Search PubMed⌕ Search

Biomedical subjects

J J Volpe

Publications and source records attributed to J J Volpe.

At least 109 records · Page 6Linked to original sources
PubMed1986

Glial differentiation in dissociated cell cultures of neonatal rat brain: noncoordinate and density-dependent regulation of oligodendroglial enzymes.

The mixed glial system of primary cultures of cells dissociated from neonatal rat brain was utilized to study glial differentiation. The investigation was addressed specifically to the possibility of noncoordinate regulation of two manifestations of oligodendroglial differentiation, i.e., activities of glycerol-3-phosphate dehydrogenase (GPDH) and of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP), as well as the effects of initial cell density on the time of onset and the intensity of expression of these aspects of oligodendroglial differentiation. Simultaneously, glutamine synthetase activity was studied to determine effects on astrocytic differentiation. GPDH exhibited a major developmental increase in specific activity between 20 and 32 days in culture. However, CNP activity exhibited a major developmental increase that commenced approximately 2 weeks earlier. The onset of these expressions of oligodendroglial differentiation was not affected by such environmental factors as initial cell density. However, the intensity of expression of the temporally separate increases in GPDH and CNP activities was markedly density-dependent. The highest activities were attained in cultures plated at the lowest cell densities. The astrocytic enzyme, glutamine synthetase, also exhibited a striking developmental increase (approximately tenfold between 13 and 30 days in culture), but initial cell density affected neither the time of onset nor the intensity of expression of this aspect of astrocytic differentiation. The data demonstrate a striking developmental increase in GPDH activity that is not coordinate with that in CNP. The noncoordinate manifestations of oligodendroglial differentiation commence as a function of time in culture, whereas the intensity of expression of this differentiation can be influenced by such environmental factors as initial cell density.(ABSTRACT TRUNCATED AT 250 WORDS)

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1986

Periventricular-intraventricular hemorrhage.

This article reviews the pathophysiology of PV-IVH, the clinical aspects, the means of establishing the diagnosis, and the problem of posthemorrhagic ventricular dilation. The most recent advances are emphasized.

Animals↗
PubMed1986

Obligatory relationship between the sterol biosynthetic pathway and DNA synthesis and cellular proliferation in glial primary cultures.

Primary cultures of newborn rat brain, which are composed predominantly of astroglia, were used to examine the relationship between the sterol biosynthetic pathway and DNA synthesis and cellular proliferation. Reduction of the fetal calf serum content of the culture medium from 10 to 0.1% (vol/vol) for an interval of 48 h between days 4 and 6 in culture resulted in a quiescent state characterized by inhibition of DNA synthesis and cellular proliferation. When 10% fetal calf serum was returned to the medium for these quiescent cells, within 24 h DNA synthesis increased markedly. Preceding the rise in DNA synthesis was an increase in sterol synthesis, which occurred within 12 h of the return of the quiescent cells to the 10% fetal calf serum. Exposure of the quiescent cells to mevinolin, a specific inhibitor of sterol synthesis at the 3-hydroxy-3-methylglutaryl-CoA reductase step, completely inhibited the increase in DNA synthesis that followed serum repletion. The increase in total protein synthesis that followed serum repletion was not similarly inhibited by mevinolin. When mevinolin was removed after causing the 24-h inhibition of DNA synthesis, the cultured cells underwent active DNA synthesis and proliferation. Thus, inhibition of the sterol biosynthetic pathway resulted in a specific and reversible inhibition of DNA synthesis and glial proliferation in developing glial cells. These findings establish a valuable system for the examination of glial proliferation, i.e., primary glial cultures subjected to serum depletion and subsequent repletion. Moreover, the data establish an obligatory relationship between the sterol biosynthetic pathway and DNA synthesis and cellular proliferation in developing glia.

Animals↗
PubMed1986

Relation of cellular phospholipid composition to oligodendroglial differentiation in C-6 glial cells.

