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Biomedical subjects

N Ashizawa

Publications and source records attributed to N Ashizawa.

At least 19 recordsLinked to original sources
PubMed2000

An enzymatic assay for myo-inositol in tissue samples.

An enzymatic assay for myo-inositol (MI) was modified. The method is based on the oxidation of MI by NAD(+)-dependent MI dehydrogenase, coupled to reoxidation of NADH by iodonitrotetrazolium chloride and diaphorase. The resultant formazan is measured spectrophotometrically. In order to remove interference by glucose, preliminary phosphorylation of glucose by hexokinase was employed before the above reaction. The assay is quantitative for MI in amounts ranging from 1 to 20 nmol. This method gives a negligible blank, even in the measurement of rat serum. The reduced MI content in the sciatic nerve and lens of streptozotocin-induced diabetic rats recovered in a dose-dependent manner by treatment with a novel potent aldose reductase inhibitor, GP-1447 ¿3-[(4,5, 7-trifluorobenzothiazol-2-yl)methyl]-5-methylphenylacetic acid¿.

Animals↗
PubMed2000

Interaction of the effects between vitamin D receptor polymorphism and exercise training on bone metabolism.

Bone metabolism is strongly influenced by heredity and environmental factors. To investigate interaction of the effects between vitamin D receptor polymorphism by Fok I and resistance exercise training on bone metabolism, young male subjects with FF genotype (F, n = 10) and Ff or ff genotypes (f, n = 10) followed 1 mo of weight training, and changes in bone metabolism were compared. An additional 14 subjects served as a sedentary control. Biomarkers of bone formation, bone-specific alkaline phosphatase, and osteocalcin were significantly increased by training in both F and f groups. 1, 25-Dihydroxyvitamin D(3), known to upregulate bone formation, was also increased by the training in the f but not in the F group. Bone resorption assessed by cross-linked NH(2)-terminal telopeptide of type I collagen was significantly suppressed by the training, and the decrease in F was greater and longer lasting than that in f group. In conclusion, stimulation of bone formation and suppression of bone resorption occurred within 1 mo in young men. Despite a significant increase in 1,25-dihydroxyvitamin D(3) in the f group but not in the F group, the response of bone metabolism to the training in the F was similar to or greater than that in f group, suggesting a functional difference between vitamin D receptor genotypes f and F.

Adult↗
PubMed2000

A fatal case of fulminant myocarditis with human herpesvirus-6 infection.

We report a case of fulminant myocarditis after steroid pulse therapy for acute hepatitis. Serological studies demonstrated a four-fold increase in the antibodies against human herpesvirus-6 (HHV-6) IgG, and a PCR showed the existence of HHV-6 virus DNA. HHV-6 virus DNA was also isolated from the liver and the heart. We believe that exacerbation of fulminant myocarditis was probably associated with the reactivation of HHV-6 due to the immunosuppressive state of the host.

Antibodies, Viral↗
PubMed1999

Involvement of receptor-type tyrosine kinase gene families in cardiac hypertrophy.

OBJECTIVE: The activation of protein tyrosine kinases (PTKs) has been postulated to be involved in cell differentiation and proliferation. To elucidate the involvement of tyrosine kinase genes in normal and pathological conditions, we analysed the expression patterns of receptor-type PTKs in the normal and hypertensive hypertrophied heart in rats. MATERIALS AND METHODS: Hypertrophied and normal rat hearts were obtained from hypertensive rats; deoxycorticosterone acetate (DOCA)-salt and 2 kidney-1 clip (2K-1C), and their sham-operated rats, respectively. A reverse transcription-polymerase chain reaction (RT-PCR) was performed using degenerated primers which were designed from highly conserved regions in the catalytic domains of receptor-type PTKs. The PCR products were ligated into a sequence vector, and subcloned by transforming bacteria. To compare the expression level of these PTK mRNAs in the normal and hypertrophied heart, we performed semi-competetive RT-PCR and immunohistochemical and Western blot analyses. RESULTS: Nucleotide sequencing of approximately 80 clones of PTKs revealed 10 receptor-type, five nonreceptor-type and two unknown types in the rat heart. Tie-2/Tek, Ryk, insulin-like growth factor-I receptor were abundantly expressed in the rat heart as members of receptor-type PTKs. Immunohistochemistry and RT-PCR demonstrated the presence of platelet-derived growth factor (PDGF)-alpha receptor, PDGF-beta receptor and fibroblast growth factor-3 receptor in both normal and hypertrophied hearts. We also confirmed the presence of Flt-1, KDR/FIk-1, and their ligand vascular endothelial growth factor, c-Met and its ligand hepatocyte growth factor (HGF), and Tie-1, Tie-2/Tek by immunohistochemistry and RT-PCR. The coexpression of cardiac HGF and c-Met in hypertrophied hearts, especially in 2K-1 C rats, was induced more intensively than that in DOCA-salt rats. CONCLUSION: These findings suggest that HGF/c-Met interactions may play an important role in cardiac hypertrophy and remodeling, probably as a result of the activation of the local renin-angiotensin system.

