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Biomedical subjects

M Tsujino

Publications and source records attributed to M Tsujino.

At least 37 records · Page 2Linked to original sources
PubMed1992

Endothelin-1 enhances calcium entry through T-type calcium channels in cultured neonatal rat ventricular myocytes.

Endothelin-1 (ET-1), a 21-amino acid vasoconstrictive peptide, increases intracellular Ca2+ level and has hypertrophic action on ventricular myocytes. To elucidate a possible role of Ca2+ entry through sarcolemmal Ca2+ channels on this ET-1 action, we examined effects of ET-1 on L-type (ICa,L) and T-type (ICa,T) Ca2+ currents in cultured neonatal rat ventricular myocytes using the patch-clamp technique. ET-1 at a concentration of 10 nM increased the maximum current density of ICa,T from -3.0 +/- 1.4 microA/cm2 in the control condition to -4.4 +/- 1.6 microA/cm2 (p < 0.01). Although the peak amplitude of ICa,L was decreased during ET-1 application (from -9.7 +/- 1.9 microA/cm2 in the control condition to -5.0 +/- 1.4 microA/cm2 [p < 0.01]), this magnitude of decrease in ICa,T (52 +/- 19%) was comparable to that of spontaneous "run-down" of ICa,L (47 +/- 26%). The enhancement of ICa,T by ET-1 was dose dependent; it was initiated as low as 0.32 nM, and the maximal response was attained at approximately 10 nM, with a half-maximal dose of 1.26 nM. The enhancement of ICa,T by ET-1 was antagonized by protein kinase C inhibitors staurosporine (0.2 microM) and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7, 20 microM) applied to the pipette solution. Extracellular application of tumor-promoting phorbol esters, phorbol 12,13-dibutyrate (PDBu) and 4 beta-phorbol 12-myristate 13-acetate, augmented ICa,T. PDBu (0.2 microM) increased the maximal current density of ICa,T from -4.2 +/- 0.5 microA/cm2 in the control condition to -5.5 +/- 1.0 microA/cm2 (p < 0.01). In the presence of H-7 (20 microM) in the pipette solution, PDBu failed to enhance ICa,T, and an inactive isomer of PDBu (4 alpha-phorbol 12,13-dibutyrate, 0.2 microM) did not augment ICa,T. Thus, ET-1 enhances Ca2+ entry through the sarcolemmal T-type Ca2+ channel, possibly through a pathway involving activation of protein kinase C. This ET-1 action may be involved in the rise of the intracellular Ca2+ level and may contribute to the induction of cardiac hypertrophy by ET-1.

Animals↗
PubMed1992

Effects of manidipine on DNA and protein syntheses in cultured vascular smooth muscle and endothelial cells and on proto-oncogene expression.

To elucidate the importance of Ca2+ influx via voltage-dependent Ca2+ channels in the mechanism of vascular remodeling, we investigated effects of a new Ca2+ channel blocker manidipine on DNA and protein syntheses stimulated by several mitogens in cultured rat vascular smooth muscle cells (VSMC) and bovine endothelial cells (EC), and growth-related immediate early proto-oncogenes expression in VSMC. Endothelin-1 (ET-1) induced receptor-mediated phosphoinositide breakdown and increased cytosolic free Ca2+ levels in rat VSMC, with concomitant increases in proto-oncogenes (c-fos c-myc) mRNA levels as well as DNA and protein syntheses. Manidipine dose-dependently (10(-9) M to 10(-6) M) inhibited DNA, and protein syntheses stimulated by 10(-7) M ET-1 in rat VSMC; manidipine was a more potent inhibitor for protein synthesis (IC50: 10(-8) M) than for DNA synthesis (IC50: 10(-7) M). Manidipine also inhibited DNA synthesis stimulated by 10 ng/mL bFGF and 2.5% FCS in rat VSMC and bovine EC; manidipine was more potent in inhibiting DNA synthesis stimulated by bFGF than that by FCS in both cells. The expression of ET-1-induced c-fos and c-myc mRNAs levels was unaffected by manidipine. These results suggest that manidipine has potent inhibitory effects on the ET-1-induced hyperplasia and/or hypertrophy of VSMC, as well as on the bFGF-induced hyperplasias of VSMC and EC, thus implicating its potential usefulness for preventing abnormal VSMC proliferation and angiogenesis associated with hypertension and atherosclerosis.

