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Biomedical subjects

J M Levine

Publications and source records attributed to J M Levine.

At least 37 records · Page 2Linked to original sources
PubMed1999

Rat optic nerve oligodendrocytes develop in the absence of viable retinal ganglion cell axons.

Retinal ganglion cell axons and axonal electrical activity have been considered essential for migration, proliferation, and survival of oligodendrocyte lineage cells in the optic nerve. To define axonal requirements during oligodendrogenesis, the developmental appearance of oligodendrocyte progenitors and oligodendrocytes were compared between normal and transected optic nerves. In the absence of viable axons, oligodendrocyte precursors migrated along the length of the nerve and subsequently multiplied and differentiated into myelin basic protein-positive oligodendrocytes at similar densities and with similar temporal and spatial patterns as in control nerves. Since transected optic nerves failed to grow radially, the number of oligodendrocyte lineage cells was reduced compared with control nerves. However, the mitotic indices of progenitors and the percentage of oligodendrocytes undergoing programmed cell death were similar in control and transected optic nerves. Oligodendrocytes lacked their normal longitudinal orientation, developed fewer, shorter processes, and failed to form myelin in the transected nerves. These data indicate that normal densities of oligodendrocytes can develop in the absence of viable retinal ganglion axons, and support the possibility that axons assure their own myelination by regulating the number of myelin internodes formed by individual oligodendrocytes.

Animals↗
PubMed1999

Salivary gland enlargement and elevated serum amylase in bulimia nervosa.

BACKGROUND: Clinical reports have described salivary gland enlargement in bulimia nervosa, particularly in patients with elevated serum amylase concentration. The goal of the current study was to provide a controlled comparison of salivary gland size in patients with bulimia nervosa and healthy volunteers. METHODS: Subjects included 17 women with bulimia nervosa and 21 healthy female control subjects. Dimensions of the parotid and submandibular salivary glands were estimated by ultrasonography. Blood samples for amylase measurement were obtained after overnight fast. RESULTS: Parotid gland size was enlarged 36% in patients with bulimia nervosa in comparison to control subjects (p < .01). For the patient group, salivary gland size was significantly correlated with frequency of bulimic symptoms and with serum amylase concentration. CONCLUSIONS: These results provide new quantitative data demonstrating increased salivary gland size in bulimia nervosa. Further studies are needed to evaluate factors responsible for salivary gland enlargement and hyperamylasemia in this disorder.

Adult↗
PubMed1999

Activation and proliferation of endogenous oligodendrocyte precursor cells during ethidium bromide-induced demyelination.

The adult brain contains a large population of glial cells with the properties of oligodendrocyte precursor cells (OPCs). The functions of this newly recognized class of glial cells in normal animals are unknown. Here, we analyzed the reactions of OPCs to a transient demyelination of the rat brainstem induced by the injection of ethidium bromide (EB) into the fourth ventricle. Within 22 h after EB injection, there is a 21% decrease in the number of OPCs within affected fiber tracts such as the spinal tract of the trigeminal nerve, most likely reflecting the toxic actions of EB. The surviving OPCs had enlarged cell bodies with fewer long processes and many membrane blebs. By 2 days after EB injection, these reactive OPCs had incorporated BrdU and increased in number. The increase in OPC cell number reached a maximum between 6-10 days after EB injection, at which time demyelination was complete. Myelin-specific marker antigens reappeared beginning at 12 days postinjection and the remyelination continued for up to 40 days. During remyelination, OPCs displayed a normal stellate morphology with an increased number of thin processes, many of which were closely associated with neurofilament-positive axonal profiles. The transient increase in the number of reactive OPCs within the demyelinated tissue and subsequent decrease in OPC number during remyelination demonstrates that the endogenous oligodendrocyte precursor population responds rapidly to the pathophysiological state of the brain. Demyelination generates a sufficient number of OPCs to participate in the repair of the demyelinated lesions.

Animals↗
PubMed1999

A light and electron microscopic study of NG2 chondroitin sulfate proteoglycan-positive oligodendrocyte precursor cells in the normal and kainate-lesioned rat hippocampus.