Animals↗
PubMed1999

Tomographical description of tennis-loaded radius: reciprocal relation between bone size and volumetric BMD.

Effects of long-term tennis loading on volumetric bone mineral density (vBMD) and geometric properties of playing-arm radius were examined. Paired forearms of 16 tennis players (10 women) and 12 healthy controls (7 women), aged 18-24 yr, were scanned at mid and distal site by using peripheral quantitative computerized tomography. Tomographic data at midradius showed that tennis playing led to a slight decrease in cortical vBMD (-0.8% vs. nonplaying arm, P < 0. 05) and increase both in periosteal and endocoritcal bone area (+15. 2% for periosteal bone, P < 0.001; and +18.8% for endocortical bone, P < 0.001). These data suggest that, together with an increase in cortical thickness (+6.4%, P < 0.01), cortical drift toward periosteal direction resulted in improvement of mechanical characteristics of the playing-arm midradius. Enlargement of periosteal bone area was also observed at distal radius (+6.8%, P < 0.01), and the relative side-to-side difference in periosteal bone area was inversely related to that in trabecular vBMD (r = -0.53, P < 0.05). We conclude that an improvement of mechanical properties of young adult bone in response to long-term exercise is related to geometric adaptation but less to changes in vBMD.

Adult↗
PubMed1999

[Preparation of ketamine tablets for treatment of patients with neuropathic pain].

Ketamine is known to have distinguished analgesic effects without anesthetic when administered in a low dose. Since ketamine is not commercially available except injection forms, we prepared ketamine tablets for the home-care medication of patients with neuropathic pain. The direct compression or wet granulation method was employed to form 150 mg of tablets containing 50 mg of ketamine. The latter method was superior to the former one in terms of content uniformity, weight variation and disintegration tests of the tablets. Ketamine contents in the tablet prepared by the wet granulation method were unchanged for 12 weeks under the conditions of 25 degrees C and 75% relative humidity (RH). The Cmax and AUC0-3 h values for ketamine after administration of the tablet were slightly smaller than those of the syrup in a healthy volunteer. However, analgesic effects of the tablet was similar to that of the syrup in a patient with neuropathic pain. And the tablet was also effective for another four patients with neuropathic pain. These results indicate that ketamine tablets are useful for the home-care medication of patients with neuropathic pain.

Adult↗
PubMed1999

The morphological changes of exocrine pancreas in chronic pancreatitis.

The following changes were found by either light or electron microscopic observation of the pancreas in spontaneously developed chronic pancreatitis models (WBN/Kob rats, spontaneously hypertensive rats, and rats with common bile-pancreatic duct stones) and in experimental models of chronic pancreatitis (alcoholic pancreatitis, ischemic pancreatitis, and obstructive pancreatitis): 1) the units of lobules, which were constituted by acinar cell deletion, ductular proliferation, and fibrosis; and 2) tortuous or helical ductal channels of pancreatic ducts with periductal fibrosis, which had many crater-like depressions and very long cilia in their inner surface. These are considered to be the results of obstructive pancreatitis, which are caused by the reactions of defensive factors against the increase of pancreatic duct pressure, including the apoptosis of acinar cells, the hyperplasia and hypertrophy of duct cells, a tighter junctional complex of duct cells, and periductal fibrosis.

Animals↗
PubMed1999

Angiotensin II promotes integrin-mediated collagen gel contraction by adult rat cardiac fibroblasts.

Remodeling is a fundamental cardiac response to injury and involves cardiac fibroblast proliferation and extracellular matrix (ECM) production. Angiotensin II (Ang II) directly promotes these changes in cardiac fibroblasts and thus, plays critical roles in cardiac hypertrophy and wound healing. Osteopontin, fibronectin and laminin mRNA were detected in total RNA harvested from cultured adult rat cardiac fibroblasts. Immunocytochemistry staining of cultured adult rat cardiac fibroblasts grown on coverslips revealed the presence of beta 3 integrins on the surfaces of the cells. In the present study, we investigated the role of Ang II in a model of wound repair using floating collagen gels harboring adult rat cardiac fibroblasts, and we determined which members of the integrin family existed on these cells. The presence of either MPIIIB10, a monoclonal antibody against osteopontin (7.2 micrograms/ml) or RGD (arginine-glycine-aspartate) peptide (10(4) M) had no effect on gel contraction. Osteopontin itself induced gel contraction; however this effect was completely neutralized by MPIIIB10 (7.2 micrograms/ml, RGD peptide (10(4) M) and a monoclonal antibody against rat beta 3 integrin (25 micrograms/ml). We identified alpha v, beta 3 and beta 5 integrins on adult rat cardiac fibroblasts by fluorescence-activated cell sorting and confirmed that RGD peptide and an antibody against beta 3 integrin completely blocked osteopontin-induced gel contraction. These results suggest that Ang II promotes cardiac wound healing and remodeling processes by inducing expression of osteopontin and beta 3 integrin by cardiac fibroblasts.

