tbuckley/cabot-search huggingface dataset:
PROTECTION OF ADRENALECTOMIZED ANIMALS AGAINST BACTERIAL INTOXICATION BY AN EXTRACT OF THE ADRENAL CORTEX
Authors: Frank A. Hartman, W. J. Merle Scott
Journal: The Journal of Experimental Medicine (1932)

1. The resistance of adrenal-deficient rats to bacterial intoxication has been significantly increased by an extract of the adrenal cortex. 2. This is shown both for acute intoxication with killed Bacillus typhosus and for chronic intoxication with killed Staphylococcus aureus. 3. During the height of the bacterial intoxication relatively large amounts of the cortical hormone are apparently required to maintain the animals. 4. It is considered probable that a human pyogenic infection imposes a severe load upon the adrenal cortex.
Treatment extension to 72 weeks of peginterferon and ribavirin in hepatitis c genotype 1-infected slow responders
Authors: Brian L. Pearlman, Carole Ehleben, Sophia Saifee
Journal: Hepatology (2007)

In hepatitis C virus (HCV) genotype 1 infection, the duration of interferon-based therapy is a critical determinant in achieving sustained virologic response (SVR). Slow or late responders to peginterferon and ribavirin may benefit from an extended treatment course. We sought to determine if therapy extension could improve response rates in a United States population of slow responders. Slow response was defined by achieving at least a 2-log decrement in HCV RNA from baseline, yet having detectable HCV RNA at 12 weeks and undetectable HCV RNA at 24 weeks (polymerase chain reaction, TaqMan, Roche; detection limit 10 IU/mL). Patients were treatment-naïve, chronically infected genotype 1-infected slow responders to 1.5 mug/kg/week of peginterferon-alpha2b and 800-1400 mg/day of ribavirin and were randomly assigned 1:1 to complete a total of 48 or 72 weeks of therapy. Dose reductions and treatment discontinuations for adverse events or laboratory abnormalities were similar between the 2 treatment arms. End-of-treatment response rates were similar in the 72-week group compared with those in the 48-week group (48% versus 45%; P value not significant). Overall, the rate of SVR was superior in patients treated for 72 weeks versus 48 weeks (38% versus 18%, respectively; P = 0.026).Extending the treatment duration from 48 weeks to 72 weeks in genotype 1-infected patients with slow virologic response to peginterferon-alpha2b and weight-based ribavirin significantly improves SVR rates. Treatment extension does not seem to increase the rate of dose reduction or therapy discontinuation.
Novel Methylated Biomarkers and a Robust Assay to Detect Circulating Tumor DNA in Metastatic Breast Cancer
Authors: Mary Jo Fackler, Zoila Lopez Bujanda, Christopher Umbricht, Wei Wen Teo, Soonweng Cho, Zhe Zhang, Kala Visvanathan, Stacie Jeter, Pedram Argani, Chenguang Wang, Jaclyn P. Lyman, Marina de Brot, James N. Ingle, Judy Boughey, Kandace McGuire, Tari A. King, Lisa A. Carey, Leslie Cope, Antonio C. Wolff, Saraswati Sukumar
Journal: Cancer Research (2014)

Abstract The ability to consistently detect cell-free tumor-specific DNA in peripheral blood of patients with metastatic breast cancer provides the opportunity to detect changes in tumor burden and to monitor response to treatment. We developed cMethDNA, a quantitative multiplexed methylation-specific PCR assay for a panel of ten genes, consisting of novel and known breast cancer hypermethylated markers identified by mining our previously reported study of DNA methylation patterns in breast tissue (103 cancer, 21 normal on the Illumina HumanMethylation27 Beadchip) and then validating the 10-gene panel in The Cancer Genome Atlas project breast cancer methylome database. For cMethDNA, a fixed physiologic level (50 copies) of artificially constructed, standard nonhuman reference DNA specific for each gene is introduced in a constant volume of serum (300 μL) before purification of the DNA, facilitating a sensitive, specific, robust, and quantitative assay of tumor DNA, with broad dynamic range. Cancer-specific methylated DNA was detected in training (28 normal, 24 cancer) and test (27 normal, 33 cancer) sets of recurrent stage IV patient sera with a sensitivity of 91% and a specificity of 96% in the test set. In a pilot study, cMethDNA assay faithfully reflected patient response to chemotherapy (N = 29). A core methylation signature present in the primary breast cancer was retained in serum and metastatic tissues collected at autopsy two to 11 years after diagnosis of the disease. Together, our data suggest that the cMethDNA assay can detect advanced breast cancer, and monitor tumor burden and treatment response in women with metastatic breast cancer. Cancer Res; 74(8); 2160–70. ©2014 AACR.
Volumetric Analysis and Three-Dimensional Glucose Metabolic Mapping of the Striatum and Thalamus in Patients With Autism Spectrum Disorders
Authors: M. Haznedar
Journal: American Journal of Psychiatry (2006)

