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J J Volpe

Publications and source records attributed to J J Volpe.

At least 73 records · Page 4Linked to original sources
PubMed1990

N-linked glycoprotein synthesis and transport during G1 are necessary for astrocytic proliferation.

The proliferation of astrocytes, purified by a selective detachment technique from mixed glial primary cultures derived from newborn rat cerebrum, was studied. The cells were synchronized by first inducing a quiescent state by removing fetal calf serum (FCS) from the culture medium for 2 days; reversal of the quiescent state by return of serum to the culture medium caused a marked increase in DNA synthesis 12-24 hr later. 2-Deoxyglucose, an inhibitor of dolichol-linked oligosaccharide and thereby N-linked glycoprotein biosynthesis, prevented not only an increase in glycoprotein biosynthesis in G1 phase of the cell cycle but also the burst of DNA synthesis that followed during S phase. Addition of mannose to the culture medium prevented the inhibitions by deoxyglucose of both glycoprotein and DNA syntheses. These data indicated an obligatory relationship in astrocytes between dolichol-linked glycoprotein synthesis and DNA synthesis. To determine whether transport of the newly synthesized glycoproteins to the plasma membrane for incorporation therein or for secretion were necessary for DNA synthesis and astrocytic proliferation, we studied cells treated with monensin, an ionophore for monovalent cations, and an inhibitor of intracellular transport of glycoproteins. The presence of monensin in the first 12 hr after repletion of serum to synchronized astrocytes prevented progression to the S phase and cell proliferation; addition of monensin after the first 12 hr, at the onset of the S phase, had no effect on progression through S phase. Lectin-staining methods combined with fluorescence microscopy demonstrated in monensin-treated cells failure of intracellular glycoproteins to be transported to the plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1990

Angelman's syndrome in infancy.

The authors report an 11-month-old patient with the clinical features of Angelman syndrome and a 15q11 x 2-12 chromosomal deletion, thus demonstrating that the clinical features may be present in infancy and so allow early diagnosis. The features included pronounced postnatal growth failure, delayed dentition and ossification of growth centers. Low amniotic fluid alpha-fetoprotein was noted at 16 weeks of gestation. Head MRI showed only generalized atrophy. Some affected patients have a genetic marker similar to the chromosomal deletion associated with Prader-Willi syndrome. The importance of awareness of the clinical symptoms of Angelman syndrome is discussed.

Chromosome Banding↗
PubMed1990

Late hydrocephalus after arrest and resolution of neonatal post-hemorrhagic hydrocephalus.

This report describes the occurrence of rapid progression of hydrocephalus after discharge from the nursery in four of 48 infants who had had previous arrest of progression of post-hemorrhagic hydrocephalus, and at least partial resolution of ventriculomegaly. This later-onset hydrocephalus occurred at a mean age of seven months; the most consistent presenting clinical feature was rapid head growth. Three of the four infants required a ventriculo-peritoneal shunt and the fourth was treated with acetazolamide, with apparent resolution of the hydrocephalus. Newborn infants with post-hemorrhagic hydrocephalus should be followed carefully throughout the first year for prompt detection of later hydrocephalus.

Cephalometry↗
PubMed1990

Specific N-linked oligosaccharides are required for oligodendroglial differentiation but probably not for astrocytic differentiation.

Primary cultures of cerebral glia derived from neonatal rat brain were utilized to determine whether specific glycoproteins are involved in oligodendroglial and astrocytic differentiation. Specific emphasis was placed on the oligosaccharide portion of glycoproteins, and inhibitors of glycoprotein processing were studied. Castanospermine, an inhibitor of glucosidase I, and thereby formation of both complex glycoproteins and high mannose glycoproteins, and deoxymannojirimycin (DMM), an inhibitor of mannosidase I and thereby formation of complex glycoproteins, were utilized. Castanospermine exposure prevented the developmental inductions of the two oligodendroglial markers, 2',3'-cyclic nucleotide 3'-phosphohydrolase and glycerol-3-phosphate dehydrogenase. The effect of castanospermine on oligodendroglial differentiation was reversible. In contrast, castanospermine had no effect on the developmental inductions of the two astrocytic markers, glutamine synthetase and lactate dehydrogenase. DMM exposure had no effect on either oligodendroglial or astrocytic differentiation. Although both inhibitors caused a marked decrease in the formation of complex glycoproteins and an increase in high mannose structures, the oligosaccharide composition of these high mannose structures differed markedly. Castanospermine caused an increase in 'abnormal', apparently glucosylated high mannose structures and a decrease in all other 'normal' high mannose oligosaccharides, whereas DMM caused an increase in most high mannose structures, especially those migrating in the region of the Man7GlcNAc standard. The data indicate that oligodendroglial differentiation requires specific N-linked oligosaccharides, probably principally of the high mannose type, and that astrocytic differentiation can proceed normally despite marked alterations in both complex and high mannose glycoproteins.

