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H Shindo

Publications and source records attributed to H Shindo.

At least 163 records · Page 9Linked to original sources
PubMed1984

[Antibacterial activity of MT-141 against anaerobic bacteria].

In vitro and in vivo antibacterial activities of MT-141, a new cephamycin, against anaerobic bacteria were compared with those of cefmetazole (CMZ), cefoxitin, cefotaxime, ceftizoxime, latamoxef and cefazolin to obtain the following results. MT-141 showed high activity against a wide variety of anaerobic bacteria including B. fragilis and C. difficile except for Eubacterium lentum, E. aerofaciens and B. furcosus. Antibacterial activity of MT-141 against anaerobic bacteria was almost independent of inoculum size, medium, pH and serum addition. In vitro development of resistance of MT-141 against P. variabilis and B. fragilis was comparable to that of CMZ. Successive parenteral administration of MT-141 into mice did not cause abnormal proliferation of C. difficile. MT-141 showed excellent therapeutic effect against experimental subcutaneous abscess in mice caused by B. fragilis.

Animals↗
PubMed1982

Analysis of therapeutic effect in experimental chemoimmunotherapy for rat ascites tumor.

The lyophilized, squalene-treated Nocardia rubra cell wall skeleton (N-CWS) was confirmed to produce tumoricidal peritoneal macrophages resulting in inhibition of tumor growth when injected locally into the syngeneic ascites fibrosarcoma, AMC 60 in ACI/N rats. Furthermore, N-CWS was found to augment therapeutic effect when administered repeatedly after a single local injection of mitomycin-C (MMC). To analyze the effects, various in vitro cytolysis assays were performed using N-CWS-activated peritoneal macrophages. When tumor target cells were exposed in vitro to MMC, the resulting cytolysis in the presence of N-CWS-activated macrophages was similar to cytolysis of intact target cells. On the other hand, when N-CWS-activated macrophages were exposed to MMC, the tumoricidal activity was lost significantly, depending on exposure to MMC. When tumor target cells and N-CWS-activated macrophages were simultaneously exposed to MMC, tumor-cell cytolysis was strikingly depressed. In the final experiment, combined injection of MMC and N-CWS into the ascites tumor resulted in remarkable increases not only in peritoneal exudate cell number, but also in in vitro tumoricidal activity of peritoneal macrophages as compared to those induced by either agent alone. In addition, the production of tumoricidal macrophages by IP injection of MMC alone was also noticeable, as described previously. These results possibly indicate the involvement of macrophage activation in induction of therapeutic effect in chemoimmunotherapy.

Adjuvants, Immunologic↗
PubMed1982

In vitro tumor cell killing by peritoneal macrophages from mitomycin C-treated rats.

The local cellular response induced by intraperitoneal injection of mitomycin C was examined in terms of cell-mediated cytotoxicity for tumor cells. An in vitro cytolysis assay involving 125I-iododeoxyuridine-labeled tumor target cells revealed that treatment of normal ACI/N rats (200 g) with a single intraperitoneal injection of mitomycin C (50, 100, or 200 micrograms) induced tumoricidal macrophages in the peritoneal cavity. The tumoricidal activity was dependent on the dose of mitomycin C injected and it was detectable as early as 1 day after the intraperitoneal injection of mitomycin C. In addition to the increased tumoricidal activity, the functional activities of the peritoneal macrophages were found to be increased with respect both to uptake of 2-deoxy-D-glucose and to phagocytosis of latex beads. Additional experiments excluded the possibility that the tumor cell cytolysis was the result of direct cytotoxicity by mitomycin C that might have been incorporated in the peritoneal macrophages or of nutrient depletion in the medium during the cytolysis assay. Furthermore, endotoxin contamination of the mitomycin C, which might have produced the activated macrophages, was not detected. The mechanism by which mitomycin C injected intraperitoneally induced the tumoricidal macrophages locally remains uncertain; however, it is possible also in clinical situations.

Animals↗
PubMed1982

Absorption, distribution, excretion and metabolism of cefmetazole in cynomolgus monkeys.

The pharmacokinetics and metabolic fate of cefmetazole (CS-1170, CMZ) were studied in cynomolgus monkeys by means of combination of radio- and bioassay techniques and that of three radioactive drugs labeled at the different moiety of the molecule. The plasma level of radioactivity after intramuscular injection of cefmetazole[methoxyl-14C] (50 mg/kg) reached the maximum level (185 microgram/ml) after 10 minutes and declined with a half-life of about 48 minutes. In the thin-layer chromatography of the plasma extracts, a single radioactive spot was detected corresponding to unchanged cefmetazole. Repeated intravenous administration for one and two weeks showed no effect on the plasma levels and half-lives. More than 75% of the intravenous or intramuscular dose was recovered in the urine by both radio- and bioassay, the most part being excreted during the first 3 hours period. On the TLC of urine, 93--97% was detected as unchanged cefmetazole. In the bile, the most part (less than 80%) was detected as unchanged cefmetazole. In the feces, about 15% of the dose was recovered, in which 30--40% was detected as intact cefmetazole. The metabolic fate of [3-35S] and [7-35S]cefmetazole was described and discussed. The whole-body autoradiography in the monkeys was also presented.

