tbuckley/cabot-search huggingface dataset:
Effect of Leptin on Arterial Thrombosis Following Vascular Injury in Mice
Authors: Peter F. Bodary
Journal: JAMA (2002)

Complications of atherosclerosis are the leading cause of morbidity and mortality in industrialized societies. Obesity has emerged as an independent risk factor for complications of atherosclerotic vascular disease. Leptin, a hormone produced by the adipocyte, increases with obesity and appears to modulate energy balance and food intake. In addition, other actions of leptin have been proposed, including an in vitro effect on platelet aggregation. Thus, the elevated plasma leptin levels in obese individuals may promote vascular thrombosis.To test the hypothesis that leptin contributes to in vivo thrombosis via the leptin receptor.Between September 2000 and September 2001, a vascular thrombosis model was used to test male 10- to 12-week-old mice completely deficient in leptin or the leptin receptor and mice with platelet leptin-receptor deficiency.Time to formation of an occlusive thrombus in the common carotid artery following experimentally induced endothelial injury.Following onset of vascular injury, wild-type mice (n = 8) formed occlusive thrombosis in a mean (SD) of 42.2 (4.6) minutes, whereas leptin-deficient (n = 5) and leptin receptor-deficient mice (n = 7) formed occlusive thrombosis in 75.2 (10.1) and 68.6 (10.3) minutes, respectively (leptin deficient vs wild-type mice, P =.008; leptin-receptor-deficient vs wild-type, P =.03). When recombinant murine leptin was administered to leptin-deficient mice (n = 4), the time to occlusion was reduced to 41.8 (6.6) minutes (P =.035 vs vehicle control). Following bone marrow transplantation from leptin receptor-deficient (donor) mice to wild-type (recipient) mice, the time to occlusion was prolonged from 22.3 (2.8) minutes in wild-type mice receiving wild-type marrow (n = 3) to 56.8 (5.0) minutes in wild-type mice receiving leptin receptor-deficient bone marrow (n = 5) (P =.003).Leptin contributes to arterial thrombosis following vascular injury in vivo and these prothrombotic effects appear to be mediated through the platelet leptin receptor.
The antibody response to specific immune complexes is under genetic control and correlates with the expression of a recurrent idiotype.
Authors: M J Caulfield, K J Luce, D Shaffer, J P Lake
Journal: The Journal of Experimental Medicine (1986)

The primary antigen-specific antibody response of various strains of mice to TEPC-15/PnC immune complexes has been examined. We found that both BALB/c and C3H mice were good responders to the PnC antigen; however, C3H mice were low responders, whereas BALB/c mice were high responders to the TEPC-15/PnC complexes. Using congenic strains on the C3H and BALB/c background, we have shown that the response to the complexes is not restricted by gene products of the H-2 complex or by the Igh (allotype) locus. However, responsiveness may be controlled by genes linked to the Igh locus, since we have shown that strains that are Ighj, Ighd, and Ighf are low responders, whereas strains that are Igha, Ighb, and Ighe are high responders to the immune complex. Moreover, responsiveness correlates with the expression of the T15 Id as measured using the anti-T15 monoclonal antibody, AB1-2. Thus, strains such as BALB/c, BALB.B, BALB.K, and CB-20, which express high levels of T15 (AB1-2) Id in their PFC response to PnC are relatively high responders to TEPC-15/PnC complexes, whereas C3H, C3H.SW, and C3H-OH, which express low levels of the T15 (AB1-2) Id, are low responders to the complexes. Finally, we found that BALB/c mice are high responders to complexes formed with T15+ antibodies, whereas they are low responders to complexes formed using T15- antibodies. The results suggest that the antigen-specific response to these immune complexes is Id-restricted.
The Ins and Outs of Mitochondrial Calcium
Authors: Toren Finkel, Sara Menazza, Kira M. Holmström, Randi J. Parks, Julia Liu, Junhui Sun, Jie Liu, Xin Pan, Elizabeth Murphy
Journal: Circulation Research (2015)

