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Biomedical subjects

H Uchimura

Publications and source records attributed to H Uchimura.

At least 37 records · Page 2Linked to original sources

Decreased plasma tryptophan associated with deep white matter lesions in elderly subjects.

The aim was to identify potentially treatable risk factors for cerebral white matter lesions often found on MRI in elderly persons. findings were assessed on 1.0 T MRI of 178 subjects living in the community and aged 60 years or older. Participants underwent standardised evaluations including standard questionnaires, a physical and neurological examination, cognitive function tests, electrocardiogram, a complete blood chemistry panel, and plasma amino acid measurements. Brain MRI infarcts, deep white matter lesions (DWMLs), and periventricular hyperintensities were found in 26%, 43%, and 29% of the 178 participants, respectively. Subjects with DWMLs were significantly older and had a higher frequency of hypertension, higher systolic blood pressure, and more brain infarcts, but lower plasma concentrations of tryptophan. In the multivariate model, greater age and lower plasma tryptophan concentrations were independently associated with DWMLs. Tryptophan concentrations were inversely related to DWML grading, whereas hypertension and brain infarction were more common in subjects with higher extents of DWMLs. The present study suggests that greater age and lower plasma tryptophan concentrations were important in producing DWMLs in elderly subjects.

Aged↗

Algorithm for the treatment of negative symptoms in chronic schizophrenia.

Negative symptoms in a chronic stage should be carefully evaluated, because chronic symptoms of schizophrenia have been influenced by drug treatments. The optimized neuroleptic treatment and analysis of psychological or environmental factors are sometimes effective to negative symptoms in a chronic stage. However, the patients with the negative symptoms still exist, and the drug effective to negative symptom is not now available in Japan. Therefore, the present algorithms for the treatment of schizophrenia may be not available, and a different algorithm should be prepared to reflect practice in Japan. We proposed here the algorithm for the treatment of negative symptoms in chronic schizophrenia in Japan.

Affective Symptoms↗

Effect of chronic haloperidol treatment on synaptic protein mRNAs in the rat brain.

Chronic haloperidol treatment caused significant decreases in the levels of synaptotagmin I and IV, synaptobrevin II, syntaxin 1A and Rab 3A mRNAs in the nucleus accumbens but not in the prefrontal cortex medial field, striatum, substantia nigra and ventral tegmental area. No significant changes in SNAP 25 and synaptophysin mRNA levels were observed in any brain region examined. The reduced expression of synaptic proteins may be related to haloperidol-induced depolarization block of mesolimbic dopamine neurons.

Animals↗

Protein kinase C modulates ischemia-induced amino acids release in the striatum of hypertensive rats.

The role of protein kinase C (PKC) in mediating the ischemia-induced release of amino acids in the striatum was studied using an in vivo brain dialysis technique in the striatum of spontaneously hypertensive rats (SHRs). Using HPLC combined with fluorescence detection methods, we investigated the concentrations of amino acids in the dialysates produced by 20 min of transient forebrain ischemia. We studied the effects of an inhibitor of PKC, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H7) and another isoquinoline analog (HA1004) with less inhibitory effect on the C kinase in ischemia-induced amino acids release. Bilateral carotid artery occlusion caused a marked reduction in the striatal blood flow by 91 +/- 6%. The extent of the cerebral blood flow (CBF) reduction were essentially the same among H7-, HA1004-, and the vehicle-treated groups. Forebrain ischemia produced a marked increase in glutamate (21-fold of the basal concentration), aspartate (19-fold) and taurine (16-fold). Pretreatment with H7 markedly attenuated the ischemia-in-duced release of these three amino acids to 3, 3 and 4-fold of the basal values, respectively. Increase of gamma-aminobutyric acid (GABA) was also attenuated by H7 (vehicle; 2.46 +/- 1.26 microM, H7; 0.62 +/- 0.75 mM). HA1004 did not affect the release of glutamate, aspartate or GABA during ischemia. The ischemia-induced release of taurine was significantly inhibited by HA1004 but the effect was much smaller than that of H7. These results thus indicate that PKC plays a major role in the ischemia-induced release of amino acids in the striatum of SHR.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Involvement of gamma-aminobutyric acid neurotransmission in phencyclidine-induced dopamine release in the medial prefrontal cortex.

