Role of cystic fibrosis transmembrane conductance regulator in patients with chronic sinopulmonary disease.

Background: Previous studies report a high frequency of mutations in the cystic fibrosis (CF) transmembrane conductance regulator gene (CFTR) in patients with idiopathic bronchiectasis. However, most studies have based their findings on preselected patient groups or have performed limited testing for CF transmembrane conductance regulator (CFTR) dysfunction. The objective of our study was to evaluate the prevalence of CFTR gene mutations and/or CFTR-related ion channel abnormalities among subjects with idiopathic chronic sinopulmonary disease and the prevalence of CF or a CFTR-related disorder in this population.

Identification, synthesis, and biological evaluation of novel pyrazoles as low molecular weight luteinizing hormone receptor agonists.

In the course of a high throughput screening, a series of pyrazole compounds were identified with luteinizing hormone receptor (LH-R) agonist activity. A focused pyrazole library was produced by solid-phase synthesis and key pyrazole regioisomers were obtained selectively in solution. Evaluation of those compounds in a cAMP assay in CHO cells transfected with h-LH receptor allowed us to propose a structure-activity relationship model for this series and led to the identification of the first low molecular weight molecule with in vitro activity in a Leydig cells assay (ED(50)=1.

Formation of human IFN-beta complex with the soluble type I interferon receptor IFNAR-2 leads to enhanced IFN stability, pharmacokinetics, and antitumor activity in xenografted SCID mice.

Interferon-beta (IFN-beta) is biologically unstable under physiologic conditions in vitro and is cleared rapidly from the bloodstream on administration in vivo. In the present study, we demonstrate that a soluble recombinant form of the type I IFN receptor subunit, sIFNAR-2, can neutralize the bioactivity of type I IFNs at high concentrations and, at lower concentrations, causes an enhancement of IFN-beta-mediated antiviral activity. The in vitro enhancement is due to the specific interaction of IFN-beta with sIFNAR-2, followed by dissociation of IFN-beta from the complex over time in culture.

Chest radiographic manifestations of severe acute respiratory syndrome in health care workers: the Toronto experience.

Objective: The purpose of this article is to describe the chest radiographic manifestations of severe acute respiratory syndrome (SARS) in previously uninfected health care workers during the early stages of an outbreak in Toronto, Canada.

Conclusion: The study group was composed of 13 patients from a single institution. Three distinct chest radiographic patterns were observed: focal peripheral air-space disease at presentation with gradual resolution (most common pattern, 10/13 patients), normal findings on chest radiography at presentation followed by focal air-space disease (2/13 patients), and normal findings on chest radiography at presentation followed by a "round" pneumonia pattern (1/13 patients).

Stability and preservative effectiveness of treprostinil sodium after dilution in common intravenous diluents.

The stability of treprostinil sodium after dilution in three common i.v. infusion vehicles was assessed.

FSH beta gene mutations in a female with partial breast development and a male sibling with normal puberty and azoospermia.

FSH is a dimeric pituitary glycoprotein hormone that regulates gonadal function. Human mutations in the FSH beta gene have been shown to produce complete deficiency states in which pubertal development and reproductive capacity are inhibited. To date, no patients with partial or complete pubertal development due to FSH beta mutations have been documented in humans.

Leukemia inhibitory factor in human reproduction.

Objective: To describe the clinical findings, expressions, interactions, and clinical implications of leukemia inhibitory factor (LIF) in human reproduction.

Design: Review of published articles.

Setting: Clinical development unit of biotechnology company.

The neutralization of type I IFN biologic actions by anti-IFNAR-2 monoclonal antibodies is not entirely due to inhibition of Jak-Stat tyrosine phosphorylation.

A panel of monoclonal antibodies (mAb) derived against human interferon-alpha/beta receptor-2 (IFNAR-2) was evaluated for their ability to antagonize the biologic effects of type 1 interferons (IFN-alpha1, IFN-alpha2a, and IFN-beta). Anti-IFNAR-2 mAb 117.7, 35.

Effects of simulated scapular protraction on anterior glenohumeral stability.

We evaluated the effect of simulated scapular protraction on anterior glenohumeral translation and in situ inferior glenohumeral ligament strain. Five fresh-frozen cadaveric glenohumeral joints were tested in the position of apprehension while simulating scapular protraction using a custom translation testing device and a differential variable reluctance transducer. The results showed a statistically significant decrease in anterior glenohumeral translation as the scapula was increasingly rotated to simulate 20 degrees of scapular protraction.

Lymphocyte activation in angina pectoris.

