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Biomedical subjects

F Kato

Publications and source records attributed to F Kato.

At least 91 records · Page 5Linked to original sources
PubMed1991

The genetic and biochemical basis of polyketide metabolism in microorganisms and its role in drug discovery and development.

The possibilities for the design of new drug screening and development strategies directed to a specific objective on the basis of genetic engineering of microorganisms is discussed from two points of view. Firstly, results of work on genetic hybrids of STREPTOMYCES species for the production of new metabolites such as mederrhodin (1) and aloespanoarin II (4) are described. Secondly, the enhanced production of known metabolites such as tetracenomycin A (2) (11) and tetracenomycin C (9) by recombinant STREPTOMYCES species is considered. Mechanistic aspects of polyketide metabolism are included.

Journal Article↗
PubMed1991

[Current status of the conservative treatment of urinary bladder for invasive bladder cancer].

During the 3 years from 1987 to 1990, we gave hyperthermia to 11 of the patients who visited our department for the treatment of invasive bladder cancer. Results and prognosis are reported. Stage and grade of the cancer before the treatment in 11 cases were T2 in 5 cases, T3 in 3 cases, T4 in 3 cases, transitional cell carcinoma (TCC) grade 2 in 8 cases, TCC grade 3 in 2 cases, and TCC grade 3 + anaplastic carcinoma in 1 case. Complications were observed in 8 of the 11 cases, such as severe heart disease and others. Pretreatment of radiation therapy, transurethral resection or chemotherapy was given in all cases. Hyperthermia was performed combined with hydroxypropyl cellulose-(HPC)-adriamycin, or radiation therapy, and the following results were obtained: complete response (CR) in 4 cases, partial response (PR) in 4 cases, no change (NC) in 2 cases and progressive disease (PD) in 1 case. Among 4 cases of PR, total cystectomy was performed in 3 cases. These 3 cases and the 4 cases of CR are alive now, but the other 4 patients died.

Carcinoma↗
PubMed1991

The genetic and biochemical basis of polyketide metabolism in microorganisms and its role in drug discovery and development.

The possibilities for the design of new drug screening and development strategies directed to a specific objective on the basis of genetic engineering of microorganisms is discussed from two points of view. Firstly, results of work on genetic hybrids of Streptomyces species for the production of new metabolites such as mederrhodin (1) and aloespanoarin II (4) are described. Secondly, the enhanced production of known metabolites such as tetracenomycin A2 (11) and tetracenomycin C (9) by recombinant Streptomyces species is considered. Mechanistic aspects of polyketide metabolism are included.

Acetates↗
PubMed1990

Isolation of bacterial strains, which hydrolyze glycyrrhizin and produce glycyrrhezic acid, from soil.

We isolated eight bacterial strains which could hydrolyze glycyrrhizin to glycyrrhezic acid. The bacterial strains were identified as three strains of Pseudomonas saccharophila, two of Plesiomonas sp., one of Pseudomonas stutzeri, one of Klebsiella pneumoniae subsp. ozaenae and one of Kluyvera ascorbata. Their capacity for the conversion of glycyrrhizin to glycyrrhezic acid was assayed by high performance liquid chromatography. P. saccharophila 11 was the most effective among the eight strains. Then, beta-glucuronidase, which is responsible for hydrolysis of glycyrrhizin, activity was assayed with p-nitrophenyl-beta-D-glucuronide as a substrate. P. saccharophila 11 showed the highest beta-glucuronidase activity among the eight strains. This indicates that P. saccharophila 11 may be useful for production of glycyrrhezic acid from glycyrrhizin by industrial fermentation.

Anti-Bacterial Agents↗
PubMed1990

Inhibition of mitochondrial respiratory chain by arylthiolated 2,3-ethylenedioxy-1,4-benzoquinones.

A series of arylthiolated 2,3-ethylenedioxy-1,4-benzoquinones as a coenzyme Q (CoQ) antagonist was tested for inhibition of succinate oxidase and reduced nicotinamide adenine dinucleotide (NADH) oxidase systems in the mitochondrial respiratory chain. The following characteristics were revealed: (1) 2,3-ethylenedioxy, 5-arylthio and 5,6-diarylthio groups were confirmed to be favorable for inhibition of both systems; (2) these analogs were more effective in the succinate oxidase system than in the NADH oxidase system; (3) 4' substituents on the benzene side ring had little effect on inhibitory activity; (4) the acting sites of these analogs had no strict stereospecificity. The reduced minus oxidized difference spectra revealed that these analogs inhibited the succinate oxidase system at the site between succinate and CoQ, and the NADH oxidase system at the site after cytochrome a + a3, suggesting these analogs might act as antagonists of CoQ in the succinate oxidase system. However, 5-(4'-nitrophenylthio)-2,3-ethylenedioxy-1,4-benzoquinone (If) strongly inhibited only the succinate oxidase system at the site after cytochrome a + a3.

