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Biomedical subjects

M Tohyama

Publications and source records attributed to M Tohyama.

At least 217 records · Page 12Linked to original sources
PubMed1994

[A therapeutic trial of experimental tuberculosis with gamma-interferon in an immunocompromised mouse model].

It has been well documented that IFN-gamma plays an important role in the host defense against Mycobacterium tuberculosis infection through activating macrophages to kill the organism. In the present study, we studied the effects of in vivo injection of monoclonal antibody against IFN-gamma (anti-IFN-gamma mAb) on the mycobacterial infection to confirm the role of this cytokine. The injection of anti-IFN-gamma mAb suppressed the enhanced expression of MHC class II and ICAM-1 on pulmonary parenchymal macrophages induced by intravenous injection of Mycobacterium bovis BCG. The number of bacilli recovered from lung of mice treated with anti-IFN-gamma mAb and injected with Mycobacterium tuberculosis H37Rv was significantly larger than that of the control infected mice. From these results, it was indicated that anti-IFN-gamma mAb blocked the activities of endogenously synthesized IFN-gamma, thus inhibited the activation of macrophages to kill the bacilli. Next, CD4+ T cell-depleted mice were prepared by injecting anti-CD4 mAb and used as immunocompromised animal. When infected with M. tuberculosis, the multiplication of the bacilli within the lungs of such immunocompromised mice was much more enhanced in comparison with the control mice with intact CD4+ T cells. Administration of IFN-gamma significantly reduced the number of the bacilli in lung. Further, in an in vitro study with human lung macrophages, IFN-gamma enhanced the killing activity of macrophages against M. tuberculosis in a dose dependent manner, and suboptimal dose of 1 alpha, 25-dihydroxyvitamin D3 synergistically augmented the effect of IFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Cellular localization of serotonin transporter mRNA in the rat brain.

Expression of serotonin (5-hydroxytryptamine, 5-HT) transporter mRNA in the rat brain was examined by in situ hybridization histochemistry with a synthetic oligonucleotide probe. 5-HT transporter mRNA was expressed in neurons in most of the raphe nuclei. The dorsal and median raphe nuclei contained intensely labeled neurons, while the caudal linear nucleus, raphe magnus nucleus, raphe pontis nucleus, raphe pallidus nucleus and the raphe obscurus nucleus contained weakly or moderately labeled neurons. The localization pattern of the 5-HT transporter mRNA-positive neurons coincides fairly well with that of 5-HT-immunoreactive neurons, indicating that 5-HT transporter is primarily located in serotonergic neurons.

Animals↗
PubMed1993

Histamine-containing nerve fibers innervate human cerebellum.

Histamine is found in nerve cell bodies of the tuberomammillary nucleus in mammalian brain. This nucleus is prominent in human brain. Samples of human cerebelli obtained from neurosurgical operations were examined for the presence of histamine-containing nerve fibers. In all samples, a moderately dense network of histamine-immunoreactive fibers was seen in the molecular layer. These fibers ran parallel to the Purkinje cell layer after traversing it perpendicularly. Numerous fibers were also seen in the granular cell layer. The results suggest that the human cerebellar cortex receives a direct input from histamine-synthesizing hypothalamic neurons, as no other histamine-containing neurons have been found in human brain.

Aged↗
PubMed1993

AMPA, KA and NMDA receptors are expressed in the rat DRG neurones.

The localization of AMPA receptor subunits (GluR1-4), a KA receptor subunit (GluR5) and NMDA receptor subunits (NR1 and NRgbs; the glutamate binding subunits of an NMDA receptor complex) was investigated using immunohistochemistry and in situ hybridization histochemistry in the rat dorsal root ganglion. Small neurones expressed GluR1-, GluR2/3-like immunoreactivities and GluR5, NR1, NRgbs mRNAs, while large neurones expressed GluR2/3-like immunoreactivity and NR1 and NRgbs mRNAs. These data suggest that the glutamatergic system plays an important role in the primary sensory afferent systems and that the composition of glutamate receptors differs according to the cell size.

Animals↗
PubMed1993

Localization of trkB mRNA in postnatal brain development.

