The use of a gamma probe and radioactive technetium to identify obscure gastrointestinal bleeding.

Lower gastrointestinal bleeding is a common cause of hospital admission. This bleeding is most often secondary to diverticuli, malignancy, or colitis. Rarely, the location of lower gastrointestinal bleeding cannot be identified after exhaustive efforts with endoscopy, angiography, and other modalities.

Syntaxin 1A is required for normal in utero development.

We have generated a syntaxin 1A knockout mouse by deletion of exons 3 through 6 and a concomitant insertion of a stop codon in exon 2. Heterozygous knockout animals were viable with no apparent phenotype. In contrast, the vast majority of homozygous animals died in utero, with embryos examined at day E15 showing a drastic reduction in body size and development when compared to WT and heterozygous littermates.

Leukocyte trafficking and pain behavioral responses to a hydrogen sulfide donor in acute monoarthritis.

Hydrogen sulfide (H(2)S) is an endogenous gaseous mediator with the ability to modulate tissue inflammation and pain. The aim of this study was to determine the effect of an H(2)S donor (Na(2)S) on leukocyte-endothelium interactions, blood flow, and pain sensation in acutely inflamed knee joints. Acute arthritis was induced in urethane anesthetized C57bl/6 mice by intra-articular injection of kaolin/carrageenan (24-h recovery), and the effect of local administration of Na(2)S on leukocyte trafficking was measured by intravital microscopy.

ING1 protein targeting to the nucleus by karyopherins is necessary for activation of p21.

ING1 proteins affect apoptosis, growth, and DNA repair by binding histones and regulating chromatin structure and gene expression. ING1 is downregulated in cancers and cytoplasmic localization is associated with poor prognosis. Here, we report that ING1b interacts with karyopherins alpha2 and beta1 through several basic nuclear localization sequences (NLS) located adjacent to the ING1b PHD region.

Novel inner membrane retention signals in Pseudomonas aeruginosa lipoproteins.

The ultimate membrane localization and function of most of the 185 predicted Pseudomonas aeruginosa PAO1 lipoproteins remain unknown. We constructed a fluorescent lipoprotein, CSFP(OmlA)-ChFP, by fusing the signal peptide and the first four amino acids of the P. aeruginosa outer membrane lipoprotein OmlA to the monomeric red fluorescent protein mCherry (ChFP).

iNOS in cardiac myocytes plays a critical role in death in a murine model of hypertrophy induced by calcineurin.

Transgenic overexpression of calcineurin (CN/Tg) in mouse cardiac myocytes results in hypertrophy followed by dilation, dysfunction, and sudden death. Nitric oxide (NO) produced via inducible NO synthase (iNOS) has been implicated in cardiac injury. Since calcineurin regulates iNOS expression, and since phenotypes of mice overexpressing iNOS are similar to CN/Tg, we hypothesized that iNOS is pathogenically involved in cardiac phenotypes of CN/Tg mice.

Challenges to the use of autoantibodies as predictors of disease onset, diagnosis and outcomes.

Autoantibodies (AA) are a serological hallmark of most autoimmune diseases. In contrast to genetic markers that show a predisposition for disease development, certain AA serve as diagnostic biomarkers and classification criteria for a number of these conditions. The role of AA is still not clearly understood: some are pathogenic, some disease specific and others serve as predictors of disease outcome, but little is known about those that protect against disease or serve as signatures of the inciting agent of autoimmunity.

Effect of beta2-adrenoceptor agonists and other cAMP-elevating agents on inflammatory gene expression in human ASM cells: a role for protein kinase A.

In diseases such as asthma, airway smooth muscle (ASM) cells play a synthetic role by secreting inflammatory mediators such as granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, or IL-8 and by expressing surface adhesion molecules, including ICAM-1. In the present study, PGE(2), forskolin, and short-acting (salbutamol) and long-acting (salmeterol and formoterol) beta(2)-adrenoceptor agonists reduced the expression of ICAM-1 and the release of GM-CSF evoked by IL-1beta in ASM cells. IL-1beta-induced IL-8 release was also repressed by PGE(2) and forskolin, whereas the beta(2)-adrenoceptor agonists were ineffective.

Osteoblastic MG-63 cell differentiation, contraction, and mRNA expression in stress-relaxed 3D collagen I gels.