Animals↗
PubMed1991

[Superoxide anion (O2-) production by polymorphonuclear leukocytes in insulin dependent diabetes mellitus (IDDM)].

The superoxide anion (O2-) production in polymorphonuclear leukocytes stimulated by phorbol myristate acetate in IDDM and non-insulin dependent diabetes mellitus (NIDDM) was determined by the method of Johnston et al, compared with that of each age matched controls. And the correlation between O2- production and hemoglobin (Hb) A1 and A1c value was investigated. The O2- production in IDDM was 24.4 +/- 7.4 (mean +/- SD, n mol per 4 X 10(5) cells) at 10 min. and 51.4 +/- 8.7 at 30 min., in NIDDM each 31.6 +/- 9.3, 60.2 +/- 14.4, and in controls each 40.5 +/- 4.2, 72.4 +/- 3.1. O2- production in IDDM was significantly lower than that in NIDDM (p less than 0.001 at 10 min. and p less than 0.01 30 min.) and controls (p less than 0.001 at 10 and 30 min.). O2- production at 10 and 30 min. possessed a negative correlation with Hba1 and A1c value (HbA1: p less than 0.01 at 10 min. p less than 0.05 at 30 min., HbA1c: p less than 0.01 at 10 and 30 min.). These findings suggest that impaired O2- production might be one of the factors accounting for depressed bactericidal activity of polymorphonuclear leukocytes in IDDM, and that a protracted hyperglycemia might shed some effect on O2- production.

Adult↗
PubMed1991

Endothelin-1 induces hypertrophy with enhanced expression of muscle-specific genes in cultured neonatal rat cardiomyocytes.

To determine whether endothelin-1 (ET-1) induces hypertrophy of cardiomyocytes, the effects of ET-1 on the expression of muscle-specific genes and a proto-oncogene, c-fos, in cultured neonatal rat cardiomyocytes were examined by Northern blot analysis. ET-1 (10(-7) M) induced about twofold to fourfold increases in the gene expression of myosin light chain 2, alpha-actin, and troponin I after 6 hours, which continued up to 24 hours. The ET-1-induced increases in mRNA levels for these muscle-specific genes were dose dependent (10(-9) to 10(-7) M). Run-on transcriptional assay showed that the changes in mRNA level for three muscle-specific genes were regulated, at least in part, at the transcriptional level. 12-O-Tetradecanoylphorbol 13-acetate (TPA), a potent protein kinase C activator, and the Ca2+ ionophore ionomycin also increased mRNA levels of three muscle-specific genes. ET-1, TPA, and ionomycin similarly induced the expression of c-fos after 30 minutes, which returned to an undetectable level after 6 hours. ET-1 remarkably and dose-dependently stimulated accumulation of total inositol phosphates in cardiomyocytes. Morphometrical evaluation showed that ET-1 significantly increased surface area of cardiomyocytes without cell proliferation. ET-1 also dose-dependently stimulated the synthesis of protein and DNA, which was unaffected by the L-type calcium channel blocker nicardipine. These data suggest that ET-1 induces hypertrophy of cardiomyocytes associated with the induction of muscle-specific gene transcripts through the possible involvement of protein kinase C activation or intracellular Ca2+ mobilization.

Animals↗
PubMed1991

[Dry cough in the elderly patients treated with angiotensin converting enzyme inhibitor].

