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Biomedical subjects

N Hashimoto

Publications and source records attributed to N Hashimoto.

At least 253 records · Page 14Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Characterization of a cry2A gene cloned from an isolate of Bacillus thuringiensis serovar sotto.

A cry2A-type gene, designated as cry2(SKW), was cloned from Bacillus thuringiensis serovar sotto SKW01-10.2-06, and some unique features of the gene were revealed. The cry2(SKW) gene encoded a polypeptide of 635 residues with a predicted molecular mass of 71,137 Da. Cry2(SKW) had 95.4% identity with Cry2Aa in amino acid sequence and was two residues longer than Cry2Aa. Two open reading frames (ORFs), designated as orf1 and orf2, were present upstream of the cry2(SKW) and showed high homology with the corresponding ORFs in the cry2Aa operon. The Orf2 from SKW01-10.2-06 contained a region of repeated sequences. However, unlike Cry2Aa, Cry2(SKW) formed the cuboidal crystalline inclusions when the cry2(SKW) gene was expressed in an acrystalliferous B. thuringiensis strain in the absence of the upstream ORFs. Furthermore, Cry2(SKW) was less toxic to a lepidopteran species, Bombyx mori, than Cry2Aa in spite of high homology between the two proteins.

Amino Acid Sequence↗

Clinicopathological features of superficial squamous cell carcinoma of the esophagus.

BACKGROUND: The depth of penetration is the crucial factor determining the prognosis of esophageal carcinoma patients. Patients with superficial esophageal carcinoma have a significantly favorable clinical course compared with those with advanced cancers. The outcome for patients with mucosal cancer is excellent with a 5-year survival rate exceeding 80%. On the other hand, submucosal cancer often metastasizes to lymph nodes or other organs, and the prognosis of these patients is far from satisfactory. METHODS: Among 165 patients with squamous cell carcinoma of the esophagus, surgically resected between December 1979 and April 1995, 30 patients (18.2%) had superficial esophageal carcinoma (SEC) confined to the epithelium, lamina propria mucosa, or submucosa. Disease profile and clinicopathological characteristics of these 30 patients were studied. RESULTS: The incidence of SEC has increased from 6.3% (2 of 32) in the first 5-year period (1979 to 1984) to 27.4% (20 of 73) in the recent 5-year period (1991 to 1995). Subjective symptoms were present in 2 (13.3%) with 15 mucosal cancers and in 4 (26.7%) with 15 submucosal cancers. The remaining 24 patients (80%) had no subjective symptoms. Twenty-two patients (73.3%) were diagnosed to have the lesions by endoscopic examination at the time of screening for gastric problems, and only 3 were detected by gastrointestinal series. None of the 15 patients with mucosal cancer had lymphatic invasion, venous invasion, or lymph node metastasis. On the other hand, in those with submucosal cancers, 9 (60%) had lymphatic invasion, 5 (33.3%) venous invasion, and 8 (53.3%) lymph node metastases. Twenty-two patients are alive without recurrence. The 3- and 5-year survival rates are 86.7% and 86.7% for patients with mucosal cancer and 72.2% and 65.0% for those with submucosal cancer, respectively. CONCLUSION: Esophagectomy with wide lymphadenectomy should be carried out for submucosal cancer, whereas esophagectomy with moderate lymphadenectomy can be preferred for mucosal cancer.

Carcinoma, Squamous Cell↗

Superficial temporal artery to anterior cerebral artery direct anastomosis in patients with moyamoya disease.

Some patients with Moyamoya disease require revascularization not only to the territory of the middle cerebral artery (MCA) but also to that of the anterior cerebral artery (ACA). To revascularize the ACA territory, we performed superficial temporal artery (STA)-ACA direct anastomosis in five patients with Moyamoya disease. After paramedian frontal craniotomy (approximately 5 cm diameter), STA-ACA anastomosis was carried out 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. Bypass flow was satisfactory in four patients. One patient who underwent simultaneous STA-ACA and STA-MCA anastomoses had poor bypass flow probably due to spontaneous leptomeningeal collateral channels between the ACA and MCA. 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 easier than in a deep operative field. A short arterial graft does not easily occlude. The diameter of a branch of the STA is small and therefore, a size discrepancy does not present a problem. Our STA-ACA anastomosis method is useful and effective for revascularization of the ACA territory in any patients with Moyamoya disease.

Adolescent↗

Direct surgery for major artery aneurysm associated with moyamoya disease.

Moyamoya disease is often accompanied by intracranial major artery aneurysms in the posterior circulation which acts as collateral channels in place of the stenotic internal carotid arteries. These major artery aneurysms are considered to have high risk of enlargement and rupture due to increased hemodynamic stress. Direct surgical intervention has been recommended for the treatment of these aneurysms, but the direct approach to them is often difficult due to interference by intertwined abnormal vessels. We have performed direct surgery for seven major artery aneurysms in five patients with Moyamoya disease. Of these three aneurysms located in the anterior circulation were successfully clipped via pterional or interhemispheric approach. Of four posterior circulation aneurysms (two at the junction of the basilar artery and the superior cerebellar artery and two at the P1-P2 junction of the posterior cerebral artery), one was approached via pterional route because collateral vessels in the basal cistern was judged not to be rich on angiograms. However, the operative field was interfered by abundant fragile collateral vessels and it was difficult to reach the distal portion of the basilar artery. In contrast, in the other three cases in which the subtemporal approach was employed, there weren't any problems in exposures of the aneurysms. Our experiences indicate that subtemporal approach is superior than the pterional approach to reach the distal portion of the basilar artery in patients with Moyamoya disease.

Adult↗

Single-step synthesis of [18F]haloperidol from the chloro-precursor and its applications in PET imaging of a cat's brain.

We have established a convenient synthesis process for the synthesis of[18F]haloperidol using a single-step 18F-for-Cl exchange reaction and a new elution system for the preparative high performance liquid chromatography (HPLC) using C18 bonded vinylalcohol copolymer gel (ODP) and a basic eluent. We successfully applied the product to cat-PET study and got clear images of the striatum, showing the usefulness of this synthesis.

Animals↗

TCR beta-independent development of CD4+ CD8+ thymocytes observed in a strain of scid mice.

Mice homozygous for severe combined immunodeficiency (scid) mutation usually halt their thymocyte development at the CD4-CD8- double negative (DN) stage due to their inability of TCR gene rearrangement. In this study, we report that SCID-bg mice, which were originally generated by mating CB-17-scid mice with KSN-bg mice, spontaneously develop dominant CD4+ CD8+ double positive (DP) thymocytes. Their thymi were mainly composed of DN, CD4-CD8+ and DP cells, and the majority of them did not present CD3. Similarly, they lacked TCR beta expression both on cell surface and in cytoplasm, which suggests that the thymocyte development to the DP stage observed in SCID-bg mice, was independent of CD3 and TCR beta expression. In spite of significant DP thymocytes in SCID-bg mice, the histology of their thymi was not so different from those of CB-17-scid mice. Analysis of bone marrow cells in SCID-bg mice showed that the development of B lineage cells was not altered when compared with CB-17-scid mice. These findings point out the fact that thymocytes in SCID-bg mice have a peculiar characteristic compared to CB-17-scid mice, and provide evidence of TCR beta-independent development of thymocytes to the DP stage.

Animals↗