Calcium is thought to play an important role in regulating mitochondrial function. Evidence suggests that an increase in mitochondrial calcium can augment ATP production by altering the activity of calcium-sensitive mitochondrial matrix enzymes. In contrast, the entry of large amounts of mitochondrial calcium in the setting of ischemia-reperfusion injury is thought to be a critical event in triggering cellular necrosis. For many decades, the details of how calcium entered the mitochondria remained a biological mystery. In the past few years, significant progress has been made in identifying the molecular components of the mitochondrial calcium uniporter complex. Here, we review how calcium enters and leaves the mitochondria, the growing insight into the topology, stoichiometry and function of the uniporter complex, and the early lessons learned from some initial mouse models that genetically perturb mitochondrial calcium homeostasis.
The RYR2-Encoded Ryanodine Receptor/Calcium Release Channel in Patients Diagnosed Previously With Either Catecholaminergic Polymorphic Ventricular Tachycardia or Genotype Negative, Exercise-Induced Long QT Syndrome
Authors: Argelia Medeiros-Domingo, Zahurul A. Bhuiyan, David J. Tester, Nynke Hofman, Hennie Bikker, J. Peter van Tintelen, Marcel M.A.M. Mannens, Arthur A.M. Wilde, Michael J. Ackerman
Journal: Journal of the American College of Cardiology (2009)
Erlotinib, Erlotinib–Sulindac versus Placebo: A Randomized, Double-Blind, Placebo-Controlled Window Trial in Operable Head and Neck Cancer
Authors: Neil D. Gross, Julie E. Bauman, William E. Gooding, William Denq, Sufi M. Thomas, Lin Wang, Simion Chiosea, Brian L. Hood, Melanie S. Flint, Mai Sun, Thomas P. Conrads, Robert L. Ferris, Jonas T. Johnson, Seungwon Kim, Athanassios Argiris, Lori Wirth, Marina N. Nikiforova, Jill M. Siegfried, Jennifer R. Grandis
Journal: Clinical Cancer Research (2014)

Abstract Purpose: The EGF receptor (EGFR) and COX2 pathways are upregulated in head and neck squamous cell carcinoma (HNSCC). Preclinical models indicate synergistic antitumor activity from dual blockade. We conducted a randomized, double-blind, placebo-controlled window trial of erlotinib, an EGFR inhibitor; erlotinib plus sulindac, a nonselective COX inhibitor; versus placebo. Experimental Design: Patients with untreated, operable stage II-IVb HNSCC were randomized 5:5:3 to erlotinib, erlotinib–sulindac, or placebo. Tumor specimens were collected before and after seven to 14 days of treatment. The primary endpoint was change in Ki67 proliferation index. We hypothesized an ordering effect in Ki67 reduction: erlotinib–sulindac &amp;gt; erlotinib &amp;gt; placebo. We evaluated tissue microarrays by immunohistochemistry for pharmacodynamic modulation of EGFR and COX2 signaling intermediates. Results: From 2005–2009, 47 patients were randomized for the target 39 evaluable patients. Thirty-four tumor pairs were of sufficient quality to assess biomarker modulation. Ki67 was significantly decreased by erlotinib or erlotinib–sulindac (omnibus comparison, two-sided Kruskal–Wallis, P = 0.04). Wilcoxon pairwise contrasts confirmed greater Ki67 effect in both erlotinib groups (erlotinib–sulindac vs. placebo, P = 0.043; erlotinib vs. placebo, P = 0.027). There was a significant trend in ordering of Ki67 reduction: erlotinib–sulindac &amp;gt; erlotinib &amp;gt; placebo (two-sided exact Jonckheere–Terpstra, P = 0.0185). Low baseline pSrc correlated with greater Ki67 reduction (R2 = 0.312, P = 0.024). Conclusions: Brief treatment with erlotinib significantly decreased proliferation in HNSCC, with additive effect from sulindac. Efficacy studies of dual EGFR–COX inhibition are justified. pSrc is a potential resistance biomarker for anti-EGFR therapy, and warrants investigation as a molecular target. Clin Cancer Res; 20(12); 3289–98. ©2014 AACR.
Screening and Brief Alcohol Counseling of College Students and Persons Not in School
Authors: Ralph Hingson, Wenxing Zha, Aaron White, Bruce Simons-Morton
Journal: JAMA Pediatrics (2015)

This study compares whether college students or their same-age, noncollege peers are more likely to be asked about their substance use, given advice about related health risks, and encouraged to reduce or stop substance use.
The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia
Authors: Diana C Blaydon, Yoshiyuki Ishii, Edel A O'Toole, Harriet C Unsworth, Muy-Teck Teh, Franz Rüschendorf, Claire Sinclair, Väinö K Hopsu-Havu, Nicholas Tidman, Celia Moss, Rosemarie Watson, David de Berker, Muhammad Wajid, Angela M Christiano, David P Kelsell
Journal: Nature Genetics (2006)
A CONTROLLED STUDY OF ALLERGEN PRODUCTION IN CULTURES OF <i>DERMATOPHADOIDES PTERONYSSINUS</i>
Authors: L. BERRENS, J. E. M. H. VAN BRONSWIJK, E. YOUNG, A. G. VAN DIJK
Journal: Allergy (1975)

