A conserved long-distance telomeric silencing mechanism suppresses mTOR signaling in aging human fibroblasts.

Telomeres are repetitive nucleotide sequences at the ends of each chromosome. It has been hypothesized that telomere attrition evolved as a tumor suppressor mechanism in large long-lived species. Long telomeres can silence genes millions of bases away through a looping mechanism called telomere position effect over long distances (TPE-OLD).

Liquid and Dry Swabs for Culture- and PCR-Based Detection of Colonization with Methicillin-Resistant Staphylococcus aureus during Admission Screening.

Rapid detection of methicillin-resistant (MRSA) colonization status facilitates isolation and decolonization and reduces MRSA infections. Liquid but not dry swabs allow fully automated detection methods. However, the accuracy of culture and polymerase chain reaction (PCR) using liquid and dry swabs has not been analyzed.

Preemptive Isolation Precautions of Patients at High Risk for Methicillin-Resistant Staphylococcus aureus in Combination With Ultrarapid Polymerase Chain Reaction Screening as an Effective Tool for Infection Control.

This sequential nonrandomized intervention study investigated the role of preemptive isolation precautions plus ultrarapid polymerase chain reaction screening for methicillin-resistant Staphylococcus aureus (MRSA). Compared with no prophylactic isolation plus conventional microbiology MRSA screening, nosocomial MRSA colonization and total MRSA incidence per 10,000 patient days significantly decreased. Infect Control Hosp Epidemiol 2016;1489-1491.

Platelet glycoproteins and fibrinogen in recovery from idiopathic sudden hearing loss.

Background: The pathomechanism and location of idiopathic sudden sensorineural hearing loss (ISSHL) is unclear. In a previous case-control study, we found elevated fibrinogen concentrations and a higher prevalence of T allele carriers of the glycoprotein (Gp) Ia C807T polymorphism in ISSHL patients.

Methodology: 127 patients with ISSHL (mean age 53.

Characterization of cholesterol homeostasis in telomerase-immortalized Tangier disease fibroblasts reveals marked phenotype variability.

We compared the consequences of an ABCA1 mutation that produced an apparent lack of atherosclerosis (Tangier family 1, N935S) with an ABCA1 mutation with functional ABCA1 knockout that was associated with severe atherosclerosis (Tangier family 2, Leu(548):Leu(575)-End), using primary and telomerase-immortalized fibroblasts. Telomerase-immortalized Tangier fibroblasts of family 1 (TT1) showed 30% residual cholesterol efflux capacity in response to apolipoprotein A-I, whereas telomerase-immortalized Tangier fibroblasts of family 2 (TT2) showed only 20%. However, there were a number of secondary differences that were often stronger and may help to explain the more rapid development of atherosclerosis in family 2.

Influence of dietary fat ingestion on asymmetrical dimethylarginine in lean and obese human subjects.

Background And Aims: Asymmetrical dimethylarginine (ADMA) may contribute to hypertension and cardiovascular disease by decreasing NO formation. In diabetic patients, a high fat meal acutely increased plasma ADMA while impairing endothelial function. We hypothesized that chronic and acute increases in dietary fat intake augment ADMA also in lean and in obese subjects without diabetes.

LMNA mutations, skeletal muscle lipid metabolism, and insulin resistance.

Context: Type 2 familial partial lipodystrophy (FPLD) is an autosomal-dominant lamin A/C-related disease associated with exercise intolerance, muscular pain, and insulin resistance. The symptoms may all be explained by defective metabolism; however, metabolism at the tissue level has not been investigated.

Objective: We hypothesized that in FPLD, insulin resistance and impaired aerobic exercise capacity are explained by a common underlying mechanism, presumably a muscular metabolic defect.

Compounds used for 'injection lipolysis' destroy adipocytes and other cells found in adipose tissue.

Background: A widely applied technique to reduce subcutaneous fat pad size involves subcutaneous injection of a phosphatidylcholine preparation ('injection lipolysis'). As the mode of action is mostly unknown, we planned to study cellular effects of the particular drug used in Germany (Lipostabil(R)).

Methods: Human preadipocytes, adipocytes, vascular and skeletal muscle cells as well as renal epithelial cells were incubated in the compound, morphological changes were described, and cell vitality was measured.

Peripheral endocannabinoid system activity in patients treated with sibutramine.

Objective: The endocannabinoid system (ECS) promotes weight gain and obesity-associated metabolic changes. Weight loss interventions may influence obesity-associated risk indirectly through modulation of the peripheral ECS. We investigated the effect of acute and chronic treatment with sibutramine on components of the peripheral ECS.

Adiponectin is a novel humoral vasodilator.

Objectives: Perivascular adipose tissue secretes an adipocyte-derived relaxing factor(s) (ADRF) that opens K(v) channels in rat arteries. Visceral fat accumulation causes adipocyte dysfunction, including hyposecretion of adiponectin. We tested the hypothesis that ADRF might be adiponectin and that adiponectin plays a role in the paracrine control of vascular tone by perivascular adipose tissue.

Dissociation between adipose nitric oxide synthase expression and tissue metabolism.

Context: Nitric oxide synthase (NOS) expression in adipose tissue is increased in obese subjects. The functional relevance is not known.

Objective: The objective was to compare adipose tissue metabolism between obese men with greater or lower adipose endothelial NOS (eNOS) or inducible NOS (iNOS) expression.

Tyramine in the assessment of regional adrenergic function.

Regional adrenergic function is difficult to assess in humans. Tyramine given through a microdialysis probe may be a useful tool in this regard. However, tyramine data is hard to interpret given the drug's complex mode of action.