The present study was designed to examine the possible involvement of gamma-aminobutyric acid (GABA) neurotransmission in the mechanism of phencyclidine (1-(1-phenylcyclohexyl)piperidine; PCP)-induced dopamine release in the medial prefrontal cortex, using in vivo microdialysis in awake, freely moving rats. Local perfusion via the dialysis probe into the medial prefrontal cortex with PCP (100 and 500 microM) and dizocilpine ((+)-5-methyl-10,11-dihydroxy-5-H-dibenzo(a,d)cyclo-heptan-5,10-im ine; MK-801, 10 and 50 microM), a selective non-competitive NMDA receptor antagonist, was found to increase extracellular dopamine levels. Co-perfusion with NMDA (1 mM) or the GABAA receptor agonist muscimol (50 microM) attenuated the effects of PCP (500 microM) and MK-801 (50 microM) on extracellular dopamine levels. The dopamine reuptake inhibitor nomifensine (50 microM) also produced an increase in extracellular dopamine levels in the medial prefrontal cortex, but this effect was not affected by co-perfusion with muscimol (50 microM). On the other hand, local perfusion with PCP (100 and 500 microM) and MK-801 (10 and 50 microM), but not nomifensine (50 microM), reduced extracellular GABA levels in the medial prefrontal cortex. Co-perfusion with NMDA (1 mM) reduced the effects of PCP (500 microM) and MK-801 (50 microM) on extracellular GABA levels. These results suggest that PCP may facilitate dopamine release in the medial prefrontal cortex, at least in part, by the inhibition of GABA release via the antagonism of NMDA receptors.

Animals↗

Ceruletide inhibits phencyclidine-induced dopamine and serotonin release in rat prefrontal cortex.

Phencyclidine (PCP; 5.0 mg/kg, i.p.) produced a greater increase in extracellular dopamine (DA) levels in the prefrontal cortex than in the striatum, while PCP increased the extracellular 5-hydroxytryptamine (serotonin; 5-HT) levels in the prefrontal cortex but not the striatum, as determined by in vivo microdialysis in awake, freely moving rats. The cholecystokinin (CCK)-related decapeptide ceruletide (120 and 400 microg/kg, i.p.), administered 60 min prior to PCP, significantly attenuated the PCP-induced increase in the extracellular levels of DA and 5-HT in the prefrontal cortex, but not in the striatum. These effects were reversed by PD 135,158, a selective CCK-B receptor antagonist (0.1 mg/kg, s.c.), administered 5 min prior to ceruletide. When administered alone, ceruletide (400 microg/kg, i.p.) significantly increased basal extracellular DA levels only in the prefrontal cortex. The selective N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (0.5 mg/kg, i.p.) also increased extracellular DA levels in the prefrontal cortex, but this effect was unaffected by ceruletide pretreatment. These results suggest that ceruletide may differentially modulate basal and PCP-induced release of DA and 5-HT in the prefrontal cortex.

Animals↗

[Analysis of transmission of Burkholderia cepacia isolates in an intrahospital by randomly amplified polymorphic DNA-PCR method].

Strains of Burkholderia cepacia isolated in our hospital from November 1995 to September 1996 were classified with randomly amplified polymorphic DNA-PCR (RAPD-PCR) and conventional biochemical tests (ID test.NF-18, API20NE, and Neg Combo 4J kit), and intrahospital isolates of B. cepacia were analysed. During the period 28 strains from inpatients and 2 from medical apparatus were isolated. Twenty four of 28 (85.7%) were from sputum. In 1996 from January to February, 20 strains were detected from 8 inpatients, and two strains were from the nebulizers at the Trauma and Critical Care Center (TCC). With typing of B. cepacia by conventional methods no epidemiological relations among isolates were found. However, DNA patterns of original isolates from the nebulizers at TCC by RAPD-PCR were identical with those of isolates in sputa from patients in other wards who had stayed at TCC, indicating that TCC was an initial source of transmission and the strain was transmitted with the patients to the wards. These results suggest that RAPD-PCR method might be a useful tool to analyse an epidemiological survey for intrahospital transmission of isolate.

Burkholderia Infections↗

Photothrombotic middle cerebral artery occlusion in spontaneously hypertensive rats: influence of substrain, gender, and distal middle cerebral artery patterns on infarct size.

