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Biomedical subjects

M Kohno

Publications and source records attributed to M Kohno.

At least 523 records · Page 29Linked to original sources
PubMed1984

Quantitative determination of the superoxide radicals in the xanthine oxidase reaction by measurement of the electron spin resonance signal of the superoxide radical spin adduct of 5,5-dimethyl-1-pyrroline-1-oxide.

Reactivities of biologically active compounds with superoxide radicals were examined by measurement of electron spin resonance (ESR) spectra of 5-hydroperoxy-2,2-dimethyl-1-pyrrolidinyloxyl formed from 5,5-dimethyl-1-pyrroline-1-oxide and the superoxide radicals generated by xanthine-xanthine oxidase system. Quantitative determination of the superoxide radicals was performed by comparing the intensity of the spin adducts with that of 4-hydroxy-2,2,6,6-tetramethyl-pipperidinooxyl whose spin concentration was determined. Methyl viologen enhanced the formation of this spin adducts, while, rutin and luteoskyrin prevented it.

Cyclic N-Oxides↗
PubMed1984

Interaction between quercetin and superoxide radicals. Reduction of the quercetin mutagenicity.

Interaction between quercetin and superoxide radicals was investigated using xanthine-xanthine oxidase system and potassium superoxide as superoxide radical generators. Superoxide radical scavenging action of quercetin was demonstrated by measurement of the electron spin resonance spectrum of the 5-hydroperoxy-2,2-dimethyl-1-pyrrolidinyloxyl adduct. Degradation of quercetin by the radicals was demonstrated spectrophotometrically. Reduction of the quercetin mutagenicity by the radicals was demonstrated in the Salmonella typhimurium strain TA 98 by the Ames test.

Animals↗
PubMed1984

Hemodynamic effects of nitroprusside on cardiovascular system.

The effects of nitroprusside (NP) on hemodynamics, especially on venous flow velocity of the inferior vena cava (IVC) were evaluated in 20 remote myocardial infarction patients. NP was given beginning at 10 micrograms/min, with subsequent increments of 10 micrograms/min every 5 minutes until the systolic blood pressure was reduced to about 30 mmHg. Pressure was measured by a catheter-tip micromanometer. Flow velocity of IVC was measured by a catheter-tip flow velocity probe. NP significantly decreased left ventricular systolic pressure, left ventricular end-diastolic pressure, mean aortic pressure, right ventricular systolic pressure, right ventricular end-diastolic pressure, mean pulmonary arterial pressure, mean pulmonary capillary wedge pressure, systemic vascular resistance index (SVRI) and left ventricular volume. Cardiac index (CI) was unchanged and stroke volume index was decreased. IVC pressure was unchanged, while right atrial (RA) pressure decreased. Subsequently, the pressure difference between IVC and RA increased significantly. The amplitude of IVC flow velocity decreased significantly. Twenty patients were classified into two groups according to whether or not the CI increased by NP. CI increased in 9 patients (group I) and decreased in 11 patients (group D). Compared to group D, control CI and the slope of end-systolic pressure-volume relation were less and the difference between IVC pressure and RA pressure was greater in group I. The patients with higher control SVRI had greater increase in CI during NP. In our study, the greater the depression of cardiac performance and the higher the SVRI, the greater the improvement of left ventricular pumping function during NP.

Adult↗
PubMed1984

A new approach to the detection of autoantibodies against insulin receptors that inhibit the internalization of insulin into human cells.

It has been shown that the conjugate of the fragment A of diphtheria toxin to insulin is cytotoxic to cultured cells bearing insulin receptors, apparently through the endocytosis of fragment A. We examined the effect of autoantibodies against insulin receptors on the cytotoxicity of the conjugate. The conjugate was cytotoxic to a rat fibroblast cell line that was resistant to the intact toxin, and the cytotoxicity was inhibited by exogenous insulin, indicating that the fragment A underwent endocytosis through insulin receptors. Immunoglobulins from three patients with type B syndrome of insulin-resistant diabetes blocked the cytotoxicity of the conjugate to Chang's liver cells in a dose-dependent manner. When the cells were pretreated with the immunoglobulins, cytotoxicity of the conjugate was also blocked. These results suggest that autoantibodies against insulin receptors interfere with the binding of the conjugate to insulin receptors or with the endocytosis of fragment A after binding. This assay system seems useful for detecting autoantibodies against the determinants that are involved in the internalization of the ligand-receptor complex.

Animals↗
PubMed1984

Effect of aminoglycoside antibiotics on cellular functions of kidney epithelial cell line (LLC-PK1): a model system for aminoglycoside nephrotoxicity.

