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Biomedical subjects

M E Lewis

Publications and source records attributed to M E Lewis.

At least 109 records · Page 6Linked to original sources

Detection of multiple strains of latent herpes simplex virus type 1 within individual human hosts.

One hundred and fifteen isolates of herpes simplex virus were recovered from parallel explant cultures of trigeminal and vagus ganglia and trigeminal nerve roots derived from 20 unselected human cadavers. Restriction enzyme patterns of strains recovered from 18 of 20 individuals could be differentiated from individual to individual, although all isolates from a single host were identical. Isolates from two individuals differed among themselves in the number and location of certain restriction enzyme sites.

Base Sequence↗

Colocalization of proenkephalin peptides in rat brain neurons.

A serial, thin-section immunocytochemical study of the anatomical distribution of Leu-enkephalin and BAM-22P (an adrenal proenkephalin peptide) demonstrated that both immunoreactivities occur within the same neurons throughout brain. However, neither peptide immunoreactivity could be observed in neurons containing dynorphin A immunoreactivity. These results are consistent with the possibility that the enkephalin precursor in brain is similar to that sequenced in adrenal, but fail to support the hypothesis that the dynorphin precursor is a major source of Leu-enkephalin in brain.

Animals↗

Enkephalin systems in diencephalon and brainstem of the rat.

The immunocytochemical distribution of [Leu]enkephalin and an adrenal enkephalin precursor fragment (BAM-22P) immunoreactivity was investigated in the diencephalon and brainstem of rats pretreated with relatively high doses of colchicine (300-400 micrograms/10 microliters intracerebroventricularly). The higher ranges of colchicine pretreatment allowed the visualization of extensive enkephalin-containing systems in these brain regions, some of which are reported for the first time. Immunoreactive perikarya were found in many hypothalamic and thalamic nuclei, interpeduncular nucleus, substantia nigra, the colliculi, periaqueductal gray, parabrachial nuclei, trigeminal motor and spinal nuclei, nucleus raphe magnus and other raphe nuclei, nucleus reticularis paragigantocellularis, vestibular nuclei, several noradrenergic cell groups, nucleus tractus solitarius, as well as in the spinal cord dorsal horn. In addition to the above regions, immunoreactive fibers were also noted in the habenular nuclei, trigeminal sensory nuclei, locus coeruleus, motor facial nucleus, cochlear nuclei, dorsal motor nucleus of the vagus, and hypoglossal nucleus. When adjacent sections of those stained for [Leu]enkephalin were processed for BAM-22P immunoreactivity, it was found that these two immunoreactivities were distributed identically at almost all anatomical locations. BAM-22P immunoreactivity was generally less pronounced and ws preferentially localized to neuronal perikarya. The results of the present as well as the preceding studies (Khachaturian et al., '83) strongly suggest substantial structural similarity between the adrenal proenkephalin precursor and that which occurs in the brain. Also discussed are some differences and parallels between the distribution of [Leu]enkephalin and dynorphin immunoreactivities.

Animals↗

Opiate receptor localization in rat cerebral cortex.

The differential distributions of [3H]naloxone-labeled and [3H]D-Ala-D-Leu-enkephalin-labeled opiate receptors in rat cerebral cortex were localized autoradiographically and quantified by grain counting and computerized densitometry. In addition, receptor distributions were compared to terminal patterns of thalamocortical projections labeled by axoplasmic transport of [3H]amino acids. Opiate receptors labeled with [3H]naloxone in a mu ligand selectivity pattern show striking laminar heterogeneity and are densest in limbic cortical areas, intermediate in the motor cortex, and fewest in the primary sensory areas. By contrast, opiate receptors labeled with [3H]D-Ala2-D-Leu5-enkephalin in a delta ligand selectivity pattern are much more homogeneously distributed across both regions and laminae within regions. Mu receptors in most cortical areas have density peaks in layers I and VI and each peak shows a density gradient that is sloped within the layer so that the highest densities are at the most superficial and the deepest portions of cortex. In addition, there is an intermediate peak whose laminar position varies depending on the area in which it is found. In rostral agranular cortex, including limbic and motor areas, the [3H]naloxone binding peaks are in layers I, III, and VI. In primary somatosensory cortex, the intermediate peak is in layer Va and in most of remaining homotypical cortex it is in layer IV. Some areas have only bilaminar labeling, in superficial and deep layers; these include portions of the sulcal and retrosplenial cortices. Piriform and entorhinal cortices have dense [3H]naloxone binding only in the deepest layer and show a descending gradient of density toward the superficial layer. The positions of the mu receptor peaks were compared with termination patterns of projections originating in the thalamus. Close correspondence was found between receptor binding in the prelimbic, primary somatosensory, and entorhinal areas and projection terminations arising from the thalamic mediodorsal, posterior, and central medial nuclei, respectively. Although regional variations in [3H]D-Ala2-D-Leu5-enkephalin-labeled receptor density are uncommon, a gradual decrease in the number of sites along the dorsomedial wall of the cortex from anterior cingulate to caudal retrosplenial limbic cortex can be observed. Laminar variations in binding density are small as well; higher concentrations of the peptide binding sites are usually found in the deep cortical layers. These findings emphasize aspects of opiate receptor architecture which may be relevant to identifying cortical "opiatergic" neurocircuitry and raise the possibility of opiate modulation of thalamocortical transmission.

