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Biomedical subjects

N Hashimoto

Publications and source records attributed to N Hashimoto.

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

Apoptosis of medial smooth muscle cells in the development of saccular cerebral aneurysms in rats.

BACKGROUND AND PURPOSE: Using an animal model, we examined the role of apoptosis in the disappearance of medial smooth muscle cells (SMCs) during the development and growth of cerebral aneurysms. METHODS: Various degrees of cerebral aneurysms were induced in the right anterior cerebral artery-olfactory artery bifurcations in 65 Sprague-Dawley rats with ligation of the left common carotid artery and renal hypertension. We performed in situ end labeling of fragmented DNA with the lesions in 45 rats and electron microscopic study in the other 20 rats. RESULTS: With in situ end labeling of fragmented DNA, 4+/-3 apoptotic medial SMCs were detected in 35 of the 45 bifurcations. Apoptotic SMCs appeared in the medial layer in the "preaneurysm" group, the site speculated to show an aneurysmal change in the near future (6+/-3), and in the media in the "early aneurysm" group, which showed characteristics such as a small depression (5+/-3). In the "progressive aneurysm" group, they appeared more frequently at the aneurysmal neck (3+/-2) than the dome (1+/-1). By electron microscopic study, shrunken medial SMCs exhibiting morphological apoptotic changes such as chromatin condensation and fragmentation of the cytoplasm and nucleus were observed in the preaneurysm and early aneurysm groups and at the neck portion in the progressive aneurysm group. In the aneurysmal dome, SMCs showed late characteristics of apoptosis such as more advanced nuclear and cytoplasmic condensation and formation of apoptotic bodies. CONCLUSIONS: The present findings indicate that there is an association between apoptosis of medial SMCs and the formation of saccular cerebral aneurysms.

Aneurysm↗
PubMed1998

Comparison of bone regeneration in a rabbit skull defect by recombinant human BMP-2 incorporated in biodegradable hydrogel and in solution.

The objective of this study is to compare bone regeneration induced by recombinant human bone morphogenetic protein-2 (rhBMP-2) incorporated into a biodegradable gelatin hydrogel with that by rhBMP-2 in aqueous solution. After treating rabbit skull defects of 6 mm diameter with the two rhBMP-2 dosage forms, both of them increased the bone mineral density (BMD) at the skull defects with implantation time to a significantly higher extent than a rhBMP-2-free aqueous solution and a rhBMP-2-free empty gelatin hydrogel (p < 0.05). There was no quantifiable difference in BMD between the two dosage forms of rhBMP-2. Histological examination revealed that the integrity of newly generated bone increased with the rhBMP-2 dose, irrespective of the dosage form. The bone defect was filled with regenerated bone 21 days after treatment.

Absorptiometry, Photon↗
PubMed1998

Endothelin ET(B) receptor-mediated action on systemic and renal hemodynamics and urine formation in deoxycorticosterone acetate-salt-induced hypertensive rats.

The pathophysiological role of endothelin ET(B) receptor-mediated action on systemic and renal hemodynamics and urine formation in deoxYcorticosterone acetate (DOCA)-salt hypertensive rats was investigated. An intravenous bolus injection of a selective ET(B) receptor antagonist, BQ788 (1 mg/kg), produced a significant increase in mean arterial pressure (MAP) of DOCA-salt treated rats, whereas the agent-induced increase in MAP was less marked in normotensive sham rats. Administration of BQ788 caused a significant and sustained reduction in renal blood flow both in DOCA-salt and sham rats. No marked effects were observed on urine formation in both groups. Alternatively, a selective ET(A) receptor antagonist, FR139317 (10 mg/kg), produced a potent hypotensive effect, accompanied by significant renal vasodilation in DOCA-salt hypertensive rats, but these effects were partially reversed by the subsequent administration of BQ788. When renal perfusion pressure was protected from FR139317-induced hypotension by an aortic clamp, significant diuresis and natriuresis were observed, events partially reversed by the subsequent administration of BQ788. Our results indicate that the ET(B) receptor-mediated action tonically functions as a hypotensive and a renal vasodilatory factor and that these effects seem to be up-regulated in DOCA-salt hypertension. We also suggest that the ET(A) receptor blockade in DOCA-salt hypertensive rats unmasks the ET(B) receptor-mediated action which partially contributes to the antihypertensive effect induced by FR139317.