The adult brain contains a large population of oligodendrocyte precursor cells that can be identified using antibodies against the NG2 chondroitin sulfate proteoglycan. The functions of this newly recognized class of glial cells in the normal or pathological brain are not well understood. To begin to elucidate these functions, we have examined the morphology and distribution of oligodendrocyte precursor cells in the hippocampus and neocortex of normal and kainate-lesioned rats by anti-NG2 immunocytochemistry using light and electron microscopy. Large numbers of oligodendrocyte precursor cells were present in all layers of the neocortex and hippocampus. These cells differed in their morphology from astrocytes, oligodendrocytes and microglia. The processes of these cells often surrounded unlabeled areas of clear cytoplasm. At the electron microscopic level, some of the profiles that were enclosed by oligodendrocyte precursor cell processes contained synaptic vesicles. Other enclosed profiles were dendrites or dendritic spines. NG2-immunopositive processes were also observed to interpose between axon terminals containing round vesicles and dendrites with thick postsynaptic densities. After kainate injection, the NG2-positive oligodendrocyte precursor cells in the hippocampus displayed reactive changes characterized by swollen cell bodies, an increased number of small, filopodial-like processes, and higher levels of immunodetectable NG2. Both viable and degenerating oligodendrocyte precursor cells were observed with electron microscopy. These observations emphasize the dynamic nature of the oligodendrocyte precursor cell and suggest that, in addition to participating in the glial reactions to excitotoxic damage, oligodendrocyte precursor cells may regulate the stability, structure and function of synapses in the normal central nervous system.

Animals↗
PubMed1999

Chondroblastoma of the temporal bone: consistent middle fossa involvement.

The objective of this study is to describe the presentation and clinical course of two patients with temporal bone chondroblastoma, and to review the literature on temporal bone chondroblastoma to identify characteristic clinical and radiological presentations, and optimal treatment regimens. MEDLINE literature searches covering the period from 1966 to January 1998, in all languages, were performed as well as a review of the bibliographies of the identified studies. Strict inclusion criteria were upheld, In total 18 studies had patients whose data could be analyzed. From the 18 studies, 34 patients were identified, but only 21 cases met the inclusion criteria. Demographic, clinical presentation, radiological, operative and treatment parameters were analyzed in this cohort of patients. Ninety-five percent of patients were found to have invasion of the middle cranial fossa and 76% were found to have erosion into the superior aspect of the external auditory canal by temporal bone chondroblastoma. The characteristic growth pattern of temporal bone chondroblastoma may result from embryonal or cartilagenous rests entrapped in the tympanosquamous suture line in the middle fossa floor. Temporal bone chondroblastoma represents a pathology that does not arise from, or have a growth pattern resembling other pathologies in the temporal bone.

Case Reports↗
PubMed1999

Solomon Asch's legacy for group research.

Asch's work has had a profound impact on how psychologists think about and study social influence in groups. To appreciate this impact, we must go beyond his classic conformity experiments and consider his broader theoretical framework. This article examines 4 of Asch's ideas that have proven to be particularly influential in later efforts to understand social influence in groups: (a) Social interaction depends on individuals' ability to represent others' positions, define themselves as members of the same group, and regulate their behavior in terms of the norms and values of the group; (b) independence is critical to effective group functioning; (c) independence and conformity are not simply mirror images that can be explained in terms of a unitary psychological process; and (d) change of meaning is an important mechanism of social influence. Finally, Asch's role as a theorist and researcher in the wider area of group dynamics is considered.

Journal Article↗
PubMed1999

Loss of p27Kip1 function results in increased proliferative capacity of oligodendrocyte progenitors but unaltered timing of differentiation.

In many tissues, progenitor cells permanently withdraw from the cell cycle prior to commitment towards a differentiated phenotype. In the oligodendrocyte lineage a counting mechanism has been proposed, linking the number of cell divisions to growth arrest and differentiation. A direct prediction of this model is that an increase in the number of cell divisions would result in a delayed onset of differentiation. Since the cell cycle inhibitor p27Kip1 is an essential component of the machinery leading to oligodendrocyte progenitor growth arrest, we examined the temporal relationship between cell cycle withdrawal and expression of late differentiation markers in vivo, in mice carrying a targeted deletion in the p27Kip1 gene. Using bromodeoxyuridine to label proliferating cells, quaking (QKI) to identify embryonic glial progenitors, NG2 to identify neonatal oligodendrocyte progenitors, and myelin basic protein to label differentiated oligodendrocytes, we found an increased number of proliferating QKI- and NG2-positive cells in germinal zones of p27Kip1(-/-) mice at the peak of gliogenesis. However, no delay was observed in these mice in the appearance of the late differentiation marker myelin basic protein in the developing corpus callosum and cerebellum. Significantly, a decrease in cyclin E levels was observed in the brain of p27Kip1 null mice coincident with oligodendrocyte growth arrest. We conclude that two distinct modalities of growth arrest occur in the oligodendrocyte lineage: a p27Kip1-dependent mechanism of growth arrest affecting proliferation in early phases of gliogenesis, and a p27Kip1-independent event leading to withdrawal from the cell cycle and differentiation.