Animals↗

Comparative distribution of opiate receptors and three opioid peptide neuronal systems in rhesus monkey central nervous system.

Using combined autoradiography-immunocytochemistry, the anatomical distribution of [3H]naloxone-labelled opiate receptors was compared to the loci of neuronal systems immunoreactive for beta-endorphin, [Leu]enkephalin and dynorphin A in rhesus monkey brain. High densities of binding were observed in relation to each of the systems, consistent with findings that each opioid precursor can synthesize one or more peptides with substantial (though not selective) activity at mu receptors.

Animals↗

The distribution of cholecystokinin and vasoactive intestinal peptide in rhesus monkey brain as determined by radioimmunoassay.

The concentration of cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in dissected cortical and subcortical areas of four rhesus monkeys' brains was determined by radioimmunoassay (RIA). Cerebral cortical samples from one human brain are included for comparison. Preliminary data from two baboon brains are described. The results are similar to previous studies on rat (1-7), human (7-12), porcine (12,13), bovine (3) and guinea pig brains (14) and indicate that: 1) both CCK and VIP are widely distributed in cortical and subcortical areas in these species, 2) CCK is generally more abundant than VIP in primate brain, and 3) the distribution of CCK and VIP in the rat brain parallel those in infrahuman primate and human brain.

Animals↗

Effects of prolonged cultivation in the presence of acyclovir on recovery of latent herpes simplex virus from human trigeminal ganglia.

The continuous presence of acyclovir prevented the in vitro reactivation of latent herpes simplex virus from cultures of human trigeminal ganglia derived from 23 randomly selected cadavers. When acyclovir was withdrawn after 30 days, herpes simplex virus was recovered from 3 of 18 cases. Herpes simplex virus was recovered in 9 of 20 (45%) control cases.

Acyclovir↗

Polynesian bronchiectasis.

Six Polynesian children aged 8-14 years with recurrent lower respiratory infections and abnormal lung mucociliary clearance were assessed for immuno-deficiency. Measurements were made in these 6 children and in 21 healthy Polynesians of serum immunoglobulins (IgG, IgM, IgA) and complement components (C3, C4), leucocyte function tests, and T and B cell populations. A further 8 Polynesian bronchiectatics were tested for sputum secretory-IgA. There was no evidence of S-IgA deficiency and 4 had high levels. There was no evidence of immunodeficiency. Nasal epithelium was obtained from 6 children using a cytology brush and ciliated epithelium was obtained in only 4. The ultrastructure was normal although few cilia were examined.

Adolescent↗

Telencephalic enkephalinergic systems in the rat brain.

The comparative distribution of Leu-enkephalin and an enkephalin precursor fragment, BAM-22P, was studied in the rat telencephalon using immunocytochemical procedures. Although the enkephalins have previously been localized to telencephalic neurons, the use of high doses of colchicine in the present study has permitted the visualization of widespread enkephalin-containing systems in cortical-limbic regions. Rats were treated intraventricularly with colchicine (300 to 400 micrograms) to enhance the visualization of neuronal perikarya. Leu-enkephalin immunoreactivity was noted in perikarya as well as processes of neurons in many telencephalic regions including the olfactory bulb, parolfactory areas, olfactory tubercle, basal ganglia, nucleus accumbens, septal nuclei, amygdala, hippocampal formation, and several paleocortical regions such as the piriform, entorhinal, and cingulate cortex, as well as regions of the frontal, parietal, and occipital neocortex. In the majority of regions investigated, analysis of sections adjacent to those processed for Leu-enkephalin histochemistry showed BAM-22P immunoreactivity to be localized to perikarya and processes in the same region. These results suggest that brain enkephalin-positive neurons may possess mechanisms for enkephalin biosynthesis similar to those found in adrenal medullary enkephalin cells.

Animals↗

Effect of benzodiazepines on cyclic GMP formation in rat cerebellar slices.

