Biomedical subjects

M Yoshioka

Publications and source records attributed to M Yoshioka.

At least 19 recordsLinked to original sources

PubMed1992

Alpha 2-adrenoceptor modulation of 5-HT biosynthesis in the rat brain.

The purpose of the present study is to clarify the modulation of the biosynthesis of serotonin (5-HT) via the alpha 2-adrenoceptors in the brain. For this purpose, 5-hydroxytryptophan (5-HTP) accumulation was determined using an HPLC-ECD system in the presence of the inhibition of aromatic L-amino acid decarboxylase. Administration of alpha 2-adrenoceptor agonist, clonidine, produced a reduction of the in vivo 5-HTP accumulation in both the rat hippocampus and dorsal raphe nucleus. In addition, alpha 2-adrenoceptor antagonist, idazoxan, increased the 5-HTP accumulation in both the hippocampus and the dorsal raphe nucleus. In rats with catecholaminergic neurons denervated by pretreatment with 6-hydroxydopamine, clonidine failed to produce a reduction of 5-HTP accumulation in the dorsal raphe nucleus. On the other hand, hippocampal 5-HTP accumulation was decreased significantly. Brain tryptophan levels were unaffected by either clonidine or idazoxan. These results suggest that alpha 2-adrenoceptors might modulate serotonin biosynthesis and this modulation might be related to the neuroanatomical differences in the rat brain.

5-Hydroxytryptophan↗

PubMed1992

Effect of clonidine on the release of serotonin from the rat hippocampus as measured by microdialysis.

The purpose of the present study is to clarify the effect of clonidine on the release of serotonin from the rat hippocampus in vivo. For this purpose, endogenous serotonin release was measured by brain microdialysis. Potassium-evoked serotonin release from the hippocampus of freely moving rats was significantly inhibited when clonidine (10(-5) M) was added to the perfusion solution, while the 5-hydroxyindoleacetic acid output remained unchanged. In catecholaminergically denervated rats, clonidine (10(-5) M) also inhibited the potassium-evoked serotonin release from the hippocampus and the 5-hydroxyindoleacetic acid output was unaffected by clonidine. These results suggest that the inhibitory effect of clonidine on serotonin release from the hippocampus might reflect the activation of alpha 2-adrenoceptors which are localized on the serotonergic nerve terminals.

Animals↗

PubMed1992

Relapsing and remitting human immunodeficiency virus-associated leukoencephalomyelopathy.

We describe a 33-year-old homosexual man with a steroid-responsive, remitting and relapsing leukoencephalopathy associated with recent human immunodeficiency virus type 1 (HIV-1) seroconversion. Biopsy of a parieto-occipital lesion revealed demyelination and astrogliosis with focal necrosis. Detailed investigations demonstrated no pathogens in the brain other than HIV-1. This patient illustrates that a neurological disorder clinically indistinguishable from multiple sclerosis may be the presenting manifestation of HIV-1 infection and may occur in the absence of clinically significant immunosuppression.

AIDS Dementia Complex↗

PubMed1992

Application of superfine fiberscope for endovasculoscopy, ventriculoscopy, and myeloscopy.

In the past three years, we have used a superfine fiberscope for endovasculoscopy, ventriculoscopy, and myeloscopy. Flexible superfine fiberscope, 0.75 mm in outer diameter, could visualize various intravascular findings. In in-vivo canine experiment, sequential changes of thrombus produced by endothelial abrasion by needle or balloon in the canine carotid artery can be clearly seen. And thrombolysis by focal arterial injection of tissue plasminogen activator was sequentially observed. In the clinical study, we could evaluate the stenotic lesions of the subclavian and vertebral arteries before and after balloon angioplasty. During ventriculoscopy, a 2 mm of mini-caliber fiberscope was introduced under ultrasound monitoring, and provided clear visualization of intraventricular tumours. In myeloscopy, draining veins of arteriovenous malformations and nerve roots of the cauda equina could be clearly seen by flexible fiberscope. From these results, it can be said that the superfine fiberscope provides clear and useful visualizations of the interior of vessels, ventricles, and the intrathecal area of the spinal canal. The new applications of this superfine fiberscope for minimally invasive neurosurgery may bring about a marked improvement of therapeutic results.

Animals↗

PubMed1992

Simultaneous detection of ferritin and HIV-1 in reactive microglia.