Angiotensin II↗
PubMed1999

Malignant pheochromocytoma with multiple hepatic metastases treated by chemotherapy and transcatheter arterial embolization.

A 62-year-old Japanese male developed multiple hepatic metastases two years after resection of pheochromocytoma of the right adrenal gland. Transcatheter arterial embolization (TAE) was performed for the purpose of the treatment of hepatic metastases resistant to 27 cycles of combined chemotherapy consisting of cyclophosphamide, vincristine, and dacarbazine. After TAE, the hepatic metastatic lesions decreased in size and hypertension passed its crisis. The present case suggests the utility of TAE for multiple hepatic metastases under careful blood pressure monitoring.

Adrenal Gland Neoplasms↗
PubMed1998

Primary sclerosing pancreatitis and cholangitis.

CONCLUSION: The clinical course of our patient suggests the association between chronic pancreatitis and primary sclerosing cholangitis (PSC), as well as the usefulness of prednisolone for the treatment of this condition. BACKGROUND: Although alterations in the pancreatic duct have been reported, the association between chronic pancreatitis and PSC remains uncertain. METHODS AND RESULTS: A long-term follow-up case of chronic pancreatitis accompanied by PSC is presented. A 58-yr-old man complaining of epigastric distress was admitted to our hospital in July 1990. Endoscopic retrograde cholangio-pancreatography (ERCP) showed a stricture of the distal common bile duct and a narrowing of the main pancreatic duct (MPD) with mild ectasia of its branches in the head of the pancreas. ERCP taken in June 1992 revealed localized narrowings in both the right and the left main hepatic ducts, and irregularity of the MPD through the entire pancreas. An ERCP taken in June 1996 showed a progression of the narrowings of the bile ducts. The patient was diagnosed as having chronic pancreatitis accompanied by PSC. ERCP revealed a remarkable improvement of the bile ducts after 4 wk of treatment with prednisolone.

Anti-Inflammatory Agents↗
PubMed1998

Effects of a single bout of resistance exercise on calcium and bone metabolism in untrained young males.

Although resistance exercise training appears to increase bone mineral density in the long term, a single bout of resistance exercise could paradoxically induce bone homeostasis disturbance, secondary to metabolic acidosis. To examine this, we obtained fasting blood and 24-hour urine samples from untrained male subjects for 5 subsequent days (control day, exercise day, and three post-exercise days), and investigated the effects of a single bout of resistance exercise on urinary calcium excretion and bone metabolism as indicated by sensitive biomarkers of bone formation and resorption. After an intense bout of resistance exercise, blood and urine became more acidic and renal net acid excretion significantly increased by 44% on the exercise day. Urinary calcium excretion significantly increased by 48% on the exercise day. Plasma procollagen type-I C-terminal concentration significantly decreased by 12% on the next day of the exercise and serum bone-specific alkaline phosphatase activity also significantly decreased by 13% and 9% on days 2 and 3, respectively, after the exercise. There was no significant change in serum osteocalcin concentration. Serum tartrate-resistant acid phosphatase activity significantly decreased by 15% on the day after the exercise and urinary deoxypyridinoline excretion decreased by 22% and 27% on days 1 and 3, respectively, after the exercise. These results suggest that the early response of bone to a bout of resistance exercise in untrained individuals was transient decreases in bone formation and resorption, whereas urinary calcium excretion increased.

Acid Phosphatase↗
PubMed1998

Amelioration of neurovascular deficits in diabetic rats by a novel aldose reductase inhibitor, GP-1447: minor contribution of nitric oxide.

The effects of a novel potent aldose reductase inhibitor, GP-1447 [3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]-5-methylphenylace tic acid] on the sciatic nerve blood flow in streptozotocin-induced diabetic rats were examined. Blood flow was analyzed in terms of mass, i.e. the volume of blood in tissue, and of velocity, i.e. the velocity of the blood flow. In diabetic rats, a 63% decrease in blood flow due to a decrease in velocity was observed. The blood mass in the same animals fluctuated, thereby increasing its range of values. Treatment with GP-1447 at a dose of 30 mg/kg per day for 4 consecutive weeks following a 3-week period without treatment ameliorated the reduced blood flow by 51%, and was accompanied by a recovery of velocity. The increase in the range of blood mass values was reversed by treatment with GP-1447. The restoration of the range of blood mass values, but not that of the blood flow, by GP-1447 was blocked by treatment with the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine. Motor nerve conduction velocity (MCV) changes in parallel with blood flow values, while it is inversely proportionate to alterations in the range of blood mass values. It is suggested that the observed beneficial effect of GP-1447 on blood flow is involved in the restoration of decreased MCV in diabetes. It would appear that GP-1447-induced amelioration of neurovascular defects is not mediated solely by the improvement of the NO system.

