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N Hashimoto

Publications and source records attributed to N Hashimoto.

At least 55 records · Page 3Linked to original sources
PubMed1998

Urine-associated horizontal transmission of Seoul virus among rats.

To understand the mode of transmission of Seoul type hantavirus in Wistar rats, we examined the shedding of the virus and antibody production in infected rats. When 1-day-old rats were inoculated with KI-83-262 strain of Seoul virus, the S segment of the viral genome was detected in lungs, clots, urine, saliva, submaxillary glands, rectums, and kidneys by nested reverse transcriptase PCR. On the other hand, when 8-week-old rats were infected with the virus, viral genome was detected only in the lungs and rectum. In uninfected newborn rats intranasally administered urine from infected newborn rats, four of six rats shed the virus into their urine. In addition, three of eight rats kept in same cage with infected animals also shed the virus into urine. Moreover, the virus genome was detected in the urine of urban rats (Rattus norvegicus) in an enzootic focus. These findings suggest that the urine containing virus from infected rats is an actual source of Seoul virus infection.

Administration, Intranasal↗
PubMed1998

In vitro growth suppression of vascular smooth muscle cells using adenovirus-mediated gene transfer of a truncated form of fibroblast growth factor receptor.

Vascular smooth muscle cell (VSMC) proliferation associated with arterial injury causes restenosis, which remains to be resolved in cardiovascular and ischemic cerebrovascular disease, especially after balloon angioplasty. Fibroblast growth factor (FGF) is a potent mitogen and a trophic factor for a variety of cells, including VSMCs. We constructed a replication-deficient adenovirus vector, designated AxCA delta FR, coding a truncated form of fibroblast growth factor receptor-1 (FGFR-1) gene lacking the intracellular domain to interrupt receptor-mediated FGF signaling, and examined its effect on the proliferation of primary-cultured rat VSMCs. We transferred the truncated form of the FGFR-1 gene to the VSMCs and confirmed its expression and localization in infected cells by Western blotting and immunofluorescence study. The VSMCs infected with AxCA delta FR degenerated and the proliferation of these cells was suppressed markedly by the infection with this virus in vitro. Our results suggest that the receptor-mediated signal of FGFs has an important role in VSMC proliferation and gene transfer of a truncated form of FGFR using adenoviral vector may be useful for the treatment of the diseases caused by excessive proliferation of VSMCs like restenosis after percutaneous transluminal angioplasty or carotid endoarterectomy.

Adenoviridae↗
PubMed1998

Regional cerebral blood flow during rewarming of cardiopulmonary bypass correlates with posthypothermic regional glucose use.

BACKGROUND AND OBJECTIVES: Although global measurements of cerebral blood flow and metabolism during and after profoundly hypothermic cardiopulmonary bypass have been performed both in experimental animals and in human beings, little is known about their regional changes. The purpose of this study was to investigate the changes in regional cerebral blood flow during profoundly hypothermic cardiopulmonary bypass and regional cerebral glucose use after cardiopulmonary bypass. METHODS: We measured regional cerebral blood flow with positron emission tomography during both the cooling (n=5) and rewarming (n=5) of hypothermic cardiopulmonary bypass in anesthetized dogs by continuously infusing 15O-labeled water. We altered the core temperature between 20 degrees and 37 degrees C. To assess the integrity of brain metabolism, we measured the regional cerebral glucose use by bolus injections of 18F-labeled 2-fluoro-2-deoxy-D-glucose. RESULTS: Regional cerebral blood flow decreased homogeneously during cooling. The regional cerebral blood flow at 20 degrees C was about one fourth of that at 37 degrees C. In contrast, at 24 degrees, 28 degrees , and 32 degrees C during rewarming, there were significant interregional differences in the regional cerebral blood flow for given temperatures (p=0.0075, 0.034, and 0.048, respectively). These interregional differences disappeared after rewarming. Although the regional cerebral blood flow significantly correlated with the regional cerebral glucose use in the control condition at 37 degrees C without cardiopulmonary bypass (r=0.75; p=0.00012), this correlation disappeared after profoundly hypothermic cardiopulmonary bypass (r=0.204; p=0.388). Regional cerebral blood flow at 32 degrees C during rewarming positively correlated with the regional cerebral glucose use after cardiopulmonary bypass (r=0.655; p=0.0017). CONCLUSION: The altered regional cerebral blood flow during rewarming of profoundly hypothermic cardiopulmonary bypass might affect regional brain metabolism.

Animals↗
PubMed1998

Expression of Nedd2/ICH-1 (caspase-2) in the developing rat retina.

