Novel components in the nuclear factor-kappa B (NF-κB) signaling pathways of endothelial cells under hyperglycemic-ischemic conditions.

Diabetes worsens the outcomes of a number of vascular disorders including peripheral arterial disease (PAD) at least in part through induction of chronic inflammation. However, in experimental PAD, recovery requires the nuclear factor-kappa B (NF-κB) activation. Previously we showed that individually, both ischemia and high glucose activate the canonical and non-canonical arms of the NF-κB pathway, but prolonged high glucose exposure specifically impairs ischemia-induced activation of the canonical NF-κB pathway through activation of protein kinase C beta (PKCβ).

Serologic Evaluations in the Distinction Between Sinusitis-Related Orbital Cellulitis and Periorbital Necrotizing Fasciitis.

Purpose: While sinusitis-related orbital cellulitis (SROC) and periorbital necrotizing fasciitis (PNF) share similar clinical presentations, they are managed differently, making rapid recognition of the appropriate clinical entity critical to optimal outcomes. This study was performed to assess whether serologic testing might help clinicians to distinguish between SROC and PNF.

Methods: A retrospective review analysis was used to compare initial complete blood counts and comprehensive metabolic panels among adult patients with SROC and PNF.

Age-associated adipose tissue inflammation promotes monocyte chemotaxis and enhances atherosclerosis.

Although aging enhances atherosclerosis, we do not know if this occurs via alterations in circulating immune cells, lipid metabolism, vasculature, or adipose tissue. Here, we examined whether aging exerts a direct pro-atherogenic effect on adipose tissue in mice. After demonstrating that aging augmented the inflammatory profile of visceral but not subcutaneous adipose tissue, we transplanted visceral fat from young or aged mice onto the right carotid artery of Ldlr recipients.

Movement-dependent electrical stimulation for volitional strengthening of cortical connections in behaving monkeys.

Correlated activity of neurons can lead to long-term strengthening or weakening of the connections between them. In addition, the behavioral context, imparted by execution of physical movements or the presence of a reward, can modulate the plasticity induced by Hebbian mechanisms. In the present study, we have combined behavior and induced neuronal correlations to strengthen connections in the motor cortex of adult behaving monkeys.

Erratum: Addendum: Miniaturized Technologies for Enhancement of Motor Plasticity.

[This corrects the article on p. 30 in vol. 4, PMID: 27148525.

Miniaturized Technologies for Enhancement of Motor Plasticity.

The idea that the damaged brain can functionally reorganize itself - so when one part fails, there lies the possibility for another to substitute - is an exciting discovery of the twentieth century. We now know that motor circuits once presumed to be hardwired are not, and motor-skill learning, exercise, and even mental rehearsal of motor tasks can turn genes on or off to shape brain architecture, function, and, consequently, behavior. This is a very significant alteration from our previously static view of the brain and has profound implications for the rescue of function after a motor injury.

Generating arbitrary chemical patterns for multipoint dosing of single cells.

Living cells reside within anisotropic microenvironments that orchestrate a broad range of polarized responses through physical and chemical cues. To unravel how localized chemical signals influence complex behaviors, tools must be developed for establishing patterns of chemical gradients that vary over subcellular dimensions. Here, we present a strategy for addressing this critical need in which an arbitrary number of chemically distinct, subcellular dosing streams are created in real time within a microfluidic environment.

Dynamic remodeling of subcellular chemical gradients using a multi-directional flow device.

Elucidation of the mechanisms by which external chemical cues regulate polarized cellular behaviors requires tools that can rapidly recast chemical landscapes with subcellular resolution. Here, we describe an approach for creating steep microscopic gradients of cellular effectors at any desired position in culture that can be reoriented rapidly to evaluate dynamic responses. In this approach, micrometre pores are ablated in a membrane that supports cell adherence, allowing dosing reagent from an underlying reservoir to enter the cell-culture flow chamber as sharp streams that are directed at subcellular targets by using a system of paired sources and drains to specify flow direction.

Microscale transport and sorting by kinesin molecular motors.

