PubMed Health⌕ Search

Biomedical subjects

N Hashimoto

Publications and source records attributed to N Hashimoto.

At least 235 records · Page 13Linked to original sources
PubMed1998

Infarct tolerance against temporary focal ischemia following spreading depression in rat brain.

A rat model of ischemic tolerance is useful for studying the intrinsic cellular mechanism of resistance to cerebral ischemia. Many types of preconditioning in the brain have been reported to induce ischemic tolerance; however, evaluation of their neuroprotective effect is primarily limited to differences in counts of surviving cells. A lesser but still large number of neurons die in the neocortex after global ischemia following ischemic tolerance. This study addressed the issue of whether any type of preconditioning could elicit a tolerance that limited the size of cerebral infarct against temporary focal ischemia. Cortical spreading depression was induced for a prolonged period and, after various intervals, the stress of temporary focal ischemia was evaluated in rats. Ten groups of male rats (n=8 each) were studied. In the first group, temporary focal ischemia was induced by occlusion of three vessels (bilateral carotid arteries and left middle cerebral artery, MCA) for 2 h (control). In the second to seventh groups, cortical spreading depression was generated by continuously infusing 4 M potassium chloride (KCl)(1.0 microliter l/h for 2 days) into the left neocortex via an osmotic pump. On days 6, 9, 12, 15, 21 and 24 (day 0=day of pump removal), temporary focal ischemia was induced in one of these groups. In the other three groups, saline was infused instead of KCl, and on day 6, 12 or 21, temporary focal ischemia was induced. All rats were sacrificed 2 days after the ischemia and the infarct volume was analyzed using TTC staining of brain slices. In a separate group of animals, regional cerebral blood flow (rCBF) at the periinfarct area (penumbra) was monitored before and during the ischemia with a laser-Doppler flowmetry (LDF) system on day 12 following saline (n=5) or KCl infusion (n=5) for 48 h. To obtain the absolute rCBF value before ischemia following saline (n=5) or KCl infusion (n=5), hydrogen clearance was examined in the same cortex under the same anesthesia. The cerebral infarct volume was gradually reduced as the interval between the induction of the spreading depression and the induction of temporary focal ischemia was extended. There was a significant reduction in infarct size between the control and the groups in which ischemia was induced on day 12 or 15. There was no significant difference in the preischemic or intraischemic rCBF between the saline and KCl-infused groups. The preconditioning method was demonstrated to limit the size of cerebral infarct after temporary focal cerebral ischemia; tolerance for cerebral infarct developed after an extended interval following a long period of spreading depression.

Animals↗
PubMed1998

Induction of infarct tolerance by platelet-derived growth factor against reversible focal ischemia.

Nerve growth factor, brain-derived neurotrophic factor, and other neurotrophic factors have been reported to have neuroprotective effects against global ischemia. To investigate whether the homodimer of platelet-derived growth factor B-chain (PDGF-BB) can protect neurons against focal temporary ischemia, PDGF-BB was administered to the rat brain for a prolonged period prior to, during, and after ischemia, since PDGF-BB protected rat neurons from global ischemia in our previous study. A total of 82 male Sprague-Dawley rats were used. Recombinant PDGF-BB, or saline was administered into the left neocortex via an implanted osmotic pump for 3 days (1.2 microg in total), 7 days (2 microgram or 4 microgram in total), or 14 days (4 microgram in total) pre-ischemia and 2 days post-ischemia. In an additional group, PDGF-BB (4 microgram in total) was administered for 14 days by osmotic pump and focal ischemia was induced after an additional 7-day interval following removal of the pump. Focal temporary ischemia was induced in the left MCA territory by bilateral CCA and MCA occlusion for 2 h. All rats were sacrificed 2 days after ischemia and the volume of cerebral infarct was analyzed using TTC staining. In a separate set of animals, regional cerebral blood flow (rCBF) was monitored by the hydrogen clearance method and laser Doppler flowmetry (LDF) of the neocortex after 14 days of intracerebral administration of PDGF-BB or saline. In the group receiving PDGF-BB (4 microgram in total) for 7 or 14 days pre-ischemia, there was a significant reduction of neocortical infarction compared to that in the control or saline-infused group. The size of cerebral infarct was smallest in the group that received PDGF-BB for 14 days, when ischemia was induced 7 days after removal of the pump. Regarding rCBF measurement, there were no significant differences in groups receiving PDGF-BB or saline infusion for 14 days. The potent neuroprotective effect of PDGF-BB on global ischemia was also demonstrated in the focal ischemia model. However, prolonged intracerebral infusion for 7 to 14 days was necessary to achieve a significant reduction of infarct volume. Neuroprotection was not due to increased collateral flow during ischemia.

Animals↗
PubMed1998

A novel myeloid cell line, Marimo, derived from therapy-related acute myeloid leukemia during treatment of essential thrombocythemia: consistent chromosomal abnormalities and temporary C-MYC gene amplification.

A novel myeloid leukemia cell line, Marimo, was established from bone marrow cells of a patient with secondary acute myeloid leukemia (AML) that had developed during the treatment of essential thrombocythemia (ET) with busulfan. Karyotype at the ET phase was 46,XX,der(15)t(1;15) (q23;p12-13), but at the blastic phase changed to 44,XX,-5,del(8)(q22), add(17)(p11),+18, psu dic(18;9) (q23;p21) x 2 lacking t(1;15). In Marimo cells, C-MYC gene was temporarily amplified by double-minutes (dmin) but disappeared at 33 months, whereas t(10;14;11)(q22;q32;q13) and t(10;14)(q22;q32) were added in vitro psu dic(18;9) x 2 and add(17)(p11) were consistently found throughout the culture. These results suggest that this AML clone is not derived from ET but rather is therapy-related.

