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Biomedical subjects

N Hashimoto

Publications and source records attributed to N Hashimoto.

At least 271 records · Page 15Linked to original sources
PubMed1998

[Insulin receptor abnormality and its clinical aspect].

About 50 cases of insulin receptor abnormality were reported after in 1985 when human insulin receptor cDNA was cloned. The abnormalities were found in syndrome of type A insulin resistance, Leprechaunism, and syndrome of Rabson-Mendenhall. We have reported 3 families with insulin receptor gene abnormality, Type C (Chiba), Type A (Yamanashi) and Type C (Hokkaidou-2). Type C (Chiba) and Type A (Yamanashi) have a deletion of from 17 to 22 exon and 14 exon of insulin receptor gene, respectively. Type C(Hokkaidou-2) shows a substitution of valine for glycine at codon 1008 in the tyrosine kinase domain. They all showed the typical symptoms of type A insulin resistance, and the insulin resistance was dominantly inherited in the family of Type C(Chiba) and Type C(Hokkaidou-2), and not in the family of Type A(Yamanashi).

Acanthosis Nigricans↗
PubMed1998

Expression of thioredoxin is enhanced in atherosclerotic plaques and during neointima formation in rat arteries.

Thioredoxin (TRX) is an intracellular enzyme that has a variety of activities as a hydrogen donor for various intracellular molecules. In the present study, we investigated the role of TRX in atherosclerotic lesions. In human atherosclerotic specimens, TRX and TRX mRNA were enhanced in endothelial cells and macrophages in the atherosclerotic plaques. In balloon-injured rat arteries, TRX expression increased from 2 to 6 weeks after injury; TRX was induced in the neointimal regenerating endothelial cells. In hybridization experiments, TRX mRNA was also induced from 2 to 6 weeks in the endothelium. In this model, inducible nitric oxide synthase immunoreactivity in the neointimal smooth muscle cells and endothelial cells increased from 2 to 6 weeks after surgical procedures were performed. During this period, the immunoreactivity of nitrotyrosine, which is a marker of nitric oxide (NO) production, also increased. We focused on the association between TRX and NO. In vitro studies using a murine endothelial cell line showed TRX and TRX mRNA induction by NO and peroxynitrite donors. Enhanced expression of TRX was detected mainly within the cytoplasm in immunocytochemical studies. In addition, TRX-transfected cells showed resistance to peroxynitrite-induced cytotoxicity. These findings indicate that TRX and the cellular redox state modified by TRX play a crucial role in arterial neointima formation in atherosclerosis.

Animals↗
PubMed1998

[Pulmonary pseudallescheriasis in a patient with diabetes mellitus and alcoholic liver cirrhosis].

A 62-year-old man with diabetes mellitus and alcoholic liver cirrhosis was admitted to the hospital because of hemoptysis. Chest X-ray films and computed tomograms showed a dense infiltrative lesion and a healed tuberculous cavity with a possible fungus ball in the upper lobe of the right lung. Bronchoscopy revealed that the hemoptysis originated from the right upper-lobe bronchus. The bleeding stopped after thrombin was applied into the bronchus. Filamentous fungi were seen in lavage fluid from the right upper-lobe bronchus. The fungi were identified as Pseudallescheria boydii, and pulmonary pseudallescheriasis was diagnosed. the patient was treated successfully with miconazole (400 mg/day) for 2 months. Pseudallescheriasis should be taken into account in the differential diagnosis of aspergilloma-like lesions.

Antifungal Agents↗
PubMed1998

[Application of a semi-automatic ROI setting system for brain PET images to animal PET studies].

ProASSIST, a semi-automatic ROI (region of interest) setting system for human brain PET images, has been modified for use with the canine brain, and the performance of the obtained system was evaluated by comparing the operational simplicity for ROI setting and the consistency of ROI values obtained with those by a conventional manual procedure. Namely, we created segment maps for the canine brain by making reference to the coronal section atlas of the canine brain by Lim et al., and incorporated them into the ProASSIST system. For the performance test, CBF (cerebral blood flow) and CMRglc (cerebral metabolic rate in glucose) images in dogs with or without focal cerebral ischemia were used. In ProASSIST, brain contours were defined semiautomatically. In the ROI analysis of the test image, manual modification of the contour was necessary in half cases examined (8/16). However, the operation was rather simple so that the operation time per one brain section was significantly shorter than that in the manual operation. The ROI values determined by the system were comparable with those by the manual procedure, confirming the applicability of the system to these animal studies. The use of the system like the present one would also merit the more objective data acquisition for the quantitative ROI analysis, because no manual procedure except for some specifications of the anatomical features is required for ROI setting.

Animals↗
PubMed1998

Protective effect of FK409, a spontaneous nitric oxide releaser, on ischemic acute renal failure in rats.

