Interactions between nitric oxide and arachidonic acid in lung epithelial cells: possible roles for peroxynitrite and superoxide

This study investigated interactions between nitric oxide synthesis and phospholipase A2 (PLA2) activation in lung epithelial cells. Nitrite formation, inducible nitric oxide synthase expression, and [3H]arachidonic acid (AA) release were determined following treatment with: (1) the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methyl esther (L-NAME) and aminoguanidine; (2) arachidonyl trifluoromethyl ketone (AACOCF3), a specific cytosolic PLA2 inhibitor; (3) S-morpholinosydnonimine (SIN-1), a nitric oxide donor which provokes peroxynitrite formation; (4) trolox, a free radical scavenger, and (5) the AA release agonists calcium ionophore, phorbol 12-myristate 13-acetate, and sodium vanadate. The results demonstrated that (1) L-NAME and aminoguanidine inhibited agonist-induced AA release by 40 and 65%, respectively; (2) AACOCF3 inhibited nitrite formation and inducible nitric oxide synthase expression in a dose-dependent manner; (3) SIN-1, together with AA release agonists, significantly increased the AA output, and (4) trolox counteracted the SIN-1 effects. Our results demonstrate cross talk between nitric oxide synthase and PLA(2) pathways, with a possible intermediary role for peroxynitrite and superoxide.     

Procedures for the analysis of differential item functioning (DIF) for small sample sizes

An item with differential item functioning (DIF) displays different statistical properties, conditional on a matching variable. The presence of DIF in measures can invalidate the conclusions of medical outcome studies. Numerous approaches have been developed to examine DIF in many areas, including education and health-related quality of life. There is little consensus in the research community regarding selection of one best method, and most methods require large sample sizes. This article describes some approaches to examine DIF with small samples (e.g., less than 200).     

Risk of tuberculosis in correctional healthcare workers

OBJECTIVE: The objective of this study was to determine the prevalence, incidence, and risk factors for occupational infection with tuberculosis among healthcare workers employed in correctional facilities. METHODS: The authors conducted a self-administered survey, clinical interview, and tuberculin skin testing. RESULTS: The overall tuberculin skin test point prevalence rate was 17.7%, the reactivity rate was 2.2%, and the annual incidence was 1.3%. At the multivariate level, after controlling for bacille Calmette-Guérin vaccination, only origin of birth remained significantly associated with prevalence of tuberculosis infection. CONCLUSIONS: Although the prevalence of tuberculin reactivity was high in this population, the risk factors were predominantly demographic rather than occupational. Nevertheless, continued vigilance to control occupational exposure to this and other respiratory pathogens is warranted, given the potential for future outbreaks of tuberculosis, as well as other known and emerging airborne pathogens.     

High-resolution serum proteomic profiling of Alzheimer disease samples reveals disease-specific, carrier-protein-bound mass signatures

BACKGROUND: Researchers typically search for disease markers using a "targeted" approach in which a hypothesis about the disease mechanism is tested and experimental results either confirm or disprove the involvement of a particular gene or protein in the disease. Recently, there has been interest in developing disease diagnostics based on unbiased quantification of differences in global patterns of protein and peptide masses, typically in blood from individuals with and without disease. We combined a suite of methods and technologies, including novel sample preparation based on carrier-protein capture and biomarker enrichment, high-resolution mass spectrometry, a unique cohort of well-characterized persons with and without Alzheimer disease (AD), and powerful bioinformatic analysis, that add statistical and procedural robustness to biomarker discovery from blood. METHODS: Carrier-protein-bound peptides were isolated from serum samples by affinity chromatography, and peptide mass spectra were acquired by a matrix-assisted laser desorption/ionization (MALDI) orthogonal time-of-flight (O-TOF) mass spectrometer capable of collecting data over a broad mass range (100 to >300,000 Da) in a single acquisition. Discriminatory analysis of mass spectra was used to process and analyze the raw mass spectral data. RESULTS: Coupled with the biomarker enrichment protocol, the high-resolution MALDI O-TOF mass spectra provided informative, reproducible peptide signatures. The raw mass spectra were analyzed and used to build discriminant disease models that were challenged with blinded samples for classification. CONCLUSIONS: Carrier-protein enrichment of disease biomarkers coupled with high-resolution mass spectrometry and discriminant pattern analysis is a powerful technology for diagnostics and population screening. The mass fingerprint model successfully classified blinded AD patient and control samples with high sensitivity and specificity.     

Lithium in children of lithium-responding parents

Six offspring of manic-depressive patients, whose parents were lithium responders, were selected on the basis of their incapacitating psychopathology for treatment with lithium. The children ranged in age from 6 to 12. A double-blind, crossover design was used over 16–18 weeks. Weekly ratings were done, and average evoked potentials (EPs) were measured at each crossover. Two children diagnosed as having a bipolar affective disorder had a clear-cut response to lithium and were strong augmenters on the EP. This, taken together with the similarity of the EP changes on lithium to those occurring in adult patients treated with lithium, supports a physiological parallel between bipolar affective illness in adults and children.     

Functional deletion of different Ly-1 T-cell-inducer subset activities by Ly-2 suppressor T lymphocytes.

T-suppressor-cell activity was analyzed by use of an intermediate culture system that allows the study of T-cell interactions in the absence of concomitant inducer effects on B cells. Activated suppressor T cells were incubated with their potential target cells [immune Ly-1+,Ly-2- (Ly-1) cells] for 24-48 hr, and then the Ly-1 cells were reisolated by removing the suppressor cells with an appropriate antiserum (Ly-2). The functional consequences of the interactions that occurred during the incubation period were then assessed. Suppressor cells deleted the functional activity of two inducer-T-cell subsets; the helper T cell, which induces B-cell production of antibody, and the T cell that induces Ly2+ T suppressor cells. This latter activity is more sensitive to suppression than is the former. As suppressor T cells inactivate the cells that are responsible for their activity (i.e., their specialized Ly-1 inducer cells), a form of negative regulation of suppressor-T-cell activity, in which the down regulation of suppressor cells is effected by their removal of their own inducer cells, can be postulated. In addition, these findings show that clonal deletion and active suppression need not be mutually exclusive mechanisms of immune unresponsiveness. Suppressor cells can produce a functional deletion of immune activity that persists after they themselves are removed, for example, by antisera, or in physiological situations by the negative form of regulation postulated.