Biomedical subjects

K Otake

Publications and source records attributed to K Otake.

At least 55 records · Page 3Linked to original sources

PubMed1996

Vestibular afferents to the dorsal vagal complex: substrate for vestibular-autonomic interactions in the rat.

Vestibular afferents to the nucleus tractus solitarii (NTS) were identified for the first time in the male Sprague-Dawley rat. Cells of vestibular origin were labeled by deposits of cholera toxin B (CT-B) centered on the general viscerosensory division of NTS and dorsal motor nucleus (DMX). Vestibular-visceral afferents derive from neurons concentrated at caudal levels of medial and inferior vestibular nuclei as observed in other species. Vestibular afferent processes were labeled in the NTS and DMX by anterograde transport of the tracer, biotinylated dextran-amine from injection deposits confined to the inferior and/or medial vestibular nuclei. Vestibular axons terminate in the NTS, predominantly at intermediate levels of the dorsal vagal complex. Projections overlapped sites in NTS that receive terminal input from first-order alimentary and cardiorespiratory afferents. The somato-visceral reflex circuit corroborates recent evidence in the rat of increases in functional activity in the vestibular nuclear complex and NTS in response to changes in gravito-inertial force [Kaufman, G.D., Anderson, J.H. and Beitz, A.J., J. Neurosci., 12 (1992) 4489-4500]. Vestibular input to the NTS and DMX may assist in compensating for the effects imposed by movements and gravity on breathing, alimentary reflex function and the systemic circulation.

Afferent Pathways↗

PubMed1996

Clustered localization of oligomeric Nef protein of human immunodeficiency virus type 1 on the cell surface.

We studied human immunodeficiency virus type 1 (HIV-1) Nef protein biochemically and histologically. HIV-1 Nef, derived from baculosystem and from cells infected with HIV-1, formed homomeric monomers, dimers, trimers, and further polymers. These oligomers were non-covalently associated. In cells infected with HIV-1, Nef molecules were clustered at the cell surface as well as cytoplasm. Our previous results have indicated that the Nef on the surface of cells infected with HIV-1 is cytotoxic against uninfected CD4+ T cells. Thus, it is very likely that the HIV-1-mediated cytotoxic reaction is due, at least in part, to the clustered localization of oligomeric Nef on the cell surface.

Animals↗

PubMed1996

Soluble Nef antigen of HIV-1 is cytotoxic for human CD4+ T cells.

We have previously shown that Nef-gene 10 fusion protein induces marked growth arrest of human primary CD4+ T cells. Here, in vitro cytostatic and cytotoxic activities of human immunodeficiency virus type 1 (HIV-1) Nef against CD4+ T cells were extensively investigated. Growth of human CD4+ cells was inhibited significantly just by the addition of purified full-length Nef to cultures. When Nef was cross-linked by anti-Nef antibodies, it became very cytocidal for CD4+ T cells. A high percentage of sera from HIV-1-infected individuals contained soluble Nef. Thus, soluble Nef in vivo may play an important role in immunodysfunction of CD4+ T lymphocytes in HIV-1 infection.

CD4-Positive T-Lymphocytes↗

PubMed1996

Human immunodeficiency virus type 1 Nef protein on the cell surface is cytocidal for human CD4+ T cells.

We have previously shown that the carboxyl-terminal region of human immunodeficiency virus type 1 (HIV-1) Nef antigen present on the outer surface of virus-infected cells has affinity for uninfected T cells. Here, the in vitro cytotoxic potential of HIV-1 Nef on the T cell surface against CD4+ T cells was investigated in detail. Human T cells expressing Nef on the cell surface by transfection with non-infectious mutant HIV-1 proviruses were demonstrated to kill CD4+ T cells efficiently. Furthermore, it was shown that the carboxyl-terminal portion of Nef was cytotoxic for CD4+ T cells and that monoclonal antibody against the carboxyl-terminal region of Nef inhibited Nef induced-cytolysis. Thus, we concluded that Nef protein on CD4+ T cells may play an important role in the specific loss of CD4+ T lymphocytes during HIV-1 infection.

CD4-Positive T-Lymphocytes↗

PubMed1996

Single neurons in Barrington's nucleus projecting to both the paraventricular thalamic nucleus and the spinal cord by way of axon collaterals: a double labeling study in the rat.

