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Biomedical subjects

M Tsang

Publications and source records attributed to M Tsang.

48 records · Page 3Linked to original sources
PubMed1991

Altered cytokine release in peripheral blood mononuclear cell cultures from patients with the chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is an idiopathic illness associated with a variety of immunologic abnormalities. To investigate potential pathogenetic mechanisms, we evaluated serum levels and peripheral blood mononuclear cell (PBMC) production of selected cytokines and immunoglobulins. Serum bioactive transforming growth factor beta (TGF-beta) levels were higher (P less than 0.01) in patients with CFS (290 +/- 46 pg/mL) than in control subjects (104 +/- 18 pg/mL), but levels of other cytokines tested were not different. Lipopolysaccharide-stimulated release of interleukin 1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha was increased (P less than 0.05) in PBMC cultures from patients with CFS versus control subjects; enhanced (P less than 0.01) IL-6 release to phytohemagglutinin was also observed. In contrast, TGF-beta release in response to lipopolysaccharide was depressed (P less than 0.01) in PBMC cultures derived from patients with CFS. No differences in IL-2 and IL-4 or immunoglobulin production were observed. The enhanced release of inflammatory cytokines by stimulated PBMC from patients with CFS suggests that these cells are primed for an increased response to immune stimuli. These data also suggest an association between abnormal regulation of TGF-beta production in vivo and in vitro with the immunologic consequence of CFS.

Cytokines↗
PubMed1991

Activities of various macrolide antibiotics against Mycobacterium leprae infection in mice.

We evaluated the activities of several macrolide antibiotics against M. leprae infections in mouse footpads. Erythromycin and azithromycin were inactive, while both roxithromycin and clarithromycin were found to be consistently active and, in fact, bactericidal. By both methods, clarithromycin was found to be superior to roxithromycin, a finding which, at least in part, may be a consequence of the higher levels of clarithromycin at the site of infection.

Animals↗
PubMed1991

Effect of low-level and intermittent minocycline therapy on the growth of Mycobacterium leprae in mice.

We evaluated the minimal concentrations of minocycline in the diet and in serum required to inhibit the growth of seven Mycobacterium leprae isolates in mice. Minocycline concentrations of 0.01 and 0.04% in the diet, which resulted in levels in serum of less than or equal to 0.17 and 0.51 microgram/ml, respectively, were consistently and completely inhibitory. Even 0.004% dietary minocycline (levels in serum, less than or equal to 0.08 microgram/ml) partially inhibited five of these strains, while 0.001% minocycline was consistently inactive. For five of these isolates, minocycline at a concentration of 0.04% in the diet given 3 days (Monday, Wednesday, Friday) and 1 day weekly completely inhibited the growth of M. leprae, and minocycline given even 1 day monthly was partially inhibitory for three of these five M. leprae isolates.

Animals↗
PubMed1990

Effective vaccination of mice against leprosy bacilli with subunits of Mycobacterium leprae.

Model vaccines against leprosy bacilli have consisted of nonvirulent, live, attenuated Mycobacterium bovis BCG and irradiated, heat-killed, or autoclaved intact M. leprae. We report that immunization with various cell wall fractions of M. leprae, progressively depleted of lipids, carbohydrates, and soluble proteins, as well as a partially purified protein(s) derived from a pellet fraction of sonicated M. leprae, conferred significant protection against subsequent infection with live leprosy bacilli. Moreover, lymphocytes from regional lymph nodes and spleens of mice immunized with these M. leprae-derived subunits responded by proliferation when stimulated with M. leprae in vitro. Our results provide the first evidence that vaccination with M. leprae-derived fractions protects mice against leprosy bacilli.

Animals↗
PubMed1990

Primary dapsone-resistant Hansen's disease in California. Experience with over 100 Mycobacterium leprae isolates.

We found that in the years 1978 through 1981 only one of 54 previously untreated patients with Hansen's disease was found to harbor dapsone-resistant Mycobacterium leprae. That single strain was only partially resistant, ie, it was resistant to 0.0001% dapsone in a mouse diet but not to higher concentrations. During the years 1983 through 1988, M leprae from 47 previously untreated patients presenting to clinics in San Francisco, Calif, and Los Angeles, Calif, grew in mice. None of these strains was found to be dapsone resistant. Thus, from 1978 through 1988 only one of 101 M leprae isolates obtained from skin biopsy specimens from patients with leprosy was found to be resistant to dapsone. We have concluded that primary dapsone resistance still does not appear to be a significant problem in California. Owing to the fact that our single resistant case and those reported from international sources are, in general, partially resistant, the potential importance of partial dapsone resistance is discussed.

Adolescent↗
PubMed1988

Noninvasive measurement of tissue carbon dioxide tension using a fiberoptic conjunctival sensor: effects of respiratory and metabolic alkalosis and acidosis.

To evaluate potential clinical applications of a newly developed, noninvasive fiberoptic conjunctival carbon dioxide (PcjCO2) sensor designed to measure continuously tissue PCO2 in a vascular bed supplied by the internal carotid artery, we studied the effects of graded respiratory and metabolic alkalosis and acidosis on PcjCO2 in a hemodynamically stable canine model. Respiratory changes were induced by varying the frequency of ventilation and metabolic changes were induced by incremental infusions of sodium bicarbonate and hydrochloric acid. Continuous measurement of end-tidal carbon dioxide tension (PETCO2) was also performed. During respiratory alkalosis and acidosis, PcjCO2 values correlated well with PaCO2 (r = 0.96, n = 106); linear regression analysis of PcjCO2 vs. PaCO2 produced a slope of 1.01 and a y-intercept of 3.94 over a PaCO2 range of 12 to 76 torr. The mean PcjCO2-PaCO2 gradient was 4 +/- 3 (SD) torr. PETCO2 values also correlated well with PaCO2 (r = 0.91), as well as with PcjCO2 values (r = 0.91). Both PcjCO2 and PETCO2 showed a much weaker correlation with PaCO2 during metabolic alkalosis and acidosis, partly because the variation in PaCO2 was less. Moreover, the PcjCO2-PaCO2 gradient increased during the metabolic portion of the study up to a mean of 10 +/- 8 (SD) torr during metabolic acidosis, implying a build-up and/or lack of washout of CO2 from the conjunctival tissues, despite the normal physiologic range of PaCO2 values. We conclude that in a hemodynamically stable canine model, PcjCO2 and PETCO2 values correlate well with PaCO2 during pure respiratory alkalosis and acidosis; the correlation weakens significantly, however, with metabolic alterations in tissue CO2 levels.