Angiotensin type 1 receptor antagonists induce human in-vitro adipogenesis through peroxisome proliferator-activated receptor-gamma activation.

Objective: In clonal animal cells, certain angiotensin receptor blockers (ARB) activate the peroxisome proliferator-activated receptor-gamma (PPARgamma). The aim of this work was to validate that observation in human cells and humans.

Methods: We investigated the induction of in-vitro adipogenesis and the activation of PPARgamma-target genes, adiponectin and lipoprotein lipase, by ARB in human preadipocytes.

Adipose tissue and circulating endothelial cell specific molecule-1 in human obesity.

Adipocytes produce the endothelial-cell specific molecule-1 (ESM-1), which inhibits leukocyte adhesion and migration through the endothelium. This study investigates ESM-1 expression and regulation in human adipose tissue. Subcutaneous abdominal adipose tissue was obtained from seventy postmenopausal women.

Activation of the peripheral endocannabinoid system in human obesity.

Obesity is the main risk factor for the development of type 2 diabetes. Activation of the central endocannabinoid system increases food intake and promotes weight gain. Blockade of the cannabinoid type 1 (CB-1) receptor reduces body weight in animals by central and peripheral actions; the role of the peripheral endocannabinoid system in human obesity is now being extensively investigated.

Adipose tissue metabolism and CD11b expression on monocytes in obese hypertensives.

At a given degree of adiposity, metabolic and cardiovascular risk varies markedly between individuals. Animal studies suggest that differentially expressed systemic activation of monocytes contributes to the obesity-associated risk variability. We tested the hypothesis that systemic monocyte activation is associated with changes in adipose tissue and skeletal muscle metabolism.

Weight loss and the renin-angiotensin-aldosterone system.

The renin-angiotensin-aldosterone system has been causally implicated in obesity-associated hypertension. We studied the influence of obesity and weight reduction on the circulating and adipose tissue renin-angiotensin-aldosterone system in menopausal women. Blood samples were analyzed for angiotensinogen, renin, aldosterone, angiotensin-converting enzyme activity, and angiotensin II.

Regulation of 11beta-HSD genes in human adipose tissue: influence of central obesity and weight loss.

Objectives: The activity of adipose 11beta-hydroxysteroid dehydrogenase (11beta-HSD) 1 is increased in obese subjects, and animal data suggest that increased cortisol formation in adipose tissue contributes to the development of the metabolic syndrome. The aim of this study was to determine whether up-regulation of human adipose 11beta-HSD1 in obesity can also be found at the gene expression level.

Research Methods And Procedures: 11beta-HSD gene expression in subcutaneous adipose tissue biopsies of 70 postmenopausal women was studied by real-time reverse-transcription polymerase chain reaction.

Endothelial cell specific molecule-1--a newly identified protein in adipocytes.

Expression of the endothelial cell-specific molecule (ESM)-1 was originally identified in lung and kidney endothelial cells, where its expression is regulated by cytokines. In vitro, ESM-1 interferes with the molecular mechanisms of immune cell migration by binding to adhesion molecules. In this study, we have explored the expression of ESM-1 in isolated human adipocytes and in rat adipose tissue depots.

The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome?

Overfeeding of rodents leads to increased local formation of angiotensin II due to increased secretion of angiotensinogen from adipocytes. Whereas angiotensin II promotes adipocyte growth and preadipocyte recruitment, increased secretion of angiotensinogen from adipocytes also directly contributes to the close relationship between adipose-tissue mass and blood pressure in mice. In contrast, angiotensin II acts as an antiadipogenic substance in human adipose tissue, and the total increase in adipose-tissue mass may be more important in determining human plasma angiotensinogen levels than changes within the single adipocyte.

Association between adiponectin and mediators of inflammation in obese women.

Low plasma levels of the anti-inflammatory factor adiponectin characterize obesity and insulin resistance. To elucidate the relationship between plasma levels of adiponectin, adiponectin gene expression in adipose tissue, and markers of inflammation, we obtained blood samples, anthropometric measures, and subcutaneous adipose tissue samples from 65 postmenopausal healthy women. Adiponectin plasma levels and adipose-tissue gene expression were significantly lower in obese subjects and inversely correlated with obesity-associated variables, including high-sensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6).

Age-related changes of Renin-Angiotensin system genes in white adipose tissue of rats.

The adipose tissue renin-angiotensin system has been implicated in the regulation of adipocyte growth and differentiation. We studied the influence of age, body weight, total body fat content, anatomical localization, and diet on the expression of angiotensinogen (AGT) and angiotensin II type 1 (AT 1 )-receptor genes in white adipose tissue of normal and postnatal overfed rats. Relative gene expression was measured in epididymal adipose tissue and liver of control and postnatal overfed (PNO) rats at the age of 4, 8, and 12 weeks using real time RT-PCR.

Angiotensin blockade prevents type 2 diabetes by formation of fat cells.

Obesity is the prime risk factor for the development of type 2 diabetes. Recent clinical trials have shown that blockade of the renin-angiotensin system, either by inhibiting the angiotensin-converting enzyme or blocking the angiotensin type 1 receptor, may substantially lower the risk for type 2 diabetes. The mechanism underlying this effect is unknown.

Mature adipocytes inhibit in vitro differentiation of human preadipocytes via angiotensin type 1 receptors.

Recent studies suggest that angiotensin II (Ang II) plays a role in the adipogenesis of murine preadipocytes. Here, we examined the role of Ang II for the differentiation of primary cultured human preadipocytes. Preadipocytes were isolated from human adipose tissue and stimulated to differentiate.