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Biomedical subjects

M Ohsawa

Publications and source records attributed to M Ohsawa.

At least 199 records · Page 11Linked to original sources
PubMed1989

Modulation of antitumor activity of grifolan by subsequent administration of (1----3)-beta-D-glucanase in vivo.

The initiation process of effector mechanism of the antitumor activity of (1----3)-beta-D-glucans has been examined in detail by applying treatment of mice with (1----3)-beta-D-glucanase, kitalase (KIT) and zymolyase (ZYM), via i.p. route after i.p. administration of (1----3)-beta-D-glucans, grifolan (GRN) and CM-curdlan (CM-CUD). A significant decrease of antitumor activity caused by GRN was observed by treatment with KIT within 48 h, and that caused by GRN administered via i.v. route was also reduced by the i.v. injection of KIT, although it was less effective than i.p. treatment. Pretreatment of mice with thioglycollate reduced the period of time to abrogate antitumor activity by the sequential treatment of KIT. Similar results were also observed on ZYM treatment after i.p. treatment of CM-CUD. These facts suggest that the period of manifestation of the antitumor activity by (1----3)-beta-D-glucans must be longer than a few days.

Adjuvants, Immunologic↗
PubMed1989

Modification of immunostimulating activities of grifolan by the treatment with (1----3)-beta-D-glucanase.

We have developed a method to control the effective time period of (1----3)-beta-D-glucan in vivo by using (1----3)-beta-D-glucanase and found that grifolan LE (GRN), a (1----3)-beta-D-glucan, administered intraperitoneally to the host required more than 2 d to exert antitumor activity. During these two days many immunological changes were induced, such as increasing the number of peritoneal exudated cells (PEC), augmentation of production of interleukin 1 (IL-1), acid phosphatase and phagocytic capacity of adherent cells in PEC. In addition, there was increased carbon clearance activity in vivo, augmentation of responsiveness of splenocytes to mitogens such as concanavalin A and lipopolysaccharide (LPS) and production of ceruloplasmin. When (1----3)-beta-D-glucanase was injected 1 d after GRN administration, IL-1 productivity and responsiveness to LPS were significantly reduced, but lysosomal enzyme activity and phagocytosis of macrophage and production of ceruloplasmin were similar to those not treated with glucanase. These facts indicate that the induction of the activities of the former group requires longer contact of host cells with the glucan, and the latter group requires a shorter period to achieve fully active stages.

Acid Phosphatase↗
PubMed1989

Physiochemical properties and antitumor activities of chemically modified derivatives of antitumor glucan "grifolan LE" from Grifola frondosa.

Antitumor glucan, grifolan LE (GRN LE), from Grifola frondosa was chemically modified to examine the structure-function relationship of the products. Modification by periodate, borohydride and acid hydrolysis of side chains of GRN LE did not alter properties such as helical conformation and antitumor activity of GRN LE. Introduction of carboxylic acid groups into the side chains by oxidation with periodate and with sodium chlorite (GRN LE-PC), and substitution with carboxymethyl (CM) or hydroxyethyl (HE) groups abolished the gel-forming ability of GRN LE. Significant antitumor activity was observed in all of the derivtives having gel-forming ability as well as some derivatives having no such ability. These results suggested that essential factors required for antitumor activity were (1----3)-beta-D-glucosyl linkages and high molecular weight, and that accessory groups could be linked to the main chain without loss of antitumor activity in a higher ratio than that of gel-forming ability.

Animals↗
PubMed1989

[A review of childhood cases of malignant lymphoma in Osaka, Japan].

Fifty-one cases of malignant lymphomas in patients under 20 years of age have been reviewed in Osaka, Japan. The breakdown of these cases revealed 6 cases (11.8%) of Hodgkin's disease (HD) and 45 cases (88.2%) of a non-Hodgkin's lymphoma (NHL). Both the HD and NHL cases were determined by using the Rye classification, as well as the Rappaport, Kiel, and LSG classifications, respectively. The results have shown that (1) the incidence of HD in childhood is the same as that seen in the adult in Japan; (2) that a NHL of the nodular type is rare in Japan as it is in Western countries; (3) that any significant differences were not present in the distribution of each histologic subtype in the cases of a NHL among Japan and Western countries, and that the lymphoblastic type was the most common. From this study it is concluded that geographical differences were not a factor in comparing cases of childhood malignant lymphomas in Japan and Western countries.

Adolescent↗
PubMed1988

Silver staining for carboxymethylated metallothioneins in polyacrylamide gels.