The effects of aminoglycoside antibiotics on cellular functions of the LLC-PK1 kidney epithelial cell line were studied as a model system for aminoglycoside nephrotoxicity. The treatment with aminoglycoside antibiotics for 3 days caused a decrease in the dome number in the confluent LLC-PK1 cells and an increase in the floating cells in the culture medium. The inhibition of dome formation was dose-dependent and the rank-order of the degree of inhibition was compatible with the rank-order of in vivo nephrotoxicity. Aminoglycosides also decreased the intracellular content of cyclic AMP, with a correlation between the alteration of dome formation and cyclic AMP content. The specific activities of N-acetyl-beta-D-glucosaminidase (marker for lysosomes), aminopeptidase and alkaline phosphatase (marker for apical membranes) and (Na++K+)-adenosine triphosphatase (marker for basolateral membranes) in the homogenate were decreased by gentamicin treatment. Lysosomal and apical membrane enzymes released into the culture medium were increased by gentamicin treatment. The ultrastructural alterations in the lysosomes of gentamicin-treated cells also were observed. Above results suggest that aminoglycoside toxicity to LLC-PK1 cells may be similar to that reported for renal tubules.

Adenosine Triphosphate↗
PubMed1983

Structure-antitumor activity relationship of a D-manno-D-glucan from Microellobosporia grisea: effect of periodate modification on antitumor activity.

An antitumor D-manno-D-glucan from Microellobosporia grisea, an actinomycete, has a tetrasaccharide repeating-unit structure, a single alpha-D-mannosyl group being located at both O-3 and O-6 of every other beta-D-(1 leads to 4)-glucosyl residue. The D-mannosyl groups and D-glucosyl residues of the mannoglucan were polyhydroxylated to various extents by controlled periodate oxidation followed by borohydride reduction. The derivatives (PA mannoglucans) were further subjected to mild hydrolysis with acid, to give partially debranched mannoglucans (PA-H mannoglucans). These derivatives were tested for antitumor activity against Ehrlich carcinoma solid tumor in mice. The PA mannoglucans having degrees of polyhydroxylation of less than approximately 50 and 2% of the D-mannosyl groups and D-glucosyl residues, respectively, showed high antitumor activities, similar to that of the original mannoglucan, whereas further polyhydroxylation resulted in a marked decrease in, or complete loss of, the activity. The PA-H mannoglucans, lacking 5-40% of the D-mannosyl branches, still had potent antitumor activities, comparable to that of the original mannoglucan. On the basis of these results, the relationship of the structure of the mannoglucan to the antitumor activity is discussed.

Animals↗
PubMed1983

Biliary and fecal steroid excretion in rats fed partially hydrogenated soybean oil.

Male Wistar rats were fed cholesterol-free or cholesterol-enriched diets containing partially hydrogenated soybean oil with different levels of trans-fatty acids or unhydrogenated soybean oil at the 10% level. The linoleic acid content of hydrogenated fat diets was adjusted to 3.6% of the total energy. Hydrogenated fat diets contained 29% and 41% trans-acids, mainly as t-18:1. Trans-fats exerted no untoward effects on growth parameters, but increased liver weight. Dietary hydrogenated fats influenced neither the concentration nor composition of biliary steroids, irrespective of the presence or absence of cholesterol in the diet. In rats fed a cholesterol-free diet, daily fecal output of neutral and acidic steroids was enhanced by hydrogenated fats and the magnitude of augmentation was proportional to the dietary level of trans-fatty acids. The increased fecal steroid excretion corresponded to an increase in total excreta. Hydrogenated fats also tended to enhance bile acid excretion when feeding a cholesterol-enriched diet. The results suggest that dietary trans-fatty acids, in relation to cis-polyunsaturated fatty acids, provoke demonstrable change in steroid homeodynamics.

Animals↗
PubMed1983

Effects of dietary trans-fat on biliary and fecal steroid excretion and serum lipoproteins in rats.

Rats were fed cholesterol-free or cholesterol-enriched diets containing olive oil or partially hydrogenated corn oil at the 10% level for ca. 30 days (c-18:1, 77.0% in the former diet and c-18:1,24.7% and t-18:1,42.5% in the latter). The linoleic acid content of these fat diets was made equivalent (1.7 energy %). After feeding cholesterol-free diets, trans fat compared to cis fat showed (a) no untoward effects on growth parameters, (b) a reduction of serum cholesterol levels without influencing concentrations of serum apolipoproteins A-1, B and E, (c) no effects on the bile flow and the concentration of biliary cholesterol and bile acids, (d) an increasing trend of fecal excretion of neutral and acidic steroids, both in terms of mg/day and mg/g feces, and (e) rather equivocal change in the composition of fecal, but not biliary steroids. Similar response patterns were also observed when cholesterol-enriched diets were fed except for a decrease in serum apo B and an ineffectiveness to increase fecal acidic steroids. Together with the results obtained from experiments simultaneously performed with safflower oil and completely hydrogenated corn oil, it seems that the steroid metabolism can be specifically modified by the geometry of dietary fats.

Animals↗
PubMed1983

Lipid droplets containing DNA-histones released in the culture medium of transformed rat fibroblasts (HY1).

