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Biomedical subjects

M Kohsaka

Publications and source records attributed to M Kohsaka.

At least 109 records · Page 6Linked to original sources
PubMed1990

A novel antifungal antibiotic, FR-900848. I. Production, isolation, physico-chemical and biological properties.

Streptoverticillium fervens produced a new antibiotic, FR-900848, which has a high specific activity against filamentous fungi. Purified by solvent extraction and column chromatography, the compound appears as colorless crystals. Its structure is C32H43N3O6, which consists of 5'-amino-5'-deoxy-5,6-dihydrouridine with an unsaturated fatty acid having unprecedented four serial and one isolated cyclopropane rings.

Animals↗
PubMed1990

[Comparisons of effects of vitamin D3 metabolites on mineralization: utilization of incisor dentin in parathyroidectomized rats].

The rat incisor is continuously growing throughout the animal's life recording the state of mineralization within its dentin at all times. Therefore, it was assumed that the incisor dentin was suitable material for studying the effects of various drugs on such mineralization. The present study set out to examine the effects of vitamin D3 metabolites on the remineralization of dentin and the serum calcium level in parathyroidectomized (PTX) rats. Male Wistar rats weighing about 200-250 g were parathyroidectomized. Each rat was given daily 12 g of a synthetic diet containing 0.1% Ca and 0.4% P (normal P) or 0.06% P (P deficient) without vitamin D. Exp. I: Three groups of rats given a normal P diet were orally administered vehicle, 25 (OH) D3 (50 IU/rat) or 1,25 (OH)2D3 (5 IU/rat) for 5 days from the 28th day after PTX, respectively. Exp. II: Two groups of rats given a normal P diet or a P deficient diet were further divided into 4 sub-groups and intramuscularly administered 0, 5,000, 10,000 or 20,000 IU of vitamin D3 on the 9th day after PTX, respectively. The active vitamin D3, 1,25 (OH)2D3 restored the mineralization of the dentin which had been suppressed following PTX, and elevated the serum calcium level to about 9 mg/dl. However, the 25 (OH) D3 neither restored the mineralization of the dentin nor elevated the serum calcium level in the PTX rats. At doses below 1,000 IU, vitamin D3 could not restore the mineralization of the dentin. However, at massive doses above 5,000 IU, the mineralization was restored in proportion to the dose. The serum calcium levels also increased in proportion to the dose. It is assumed that the increase of the serum calcium level was mainly due to the enhancement of calcium absorption from the intestine by vitamin D3. Both remineralization of the incisor dentin and increase of the serum calcium level were more marked in groups of rats given a P deficient diet than in those given a normal P diet. In all cases in the present experiments, the degree of mineralization of the dentin seemed to correspond with the degree of elevation of the serum calcium levels. These results suggest that the remineralization of the dentin in the PTX rats was attributable to the effect of the vitamin D3 metabolites on serum calcium regulation. Relative biological activities of 1,25 (OH)2D3, 25 (OH) D3 and vitamin D3 on the remineralization of dentin were estimated to be 1, less than 0.02 and less than 0.001, respectively.

Animals↗
PubMed1990

[An analysis of ictal EEGs by a newly developed ambulatory cassette EEG system].

We evaluated the efficiency of a newly developed cassette EEG recording device and our system for detecting and analyzing ictal EEGs in epileptic children. We got 13 ictal records from 16 epileptic children. We could precisely differentiate and diagnose their classifications of seizures by comparative analyses of ictal records and clinical symptoms. We discussed the characteristics of our system, and described actual analysis methods in 3 cases as examples. It was concluded that our system offered valuable information about ictal events in epileptic children.

Adolescent↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

A new immunomodulator, FR-901235.

FR-901235 is a new type of immunoactive substance produced by an imperfect fungus, Paecilomyces carneus F-4882. The mitogen-induced lymphocyte proliferation which had been suppressed by addition of immunosuppressive factor, was restored to a normal level by the addition of FR-901235. Furthermore, the subsequent administration of FR-901235 partially restored the impaired delayed-type hypersensitivity to sheep red blood cells in tumor-bearing mice.

