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Biomedical subjects

K Ota

Publications and source records attributed to K Ota.

At least 667 records · Page 37Linked to original sources

[Protective effect of coenzyme Q10 in cardiotoxicity induced by adriamycin].

Cardiotoxicity induced by adriamycin and protective effect by coenzyme Q10 were studied in 80 closely-followed patients receiving chemotherapy with adriamycin. Serial electrocardiograms were recorded immediately before and after the administration of adriamycin each times. The electrocardiographic parameters (heart rate, P-Q duration, QRS-duration, QRS voltage and QTc-duration) were analyzed. In patients treated with adriamycin alone, QTc-duration was prolonged significantly. On the other hand, in patients treated with adriamycin plus coenzyme Q10, QTc-duration was not significantly prolonged. This Suggests that coenzyme Q10 may reduce negative inotropic action induced by adriamycin. Further, the QRS voltage was also significantly decreased in patients treated with adriamycin alone, but was not decreased in patients treated with adriamycin plus coenzyme Q10. These findings suggest that some electrocardiographic changes due to adriamycin may be prevented by coenzyme Q10.

Coenzymes↗

Microsomal and cytosolic epoxide hydrolases in rhesus monkey liver, and in normal and neoplastic human liver.

The cytosolic epoxide hydrolase (EH-LC) was observed in rhesus monkey liver cytosol, and in both normal and neoplastic human liver. Microsomal epoxide hydrolase (EH-LM) was detected not only in the microsomes of normal and neoplastic human liver and normal rhesus monkey liver, but also in the cytosol of these tissues. No apparent differences were observed between the EH-LM in liver cytosol and that in microsomes. No major differences were observed between the levels of EH-LM in the cytosol of normal and that in neoplastic human liver.

Animals↗

Radiometric assays for mammalian epoxide hydrolases and glutathione S-transferase.

A number of epoxides, including cis- and trans-stilbene oxides, were assayed as substrates for epoxide hydrolases (EHs) by gas-liquid chromatography. Radiolabeled stilbene oxides were prepared by sodium borotritide reduction of desyl chloride followed by ring closure with base treatment. Rapid radiometric assays for EHs were performed by differential partitioning of the epoxide into dodecane, while the product diol remained in the aqueous phase. Glutathione (GSH) transferase was similarly assayed by partitioning the epoxide and diol, if formed metabolically, into 1-hexanol, while the GSH conjugate was retained in the aqueous phase. The cytosolic EH rapidly hydrates the trans isomer while the cis is very poorly hydrated. In contrast, the cis is a better substrate for the microsomal EH than the trans. GSH transferase utilized both epoxides as substrates, but conjugation is faster with the cis isomer. Cytosolic EH activity is high in mouse but very low in rat and guinea pig. Microsomal EH activity, in contrast, is highest in guinea pig, intermediate in rat, and the lowest in mouse. GSH transferase activity, which is high in all three species, can be inhibited by chalcone, with an I50 of 3.1 X 10(-5) M. These assays facilitate the rapid evaluation and direct comparison of epoxide-metabolizing systems in cell homogenates used in short-term mutagenicity assays, cell or organ culture, and possibly in vivo.

Animals↗

Differential induction of cytosolic epoxide hydrolase, microsomal epoxide hydrolase, and glutathione S-transferase activities.

