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Biomedical subjects

M Shaw

Publications and source records attributed to M Shaw.

At least 73 records · Page 4Linked to original sources
PubMed1998

The activation of protein kinase B by H2O2 or heat shock is mediated by phosphoinositide 3-kinase and not by mitogen-activated protein kinase-activated protein kinase-2.

Protein kinase B (PKB) isoforms became activated [and glycogen synthase kinase-3 (GSK3) became inhibited] when mouse Swiss 3T3 fibroblasts were exposed to oxidative stress (H2O2) or heat shock, but not when they were exposed to osmotic shock (0.5 M sorbitol or 0. 7 M NaCl), chemical stress (sodium arsenite), the protein-synthesis inhibitor anisomycin, or UV radiation. In contrast, all seven stimuli activated mitogen-activated protein kinase-activated protein kinase-2 (MAPKAP-K2). The activation of MAPKAP-K2 was suppressed by the drug SB 203580, but not by inhibitors of phosphoinositide (phosphatidylinositide, PI) 3-kinase. In contrast, the activation of PKB isoforms and the inhibition of GSK3 by oxidative stress or heat shock were prevented by inhibitors of PI 3-kinase, but not by SB 203580. Thus the activation of PKB by oxidative stress or heat shock is mediated by PI 3-kinase and not by MAPKAP-K2. PKBalpha and PKBgamma were also activated by heat shock and oxidative stress in human embryonic kidney 293 cells and PKBgamma was activated by heat shock in NIH 3T3 cells; in each case activation was suppressed by inhibitors of PI 3-kinase. The activation of PKB isoforms by H2O2 may underlie some of the insulin-mimetic effects of this compound.

3T3 Cells↗
PubMed1998

Continuing high prevalence of HIV and risk behaviors among young men who have sex with men: the young men's survey in the San Francisco Bay Area in 1992 to 1993 and in 1994 to 1995.

Several recent studies have shown high rates of HIV infection and risk behavior among young men who have sex with men (MSM). To assess the direction of the epidemic in this population, we replicated a venue-based study performed in the San Francisco Bay Area during 1992 and 1993. From May 1994 to September 1995, we surveyed 675 MSM aged between 17 and 22. After statistical adjustment for age, ethnicity, residence, and site of recruitment, seroprevalence did not change significantly between the 1992 to 1993 (8.4%) and the 1994 to 1995 (6.7%) surveys. Similarly, no significant changes were found in the rates during the previous 6 months of unprotected receptive anal intercourse (23.4% versus 24.9%), injection drug use (8.0% versus 7.8%), or needle sharing among injection drug users (56.3% versus 64.5%) between the two surveys. Despite the increased attention that the problem of high risk behavior among young MSM has received, effective prevention interventions for MSM are needed as profoundly now as they had been several years ago.

Adolescent↗
PubMed1998

Interleukin 6 dependence of anti-DNA antibody production: evidence for two pathways of autoantibody formation in pristane-induced lupus.

Pristane induces a lupus-like syndrome in nonautoimmune mice characterized by the development of glomerulonephritis and lupus-associated autoantibodies. This is accompanied by overproduction of interleukin (IL)-6, a cytokine linked with autoimmune phenomena. The goal of this study was to evaluate the role of IL-6 in autoantibody production in pristane-induced lupus. BALB/cAn IL-6-deficient (-/-) and -intact (+/+) mice were treated with pristane or phosphate-buffered saline, and autoantibody production was evaluated. Pristane induced high levels of immunoglobulin (Ig)G anti-single-stranded DNA, -double-stranded (ds)DNA, and -chromatin antibodies in IL-6(+/+), but not IL-6(-/-) mice by enzyme-linked immunosorbent assay. High titer IgG anti-dsDNA antibodies also were detected in sera from +/+, but not -/-, mice by Crithidia luciliae kinetoplast staining. The onset of IgG anti-dsDNA antibody production in +/+ mice occurred >5 mo after pristane treatment, well after the onset of nephritis, suggesting that these antibodies are not directly responsible for inducing renal disease. In contrast to anti-DNA, the frequencies of anti-nRNP/Sm and anti-Su antibodies were similar in pristane-treated IL-6(-/-) and IL-6(+/+) mice. However, levels were higher in the +/+ group. These results suggest that IgG anti-DNA and chromatin antibodies in pristane-treated mice are strictly IL-6 dependent, whereas induction of anti-nRNP/Sm and Su autoantibodies is IL-6 independent. The IL-6 dependence of anti-DNA, but not anti-nRNP/Sm, may have implications for understanding the patterns of autoantibody production in lupus. Anti-DNA antibodies are produced transiently, mainly during periods of disease activity, whereas anti-nRNP/Sm antibody levels are relatively insensitive to disease activity. This may reflect the differential IL-6 dependence of the two responses.