BACKGROUND AND PURPOSE: To analyze the effects of substrain and gender differences in spontaneously hypertensive rats (SHR) and distal middle cerebral artery (MCA) branching patterns on infarct size, we compared infarct volumes produced by photothrombotic distal MCA occlusion using SHR/Kyushu and SHR/Izumo (Izm). METHODS: Twenty-four male and 8 female SHR/Kyushu, 15 male and 5 female SHR/Izm, and 6 male Wistar-Kyoto rats (WKY)/Izm (5 to 7 months old) were subjected to photothrombotic distal MCA occlusion, and infarct volumes were determined. RESULTS: Although blood pressure levels were essentially the same between the two substrains of hypertensive rats, infarct volumes were significantly larger in the SHR/Kyushu substrain than in SHR/Izm of either sex (P<0.001); infarct volumes in male and female SHR/Kyushu were 83.8+/-11.7 and 58.5+/-9.2 mm3, and those in male and female SHR/Izm were 61.5+/-10.7 and 34.8+/-7.9 mm3, respectively (values are mean+/-SD). Male SHR/Kyushu that had simple Y-shaped MCA showed smaller infarcts (75.8+/-14.6 mm3, n=11) than those with more branching (regular) MCA (93.2+/-19.1, n=13), the difference being significant (P=0.022). Male SHR/Izm with simple distal MCA also produced smaller infarctions than those with regular MCA (51.0+/-3.7 versus 68.9+/-8.7 mm3, P=0.0004). CONCLUSIONS: Photothrombotic occlusion of distal MCA in hypertensive rats provides a simple and reproducible model of focal ischemia. Most importantly, this study emphasizes the substantial variabilities in infarct sizes caused by the differences in substrains of SHR, gender, and distal MCA patterns.

Animals↗

AMPA receptor antagonist, YM90K, reduces infarct volume in thrombotic distal middle cerebral artery occlusion in spontaneously hypertensive rats.

We examined the effects of a potent and selective antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtype of glutamate receptor, YM90K, on brain infarction using a newly developed stroke model of thrombotic distal middle cerebral artery occlusion. Male spontaneously hypertensive rats (5-7 months old) were subjected to photochemically-induced distal middle cerebral artery occlusion as previously described [Stroke 26 (1996) 333-336]. Intravenous infusion of YM90K (n = 8) (5 mg/kg per h for 1 h) or the same amount of vehicle (n = 8) (alkaline saline) was started 5 min after distal middle cerebral artery occlusion. Penumbral cerebral blood flow was determined with laser-Doppler flowmetry. Three days after the ischemic insult, brains were stained with 2,3,5-triphenyltetrazolium chloride and infarct volumes were determined. One hour infusion of YM90K significantly reduced infarct volume by 34% (93 +/- 23 mm3 in control group vs. 61 +/- 25 mm3 in YM90K-treated group, P = 0.017). There were no significant differences in the degrees of cerebral blood flow reduction after distal middle cerebral artery occlusion between the YM90K treated and control groups. YM90K reduces infarct volume in experimental ischemia produced by photothrombotic distal middle cerebral artery occlusion in rats. The present results demonstrated beneficial effects of AMPA receptor blockade on acute ischemic stroke.

Animals↗

Differentiation and morphogenesis in pellet cultures of developing rat retinal cells.

We previously developed a reaggregate cell culture system (pellet cultures) in which retinal neuroepithelial cells proliferate and give rise to rod photoreceptor cells (rods) in vitro (Watanabe and Raff, 1990, Neuron 4:461-467). In the present study, we analyzed cell differentiation and morphogenesis in pellet cultures by using both cell-type-specific markers with immunofluorescence and electron microscopy. We demonstrated that, in addition to rods, the other major retinal cell types, including amacrine cells, bipolar cells, Müller cells, and ganglion cells were all present in the pellets, where most were able to develop from dividing precursor cells in vitro. The different cell types in the pellets became organized into two distinct structures: dark rosettes and pale rosettes. The cellular composition of these structures indicated that the dark rosettes correspond to the outer nuclear layer and the pale rosettes to the inner nuclear layer of the normal retina. Ultrastructural studies have indicated that the thin layer of neuronal processes surrounding the dark rosettes correspond to the outer plexiform layer, and the central region of the pale rosettes correspond to the inner plexiform layer of the normal retina. Other features of normal retinal development also occurred in the pellets, including programmed cell death and the formation of inner and outer rod cell segments and synapses. Thus, pellet cultures provide a convenient way to study different aspects of retinal development where one can control the size and the cellular composition of the initial reaggregate.