Three major enzyme systems have been shown to metabolize epoxidized xenobiotics in vertebrate tissues, and this study demonstrates that these enzyme systems can be differentially induced. The cytosolic epoxide hydrolase activity was routinely monitored with trans-beta-ethylstyrene oxide, the microsomal epoxide hydrolase activity with benzo(a)pyrene, 4,5-oxide, and the glutathione S-transferase activity with 2,4-dichloro-4-nitrobenzene. Commonly used inducers of microsomal mixed-function oxidase, microsomal epoxide hydrolase, and cytosolic glutathione S-transferase activities failed to cause significant induction of the cytosolic epoxide hydrolase while leading to the expected induction of the other epoxide metabolizing enzymes. The compounds tested by ip injection into male Swiss-Webster mice included phenobarbital, 3-methylcholanthrene, Aroclor 1254, trans- and cis-stilbene oxides, pregnenolone-16 alpha-carbonitrile, chalcone, and 4-bromochalcone. To determine if there were strain, sex, or species differences, the enzymes were monitored in male C57BL/6 mice, female Swiss-Webster mice, and male Sprague-Dawley rats following ip injection of phenobarbital, 3-methylcholanthrene, and/or pregnenolone-16 alpha-carbonitrile. The time dependence of enzyme induction was followed in Sprague-Dawley rats following trans-stilbene oxide administration. Male Swiss-Webster mice were additionally exposed to dietary alpha-naphthoflavone and 2(3)-tert-butyl-4-hydroxyanisole while male Sprague-Dawley rats were fed 2,6-di-tert-butyl-4-methylphenol. In no case was significant induction of cytosolic epoxide hydrolase activity observed. Dietary di-(2-ethylhexyl)phthalate, 2-ethyl-l-hexanol, and clofibrate proved to be potent inducers of the cytosolic epoxide hydrolase in male Swiss-Webster mice while probucol (a nonperoxisome proliferating hypolipidemic drug) failed to cause significant induction. Data from isoelectric focusing experiments and other data are consistent with the epoxide hydrolase activities induced by 2-ethyl-l-hexanol and clofibrate being due to the same protein that is present in control animals. The lack of induction of the cytosolic epoxide hydrolase by a variety of compounds which were selected to demonstrate induction of other xenobiotic metabolizing enzymes, may indicate that the cytosolic epoxide hydrolase has a constitutive role whereas its induction by clofibrate could be related to some of the pharmacological and/or carcinogenic actions of this drug.

Animals↗

Serological analysis of cell surface antigens of HL-60 cells before and after treatment with a phorbol ester tumor promoter.

The human HL-60 cell line derived from acute promyelocytic leukemia, consisting of promyelocytic type of cells, was able to differentiate into adherent cells with monocytemacrophage features by the treatment with 12-0-tetradecanoyl phorbol-13-acetate (TPA). Cell surface antigens of HL-60 cells before and after TPA treatment were studied with monoclonal antibodies and four hybridoma clones producing IgM antibodies were established. Two antibodies (HL-21 and HL-47) reacted only with the immunizing TPA-treated HL-60 cells, and HL-1 antibody produced against untreated cells was reactive with both TPA-treated and untreated cells, but HL-5 antibody reacted predominantly with the immunizing untreated cells. Serological reactivity against various types of normal hematopoietic cells and acute leukemias (diagnosed by the French-American-British classification) was studied by immune adherence assay and immuno-electron microscopy. HL-21 antibody was reactive with monocytes and most cases of M4 and M5 types of acute non-lymphocytic leukemia cells. HL-47 antibody did not react with the cells of myelocyte-monocyte lineage or mature lymphocytes, but it did react with one-third of acute lymphocytic leukemia (L1 and L2) cases. Since all HL-47+ cases were included in the group of common ALL antigen positive cases, it was estimated that HL-47 is a differentiation antigen present on lymphocyte precursors, from which null-cell type acute lymphocytic leukemia cells generally originate. HL-1 antibody reacted with the cells of myelocyte-monocyte lineage as well as those of most acute non-lymphocytic leukemias. HL-5 antibody reacted with granulocytes and M2 type of acute myelocytic leukemia cases, and also with M5 type of acute monocytic leukemia cases. Serological studies of these antibodies revealed that TPA can induce to differentiate HL-60 cells not only into HL-21+ macrophage-like cells, but also into HL-47+ lymphoid stem cells. In addition, these antibodies were demonstrated to be very valuable for differential diagnosis of acute leukemias.

Antibodies, Monoclonal↗

Two monoclonal antibodies detecting allotypic determinants of HLA-A.