Objective: In patients with autism, behavioral deficits as well as neuroimaging studies of the anterior cingulate cortex suggest ventral rather than dorsal striatal and thalamic abnormalities in structure and function. The authors used imaging studies to map volumetric and metabolic differences within the entire dorsoventral extent of the striatum and thalamus. Method: Magnetic resonance imaging (MRI) and positron emission tomography (PET) were used to measure volumes and metabolic activity in the thalamus, caudate, and putamen in 17 patients with autism or Asperger's disorder and 17 age- and sex-matched comparison subjects. Subjects performed a serial verbal learning test during the [ 18 F]-fluorodeoxyglucose uptake period. The regions of interest were outlined on contiguous axial MRI slices. After PET/MRI coregistration, region-of-interest coordinates were applied to the PET scan for each individual. Between-group differences in metabolism were assessed by three-dimensional statistical probability mapping. Results: The patients with autism spectrum disorders had greater volumes of the right caudate nucleus than comparison subjects as well as a reversal of the expected left-greater-than-right hemispheric asymmetry. Patients also had lower relative glucose metabolic rates bilaterally in the ventral caudate, putamen, and thalamus. Patients with autism had lower metabolic activity in the ventral thalamus than those with Asperger's disorder, but they did not differ from comparison subjects in metabolic activity in the caudate nucleus. Conclusions: These results are consistent with a deficit in the anterior cingulate-ventral striatum-anterior thalamic pathway in patients with autism spectrum disorders. The results also suggest an important role for the caudate in helping support working-memory demands.
Interactions Between Variants in the β3-Adrenergic Receptor and Peroxisome Proliferator–Activated Receptor-γ2 Genes and Obesity
Authors: Wen-Chi Hsueh, Shelley A. Cole, Alan R. Shuldiner, Brock A. Beamer, John Blangero, James E. Hixson, Jean W. MacCluer, Braxton D. Mitchell
Journal: Diabetes Care (2001)

OBJECTIVE—Previous studies have reported modest associations between measures of obesity and the Trp64Arg variant of the β3-adrenergic receptor (ADRβ3) and the Pro12Ala variant of the peroxisome proliferator–activated receptor (PPAR)-γ2. We hypothesized that these single gene variants may mark mutations that act through convergent pathways to produce synergistic effects on obesity. RESEARCH DESIGN AND METHODS—The sample included 453 subjects from 10 large Mexican-American families participating in the population-based San Antonio Family Heart Study. The effects of each gene variant singly and jointly were estimated as fixed effects using the measured genotype approach framework. Analyses were conditioned on the pedigree structures to account for the correlations among family members. Statistical significance was evaluated by the likelihood ratio test with adjustment for age, sex, and diabetes status. RESULTS—The allele frequencies for the ADRβ3 Trp64Arg and PPARγ2 Pro12Ala variants were 18 and 12%, respectively. The ADRβ3 variant was not significantly associated with any of the obesity-related traits, but subjects with the PPARγ2 variant (n = 98) had significantly higher levels of fasting insulin (P = 0.03), leptin (P = 0.009), and waist circumference (P = 0.03) than those without. Subjects with both gene variants (n = 32) had significantly higher BMI, insulin, and leptin levels than those with only the PPARγ2 variant (n = 66) (P for interaction: 0.04, 0.02, and 0.01 for BMI, fasting insulin, and leptin, respectively). CONCLUSIONS—Our results suggest that epistatic models with genes that have modest individual effects may be useful in understanding the genetic underpinnings of typical obesity in humans.
Troglitazone Decreases the Proportion of Small, Dense LDL and Increases the Resistance of LDL to Oxidation in Obese Subjects
Authors: Cees JJ Tack, Paul Smits, Pierre NM Demacker, Anton FH Stalenhoef
Journal: Diabetes Care (1998)

