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Biomedical subjects

Y Takagi

Publications and source records attributed to Y Takagi.

At least 505 records · Page 28Linked to original sources
PubMed1988

Role of calcium and protein kinase C in ANP secretion by cultured rat cardiocytes.

The secretory mechanism of rat atrial natriuretic peptide (rANP) was studied in vitro with the use of primary culture of atrial myocytes from neonatal rats. Norepinephrine, phenylephrine, and carbamylcholine stimulated immunoreactive (IR) rANP secretion, whereas neither angiotensin II, arginine vasopressin, nor isoproterenol affected its secretion. The stimulatory effects of carbamylcholine and phenylephrine were blocked by atropine and prazosin, respectively. 12-O-tetradecanoylphorbol-beta-acetate (TPA), protein kinase C activator, induced a dose-dependent increase in IR rANP secretion, and TPA combined with Ca2+ ionophore ionomycin produced a synergistic effect. Ca2+-channel agonist BAY K 8644 also stimulated IR rANP secretion, the effect of which was blocked by Ca2+-channel antagonist nifedipine. These data suggest that alpha 1-adrenergic and muscarinic cholinergic agonists have direct action on rat cardiocytes to stimulate ANP secretion that involves receptor-mediated mobilization of intracellular Ca2+ and activation of protein kinase C.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Concomitant increase in cytosolic free calcium and phosphorylation of myosin light chain by vasoconstrictive hormones in cultured rat vascular smooth muscle cells.

Using the fluorescent Ca2+ indicator quin-2 to measure the cytosolic Ca2+ concentration [( Ca2+]i) and glycerol-urea polyacrylamide gel electrophoresis combined with radioimmunoblotting to assess phosphorylation of 20 k-dalton (Da) myosin light chain (MLC), the effects of angiotensin (A) II and arginine-vasopressin (AVP), both potent vasoconstrictive hormones, on changes in [Ca2+]i and phosphorylation levels of 20 k-Da MLC were studied in cultured rat vascular smooth muscle cells (VSMC). AII and AVP induced immediate (within 1 min) and dose-dependent increases in both [Ca2+]i and phosphorylation of 20 k-Da MLC. Pretreatment of VSMC with AII receptor antagonist and V1 receptor antagonist, completely blocked increases in [Ca2+]i by AII and AVP, respectively. Phosphorylation of 20 k-Da MLC stimulated by these agonists was also inhibited by their specific antagonists. These data suggest that receptor-mediated increases in [Ca2+]i by AII and AVP are closely associated with phosphorylation of 20 k-Da MLC in VSMC. The present methods should provide a suitable in vitro cell model for investigation of the molecular mechanism by which vasoactive hormones act on cells to induce contraction of vascular smooth muscle.

Aminoquinolines↗
PubMed1988

[Long term prognosis after massive small bowel resection in children].

Eight survivors after massive small bowel resection were reviewed for a period of 2 to 19 years to assess the long term prognosis of patients. The primary diseases of short bowel syndrome were congenital intestinal atresia (6) and midgut volvulus (2). The length of the residual small intestine ranged between 27 and 75 cm and ileocecal valve was also resected in 3 cases. All cases had been already weaned from parenteral nutrition and six children tolerate normal meals and two have still enteral formula at home now. Near normal somatic growth was achieved in cases which received intensive nutritional supports after operation. The D-Xylose absorption test revealed gradual improvement except one with the shortest intestine (27 cm) and fat absorption was disturbed in patients who had less than 45 cm residual intestine. Late metabolic complications, such as renal calculus, cholelithiasis and pathologic fractures were encountered in three cases.

Child, Preschool↗
PubMed1988

Antitumour activity of new semi-synthetic anthracyclines containing fluorotalopyranose.

