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Biomedical subjects

P Levitt

Publications and source records attributed to P Levitt.

At least 109 records · Page 6Linked to original sources
PubMed1984

Sustained release nitroglycerin improves myocardial thallium-201 images in men with coronary artery disease.

Ten men with coronary disease and angina-limited exercise participated in a study of the effects of sustained release nitroglycerin capsules on exercise performance and myocardial thallium images. Dose titration to ascertain the maximally tolerated dose, 6.5 to 26 mg orally four times a day, followed by double-blind, placebo-controlled cross-over treatment was undertaken. Following the administration of sustained release nitroglycerin exercise performance and exercise thallium images improved and appeared to remain so for four hours.

Administration, Oral↗
PubMed1984

A monoclonal antibody to limbic system neurons.

A monoclonal antibody produced against hippocampal cell membranes labeled the surface of neurons in the rat limbic system. With a few exceptions, all nonlimbic components were unstained. This specific distribution of immunopositive neurons provides strong evidence of molecular specificity among functionally related neurons in the mammalian brain and supports the concept of a limbic system.

Animals↗
PubMed1984

Dopaminergic but not noradrenergic mediation of hyperactivity and performance deficits in the developing rat pup.

The relative contribution of dopamine (DA) and norepinephrine (NE) in behavioral arousal was examined in developing rat pups using intracisternal 6-hydroxydopamine (6-OHDA) either alone or following pretreatment with desmethylimipramine (DMI). Such treatments were designed to examine the effects of preferential reduction of DA (DA depletion), NE (NE depletion), or both catecholamines (CA depletion) in the development of motor activity and escape performance. General motor activity increased with age and, over all ages, DA-depleted pups tended to exhibit greater activity. This was most apparent at 15 days of age, where DA-depleted pups were significantly more active than controls, NE-depleted, or CA-depleted pups. DA-depleted pups failed to exhibit the steep decline in activity over time (habituation of activity) demonstrated by the control and NE-depleted pups, while pups depleted of both CA fell into an intermediate position in habituation. Escape latency in a T-maze at 20 days and shuttle box at 26 days of age indicated comparable performance to controls for NE-depleted pups, while those animals in DA-depleted and CA-depleted groups appeared unable to perform the task. Brain CA concentrations (determined by a radioenzymatic assay) indicated preferential reduction of DA in the DA-depleted group to concentrations 25% of controls, reduction of NE to 62% of controls in the NE-depleted group, and reductions of DA to 42% and NE to 60% in the CA-depleted group. These results suggest that preferential reduction of brain DA in the developing rat pup increases motor activity and impairs habituation of activity during the stage of behavioral arousal in week 3 of postnatal life.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1984

Anatomy of cerebellar Purkinje cells in the rat determined by a specific immunohistochemical marker.

In the present study we have used guanosine 3':5'-phosphate-dependent protein kinase antiserum, a specific immunohistochemical marker for cerebellar Purkinje cells, [ Lohmann , Walter, Miller, Greengard and De Camilli (1981) Proc. natn . Acad. Sci. U.S.A. 78, 653-657], to carry out a detailed analysis of the architecture and projections of Purkinje cells in the adult rat. We have obtained a novel view of aspects of Purkinje cell morphology that were already known and, in addition, we have provided some new information, in particular on the targets of Purkinje cell axons and their pattern of innervation, and on the morphology and course of Purkinje cell axons. Furthermore, we have found a few cells positive for guanosine 3':5' phosphate-dependent protein kinase which are very similar morphologically to Purkinje cells but are located outside of the cerebellar cortex. A unique feature of Purkinje cells is their peculiar monoplanar shape. Not only do their dendritic arbors lie in planes perpendicular to the major axis of the folia, but their axons, including the collaterals, also travel roughly in the same planes. Thus, Purkinje cells can be imagined as lying in longitudinal sheets radiating from the deep cerebellar nuclei. In these sheets, Purkinje cell axons originating from cells located at different rostrocaudal levels of the cortex converge towards the deep cerebellar nuclei without intersecting each other. It is as a result of this precise organization that Purkinje cell axons reach the deep cerebellar nuclei with a mediolateral and rostrocaudal topology that closely reflects the position of their parent cells in the cerebellar cortex. In the subcortical rays of white matter, Purkinje cell axons are interspersed with other axons, being excluded only from longitudinal strips which correspond to the cerebellar raphes . Upon converging towards the deep cerebellar nuclei they segregate into tracts of white matter that alternate with tracts of white matter from which they are excluded. The great majority of Purkinje cell axons terminate in the deep cerebellar nuclei. Recurrent collaterals terminate in close proximity to the Purkinje cell layer. Dense innervation by these axons is found around large interneurons ( Lugaro and Golgi cells) and around the Purkinje cell pinceaux . No direct input of recurrent collaterals to Purkinje cell somata is evident in immunostained material. A substantial number of Purkinje cell axons continue beyond the cerebellar nuclei to innervate nearby regions in the brain stem.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Emergence of cyclic guanosine 3':5'-monophosphate-dependent protein kinase immunoreactivity in developing rhesus monkey cerebellum: correlative immunocytochemical and electron microscopic analysis.