To determine the role of immune responses in the etiology of coronary angioplasty, the distribution of blood lymphocytes and levels of soluble immune factors in sera of patients with primary unstable angina were determined at pre and post coronary angioplasty. Our data showed (1) an increase in the numbers of lymphocytes bearing lymphocyte activating gene-3 (LAG-3) and CD40 in the blood and (2) an increase in levels of sIL2-R and sVCAM-1 in the sera of patients with unstable angina, compared with normal subjects. In contrast, there were no changes in these values in blood or sera of patients shortly after coronary angioplasty.

Quantitative analysis of a drug in an animal feed employing sample preparation by supercritical fluid extraction.

A pharmaceutical agent has been quantified in a rat feed matrix wherein sample preparation was achieved by supercritical fluid extraction. Spiking levels ranged from 0.0335% to 1.

Assessment of supercritical fluids for drug analysis.

Supercritical fluid (SF) CO2 is receiving a great deal of interest in the scientific and engineering community as a replacement for toxic organic solvents. Analytical chemists employ large quantities of organic solvents during preparation of the sample for analysis. The application of SF extraction with CO2 and modified CO2 to the isolation of active drug components and metabolites from various pharmaceutical and biological matrices is reviewed.

Detection of the lymphokine migration inhibitory factor in normal and disease-affected lung by antibody and by its major binding protein, the interferon antagonist sarcolectin.

Human migration inhibitory factor (MIF) is suggested to play a notable role in regulation of macrophage functions in host defense. A major binding component for the lymphokine in human tissue is the interferon antagonist sarcolectin. This high-affinity interaction gives access to MIF by affinity chromatography on immobilized sarcolectin and may be of significance for in situ activity of MIF.

Molecular cloning and functional expression of a cDNA encoding glycosylation-inhibiting factor.

By using probes based on partial amino acid sequence of glycosylation-inhibiting factor (GIF) from a mouse T-cell hybridoma, a full-length cDNA encoding mouse GIF was isolated. A cDNA clone encoding human GIF was isolated from cDNA libraries of a GIF-producing human T-cell hybridoma by using mouse GIF cDNA as a probe. The cDNAs encode a putative 12.

Alteration of human lung parenchyma associated with primary biliary cirrhosis.

The clinical history, radiological and histomorphological alterations of the lung parenchyma in a patient suffering from primary biliary cirrhosis are described. The 70-year-old woman had developed a primary biliary cirrhosis, verified by serological abnormalities (AMA positivity, elevated IgM levels) and by liver biopsy. The lung parenchyma displayed immature epithelioid granulomas and characteristics of a chronic organizing pneumonia.

IL-10 inhibits the synthesis of migration inhibitory factor and migration inhibitory factor-mediated macrophage activation.

IL-10, in addition to being a cytokine synthesis-inhibitory factor, is a cytokine that exerts multiple effects on various cell types. Recombinant human migration inhibitory factor (MIF) inhibits the migration of human monocytes as well as that of guinea pig and murine macrophages. In addition, it has recently been shown to activate human monocyte-derived macrophages to suppress the growth of and/or kill both intracellular parasites and extracellular tumor targets in vitro and to have adjuvant activity in vivo.

The major binding protein of the interferon antagonist sarcolectin in human placenta is a macrophage migration inhibitory factor.

The interferon antagonist and growth promotor sarcolectin has affinity for negatively charged carbohydrates. Isolation of cellular binding proteins will be a step to elucidate its physiological significance. Thus, resin-immobilized sarcolectin was employed as affinity ligand for chromatographic fractionation of extract from human placenta.

Recombinant migration inhibitory factor induces nitric oxide synthase in murine macrophages.

A recombinant form of migration inhibitory factor (MIF) obtained from COS-1 cells transfected with a cDNA library from a human T cell hybridoma is able to activate, in a dose-dependent manner, murine macrophages to express nitric oxide (NO) synthase and to produce high levels of NO in vitro. The time course of the induction of NO synthase is similar to that produced by the IFN-gamma. Enzyme activity peaks at 24 h and is undetectable by 72 h.

Inhibition of growth of Mycobacterium avium in murine and human mononuclear phagocytes by migration inhibitory factor.

Infections caused by Mycobacterium avium, the most common form of diseminated bacterial disease in AIDS patients, are difficult to treat because of their resistance to many antimycobacterial drugs. The results of the present study show that recombinant migration inhibitory factor, a 12-kDa molecule recently isolated by COS-1 cell expression screening of cDNA from a human T-cell hybridoma, has potent inhibitory activity on the growth of a panel of clinical isolates of M. avium within both bone-marrow-derived murine macrophages and cultured human blood monocytes.