M.W. McGowan

Bio: M.W. McGowan is an academic researcher from Wayne State University. The author has contributed to research in topics: Hydrogen peroxide & Peroxidase. The author has an hindex of 8, co-authored 13 publications receiving 1357 citations.

A peroxidase-coupled method for the colorimetric determination of serum triglycerides.

Abstract: We describe an enzymatic method for rapid, precise measurement of serum triglycerides with use of sample:reagent ratios as large as 1:200. Hydrolysis of triglycerides is catalyzed by lipase to produce glycerol and free fatty acids. The glycerol generated is then phosphorylated by adenosine 5'-triphosphate in the presence of glycerol kinase. Oxidation of the resulting glycerol 3-phosphate to produce hydrogen peroxide is catalyzed by L-alpha-glycerophosphate oxidase. An intense red chromogen is produced by the peroxidase-catalyzed coupling of 4-aminoantipyrene and sodium 2-hydroxy-3,5-dichlorobenzenesulfonate with hydrogen peroxide. This sensitive chromogen system not only permits use of unusually small sample volumes, it also facilitates a linear response to serum triglyceride concentrations up to at least 10 g/L while displaying good Ringbom (measure of accuracy) characteristics.

A procedure for the determination of high-density lipoprotein choline-containing phospholipids.

Abstract: Summary: A procedure for the determination of senim high-density lipoprotein choline-containing phospholipids is described. The choline-containing phospholipids represent 91—97% of the total serum and high-density lipoprotein phospholipids, which have previously been determined in relation to liver disease, neoplastic disorders, diabetes rnellitus and atherosclerosis. The eiizymatic assay is quick, simple and precise. No interference was found from the precipitating agents used to isolate the high-density lipoprotein fraction. Several serum samples were assayed for high-density lipoprotein cholesterol and choline-containing phospholipids . From this preliminary data there would appear to be a correlation between these two lipid classes.

Enzymatic colorimetry of lecithin and sphingomyelin in aqueous solution.

Abstract: A procedure for the enzymatic determination of lecithin and sphingomyelin in aqueous solution is described. The phospholipids are first dissolved in chloroform:methanol (2:1 by vol), the solvent is evaporated, and the residue is redissolved in an aqueous zwitterionic detergent solution. The enzymatic reaction sequences of both assays involve hydrolysis of the phospholipids to produce choline, which is then oxidized to betaine, thus generating hydrogen peroxide. The hydrogen peroxide is subsequently utilized in the enzymatic coupling of 4-aminoantipyrine and sodium 2-hydroxy-3,5-dichlorobenzenesulfonate, an intensely red color being formed. The presence of a non-reacting phospholipid enhances the hydrolysis of the reacting phospholipid. Thus we added lecithin to the sphingomyelin standards and sphingomyelin to the lecithin standards. This precise procedure may be applicable to determination of lecithin and sphingomyelin in amniotic fluid.

Enzymic colorimetric determination of phosphatidylglycerol in amniotic fluid.

Abstract: We describe a procedure for the enzymic, colorimetric determination of phosphatidylglycerol in amniotic fluid. After extraction into chloroform:methanol (2:1 by vol) and evaporation, the phospholipid-containing residue is redissolved in a non-ionic detergent, which thus provides an aqueous sample. The subsequent enzymic reaction sequence involves phospholipase-catalyzed hydrolysis of glycerol from its phospholipid. Subsequent enzyme-catalyzed reactions phosphorylate this glycerol and oxidize the resulting glycerol phosphate to produce hydrogen peroxide, which is reacted to produce an intense red chromogen in the peroxidase-catalyzed coupling of 4-aminoantipyrine and 2-hydroxy-3,5-dichlorobenzenesulfonate. When used in conjunction with previously reported enzymic techniques for determination of lecithin and sphingomyelin, this procedure may provide an accurate and precise "lung profile" for assessment of fetal lung maturity.

A peroxidase-coupled method for the colorimetric determination of serum triglycerides.

Abstract: We describe an enzymatic method for rapid, precise measurement of serum triglycerides with use of sample:reagent ratios as large as 1:200. Hydrolysis of triglycerides is catalyzed by lipase to produce glycerol and free fatty acids. The glycerol generated is then phosphorylated by adenosine 5'-triphosphate in the presence of glycerol kinase. Oxidation of the resulting glycerol 3-phosphate to produce hydrogen peroxide is catalyzed by L-alpha-glycerophosphate oxidase. An intense red chromogen is produced by the peroxidase-catalyzed coupling of 4-aminoantipyrene and sodium 2-hydroxy-3,5-dichlorobenzenesulfonate with hydrogen peroxide. This sensitive chromogen system not only permits use of unusually small sample volumes, it also facilitates a linear response to serum triglyceride concentrations up to at least 10 g/L while displaying good Ringbom (measure of accuracy) characteristics.