Since dry cough has recently been recognized as a side effect of angiotensin converting enzyme (ACE) inhibitors employed in the treatment of hypertension or congestive heart failure, the incidence of dry cough in elderly patients receiving ACE inhibitors was investigated. There were 237 out-patients on either captopril, enalapril, or delapril, in August and November 1989. Questionnaires concerning dry cough and smoking were completed by 184 patients. Patients either less than 50 years of age, or with chronic pulmonary disease were excluded. The remaining 168 patients, 63 males, 105 females, with a mean age of 73 years were analyzed for the incidence of a dry cough in relation to age, sex, smoking, and type of drugs. The overall incidence of a dry cough was 21/168 (12.5%), 7/63 (11.1%) for males and 14/105 (13.3%) for females, and was less frequent with advancing age; in the 51-60 age group 4/11 (36.4%), in the 61-70 age group 5/39 (12.8%), in the 71-80 age group 9/75 (12.0%), in the 81-90 age group 3/40 (7.5%), in the 91- age group 0/3 (0%). Enalapril showed significantly higher incidence of dry cough than captopril (16/93, 17.2% vs 7/88, 8.0%, p less than 0.05). Delapril showed an incidence 4/11, 36.4%, however, 9 out of the 11 patients who were given delapril had had a history of a dry cough with captopril or enalapril, and in 4 out of these 9 patients the dry cough disappeared by replacement of captopril or enalapril by delapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

[Pharmacokinetics of cefodizime in patients undergoing hemodialysis].

The object of this study was to establish the most effective regimen of cefodizime (CDZM) for patients with chronic renal failure undergoing hemodialysis (HD). T 1/2 beta of CDZM upon 1 g intravenous administration was 3.50 +/- 0.72 hours in an on-HD group, and it was 11.26 +/- 3.89 hours in an off-HD group. When CDZM was administered consecutively at a dose of 1 g or 2 g only after HD, the serum concentration of CDZM was maintained at levels sufficient to exert antibacterial activity, and no tendency for accumulation was observed. The most effective regimen of CDZM to HD patients, therefore, has been that in which concluded to administration was done only after completion of HD, in a dose of 1 g for mild infections and that of 2 g for severe infections.

Cefotaxime↗
PubMed1990

Regression of left ventricular hypertrophy in patients with essential hypertension: outcome of 12 years antihypertensive treatment.

To assess the regression of cardiac hypertrophy during long-term (12 years) antihypertensive treatment, the following parameters were determined in 93 patients with essential hypertension: SV1 + RV5 by electrocardiography (ECG), and septal wall (SW) and posterior wall (PW) thickness by echocardiography (UCG). The patients were treated with a thiazide diuretic alone (group 1), thiazide + beta-blocker (group 2), thiazide + methyldopa or nifedipine (group 3) or nifedipine or methyldopa alone (group 4). The blood pressure decreased gradually within 6 months of treatment. According to ECG, regression of left ventricular hypertrophy occurred during the initial 7 years in all groups, whereas in the subsequent 5 years, statistically significant regression was found only in the patients treated with thiazide + other drugs (group 3). By UCG, which was taken only at the 7th and 12th year, regression was detectable during the last 5 years in all groups. The apparent incidence of regression of hypertrophy was lower in the thiazide-alone group (group 1) than in the thiazide + beta-blocker group (group 2), most likely due to mild hypertension in group 1. A cardiovascular accident (nonfatal myocardial infarction) occurred only in 1 patient. We conclude that during long-term antihypertensive treatment, persistent, progressive reversal of cardiac hypertrophy takes place.

Adrenergic beta-Antagonists↗
PubMed1990

[Activation and regulation of macrophages induced by inoculation of cryodestroyed tumor cells].