Three mouse hybridomas producing cytotoxic antibodies against HLA were established. By standard microcytotoxicity test against panels of normal controls, the antigen defined by MA-9 antibody (IgM) showed a good correlation with HLA-A9 alloantigen detected by conventional typing alloantisera (r = 1.0). Family studies also showed that MA-9 determinant segregated with HLA-A9. MA-10 antibody (IgM) reacted with all HLA-A10 positive lymphocyte donors and cross-reacted with two thirds of HLA-AW33 positive donors. Ml-1 antibody (IgG2a) reacted with all the panel cells tested and immunoprecipitated a molecule of 43,000 daltons from Nonidet P-40 lysates of 3H-glucosamine-labelled cells. The results showed that MA-9 and MA-10 antibodies can be used as routine tissue typing reagents.

Adult↗

Mammary growth and plasma progesterone level during pregnancy in the house musk shrew, Suncus murinus Linnaeus.

The process of growth of the mammary gland and change in the plasma concentration of progesterone were investigated throughout the course of pregnancy (30 days) in the home musk shrew, Suncus murinus L. Development of the mammary gland of the musk shrew was limited during the first half of pregnancy. Extensive branching of ducts and conspicuous alveolar formation and a marked increase in the DNA content of the gland started between day 15 and 20 of pregnancy, and continued until term. Milk synthesis indicated by accumulation of the secondary fluid in the alveolar lumen and a sudden rise in the RNA/DNA ratio of the gland tissue seemed to be initiated 1 or 2 days before parturition. No lactose was detected in either the mammary tissue or milk of the house musk shrew. Plasma concentration of progesterone was very low until mid-pregnancy and began to rise after day 15, reaching a peak of 10--13 ng/ml around day 25. The steroid level started to fall shortly before parturition and returned to the basal level in post-parturient animals. Ovariectomy interrupted pregnancy in some animals, but not in others. When pregnancy was maintained, the mammary development and the plasma level of progesterone were normal.

Adrenal Glands↗

Ultrasonic endoscopy.

With the use of a linear scan type ultrasonic endoscope, the possibility of gastric fiberscopy with ultrasonic procedure in the estimation of the extent of deep infiltration of gastric cancer and in the transgastric diagnosis of pancreatic tumors was studied. Results revealed that the echogenicity of the tumor was more clearly recorded by ultrasonic endoscopy than routine ultrasonography taken via the abdominal wall. With improvements in both the probe and manipulation technique, the device is expected to achieve far-reaching contributions to the diagnosis of the deep invasion of gastric cancer and small-sized pancreatic tumors.

Adult↗

[Effect of peplomycin by continuous infusion on Ehrlich carcinoma].

The effect of peplomycin by three different treatment schedules was studied in mice bearing Ehrlich Effeit of carcinoma. continuous i.p. infusion of peplomycin via an osmotic minipump was compared to those by intermittent injection and daily injection. Equivalent total doses of the drug were administered in all three schedules. Continuous infusion for 7 days produced marked inhibition of tumor growth, which was significantly better than intermittent injection or daily injection of the same total dose. The effect of bleomycin by continuous infusion was significantly better than that by intermittent injection, but was as equally effective was daily injection. The results indicate that the continuous infusion of peplomycin is a useful treatment method.

Animals↗

[Comparative effect of administration schedules on the antitumor activities of 3 water-soluble nitrosoureas, ACNU, GANU and MCNU against L1210 leukemia].

ACNU, GANU and MCNU, water-soluble nitrosoureas, have been evaluated in terms of influence of treatment schedule on antitumor activity in mice bearing L1210 leukemia. The results obtained were as follows: 1) ACNU produced a significant increase in life span and long-term survivors by administration on day 1 only, once every 8 days for 2 doses or once every 4 days for 3 doses, and the compound was most effective when given on day 1 only. 2) GANU produced a significant increase in life span and long-term survivors by same administration schedules as ACNU, and the compound was most effective when given every 8 days for 2 doses. 3) MCNU produced a significant increase in life span and long-term survivors by each administration including daily treatment, and the compound was most effective when given every 4 days for 3 doses. 4) ACNU and MCNU displayed the same level of activity as CCNU when the drugs were given on day 1 only. Daily treatment with MCNU was as effective as daily treatment with CCNU. Our results suggest that ACNU, GANU and MCNU should be administered by intermittent schedule as lipid-soluble nitrosoureas such as BCNU, CCNU and MeCCNU.