Expression and localization of Nedd2/ICH-1 (caspase-2) were examined in the developing rat retina. The expression of Nedd2 mRNA was conspicuous in the prenatal period and down-regulated in the postnatal period. In contrast, the expression of an alternatively spliced form of Nedd2 encoding a truncated protein, which has been shown to protect against programed cell death (PCD), was faint in the prenatal period but increased gradually in the postnatal period. Nedd2 immunoreactivity was observed in almost all cells of the ganglion cell layer (GCL) during the perinatal period, when some nuclei in the GCL showed pyknosis or fragmentation. Nedd2-positive cells in the neuroblastic layer (NBL) were present in patches at embryonic day 19, and began to assume a stratified arrangement at postnatal day 3, when nuclei showing PCD were observed in places across the NBL. At postnatal day 14, only faint Nedd2 immunoreactivity was observed in the GCL and the inner nuclear layer, and no Nedd2 immunoreactivity was present in the outer nuclear layer. These findings demonstrate the cell type- and differentiation-specific patterns of the Nedd2 expression in the developing retina.

Alternative Splicing↗
PubMed1998

Increases in levels of brain-derived neurotrophic factor mRNA and its promoters after transient forebrain ischemia in the rat brain.

Expression of brain-derived neurotrophic factor (BDNF) may play a role in the mechanism of neuronal cell death after cerebral ischemia. We investigated the changes in levels of mRNAs encoding BDNF and its promoters in the rat brain after transient forebrain ischemia. Transient forebrain ischemia was induced by occlusion of bilateral common carotid arteries and systemic hypotension for 8 min. The alterations in BDNF gene expression in the hippocampus and in the cerebral cortex were examined by in situ hybridization using a mouse BDNF cDNA probe and cDNA probes including exon-specific promoters. BDNF transcripts were rapidly enhanced after the ischemic insult, both in the hippocampus and the cerebral cortex. NBQX suppressed the enhanced gene expression of BDNF markedly in the dentate gyrus (DG). In contrast, MK-801 had little effect on BDNF expression. In the piriform cortex, MK-801 or NBQX reduced the expression only moderately. After the ischemic insult, promoter specific BDNF 5'-exon I and exon III were increased remarkably in the DG. The increase in exon I in DG was suppressed partially by MK-801 and NBQX, while the increase in exon III in CA3 was suppressed by MK-801 but that in DG was not suppressed by either antagonist. In the piriform cortex, exon III was increased remarkably and this increase was not influenced by either agonist. These results suggest that the gene expression of BDNF was enhanced by transient ischemia both in the hippocampus and the cerebral cortex and that the cerebral ischemia stimulated at least two different promoter- and neuron type-specific pathways regulating expression of the BDNF gene mediated by glutamate receptors of non-NMDA type and NMDA type.

Animals↗
PubMed1998

Putative origin of Yersinia pseudotuberculosis in western and eastern countries. A comparison of restriction endonuclease analysis of virulence plasmids.

Yersinia pseudotuberculosis isolates from Russia east of Moscow, Korea and mainland China were used for restriction endonuclease analysis of virulence plasmid (REAP) and findings were compared with REAP of isolates from Japan and Western countries. An identical REAP pattern of each serogroup 1a, 1b, 3, 4a and 4b strain was observed among isolates from Russia, Korea, mainland China, and Japan but such was absent in West European strains. Therefore, the possibility that the origin of Y. pseudotuberculosis between West Europe and eastern Eurasia east of Moscow may be from a different clone should be considered.

Animals↗
PubMed1998

Development of step-specific PET tracers for studying fatty acid beta-oxidation: biodistribution of [1-(11)C] octanoate analogs in rats and a cat.

To evaluate the potential of [1-(11)C]-3-(R,S)-methyloctanoate (BMOA), [1-(11)C]-2-octynoate, and [1-(11)C]-2-decynoate as PET tracers for studying particular steps in fatty acid beta-oxidation, we examined the pharmacokinetics of these compounds in rats and a cat. In rats given these compounds, high levels of radioactivity accumulated in the heart, liver, and kidneys, suggesting their potential as tracers for studying beta-oxidation in these tissues. These organs were clearly visible with PET in a cat given BMOA, indicating the utility of BMOA for imaging these organs.

Animals↗
PubMed1998

Three-vessel occlusion using a micro-clip for the proximal left middle cerebral artery produces a reliable neocortical infarct in rats.