1-Deoxynojirimycin↗
PubMed1990

Hypoxic injury to developing glial cells: protective effect of high glucose.

Hypoxic injury to differentiating glial cells is a critical event in the development of periventricular leukomalacia, the major hypoxic-ischemic lesion of the premature infant. This study has addressed the effects of hypoxia on differentiating glial cells, primarily astrocytes. Primary cultures of dissociated newborn rat brain, which are composed predominantly of differentiating astroglia, were used. Efflux of lactate dehydrogenase, an enzyme enriched in astroglia, was used to quantitate cellular injury. Three major findings are reported. First, differentiating astrocytes were resistant to hypoxic injury for many hours, although by 24 h of hypoxia severe cellular injury (lactate dehydrogenase efflux of 86% of total and morphologic changes) was obvious. Second, increase of glucose in the culture medium from the approximately physiological concentration of 5.6 to 15 mM had a marked protective effect versus hypoxia, i.e. lactate dehydrogenase efflux was totally prevented during 24 h of hypoxia in 15 mM glucose. Third, the protective effect of high glucose appeared to be related to increased utilization by glycolysis, because there was a direct correlation between the resistance to hypoxic cellular injury and the amount of lactate generated and of glucose consumed by the cells. Thus, the cells with the lowest lactate dehydrogenase efflux (and highest glucose supplementations) had medium lactate concentrations as high as 32-36 mM. These concentrations of lactate are approximately double the reported threshold concentration of lactate considered to produce cellular necrosis in in vivo models of hypoxic injury, primarily in mature animals. The data raise the possibility that hypoxic injury to differentiating glia can be prevented or ameliorated by increase in glucose availability.

Animals↗
PubMed1990

Clinical features of bilirubin encephalopathy.

Clinical features of bilirubin encephalopathy vary depending on the age of the infant and the degree of hyperbilirubinemia. In term infants with hyperbilirubinemia, three distinct clinical phases are apparent in the first weeks of life, and long-term consequences include extrapyramidal disturbances (particularly athetosis), hearing loss, gaze abnormalities (particularly limitation of upward gaze), and, in a minority, intellectual deficits. In term infants with moderate hyperbilirubinemia, minor delay in motor development during the first year has been demonstrated, but with longer follow-up this delay is not apparent. Associated conditions such as sepsis, anoxia, and acidosis may increase the likelihood of neurotoxicity of bilirubin in these infants. The clinical consequences of moderate hyperbilirubinemia in premature infants are unclear. No acute clinical syndrome is recognizable during the first weeks. The results of follow-up studies are variable. Hearing loss is the commonest consequence. Follow-up through age 2 years in one large study suggests that static encephalopathy may be a sequel. Longer follow-up is needed to understand the clinical consequences of moderate hyperbilirubinemia in this important group of infants.

Humans↗
PubMed1989

Intraventricular hemorrhage in the premature infant--current concepts. Part I.

