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Biomedical subjects

M Ishizuka

Publications and source records attributed to M Ishizuka.

At least 19 recordsLinked to original sources

Antimicrobial benzopyrans from the receptacle of sunflower.

The antimicrobial substances in sunflower (Helianthus annuus) were investigated. Two antifungal benzopyran derivatives, 6-acetyl-2,2-dimethyl-1,2-benzopyran (1) and 6-acetyl-7-hydroxy-2,2-dimethyl-1,2-benzopyran (2), were isolated from the ethanol extract of sunflower receptacles. The antimicrobial activities of isolated compounds 1 and 2 and their related compounds (precocenes) were evaluated by the paper disk method, using Pyricularia oryzae as the test fungus.

Anti-Infective Agents

Alterations of cytochrome P450-dependent monooxygenase activities in Eriocheir japonicus in response to water pollution.

Eriocheir japonicus, fresh-water crabs inhabiting rivers and estuaries in Japan, were investigated for cytochrome P450 (CYP)-dependent drug-metabolizing enzyme activities to see if these activities reflect the river pollution gradient. From the laboratory dose-response experiments, we found that the polycyclic aromatic hydrocarbon (PAH) 3-methylcholanthrene induced total CYP contents, ethoxycoumarin O-deethylase activity, and bunitrolol 4-hydroxylase activity in crab hepatopancreas. In the field studies, crabs collected from the river with the highest concentration of PAHs exhibited the highest levels of CYP, the highest activities of benzo[a]pyrene 3-hydroxylase, imipramine 2-hydroxylase, bunitrolol 4-hydroxylase, ethoxycoumarin O-deethylase, and the ability to metabolically activate benzo[a]pyrene, but erythromycin N-demethylase activity was not induced. The correlation between PAH levels and drug-metabolizing enzyme activities in female crabs were not as marked as in male crabs. The levels and activities of CYP did not appear to reflect the concentrations of organochlorines and polychlorinated biphenyl congeners (PCBs) studied in the fat of crab hepatopancreas.

Animals

Growth inhibition of K-ras-expressing tumours by a new vinca alkaloid, conophylline, in nude mice.

Conophylline, a new vinca alkaloid isolated from the plant Ervatamia microphylla induced normal flat morphology in K-ras-NRK and K-ras-NIH cell lines, and lowered the increased uptake of 2-deoxyglucose in K-ras-NRK cells. Conophylline inhibited the growth of K-ras-NRK cells, but this inhibition was reversible. The alkaloid also inhibited the growth of K-ras-NRK and K-ras-NIH3T3 tumours transplanted into nude mice. On the other hand, it showed no effect on survival of the mice loaded with L1210 leukaemia. Thus, conophylline is a new antitumour vinca alkaloid that induced normal phenotypes in ras-expressing cells.

Animals

[A case of acromegaly associated with variegated spinal disorders].

A case of acromegaly associated with variegated spinal disorders was reported. The spinal disorders were multiple cervical disc herniations, spinal epidural cavernous angioma, multiple ossification of the spinal ligament and lumbar canal stenosis. A 51-year-old woman with acromegaly, complaining of disturbances of delicate hand movement and gate, consulted our department. Her past history included diabetes mellitus, hypertension and progressing enlargement of her extremities. Serum growth hormone level was 65.7 ng/ml and somatomedin-c level was 746 ng/ml. Brain MRI showed a pituitary tumor extending to the right cavernous sinus. Cervical MRI revealed disc herniations at C5/6 and C6/7. Thoracic MRI revealed osteoporosis, ossification of the posterior longitudinal ligament and multiple ossification of yellow ligament. Lumbar MRI disclosed ossification of yellow ligament and canal stenosis. Anterior fusion of C5-C7 and an intracapsular removal of the pituitary tumor were performed. Its pathology was that of eosinophilic adenoma. After 3 months, she suffered from paraparesis. On repeating MRI examination with Gd-DTPA, a spinal epidural mass was found at T4. Under laminectomy of Th3-5 and Th8-11, the epidural mass and ossified yellow ligament were removed. The epidural mass was cavernous angioma. She was able to walk without any assistance. An association of spinal canal stenosis with acromegaly is well known. But the association of disc herniation and with the ossification of spinal ligaments is rather rare in the literature. Spinal epidural cavernous angioma is very rare. We discussed the etiological aspects and the management of spinal disorders with acromegaly.

Acromegaly

Radiographic diagnosis and surgical repair of a sciatic hernia: report of a case.

We report the case of a 44-year-old woman who presented with a reducible painless swelling in her left buttock. The mass was preoperatively diagnosed as a sciatic hernia by herniography, which showed the peritoneal sac through the sciatic foramen, and by enterography, intravenous pyelography, and cystography, which demonstrated that the small intestine and urinary bladder had herniated into the sac. The diagnosis and management of this patient are described, followed by a review of the literature on sciatic hernias.