The lipid treatment assessment project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals.

Abstract: Methods: Adult patients with dyslipidemia, who had been receiving the same lipid-lowering therapy for at least 3 months, were assessed at investigation sites. Lipid levels were determined once in each patient at the time of enrollment. The primary end point was the success rate, defined as the proportion of patients who achieved their LDL-C target level as specified by NCEP guidelines. Results: A total of 4888 patients from 5 regions of the United States were studied. Of these, 23% had fewer than 2 risk factors for coronary heart disease (CHD) and no evidence of CHD (low-risk group), 47% had 2 or more risk factors and no evidence of CHD (high-risk group), and 30% had established CHD. Overall, only 38% of patients achieved NCEP-specified LDL-C target levels; success rates were 68% among low-risk patients, 37% among high-risk patents, and 18% among patients with CHD. Drug therapy was significantly (P#.001) more effective than nondrug therapy in all patient risk groups. However, many patients treated with lipid-lowering drugs did not achieve LDL-C target levels. Conclusions: Large proportions of dyslipidemic patients receiving lipid-lowering therapy are not achieving NCEP LDL-C target levels. These findings indicate that more aggressive treatment of dyslipidemia is needed to attain goals established by NCEP guidelines. Arch Intern Med. 2000;160:459-467

Beta-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte-beta-cell relationships

Abstract: Hyperinsulinemia, loss of glucose-stimulated insulin secretion (GSIS), and peripheral insulin resistance coexist in non-insulin-dependent diabetes mellitus (NIDDM). Because free fatty acids (FFA) can induce these same abnormalities, we studied their role in the pathogenesis of the NIDDM of obese Zucker diabetic fatty (ZDF-drt) rats from 5 weeks of age (before the onset of hyperglycemia) until 14 weeks. Two weeks prior to hyperglycemia, plasma FFA began to rise progressively, averaging 1.9 +/- 0.06 mM at the onset of hyperglycemia (P < 0.001 vs. controls). At this time GSIS was absent and beta-cell GLUT-2 glucose transporter was decreased. The triacylglycerol content of prediabetic islets rose to 10 times that of controls and was correlated with plasma FFA (r = 0.825; P < 0.001), which, in turn, was correlated with the plasma glucose concentration (r = 0.873; P < 0.001). Reduction of hyperlipacidemia to 1.3 +/- 0.07 mM by pair feeding with lean littermates reduced all beta-cell abnormalities and prevented hyperglycemia. Normal rat islets that had been cultured for 7 days in medium containing 2 mM FFA exhibited increased basal insulin secretion at 3 mM glucose, and first-phase GSIS was reduced by 68%; in prediabetic islets, first-phase GSIS was reduced by 69% by FFA. The results suggest a role for hyperlipacidemia in the pathogenesis of NIDDM; resistance to insulin-mediated antilipolysis is invoked to explain the high FFA despite hyperinsulinemia, and sensitivity of beta cells to hyperlipacedemia is invoked to explain the FFA-induced loss of GSIS.

Antibodies to cachectin/tumor necrosis factor reduce interleukin 1 beta and interleukin 6 appearance during lethal bacteremia.

Abstract: Cytokines secreted in response to invading micro-organisms are important mediators of detrimental hemodynamic and metabolic changes in the host. To test whether cachectin/TNF plays a role in triggering release of other cytokines in the setting of infection, anesthetized baboons were passively immunized against systemic cachectin/TNF before infusion of a LD100 dose of live Escherichia coli. Bacteremia led to significant increases in circulating levels of cachectin/TNF, IL-1 beta, and IL-6. Although bacterial endotoxin/lipopolysaccharide is a potent stimulus for the synthesis and release of IL-1 and IL-6 in vitro, specific neutralization of cachectin/TNF in vivo with mAb pretreatment significantly attenuated both the IL-1 beta and the IL-6 responses despite fulminant overwhelming bacteremia. These data suggest that cachectin/TNF is essential for the initiation or amplification of IL-1 and IL-6 release during lethal gram-negative septic shock syndrome.