OBJECTIVE Insulin resistance is associated with a predominance of small, atherogenic LDL particles that are more prone to oxidative modification. Treatment with the insulin-sensitizer troglitazone may improve LDL composition and resistance to oxidation. RESEARCH DESIGN AND METHODS In a randomized double-blind crossover design, 15 obese subjects were treated with either 400 mg troglitazone daily or placebo for 8 weeks. Insulin sensitivity (clamp), (apo)lipoproteins, LDL subclass pattern, plasma TBARS, and ex vivo LDL oxidation were determined. RESULTS Troglitazone treatment improved insulin sensitivity. LDL cholesterol increased from 2.58 ± 0.18 to 2.77 ± 0.20 mmol/1 (P = 0.03) because of an increase in large (buoyant) LDL1 (from 0.45 ± 0.04 to 0.62 ± 0.09 mmol/1, P = 0.008). Because small (dense) LDL3 decreased, LDL1:LDL3 ratio increased (P = 0.02). Plasma TBARS concentration declined significantly, and the lag time of ex vivo LDL oxidation showed a small but significant increase. CONCLUSIONS In obese subjects, treatment with troglitazone improves insulin sensitivity, increases the ratio of large buoyant to small dense LDL, and appears to enhance the resistance of the LDL particle to oxidation. These qualitative changes in lipoproteins may have a beneficial effect on cardiovascular risk profile and compensate for a small increase in LDL cholesterol.
Intercalated disc abnormalities, reduced Na+ current density, and conduction slowing in desmoglein-2 mutant mice prior to cardiomyopathic changes
Authors: Stefania Rizzo, Elisabeth M. Lodder, Arie O. Verkerk, Rianne Wolswinkel, Leander Beekman, Kalliopi Pilichou, Cristina Basso, Carol Ann Remme, Gaetano Thiene, Connie R. Bezzina
Journal: Cardiovascular Research (2012)

Mutations in genes encoding desmosomal proteins have been implicated in the pathogenesis of arrhythmogenic right ventricular cardiomyopathy (ARVC). However, the consequences of these mutations in early disease stages are unknown. We investigated whether mutation-induced intercalated disc remodelling impacts on electrophysiological properties before the onset of cell death and replacement fibrosis.Transgenic mice with cardiac overexpression of mutant Desmoglein2 (Dsg2) Dsg2-N271S (Tg-NS/L) were studied before and after the onset of cell death and replacement fibrosis. Mice with cardiac overexpression of wild-type Dsg2 and wild-type mice served as controls. Assessment by electron microscopy established that intercellular space widening at the desmosomes/adherens junctions occurred in Tg-NS/L mice before the onset of necrosis and fibrosis. At this stage, epicardial mapping in Langendorff-perfused hearts demonstrated prolonged ventricular activation time, reduced longitudinal and transversal conduction velocities, and increased arrhythmia inducibility. A reduced action potential (AP) upstroke velocity due to a lower Na(+) current density was also observed at this stage of the disease. Furthermore, co-immunoprecipitation demonstrated an in vivo interaction between Dsg2 and the Na(+) channel protein Na(V)1.5.Intercellular space widening at the level of the intercalated disc (desmosomes/adherens junctions) and a concomitant reduction in AP upstroke velocity as a consequence of lower Na(+) current density lead to slowed conduction and increased arrhythmia susceptibility at disease stages preceding the onset of necrosis and replacement fibrosis. The demonstration of an in vivo interaction between Dsg2 and Na(V)1.5 provides a molecular pathway for the observed electrical disturbances during the early ARVC stages.
Sensitivity of the Hypothermic Myocardium to Calcium
Authors: E. T. ANGELAKOS, S. DEUTSCH, L. WILLIAMS
Journal: Circulation Research (1957)

