3-O-isobutyrylkinamycin C and 4-deacetyl-4-O-isobutyrylkinamycin C, new antibiotics produced by a Saccharothrix species.
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Biomedical subjects
Publications and source records attributed to T Takeuchi.
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It was reported that doxorubicin inhibited virus reverse transcriptase. We have synthesized various new 14-O-acyladriamycins. The derivatives having a 17-O-benzoyl group with hydrophobic aliphatic side chains showed stronger inhibitory activity on human immunodeficiency virus reverse transcriptase and lower cytotoxicity on mouse leukemia cells.
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Deoxyspergualin has strong immunosuppressive activity in animals. However, it shows less in vitro immunosuppressive activity at the therapeutic concentration used for in vivo administration. Recently, we reported that there are some technical problems with in vitro experiments. In this report, the effects of spergualins were examined under in vitro conditions which excluded these problems, and compared with cyclosporine A (CYA). Spergualins have suppressive effects on mixed lymphocyte response (MLR) and cytotoxic T lymphocyte induction. Furthermore, interleukin-2 (IL-2) induced proliferation of concanavalin A blasts and CTLL-2 were inhibited at low concentration. However, spergualins have little effect in the early stage of MLR or the mitogen response. These results suggest that spergualins act on the proliferation and differentiation of T cells which respond to growth factors, such as IL-2.
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Mannostatins have been isolated as part of a program designed to find microorganism-produced inhibitors of alpha-D-mannosidase from Streptoverticillium verticillus var. quintum. They were purified by sequential use of active carbon and Dowex resins and then isolated as colorless powders. Mannostatins A and B have the molecular formula, C6H13NO3S and C6H13NO4S, respectively. They were competitive with the substrate, and the inhibition constants (Ki) of mannostatins A and B were 4.8 x 10(-8) M.
IC201 was found in cultured broth of Streptomyces cirratus as an antitumor antibiotic which was effective in retarding growth of the established solid tumor of Ehrlich carcinoma by treatment starting 8 days after tumor inoculation. It retarded growth of the established solid tumor of IMC carcinoma but had no cytotoxicity at 100 micrograms/ml. IC201 treatment kept NK cell activity of tumor-bearing mice at normal level and stimulated cytostatic activity of peritoneal macrophages. It stimulated phagocytosis of yeast and phorbol myristate acetate-elicited superoxide production by peritoneal macrophages. The addition of IC201 to P388D1 cell cultures enhanced release of interleukin 1 (IL-1) into cultured supernatant but it affected lipopolysaccharide-induced IL-1 production. Although the addition to macrophage-depleted cultures did not show any stimulatory effect, mixed lymphocyte culture reaction was augmented in cultures using spleen cells as stimulator cells taken from mice given IC201. Results indicate that IC201 primarily activates macrophages and the activation may cause modulation of immune responses.
The synthesis and biological evaluation of D-forphenicinol-cephalosporins are described. 7-Amino-3-(substituted)-3-cephem-4-carboxylic acid esters were coupled with N-tert-butoxy-carbonyl-D-forphenicinol derivatives. Most of cephalosporin analogs in this series had good antibacterial activities and were well absorbed from the gastrointestinal tract in mice. Among them, 7-(mono-O-methyl-D-forphenicinol)-3-propenyl analog showed the most significant result in biological evaluations.
The results of an epidemiological survey in a 190-patient institution for mentally retarded were reported. Twenty percent of the patients had either cysts or trophozoites of Entamoeba histolytica in their stools, and 38% were positive serologically. The amebic outbreak revealed a sex-independent but age-dependent distribution; younger patients had more serious symptoms in cases invasive amebiasis. A high prevalence of amebic infection was found in the heavily retarded patients, and the positive cases tended to concentrate in certain training classes. Further demographic analysis suggests that the amebic infection was possibly caused by abnormal behavior of heavily retarded patients.
We have measured the plasma PIVKA-II levels in 188 cases of various liver disease with HCC and malignant diseases in other organs by an EIA, using a monoclonal antibody (E-1023 kit, Eisai), and also have measured the plasma vitamin K levels in cases of HCC and cholestasis by an HPLC. Plasma PIVKA-II was detected in many cases of HCC (67%, 35 of 52 cases) and cholestasis (60%, 6 of 10 cases). In contrast, the positivities of PIVKA-II in the other diseases including benign liver diseases were very low. Combination assays of PIVKA-II and vitamin K revealed that PIVKA-II correlates with vitamin K in cholestasis but not in HCC, suggesting that PIVKA-II in HCC does not depend on a systemic deficiency of vitamin K. From these results, it was concluded that PIVKA-II is a reliable marker which can reflect the clinical course of HCC.
