Workshop on viral infection and diabetes mellitus in man.
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Biomedical subjects
Publications and source records attributed to J E Craighead.
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Masses of homogeneous electron-dense material accumulate in the cytoplasmic inclusions of cultured fibroblasts which have been infected with "wild" and "adapted" strains of human cytomegalovirus. The substance appears to be produced by microtubular membranes and the Golgi apparatus; ultrastructural histochemistry suggests that it is not lysosomal in nature nor is it comprised of lipids or polysaccharides. The dense material "buds" into cytoplasmic tubules forming circumscribed bodies having an investing membrane similar to the viral envelope. After transport to the extracellular milieu in cytoplasmic tubules and vesicles, virions and dense bodies can be demonstrated by immune electron microscopy. The homogeneous dense body appears to be a unique product of the cytomegalovirus-infected cell which possesses a limiting membrane having antigenic determinants common with the viral envelope.
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Polycation treatment of L cell monolayers affected plaquing efficiency of both the r(+) and r variants of the encephalomyocarditis virus. Plaque formation by r(+) variant was decreased markedly by three structurally different types of synthetic basic polymers, diethylaminoethyl dextran, hexadimethrene (polybrene), and basic polyamino acids. In contrast, these same substances increased substantially the number of plaques formed by the r variant. The effect on the two variants was observed when polycations were applied to the cells before or simultaneously with the introduction of virus. The molar concentration and size of the polymer proved important. Thus, basic polyamino acids of low molecular weight were significantly more inhibitory for the r(+) variant than were those of high molecular weight. On the other hand, plaquing efficiency of the r variant was increased by relatively large polyamino acids, but not by polymers of small size. Basic polyamino acids inhibited r(+) plaque formation to a greater degree at low than at high pH values. However, plaquing efficiency of the r variant in polycation-treated cultures was not affected by changes in pH. Basic polymers appear to bind to cell membranes and affect either attachment or uptake of the viruses. The evidence suggests that the substances influence by different mechanisms the interaction of the r(+) and r variants with cells.
Hyperglycemia and lesions of the pancreatic islets of Langerhans developed in some, but not all, adult mice infected with a variant of the encephalomyocarditis virus. Large amounts of virus were recovered from the pancreas during acute stages of infection. At this time blood glucose concentrations were markedly elevated and the islets of Langerhans exhibited focal necrosis and degranulation of beta cells. Evidence of abnormal glucose metabolism persisted for varying periods after recovery from the infection. The islets of Langerhans of chronically hyperglycemic mice were distorted and decreased in size, and the beta cells were degranulated. Encephalomyocarditis virus appears to cause diabetes mellitus by reducing the mass of functional beta cells of the islets of Langerhans.
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