Lipid droplets appeared during the growing phase in the culture medium of incompletely transformed rat fibroblasts (HY1) induced by AccI-H fragments of adenovirus 12 DNA. These droplets consisted of neutral lipids, DNA, histones and RNA. Electron microscopic observations showed that the droplets had no lipid-bilayers on their surfaces which accounted for the tendency of the droplets to readily fuse together and become larger, and that the inner structures of the droplets looked like networks of fibrous matter. Experiments with DNA hybridization showed that the droplet DNA was composed of both cellular and adenoviral DNA, and that the cellular DNA in the droplets seemed to be derived from various cell DNA sequences. These results suggest that the droplets were derived from parts of the nuclear components of HY1 cells. The mechanisms for droplet release are discussed.

Adenoviridae↗
PubMed1983

Combination therapy of murine tumors with a degraded D-manno-D-glucan (DMG) from Microellobosporia grisea, and cyclophosphamide.

DMG, a degraded D-manno-D-glucan with a host-mediated antitumor activity did not significantly enhance nor inhibit the development of suppressor cells for either the antibody-forming response or the delayed hypersensitivity reaction to sheep red blood cells. Cyclophosphamide (CY), which inhibited the generation of suppressor cells, was combined with DMG in treatment of murine syngeneic tumors to obtain a higher antitumor activity. The antitumor activity of the combination against MH134 hepatoma was synergistically higher than that of either component alone. A marked antitumor effect of the combination treatment against MM46 mammary carcinoma was also shown. High levels of antitumor delayed hypersensitivity reactions were observed with this combination therapy. The possible roles of DMG and CY in this combination therapy are discussed.

Animals↗
PubMed1983

Effects of human fibroblast interferon on human gliomas transplanted into nude mice.

Daily intratumor injection of human fibroblast interferon (HuIFN-beta) resulted in significant growth inhibition of human gliomas transplanted into nude mice. Light and electron microscope examinations were conducted to estimate the efficacy of HuIFN-beta. A 29-day daily treatment with HuIFN-beta induced complete regression of oligodendroglioma KG-1--a slowly growing tumor line positive for S-100 protein and negative for glial fibrillary acidic protein (GFAP)--in 9 out of 10 mice receiving 6 X 10(5) IU and 6 out of 9 given 1 X 10(5) IU. In mice with glioblastoma multiforme TMIMS-583, which showed more rapid growth and was positive for GFAP, dose-dependent growth inhibition was observed during 23 days of HuIFN-beta administration. Pathological changes of TMIMS-583 induced by HuIFN-beta were characterized by a decrease of the metaphase tumor cells, by enhanced degeneration of tumor cells with stromal reaction and round cell infiltrates, and by prominence of multinuclear giant cells containing glial filaments. Tumor weights were well correlated with the number of tumor cells in the metaphase (r = 0.89).

Adult↗
PubMed1983

Effects of human fibroblast interferon on human tumors transplanted into nude mice: sensitivity of malignant melanoma.

The antitumor effects of human fibroblast interferon (HuIFN-beta) on three lines of human malignant melanoma (AM-1, SK-14, SK-2) were studied using a nude mouse-human tumor xenograft system. The sensitivity of melanoma to interferon in relation to melanin productivity was investigated. Intratumoral administration of 6 X 10(5) IU of HuIFN-beta significantly inhibited proliferation of AM-1 and SK-14, but did not inhibit that of SK-2. The sensitivity to HuIFN-beta was in the order of SK-14, AM-1 and SK-2, and was well correlated with the susceptibility of cell division observed histologically. Although these tumors differ in production of melanin, difference in sensitivity to HuIFN-beta due to melanin productivity was not clear. The relationship between the antitumor effect and the administration method was studied with SK-14, which was the most sensitive to HuIFN-beta. Antitumoral activities depending on the routes of administration were in the order of intratumoral, peritumoral-subcutaneous and intraperitoneal. Intratumoral and subcutaneous administrations of high doses brought about complete disappearance of the tumor cells or decrease in size of the tumor mass.

Animals↗
PubMed1983

Antitumor activity of polysaccharide TC-13 extracted from rare actinomycetes.

The antitumor activities of mycelia and a hot-water extract of mycelia of rare actinomycetes were examined by three different antitumor assays in ddY mice with Ehrlich solid tumor. A new antitumor polysaccharide, TC-13, was prepared from the hot-water extract of Microellobosporia grisea by precipitation with cetylpyridinium chlorideborate complex and gel filtration. TC-13 was mainly composed of glucose and mannose with peptideglycan. Its molecular weight was determined to be 2-30 X 10(4) by gel filtration. Comparative studies suggested that the antitumor activity of TC-13 was equal to, or stronger than those of other antitumor agents (e.g., lentinan, PS-K, OK432 and yeast mannan). Screening methods for antitumor activity of actinomycetes were also discussed.

Actinomycetales↗