The relation of the polar head group composition of cellular phospholipids to a biochemical expression of oligodendroglial differentiation was studied in cultured C-6 glial cells. Induction of the oligodendroglial enzyme, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP), was determined after alteration of the polar head group composition of phospholipids by exposure of the cells to choline analogues, especially N,N'-dimethylethanolamine. To accomplish the phospholipid alteration, cells were grown in the presence of the analogue in medium free of exogenous lipid, i.e., first for 24 h in 10% delipidated serum and then for 48 h in serum-free medium. The 48-h exposure to serum-free medium resulted in untreated C-6 cells in a several fold increase in CNP activity, but in cells treated with 2.5 mM N,N'-dimethylethanolamine, total inhibition of this induction was observed. A graded, concentration-dependent inhibitory effect of the analogue on the induction of CNP was defined. The effect of the analogue was relatively specific, e.g., the activity of another plasma membrane enzyme of C-6 cells, (Na+ + K+)-activated ATPase, was not affected. Morever, there was no evidence of a toxic effect of the analogue; thus, total protein synthesis and cell growth were not altered, and the induction of CNP in serum-free medium recurred after removal of the analogue. N,N'-Dimethylethanolamine was shown to be incorporated into cellular phospholipids, primarily at the expense of phosphatidylcholine. The data define an important role for the polar head group composition of membrane phospholipids in oligodendroglial differentiation in this model system.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1986

Periventricular intraparenchymal echodensities in the premature newborn: critical determinant of neurologic outcome.

Controversy exists concerning the degree of importance of periventricular intraparenchymal echodensities (IPE) observed on neonatal ultrasound scans in the determination of subsequent neurologic disability in premature infants. In this report, IPE was studied in 75 infants weighing less than 2,000 g at birth to determine the basic characteristics of the lesion, the likely pathogenesis, the outcome, and the aspects of the ultrasonographic appearance in the acute period of neonatal illness that are important for prediction of outcome. IPE was defined as any periventricular echodensity greater than 1 cm in at least one dimension. IPE was strikingly associated with large areas of intraventricular hemorrhage (IVH) (81% of cases). IPE was distinctly asymmetric. Thus, the lesion was either exclusively unilateral (67%) or bilateral with marked predominance on one side. The associated IVH was asymmetric in approximately 80% of cases, and in all 50 cases of large asymmetric IVH, IPE occurred on the same side as the larger amount of intraventricular blood. Moreover, more than 50% of such cases of IPE associated with large asymmetric IVH were progressive. Neuropathologic correlation showed that IPE represented hemorrhagic necrosis of periventricular tissue. Concerning pathogenesis, these data raise the possibility that large asymmetric IVH is related etiologically to IPE. Outcome varied with the severity of the IPE. Thus, the mortality rate among the 38 infants with extensive IPE was 79%. Of the survivors with extensive IPE, all had subsequent major motor deficits and all but one exhibited cognitive function less than 80% of normal. Among the 37 infants with localized IPE, the mortality rate was 38%. Of the survivors, although 79% had major motor deficits, 43% had cognitive function greater than 80% of normal. Thus, the findings demonstrate that with extensive IPE there is little or no chance for survival with normal neurologic and cognitive outcome, but with localized IPE, although major motor deficits are common, an appreciable proportion of infants have cognitive function in the normal range. Careful, quantitative assessment of the ultrasonographic features of IPE in the acute period of illness in the premature infant is of major value in estimating outcome.

Brain↗
PubMed1985

Zn2+, not Ca2+, is the most effective cation for activation of dolichol kinase of mammalian brain.

The cation specificity of dolichol kinase of mammalian brain and the potential involvement of a Ca2+-calmodulin system in regulation of this enzyme have been studied. Among 10 divalent cations examined, Zn2+ was found to be most effective for the activation of dolichol kinase of rat and calf brain and cultured C-6 glial cells. The activations with Ca2+, Co2+, and Mg2+ were 53%, 32%, and 18% of the full activation with Zn2+, respectively. No combinations of the cations could activate the enzyme as much as Zn2+ alone. A role for a Ca2+-calmodulin system in the regulation of brain dolichol kinase was not supported by our data. First, the concentration of free Ca2+ required for the maximum activation of dolichol kinase was two to three orders of magnitude greater than the concentration required by typical calmodulin-dependent enzymes. Second, neither the depletion of calmodulin from the microsomal fraction nor the addition of exogenous calmodulin caused an alteration in the activation of dolichol kinase by Ca2+ (or Zn2+). Third, antagonists of calmodulin failed to suppress the activation of the enzyme by Ca2+ (or Zn2+). The data raise the possibility that Zn2+ is involved in the regulation of dolichol kinase in brain.

