TRAM regulates the exposure of nascent secretory proteins to the cytosol during translocation into the endoplasmic reticulum

Translocational pausing is a mechanism used by certain specialized secretory proteins whereby discrete domains of a nascent chain destined for the endoplasmic reticulum lumen are transiently exposed to the cytosol. Proteoliposomes reconstituted from total endoplasmic reticulum proteins properly assemble translocationally paused intermediates. The capacity of the translocon to correctly pause the nascent chain is dependent on a glycoprotein fraction whose active component is TRAM. In the absence of TRAM, the normally sealed ribosome-membrane junction still opens in response to a pause transfer sequence. However, nascent chain domains that are not exposed to the cytosol in the presence of TRAM are so exposed in its absence. Thus, TRAM regulates which domains of the nascent chain are visible to the cytosol during a translocational pause.     

Tuberculosis and iron overload in Africa: a review

Both pulmonary tuberculosis and dietary iron overload are common conditions in sub-Saharan Africa. The incidence of tuberculosis has increased markedly over the last decade, primarily as a result of the rapid spread of infection with the human immunodeficiency virus (HIV). Dietary iron overload affects up to 10% of adults in rural populations and is characterized by heavy iron deposition both in parenchymal cells and in macrophages. Mycobacterium tuberculosis grows within macrophages and, at the same time, the antimicrobial function of macrophages is important in the body's defence against tuberculosis. In vitro, the loading of macrophages with iron reduces the response of these cells to activation by interferon-gamma and diminishes their toxicity against micro-organisms. In the clinical setting, dietary iron overload appears to increase the risk for death from tuberculosis even in the absence of the acquired immunodeficiency syndrome. The combination of dietary iron overload and infection with the HIV, with impaired function of both macrophages and T-cells, may make patients especially vulnerable to tuberculosis. It is possible that the prevention and treatment of dietary iron overload could contribute to the control of tuberculosis in African populations.     

Anti-MOC-31: a potential addition to the pulmonary adenocarcinoma versus mesothelioma immunohistochemistry panel

MOC-31 expression has recently been advocated as an immunohistochemical marker for distinguishing mesothelioma from adenocarcinoma in tissue sections. We studied formalin-fixed, paraffin-embedded tissue from 23 pleural mesotheliomas and 23 primary pulmonary adenocarcinomas for immunoreactivity with anti-MOC-31, a human epithelial-related antigen. All of the 23 adenocarcinomas strongly expressed the marker, whereas only one of the mesotheliomas showed weak reactivity. These results demonstrate the usefulness of anti-MOC-31 in differentiating pulmonary adenocarcinoma from mesothelioma.     

Production of tumor necrosis factor (TNF) by macrophages and T-lymphocytes of rodents as affected by acute gamma-irradiation

BACKGROUND: The current classification dividing patients with functional gastrointestinal symptoms into subgroups remains controversial. AIMS: To determine whether distinct symptom groupings exist in the community. METHODS: A random sample of Sydney residents in Penrith, Australia was mailed a validated self report questionnaire. Gastrointestinal symptoms including the Rome criteria for irritable bowel syndrome (IBS) and dyspepsia were measured. RESULTS: Among 730 respondents, the 12 month age and gender adjusted prevalence (adjusted to the Australian population) of IBS, dyspepsia, and gastro-oesophageal reflux were 11.8% (95% confidence interval (CI) 9.3 to 14.3%), 11.5% (95% CI 9.6 to 14.6%), and 17.5% (95% CI 14.2 to 19.9%), respectively. In total, 60% of the population reported four or more gastrointestinal symptoms. There was considerable overlap of IBS with dyspepsia and among the dyspepsia subgroups by application of the Rome criteria. Independently, 10 symptom groupings were identified by factor analysis. The underlying constructs measured by these factors were generally the major abdominal syndromes recognised by the Rome classification: dyspepsia, IBS, reflux, painless constipation, painless diarrhoea, and bloating, in addition to a number of more specific symptom groupings. CONCLUSION: Gastrointestinal symptoms are common and overlap in the community, but distinct upper and lower abdominal symptom groupings can be identified.     

Antibacterial and antifungal activity of aromatic constituents of essential oils

Five aromatic constituents of essential oils (cineole, citral, geraniol, linalool and menthol) were tested for antimicrobial activity against eighteen bacteria (including Gram-positive cocci and rods, and Gram-negative rods) and twelve fungi (three yeast-like and nine filamentous). In terms of antibacterial activity linalool was the most effective and inhibited seventeen bacteria, followed by cineole, geraniol (each of which inhibited sixteen bacteria), menthol and citral aromatic compounds, which inhibited fifteen and fourteen bacteria, respectively. Against fungi the citral and geraniol oils were the most effective (inhibiting all twelve fungi), followed by linalool (inhibiting ten fungi), cineole and menthol (each of which inhibited seven fungi) compounds.     

Whole body nitric oxide synthesis in healthy men determined from [15N] arginine-to-[15N]citrulline labeling

The rates of whole body nitric oxide (NO) synthesis, plasma arginine flux, and de novo arginine synthesis and their relationships to urea production, were examined in a total of seven healthy adults receiving an L-amino acid diet for 6 days. NO synthesis was estimated by the rate of conversion of the [15N] guanidino nitrogen of arginine to plasma [15N] ureido citrulline and compared with that based on urinary nitrite (NO2-)/nitrate (NO3-) excretion. Six subjects received on dietary day 7, a 24-hr (12-hr fed/12-hr fasted) primed, constant, intravenous infusion of L-[guanidino-15N2]arginine and [13C]urea. A similar investigation was repeated with three of these subjects, plus an additional subject, in which they received L-[ureido-13C]citrulline, to determine plasma citrulline fluxes. The estimated rates (mean +/- SD) of NO synthesis over a period of 24 hr averaged 0.96 +/- 0.1 mumol .kg-1.hr-1 and 0.95 +/- 0.1 mumol.kg-1.hr-1, for the [15N]citrulline and the nitrite/nitrate methods, respectively. About 15% of the plasma arginine turnover was associated with urea formation and 1.2% with NO formation. De novo arginine synthesis averaged 9.2 +/- 1.4 mumol. kg-1.hr-1, indicating that approximately 11% of the plasma arginine flux originates via conversion of plasma citrulline to arginine. Thus, the fraction of the plasma arginine flux associated with NO and also urea synthesis in healthy humans is small, although the plasma arginine compartment serves as a significant precursor pool (54%) for whole body NO formation. This tracer model should be useful for exploring these metabolic relationships in vivo, under specific pathophysiologic states where the L-arginine-NO pathway might be altered.     

Peripheral blood from human immunodeficiency virus type 1-infected patients displays diminished T cell generation capacity

An organ culture chimera system was used to assess the effect of human immunodeficiency virus type 1 (HIV-1) infection on the T cell-generation capacity of precursors derived from human peripheral blood. Peripheral blood mononuclear cells from HIV-1-infected patients and uninfected controls were placed on fetal thymus lobes of NOD/LtSz-scid/scid mice. Blood from the HIV-1-infected patients consistently produced fewer CD4 and CD8 cells compared with blood from controls (P < .01). Addition of zidovudine to the cultures did not alter this profile. Limit dilution experiments suggested that there were fewer functional precursors in the infected patients. These results were not dependent on the patient's level of peripheral CD4 cells; even samples from patients with normal CD4 cell counts were unable to generate T cells in organ cultures. The results are consistent with a loss in the capacity of HIV-1-infected patients to produce functional T cell progenitors in their peripheral blood.