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Biomedical subjects

T Aoyagi

Publications and source records attributed to T Aoyagi.

At least 217 records · Page 12Linked to original sources
PubMed1992

Benarthin: a new inhibitor of pyroglutamyl peptidase. III. Synthesis and structure-activity relationships.

Benarthin, a new inhibitor of pyroglutamyl peptidase (PG-peptidase), has been isolated from the culture filtrate of Streptomyces xanthophaeus MJ244-SF1. The structure of benarthin has been determined to be L-(2,3-dihydroxybenzoyl)arginyl-L-threonine. This structure was confirmed by the total synthesis of benarthin. Moreover, we synthesized benarthin derivatives to obtain information on the relationship between structure and inhibitory activity. The results indicated that the catechol group of benarthin is the essential moiety for the inhibition of PG-peptidase.

Dipeptides↗
PubMed1992

Aminopeptidase activity of an antitumor antibiotic, C-1027.

An antitumor antibiotic C-1027, a complex protein consisting of an apoprotein and a non-covalently bound chromophore, showed some aminopeptidase activity, 1/15 (on the basis of activity per mg protein) that of porcine kidney enzyme [E.C. 3.4.11.2] by use of L-phenylalanyl 4-methyl-coumaryl-7-amide as the substrate. Neither the apoprotein alone nor the chromophore alone were active. Amastatin and bestatin but not leupeptin inhibited the activity. The enzyme activity of the holo-antibiotic, as opposed to that of the porcine kidney enzyme, was readily lost by UV irradiation, indicating that the intact structure of the chromophore was needed to maintain the native conformation of the holo-antibiotic. The cytotoxicity of the holo-antibiotic, but not that of the chromophore, to Ehrlich carcinoma cells in vitro was reduced to 1/5 by 1 microgram/ml of amastatin which alone had no effect on cell growth. The porcine aminopeptidase was not cytotoxic at all even at higher concentrations (higher enzyme activities/ml). Amastatin possibly occupied the catalytic domain of the holo-antibiotic, interfering with the binding of the holo-antibiotic with some cell-surface protein(s). Amastatin did not inhibit the holo-antibiotic to cleave isolated DNA.

Aminoglycosides↗
PubMed1992

Benastatins A and B, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. I. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Benastatins have been isolated as part of a program designed to find microorganism-produced inhibitors of glutathione S-transferase from Streptomyces sp. MI384-DF12. They were purified by chromatography of reversed-phase silica gel, silica gel and Capcell Pak C18 (HPLC) followed by solvent extraction and then isolated as yellow powders. Benastatins A and B have the molecular formulae, C30H28O7 and C30H30O7, respectively. They were competitive with 3,4-dichloronitrobenzene as the substrate, and the inhibition constants (Ki) of benastatins A and B were 5.0 x 10(-6) and 3.7 x 10(-6), respectively.

Animals↗
PubMed1992

Benastatins A and B, new inhibitors of glutathione S-transferase, produced by Streptomyces sp. MI384-DF12. II. Structure determination of benastatins A and B.

Benastatins A and B, new inhibitors of glutathione S-transferase, have been isolated from the culture broth of Streptomyces sp. MI384-DF12. By X-ray crystallography, benastatin A was determined to be 8,13-dihydro-1,7,9,11-tetrahydroxy-13-dimethyl-8-oxo-3-pentyl- benzo[a]naphthacene-2-carboxylic acid. The structure of benastatin B was elucidated by NMR studies.

Benz(a)Anthracenes↗
PubMed1992

Nagstatin, a new inhibitor of N-acetyl-beta-D-glucosaminidase, produced by Streptomyces amakusaensis MG846-fF3. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Nagstatin, a new inhibitor of N-acetyl-beta-D-glucosaminidase (NAG-ase) was discovered in the fermentation broth of Streptomyces amakusaensis MG846-fF3. It was purified by chromatography on Dowex 50W, Avicel and Sephadex LH-20 followed by the treatment of active carbon and then isolated as colorless powder. Nagstatin has the molecular formula of C12H17N3O6. It is competitive with the substrate, and the inhibition constant (Ki) was 1.7 x 10(-8) M.

Acetylglucosaminidase↗
PubMed1992

Cyclooctatin, a new inhibitor of lysophospholipase, produced by Streptomyces melanosporofaciens MI614-43F2. Taxonomy, production, isolation, physico-chemical properties and biological activities.

Cyclooctatin has been isolated from Streptomyces melanosporofaciens MI614-43F2 as part of a program designed to find microorganism-produced inhibitors of lysophospholipase. It was purified by chromatography on silica gel, Capcell Pak C18 (HPLC) and Sephadex LH-20 followed by solvent extraction and then isolated as a colorless powder. Cyclooctatin has the molecular formula of C20H34O3. It is competitive with the substrate, and the inhibition constant (Ki) was 4.8 x 10(-6) M.

Animals↗
PubMed1992

Biosynthesis of benastatin A.

The biosynthesis of benastatin A, produced by Streptomyces sp. MI384-DF12, has been studied by feeding experiments with 14C- and 13C-labeled compounds followed by measurement of radioactivity and 13C NMR analysis. The results indicate that benastatin A is derived from two methionine units and fourteen acetate units, condensed in the "head-to-tail" fashion of typical polyketide biosynthesis.

Benz(a)Anthracenes↗
PubMed1992

[Immunological study of interferon-gamma therapy for advanced renal cell carcinoma].

