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Biomedical subjects

M Shaw

Publications and source records attributed to M Shaw.

At least 37 records · Page 2Linked to original sources
PubMed1999

Role of protein kinase B and the MAP kinase cascade in mediating the EGF-dependent inhibition of glycogen synthase kinase 3 in Swiss 3T3 cells.

Epidermal growth factor (EGF), insulin-like growth factor 1 (IGF1) and phorbol myristate acetate (PMA) induce the inhibition of glycogen synthase kinase 3 (GSK3) by stimulating the phosphorylation of an N-terminal serine. Here, we show that protein kinase B (PKB) plays a key role in mediating EGF-induced inhibition of GSK3alpha and that the classical MAP kinase (MAPK) cascade has two functions in this process. Firstly, it makes a transient contribution to EGF-induced inhibition of GSK3alpha. Secondly, it shortens the duration of PKB activation and GSK3alpha inhibition. In contrast, PKB alone mediates the IGF1-induced inhibition of GSK3alpha, while the MAPK cascade mediates the inhibition of GSK3alpha by PMA.

3T3 Cells↗
PubMed1999

The anesthetic record: accuracy and completeness.

PURPOSE: To evaluate if anesthesia training and experience influenced chart completion and accuracy. METHODS: One hundred and twenty-four subjects, including medical students, anesthesia residents and community and university based clinical anesthesiologists, were given a standardized patient in a simulator environment and asked to conduct induction and maintenance of anaesthesia. Three critical events were introduced resulting in changes in BP, HR, PETCO2 and SpO2. Subjects were instructed to manage the patient and the anesthetic chart, as was their customary practice. Discrepancy, calculated as the difference between the actual and charted values divided by the actual physiological value was compared by level of training with a two-way repeated measures analysis of variance (ANOVA) for all four physiological variables. The completeness of charting, defined as at least one data point recorded for each of the four physiological variables of the three critical events, was compared across level of training, age of participants and number of years in practice. RESULTS: The overall completeness of charting remained low (< 37%) with no relationship based on the anesthesiologist's age, level of training or number of years in practice. There was discrepancy in charting for all physiological variables (HR, BP, PETCO2 and SpO2, P < 0.0001), with a marked difference in the degree of discrepancy within each level of training. Training resulted in no differences in charting discrepancy. CONCLUSION: Charting of data to the anesthetic record remained incomplete and inaccurate in all groups based on level of training, age and number of years in practice.

Adult↗
PubMed1999

Clinical application of a new disposable lithotripter: a prospective multicenter study.

BACKGROUND: Mechanical lithotripsy has become a well-accepted method of bile duct stone fragmentation and removal. The Olympus lithotripter (Olympus American, Melville, NY) is the standard reusable lithotripter at the institutions that participated in this study. A disposable device with a preassembled pistol grip may perform equally well and facilitate operation. METHODS: Twenty patients with bile duct stones were evaluated as part of a multicenter prospective study. Data were obtained regarding stone size and number, bile duct diameter, and configuration, ease of cannulation, basket function, stone capture and crushing success, and complications. RESULTS: The maximum stone size averaged 16.5 +/- 1.2 mm (range 10 to 30 mm). Sixteen patients had multiple stones (median 5, range 2 to 12). The mean bile duct diameter was 20.5 +/- 1.5 mm (range 12 to 38 mm). Cannulation was successful in all within 5 attempts. Basket deployment failed in 1 patient because of stone size and the basket was misshapen in 14. Bile duct clearance was complete in 16 subjects (80%), incomplete in 2 patients, and failed in 2 patients. Abnormal duct configuration (sigmoid, stricture) was noted in 2 of 4 patients with failed capture and 7 of 16 patients with successful clearance. No statistically significant difference was observed between the bile duct diameter, maximum stone size, number of stones, and successful clearance. CONCLUSION: The disposable lithotripter is easy to use and, compared with the published results for the reusable lithotripter, performs almost as well.

Adult↗
PubMed1999

Mortality and migration in Britain, first results from the British Household Panel Survey.