The appearance of cyclic guanosine 3':5'-monophosphate-dependent protein kinase (cGK), an enzyme that may be involved in the regulation of various aspects of neuronal function and that is highly concentrated in cerebellar Purkinje cells, was studied in the developing and adult monkey cerebellum by indirect immunofluorescent staining. The appearance and distribution of cGK immunoreactivity were then correlated with the stages of Purkinje cell differentiation and with the establishment of synaptic inputs to Purkinje cells as revealed by electron microscopy and by the presence of synapsin I, a specific nerve terminal marker. In the adult monkey, in analogy with previous observations in the adult rat, cGK immunoreactivity was detected throughout the cytoplasm of all Purkinje cells and was not seen in other neurons. During ontogenesis, cGK immunoreactivity appeared for the first time in Purkinje cells at the 97th embryonic day (E97). On this day it was detectable in Purkinje cells situated in the posterior lobe concurrently with the emergence of synapsin I immunoreactivity surrounding their somata. The cGK-positive cells had entered the phase of rapid dendritic growth and had begun establishing axosomatic synapses. By E102, Purkinje cells in the posterior lobe and in most of the anterior lobe were cGK positive. By E125, all Purkinje cells had received synaptic contacts and had become cGK positive. In addition to typical Purkinje cells situated in the cortex, we found another population of cGK-positive neurons present transiently in the prospective cerebellar white matter. These neurons, which were observed only during the second half of gestation, had morphological similarities to Purkinje cells. The emergence of cGK in these neurons also coincided with their dendritic proliferation and with the appearance of synapsin I immunoreactivity around their cell bodies. Subcortical cGK-positive cells were not observed in postnatal animals. Such neurons may be Purkinje cells which, failing to reach the cortical plate, subsequently degenerate. The close temporal correlation between appearance of cGK immunoreactivity, onset of synaptic inputs, and dendritic proliferation, both in typical Purkinje cells and in the Purkinje cell-like cells in subcortical areas, suggests that expression of high levels of cGK may be an important aspect of the neuronal differentiation of these cells.

Animals↗
PubMed1983

Specificity of antisera prepared against pure bovine MAO-B.