We demonstrate a new three-vessel occlusion model of temporary focal ischemia in Sprague-Dawley rats (n=13). Under a surgical microscope, bilateral carotid arteries and the left middle cerebral artery (MCA) were occluded for 2 h using a snare for the neck and a micro-clip for the MCA. The reduction of regional cerebral blood flow (rCBF) monitored by laser Doppler flowmetry was 28% on average compared to the preischemic control value (100%) during ischemia. At that level of CBF reduction, there was no thrombus formation in the proximal MCA trunk, and a full recovery of rCBF was confirmed in the ischemic core within 5 min of reflow. Two days later, the cerebral infarct was limited to the neocortex, and the size and variability of the infarct are considered feasible for the assessment of any therapeutic challenge against the ischemic damage due to temporary focal ischemia in this model.

Animals↗
PubMed1998

Isomerization of ceftibuten in aqueous solution.

The isomerization reactions of ceftibuten and ceftibuten-related compounds in aqueous solution were investigated to estimate the substitution effect on the isomerization reaction and identify the three proximal dissociation constants of ceftibuten kinetically from the pH-rate profiles. The isomerization reaction of ceftibuten-related compounds was influenced by the substituents near the double bond at the C7-side chain, and the electron-withdrawing substituent was found to increase the isomerization rate. Ceftibuten isomerized at the C7-side chain, and the isomerization rate was influenced by the dissociation of the C7-side chain carboxylic acid and aminothiazole in the acidic pH region. The dissociation constants of ceftibuten were assigned by comparing the isomerization rates of ceftibuten with its related compounds at various pH conditions, and the pKas 2.3, 3.2, and 4.5 were attributed to the 4-carboxylic acid, 7-carboxylic acid, and 7-aminothiazole, respectively.

Ceftibuten↗
PubMed1998

Activation of two types of Ca2+-permeable nonselective cation channel by endothelin-1 in A7r5 cells.

1. In A7r5 cells loaded with the Ca2+ indicator fura-2, we examined the effect of a Ca2+ channel blocker SK&F 96365 on increases in intracellular free Ca2+ concentrations ([Ca2+]i) and Mn2+ quenching of fura-2 fluorescence by endothelin-1 (ET-1). Whole-cell patch-clamp was also performed. 2. Higher concentrations (> or = 10 nM) of ET-1 (higher [ET-1]) evoked a transient peak and a subsequent sustained elevation in [Ca2+]i: removal of extracellular Ca2+ abolished only the latter. A blocker of L-type voltage-operated Ca2+ channel (VOC) nifedipine at 1 microM reduced the sustained phase to about 50%, which was partially sensitive to SK&F 96365 (30 microM). 3. Lower [ET-1] (< or = 1 nM) evoked only a sustained elevation in [Ca2+]i which depends on extracellular Ca2+. The elevation was partly sensitive to nifedipine but not SK&F 96365. 4. In the presence of 1 microM nifedipine, higher [ET-1] increased the rate of Mn2+ quenching but lower [ET-1] had little effect. 5. In whole-cell recordings, both lower and higher [ET-1] induced inward currents at a holding potential of -60 mV with linear I-V relationships and reversal potentials close to 0 mV. The current at lower [ET-1] was resistant to SK&F 96365 but was abolished by replacement of Ca2+ in the bath solution with Mn2+. The current at higher [ET-1] was abolished by the replacement plus SK&F 96365. 6. In a bath solution containing only Ca2+ as a movable cation, ET-1 evoked currents: the current at lower [ET-1] was sensitive to Mn2+, whereas that at higher [ET-1] was partly sensitive to SK&F 96365. 7. These results indicate that in addition to VOC, ET-1 activates two types of Ca2+-permeable nonselective cation channel depending on its concentrations which differ in terms of sensitivity to SK&F 96365 and permeability to Mn2+.

Animals↗
PubMed1998

Plasma levels of carboxy terminal propeptide of type I procollagen and pyridinoline cross-linked telopeptide of type I collagen in healthy school children.

The aim of this study was to reveal the relationship of the plasma levels of the carboxy terminal propeptide of type I procollagen (PICP) and the pyridinoline cross-linked carboxyterminal telopeptide domains of type I collagen (ICTP) to age and height velocity (HV), and to compare PICP and ICTP levels in those who have not reached their final height with those who have. PICP and ICTP levels were measured by RIA in 271 healthy children (161M, 110F) aged from 10 to 15 y. The HV was calculated from their health check-up cards. The subjects were divided into two groups in this study: the final height (FH) group whose HV was <1.0 cm/y, and the non-final height (NFH) group whose HV in the last year was > or =1.0 cm/y. PICP and ICTP levels almost paralleled the values of age-related changes of HV. Furthermore PICP and ICTP levels significantly correlated with HV. PICP and ICTP levels of the FH group were higher than those of adults previously reported. The values will be useful as reference for healthy children and growth disorder. Before reaching final height, PICP and ICTP can be useful makers of not only bone turnover but also of linear growth. Bone turnover rate is still increasingly active just after linear growth has been completed, and then it become similar to the levels of adults.