We investigated the localization of trkB mRNA, which encodes a putative component of high-affinity brain-derived neurotrophic factor (BDNF) or the neurotrophin-3 (NT-3) receptor, in the postnatal rat brain by in situ hybridization histochemistry. At birth, trkB mRNA was strongly expressed in various regions with the thalamus and cerebral cortex showing the strongest expression. As the rat grows, expression generally persisted or declined in most regions with the exception of the hippocampus where trkB mRNA expression increased during postnatal development. In the adult brain, trkB mRNA was detected in the olfactory system, cerebral cortex, hippocampal formation, amygdala, and cerebellar cortex. These findings, together with the developmental profiles of BDNF and NT-3 mRNA expressions, suggest that trkB product (gp145trkB) mainly transduces NT-3 signals early in the postnatal period, and BDNF signals later in the period.

Aging↗
PubMed1993

MFH-1, a new member of the fork head domain family, is expressed in developing mesenchyme.

We have isolated a novel mouse gene, MFH-1 (mesenchyme fork head 1) that is related to the Drosophila fork head and rat HNF3 genes. MFH-1 encodes a distinct fork head domain that is classified into a distinct subfamily. A recombinant MFH-1 protein could bind to the HNF3 binding site. MFH-1 is expressed temporally in developing embryos, first in the non-notochordal mesoderm and later in areas of mesenchymal condensation in the trunk, head, and limbs. Our results suggest that MFH-1 might be involved in the formation of special mesenchymal tissues.

Amino Acid Sequence↗
PubMed1993

The innervation of calcitonin gene-related peptide to the Purkinje cells and granule cells in the developing mouse cerebellum.

The present study analyzed the ontogeny of calcitonin gene-related peptide-like immunoreactive (CGRP-IR) structures in the mouse cerebellum. No CGRP-IR neurons were detected at any stage, but three types of CGRP-IR fibers were seen: (1) CGRP-IR dense fiber plexuses which appeared transiently in the developing cerebellum, (2) thin varicose fibers, and (3) mossy fiber-like fibers. The CGRP-IR dense fiber plexuses appeared in the developing Purkinje cell layer at postnatal day 2. From postnatal days 6 to 11, these fibers formed pericellular nests around Purkinje cells. After that stage, these fibers rapidly disappeared and no such plexuses were seen in the adult cerebellum. CGRP-IR fiber plexuses were not evenly distributed, and they had a parasagittal banded pattern in the frontal sections. These plexuses existed in the region of all vermis, crus 1 of the ansiform lobe, simplex lobule, and flocculus, while the other lobules were devoid of such fibers. Under electron microscopy, these CGRP-IR fibers were seen to make synaptic contacts with somatic spines of Purkinje cells, suggesting that CGRP-IR plexuses were closely related to the developing Purkinje cells. Mossy fiber-like CGRP-IR fibers appeared in the granular layer on postnatal day 2, and increased in number to reach a peak on postnatal day 12. Thereafter, they decreased slightly to reach a plateau on postnatal day 30. Under electron microscopy these CGRP-IR fibers were revealed to be the mossy fibers which regulated the granule cells. Thin varicose CGRP-IR fibers were rarely seen at birth, but on postnatal day 8, many fibers appeared in all layers and increased by postnatal day 30. They distributed equally throughout the cerebellar cortex with a slight predominance in density in the molecular and Purkinje cell layer. Immunoelectron microscopic analysis showed that these fibers made synaptic contacts with small dendrites in the molecular layer.

Aging↗
PubMed1993

Upregulation of fibroblast growth factor-receptor messenger RNA expression in rat brain following transient forebrain ischemia.

Recently, we demonstrated that transient forebrain ischemia in rats leads to an early and strong induction of basic fibroblast growth factor (bFGF) synthesis in astrocytes in the injured brain regions. In this study, in order to clarify the targets of such raised endogenous bFGF levels, the messenger RNA (mRNA) expression of its receptors (flg and bek) in the hippocampus following transient forebrain ischemia induced by four-vessel occlusion for 20 min was investigated using an in situ hybridization technique. Transient forebrain ischemia induced an increase in the number of flg mRNA-positive cells from an early stage (24 h after ischemia) in the hippocampal CA1 subfield where delayed neuronal death occurred later (48-72 h after ischemia). This increase became more marked with the progression of neuronal death and was still evident in the same area 30 days later. The time course of the appearance and distribution pattern of flg mRNA-positive cells in the CA1 subfield were quite similar to those of bFGF mRNA-positive cells. On the other hand, in situ hybridization for bek mRNA showed only slight and transient (observed 72 h and 5 days after ischemia) increases in the number of mRNA-positive cells in the CA1 subfield following ischemia. The use of in situ hybridization and glial fibrillary acidic protein immunohistochemistry in combination demonstrated that the cells in the CA1 subfield that exhibited ischemia-induced flg or bek mRNA expression were astrocytes. These data indicate that transient forebrain ischemia induces upregulation of fibroblast growth factor-receptor expression, accompanied by increased bFGF expression in astrocytes, and suggest that the increased astrocytic bFGF levels in injured brain regions act on the astrocytes via autocrine systems and are involved in the development and maintenance of astrocytosis.