Animals↗
PubMed1998

A comparison of UVB-carcinogenesis between nude mice and nude beige mice.

To gain an insight into the relationship between UVB-carcinogenesis and natural killer activity, we examined ultraviolet light-induced carcinogenesis in mice with high natural killer, activity (KSN) and mice with natural killer deficiency (KSN-bg). We exposed mice six times a week to three levels of daily ultraviolet B (UVB) doses; 320, 160 and 0 J/m2/day. During the latency period of skin tumor development in KSN mice, we detected no suppression of the natural killer activity at both 320 and 160 J/m2/day. Even at 1340 J/m2/day, we could not detect any significant suppression of NK activity in KSN mice. When we irradiated spleen cells in vitro, we observed NK activity suppression. Next, we compared the carcinogenic effects of UVB-irradiation on KSN and KSN-bg mice. At 320 J/m2/day, we detected no significant differences between them. In contrast, at 160 J/m2/day, KSN-bg mice showed a significantly higher rate of skin tumor induction than KSN mice (p < 0.05). Most UVB-induced tumors were squamous cell carcinoma, the rest were spindle cell carcinoma, papilloma and mixed type. Our results suggest that NK activity plays a protective role against UVB-carcinogenesis from low daily-doses of UVB-irradiation.

Animals↗
PubMed1998

Production of exfoliative toxin A by Staphylococcus aureus isolated from mastitic cow's milk and farm bulk milk.

The production of exfoliative toxins A and B (ETA and ETB) by Staphylococcus aureus isolated from mastitic cow's milk and farm bulk milk was examined by the reverse passive latex agglutination method (RPLA). ETA was detected in 2 (1.2%) of 162 isolates from mastitic cow's milk and in 1 (0.6%) of 166 isolates from farm bulk milk. RPLA titers of these isolates were much lower than in human isolates. No ETB was detected in any of the isolates tested. These ETA-positive isolates belonged to bovine ecovar. They were non-typable using the international phage set for human strains. When these ETA-positive isolates were subcutaneously inoculated into neonatal mice, general exfoliation of the epidermis accompanied by the so-called Nikolsky sign was not recognized. By the immunoblotting and PCR methods, however, ETA and eta gene were recognized in the ETA-positive isolates from mastitic cow's milk and farm bulk milk. These data suggest that ETA is also produced by bovine isolates of S. aureus, but in smaller quantities.

Animals↗
PubMed1998

Serum levels of soluble interleukin-2 receptor in patients with various renal diseases.

To clarify the serum levels of soluble interleukin-2 receptor (sIL-2R) in patients with renal diseases, we examined 281 patients without various renal diseases with or without systemic disease (including 197 patients without systemic diseases and 84 patients with systemic diseases). The sIL-2R level was significantly higher in patients with renal diseases, than in healthy volunteers. In the group of renal diseases, the sIL-2R level in patients with rapidly progressive nephritic syndrome was especially higher than in patients with other renal diseases. In patients without systemic diseases, the serum level of sIL-2R was significantly and positively correlated with the urinary excretion of protein, and the serum levels of creatinine and uric acid, and was negatively correlated with the glomerular filtration rate (GFR). In the patients with systemic diseases, the correlation between the serum levels of sIL-2R and the serum levels of creatinine or GFR were not as strong as observed in the patients without systemic diseases. The serum level of sIL-2R was outside the normal range in patients with systemic diseases with a serum level of creatinine above 2.0 mg/100 ml. These findings suggest that the serum levels of sIL-2R in patients with renal disease may increase and correlate with the impaired renal function, that he increased sIL-2R levels in patients with systemic diseases may be dependent on the activity of systemic disease, and that it may be not useful indicator of diseases activity in patients with systemic diseases when the serum level of creatinine was above 2.0 mg/100 ml.

Adult↗
PubMed1998

Direct anastomotic bypass for cerebrovascular moyamoya disease.

Therapeutic result and pitfalls in the surgical treatment of cerebrovascular moyamoya disease are evaluated. During the recent 15 years, 268 patients with moyamoya disease have been treated in our clinic. Among them, 238 patients showed ischemic symptoms. Superficial temporal artery to middle cerebral artery anastomoses combined with temporal muscle grafting (encephalo-myo-synangiosis) were performed for most of the cases. Complete remission and clinical improvement were obtained in 34.0% and 64.2% of the patients, respectively. Symptomatic aggravation due to ischemic complication followed the operation in five patients (1.9%). Normocapnic control during general anesthesia with sufficient hydration is essential to avoid perioperative ischemic complications. Omental graft was performed in 16 patients. In 13 patients, omental graft was performed for the progressing ischemia in the posterior cerebral artery or anterior cerebral artery distribution. In the other three patients, omental graft was used for marked brain atrophy.

