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Biomedical subjects

M Sawamura

Publications and source records attributed to M Sawamura.

At least 55 records · Page 3Linked to original sources
PubMed1996

The region responsible for stroke on chromosome 4 in the stroke-prone spontaneously hypertensive rat.

To detect genetic loci responsible for stroke susceptibility, we produced 107 male F2 progenies crossed between stroke-prone spontaneously hypertensive rats (SHRSP/Izm) and normotensive Wistar Kyoto rats (WKY/Izm) and followed them up until they developed cerebral stroke. One hundred and twenty-five simple sequence repeat (SSR) markers were analyzed in these F2 rats. Nine of 107 F2 rats suffered from macroscopically overt stroke. In these 9 rats, the segregation ratio of 3 genotypes at 6 SSR marker loci on chromosomes 2, 4, 9, and 10 was highly distorted from the expected value (the observed sp/sp:sp/wky:wky/ wky ratio was either 6:3:0 or 6:2:1, while the expected was 1:2:1, p < 0.01 by chi 2 test). Further, the brain weight was significantly heavier (p < 0.001) in the F2 rats suffering from stroke, suggesting that the brain weight was a parameter for stroke. The brain weight of F2 rats cosegregated with D4Mit19, D4Mgh7, and D4Mgh8 (p = 0.0015, 0.0014, and 0.0040 by ANOVA, respectively) on chromosome 4 supporting genetic effects of this genetic loci on the pathogenesis of cerebral stroke. Blood pressure did not cosegregate with these markers on chromosome 4. These results suggest that a region on chromosome 4, independently of hypertension, determines genetic susceptibility to cerebral stroke.

Animals↗
PubMed1996

Direct inhibitory effects of taurine on norepinephrine-induced contraction in mesenteric artery of stroke-prone spontaneously hypertensive rats.

The effect of taurine on vascular reactivity was investigated in the mesenteric artery of Wistar Kyoto (WKY), and stroke-prone spontaneously hypertensive rats (SHRSP). Administration of taurine significantly decreased blood pressure of SHRSP but not WKY. The mesenteric artery of taurine-treated SHRSP was excised to observe the contractile responses to transmural electrical stimulation and to several vasoactive substances. Vasocontraction induced by norepinephrine (NE) was significantly decreased by taurine. However, contraction elicited by the other substances tested was not affected. Consistently, when the vessels of SHRSP were pretreated with taurine in vitro, only the NE-induced vasocontraction was specifically attenuated. No effect was observed in WKY vessels. These results indicate that the hypotensive effect of taurine is accounted for at least in part its direct action on blood vessels.

Analysis of Variance↗
PubMed1996

Effects of oral taurine supplementation on lipids and sympathetic nerve tone.

OBJECTIVES: To assess effects of oral taurine supplementation on lipids and sympathetic nerve tone in healthy young men on experimental high fat and cholesterol diets. METHODS: Twenty-two healthy male volunteers, aged 18-29 years, were recruited for this randomized control trial after informed consent according to the Ethical Committee of Shimane Medical University. Volunteers were randomly allocated into 2 study groups and given experimental diet of identical regimen [total calorie 2500 kcal, cholesterol 1000 mg, polyunsaturated fat/saturated fat (P/S) ratio 0.52, fat 40% of total energy intake (%E), protein 14%E, carbohydrate 46%E] to raise serum cholesterol (CHO) level for 3 weeks. Alcohol intake, smoking and strenuous physical activities were prohibited. Taurine powder (6 g/day) was supplied to one group (T-group, N = 11) and placebo capsules to the other (C-group, N = 11), by a single-blind approach. Blood samples and 24 h urine specimens were obtained once every week. Two men in the C-group dropped out due to upper respiratory infection. There were no difference in age, body mass index (BMI) or blood pressure (BP) between the groups. Statistical analysis was performed by analysis of variance (ANOVA, repeated measurement) and Student's t-test. RESULTS: There were no changes in BMI and BP in either group during the period. Significant increases in total CHO (25.4 +/- 17.5 mg/dl, mean +/- SD), LDL-CHO (17.1 +/- 14.5) and LDL (43.9 +/- 37.6) were observed in C-group but were attenuated in the T-group. The T-group showed significant increases in VLDL-CHO, VLDL and TG. The T-group had significantly lower urinary norepinephrine excretion than the C-group in the last week. CONCLUSION: Oral taurine supplementation attenuated increases in T-CHO, LDL-CHO and LDL in healthy men on high fat cholesterol diets but induced significant increases in VLDL-CHO, VLDL and TG, which could be explained by a possible effect of taurine on lipoprotein lipase. Significantly lower urinary norepinephrine excretion observed by the taurine administration implies the suppression of the sympathetic nervous system.