Acidosis, Respiratory↗
PubMed1985

Continuous monitoring of tissue pH with a fiberoptic conjunctival sensor.

To assess the relationship between conjunctival pH (pHcj), arterial pH (pHa), and cardiorespiratory variables during normal and low-flow conditions, hemorrhagic hypotension was induced in eight dogs. Conjunctival pH became significantly less than control values after a hemorrhage volume of 15 mL/kg (P less than .05); mean arterial pressure (MAP) did not fall until blood loss was 20 mL/kg. There was poor correlation between pHcj and pHa, cardiac index (CI), or MAP. There was a high degree of correlation, however, between pHcj-pHa difference (delta pH) and MAP (r = -0.886), CI (r = -0.846), and tissue oxygen extraction ratio (r = .896). The results of these experiments indicate that pHcj is a sensitive monitor of peripheral tissue perfusion, and that the degree of physiologic compromise associated with hemorrhage can be determined by analysis of the difference between arterial and conjunctival pH.

Animals↗
PubMedDate not supplied

Wnt-mediated relocalization of dishevelled proteins.

The Wnt family of proto-oncogenes encodes secreted signaling proteins that are required for mouse development. The Drosophila Wnt homolog, the wingless (Wg) segment polarity gene, mediates a signal transduction pathway in which the downstream elements appear to be conserved through evolution. One such element, the dishevelled gene product, becomes hyperphosphorylated and translocates to the plasma membrane in response to Wg (Yanagawa et al., 1995). We report here that the mouse Dishevelled-1 (Dvl-1) and Dishevelled-2 genes encode proteins that are differentially localized in Wnt-overexpressing PC12 cell lines (PC12/Wnt). Whereas Dvl-1 and Dvl-2 proteins are limited to the soluble fraction of parental PC12 cells, PC12/Wnt cells display a subset of Dvl-1 protein associated with the membrane and Dvl-2 protein with the cytoskeletal fraction. These results suggest a conserved role for Dvl in Wnt/wg signal transduction.

Adaptor Proteins, Signal Transducing↗
PubMedDate not supplied

Transforming growth factor-beta protects human neurons against beta-amyloid-induced injury.

Deposition of amyloid fibrils in the brain is a histopathologic hallmark of Alzheimer disease (AD) and beta-amyloid protein (A beta), the principal component of amyloid fibrils, has been implicated in the neuropathogenesis of AD. In the present study, we first developed an in vitro model of A beta-induced neurodegeneration using human fetal brain-cell cultures and then tested the hypothesis that cytokines modulate A beta-induced neurodegeneration. When brain-cell cultures were exposed to A beta, marked neuronal loss (60% of neurons by microscopic assessment) and functional impairment (i.e., reduction in uptake of [3H]gamma-aminobutyric acid) were observed after 6 d of incubation. A beta-induced neurodegeneration was dose-dependent with maximal effect at 100 microM. Although interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-alpha had a nominal effect, both the beta 1 and beta 2 isoforms of transforming growth factor-beta dose-dependently protected > 50% of neurons against A beta-induced injury. IL-4 also proved to be neuro-protective. A beta-induced neurodegeneration was accompanied by microglial cell proliferation and enhanced release of IL-1, IL-6, and TNF-alpha. These findings are consistent with the emerging concept that AD is an inflammatory disease and may lead to new therapeutic strategies aimed at reducing A beta-induced neurotoxicity.

Amyloid beta-Peptides↗
PubMedDate not supplied

The roles of IL-4, TGF-beta and LPS in IgA switching.

CH12.LX B cells have been used as a lymphoma model of MHC restricted, antigen-dependent B cell differentiation. These B cells express surface IgM and secrete IgM. Most recently we have demonstrated that CH12.LX is a model of cytokine driven IgA differentiation. Recently, transforming growth factor beta (TGF-beta) has been shown to be a probable switch factor for IgA in LPS-stimulated mouse lymphocytes, therefore we chose CH12.LX B cells to study the effect of IL-4, TGF-beta and LPS in IgA isotype switching. Adding TGF-beta to the monoclonal cell line CH12.LX results in induction of mIgA expression but no enhancement of IgA secretion similar to the effect of IL-4. The addition of LPS serves as a non-specific stimulus to enhance the secretion of the expressed immunoglobulin, but has no IgA specific activity of its own. IL-4 and TGF-beta together are synergistic for mIgA expression. Pretreatment studies show that TGF-beta added after IL-4 is the same as TGF-beta alone whereas the converse is the same as adding both cytokines together. TGF-beta acts by increasing the steady state levels of alpha message, whereas northern analysis indicates that IL-4 does not induce alpha message the way TGF-beta does. These data confirm that TGF-beta by itself is an isotype switch factor for IgA. In addition, IL-4 and TGF-beta cause mIgA expression through different mechanisms. CH12.LX B cells serve as a valuable model to study the role of multiple signals required for mIgA expression and IgA secretion.

Animals↗