Barrington's nucleus, a center for the micturition reflex in the pontine tegmentum, was recently reported to send projection fibers to the paraventricular thalamic nucleus (PVT). In the present study, we examined whether or not Barrington's nucleus neurons projecting to the PVT issue axon collaterals to the lowest lumbar cord segment (L6) containing the spinal micturition center. Our retrograde double-labeling study revealed that a subset of Barrington's nucleus neurons send projection fibers to both the L6 and the thalamic midline including the PVT via axon collaterals. Such neurons projecting directly to the thalamic midline and L6 by way of axon collaterals were additionally scattered in the locus coeruleus, subcoeruleus nucleus and sublaterodorsal nucleus.

Animals↗

PubMed1996

Distribution of Ca2+/calmodulin-dependent protein kinase kinase alpha in the rat central nervous system: an immunohistochemical study.

Ca2+/calmodulin-dependent protein kinase IV (CaM-kinase IV) is activated by CaM-kinase IV kinase. We provided a rabbit antiserum against 20 amino acid residues at the carboxyl-terminal end of CaM-kinase IV kinase, and examined regional and intracellular distribution of CaM-kinase IV kinase immunohistochemically in the central nervous system of the rat by light and electron microscopy. The immunoreactivity was found in cellular nuclei of virtually all neurons. However, the immunoreactivity was weak in the nuclei of the granule cells in the cerebellar cortex, although the nuclei of the granule cells were reported to contain high CaM-kinase IV activity. Thus, it was suggested that other types of CaM-kinase IV kinase might exist in the cerebellum, and the present CaM-kinase IV kinase was named as CaM-kinase kinase alpha.

Amino Acid Sequence↗

PubMed1996

Central and primary visceral afferents to nucleus tractus solitarii may generate nitric oxide as a membrane-permeant neuronal messenger.

An anatomical basis was sought for the postulated roles of nitric oxide (NO) as a labile transcellular messenger in the dorsal vagal complex (NTS-X). The diaphorase activity of NO synthase was used as a marker of neurons in NTS-X that are presumed to convert L-arginine to L-citrulline and NO. Nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) staining patterns in the nucleus tractus solitarii (NTS) were spatially related to terminal sites of primary visceral afferents from 1) orosensory receptors (e.g., rostral-central nucleus); 2) soft palate, pharynx, larynx, and tracheobronchial tree (e.g., dorsal, intermediate, and interstitial nuclei); 3) esophagus (nucleus centralis); 4) stomach (nucleus gelatinosus); 5) hepatic and coeliac nerves (nucleus subpostrema); and 6) carotid body and baroreceptors (medial commissural and dorsal-lateral nuclei). Primary visceral afferents were identified as sources of NADPHd-stained fiber plexuses in the NTS-X based on three findings: 1) the presence of NADPHd in nodose ganglion cells with morphological features of first-order sensory relay neurons; 2) retrograde transport of Fluoro-Gold (FG) or cholera toxin B (CT-B) from NTS-X to NADPHd-positive nodose ganglion neurons; and 3) striking reductions of NADPHd-stained processes within primary vagal projection fields ipsilateral to unilateral nodose ganglionectomy. A central origin of NADPHd-stained processes in NTS-X was identified in the medial parvicellular subdivision of the paraventricular hypothalamic nucleus. We conclude that NO of peripheral and central origin may modulate viscerosensory signal processing in the NTS-X and autonomic reflex function.

Afferent Pathways↗

PubMed1996

In vitro cytocidal effects of human immunodeficiency virus type 1 Nef on unprimed human CD4+ T cells without MHC restriction.

We have previously shown that the C-terminal region of human immunodeficiency virus type 1 (HIV-1) Nef antigen present on the outer surface of virus-infected cells has an affinity for uninfected T cells and that the Nef protein is responsible for T cell death. To exclude completely the possibility of MHC restriction of this cytotoxic activity, the in vitro cytotoxic potential of HIV-1 Nef against various CD4+ T cell lines as well as naive T lymphocytes was investigated using a baculovirus expression system. Insect cells expressing myristoylated Nef on their cell surface were shown to kill a proportion of CD4+ T cells within 8 h. However, N-terminal truncated and unmyristoylated Nef proteins were not present on the outer surface of insect cell membranes and failed to show any killing activity. Monoclonal antibodies against the C-terminal region of Nef inhibited cytolysis. Thus, we conclude that specific Nef-mediated cytolysis is induced by contact with unprimed CD4+ T lymphocytes without MHC restriction.