Adolescent↗
PubMed1996

Pravastatin affects blood pressure and vascular reactivity.

To investigate the effect of endogenous cholesterol synthesis on blood pressure and vascular response, a HMG CoA reductase inhibitor, pravastatin (1 or 10 mg/kg per day) was administered orally for 2 or 4 weeks to spontaneously hypertensive rats (SHR/lzm) and normotensive Wistar-Kyoto (WKY/lzm) rats. Blood pressure was significantly increased in the pravastatin-treated groups of both strains, occurring in WKY after a longer treatment period than in SHR. The thoracic aortas from SHR and WKY were pretreated with pravastatin (10(-4)M). The vascular response to norepinephrine in terms of both contractility and sensitivity, was increased in the pravastatin-treated SHR aorta but not in the WKY aorta. The increased response was not observed in the presence of mevalonate. Acetylcholine-induced vascular relaxation in the aortas from both strains was not affected by pravastatin pretreatment. These results suggest that the vascular response to norepinephrine may be affected by the intracellular cholesterol synthesis pathway.

Animals↗
PubMed1996

Cosegregation of the new region on chromosome 3 with salt-induced hypertension in female F2 progeny from stroke-prone spontaneously hypertensive and Wistar-Kyoto rats.

1. We investigated candidate loci for salt-sensitive high blood pressure (BP) in F2 progeny from crossing Wistar-Kyoto and stroke-prone spontaneously hypertensive rats. 2. In female F2 progeny, systolic and diastolic BP on the 12th day and the seventh month after salt loading was strongly linked with the D3Mgh12 and D3Mgh6 loci on chromosome 3, respectively. 3. These loci were linked with BP only in female F2 progeny, not in males. 4. These results indicate that hormonal factors may influence salt sensitivity, particularly with respect to gender differences.

Animals↗
PubMed1996

Tumor necrosis factor-alpha and interleukin 4 in myeloma cell precursor differentiation.

Multiple myeloma is a B-cell malignancy characterized by the accumulation of a clonal population of plasma cells in the bone marrow that secrete a monoclonal immunoglobulin protein. It has been regarded as a tumor arising at the B, pre-B lymphocyte, or even stem cell level. Precursor cells are presumed to proliferate and differentiate, giving rise to clonal expansion in plasma cells. Peripheral blood mononuclear cells (PBMC) from 36 patients with multiple myeloma, 12 with monoclonal gammopathy of undetermined significance (MGUS), and 21 healthy controls were cultured in vitro in the presence of tumor necrosis factor-alpha (TNF-alpha) and interleukin 4 (IL-4). We have demonstrated that monoclonal plasma cells can be induced in different proportions from PBMC obtained from myeloma patients when exposed in vitro to TNF-alpha and IL-4. Although myeloma cell precursors cannot be distinguished from other cells by morphology, a high number of monoclonal plasma cells was detected in our culture system on day 4 even when plasma cells accounted for less than 0.2% of the cells seeded on day 0. In 16 of the 36 patients with myeloma, monoclonal plasma cells appeared after 4 days. These changes were not observed in PBMC from patients with MGUS or from controls. These findings thus suggest that circulating myeloma cell precursors differentiate into plasma cells in the presence of TNF-alpha and IL-4, and the variation in the number of myeloma cell precursors in peripheral blood could therefore be used as a prognostic parameter in response to chemotherapy in myeloma patients.

Cell Differentiation↗
PubMed1995

Steroid-responsive pulmonary disorders associated with myelodysplastic syndromes with der(1q;7p) chromosomal abnormality.

We report three patients with pulmonary disorders associated with myelodysplastic syndromes (MDS). All three patients had symptoms of pyrexia and respiratory discomfort. One patient had pulmonary eosinophilia with bilateral pleural effusion, one had interstitial pneumonia, and one had bilateral pleural effusion caused by systemic vasculitis. Elevated C-reactive protein (CRP) levels, polyclonal hypergammaglobulinemia, and morphological abnormalities in peripheral blood were observed in all three patients. The bone marrow of these patients revealed trilineage dysplasia and eosinophilia. Cytogenetic analysis showed [46,XY,-7,+der(1q;7p)]. Antibiotic treatment was not effective. However, improvement was dramatic after corticosteroid treatment; CRP levels were reduced and the hypergammaglobulinemia was improved. These cases suggest that MDS with [-7,+der(1q;7p)] may be correlated with bone marrow eosinophilia and that an immunologic abnormality may be involved in the pulmonary disorders.