Animals↗
PubMed1985

Reduction in intraventricular hemorrhage by elimination of fluctuating cerebral blood-flow velocity in preterm infants with respiratory distress syndrome.

In a previous study of preterm infants requiring mechanical ventilation for the respiratory distress syndrome, we demonstrated a striking association of fluctuating cerebral blood-flow velocity in the first day of life with the subsequent occurrence of intraventricular hemorrhage. Because this fluctuating pattern could be eliminated by muscle paralysis, we conducted a prospective study of preterm infants receiving mechanical ventilation for the respiratory distress syndrome in which we evaluated the effect of paralysis and this flow-velocity pattern on the incidence and severity of intraventricular hemorrhage. Twenty-four infants with the fluctuating pattern in the first hours of life were identified and randomly selected to serve as controls (10) or to be subjected to muscle paralysis (14). Intraventricular hemorrhage developed in all 10 control infants but in only 5 of the 14 infants subjected to muscle paralysis. Moreover, in 4 of the 5 paralyzed infants in whom hemorrhage developed, it did so after cessation of the paralysis. Seven of the 10 control infants had Grade III hemorrhage, the most severe variety of intraventricular hemorrhage, whereas none of the paralyzed infants had Grade III hemorrhage. We conclude that elimination of fluctuating cerebral blood-flow velocity in preterm infants with respiratory distress syndrome markedly reduces the incidence and severity of intraventricular hemorrhage.

Blood Flow Velocity↗
PubMed1985

Positron emission tomography in the asphyxiated term newborn: parasagittal impairment of cerebral blood flow.

Hypoxic-ischemic encephalopathy secondary to perinatal asphyxia in the term newborn is the most common recognized cause of the subsequent motor deficits often grouped under the rubric "cerebral palsy." In order to provide insight into the basic nature and pathogenesis of the brain injury in such infants, we studied regional cerebral blood flow (CBF) by positron emission tomography (PET) in 17 asphyxiated term infants during the acute period of illness. A consistent and apparently unifying abnormality was observed, namely, a relative decrease in CBF to parasagittal regions, generally symmetrical and more marked posteriorly than anteriorly. Thus, parasagittal values for CBF were generally 25 to 50% lower than those for the sylvian cortex; in the normal or near normal infant, parasagittal values are only approximately 10% lower than those for the sylvian cortex. (Additional normal findings for regional CBF were 50% higher flows to the cerebral cortex than to the cerebral white matter and flows to the basal ganglia and thalamus at least as high as those to the cerebral cortex). That the relative deficit in CBF to parasagittal regions reflects tissue injury was indicated by the close topographic correlation on technetium brain scans in 3 patients of increased tissue uptake of radionuclide and the CBF abnormality. Moreover, the single patient studied at postmortem examination exhibited parasagittal ischemic cerebral injury that correlated well with the PET abnormality of regional CBF. The topography of the PET abnormality, i.e., the cerebrovascular watershed regions, suggests that the brain injury is basically ischemic and that the pathogenesis relates to impaired cerebral perfusion, perhaps secondary to systemic hypotension occurring in association with the perinatal asphyxia. Experimental data support this formulation.

Asphyxia Neonatorum↗
PubMed1985

Cholesterol biosynthesis and its regulation in dissociated cell cultures of fetal rat brain: developmental changes and the role of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

Primary cultures of cells dissociated from fetal rat brain were utilized to define the developmental changes in cholesterol biosynthesis and the role of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in the regulation of these changes. Cerebral hemispheres of fetal rats of 15-16 days of gestation were dissociated mechanically into single cells and grown in the surface-adhering system. Cholesterol biosynthesis, studied as the rate of incorporation of [14C]acetate into digitonin-precipitable sterols, was shown to exhibit two distinct increases in synthetic rates, a prominent increase after 6 days in culture and a smaller one after 14 days in culture. Parallel measurements of HMG-CoA reductase activity also demonstrated two discrete increases in enzymatic activity, and the quantitative and temporal aspects of these increases were virtually identical to those for cholesterol synthesis. These data indicate that cholesterol biosynthesis undergoes prominent alterations with maturation and suggest that these alterations are mediated by changes in HMG-CoA reductase activity. The timing of the initial prominent peak in both cholesterol biosynthesis and HMG-CoA reductase activity at 6 days was found to be the same as the timing of the peak in DNA synthesis, determined as the rate of incorporation of [3H]thymidine into DNA. The second, smaller peak in reductase activity and sterol biosynthesis at 14 days occurred at the time of the most rapid rise in activity of the oligodendroglial enzyme, 2':3'-cyclic nucleotide 3'-phosphohydrolase (CNP). These latter observations suggest an intimate relationship of the sterol biosynthetic pathway with cellular proliferation and with oligodendroglial differentiation in developing mammalian brain.