Antisera have been prepared against purified bovine MAO-B that appear to react selectively with MAO-B and not MAO-A, Rabbit and mouse antisera indirectly immune precipitated [125I]bovine MAO-B using inactivated Staphylococcus aureus cells, and binding of antibodies to bovine and rat MAO-B did not inhibit enzyme activity. Two continuous rat cell lines, hepatoma line MH1C1 and glioma line C6, were used to elucidate the specificity of the antisera. MH1C1 cells, which express both MAO-A and MAO-B, showed immune-specific staining with rabbit antiserum, and staining was blocked with pure MAO-B. Further, MAO-B activity and [3H]pargyline-labeled MAO molecules could be immune precipitated from solubilized mitochondrial preparations of MH1C1 cells; and immune fixation of mitochondrial proteins following SDS polyacrylamide gel electrophoresis (SDS-PAGE) revealed staining of the MAO-B, but not of the MAO-A, flavin-containing subunit. In contrast, no immune-specific immunocytochemical staining was observed in C6 cells, which have only MAO-A activity; no MAO-A activity or [3H]pargyline-labeled MAO could be immune precipitated from solubilized mitochondrial preparations of these cells, and no stained bands were observed for mitochondrial proteins resolved by SDS-PAGE and processed for immune fixation. Further support for the selectivity of this antiserum for MAO-B comes from immunocytochemical staining of rat tissues which express varying amounts of MAO-A and MAO-B activities. Hypothalamus and liver, with high levels of MAO-A and MAO-B activities showed a large number of immunoreactive cells, whereas spleen, heart and superior cervical ganglia, with high MAO-A and low MAO-B activities showed only a few or no stained cells. Catecholamine neurons in the substantia nigra, thought to contain MAO-A, did not show immune-specific staining. Skeletal muscle cells with low MAO-A and MAO-B activities did not stain. These studies provide additional evidence that MAO-A and MAO-B are distinct molecules, differentially expressed in different cell types.

Animals↗
PubMed1983

Early divergence and changing proportions of neuronal and glial precursor cells in the primate cerebral ventricular zone.

Immunocytochemical staining with antisera directed against glial fibrillary acidic protein (GFA) was used to examine the cellular composition of the proliferative ventricular zone (VZ) in the occipital lobe of rhesus monkey fetuses during the first half of their 165-day gestational period. Electron microscopic analysis revealed a small number of GFA-positive cells in specimens of embryonic (E) ages E39 and E40. By E47 about 28% of the cells in the VZ were immunoreactive. This percentage increased to 37% at E61 and reached 60% by E80. The fraction of GFA-positive mitotic figures followed the same general tendency with 34, 47, and 80% being labeled at E47, E61, and E80, respectively. The present results reveal the existence of two basic classes of cells, GFA positive and GFA negative, indicating that in the primate brain, glial and neuronal precursor cells may coexist in the ventricular zone at embryonic ages when few, if any, neurons have become postmitotic.

Animals↗
PubMed1982

The time of genesis, embryonic origin and differentiation of the brain stem monoamine neurons in the rhesus monkey.

Neurogenesis of the locus coeruleus (LC), substantia nigra (SN) and raphe nuclei (RN) was analyzed in autoradiograms prepared from postnatal rhesus monkeys that had been exposed to a pulse of [3H]thymidine on selected embryonic (E) days of the 165-day gestational period. Heavily labeled monoamine (MA) neurons were present only in monkeys exposed to the isotope between E27 and E36 with the peak around E30-E33. The majority of neurons generated on E30 eventually become situated in the medial part of the LC, whereas most cells of the lateral portion are generated on E32 and E33, indicating the existence of a mediolateral spatiotemporal gradient. Proliferation of neurons destined for the compact portion of the LC peaks around E32, whereas production of subcoeruleus cells proceeds more evenly throughout the E30-E33 period. SN neurons are generated between E36 and E43, with peak labeling around E38-E40, and no appreciable spatiotemporal gradients. Neurons of the ventral tegmental area are also generated between E38 and E43. Neurogenesis of the RN occurs between E28 and E43 with only a moderate rostrocaudal spatiotemporal gradient. Neurons of raphe dorsalis and centralis superior undergo final mitosis between E28 and E35, with the peak on E30, whereas cells of raphe magnus, pontis, obscurus and pallidus are produced between E35 and E43, with the peak between E38 and E40. In general, MA neurons that project to different targets may be produced simultaneously within each nucleus irrespective of any spatiotemporal gradients. Examination of another series of fetuses sacrificed at various short intervals after exposure to [3H]TdR revealed that all MA neurons arise in the ventricular zone with each MA nucleus being generated at a specific level of the brain stem. Postmitotic MA cells migrate to their final location along specific pathways, and settle in patterns corresponding to the sequence of their genesis. Morphometric analysis indicated that after reaching their final destinations, the somas and nuclei of all MA neurons grow according to the same tempo and sequence irrespective of the developmental schedules of their synaptic targets.

Animals↗
PubMed1982

Immunocytochemical demonstration of monoamine oxidase B in brain astrocytes and serotonergic neurons.