Animals↗

PubMed1996

Benign cementoblastoma. Case report.

Benign cementoblastoma is a rare benign odontogenic tumour of mesenchymal origin. A case of a 24-year-old man with benign cementoblastoma is presented. The lesion manifested as a round, radiopaque mass attached to the root of the left first molar of the mandible. The tooth was extracted and the lesion was removed. A diagnosis of benign cementoblastoma was made microscopically. There has been no evidence of recurrence during the three-year follow-up period. A review of the literature and a discussion of the histologic features of this case are included.

Adult↗

PubMed1996

[Effects of surfactant TA on adherence and structure of human peripheral blood neutrophils].

Artificial surfactant is used to treat patients with the adult respiratory distress syndrome; we studied its effects on neutrophil function. Neutrophils were isolated from healthy volunteers and their adherence to plastic surfaces was used as an index of their function. Surfactant TA (S-TA, 0.16-5 mg/mL) dose-dependently inhibited neutrophil adherence stimulated by n-formyl-methionyl-leucyl-phenyl-alanine, phorbol myristate acetate, and tumor necrosis factor. This inhibition was observed whether untreated S-TA or heated S-TA was used. Electron microscopy revealed an increase in the number of apoptotic neutrophils with pyknotic nuclei and smooth cell surfaces after treatment with S-TA which suggests that neutrophils apoptosis was increased. The number of apoptotic neutrophils increased with increasing time of incubation with S-TA, and was also high in the presence of G-CSF, which inhibits neutrophil apoptosis. These results show that S-TA can inhibit neutrophil function, and they suggest that S-TA therapy for the adult respiratory distress syndrome not only corrects the surface-tension abnormality, but can also inhibit infiltration of neutrophils.

Apoptosis↗

PubMed1995

Sites of origin of corticotropin-releasing factor-like immunoreactive projection fibers to the paraventricular thalamic nucleus in the rat.

Neurons containing the peptide corticotropin-releasing factor (CRF) are thought to play a pivotal role in orchestrating autonomic and behavioral responses to stress. CRF afferents to the thalamus are almost entirely concentrated in the midline nuclei, especially in the paraventricular thalamic nucleus. In chloral hydrate-anesthetized male Wistar rats, we sought to determine the sites of origin of the CRF projection fibers to the thalamus, employing a combination of retrograde neuronal tracing and immunocytochemistry for CRF. Prethalamic neurons showing CRF immunoreactivity were detected in the continuum formed by the central nucleus of amygdala and the bed nucleus of the stria terminalis. Additional sources of the CRF fibers to the thalamus were also detected in the parabrachial nuclei and ventrolateral medulla.

Animals↗

PubMed1995

Adrenergic innervation of forebrain neurons that project to the paraventricular thalamic nucleus in the rat.

The paraventricular thalamic nucleus (PVT) lies in a pivotal position between the sensorium and a neural network involved in viscerolimbic integration. The aim of this study was to identify pathways used by adrenergic afferents to influence the outflow of the PVT. Potential disynaptic adrenergic projections to the PVT were investigated in chloral hydrate-anesthetized male Sprague-Dawley rats. PVT afferents were retrogradely labeled with cholera toxin B subunit on tissues processed with phenylethanolamine N-methyltransferase (PNMT) immunohistochemistry for displaying putative adrenergic innervation. In several regions of subcortical forebrain, PNMT-immunoreactive terminal-like varicosities were found to be closely associated with the soma and proximal dendritic segments of neurons retrogradely labeled from the PVT. These cell groups formed two topographically organized projection systems. The lateral telencephalic system was composed of a cell continuum formed by the central nucleus of amygdala, sublenticular substantia innominata and bed nucleus of the stria terminalis. The medial diencephalic system included the lateral hypothalamic area, perifornical nucleus, dorsomedial and periventricular hypothalamic nuclei. Adrenergic neurons in the medulla oblongata may modulate the activity of midline thalamic circuit neurons implicated in behavior.

Adrenergic Fibers↗

PubMed1995

Monoamines and nitric oxide are employed by afferents engaged in midline thalamic regulation.