Animals↗
PubMed1998

Lactic acid bacteria as antigen delivery vehicles for oral immunization purposes.

In vaccination programmes in which large numbers of subjects are involved, the oral route of administration is more convenient as compared to the more frequently used parenteral route. This is particularly relevant when vaccines are to be applied in less industrialized countries. Lactic acid bacteria in general and strains of Lactobacillus in particular have a variety of properties which make them attractive candidates for oral vaccination purposes, e.g. GRAS status, adjuvant properties, mucosal adhesive properties and low intrinsic immunogenicity. An overview is given of current research aimed at unravelling the relationship between structure and properties of surface proteins of lactobacilli and in vivo colonization, in particular of species capable of adhering to epithelial cells in vitro. Secondly, the state of the art will be discussed with respect to antigen presentation by lactic acid bacteria. Finally, some preliminary immunological data of recombinant lactic acid bacterial strains expressing antigens from pathogens will be presented.

Administration, Oral↗
PubMed1998

Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness.

An avian H5N1 influenza A virus (A/Hong Kong/156/97) was isolated from a tracheal aspirate obtained from a 3-year-old child in Hong Kong with a fatal illness consistent with influenza. Serologic analysis indicated the presence of an H5 hemagglutinin. All eight RNA segments were derived from an avian influenza A virus. The hemagglutinin contained multiple basic amino acids adjacent to the cleavage site, a feature characteristic of highly pathogenic avian influenza A viruses. The virus caused 87.5 to 100 percent mortality in experimentally inoculated White Plymouth Rock and White Leghorn chickens. These results may have implications for global influenza surveillance and planning for pandemic influenza.

Amino Acid Sequence↗
PubMed1998

An evaluation of the markers p53 and Ki-67 for their predictive value in prostate cancer.

BACKGROUND AND OBJECTIVES: p53 and Ki-67 are but two markers being evaluated for their predictive value in prostate cancer. The purpose of this study was to compare p53 and Ki-67 with age, stage, Gleason score, and ploidy for their prognostic abilities in prostate cancer. METHODS: Prostate cancer specimens from 134 patients were immunohistochemically stained for p53 and Ki-67 expression and differences evaluated by SPSS analysis of variance (ANOVA) methods. The dependent variable was patient survival and the independent variables were age, stage, Gleason score, and ploidy. RESULTS: In decreasing order of prediction of survival were stage (P < 0.001), Gleason score (P < 0.001), age (P = 0.1869), Ki-67 (P = 0.2284), p53 (P = 0.4282) and ploidy (P = 0.8141). CONCLUSION: It is concluded that stage and Gleason score are significant predictors of survival while p53, Ki-67, age and ploidy are not.

Aged↗
PubMed1998

Development of a digestive health status instrument: tests of scaling assumptions, structure and reliability in a primary care population.

BACKGROUND: The absence of valid and reliable health status measures for functional gastrointestinal illness has limited research and patient care for this common group of disorders. A self-report survey has been developed. METHODS: Initial development focused on extensive pre-testing of patients, primary care physicians and gastroenterologists. The disease-specific portion included the Rome criteria for dyspepsia subgroups and the Manning and Rome criteria for irritable bowel syndrome. The Short Form-36 was added. Psychometric analyses included techniques of multitrait scaling, scale internal consistency and criterion validation. RESULTS: Six hundred and ninety patients presenting to their primary care physician for treatment of heartburn, abdominal pain or discomfort completed the 98 question survey. The disease-specific portion revealed five components including reflux, dysmotility, a two-domain bowel dysfunction complex, and a pain index. Internal consistency measures demonstrated good to excellent reliability. Scaling successes were observed on multitrait scaling. The disease-specific portion was reduced to 34 questions. Criterion validity was demonstrated with the correlation of the disease-specific questions to the SF-36. CONCLUSIONS: The psychometric analyses lend credence to the concept of stomach and bowel symptom subgrouping as proposed by expert consensus. The psychometric properties of the five summated disease-specific scales compare favourably with standardized health status measures.

Adult↗
PubMed1998

Performance characteristics of a 'to and fro' disposable soda lime canister.

The performance of the Intersurgical disposable soda lime canister was compared to British Pharmacopoeia standards for carbon dioxide absorption and to other carbon dioxide absorber systems. This canister system more than adequately fulfilled the equivalent of the British Pharmacopoeia standard for CO2 absorption. It performed efficiently for over 3 h of continuous use, absorbing 200 ml.min-1 at varying combinations of tidal volume and ventilation rate. Efficiency was not dependent on close matching of tidal volume with canister volume and there was no channelling of gases. Heat was generated by the reaction between soda lime and CO2 and the maximum temperature recorded in the system was 42.1 degrees C. Under clinical conditions this should pose no threat of thermal injury to the patient.