New cholecystokinin (CCK) receptor antagonist, CR 1409 (lorglumide), was evaluated for anti-CCK activity on pancreatic exocrine secretion in anesthetized rats in vivo, compared with proglumide. Both CR 1409 in a dose range of 0.04-25 mg/kg-hr and proglumide in a dose range of 30-600 mg/kg-hr given intravenously, showed significant inhibitory effect on pancreatic secretion in terms of juice volume and amylase output stimulated by intravenous CCK-8 (0.06 micrograms/kg-hr), in a dose-related manner. CR 1409 is about 1000 times more potent than proglumide, based on ED 50. Furthermore, intravenous administration of either CR 1409 (5 mg/kg-hr) or proglumide (600 mg/kg-hr) resulted in significant suppression on pancreatic secretion stimulated by intraduodenal casein in a dose of 400 mg/hr. Thus, very potent CCK receptor antagonist, CR 1409, inhibited pancreatic exocrine secretion stimulated by not only exogenous CCK, but also intraduodenal casein in rats.
A 37-year-old male was presented with an upper abdominal mass. A retroperitoneal bulky tumor was detected and operative biopsy revealed seminoma. The right testis was undescended and atrophic which was located at the left inguinal lesion. Pathologically, the primary tumor cells were not found in the left orchiectomied testis, but only scar and fibrosis were compatible with a burned-out testicular tumor. This patient showed partial regression by multidisciplinary therapy including combined chemotherapy with CDDP, etoposide and peplomycin, and is still on the same condition and alive for 3 years. In case of extragonadal germ cell tumor without apparent testicular involvement, it is a problem to differentiate primary extragonadal germ cell tumor from occult and burned-out testicular tumor. Testis should be examined by all means available including careful exploration.
We examined the relationship of the serum levels of antibody against acetylcholine receptors to the serum levels of 13 enzymes, including various hydrolytic enzymes, poly(ADP-ribose)synthetase (Poly(ADP-ribose)Syn), and sialyltransferase (NANA-trans), in patients with myasthenia gravis. The patients were divided into two groups, depending on the presence or absence of thymoma. In spite of the absence of significant difference in the absolute levels of individual enzymatic activities between the two groups, the network relationships of such enzymes were quite different between the two groups. Of the 13 enzymes examined, only Poly(ADP-ribose)Syn showed a weak but significant correlation with the level of the antibody in the patients without thymoma. A multivariate study more clearly suggested the relationship between the antibody formation and Poly(ADP-ribose)Syn in the patients without thymoma. Such observations were not found in the patients with thymoma.
Adhesion of P. aeruginosa to normal and injured rat tracheas was examined. Rat tracheas were injured by exposure to 0.1N HCl for 10 min, and incubated with P. aeruginosa. Adhesion was quantitated by direct count of the number of bacteria attached to a fixed surface area as viewed by scanning electron microscopy. P. aeruginosa adhered to injured tracheas much more than to normal tracheas. The adhesion of P. aeruginosa, preincubated with mucin and sugars, to acid injured trachea was examined. Mucin, N-acetylneuraminic acid and N-acetyl-D-galactosamine inhibited the adhesion of P. aeruginosa to injured tracheas, but not N-acetylglucosamine, L-fucose, D-mannose and D-galactose. Periodate oxidation and neuraminidase treatment of acid injured tracheas reduced the adhesion of P. aeruginosa. These data suggest that N-acetylneuraminic acid (sialic acid) is the receptor for P. aeruginosa or a part of the receptor in acid injured rat trachea and in tracheobronchial mucin.
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A novel monoclonal antibody (MAb), OPD4, reactive with a helper/inducer (H/I) subset of T cells in formalin-fixed, paraffin-embedded tissue sections, has been identified through immunization with an activated H/I T cell line, namely DL40. The antibody is an IgG1 antibody and it recognizes an antigen with a molecular weight of 200 kd, corresponding to that of leukocyte common antigen. OPD4+/CD4+ T cells provided better help for pokeweed mitogen-stimulated polyclonal IgG production than OPD4-/CD4+ T cells. OPD4 recognized the H/I T cell subset even in paraffin-embedded tissue sections, but did not recognize nonhematopoietic cells, suppressor/cytotoxic T cells, B cells, monocytes in the peripheral blood, or other normal hematopoietic cells as examined by the flow cytometric and immunoperoxidase methods. Besides the lymphoid cells, OPD4 reacted with a number of histiocytes (epithelioid cells) in tissues from sarcoidosis and tuberculosis. For the neoplastic lesions, OPD4 reacted with approximately half of the cases of T cell lymphomas. Consequently, OPD4 may be useful for the diagnosis and study of malignant lymphomas and other related lesions.