Although the incidence of periventricular-intraventricular hemorrhage (IVH) has decreased in recent years, the increasing survival rates for the smallest premature infants indicate that the lesion will continue to be a major problem in neonatal intensive care facilities. The neuropathology is characterized by an elemental lesion, bleeding into the subependymal germinal matrix, with subsequent rupture into the lateral ventricle. Important neuropathological consequences are germinal matrix destruction, posthemorrhagic hydrocephalus, and periventricular hemorrhagic infarction. The last of these appears to be a venous infarction and is a critical determinant of neurological outcome. Neuropathological accompaniments, not caused by the IVH, include periventricular leukomalacia and pontine neuronal necrosis. The pathogenesis of IVHs is related to intravascular, vascular, and extravascular factors. Intravascular factors involve primarily control of blood flow and pressure in the microcirculation of the germinal matrix. Particular pathogenetic importance can be attached to fluctuations in cerebral blood flow, abrupt increases in flow, decreases in flow with injury to matrix vessels, increases in cerebral venous pressure, and, in selected infants, disturbances of platelet function and coagulation. Vascular factors relate to the microcirculation of the matrix, the site of the initial bleeding. A maturation-dependent alteration in vascular integrity and a vulnerability of matrix vessels to ischemic injury appear important. Extravascular factors include those relevant to mesenchymal and glial support for matrix vessels and to local fibrinolytic activity in the germinal matrix. The latter may be a manifestation of the proteolytic activity now recognized to be of general importance in developmental remodeling of the mammalian central nervous system.

Blood Flow Velocity↗
PubMed1989

Intraventricular hemorrhage in the premature infant--current concepts. Part II.

Diagnosis of periventricular-intraventricular hemorrhage (IVH) and its neuropathological consequences and accompaniments in the living infant has been facilitated greatly by the introduction of real-time cranial ultrasonography. The major advantages of the technique include high-resolution capability, portable instrumentation, lack of ionizing radiation, and relative affordability. Prognosis in infants with IVH relates to the mechanisms of brain injury, the most important of which are prior hypoxic-ischemic insults, posthemorrhagic hydrocephalus, and periventricular hemorrhagic infarction. The last of these is most critical and it is now clear that careful quantitative assessment of the ultrasonographic appearance of the periventricular parenchyma in the infant with IVH during the acute period of illness is of major value in estimating outcome. Prevention of IVH remains the most important goal. Prenatal interventions include prevention of premature birth (currently a very elusive goal in the United States), transportation of the premature infant to a tertiary facility in utero rather than after birth (an approach of proven value), prenatal administration of phenobarbital or vitamin K (initially promising data that require confirmation and amplification), and optimal management of labor and delivery. Postnatal interventions include careful resuscitation of newborns, correction of fluctuating cerebral blood flow velocity, correction or prevention of other major hemodynamic disturbances, and correction of abnormalities of coagulation. Of these interventions the use of muscle paralysis to correct fluctuating cerebral blood flow velocity has shown the most striking benefit vis-à-vis prevention of IVH. Postnatal pharmacological interventions that have been studied in detail include the use of phenobarbital, indomethacin, ethamsylate, and vitamin E. No single agent among this group has been shown consistently to lead to a decrease in incidence and severity of IVH.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral Hemorrhage↗
PubMed1989

Ethanol in clinically relevant concentrations enhances expression of oligodendroglial differentiation but has no effect on astrocytic differentiation or DNA synthesis in primary cultures.

Primary cultures of cerebral glia derived from newborn rat brain were utilized to evaluate the effects of ethanol on DNA synthesis and cellular differentiation. Glutamine synthetase was employed as a marker for astrocytic differentiation and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP), for oligodendroglial differentiation. Concentrations of ethanol of 17-86 mM, i.e., a concentration range comparable to that observed in humans, were utilized. No effect of ethanol on DNA synthesis was observed, despite the use of synchronized cultures. Similarly, no effect of ethanol on the developmental increase of glutamine synthetase activity was seen, despite the use of astrocytes purified by the selective detachment technique and a prolonged duration of exposure to ethanol (17 days). In contrast, however, a striking enhancement of CNP activity was demonstrable in both mixed glial cultures and in oligodendroglia purified by the selective detachment technique. In the latter cells, the stimulatory effect of ethanol was evident within 9 days of exposure, and after 17 days of exposure, ethanol-treated cells exhibited a two-fold higher CNP activity than did control cells. This peak effect was observed at an ethanol concentration of only 17 mM. Thus, these data indicate that (1) clinically relevant concentrations of ethanol have no effect on either DNA synthesis or on at least one expression of astrocytic differentiation in glial primary cultures, but (2) these concentrations exert a striking enhancement of CNP activity, a marker of oligodendroglial differentiation. The findings have implications both for the effects of ethanol on the developing nervous system and the regulation of oligodendroglial differentiation.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗
PubMed1989

Effect of maternal cocaine use on the fetus and newborn: review of the literature.

