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J J Volpe

Publications and source records attributed to J J Volpe.

At least 163 records · Page 9Linked to original sources
PubMed1981

Selective decrease of the viability and the sterol content of proliferating versus quiescent glioma cells exposed to 25-hydroxycholesterol.

The effects of 25-hydroxycholesterol (25-OHC), a potent inhibitor of sterol synthesis, on the growth, viability, and sterol content of C-6 rat glioma cells have been studied. Suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and sterol synthesis in cells that were proliferating in medium supplemented with lipoprotein-poor fetal calf serum caused an arrest of growth after 24 hr. Prolonged incubation of serum-supplemented cells with 25-OHC resulted in a loss of morphological integrity and an 80% decline in cell viability, determined by trypan blue dye exclusion. In contrast, C-6 cells that were induced to enter a quiescent state by removal of serum from the medium remained viable and morphologically differentiated in the presence of 25-OHC. Following the addition of whole fetal calf serum to the medium, serum-free cells that had been incubated with 25-OHC for 3 days were able to resume proliferation. the selective killing of proliferating C-6 glioma cells by 25-OHC was correlated with a 45 to 50% decline in the sterol/phospholipid molar ratio, whereas the sterol/phospholipid ratio in the quiescent cells was not affected by 25-OHC. The results suggest that inhibitors of sterol synthesis may have potential as agents that might selectively decrease the growth and viability of glioma cells in the central nervous system without detriment to the normal nondividing neural cells.

Animals↗
PubMed1981

Normal pressure hydrocephalus in the newborn.

The entity of normal pressure hydrocephalus (NPH) following intraventricular hemorrhage in the newborn has been characterized. Of 87 infants with intraventricular hemorrhage, 20 had early and rapidly progressive hydrocephalus with intracranial hypertension and/or death. In 47 cases there was no increase in ventricular size and in 20 cases there was progressive increase in ventricular size with normal intracranial pressure, ie, NPH. Of these infants with NPH, nine had spontaneous arrest with or without resolution of ventriculomegaly, beginning within 31 days of onset. In 11 cases, after a stable period of NPH lasting 12 to 84 days, there was progressive increase in ventricular size accompanied ultimately by raised intracranial pressure. A relationship between the degree of ventriculomegaly and severity of intraventricular hemorrhage was demonstrated. The data thus define a state of NPH after intraventricular hemorrhage and indicate that approximately half of such cases will not develop progressive hydrocephalus with increased intracranial pressure. If arrest or onset of resolution of ventriculomegaly is not apparent within approximately one month, continued progression and necessity for intervention are to be expected. Serial measurements of intracranial pressure and ventricular size in newborns with posthemorrhagic ventricular dilation allow the diagnosis of NPH and permit early recognition of rapidly progressive ventricular dilation with intracranial hypertension which may follow a stable period of NPH. Such early recognition of this potentially harmful state allows prompt ventricular drainage, thereby preventing brain compression.

Cerebral Hemorrhage↗
PubMed1980

Changes in sterol biosynthesis accompanying cessation of glial cell growth in serum-free medium.

C-6 glioma cells, grown in medium supplemented with 5% delipidated foetal calf serum, were induced to enter a quiescent state by removing serum from the medium. Within 24h there was a 75-80% decline in the rate of incorporation of [(14)C]acetate or (3)H(2)O into digitonin-precipitable sterols. Experiments with [(3)H]mevalonolactone as a labelled sterol precursor suggested that the decline in sterol synthesis was regulated primarily at a point in the pathway before the formation of mevalonate. The specific activities of 3-hydroxy-3-methylglutaryl-CoA synthase and 3-hydroxy-3-methylglutaryl-CoA reductase decreased sharply in conjunction with the decline in sterol synthesis in the serum-free cultures; however, the activity of acetoacetyl-CoA thiolase was altered only slightly. The magnitude of the initial decline in reductase activity was not affected when 50-mm-NaF was included in the preincubation and assay buffers to prevent activation of physiologically inactive enzyme. However, after 6h of serum deprivation the decline in 3-hydroxy-3-methylglutaryl-CoA reductase activity was due to a decrease in the amount of latent activity. The sterol concentration in C-6 cells was unchanged after 24h in serum-free medium, although a 20% decrease in the sterol/fatty acid molar ratio occurred as a result of a small increase in the fatty-acid concentration. Incorporation of (3)H(2)O into fatty acids was inhibited in the serum-deprived glial cells; however, this inhibition developed more slowly and was not as pronounced as the diminution in sterol synthesis. The results suggest that in C-6 glia, which resemble the glial stem cells of the developing brain, the decreased demand for membrane sterols in the quiescent state results in a decline in sterol synthesis, mediated primarily through co-ordinate changes in the activities of 3-hydroxy-3-methylglutaryl-CoA synthase and 3-hydroxy-3-methylglutaryl-CoA reductase.

