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Biomedical subjects

J J Volpe

Publications and source records attributed to J J Volpe.

At least 127 records · Page 7Linked to original sources
PubMed1984

Dolichol deposition in developing mammalian brain: content of free and fatty-acylated dolichol and proportion of specific isoprenologues.

Dolichol serves a critical role in N-linked glycoprotein synthesis as the carrier of saccharide moieties. In this study the deposition of dolichol was investigated in developing rat brain. The contents of both the free and fatty-acylated forms of dolichol as well as the specific isoprenologues of dolichol were determined. Two distinctive phases of rapid dolichol deposition were observed; the first during brain development, and the second, with aging. The predominant form of brain dolichol was shown to be the free derivative at all ages; however, during the two phases of rapid deposition of total dolichol, fatty-acylated dolichol became detectable and increased transiently. The rapid rate of increase of brain dolichol during development occurred later than that of brain cholesterol, which shares a common biosynthetic pathway with dolichol. Thus, the peak rate of increase of dolichol occurred at 25 days postnatal, and of cholesterol, at 18 days postnatal. A distinct ontogenetic alteration in the proportion of the individual molecular species (isoprenologues) of dolichol also was defined. These observations suggest that dolichol is particularly involved in developmental events of the third to sixth postnatal weeks in rat brain, e.g. myelination and synaptogenesis.

Age Factors↗
PubMed1984

Relation of cholesterol to astrocytic differentiation in C-6 glial cells.

The relation of cellular cholesterol content to a biochemical expression of astrocytic differentiation was investigated in cultured C-6 glial cells. The astrocytic marker, glutamine synthetase, was studied. Cellular sterol content was perturbed with compactin, a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase and, thereby, cholesterol biosynthesis. Depletion of cellular sterol resulted in 72 h in a more than twofold increase in glutamine synthetase activity. Production of various degrees of sterol depletion with different concentrations of compactin demonstrated a striking inverse relationship between glutamine synthetase activity and the cellular sterol/phospholipid molar ratio. That the effect of compactin, in fact, is mediated by depletion of sterol was shown further by prevention of the compactin-induced increase in synthetase activity by simultaneous addition of exogenous cholesterol. Moreover, addition of cholesterol alone to the culture medium led to both a decrease in glutamine synthetase activity and an increase in the sterol/phospholipid molar ratio. The possibility that the compactin-induced increase in glutamine synthetase activity is caused by an increase in synthesis of the enzyme was suggested by prevention of the increase by cycloheximide. The data suggest that astrocytic differentiation is stimulated by a decrease in cellular sterol content. When considered with our previous observation that oligodendroglial differentiation is inhibited by such a decrease, the findings suggest that cellular sterol content is a critical determinant of the direction of glial differentiation, i.e., whether along astrocytic or oligodendroglial lines.

Animals↗
PubMed1984

Cytoskeletal structures and oligodendroglial differentiation in C-6 glial cells.

The relationship of the cytoskeleton to a biochemical expression of oligodendroglial differentiation was studied in cultured C-6 glial cells. Specifically, we investigated the effect of the cytoskeletal perturbants, colchicine and cytochalasin D, on the induction of the oligodendroglial marker enzyme, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP), caused by removal of serum from the culture medium. Each drug inhibited CNP induction in a concentration-dependent manner, and essentially complete inhibition of induction was observed with 0.25 microM colchicine or 2.0 microM cytochalasin D. Detailed study of the effect of colchicine was carried out. This antimicrotubular agent not only totally prevented induction if added at the onset of serum removal, but also prevented further induction when added at various times after serum removal. That the effect of colchicine related to the drug's effect on microtubules was supported by the demonstration that lumicolchicine, a colchicine isomer which has no effect on microtubules, had no effect on the CNP induction. Moreover, colchicine, but not lumicolchicine, prevented the morphological signs of differentiation provoked by serum removal. The effect of colchicine was reversible and relatively specific. Thus, no concomitant effect of colchicine on the activity of another plasma membrane enzyme of C-6 cells, i.e., (Na+ + K+)-activated ATPase, or on the rate of incorporation of [3H]leucine into total protein of intact cells could be discerned. The possibility that the site of the effect of colchicine is on intracellular events was suggested by the observation that the drug inhibited the induction of CNP by dibutyryl cyclic AMP. The data suggest that the cytoskeleton is involved in oligodendroglial differentiation.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1984

Bacterial meningitis in infancy: effects on intracranial pressure and cerebral blood flow velocity.