The recent epidemic of cocaine abuse, especially among young individuals, has caused increasing concern about the potential hazards of prenatal cocaine exposure on the developing fetus and newborn. Although large-scale epidemiologic studies and long-term data are lacking, a review of the literature suggests strongly that the popular belief about the relative safety of cocaine is unfounded and that maternal cocaine abuse during pregnancy may be associated with increased perinatal morbidity and mortality.

Abnormalities, Drug-Induced↗
PubMed1989

Neurologic complications of captopril treatment of neonatal hypertension.

The occurrence of neurologic abnormalities is described in a series of nine infants with chronic hypertension, in whom antihypertensive therapy decreased BP markedly and for a prolonged period, although to levels often within the normal range. All infants had mean systolic BPs greater than 113 mm Hg and elevated renin values to a mean of 134 +/- 128 ng/mL/h. Antihypertensive therapy, such as captopril, an inhibitor of angiotensin I-converting enzyme, consistently lowered the systolic BP by 20% from baseline per dose. However, the nine infants exhibited a total of 17 episodes of striking decreases in systolic BP of greater than 40% from baseline; the markedly decreased systolic BP values were usually within the normal range for corrected age. Seven of the 17 episodes were characterized by marked decrease in systolic BP, ie, decreased by 57% +/- 10%, and were prolonged, ie, remained at the lower values for 17 +/- 6 hours despite therapeutic interventions. These seven episodes were accompanied by oliguria (urine output less than 1 mL/kg/h) and neurologic abnormalities (ie, seizures). In the remaining ten episodes, the systolic BP decreased by 50% +/- 8%, but the decreases were relatively brief, ie, remained at the lower values for 2.8 +/- 2 hours. These briefer episodes were not accompanied by renal or neurologic signs. These data indicate a particular vulnerability of the cerebral and renal circulation in premature infants with chronic hypertension to decreases in systolic BP to levels that would otherwise be considered in the normal range. The findings suggest that adaptive responses in both cerebral and renal blood flow are altered by chronic hypertension in such infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Diseases↗
PubMed1989

Intraventricular hemorrhage and brain injury in the premature infant. Neuropathology and pathogenesis.

Intraventricular hemorrhage of the premature infant originates in the subependymal germinal matrix. Important neuropathological complications of the hemorrhage are post-hemorrhagic hydrocephalus and periventricular hemorrhagic infarction. The latter infarction and the ischemic lesion, periventricular leukomalacia, are the most important forms of brain injury in the premature infant. Pathogenesis of intraventricular hemorrhage relates to intravascular, vascular, and extravascular factors.

Cerebral Hemorrhage↗
PubMed1989

Intraventricular hemorrhage and brain injury in the premature infant. Diagnosis, prognosis, and prevention.

Diagnosis, prognosis, and prevention of intraventricular hemorrhage are reviewed. Diagnosis is accomplished best by real-time cranial ultrasonography. Prognosis depends primarily on the severity of any periventricular parenchymal injury that accompanies the intraventricular hemorrhage. Prevention of the hemorrhage is based on both prenatal and postnatal interventions. These can be formulated best when considered in the context of the pathogenesis, as outlined in the previous article.

Cerebral Hemorrhage↗
PubMed1989

Perinatal asphyxia: clinical aspects.

This article reviews the significance of hypoxic-ischemic encephalopathy and the associated patterns of cerebral injury in the context of the most probable timing of the insult and prognosis. The evolution of the clinical features of significant hypoxic-ischemic encephalopathy, and the diagnostic value of imaging and electrophysiologic and metabolic studies are discussed. Current approaches to management are outlined.

Asphyxia Neonatorum↗