To investigate the molecular aspects of osteoblastic interactions with a type I collagen matrix, human osteoblast-like MG-63 cells were cultured in three-dimensional (3D) collagen I gels. MG-63 cells in collagen gels expressed higher osteocalcin mRNA levels than cells in monolayer (2D) on polystyrene surfaces. Gel contraction was assessed via releasing the collagen gels from attachment following 24 h incubation in serum free, TGF-beta1-treated, or 1,25-(OH)(2)D(3)-treated media.

The relationship between meiotic recombination in human spermatocytes and aneuploidy in sperm.

Background: We have previously demonstrated that a decreased recombination frequency between human X and Y chromosomes is associated with the production of aneuploid 24,XY sperm. This study's aim was to determine the relationship between recombination frequency in human pachytene spermatocytes and aneuploidy frequencies in individual chromosomes in sperm from the same men.

Methods: Six previously fertile vasectomy reversal patients donated testicular tissue for meiotic analysis of pachytene spermatocytes using immunocytogenetic techniques for visualization of the synaptonemal complex and recombination sites (MLH1).

Roflumilast: an oral, once-daily selective PDE-4 inhibitor for the management of COPD and asthma.

Background: Roflumilast is a selective phosphodiesterase-4 inhibitor with a broad range of anti-inflammatory actions. Studies in asthma and chronic obstructive pulmonary disease (COPD) have demonstrated that it can improve lung function and reduce inflammation.

Objective: To review the clinical data on roflumilast in COPD and asthma.

A highly sensitive technique to measure myosin regulatory light chain phosphorylation: the first quantification in renal arterioles.

Phosphorylation of the 20-kDa myosin regulatory light chains (LC(20)) plays a key role in the regulation of smooth muscle contraction. The level of LC(20) phosphorylation is governed by the relative activities of myosin light chain kinase and phosphatase pathways. The regulation of these two pathways differs in different smooth muscle types and in the actions of different vasoactive stimuli.

Sarcomere mechanics in uniform and nonuniform cardiac muscle: a link between pump function and arrhythmias.

Starling's law and the end-systolic pressure-volume relationship (ESPVR) reflect the effect of sarcomere length (SL) on the development of stress (sigma) and shortening by myocytes in the uniform ventricle. We show here that tetanic contractions of rat cardiac trabeculae exhibit a sigma-SL relationship at saturating [Ca2+] that depends on sarcomere geometry in a manner similar to that of skeletal sarcomeres and the existence of opposing forces in cardiac muscle shortened below slack length. The sigma-SL -[Ca2+](free) relationships (sigma-SL-Ca relationships) at submaximal [Ca2+] in intact and skinned trabeculae were similar, although the sensitivity for Ca2+ of intact muscle was higher.

Vibrio parahaemolyticus inhibition of Rho family GTPase activation requires a functional chromosome I type III secretion system.

Vibrio parahaemolyticus is a leading cause of seafood-borne gastroenteritis; however, its virulence mechanisms are not well understood. The identification of type III secreted proteins has provided candidate virulence factors whose functions are still being elucidated. Genotypic strain variability contributes a level of complexity to understanding the role of different virulence factors.

Molecular determinants of Rem2 regulation of N-type calcium channels.

Rem2 belongs to the RGK family of small GTPases whose members are known to interact with the voltage gated calcium channel beta subunit, and to inhibit or abolish calcium currents. To identify the underlying functional domains of Rem2, we created several N- or C-terminally truncated Rem2 proteins and examined their abilities to interact with the Ca(v) beta subunit and to regulate the activities of Ca(v)2.2 N-type calcium channels.

Cardiovascular and cerebrovascular responses to acute isocapnic and poikilocapnic hypoxia in humans.

We examined the cardiovascular and cerebrovascular responses to acute isocapnic (IH) and poikilocapnic hypoxia (PH) in 10 men (25.7 +/- 4.2 yr, mean +/- SD).

Role of methotrexate in the treatment of chronic cholestatic disorders.

This article examines the therapeutic potential of methotrexate (MTX) in the treatment of cholestatic liver disease, with specific reference to its use in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). In PBC patients, evidence suggests that a particular subset of patients may benefit, either biochemically or symptomatically, from the addition of MTX to their therapeutic regimen. How best to define these potential MTX responders remains unclear, but may warrant a "therapeutic trial" in some patients with more aggressive disease or in patients with refractory and disabling PBC-related symptoms.