Animals↗
PubMed1999

Cells expressing the NG2 antigen contact nodes of Ranvier in adult CNS white matter.

The NG2 antibody, which recognises an integral membrane chondroitin sulphate, labels a significant population of cells in adult CNS white matter tracts of the rat optic nerve and anterior medullary velum (AMV). Adult NG2+ cells are highly complex with multiple branching processes and we show by EM immunocytochemistry that they extend perinodal processes, which contact nodes of Ranvier. NG2+ cells do not react to conventional immunohistochemical markers for adult glia and so we reservedly term them NG2P cells. In vitro, NG2 labels oligodendrocyte-type-2 astrocyte (O-2A) progenitors that can give rise to oligodendrocytes or type-2 astrocytes, depending on the culture medium. Thus, it is possible that NG2P cells may be derived from the same stem cells as oligodendrocytes. Interestingly, NG2+ cells identified previously in adult CNS displayed phenotypic characteristics of O-2Aadult progenitors and it is possible that, like them, NG2P cells might retain the capacity of generating oligodendrocytes in the adult CNS. This may be an important role of NG2P cells in demyelinating diseases such as multiple sclerosis. It is significant therefore that the perinodal processes of NG2P cells contact the only sites of exposed axolemma in myelinated axons, so that NG2P cells are ideally situated to detect and respond to changes in axonal function during demyelination. A further implication of our finding is that NG2P cells may perform functions at nodes of Ranvier previously attributed to perinodal astrocytes, including the clustering and maintenance of sodium channels in the axon membrane at nodes, during development and following demyelination.

Animals↗
PubMed1998

Multiple classes of the oligodendrocyte lineage are highly vulnerable to excitotoxicity.

We have recently shown that galactocerebroside (Gal-C)-expressing oligodendrocytes are highly vulnerable to (AMPA)/kainate receptor-mediated death. Here we examined the vulnerability of cells at different developmental stages of the oligodendrocyte lineage to AMPA/kainate receptor-mediated excitotoxicity. Oligodendrocyte precursor cells, pre-oligodendrocytes and mature oligodendrocytes were killed by 24 h exposures to low concentrations of kainate (30-100 microM). Death was attenuated by the AMPA/kainate receptor antagonist 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2,3-dione (NBQX). The high vulnerability of oligodendrocytes and their precursors to AMPA/kainate receptor excitotoxicity may represent an important mechanism of white matter damage resulting from trauma or ischemia in the perinatal and adult central nervous system (CNS).

Animals↗
PubMed1998

Dynamic behavior of the ends of growing parallel fibers in early postnatal rat cerebellum.

The molecular layer of the cerebellum contains parallel fibers, the axons of granule neurons. We have examined the morphology and behavior of parallel fiber growth cones in the early postnatal rat cerebellum using the fluorescent tracer DiI. Parallel fiber growth cones distributed into three categories based on size and shape: short torpedo-like, long torpedo-like, and lamellopodial in form. The torpedo-like growth cones were modified by the addition of lamellopodia and/or filopodia, and the lamellopodial growth cones were often decorated with a filopodium. These three different growth cone morphologies were found throughout the growing region of the molecular layer. The nascent axons elaborated by premigratory granule neurons differed form the longer axons of more developed neurons in that they often had forked growth cones and extensive lamellopodial decoration along the axon shaft. Growth cones in living slices closely resembled those observed in the fixed preparations. The living growth cones exhibited frequent lamellopodial rearrangement and a side-to-side headwaving movement. The axon proximal to the growth cone was also dynamic. The axons curved and undulated, and mobile swellings formed along the axon shaft. These observations show that the growth cones of parallel fibers are similar to growth cones described for axons in other developing systems in terms of size, morphological characteristics, and dynamic behavior.

Aging↗
PubMed1998

Response of the oligodendrocyte progenitor cell population (defined by NG2 labelling) to demyelination of the adult spinal cord.

Elucidation of the response of oligodendrocyte progenitor cell populations to demyelination in the adult central nervous system (CNS) is critical to understanding why remyelination fails in multiple sclerosis. Using the anti-NG2 monoclonal antibody to identify oligodendrocyte progenitor cells, we have documented their response to antibody-induced demyelination in the dorsal column of the adult rat spinal cord. The number of NG2+ cells in the vicinity of demyelinated lesions increased by 72% over the course of 3 days following the onset of demyelination. This increase in NG2+ cell numbers did not reflect a nonspecific staining of reactive cells, as GFAP, OX-42, and Rip antibodies did not co-localise with NG2 + cells in double immunostained tissue sections. NG2 + cells incorporated BrdU 48-72 h following the onset of demyelination. After the onset of remyelination (10-14 days), the number of NG2+ cells decreased to 46% of control levels and remained consistently low for 2 months. When spinal cords were exposed to 40 Grays of x-irradiation prior to demyelination, the number of NG2+ cells decreased to 48% of control levels by 3 days following the onset of demyelination and remained unchanged at 3 weeks. Since 40 Grays of x-irradiation kills dividing cells, these studies illustrate a responsive and nonresponsive NG2+ cell population following demyelination in the adult spinal cord and suggest that the responsive NG2+ cell population does not renew itself.