The susceptibility of the dog heart to ventricular fibrillation (VF) induced by CaCl 2 infusions is several fold greater in hypothermia than in normothermia, i.e., both the amount of CaCl 2 infused and the terminal plasma levels are found to be less in hypothermia. Dogs rendered hypercalcemic prior to hypothermia induction also succumb to ventricular fibrillation, and at relatively high heart temperatures (22-27 C.), whereas those rendered hypocalcemic by Na-EDTA infusions succumb to asystole at much lower temperatures (14-18 C.). The calcium sensitivity is not pH dependent either at normal or low temperatures.
Role for mast cells in Schnitzler's syndrome: here mast cells master a rash, too
Authors: N. Kambe
Journal: British Journal of Dermatology (2015)

Journal Article Role for mast cells in Schnitzler's syndrome: here mast cells master a rash, too Get access N. Kambe N. Kambe Department of Dermatology Chiba University Graduate School of Medicine 1‐8‐1 Inohana Chuo‐ku Chiba 260‐8670 Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 2, 1 August 2015, Pages 323–324, https://doi.org/10.1111/bjd.13975 Published: 01 August 2015
CAST and beyond. Implications of the Cardiac Arrhythmia Suppression Trial. Task Force of the Working Group on Arrhythmias of the European Society of Cardiology.
Authors: M Akhtar, G Breithardt, A J Camm, P Coumel, M J Janse, R Lazzara, R J Myerburg, P J Schwartz, A L Waldo, H J Wellens
Journal: Circulation (1990)
Prediction of Coronary Heart Disease Using Risk Factor Categories
Authors: Peter W. F. Wilson, Ralph B. D’Agostino, Daniel Levy, Albert M. Belanger, Halit Silbershatz, William B. Kannel
Journal: Circulation (1998)

Background —The objective of this study was to examine the association of Joint National Committee (JNC-V) blood pressure and National Cholesterol Education Program (NCEP) cholesterol categories with coronary heart disease (CHD) risk, to incorporate them into coronary prediction algorithms, and to compare the discrimination properties of this approach with other noncategorical prediction functions. Methods and Results —This work was designed as a prospective, single-center study in the setting of a community-based cohort. The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up. During the 12 years of follow-up, a total of 383 men and 227 women developed CHD, which was significantly associated with categories of blood pressure, total cholesterol, LDL cholesterol, and HDL cholesterol (all P &lt;.001). Sex-specific prediction equations were formulated to predict CHD risk according to age, diabetes, smoking, JNC-V blood pressure categories, and NCEP total cholesterol and LDL cholesterol categories. The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used. After adjustment for other factors, ≈28% of CHD events in men and 29% in women were attributable to blood pressure levels that exceeded high normal (≥130/85). The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol (≥200 mg/dL) was 27% in men and 34% in women. Conclusions —Recommended guidelines of blood pressure, total cholesterol, and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample. A simple coronary disease prediction algorithm was developed using categorical variables, which allows physicians to predict multivariate CHD risk in patients without overt CHD.
Gestational Weight Gain and Pregnancy Outcomes in 481 Obese Glucose-Tolerant Women
Authors: Dorte M. Jensen, Per Ovesen, Henning Beck-Nielsen, Lars Mølsted-Pedersen, Bente Sørensen, Christina Vinter, Peter Damm
Journal: Diabetes Care (2005)

To investigate the effect of gestational weight gain in obese glucose-tolerant women.We performed a historical cohort study of 481 women with prepregnancy BMI > or = 30 kg/m2 and a normal 2-h 75-g oral glucose tolerance test (OGTT) during the third trimester (according to World Health Organization criteria). Data on OGTT results and clinical outcomes were collected from medical records. Four groups were defined according to weight gain: group 1, <5.0 kg (n = 93); group 2, 5.0-9.9 kg (n = 134); group 3, 10.0-14.9 kg (n = 132); and group 4, > or = 15.0 kg (n = 122).Birth weight increased significantly with increasing weight gain (mean grams +/- SD): group 1, 3,456 +/- 620; group 2, 3,624 +/- 675; group 3, 3,757 +/- 582; and group 4, 3,784 +/- 597 (P < 0.001). The birth weight in group 1 was similar to that of the background population of primarily normal-weight women (3,478 g). In multivariate analyses, increasing weight gain was associated with significantly higher rates of hypertension (OR 4.8 [95% CI for group 4 vs. group 1: 1.7-13.1]), cesarean section (3.5 [1.6-7.8]), induction of labor (3.7 [1.7-8.0]), and large-for-gestational-age infants (4.7 [2.0-11.0]). There was no difference in rates of small-for-gestational-age infants. Significant predictors for birth weight (determined by multiple linear regression) were gestational weight gain, 2-h OGTT result, pre-gestational BMI, maternal age, gestational age, and smoking.Increasing weight gain in obese women is associated with increasing pregnancy complications. Our data suggest that minimal gestational weight gain might normalize birth weight. Prospective studies should be performed to clarify the safety of recommending limited gestational weight gain.
Experimental granulomatous colitis in mice is abrogated by induction of TGF-beta-mediated oral tolerance.
Authors: M F Neurath, I Fuss, B L Kelsall, D H Presky, W Waegell, W Strober
Journal: The Journal of Experimental Medicine (1996)