How well do we communicate autopsy findings to next of kin?

Context: A failure of communication among families, physicians, and pathologists is recognized as a major cause of declining autopsy rates and may be involved in increased litigation.

Objective: To determine how effectively autopsy results are communicated to the next of kin and how satisfied families are with the process from consent to relaying of the results.

Design: A retrospective telephone survey of next of kin of 106 consecutive patients autopsied at a major teaching hospital.

Basic helix-loop-helix transcription factors cooperate to specify a cortical projection neuron identity.

Several transcription factors are essential determinants of a cortical projection neuron identity, but their mode of action (instructive versus permissive) and downstream genetic cascades remain poorly defined. Here, we demonstrate that the proneural basic helix-loop-helix (bHLH) gene Ngn2 instructs a partial cortical identity when misexpressed in ventral telencephalic progenitors, inducing ectopic marker expression in a defined temporal sequence, including early (24 h; Nscl2), intermediate (48 h; BhlhB5), and late (72 h; NeuroD, NeuroD2, Math2, and Tbr1) target genes. Strikingly, cortical gene expression was much more rapidly induced by Ngn2 in the dorsal telencephalon (within 12 to 24 h).

Receptor for advanced glycation end products (RAGEs) and experimental diabetic neuropathy.

Objective: Heightened expression of the receptor for advanced glycation end products (RAGE) contributes to development of systemic diabetic complications, but its contribution to diabetic neuropathy is uncertain. We studied experimental diabetic neuropathy and its relationship with RAGE expression using streptozotocin-induced diabetic mice including a RAGE(-/-) cohort exposed to long-term diabetes compared with littermates without diabetes.

Research Design And Methods: Structural indexes of neuropathy were addressed with serial (1, 3, 5, and 9 months of experimental diabetes) electrophysiological and quantitative morphometric analysis of dorsal root ganglia (DRG), peripheral nerve, and epidermal innervation.

Roles and responsibilities of family physicians on geriatric health care teams: Health care team members' perspectives.

Objective: To examine the beliefs and attitudes of FPs and health care professionals (HCPs) regarding FPs' roles and responsibilities on interdisciplinary geriatric health care teams.

Design: Qualitative study using focus groups.

Setting: Calgary Health Region.

TGFbeta ligands promote the initiation of retinal ganglion cell dendrites in vitro and in vivo.

Each type of neuron develops a unique morphology critical to its function, but almost all start with the basic plan of one long axon and multiple short, branched dendrites. Though extrinsic signals are known to direct many steps in the development of neuronal structure, little is understood about the initiation of processes, particularly dendrites. We find that Xenopus retinal ganglion cells (RGCs) explanted early will extend axons and not dendrites in dissociated cultures.

Toll-like receptor 9-dependent macrophage activation by Entamoeba histolytica DNA.

Activation of the innate immune system by bacterial DNA and DNA of other invertebrates represents a pathogen recognition mechanism. In this study we investigated macrophage responses to DNA from the intestinal protozoan parasite Entamoeba histolytica. E.

Advances in understanding newer autoantibodies and their role as biomarkers in systemic lupus erythematosus.

Autoantibodies (AAs) were first associated with systemic lupus erythematosus (SLE) in the 1950s and since then > 155 have been described in SLE sera. Of these, only a few have achieved recognition as important biomarkers in the classification, diagnosis, prediction, prognosis and pathogenesis of the disease. Although some long-established AAs, such as anti-dsDNA, anti-Sm and anticardiolipin, have taken center stage in classification criteria and pathogenic studies, some of the newer and less understood AAs may have equally important disease relevance.

A LysR-type transcriptional regulator in Burkholderia cenocepacia influences colony morphology and virulence.

Burkholderia cenocepacia strain K56-2 typically has rough colony morphology on agar medium; however, shiny colony variants (shv) can appear spontaneously. These shv all had a minimum of 50% reduction in biomass formation and were generally avirulent in an alfalfa seedling infection model. Three shv-K56-2 S15, K56-2 S76, and K56-2 S86-were analyzed for virulence in a chronic agar bead model of respiratory infection and, although all shv were able to establish chronic infection, they produced significantly less lung histopathology than the rough K56-2.