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Biomedical subjects

H Osada

Publications and source records attributed to H Osada.

At least 163 records · Page 9Linked to original sources
PubMed1996

Structure-activity relationship within a series of degradation products of tautomycin.

Tautomycin, a protein serine/threonine phosphatase inhibitor, was chemically degraded, and five derivatives were investigated for their biological activities. None of them exerted any inhibitory effects on the activity of protein phosphatase types 1 and 2A. However, one derivative, named TM2a, induced a significant morphological change (bleb-formation) of human myeloid leukemia K562 cells. TM2b, the trimethyl ester of TM2, did not induce bleb-formation. Thus, the maleic anhydride structure played an important role in the biological activity. The biological properties of TM2a toward K562 cells resembled those of a phorbol ester, rather than of tautomycin. The phorbol ester-induced bleb formation was abrogated by a non-specific inhibitor of protein kinases, staurosporine, and by an inhibitor of protein kinase C (PKC), H-7, but TM2a-induced bleb formation was abrogated only by staurosporine. Enhanced phosphorylation of the two proteins was observed after their exposure to TM2a. This suggest that the effect was not due to any inhibition of protein phosphatase 1 or 2A, but rather to the activation of an unidentified kinase, possibly of the PKC family, or to inhibition of a protein phosphatase other than type 1 or 2A.

Antifungal Agents↗
PubMed1996

Sparoxomycins A1 and A2, new inducers of the flat reversion of NRK cells transformed by temperature sensitive Rous sarcoma virus. I. Taxonomy of the producing organism, fermentation and biological activity.

Streptomyces sparsogenes SN-2325 isolated from a soil sample collected in Hokkaido, was found to produce sparoxomycins A1 and A2, new modulators of proliferation of mammalian cells. Sparoxomycins A1 and A2 reverse the morphology of temperature-sensitive mutant Rous sarcoma virus-infected NRK cells (src(ts)-NRK cells) from the transformed phenotype to the normal phenotype at the permissive temperature.

Animals↗
PubMed1996

Morphology reversion activity of phosmidosine and phosmidosine B, a newly isolated derivative, on src transformed NRK cells.

An antifungal antibiotic, phosmidosine (1) was previously isolated (J. Antibiotics 44: 375 approximately 381, 1991). Phosmidosine derivatives, phosmidosines B (2) and C (3) were newly isolated as detransforming compounds from the fermentation broth of Streptomyces sp. strain RK-16 which is a producer strain of phosmidosine (1). The structures of 2 and 3 were established by spectroscopic methods, including UV, HRFAB-MS, and NMR. 1 and 2 showed the inhibitory activity of the cell cycle progression and the morphological reversion activity on srcts-NRK cells. On the other hand, 3 had no activity. These results indicate that the prolyl group in phosmidosine derivatives plays an important role in the inhibitory activity against the cell cycle progression and the morphological reversion activity on srcts-NRK cells.

Animals↗
PubMed1996

Novel mammalian cell cycle inhibitors, tryprostatins A, B and other diketopiperazines produced by Aspergillus fumigatus. I. Taxonomy, fermentation, isolation and biological properties.

Two novel diketopiperazines named tryprostatins A (1) and B (2) and a new natural product belonging to the diketopiperazine series, designated as demethoxyfumitremorgin C (3), together with four known diketopiperazines, fumitremorgin C (4), 12,13-dihydroxyfumitremorgin C (5), fumitremorgin B (6) and verruculogen (7), were isolated from the fermentation broth of Aspergillus fumigatus BM939 by the combined use of solvent extraction, silica gel column chromatography, preparative TLC and repeated-preparative HPLC. The diketopiperazines showed an inhibitory activity on the cell cycle progression of mouse tsFT210 cells in the M phase with the MIC values of 16.4 microM (1), 4.4 microM (2), 0.45 microM (3), 4.1 microM (4), 60.8 microM (5), 26.1 microM (6) and 12.2 microM (7), respectively.

Animals↗
PubMed1996

Novel mammalian cell cycle inhibitors, tryprostatins A, B and other diketopiperazines produced by Aspergillus fumigatus. II. Physico-chemical properties and structures.

Two novel diketopiperazines named tryprostatins A and B and a new natural product belonging to the diketopiperazine series, designated as demethoxyfumitremorgin C, together with four known diketopiperazines, fumitremorgin C, 12,13-dihydroxyfumitremorgin C, fumitremorgin B and verruculogen, are new M phase inhibitors of the mammalian cell cycle, which were isolated from the secondary metabolites of Aspergillus fumigatus. The structures of tryprostatins A, B and demethoxyfumitremorgin C were determined mainly by the use of spectroscopic methods especially by detailed analyses of their 1H and 13C NMR spectra with the aid of 2D NMR techniques including pulse field gradient heteronuclear multiple-bond correlation (PFG-HMBC) spectroscopy. Their absolute configurations were determined on the basis of the optical rotational values and CD spectra.

