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H Kuga

Publications and source records attributed to H Kuga.

31 records · Page 2Linked to original sources
PubMed1992

Camptothecin analog (CPT-11)-sensitive human pancreatic tumor cell line QGP-1N shows resistance to SN-38, an active metabolite of CPT-11.

In the course of our study to determine the cross-sensitivity between CPT-11 and its active metabolite, SN-38, we found a SN-38-resistant human pancreatic tumor cell line, QGP-1N, which shows sensitivity to CPT-11. The IC50 of SN-38 was 152 times greater for QGP-1N than for SUIT-2, also a human pancreatic tumor cell line, whose IC50 of CPT-11 was similar to that for QGP-1N. The uptakes of CPT-11 and SN-38 and the intracellular conversion of CPT-11 to SN-38 could not explain the difference in sensitivity. DNA synthesis of QGP-1N cells was inhibited by CPT-11 which did not affect that of SUIT-2, while SN-38 inhibited the DNA synthesis of SUIT-2 at lower concentrations than that of QGP-1N. The inhibition test of topoisomerase I catalytic activity by CPT-11 or SN-38 revealed no difference in the biochemical properties of the topoisomerase I enzymes to the compounds between these two cell lines. These results indicate that CPT-11 should have its own inhibitory effect on DNA synthesis through a yet unknown mechanism in QGP-1N cells, although SN-38 plays an essential role in the antitumor activity of CPT-11 in SUIT-2 cells. In some cases, the antitumor effect of CPT-11 might be consequent not only on SN-38 but also on CPT-11 itself.

Antineoplastic Agents, Phytogenic↗
PubMed1991

Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11.

It is known that 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), a semisynthesized derivative of camptothecin (CPT), has a potent antitumor activity in vivo, but 7-ethyl-10-hydroxycamptothecin (SN-38), a metabolite of CPT-11, shows much stronger cytotoxicity in vitro than CPT-11. In this study, we demonstrated that the relaxation of SV40 DNA plasmids by type I DNA topoisomerase prepared from P388 murine leukemia cells was inhibited by 50% by SN-38 at approximately 1 microM, although CPT-11 at 1 mM slightly inhibited the relaxation. SN-38 and CPT showed strong, time-dependent inhibitory activity against DNA synthesis of P388 cells. However, CPT-11 weakly inhibited DNA synthesis independently of time with coincident inhibition of the total thymidine uptake by the cells. By alkaline and neutral elution assays, it was demonstrated that SN-38 caused much more frequent DNA single-strand breaks in P388 cells than did CPT-11. The same content of SN-38 and a similar frequency of single-strand breaks were detected in the cells treated with SN-38 at 0.1 microM or with CPT-11 at 100 microM. Therefore, single-strand breaks by CPT-11 seem to be due to SN-38 produced from CPT-11 in cells. These results indicate that CPT-11 itself possesses a marginal antiproliferative effect but that SN-38 plays an essential role in the mechanism of action of CPT-11.

Animals↗
PubMed1990

Stimulation of all T cells bearing V beta 1, V beta 3, V beta 11 and V beta 12 by staphylococcal enterotoxin A.

To determine the molecular mechanisms of T cell stimulation by staphylococcal enterotoxin A (SEA), we examined the expression of T cell receptor (TcR) V beta on the T cells from four strains of mice stimulated in vitro with SEA, using flow cytometric analysis for the number of T cells bearing V beta 3, V beta 6, V beta 8, V beta 11 and RNA blotting analysis for the amount of transcripts of V beta 1, V beta 5 and V beta 12. The number of T cell blasts bearing V beta 1, V beta 3, V beta 1 or V beta 12 were increased in the T cell blasts proliferating in vitro in response to SEA in C57BL/6 mice. In AKR/J mice, which contain few V beta 11- or V beta 12-bearing T cells due to a tolerance to the self-MHC class II IE-antigens, T cells bearing V beta 1 or V beta 3 responded to SEA. SEA enriched only V beta 1-bearing T cells in BALB/c mice carrying Mls-2a which lack Mls-1a-reactive V beta 3-bearing T cells as well as V beta 11- and V beta 12-bearing T cells. In spite of the presence of V beta 1-bearing T cells, C3H/He T cells exhibited a very low responsiveness to SEA. T cell repertoires skewed by clonal deletion of self-reactive T cells may in part account for the different sensitivity to SEA among the different strains. A tolerance to SEA can be established in C57BL/6 mice which have been primed i.v. with SEA and treated i.p. with 200 mg/kg of cyclophosphamide 2 days later. All mature T cells bearing V beta 3 or V beta 11 were virtually abolished in the periphery of tolerant mice. These results suggest that most T cells reactive to SEA bear V beta 1, V beta 3, V beta 11 or V beta 12 and that clonal deletion of mature T cells reactive to SEA may account for the cellular mechanisms for cyclophosphamide-induced tolerance to SEA.