The contribution of nitric oxide (NO) to ischemic acute renal failure (ARF) is controversial. In the present study, we investigated the effect of FK409 ((+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexanamide ), a spontaneous NO donor, on ischemic ARF in rats. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal functional parameters such as blood urea nitrogen, plasma creatinine, creatinine clearance, urine flow, urinary osmolality and fractional excretion of sodium were measured to test the effectiveness of the drug. Renal function in untreated ARF rats markedly decreased at 24 hr after reperfusion and thereafter tended to recover gradually. Intravenous bolus injection of FK409 at a dose of 1 mg/kg before the occlusion markedly attenuated the ischemic ARF-induced decreases in renal function, to the same extent as verapamil (1 mg/kg i.v.). The protective effect of FK409, at a dose of 3 mg/kg, was much more potent than that of the lower dose. Histopathological examination of the kidney of untreated ARF rats revealed severe renal damages, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion. These renal damages were significantly attenuated by treatment with FK409, at each dose given and this attenuation exceeded that seen with verapamil treatment. FK 409 administration led to a dose-dependent increase in NO metabolites concentration in renal venous blood immediately after the reperfusion. These findings suggest that NO has a crucial role in the pathogenesis of ischemic ARF. Spontaneous NO donors may be clinically effective in cases of ischemic ARF.

Acute Kidney Injury↗
PubMed1997

3-nitropropionic acid induces poly(ADP-ribosyl)ation and apoptosis related gene expression in the striatum in vivo.

Impaired energy metabolism plays an important role in neuronal cell death after brain ischemia, and apoptosis has been implicated in cell death induced by metabolic impairment. In the present study, metabolic impairment was induced by 3-nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase. In order to clarify the involvement of poly(ADP-ribosyl)ation and apoptotic pathway in 3-NP induced cell death, we examined poly(ADP-ribosyl)ation and the apoptosis related gene protein expression after systemic administration of 3-NP by immunohistochemistry. Poly(ADP-ribosyl)ation was evidently detected in the striatal lesion but not in any other region. Immunoreactive ratio of Bcl-2 to Bax significantly increased both in the striatum and cortex. The data suggest that striatal cell death involves poly(ADP-ribosyl)ation and also apoptotic pathway in part following administration of 3-NP.

Animals↗
PubMed1997

Characteristics of protein kinase C-independent exocytosis in human platelets.

We evaluated the characteristics of the protein kinase C (PKC)-independent mechanism for ATP release in platelet-rich plasma. When ADP (10 microM) and U46619 (1 microM) were both added as agonists, a significant release was observed immediately after stimulation. The PKC inhibitor, Ro-31-7549 (10 microM), or a cyclooxygenase inhibitor, aspirin (400 microM) or indomethacin (20 microM), partially inhibited ATP release with little effect on platelet aggregation. The ATP release observed in the presence of Ro-31-7549 was abolished by a cyclooxygenase inhibitor or by preventing aggregation without stirring. In the nonstirred condition, thromboxane B2 formation was reduced by 93%. When sodium arachidonate (1 mM) rather than U46619 was used with ADP, ATP release in the presence of Ro-31-7549 was abolished by stopping the stirring with no effect on thromboxane B2 formation. In contrast, ADP/U46619-induced ATP release observed in the presence of aspirin was only partially inhibited when the stirring was stopped. This release was also inhibited dose-dependently by Ro-31-7549 at concentrations between 1 and 10 microM. These results suggest that PKC-independent ATP-release in this system requires aggregation and is inhibited by a cyclooxygenase inhibitor, while PKC-dependent exocytosis is insensitive to aggregation and a cyclooxygenase inhibitor.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Two distinct chondroitin sulfate ABC lyases. An endoeliminase yielding tetrasaccharides and an exoeliminase preferentially acting on oligosaccharides.

Crude enzyme obtained from chondroitin sulfate-induced Proteus vulgaris NCTC 4636 has been fractionated into 1) an endoeliminase capable of depolymerizing chondroitin sulfate and related polysaccharides to produce, as end products, a mixture of Delta4-unsaturated tetra- and disaccharides and 2) an exoeliminase preferentially acting on chondroitin sulfate tetra- and hexasaccharides to yield the respective disaccharides. Isolation of the two enzymes was achieved by a simple two-step procedure: extracting the enzymes from intact P. vulgaris cells with a buffer solution of nonionic surfactant and then treating the extract by cation-exchange chromatography. Each of the enzymes thus prepared was apparently homogeneous as assessed by SDS-polyacrylamide gel electrophoresis and readily crystallized from polyethylene glycol solutions. Both enzymes acted on various substrates such as chondroitin sulfate, chondroitin sulfate proteoglycan, and dermatan sulfate at high, but significantly different, initial rates. They also attacked hyaluronan but at far lower rates and were inactive to keratan sulfate, heparan sulfate, and heparin. Our results show that the known ability of the conventional enzyme called "chondroitinase ABC" to catalyze the complete depolymerization of chondroitin sulfates to unsaturated disaccharides may actually result from the combination reactions by endoeliminase (chondroitin sulfate ABC endolyase) and exoeliminase (chondroitin sulfate ABC exolyase).

