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Biomedical subjects

H Ohkuma

Publications and source records attributed to H Ohkuma.

At least 73 records · Page 4Linked to original sources

Studies on the mode of antifungal action of pradimicin antibiotics. II. D-mannopyranoside-binding site and calcium-binding site.

Based on the structure-activity relationship data of BMY-28864 and related pradimicin derivatives, the calcium salt-forming ability and the D-mannopyranoside-specific visible absorption maximum shift of BMY-28864 were analysed in the ternary complex formation of BMY-28864 with D-mannopyranoside and calcium. The free C-18 carboxyl group of BMY-28864 was proved to be the sole site for binding to calcium, while no hydroxyl groups of the aglycone were involved in calcium salt formation. The stereospecific D-mannopyranoside-recognizing ability of BMY-28864 was completely abolished by removal of the C-5 disaccharide moiety, and, more particularly, of the C-5 thomosamine moiety. Close relationship of these findings with the antifungal action was also supported by the in vitro antifungal assay and the potassium leakage induction test.

Anthracyclines↗

Synthesis and antifungal activities of pradimicin A derivatives modification of the alanine moiety.

Chemical modifications of the carboxyl group in the alanine moiety of pradimicin A were performed and in vitro and in vivo antifungal activities of the derivatives were examined in comparison with those of pradimicin A. The amide derivatives showed activities comparable to pradimicin A, indicating that the free carboxyl group can be modified without impairing the antifungal activity.

Alanine↗

5-Hydroxyanthranilic acid derivatives as potent 5-lipoxygenase inhibitors.

Three new 5-lipoxygenase inhibitors, designated as BU-4601 A, B and C, were found in the fermentation broth of Streptomyces sp. strain No. AA2807. Their structures were identified as isodecyl, isoundecyl and isolauryl esters of 5-hydroxyanthranilic acid, respectively. Based on their structures, five related esters were synthesized and evaluated for biological activity as inhibitors of 5-lipoxygenase. Both naturally-occurring and chemically-synthesized compounds exhibited almost equal levels of 5-lipoxygenase inhibitory activities in vitro.

Animals↗

[Age-related changes in Bruch's membrane of the senescence accelerated mouse].

We studied pathological changes in Bruch's membrane of Senescence Accelerated Mouse (SAM) P/1. Tannic acid was used to demonstrate collagen fibers and microfibrils in Bruch's membrane. With aging, thickening of Bruch's membrane, especially thickening of the basement membrane of the choriocapillaris, was remarkable. The distance between collagen fibers also became wider, and many more fine fibrils appeared around each collagen fibril with aging. These changes were observed mor in the posterior area than in the periphery.

Aging↗

[Fibronectin in the chorioretinal wound after laser photocoagulation].

Fibronectin (Fn) is a glycoprotein which mediates adhesion, extension, migration, and chemotaxis of the cells. We did a histochemical study of the time course of appearance and distribution of Fn in the chorioretinal wound after laser photocoagulation. In the normal chorioretinal tissue, Fn was detected in the internal limiting membrane, Bruch's membrane, and the endothelium of chorioretinal vessels. Shortly after laser photocoagulation, Fn appeared on Bruch's membrane and in the endothelium of choroidal vessels and choroidal stroma, and was prominent by one week after laser photocoagulation. Although Fn disappeared when wound healing was accomplished, it was still detected on Bruch's membrane one month after laser photocoagulation. These findings suggest that Fn is related to chorioretinal wound healing after laser photocoagulation.

Animals↗

[The effect of corticosteroid on the repair of the retinal pigment epithelium].

The effect of corticosteroid on the repairing process of the retinal pigment epithelial cells (RPE) after laser photocoagulation was investigated. Mild-intensity krypton red laser photocoagulations were performed on the monkey retina. After laser photocoagulations, betamethasone (0.5 mg/kg) were administered intramuscularly every day for 1-14 days. Moreover, the same doses of betamethasone were also administered intramuscularly for one week from the 1st to 7th day after laser photocoagulation on other monkeys. The photocoagulated lesions were observed with light and transmission electron microscopy. In monkeys that received corticosteroids, the migration and the proliferation of RPE were markedly inhibited, and the metaplasia to fibroblast-like cells of RPE was not observed. These results showed that large doses of corticosteroid inhibited the repair process of the injured RPE.

Animals↗

[Changes in the intermediate stage of retinal degeneration after intravitreal injection of ornithine].

We reported previously that intravitreal injection of a small amount of 1-ornithine hydrochloride in monkey eyes damages the retinal pigment epithelium (RPE), selectively. At one year after administration, sharply demarcated chorioretinal atrophy was seen. This paper describes the intermediate stage of retinal degeneration caused by ornithine. Two weeks following intravitreal injection of ornithine, RPE cells at the equator became necrotic and disappeared. However RPE regenerated to cover Bruch's membrane at the border of RPE degenerated area. In 2 months at an area where RPE cells disappeared, the photoreceptors and choriocapillaris degenerated to disappear. However, in the area in where RPE regenerated, they maintained their structure. This report demonstrated that damage of RPE resulted in disappearance of the photoreceptor and choriocapillaris.

