[Endothelin-1 as an autocrine factor in hypertrophy of cardiomyocytes].
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Biomedical subjects
Publications and source records attributed to S Adachi.
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The cytostatic effect of medroxyprogesterone acetate (MPA; an oral luteohormone preparation) on two cell lines of ovarian carcinoma cultured in vitro (SHIN-3 and MN-1) was studied. At the same time, changes in the morphology and colony formation of these cancer cells after exposure to the drug were examined. 1) The doubling time of SHIN-3 cells in the logarithmic growth phase was prolonged 2.5 times at a MPA dose of 10(-8)M and 3.2 times at a MPA dose of 10(-5)M. The drug, however, exerted no significant cytostatic effect on MN-1 cells. 2) When the IC50 of MPA was assessed by counting live SHIN-3 cells in an FCS-added medium, it was 2.7 x 10(-5)M. When the same assessment was done with a medium without serum, IC50 was 6.4 x 10(-6)M. 3) After 120 hours of incubation in a medium containing 10(-8)M of MPA, CA125 (a tumor marker) production by SHIN-3 cells was suppressed by 35%. The suppression rate was 79% for SHIN-3 cells incubated in a medium containing 10(-5) of MPA. 4) The cytoplasm of SHIN-3 cells, incubated in a MPA-added medium, showed the formation of small mucous vacuoles and expansive degeneration, accompanied by a marked increase in size and thinning of the nucleus. 5) In an experiment on colony formation with collagen gel, the colony size decreased MPA concentration dependently, and was accompanied by the appearance of lobulated colonies.(ABSTRACT TRUNCATED AT 250 WORDS)
We succeeded in establishing a cell line (KEN-3) for subculture from a fibrosarcoma which originated in the ovary in a girl aged 17 years. Its characteristics and sensitivity to anticancer agents are reported in this paper. 1. Characteristics of established cell line. Lined cells consist of multinucleated giant cells mixed among many spindle-shaped cells. They grow in small colonies and have none of the pavement-like arrangement characteristic of epithelial tumor cells. The number of chromosomes ranged from 45 to 128 (mode: pseudo-triploidy region, 65). The doubling time, cellular density and plating efficiency were 76.9 hours, 5.4 x 10(5)/cm2 and 30.2%, respectively. Concerning tumor markers, CEA and sialyl SSEA-1 were only produced in small quantities. Subculture was possible subcutaneously in the nude mouse with no capacity for the production of ascites. 2. Susceptibility to anticancer agents and GP170 expression. The in vitro susceptibility to about 12 types of anticancer agents was investigated with the MTT assay. IC50/PPC was shown to be less than 1 for Adriamycin only. The sensitivity to CDDP (IC50/PPC: 4.8) was low, and no sensitivity was observed at all to DTIC, which is used frequently for mesenchymal tumors. GP170 (mdr-1 products) was positive in established cells in immunohistochemical stain.
We investigated the effect of high dose methotrexate (HDMTX) therapy on plasma hypoxanthine (Hx) and uridine (UR) concentrations in 12 children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL). The initial plasma Hx level before the first administration of HDMTX (1 g/m2) was significantly higher in patients (25.5 +/- 17.5 microM) than that in healthy adult controls (4.0 +/- 1.4 microM). By 48 or 72 hours after the beginning of MTX infusion, the Hx concentration had decreased to 7.9 +/- 7.7 microM and 4.7 +/- 4.1 microM, respectively. This decrease of plasma Hx concentration after MTX infusion was also observed with the second course of HDMTX (3 g/m2) therapy. On the other hand, the plasma UR level did not change significantly. The in vitro treatment with 2 microM MTX of hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-deficient mutant cells selected from HL-60 lowered the excretion of Hx into the culture medium. These data suggest a possible new explanation of the synergism of HDMTX and 6-thiopurines, for example 6-mercaptopurine and 6-thioguanine, since plasma Hx is considered to counteract 6-thiopurine toxicity through competition at the level of HGPRT.
