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Biomedical subjects

H Umezawa

Publications and source records attributed to H Umezawa.

At least 37 records · Page 2Linked to original sources
PubMed1991

Synthesis of 3'-deoxy-3'-fluorokanamycin A and 3',4'-dideoxy-3'-fluorokanamycin A.

3'-Deoxy-3'-fluorokanamycin A (14) has been prepared by condensation of 6-azido-2,4-di-O-benzyl-3,6-dideoxy-3-fluoro-alpha-D-glucopyranlsyl++ + bromide (8) and 6-O-(2-O-acetyl-4,6-O-cyclohexylidene-3-deoxy- 3-tosylamino-alpha-D-glucopyranosyl)-2-deoxy-1,3-di-N-tosylstre ptamine (10). Compound 8 was obtained from 3-deoxy-3-fluoro-1,2:5,6-di-O-isopropylidene-D-glucofuranose in seven steps. 3',4'-Dideoxy-3'-fluorokanamycin A (22) has been prepared from 12 through selective 4'-chlorodeoxygenation, a key reaction. Both 14 and 22 were more active than 3'-deoxykanamycin A against both sensitive and resistant bacteria.

Anti-Bacterial Agents↗
PubMed1991

Ascorbic acid and adriamycin toxicity.

Adriamycin (ADR) is effective against a wide range of human neoplasms. However, its clinical use is compromised by serious cardiac toxicity, possibly through induction of peroxidation in cardiac lipids. Ascorbic acid, a potent antioxidant, was examined for effect in reducing ADR toxicity in mice and guinea pigs. Ascorbic acid had no effect on the antitumor activity of ADR in mice inoculated with leukemia L1210 or Ehrlich ascites carcinoma, but it significantly prolonged the life of animals treated with ADR. ADR elevated lipid peroxide levels in mouse heart, and ascorbic acid prevented the elevation. The significant prevention of ADR-induced cardiomyopathy in guinea pigs by ascorbic acid was proved by electron microscopy. Ascorbic acid and the derivatives may delay general toxicity of ADR and also prevent the cardiac toxicity. The results also suggest the clinical efficacy of the combined treatment of ADR and ascorbic acid or the derivatives.

Animals↗
PubMed1990

Local cerebral blood flow and glucose metabolism in hydrostatic brain oedema.

Two hydrostatic factors such as acute hypertension and decompressive craniectomy were chosen and assessment was focused on how the hydrostatic pressure gradient altered the cerebrovascular dynamics and metabolism during the process of development of brain oedema. Hydrostatic oedema was induced by bolus injection of autologous blood through the common carotid artery in Sprague-Dawley rats. Rats were divided into two groups, one with craniectomy (Cr+) and the other without craniectomy (Cr-). Animals were sacrificed immediately, 24 and 48 h after the hypertensive insult. Brain water content was determined by the gravimetric method. Regional cerebral blood flow (rCBF) and glucose metabolism (1CGU) were measured by quantitative autoradiographic methods using 14C-iodoantipyrine and 14C-deoxyglucose, respectively. The hypertensive insult produced multifocal lesions stained by Evans blue. In the brains of the Cr- group, there was a transient increase in water content and no significant change of rCBF and 1CGU. In the Cr+ group, the increase in water content was pronounced and continued until 48 h later. In addition, misery perfusion was observed at 24 h after the insult and both rCBF and 1CGU were significantly decreased after 48 h. These results indicate that the increased hydrostatic pressure gradient enhances tissue damage and causes the reopening of blood-brain barrier.

Animals↗
PubMed1990

Post-ischaemic treatment with the prostacycline analogue TTC-909 reduces ischaemic brain injury.

The effects of stable PGI analogue TTC-909 on CBF and glucose metabolism was studied in the chronic stage of cerebral ischaemia produced by occluding the distal MCA in SHRSP. Administration of TTC-909 (100 ng/kg/day during 7 days) prevented the development of ischaemic oedema and improved secondary metabolic derangement coupled to flow in postischaemic tissues, particularly in the ischaemic rim.

Animals↗
PubMed1989

The differentiation-promoting potential of a cytostatic fluoro-pyranosyl adriamycin analog (FAD 104).

Acute toxicity to the hematopoietic cell renewal system is a critical side effect of most anticancer agents. Here we compared the effects of FAD-104 to those of the parent compound adriamycin (ADM) and of epi-adriamycin (epi-ADM) on the growth and differentiation of normal as well as leukemic human myeloid progenitor cells. FAD-104 was less toxic to myeloid colony-forming cells (GM-CFU) than ADM or epi-ADM. In addition, FAD-104 but not ADM induced a clonal down-grading in both normal and leukemic blast cells, and it stimulated the terminal differentiation of myeloid leukemia cells. Therefore, FAD-104 may be useful in the treatment of some forms of myeloid leukemia.

Antineoplastic Agents↗
PubMed1989

Mannostatins A and B: new inhibitors of alpha-D-mannosidase, produced by Streptoverticillium verticillus var. quintum ME3-AG3: taxonomy, production, isolation, physico-chemical properties and biological activities.

Mannostatins have been isolated as part of a program designed to find microorganism-produced inhibitors of alpha-D-mannosidase from Streptoverticillium verticillus var. quintum. They were purified by sequential use of active carbon and Dowex resins and then isolated as colorless powders. Mannostatins A and B have the molecular formula, C6H13NO3S and C6H13NO4S, respectively. They were competitive with the substrate, and the inhibition constants (Ki) of mannostatins A and B were 4.8 x 10(-8) M.