Using ferritin as a marker of reactive microglia, we demonstrated a close association between proliferation of reactive microglia and expression of human immunodeficiency virus type 1 (HIV-1) in brain tissue from autopsied cases of acquired immunodeficiency syndrome (AIDS). An increased number of ferritin-positive reactive microglia was observed in formalin-fixed paraffin-embedded brain sections from all 13 AIDS cases examined. Similar findings were observed in brain tissue from other neurological diseases (subacute sclerosing panencephalitis, herpes simplex encephalitis and multiple sclerosis). Multinucleated giant cells were found in 7 of the AIDS cases which were also intensely labeled for ferritin. Dual-label immunohistochemistry using anti-ferritin and cell-specific markers showed that ferritin-positive cells were distinct from astrocytes, neurons and endothelia using anti-glial fibrillary acidic protein (anti-GFAP), anti-neurofilament protein and Ulex europaeus agglutinin 1, respectively. In 5 AIDS brains, only ferritin-positive cells were shown to contain HIV-1 gp41 antigen using dual-label immunohistochemistry. In addition, HIV-1 RNA was localized in ferritin-positive reactive microglia but not in GFAP-positive astrocytes using immunohistochemistry combined with in situ hybridization. Ferritin-positive reactive microglia and multinucleated giant cells were co-labeled with the microglial marker, Ricinus communis agglutinin 1 (RCA-1). However, RCA-1 also extensively stained resting microglia only a few of which were co-labeled for ferritin. The density of ferritin-positive cells was correlated with the presence of HIV-1 RNA-positive cells in AIDS brain. Thus, ferritin immunoreactivity can be used as an activation marker of microglia in archival paraffin sections and reflects the extent of inflammation in HIV-1-infected brain.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Clinical variation within sibships in Fukuyama-type congenital muscular dystrophy.

A family in which three siblings were affected with severe cerebral malformations in association with ocular anomalies and muscle disease is reported. One sibling was diagnosed as having Fukuyama type congenital muscular dystrophy (FCMD) because he showed severe hypotonia with dystrophic findings on a muscle biopsy in addition to pachygyria on CT. At the age of 3 years, retinal detachment developed in both eyes. Another sibling exhibited at birth such characteristic features as pachygyria, cephalocele, hydrocephalus, retinal detachment in both eyes, elevated serum creatine kinase activity and arthrogryposis multiplex congenita. We consider these findings to be more consistent with Walker-Warburg syndrome (WWS) than with FCMD. Anencephaly found in the third sibling was regarded as WWS with extreme brain abnormality. The appearance of two syndromes (FCMD and WWS) in the three members of the same family suggests that these syndromes could be allelic with variable phenotypes.

Brain↗

PubMed1992

HIV-1 in postmortem brain tissue from patients with AIDS: a comparison of different detection techniques.

OBJECTIVE: The presence of HIV-1 in postmortem brain tissue from 31 patients with AIDS and 12 HIV-1-negative controls was investigated. DESIGN: Most laboratories have access to the methods used. We readily applied in situ hybridization and immunohistochemistry to archival formalin-fixed paraffin-embedded (FFPE) brain specimens. METHODS: The techniques used to detect HIV-1 were explant culture, in situ hybridization with 35S-labeled polymerase (pol) gene riboprobes and immunohistochemistry with monoclonal antibody to gp41. RESULTS: HIV-1 was isolated from explant cultures in 13 out of 20 (65%) patients, whereas HIV-1-infected cells were detected in FFPE brain tissue from nine out of 26 (35%) patients examined by in situ hybridization and in seven out of 26 (27%) patients examined by immunohistochemistry. CONCLUSIONS: Although the isolation technique was the most sensitive of the three techniques tested, infected cells may be identified with in situ hybridization in conjunction with immunohistochemistry.

AIDS-Related Opportunistic Infections↗

PubMed1992

Relationship between an 85 kDa protein and the protective effects of Mycoplasma pneumoniae.

In the immunoblot analysis, sera from patients infected with Mycoplasma pneumoniae reacted with the 168 kDa (P1) and the 85 kDa proteins of virulent strain FH-P24 and P24-S1 mutant strain but not with the 85 kDa protein of P24-S11. Sera of hamsters and BALB/c mice, which had been immunized with live vaccines, were tested. In FH-P24 immunized animals, 100% or 80%, and in P24-S1, 40% of hamsters and 60% of BALB/c mice, developed antibodies against the 85 kDa protein, but antibodies were not detected in sera of P24-S11 immunized animals. The correlation between the development of antibodies to 85 kDa protein in the sera of vaccinated animals and the effects of protection by living vaccines were suggested.

