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M H Metzger

Publications and source records attributed to M H Metzger.

8 recordsLinked to original sources

Factors associated with self-reporting of chronic health problems in the French GAZEL cohort.

The objective of this study was to examine factors associated with self-reporting of chronic health problems. The self-reports were obtained from a questionnaire sent by mail to the French GAZEL cohort, composed of workers of a French company. The disorders reported in the questionnaire were compared with diagnoses from the sick-leave database of the company. Associations between self-reporting and characteristics were studied by multiple logistic regression analyses. Three types of characteristics were analyzed: individual, methodological and disorder-related (i.e., prevalence of chronic disorders in the general population, probable disability and probable life risk scores). In 1992, the cohort consisted of 16,534 subjects aged 38 to 53 years. The reporting rate (number of self-reports in the questionnaire divided by number of records in the sick-leave database for the disorder considered) varied from 8.9% to 100%. Self-reporting was associated with individual characteristics (gender, family status, place of residence, annual number of sick days and sick leaves), disorder-related characteristics (probable disability, prevalence) and methodological characteristics (precision of the formulation, delay between the last sick-day and the patient report). By body system, the characteristics associated with self-reporting varied greatly but the annual number of sick days, probable disability and precision of formulation were the variables which remained most often in the models. These characteristics should be particularly taken into consideration in the interpretation of epidemiological results based on self-reporting.

Adult↗

Can inaccuracy of reported parental history of diabetes explain the maternal transmission hypothesis for diabetes?

BACKGROUND: The mode of inheritance of type 2 diabetes mellitus is still under discussion. Several studies have suggested an excess maternal transmission, however, more recent studies could not always confirm these findings. METHODS: We investigated the frequency of a maternal and paternal history of diabetes among diabetic and non-diabetic subjects and assessed the association between diabetes and a parental history of diabetes among participants of the MONICA Augsburg study. As an extension to previous studies, unknown parental status was taken into account. RESULTS: Of the 542 diabetic probands, 25.3% reported a positive maternal history of diabetes and 10.9% reported a positive paternal history of diabetes. Among the 12,209 non-diabetic participants a positive maternal history was also more common than a positive paternal history (12.5% versus 7.1%). Conversely, an unknown paternal status was more common than an unknown maternal status in both groups (diabetic subjects: 27.9% versus 16.8%, non-diabetic subjects: 16.8% versus 8.4%). Adjusted odds ratios (OR) for the association between a parental history of diabetes and diabetes status were similar for a positive maternal (OR = 2.9, 95% CI : 2.3-3.6) and paternal history (OR = 2.8, 95% CI : 2.1-3.8) and for an unknown maternal (OR = 1.3, 95% CI : 1.0-1.8) and paternal history (OR = 1.5, 95% CI : 1.2-1.9). CONCLUSION: Our findings do not support a strong excess maternal transmission of diabetes. Epidemiological biases and failure to account for 'don't know' responses may in part explain the previously observed predominance of a maternal history of diabetes.

Bias↗

Tyrosine phosphorylation of the CD3-epsilon subunit of the T cell antigen receptor mediates enhanced association with phosphatidylinositol 3-kinase in Jurkat T cells.

T cell receptor signaling results both in T cell proliferation and apoptosis. A key enzyme at the intersection of these downstream pathways is phosphatidylinositol 3'-kinase (PI 3-kinase). In a previous report, we showed that the p85alpha subunit of the PI 3-kinase preferentially associated with the CD3-zeta membrane-proximal immunoreceptor tyrosine-based activation motif of the zeta chain (zetaA-ITAM) (Exley, M., Varticovski, L., Peter, M., Sancho, J., and Terhorst, C. (1994) J. Biol. Chem. 269, 15140-15146). Here, we demonstrate that tyrosine phosphorylation of CD3-epsilon can recruit the PI 3-kinase enzyme in a T cell activation-dependent manner. In vivo studies with Jurkat cells stably transfected with a CD8-CD3-epsilon chimera (termed CD8-epsilon) shows that ligation of endogenous CD3-epsilon or CD8-epsilon by specific antibodies induces tyrosine phosphorylation of CD3-epsilon or CD8-epsilon, respectively. Increased tyrosine phosphorylation correlates with increased binding of p85alpha PI 3-kinase and recruitment of PI 3-kinase enzymatic activity to CD3-epsilon or CD8-epsilon proteins. Mutagenesis studies in COS-7 cells, transiently transfected with CD8-epsilon, p85alpha, and Fyn cDNAs in various combinations, show that both Tyr170 and Tyr181 within the CD3-epsilon-ITAM are required for efficient binding of p85alpha PI 3-kinase. Thus, replacement of Tyr170 by Phe (Y170F), or Tyr181 by Phe (Y181F) significantly reduces binding of p85alpha PI 3-kinase, whereas it does not affect binding of Fyn. Further in vitro experiments suggest that a direct binding of the tandem SH2 domains of p85alpha PI 3-kinase to the two phosphorylated tyrosines in a single CD3-epsilon-ITAM may occur. The data also support a model in which a single CD3 subunit can recruit distinct effector molecules by means of TCR-mediated differential ITAM phosphorylation.