Animals↗

[Histological observations on the sclera in uveal effusion].

The author performed sclerectomy in six cases of uveal effusion syndrome and examined the excised sclera histologically. From the findings of the sclera during the surgery and histological findings of the excised sclera, uveal effusion syndrome was divided into three groups: 1) nanophthalmos, 2) non-nanophthalmos with hypertrophic sclera, 3) non-nanophthalmos with normal thick sclera. In all cases, glycosaminoglycans were found to be deposited around the scleral collagen fibers. In the nanophthalmic eyes (group 1) and non-nanophthalmic eyes with the hypertrophic sclera (group 2), much glycosaminoglycans were demonstrated around the collagen bundles and enlarged the collagen bundle spaces. In these groups, sclerectomy procedures were successful and, based on the successful result of the operation, the cause of uveal effusion was considered to be disturbance of outflow of intraocular fluid through the hypertrophic sclera. In non-nanophthalmic eyes with normal thick sclera (group 3), few glycosaminoglycans was demonstrated around the collagen bundles with less abnormality, and sclerectomy procedure was not effective. In this group, the occurrence of uveal effusion was another cause but abnormal sclera.

Adult↗

Management of giant serpentine aneurysms of the middle cerebral artery--review of literature and report of a case successfully treated by STA-MCA anastomosis only.

Thirty-eight cases of giant serpentine aneurysms (GSA), including 17 GSA of the middle cerebral artery (MCA), were reviewed in the literature. The treatment possibilities of GSA of the MCA are discussed together with our own case who was a 39-year-old male with a GSA of the right MCA and was treated only by STA-MCA anastomosis. The pathogenetic mechanism of progressive enlargement of the aneurysm is also discussed.

Adult↗

Sultriecin, a new antifungal and antitumor antibiotic from Streptomyces roseiscleroticus. Production, isolation, structure and biological activity.

Streptomyces roseiscleroticus L827-7 (ATCC 53903) produced a novel antifungal and antitumor antibiotic, sultriecin. It exhibited in vitro antifungal activity and potent in vivo antitumor activity against P388 and L1210 leukemias, and B16 melanoma. Sultriecin is composed of several unique structural units; a conjugated triene, an alpha,beta-unsaturated delta-lactone, and a sulfate functionality.

Animals↗

[Laser photocoagulation of experimentally produced choroidal neovascularization. 2. Comparison of effects by dye and argon blue-green lasers].

Choroidal neovascularization was produced in 18 eyes of 12 rhesus monkeys by application of intense krypton laser photocoagulation. Eight weeks or later, a total of 34 choroidal neovascularizations were treated either by dye laser at wavelengths of 577 or 630 nm or by argon blue-green laser. The treated lesions were evaluated clinically and histopathologically from 24 hours to 3 months after treatment. All the treated lesions were apparently healed by each of the 3 laser modalities. Histopathologically, all the treated choroidal neovascularizations were occluded 24 hours after treatment. At 2 weeks to 3 months after treatment, newly-formed choroidal vessels were present in 3 of 9 lesions (33%) after 577 nm dye laser treatment, in 8 of 9 lesions (89%) after 630 nm dye laser treatment, and in 5 of 8 lesions (62%) after argon blue-green laser. These results seemed to show the clinical superiority of 577 nm dye laser in treating choroidal neovascularization.

Animals↗

[Laser photocoagulation for experimental choroidal neovascularization. 1. Mild dye laser photocoagulation].

The author treated experimentally produced choroidal neovascularization (ChNV) with mild dye laser photocoagulation (PHC). We treated these ChNVs with 590 nm wavelength, 200 microns spot size, 0.2 second duration and 50 mW of power. Eleven eyes of nine rhesus monkeys were used. Then these ChNVs were examined clinically and histopathologically at 24 hours, 2 weeks and a month after therapeutic PHC. Small ChNVs, less than 1/3 disc diameter healed successfully and histopathologically most of them were coagulated and disappeared. A few poorly developed ChNVs remained, but were well enveloped by the proliferating retinal pigment epithelial (RPE) cells. On the other hand, ChNVs of more than 1/3 disc diameter did not respond to weak PHC, grew actively over a month, and were not completely surrounded by proliferating RPE cells. These results suggest that by mild PHC, small ChNVs may be treatable, however, in large ChNVs, mild PHC may rather accelerate their activity.

Animals↗

[Two cases of failure of a programmable pressure valve].