Immunologic and anti-tumor effects of interferon-gamma were studied in six patients with advanced renal cell carcinoma. A daily dose of 10 x 10(6) JRU/m2 of interferon-gamma (IFN-gamma) was given consecutively for five days and the treatment reiterated nine days later. Then the same dose was given every two days for three times and this regimen was also reiterated nine days later. Peripheral blood lymphocytes were analyzed before and one, three, five and eight weeks after the initial administration of IFN-gamma. Although the total number of lymphocytes and monocytes were not changed, CD8 (23.4 to 31.2%, p < 0.05), CD16 (12.4 to 19.3%, p < 0.01) and LeuHLA-DR (29.0 to 39.5%, p < 0.01) positive lymphocytes were significantly increased after the therapy. Non-induced LAK activity (0.6 to 10.8%, p < 0.05) and serum neopterin (3.5 to 10.8 nmol/L, p < 0.01) were also increased. These immunological parameters drastically changed during the consecutive administration of IFN-gamma, and tended to return to the previous value after this period. However, tumor regression was not clinically obtained. Our findings indicate that interferon-gamma stimulated the anti-tumor activity of the host, and administration of IFN-gamma is thought to be of immunological significance even in the advanced high stage cases.

Aged↗
PubMed1992

Fibroblast growth factors released by wounded endothelial cells stimulate proliferation of synovial cells.

We demonstrated that vascular endothelial cells mechanically wounded by scraping from the substratum were able to release growth promoting factors for synovial cells as well as for endothelial cells. The wounded endothelial cell conditioned medium stimulated the proliferation of synovial cells derived from different human donors dose dependently and induced transit of growth arrested synovial cells (predominant in the G0 and G1 phases), through the S phase and into the G2 and M phases. When the wounded endothelial cell conditioned medium was applied to heparin-sepharose columns, mitogenic activity was eluted with 2.0 M NaCl. The mitogenic activity in wounded endothelial cell conditioned medium, which was heat sensitive, was inhibited by protamine sulfate and a specific mouse monoclonal antibody against basic fibroblast growth factor (bFGF). Our results are evidence that the wounded endothelial cell conditioned medium contained growth promoting factors for synovial cells, including bFGF. We also showed the presence of bFGF in the endothelial cells of the small blood vessels and stromal synovial fibroblast-like cells in patients with rheumatoid arthritis (RA). Our results suggest that the endothelial cells in the luxuriant capillaries in the synovial tissues from patients with RA may have a critical role in the stimulation of neighboring synovial cell proliferation, resulting in pronounced synovial hyperplasia.

Antibodies, Monoclonal↗
PubMed1992

[Polymerase chain reaction for identification of Mycobacterium in sputa].

Polymerase chain reaction was applied to the diagnosis of mycobacterial infections. This reaction could detect bacteria in clinical specimens within a few hours. Sensitivities of the five primer systems reported in 1990 were compared. It was proved that the primer system reported by Eisenach et al. was as sensitive as culture on Ogawa's medium for the detection of Mycobacterium tuberculosis in sputa. Other systems were found to be less sensitive than this system, and the nested PCR should be applied to make these systems highly sensitive. For the practical application of PCR method, we should improve the detection system to fit for the practice in clinical laboratory. High cost of PCR system could be another barrier for the practical application.

Base Sequence↗
PubMed1992

[Study on local recurrence in patients undergoing curative surgical resection of lung cancer].

Clinical features of recurrence in patients of lung cancer undergoing curative surgical resection were examined with special reference to the local recurrence. Subjects were 308 patients, consisting of 160 adenocarcinomas, 121 squamous cell carcinomas, 15 large cell carcinomas, 12 small cell carcinomas. They underwent curative resection in our department between 1973 and 1987. Local recurrence developed in 54 patients (18%). There was no significant difference in the incidence of local recurrence among the four histological types of carcinoma. According to the pathological stage, the incidence was 9% in stage I, 15% in stage II, and 35% in stages IIIA+IIIB. The local recurrence was subdivided into the following patterns: 1) lymphatic metastases to the hilar, mediastinal, or supraclavicular sites, 2) recurrence at the surgical margin, 3) malignant pleuritis or pericarditis, 4) so-called "endobronchial metastasis". The incidence of recurrence according to the patterns was 15%, 2%, 2% and 1%, respectively. The incidence of recurrence due to lymphatic metastases was correlated significantly with the pN factor but not with the pT factor. Patients with central type lung cancer showed a significantly higher incidence of lymphatic recurrence than patients with the peripheral type. Patients having postoperative radiotherapy to prevent local recurrence showed a lower incidence of lymphatic recurrence than patients having no radiotherapy. In conclusion, lymphatic recurrence was the most frequent pattern in local recurrence after curative resection of lung cancer, and therefore improvements in the operative procedure of lymphatic dissection, as well as in postoperative adjuvant therapy including radiotherapy will be urgently required for the purpose of reducing local recurrence.

Adenocarcinoma↗
PubMed1992

[CT findings of six cases with intracranial tuberculosis in National Higashi-Saitama Hospital].

We have experienced 6 cases of intracranial tuberculosis since 1985. 2 cases were diagnosed as intracranial tuberculoma without tuberculous meningitis, and 4 cases were diagnosed as tuberculous meningitis. Brain CT showed intracranial tuberculomas in three of them, and showed cerebral infarcts in two cases, and showed hydrocephalus in two cases. Brain CT on intracranial tuberculosis showed various findings. In two cases with tuberculous meningitis, brain CT showed many tuberculomas with ringed or nodular enhancement appeared after adequate chemotherapy had been started. About 1 year later, a few tuberculomas were found with homogeneous enhancement and were enlarged while the chemotherapy was continued. But later they were reduced in size. The above facts may suggest that intracranial tuberculoma could appear and be enlarged on cranial CT in spite of adequate anti-tuberculous chemotherapy during a course of tuberculous meningitis. They also suggest that the continuation of adequate chemotherapy might be necessary to the treatment of intracranial tuberculomas.

Aged↗