The effects of acute bacterial meningitis on intracranial pressure (ICP) and cerebral blood flow velocity (CBFV) were studied in four older infants (mean age, 5.75 months) and in four newborns. ICP and CBFV were affected in the older infants, but not in the newborns. In the older infants, ICP was markedly elevated in the first 2 days of illness (mean peak ICP, 240 mm H2O). With resolution of intracranial hypertension in the next few days, CBFV increased approximately 80%. In the newborns, there was no marked elevation of ICP or change in CBFV. Impaired cerebral perfusion, due to intracranial hypertension, is a potential cause of brain injury in older infants. Other mechanisms of brain injury may be more important in newborns.

Age Factors↗
PubMed1984

Normal neurologic development and marked reconstitution of cerebral mantle after postnatal treatment of intrauterine hydrocephalus.

We treated an infant who had severe congenital hydrocephalus and a massively enlarged head at birth. Despite extreme attenuation of the cerebral mantle, placement of a ventriculoperitoneal shunt at 4 weeks of age was followed by essentially normal neurologic development after several months. In addition, there was a striking reconstitution of the cerebral mantle.

Brain↗
PubMed1984

A potential mechanism of pathogenesis for early posthemorrhagic hydrocephalus in the premature newborn.

Ventricular dilation is common following intraventricular hemorrhage. Neuropathologic studies have demonstrated that chronic posthemorrhagic hydrocephalus most commonly is a result of an obliterative arachnoiditis in the posterior fossa or is due to obstruction of flow of CSF within the ventricular system. Recent use of ultrasound scanning has demonstrated the occurrence of ventricular dilation within days of intraventricular hemorrhage (prior to the expected time of development of arachnoiditis). In the case described, serial real-time ultrasound scans demonstrated small mobile particles within dilated ventricles seven days following intraventricular hemorrhage. There was no obstruction of CSF flow within the ventricular system. Thus, in this case, ventricular dilation may have been secondary to plugging of arachnoid villi by the small particulate matter and, as a consequence, decrease in CSF reabsorption.

Cerebral Hemorrhage↗
PubMed1983

Effect of tunicamycin on 3-hydroxy-3-methylglutaryl coenzyme A reductase in C-6 glial cells.

The effects of tunicamycin on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and cholesterol biosynthesis have been studied in cultured C-6 glial cells. Depending on culture conditions, exposure to tunicamycin caused either a marked inhibition of induction of HMG-CoA reductase activity or, under steady state conditions, a marked reduction in enzymatic activity. Incorporation of [14 C]acetate into sterols was affected similarly. After a 24-h exposure, a 50% reduction in reductase activity was observed with a concentration of 0.05 micrograms/ml, and a maximal, 65-70% reduction occurred with 0.10 micrograms/ml of the drug. The effect of tunicamycin on reductase activity and on sterol synthesis was apparent 4 h after addition of the drug and nearly maximal after 6 h. The relative specificity of the effect of tunicamycin was indicated by the finding of no change in the activities of NADPH-cytochrome c reductase, acetyl-CoA carboxylase, or fatty acid synthetase, in incorporation of [3H]leucine into total protein, or in the rate of increase in cellular protein and phospholipid at concentrations of tunicamycin that caused the marked effect on HMG-CoA reductase. The reversibility of the effect of tunicamycin was shown by observing total recovery of reductase activity within 24 h after removal of the drug following a 24-h exposure. That the effect of tunicamycin on reductase is related to the drug's effect on glycoprotein synthesis was shown in two ways. First, the range of concentrations over which tunicamycin led to the decrease in reductase activity was essentially identical with the range over which the drug led to a decrease in incorporation of [3H]mannose into protein. Second, incubation of C-6 cells with N-acetylglucosamine simultaneously with tunicamycin was accompanied by prevention of the drug's effect on both HMG-CoA reductase and glycoprotein synthesis. These data suggest that glycoprotein synthesis is necessary for the expression of HMG-CoA reductase activity and, thereby, cholesterol synthesis in glial cells. Moreover, a link between glycoprotein and cholesterol biosynthesis could play a role in the mediation of certain maturational events in cells of neural origin.