Animals↗
PubMed1993

Aneurysmal dilatation of ductus arteriosus during lipo-prostaglandin E1 therapy for diaphragmatic hernia.

We report a case of congenital diaphragmatic hernia in which aneurysmal dilatation of ductus arteriosus developed after lipo-prostaglandin E1 (PGE1) therapy for persistent fetal circulation. After surgery Lipo-PGE1 was used at a dosage of 5 ng/kg per minute from days 2-9 during which aneurysmal dilatation (7 mm in diameter) developed and remained thereafter. Ductus arteriosus ligation was then performed. Lipo-PGE1 may promote ductus arteriosus dilatation in cases of persistent fetal circulation.

Alprostadil↗
PubMed1993

Expression of muscarinic and nicotinic receptor mRNA in the salivary gland of rats: a study by in situ hybridization histochemistry.

Expression of muscarinic receptor mRNA subtypes (m1-5) and nicotinic receptor subunits (alpha 2-4, and beta 2) was examined in the rat submandibular gland by in situ hybridization histochemistry, using oligonucleotide probes for the muscarinic receptor and RNA probes for the nicotinic receptors. m2, alpha 3, and beta 2 mRNA were strongly expressed in the submandibular ganglion, and m3, alpha 2, alpha 3, alpha 4, and beta 2 were expressed in the striated and interlobular duct cells. Both muscarinic and nicotinic receptors were coexpressed in the same ganglion neurons, while none of these mRNA were detected in the terminal secretory units.

Animals↗
PubMed1993

Ontogeny of dopamine transporter mRNA expression in the rat brain.

The ontogeny of dopamine transporter (DAT) gene expression was studied in the rat brain. DAT mRNA was first detected in neurons of the ventrocaudal mesencephalon on embryonic day 14 (E14). By E18, intensely expressing neurons in the ventral tegmental area and substantia nigra resembled the pattern found in adult midbrain. DAT mRNA is not abundant in the hypothalamus and the olfactory bulb at any stage of development. These results parallel those noted for tyrosine hydroxylase gene expression in mesencephalon.

Animals↗
PubMed1993

Changes in preproenkephalin mRNA after unilateral and bilateral labyrinthectomy in the rat medial vestibular nucleus.

We examined the expression of preproenkephalin (PPE) mRNA in the vestibular nuclei in rats using in situ hybridization histochemistry. In normal rats, PPE mRNA-positive cells were observed in the medial and spinal vestibular nuclei. After unilateral labyrinthectomy, PPE mRNA was increased in the medial vestibular nucleus on the operated side from the 1st through the 3rd day after the surgery. It is suggested that the changes in PPE mRNA level after labyrinthectomy are involved in vestibular compensation.

Animals↗
PubMed1993

Characteristic localization of non-NMDA type glutamate receptor subunits in the rat pituitary gland.

While the involvement of the glutamate receptors in the hypothalamo-hypophyseal system has been clarified at the hypothalamic level, the existence of glutamate receptors in the pituitary gland has remained obscure. We investigated the localization of the glutamate receptors, the non-NMDA type receptor subunits (GluR1-4) in particular, by immunocytochemistry using specific antibodies. The antibodies specific to GluR1, GluR2/3 and GluR4 exhibited the characteristic localization of the receptor molecules in each lobe of the pituitary gland. GluR1- and GluR2/3-positive cells were identified in the anterior and intermediate lobe, and intense terminals of GluR4 and weak terminals of GluR2/3 were observed in the posterior lobe. Such immunoreactivity appeared to be at the axonal terminal of the neurosecretory magnocellular cells. This was confirmed by in situ hybridization histochemistry using specific oligodeoxynucleotide probes and by immunocytochemistry in the neurosecretory magnocellular neurons. The GluR4 mRNA-positive signal and GluR4 immunoreactivity were abundantly observed in magnocells of paraventricular and supraoptic nuclei. In addition to the positive fibers, some pituicytes in the posterior lobe exhibited GluR2/3 immunoreactivity. This suggests that pituicytes have non-NMDA type glutamate receptors. Thus, present study suggests that some anterior pituitary cells and pituicytes in the neural lobe are regulated by the glutamate.