A bolus of carboplatin (CBDCA) 200-450mg/body (148-292mg/m2) with 500ml saline was administrated into the abdominal cavity (ip) of 4 patients with ovarian cancer and 2 patients with uterine endometrial cancer, and concentrations of free and total platinum (Pt) in the blood and ascites were measured with the passage of time. Moreover, the results were analyzed with a 2-compartment model and moment analyses in order to study in vivo kinetics of CBDCA at the time of the ip administration. 1) The shift of Pt to blood through ip administration depended on the peritoneal clearance. Cmax in blood was seen one hour after ip in patients with a normal peritoneum, and was seen between 4 and 6 hours after ip in patients with peritonitis carcinomatosa. The level was lower in the latter group. 2) The non-binding rate of Pt with protein in the ascites at the time of the ip administration was correlated with the CBDCA concentration in the ascites. 3) The non-binding rate was 80% or more both in the ascites and in the blood within 4 hours after ip. The high level of the nonbinding rate appeared to cause prolongation of the presence of the free-Pt in the ascites and blood, especially in patients with peritonitis carcinomatosa. 4) AUC level in blood was equal to or higher than that observed when the same dose was administered iv. The levels of free-Pt and AUC in the abdominal cavity were 2 to 5 times higher than those in blood in patients with a normal peritoneum, and 7 to 14 times higher in patients with peritonitis carcinomatosa.(ABSTRACT TRUNCATED AT 250 WORDS)
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It is obvious that there are many controversies regarding to the treatment of aortic dissection. In this report, we discuss following points such as 1) classification, 2) thrombosed type dissection, and 3) simultaneous graft replacement of ascending and aortic arch with the reconstruction of cervical branches. From the patho-morphological status, dissection will be classified into two types, localized and extended types. From the anatomical and surgical points of view, it will be also classified as 1) ascending-arch, 2) descending-thoracoabdominal, and 3) abdominal. With the combination of these two, dissection will be classified more clearly. The thrombosed type will be incorporated into localized type. We have experienced 76 cases of this dissection, and clinical features and outcome by medical treatment only are presented. The simultaneous reconstruction of ascending aorta and aortic arch for the dissection at ascending-arch type was undertaken in total of 35 patients. The surgical results as well as follow up data are presented and the benefit of this extended procedure is presented as well.
Magnetic resonance imaging has played a role in the diagnosis of thoracic disease; however, the role has been limited compared with that of CT. In the past year, there were a few additional reports of MR imaging in the diagnosis of thoracic disease, which include a multi-institutional study comparing MR imaging with CT and histopathologic correlative studies evaluating gadopentetate dimeglumine-enhanced MR imaging. Furthermore, several excellent reviews of MR imaging of thoracic disease were published. In general, the recent literature supports information previously reported. In the future, developments in lung parenchymal imaging and pulmonary vascular imaging are anticipated.
A 15-month-old girl, who was diagnosed asplenia, underwent Blalock-Taussig shunt using EPTFE tubular graft. Postoperatively, discharge containing high concentrations of protein continued to drain from pleural drainage. On the 23rd postoperative day, extirpation of seroma (4 x 3 x 3 cm) and wrapping of the graft using processed porcine pericardium were performed. However, pleural discharge did not decrease and caused atelectasis. On the 38th postoperative day, extirpation of seroma (4.5 x 6 x 14 cm) and partial lobectomy were performed. Pleural effusion persisted with decreasing quantity until the graft was obstructed. Ultimately on the 79th postoperative day, central shunt using Golaski tubular graft was successfully replaced. Thus, the occurrence of seroma should be borne in mind when EPTFE graft is used for shunt operation.
We have attempted to establish dog experimental model similar to clinical MNMS. Thirty-five dogs were divided into four groups; G-1: Ligation of abdominal aorta. (N = 5), G-2: Ligations as above for 6 hours and reperfusion. (N = 12), G-3: Same as G-2+ligation of superior epigastric arteries (N = 13), G-4: Same as G-2+transection of abdominal muscles (N = 5). Biochemicals, electrolytes and blood gas analysis in artery and vein were measured before, 6 hours after clamp, 5 minutes, 1 hour, 6 hours after reperfusion. Skeletal muscle PCO2, pH of lower leg were continuously measured. In G-1, no dog showed MNMS, in G-2, half of the dogs developed MNMS, in G-3, MNMS developed 9, but not in 4. In G-4, 4 dogs died during aortic cross-clamping. Satisfactory results were obtained in G-3. From the results of statistical analysis, the measurement of GOT, LDH, CPK, Cr and tissue PCO2, pH showed high significance between MNMS (+) and (-), and had correlation with K, BE, pH of artery and vein after reperfusion. Therefore, we consider that above factors are appropriate predictors for MNMS.
