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J J Volpe

Publications and source records attributed to J J Volpe.

At least 145 records · Page 8Linked to original sources
PubMed1982

Interrelationships of ubiquinone and sterol syntheses in cultured cells of neural origin.

Ubiquinone synthesis has been studied in cultured C-6 glial and neuroblastoma cells by utilizing an inhibitor, 3-beta-(2-diethylaminoethoxy) androst-5-en-17-one hydrochloride (U18666A), of cholesterol biosynthesis. Exposure of C-6 glial cells to nanomolar quantities of U18666A caused a marked inhibition of total sterol synthesis from [14C]acetate or [3H]mevalonate within minutes. A 95% inhibition was apparent after a 3-h exposure to 200 ng/ml of U18666A. These observations, together with studies of the incorporation of radioactivity from the two precursors into cholesterol, desmosterol, lanosterol, and squalene, indicated that although the most sensitive site to inhibition by U18666A is desmosterol reduction to cholesterol, a major site of inhibition is demonstrable at a more proximal site, perhaps squalene synthetase. As a consequence of the latter inhibition, exposure of C-6 glial cells to U18666A caused a marked stimulation of incorporation of [14C]acetate or [3H]mevalonate into ubiquinone. Over a wide range of U18666A concentrations, the increase in ubiquinone synthesis was accompanied by an approximately similar decrease in total sterol synthesis. Whereas in the absence of U18666A only approximately 7% of the radioactivity incorporated from [3H]mevalonate into isoprenoid compounds was found in ubiquinone, in the presence of the drug approximately 90% of incorporated radioactivity was found in ubiquinone. The reciprocal effects of U18666A on ubiquinone and sterol syntheses were apparent also in the neuronal cells. THe data thus demonstrate a tight relationship between ubiquinone and sterol biosyntheses in cultured cells of neural origin. In such cells ubiquinone synthesis is exquisitely sensitive to the availability of isoprenoid precursors derived from the cholesterol biosynthetic pathway.

Acetates↗
PubMed1982

Relationship of pneumothorax to occurrence of intraventricular hemorrhage in the premature newborn.

The relationship of pneumothorax to the occurrence of intraventricular hemorrhage (IVH) has been studied in the premature newborn. The major objective of the study was to determine whether the systemic hemodynamic changes that occur with pneumothorax are reflected in the cerebral circulation and whether these changes play a role in pathogenesis of IVH. Blood flow velocity was measured in the anterior cerebral arteries by a transcutaneous Doppler technique in nine infants who developed pneumothorax in the first 3 days of life. At the time of pneumothorax there was a marked increase in flow velocity, especially during diastole, and, with resolution of pneumothorax, flow velocity returned to normal levels over the ensuing hours. The changes in flow velocity correlated closely with systemic hemodynamic changes that occurred with pneumothorax, ie, and increase in mean systemic blood pressure, especially diastolic pressure. IVH, documented by serial ultrasound scans, was observed shortly after pneumothorax in the nine infants. The data thus demonstrate a marked increase in flow velocity in the cerebral circulation at the time of pneumothorax. This increase is of importance in the genesis of IVH as is suggested further by the occurrence of IVH soon after the cerebral hemodynamic changes.

Birth Weight↗
PubMed1982

Decrease in pulsatile flow in the anterior cerebral arteries in infantile hydrocephalus.

