TNF-alpha-mediated reduction in PGC-1alpha may impair skeletal muscle function after cigarette smoke exposure.

Skeletal muscle dysfunction contributes to exercise limitation in COPD. In this study cigarette smoke exposure was hypothesized to increase expression of the inflammatory cytokine, TNF-alpha, thereby suppressing PGC-1alpha, and hence affecting down stream molecules that regulate oxygen transport and muscle function. Furthermore, we hypothesized that highly vascularized oxidative skeletal muscle would be more susceptible to cigarette smoke than less well-vascularized glycolytic muscle.

Exercise-induced VEGF transcriptional activation in brain, lung and skeletal muscle.

Muscle VEGF expression is upregulated by exercise. Whether this VEGF response is regulated by transcription and/or post-transcriptional mechanisms is unknown. Hypoxia may be responsible: myocyte P(O2) falls greatly during exercise and VEGF is a hypoxia-responsive gene.

The better colectomy project: association of evidence-based best-practice adherence rates to outcomes in colorectal surgery.

Objective: To evaluate whether adherence to evidence-based best practices in colorectal surgery predicts improved postoperative outcomes.

Summary And Background Data: Over a quarter of a million colon and rectal resections are performed annually in the United States. The average postoperative complication rate for these procedures approaches 30%.

The major histocompatibility complex conserved extended haplotype 8.1 in AIDS-related non-Hodgkin lymphoma.

Background: Two single nucleotide polymorphisms (SNPs) in adjacent genes, lymphotoxin alpha (LTA +252G, rs909253 A>G) and tumor necrosis factor (TNF -308A, rs1800629 G>A), form the G-A haplotype repeatedly associated with increased risk of non-Hodgkin lymphoma (NHL) in individuals uninfected with HIV-1. This association has been observed alone or in combination with human leukocyte antigens HLA-B*08 or HLA-DRB1*03 in the major histocompatibility complex (MHC). Which gene variant on this highly conserved extended haplotype (CEH 8.

Atopic disease and risk of non-Hodgkin lymphoma: an InterLymph pooled analysis.

We performed a pooled analysis of data on atopic disease and risk of non-Hodgkin lymphoma (NHL) from 13 case-control studies, including 13,535 NHL cases and 16,388 controls. Self-reported atopic diseases diagnosed 2 years or more before NHL diagnosis (cases) or interview (controls) were analyzed. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were computed in two-stage random-effects or joint fixed-effects models, and adjusted for age, sex, and study center.

Analysis of endocrine disruption in Southern California coastal fish using an aquatic multispecies microarray.

Background: Endocrine disruptors include plasticizers, pesticides, detergents, and pharmaceuticals. Turbot and other flatfish are used to characterize the presence of chemicals in the marine environment. Unfortunately, there are relatively few genes of turbot and other flatfish in GenBank, which limits the use of molecular tools such as microarrays and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) to study disruption of endocrine responses in sentinel fish captured by regulatory agencies.

Muscle-specific VEGF deficiency greatly reduces exercise endurance in mice.

Vascular endothelial growth factor (VEGF) is required for vasculogenesis and angiogenesis during embryonic and early postnatal life. However the organ-specific functional role of VEGF in adult life, particularly in skeletal muscle, is less clear. To explore this issue, we engineered skeletal muscle-targeted VEGF deficient mice (mVEGF-/-) by crossbreeding mice that selectively express Cre recombinase in skeletal muscle under the control of the muscle creatine kinase promoter (MCKcre mice) with mice having a floxed VEGF gene (VEGFLoxP mice).

Paracetamol availability in pharmacy and non-pharmacy outlets in Dublin, Ireland.

Introduction: In 2004, there were 11,092 presentations to Irish hospitals with deliberate self-harm, including 7,933 cases of drug overdose, of which 31% involved paracetamol. Limiting the availability of paracetamol reduces morbidity and mortality associated with paracetamol overdose.

Aim: The present study aimed to determine the level of compliance with statutory regulations governing the sale of paracetamol in Ireland.

Tumor necrosis factor antagonism normalizes rapid eye movement sleep in alcohol dependence.

Background: In alcohol dependence, markers of inflammation are associated with increases in rapid eye movement (REM) sleep, which is thought to be a prognostic indicator of alcohol relapse. This study was undertaken to test whether blockade of biologically active tumor necrosis factor-alpha (TNF-alpha) normalizes REM sleep in alcohol-dependent adults.

Methods: In a randomized, placebo-controlled, double-blind, crossover trial, 18 abstinent alcohol-dependent male adults received a single dose of etanercept (25 mg) versus placebo in a counterbalanced order.

Population differences in immune marker profiles associated with human T-lymphotropic virus type I infection in Japan and Jamaica.