Animals↗

Age-related changes in the DNA and RNA content of the brain in spontaneously hypertensive rats.

To elucidate the effects of aging accompanied with hypertension on brain nucleic acid, we measured both the DNA and RNA contents of six specific brain regions in adult (5-6 months old) and aged (18-22 months old) female spontaneously hypertensive rats (SHRs). Although no statistical difference was observed in the RNA content, the DNA content did tend to increase in the hippocampal CA1 of aged SHR (4.24 +/- 0.55 ng/microgram protein, mean +/- SD, n = 6) in comparison to that of adult SHR (3.21 +/- 0.71 ng/microgram protein, n = 4). Hence, aged SHRs showed a significant decrease in the RNA to DNA ratio in the CA1 subfield of the hippocampus (3.79 +/- 0.61) compared to adult SHR (5.27 +/- 0.81). On the other hand, no other regions, except for the dorsolateral region of the striatum, showed any difference in the RNA/DNA ratio between aged and adult SHR. We therefore conclude that subtle changes in the nucleic acid occur in vulnerable regions of the brain in aged SHRs.

Aging↗

[Isolation frequency and biological characteristics of the multiple-antibiotic resistant Pseudomonas aeruginosa isolated from clinical specimens].

Isolation frequency of multiple-antibiotic resistant Pseudomonas aeruginosa (MARPA) was 11.9% (fifty six strains) of a total of four-hundred seventy-one strains of P. aeruginosa isolated from clinical specimens at the Kyorin University Hospital from October 1994 to December 1996. Eighteen strains of MARPA and thirteen strains of antibiotic sensitive P. aeruginosa (ASPA) isolated from clinical specimens in internal medicine ward A were determined O serotype, and characterized with production of pyocyanin, pyoverdin, hemolysin, elastase, and caseinase. Sixteen strains (88.9%) of MARPA were identified as serotype C. The ability to produce pyocyanin, hemolysin, elastase, and caseinase was not detected in all MARPA. One side, thirteen strains of ASPA showed various serotypes, i.e., B: 5 strains (38.4%), G: 4 strains (30.8%), C: 2 strains (15.4%), E: 1 strain (7.7%) and unknown type: 1 strain (7.7%), and the production of both hemolysin and pyoverdin was observed in 13 strains (100%), pyocyanin in 8 strains (61.5%), elastase and caseinase in 9 strains (69.2%) of ASPAs, which suggests that ASPAs do maintain the synthetic ability of pathogenic factors and pigments, but MARPAs do not. These results indicate that from epidemiological points of view the current strains of MARPA spread from one clone within the internal medicine ward A with nosocomial outbreak by serotype C.

Ampicillin Resistance↗

[Properties of extracellular products produced by group A streptococci isolated from patients with streptococcal toxic shock syndrome].

Extracellular products of group A streptococci isolated from patients with streptococcal toxic shock syndrome (STSS) were examined. The outline of the discussion of the 3 products are as follows; streptolysin O (SLO), proteinase and erythrogenic toxin. SLO and proteinase showed a relatively large amount of products more than erythrogenic toxin. SLO produced by group A streptococci isolated from the patient with STSS had an isoelectric point (pI) of 6.0 and a molecular weight of 64,000 and showed hemolytic activity in the presence of 2-mercaptoethanol (2-ME). Furthermore, the hemolytic activities of all components were inhibited by gamma-globulin and cholesterol. Proteinase had pIs of 8.7 and 8.9, and a molecular weight of 21,000. These data suggest that STSS clinical criteria probably reflects a characteristic of a large amount of products of individual S. pyogenes isolates.

Bacterial Proteins↗

[Serum soluble CD8 and soluble interleukin-2-receptor levels during interferon therapy in chronic hepatitis C].