Animals↗
PubMed1993

Differential immunocytochemical localization of GABAA receptor gamma 1 and gamma 2 subunits in the rat brain.

Subunit-specific polyclonal antisera against the GABAA receptor gamma 1 and gamma 2 subunits were raised in rabbits and used for immunoblotting and immunocytochemistry of the rat brain. Each subunit protein was differentially distributed even in the region like cerebellar cortex where mRNAs of both subunits were distributed in the same manner. This may indicate that GABAA receptor gamma 1 and gamma 2 subunit proteins are subject to a subunit-specific subcellular sorting mechanism.

Amino Acid Sequence↗
PubMed1993

Differential expression of two members of FGF receptor gene family, FGFR-1 and FGFR-2 mRNA, in the adult rat central nervous system.

The fibroblast growth factor (FGF) receptor gene family now contains four members that encode homologous receptor-tyrosine kinases (RTKs) to each other. We have demonstrated that one of the members, FGFR-1 (also termed as flg), is expressed in the widespread but specific neuronal populations in the adult rat central nervous system (CNS). In the present study, we examined the expression pattern of another member, FGFR-2 (also termed as bek) and compared it with that of FGFR-1. In contrast with FGFR-1, we detected FGFR-2 expression primarily in the fiber tracts of the adult rat CNS, suggesting that the oligodendrocytes are the main sites of the FGFR-2 expression. These findings indicate that FGF may regulate neurons and glial cells through different subtypes of its cognate receptor.

Animals↗
PubMed1993

Synaptic contact between vestibular afferent nerve and cholinergic efferent terminal: its putative mediation by nicotinic receptors.

The topography and fine structure of cholinergic efferent fibers were examined in the rat vestibular labyrinth using choline acetyltransferase (ChAT) immunohistochemistry. Fiber plexus of cholinergic fibers were observed beneath the sensory cell layer in all vestibular end-organs. Electron microscopic examination revealed that cholinergic fibers make synaptic contacts with chalices of vestibular nerve branches that surround type I hair cells. In situ hybridization histochemistry of nicotinic acetylcholine receptor subunit mRNAs showed that rat vestibular ganglion cells express both alpha 4 and beta 2 subunit mRNAs. These findings suggest that cholinergic efferents modulate vestibular information from type I hair cells by nicotinic receptors at the level of nerve chalices.

Acetylcholine↗
PubMed1993

Sympathetic and parasympathetic ganglia express non-NMDA type glutamate receptors: distinct receptor subunit composition in the principle and SIF cells.

The presence of non-NMDA glutamate receptors in the rat sympathetic and parasympathetic ganglia was examined by immunocytochemistry using specific antibodies against AMPA-type excitatory amino acid receptor subunits (GluR1-4). Three kinds of antibodies specific to the GluR1, GluR2 and 3, and GluR4 subunits were used. The superior cervical ganglion and pterygopalatine ganglion were examined as representatives of sympathetic and parasympathetic ganglia. In the superior cervical ganglion, GluR1- and GluR2/3-like immunoreactivity was observed in most principal neurons and SIF cells. In contrast, GluR4-like immunoreactivity was not observed in the principal cells; however, SIF cells exhibited intense immunoreactivity of GluR4. In the pterygopalatine ganglion, the profile of the immunoreactivity was similar to that seen in the superior cervical ganglia. The subunit compositions between the principal cells and SIF cells were different, whereas the compositions in cell species involved in the autonomic ganglia, sympathetic and parasympathetic ganglia were identical. This suggests that glutamate is another important preganglionic transmitter together with acetylcholine, and the responses elicited in the principal cells and SIF cells might be different because of the difference in subunit composition.

Animals↗