Acetylglucosamine↗
PubMed1983

Fluctuating cerebral blood-flow velocity in respiratory-distress syndrome. Relation to the development of intraventricular hemorrhage.

We studied whether changes in cerebral blood-flow velocity occur during the respiratory-distress syndrome and whether, if present, they are related to the subsequent occurrence of intraventricular hemorrhage. Fifty infants weighing less than 1500 g at birth who required mechanical ventilation for the respiratory-distress syndrome were studied from the first hours of life. Blood-flow velocity in the anterior cerebral artery was measured at the anterior fontanel by means of the Doppler technique. At 12 hours of age, the infants had blood-flow velocity patterns that were either stable or fluctuating and that reflected the patterns of simultaneously recorded blood pressure. Intraventricular hemorrhage subsequently developed in 21 of 23 infants with the fluctuating pattern (in most of them, within the next 24 hours), but in only 7 of 27 infants with the stable pattern. Preliminary data suggest that the cerebral hemodynamic fluctuations are related to the respiratory disease and particularly to the mechanics of respiration. We conclude that the fluctuating pattern of cerebral blood-flow velocity in infants with the respiratory-distress syndrome indicates an extreme risk of the development of intraventricular hemorrhage and may represent a major and potentially preventable etiologic factor.

Blood Flow Velocity↗
PubMed1983

Doppler ultrasonography in the determination of neonatal brain death.

Both clinical and electroencephalographic criteria for brain death have limited value in the newborn. A simple test to determine the cessation of cerebral blood flow would be a useful adjunct to the determination of brain death in this population. In contrast to the invasive techniques used in older patients to estimate cerebral blood flow, the Doppler technique to estimate cerebral blood flow velocity from the anterior fontanelle of the newborn is noninvasive and can be used at bedside. In this study we define the changes in the flow velocity pattern in the anterior cerebral and the common carotid arteries in six newborn infants with clinical criteria for brain death: coma, absent brainstem function, and dependence on mechanical ventilation. A characteristic sequence of deterioration of the flow velocity waveform in both vessels was defined. This sequence consisted of (1) loss of diastolic flow, (2) appearance of retrograde flow during diastole, (3) diminution in systolic flow in the anterior cerebral artery, and, ultimately, (4) no detectable flow in the anterior cerebral artery, despite considerable flow in the common carotid artery. This constellation of findings suggests a progressive increase in cerebrovascular resistance and a progressive decrease in cerebral perfusion, compatible with the diffuse cerebral necrosis and edema documented postmortem. We conclude that the transcutaneous Doppler technique is a useful complement to other noninvasive methods, especially clinical assessment, in the determination of brain death in the newborn.

Blood Flow Velocity↗
PubMed1983

Seizures in the preterm infant: effects on cerebral blood flow velocity, intracranial pressure, and arterial blood pressure.

The relationship of neonatal seizures to changes in the cerebral circulation was studied in 12 premature newborn infants. The objectives of the study were to determine whether important alterations in cerebral hemodynamics occur with neonatal seizures and whether such alterations relate to systemic hemodynamic events. Blood flow velocity in the anterior cerebral arteries was measured by a transcutaneous Doppler technique. A marked increase in cerebral blood flow velocity was documented with seizures in every patient. The prominent changes in the cerebral circulation occurred despite the fact that 10 of the 12 infants had only subtle seizures and all 12 were receiving mechanical ventilation at the time of the seizures. Accompanying the increase in cerebral flow velocity was a marked increase in intracranial pressure. The cerebral hemodynamic changes appeared to reflect directly changes in systemic hemodynamic events, that is, a marked increase in blood pressure at the time of seizures. The increase in cerebral blood flow velocity with seizures, an apparent adaptive physiologic response in older individuals, may be maladaptive in the newborn infant with certain vulnerable capillary beds, such as the germinal matrix in the premature infant or the margins of an infarct in the asphyxiated infant.