A sensitive method for detecting metallothioneins (MTs) by use of silver staining after sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of carboxymethylated MTs was developed. Carboxymethylation of metallothioneins is indispensable because it prevents their aggregation, thereby allowing each of them to be detected as a single band by SDS-PAGE. However, when the gel was subjected to the silver-staining method of C. R. Merril, D. Goldman, S. A. Sedman, and M. H. Ebert [(1981) Science 211, 1437-1438], the image of carboxymethylated purified MTs was totally negative. Pretreatment of the gel with 1% sodium thiosulfate just prior to the silver-staining procedure successfully reversed the negative image of carboxymethylated MTs. Further, they could be detected with a limit of nanogram levels per lane. This method can be applied to MTs in cell extracts from cultured cell lines treated with cadmium or to those from liver of cadmium-intoxicated mice.

Animals↗
PubMed1988

Glutathione and metallothioneins as cellular defense against cadmium toxicity in cultured Chinese hamster cells.

To evaluate the protective role of cell glutathione (GSH) against the toxicity of cadmium, the effect of GSH depletion on the metal toxicity was investigated and the role of glutathione was compared with that of zinc-induced metallothioneins (MTs). A 6-h incubation of cultured Chinese hamster V79 cells with 0.2 mM L-buthionine-SR-sulfoximine (BSO), a selective inhibitor of gamma-glutamylcysteine synthetase, resulted in approx. 95% depletion of GSH in the cells. The depletion of GSH did not influence the rate of cell growth, the amount of cell protein or the chromosome structure during culture for at least 24 h. Cells depleted or not depleted of GSH were challenged with (1-5).10(-5) M CdCl2 for 2 h and subsequent cell growth was evaluated. The cytotoxicity of cadmium was enhanced with increasing duration of BSO pretreatment and was correlated with the decrease of cell GSH, indicating that GSH constitutes a cellular defense against toxicity by cadmium. Inducibility of MTs by zinc was investigated in cultured V79 cells. Incubation of the cells with 1.10(-4) M zinc acetate did not result in accumulation of MTs over the control values for up to 2 h. Thereafter, however, the synthesis of MTs increased with increasing duration of zinc treatment and an approx. 9-fold increase in the amount of MTs was observed 10 h after addition of zinc. Depletion of cell GSH by BSO did not much influence the increased accumulation of MTs by zinc. In contrast, zinc at the same concentration did not influence the level of cell glutathione up to 12 h. The cytotoxicity of cadmium was markedly reduced in the cells pretreated with zinc and the protective effect of zinc was dependent upon duration of pretreatment, being parallel with the increased accumulation of MTs. Protection of cells from cadmium toxicity by zinc pretreatment was as or a little more effective in the cells depleted of GSH as in those not depleted. Thus, glutathione appears to be an intrinsic protector against cadmium toxicity, while MTs serve as an induced cellular defense that is mobilized against heavy metal stress, but takes more than 2 h to accumulate in significant amounts. Accordingly, it is suggested that GSH and MTs have cooperative protective roles against cadmium toxicity, as an initial defense for the former and a second-stage defense for the latter.

Acetates↗
PubMed1988

Proline carrier mutant of Escherichia coli K-12 with altered cation sensitivity of substrate-binding activity: cloning, biochemical characterization, and identification of the mutation.

Two putP mutants of Escherichia coli K-12 that were defective in proline transport but retained the binding activities of the major proline carrier were isolated (T. Mogi, H. Yamamoto, T. Nakao, I. Yamato, and Y. Anraku, Mol. Gen. Genet. 202:35-41, 1986). One of these mutations and three null-type mutations (K. Motojima, I. Yamato, and Y. Anraku, J. Bacteriol. 136:5-9, 1978) were cloned into a pBR322 putP+ hybrid plasmid (pTMP5) by in vivo recombination. Cytoplasmic membrane vesicles were prepared from the mutant strains and strains harboring pTMP5 putP plasmids, and the properties of the proline-binding reaction of the mutant putP carriers in membranes were examined under nonenergized conditions. The putP19, putP21, and putP22 mutations, which were mapped in the same DNA segment of the putP gene (Mogi et al., Mol. Gen. Genet. 202:35-41, 1986), caused the complete loss of proline carrier activity. The proline carriers encoded by the mutant putP genes, putP9 and putP32, and putP32 in pTMP5-32, which was derived from in vivo recombination with the putP32 mutation, had altered sodium ion and proton dependence of binding affinities for proline and were resistant to N-ethylmaleimide inactivation without changes in the specificities for substrates and alkaline metal cations. The nucleotide sequence of the putP32 lesion located on the 0.35-megadalton RsaI-PvuII fragment in the putP gene in pTMP5-32 was determined; the mutation changed a cytosine at position 1001 to a thymine, causing the alteration of arginine to cysteine at amino acid position 257 in the primary structure of the proline carrier. It was shown that this one point mutation was enough to produce the phenotype of pTMP5-32 by in vitro DNA replacement of the AcyI-PvuII fragment of the wild-type putP gene with the DNA fragment containing the mutated nucleotide sequence.