Aspergillus fumigatus↗
PubMed1996

Sparoxomycins A1 and A2, new inducers of the flat reversion of NRK cells transformed by temperature sensitive Rous sarcoma virus. II. Isolation, physico-chemical properties and structure elucidation.

Sparoxomycins A1 and A2, isolated from the fermentation broth and mycelium of Streptomyces sparsogenes SN2325, are new inducers of the flat reversion of NRK cells transformed by temperature sensitive Rous sarcoma virus. Sparoxomycins A1 and A2 were isolated by active carbon chromatography, centrifugal partition chromatography (CPC), ODS column chromatography and preparative HPLC. The structure of sparoxomycins were determined by spectroscopic evidences. Stereochemical assignments of these inducers were executed from the analyses of CD spectra.

Antibiotics, Antineoplastic↗
PubMed1996

[Indication and method of chest wall reconstruction].

Fifty two patients with chest wall resection were reviewed, with emphasis upon 16 patient with chest wall reconstruction. The latter 16 patient consisted of 6 with metastatic tumor, 3 of primary lung cancer, 2 of breast cancer, one of primary chest wall tumor, and others. Before 1985, reconstruction after chest wall resection was conducted in four cases by using methyl methacrylate (Resin). One patient developed erosion of the overlying skin due to protrusion of the edge of Resin-plate with delayed wound healing. Since 1986, we have employed muscle or myocutaneous flap and/or Marlex mesh in reconstruction of the chest wall defect. Twelve patients underwent surgery in this way. Neither paradoxical movement of the chest wall nor respiratory distress developed in the postoperative course of any patient. Thirty six of fifty two patients underwent chest wall resection without following reconstruction as in the former group. Of them one patient of anterior chest wall resection developed respiratory failure. We conclude that rib resection involving as many as three or more in the anterior chest wall, or four rib resection or more in the lateral chest wall, if the area of the defect is greater than 100 cm2, chest wall reconstruction is indicated. Moreover, we believe that muscle or myocutaneous flap and/or Marlex mesh in the best way of reconstruct in following chest wall resection.

Biocompatible Materials↗
PubMed1995

Distinct mutational spectrum of the p53 gene in lung cancers from Chinese women in Hong Kong.

Accumulating evidence suggests that the p53 gene is a good target for molecular epidemiological studies to search for risk factors in carcinogenic events. The lung cancer incidence for females in Hong Kong is unusually high, ranking among the highest in the world despite a low percentage with a history of smoking. To gain insights into possible etiological risk factors responsible for this high incidence, we examined p53 mutations in 35 lung cancer specimens from Chinese females living in Hong Kong and compared them with 35 matched cases from Japanese women as well as previously reported p53 mutations in the world literature. p53 mutations in exons 5-8 were present in 20 and 31% of the Hong Kong and Japanese cases, respectively. Notably, single-base deletions within runs of identical bases were observed in 3 (43%) of the 7 mutations in the Hong Kong cases, in contrast to the absence of such mutations in the controls and the extreme scarcity in the literature, suggesting that distinct environmental and/or genetic factor(s) might be involved. Although the frequent occurrence of characteristic single-base deletions could be a reflection of mutator mutations leading to inefficient mismatch repair of slipped strand mispairings, none of the lung cancer specimens exhibited such microsatellite instabilities.

Adult↗
PubMed1995

Association of erythroid transcription factors: complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1.

The RBTN2 LIM-domain protein, originally identified as an oncogenic protein in human T-cell leukemia, is essential for erythropoiesis. A possible role for RBTN2 in transcription during erythropoiesis has been investigated. Direct interaction of the RBTN2 protein was observed in vivo and in vitro with the GATA1 or -2 zinc-finger transcription factors, as well as with the basic helix-loop-helix protein TAL1. By using mammalian two-hybrid analysis, complexes involving RBTN2, TAL1, and GATA1, together with E47, the basic helix-loop-helix heterodimerization partner of TAL1, could be demonstrated. Thus, a molecular link exists between three proteins crucial for erythropoiesis, and the data suggest that variations in amounts of complexes involving RBTN2, TAL1, and GATA1 could be important for erythroid differentiation.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Retinoic acid enhances plasminogen activation on the cell surface.

The importance of cell-associated plasminogen activation in the extracellular matrix degradation processes is becoming increasingly evident. To elucidate the modulators of net plasminogen activation on the cell surface, we have recently established an assay system. Using this system, we examined the effects of several candidate modulators on cell surface plasminogen activator in the human fibrosarcoma cell line HT-1080 and the SV40-transformed human lung fibroblast cell line WI-38 VA 13 2RA. Although the majority of the candidates had no effect or a selective effect on either cell line, only retinoic acid markedly enhanced cell surface plasminogen activator activity in both HT-1080 and WI-38 VA13 2RA cells in a time-dependent manner. The effect of retinoic acid was neutralized by actinomycin D. The enhanced activity was inhibited by anti-uPA IgG and by pretreatment with phosphatidylinositol-specific phospholipase C. These findings suggest that retinoic acid increases the amount of receptor-bound uPA via de novo synthesis, and that it plays an important role in modulating cell-associated plasminogen activation.

