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H Nishimura

Publications and source records attributed to H Nishimura.

At least 73 records · Page 4Linked to original sources
PubMed1991

Staurosporine, a protein kinase inhibitor, attenuates basal forebrain-lesion-induced amnesia and cholinergic neuronal deficit.

We have investigated whether administration of staurosporine, which has been reported to induce differentiation in the human neuroblastoma cell in vitro, attenuates amnesia induced by basal forebrain lesion in rats. Multiple dosage of staurosporine at the doses of 0.05 and 0.1 mg/kg (i.p.) attenuated the impaired performance of the water maze task. Moreover, staurosporine (0.1 mg/kg) reversed the decrease of choline acetyltransferase activity in the fronto-parietal cortex. These results suggest that staurosporine attenuates amnesia through reversal of deficits in cholinergic neurons induced by basal forebrain lesion, and that neurotrophic factor-like substances may open the way for novel therapeutic approaches to Alzheimer's disease.

Alkaloids↗
PubMed1991

Contribution of the gene linked to the T cell receptor beta chain gene complex of NZW mice to the autoimmunity of (NZB x NZW)F1 mice.

We have investigated the contribution to the autoimmune disease of (NZB x NZW)F1 (NZB/W) mice made by the T cell receptor beta (TcR beta) chain gene complex, or genes linked to it, that are derived from the NZW strain. For this we developed the NZW.TcR beta NZB strain, a NZW congenic line carrying the TcR beta of NZB type, and produced NZB x NZW.TcR beta NZB (NZB/W.TcR beta NZB)F1 mice. We compared the amounts of anti-DNA and anti-histone antibodies and also the severity of lupus nephritis in these mice with those in the original NZB/W F1 mice. We obtained evidence for significantly lower serum levels of autoantibodies to double-stranded and single-stranded DNA and histone, and a later onset and a lower incidence of proteinuria in the NZB/W.TcR beta NZB F1 mice than in the original NZB/W F1 mice. These findings clearly indicate that the gene(s) within or closely linked to the TcR beta chain gene complex on chromosome 6 of the NZW strain acts to intensify the feature of systemic lupus erythematosus in the NZB/W F1 strain. The significant relationship of this finding to the strict dependency of NZB/W F1 disease on the H-2d/H-2z heterozygosity is discussed.

Animals↗
PubMed1991

Immunohistochemical localization of metallothionein in the eye of rats.

In order to elucidate possible physiological roles of metallothionein (MT), we have studied immunohistological localization of MT in the eye of the rat, using an avidin-biotin peroxidase complex method. As a result, strong MT immunostaining was observed in the epithelium of the lens and cornea. In the retina, considerably strong MT immunostaining was observed in the pigment cell layer while the nerve fiber layer and inner plexiform layer showed weak MT staining. Glial cells in the optic nerve were found to have marked MT staining. The present result is consistent with the hypothesis that MT may be involved not only in activation of zinc enzymes and cell proliferation through supply of zinc ions, but also in a protective mechanism in the blood-retina barrier.

Animals↗
PubMed1991

Humoral factor mediates acetylcholine-induced endothelium-dependent relaxation of chicken aorta.

A superfusion cascade system was used to determine whether endothelium-dependent vasorelaxation induced by acetylcholine (ACh) is mediated by a humoral factor(s) in the domestic fowl. An abdominal aorta (5 cm in length) with intact endothelium, excised from the donor bird, was mounted in an organ bath and perfused with avian Ringer solution. The vasorelaxing activity of the effluent was determined by an endothelium-denuded aortic ring (bioassay ring) equilibrated and precontracted with phenylephrine (PHE) (10(-6) M). The effluent (containing PHE) from the donor aorta with intact endothelium did not significantly change the PHE-induced tension of the bioassay rings. ACh (10(-6) M), when added to the perfusion medium that runs through the control polyethylene tubing, produced further contraction of the PHE-precontracted endothelium-denuded bioassay rings, whereas ACh caused relaxation of the rings when added to the perfusate that passes through the endothelium-intact donor aorta. The ACh-induced relaxation of the bioassay ring was slightly potentiated by superoxide dismutase (100 U/ml). Hemoglobin (10(-5) M) increased the basal tension of the bioassay rings and completely inhibited the ACh-induced relaxation of the rings. These results suggest that ACh-induced relaxation of fowl aorta is, at least partially, mediated by a humoral factor(s) that resembles endothelium-derived relaxing factor demonstrated in mammals.