The effect of ventriculomegaly with or without elevated intracranial pressure (ICP) on pulsatile flow in the anterior cerebral artery has been studied by a noninvasive Doppler technique in 11 infants with hydrocephalus. The cause of hydrocephalus was intraventricular hemorrhage in nine infants, Arnold-Chiari malformation in one, and bacterial meningitis in one. The pulsatility index (PI) (inversely related to pulsatile flow) was calculated from the systolic and diastolic amplitudes of flow in the anterior cerebral artery. All 11 patients with elevated PI had marked ventriculomegaly, and all but two had raised ICP. Four patients with massive ventriculomegaly and elevated ICP had maximal PI (ie, 1.00). The finding of elevated PI with ventriculomegaly and normal ICP, observed in two patients, suggested that ventriculomegaly is a more critical factor than ICP in the pathogenesis of the impaired flow. Treatment of ventriculomegaly in seven patients resulted in a decrease in PI. Of the four untreated patients, three died and one was not available for further study. Compromised flow in the anterior cerebral artery may be a sensitive barometer of impending ischemic injury with evolving ventriculomegaly, particularly following intraventricular hemorrhage. The PI may be a valuable parameter for the study of the mechanism of brain injury and for determination of optimal timing of corrective intervention.

Cerebral Arteries↗
PubMed1982

Hemorrhagic periventricular leukomalacia: diagnosis by real time ultrasound and correlation with autopsy findings.

Hemorrhage into areas of periventricular leukomalacia may occur and range in size from microscopic to massive. Hitherto, the definitive diagnosis has been made only at autopsy. A case is described in which the diagnosis of hemorrhagic periventricular leukomalacia was made antemortem by real-time ultrasound scanning and confirmed at autopsy. Periventricular/intraventricular hemorrhage, a more common hemorrhagic lesion, may extend into periventricular with matter in a location ventral and medial to hemorrhagic periventricular leukomalacia. Real-time ultrasound scanning is a safe and reliable means of defining the topography of these two hemorrhagic lesions and, thereby, of suggesting the correct diagnosis.

Brain↗
PubMed1981

Changes in synthesis of sterols and fatty acids associated with inhibition of growth of L-M cells at high cell density.

The relationship between cell density and de novo synthesis of sterols and fatty acids has been studied in monolayer cultures of L-M cells grown in serum-free medium. Incorporation of radioactivity from [14C] acetate or 3H2O into sterols and fatty acids declined sharply as cultures approached stationary phase. The activities of 3-hydroxy-3-methylglutaryl-CoA reductase and 3-hydroxy-3-methylglutaryl-CoA synthase declined in conjunction with the decrease in sterol synthesis; however, the activity of acetoacetyl-CoA thiolase did not decrease until after sterol synthesis had begun to decline. The magnitude of the initial decline in reductase activity was not diminished when activation of latent enzyme activity was prevented by addition of fluoride to cell homogenates. The diminution in the rate of fatty acid synthesis at high cell density was accompanied by a decrease in the activity of fatty acid synthetase, whereas the activity of acetyl-CoA carboxylase increased slightly. The data suggest that lipogenesis is regulated in coordination with the changes in the rate of cell proliferation that occur when L-M cells attain a high density in monolayer culture. Moreover, these studies establish the feasibility of using the L-M cell culture system to investigate the relationship between cell density and the enzymatic regulation of lipogenesis.

Acetyl-CoA C-Acetyltransferase↗
PubMed1981

Seizures, hypoxic-ischemic brain injury, and intraventricular hemorrhage in the newborn.