Cyclopentanes↗
PubMed1989

Changes in relationship between blood glucose level and plasma 1,5-anhydroglucitol level in KK mice.

We compared the relationship of the blood glucose level to the plasma 1,5-anhydroglucitol (1,5AG) level between KK mice with abnormal glucose metabolism and ICR mice as controls. Although the plasma 1,5AG level did not show any significant correlation with the blood glucose level in the controls, it tended to logarithmically decrease with the rise in the blood glucose level in KK mice. Thus it is possible that the plasma 1,5AG level is specifically related to the abnormal glucose metabolism in this model of diabetes mellitus and that its routine examination in diabetic patients may help delineate the metabolic derangement in the disease.

Animals↗
PubMed1989

Multiple enzymes related to differentiation of lymphocyte subpopulations in man.

We studied the relation of various enzymes to subpopulations of lymphocytes in man. T cell-rich fractions were separated with a nylon column from mononuclear cells in the buffy coat. Comparing the enzymatic profiles of the two fractions, we found that the difference between the two groups came from the dominancy of B cells and/or macrophages in the former fraction, and from that of T cells in the latter. The enzymes characterizing T cells included N-Ac-beta-D-glucosaminidase (GlcNAc-ase), prolyl endopeptidase (Post-Pro-Enz), and dipeptidyl aminopeptidase IV (DAP-IV), whereas those characterizing B cells and/or macrophages include poly(ADP-ribose) synthetase, leucine aminopeptidase (Leu-AP), AP-B, cathepsin B, sialidase, and AP-A. Inhibitors of these enzymes may lead to modification of the function of T and B cells.

B-Lymphocytes↗
PubMed1988

Determination of deoxyspergualin by gas chromatography-selected-ion monitoring.

A gas chromatographic-selected-ion monitoring method was developed for the sensitive and specific determination of deoxyspergualin in dog plasma using a capillary column and a C8-amide homologue of deoxyspergualin as an internal standard. Extraction and purification of deoxyspergualin from its constituents, 7-guanidinoheptanamide and glyoxylylspermidine, and its possible metabolites was achieved by using CM-Sephadex C-25 column chromatography with stepwise elution with sodium chloride solution. Treatment of deoxyspergualin with acetylacetone resulted in the formation of the volatile pyrimidine derivative of 7-guanidinoheptanamide accompanying hydrolytic cleavage in the alpha-hydroxyglycine moiety of deoxyspergualin. Deoxyspergualin could be determined in a concentration of 10 ng/ml in plasma. The method was applied to the determination of deoxyspergualin in plasma during and after intravenous infusion into dogs.

Animals↗
PubMed1988

Benadrostin, new inhibitor of poly(ADP-ribose) synthetase, produced by actinomycetes. I. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Benadrostin, a new inhibitor of poly(ADP-ribose) synthetase was discovered in the fermentation broth of Streptomyces flavovirens MH499-O'F1. It was purified by chromatography followed by solvent extraction and then isolated as colorless prisms. Benadrostin has the molecular formula of C8H5NO4. It was competitive with the substrate, and the inhibition constant (Ki) was 34 microM.

Fermentation↗
PubMed1988

Protease-inhibitory activities of leupeptin analogues.

Thirty analogues of leupeptin were synthesized and examined for their inhibitory activities against trypsin, papain, plasmin, kallikrein, thrombin and urokinase in vitro. Benzoyl- and alpha-naphthalenesulfonyl-L-leucyl-L-argininal were 8 times more inhibitory to papain, benzyloxycarbonyl-L-pyroglutamyl-L-leucyl-L-argininal 10 times more to trypsin and plasmin, and DL-2-pipecolyl-L-leucyl-L-argininal 25 times more to kallikrein than leupeptin. Against urokinase, only L-pyroglutamyl-L-leucyl-L-argininal exhibited a potent inhibitory activity. alpha-Naphthalensulfonyl-, dansyl- and benzyloxycarbonyl-(2S,3R)-3-amino-2-hydroxy-4-phenylbutyryl-L-leucyl-L- argininal were inhibitory to thrombin.

Fibrinolysin↗
PubMed1988

The antiproliferative action of deoxyspergualin is different from that induced by amine oxidase.

The amine oxidase activities contained in calf serum and human serum were detected at levels of 90.8 and less than 0.1 nmol O2/minute/ml serum, respectively, by measuring oxygen consumption coupled with spermidine oxidation. Deoxyspergualin (NKT-01) and spergualin (SGL) containing spermidine in their structure were also oxidized in calf serum at the rate of 3.6 and 11.6 nmol O2/minute/ml serum, respectively. To investigate whether amine oxidase is essential for NKT-01 and SGL to exhibit their antiproliferative activities or not, the in vitro activities of NKT-01, SGL and polyamines against L1210 cells were examined in the presence of calf or human serum. Polyamines exhibited antiproliferative activity only in the presence of calf serum, while NKT-01 and SGL inhibited cell growth in the presence of both calf and human serum. In the presence of calf serum the activity of NKT-01 was inhibited by aminoguanidine, an amine oxidase inhibitor. Aminoguanidine did not inhibit the activity of NKT-01 in the presence of human serum. The activity of NKT-01 was shown at much lower concentrations in the presence of human serum than that in the presence of calf serum, and was strongly dependent on incubation time. The in vivo activities of NKT-01, SGL and SGL derivatives correlated with their in vitro activities in the presence of human serum. These results suggest that the in vivo antitumor activities of NKT-01, SGL and SGL derivatives may be attributed to a mechanism different from those of amine oxidase-oxidized product and represent a novel growth inhibitory action.

Amine Oxidase (Copper-Containing)↗