Search PubMed⌕ Search

Biomedical subjects

T Shiba

Publications and source records attributed to T Shiba.

At least 253 records · Page 14Linked to original sources
PubMed1981

Immunological studies on the drug-induced allergic hepatitis.

The possible involvement of cell-mediated immunity in the pathogenesis of drug-induced allergic hepatitis was investigated in 21 patients; 6 patients with cholestasis, two cases with the hepatitis resembling viral hepatitis and 13 cholestatic hepatitis. The peripheral blood lymphocytes from all these patients showed the positive lymphocyte transformation and MIF production when stimulated by the offending drug in the presence of liver specific lipoprotein. By injection of the culture medium prepared from activated lymphocytes into mesenteric vein of rat, a marked reduction of bile flow and bile acid secretion was observed in 12 cases among 17 patients tested. Active material which caused the reduction of bile flow was fractionated by a gel filtration and was identified to have similar molecular size to MIF. Morphologically, a dilated bile canaliculus with diminution of microvilli and vesicles around the dilated bile canaliculus were observed by an electron microscopy after injection of culture supernatant or their fractionated material into mesenteric vein of rat. No such changes could be seen in rats by administering the supernatant of lymphocytes from normal individuals prepared as above. Macrophage activating factor (MAF), a kind of lymphokines, was also detected in the culture medium of activated lymphocytes from seven patients among eight cases tested. The MAF-activated macrophages were shown to exhibit a cytotoxic effect on the separated liver cells by judging from the inhibition of albumin biosynthesis. Moreover, the antibody-dependent cell-mediated cytotoxic reaction as well as lymphocyte-mediated cytotoxicity were also demonstrated in three cases among nine patients tested. These observations suggest that diverse immune reactions were possible correlated to the pathogenesis of the drug-induced allergic hepatitis although their exact participation or relative significances are remained to be elucidated.

Bile Acids and Salts↗
PubMed1981

Application of Ca2+-selective electrode for determination of Ca2+ efflux from smooth muscles into Ca2+-free physiological solution.

The Ca2+ efflux from smooth muscle into a Ca2+-free physiological solution was continuously monitored by using a Radiometer Ca2+-selective electrode and examined for its availability for determination of Ca2+ effluxed from the smooth muscle. The results show that the Ca2+ electrode used here is sufficiently sensitive to investigate Ca2+ efflux from the smooth muscle into the Ca2+-free solution. Further, this method is suitable for the continuous recording of free ionized Ca2+ effluxed from the smooth muscle into the Ca2+-free physiological solution.

Animals↗
PubMed1981

Stimulation of nonspecific resistance to infection induced by 6-O-acyl muramyl dipeptide analogs in mice.

The experimental system utilized in investigating the correlation between the chemical structures of muramyl peptides and their protective activities in the sepsis type of systemic infections caused by Escherichia coli was applied in evaluating the enhancement of resistance to infection induced by 32 synthetic glycopeptide analogs, including 6-O-acyl derivatives and 1-alpha-O-benzyl derivatives of muramyl dipeptide (N-acetyl muramyl-L-alanyl-D-isoglutamine). In assessing the 6-O-acyl derivatives of muramyl dipeptide, we found that the degree of protective activity was attributable to the kinds of fatty acids introduced. Acylation of the 6-hydroxy group on the muramic acid moiety in muramyl dipeptide with natural mycolic acid or a synthetic fatty acid possessing either an alpha-branched or an alpha-branched, beta-hydroxylated group resulted in a decrease in or a disappearance of the protective activity of muramyl dipeptide. Acylation with a normal fatty acid or an iso fatty acid resulted in a retention or enhancement of muramyl dipeptide activity. The activity of acylated derivatives containing linear fatty acids was stimulated by increasing the chain length up to 18 carbon atoms. The highest degree of protective activity occurred with the derivatives acylated with straight-chain fatty acids, particularly with the derivatives acylated with palmitic acid and arachidic acid. Benzylation of the 1-hydroxy group of muramyl dipeptide resulted in a decrease in or a loss of protective activity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1981

Determination of calcium ions effluxed from smooth muscle into Ca2+-free physiological solution by means of Ca2+-selective electrode.

In order to measure Ca2+ efflux from the smooth muscle into a Ca2+-free physiological solution, the method using a Radiometer Ca2+-sensitive electrode was applied and compared with the method using an atomic absorption spectrophotometer to examine its usefulness. The results obtained show that the Ca2+ electrode used here can accurately and continuously monitor free calcium ions effluxed from the smooth muscle into a Ca2+-free solution. The Ca2+-sensitive electrode used here is a useful tool to investigate Ca2+ efflux from the smooth muscle into a Ca2+-free physiological solution.

Acetylcholine↗
PubMed1981

Immunological studies on chronic active hepatitis: possible involvement of macrophage-mediated cytotoxicity in its immunopathogenesis.

The possible involvement of cell-mediated immune responses to liver-specific protein in the pathogenesis of liver injury was investigated. The subjects consisted of seven patients with acute hepatitis, 12 cases with chronic active hepatitis, four cases with chronic inactive hepatitis, and three cases with liver cirrhosis. When peripheral blood lymphocytes from these patients were cultured in the presence of liver specific protein, and lymphocyte transformation was determined by measuring the uptake of [3H]thymidine into acid-insoluble materials, positive blastogenesis was seen in two cases with acute hepatitis and in six cases with chronic active hepatitis. The macrophage activating factor (MAF), a kind of lymphokine, was also detectable in the culture medium of activated lymphocytes from six patients who showed positive blastogenesis by estimating [3H]glucosamine incorporation into macrophages. Furthermore, the MAF-activated macrophages wer shown to be cytotoxic for the isolated liver cells causing marked inhibition of albumin synthesis. This macrophage-mediated cytotoxicity was detected in eight cases that showed positive lymphocyte transformation. These observations suggest that macrophage-mediated cytotoxicity plays a role in the pathogenesis of chronic active hepatitis.