Blood Flow Velocity↗
PubMed1983

Relation of cholesterol to oligodendroglial differentiation in C-6 glial cells.

The relation of cellular cholesterol content of a biochemical expression of oligodendroglial differentiation was studied in cultured C-6 glial cells. Induction of the oligodendroglial marker enzyme 2':3'-cyclic nucleotide 3'-phosphohydrolase (CNP) was determined after alteration of the sterol content of cellular membranes by exposure to compactin, a specific inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol synthesis. The sterol content and, as a consequence, the sterol/phospholipid molar ratio of C-6 glial cells were decreased by treating the cells, in 10% lipoprotein-poor serum, with various concentrations of compactin for 24 h. The degrees of sterol depletion thus produced were maintained for 48 h after removal of the compactin if the cells were maintained in serum-free medium, the culture conditions necessary for induction of CNF in untreated cells. Forty-eight hours after removal of serum, no induction of CNP occurred in cells previously treated with 0.5 micrograms/ml of compactin, whereas untreated cells exhibited a three- to fourfold increase in CNP activity. Intermediate degree of sterol depletion resulted in intermediate degrees of inhibition of the CNP induction. Moreover, the morphological expressions of glial differentiation observed in the untreated cells did not occur in the sterol-depleted cells. That the effect of compactin on the induction of CNP relates to depletion of sterol was indicated by the finding that when low-density lipoprotein was added to the compactin-treated cells, the induction of CNP, the morphological expressions of differentiation, and the sterol/phospholipid molar ratios were preserved. The degree of sterol depletion that totally prevented the induction of CNP had no effect on (Na+ R K+)-activated ATPase activity, total protein synthesis, and cell viability. The data define a critical role for sterol in oligodendroglial differentiation in this model system.

Animals↗
PubMed1983

Positron emission tomography in the newborn: extensive impairment of regional cerebral blood flow with intraventricular hemorrhage and hemorrhagic intracerebral involvement.

Of all patients with intraventricular hemorrhage, those with hemorrhagic intracerebral involvement exhibit the highest rates of mortality and neurologic morbidity and, indeed, account for the vast majority of all neurologic impairment in infants with intraventricular hemorrhage. Insight into the basic nature of the critical cerebral involvement requires determination of regional cerebral blood flow, previously not possible. Positron emission tomography (PET) now provides the capability of measuring regional cerebral blood flow with high resolution and little risk. In this study, we utilized PET in six premature infants (920 to 1,200 g) with major intraventricular hemorrhage and hemorrhagic intracerebral involvement to measure regional cerebral blood flow during the acute period (5 to 17 days of age). Cerebral blood flow was determined after intravenous injection of H2O, labeled with the positron-emitting isotope, 15O (oxygen 15). Findings were similar and dramatic in all six infants. In the area of hemorrhagic intracerebral involvement, little or no cerebral blood flow was detected. However, in addition, surprisingly, a marked two- to fourfold reduction in cerebral blood flow was observed throughout the affected hemisphere, well posterior and lateral to the intracerebral hematoma, including cerebral white matter and, to a lesser extent, frontal, temporal, and parietal cortex. In the one infant studied a second time, ie, at 3 months of age, the extent and severity of the decreased cerebral blood flows in the affected hemisphere were similar to those observed on the study during the neonatal period. At the three autopsies, the affected left hemisphere showed extensive infarction, corroborating the PET scans. These observations, the first demonstration of the use of PET in the determination of regional cerebral blood flow in the newborn, show marked impairments in regional cerebral blood flow in the hemisphere containing an apparently restricted intracerebral hematoma, indicating that the hemorrhagic intracerebral involvement is only a component of a much larger lesion, ischemic in basic nature, ie, an infarction. This large ischemic lesion explains the poor neurologic outcome in infants with intraventricular hemorrhage and hemorrhagic intracerebral involvement.

Acute Disease↗
PubMed1983

Intracerebellar hemorrhage in a premature newborn: diagnosis by real-time ultrasound and correlation with autopsy findings.