Adult

Low molecular weight immunomodulators produced by microorganisms.

In order to develop a new class of low molecular weight immunomodulators for the treatment of incurable diseases involving cancer, hematologic diseases and inflammation, we have sought cytokine inducers and inhibitors of cell adhesion to the extracellular matrix among the low molecular compounds produced by microorganisms. Cytogenin, cytoblastin (a monokine inducer), conagenin (a lymphokine inducer) and delaminomycins and IC-101 (inhibitors of cell adhesion to extracellular matrices) have been recently found in our institute. In this report, we describe the principles of screening and structures, and discuss their biological activities.

Actinobacteria

Surgical treatment of the fractured and dislocated condylar process of the mandible.

Most fractures of the mandible can be managed conservatively. This report is a retrospective evaluation of the clinical and radiological results in 17 patients with 21 dislocated fractures submitted to open reduction and fixation, employing steel wires and maxillomandibular fixation. Follow-up ranged from 7 to 55 months, (mean 29.5). Functional assessment showed good opening movements (mean 41.9 mm). There were no cases of ankylosis, pain, or paralysis of the facial nerve. Radiological assessment was normal when the lateral pterygoid muscle was maintained adherent to the fractured proximal segment. Radiological signs of bone resorption occurred when the fractured segment was detached from the lateral pterygoid muscle. In our opinion, dislocated condylar process fractures can be managed surgically and with steel wire ligatures and maxillomandibular fixation. Whenever possible, the lateral pterygoid muscle should be inserted into the fractured proximal segment, i.e. as an osteomuscular flap.

Adolescent

Antitumor activity of cytogenin.

Antitumor effect of cytogenin against IMC carcinoma in mice was investigated. Since cytogenin did not show cytotoxicity against tumor cells in vitro at 50 micrograms/ml and toxicity at more than 2,000 mg/kg i.p., it was considered that the antitumor effect is due to host mediated events. Cytogenin showed antitumor activity against a syngeneic murine transplantable tumor, IMC carcinoma by oral administration depending upon schedule of administration. The optimum effect was observed by the administration starting day 8 after transplantation of tumor cells, every other day for 10 times or every 2nd day for 7 times. The antitumor effect was reduced in immunosuppressed mice given anti-asialo GM1 serum and in athymic mice, but not in mice irradiated with X ray. The antitumor effector cells activated by cytogenin were determined to be macrophages and T cells.

Animals

Improvement of efficacy of antitumor agents by conagenin.

The antitumor efficacy of antitumor agents at sublethal doses was investigated in combination with conagenin (CNG) against murine leukemias. Mice were inoculated with 1 x 10(3) L1210 cells i.v. and given 300 mg/kg of cyclophosphamide (CY) i.p. on days 1 and 2 or on days 1, 5 and 9 after the tumor inoculation, and 5 mg/kg of CNG daily for 10 days. The administration of CNG was effective in increasing the number of cured mice and in prolonging the survival period of mice significantly, on both schedules of CY treatment. Moreover, the antitumor effect of CY against EL-4 was enhanced by CNG in increasing the number of cured mice, in CY treatment on days 1 and 2, and on days 1, 5 and 9. The effect of CNG was examined with mitomycin C (MMC) and adriamycin (ADM) at sublethal doses against leukemias. The antitumor effects of MMC at 10 mg/kg against L1210, and ADM at 15 mg/kg against P388 administered on days 1 and 5 were enhanced by CNG. Although mice treated with ADM at 15 mg/kg died earlier than non-treated controls on days 1 and 2 against L1210, P388 and EL-4, CNG with ADM was effective in prolonging the survival period.

Adjuvants, Immunologic

Action of cytogenin on lymphoid cells and their cytokine production.

Action of cytogenin on macrophages and T cells was investigated. Phagocytosis of yeast and production of PMA-elicited superoxide anion by macrophages taken from mice given cytogenin po were augmented. Cytogenin enhanced productions of IL-1 alpha by macrophages and IFN gamma and GM-CSF by spleen cells although it did not enhanced production of TNF alpha by macrophages and IL-6 by macrophages and spleen cells. Macrophages stimulated with cytogenin caused to stimulate proliferation of purified T cells in Intercell cultures in which each cell population was cultured without contact. Results suggest that cytogenin primarily activates macrophages to produce monokines such as IL-1 alpha and it causes to stimulate proliferation and differentiation of T cells resulting in production of lymphokines such as IFN gamma and GM-CSF.

Animals

Modulation of macrophage activity in tumor bearing mice by cytogenin.