Cell Line, Transformed↗
PubMed1995

RK-682, a potent inhibitor of tyrosine phosphatase, arrested the mammalian cell cycle progression at G1phase.

A specific inhibitor of protein tyrosine phosphatase (PTPase), RK-682 (3-hexadecanoyl-5-hydroxymethyl-tetronic acid) was isolated from microbial metabolites. In vitro, RK-682 inhibited dephosphorylation activity of CD45 and VHR with IC50 54 and 2.0 microM, respectively. In situ, sodium orthovanadate and RK-682 enhanced the phosphotyrosine level of Ball-1 cells, a human B cell leukemia, but not the phosphoserine/threonine level. The PTPase inhibitors, however, had the different arrest point on the cell cycle progression. Sodium orthovanadate inhibited the cell cycle progression at G2/M boundary phase, on the other hand, RK-682 inhibited the G1/S transition.

Aniline Compounds↗
PubMed1995

The oncogenic LIM protein Rbtn2 causes thymic developmental aberrations that precede malignancy in transgenic mice.

RBTN2 is activated by the chromosomal translocation t(11;14) (P13;p11) in some T cell leukaemias. Histologically similar T cell tumours develop with long latency in transgenic mice when either CD2 or thy1.1 promoters control rbtn2 expression. During the asymptomatic period, perturbation of T cell differentiation occurs in the thymus. The major anomalies present during this phase are an increase in the percentage of large thymocytes lacking CD4 and CD8 markers and also of small thymocytes express both the T cell marker CD3 and the B cell-specific form of CD45. These abnormal T cell populations can be clonal and thus a primary result of aberrant expression of the LIM-protein Rbtn2 is alteration of T cell differentiation preceding overt malignancy. These data provide a biological explanation for the role of Rbtn2 in tumorigenesis and presumably RBTN2 expression in T cells after the translocation t(11;14) in children has the same effect.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers.

Accumulating evidence suggests that deregulation of the insulin-like growth factor II (IGF2) and H19 genes at 11p15, due to loss of imprinting (LOI), plays a role in the oncogenesis of Wilms' tumors. We previously reported LOI of IGF2 in carcinomas of the lung, a common cancer of adults. We show here that LOI of H19 is also a frequent event in lung cancer development, and correlated with hypomethylation of the promoter region. Furthermore, the present study also revealed that overexpression of H19 is often associated with LOI of H19 in lung cancers retaining both parental alleles, showing a contrast to LOI in Wilms' tumors. Interestingly, in contrast to frequent LOI of the imprinted genes at 11p15, LOI was not observed for the remaining gene known to be imprinted in man, SNRPN at 15q12.

Adult↗
PubMed1995

Extracellular phosphorylation of membrane protein modifies theta burst-induced long-term potentiation in CA1 neurons of guinea-pig hippocampal slices.

The involvement of ecto-protein kinase activity in activity-dependent long-term potentiation (LTP) was studied in CA1 neurons of guinea-pig hippocampal slices. Application of 5 microM K-252b, an ecto-protein kinase inhibitor, blocked LTP induced by a theta-burst stimulation (3 bursts composed of 5 pulses at 100 Hz with inter-burst intervals of 200 ms). On the other hand, under 10 microM RK682, an ecto-phosphatase inhibitor, a robust LTP was induced by a weak theta-burst stimulation (3 bursts composed of 3 pulses) which was just at the threshold for the induction of LTP in the control perfusate. These findings suggest that ATP released from presynaptic terminals during the burst stimulation plays an important role in the induction of LTP through phosphorylation of extracellular domains of synaptic membrane proteins, as the substrate for ecto-protein kinase.

Animals↗
PubMed1995

The mechanism of ATP-induced long-term potentiation involves extracellular phosphorylation of membrane proteins in guinea-pig hippocampal CA1 neurons.

The mechanism of ATP-induced long-term potentiation was studied pharmacologically using guinea-pig hippocampal slices. Application of 1-10 microM ATP for 10 min transiently depressed and then slowly augmented the synaptic transmission in CA1 neurons leading to long-term potentiation (LTP). This ATP-induced LTP was blocked by the addition of K-252b, an ecto-protein kinase inhibitor, but was enhanced by the addition of RK682, an ecto-phosphatase inhibitor, both of which do not permeate the cell membrane. These results suggest that ATP applied to the perfusate provides enough substrate for ecto-protein kinase to induce LTP through phosphorylation of extracellular domains of membrane proteins in CA1 neurons.

Adenosine Triphosphate↗