Acetylcholine↗
PubMed1991

Fuzzy realization in clinical test database system.

To be able to obtain useful information from medical data easily and quickly in daily use for the hospital staff, it is necessary to construct a proper database system using methodologies suitable for the nature of medical data. From this viewpoint we have developed the clinical test relational database system at Hiroshima University Hospital, which provides the functions of easy on-line retrieval and statistical analysis. Fuzzy query processing based on the fuzzy set theory is adopted in the system. This enables us to use natural linguistic representation and makes it easy to introduce medical knowledge representation. Fuzzy set approaches turn out to be superior in clinical evaluation of laboratory data to the ordinary clear-cut definition of normalcy.

Artificial Intelligence↗
PubMed1991

Nine phenethyl alcohol glycosides from Stachys sieboldii.

Three new phenethyl alcohol glycosides together with six known compounds have been isolated from the leaves of Stachys sieboldii. On the basis of chemical and spectral analyses, the structures of three new compounds named stachysosides A, B and C have been established as 2-(3,4-dihydroxyphenyl)ethyl O-alpha-L-arabinopyranosyl-(1----2)-alpha-L-rhamnopyranosyl- (1----3)-4-O-E-caffeoyl-beta-D-glucopyranoside, 2-(3,4-dihydroxyphenyl)ethyl O-alpha-L-arabinopyranosyl-(1----2)-alpha-L-rhamnopyranosyl- (1----3)-4-O-E-feruloyl-beta-D-glucopyranoside and 2-(3-hydroxy-4-methoxyphenyl)ethyl O-alpha-L-arabinopyranosyl-(1----2)-alpha-L-rhamnopyranosyl- (1----3)-4-O-E- feruloyl-beta-D-glucopyranoside, respectively.

Carbohydrate Sequence↗
PubMed1991

CD5+ B cells in autoimmune disease and lymphoid malignancy.

Evidence is accumulating that CD5+ B cells belong to a developmental lineage distinct from that of conventional B cells and mainly participate in natural immunity. They have attracted attention because of their involvement in autoimmunity and lymphoid malignancy in both mice and humans. Patients with rheumatoid arthritis and Sjögren's syndrome were found to show a striking increase in the number of CD5+ B cells. B cell-chronic lymphocytic leukemia cells frequently express CD5. However, there are arguments against the role for CD5+ B cells in autoimmune disease, particularly in murine and human systemic lupus erythematosus (SLE). Whereas most IgM anti-DNA antibodies are produced by CD5+ B cells, high-affinity, pathogenic IgG antibodies are produced mainly by CD5- B cells. Either of two possibilities can explain the failure of CD5 expression of B cells responsible for producing IgG anti-DNA antibodies: either the cells are conventional B cells or the cells are CD5+ B cells that lack CD5 expression. In studies using SLE-prone NZB x NZW F1 mice and their H-2-congenic progeny, we discussed herein the possibility that CD5+ B lineage cells are also responsible for the pathogenic IgG autoantibody production by phenotypic switching from CD5+ to CD5-, probably under a particular genetic background. A line of H-2-congenic NZB x NZW F1 progeny failed to produce IgG anti-DNA antibodies, but in turn, showed a marked clonal proliferation of CD5+ B cells. Thus, it appears that genetically determined signals for either proliferation or differentiation would lead CD5+ B cells to cause distinct disease, i.e., autoimmune disease or lymphoid malignancy. Further studies using H-2-congenic New Zealand mice may provide insights into the correlation between autoimmunity and related lymphoid malignancy.

Animals↗
PubMed1991

TNF susceptibility-related gene expression.

A series of BWL hybridoma lines has been generated by cell fusion of a TNF-resistant BW5147 cell line and a highly TNF-sensitive WR19L cell line, and has exhibited a wide variety of TNF susceptibility. A cDNA library, BWL47rp10, from a TNF-susceptible hybridoma line BWL47 has been screened by hybridization with a 32P-labeled subtraction cDNA probe from WR19L cells. Thirty-nine candidates for TNF susceptibility were cloned, and 20 clones larger than 1.0 kb have been examined so far. A cDNA clone, 10-2, hybridized to mRNA of 1.8 kb. It was expressed higher in highly TNF-sensitive cells, especially in BWL47, BWL40, and BWL57 cells. Thus, at least, the expression of the mRNA identified with cDNA 10-2 correlated well with TNF susceptibility in BWL cells, although its functional identity remains to be determined.

Animals↗
PubMed1991

Regulation of glucose transporter synthesis in cultured human skin fibroblasts.