Animals↗

Evaluation of serum neuron-specific enolase as a tumor marker for carcinoma of the lung.

Serum neuron-specific enolase (NSE) was measured in 80 normal subjects, 20 patients with small cell carcinoma of the lung (SCCL) and 54 patients with non-small cell carcinoma (non-SCCL). The mean value in the control group was 2.1 +/- 0.4 ng/ml (range, from 1.3 to 3.0 ng/ml). Serum levels exceeding 7.5 ng/ml were tentatively defined as positive. Thirteen of 20 patients (65%) with SCCL had positive serum NSE levels, whereas 6 of 54 patients (11%) with non-SCCL had positive levels. Positive NSE in sera of patients was observed only in patients with advanced clinical stage of SCCL or non-SCCL. No correlation between serum NSE levels and metastatic sites could be found. The serum NSE levels in subtypes of SCCL were positive in 9 of 10 patients with oat cell carcinoma and 4 of 10 patients with intermediate cell carcinoma. Histological types of all positive cases with non-SCCL included large cell carcinoma. Serum NSE levels changed in parallel with the clinical course during the treatments. The data suggested that serum NSE may be a useful marker for monitoring the clinical course of lung carcinoma, especially of SCCL. Furthermore, the detection of NSE in non-SCCL is of interest in relation to the histogenesis of lung carcinomas which exhibit the properties of neuroendocrine tumors.

Adenocarcinoma↗

[Combination treatment of radiation and chemotherapy of lung cancer --from a view-point of therapeutic ratio].

The methods of combination treatment of inoperable lung cancer in our hospital were evaluated from the view-point of therapeutic ratio. In the case of combination of standard doses radiotherapy with usual doses of chemotherapy, there were some problematic side effects, though direct effect was remarkable. In the case of low doses radiotherapy combined with chemotherapy, a fairly good effect was obtained with lesser side effects, resulting in a better long term survival rate, that is a higher therapeutic ratio.

Adenocarcinoma↗

[Neuron-specific enolase as a new tumor marker].

Enolase is a glycolytic enzyme widely distributed in each mammalian tissue and consists of three distinct subunits alpha, beta, and gamma. In the brain enolase exhibits three dimetric isozymic forms: alpha alpha, alpha gamma and gamma gamma. The gamma protein subunit has recently been found to be identical with the nervous system-specific and species-nonspecific protein, 14-3-2; therefore, alpha gamma and gamma gamma types of enolase were characterized as neuron-specific enolase (NSE). NSE has been also detected in the pituitary gland, thyroid gland, adrenal medulla and pancreas, all of which contain neuroendocrine cells. Recently NSE was observed by immunostaining or radioimmunoassay in neuroendocrine tumor such as glucagonomas, insulinomas, gut carcinoids, medullary thyroid carcinomas or neuroblastomas. Furthermore, small cell carcinoma of the lung which has been known to frequently exhibit neuroendocrine properties was found to produce NSE. In this paper NSE as a tumor marker in various cancers was evaluated by immunostaining or enzyme immunoassay which was developed by a co-worker Kato. The data revealed that serum NSE was clinically useful as a tumor marker, especially a monitoring marker of disease extent. NSE productions were also observed in adenocarcinoma of the colon or the lung and large cell carcinoma of the lung as well as small cell carcinoma of the lung and the esophagus, all of which were considered to share the biochemical features of neuroendocrine tumor. The evidence challenges a speculation that small cell carcinoma of the lung has an origin separated from the other histological types of lung carcinoma. In this meaning NSE is an important tumor marker for both clinical medicine and basic research.

Animals↗