Two cases of a programmable pressure valve trouble are reported. Case #1 was that of a 49-year-old male who had received a ventriculoperitoneal shunt (VPS) using a Sophy programmable pressure valve (Model S3) after the removal of the fourth ventricle ependymoma. After the VPS, the patient went through several episodes of complaining of headache due to the spontaneous movement of the rotor from the high pressure position to the medium or low pressure position. The symptom had disappeared after exchanging the valve for a new one and by setting the valve pressure at high. Examination of the removed valve revealed that the bending-degree of the spring tip was insufficient, and that the opening pressures at the medium and high pressure positions were both lower than the desired range. Case #2 was that of a 62-year-old female who had received a VPS for normal pressure hydrocephalus using a Sophy programmable pressure valve (Model S3) with the valve pressure set a high. However, her symptoms did not improve, so an attempt was made to change the valve pressure from the high pressure position to the medium pressure position with a ring magnet. But the rotor could not be moved. The valve was exchanged and the valve pressure was set at medium, and the symptoms of the patient improved postoperatively. Examination of the removed valve revealed that the movement of the rotor with a ring magnet was not able to be carried out smoothly.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral Ventricle Neoplasms↗

[Histological changes in the retinal pigment epithelium and Bruch's membrane in senescence accelerated mouse].

Senescence associated changes of the retinal pigmented epithelium (RPE) and Bruch's membrane were investigated in senescence accelerated mouse (SAM), which is an aging model mouse, by light and electron microscopy. The most characteristic changes in RPE were swelling of basal infoldings, extension of intercellular space and accumulation of lipofuscin granules. In Bruch's membrane, discontinuation of elastic layer and abnormal increase of fine fibrils in the outer collagenous layer were observed. The aging changes in SAM were severer in the posterior retina than in the peripheral one. Moreover, these changes were seen younger age than in those of the normal BALB/c mouse.

Aging↗

Reductive and nucleophilic activation products of dynemicin A with methyl thioglycolate. A rational mechanism for DNA cleavage of the thiol-activated dynemicin A.

The reaction products of methyl thioglycolate with dynemicin A, dynemicin H and dynemicin S, were isolated by HPLC purification and identified spectroscopically. The major product, dynemicin H (C30H23NO9), was determined to be a C-8 hydrogen analogue of dynemicins L and N in which the enediyne core is aromatized. The minor product, dynemicin S (C33H27No11S), is an adduct of methyl thioglycolate at the C-8 position. By using NADPH instead of methyl thioglycolate, the reaction with dynemicin A also gives the same major product (dynemicin H). The nucleotide-specific cleavage of dynemicin A induced by addition of methyl thioglycolate is remarkably similar to that induced by addition of NADPH, whereas dynemicins H and S show no DNA cleavage activities. The formation of dynemicins H and S provides a rationale for the reductive and nucleophilic activations of dynemicin A.

Alkenes↗

Role of platelet function in symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

To evaluate the role of platelet function in the pathogenesis of cerebral vasospasm, we compared sequential changes of platelet aggregability and beta-thromboglobulin and thromboxane B2 concentrations in blood samples from the internal jugular and peripheral vein of 13 patients with aneurysmal subarachnoid hemorrhage. Platelet function in blood from the internal jugular vein tended to be enhanced during days 0-1 but recovered to the normal range during days 2-4. After day 5, platelet function showed various patterns depending on the presence of symptomatic vasospasm. In patients without symptomatic vasospasm, sequential changes were relatively minor, with normal or slightly high values. Patients with symptomatic vasospasm already showed high platelet aggregability during the early stage of vasospasm. The concentration of beta-thromboglobulin increased several days after the onset of vasospasm, reaching 80 ng/ml or more in patients with a poor prognosis. Two of the five patients with symptomatic vasospasm showed markedly high concentrations of thromboxane B2 after day 8. These results suggest that vasospasm activates platelets and promotes aggregability and that the resulting increased tendency for thrombus formation may affect the patient's prognosis during the advanced stage.

Adult↗

Dynemicins, new antibiotics with the 1,5-diyn-3-ene and anthraquinone subunit. I. Production, isolation and physico-chemical properties.

Dynemicin A, a novel antibiotic containing the bicyclo[7.3.1]-1,5-diyn-3-ene and 1,4,6-trihydroxyanthraquinone functionalities, was isolated from the culture broth of Micromonospora chersina sp. nov. M956-1. The antibiotic exhibited potent in vitro antibacterial and cytotoxic activity, and in in vivo, it cured mice from lethal Staphylococcus aureus infection and prolonged survival time of mice inoculated with murine tumors. Three satellite components, dynemicins L, M and N, were also isolated from the culture broth and chemically characterized.

Animals↗

Maduropeptin, a complex of new macromolecular antitumor antibiotics.

Maduropeptin, a complex of new macromolecular antitumor antibiotics, is a metabolite of Actinomadura madurae H710-49. The active components maduropeptins A1, A2 and B are acidic chromopeptides with MW of around 22,500 and composed of 14 types of amino acids and an unstable chromophore. The antibiotics are active in vitro against Gram-positive bacteria and highly cytotoxic to tumor cells. They produced significant prolongation of survival time of mice implanted with P388 leukemia and B16 melanoma.

Actinomyces↗