Animals↗
PubMed1990

[A combined treatment with 8 MHz radiofrequency hyperthermia, HPC-adriamycin, immunotherapy, radiation, systemic chemotherapy and irradiation for invasive bladder carcinoma].

Hyperthermia was induced for the treatment of invasive bladder carcinoma in order to study its usefulness. The subjects were 12 cases of invasive bladder cancer; including 5 cases of T2, 3 cases of T3, 2 cases of T4, and 2 cases of recurrence after total cystectomy. As previous treatment, 4 patients received radiotherapy and the other received TUR, systemic chemotherapy, and intravesical injection of anticancer drugs. For hyperthermia treatment, a Thermotron RF-8 was used for heating a deep seated tumor. Each case received hyperthermia 2 to 10 times. Combined therapy included injection of HPC-adriamycin into the urinary bladder in 5 cases, immunotherapy in 3 cases, M-VAC therapy in one case, radiotherapy in one case, radiotherapy and intra-arterial injection in one case, and Peplomycin and OK-432 local injection in one case. The treatment results showed a 75% effectiveness; with CR in 4 cases, PR in 5 cases, MR in 2 cases and PD in one case. Three patients died and 9 survived. Of four patients who had received radiotherapy as a previous treatment 3 cases obtained CR and one case MR. Therefore, it was considered that a favorable treatment effect with hyperthermia could be obtained after radiotherapy.

Aged↗
PubMed1990

Effects of the new centrally acting muscle relaxant 7-chloro-N,N,3-trimethylbenzo[b]furan-2-carboxamide on motor and central nervous systems in rats.

Effects of KW-6629 (7-chloro-N,N,3-trimethylbenzo[b]furan-2-carboxamide) were studied with special reference to the effect on motor and central nervous systems using rats. The drug effectively reduced the motor coordination (rotarod), the anemic decerebrate rigidity, the crossed extensor reflex, and the gamma-activity indirectly recorded from muscle afferent discharges without showing the direct inhibitory effect on muscle spindles. KW-6629 depressed the polysynaptic and dorsal root reflexes without showing marked effect on the monosynaptic reflex in intact spinal cord rats. KW-6629 produced high-amplitude slow wave in the cerebral cortex in electroencephalogram (EEG). KW-6629 did not reduce the EEG after-discharges and behavioral convulsion (amygdaloid kindling). KW-6629 had no effect on the neuromuscular junction. These results suggest that KW-6629 is a centrally acting muscle relaxant which has a site of action in supraspinal structures.

Animals↗
PubMed1990

Experimental chemonucleolysis with chondroitinase ABC.

Chemonucleolysis has recently become an established treatment for intervertebral disc protrusion. However, the exact mechanism of chemonucleolysis is still unknown. If mechanisms of chemonucleolysis include diminution of intradiscal pressure followed by subsequent regeneration of the nucleus pulposus, then a more selective enzyme for glycosaminoglycan, chondroitinase ABC, might be used for chemonucleolysis instead of chymopapain. Thus experimental chemonucleolysis with chondroitinase ABC compared with chymopapain was investigated. In rabbits, chondroitinase ABC is as effective for chemonucleolysis as chymopapain, but the chemonucleolysis process with chondroitinase ABC was milder than with chymopapain. At an early chemonucleolysis phase, chondroitinase ABC action was chiefly limited to digestion of the matrix, and a large number of cells in the nucleus pulposus remained. During long-term observations of chemonucleolysis with chondroitinase ABC, nuclear structure was restored to a nearly normal state. Although limited, this study indicates that chondroitinase ABC might be more suitable than chymopapain for chemonucleolysis.

Animals↗
PubMed1990

[Experimental study of chemical spinal fusion in the rabbit by means of bone morphogenetic protein].

Bone morphogenetic protein (BMP) is known to induce mesenchymal cell production of cartilage. During the regeneration process after chemonucleolysis, fibroblastic cells are supposed to migrate into the disc space. These migrated cells could contain BMP-responding cells. The present study was undertaken to investigate anterior spinal fusion of rabbits produced by intradisc injection of BMP after chemonucleolysis with chymopapain. After intradisc injection of BMP, roentgenographs revealed calcification of disc space. Calcification was more obvious in discs pretreated with chymopapain than in non-pretreated discs. Histology showed this calcification to be ossification of the nucleus pulposus and the anterior longitudinal ligament. Ossification was more obvious along the anterior longitudinal ligament than in the nucleus pulposus. In some cases, ossification led to the formation of bony bridges along the anterior longitudinal ligament. These results indicate that anterior spinal fusion can be produced by intradisc injection of chemicals.