The present study was designed to see the effects of glucose on glucose transporter expression and glucose transport activity using cultured human skin fibroblasts. When the cells were incubated with various concentrations of glucose (11.1-44.4 mM), no differences were found in the HepG2 glucose transporter mRNA, protein levels and basal and insulin-stimulated 2-deoxyglucose uptake. Glucose deprivation, however, resulted in approximately 4-fold increases in the mRNA and 3-fold increases in the protein and the basal 2-deoxyglucose uptake. Chronic exposure to insulin increased the glucose transporter protein levels to similar degrees in the cells incubated with 11.1, 22.2 and 44.4 mM glucose accompanied by increases in the glucose transport activity. Effects of insulin on the glucose transporter mRNA and protein levels, however, were not evident in the glucose-deprived cells. It is concluded that glucose transport activity correlates closely with HepG2 glucose transporter expression in cultured human fibroblasts and that glucose (11.1-44.4 mM) does not affect the glucose transporter expression and glucose transport activity.

Blotting, Western↗
PubMed1991

Community-acquired influenza C virus infection in children.

To clarify the epidemiologic and clinical features of community-acquired influenza C infection in children, we took specimens throughout the year from a larger number of patients with acute respiratory illnesses in a pediatric clinic in Yamagata, Japan. During a 2-year survey, 20 strains of influenza C virus were isolated from 13,426 specimens. These isolates were recovered throughout the year. The ages of patients with influenza C virus isolates ranged from 2 months to 11 years and peaked at the age of 1 year. The clinical diagnosis of patients with influenza C virus infection included bronchitis in one child and pneumonia in four. Community-acquired influenza C infection in children can cause a variety of respiratory illnesses that cannot be clinically differentiated from those caused by other viruses.

Child↗
PubMed1991

Regional variation in oral mucosal drug absorption: permeability and degree of keratinization in hamster oral cavity.

The regional permeability of oral mucosa to salicylic acid was investigated in vivo in hamsters along with histological variations, especially the degree of keratinization. Histological sections from six regions, i.e., sublingual mucosa, buccal mucosa, dorsum of tongue, ventral surface of tongue, labial mucosa, and cheek pouch mucosa, were prepared to assess the degree of keratinization. The area under the plasma concentration-time curve of salicylic acid following the administration of salicylic acid to the oral mucosa with a film dosage form and the thickness of stratum corneum of each site were in inverse proportion to each other, suggesting that the stratum corneum layer represents the principle barrier to drug absorption.

Absorption↗
PubMed1991

Antigenic characterization of the nucleoprotein and matrix protein of influenza C virus with monoclonal antibodies.

Monoclonal antibodies against the nucleoprotein (NP) and matrix (M) protein of influenza C virus were prepared and characterized. At least two non-overlapping or partially overlapping antigenic sites were delineated on each of the proteins by competitive binding assays. Western blot analysis showed that two antigenic sites on the M protein were highly resistant to conformational changes whereas two sites on NP were sensitive. No antigenic variation was seen in either the NP or the M protein when the reactivity of monoclonal antibodies with 23 different influenza C strains isolated over a 41 year period was studied by radioimmunoprecipitation and enzyme-linked immunosorbent assay. Immunofluorescence analysis with the monoclonal antibodies revealed that both the NP and M proteins migrated to the cell nucleus during the replication cycle of influenza C virus.

Animals↗
PubMed1991

Localization of metallothionein in hair follicles of normal skin and the basal cell layer of hyperplastic epidermis: possible association with cell proliferation.

Metallothionein is a low-molecular-weight metal-binding protein. Although it is inducible by a variety of agents and ubiquitously present in many tissues, its physiologic functions are still not clear. The present study was undertaken to determine the possible functions of metallothionein in both the proliferation and differentiation of epidermal keratinocytes. Metallothionein was detected immunohistochemically in hair matrix cells of the bulb and cells of the outer root sheath of anagen hair follicles, but not in dermal papillae in normal skin in the back of mice. In hyperplastic epidermal tissue, induced by either a phorbol ester tumor promoter or cholera toxin, the basal cells of the interfollicular epidermis stained strongly for metallothionein. Elevated expression of mRNA of the metallothionein gene was also demonstrated when the skin was stimulated by agents that induced hyperplasia. Papillomas produced by two-stage carcinogenesis protocols also stained for metallothionein. These observations suggest that metallothionein is involved in the proliferation of epidermal keratinocytes.