The identification of intracerebellar hemorrhage in a living premature infant by real-time ultrasound scan and confirmation of the findings at autopsy are described. This represents the first demonstration of the value of this noninvasive, convenient, and safe means of brain imaging in diagnosis of this lesion. Previous studies have described the role of the computed tomography (CT) scan in identification of intracerebellar hemorrhage in the newborn. Because infants with intracerebellar hemorrhage are usually critically ill, a means of identification of the lesion that could be utilized at the bedside rather than an approach that requires transport to a CT scanner is needed. This study indicates that portable real-time ultrasound scanning can satisfy that need.

Cerebellar Diseases↗
PubMed1983

Suctioning in the preterm infant: effects on cerebral blood flow velocity, intracranial pressure, and arterial blood pressure.

The relationship of suctioning to changes in the cerebral circulation was studied in 35 premature newborn infants. The objectives of the study were to determine whether important alterations occur in cerebral hemodynamics with suctioning and whether such alterations relate to systemic hemodynamic events. A transcutaneous Doppler technique was used to measure blood flow velocity in the anterior cerebral arteries. A prominent increase in cerebral blood flow velocity was documented in nearly all patients. Accompanying the increase in cerebral flow velocity was a marked increase in blood pressure; thus, the increased cerebral flow velocity appeared to reflect directly changes in systemic hemodynamic events. Also accompanying the increase in cerebral flow velocity was a marked increase in intracranial pressure. These data suggest potentially deleterious effects of suctioning in the preterm infant at risk for the occurrence of intraventricular hemorrhage and raise questions regarding the advisability of routine suctioning of such infants.

Blood Flow Velocity↗
PubMed1982

Cerebral blood flow velocity in relation to intraventricular hemorrhage in the premature newborn infant.

The relation of IVH to blood flow velocity in the anterior cerebral arteries has been studied in the premature newborn infant. The objectives of the study were to determine the effect of IVH on cerebral blood flow velocity, measured by a noninvasive Doppler technique, and to assess the reliability of this technique in the diagnosis of the hemorrhage. Thirty-two premature newborn infants with IVH were identified by real-time ultrasound scanning: IVH was present in the first 24 hours of life in approximately 50%, progressed postnatally in approximately 20%, and was severe in approximately 50%. Cerebral blood flow velocity, determined daily in the first five days of life, was compared to the time of occurrence of IVH and to simultaneous measurements of systemic blood pressure and blood gases. No consistent relationship between timing or severity of IVH and cerebral blood flow velocity could be discerned. We conclude that cerebral blood flow velocity in the anterior cerebral arteries is not likely to be affected by IVH and that the noninvasive Doppler technique for measurement of this velocity is not reliable for diagnosis of the lesion.

Blood Flow Velocity↗
PubMed1982

Intraventricular hemorrhage in the premature infant.

Periventricular-intraventricular hemorrhage is the most important adverse neurologic event of the newborn period. It is very common and can be very severe. Such hemorrhage begins in the germinal matrix but may spread into and throughout the ventricular system. It may be accompanied by hemorrhage within the brin parenchyma. The pathogenesis of periventricular-intraventricular hemorrhage is still imperfectly understood, but relates to the anatomy and physiology of the developing cerebral vasculature and to the biophysical and biochemical environment in which that development proceeds. Periventricular-intraventricular hemorrhage may be marked by a catastrophic clinical deterioration, but is more commonly accompanied by a saltatory progression that may be difficult to detect clinically. Both concomitant neonatal disease and therapeutic intervention for such disease have been implicated in the initiation and exacerbation of periventricular-intraventricular hemorrhage. Real-time ultrasound scanning with portable instruments is now the best procedure for identifying this lesion and for assessing its sequelae. Prognosis relates principally to the severity of the lesion. Early management must be particularly directed to the maintenance of cerebral perfusion. Later management is predominantly the therapy of posthemorrhagic hydrocephalus. There is no currently available therapeutic modality that will prevent progressive posthemorrhagic hydrocephalus.

Cerebral Hemorrhage↗