Clinical manifestations of noncoronary atherosclerotic vascular disease after moderate dose irradiation.

Background: Accelerated atherosclerosis and carotid stenosis are well-established risks occurring after high radiation doses that are used to treat cancers of the head and neck. Noncoronary vascular disease has been observed and may relate to more moderate dose irradiation.

Methods: A search of patients treated for Hodgkin disease, non-Hodgkin lymphoma, or seminoma was performed to identify cases with noncoronary vascular complications after irradiation.

The impact of preoperative weight loss in patients undergoing laparoscopic Roux-en-Y gastric bypass.

Background: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is a widely performed bariatric operation. Preoperative factors that predict successful outcomes are currently being studied. The goal of this study was to determine if preoperative weight loss was associated with positive outcomes in patients undergoing LRYGBP.

Ab initio protein structure prediction using a combined hierarchical approach.

As part of the third Critical Assessment of Structure Prediction meeting (CASP3), we predict the three-dimensional structures for 13 proteins using a hierarchical approach. First, all possible compact conformations of a protein sequence are enumerated using a highly simplified tetrahedral lattice model. We select a large subset of these conformations using a lattice-based scoring function and build detailed all-atom models incorporating predicted secondary structure.

Molecular epidemiologic evaluation of transmissibility and virulence of Mycobacterium tuberculosis.

Discovery of genotypic markers associated with increased transmissibility in Mycobacterium tuberculosis would represent an important step in advancing mycobacterial virulence studies. M. tuberculosis strains may be classified into one of three genotypes on the basis of the presence of specific nucleotide substitutions in codon 463 of the katG gene (katG-463) and codon 95 of the gyrA gene (gyrA-95).

Visualizing lymphocyte recognition.

Studies of T cell recognition have entered new territory now that some of the basic issues of genetics, biochemistry and structure have been addressed, at least in outline form. In the present work, the focus is on a new aspect of T cell recognition that goes beyond classical biochemistry to ask, how to TCR and other cell surface molecules cooperate to initiate and control recognition?'

Isolation and utilization of human dendritic cells from peripheral blood to assay an in vitro primary immune response to varicella-zoster virus peptides.

A human dendritic cell-based assay used to monitor a T cell proliferation response to viral peptides in vitro is described. Dendritic cells and autologous CD4+ T cells were isolated from peripheral blood by a series of density-gradient centrifugations or magnetic bead separations (or both). Peptides corresponding to residues of the immediate early protein, IE62, of varicella-zoster virus (VZV) were used as stimulating antigens, and persons with no history of varicella and no humoral or cellular immunity to VZV served as naive donors for the assays.

Recognizing eating disorders in women.

Anorexia nervosa (AN) and bulimia nervosa (BN) are currently classified as eating disorders. Both disorders are the product of a complex interaction between psychological and physiological processes and both show considerable comorbidity with other psychiatric disorders. Physiological and endocrine abnormalities, including primary or secondary amenorrhea and menstrual dysfunction, are common and for the most part a function of the severity of weight loss, malnutrition and/or abnormal eating habits.

Effects of partial left ventriculectomy on left ventricular geometry and wall stress in excised porcine hearts.

Background And Aims Of The Study: Partial left ventriculectomy (PLV, the "Batista procedure") has received recent attention as a surgical treatment for patients with dilated cardiomyopathy and end-stage congestive heart failure; however, the mechanisms responsible for the purported short-term improvement in left ventricular (LV) function are poorly characterized. This study examined the effects of PLV on three-dimensional (3-D) LV geometry, wall stress and passive LV mechanics in excised porcine hearts.

Methods: Thirty-three radio-opaque tantalum markers were placed into the LV wall of nine freshly excised, porcine hearts (arrested with cold crystalloid cardioplegia) to measure three dimensional LV geometry and volume.

The impact of price labeling of muscle relaxants on cost consciousness among anesthesiologists.

Study Objective: To determine whether placing price labels on the vial caps of muscle relaxants increases cost consciousness among anesthesiologists.

Design: Retrospective study.

Setting: University hospital departments of anesthesia and pharmacy.

The pathophysiology of peripheral arterial disease: rational targets for drug intervention.

The most common cause of peripheral arterial disease (PAD) is atherosclerosis, which begins with an alteration in endothelial biology due to hypercholesterolemia, diabetes mellitus, hypertension, tobacco use, elevated levels of lipoprotein(a) or homocystinemia. With chronic and severe arterial disease, changes begin to occur in the microcirculation, including obstruction at the microvascular level and tissue injury. Based on insights into the vascular biology of PAD, new therapies have been developed and are at various stages of clinical trials.

Loss of three-dimensional canine mitral annular systolic contraction with reduced left ventricular volumes.

Background: We have recently described an inhomogeneous pattern of systolic contraction of the mitral annulus (MA) in normovolemic dogs: the posterior annulus shortens, and the anterior annulus lengthens. MA dynamics, however, have not been studied in volume-depleted hearts.

Methods And Results: Eight radiopaque markers were placed equidistant from each other around the MA in seven dogs.

Mitochondrial DNA polymerase gamma is expressed and translated in the absence of mitochondrial DNA maintenance and replication.

