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Biomedical subjects

H Osada

Publications and source records attributed to H Osada.

At least 253 records · Page 14Linked to original sources
PubMed1990

New pyrrolobenzodiazepine antibiotics, RK-1441A and B. II. Isolation and structure.

Antibacteriophage antibiotics, RK-1441A and B, related to neothramycin were isolated from the culture broth of Streptomyces sp. and their structures were deduced from spectroscopic analyses. The structure of RK-1441A was 8,11-dihydroxy-3,7-dimethoxy-5-oxo-1H-pyrrolo[2,1-c:1,4]benzodiazepine. RK-1441B is a tautomeric mixture at C-3 of the structure, 3,8,11-trihydroxy-7-methoxy-5-oxo-1H-pyrrolo[2,1-c:1,4]benzodiazepine.

Anti-Bacterial Agents↗
PubMed1990

New pyrrolobenzodiazepine antibiotics, RK-1441A and B. I. Biological properties.

Streptomyces griseus and bacteriophage B were used for an assay system detecting anti-bacteriophage antibiotics. Streptomyces sp. RK-1441 was found to produce antibacteriophage antibiotics, RK-1441A and B, which are pyrrolo[1,4]benzodiazepine group antibiotics related to neothramycin. Both RK-1441A and B had antibacteriophage activity. The former showed antimicrobial activity on a hypersensitive strain of E. coli for antitumor antibiotics, but the later did not show the activity. Restriction enzyme assay suggested that RK-1441A formed adducts with guanine residues in DNA strands. RK-1441B was not active in vitro, but it might be converted to the active form in host organisms.

Anti-Bacterial Agents↗
PubMed1990

[Results of pulmonary resections in elderly patients with primary lung cancer].

Forty-one patients over the age of 70 years, who had been operated upon for a primary lung cancer during 13 years until August, 1988, were reviewed. There were 32 males and 9 females, among whom the oldest was an 85-year-old male. These patients composed of 28.7% of the patients who had undergone a resectional lung surgery due to a primary lung cancer during the same period of time. These included 26 patients of stage I, 11 of IIIA, 3 of IIIB and 2 of IV. Twenty-two of them were with a squamous cell carcinoma, 18 with an adenocarcinoma, and one with a small cell carcinoma. Thirty-two patients underwent a lobectomy, including two undergoing a sleeve lobectomy. Three patients underwent a left pneumonectomy, and seven underwent a segmentectomy or a wedge resection. A combined chest wall resection was done in 5 of them. One patient underwent the second surgery for a metastasis to the contralateral lung following a left pneumonectomy. Our safety criteria of pulmonary functions for surgery were as follows; a predicted postoperative %VC greater than 40% for any type of pulmonary resection, a preoperative FEV1.0 greater than 1,000 ml for lobectomy and that greater than 1,300 ml for left pneumonectomy. These criteria were identical to those for patients younger than 70 years of age. But some patients even with respiratory functions slightly less than these lower limits did tolerate lobectomies or pneumonectomies. The latter patients, however, cleared what we call "one-flight test" as well as the other patients did.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1989

Interdigitating cell sarcoma (ICS). Evidence of interdigitating cell origin, immunocytochemical studies with monoclonal anti-ICS antibodies.

Three independent mouse monoclonal antibodies (mAbs) ID1 (IgG3), ID2 and ID3 (IgM) were raised against whole cells of a surgically resected human interdigitating cell sarcoma (ICS). In immunoperoxidase staining, these mAbs strongly stained the cytoplasm of ICS neoplastic cells as well as interdigitating cells in normal lymphoid tissues. These mAbs also detected monocyte/macrophages and dendritic cells, although their staining was highly variable depending on tissue distribution of the cells. Additional immuno-histological and enzyme histochemical study revealed that the neoplastic cells of ICS had cytoplasmic acid phosphatase and membranous alkaline phosphatase activity, and also possessed S100 beta protein, Ki-1 antigen. DAKO-macrophage antigen, and weak vimentin activity. Neither rearrangement of immunoglobulin heavy chain gene nor of T-cell receptor genes was detected in the DNA of ICS by Southern hybridization. These observations provide further confirmation of our previous finding (Nakamura et al. 1988, 1989) that the origin of ICS is interdigitating rather than lymphoid cell, and indicate that our mAbs could be useful as a cellular differentiation marker of interdigitating cells and for diagnosis of ICS.

Animals↗
PubMed1989

Purification and characterization of a newly identified growth factor specific for epithelial cells.

