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Biomedical subjects

O Nakayama

Publications and source records attributed to O Nakayama.

13 recordsLinked to original sources

WS-7528, a new isoflavanone with estrogen activity isolated from Streptomyces sp. No. 7528. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

WS-7528, produced by Streptomyces sp. No. 7528, was extracted from cultured broth, purified by solvent extraction followed by chromatography on silica gel and then isolated as pale yellow powder (C16H14O5, mp 95-98 degrees C). WS-7528 inhibited estrogen binding to its receptor protein in rat uterine cytosol. The IC50 value of WS-7528 for partially purified rat uterine cytosol receptor was 5.7 x 10(-8) M. This compound was found to induce the growth of the estrogen dependent cell line MCF-7. WS-7528 was tested orally and subcutaneously in immature rats to confirm its effect on the growth of the uterus. WS-7528 has also weak anti-inflammatory activity on the carrageenin paw edema of the rat model.

Animals

WS-9659 A and B, novel testosterone 5 alpha-reductase inhibitors isolated from a Streptomyces. I. Taxonomy, fermentation, isolation, physico-chemical characteristics.

WS-9659 A and B, produced by Streptomyces sp. No. 9659, were extracted from cultured broth, purified by solvent extraction followed by chromatography on silica gel and then isolated as prisms (C22H24N2O, mp 161 approximately 162 degrees C, C22H23N2OCl, mp 152 approximately 153 degrees C). WS-9659 A and B have testosterone 5 alpha-reductase inhibitory activity. The IC50 values of WS-9659 A and B for partially purified rat prostate testosterone 5 alpha-reductase were 5.0 x 10(-7) M and 1.0 x 10(-5) M, respectively.

5-alpha Reductase Inhibitors

WS-9659 A and B, novel testosterone 5 alpha-reductase inhibitors isolated from a Streptomyces. II. Structural elucidation of WS-9659 A and B.

On the basis of spectroscopic and chemical evidence, the structures of WS-9659 A and B isolated as inhibitors of testosterone 5 alpha-reductase from a Streptomyces have been established as 1 and 2, respectively. The reductase inhibitory activities of the derivatives 5 and 6, and degradation products 3 and 8 were considerably less active and substantially inactive, respectively.

5-alpha Reductase Inhibitors

WS-9659 A and B, novel testosterone 5 alpha-reductase inhibitors isolated from a Streptomyces. III. Biological characteristics and pharmacological characteristics.

WS-9659 A, a novel phenazine, produced by a Streptomyces sp., had testosterone 5 alpha-reductase inhibition activity on rat, dog and human prostates. However, WS-9659 A did not show any inhibitory activities for aldose reductase on rabbit lenses and lactate dehydrogenase on pig hearts. WS-9659 A was a competitive inhibitor against testosterone 5 alpha-reductase on rat prostates by use of testosterone as a substrate. Radio receptor binding assay of androgen receptor of rat prostates revealed that WS-9659 A had no affinity for this receptor. WS-9659 A was tested subcutaneously in immature castrated rats to confirm its effect on the growth of the ventral prostates induced by testosterone propionate.

5-alpha Reductase Inhibitors

New antitumor antibiotic, FR-900462. I. Taxonomy of the producing strain.

A new species of the genus Streptomyces, the proposed name of which is Streptomyces tokashikiensis sp. nov., is described. Soil isolate, strain No. 7124, produces a new antitumor antibiotic FR-900462. The organism is characterized by the presence of spores on the substrate hyphae. Strain No. 7124 is closely related to Streptomyces spiralis in morphological and cultural characteristics, but there are differences in spore surface, growth-permissible temperature, and carbohydrate utilization pattern. Therefore, it was decided to designate strain No. 7124 as a new species within the genus Streptomyces.

Antibiotics, Antineoplastic

A new immunomodulator, FR-900490.

FR-900490 is a new type of immunoactive substance produced by a fungus Discosia sp. F-11809. The colony forming units in culture (cfu-c) in bone marrow cells, which were suppressed by immunosuppressive factor obtained from the serum of sarcoma 180 tumor bearing mouse, was restored to normal level by the addition of FR-900490 in vitro. Furthermore, in mitomycin C (MMC)-treated mice the subsequent administration of FR-900490 caused a significant increase of cfu-c in bone marrow cells depressed by MMC.

Adjuvants, Immunologic

A new immunomodulator, FR-900483.

FR-900483 is a new immunoactive substance produced by a fungus, Nectria lucida F-4490. Concanavalin A-stimulated lymphocyte proliferation, which had been suppressed by addition of immunosuppressive factor, was restored to a normal level by the addition of FR-900483. Furthermore, FR-900483 restored the capacity of immunosuppressed mice to produce antibody against sheep red blood cells.

Adjuvants, Immunologic

Studies of an immunomodulator, swainsonine. I. Enhancement of immune response by swainsonine in vitro.

Swainsonine isolated from Metarhizium sp., was found to enhance the activities of the mouse immune system in vitro. Concanavalin A stimulated lymphocyte proliferation and proliferative response in mixed lymphocytes culture, which were suppressed by immunosuppressive factor obtained from serum of sarcoma 180 tumor bearing mouse, were restored to normal levels by the addition of swainsonine. Furthermore, the concanavalin A induced incorporation of [3H]thymidine into mouse spleen cells was remarkably increased by treatment with swainsonine over a wide dose range, From studies using fluorescence activated cell sorting, swainsonine was shown to enhance the expression of concanavalin A receptors of spleen cells.

Adjuvants, Immunologic