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Biomedical subjects

S Lesage

Publications and source records attributed to S Lesage.

66 records · Page 4Linked to original sources
PubMed1992

Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus.

Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent (type 2) diabetes mellitus (NIDDM) which is characterized by an early age at onset and an autosomal dominant mode of inheritance. Except for these features, the clinical characteristics of patients with MODY are similar to those with the more common late-onset form(s) of NIDDM. Previously we observed tight linkage between DNA polymorphisms in the glucokinase gene on the short arm of chromosome 7 and NIDDM in a cohort of sixteen French families having MODY. Glucokinase is an enzyme that catalyses the formation of glucose-6-phosphate from glucose and may be involved in the regulation of insulin secretion and integration of hepatic intermediary metabolism. Because the glucokinase gene was a candidate for the site of the genetic lesion in these families, we scanned this gene for mutations. Here we report the identification of a nonsense mutation in the gene encoding glucokinase and its linkage with early-onset diabetes in one family. To our knowledge, this result is the first evidence implicating a mutation in a gene involved in glucose metabolism in the pathogenesis of NIDDM.

Base Sequence↗
PubMed1992

Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus.

Non-insulin-dependent diabetes mellitus (NIDDM) is a major health problem, affecting 5% of the world population. Genetic factors are important in NIDDM, but the mechanisms leading to glucose intolerance are unknown. Genetic linkage has been investigated in multigeneration families to localize, and ultimately identify, the gene(s) predisposing to NIDDM. Here we report linkage between the glucokinase locus on chromosome 7p and diabetes in 16 French families with maturity-onset diabetes of the young, a form of NIDDM characterized by monogenic autosomal dominant transmission and early age of onset. Statistical evidence of genetic heterogeneity was significant, with an estimated 45-95% of the 16 families showing linkage to glucokinase. Because glucokinase is a key enzyme of blood glucose homeostasis, these results are evidence that a gene involved in glucose metabolism could be implicated in the pathogenesis of NIDDM.

Adenosine Deaminase↗
PubMed1992

Immunological characterization of rat kininogens with monoclonal antibodies to T-kininogen. Distinction between the different domains of T-kininogen and the multiple rat kininogens.

A panel of 16 monoclonal antibodies (mAb) were produced against rat T-kininogen to characterize this family of proteins. These mAbs bound 125I-T-kininogen by radioimmunoassay as well as reacting strongly with immobilized T-kininogen in an enzyme-linked immunosorbent assay (ELISA). The reactivity of these antibodies with proteolytic fragments of T-kininogen demonstrated the recognition of several different epitopes. One antibody was specific for the domain 1 of the heavy chain and/or the light chain, twelve antibodies were specific for domain 2 and three antibodies were specific for domain 3. All monoclonal antibodies recognized the two forms of T-kininogen encoded by the two different T-kininogen genes, TI and TII kininogen, except antibody TK 16-3.1 which uniquely reacted with TII kininogen. Two antibodies recognizing domain 2 cross-reacted with the high-molecular-mass kininogen (H-kininogen), whereas all the other monoclonal antibodies were specific to T-kininogen and did not recognize the heavy chain of H-kininogen. None of the antibodies tested altered the thiol protease inhibitory activity of T-kininogen, its partial proteolysis by rat mast cell chymase or the hydrolysis of H-kininogen by rat urinary kallikrein. The use of these antibodies in the development of sensitive ELISA to measure T-kininogen levels in plasma, urine, liver microsomes and hepatocytes is described. Two different forms of T-kininogen were distinguished by these monoclonal antibodies in Western blotting using rat plasma. The localization of T-kininogen was defined using these monoclonal antibodies by immunohistochemistry in rat liver hepatocytes and rat kidney.

Animals↗
PubMed1992

Characterization of lymphocyte subpopulations in cord blood.