Adolescent↗
PubMed1998

Enhanced poly(ADP-ribosyl)ation after focal ischemia in rat brain.

Nitric oxide from neuronal cells plays detrimental roles in glutamate neurotoxicity and in focal brain ischemia. Nitric oxide directly damages DNA, and breaks in the DNA strands activate poly(ADP-ribose) polymerase (PARP), which brings poly(ADP-ribosyl)ation of the nuclear proteins. The excessive activation of PARP is thought to cause depletion of ATP and the energy failure resulting in cell death. To clarify the involvement of poly(ADP-ribosyl)ation in ischemic insult, we examined poly(ADP ribosyl)ation by immunohistochemical methods and the protective effect of 3-aminobenzamide, which is a PARP inhibitor, on focal brain ischemia using an intraluminal permanent middle cerebral artery occlusion model in rats. Poly(ADP ribosyl)ation was widely and markedly detected 2 hours after the ischemic insult in the cerebral cortex and striatum in which infarction developed 24 hours later. The enhanced immunoreactivity of poly(ADP-ribose) gradually decreased, and 16 hours later, no immunoreactivity was detected. Intraventricular administration of 3-aminobenzamide (1 to 30 mg/kg) 30 minutes before the ischemic insult decreased infarction volume in a dose-dependent manner along with the immunohistochemical reduction of poly(ADP-ribosyl)ation. Pretreatment with 7-nitroindazole (25 mg/kg, intraperitoneally), a selective neuronal nitric oxide synthetase inhibitor, partially reduced poly(ADP-ribosyl)ation. These data suggest the involvement of poly(ADP-ribosyl)ation in the development of cerebral infarction.

Animals↗
PubMed1998

Direct revascularization to the anterior cerebral artery territory in patients with moyamoya disease: report of five cases.

OBJECTIVE: In some patients with moyamoya disease, the development of spontaneous leptomeningeal collateral channels between the anterior cerebral artery (ACA) and other major arteries is poor. These patients require revascularization not only to the territory of the middle cerebral artery (MCA) but also to that of the ACA. For reliable revascularization to the ACA territory, we performed superficial temporal artery (STA)-ACA direct anastomosis in 5 of 58 patients with moyamoya disease who underwent cerebral revascularization at our institute during the last 8 years. METHODS: Because two patients presented with ischemic symptoms corresponding to the ACA territory after the ipsilateral STA-MCA anastomosis, we subsequently performed STA-ACA anastomosis. In three patients in whom hypoperfusion in the ACA territory was suspected based on preoperative angiograms and/or stimulated cerebral blood flow studies, we performed STA-ACA and STA-MCA anastomoses during a single operative procedure. After paramedian frontal craniotomy (diameter, approximately 5 cm), STA-ACA anastomosis was performed at the convexity, using a cortical branch of the ACA as a recipient. An interposed STA graft was used in four patients; all of the grafts were shorter than 4 cm. RESULTS: Bypass flow was satisfactory in four patients. One patient who underwent simultaneous STA-ACA and STA-MCA anastomoses had poor bypass flow, probably caused by spontaneous leptomeningeal collateral channels between the ACA and MCA. No patient had an ischemic attack after surgery. CONCLUSION: Our method using a cortical branch of the ACA as a recipient and a branch of the STA for the interposed graft can be performed at the convexity and much more easily than in a deep operative field. Our experience with STA-ACA anastomosis indicates that this procedure is effective for revascularization of the ACA territory in patients with moyamoya disease.

Adolescent↗
PubMed1998

Consistent injury in the striatum of C57BL/6 mice after transient bilateral common carotid artery occlusion.

OBJECTIVE: The recent availability of transgenic mice enables us to study the functional role of single gene products in cerebral ischemia. To establish an experimental murine model of transient forebrain ischemia, this study examined the temporal profile of ischemic neuronal damage in the striatum after bilateral common carotid artery occlusion. METHODS: C57BL/6 mice, which are frequently used for genetic manipulations, were subjected to 15-minute bilateral common carotid artery occlusion. Ischemic injury was examined (4, 8, 24, 48, and 96 h after reperfusion) by Nissl staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end-labeling, and nuclear staining with Hoechst 33258 dye. RESULTS: Regional cerebral blood flow was decreased to 11 +/- 6% of control values during the ischemic insult. Striatal injury was observed in 95% of animals examined after 15-minute bilateral common carotid artery occlusion. The number of small and medium-size neurons in the striatum was significantly (P < 0.05) decreased 8 hours after reperfusion and continued to decrease until 96 hours, whereas the number of large neurons remained constant. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end-labeling-positive cells appeared in the dorsomedial region of the striatum 48 hours after the ischemic insult and throughout the striatum 96 hours after the ischemic insult. Brain sections stained with Hoechst 33258 dye also demonstrated apoptotic nuclei 96 hours after the ischemic insult. CONCLUSION: Striatal injury after transient forebrain ischemia is reproducible in C57BL/6 mice and is a good model to study the molecular mechanisms of ischemic injury, including delayed neuronal death, using transgenic mice.