Adjuvants, Immunologic↗
PubMed1989

FK409, a novel vasodilator isolated from the acid-treated fermentation broth of Streptomyces griseosporeus. I. Taxonomy, fermentation, isolation, and physico-chemical and biological characteristics.

FK409, a novel vasodilator with anti-platelet aggregation activity, has been isolated from the acid-treated fermentation broth of Streptomyces griseosporeus No. 16917, which was cultured on a medium containing NaNO3 for 4 days. FK409 was purified from the culture-filtrate by extraction with ethyl acetate after adjusting the pH to 3.0 with HC1, followed by silica gel chromatography. The molecular formula of this compound was determined to be C8H13N3O4. In vitro, FK409 showed a potent relaxation activity on noradrenaline induced contraction of rat aorta. In addition to the vasodilating activity, this compound also showed potent anti-aggregation activities towards rabbit platelets. In vivo, intravenously administered FK409 resulted in marked blood pressure lowering in rats.

Animals↗
PubMed1989

FK409, a novel vasodilator isolated from the acid-treated fermentation broth of Streptomyces griseosporeus. II. Structure of FK409 and its precursor FR-900411.

In a purification study of novel vasodilator FK409 from the fermentation broth of Streptomyces griseosporeus, we found the existence of FR-900411, a precursor of FK409 in the broth, suggesting that FK409 was derived from FR-900411 via a chemical reaction. We therefore isolated FR-900411 from the broth. The structure of FK409 and FR-900411 were determined to be 1 and 2 respectively, on the basis of spectroscopic and chemical evidence.

Alkadienes↗
PubMed1989

FK409, a novel vasodilator isolated from the acid-treated fermentation broth of Streptomyces griseosporeus. III. Reaction mechanism and synthesis.

FK409 (1), a novel vasodilator, is a semi-artificial fermentation product of Streptomyces griseosporeus No. 16917, which was cultured in a medium containing nitrate. And the acid-treatment of the broth is essential for the generation of FK409. FK409 was considered to be formed via a novel synchronous nitrosation-nitration reaction of FR-900411 (2) which was produced by the strain as a precursor of FK409. The conversion of FK-900411 to FK409 proceeded under acidic conditions with nitrite formed by microbial reduction of nitrate. Total synthesis of FK409 was achieved starting from (E)-2-ethyl-2-butenal (3) via a nitrosation reaction of FR-900411 (2) as a key step.

Alkadienes↗
PubMed1989

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↗
PubMed1989

[Comparisons of bioavailability of various calcium salts. Utilization incisor dentin in parathyroidectomized rats].

In the present study, we compared the bioavailability of various calcium salts in the diet such as calcium lactate, calcium carbonate and calcium phosphate by examining the effects of these calcium salts on serum calcium concentration and on the mineralization of incisor dentin in parathyroidectomized (PTXed) rats. Each rat was given daily 12 g of a low calcium (0.1% Ca) diet beginning from 3 days before the operation and continuing for 11 days after. Then the diet was changed to those containing various calcium salts (1.5% Ca). The serum calcium and phosphorous concentrations were examined every three days, just before feeding time and 6 hours after. The degree and site of the mineralization of incisor dentin were examined histologically by a time marking method using lead acetate. In the PTXed rats maintained on a low calcium diet, the serum calcium concentration decreased to about 4.5 mg/dl and the mineralization of incisor dentin was inhibited. On the 11th day, just before feeding on diets containing various calcium salts, the serum calcium concentrations were very similar for each group, but at 6 hours after feeding, concentration was 7.6 mg/dl in the calcium lactate group, 6.2 mg/dl in the calcium carbonate group and 4.8 mg/dl in the calcium phosphate group. On the 17th day following administration of the high calcium diets, the serum calcium concentrations were 9.8 mg/dl in the calcium lactate group, 8.4 mg/dl in the calcium carbonate group and 4.4 mg/dl in the calcium phosphate group. Mineralization of the incisor dentin was best in the calcium lactate group, moderate in the calcium carbonate group and poor in the calcium phosphate group. We also examined the effects of dietary phosphorus contents on serum calcium concentrations and on the mineralization of incisor dentin using PTXed rats. On the 17th day following the administration of diets (1.5% Ca, with calcium lactate) containing various amounts of phosphorus, the serum calcium concentrations in the calcium lactate group were 8.8 mg/dl (0.4% P), 6.9 mg/dl (0.8% P) and 4.2 mg/dl (1.6% P) respectively. Mineralization of incisor dentin was also inhibited in rats fed a high phosphorus diet. These results suggest that in PTXed rats, absorption of calcium from the intestines and mineralization of the incisor dentin is best by the administration of calcium lactate, moderate by calcium carbonate and poor by calcium phosphate, and that phosphorus in the diet inhibits calcium absorption from the intestines.