27 cord blood samples from healthy newborns were processed according to a "whole blood" flow cytometric analysis. The CD3-positive T cells are characterized by their variability: 44.8 +/- 13.3% of lymphocytes with a lower expression of the gamma delta T cell receptor. The majority of the CD3+ cells are CD38+. Newborn T cells have less ability than adult T cells to express IL-2 receptors as well as HLA-DR. The CD4-positive T cells are equal to 31.0 +/- 10.8% of lymphocytes with a great prevalence of the CD4+/CD45RA+ population. The CD3+/CD8+/CD11b+ cells are increased to 23.4 +/- 7.1% of lymphocytes. The CD57 antigen is not expressed. The NK population, CD16+/CD56+ is increased to 25 +/- 11% of lymphocytes. 68% of CD19+ cord blood B lymphocytes coexpressed CD5. Thus the "suppressive" and "naïve" cells are prominently represented in cord blood.

Antigens, CD↗
PubMed1990

Free amino acid turnover in methanogens measured by 15N NMR spectroscopy.

Turnover of the nitrogen moiety from free amino acid pools in two thermophilic methanogens, Methanobacterium thermautotrophicum delta H and Methanococcus thermolithotrophicus SN1, has been monitored with 15N NMR spectroscopy. In cells growing exponentially on 15NH4Cl, glutamate was the major soluble 15N-labeled species in both organisms. When the Mb. thermoautotrophicum cells were harvested, washed, and resuspended into medium containing 14NH4Cl, the resonance for [15N]glutamate decreased with a half-life of 0.5 h. This is considerably faster than the turnover rate for the carbon side chain of glutamate (7 h) obtained when a 13CO2 pulse followed by a 12CO2 chase was incorporated into the 15N/14N-labeling experiment. Such behavior is consistent with recycling of the glutamate carbon skeleton via alpha-ketoglutarate after transamination reactions remove the 15N for biosynthesis of other amino acids, nucleic acids, etc. When the cells were in stationary phase, 15N turnover was considerably slower indicating that transaminase activity had also decreased. Mc. thermolithotrophicus has a much more fragile cell wall and easily lyses. To avoid cell loss in the 15N/14N experiment, 15NH+4 growth followed by 14NH4+ dilution was used. In this organism the glutamate-labeled nitrogen turns over quite rapidly (t1/2 approximately 9 min), at a rate comparable to that for the carbon skeleton (t1/2 approximately 10 min). Beta-Glutamate, the second major carbon and nitrogen pool in this organism, turns over its 15N label very slowly. Therefore, this beta-amino acid does not appear to serve as a nitrogen donor in Mc. thermolithotrophicus.

Amino Acids↗
PubMed1989

Beta-aminoglutaric acid is a major soluble component of Methanococcus thermolithotrophicus.

13C- and 15N-NMR spectroscopy have been used to identify beta-aminoglutaric acid (beta-glutamic) as a major soluble component of the thermophilic, autotrophic marine methanogen Methanococcus thermolithotrophicus. This rare, non-protein amino acid has been recognized as a major dissolved free amino acid in marine sediments, but the microorganism responsible for its production has not previously been identified. The concentration of beta-aminoglutarate (beta-glutamate) is about one half that of free alpha-glutamate and increases (relative to the alpha-isomer) as cells enter the stationary phase. Analysis of the 13C label distribution in a 13CO2-pulse/12CO2-chase experiment shows that label enters the beta-aminoglutarate pool after it has decayed from other small soluble molecules. This implies that beta-aminoglutarate is a catabolic product of the cells. Preliminary biosynthesis studies with labeled precursors indicate that only a single acetate moiety is incorporated in this unusual compound. This information is used to suggest possible biosynthetic pathways.

Anaerobiosis↗
PubMed1984

Control of bacterial speck of tomato by copper and ethylenebisdithiocarbamate fungicides: their efficacy and residues on leaves.

Field studies were conducted to determine the synergism, persistence, and efficacy of a tank-mix spray of cupric hydroxide and mancozeb for control of bacterial speck of tomato. The increased efficacy of the cupric hydroxide-mancozeb mixture could not be attributed to the formation of a bacteriostatic compound in the tank mixture nor to a greater persistence of the mixture on the tomato foliage.

Bacteria↗