The authors have synthesized 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl) adriamycinone (FT-ADM) which exhibited strong antitumour activity and weak toxicity. These characteristics of FT-ADM are partly due to the presence of a 2'-fluoro atom which strengthens the glycoside bond. FT-ADM, however, is sparingly soluble in water because of lack of the 3'-amino group of adriamycin. To increase the solubility of FT-ADM, a hydrophilic group was added at the 14-OH group. Then, the 14-hemisuccinate, 14-hemiglutarate, 14-hemiadipiate, 14-hemipimelate and 14-hemisuberate derivatives of FT-ADM were synthesized. Among them, the 14-hemipimelate derivative (FAD-104) was selected for further development because of its potent antitumour activity and weak toxicity. When drugs were injected intraperitoneally every day from day 1 to 9, FAD-104 showed an apparently stronger antitumour effect against mouse L-1210 leukaemia than adriamycin with lower toxicities. FAD-104 was also more effective than adriamycin on L-1210 using other administration schedules. A characteristic feature is that FAD-104 is effective over a very broad range, which will be advantageous for safe clinical use. FAD-104 also showed marked antitumour effect against L-1210 when it was injected intravenously either once on day 1 or three times on days 1, 5 and 9. Thus, FAD-104 may be a more potent antitumour anthracycline than adriamycin.

Animals↗
PubMed1988

[Correlation between histological grading and the prognosis of prostatic carcinoma--a comparative study of the Japanese General Rules of Prostatic Cancer (JGRPC) and Gleason's classification].

One hundred and sixty-seven patients with newly diagnosed, previously untreated prostatic adenocarcinoma, during the period between July, 1971 and March, 1934, were studied. The histopathologic specimens of the prostate were classified by the Japanese General Rules of Prostatic Cancer (JGRPC) and by Gleason's classification. The number of patients with well, moderately and poorly differentiated prostatic carcinomas according to the JGRPC classification was 42, 74 and 51 respectively, and the number of the patients with Gleason's pattern 1, 2, 3, 4, and 5 was 24, 20, 32, 43 and 48, respectively. The number of patients with Gleason's score (primary plus secondary pattern) 2 to 4, 5 to 7 and 8 to 10 groups was 40, 76 and 51 respectively. There was no significant difference in survival rate between well and moderately differentiated groups, but the survival rate of the group with poorly differentiated tumor was significantly lower than that of the moderately differentiated (p less than 0.01) and well differentiated (p less than 0.001) groups. There was no significant difference in 10-year survival rate between the score 2-4 and score 5-8 groups, but the score 9-10 group had a significantly lower survival rate than the score 5-8 group (p less than 0.01) and score 2-4 (p less than 0.005) group. JGRPC and Gleason's classification are thought to be equally useful in estimating prognosis of prostatic cancer, but the former is more concise and easily applicable than the latter.

Adenocarcinoma↗
PubMed1988

Platelet-enhanced apolipoprotein E production by human macrophages: a possible role in atherosclerosis.

Cholesterol-loaded human monocyte-derived macrophages increase their production of apolipoprotein E (apoE). Although cholesterol loading is often achieved with modified plasma lipoproteins, macrophages can be loaded also by coculture with platelets. Therefore, the relationship between platelet-mediated cholesteryl ester accumulation and apoE secretion was examined. Macrophages were isolated by adherence and cultured for 6 days in serum-free medium. Secreted apoE was measured with a sensitive solid-phase radioimmunoassay. Maximum apoE secretion by the adherent macrophages from 5 x 10(6) peripheral blood mononuclear cells was obtained with 3 x 10(8) platelets and was ten-fold greater than control cells cultured in the absence of platelets. Platelet-mediated apoE secretion was consistently greater than that obtained by culture with either native or acetylated low density lipoproteins. Whereas the 1000 g supernatants of unstimulated platelets were poor inducers of apoE secretion, substances rich in cholesterol that were shed from thrombin-stimulated platelets and recovered in the 1000 g supernatants were almost as active as intact platelets. In all studies, platelet-induced secretion of apoE paralleled the capacity of platelets to induce macrophage cholesterol accumulation, indicating that macrophage apoE secretion was readily influenced by macrophage cholesterol metabolism.

Apolipoproteins E↗
PubMed1987

Synthesis of antitumor-active 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl)-daunomycinone and -adriamycinone.