Cyclic 3',5' guanosine monophosphate (cGMP) levels, stimulated in brain slices by ouabain, potassium, and sodium azide depolarization, have been found to be inhibited in a dose-dependent fashion by both behaviorally active and inactive benzodiazepines. ED50's for these benzodiazepines bear no relation to potencies established from receptor membrane binding studies; however, these values do correspond to ED50's calculated for several known membrane stabilizing agents tested in this system. The concentration of [3H]flunitrazepam necessary to saturate the benzodiazepine receptor in identical slice preparations is considerably lower than that needed to initiate inhibition of depolarization-induced cGMP stimulation. Some of the reported in vivo actions of benzodiazepines on cGMP formation may be the result of membrane stabilizing actions of the benzodiazepines or mediated indirectly.

Animals↗

Equivalence of parieto-preoccipital subareas for visuospatial ability in monkeys.

Parieto-preoccipital lesions in monkeys produce a variety of behavioral deficits, many of which can be classified as either visuospatial or tactual. Since the lesions typically invade a number of cytoarchitectonic areas, the diverse behavioral effects could be a consequence of damage of different functional systems. To determine whether visuospatial ability depends critically on particular parieto-preoccipital -- or on a particular combination of them, monkeys with lesions of one, two, or all three of these sectors were tested both on the "landmark' task, a visual distance discrimination, and, for comparison, on a visual pattern discrimination. Impairment was found only on the landmark task, and the severity of the impairment depended on the number of sectors included in the removal, completely independent of their locus. In an attempt to integrate these results with current neurobiological data, we propose that the parieto-preoccipital region consists of two subdivisions that are organized hierarchically for the mediation of spatial perception. The lower-order subdivision, composed largely of the modality-specific preoccipital area, dorsal OA, is postulated to serve visuospatial processes selectively. The higher-order subdivision, composed mainly of the poly-sensory parietal area, PG, is postulated to serve a supramodal spatial ability to which both the visual and tactual modalities contribute.

Animals↗

Corticotropin and beta-endorphin-like materials are native to unicellular organisms.

Multiple molecular forms of immunoreactive corticotropin (ACTH) and beta-endorphin were present in extracts of a unicellular eukaryote (Tetrahymena pyriformis). One form of immunoreactive ACTH reacted similarly with two different ACTH antisera (one specific for the 11-24 sequence and the other with determinants within sequences 1-14 and 17-39) and migrated with synthetic hACTH-(1-39) in a gel filtration system. This form also exhibited ACTH bioactivity in a dispersed rat adrenal cell bioassay system, with a mean immunoassay/bioassay ratio of 1.5. Gel filtration revealed multiple size classes of immunoreactive beta-endorphin; a major peak of radioreceptor activity was detected which exhibited a K(av) similar to that of authentic beta-endorphin. A major portion of immunoreactive beta-endorphin-sized material exhibited retention times similar to those of synthetic human and camel beta-endorphin upon reverse-phase high-pressure liquid chromatography. These distinctive properties and specificities would seem to exclude the presence of limited homologies with sequences present in other proteins. High molecular weight material containing both ACTH and beta-endorphin antigenic determinants was also demonstrated, suggesting, but not proving, the presence of a common precursor molecule.

Journal Article↗

Factors affecting recovery of latent herpes simplex virus from human trigeminal ganglia.

The rate of recovery of herpes simplex virus (HSV) from human trigeminal ganglia explant monolayers is affected by two factors: (1) time elapsed from the death of an individual to the establishment of in vitro culture of ganglia and (2) surface area onto which ganglia are explanted. Spontaneous reactivation of HSV from human trigeminal ganglia can be maximized when ganglia are obtained within 12 h of death and explanted into surface area of 250 cm2. Viruses isolated by explantation of human trigeminal ganglia were found to be uniformly HSV type 1 by restriction enzyme analysis.

Adolescent↗

Opiate receptor gradients in monkey cerebral cortex: correspondence with sensory processing hierarchies.

In order to obtain information on the possible functions of endogenous opiates in the primate cerebral cortex, we assessed the distribution of mu-like opiate receptors (which selectively bind 3H-labeled naloxone) and delta-like opiate receptors (which selectively bind 3H-labeled D-Ala2, D-Leu5-enkephalin) throughout the cerebral cortex of the rhesus monkey. Stereospecific [3H]naloxone binding sites increased in a gradient along hierarchically organized cortical systems that sequentially process modality-specific sensory information of a progressively more complex nature. Specific [3H]enkephalin binding sites, in contrast, were relatively evenly distributed throughout the cerebral cortex. These results, in combination with electrophysiological studies of monkeys and humans, suggest that mu-like opiate receptors may play a role in the affective filtering of sensory stimuli at the cortical level, that is, in emotion-induced selective attention.

Animals↗