Amino Acid Sequence↗
PubMed1988

Distribution of grifolan NMF-5N (I/B), a chemically modified antitumor beta-glucan in mice.

The distribution of a 3H-labeled chemically modified antitumor beta-glucan, grifolan NMF-5N (I/B), in various tissues after an injection into mice was examined in order to obtain information on distribution of the parent antitumor beta-glucan, grifolan NMF-5N. Grifolan NMF-5N was treated with sodium metaperiodate and sodium borotritide to obtain tritium-labeled grifolan NMF-5N [3H-grifolan (I/B)]. When 3H-grifolan (I/B) was administered into normal mice by intraperitoneal (i.p.) or intravenous (i.v.) injection, radioactivity was detected in various mouse tissues. Next, 3H-grifolan (I/B) was injected into tumor-bearing mice 7 d after the tumor inoculation, which is the most effective administration timing for the antitumor effect of grifolan NMF-5N. The results indicated a strong radioactivity in spleens and tumor masses. These results suggested a close relationship between the antitumor activity and the distribution of grifolan NMF-5N in mice.

Animals↗
PubMed1988

Giant aneurysms of the vertebral artery. Report of five cases.

The authors report five cases of surgically treated giant vertebral artery aneurysm. Two giant serpentine aneurysms were managed with aneurysmectomy, a giant semifusiform aneurysm with trapping and partial aneurysmectomy, and the other two saccular giant aneurysms with clipping. Surgical results were satisfactory in all cases. In particular, the two patients who underwent complete aneurysmectomy showed remarkable improvement after the second procedure of a two-stage operation that consisted of initial proximal occlusion and secondary evacuation of clots in the aneurysm when advanced thrombosis was identified. Aneurysmectomy in a two-stage operation was the best treatment for these partially thrombosed giant aneurysms which completely concealed the distal artery under a tight thinned medulla.

Aged↗
PubMed1988

Induction of anti-nuclear antibodies in mice orally exposed to cadmium at low concentrations.

Anti-nuclear antibodies (ANA) in serum were detected in male ICR mice fed drinking water containing 3, 30 and 300 ppm Cd as CdCl2 for 10 weeks. In response to Cd exposure, ICR mice developed ANA of the IgG class giving nuclear patterns moderately stained by immunofluorescence or immunoenzyme method. Positive immunofluorescence staining of ANA was obtained in 50, 89 and 90% of ICR mice exposed to 3, 30 and 300 ppm Cd, respectively. Their spleen cells also showed an enhancement of antibody forming response to sheep red blood cells (SRBC) without the SRBC priming. When mice were primed with SRBC after exposure to Cd, however, a significant suppression of the antibody forming response was observed in mice fed 300 ppm Cd but not in those fed 3 ppm Cd. No significant differences in delayed-type hypersensitivity reaction to SRBC were observed between Cd-fed and control animals. Inbred BALB/c mice were less susceptible to the induction of ANA by Cd, as induced only in 300 ppm Cd-fed mice. Thus environmental exposure to Cd can induce ANA in ICR mice with a high susceptibility, presumably accompanied with a non-specific stimulation of antibody formation.

Administration, Oral↗
PubMed1988

Serum CA 125 levels in patients with endometriosis: changes in CA 125 levels during menstruation.

We investigated serum CA 125 levels in 120 patients with benign gynecologic disease, and examined variations in CA 125 levels during the menstrual cycle in six normally cycling women. CA 125 levels were elevated transiently during menstruation, suggesting that blood samples taken during menstruation can give a false-positive result. Whereas the CA 125 values during the nonmenstrual part of the cycle were significantly higher in the patients with adenomyosis and advanced endometriosis (stages III and IV) than in those with a normal pelvis, there was no difference between the patients with mild endometriosis (stages I and II) and the normal-pelvis group. CA 125 levels during menstruation were significantly elevated, not only in women with adenomyosis and advanced endometriosis, but also in those with mild endometriosis, compared with those with a normal pelvis. These data suggest that the measurement of serum CA 125 during menstruation may increase the rate of detection of endometriosis over that in studies done during other phases of the cycle.

Antigens, Neoplasm↗
PubMed1988

[Clinical assessment of body hair growth in Japanese women. The relationship between a grade of hirsutism and the menstrual status].