As biomolecular detection systems shrink in size, there is an increasing demand for systems that transport and position materials at micron- and nanoscale dimensions. Our goal is to combine cellular transport machinery-kinesin molecular motors and microtubules-with integrated optoelectronics into a hybrid biological/engineered microdevice that will bind, transport, and detect specific proteins, DNA/RNA molecules, viruses, or cells. For microscale transport, 1.

Association of fibrinogen and lipoprotein(a) as a coronary heart disease risk factor in men (The Quebec Cardiovascular Study).

Fibrinogen has been prospectively found to correlate with coronary heart disease (CHD) but a similar association has not been well established for lipoprotein (a) (Lp(a)). Plasma lipids, Lp(a), and fibrinogen levels were measured in 2,125 men (aged 47 to 76 years) who were free of clinical CHD. During a 5-year follow-up period, 116 first CHD events were documented.

Apolipoprotein E polymorphism and the relationships of physical fitness to plasma lipoprotein-lipid levels in men and women.

Purpose: A high level of cardiovascular fitness is generally associated with a plasma lipoprotein-lipid profile predictive of a low cardiovascular disease risk. We have investigated whether apolipoprotein (apo) E polymorphism could alter the relationships of physical fitness to plasma lipoprotein-lipid levels in a sample of healthy untrained subjects (64 premenopausal women and 65 men).

Methods: Subjects were grouped according to gender and apo E phenotype determined by isoelectric focusing electrophoresis.

Contribution of receptor negative versus receptor defective mutations in the LDL-receptor gene to angiographically assessed coronary artery disease among young (25-49 years) versus middle-aged (50-64 years) men.

Elevated plasma LDL-cholesterol (LDL-C) levels are associated with an increased risk of coronary artery disease (CAD). Familial hypercholesterolemia (FH), a monogenic trait due to mutations in the LDL-receptor (R) gene is characterized by raised plasma LDL-C levels and premature CAD. The aim of the present investigation, derived from the study of a population of 1465 unrelated men aged 25 to 64 years, was to compare the expression of CAD assessed by coronary angiography in young (aged 25-49 years) versus middle-aged (50-64 years) heterozygous FH patients of French Canadian descent.

Relative contribution of low-density lipoprotein receptor and lipoprotein lipase gene mutations to angiographically assessed coronary artery disease among French Canadians.

Men with low-density lipoprotein receptor gene mutations causing familial hypercholesterolemia (FH) are at high risk of premature coronary artery disease (CAD). The dyslipidemic state found among patients who are heterozygous for mutations in the lipoprotein lipase (LPL) gene may also increase the risk of CAD. In the present study, the association of the heterozygous forms of low-density lipoprotein receptor gene mutations causing FH as well as of LPL gene mutations causing (P207L and G188E) or not causing (D9N and N291S) complete loss of LPL activity with angiographically assessed CAD was estimated in a cohort of 412 French Canadian men aged <60 years who consecutively underwent coronary angiography for the investigation of retrosternal pain.

Leptinemia is not a risk factor for ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study.

Objective: To investigate the possibility that leptin levels may be predictive of the risk of ischemic heart disease (IHD) through the relationship of leptin to body fat.

Research Design And Methods: The Quebec Cardiovascular Study cohort consisted of 2,103 French-Canadian men without IHD in 1985 who were followed until 1990, by which time 114 had experienced an IHD event. These 114 men were then individually matched for age, BMI, cigarette smoking, and alcohol intake with 114 subjects who were free of IHD at follow-up.

Relationships of abdominal obesity and hyperinsulinemia to angiographically assessed coronary artery disease in men with known mutations in the LDL receptor gene.

Background: Patients with a mutation in the LDL receptor gene (familial hypercholesterolemia, or FH) are characterized by substantial elevations in plasma LDL cholesterol and are at higher risk of developing coronary artery disease (CAD). Correlates of abdominal obesity may also contribute to the risk of ischemic cardiac events. Whether the hyperinsulinemic-insulin-resistant state of abdominal obesity affects coronary atherosclerosis among FH patients has not been determined.

Is lipoprotein(a) an independent risk factor for ischemic heart disease in men? The Quebec Cardiovascular Study.