Mitochondria are essential organelles in all eukaryotic cells where cellular ATP is generated through the process of oxidative phosphorylation. Protein components of the respiratory assembly are gene products of both mitochondrial and nuclear genes. The mitochondrial genome itself encodes several protein and nucleic acid components required for such oxidative phosphorylative processes, but the vast majority of genes encoding respiratory chain components are nuclear.

Circuit simulation of genetic networks.

Genetic networks with tens to hundreds of genes are difficult to analyze with currently available techniques. Because of the many parallels in the function of these biochemically based genetic circuits and electrical circuits, a hybrid modeling approach is proposed that integrates conventional biochemical kinetic modeling within the framework of a circuit simulation. The circuit diagram of the bacteriophage lambda lysislysogeny decision circuit represents connectivity in signal paths of the biochemical components.

Job strain and the prevalence and outcome of coronary artery disease.

Background: It has been hypothesized that jobs that have both high psychological demands and low decision latitude ("job strain") can lead to coronary disease. The objective of this study was to test whether job strain was correlated with the presence of coronary disease at angiography or with long-term outcome in patients with angiographic coronary disease.

Methods And Results: Employed patients under the age of 65 years undergoing diagnostic coronary angiography completed a self-administered questionnaire about their job duties and work environment.

A method to assess endocardial regional longitudinal curvature of the left ventricle.

Knowledge of the instantaneous geometry of the left ventricular (LV) chamber is necessary to calculate LV function and wall stresses. We describe a method utilizing myocardial markers that does not rely on any a priori assumptions of global LV geometry. Five dogs underwent placement of 25 endocardial and 3 epicardial miniature LV markers.

Pharmacokinetic/dynamic assessment in drug development: application to the investigational opioid mirfentanil.

The safety, pharmacokinetics, and pharmacodynamics of the investigational partial opioid agonist, mirfentanil, were determined in a dose-escalating, Phase 1 study in healthy male volunteers. Hemodynamic, central nervous system, and respiratory monitoring were used for safety assessment. The electroencephalogram (EEG) was evaluated as a surrogate measure of drug effect.

Effect of aging on beta 2-adrenergic receptor-stimulated flux of K+, PO4, FFA, and glycerol in human forearms.

beta-Adrenergic responses have been shown to decline with aging, particularly in the cardiovascular system. We infused terbutaline, a selective beta 2-adrenoceptor agonist, into the brachial artery of 10 young (mean age 25 yr, range 22-31 yr) and 9 elderly (mean age 73 yr, range 68-81 yr) healthy subjects to examine its effects on nutrient flux. Forearm K+, PO4, free fatty acid (FFA), and glycerol uptake were determined by measurement of forearm blood flow (using dye dilution) and brachial arterial and deep venous plasma substrate concentrations.

Multifunctional Ca2+/calmodulin-dependent protein kinase mediates Ca(2+)-induced enhancement of the L-type Ca2+ current in rabbit ventricular myocytes.

The intracellular mechanism underlying the Ca(2+)-induced enhancement of the L-type Ca2+ current (ICa) was examined in adult rabbit cardiac ventricular myocytes by using patch-clamp methodology. Internal Ca2+ was elevated by flash photolysis of the Ca2+ chelator Nitr 5, and intracellular Ca2+ levels were simultaneously monitored by Fluo 3 fluorescence. Flash photolysis of Nitr 5 produced a rapid (< 1-second) elevation of internal Ca2+, which led to enhancement (39% to 51% above control) of the peak inward Ca2+ current after a delay of 20 to 120 seconds.

Health caring. Psychosocial support for patients with cancer.

Psychosocial treatments, including group, individual, and family therapies, are of proven efficacy and deserve inclusion as standard components of biomedical treatment for patients with cancer. Four issues regarding such treatment are reviewed. The first is need.

Regulation of hormone-sensitive lipase during fasting.

Hormone-sensitive lipase (HSL) is the rate-limiting enzyme in lipolysis. The activity of HSL is thought to be primarily regulated by phosphorylation-dephosphorylation reactions. Although FFA levels are elevated during fasting, it has been difficult to demonstrate an increase in HSL activity with fasting.

Identification and localization of ERD2 in the malaria parasite Plasmodium falciparum: separation from sites of sphingomyelin synthesis and implications for organization of the Golgi.

The ERD2 gene product in mammalian cells and yeast is a receptor required for protein retention in the endoplasmic reticulum (ER); immunolocalization studies indicate that the protein is concentrated in the cis Golgi. We have identified a homologue of ERD2 in the malaria parasite, Plasmodium falciparum (PfERD2). The deduced protein sequence is 42% identical to mammalian and yeast homologues and bears striking homology in its proposed tertiary structure.

Gene replacement in Toxoplasma gondii with chloramphenicol acetyltransferase as selectable marker.

A system for stable transformation of Toxoplasma gondii tachyzoites was developed that exploited the susceptibility of Toxoplasma to chloramphenicol. Introduction of the chloramphenicol acetyltransferase (CAT) gene fused to Toxoplasma flanking sequences followed by chloramphenicol selection resulted in parasites stably expressing CAT. A construct incorporating the tandemly repeated gene, B1, targeted efficiently to its homologous chromosomal locus.