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Biomedical subjects

J J Volpe

Publications and source records attributed to J J Volpe.

At least 19 recordsLinked to original sources
PubMed1992

Glycoprotein processing is required for completion but not initiation of oligodendroglial differentiation from its bipotential progenitor cell.

The role of N-linked glycoproteins in the development of oligodendroglia has been studied in a culture system that initially contains the progenitor cell for oligodendroglia and type 2 astrocytes. The progenitor cells, derived from mixed glial primary cultures of newborn rat cerebrum, were studied under culture conditions that we have shown previously to induce oligodendroglial differentiation. Castanospermine was used to inhibit processing of N-linked glycoproteins by its inhibitory action on glucosidase I, the enzyme responsible for the initial trimming of glucose residues from the glucosylated high mannose core oligosaccharide derived from the dolichol pathway. Exposure to castanospermine had no effect on the initial commitment of the progenitors to oligodendroglial differentiation, i.e. 95% of both control and castanospermine-treated cells became galactocerebroside (GC) positive. However, the developmental inductions of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) and glycerol-3-phosphate dehydrogenase (GPDH) and the elaboration of a network of fine interconnecting processes were prevented by the castanospermine exposure. No effect of castanospermine on cell number was observed. A major effect of the inhibitor on glycoprotein processing was manifested by an accumulation of high mannose glycoproteins, of abnormal oligosaccharide structure, compatible with the inhibition of glucosidase I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Establishment of a culture system for the study of oligodendroglial development: complementary effects of boiled serum and astrocyte extract.

Mixed glial primary cultures derived from neonatal rat brain were used to isolate the progenitor glial cell with the capacity to differentiate into oligodendroglia or type 2 astrocytes depending on the culture medium. Subcultures composed primarily of this progenitor were utilized, first, to study the regulation of oligodendroglial differentiation by two factors added to chemically defined medium (CDM), i.e. boiled fetal calf serum (FCS) and cellular extract of type 1 astrocytes, and, second, to devise culture conditions that would cause the progenitor cells to differentiate virtually exclusively along oligodendroglial lines (judged by immunologically identified expression of galactocerebroside; GC) and with high specific and total activity of the oligodendroglial enzymes, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) and glycerol-3-phosphate dehydrogenase (GPDH). Addition of untreated FCS to CDM of the progenitors resulted in 6 days in richly cellular, mixed glial cultures composed of slightly more GFAP-positive astrocytes than oligodendroglia. Addition of boiled FCS to CDM of the progenitors resulted in 6 days in cultures composed almost exclusively (95%) of GC-positive cells and with high specific activity of CNP. This effect of boiled serum, compared to untreated serum, was related to virtual elimination of astrocytes, in the presence of continued differentiation to GC-positive oligodendroglia. Addition of type 1 astrocyte extract as well as boiled FCS to CDM was necessary to generate high specific activity of GPDH. Additionally, the total number of oligodendroglia increased 2-fold when astrocyte extract as well as boiled FCS was added to the CDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Brain injury in the premature infant--current concepts of pathogenesis and prevention.

Brain injury in the premature infant and, particularly, the prevention of that injury is an enormous problem. With modern neonatal intensive care, approximately 85% of very low birth weight infants survive, and of these survivals, approximately 5-15% exhibit major spastic motor deficit, grouped under the rubric, 'cerebral palsy', and an additional 25-50% exhibit less prominent developmental disabilities, particularly school failure.

Brain Injuries↗
PubMed1991

Positron emission tomography in newborn infants.

Positron emission tomography (PET) is a technique that permits the noninvasive in vivo measurement of a variety of cerebral physiologic and biochemical processes. Numerous complex methodologic and technical features must be considered when PET is applied to the study of the newborn's cerebral physiology and neurologic disease. Although the application of PET to newborn infants is still in its formative stages, important information regarding perturbations of cerebral blood flow in neurologic diseases has been obtained and striking developmental changes in cerebral metabolism are apparent.

Blood Volume↗
PubMed1990

Glutamine synthetase activity of developing astrocytes is inhibited in vitro by very low concentrations of lead.

This study has dealt with the inhibition by lead of glutamine synthetase (GS) activity in homogenates of mixed glial primary cultures, 95% enriched in differentiating astrocytes. A 70% inhibition was observed with a lead concentration of only 2.5 microM. Prevention of the inhibition by addition of EDTA or dithiothreitol is compatible with the conclusion that the effect is mediated by binding of lead ion to sulfhydryl moieties of the enzyme. Among several other cations tested, only mercury, which has a similarly high binding affinity for sulfhydryl moieties, inhibited the enzyme. The inhibitory effect of lead was relatively specific, since no inhibition of another astrocytic marker enzyme, lactate dehydrogenase, of the oligodendroglial marker enzyme, 2',3'-cyclic nucleotide 3'-phosphohydrolase, or of the plasma membrane marker, Na,Ka-ATPase, was observed with concentrations of lead that produced a 70% decrease of GS. Because of the critical role of GS in regulation of extracellular glutamate, the findings raise the possibility that glutamate-induced neuronal injury is involved in the genesis of the cognitive defects associated with chronic low-level lead exposure in young children.

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