[Therapeutic effect of vancomycin hydrochloride, a nonabsorbable antibiotic, on intractable (lactulose resistant) chronic hepatic encephalopathy in cirrhotic patients].
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Biomedical subjects
Publications and source records attributed to A Sakurai.
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The effect of sialylated TBG and desialylated TBG on thyroxine (T4) uptake by human peripheral mononuclear cells was investigated in vitro. [125I]-T4 uptake was observed when the cells were incubated with free [125I]-T4. The uptake was inhibited in a concentration dependent manner when TBG was added. During the incubation, [125I]-T4 binding to TBG was observed. [125I]-T4 incorporation into cells was also observed when the cells were incubated with [125I]-T4-sialylated TBG or with [125I]-T4-desialylated TBG complex. The uptake was related to the temperature and length of time of the incubation. The amount of [125I]-T4 incorporated into the cells incubated with [125I]-T4-sialylated TBG was greater than that into the cells incubated with [125I]-T4-desialylated TBG during the early 0-20 min. incubation, whereas the amount of [125I]-T4 incorporated into the cells incubated with [125I]-T4-desialylated TBG became greater than that into the cells incubated with [125I]-T4-sialylated TBG after 20 min. of incubation. Pretreatment of the cells with methylamine blocked [125I]-T4 uptake in both cases, i.e. incubated with [125I]-T4-sialylated TBG and incubated with [125I]-T4-desialylated TBG. The results suggest that TBG plays a role not only as a carrier protein for T4 in circulation but also as a protein which can transport T4 from the extracellular into the intracellular space, so that the mechanism of T4 transport mediated by desialylated TBG is different from that mediated by sialylated TBG, and that the T4 transport system in both cases, mediated by sialylated TBG and by desialylated TBG, may be related to the internalization of T4-TBG-TBG receptor complex or of T4-T4 receptor complex if TBG receptors are present in the outer surface of the cell membrane.
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We have developed hybridoma cell lines, each of which secretes a monoclonal antibody (MoAb) to rat renal and hepatic tissue antigens, from Lewis rat with Heymann's nephritis. Three antibodies bind to the brush border of proximal tubular epithelium (BB), one in a fine net-like pattern (no. 3-11), another one in a coarse granular pattern (no. 1-8) and the third one in a typical pattern (no. 3-9). Three antibodies bind to glomerulus in characteristic patterns but not to BB. After repeated intravenous injections of MoAb (no. 3-11), granular mesangial deposits of rat IgG were observed and of MoAb (no. 1-8), fine granular deposition along capillary walls. These monoclonal autoantibodies should be of value in research on the mechanism of autoimmune membranous nephropathy.
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Cytotoxic factor was produced from murine macrophage-like cell line, J774, after stimulation with 12-o-tetradecanoyl phorbol-13-acetate (TPA) and lipopolysaccharide (LPS). J774-derived cytotoxic factor is a glycoprotein with a molecular weight of 39,000 by gel filtration and 18,000 by SDS-PAGE, and with an isoelectric point of below 4.3. J774-derived cytotoxic factor exhibited cytotoxicity to L(S) cells, not cytotoxic to L(R) cells, and a necrotizing action against transplanted Meth A sarcoma. J774-derived cytotoxic factor and murine serum tumor necrosis factor (TNF) were identical as regards properties.
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Two human hematopoietic cell lines (TYS and TYH) with monocytic characteristics were derived from the peripheral blood of a patient with acute myelomonocytic leukemia and of another with a follicular large-cell type of malignant lymphoma. The TYS cells, derived from the leukemia patient, revealed a monocytic appearance with microvilli at one side and had many granules and vacuoles. They showed strongly positive reactions with alpha-NBE, NASDAE, and AcP, and were reactive with monoclonal antibodies such as OKlal, 12 and Bl. The TYS cells, which phagocytized carbon particles and antibody-coated SRBC but not latex particles, released lysosomal enzymes and tumoricidal factor into the supernatant. The TYH cells, derived from the malignant lymphoma patient, had abundant cytoplasm and pseudopods detectable by electron microscopy with a monocytoid appearance and virus-like particles in the cytoplasm. They showed strongly positive reactions with alpha-NBE, NASDAE and beta-Gase, but no reactivity with monoclonal antibodies or with surface markers except Fc gamma-R. TYH cells phagocytized latex particles very well. Two different human monocyte-histiocyte lineages were thus established. During culture, the TYS and TYH cells maintained their characteristics over 28 and 16 months of passage, respectively.
Good production of tumor necrosis factor (TNF) in the rabbit was obtained using Propionibacterium acnes IID 912 as a priming agent and subsequent administration of lipopolysaccharide. The physicochemical characteristics of rabbit TNF were very similar to those of murine TNF. The molecular weight of rabbit TNF was 39,000 as estimated by gel filtration, and 18,000 by SDS-PAGE. The isoelectric point was determined as pH 4.0 by isoelectric focusing. Rabbit TNF was stable within the pH range of 5.5 to 11.0, and was stable at 56 degrees C for 8 hr. It was digested by trypsin, pancreatic protease and elastase, but was resistant to neuraminidase. The amino acid sequence of rabbit TNF was determined as Ser-Ala-Ser-Arg-Ala-Leu- .... Monoclonal antibody against rabbit TNF completely inhibited both the in vivo and in vitro activity of rabbit TNF. However, this antibody could not inhibit the action of murine TNF. Antitumor activity of rabbit TNF was shown against murine and human cancer cells in vivo and in vitro, and rabbit TNF was also capable of distinguishing malignant cells from normal cells.