The neurochemical identities of afferents to the midline thalamus were investigated in chloral hydrate-anesthetized adult Sprague-Dawley rats. The retrograde tracers, FluoroGold or cholera toxin B subunit, were centered on the paraventricular thalamic nucleus (n.Pvt), a periventricular member of the diffuse thalamocortical projection system that is reciprocally linked with visceral areas of cerebral cortex and implicated in food intake and addictive behavior. Tissues were processed with antisera raised against 5-HT, the catecholamine-synthesizing enzymes, tyrosine hydroxylase or phenylethanolamine N-methyltransferase or the cholinergic anabolic enzyme, ChAT. Serotonergic afferents principally derive from dorsal and median constituents of the mesopontine raphé. Previously unrecognized sources of catecholaminergic afferents were detected. Adrenergic afferents were traced to neurons in the C1 and C3 areas of rostral medullary reticular formation and periventricular gray, respectively, and the C2 area corresponding to the dorsal general viscerosensory field of nucleus tractus solitarii. Noradrenergic afferents arise principally from neurons in the locus ceruleus and A5 area. Dopaminergic projections to the n.Pvt derive from the A14, A13 and A11 cell groups in diencephalon. Afferents presumed to generate nitric oxide (NO) as a diffusible membrane-permeant transcellular signal were detected by processing retrogradely labeled tissues histochemically for NADPH-diaphorase, a molecule associated with nitric oxide synthase. NO in the n.Pvt is generated predominantly by noncholinergic neurons in the lateral hypothalamic area and mesopontine tegmentum. In striking contrast, extensive interactions were predicted between NO and ACh in the central medial and other loci in the nondiscriminative thalamus. We conclude that the n.Pvt is a site of interaction of NO and monoaminergic afferents derived from nuclei implicated in sensory gating, regulation of electrocortical neural activity and behavior. Taken collectively, our data predict that the labile transcellular messenger NO may enable structurally differentiated subnuclei of the diffuse thalamocortical projection system to act in concert as a functionally unified unit.

Adrenergic Fibers↗

PubMed1994

The carboxyl-terminal region of HIV-1 Nef protein is a cell surface domain that can interact with CD4+ T cells.

Our previous studies have shown that the HIV-1 Nef Ag is expressed, at least in part, on the surface of infected cells. We demonstrated this by using membrane immunofluorescence and flow cytometry with Nef murine mAbs. To identify the domain of Nef exposed on the cell surface, epitope mapping of these and a new mAb was performed by ELISAs by using several recombinant truncated Nef fusion proteins and synthetic peptides. The results showed that mAbs F1, E7, E9, and 4H4 recognized Nef epitopes located at amino acid residues 148-157, 192-206, 158-206, and 1-33, respectively. The intensity of cell surface Nef staining was stronger with mAbs E7 and E9 than with F1, and there was no staining by 4H4, which indicates that the carboxyl-terminal region of Nef is predominantly exposed on the surface of HIV-1-infected T cell lines and PBMC. This surface Nef domain displayed high affinity for the surface of uninfected CD4+ T cells, because the binding of a soluble form of recombinant Nef protein to the cell surface was specifically blocked by the E7 and E9 mAbs or by synthetic peptides that contained the carboxyl-terminal region of Nef. In addition, syncytium formation between infected and uninfected cells also was specifically reduced by the same mAbs or peptides. Thus, the cell surface domain of Nef seems to play an important role in the interaction between HIV-1-infected and CD4+ uninfected T cells.

Antibodies, Monoclonal↗

PubMed1994

Hypothalamic dysfunction in Parkinson's disease patients.

Ten patients with idiopathic Parkinson's disease (PD) (3 men and 7 women, group A) who had received no treatment for the disease; 102 patients with PD (36 men and 66 women, group B) who had undergone treatment and 45 healthy volunteers (15 men and 30 women, control group) were subject to thyrotropin-releasing hormone (TRH) tests and levodopa tests. In group A basal plasma prolactin (PRL) levels were significantly higher than in the controls both before and during treatment. Peak plasma PRL levels during TRH tests were significantly higher before treatment, but returned to the control levels during treatment. Nadir plasma PRL levels during levodopa tests were significantly increased before and during treatment. In group B basal plasma thyroid-stimulating hormone (TSH) and PRL levels were significantly higher than in the control group. Peak plasma PRL levels during TRH tests and nadir plasma PRL levels during levodopa tests were also significantly increased. The results strongly suggest a disturbance of pituitary hormone secretion due to hypothalamic dysfunction in PD patients.