Animals↗

PubMed1992

Proposal of a new scheme for the serological typing of Enterococcus faecalis strains.

No systematic study on serotyping of Enterococcus faecalis has been reported since 1964 when M.E. Sharpe conducted serotyping of group D streptococcus in U.K. So, we attempted to re-evaluate serotyping of E. faecalis. For this purpose, we received 42 Sharpe's strains and first examined for their biochemical characteristics as E. faecalis. Only 9 of the 42 strains were identified as E. faecalis. We raised rabbit antisera against a large number of E. faecalis strains, including the 9 Sharpe's strains, 2 strains obtained from CDC in U.S.A. and 36 strains isolated from patients hospitalized in different cities of Japan. From the results of cross-agglutination tests and absorption tests performed on these antisera using a large number of E. faecalis strains, we were able to classify 21 distinct serotype strains and to prepare 21 monospecific typing antisera by absorption of the antisera to the type strains with appropriate cross-agglutinating strains. When 832 E. faecalis strains were serotyped with the 21 typing antisera, 638 strains (76.7%) were typable. Thus, we propose a provisional scheme of 21 distinct serovars in E. faecalis.

Agglutination Tests↗

PubMed1992

Plasma adenosine concentrations are elevated in conscious spontaneously hypertensive rats.

1. Plasma levels of adenosine were measured in unrestrained, conscious spontaneously hypertensive rats (SHR) to examine the potential role of adenosine, a naturally occurring substance with profound cardiovascular actions, in cardiovascular regulation in these genetically hypertensive rats. 2. We employed a specific and sensitive assay for adenosine based on fluorescent determination of adenine compounds by high performance liquid chromatography. 3. Plasma adenosine concentrations were significantly higher in 13 week old SHR with hypertension than in Wistar-Kyoto rats (0.165 +/- 0.022 vs 0.096 +/- 0.008 mumol/L; P less than 0.05). 4. These observations indicate that plasma adenosine levels are increased in conscious SHR with established hypertension, and also suggest that adenosine may be at least partly involved in the pathophysiology of high blood pressure in SHR.

Adenosine↗

PubMed1992

Pharmacological characterization of 5-hydroxytryptamine-induced excitation of afferent cervical vagus nerve in anaesthetized rats.

1. An excitatory response to 5-hydroxytryptamine (5-HT) was measured from the afferent vagus nerve of anaesthetized rats. Measurements were determined by an extracellular recording from the whole nerve. 2. Intravenous bolus injection of 5-HT (1.56-100 micrograms kg-1) evoked a dose-dependent excitation of afferent vagus nerve activity. This response was blocked not only by a selective 5-HT3 receptor antagonist, GR38032F (10 and 100 micrograms kg-1), but also by a 5-HT2 receptor antagonist, ketanserin (10 and 100 micrograms kg-1). 3. Both a 5-HT3 receptor agonist, 2-methyl-5-HT (3.12-100 micrograms kg-1), and a 5-HT2 receptor agonist, alpha-methyl-5-HT (3.12-50 micrograms kg-1), produced a dose-dependent excitation of afferent vagus nerve activity. These excitatory effects were antagonized by GR38032F (10 micrograms kg-1) and ketanserin (10 micrograms kg-1), respectively. 4. A 5-HT1 like receptor agonist, 5-carboxamidotryptamine (50 micrograms kg-1), and a putative 5-HT4 receptor agonist, 5-methoxytryptamine (100 micrograms kg-1), failed to produce excitatory effects on the afferent vagus nerve. 5. These results suggest that the 5-HT-induced excitatory response of the afferent vagus nerve might be mediated not only via 5-HT3 receptors but also via 5-HT2 receptors in anaesthetized rats. It is unlikely, however, that either 5-HT1-like or putative 5-HT4 receptors are involved in the excitatory response of the afferent vagus nerve to 5-HT.

Animals↗

PubMed1992

Metabolic disposition of DQ-2556, a new cephalosporin, in rats, rabbits, dogs, and monkeys.