A growth factor specific for epithelial cells was identified in conditioned medium of a human embryonic lung fibroblast cell line. The factor, provisionally termed keratinocyte growth factor (KGF) because of its predominant activity on this cell type, was purified to homogeneity by a combination of ultrafiltration, heparin-Sepharose affinity chromatography, and hydrophobic chromatography on a C4 reversed-phase HPLC column. KGF was both acid and heat labile and consisted of a single polypeptide chain of approximately 28 kDa. Purified KGF was a potent mitogen for epithelial cells, capable of stimulating DNA synthesis in quiescent BALB/MK epidermal keratinocytes by greater than 500-fold with activity detectable at 0.1 nM and maximal at 1.0 nM. Lack of mitogenic activity on either fibroblasts or endothelial cells indicated that KGF possessed a target cell specificity distinct from any previously characterized growth factor. Microsequencing revealed an amino-terminal sequence containing no significant homology to any known protein. The release of this growth factor by human embryonic fibroblasts raises the possibility that KGF may play a role in mesenchymal stimulation of normal epithelial cell proliferation.

Animals↗
PubMed1989

bcl-2 gene rearrangement analysis in Japanese B cell lymphoma; novel bcl-2 recombination with immunoglobulin kappa chain gene.

The rearrangement of bcl-2 gene was studied in 56 Japanese B cell lymphoma cases to investigate the contribution of bcl-2 gene to lymphomagenesis in Japan. Ten out of 56 cases showed bcl-2 gene rearrangement; it was detected in only 5 out of 16 follicular lymphoma cases (31%) and in 5 out of 40 diffuse B cell lymphoma cases (13%). The incidence of bcl-2 gene involvement in Japanese follicular lymphomas was lower than those reported in the United States. This might contribute to the lower incidence of follicular lymphoma cases in Japan. Novel recombination between bcl-2 and Ig kappa genes at the 5' region of bcl-2 and J kappa 4 segment was observed in one follicular lymphoma case, suggesting that bcl-2 gene is transcriptionally activated by Ig kappa enhancer. It was also suggested that this case had originated from a more differentiated B cell than most follicular lymphomas with bcl-2-Ig H recombination.

B-Lymphocytes↗
PubMed1989

A new biological role of sangivamycin; inhibition of protein kinases.

During the screening for the inhibitors of protein kinase C (PKC), we found that a streptomycete produced an inhibitor in our bleb-forming assay (Osada et al., J. Antibiotics 41: 925, 1988). The inhibitor was isolated and identified as sangivamycin (4-amino-5-carboxamide-7-(D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine). Biological activity of sangivamycin was compared with that of other 7-deazaadenosine group antibiotics, tubercidin and toyocamycin. Sangivamycin showed a strong inhibitory activity against bleb-formation of K562 cells and PKC. On the other hand, tubercidin and toyocamycin had only weak activities in both assays. This paper deals with a new biological activity of sangivamycin, that of an inhibitor of protein kinases, especially PKC.

Anti-Bacterial Agents↗
PubMed1989

Comparison of the effect of tautomycin and phorbol ester on protein kinase C in a cell-free system.

The effect of tautomycin (TM) on protein kinase C (PKC) was studied in a cell-free system. TM, like phorbol dibutyrate (PDBu), enhanced both base-line and Ca2+/phospholipids-dependent protein kinase activity. However, PDBu but not TM increased the affinity of the enzyme for calcium ions (Ca2+), suggesting that TM is a new activator of PKC, distinct from PDBu. In the presence of 10 micrograms/ml phosphatidyl inositol, the activity of PKC reached maximum at 10(-3) M Ca2+ concentration when the other co-factors were absent. Both TM and PDBu increased the maximum level of PKC activity at the optimum concentration of Ca2+, suggesting that they interacted with the site of PKC which is distinct from the site where Ca2+ interacts. TM and PDBu did not activate the enzyme when protamine sulfate in place of histone III-S was used as a substrate, indicating that they activate PKC by affecting the regulatory domain of the enzyme.

Antifungal Agents↗
PubMed1989

Epiderstatin, a new inhibitor of the mitogenic activity induced by epidermal growth factor. I. Taxonomy, fermentation, isolation and characterization.

Inhibitors of mitogenic activity induced by epidermal growth factor (EGF) were screened from culture broths of soil microorganisms. A strain of actinomycetes has been found to produce a new glutarimide antibiotic named epiderstatin which inhibits the incorporation of [3H]thymidine into quiescent animal cells stimulated by EGF. Taxonomic studies have revealed that the producing strain belongs to a subspecies of Streptomyces pulveraceus, thus the name, Streptomyces pulveraceus subsp. epiderstagenes was given to this strain. The molecular formula (C15H20N2O4) and UV profile (lambda max 295 nm) of the antibiotic are distinct from other known antibiotics. It inhibited the incorporation of [3H]thymidine into quiescent cells stronger than into growing cells.