Cryosurgery provides two prominent features, that is in situ destruction of malignant tumor and potential immunotherapy against tumor. In order to investigate the immunological response after cryosurgery, immunological system of macrophage activation were studied in an experimental tumor system using BALB/c mice and syngeneic Meth-A fibrosarcoma. The mice inoculated the cryodestroyed Meth-A (Cryo-Meth-A mice) acquired antitumor potency in Meth-A challenge test, and the mice inoculated the Mitomycin C treated Meth-A (MMC-Meth-A mice) also acquired antitumor potency. Spleen cells of Cryo-Meth-A mice showed antitumor activity in Winn assay, and spleen cells of MMC-Meth-A mice also showed antitumor activity. The effector cells in Cryo-Meth-A mice were mainly macrophages and natural killer (NK) cells. On the other hand, they were mainly macrophages and cytotoxic T lymphocytes (CTL) in MMC-Meth-A mice. The maximum macrophage cytostatic activity of Cryo-Meth-A mice was noted on 14 days after inoculation (Day 14), whereas it appeared on Day 7 and continued until Day 14 in MMC-Meth-A mice. Macrophages of Cryo-Meth-A mice enhanced the production activity of interleukin 1 (IL-1), interferon (IFN) and prostaglandin E2 (PGE2). On the other hand, macrophages of MMC-Meth-A mice enhanced production activity of tumor necrosis factor (TNF) and increased Ia antigen positive ratio. These findings suggest that macrophages of both groups are activated by different immunological mechanisms. It was found that Cryo-Meth-A played a role as an alpha-IFN inducer, and the macrophages stimulated with Cryo-Meth-A produced alpha-IFN in vitro. Intraperitoneal (i.p.) administration of the anti-alpha-IFN antibody carried down-regulation of macrophage cytostatic activity and NK activity of Cryo-Meth-A mice, whereas MMC-Meth-A mice were not. In addition to these findings, CTL activity enhanced some extent by i.p. administration of the anti-alpha-IFN antibody. These facts suggest that the alpha-IFN have two ways of immunological regulation, the first one is the activation of macrophage cytostatic activity and NK activity, and the other is down-regulation of CTL activity by suppression of Ia antigen expression of macrophages. These results suggest that cryodestruction changes the tumor antigen of Meth-A cells, thereby Cryo-Meth-A induces peculiar immunological response.

Animals↗
PubMed1989

Amino acid sequences of cytotoxin-like basic proteins derived from cobra venoms.

Amino acid sequences of cytotoxin-like basic proteins (CLBPs), purified from the venoms of Formosan cobra (Naja naja atra) and Indian cobra (Naja naja), were reinvestigated. The determined sequences differed from those reported previously by Takechi et al. [(1985) Biochem. Int. 11, 795-802; (1987) Biochem. Int. 14, 145-152]. The sequence of CLBPs at residues 25-30 was found to be hydrophilic as compared with those of cytotoxins. The difference in the hydrophobicity of this region might be responsible for the difference in their cytotoxic activities.

Amino Acid Sequence↗
PubMed1989

Isolation and characterization of new thiol protease inhibitors estatins A and B.

New thiol protease inhibitors, estatins A and B, were isolated from the culture filtrate of Myceliophthora thermophila M4323. The basic, water-soluble inhibitors were characterized as having an agmatine, trans-epoxysuccinic acid and L-phenylalanine or L-tyrosine moieties in the structure. The molecular formulas C18H25N5O5 and C18H25N5O6 for A and B were indicated by elemental analysis and fast atom bombardment MS. Estatins were specific inhibitors against thiol proteases such as papain, ficin and bromelain. They suppressed IgE antibody production in mice, but not IgG.

Agmatine↗
PubMed1988

[Pharmacokinetics of cefmenoxime in renal-failure patients undergoing continuous arteriovenous hemofiltration].

We investigated the pharmacokinetics of cefmenoxime (CMX) administrated to renal-failure patients undergoing continuous arteriovenous hemofiltration (CAVH). CAVH was carried out with a filter (0.5 m2) employing a PAN-50P (hollow fiber type) made of polyacrylonitrile membrane, with a blood flow rate of 100 ml/min and a filtration rate of 1,200 ml/hr. At 5 and 300 minutes after the CMX administration, the concentrations of CMX in the serum were 126.8 mg/L and 31.5 mg/L, respectively. The T1/2 beta was 3.55 hours. In 300 minutes after the administration of CMX, the total amount of CMX contained in the filtrate corresponded to 11.6% of the administered dose.

Acute Kidney Injury↗
PubMed1988

[Pharmacokinetics of cefotiam in patients undergoing continuous ambulatory peritoneal dialysis].

The pharmacokinetics of cefotiam (CTM) was investigated in 7 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). One gram of CTM was infused either intravenously (i.v. group) or intraperitoneally (i.p. group). In the i.v. group, the serum concentration of CTM at 6 hours after infusion was 25.9 mg/L and the half-life value was 5.09 hours, while the peak value of CTM in dialysate was 12.4 mg/L. In the i.p. group without peritonitis, the dialysate concentration of CTM at 6 hours after infusion was 108.6 mg/L. The serum concentration at 15 minutes after infusion was 3.0 mg/L, the corresponding peak value was 14.0 mg/L at 4 and 6 hours after infusion.

Adult↗