An antiserum to monoamine oxidase B (MAO-B) was used to define the distribution of this metabolic enzyme in the adult rat brain immunocytochemically. MAO-B is specifically located in two major central nervous system cell classes, astrocytes and serotonin-containing neurons. Double-immunofluorescence experiments using antisera to glial fibrillary acidic protein and MAO-B showed that both protoplasmic and fibrillary astrocytes throughout the brain contain MAO-B, whereas oligodendrocytes do not contain the enzyme. Areas lacking a blood-brain barrier, such as the specialized circumventricular organs, also contain MAO-B-positive cells. A double-immunofluorescence experiment using antisera to serotonin and MAO-B enabled the positive identification of neurons containing both molecules. The catecholamine-containing neurons of the brain did not contain detectable amounts of MAO-B. The specific distribution of MAO-B in the adult central nervous system indicates that the role of MAO-B in monoamine metabolism may be more specifically defined than previously believed.

Animals↗
PubMed1981

Mutant mouse tottering: selective increase of locus ceruleus axons in a defined single-locus mutation.

The central catecholamine neuron system in the mutant mouse tottering was examined by fluorescence histochemistry and biochemical analysis of catecholamine content. This single-locus neurological mutation expresses a reproducible alteration in central nervous system physiology characterized by spontaneous spike-wave and focal motor seizures in the absence of any previously recognized disturbance of cellular organization or brain size. Histochemical analysis showed a significant increase in the number of noradrenergic axons in terminal fields innervated by the nucleus locus ceruleus when compared with the wild type. A concomitant 100-200% rise in norepinephrine levels is found in the same areas, including hippocampus, cerebellum, and dorsal lateral geniculate. Catecholamine fibers and transmitter content in areas innervated by a second major noradrenergic system arising from the brainstem lateral tegmental neurons are unaltered. The terminal axons and transmitter content were both unchanged in nuclei receiving a dense dopaminergic innervation. Despite the hypertrophy of the locus ceruleus axonal plexus, the number and size of locus ceruleus cell somata were identical in both wild-type and tottering mice. These findings are consistent with a specific gene-linked alteration of developmental events controlling the number of axons produced by a single neuronal population in the mammalian brain.

Animals↗
PubMed1981

Coexistence of neuronal and glial precursor cells in the cerebral ventricular zone of the fetal monkey: an ultrastructural immunoperoxidase analysis.

The cytological composition of the proliferative zones in the fetal monkey occipital lobe was examined at the light and electron microscopic levels by immunoperoxidase localization of glial fibrillary acid protein (GFA), a protein that is present in astrocytes and radial glial cells but not neurons. During the peak of neurogenesis at embryonic day 80, two distinct classes of proliferative cells, GFA-positive and GFA-negative, are intermixed in the ventricular and subventricular zones. Both cell types are readily recognized in different phases of the mitotic cycle along the ventricular surface. The results indicate that, contrary to prevailing views, (1) glial and neuronal cell lines coexist within the fetal proliferative zones and (2) the onset of glial phenotypic expression occurs prior to the last cell division.

Animals↗
PubMed1980

Immunoperoxidase localization of glial fibrillary acidic protein in radial glial cells and astrocytes of the developing rhesus monkey brain.