The metabolic disposition of DQ-2556 was studied in rats, rabbits, dogs, and monkeys after an intravenous administration of 20 mg of 14C-labeled drug per kg of body weight. The serum data were analyzed by the two-compartment open model. The mean half-lives for the drug in serum at excretion phase were 18.1, 54.4, 21.8, and 63.6 min in rats, rabbits, dogs, and monkeys, respectively. The volume of distribution and total body clearance ranged from 0.18 to 0.30 liter/kg and 0.065 to 0.45 liter/h/kg, respectively. This compound was distributed to the tissues rapidly and well, especially to the kidney, trachea, liver, thyroid, skin, and lung. Tissue concentrations declined rapidly in a few hours and then very slowly. However, no accumulation was observed in any tissues. The results of a protein-binding study by ultracentrifugation indicated that DQ-2556 was 20 to 30% bound to serum proteins in animals and its affinity was low. Almost 90% of the administered radioactivity was excreted into urine in all species. Biliary excretion in rats was 3.1% of the dose. Nearly 70% of the dose or more was excreted into urine as unchanged drug, and the amounts of urinary metabolites were small except in rabbits, in which substantial amounts of polar metabolites were detected.

Animals↗

PubMed1992

Changes in intestinal absorption of nutrients and brush border glycoproteins after total parenteral nutrition in rats.

The effect of total parenteral nutrition on nutrients absorption and glycoprotein changes of brush border membrane was examined in rat small intestine. In total parenteral nutrition rats, a marked decrease in activity of brush border enzymes was observed mainly in the proximal and middle segments of the intestine. Galactose perfusion of jejunal segment showed that hexose absorption was significantly inhibited, while intestinal absorption of glycine or dipeptide, glycylglycine was not significantly affected by total parenteral nutrition treatment. When brush border membrane glycoprotein profile was examined by [3H]-glucosamine or [3H]-fucose incorporation into jejunal loops, significant changes were observed in the glycoprotein pattern of brush border membrane especially in the high molecular weight range over 120 kDa after total parenteral nutrition treatment, suggesting strong dependency of glycoprotein synthesis on luminal substances. Molecular weight of sucrase isomaltase in brush border membrane detected by specific antibody showed no significant difference, however, in total parenteral nutrition and control rats. Also, molecular weight of specific sodium glucose cotransporter of intestinal brush border membrane detected by selective photoaffinity labelling was not altered in total parenteral nutrition rats. It may be that prolonged absence of oral food intake may produce significant biochemical changes in brush border membrane glycoprotein and absorptive capacity of small intestine, but these changes were not observed in all brush border membrane glycoproteins.

Animals↗

PubMed1992

Intestinal microcirculatory changes during fat absorption and the effect of cholecystokinin inhibitor.

The major objective of this study was to estimate how microvascular changes occur in the intestinal segment in relation to fat absorption and also to assess the role played by cholecystokinin (CCK) in fat-induced intestinal hyperemia. A 12-cm loop of rat middle small intestine was exposed to a 120-min infusion of oleic acid micelle solution containing [14C]oleic acid. Time-course changes of vascular diameter and red blood cell (RBC) velocity of submucosal arterioles, venules, and periglandular and muscular capillaries were determined simultaneously in their different order of branching by using intravital microscopy equipped with a high-speed video camera system. Lymphatic transport of oleic acid was also monitored by collecting lymph from intestinal lymphatics. The instillation of micelle produced significant dilatation of submucosal arterioles and venules and significant increase in RBC velocity in submucosal microvessels and periglandular capillaries at 15 to 30 min after the fat instillation. This corresponds well to the appearance of [14C]oleic acid in intestinal lymph. This microvascular dilatation and RBC velocity increase continued throughout the exposure to fat and started to attenuate 30 min after restoration to saline infusion. There was also heterogeneity in microvascular responses among different orders of branches to fat administration, and RBC velocity increase was not observed in muscular capillaries. Local intra-arterial infusion of CCK inhibitor, loxiglumide (CR 1505, 10 mg.kg-1.h-1), significantly attenuated both fat-induced microvascular dilatation and RBC velocity increase but not the fat absorptive function. Our results indicate that CCK plays a significant role in intestinal hyperemia induced by fat absorption. However, CCK-mediated intestinal microvascular change was not a prerequisite for fat absorption.

Animals↗

PubMed1992

NG-methyl-L-arginine, an inhibitor of L-arginine-derived nitric oxide synthesis, stimulates renal sympathetic nerve activity in vivo. A role for nitric oxide in the central regulation of sympathetic tone?