The natural history of human T-lymphotropic virus type I (HTLV-I) has been shown to differ markedly by geographic area. The differences include contrasting patterns of risk of adult T-cell lymphoma (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which may be due in part to differences in host immune response to infection. To characterize variations in host immunity across populations, we compared serologic immune marker patterns in HTLV-I-endemic populations in Japan and Jamaica.

Serum levels of soluble vascular cell adhesion molecule-1, tumor necrosis factor-alpha, and interleukin-6 in in vitro fertilization cycles.

Objective: To assess whether gonadotropin-induced changes in E(2) alter serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and proinflammatory cytokines.

Design: Prospective collection of serum in patients undergoing IVF.

Setting: University hospital.

Spaced education improves the feedback that surgical residents give to medical students: a randomized trial.

Background: Surgery residents teach medical students; feedback is one critical teaching skill. We investigated whether feedback given by surgery residents to students could be improved through an online spaced education program.

Methods: Surgery residents were randomized to receive either a weekly spaced education e-mail during a 9-month period containing teaching bullets on how to provide effective feedback, or no intervention.

Dynamic regulation of uncoupling protein 2 content in INS-1E insulinoma cells.

Uncoupling protein 2 (UCP2) regulates glucose-stimulated insulin secretion in pancreatic beta-cells. UCP2 content, measured by calibrated immunoblot in INS-1E insulinoma cells (a pancreatic beta-cell model) grown in RPMI medium, and INS-1E mitochondria, was 2.0 ng/million cells (7.

The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3.

Induction of type I IFNs is a fundamental cellular response to both viral and bacterial infection. The role of the transcription factor IRF3 is well established in driving this process. However, equally as important are cellular mechanisms for turning off type I IFN production to limit this response.

Skeletal muscle capillarity during hypoxia: VEGF and its activation.

Long-term exposure of humans and many mammals to hypoxia leads to the activation of several cellular mechanisms within skeletal muscles that compensate for a limited availability of cellular oxygen. One of these cellular mechanisms is to increase the expression of a subset of hypoxia-inducible genes, including the expression of vascular endothelial growth factor (VEGF). The VEGF promoter contains a hypoxic response element (HRE) that can bind the transcription factor, hypoxia-inducible factor-1alpha; (HIF-1alpha), and initiate transcriptional activation of the VEGF gene.

Sleep loss activates cellular inflammatory signaling.

Background: Accumulating evidence suggests that sleep disturbance is associated with inflammation and related disorders including cardiovascular disease, arthritis, and diabetes mellitus. This study was undertaken to test the effects of sleep loss on activation of nuclear factor (NF)-kappaB, a transcription factor that serves a critical role in the inflammatory signaling cascade.

Methods: In 14 healthy adults (seven women; seven men), peripheral blood mononuclear cell NF-kappaB was repeatedly assessed, along with enumeration of lymphocyte subpopulations, in the morning after baseline sleep, partial sleep deprivation (awake from 11 pm to 3:00 am), and recovery sleep.

Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium.

Some autoimmune disorders are increasingly recognized as risk factors for non-Hodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of self-reported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (CI) in a joint fixed-effects model.

Doxycycline treatment prevents alveolar destruction in VEGF-deficient mouse lung.

In vivo lung-targeted VEGF gene inactivation results in pulmonary cell apoptosis, airspace enlargement, and increased lung compliance consistent with an emphysema-like phenotype. The predominant hypothesis for the cause of lung destruction in emphysema is an imbalance between active lung protease and anti-protease molecules. Therefore, we investigated the role of protease (e.

Elevated expression of activation induced cytidine deaminase in peripheral blood mononuclear cells precedes AIDS-NHL diagnosis.

Non-Hodgkin's B cell lymphoma (NHL) is a common cancer in HIV infection. Many NHL are thought to result from errors in class switch recombination and/or somatic hypermutation, processes that occur in germinal center B cells, and require the activity of activation induced cytidine deaminase (AID). Since NHL is a common cancer in HIV infection, and expression of AID could contribute to the development of NHL, we hypothesized that AID expression would be elevated in those who went on to develop AIDS-associated NHL (AIDS-NHL).

A colorectal curriculum for general surgery residents: are we ready for needs assessment?

Objective: The traditional scope of general surgery (GS) has been broadly encompassing. Although it is generally accepted that we need a more defined curriculum for GS training, the criteria for limiting its scope remain controversial. One approach is to perform a needs assessment, defined based on an analysis of current GS practice.

VEGF in biological control.

Vascular endothelial growth factor A (VEGF-A) belongs to a family of heparin binding growth factors that include VEGF-B, VEGF-C, VEGF-D, and placental-like growth factor (PLGF). First discovered for its ability to regulate vascular endothelial cell permeability, VEGF is a well-known angiogenic factor that is important for vascular development and maintenance in all mammalian organs. The development of molecular tools and pharmacological agents to selectively inhibit VEGF function and block angiogenesis and/or vascular permeability has led to great promise in the treatment of various cancers, macular degeneration, and wound healing.