This study investigates the extent to which current geographical variations in mortality are influenced by patterns of migration since birth. It is based on a longitudinal study of migrants which consists of a representative sample of 10264 British residents born after 1890 and enumerated as part of the British Household Panel Study in 1991. Between 1991 and 1996, 527 of the study members died and these deaths were analysed by area of residence at birth and in 1991 at both the regional and local district geographical scales. These were compared with findings from the Office for National Statistics Longitudinal Study. The British Household Panel Survey sample replicates the results of work conducted on the Longitudinal Study which finds that geographical variations in age-sex standardised mortality ratios at the regional scale cannot be attributed to selective migration. However, for the British Household Panel Survey sample, the major geographical variations at district level could be attributed to selective migration. Geographical variations in mortality are not well understood. Restrictions on what it is possible to analyse in the Office for National Statistics Longitudinal Study may have resulted in the underestimation of the importance of local lifetime selective migration in producing the contemporary map of mortality variation across Britain. The British Household Panel Survey is a small, recent, but very flexible study, which can be used to investigate the effects of lifetime migration on mortality patterns for all of Britain. This first report of its results on mortality shows that it produces findings which accord with the much larger Longitudinal Study, but which can be taken further to show that selective migration over the whole life-course at the local level does appear to have significantly altered the geographical pattern of mortality seen in Britain today.

Age Factors↗
PubMed1999

Perioperative management of selected problems in patients with rheumatic diseases.

Patients undergoing surgery are subject to multiple perioperative problems. This article reviews several issues that occur in surgical patients with rheumatic diseases, including management of medications, diagnosis of fat embolism syndrome, prophylaxis against endocarditis, postoperative fever, and perioperative myocardial infarction.

Embolism, Fat↗
PubMed1999

Where the poor die in a rich city: the case of Oxford.

Research to date has established that there is a relationship between high mortality rates and area deprivation in Britain. However, the majority of this research has looked at the regional level and the few studies that have looked at a smaller area level have tended to focus on London or the North. At a national level a relationship between housing tenure and mortality has also been found. This paper considers the relationship between mortality and place and in particular housing, at ward level in a city in the South East of England. It is found that, in Oxford, there is no straightforward relationship between housing tenure and mortality rates. Rather, it is pockets of poverty within Oxford, expressed in different types of housing, that are associated with high mortality rates. Whilst the very poorest live in the worst quality and least preferred housing, the extent of this relationship is likely to differ in different areas, according to the historical and current patterns of housing provision. A method of identifying such areas nationally is needed, as a reliance on national studies, particular those on tenure, is likely to obscure the true picture and extent of geographical inequalities in health.

Adolescent↗
PubMed1999

Expression of the protective antigen of Bacillus anthracis by Lactobacillus casei: towards the development of an oral vaccine against anthrax.

Bacillus anthracis is the causative organism of the disease anthrax. The ability of the organism to form resistant spores and infect via the aerosol route has led to it being considered as a potential biological warfare agent. The current available human vaccines are far from ideal, they are expensive to produce, require repeated doses and may invoke transient side-effects in some individuals. There is also evidence to suggest that they may not give full protection against all strains of B. anthracis. A new generation of anthrax vaccine is therefore needed. The use of Lactobacillus as a vector for expression of heterologous proteins from pathogens supplies us with a safe system, which can be given orally. Lactobacilli are commensals of the gut, generally regarded as safe and have intrinsic adjuvanticity. Oral vaccines may stimulate the mucosol immune system to produce local IgA responses in addition to systemic responses. These vectors are delivered at the mucosal surface, the site where the infection actually occurs and where the first line of defence lies. The gene encoding the protective antigen (PA) of B. anthracis, an immunogenic non-toxic component of the two toxins produced, is being cloned into different homologous vectors and subsequently transformed to various Lactobacillus strains. High intracellular expression levels for the PA in Lact. casei were achieved. Mucosal antigen presentation and humoral and cellular immune responses following immunization with transformants expressing PA in various ways (intracellular, surface-anchored and extracellular) are being studied.