The title compounds (17 and 23) were prepared by coupling 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl bromide (15) with daunomycinone. The key step in the preparation of 15 was the epoxide-ring opening of methyl 2,3-anhydro-4-O-benzyl-6-deoxy-alpha-L-gulopyranoside with KHF2 in ethylene glycol, whereupon 2-fluoro-alpha-L-idopyranoside was obtained. Compounds 17 and 23 showed strong antitumor activity.

Animals↗
PubMed1987

Ventricular myocytes from neonatal rats are more responsive to dexamethasone than atrial myocytes in synthesis of atrial natriuretic peptide.

Using the primary culture of neonatal rat ventricular myocytes, synthesis and secretion of rat atrial natriuretic peptide (rANP) were studied. Ventricular myocytes in culture, although contained less amounts of cellular immunoreactive (IR)-rANP, secreted substantial amounts of IR-rANP at a rate comparable to that of atrial myocytes. Dexamethasone markedly stimulated synthesis and secretion of IR-rANP by cultured ventricular myocytes in a dose-dependent manner (10(-10)-10(-6) M), of which effect was far more potent than that in atrial myocytes. Testosterone and triiodothyronine also stimulated synthesis and secretion of ventricular IR-rANP to the extent comparable to that of atrial IR-rANP. The present study suggests that tissue-dependent difference in glucocorticoids sensitivity plays an important role in the regulation of developmental ANP gene expression in mammalian heart.

Age Factors↗
PubMed1987

Binding of synthetic beta-human atrial natriuretic peptide to cultured rat vascular smooth muscle cells.

We have studied the effects of synthetic beta-human atrial natriuretic peptide (beta-hANP), an antiparallel dimer of alpha-hANP, on receptor binding and cGMP generation in cultured rat vascular smooth muscle cells and compared the effects with those of alpha-hANP. Characteristics of temperature-dependent binding and degradation of 125I-beta-hANP were similar to those of 125I-alpha-hANP. Scatchard analysis indicated a single class of binding sites for beta-hANP with a maximal binding capacity one-half that of alpha-hANP. Parallel and antiparallel dimers were equipotent in inhibiting the binding and stimulating intracellular cGMP formation, of which the maximal effect was about one-half that of alpha-hANP. Reverse-phase high performance liquid chromatography revealed that most of beta-hANP added to cells was converted to a small molecular mass component corresponding to alpha-hANP after incubation. These data suggest that the less potent effect of beta-hANP in receptor binding and cGMP generation may be partly accounted for by the possible conversion of beta-hANP to alpha-hANP at the site of target cells.

Animals↗
PubMed1987

Effects of steroid and thyroid hormones on synthesis of atrial natriuretic peptide by cultured atrial myocytes of rat.

The in vitro effects of various steroid and thyroid hormones on synthesis of rat atrial natriuretic peptide (rANP) were studied using new-born rat atrial myocytes in culture. Dexamethasone, testosterone and triiodothyronine markedly stimulated both synthesis and secretion of immunoreactive (IR)-rANP with the same peak after 4-day-culture. Dexamethasone and testosterone dose-dependently (10(-7)-10(-6) M) stimulated synthesis of IR-rANP and were the most potent among various steroids tested. Triiodothyronine (T3) also stimulated synthesis of IR-rANP in a dose-dependent manner (10(-8)-10(-7) M), of which effect was more potent than that of tetraiodothyronine, whereas reverse T3 was ineffective. The present study clearly shows that glucocorticoids, androgens and thyroid hormones directly stimulate synthesis of ANP by atrial myocytes and suggests that ANP may play a potential role in mediating and/or modulating the biological effects by these hormones in the cardiovascular system.

Adrenal Cortex Hormones↗
PubMed1987

Down-regulation of atrial natriuretic peptide receptor and cyclic GMP response in cultured rat vascular smooth muscle cells.

Treatment of cultured rat vascular smooth muscle cells with human atrial natriuretic peptide (hANP) or Met(O)12hANP caused a similar and marked reduction (approximately 80%) of ANP receptor number (down-regulation). A second challenge with hANP stimulated the accumulation of intracellular cGMP in the down-regulated cells to the same extent as in control cells. These data suggest that ANP receptor sites are functionally heterogenous, the more abundant site being uncoupled from guanylate cyclase but susceptible to down-regulation.

Animals↗