In previous studies we showed that a chronic colitis associated with a Th1 T cell response can be induced by the rectal administration of the haptenizing reagent 2,4,6-trinitrobenzene sulfonic acid (TNBS). We report here that oral administration of haptenized colonic proteins (HCP) before rectal administration of TNBS effectively suppresses the ability of the latter to induce colitis. This suppression (oral tolerance) appears to be due to the generation of mucosal T cells producing TGF-beta and Th2-type cytokines after oral HCP administration. Peyer's patch and lamina propria CD4+ T cells from HCP-fed animals stimulated with anti-CD3/anti-CD28 had a 5-10-fold increase in their production of TGF-beta and secreted increased amounts of IL-4 and IL-10 but lower levels of IFN-gamma in comparison to T cells from ovalbumin-fed control animals. In addition, the colons of HCP-fed mice showed strikingly increased TGF-beta but decreased IL-12 expression by immunohistochemical studies and isolated mononuclear cells from HCP-fed animals secreted less IL-12 heterodimer. Finally, and most importantly, the suppressive effect of orally administered HCP was abrogated by the concomitant systemic administration of anti-TGF-beta or rIL-12 suggesting a reciprocal relationship between IL-12 and TGF-beta on tolerance induction in TNBS-induced colitis. In parallel studies we demonstrated that TNBS-induced colitis can be transferred to naive recipient animals with purified CD4+ T cells from the colon of TNBS-treated animals and that such animals develop lethal pancolitis when exposed to very low doses of TNBS. Feeding of HCP suppressed this sensitivity to TNBS, indicating that oral feeding can suppress the response of pre-committed T cells in vivo. These studies suggest for the first time that TGF-beta production can abrogate experimental granulomatous colitis even after such colitis is established, and thus, that regulation of TGF-beta levels may have relevance to the treatment of human inflammatory bowel disease.
Acquired von Willebrand disease in Wilms' tumor patients.
Authors: M J Coppes, S W Zandvoort, C R Sparling, A O Poon, S Weitzman, V S Blanchette
Journal: Journal of Clinical Oncology (1992)

PURPOSE A prospective study was performed to determine the incidence of acquired von Willebrand disease (vWD) in children with newly diagnosed Wilms' tumor. PATIENTS AND METHODS Fifty consecutive children with newly diagnosed Wilms' tumor were evaluated. Detailed family and bleeding histories were obtained in all cases. Laboratory evaluation included measurement of the circulating platelet count, bleeding time (BT), factor VIII (FVIII) and von Willebrand factor (vWF) levels, and ristocetin cofactor (RCoF) activity. A vWF multimer analysis was obtained in all cases in which vWD was suspected. RESULTS Four of 50 (8%) consecutive children with a diagnosis of Wilms' tumor were found to have acquired vWD. Laboratory findings indicated type III vWD in two patients and type I vWD in the other two. CONCLUSIONS The incidence of acquired vWD in association with Wilms' tumor merits further study through a large prospective trial. Such a trial should include careful family and clinical bleeding histories plus measurement of a platelet count, BT, coagulant FVIII and vWF levels, RCoF activity, and vWF multimer analysis. The response to 1-desamino-8-D-arginine vasopressin (DDAVP) should be tested in all patients with Wilms' tumor and acquired vWD, including patients with a type III profile, before an invasive procedure is performed. Successful use of DDAVP may avoid exposure of affected patients to blood products.