Chondroitin Lyases↗
PubMed1997

Ameliorating effect of an endothelin ETA receptor antagonist on renal function of DOCA-salt hypertensive rats.

The effects of FR139317 ((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1 H-azepinyl)]-carbonyl]amino-4-methyl-pentanoyl]amino-3[3-(1-methyl -1 H-indolyl)]propionyl]amino-3-2(2-pyridyl)propionic acid), an endothelin ETA receptor antagonist, on renal hemodynamics and urine formation were examined using anesthetized deoxycorticosterone acetate (DOCA)-salt hypertensive rats, in which renal perfusion pressure was protected from FR139317-induced hypotension with an aortic clamp. An intravenous injection of FR139317 (10 mg/kg) to sham-operated normotensive control rats produced no significant changes in renal hemodynamic and excretory responses. In DOCA-salt hypertensive rats, FR139317 caused sustained renal vasodilation. Urine flow and urinary excretion of sodium were increased significantly following drug injection. We suggest that endothelin-1 and the endothelin ETA receptor play an important role in water and sodium retention, and in renal vasoconstriction in this model of hypertension.

Animals↗
PubMed1997

Clonotypic analysis of T cells in patients with autoimmune and viral hepatitis.

The immunopathogenesis of autoimmune hepatitis (AIH), and the role of T cells in the onset and maintenance of this disease, are still unclear. Since T cells expand clonally after stimulation by an antigen, it is important to analyze the behavior of T cells at a clonal level. We have established recently a novel system, using reverse transcriptase-polymerase chain reaction (RT-PCR) and subsequent single-strand conformation polymorphism (SSCP) that allows the identification of clonal accumulation of T cells in a lymphocyte population. Using this system, we demonstrated that oligoclonal T cells were accumulated in the liver of patients with AIH, and that identical T-cell clonotypes were detected in two different regions of the liver, although these features were also observed in cases with viral hepatitis. Only in cases with AIH, however, nearly all identical T cells were found to belong to CD8+ subset and there were very few CD4+ T cells in this population. Our results suggest that common antigens presented to CD8+ T cells in the context of HLA class I molecule are distributed diffusely in the liver of AIH. These findings also suggest that antigens recognized by CD4+ T cells may be relatively heterogeneous in the liver with AIH.

Adult↗
PubMed1997

Effectiveness of intra-arterially infused papaverine solutions of various concentrations for the treatment of cerebral vasospasm.

We evaluated the effect of intra-arterially infused papaverine solutions of various concentrations on cerebral vasospasm following subarachnoid haemorrhage. A total of 90 vascular territories in 46 patients with symptomatic cerebral vasospasm after subarachnoid haemorrhage were treated with intra-arterial infusions of papaverine. In all patients, papaverine was infused at the top of the internal carotid artery (ICA). Of the 90 vascular territories, 30 vascular territories in 14 patients were treated with an infusion of 0.1-0.2% (weight/volume) papaverine (Group 1), 30 vascular territories in 16 patients were treated with a 0.4% (w/v) papaverine infusion (Group 2), and 30 vascular territories in 16 patients were treated with an infusion of 0.8-2.0% (w/v) papaverine (Group 3). Among the three groups, we compared the vasodilatory effects of papaverine by assessing the angiographical and clinical improvements following the treatment. When 0.4% (w/v) papaverine was infused, 24 vascular territories (80%) were successfully dilated and 7 patients (44%) showed a marked reversal of neurological deficits due to vasospasm. Therefore, 80 mg/20 ml (0.4% (w/v)) papaverine infused over a 10-minute period proved to be a beneficial concentration. Transient focal neurological deficits due to the infusion of papaverine occurred in 1 Group 1 patient (7%), 1 Group 2 patient (6%), and 7 Group 3 patients (44%). Highly concentrated papaverine had a higher risk of temporary deterioration. In conclusion, the papaverine concentration of 0.4% (w/v) infused at the top of the ICA was a safe and adequate concentration for treating cerebral vasospasm.

Adult↗
PubMed1997

Improvement of oxygen metabolic reserve after extracranial-intracranial bypass surgery in patients with severe haemodynamic insufficiency.

The effectiveness of extracranial-intracranial arterial bypass (EC-IC bypass) surgery on impaired haemodynamic status was studied in 12 patients with reduced regional cerebral perfusion pressure (rCPP) and elevated regional oxygen extraction fraction (rOEF) in the area distal to the symptomatic arterial lesion. Postoperative positron emission tomography (PET) study demonstrated a statistically significant decrease of rOEF in the operated hemispheres with disappearance of the pre-operative interhemispheric rOEF difference. Regional cerebral blood flow (rCBF) and regional cerebral oxygen metabolism (rCMRO2) were also increased in the operated hemispheres with disappearance of the pre-operative interhemispheric differences. Regional CBF/regional cerebral blood volume (rCBV) ratios of the symptomatic hemispheres were increased after surgery, but were still lower than in the contralateral hemispheres. We conclude that EC-IC bypass surgery improves impaired cerebral oxygen metabolic reserve.

Aged↗