Animals↗
PubMed1998

Reactions of oligodendrocyte precursor cells to alpha herpesvirus infection of the central nervous system.

Adult animals harbor an abundant population of oligodendrocyte precursor cells (OPCs) whose functions, other than providing a pool of precursors for oligodendrocytes, are unknown. Previous studies have demonstrated that these unusual glial cells, which can be identified by virtue of their expression of the NG2 chondroitin sulfate proteoglycan, react to traumatic brain injury. To determine the generality of the ability of OPCs to react to neuropathological insults, we have examined the reactions of OPCs to infection of the brainstem with virulent and attenuated strains pseudorabies virus (PRV). When motor neurons within the dorsal vagal complex are infected with PRV, OPCs immediately adjacent to the infected neurons display dramatic reactive changes. These changes are characterized by (1) cell bodies that stain more heavily with antibodies against NG2 than do non-reactive OPCs, (2) an increased density of processes, and (3) the appearance of fine filopodia on the cell body and processes. The onset of these morphological changes was rapid, and they occurred simultaneously with the appearance of viral antigens in motor neurons. At late stages of infection, the soma of OPCs elaborated fewer processes. A small number of the reactive OPCs contain viral antigens. These findings extend the range of neuropathological situations to which OPCs react indicating that this cell population is extremely dynamic. They also suggest that the reaction of OPCs and the consequences of these reactions to brain function must be considered in any procedure, either experimental or clinical, in which viruses are introduced into the central nervous system.

Animals↗
PubMed1997

Decreased serotonin function in bulimia nervosa.

BACKGROUND: Evidence that serotonin-active antidepressant medications decrease binge eating in patients with bulimia nervosa has fueled interest in the hypothesis that abnormal serotonergic neurotransmitter function contributes to symptoms of the disorder. To evaluate this hypothesis, we employed pharmacological challenge testing to compare serotonin function in patients with bulimia nervosa and healthy controls. METHODS: Neuroendocrine response patterns were compared for 15 nonhospitalized, medication-free, normal-weight women with bulimia nervosa and 14 age-matched healthy female controls. Behavioral assessment included ratings of eating disorder symptoms, depression, and anxiety. Serotonergic response patterns were assessed by measuring the increase in serum prolactin concentration during 5 hours following single-dose, oral administration of 60 mg of d,l-fenfluramine hydrochloride (Pondimin). RESULTS: For patients with bulimia nervosa, the fenfluramine-stimulated increase in serum prolactin concentration was significantly less than for controls. Within the patient group, the frequency of binge eating episodes during the 4 weeks prior to the study exhibited a significant inverse correlation with serotonin-stimulated prolactin secretion. CONCLUSION: Our study provides new evidence that impaired central nervous system serotonergic responsiveness may contribute to the onset or maintenance of abnormal eating patterns in patients with bulimia nervosa.

Adult↗
PubMed1997

Identification of a neuronal cell surface receptor for a growth inhibitory chondroitin sulfate proteoglycan (NG2).

The NG2 chondroitin sulfate proteoglycan inhibits neurite outgrowth from neonatal rat cerebellar granule neurons when presented to the neurons as a component of the substrate. To begin to understand the cellular mechanisms by which this inhibition occurs, we investigated the hypothesis that cerebellar granule neurons express cell surface receptors for NG2 and that these receptors are linked to cellular signaling pathways. Here, we show that the NG2 core protein binds specifically and with high affinity to cerebellar granule neurons. Using protein cross-linking techniques and immunoprecipitation, a 280-kDa membrane cell surface protein of granule neurons was identified as an NG2-binding site. Treatment of the neurons with pertussis toxin reversed the growth inhibition, suggesting a role for pertussis toxin-sensitive G proteins in the inhibitory response. Treatment of the neurons with pharmacological agents that increase either intracellular calcium or intracellular cyclic AMP levels partially reversed the growth inhibition induced by NG2. These results suggest that the growth-inhibitory actions of NG2 proteoglycan are due to an interaction with a specific cell surface receptor that is linked, either directly or indirectly, to intracellular second messenger systems.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1997

Bedrail use.

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Beds↗