Three hundred and sixty-nine volunteer women and 308 outpatients were studied to clarify the criteria of hirsutism and the relationship between a grade of hirsutism and menstrual status in Japanese women. The body hair growth was assessed according to the modified score system described by Ferriman and Gallway. The menstrual status was classified into six groups based on basal body temperature. The hair growth score calculated in volunteers tended to be lower than that of western women in most sites. Therefore one criterion of hirsutism in Japanese women should be a score of more than 6 points in our system. There was a close correlation between body hair growth and menstrual status. As a result, it can be considered that the systematic assessment of body hair growth is useful in diagnosing and treating some irregular menstrual patients.

Adolescent↗
PubMed1987

Metallothioneins of monocytes and lymphocytes.

Monocytes and lymphocytes were separated from human peripheral blood, and their capacity to synthesize metallothioneins (MTs) was examined. Both cell types can produce proteins electrophoretically similar to HeLa cell MTs. These proteins are inducible by Cd2+ and specifically precipitable by anti-MT serum. To have an insight into the capacity of T- and B-lymphocytes to produce MTs, sensitivity to Cd2+ of both cell types was estimated during mitogen-specific blastogenesis. Lymphocytes were prepared from mouse spleen and stimulated by concanavalin A (ConA) or lipopolysaccharide (LPS) in the presence of Cd2+. [3H]thymidine incorporation, as well as [3H]uridine incorporation in an earlier stage, was more severely inhibited by Cd2+ in ConA-induced mitogenesis than in LPS-induced mitogenesis, indicating T-lymphocytes are more sensitive to Cd2+ toxicity. This may reflect lower capacity of T-lymphocytes to synthesize MTs in response to Cd2+.

Animals↗
PubMed1987

Indirect evidence for the induction of a prooxidant state by cadmium chloride in cultured mammalian cells and a possible mechanism for the induction.

The effects of scavengers of active oxygen species on cadmium chloride (CdCl2)-induced inhibition of cell growth and DNA synthesis and on the metal-induced clastogenesis were investigated to evaluate whether cadmium could induce a prooxidant state in cultured Chinese hamster V79 cells. Inhibition by CdCl2 of cell growth and [3H]thymidine incorporation into the acid-insoluble fraction of cells and the metal-induced clastogenesis were suppressed in part by the presence of the diffusible radical scavenger, butylated hydroxytoluene (BHT). The action of BHT was concentration-dependent and did not affect the intracellular level of cadmium. D-Mannitol, a hydroxyl radical scavenger, also significantly suppressed Cd-induced inhibition of cell growth and [3H]thymidine incorporation. Catalase was marginally suppressive on Cd-induced inhibition of cell growth. These results suggest that cadmium can induce a prooxidant state in cultured mammalian cells. The mechanism by which cadmium induces a prooxidant state was investigated by measuring the effect of cadmium on those enzymes which constitute a cellular defense against active oxygen and on the level of the intracellular antioxidant, glutathione (GSH). 2-h treatments with CdCl2 over a concentration range of 2-10 X 10(-5) M did not influence superoxide dismutase, catalase, GSH peroxidase or GSSG reductase. In contrast, the level of glutathione was decreased to approximately 40% by treatment with 2 X 10(-5) M cadmium. The decrease in glutathione level may be responsible for a role by active oxygen in Cd-induced inhibition of cell growth and DNA synthesis and the metal-induced clastogenesis.

Animals↗
PubMed1987

Dependence on Salmonella typhimurium enzymes of mutagenicities of nitrobenzene and its derivatives in the presence of rat-liver S9 and norharman.

Dependence on S. typhimurium enzymes of mutagenicities of nitrobenzene (NB) and o-, p-chloronitrobenzenes (o-, p-CNBs), which are only mutagenic in the presence of S9 and norharman (NOH), was investigated using a nitroreductase-deficient strain TA98NR and an esterifying enzyme-deficient strain TA98/1,8-DNP6. NB exhibited mutagenicity towards TA98 but did not towards TA98NR strain in spite of the presence of S9 in the assay system. The mutagenicity of o-CNB towards TA98NR was significantly lower than that of o-CNB towards TA98. In contrast to NB and o-CNB, synthesized phenylhydroxylamine (PHA) and o-chlorophenylhydroxylamine (o-CPHA) exhibited approximately the same mutagenicity towards both tester strains. These results indicate that the nitroreduction required for the appearance of mutagenicity of the nitrobenzene derivatives in the presence of S9 and NOH is dependent on the nitroreductase of the tester strain. In addition, the mutagenicities of PHA and p-CPHA were significantly higher towards TA98/1,8-DNP6 than towards TA98, suggesting that the esterification of their hydroxylamines produced inactivation rather than activation. From these results, it was concluded that S9 and NOH play a role in metabolic activation other than the reduction of the nitro group to hydroxylamine and subsequent esterification for the mutagenesis of NB and its derivatives.

Alkaloids↗