Continuous production of endothelium-derived nitric oxide (NO) in peripheral vessels has been shown to modulate vascular resistance and blood pressure. NO is also formed in the brain upon activation of glutamate receptors, which are thought to mediate central autonomic reflexes. In the present study we assessed whether NO plays a role in central autonomic regulation. For this, we have investigated the effects of NG-methyl-L-arginine (NMA), a selective inhibitor of NO synthesis from L-arginine, on sympathetic renal nerve activity (RNA), blood pressure, and heart rate in the anesthetized rat. NMA elicited a dose-dependent sustained increase in blood pressure (approximately 20 and 30 mm Hg, 5 minutes after 10 and 50 mumol/kg i.v., respectively). Heart rate and RNA decreased transiently (15 beats per minute and 40%, respectively); RNA subsequently increased (100%) while blood pressure remained elevated. Baroreceptor deafferentation markedly altered these responses to NMA; the transient decreases in heart rate and RNA were abolished, whereas the increases in RNA and blood pressure were significantly potentiated. After spinal C-1-C-2 transection, there was no increase in RNA, and blood pressure increased to a smaller extent. L-Arginine blocked the NMA-induced increases in blood pressure and RNA. Thus, in addition to modulating vascular resistance by a peripheral action, NO may also play a role in the central regulation of sympathetic tone.

Animals↗

PubMed1992

Ganglioside composition and its relation to clinical data in brain tumors.

The ganglioside composition of 15 cases of meningioma, 15 cases of astrocytoma, 5 cases of neurinoma, 4 cases of ependymoma, 3 cases of metastatic brain tumor and 1 case each of mixed glioma, oligodendroglioma, medulloblastoma, embryonal carcinoma, and cultured glioma cell line were analyzed by thin-layer chromatography. The GM2, GD3, and GD2 content of the tumors was determined using specific monoclonal antibodies (MAb). Cases were grouped according to the difference in ganglioside pattern and various clinical features. In meningiomas and astrocytomas, GM3 and GD3 were the major gangliosides. The tumor content of the rather simple gangliosides (GM3, GM2, GD3, GD2) increased or was almost equal to that of normal tissue (leptomeninges tissue in the case of meningiomas, and brain tissue in the case of astrocytomas), while the tumor content of complex gangliosides (GM1, GD1a, GT1a, GT1b) decreased as compared with normal tissue. The GM3 content of meningiomas increased in middle-aged patients, who comprised the majority of the patients with these tumors. The GD2 content decreased in middle-aged patients with initial symptoms of meningioma within a year. The GM3 content of astrocytomas decreased in patients who underwent radiotherapy. The amount of GM3 and GD3 increased in small tumors. GM3 may be related to the early proliferative stage. The ganglioside patterns of brain tumors are shown in this study to differ according to clinical features and also to be changeable in their clinical courses.

Aging↗

PubMed1992

Synthesis and structure-activity relationships of substituted 2-[(2-imidazolylsulfinyl)methyl]anilines as a new class of gastric H+/K(+)-ATPase inhibitors. II.

A series of 2-[(2-imidazolylsulfinyl)methyl]anilines (2) having various substituents on their imidazole and aniline rings was synthesized and examined for their H+/K(+)-ATPase (adenosine triphosphatase) inhibitory effects and antisecretory activity against histamine-stimulated gastric acid secretions in Heidenhain pouch dogs. Although substitutions on the imidazole ring did not enhance biological activity, substitutions on the aniline ring by electron-donating substituents potently enhanced the enzyme inhibitory activity and also showed an inhibitory effect on histamine-stimulated gastric acid secretion after oral administration. In particular, the in vitro activity of the dimethyl (2u--w) and trimethyl (2ac) derivatives was about 10 times that of omeprazole. Also, 4-methyl (2k), 4-methoxy-5-methyl (2y) and 3,5-dimethyl-4-methoxy (2ab) derivatives showed a potent antisecretory effect of more than 80% after oral administration at 6 mg/kg. Although these aniline derivatives have relatively low stabilities in aqueous solution, replacement of the isobutyl group at the aniline nitrogen atom with N-(2-methoxyethyl) group enhanced the stability.

Adenosine Triphosphatases↗

PubMed1992

[Peripheral serotonin receptors: respiratory and circulatory modulation].

The wide distribution of serotonin (5-HT) receptors and 5-HT-mediated effects suggest that 5-HT has important physiological and/or pathophysiological roles in the peripheral nervous system. Recent studies about the localization and release of 5-HT in the peripheral nervous system suggest that 5-HT likely plays a functional role in regulating discharge of autonomic neurons and modulating sensory afferent neurons. The electrophysiological approach has the merit of measuring a direct effect of 5-HT on its receptor. In this review, much of our described work focuses on effects mediated via 5-HT3-receptors on respiration and circulation using electrophysiological techniques, and we consider whether these actions of 5-HT have physiological and/or pathophysiological significance.

Animals↗