Aldehyde Reductase↗
PubMed1998

[Tuberculosis in circulation system].

Tuberculous pericarditis develops either via hematogenous or lymphangeal spread, or directly from pulmonary lesions. Tuberculous pericarditis begins with fibrin deposits, granuloma formation, and the presence of live acid-fast bacilli. A pericardial effusion, which is serous but often contains some blood with a high level of protein. Recently, PCR technology has been employed to amplify M. Tuberculosis DNA from pericardial fluid. The elevation of ADA (> 45 U/l) is supportive of the diagnosis. Tuberculous pericarditis is detected clinically either in the effusive stage by nonspecific systemic syndrome or after the development of constrictive pericarditis. The short-course treatment of tuberculous pericarditis should consist of three-drug regimen, such as INH, RFP, PZA, SM, EB. The use of prednisolone is controversial. Tuberculous myocarditis is extremely rare because of low affinity between M. Tuberculosis and myocardium. Most cases of tuberculous pericarditis are clinically silent and diagnosed at autopsy.

Humans↗
PubMed1997

Myocardial osteopontin expression is associated with left ventricular hypertrophy.

BACKGROUND: Osteopontin (OP) has been identified in cultured rat cardiac fibroblasts, where it contributes to angiotensin II (AII)-induced remodeling processes; in cultured cardiomyocytes; and in macrophages in cardiac tissues with inflammation. However, the presence of OP has not been reported in histological sections of myocardial tissue. In the present study, we investigated (1) the regulation of OP mRNA expression in cultured rat cardiomyocytes; (2) the localization of OP mRNA in neonatal and adult normal and hypertrophied rat hearts; and (3) the histology of OP expression in myocardial specimens from humans either with myocyte hypertrophy or with no pathological changes. METHODS AND RESULTS: Cultured neonatal cardiomyocytes expressed OP mRNA and were immunoreactive for OP. Endothelin-1 (ET-1) and norepinephrine (NE) increased both OP and atrial natriuretic peptide (ANP) mRNA levels twofold to threefold (P<.01). OP mRNA was prominent in ventricular tissue from neonatal and adult rats with renovascular hypertension and aortic banding, whereas barely detectable levels were observed in normal adult cardiac tissue. ANP and OP mRNA levels in normal and hypertrophied ventricles correlated (r2=.87, P<.001). OP immunoreactivity and mRNA transcripts were predominantly found in cardiomyocytes not associated with inflammatory cells in sections from neonatal and adult hypertrophied hearts. No staining was detectable in normal adult hearts. Human myocardium with extensive fibrosis and cardiomyocyte hypertrophy obtained from explanted hearts with either idiopathic (n=5) or ischemic cardiomyopathy (n=7) demonstrated substantial myocyte immunoreactivity for both OP and ANP in right and left ventricles that was not associated with leukocyte infiltration. In situ hybridization identified cardiomyocytes as the major source of OP mRNA transcripts in these hearts. In contrast, OP immunoreactivity was not detectable in four of five endomyocardial biopsies with normal histology. CONCLUSIONS: The present study provides the first evidence that cardiomyocytes are a prominent source of OP in vivo and suggests that induction of OP expression is strongly associated with ventricular hypertrophy.

Animals↗
PubMed1997

Scanning electron microscope examination of pancreatic ducts in stroke-prone spontaneously hypertensive rats (SHRSP).

CONCLUSION: Ischemic injury to the pancreatic ductal cells causes stasis of pancreatic juice, which in turn induces chronic pancreatitis. BACKGROUND: The pathogenesis of chronic ischemic pancreatitis is still unclear. METHODS: In 12-, 24-, and 36-wk-old male stroke-prone spontaneously hypertensive rats (SHRSP), which have sclerotic arterioles with a marked narrowing lumen in the pancreas, pancreatic tissue was examined using light and scanning electron microscopy. Corrosion casts of pancreatic ducts and blood vessels were examined using scanning electron microscopy. RESULTS: Ductular proliferation, tortuous ductal channels, crater-like depressions of ductal inner surfaces, and long cilia of ductal cells were found to be sporadically distributed throughout the pancreatic tissue. Similar pancreatic abnormalities had been found in previous studies using WBN/Kob rats that exhibited pancreatic juice stasis. A few interlobular ducts in the pancreatic tissue of the SHRSP had an inner surface that was gyrus-like in appearance, a feature not found in WBN/Kob rats.

Aging↗