Allergenic substances have been isolated from cultures of Dermatophagoides pteronyssinus on wheat germ flakes and powdered yeast; as controls, non-sterile nutrient medium containing no mites, as well as sterile medium, were maintained and extracted under identical conditions. Chemical purification and analyses indicated the occurrence of skin-active allergens in all three preparations. This was confirmed by the assay of skin-reactivity in vivo and complement-inactivating capacity in vitro. Quantitatively, the medium containing bacteria and fungi contained more allergen than the sterile control, but less than the mite-infected medium. The evidence indicates that degradation reactions of nutrient components proceed faster in the non-sterile media than in the sterile control. The results of immunochemical analyses demonstrate that degradation reactions, give rise to the introduction of lysine-sugar structures inot high-molecular weight components from the medium. It is concluded that mites and micro-organisms have a role in allergen formation by promoting degradation reactions among nutrient constituents.
Contact dermatitis from antioxidants.
Authors: JYTTE ROED-PETERSEN, NIELS HJORTH
Journal: British Journal of Dermatology (1976)

In a search for contact sensitivity to antioxidants we patch tested consecutive patients referred with eczematous dermatitis. Six cases of allergic contact sensitivity to nordihydroguaiaretic acid (NDGA) were observed. Three had been sensitized by one brand of cream containing 0-1% NDGA, in three patients the source of sensitization could not be traced. In four patients we found positive patch tests to butylated hydroxyanisole and/or to butylated hydroxytoluene. In two cases the positive patch tests were relevant, since both patients remained asymptomatic when antioxidants were avoided in food. They both had acute flares of vesicular eczema on the fingers after oral administration of small amounts. Gallate esters and Vitamin E (d,1-alpha-tocopherol) each gave one unexplained positive patch test. The present data suggest that further search for hidden sensitizers in topical medicaments and cosmetics is warranted. A declaration of all ingredients in industrial products should be placed on the label.
Effect of Family History of Type 2 Diabetes on the Intima-Media Thickness of the Common Carotid Artery in Normal-Weight, Overweight, and Obese Glucose-Tolerant Young Adults
Authors: Nicola Pannacciulli, Giovanni De Pergola, Marco Ciccone, Paolo Rizzon, Francesco Giorgino, Riccardo Giorgino
Journal: Diabetes Care (2003)

To evaluate the effect of a first-degree family history of type 2 diabetes on the intima-media thickness of the common carotid artery (IMT-CCA), a surrogate marker of coronary atherosclerosis, in glucose-tolerant young adults.IMT-CCA was measured by high-resolution B-mode ultrasound imaging in 401 individuals aged 18-45 years with normal glucose tolerance (NGT). A total of 213 subjects had no family history of type 2 diabetes until the third generation (FH(-)), and 188 subjects had a family history of type 2 diabetes (FH(+)), defined as having one or both parents with type 2 diabetes. Other measurements included: central fat accumulation, evaluated by waist circumference; insulin resistance, estimated by homeostasis model assessment for insulin resistance (HOMA(IR)); systolic and diastolic blood pressure; fasting and postload concentrations of glucose; fasting insulin levels; and lipid profile.IMT-CCA and both 1- and 2-h postchallenge glucose concentrations were significantly higher in FH(+) than in FH(-) subjects. IMT-CCA was positively correlated with age, BMI, waist circumference, triglycerides, systolic and diastolic blood pressure levels, basal glucose concentrations, 1- and 2-h postchallenge glucose concentrations, and HOMA(IR). IMT-CCA was inversely associated with HDL cholesterol. After multivariate analysis, IMT-CCA maintained a significant association with family history of type 2 diabetes, BMI, waist circumference, HDL cholesterol, diastolic blood pressure, and fasting glucose.This study indicates that a genetic predisposition to type 2 diabetes, probably in association with slightly elevated glucose levels, may accelerate the development of atherosclerosis and increase the risk for coronary heart disease in glucose-tolerant individuals.
The management of soft tissue ankle injuries.
Authors: D. Crean
Journal: British Journal of Sports Medicine (1981)