Animals↗
PubMed1988

Ultrastructural investigations on the anterior adductor muscle of a brachiopoda, Lingula unguis.

The brachiopoda, Lingula unguis, has a pair of anterior adductors located in the center of the shell. Each muscle consists of an opaque and a translucent portion which is constructed of smooth and obliquely-striated muscle respectively. According to our ultrastructural observations, the opaque portion seems to have two types of cells. They differ only in the diameters of their thick myofilaments. The fine structure of their cell organelles resembles each other. We measured the diameters of the thick myofilaments in each type of cell to distinguish between the two cell types. About 500 measurements of myofilament diameters were made for each type of cell and statistically analyzed. For one type of cell, the distribution of diameters of the thick myofilaments fit a normal distribution curve with a peak at 37-60 nm. The distribution of diameters of the thick myofilaments for the other type fit a curve in which two normal distribution curves having peaks at 37-60 and 75-97 nm respectively partially overlapped. According to these results, we suggest that the opaque portion contains two types of cells, each having a different distribution of thick myofilament sizes.

Animals↗
PubMed1987

Jietacins A and B, new nematocidal antibiotics from a Streptomyces sp. Taxonomy, isolation, and physico-chemical and biological properties.

Jietacins A and B, new azoxy antibiotics, were isolated from the culture broth of a streptomycete. The antibiotics have the molecular formulae of C18H34N2O2 and C19H36N2O2, respectively. Both possess an azoxy group. They have potent activity against the pine wood nematode, Bursaphelenchus lignicolus, and are weakly active against some fungi.

Animals↗
PubMed1986

Adecypenol, a unique adenosine deaminase inhibitor containing homopurine and cyclopentene rings. Taxonomy, production and enzyme inhibition.

Adecypenol, which exhibits potent inhibitory activity against calf intestinal adenosine deaminase (EC 3.5.4.4), was isolated from the cultured broth of Streptomyces sp. OM-3223. Adecypenol was classified as a semi-tight binding inhibitor. The Ki value against calf intestinal adenosine deaminase was 4.7 X 10(-9) M. No acute toxicity of adecypenol was observed at 100 mg/kg in mice. Adecypenol exhibited no antimicrobial activity against various bacteria and fungi at the concentration of 1.0 mg/ml.

Adenosine Deaminase Inhibitors↗
PubMed1986

Clostomicins, new antibiotics produced by Micromonospora echinospora subsp. armeniaca subsp. nov. I. Production, isolation, and physico-chemical and biological properties.

A soil isolate named as Micromonospora echinospora subsp. armeniaca subsp. nov. KMR-593 was found to produce at least five related antibiotics, clostomicins, active against Gram-positive bacteria including anaerobes. From the physico-chemical properties, one of these components was identified with lipiarmycin and others were found to be new antibiotics. Each component includes two chlorine atoms and the molecular weights of A and B2, C, and D are 1,058, 1,042 and 1,056, respectively. The structural differences were characterized by NMR analyses.

Aminoglycosides↗
PubMed1985

Adechlorin, a new adenosine deaminase inhibitor containing chlorine production, isolation and properties.

Adechlorin exhibiting a potent inhibitory activity against calf intestinal adenosine deaminase was isolated from the cultured broth of Actinomadura sp. OMR-37. The molecular formula was C11H15N4O4Cl. The aglycone of adechlorin was identical with that of the known adenosine deaminase inhibitors coformycin and 2'-deoxycoformycin. Adechlorin did not exhibit inhibitory activity against various bacteria and fungi at 1.0 mg/ml. The Ki values for adechlorin, coformycin and 2'-deoxycoformycin against adenosine deaminase were determined to be 5.3 X 10(-10) M, 2.1 X 10(-10) M and 7.6 X 10(-11) M, respectively. Adechlorin as well as coformycin and 2'-deoxycoformycin enhanced the antiviral activity of Ara-A. The acute toxicity of adechlorin in mice was less than those of coformycin and 2'-deoxycoformycin.

Actinomycetales↗
PubMedDate not supplied

Construction of a transplantable tissue-engineered artificial peritoneum.

BACKGROUND: Peritoneal defects lead to serious postoperative problems. Thus the development of physiological material to cover peritoneal defects is very desirable. AIM: The aim of this study was to develop a transplantable artificial peritoneum. METHOD: The artificial peritoneum consisted of collagen gel, fibroblasts, and mesothelial cells, and histological features were analyzed. The artificial peritoneum at the site of a peritoneal defect in the rat was transplanted to the abdominal wall. RESULTS: Histological examination revealed that the artificial peritoneum consisted of a flat mesothelial monolayer upon a stromal matrix. All transplanted artificial peritoneums adapted well to the host and prevented severe adhesion. CONCLUSION: Our artificial peritoneum may be a useful transplantable bioengineered material for repair of surgical peritoneal defects.

Abdominal Wall↗