Animals↗
PubMed1981

Relationship between inhibition of pressor response to angiotensin I and blood concentration of captopril following a single oral administration to dogs.

The time courses for the inhibition of the pressor response to AI and for the blood concentration of captopril and its metabolites were determined following a single oral administration of captopril at a dose of 0.8 or 2.5 mg/kg to normal dogs. Captopril was rapidly absorbed from the gastro-intestinal tract attaining a maximum blood concentration 1-1.5h after its administration. The inhibition of the pressor response to AI was closely related with the blood concentration of unchanged captopril but not of total captopril. The blood concentrations of captopril which produced 50 and 100% inhibition were estimated to be 0.1 and 0.4 millimicron/ml respectively. At 2.5 mh/kg the maximum blood concentration attained was 4 times higher than the concentration required to completely inhibit the pressor response to AI, suggesting that a fraction of the absorbed captopril was in excess of the therapeutic requirement.

Administration, Oral↗
PubMed1981

Geometry of the phosphodiester backbone in the A form of deoxyribonucleic acid determined by phosphorus-31 nuclear magnetic resonance spectroscopy.

31P NMR spectra were obtained from poly(dA-dT) . poly(dA-dT) fibers which gave an X-ray diffraction pattern similar to that of the A form of natural deoxyribonucleic acid (DNA). The analysis of the line shape indicated that the A form of poly(dA-dT) . poly(dA-dT) has a single uniform backbone conformation; the orientation of the phosphodiester group relative to the helical axis was determined to be beta = 70 degrees and gamma = 52 degrees. The 31P NMR spectra of poly(dA-dT) . poly(dA-dT) were in remarkable contrast to the 31P NMR spectra of the A form of natural DNA, which exhibited an unusual line shape. The origins of the abnormalities in the line shape for the A form of natural DNA are discussed in terms of phosphodiester orientations.

Animals↗
PubMed1981

In vitro studies on the metabolic pathway of SQ 14225 (Captopril) and mechanism of mixed disulfide formation.

The metabolic pathway of SQ 14225 (Captopril) and the mechanism of the mixed disulfide formation with endogenous sulfhydryl compounds were studied in in vitro cell free systems. In the rat liver 9000 x g supernatants, SQ 14225-14C was metabolized to one major metabolite, glutathione-SQ 14225 mixed disulfide (GSSQ), and two minor metabolites including SQ 14551, a symmetrical disulfide of SQ 14225. The formation of GSSQ was markedly accelerated by the addition of oxidized glutathione (GSSG), but not affected by the addition of reduced glutathione (GSH), indicating that GSSQ was formed by the thiol-disulfide interchange between SQ 14225 and GSSG. Although the thiol-disulfide interchange was also observed between SQ 14225 and L-cystine, L-homocystine and SQ 14551 as well as GSSG, only the formation of GSSQ was a rapid reaction and markedly decreased by heat treatment of the liver 9000 x g supernatants. These findings demonstrate that the formation of GSSQ is catalyzed by a GSSG specific enzyme which is supposed to be thioltransferase (Glutathione: Disulfide Oxidoreductase). Although GSSQ was stable in the rat liver 9000 x g supernatants, it was rapidly hydrolyzed to cysteine-SQ 14225 mixed disulfide (CySSQ) in the rat kidney 9000 x g supernatants. A specific inhibitor of gamma-glutamyltranspeptidase, anthglutin, inhibited the hydrolysis. GSSQ-14C administered to a beagle dog was excreted into the urine in the form of CySSQ. Thus, it was speculated that CySSQ excreted into the urine as a major metabolite of SQ 14225 was derived from GSSQ formed in the liver followed by hydrolysis in the kidney.

Animals↗
PubMed1981

Antigen restricted hybridization between antigen primed macrophage and thymic RNA.

Antigen primed macrophage and thymic RNAs hybridize in an antigen restricted fashion. Thymic RNA complementary to the antigen-stimulated macrophage RNA can be obtained from mice inoculated with antigen three days earlier. The ratio of thymic and macrophage RNAs for the optimal hybridization was 50 : 1. The optimal incubation time for hybridization was 32 hours at 60 degrees C. Hybrid RNAs were insensitive to various kinds of RNase. The 31p Fourier transform nuclear magnetic resonance spectra identified hybrid RNA molecules form single stranded RNS's.

Animals↗
PubMed1981

[Biochemical study of human articular cartilage and meniscus on aging and joint disease (author's transl)].