Administration, Oral↗
PubMed1999

Pseudosubluxation of C2 on C3 in polytraumatized children--prevalence and significance.

AIM: Pseudosubluxation of C2 on C3 is a recognized physiological variant in the upper cervical spine radiographs of normal children. The aim of this study was to determine the prevalence of this variant in children admitted with serious polytrauma, and to explore its significance in this setting. PATIENTS AND METHODS: A retrospective review was performed of 138 patients under 16 years of age admitted with polytrauma via The Helicopter Emergency Medical Service. All patients wore hard collars and underwent immediate horizontal beam lateral cervical spine radiography. Normal and C2/C3 pseudosubluxation groups were defined using standard criteria. The two groups were compared in terms of age, presence of an endotracheal tube, injury severity, and outcome. RESULTS: There were 108 (78.3%) children in the normal group and 30 (21.7%) in the C2/C3 pseudosubluxation group. No significant differences in sex ratio, intubation status, injury severity, or outcome were found. Patients in the pseudosubluxation group were significantly younger. CONCLUSION: In paediatric polytrauma it is essential to establish the integrity of the cervical spine promptly as this will deter unnecessary further imaging and investigation. In our study 21.7% of cases had C2/C3 pseudosubluxation on admission radiographs. We have shown that C2/C3 pseudosubluxation has no significant association with intubation status, injury severity, or outcome. We conclude that C2/C3 pseudosubluxation can be considered a benign variant even in the setting of polytrauma.

Adolescent↗
PubMed1999

Immunopathogenesis of environmentally induced lupus in mice.

Systemic lupus erythematosus (SLE) is a systemic autoimmune syndrome defined by clinical and serologic features, including arthritis, glomerulonephritis, and certain autoantibodies such as anti-nuclear ribonucleoprotein (nRNP)/Smith antigen (Sm), DNA, and ribosomal P. Although lupus is considered primarily a genetic disorder, we recently demonstrated the induction of a syndrome strikingly similar to spontaneous lupus in many nonautoimmune strains of mice exposed to the isoprenoid alkane pristane (2,6,10,14-tetramethylpentadecane), a component of mineral oil. Intraperitoneal injection of pristane leads to the formation of lipogranulomas consisting of phagocytic cells that have engulfed the oil and collections of lymphocytes. Subsequently, pristane-treated BALB/c and SJL mice develop autoantibodies characteristic of SLE, including anti-nRNP/Sm, antiribosomal P, anti-Su, antichromatin, anti-single-stranded DNA, and anti-double-stranded DNA. This is accompanied by a severe glomerulonephritis with immune complex deposition, mesangial or mesangiocapillary proliferation, and proteinuria. All inbred mice examined appear to be susceptible to this novel form of chemically induced lupus. Pristane-induced lupus is the only inducible model of autoimmunity associated with the clinical syndrome as well as with the characteristic serologic abnormalities of SLE. Defining the immunopathogenesis of pristane-induced lupus in mice may provide insight into the causes of spontaneous (idiopathic) lupus and also may lead to information concerning possible risks associated with the ingestion or inhalation of mineral oil and exposure to hydrocarbons in the environment.

Animals↗
PubMed1999

Medical issues relating to the Sydney Olympic Games.

The Sydney Olympic Games in 2000 represent a significant medical and sporting challenge. Prior planning is the key to optimal performance, and team medical staff should be familiar with major medical and injury concerns of athletes and officials well prior to departure. A comprehensive team medical kit should be organised. Travel will be over great distances for many teams, so particular attention to optimising sleep and hydration is essential. The Olympic village experience can be overwhelming for some athletes, and medical staff should provide informed advice on food, transport and safety issues. Heat is less likely to be an issue than at recent summer Olympic Games, but should not be ignored completely. Major incidents can occur at any major sporting festival, and team medical staff should be appropriately prepared for these. All team medical staff should be aware of the current list of banned substances, and seek to minimise drug use by their athletes. After the event, an appropriate debriefing session should be held with a view to planning improvements for the future.

Anniversaries and Special Events↗
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↗