The anatomy of the ankle, and the types of sporting injuries that occur in this joint, are described. Traditional treatment of soft tissue injuries involves immobilisation, and the value of this is questioned. An alternative treatment strategy is described, and involves immobilisation and compression for twenty-four hours, followed by rapid mobilisation using a balance board. This alternative strategy can bring about full functional mobility in 94% of patients within 14 days.
Combined effect of vegetable protein (soy) and soluble fiber added to a standard cholesterol-lowering diet
Authors: David J.A. Jenkins, Cyril W.C. Kendall, Christine C. Mehling, Tina Parker, A.Venket Rao, Sanjiv Agarwal, Renato Novokmet, Peter J.H. Jones, Mahmoud Raeini, Jon A. Story, Emily Furumoto, Edward Vidgen, Larry C. Griffin, Stephen C. Cunnane, Mary Ann Ryan, Philip W. Connelly
Journal: Metabolism (1999)
Genetically low vitamin D concentrations and increased mortality: mendelian randomisation analysis in three large cohorts
Authors: S. Afzal, P. Brondum-Jacobsen, S. E. Bojesen, B. G. Nordestgaard
Journal: BMJ (2014)

<b>Objective</b> To test the hypothesis that genetically low 25-hydroxyvitamin D concentrations are associated with increased mortality. <b>Design</b> Mendelian randomisation analysis. <b>Setting</b> Copenhagen City Heart Study, Copenhagen General Population Study, and Copenhagen Ischemic Heart Disease Study. <b>Participants</b> 95 766 white participants of Danish descent from three cohorts, with median follow-up times of 19.1, 5.8, and 7.9 years, genotyped for genetic variants in <i>DHCR7</i> and <i>CYP2R1</i> affecting plasma 25-hydroxyvitamin D concentrations; 35 334 also had plasma 25-hydroxyvitamin D measurements. Participants were followed from study entry through 2013, during which time 10 349 died. <b>Main outcome measures</b> All cause mortality and cause specific mortality, adjusted for common risk factors for all cause mortality based on the World Health Organization's global health status. <b>Results</b> The multivariable adjusted hazard ratios for a 20 nmol/L lower plasma 25-hydroxyvitamin D concentration were 1.19 (95% confidence interval 1.14 to 1.25) for all cause mortality, 1.18 (1.09 to 1.28) for cardiovascular mortality, 1.12 (1.03 to 1.22) for cancer mortality, and 1.27 (1.15 to 1.40) for other mortality. Each increase in <i>DHCR7</i>/<i>CYP2R1</i> allele score was associated with a 1.9 nmol/L lower plasma 25-hydroxyvitamin D concentration and with increased all cause, cancer, and other mortality but not with cardiovascular mortality. The odds ratio for a genetically determined 20 nmol/L lower plasma 25-hydroxyvitamin D concentration was 1.30 (1.05 to 1.61) for all cause mortality, with a corresponding observational multivariable adjusted odds ratio of 1.21 (1.11 to 1.31). Corresponding genetic and observational odds ratios were 0.77 (0.55 to 1.08) and 1.13 (1.03 to 1.24) for cardiovascular mortality, 1.43 (1.02 to 1.99) and 1.10 (1.02 to 1.19) for cancer mortality, and 1.44 (1.01 to 2.04) and 1.17 (1.06 to 1.29) for other mortality. The results were robust in sensitivity analyses. <b>Conclusions</b> Genetically low 25-hydroxyvitamin D concentrations were associated with increased all cause mortality, cancer mortality, and other mortality but not with increased cardiovascular mortality. These findings are compatible with the notion that genetically low 25-hydroxyvitamin D concentrations may be causally associated with cancer and other mortality but also suggest that the observational association with cardiovascular mortality could be the result of confounding.
Recent Approaches to the Treatment of Acute Lymphocytic Leukemia in Childhood
Authors: J S Holcenberg, B M Camitta
Journal: The Annual Review of Pharmacology and Toxicology (1981)

Acute lymphocytic leukemia (ALL) is the most common malignancy in childhood accounting for 35--40% of cancers in this age group. At the time of diagnosis approximately a trillion ( 1012) leukemic cells are present throughout the body (1). The bone marrow has been replaced and sup­ pressed by leukemic cells causing a cessation of normal blood cell produc­ tion. Previously both physicians and parents equated a diagnosis of acute lymphocytic leukemia with a certainty of rapid death. This dire prognosis has changed dramatically in the last 20 yeats. Now a complete bone marrow remission can be induced in 95% of children with ALL. Moreover, one half of these children will have a prolonged leukemia-free survival and probable cure. This chapter reviews the therapeutic advances that have led to this great improvement in survival, the current problems associated with this treat­ ment, and approaches to achieve more specific and effective therapy. Recent articles have summarized the first two topics (1-7), so we concentrate on new directions for therapy. Innovative new approaches are needed since the percentage of patients who achieve long-term leukemia·free survival has not increased appreciably in the last 10 years.
Statistical Analysis of DNA Microarray Data in Cancer Research
Authors: Jianqing Fan, Yi Ren
Journal: Clinical Cancer Research (2006)