We studied biochemically the changes associated with aging and disease in the collagen of articular cartilages and menisci. Pepsin soluble and insoluble collagen were obtained by the method of Miller (1971) from the articular cartilages of seven healthy young and adult, six healthy aged subjects, and of six osteoarthritic and six rheumatoid arthritic patients. One portion of pathological cartilage was histologically examined to eliminate any possible contamination of the fibrous tissue and subchondral bone, and to classify the pathological findings. By the method of Miller, the pepsin soluble and insoluble collagen were also obtained from four adult and six aged menisci. Amino acid composition and carbohydrate contents were studied in insoluble collagen. The type of soluble collagen were analyzed with SDS disc electrophoresis. The amount of crosslinks in insoluble collagen was analyzed by the method of Masuda (1976) using automatic amino acid analyzer. The results obtained where shown as follow: 1) Solubility of collagen by pepsin decreased with aging on articular cartilages and menisci. In osteoarthritis and rheumatoid arthritis, the solubility of collagen by pepsin was different between the samples, and generally higher than that of collagen from the aged articular cartilages. 2) In respect to aldimine crosslinks of insoluble collagen, the dihydroxylysinonorleucine (DHLNL), hydroxylysinonorleucine (HLNL) and lysinonorleucine (LNL) increased with aging. DHLNL and HLNL were present in the nonreduced collagen in vitro. It was shown that the aldimine crosslinks had been already reduced in vivo. 3) The contents of carbohydrate of insoluble collagen from articular cartilage showed lower values than that of type II collagen as described previously. The hexosamine contents increased and those of uronic acid and hexose decreased with aging. In osteoarthritic and rheumatoid arthritic articular cartilages, the contents of uronic acid were lower than that of healthy aged group. The carbohydrate contents of menisci were similar to that of type I collagen. 4) concerning the type of collagen, healthy articular cartilages consisted of type II collagen. In collagen of aged cartilages and those of fibrillated and osteophytic cartilages in osteoarthritic and rheumatoid arthritic patients, the type II collagen were mixed with type I collagen ranging from 13.8% to 64.5%, although the analysis of articular cartilages in this study showed histological characteristics of hyaline cartilage. The type of soluble collagen in adult and aged menisci were composed of type I collagen in spite of aging.

Adolescent↗
PubMed1980

Conformation of 145 base pair length poly (dG-dC) . poly (dG-dC) in solution and in association with histones.

We have studied the conformation of poly (dG-dC) . poly (dG-dC) in three conditions; i) associated with histones octamers, ii) alone at ionic strength 0.1, and ii) in solutions of over 2.5 M NaCl. The circular dichroism spectrum for the polymer bound to histones differs from that for the free polymer; the difference spectrum is similar to those for native and poly (dA-dT) . poly (dA-dT) core particles. Under the first two conditions, the 31P NMR spectrum is symmetric with line widths of 91 and 41 Hz, respectively, at 109.3 MHz. In high salt, two 31P peaks of equal intensity are observed, confirming recent results of Patel et al. (1) and indicating an alternating geometry for the phosphodiester backbone. Using this highly homogeneous DNA, we confirm that the Pohl-Jovin transition (2) is an intramolecular rearrangement, not requiring complete strand separation.

Circular Dichroism↗
PubMed1980

Direct observation of peptide exchange by stable isotope enrichment.

A method for the kinetic determination of peptide exchange using stable isotope enrichment is described. Synthetic 90% enriched (epsilon-13C)His 12 ribonuclease (RNase) (1-15) peptide was used as a probe to follow peptide exchange in the RNase S system by 13C nuclear magnetic resonance spectroscopy. The rate constant, k1, for dissociation of the RNase S complex containing the synthetic (1-15) peptide was found to be (4.1 +/- 0.3) x 10(-4) s-1 and its dissociation constant Kd, (0.2 +/- 0.8) x 10(-7) M, was greater than that of RNase S with natural S-peptide (residues 1 to 20) by a factor of five at 4 degrees C. This differences corresponds to the difference of the enthalpy of binding between the (1-15) and (1-20) peptides, which we determined to be 1.7 +/- 0.4 kcal/mol. This small enthalpy difference may originate from hydrogen bonding between Ser 16 and His 48 in the RNase S complex.

Carbon Isotopes↗
PubMed1980

Nonuniform backbone conformation of deoxyribonucleic acid indicated by phosphorus-31 nuclear magnetic resonance chemical shift anisotropy.

31P nuclear magnetic resonance of highly oriented DNA fibers has been observed for three different conformations, namely, the A, B, and C forms of DNA. At a parallel orientation of the fiber axis with respect to the magnetic field, DNA fibers in both the A and B forms exhibit a single, abnormally broad resonance; in contrast, fibers in the C form show almost the full span of the chemical shift anisotropy (170 ppm). The spectra of the fibers oriented perpendicular indicate that the DNA molecules undergo a considerable rotational motion about the helical axis, with a rate of greater than 2 x 10(3) s-1 for the B-form DNA. Theoretical considerations indicate that the 31P chemical shift data for the B-form DNA fibers are consistent with the atomic coordinates of the phosphodiester group proposed by Langridge et al. [Langridge, R., Wilson, H. R. Hooper, C. W., Wilkins, M. H. F., & Hamilton, L. D. (1960) J. Mol. Biol. 2, 19--37] but not with the corresponding coordinates proposed by Arnott and Hukins [Arnott, S., & Hukins, D. W. L. (1972) Biochem. Biophys. Res. Coomun. 47, 1504--1509], and also lead to the conclusion that the phosphodiester orientation must vary significantly along the DNA molecule. The latter result suggests that DNA has significant variations in its backbone conformation along the molecule.

Animals↗