Adrenal Cortex Hormones↗
PubMed1995

Synthesis and cellular characterization of the detransformation agent, (-)-depudecin.

BACKGROUND: (-)-Depudecin is a fungal metabolite that reverts the rounded phenotype of NIH3T3 fibroblasts transformed with v-ras and v-src oncogenes to the flat phenotype of the nontransformed parental cells. The mechanism of action of this detransformation agent is unknown. Although depudecin appears to be an excellent molecule for probing signaling pathways that regulate changes in the cytoskeletal architecture, reagents based on depudecin are not available as it has not yet been successfully synthesized. We therefore set out to synthesize (-)-depudecin. RESULTS: An asymmetric synthesis of (-)-depudecin has been developed. A cell staining assay has been used to reveal the ability of synthetic depudecin, but not several structural variants, to induce a flattened morphology in v-Ha-ras-transformed NIH3T3 cells. This assay also shows that depudecin induces an intricate network of actin stress fibers in these cells and in MG63 osteosarcoma cells and reveals the essential role of the epoxide and hydroxyl moieties in depudecin. Cycloheximide and actinomycin D inhibited the ability of depudecin to induce a morphological change, suggesting that both mRNA synthesis and de novo protein synthesis are required for depudecin-mediated suppression of the transformed phenotypes in ras-transformed cells. CONCLUSIONS: The synthetic procedure provides access to (-)-depudecin and could be readily modified to produce depudecin-related reagents for the identification of depudecin's cellular target(s). This target appears to be involved in the regulation of the assembly of the actin microfilament component of the cytoskeleton in mammalian cells.

3T3 Cells↗
PubMed1995

A new locus on chromosome 3 strongly linked with salt-sensitive high blood pressure in female F2 from SHRSP and WKY rats.

1. We investigated candidate loci for salt-sensitive high blood pressure in F2 progeny from crossing Wistar-Kyoto rats and stroke-prone spontaneously hypertensive rats. 2. The average systolic and diastolic blood pressure did not increase in male and female F2 progeny by the 12th day after salt loading. 3. In female F2 progeny, systolic and diastolic blood pressure became strongly linked with the MITR244 locus on chromosome 3, 1 month and 12 days after salt loading. 4. This locus became linked with blood pressure only in the female F2 progeny and not in the males. 5. These results indicate that hormonal factors and gender differences, in particular, might influence salt sensitivity.

Animals↗
PubMed1995

HMG-CoA reductase inhibitor affects blood pressure and vascular reactivity.

1. To investigate the effect of endogenous cholesterol synthesis on blood pressure and vascular response, a HMG CoA reductase inhibitor, pravastatin (1 or 10 mg/kg) was administered orally for 2 or 4 weeks to 8-13 week old spontaneously hypertensive rats (SHR/Izm) and normotensive Wistar-Kyoto (WKY/Izm) rats. 2. Blood pressure was significantly increased in the pravastatin-treated groups of both strains, but the elevation was observed in WKY after a longer treatment than in SHR. 3. After the thoracic aorta from 10-12 week old SHR and WKY was pretreated with pravastatin (10(-4) mol/L), the vascular response to norepinephrine was increased in pravastatin-treated SHR aorta but not in the WKY aorta in both contractivity and sensitivity. 4. These experiments suggest that the vascular response is affected by intracellular cholesterol synthesis pathway.

Animals↗
PubMed1995

Effect of lovastatin and fluoromevalonate on phosphatidylinositol 3-kinase activity stimulated with PDGF.