Amino Acid Sequence↗

Trends in coronary heart disease morbidity and mortality and acute coronary care and case fatality from 1985-1989 in southern Germany and south-western France.

BACKGROUND: Although it has been shown that coronary heart disease mortality rates are decreasing in industrialized countries, little is known about time trends in coronary heart disease incidence. Further, although a number of randomized clinical trials have shown that percutaneous transluminal coronary angioplasty and thrombolysis improve survival of acute myocardial infarction patients, it is not known if widespread use of these therapeutic procedures has contributed to a decrease in in-hospital case fatality on a population basis. METHODS: The change over time of coronary heart disease attack, incidence and mortality rates was assessed in men and women (35 to 64 years) using data collected between 1985 and 1989 by the Augsburg (Germany) and Toulouse (France) MONICA Centres. Acute coronary care and 28-day case fatality for hospitalized 24-h survivors were also assessed. RESULTS: Men and women from Augsburg had higher age-standarized attack, incidence and mortality rates than their Toulouse counterparts. In both centres, attack, incidence and mortality rates declined in men, but increased in women. Patients in Toulouse received more percutaneous transluminal coronary angioplasty and thrombolysis and had lower 28-day case fatality than patients in Augsburg. The therapeutic procedures, percutaneous transluminal coronary angioplasty and thrombolysis increased in both centres; however, only in Toulouse was this increase associated with a decrease (non significant) in 28-day hospital case fatality. CONCLUSION: The increase in morbidity and mortality rates of coronary heart disease in women stresses the need for preventive measures in this group. The absence of a favourable effect of acute coronary care on 28-day fatality for hospitalized 24-h survivors in the Augsburg centre will be further investigated.

Adult↗

[Predictive factors for institutionalization in the context of geriatric planning in the Gironde department (France)].

The objective of this study was to investigate the predictive factors over five years follow-up of institutionalization, relevant for starting interventions in the area of Gironde (South Western France). This study deals with a longitudinal study of community residents aged 65 years and older. Of the 2792 subjects initially included in the cohort in year 1988, 2493 were selected for this study, leading to the subjects whose type of housing was known at least once over the five year follow-up (1989-1993). The statistical analysis was made with a discrete Cox proportional hazard model. Of the 2493 subjects, 150 entered an institution during the five years of follow-up, leading to a cumulative incidence of 7.1%. In the multivariate analysis, the predictive factors found in this study were age, absence of phone in the house, living in home for the aged, cognitive decline evaluated with the Mini-Mental-Status-Examination (MMSE), dependency for one item of the Lawton's scale (Instrumental Activities of Daily Living or IADLs), namely the inability to do shopping, and limited social contact with the family. These different indicators are a basis for decision making to target home care services fitted to the needs of the area.

Activities of Daily Living↗

Amino acid substitutions in the yeast Pichia stipitis xylitol dehydrogenase coenzyme-binding domain affect the coenzyme specificity.

Directed mutagenesis has been used to identify a set of amino acids in the Pichia stipitis xylitol dehydrogenase, encoded by the xylitol dehydrogenase gene XYL2, which is involved in specific NAD binding. Within the binding domain, a characteristic beta alpha beta-fold is centered around a glycine motif GXGXXG also containing conserved aspartate and lysine/arginine residues. The mutation D207-->G and the double mutation D207-->G and D210-->G increased the apparent Km for NAD ninefold and decreased the xylitol dehydrogenase activity to 47% and 35%, respectively, as compared to the unaltered enzyme. The introduction of the potential NADP-recognition sequence (GSRPVC) of the alcohol dehydrogenase from Thermoanaerobium brockii into the xylitol dehydrogenase allowed the mutant enzyme to use both NAD and NADP as cofactor with equal apparent Km values. Although this mutant enzyme displayed an unaltered NADP acceptance, the reduction of the NAD specificity in the stably expressed enzyme variant is an important first step towards the long-term goal to reverse the coenzyme specificity from NAD to NADP. The mutagenized XYL2 gene could still mediate growth of Saccharomyces cerevisiae transformants on xylose minimal-medium plates when expressed together with the xylose reductase gene (XYL1).

Alcohol Dehydrogenase↗

Isolation and characterization of the Pichia stipitis transketolase gene and expression in a xylose-utilising Saccharomyces cerevisiae transformant.

The gene TKT from P. stipitis, encoding the enzyme transketolase (EC 2.2.1.1), was cloned from a genomic library by hybridization with a S. cerevisiae TKT1-gene-specific probe. The nucleotide sequence determined contains an open-reading frame of 2085 base pairs (bp) encoding a protein of 695 amino acids with a predicted molecular mass of 75113 Da. The TKT gene was actively expressed in S. cerevisiae when placed under the control of the homologous PDC1(-15) promoter and could complement a S. cerevisiae tkt deletion. The TKT protein was immunologically detectable using S. cerevisiae transketolase-specific antiserum. Overexpression of the P. stipitis TKT gene in a xylose-utilizing S. cerevisiae XYL1/XYL2 integrant led to a drastically extended generation time during growth on xylose minimal medium under aerobic conditions.

Base Sequence↗