Objectives: This study was undertaken to determine whether lipoprotein(a) [Lp(a)] is an independent risk factor for ischemic heart disease (IHD) and to establish the relation of Lp(a) to the other lipid fractions.

Background: Several, but not all, studies have shown that elevated Lp(a) concentrations may be associated with IHD; very few have been prospective.

Methods: A 5-year prospective follow-up study was conducted in 2,156 French Canadian men 47 to 76 years old, without clinical evidence of IHD.

Geographic distribution of French-Canadian low-density lipoprotein receptor gene mutations in the Province of Quebec.

A total of 35 homozygous and 1320 heterozygous patients with familial hypercholesterolemia (FH) was screened for the presence of six low-density lipoprotein receptor (LDLR) gene mutations previously reported among French-Canadians. The geographic distribution of patients' birthplaces and the relative prevalence of these six mutations in the LDLR gene in the province of Quebec were compared. For this purpose, the 16 administrative regions of the province of Quebec were grouped into seven geographic regions.

Associations of HDL2 and HDL3 subfractions with ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study.

Individuals with elevated plasma concentrations of HDL cholesterol are at lower risk for ischemic heart disease (IHD). Whether the cardioprotective effects of HDL can be attributed to one or both HDL subfractions (HDL2 and HDL3) remains, however, controversial. The relationship of HDL subfractions to the incidence of IHD was investigated in a sample of 1169 French-Canadian men younger than 60 years and living in the Quebec City suburbs.

Comparison of the effect of two low-density lipoprotein receptor class mutations on coronary heart disease among French-Canadian patients heterozygous for familial hypercholesterolaemia.

The aim of this study was to compare the age at first elective coronary angiogram and the age at first revascularization (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) in 102 patients without familial hypercholesterolaemia (FH), who were matched for age and sex with 76 heterozygous FH patients carrying a defective allele at the low-density lipoprotein (LDL) receptor gene (LDL-R) and 26 heterozygous FH patients bearing a null mutation at the LDL-R. The prevalence of diabetes was significantly higher in the non-FH group than in the two FH groups (P < 0.05).

Simvastatin further enhances the hypocholesterolemic effect of soy protein in rabbits.

Objective: The effects of three dietary proteins (casein, cod, soy) and low dose simvastatin, an inhibitor of hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase, on serum lipids were investigated.

Methods: New Zealand rabbits were fed purified diet (20% protein, 11% fat and 0.06% cholesterol) for 28 days.

The MspI polymorphism of the apolipoprotein A-II gene as a modulator of the dyslipidemic state found in visceral obesity.

The aim of the present study was to examine the effect of variation at the apolipoprotein (apo) A-II gene locus on lipoprotein levels in visceral obesity. A total of 145 sedentary men, free from metabolic disorders requiring pharmacotherapy, were classified into two groups on the basis of their apo A-II-MspI genotype determined by the polymerase chain reaction: 1) 43 M1 carriers or M1M2, including two M1M1 homozygotes and 41 M1M2 heterozygotes, and 2) 102 M2M2 homozygotes for the presence of a MspI restriction site. The two genotypic groups did not differ for body mass index (BMI, expressed in kg/m2), body fat mass, visceral adipose tissue (AT) accumulation, as well as for insulin, glucose and free fatty acids levels measured in the fasting state and in response to an oral glucose tolerance test.

Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study.

Background: Case-control studies have reported that patients with ischemic heart disease (IHD) have a higher proportion of small, dense LDL particles than do healthy control subjects. The extent to which the risk attributed to small LDL particles may be independent of concomitant variations in plasma lipoprotein-lipid concentrations remains to be clearly determined, however, particularly through prospective studies.

Methods And Results: Baseline characteristics were obtained in 2103 men initially free of IHD, among whom 114 developed IHD during a 5-year follow-up period.

Associations between 12 year changes in body fatness and lipoprotein-lipid levels in men and women of the Québec Family Study.

Objective: To investigate the associations between 12 year changes in body composition, subcutaneous fat distribution vs changes in plasma lipoprotein-lipid levels.

Design: 12 year prospective study.

Subjects: A sample of 95 women and 93 men of the Québec Family Study initially tested in 1980.