Anastomosis, Surgical↗
PubMed1998

Role of transforming growth factor-beta1 in the pathogenesis of moyamoya disease.

OBJECT: Prominent features of moyamoya disease are intimal thickening of the cerebral arterial trunks and abundant angiogenesis for collateral blood supplies, but its pathogenesis is still unknown. The aim of this study was to test the possibility that transforming growth factor-beta1 (TGFbeta1) may play a role in the pathogenesis of moyamoya disease. METHODS: The authors used reverse transcription-polymerase chain reaction to analyze the expression level of TGFbeta1 in smooth-muscle cells cultured from the superficial temporal arteries (STAs) and measured the serum level of TGFbeta1 by using enzyme-linked immunosorbent assay. Although the STA is not predominantly involved with moyamoya disease, it has been used in studies of the pathogenesis of this disease. In this report, the STAs from six patients with moyamoya disease and four with arteriosclerotic cerebrovascular disease, along with sera from 14 patients with moyamoya disease and 10 normal healthy volunteers, were studied. The expression of TGFbeta1 was significantly higher in cultured smooth-muscle cells derived from the STAs of patients with moyamoya disease than in those derived from the STAs of patients with arteriosclerotic cerebrovascular disease (p < 0.05). The serum level of TGFbeta1 was also significantly higher in patients with moyamoya disease than in controls (p < 0.0005). CONCLUSIONS: Taking into account the functional roles of TGFbeta1 in the expression of connective tissue genes and angiogenesis, these investigators suggest that TGFbeta1 is associated with the pathogenesis of moyamoya disease, including abundant neovascularization, although their findings do not necessarily mean that TGFbeta1 is a causative factor in this disease.

Adolescent↗
PubMed1998

Middle cerebral artery blood flow velocity during laparoscopic surgery in head-down position.

Laparoscopic surgery using intraperitoneal CO2 insufflation has become popular in many fields of surgical procedures. In this study, the authors examined the effects of intraperitoneal CO2 insufflation on the middle cerebral artery blood flow velocity (MCABFV) of patients in the head-down position. Fourteen patients undergoing laparoscopic surgery in the head-down position were studied. The MCABFV was measured at the following times: before CO2 insufflation and 15, 30, and 45 min after insufflation. The MCABFV increased significantly (61.4 +/- 14.5, 71.1 +/- 25.5, and 67.2 +/- 18.9 cm/s at 15, 30, and 45 min after insufflation, respectively) as compared with control (49.8 +/- 13.5 cm/s) following the CO2 insufflation. A positive correlation was observed between blood flow velocity and PaCO2 (y = 1.718 + 2.102x; r = 0.669). Our results suggest that the cerebral BFV is increased by intraperitoneal CO2 insufflation during laparoscopic surgery.

Adult↗
PubMed1998

Subtraction CT angiography with controlled-orbit helical scanning for detection of intracranial aneurysms.

PURPOSE: Our goal was to evaluate the utility of subtraction three-dimensional CT angiography for the detection of intracranial aneurysms. METHODS: Thirty-six patients with intracranial aneurysms were examined using newly devised controlled-orbit helical scanning and conventional angiography. Three-dimensional CT angiograms and subtraction 3-D CT angiograms were compared with conventional angiograms for their characterization of intracranial aneurysms. RESULTS: Fifty aneurysms were depicted on conventional angiograms, of which 48 (96%) were seen on the 3-D CT angiograms. Three-dimensional CT angiography was superior or equivalent to conventional angiography for depicting the shape, direction, and location of 33 (66%) of 50 aneurysms; however, it was often less useful than conventional angiography in delineating intracranial aneurysms adjacent to bone. Subtraction 3-D CT angiograms were obtained in 32 patients with a total of 46 aneurysms (in four cases, aneurysms were not depicted owing to excessive motion artifacts), and were superior or equivalent to conventional angiograms in all 46 cases. CONCLUSIONS: Subtraction 3-D CT angiography with the use of controlled-orbit helical scanning is effective in the detection of intracranial aneurysms.

Adult↗
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↗