Peroxidase-antiperoxidase (PAP) immunohistochemical staining, utilizing a specific antibody to the glial fibrillary acidic protein (GFA), was employed to analyze gliogenesis in the central nervous system of rhesus monkeys ranging in age from embryonic day 38 (E38) to birth (E165) and through the second postnatal month. All major subdivisions of the brain contain glial cells, recognized by the presence of dark brown horseradish peroxidase (HRP) reaction product. Neuronal elements are not stained with this immunocytochemical technique. The first class of glial cells to appear during development are the radial glial cells; the radial fibers fan out from the ventricular and subventricular zones, where their cell bodies reside, to the pial surface where they terminate with conical endfeet. These glial cells appear within the first third of gestation, being present in the spinal cord and brainstem by E41; in the diencephalon by E45; and in the telencephalon and cerebellum by E47. The next class of glia to appear is the Bergmann glial cell of the cerebellar cortex, which can be stained by E54. Bergmann glial cells located below the Purkinje cell layer issue parallel processes which extend up to the pial surface. Within each major subdivision of the brain, massive numbers of elongated glial fibers continually alter their distinctive patterns to maintain constant ventricular-pial surface relationships during the major tectogenetic changes which occur throughout embryonic development. In Nissl-counterstained sections columns of migrating neurons are observed juxtaposed to GFA-positive radial and Bergmann glial fibers. Radial glial cells assume a variety of transitional forms during the process of their transformation into maturea astrocytes. This transformation occurs in each structure at specific embryonic ages and is initiated after neuronal migration has begun to subside. The number of astroglial cells increases at an accelerated pace after neurogenesis is complete. The immunohistochemical localization of radial fibers at relatively early stages of embryonic development indicates that glial cells are present concomitantly with neurons, raising the possibility that at least two distinct populations of cell precursors compose the proliferative zones. Furthermore, the demonstration of large numbers of radial glial cells in all brain regions during the peak of neuronal migration and a close structural relationship between elongated glial fibers and migrating neurons support the concept that glia play a significant role in the guidance and compartmentalization of neuronal elements during development.

Animals↗
PubMed1979

Origin and organization of brainstem catecholamine innervation in the rat.

The catecholamine (CA) innervation of the rat brainstem was studied by biochemical analysis of discrete nuclei or areas and by glyoxylic acid-formaldehyde freeze dry fluorescence histochemistry. CA assays demonstrate that the highest norepinephrine (NE) content in brainstem is present in the trigeminal motor nucleus, nucleus tractus solitarius, dorsal motor nucleus of the vagus and nucleus raphe dorsalis. Bilateral locus coeruleus (LC) lesions do not significantly alter NE content in these nuclei but do decrease NE content in the superior and inferior colliculi, medial geniculate body, interpeduncular nucleus, pontine nuclei and the main sensory trigeminal nucleus (60-75%). Dopamine (DA) and epinephrine (E) are found in significant concentration in only a few of the nuclei examined. Fluorescence histochemical analysis indicates that two groups of NE axons innervate rat brainstem. LC neuron axons with a distinctive morphology principally innervate sensory and association nuclei of the brainstem. These disappear completely after bilateral LC lesions. The second group of axons originates from lateral and dorsal tegmental NE cell groups. Primary motor and visceral nuclei are densely innervated by fine and thick axons from these groups. Lesions of LC do not alter the NE innervation in any of the nuclei which contain axons of the second group. These results indicate that the brainstem NE innervation is divided into two major systems. The locus coeruleus complex innervates mainly primary sensory and association nuclei whereas the lateral tegmental NE neurons innervate primary motor and visceral nuclei. Although some overlap is present, the LC and lateral tegmental NE systems predominantly innervate separate and functionally distinct areas of the brainstem. DA and E neurons provide a very minor component of the brainstem CA innervation.

Animals↗
PubMed1979

Development of the noradrenergic innervation of neocortex.

The development of the noradrenaline (NA)-neuron innervation of rat neocortex was studied by fluorescence histochemistry, high affinity uptake of [3H-]NA, and biochemical assay of regional NA content. Fluorescence histochemistry indicates that NA axons enter areas of developing neocortex prenatally and the innervation matures rapidly during early postnatal life. Frontal and lateral neocortical areas are the first to be innervated followed by occipital and parietal areas. All cortical layers receive innervation. The distribution and density of neocortical NA innervation achieves the adult pattern by the end of the first postnatal week. High affinity uptake studies confirm the observations from fluorescence histochemistry and show a very rapid maturation of the NA axon innervation with adult levels of uptake occurring by postnatal day 9. Following birth, there is a brief rise in NA content from PO to P2 in all neocortical areas. NA content then drops to low levels in all areas by P4. This is followed by a gradual increase in NA content in all areas occuring over several months. This pattern of development of NA axon innervation of neocortex demonstrates that the density and distribution of NA axons in developing neocortex matures much earlier than shown in previous studies whereas the NA content of the developing axonal plexus achieves adult levels later in postnatal life.

Adrenergic Fibers↗