Cell Line↗
PubMed1998

Cell electrophoretic mobility and glycerol lysis of human erythrocytes in various diseases.

Using an automated cell electrophoresis system equipped with an image processor, we studied electrophoretic mobilities of erythrocytes of healthy donors and of patients suffering from systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), hypergammaglobulinemia and diabetes mellitus (DM). On average, erythrocytes from SLE patients showed mean electrophoretic mobilities (EPM) which were significantly lower (p < 0.005) than the EPM of red blood cells of normal donors. Evaluation of mean EPM and standard deviations revealed that three groups of SLE patients could be distinguished regarding the electrophoretic behavior of their erythrocytes. Some patients had red blood cells with normal EPM, others had erythrocytes with significantly reduced EPM, and a third group appeared to have both kinds of erythrocytes. In addition, erythrocytes of various SLE patients showed enhanced resistance to lysis by glycerol and their membranes contained less quantities of band 3 proteins.

Arthritis, Rheumatoid↗
PubMed1998

Enhanced human tumor cell transplantability in a new congenic immunodeficient mouse; KSN-BNX.

We introduced two mutant genes (beige; bg that induces the deficiency of natural killer (NK) activity and xid that decreases the production of immunoglobulin) into KSN nude mice with high reproductive performances. We produced KSN bg/bg(nu/nu) (KSN-bg), KSN-xid/xid(nu/nn) (KSN-xid), KSN xid/xid,bg/bg(nu/nu) (KSN-BNX) and KSN-nu/+ (KS) mice by back-cross (cross-intercross method). All strains showed as high a reproductivity rate as the parental KSN mice. KSN-xid and KSN-BNX mice had a reduced percentage of B220 positive cells in the spleens compared to KSN and KSN-bg mice, but they showed increased percentages of Thy-1 and asialo GM1 positive cells. The serum immunoglobulin concentrations of KSN-BNX were as low as KSN-xid. Both KSN-bg and KSN-BNX mice showed deficient NK activity in spleens, whereas KSN-xid mice showed an elevated NK activity. Compared to nude mice, the growth of both human tumor cell TCO-1 and BxPc-3 transplanted subcutaneously was enhanced in KSN-BNX mice. However Panc-1 cells that was rejected in nude mice was not accepted in KSN-BNX mice. Liver metastasis of human pancreatic tumor cells; Capan-1, BxPc-3 and MIAPaCa-2 were studied. No significant difference was observed in the percentage of metastasis formed mice between nude and KSN-BNX mice.

Animals↗
PubMed1998

A missense mutation in the CD38 gene, a novel factor for insulin secretion: association with Type II diabetes mellitus in Japanese subjects and evidence of abnormal function when expressed in vitro.

Cyclic adenosine 5'diphosphate-ribose (cADPR) is thought to have a second messenger role in insulin secretion through mobilisation of Ca2+. As human lymphocyte antigen CD38 has both ADP-ribosyl cyclase and cADPR hydrolase activity, it may be important in glucose-induced insulin secretion in islets. Thirty one randomly selected Japanese patients with Type II diabetes mellitus who had first-degree and/or second-degree relative(s) with Type II diabetes mellitus were screened for mutations of this gene using single-stranded conformation polymorphism. Two variant patterns in exon 3 and exon 4 of the CD38 gene were identified. The variant in exon 3 resulted in an amino acid substitution from Arg140 (CGG) to Trp (TGG). The Arg140Trp mutation was observed in 4 of 31 patients, and allele frequencies were significantly different in patients and the control subjects (p = 0.004). One patient with this mutation has two missense mutations on beta cell/liver glucose transporter (GLUT2) gene; her mother, who has impaired glucose tolerance, also has this mutation on the CD38 gene and one missense mutation on the GLUT2 gene. Enzyme activity studies using COS-7 cells expressing the Arg140Trp mutation showed a reduction in ADP-ribosyl cyclase and cADPR hydrolase activity of around 50%. The Arg140Trp mutation on CD38 thus appears to contribute to the development of Type II diabetes mellitus via the impairment of glucose-induced insulin secretion in the presence of other genetic defects.

ADP-ribosyl Cyclase↗
PubMed1998

Cerebral aneurysm associated with persistent primitive olfactory artery aneurysm.

Persistent primitive olfactory artery is a rare vascular anomaly but has a clinical importance because of its high association with cerebral aneurysm. We describe a patient with bilateral persistent primitive olfactory arteries associated with an unruptured saccular aneurysm on the left persistent primitive olfactory artery. Seven reported cases with this anomalous artery including ours are reviewed and classified into two variants. This anomalous artery arises from the terminal portion of the internal carotid artery and courses anteromedially along the ipsilateral olfactory tract and makes a hair-pin curve posterior to the olfactory bulb, becoming the distal anterior cerebral artery (variant 1) or the ethmoidal artery (variant 2). Out of 7 reported cases, 4 cases are associated with saccular aneurysms. The aneurysm in variant 1 is located on the hair-pin curve at which an apparent arterial branch is sometimes absent. Two patients suffer from anosmia. Persistent primitive olfactory artery should be kept in mind because of its high association with intracranial saccular aneurysms and unique clinical presentation.

Arteries↗
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 the KI-83-262 strain of Seoul virus, 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 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 the 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 the Seoul virus infection.

Administration, Intranasal↗
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↗