Acetates↗
PubMed1980

Porencephaly from periventricular intracerebral hemorrhage in a premature infant.

In two thirds of the premature infants who survived large periventricular intracerebral hemorrhage, a porencephalic cyst developed at the site of parenchymal hemorrhage. The porencephaly seems to develop as a result of local parenchymal destruction by the hemorrhage itself. These cysts can occur in the absence of posthemorrhagic hydrocephalus or increased intracranial pressure. Three of four infants who were observed for at least five months had lateralized motor deficit that corresponded to the cyst.

Brain↗
PubMed1980

Failure of daily lumbar punctures to prevent the development of hydrocephalus following intraventricular hemorrhage.

A prospective study of 48 infants with periventricular-intraventricular hemorrhage was carried out to evaluate the role of daily lumbar punctures, instituted from the time of diagnosis of the hemorrhage, in prevention of posthemorrhagic hydrocephalus and improvement in immediate outcome. The data lead to the following conclusions: (1) minor hemorrhage (Grade I) is associated with minimal risk of death or hydrocephalus; (2) moderate hemorrhage (Grade II) is associated with low risk of death and intermediate risk of hydrocephalus, and serial lumbar punctures do not reduce these risks; and (3) severe hemorrhage (Grade III) is associated with high risks of death or hydrocephalus or both, and serial lumbar punctures also do not reduce these risks.

Brain↗
PubMed1979

Activation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in homogenates of developing rat brain.

The specific activity of 3-hydroxy-3-methylglutaryl-CoA reductase increases when homogenates of developing rat brain are incubated at 37 degrees C or kept on ice. This increase is completely blocked by the addition of F- to the homogenization medium and the assay mixture. The capacity for activation of the reductase is greatest during the early postnatal period and declines as brain maturation proceeds. The data suggest that catalytic modification of the reductase may play a role in the regulation of cholesterol synthesis in the developing brain.

Aging↗
PubMed1979

Microtubules and the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

Cultured C-6 glial cells were utilized to evaluate the effect of antimicrotubular drugs on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol synthesis. Colchicine, Colcemid, and vinblastine (1.0 muM) caused a marked reduction in HMG-CoA reductase activity and, as a consequence, the rate of cholesterol synthesis in these cells. No effect was observed with lumicolchicine, a mixture of colchicine isomers with no effect on microtubules. The effect of colchicine was apparent within 1 h after addition to the culture medium, and, after 6 h, HMG-CoA reductase activity in treated cells was only approximately 15 to 30% of that in untreated cells. Reductase activity was very sensitive to the concentration of drug added, i.e. cells treated with just 0.1 muM colchicine for 6 h exhibited a 50% lower enzymatic activity than did untreated cells. The lack of a generalized, nonspecific toxic effect on the cells was indicated by the finding of no change in the activities of fatty acid synthetase and NADPH-cytochrome c reductase and the rate of total protein synthesis in cells treated with colchicine (1 muM) for 6 h. A close temporal and quantitative correlation was observed between the effects of colchicine on HMG-CoA reductase and on a parameter of microtubular function, i.e. maintenance of glial cell shape. The data suggest that microtubules are involved in the regulation of HMG-CoA reductase and cholesterol synthesis in C-6 glial cells.