Abstract Microarray techniques have been widely used to monitor gene expression in many areas of biomedical research. They have been widely used for tumor diagnosis and classification, prediction of prognoses and treatment, and understanding of molecular mechanisms, biochemical pathways, and gene networks. Statistical methods are vital for these scientific endeavors. This article reviews recent developments of statistical methods for analyzing data from microarray experiments. Emphasis has been given to normalization of expression from multiple arrays, selecting significantly differentially expressed genes, tumor classifications, and gene expression pathways and networks.
Dairy Consumption and the Incidence of Hyperglycemia and the Metabolic Syndrome
Authors: Frédéric Fumeron, Amel Lamri, Charbel Abi Khalil, Riphed Jaziri, Isabelle Porchay-Baldérelli, Olivier Lantieri, Sylviane Vol, Beverley Balkau, Michel Marre
Journal: Diabetes Care (2011)

OBJECTIVE In the French Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort, cross-sectional analyses have shown that a higher consumption of dairy products and calcium are associated with a lower prevalence of the metabolic syndrome (MetS). We assess the influence of dairy products on 9-year incident MetS and on impaired fasting glycemia and/or type 2 diabetes (IFG/T2D). RESEARCH DESIGN AND METHODS Men and women who completed a food frequency questionnaire at baseline and after 3 years were studied (n = 3,435). Logistic regression models were used to study associations between the average year 0 and year 3 consumption of milk and dairy products, cheese, dietary calcium density, and incident MetS and IFG/T2D after adjusting for 1) sex, age, alcohol, smoking, physical activity, fat intake and 2) additionally for BMI. Associations between dairy products and continuous variables were studied by repeated-measures ANCOVA, using the same covariates. RESULTS Dairy products other than cheese, and dietary calcium density, were inversely associated with incident MetS and IFG/T2D; cheese was negatively associated with incident MetS. All three parameters were associated with lower diastolic blood pressure, and with a lower BMI gain. Higher cheese intake and calcium density were associated with a lower increase in waist circumference and lower triglyceride levels. Calcium density was also associated with a lower systolic blood pressure and a lower 9-year increase in plasma triglyceride levels. CONCLUSIONS A higher consumption of dairy products and calcium was associated with a lower 9-year incidence of MetS and IFG/T2D in a large cohort drawn from the general population.
Anaphylactic shock depends on PI3K and eNOS-derived NO
Authors: A. Cauwels
Journal: Journal of Clinical Investigation (2006)

Anaphylactic shock is a sudden, life-threatening allergic reaction associated with severe hypotension. Platelet-activating factor (PAF) is implicated in the cardiovascular dysfunctions occurring in various shock syndromes, including anaphylaxis. Excessive production of the vasodilator NO causes inflammatory hypotension and shock, and it is generally accepted that transcriptionally regulated inducible iNOS is responsible for this. Nevertheless, the contribution of NO to PAF-induced shock or anaphylactic shock is still ambiguous. We studied PAF and anaphylactic shock in conscious mice. Surprisingly, hyperacute PAF shock depended entirely on NO, produced not by inducible iNOS, but by constitutive eNOS, rapidly activated via the PI3K pathway. Soluble guanylate cyclase (sGC) is generally regarded as the principal vasorelaxing mediator of NO. Nevertheless, although methylene blue partially prevented PAF shock, neither 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) nor sGCα1 deficiency did. Also, in 2 different models of active systemic anaphylaxis, inhibition of NOS, PI3K, or Akt or eNOS deficiency provided complete protection. In contrast to the unsubstantiated paradigm that only excessive iNOS-derived NO underlies cardiovascular collapse in shock, our data strongly support the unexpected concept that eNOS-derived NO is the principal vasodilator in anaphylactic shock and define eNOS and/or PI3K or Akt as new potential targets for treating anaphylaxis.
Changing Human Service Delivery Systems: Their Influences on Psychiatric Training
Authors: ROBERT S. DANIELS
Journal: American Journal of Psychiatry (1973)

Human service delivery systems are the focus of problems and controversy in 1973. The systems that pertain to mental health and illness have incorporated many of the innovations in organization, delivery, and administration that appeared in the 1950s and 1960s. The author argues that these may evolve into arrangements in which mental health delivery is either separate (as in the community mental health center) or integrated in varying degrees with other health care systems and that the choice of arrangements will affect the training of psychiatrists.