1. Phosphatidylinositol 3-kinase (PI3K) appears to have a crucial role in cellular proliferation induced by platelet-derived growth factor (PDGF). However, the mode of activation of the enzyme has been unclear so far. In the present study, we investigated the effects of a cholesterol lowering drug on [3H]-thymidine ([3H]-TdR) incorporation and PI3K activity in cultured vascular smooth muscle cells (VSMC) stimulated with PDGF. 2. PDGF stimulated both [3H]-TdR incorporation and PI3K activity immunoprecipitated with antiphosphotyrosine antibody in a dose dependent manner (ED50 was 4 ng/mL for [3H]-TdR uptake and 3 ng/mL for PI3K activity). Lovastatin inhibited serum-stimulated [3H]-TdR incorporation dose dependently. PI3K activity induced by PDGF was also inhibited in a dose dependent manner; however, its activity was 61% at 10(-6) mol/L, 72% at 10(-5) mol/L and 8% at 10(-4) mol/L of the control value. 3. These inhibitory effects of lovastatin were completely abolished by adding 1 mmol/L mevalonic acid (MVA), suggesting that MVA metabolites had some important role on the PI3K activation and cellular proliferation. 4. Fluoromevalonate (Fmev), a competitive inhibitor of mevalonate diphosphate (MVA-PP) decarboxylase, inhibited [3H]-TdR incorporation at concentrations more than 10(-6) mol/L. Moreover, marked inhibitory effect was observed at concentrations of 10(-7) and 10(-8) mol/L (76% of control). PI3K activity was also reduced by 10(-3) mol/L Fmev (0.2% of control). However, in contrast to [3H]-TdR uptake, there was no inhibitory effect detected at concentrations up to 10(-4) mol/L. 5. These results suggest that PDGF-stimulated PI3K activity as well as cellular proliferation was modified by protein isoprenylation.

Animals↗
PubMed1995

Increased intraplatelet and urinary transforming growth factor-beta in patients with multiple myeloma.

The concentrations of transforming growth factor-beta (TGF-beta) in platelets, plasma and urine from 27 patients with multiple myeloma (MM) and from 22 normal controls were measured by sandwich enzyme-linked immunosorbent assay using a monoclonal antibody specific for human TGF-beta 1+2+3. A significantly increased intraplatelet TGF-beta (24.6 +/- 9.6 vs. 17.8 +/- 8.8 ng/10(5) platelets, p < 0.01) and urinary TGF-beta (1.4 +/- 0.8 vs 1.0 +/- 0.4 ng/mg Cr, p < 0.02) were observed in MM patients compared with normal controls. The mean platelet TGF-beta level in MM patients with osteolytic lesions was more increased than in those without osteolytic lesions (29.6 +/- 7.7 vs 18.4 +/- 8.2 ng/10(5) platelets, p < 0.001). In this study, we evaluated the possible role of TGF-beta in the pathogenesis of myeloma, especially in osteolytic lesions.

Aged↗
PubMed1995

Histamine excess symptoms in basophilic crisis of chronic myelogenous leukemia.

We encountered a patient with chronic myelogenous leukemia in basophilic crisis accompanied with histamine excess symptoms including bronchial asthma and gastric ulcer. The concentrations of histamine and histidine decarboxylase in leukemic cells containing granules typical for basophils were similar to those in mature basophils. His histamine excess symptoms rapidly disappeared concomitant with the reduction of blast cells after chemotherapy. We speculate that his histamine excess symptoms were induced by the leukemic cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

In search of genes causing spontaneous hypertension.

1. Basal high blood pressure (BP) in the male and female F2 progeny produced by crosses between Wistar Kyoto rats (WKY/lzm) and stroke-prone spontaneously hypertensive rats (SHRSP/lzm) linked strongly with the leukosialin locus on chromosome 1. 2. Excess salt intake caused elevation of BP and the response was larger in the females than the males. 3. In the male F2 progeny, salt-sensitive hypertension significantly cosegregated with the RR1023 marker on chromosome 10, rather than with the angiotensin converting enzyme locus. 4. In the female F2 progeny, salt-sensitive hypertension significantly linked with the MitR244 marker on chromosome 3.

Analysis of Variance↗
PubMed1995

Ethnicity, environment and salt-sensitivity in cardiac study: epidemiological implications for prevention.

1. An association between Na and blood pressure (BP) was studied in the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study, an international cross-sectional epidemiological study, involving 55 populations from 25 nations. 2. The partial regression coefficient of BP against 24 h urinary Na was calculated in a multiple linear regression model, by adjusting other confounding factors. This demonstrated different distribution in each of several groups stratified according to their ethnicity and geographical location. 3. The relationship of urinary K to BP regression against urinary Na excretion was investigated to clarify its role in the association of Na with BP. 4. Urinary Na/K ratio showed a significant inverse linear relationship with the regression coefficient of BP on urinary Na excretion among seven Japanese populations. 5. The effect of K was to increase urinary Na excretion, as the ratio of Na/K might modify the association between Na and BP.

Blood Pressure↗