Administration, Oral↗

PubMed1994

Afferents to the midline thalamus issue collaterals to the nucleus tractus solitarii: an anatomical basis for thalamic and visceral reflex integration.

The goal of this study was to establish a structural basis for thalamic and visceral integration. We sought to define neural networks that convey visceral or integrated environmental stimuli to the diffuse thalamocortical relay system and that link periodic changes in forebrain and visceral reflex function. Our experiments were designed to determine whether afferents to the midline-intralaminar thalamic nuclei (MIT) issue collaterals to the general viscerosensory division of the nucleus tractus solitarii (NTS). Experiments were performed on anesthetized male Sprague-Dawley rats. Two tracers, FluoroGold and rhodamine latex microbeads, were stereotaxically centered on the MIT and NTS, respectively, in each animal. Subsets of midline thalamic afferents were identified that issue collaterals to the solitary complex. In the cerebral cortex, dually labeled soma were detected in layer V of the insular and infralimbic areas. In the subcortical forebrain, the lateral septal nucleus, anterolateral area of the bed nuclei of stria terminalis, medial preoptic nucleus, medial and central amygdaloid nuclei, caudal lateral hypothalamic area, supramammillary nucleus, and parvicellular division of the paraventricular hypothalamic nucleus constitute other newly identified sources of collateral projection. In the midbrain and pons, collateral projection cells were observed in the periaqueductal gray, dorsal raphe nucleus, mesencephalic reticular formation, laterodorsal tegmental nucleus, lateral and medial parabrachial nuclei, and noradrenergic A5 area. In the lateral parabrachial nucleus, dually labeled neurons were detected in the dorsal-lateral division. In the medulla, collaterals are derived from cells in the rostral and caudal ventrolateral reticular formation and parapyramidal area. Dually labeled cells were also found in the cerebellar fastigial nucleus. Collaterals may coordinate changes in visceral reflex excitability and thalamocortical rhythms during phases of sleep-wake cycle and behavioral expression.

Animals↗

PubMed1993

Projections from the commissural subnucleus of the solitary tract onto catecholamine cell groups of the ventrolateral medulla.

Efferent projections of the commissural subnucleus of the solitary tract (COM) to the ventrolateral medulla were studied in the cat using anterograde labeling with biocytin combined with dopamine beta-hydroxylase immunohistochemistry. COM neurons were observed to send their axons densely to the areas of distribution of respiration-related neurons in the ventrolateral medulla, e.g. ventral respiratory group, Bötzinger complex. Axon terminals from COM neurons were further found in the areas of distribution of catecholamine neurons (C1 and A1 cell groups), that were distributed in the close vicinity of the reported respiration-related areas in the ventrolateral medulla. Putative synaptic contacts of axon terminals from COM neurons with catecholamine neurons were often observed in the C1 area.

Animals↗

PubMed1993

Galanin as a physiological neurotransmitter in hemodynamic control of arginine vasopressin release in rats.

Previous neuroanatomical studies have revealed a localization of galanin in several nuclei in the brain stem which are involved in the hemodynamic control of arginine vasopressin (AVP) release. The present study, therefore, investigates the contribution of endogenous galanin to the plasma volume-mediated control of AVP release in conscious rats. Injection of synthetic rat galanin (12.5-50 pmol/rat) into the cisterna magna (i.c.s.) suppressed plasma AVP increased by polyethylene glycol-induced hypovolemia (2.45 +/- 0.24 pg/ml at 50 pmol/rat vs. the vehicle group 5.72 +/- 0.69 pg/ml, p < 0.01). In contrast, when plasma AVP was suppressed by isotonic plasma volume expansion, immunoneutralization of endogenous galanin by antigalanin-antibody i.c.s. significantly reversed the suppression (1.02 +/- 0.07 pg/ml vs. vehicle group 0.63 +/- 0.05 pg/ml, p < 0.01) without altering the mean arterial blood pressure. These results suggest that endogenous galanin is physiologically involved in the plasma volume-mediated control of AVP release through an inhibitory action on this pathway.

Animals↗