The antitumor activities and capacity for tumor necrosis factor (TNF) production of traditional Chinese herbal preparations (Zhu-ling-tang, Xiao-chai-hu-tang), crude drugs (Polyporus, Hoelen, Bupleuri radix, Angelica radix, Cnidii rhizoma, Cinnamomum cortex), and Krestin (PSK) were investigated. These drugs were given to DDY mice in the drinking water before and after transplantation of Ehrlich tumors, and the development of the intradermally transplanted Ehrlich tumors and survival rate were observed. A good survival rate and sometimes a complete cure were found in the groups administered Bupleuri radix, Xiao-chai-hu-tang, Angelica radix, or Cinnamomum cortex, while the group given Hoelen showed poor results. To examine the capacity for TNF production these drugs were given to DDY mice PO as initial stimulating agents, to stimulate the reticuloendothelial system (RES) prior to lipopolysaccharide injection. The TNF activity was tested from the cytotoxicity against L cells. Significant differences in capacity for TNF production were observed among the drugs. Relatively high levels of TNF activity were noted in the groups given Angelica radix, Bupleuri radix, Cnidii rhizoma, or Cinnamomum cortex, very low activities in the groups given Xiao-chai-hu-tang, Zhu-ling-tang, or Krestin, and no TNF activities in the groups given Polyporus or Hoelen. The TNF capacity for production broadly paralleled the survival rate of the mice transplanted to Ehrlich tumors. Our findings suggest that one mechanism underlying the antitumor activities of these drugs is based on stimulation of the RES and is closely related of TNF production.
The relationship between tumour necrosis factor (TNF) and macrophages or macrophage-like cell line, especially the lysosomal enzymes was investigated. The serum lysosomal enzymes and LDH activities were increased in proportion to the TNF production even in different strains of mice. Lysosomal enzymes and TNF activity were released into the supernatant of the culture medium of macrophage-enriched peritoneal exudate cells (PEC) or spleen cells derived from Propionibacterium acnes-primed mice after addition of lipopolysaccharide (LPS). After passage through a Sephadex G-10 column, TNF activity could not be detected in the supernatant of these spleen cells after addition of LPS. Also TNF activity could not be detected in the supernatant following destruction of PEC. These results suggest that TNF producibility is strongly related to the degree of activation of macrophages, especially the lysosomal enzymes. The murine macrophage-like cell line, J774, also released TNF activity and lysosomal enzymes after addition of LPS.
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The role of hypoglycemia in tumor necrosis factor (TNF) production was examined. TNF was produced from sera of animals presensitized with reticuloendothelial system stimulants after lipopolysaccharide (LPS) challenge. Blood glucose was strongly reduced during TNF production. Glucose administration to presensitized mice (before LPS challenge) caused inhibition of TNF production. Exogenous insulin injection inhibited TNF production in a dose-related manner. Peritoneal exudate cells (PEC) from Propionibacterium acnes-primed mice revealed increased glucose consumption during in vitro TNF production but showed no relationship between the degree of glucose consumption and the ability to produce TNF. Insulin addition to the culture medium caused inhibition of TNF production from PEC, which indicated that insulin may block TNF production from macrophages. Administration of highly purified TNF (without concomitant LPS) induced extensive tumor necrosis but did not induce hypoglycemia; LPS induced moderate necrosis with accompanying hypoglycemia; insulin induced hypoglycemia but did not induce tumor necrosis. It is concluded that hypoglycemia does not accompany the action of TNF.
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Anorectal manometry was carried out in 65 children with idiopathic chronic constipation. Forty-five had no megarectum, and 20 had megarectum. Patients without megarectum showed normal anorectal pressures, recto-anal reflex, rectal sensation and rectal compliance, but motility of the colon was disturbed in these patients. Patients with megarectum also had normal anorectal pressures, recto-anal reflex and rectal sensation, but they showed remarkably high rectal compliance, or excessive rectal reservoir. Patients without megarectum were treated with laxatives and all of them were cured within 6 months after institution of therapy. Patients with megarectum were treated with rectal washout and suppository and 14 out of 20 were cured within 10 months. Six out of 20 patients with megarectum, however, were resistant to conservative therapy and necessity of surgical treatment to reduce the excessive rectal reservoir was proposed for these patients.
The antitumor activity of highly purified tumor necrosis factor (TNF) was tested against eight kinds of murine tumor and five kinds of human tumor heterotransplanted into nude mice. Mice were treated by intravenous or intratumoral injection of TNF, commencing when the tumors were well established. TNF showed an excellent curative effect against all kinds of murine and human tumors tested. Meth A sarcoma, Colon 26, Ehrlich, sarcoma 180, MM 46, MH 134, B16 melanoma, and Lewis lung tumors transplanted into mice underwent tumor necrosis and regression following a single injection of TNF. Sometimes a complete cure was observed in Meth A sarcoma, sarcoma 180, Ehrlich, and MM 46 tumors. Human cancers, SEKI, HMV-I, KATO-III, MKN 45, or KB, heterotransplanted into nude mice, also exhibited tumor necrosis and regression in size following several intratumoral injections of TNF. A great difference in curative effects of TNF was observed in Meth A sarcomas between those transplanted into BALB/c nu/+ and into BALB/c nu/nu mice: following a single intravenous administration the effect was stronger in BALB/c nu/+ than in nu/nu mice. In contrast, tumor necrosis was almost the same in nu/+ and nu/nu mice following intratumoral administration. The present results thus indicate that TNF from mice had an antitumor activity against not only murine tumors but also human tumors. In addition to direct cytotoxicity against tumor cells, TNF induced a host-mediated factor which contributed to the antitumor effects.