Markers of inflammation and coagulation indicate a prothrombotic state in HIV-infected patients with long-term use of antiretroviral therapy with or without abacavir

Background: Abacavir (ABC) treatment has been associated with an increased incidence of myocardial infarction. The pathophysiological mechanism is unknown. In this study markers of inflammation and coagulation in HIV-infected patients using antiretroviral therapy with or without ABC were examined to pinpoint a pathogenic mechanism. Given the important role of high sensitivity C-reactive protein (hsCRP) levels in predicting cardiovascular risk, patient groups were also analyzed according to hsCRP levels.Method

Chronologic Change and Clinicopatiologic Characteristics of Gastric Cancer Patients Over 70 Years of Age

Chronologic change and clinicopathology of 299 gastric cancer patients over 70 years of age (old group) were examined by comparing with those of 307 patients under 50 years of age (young group), and the histogenesis was discussed. The patients of the old group increased significantly in frequency from 9.9 % in the 1960's to 33.9 % in the 1990's, and the patients of the young group decreased clearly from 23.5 % in the 1960's to 9.4 % in the 1990's. However, no significant difference was found in the frequency of patients between 50 and 69 among 4 periods from the 1960's to the 1990's. In 6 out of 12 clinicopathologic factors, significant difference were found between both groups; male, tumor of lower 3rd of the stomach, macroscopic localized type in advanced cancer and protruded and elevated types in early cancer, liver metastasis, differntiated adenocarcinoma and venous invasion were significantly more in the old group than in the young group. From the results, it is suggested that the frequency of gastric cancer in Japan increases recently in the old group and decreases in the young group. Histogenetically, differentiated adenocarcinoma originating from intestinal metaplasia is suggested to arise more frequently in the former than in the latter

One frame and several new infinite families of Z-cyclic whist designs

AbstractIn 2001, Ge and Zhu published a frame construction which they utilized to construct a large class of Z-cyclic triplewhist designs. In this study the power and elegance of their methodology is illustrated in a rather dramatic fashion. Primarily due to the discovery of a single new frame it is possible to combine their techniques with the product theorems of Anderson, Finizio and Leonard along with a few new specific designs to obtain several new infinite classes of Z-cyclic whist designs. A sampling of the new results contained herein is as follows: (1) Z-cyclic Wh(33p+1), p a prime of the form 4t+1; (2) Z-cyclic Wh(32n+1s+1), for all n⩾1, s=5,13,17; (3) Z-cyclic Wh(32ns+1), for all n⩾1, s=35,55,91; (4) Z-cyclic Wh(32n+1s), for all n⩾1, and for all s for which there exist a Z-cyclic Wh(3s) and a homogeneous (s,4,1)-DM; and (5) Z-cyclic Wh(32ns) for all n⩾1, s=5,13. Many other results are also obtained. In particular, there exist Z-cyclic Wh(33v+1) where v is any number for which Ge and Zhu obtained Z-cyclic TWh(3v+1)

HIF1/2-exerted control over glycolytic gene expression is not functionally relevant for glycolysis in human leukemic stem/progenitor cells

Background Hypoxia-inducible factors (HIF)1 and 2 are transcription factors that regulate the homeostatic response to low oxygen conditions. Since data related to the importance of HIF1 and 2 in hematopoietic stem and progenitors is conflicting, we investigated the chromatin binding profiles of HIF1 and HIF2 and linked that to transcriptional networks and the cellular metabolic state. Methods Genome-wide ChIPseq and ChIP-PCR experiments were performed to identify HIF1 and HIF2 binding sites in human acute myeloid leukemia (AML) cells and healthy CD34(+) hematopoietic stem/progenitor cells. Transcriptome studies were performed to identify gene expression changes induced by hypoxia or by overexpression of oxygen-insensitive HIF1 and HIF2 mutants. Metabolism studies were performed by 1D-NMR, and glucose consumption and lactate production levels were determined by spectrophotometric enzyme assays. CRISPR-CAS9-mediated HIF1, HIF2, and ARNT(-/-) lines were generated to study the functional consequences upon loss of HIF signaling, in vitro and in vivo upon transplantation of knockout lines in xenograft mice. Results Genome-wide ChIP-seq and transcriptome studies revealed that overlapping HIF1- and HIF2-controlled loci were highly enriched for various processes including metabolism, particularly glucose metabolism, but also for chromatin organization, cellular response to stress and G protein-coupled receptor signaling. ChIP-qPCR validation studies confirmed that glycolysis-related genes but not genes related to the TCA cycle or glutaminolysis were controlled by both HIF1 and HIF2 in leukemic cell lines and primary AMLs, while in healthy human CD34(+) cells these loci were predominantly controlled by HIF1 and not HIF2. However, and in contrast to our initial hypotheses, CRISPR/Cas9-mediated knockout of HIF signaling did not affect growth, internal metabolite concentrations, glucose consumption or lactate production under hypoxia, not even in vivo upon transplantation of knockout cells into xenograft mice. Conclusion These data indicate that, while HIFs exert control over glycolysis but not OxPHOS gene expression in human leukemic cells, this is not critically important for their metabolic state. In contrast, inhibition of BCR-ABL did impact on glucose consumption and lactate production regardless of the presence of HIFs. These data indicate that oncogene-mediated control over glycolysis can occur independently of hypoxic signaling modules.</p

Type D Personality Associated With Increased Risk for Mortality in Adults With Congenital Heart Disease

Background Type D personality has been previously shown to increase the risk for mortality in patients with acquired heart disease.ObjectiveWe aimed to compare mortality in adult patients with congenital heart disease (CHD) with and without type D.Methods Survival was assessed using prospective data from the Dutch national Congenital Corvitia registry for adults with CHD. Patients were randomly selected from the registry and characterized at inclusion in 2009 for the presence of type D using the DS14 questionnaire.Results One thousand fifty-five patients, with 484 (46%) males, a mean (SD) age of 41 (14) years, 613 (58%) having mild CHD, 348 (33%) having moderate CHD, and 94 (9%) having severe CHD, were included. Type D personality was present in 225 patients (21%). Type D was associated with an increased risk for all-cause mortality independent of age, sex, New York Heart Association class, number of prescribed medications, depression, employment status, and marital status (hazard ratio, 1.94; 95% confidence interval, 1.05–3.57; P = .033).Conclusion Type D personality was associated with an increased risk for all-cause mortality in adult patients with CHD