Animals↗
PubMed1985

Dolichol in human brain: regional and developmental aspects.

Distinct regional differences in dolichol content were defined in human brain from 15 to 76 years of age. Concerning the regional distribution of dolichol, levels were: higher in cortical gray matter than in subcortical white matter, highest among cortical regions in temporal gray matter, highest among all brain regions in thalamus, and lowest among all brain regions in lower brain stem and spinal cord. The developmental changes in the contents of dolichol were found to be different among brain regions. For example, among regions with the highest levels of dolichol, in thalamus there was a six to sevenfold increase, but in parietal gray matter, only a 2.5-fold increase. Regional and developmental changes in the proportions of the individual molecular species (isoprenologues) of dolichol were also observed. The findings indicate that the metabolism of dolichol is not uniform among regions of developing and aging human brain and may have implications for the role of dolichol in normal and diseased human brain.

Adolescent↗
PubMed1985

Positron emission tomography in the newborn: effect of seizure on regional cerebral blood flow in an asphyxiated infant.

Regional cerebral blood flow (CBF) was measured by positron emission tomography (PET) with 15O-labeled water in an asphyxiated infant during a seizure. After intrauterine asphyxia, the infant had a syndrome characteristic of hypoxic-ischemic encephalopathy. During a PET scan on the second postnatal day, the infant had a focal seizure with deviation of eyes to the right and clonic jerking of the right arm. Regional blood flow was highest, about 80 ml/100 g/min, in the left temporal-parietal frontal region of the left hemisphere, the site of origin of the seizure; blood flow in the same region on the other side was about 57 ml/100 g/min. These observations extend to the newborn previous demonstrations in older patients of a focal increase of CBF at the cerebral site of origin of a focal seizure.

Asphyxia Neonatorum↗
PubMed1985

Serial lumbar punctures for at least temporary amelioration of neonatal posthemorrhagic hydrocephalus.

Serial lumbar punctures for the management of neonatal posthemorrhagic hydrocephalus without intracranial hypertension were evaluated in 16 infants. Cranial ultrasonography to evaluate ventricular size and the Ladd monitor at the anterior fontanel to measure intracranial pressure were utilized immediately before and after lumbar puncture. In 12 patients, a decrease in ventricular size and in anterior fontanel pressure could be effected with each lumbar puncture. In these infants, cessation of progression of the hydrocephalus and intermittent decreases in ventricular size were accomplished. In four patients, lumbar punctures were not successful in decreasing ventricular size or lowering intracranial pressure. Two criteria could be defined to determine whether lumbar puncture could provide at least temporary benefit for the treatment of posthemorrhagic hydrocephalus. The first of these is to establish the presence of communication between lateral ventricles and lumbar subarachnoid space by effecting a decrease in ventricular size and a decrease in intracranial pressure by removal of CSF. The second criterion is to ascertain a critical volume of CSF (usually relatively large) that must be removed in order to effect the above changes. Cranial ultrasonography and measurement of intracranial pressure by application of the Ladd monitor to the anterior fontanel are extremely valuable in the evaluation of lumbar punctures in the management of posthemorrhagic hydrocephalus.

Cerebral Hemorrhage↗
PubMed1985

Pathogenesis and management of hypoxic-ischemic encephalopathy in the term newborn.

The pathogenesis and management of hypoxic-ischemic encephalopathy in the term infant is reviewed. Specifically, the potential significance of a variety of factors on the pathogenesis of brain injury is discussed including changes in cerebral blood flow, brain swelling, carbohydrate status, alterations in ion homeostasis, and synaptic activity. Management is reviewed in terms of prevention, supportive care, corrections of metabolic derangements, control of seizures, and prevention of fluid overload.