We examined the relationship between the changes of serum soluble CD8 (sCD8) and soluble interleukin-2 receptor (sIL-2R) levels and effectiveness of interferon (IFN) in patients with chronic hepatitis (CH) C. Changes in sCD8 levels were parallel with fluctuations of alanine aminotransferase (ALT) in CH patients during IFN treatment but decreases of sCD8 levels were slower than those of ALT. In IFN effective and ALT decreased patients sCD8 levels is also decreased. sIL-2R levels was increased transiently during administration of IFN in most cases. It was suggested that decrease in sCD8 levels is indicative of the effectiveness of IFN therapy.

Adult↗

Localization and ontogeny of GLUT3 expression in the rat retina.

This study investigates the presence, localization, and developmental expression of a neuron-specific facilitated-diffusion glucose transporter, GLUT3, in the rat retina so as to elucidate molecular mechanisms regulating glucose homeostasis in support of the visual function. Immunoblot analysis using anti-GLUT3 antibody (ALM3-C) revealed the presence of GLUT3 as a heterogeneously glycosylated protein with an average molecular weight of approximately 44 kDa. Although immunofluorescence staining showed it to be localized primarily in the inner and outer plexiform layers, some of the cell bodies in the inner nuclear layer also showed weak immunoreactivity. Immunoblot analysis of developing rat retinal tissues revealed the presence of the GLUT3 protein as early as embryonic day 15 (E15), and immunofluorescence staining revealed its expression in the inner plexiform layer near the time of birth and in the outer plexiform layer at postnatal day 14 (P14), i.e., when the eyes normally open and retinal activity commences. The protein's abundance remained at a relatively low level during the embryonic stages and up until the end of the first postnatal week (P7), though a transient increase was confirmed to occur at E18. From P13, however, the abundance steadily increased, rapidly reaching the adult level at P24. Based on these observations, we hypothesize that GLUT3 is expressed in some subsets of retinal neurons, being preferentially abundant in their neuronal processes, and that its ontogeny is closely associated with morphological and functional development of the retina. As such, this suggests that GLUT3 plays some important role(s) in the retina where glucose metabolism is essential.

Animals↗

Angiotensin II increases norepinephrine turnover in the anteroventral third ventricle of spontaneously hypertensive rats.

We evaluated the effect of angiotensin II (Ang II) administered by intracerebroventricular injection on norepinephrine turnover in the anteroventral third ventricle in adult spontaneously hypertensive rats (SHR, n = 35) and age-matched Wistar-Kyoto rats (WKY, n = 38). Ang II (100 ng) or saline (vehicle control) was administered into the cerebral ventricle 30 minutes after injection of alpha-methyl-p-tyrosine (250 mg/kg IP). Norepinephrine turnover was assessed by evaluation of the norepinephrine concentration before and 1 hour after such administration. The pressor response to Ang II administration was significantly greater in SHR than in WKY (+43 +/- 3 versus +23 +/- 2 mm Hg, P < .01). Baseline norepinephrine turnover (response to saline) was reduced in the ventral median preoptic nucleus of SHR. Ang II significantly increased norepinephrine turnover in the organum vasculosum lamina terminalis and ventral median preoptic nucleus of SHR (organum vasculosum lamina terminalis: 40 +/- 5% by Ang II versus 18 +/- 6% by saline, P < .05; ventral median preoptic nucleus: 32 +/- 3% by Ang II versus 21 +/- 2% by saline, P < .05) but not of WKY (37 +/- 5% versus 29 +/- 5%, P = NS, and 30 +/- 2% versus 32 +/- 3%, P = NS, respectively). Thus, norepinephrine turnover in the anteroventral third ventricle region induced by intracerebroventricular administration of Ang II was increased in SHR. This effect may contribute to the enhanced pressor response to central Ang II seen in this model.

Angiotensin II↗

Potentiation of phencyclidine-induced dopamine release in the rat striatum by the blockade of dopamine D2 receptor.

Local perfusion with phencyclidine (PCP) increased extracellular dopamine levels in the rat striatum in a dose-dependent manner, as measured by in vivo microdialysis. While pretreatment with SCH 23390, a selective dopamine D1 receptor antagonist, had no significant effect on PCP-induced increases in extracellular dopamine levels, pretreatment with YM-09151-2 (cis-N-(1- benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylamin obenzamide), a selective dopamine D2 receptor antagonist, markedly potentiated the effect of PCP. These results suggest that the blockade of dopamine D2 presynaptic autoreceptors strongly potentiates the PCP-induced dopamine release in the striatum.

Animals↗