Animals↗
PubMed1989

Epiderstatin, a new inhibitor of the mitogenic activity induced by epidermal growth factor. II. Structure elucidation.

The structure of a novel antibiotic, epiderstatin, was determined as 4-[3-((Z)-3,5-dimethyl-2-oxopiperidin-6-ylidene)-2-oxopropyl]-2, 6-piperidinedione by spectroscopic analyses of 1H NMR, 13C NMR, 1H-1H correlation spectroscopy (COSY), 13C-1H COSY, heteronuclear multiple bond correlation spectroscopy, UV and IR spectra. The antibiotic belongs to the glutarimide antibiotics, however, the characteristic feature of epiderstatin is that it has a piperidone ring instead of a cyclohexanone ring.

Antibiotics, Antineoplastic↗
PubMed1989

Partial purification of a macrophage-activating factor for glucose consumption (MAF-G) produced by a human T-cell hybridoma and its relation to a growth-promoting factor.

A material that enhances the glucose consumption of oil-induced peritoneal macrophages of guinea pig, the activity being named MAF-G activity, was purified approximately 780-fold from human T cell hybridoma conditioned medium. A material showing growth-promoting activity was co-purified with that showing the MAF-G activity from the same conditioned medium. The two materials showed an identical isoelectric point of pH 4.7. When the partially purified MAF-G increased glucose consumption, it did not induce glucose carbon-1 oxidation. MAF-G activity was inhibited by mitomycin C and colchicine, which inhibit DNA synthesis and mitosis, respectively, but not by 2-deoxy-D-glucose, an inhibitor of glucose metabolism. The partially purified MAF-G also enhanced the glucose consumption and proliferation of human monocytes. These observations suggest that MAF-G may be identical with the growth-promoting factor for macrophages.

Animals↗
PubMed1989

Identification of myeloid origin in undifferentiated congenital leukemia by in vitro marrow culture study.

A case of congenital leukemia that originally did not express any lineage-specific antigenic markers is presented. The blast cell morphologic appearance was L1 according to French-American-British (FAB) classification and showed lymphoid characteristics by cytochemical staining and transmission electron microscopy. However, immunophenotyping using a variety of monoclonal antibodies did not confirm the lymphoid origin. Furthermore, the immunoglobulin heavy chain and T-cell receptor beta-chain genes were in germ-line configuration. The in vitro culture study defined the leukemia as of myeloid origin. The semisolid methylcellulose culture showed an acute non-lymphocytic leukemia-type growth pattern. Bone marrow blasts underwent myeloid differentiation with positive myeloperoxidase and butyrate esterase activity during a suspension culture. These findings indicate that this case represents an acute undifferentiated leukemia that has probably arisen from the malignant transformation of stem cells of myeloid progeny.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Rapid screening method for inhibitors of protein kinase C.

Specific inhibitors of protein kinase C (PKC) were screened for with a unique detection system, named bleb forming assay. When K562, a human chronic myeloid leukemia cell, was treated with phorbol 12,13-dibutylate (PDBu) or teleocidin which are activators of PKC, many blebs appeared on the cell surface of K562 within 10 minutes. This appearance of blebs is inhibited by staurosporine and H7 which are known to be PKC inhibitors. Teleocidin and PDBu did not induce bleb formation of HL60, a human acute promyelocytic leukemia cell, and the mouse Friend leukemia cell, even though their morphology was changed 24 hours after treatment with teleocidin or PDBu. Many inducers of terminal differentiation of K562 have the same effect on HL60 and Friend cells. However, the bleb inducing activity of PKC activators seems to be specific for K562. The bleb forming assay satisfied the criteria (simplicity and specificity) required for preliminary screening of activators or inhibitors of PKC. Teleocidins A and B, and tautomycin (a new antibiotic isolated in our laboratory) were identified as activators of PKC, and also staurosporine and isoflavones (daidzein and genistein) as inhibitors.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

Induction of morphological change of human myeloid leukemia and activation of protein kinase C by a novel antibiotic, tautomycin.

A novel antibiotic tautomycin induced many blebs on the surface of K562 human chronic myeloid leukemia cells, similar to the morphological changes induced by phorbol esters. However, tautomycin did not induce nitroblue tetrazolium reducing activity, when HL60 human promyelocytic leukemia cells were caused to differentiate by quinomycin into mature granulocytes. It did not induce spread of HL60 cells, one of the phenotypes of mature macrophages. In addition, it did not compete with phorbol dibutyrate to bind to the cell surface of K562 cells. However, tautomycin significantly activated protein kinase C (PKC) extracted from K562 cells. These results indicate that tautomycin is a new activator of PKC, distinct from phorbol esters.

Anti-Bacterial Agents↗