Animals↗
PubMed1988

Immunosuppressive effect of FK506 on collagen-induced arthritis in rats.

FK506, a new immunosuppressive agent, was given intramuscularly to rats for 12 days, starting on the day of type II collagen immunization. FK506 in doses of 0.32 mg/kg or more suppressed arthritis and also suppressed humoral and skin test response to type II collagen. FK506 suppressed arthritis only when given during the afferent limbs of immune response (0-4 days), whereas the drug was only marginally effective when treatment was started during the efferent limbs of immune response (7-11 days). FK506-induced immunosuppression continued and/or was maintained throughout the experiments (50 days). These rats immunized with type II collagen and treated with FK506 failed to develop arthritis even following a secondary immunization 50 days later but were fully capable of developing experimental allergic encephalomyelitis. This result suggest that FK506-treated rats develop specific unresponsiveness toward the type II collagen. It is concluded that FK506 is a strong immunosuppressive drug on collagen-induced arthritis.

Animals↗
PubMed1988

Immunosuppressive effect of FK506 on experimental allergic encephalomyelitis in rats.

We investigated the effect of a new immunosuppressant, FK506, on the development of experimental allergic encephalomyelitis (EAE) in rats. EAE developed in 100% of rats immunized with myelin basic protein (MBP) in complete Freund's adjuvant. FK506 in doses of 1.0 mg/kg/day or more prevented the clinical signs of EAE for at least 50 days, when administered intramuscularly 5 days a week for 2 weeks starting on the day of immunization (days 0-4 and days 7-11), and a similar result was obtained, when the compound was given for 5 days (days 0-4). FK506, however, showed a significant but weak effectiveness when started from 7 days after immunization. Delayed-type hypersensitivity (DTH) to MBP developed before EAE, and anti-MBP antibody levels increased. Both humoral and cellular immune response to MBP were completely suppressed in rats treated with FK506. From these results, it is presumed that immunosuppression of cell-mediated immunity and/or humoral immunity by the treatment of FK506 actually causes the decreased incidence noted in the experiment for the development of EAE.

Animals↗
PubMed1988

Effect of Nocardia rubra cell wall skeleton on interleukin 1 production from mouse peritoneal macrophages.

Nocardia rubra cell wall skeleton (N-CWS) was shown to augment interleukin 1 (IL-1) production from peritoneal resident and exudate macrophages in C3H/HeN mice. The mol. wt of the N-CWS-induced IL-1 product was about 17,000 daltons, which is a similar weight to that obtained by lipopolysaccharide stimulation. The stimulation of IL-1 production by N-CWS was seen as early as 8 h after the start of incubation and peak production was observed at 48 h. Profound effects were seen with 10 micrograms/ml or more of N-CWS. Experiments on the regulation of the N-CWS-augmented IL-1 production showed that prostaglandin E2 inhibited the augmentation, and indomethacin (cyclo-oxygenase inhibitor) further augmented it. Leukotriene B4 and AA861 (lipoxygenase inhibitor) had no effect. Our findings suggest that the previously reported adjuvant effect of N-CWS may, in part, be mediated via its ability to stimulate IL-1 production; and that such a stimulation may be blocked by prostaglandins.

Animals↗