Animals↗
PubMed1979

A potential role for phospholipids in the regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in cultured C-6 glial cells. Effects of N,N-dimethylethanolamine.

The relation of the activity of the microsomal enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase, to cellular phospholipid composition was studied in C-6 glial cells. Phospholipid composition was perturbed by growth of cells in the naturally occurring amino alcohol, N,N-dimethylethanolamine. After growth of C-6 glia in 5 mM N,N-dimethylethanolamine for 24 h, reductase activity was diminished by 50%. A similar diminution in cholesterol synthesis was observed. This effect was not accompanied by any parallel change in cell growth, DNA synthesis, protein synthesis, fatty acid synthetase activity, or microsomal NADPH-cytochrome c reductase activity. The inhibition of reductase activity by N,N-dimethylethanolamine was prevented by the addition of equimolar concentrations of choline to the culture medium and, also, could be reversed completely by removal of N,N-dimethylethanolamine from the culture medium. The effect of N,N-dimethylethanolamine on reductase was associated with the formation of phosphatidyl-N,N-dimethylethanolamine which accumulated primarily at the expense of phosphatidylcholine and, after 24 h, accounted for 27% of total phospholipid phosphorus. The data demonstrate that incorporation of N,N-dimethylethanolamine into the polar head group of cellular phospholipids has a major impact on the regulation of the reductase. These observations may have particular relevance for the mechanisms of regulation of this enzyme, the cellular adaptation to alterations in membrane lipid composition, and the regulation of cholesterol synthesis in the developing nervous system.

Cells, Cultured↗
PubMed1979

Induction of an oligodendroglial enzyme in C-6 glioma cells maintained at high density or in serum-free medium.

The relationship between cell density and the activity of 2':3'-cyclic nucleotide 3'-phosphohydrolase (CNP), an enzyme believed to be specific to oligodendroglial cells and myelin in the brain, has been studied in cultured C-6 glioma cells. Over a 12-day period, the specific activity of CNP underwent a 4-fold increase in conjunction with an increase in the cell density (total protein/flask) and a decline in the growth rate of the cultures. In contrast, the specific activity of Na+,K+-ATPase was not influenced by cell density. Experiments with cultures seeded at different initial densities indicated that the increase in CNP activity coincided with the attainment of a specific cell density rather than with the length of time that the cells were maintained in culture. Arrest of cell proliferation in non-confluent C-6 cells by means of thymidine blockade was not sufficient to cause an increase in the activity of CNP; however, removal of serum from the culture medium resulted in a 3-fold induction of the enzyme in the absence of a high degree of cell contact. The induction of CNP in cells maintained in serum-free medium paralleled the development of a series of distinct morphological changes reminiscent of glial differentiation, which occurred within 48 hours after removal of the serum. Inhibition of protein synthesis by cycloheximide prevented the induction of CNP in serum-free cultures. The demonstration that an enhancement of an oligodendroglial characteristic in C-6 glioma cells can be obtained by growing the cells to high density or by removing serum from the medium, provides further support for the suggestion that these cells may be analogous to the glial stem cells present in the developing brain.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1979

Reduction of cholesterol synthesis by methylxanthines in cultured glial cells.

Methylxanthines are shown in this study to decrease cholesterol synthesis in cultured C-6 glial cells. Aminophylline (10(-3) M) produced a rapid decline in cholesterol synthesis so that by 6 hr, synthesis in treated cells was less than 20% of that in untreated cells, and by 24 hr, less than 10%. Aminophylline induced parallel changes in 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, the rate-limiting enzyme in cholesterol synthesis. Theophylline and caffeine produced similar effects. Thus, methyxanthines caused a specific, enzyme-mediated reduction in cholesterol synthesis in C-6 glial cells to the developing nervous system, cholesterol synthesis was studied in the presence of 10(-4)M aminophylline. This represents a theophylline concentration in the culture medium that is of the same order of magnitude as that produced in whole brain of animals administered therapeutic doses of aminophylline. Under these conditions, cholesterol synthesis was reduced to approximately 60% of control after 48 and 72 hr.

Aminophylline↗