The review deals with neonatal seizures, perinatal hypoxic-ischemic brain injury, and neonatal intraventricular hemorrhage. neonatal seizures are the most prominent signals of the largest number of neonatal neurological disorders. The convulsive phenomena may be subtle. The predominant etiological process is hypoxic-ischemic encephalopathy. Prognosis is related primarily to the neurological disease responsible for the seizures. Treatment may be specific for the underlying disorder (e.g., glucose or calcium) or less specific (i.e., therapy with anticonvulsant drugs). Prompt control of the seizures is important to avoid brain injury secondary to the effects of the seizures on ventilation, perfusion, and brain metabolism. Hypoxic-ischemic encephalopathy in the newborn most often is a consequence of intrauterine asphyxia. Diagnosis depends primarily on recognition of the clinical syndrome but also on a variety of neurodiagnostic techniques, including radionuclide and CT brain scans. Prognosis is estimated best by a combination of clinical analysis and specialized neurodiagnostic studies. management is based principally on vigorous support, particularly of ventilation and perfusion, maintenance of adequate glucose influx, and control of seizures. Intraventricular hemorrhage is the most common type of neonatal intracranial hemorrhage. The neuropathology is characterized by bleeding from capillaries of the subependymal germinal matrix. Secondary rupture of the ependymal lining then causes intraventricular hemorrhage. Pathogenesis relates to the anatomy of the germinal matrix, the distribution and regulation of cerebral blood flow, and the structure and vulnerability of periventricular capillaries. Precise diagnosis requires a brain imaging procedure; portable, real-time ultrasound is the preferred approach for critically ill infants. Prognosis relates to the severity of the hemorrhage as well as any preceding hypoxic-ischemic insults and the subsequent occurrence of hydrocephalus. Choice of therapy for posthemorrhagic ventricular dilatation depends upon severity and rapidity of progression and ranges from close observation only to ventriculoperitoneal shunting.

Brain Ischemia↗
PubMed1981

Effects of prior sterol depletion on neurite outgrowth in neuroblastoma cells.

The effect of decreasing cellular sterol content on neurite outgrowth in C1300 (Neuro 2A) neuroblastoma cells in serum-free medium has been studied. Sterol-depleted, undifferentiated neuroblastoma cells were obtained by growing cells for 24 h in medium containing lipoprotein-poor serum and 25-hydroxycholesterol (25-OHC). Under these conditions the activity of 3-hydroxy-3-methyl-glutaryl-CoA reductase and the incorporation of [14C] acetate into sterols were almost completely suppressed, and the sterol/phospholipid ratio of the cells declined to 60% of that in cultures grown without 25-OHC. The sterol-depleted cells were viable and exhibited rats of DNA, RNA, protein and fatty acid synthesis comparable to those measured in control cultures. Sterol depletion had no detectable effect on the number of cells that were able to undergo morphological differentiation within 3 h after removal of serum from the medium. However, by 24 h most of the sterol-depleted cells had retracted their neurites. The observation that addition of low-density lipoprotein was able to restore neurite outgrowth in cultures treated with 25-OHC indicates that the inability of sterol-depleted cells to maintain their neurites is related specifically to the decline in the sterol content rather than to a general cytotoxic effect of 25-OHC. Our findings suggest that incorporation of cholesterol into the cell membrane is important for long-term maintenance and elongation of neuroblastoma neurites, but that the initial morphological change (e.e., within 3 h after removal of serum) is apparently a separate and distinct event, not dependent on the availability of cholesterol.

Animals↗
PubMed1981

The effect of patent ductus arteriosus on flow velocity in the anterior cerebral arteries: ductal steal in the premature newborn infant.

Marked changes in blood flow velocity in the anterior cerebral arteries, measured by a Doppler technique, have been related to PDA in premature infants. Thus, 55 premature infants of birth weight less than 2,000 gm were studied. Ten developed PDA between days three and ten of life. A sharp decrease in diastolic flow velocity and an increase in pulse amplitude in the ACA was observed with the occurrence of PDA. Return of these values to normal occurred promptly following closure of the lesion. These changes in flow velocity and pulse amplitude in the ACA appear to be determined principally by changes in systemic diastolic pressure which accompany PDA. There was no consistent relationship between the changes in flow velocity and arterial PCO2 values. These data suggest that PDA may be involved in the genesis of ischemic and hemorrhagic cerebral injury in the premature newborn infant. Thus, the decrease in flow velocity appears to represent a "steal" of blood from the cerebral arteries, analogous to other documented steal phenomena observed in older patients. Major fluctuations of blood flow velocity in the ACA, with opening and closure of the PDA, and the increase in amplitude of each pulse with PDA may, in the presence of disturbed autoregulation, cause rupture of the capillaries of the germinal matrix and thus, IVH.

Blood Flow Velocity↗