Animals↗
PubMed1988

Medullary inspiratory neurons with stable respiratory rhythm and little correlation to phrenic high-frequency oscillation.

Respiratory neurons with a highly stable rhythm have been proposed to be involved in the central neural mechanism responsible for the respiratory rhythmogenesis. In the present study it was examined whether the stably discharging inspiratory neurons are related to the high-frequency oscillation (HFO) in the phrenic nerve activity. Experiments were performed on 27 vagotomized rabbits anesthetized with diethyl ether, immobilized with gallamine triethiodide, and ventilated artificially. Spike-triggered averaging was used to evaluate the degree of the correlation between inspiratory unit spikes and the phrenic HFO. Twenty out of the 35 inspiratory units examined were related to HFO and were located in the medullary reticular formation (n = 19; n, number of units) and in the vicinity of the nucleus tractus solitarius (n = 1). The correlation to HFO decreased after the intravenous injection of thiamylal. The inspiratory units with little correlation to HFO were located in the reticular formation of the pons (n = 3) and medulla (n = 12). The inspiratory neurons with a stable respiratory rhythm (n = 4) had little correlation to HFO and located in the lateral region of the medullary reticular formation. These results suggest that the central neural mechanisms responsible for phrenic HFO are not directly related to the respiratory rhythmogenesis.

Action Potentials↗
PubMed1987

Extra- and intra-cellular digestion of elastic fibers by macrophages in annular elastolytic giant cell granuloma. An ultrastructural study.

A case of annular elastolytic giant cell granuloma was studied with the electron microscope using acid orcein stain. Elastic fibers were digested by multinucleate giant cells (MGCs) in 2 steps: the first step was the extracellular digestion and the second was the intracellular digestion. In the first step, the orcein-reactive amorphous materials of the elastic fibers surrounded by MGCs at first disappeared, and then the fine filaments appeared in elastic fibers. This process advanced in extracellular spaces of MGCs. In the next step, the fine filaments were phagocytosed by MGCs and were digested in phagocytic vacuoles.

Aged↗
PubMed1987

Inhibition of mutagenicity by glycyrrhiza extract and glycyrrhizin.

The effects of Glycyrrhiza extract and one of its components, glycyrrhizin, on the mutagenicities of several mutagens were investigated by means of a modification of the Ames' test. Both inhibited the mutagenicities of 3-amino-1,4-dimethyl-5 H-pyrido[4,3-b]-indole (Trp-P-1) and 3-amino-1-methyl-5 H-pyrido[4,3-b]indole. Since the Glycyrrhiza extract and glycyrrhizin inhibited the mutagenicity of activated Trp-P-1, it was clear that their inhibitory effects were not due to inhibition of the enzyme activity of the S9 fraction. Both Glycyrrhiza extract and glycyrrhizin also inhibited the mutagenicities of benzo[a]pyrene, 3-methylcholanthrene, 2-naphthylamine, 2-amino-6-methyldipyrido[1,2-a:3',2'-d]-imidazole, dimethylnitrosoamine and dimethylaminoazobenzene. The mutagenicity of 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF-2) was inhibited by the Glycyrrhiza extract but not by glycyrrhizin. This suggested that a component different from glycyrrhizin, present in the Glycyrrhiza extract, inhibited the mutagenicity of AF-2.

Drugs, Chinese Herbal↗
PubMed1987

Possible involvement of Ly-1 B cells in the effector phase of IgG suppression mediated by suppressor T cell factor.

The effector phase of IgG suppression mediated by an antigen-specific suppressor T cell factor (TsF) was studied. The monoclonal TsF of an inducer type derived from a KLH-specific suppressor T cell hybridoma (34S-704) suppressed IgG response mounted by DNP-primed B cells (anti-Thy-1 treated spleen cells) and KLH-specific cloned helper T cells only in the presence of unprimed Thy-1-, Ly-1+, I-J+, Ig+ cells. The addition of naive Ly-1+ cells to the culture of DNP-primed Ly-1/Thy-1 depleted B cells and KLH-Th clones augments anti-DNP IgG responses, and KLH-TsF suppressed the enhanced parts of IgG responses. The Ly-1+ cell seems to be a target of TsF, because naive spleen cells treated either with anti-Ly-1 or with anti-MIg failed to absorb TsF, whereas TsF activity was absorbed with whole spleen cells and anti-Thy-1 treated spleen cells. The functional role of Ly-1 B cells and possible mechanisms in the effector phase of TsF-mediated IgG suppression will be discussed.

Animals↗