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Two mutant proteins of human myoglobin (Mb) that exhibit altered axial ligations were prepared by site-directed mutagenesis of a cloned gene for human Mb. The normal axial ligand residue, histidine 93(F8), was replaced with cysteine or tyrosine, resulting in H93C or H93Y Mb, respectively. Cysteine or tyrosine coordination to the ferric heme iron is verified by electronic absorption, 1H-NMR, EPR spectra, and redox potentials of Fe2+/Fe3+ couple. Their mono-oxygenation activities of styrene are also discussed.
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The cytotoxicity and DNA lesions induced by methotrexate (MTX) were compared in wild-type, hypoxanthine-guanine phosphoribosyltransferase-deficient (HGPRT-) and thymidine-kinase-deficient (TK-) HL-60 cells. TK- and HGPRT- cells were approximately 10 and 3 times more sensitive to MTX than wild-type cells, respectively. Following incubation with 2 microM MTX for 16 hr, TK- cells showed a significantly higher number of DNA strand breaks. Concomitantly, DNA fragmentation at the nucleosomal linker region was detected more prominently in TK- cells. Although MTX tended to decrease TTP pools similarly in all 3 cells types, the initial TTP level in TK- cells was only about one-fifth of that found in the wild type. These results indicate that the thymidine salvage pathway has a pivotal role in mediating MTX-induced toxicity and DNA lesions.
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Although alcohol is known to enhance hepatocarcinogenesis, the mechanism of this action remains to be explained. To test the hypothesis that ethanol depletes the liver of antitumor promoters such as retinoid, we measured the retinoid concentration in hepatocellular carcinoma tissues and noncancerous surrounding liver tissues in humans known to have a history of alcohol consumption. By high-performance liquid chromatography, the retinoid contents of 29 surgically resected hepatocellular carcinoma specimens and their noncancerous surrounding tissues were measured. Retinoid contents were decreased in both the cancerous and the surrounding noncancerous liver tissues of patients with a high intake of alcohol. The levels correlated inversely with the estimated cumulative lifetime ethanol consumption. The decrease in the retinoid content of hepatic parenchymal cells paralleled that in stellate cells. When compared with the surrounding liver tissues, the cancerous liver tissues were in the state of retinoid deficiency. In summary, alcohol abuse may help promote the hepatocarcinogenesis in man by depleting the liver of the antitumor promoter, retinoid.
Nine element concentrations in the lung tissues of 2,274 autopsies were determined in Japan by atomic absorption spectrometry. The metals determined were iron, calcium, magnesium, zinc, copper, cobalt, nickel, lead, and chromium. The range, mean, standard deviation, mode and median are described for each metal. Moreover, these data were analyzed statistically, based on their sex, age, degree of lung contamination (color and the amount of particle deposition), severity of pulmonary emphysema and cause of death. Iron, calcium, magnesium, zinc, copper and cobalt concentrations in the lung tissue seemed to be affected mostly by physiological variation and the levels in the blood. On the other hand, nickel, lead and chromium concentrations might reflect environmental exposure. Chromium concentration especially increased with age and showed a significantly positive correlation with the degree of contamination and severity of emphysema.
Concentrations of nine metals (Fe, Ca, Mg, Zn, Cu, Co, Ni, Pb and Cr) concentrations in lung tissues from 224 lung cancer cases were compared with those in other cases to achieve an understanding of their contribution to the development of lung cancer and the varieties after the development of cancer. Comparisons of metal concentrations in each cell type of lung cancer were also performed. All cases were collected from routine autopsies in Tokyo and Saitama, Japan. The copper concentration in tissue from lung cancers was significantly higher than that in other specimens, although calcium, magnesium, zinc and cobalt concentrations in lung cancers were significantly lower than those in other cases. There were no significant differences in the 99% intervals (excluding extremely high values for occupationally exposed cases) for chromium, nickel and lead concentrations between lung cancers and other cases, although these values were lower in lung cancers. However, in comparisons of men only, the chromium concentration, the degree of lung contamination and the severity of pulmonary emphysema in lung cancer cases were significantly higher than those in other specimens. Moreover, percentages of lung cancer in men at each degree of contamination and each severity of emphysema increased with increasing grades. Thus, this finding could be evidence that the exposure to contaminants other than chromium and nickel in the air had affected the development of lung cancer, except for occupationally exposed individuals. Therefore, almost all chromium and nickel in lung tissue might not deposit in carcinogenic forms such as hexavalent chromium or nickel subsulfide.(ABSTRACT TRUNCATED AT 250 WORDS)