Blood Glucose↗
PubMed1985

Episodes of apnea and bradycardia in the preterm newborn: impact on cerebral circulation.

The effect of episodes of apnea with bradycardia on cerebral circulation was studied during 101 episodes in 15 premature infants. The objectives of the study were to determine whether important alterations occur in cerebral hemodynamics with apnea and bradycardia and whether such alterations relate to systemic hemodynamic events. The transcutaneous Doppler technique was used to measure blood flow velocity in the anterior cerebral arteries. With episodes of apnea complicated by mild-to-moderate bradycardia (heart rate less than 120 or greater than 80), a decrease in diastolic flow velocity was noted with little or no change in systolic flow velocity. With episodes complicated by severe bradycardia (heart rate less than 80), the diastolic flow velocity fell to the electronic base line, and a progressive decrease in systolic flow velocity also was observed. Accompanying the changes in cerebral blood flow velocity were similar changes in arterial blood pressure. These data suggest potential deleterious hypoxic-ischemic effects on brain from apnea with severe bradycardia in the preterm infant.

Apnea↗
PubMed1984

Rapidly progressive posthemorrhagic hydrocephalus. Treatment with external ventricular drainage.

Nineteen premature infants with progressive posthemorrhagic hydrocephalus with increased intracranial pressure were treated with external ventricular drainage. Progression of hydrocephalus was arrested during the drainage period in each patient. Three of the 19 infants required no further therapy. Sixteen had recurrence of progressive ventricular dilatation, and all but one eventually had placement of a ventriculoperitoneal shunt, although under more favorable medical conditions than existed at the time of institution of external ventricular drainage. Three of the 19 infants died of causes unrelated to the external ventricular drainage. Of the 16 survivors, seven infants had a developmental quotient or formal IQ of over 75. Outcome was poorest for those infants with accompanying intracerebral hemorrhage. We consider ventriculostomy to be an effective temporizing measure in small infants with rapidly progressive posthemorrhagic hydrocephalus with increased intracranial pressure in whom ventricular decompression is necessary and placement of a ventriculoperitoneal shunt is not feasible.

Catheterization↗
PubMed1984

Outcome of neonatal intraventricular hemorrhage with periventricular echodense lesions.

The incidence of periventricular-intraventricular hemorrhage (PV-IVH) in a group of 460 preterm infants with birth weight less than 2,250 gm, studied by cranial ultrasonography, was 39%. Sixty-four (36%) of the infants with periventricular-intraventricular hemorrhage had, in addition, periventricular intraparenchymal echodensity (IPE) evident on ultrasound scan. Thirty-three of the 64 infants had large IPE, and 31 had small IPE. Large IPE consisted of globular echodensity, most often on the side of maximum intraventricular hemorrhage, extending from the external angle of the lateral ventricle into major portions of the white matter of the frontal and parietal lobes; small IPE, often bilateral, consisted of linear echodensity extending for a few millimeters from the external angle of the lateral ventricle into the periventricular white matter. The outcome for infants with large and small IPE differed markedly. Mortality was greatest (94%) for infants with large IPE and birth weight less than 1,000 gm. All survivors with large IPE, regardless of birth weight, had moderate to severe neurological deficits evident on follow-up. In contrast, infants with small IPE and birth weight less than 1,000 gm had a mortality of 38%. Moreover, 70% of all survivors with small IPE were free of neurological deficits on follow-up. The difference in outcome appeared to relate in largest part to the severity of the parenchymal involvement. These data have major significance for decisions concerning management of infants with periventricular-intraventricular hemorrhage and intraparenchymal involvement.

Cerebral Hemorrhage↗
PubMed1984

Value of ultrasound for identification of acute hemorrhagic necrosis of thalamus and basal ganglia in an asphyxiated term infant.

An infant with profound intrapartum and postpartum asphyxia demonstrated striking bilateral echodensities in the region of the thalamus and basal ganglia on ultrasound scan. Neuropathological examination confirmed the presence of symmetrical areas of hemorrhagic necrosis involving the thalamus, caudate, putamen, and globus pallidus. The findings demonstrate the value of ultrasonography in the identification of this variety of perinatal hypoxic-ischemic injury.

Asphyxia Neonatorum↗