Animals↗
PubMed1991

A constitutive thiamine metabolism mutation, thi80, causing reduced thiamine pyrophosphokinase activity in Saccharomyces cerevisiae.

We identified a strain carrying a recessive constitutive mutation (thi80-1) with an altered thiamine transport system, thiamine-repressible acid phosphatase, and several enzymes of thiamine synthesis from 2-methyl-4-amino-5-hydroxymethylpyrimidine and 4-methyl-5-beta-hydroxyethylthiazole. The mutant shows markedly reduced activity of thiamine pyrophosphokinase (EC 2.7.6.2) and high resistance to oxythiamine, a thiamine antagonist whose potency depends on thiamine pyrophosphokinase activity. The intracellular thiamine pyrophosphate content of the mutant cells grown with exogenous thiamine (2 x 10(-7) M) was found to be about half that of the wild-type strain under the same conditions. These results suggest that the utilization and synthesis of thiamine in Saccharomyces cerevisiae is controlled negatively by the intracellular thiamine pyrophosphate level.

Acid Phosphatase↗
PubMed1991

Agents that modify EDRF formation alter antiplatelet properties of brain arteriolar endothelium in vivo.

In the presence of circulating Evans blue a helium-neon laser injures the endothelium of brain surface arterioles in situ. The injury is known to selectively eliminate endothelium-dependent responses. The present study documents in mice the fact that such endothelial sites become selectively attractive to passing platelets that have been activated as a result of more severe injury upstream. We then test the hypothesis that the "capture" of platelets at the downstream site is due to loss of "classical" endothelial-dependent relaxing factor of acetylcholine (EDRFACh) at that site. EDRFACh is known to inhibit platelet adhesion/aggregation and is synthesized from L-arginine. We show that agents that would either enhance or reduce the synthesis of local EDRFACh reduce or increase the incidence of capture as predicted by the hypothesis. Thus NG-monomethyl-L-arginine (L-NMMA) and arginase that would reduce synthesis of EDRFACh enhanced platelet capture. L-Arginine, which would enhance synthesis of EDRFACh, inhibited platelet capture. In addition, L-NMMA and arginase enhanced platelet aggregation over the more severely damaged site upstream from the site of capture. Ex vivo studies of platelets harvested from treated mice showed that the platelets themselves were unaffected by the treatments that, except for arginase given intravenously, all involved topical application of the tested drugs.

Acetylcholine↗
PubMed1991

Rescue of motoneurons from the axotomized state by regeneration into a sensory nerve in cats.

1. We studied the electrical properties of spinal motoneurons, the axons of which had regenerated into a cutaneous nerve. 2. In cats, all or part of the medial gastrocnemius (MG) muscle nerve was cut and directed distally into the caudal cutaneous sural (CCS) nerve, a sensory (primarily cutaneous) nerve. One or 2 yr later, electrical properties [conduction velocity (CV), rheobase (Irh), input resistance (RN), afterhyperpolarization (AHP), and excitatory postsynaptic potentials (EPSPs)] of MG motoneurons that had cross-regenerated into the CCS nerve were determined. These were compared with properties of normal and of axotomized MG motoneurons and with data from previous studies in which MG motoneurons had reinnervated their own or a foreign muscle. 3. Electrical stimulation of the MG-innervated CCS nerve produced no detected mechanical activity, indicating an absence of muscle innervation. Tactile stimulation of skin did not activate these motoneurons; i.e., they did not acquire properties of cutaneous afferents. 4. The CV and Irh of MG motoneurons axotomized 11 mo declined by 48 and 60%, respectively. 5. The CV of MG motoneurons that had regenerated through CCS was only slightly slower than normal, similar to that of MG motoneurons that reinnervated the "slow" muscle soleus (Foehring and Munson 1990). 6. The Irh and RN were also similar to those of MG motoneurons that had regenerated into the soleus muscle. 7. Electrical stimulation of the lateral gastrocnemius-soleus nerve generated EPSPs of normal or almost normal amplitude in MG motoneurons axotomized for 11 mo or cross-regenerated into CCS up to 2 yr.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1991

Selective synthesis of 2,4-bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine as a protein modifier.

2,4-Bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine, a protein modifier with two polyethylene glycol chains (activated PEG2) was synthesized from monomethoxypolyethylene glycol and cyanuric chloride using zinc oxide as a catalyst by the improved method of a previous study (Matsushima et al., Chem. Lett. 7, 773, 1980). The product was identified as activated PEG2 without contamination of by-products with chromatographic and structural analysis.

Catalysis↗