Animals↗
PubMed1998

Effects of FR139317 on renal responses to acute nitric oxide blockade in anaesthetized rats.

1. Effects of FR139317, an endothelin ETA receptor antagonist, on renal haemodynamic and excretory responses to acute nitric oxide (NO) blockade were examined using anaesthetized rats. 2. Intrarenal arterial infusion of NG-nitro-L-arginine (NOARG), the NO synthase inhibitor, at a rate of 40 micrograms/kg per min, produced a significant decrease in renal blood flow, with no change in systemic blood pressure. There were significant decreases in urine flow and urinary excretion of sodium during infusion of NOARG. In animals pretreated with FR139317, similar renal responses to the NOARG infusion were observed. 3. These results suggest that an action of endothelin-1 via ETA receptors does not greatly contribute to the renal haemodynamic and excretory responses to acute blockade of renal NO production.

Anesthesia↗
PubMed1998

Distal posterior cerebral artery aneurysm associated with multiple aneurysms.

True congenital peripheral aneurysms of the cerebral arteries are rare and may constitute a special entity. We report a rare case of nonmycotic peripheral aneurysm of the posterior cerebral artery (PCA) found in association with aneurysms of distal middle cerebral artery (MCA), junction between basilar artery (BA) and superior cerebellar artery (SCA) and MCA trunk. Our present case was a 37-year-old man with a history of abrupt loss of consciousness. Cerebral angiography revealed a right PCA aneurysm originating at the junction between the trunk of the PCA and the posterior temporal branch, and also aneurysms of the right distal MCA, at the right BA-SCA junction and at the trunk of right MCA just distal to the anterior temporal artery. Distal PCA aneurysm causing subarachnoid hemorrhage was successfully clipped and all the other aneurysms were treated in a one-stage procedure. Pathological examination of the surgically excised distal PCA aneurysmal sac demonstrated no infectious etiology. There have not been any similar cases showing an association of vascular anomalies with distal PCA aneurysm. This is the only reported case with the association of nonmycotic peripheral aneurysms involving the MCA and PCA.

Adult↗
PubMed1998

Different contributions of the endothelin ET(A) receptor to hypertension induced by acute or chronic inhibition of nitric oxide synthesis.

The effects of FR139317((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carb onyl] amino-4-methyl-pentanoyl] amino-3-[3-(1-methyl-1H-indoyl)]propionyl]-amino-3-(2-pyridyl)prop ionic acid), an endothelin ET(A) receptor antagonist, on systemic and renal haemodynamic responses and excretory responses to chronic or acute nitric oxide (NO) synthase inhibition with NG-nitro-L-arginine (NOARG) have been examined. An intravenous bolus injection of FR139317 (10 mg kg(-1)) to chronic NO-deficient hypertensive rats (2.74 mM NOARG in drinking water for 4 weeks) elicited only a slight decrease in mean arterial pressure (MAP), to the same extent as seen in normotensive control rats. Injection of this drug induced no alteration of the renal haemodynamics of this chronic hypertensive model. Urine formation in control rats was significantly reduced by administration of FR139317. No significant decrease in urine formation was observed in the chronic NO-deficient rats. Acute intravenous injection of NOARG (5 mg kg(-1)) induced a gradual and significant increase in MAP, with a significant decrease in renal blood flow. A slight but insignificant diuretic effect was observed. In animals pretreated with FR139317 (10 mg kg(-1) i.v.) NOARG induced a significantly less potent increase in MAP, whereas similar renal haemodynamic responses to NOARG were observed. In contrast to the FR139317-untreated group, urine formation tended to decrease after administration of NOARG. These results suggest that endothelin, via the ET(A) receptor, contributes to the systemic pressor response to acute NO synthase inhibition, although renal vasoconstriction and functional changes induced by acute NO synthase inhibition are independent of ET(A) receptor-related effects. These results imply that action of endothelin via the ET(A) receptor is not involved in the maintenance of sustained hypertension induced by chronic NO synthase inhibition.

Animals↗