Cytogenin recovered the reduced mitogenic response to Con A of spleen cells of tumor bearing mice in vitro. The suppressive factor(s) was detected in adherent cell population in spleen cells. The reduced antitumor effector activity of spleen cells taken from tumor bearing mice was also augmented by the treatment with cytogenin in vitro. The effect of cytogenin was neutralized by the treatment with anti-Mac 1 serum. Administration of cytogenin inhibited the production of nitric oxide by macrophages which is known as one of suppressor factors. Results indicate that one possible action of cytogenin exhibiting antitumor activity in tumor bearing mice may be due to modulation of Mac 1 positive cells.

Animals

Effects of cytogenin on spontaneous arthritis in MRL/1 mice and on pristane-induced arthritis (PIA) in DBA/1J mice.

Cytogenin, 8-hydroxy-3-hydroxymethyl-6-methoxyisocoumarin, has low cytotoxicity on murine and human tumour cells in vitro. It augments or suppresses phagocytosis of macrophages and lymphocyte proliferation. It has been reported that cytogenin has a potent inhibitory effect clinically on adjuvant arthritis in Lewis rats and on type II collagen-induced arthritis in DBA/1J mice. Our experimental findings provide evidence that cytogenin has beneficial effects on spontaneous polyarthritis in MRL/1 mice and pristane-induced arthritis in DBA/1J mice. The results suggest that the mode of the anti-arthritic action of cytogenin is different from those of NSAIDs; although the precise mode of action remains unclear, cytogenin may become an excellent therapeutic agent for rheumatoid arthritis.

Animals

An Escherichia coli cyoE gene homologue in thermophilic Bacillus PS3 encodes a thermotolerant heme O synthase.

The cyoE gene of the Escherichia coli bo-type quinol oxidase operon (cyoABCDE) has been previously shown to encode heme O synthase. To demonstrate a catalytic role of a cyoE homologue (the caaE gene) in the gene cluster for caa3-type cytochrome c oxidase of thermophilic Bacillus PS3, we have carried out genetic complementation analysis using the chimeric operon cyoABCD-caaE and heme O synthase assay using the CaaE-overproduced E. coli membranes. We found that the caaE gene encodes a thermotolerant heme O synthase which provides an intermediate for heme A biosynthesis.

Alkyl and Aryl Transferases

The novel immunostimulant N-563, an analogue of deoxyspergualin, promotes resistance to Candida albicans infection in mice.

An analogue of deoxyspergualin, N-563 has an immunostimulating activity whereas the mother compound has been found to be a potent immunosuppressant. In this study, the protective effect of the analogue against C. albicans infection was investigated in normal and immunosuppressed mice. In normal mice, N-563 treatment at 10 mg/kg for 3 days prior to infection significantly prolonged the survival time. In immunosuppressed mice treated with a single dose of cyclophosphamide 4 days prior to infection, N-563 at 3 and 10 mg/kg for 3 days prior to infection also significantly prolonged the survival time of mice. In addition, it augmented the phagocytic activity of neutrophils and enhanced the delayed type hypersensitivity reaction against C. albicans. Coincidentally, N-563 appeared to protect against secondary infection with C. albicans in the delayed type hypersensitivity-positive mice.

Adjuvants, Immunologic

Effect of conagenin on thrombocytopenia induced by antitumor agents in mice.

The effect of conagenin (CNG) on myelosuppression induced by antitumor agents was investigated. The daily administration of CNG prevented reduction in the number of platelets (PLT) observed in peripheral blood of mice given mitomycin C (10 mg/kg) but did not prevent reduction in the number of leukocytes (WBC). The effect on PLT was also confirmed in mice given cyclophosphamide (100 mg/kg). In mice given repeated doses of 5-fluorouracil (10 mg/kg), CNG prevented the reduction of PLT as well as WBC and maintained them at normal levels. CNG prevented reduction of the production of interleukin-2, 3 and 6 in cultured supernatants of spleen cells taken from mice given 5-fluorouracil. These results suggest that CNG modulates production of lymphokines which are responsible for thrombopoiesis.

Animals

Biosynthesis of antitumor antibiotic, cytogenin.

The biosynthesis of antitumor antibiotic cytogenin, 3-hydroxymethyl-6-methoxy-8-hydroxy-isocoumarin, was studied by feeding 14C- or 13C-labeled compounds to culture of the producing organism, Streptoverticillium eurocidicum MI43-37F11. 14C-Acetate and 14C-methionine were efficiently incorporated into cytogenin as precursors. 13C NMR studies proved that the carbon skeleton of cytogenin is derived from pentaketide intermediate due to head-to-tail condensation of five acetate units and methyl group of 6-OCH3 is derived from methionine. It was suggested that 3-hydroxymethyl and/or 6-methoxy group of cytogenin were metabolized by hydroxylation and/or methylation from three intermediates.

Acetates