Absorption↗
PubMed1998

Pituitary-adrenal, hormonal changes during induced hypotension with labetol or isoflurane for middle-ear surgery.

BACKGROUND: Pituitary-adrenal secretion during induced hypotension for middle-ear surgery has received little attention. Previous work failed to differentiate the effects of induced hypotension from surgical stimulation. We have undertaken a preliminary study examining the effects of hypotension, achieved with labetalol or isoflurane, on pituitary-adrenal secretion before, during and after middle-ear surgery. METHODS: Twenty-four patients were allocated randomly to 3 groups. The control group were anaesthetised with isoflurane, and normotension maintained for 30 min before hypotension was induced with isoflurane and surgery started. In the labetalol group, this drug was given i.v. to obtain a mean arterial pressure (MAP) of 60 mm Hg for 30 min before surgery and hypotension maintained with labetalol during the operation. In the isoflurane group, hypotension was induced to a MAP of 60 mm Hg for 30 min before surgery and continued throughout the procedure. All 3 groups received metoprolol i.v. before hypotension was established. Blood samples were collected before induction of anaesthesia, during anaesthesia alone (normotensive or hypotensive), surgery with hypotension, and recovery. They were analysed for adrenocorticotropic hormone (ACTH), arginine vasopressin (AVP), cortisol and aldosterone. RESULTS: Induced hypotension before surgery failed to stimulate release of ACTH, AVP and cortisol. No significant increase in these hormones occurred until the postoperative period. Aldosterone concentrations increased significantly during anaesthesia and hypotension in the labetalol and isoflurane groups (P<0.05) and continued to rise significantly in all 3 groups during surgery. However, there was no significant difference in aldosterone concentration before surgery between the control and the 2 hypotensive groups. CONCLUSION: ACTH, AVP and cortisol secretion were not stimulated by induced hypotension to MAP of 60 mm Hg before surgery. Increased aldosterone secretion occurred and a further study with a larger sample size is needed.

Adrenal Cortex Hormones↗
PubMed1998

Paclitaxel, bropirimine and linomide: effect on growth inhibition in a murine prostate cancer model by different growth regulatory mechanisms.

Paclitaxel, bropirimine and linomide therapy was evaluated in a murine prostate cancer model. All drugs were effective in impeding tumor growth but the mechanisms of action varied. Paclitaxel inhibited bcl-2 expression suggesting an apoptotic mechanism. Bropirimine, while inhibiting bcl-2 expression also significantly depressed tumor necrosis factor-alpha (TNF-alpha) expression. In the bropirimine treated group there was also a correlation between angiogenesis and cyclin D expression. Finally, linomide significantly decreased angiogenesis. Since the mechanism of action of these drugs differ, combining them at lower doses might maintain therapeutic efficacy while reducing toxicity.

Animals↗
PubMed1998

Expression of the sialosyl-Tn epitope on CD45 derived from activated peripheral blood T cells.

The cell surface protein tyrosine phosphatase CD45 is a major target of IgM anti-T cell autoantibodies in systemic lupus erythematosus (SLE). The autoreactive determinants on CD45 are O-linked glycans expressed on activated T cells and certain T cell lines, rather than linear or conformational polypeptide epitopes or N-linked glycans. To identify oligosaccharide structures that may play a role in the functional interactions of CD45 or are candidate target epitopes of SLE anti-CD45 autoantibodies, autoreactive CD45 purified from Jurkat T cells and non-autoreactive CD45 purified from CLL B cells were tested by ELISA for expression of mucin-type O-glycan structures. Monoclonal antibodies (mAbs) directed against blood group A, type 1 H chains, type 2 H chains, T, Le(a), sialylated-Le(a), Le(b), sialylated-Le(c), Le(x), sialylated-Le(x), multi-fucosylated Le(x), Le(y), and sialylated-extended Le(v) failed to react with CD45 from either B cells or T cells. However, mAbs directed against Tn (galNAcalpha1-->O-ser/thr) or sialosyl-Tn (neuNAcalpha2-6gaINAcalpha1-->O-ser/thr) structures reacted with CD45 derived from Jurkat T cells, but not from CLL B cells. Anti-Tn mAbs also reacted in western blotting procedures with CD45 isolated from Jurkat T cells, but did not react with CD45 isolated from CEM, MOLT-3, or PEER T cells; Daudi, Raji, or CLL B cells; or resting or Con A-activated PBL. However, anti-sialosyl-Tn mAbs stained blots of CD45 isolated from Jurkat and CEM T cells and Con A-activated PBL, a pattern of reactivity similar to that of the anti-CD45 autoantibodies. Flow cytometric analyses demonstrated that the sialosyl-Tn epitopes are expressed on a subpopulation of CD4 +/CD8- T cells.

Antibodies, Monoclonal↗