic thrombocytopenic purpura (TTP), patients often describe problems with memory, concentration, and endurance. We have previously reported the occurrence of depression and cognitive impairment in these patients. In this study, we describe the frequency, severity, and clinical course of depression and cognitive impairment. Fifty‐two (85%) out of 61 eligible Oklahoma Registry patients who had recovered from TTP, documented by ADAMTS13 activity &lt;10%, have had at least one (median, four) evaluation for depression over 11 years using the Beck Depression Inventory‐II; 31 (59%) patients screened positive for depression at least once; in 15 (29%), the results suggested severe depression at least once. Nine of these 15 patients had a psychiatric interview, the definitive diagnostic evaluation; the diagnosis of major depressive disorder was established in eight (89%) patients. In 2014, cognitive ability was evaluated in 33 patients by the Montreal Cognitive Assessment and the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Both tests detected significant cognitive impairment in the patients as a group. Fifteen out of the 33 patients had been evaluated by extensive cognitive tests in 2006. The 2014 RBANS results were significantly worse than the 2006 results for the overall score and two out of the five RBANS domains (immediate and delayed memory). Neither depression nor cognitive impairment was significantly associated with the occurrence of relapses or ADAMTS13 activity &lt;10% during remission. These observations emphasize the importance of screening evaluations for depression and cognitive impairment after recovery from acquired TTP. Am. J. Hematol. 90:709–714, 2015. © 2015 Wiley Periodicals, Inc.
Cysteinyl‐leukotrienes and their receptors in asthma and other inflammatory diseases: Critical update and emerging trends
Authors: Valérie Capra, Miles D. Thompson, Angelo Sala, David E. Cole, Giancarlo Folco, G. Enrico Rovati
Journal: Medicinal Research Reviews (2006)

Cysteinyl-leukotrienes (cysteinyl-LTs), that is, LTC4, LTD4, and LTE4, trigger contractile and inflammatory responses through the specific interaction with G protein-coupled receptors (GPCRs) belonging to the purine receptor cluster of the rhodopsin family, and identified as CysLT receptors (CysLTRs). Cysteinyl-LTs have a clear role in pathophysiological conditions such as asthma and allergic rhinitis (AR), and have been implicated in other inflammatory conditions including cardiovascular diseases, cancer, atopic dermatitis, and urticaria. Molecular cloning of human CysLT1R and CysLT2R subtypes has confirmed most of the previous pharmacological characterization and identified distinct expression patterns only partially overlapping. Interestingly, recent data provide evidence for the immunomodulation of CysLTR expression, the existence of additional receptor subtypes, and of an intracellular pool of CysLTRs that may have roles different from those of plasma membrane receptors. Furthermore, genetic variants have been identified for the CysLTRs that may interact to confer risk for atopy. Finally, a crosstalk between the cysteinyl-LT and the purine systems is being delineated. This review will summarize and attempt to integrate recent data derived from studies on the molecular pharmacology and pharmacogenetics of CysLTRs, and will consider the therapeutic opportunities arising from the new roles suggested for cysteinyl-LTs and their receptors.
Mortality and Predictors of Mortality in a Cohort of Brazilian Type 2 Diabetic Patients
Authors: Gil F. Salles, Katia V. Bloch, Claudia R.L. Cardoso
Journal: Diabetes Care (2004)

OBJECTIVE—To investigate mortality rates and predictors of mortality in Brazilian type 2 diabetic patients. RESEARCH DESIGN AND METHODS—A prospective follow-up study was carried out with 471 type 2 diabetic outpatients. Primary end points were all-cause, diabetes-related, and cardiovascular deaths. Excess mortality in this cohort was evaluated by calculating standardized mortality ratios (SMRs) in relation to those of the Rio de Janeiro population. Predictors of mortality were assessed by Kaplan-Meier survival curves and by uni- and multivariate Cox survival analyses. RESULTS—During a median follow-up of 57 months (range 2–84 months), 121 (25.7%) patients died, 91 (75.2%) from diabetes-related causes and 44 (36.4%) from cardiovascular diseases. After adjusting for age and sex, the all-cause SMR was 3.36 (95% confidence interval [CI] 2.81–4.02) and the cardiovascular SMR was 3.28 (CI 2.44–4.41). In the Cox multivariate analysis, the predictors of mortality were older age, increased 24-h proteinuria, preexisting vascular disease, presence of frequent ventricular premature contractions and prolonged maximum heart rate−corrected QT interval on baseline electrocardiogram, and decreased serum HDL cholesterol. The use of β-blockers was a protective factor. In Kaplan-Meier curves, these variables were capable of distinguishing subgroups of patients with significantly different prognoses. CONCLUSIONS—Brazilian type 2 diabetic patients had a more than threefold excess mortality than the general population, largely because of increased cardiovascular mortality risk. Several clinical, laboratory, and electrocardiographic predictors of mortality were identified that could possibly be modified to decrease the mortality burden of type 2 diabetes in Brazil.
The Medical Costs of Gunshot Injuries in the United States
Authors: P J Cook, B A Lawrence, J Ludwig, T R Miller
Journal: JAMA (1999)

The cost of treating gunshot injuries imposes a financial burden on society. Estimates of such costs are relevant to evaluation of gun violence reduction programs and may help guide reimbursement policies.To develop reliable US estimates of the medical costs of treating gunshot injuries and to present national estimates for the sources of payment for treating these injuries.Cost analysis using E-coded discharge data from hospitals in Maryland for 1994-1995 and New York for 1994 and from emergency departments in South Carolina for 1997. Other sources of data included the National Electronic Injury Surveillance System for 1994 incidence of nonfatal gun injuries, the National Spinal Cord Injury Statistical Center database for 1988-1992 estimates of lifetime medical costs of gun injuries, and the 1994 Vital Statistics census for incidence of fatal gun injuries.Estimated national acute-care and follow-up treatment costs and payment sources for gunshot injuries.At a mean medical cost per injury of about $17000, the 134445 (95% confidence interval [CI], 109465-159425) gunshot injuries in the United States in 1994 produced $2.3 billion (95% CI, $2.1 billion-$2.5 billion) in lifetime medical costs (in 1994 dollars, using a 3% real discount rate), of which $1.1 billion (49%) was paid by US taxpayers. Gunshot injuries due to assaults accounted for 74% of total costs.Gunshot injury costs represent a substantial burden to the medical care system. Nearly half this cost is borne by US taxpayers.