Adult↗
PubMed1981

Possible involvement of macrophage-mediated hepatocytotoxicity in chronic active hepatitis: the induction of liver cell injury by culture supernatant of MAF-activated macrophages.

When peripheral blood lymphocytes from patients with various types of hepatitis were stimulated in vitro with liver specific protein, lymphocyte transformation and MIF production were demonstrated in many cases, especially in chronic active hepatitis. The culture supernatant of these activated lymphocytes was also shown to contain MAF, a kind of lymphokine, which activated the peritoneal macrophages of guinea pigs. When the culture fluid of MAF-activated macrophages was added to isolated liver cells, a significant inhibition of their albumin biosynthesis was detected. The active principle which caused the impairment of liver function was fractionated by gel filtration using a Sephadex G-75 column, and it was found that the active material was a protein-like substance with a molecular weight of about 10,000-40,000. The results suggest the possibility that the soluble substance released from the activated macrophage may be involved at least partially in the immunological pathogenesis of chronic active hepatitis among many other immunological processes.

Adult↗
PubMed1980

The translocation inhibitor tuberactinomycin binds to nucleic acids and blocks the in vitro assembly of 50S subunits.

Binding studies were performed with a [14C]-labelled derivative of viomycin, tuberactinomycin 0 (TUM O). TUM O bound to 30S and 50S subunits. The binding component was the RNA, since ribosomal proteins did not bind the drug. Other RNAs such as tRNA, phage RNA (MS2), and homopolynucleotides also bound the drug. Striking differences in the binding capacity of the various homopolynucleotides were found. Poly(U) bound strongly, poly(G) and poly(C) bound intermediately, whereas poly(A) showed a very low binding. DNA also bound TUM O, although with native DNA the binding was only weak. Finally the effects of viomycin on the assembly in vitro of the 50S subunit from E. coli were tested. A very strong inhibition was found: when the reconstitution was performed at 0.5 x 10(-6) M viomycin the particles formed sedimented at about 50S, but showed a residual activity of less than 10%. The inhibitory power of viomycin with respect to the in vitro assembly is more pronounced than that found in in vitro systems for protein synthesis.

Binding Sites↗
PubMed1980

Immunological studies on drug-induced allergic hepatitis--hepatocellular injury by macrophage-mediated cytotoxicity.

When the peripheral blood lymphocytes from patients with drug-induced allergic hepatitis were stimulated with a specific drug in vitro in the presence of a liver cytosol fraction containing liver specific antigen, lymphocyte transformation was seen in eight out of 11 patients. The macrophage activating factor (MAF), a kind of lymphokines, was also detectable in the culture medium of activated lymphocytes from seven out of eight patients who showed positive blastogenesis evaluated the uptake of 3H-glucosamine into macrophages. MAF-activated macrophages exhibited a cytotoxic effect on separated liver cells resulting in a marked inhibition of albumin synthesis. This macrophage-mediated cytotoxicity was also observed in eight out of 11 patients who showed positive lymphocyte transformation. These observations suggest that macrophage-mediated cytotoxicity may play some role in the pathogenesis of drug-induced allergic hepatitis.

Adult↗
PubMed1980

Polyclonal B cell activation by cell wall preparations of gram-positive bacteria. In vitro responses of spleen cells obtained from Balb/c, nu/nu, nu/+, C3H/He, C3H/HeJ and hybrid (DBA/N x Balb/c)F1 mice.

The effects of polyclonal B cell activation (PBA) of cell walls and their cell wall fractions obtained from several kinds of gram-positive bacteria were studied using the anti-sheep red blood cell (SRBC) or anti-trinitrophenylated (TNP) SRBC plaque forming cell (PFC) responses of cultured spleen cells from Balb/c, athymic nu/nu, their littermates (nu/+), C3H/He (LPS-responder), C3H/HeJ (LPS-nonresponder), (CBA/N x Balb/c) F1 male with an X-linked defect in B cell function and the F1 female mice. The cell walls of Staphylococcus epidermidis (ATCC 155), Lactobacillus plantarum (ATCC 8014), Micrococcus lysodeikticus (NCTC 2665), Mycobacterium rhodochrous (ATCC 184), Streptomyces gardneri (ATCC 23911) and Nocardia corynebacteriodes (ATCC 14898) had the ability to induce polyclonal B cell responses in the spleen cells of Balb/c, nu/nu, nu/+, C3H/He and C3H/HeJ mice. The cell wall fractions prepared by enzymatic digestion from the cell walls of S. epidermidis, S. gardneri or N. corynebacteriodes were also capable of inducing polyclonal B cell responses. The responses of spleen cells from (CBA/N x Balb/c) F1 male mice to these active preparations, except the cell walls of M. rhodochrous which possess this ability. The PBA-ability of synthetic peptidoglycan, muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine, MDP), was also examined, and a similar activity was observed in MDP.

Animals↗
PubMed1980

Arthritis-inducing ability of a synthetic adjuvant, N-acetylmuramyl peptides, and bacterial disaccharide peptides related to different oil vehicles and their composition.

A synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), failed to produce polyarthritis with a wide dose range in a water-in-oil emulsion of mineral oil such as liquid paraffin, Drakeol, or heavy mineral oil. MDP, however, produced moderate to severe arthritis with almost 100% incidence in a water-in-oil emulsion made up of Difco incomplete adjuvant, which consists of Bavol F as an oil vehicle and Arlacel A as an emulsifier. N-acetylmuramyl-L-alanyl-L-isoglutamine did not produce arthritis, whereas 4,6-diacetyl-MDP produced the disease. Bacterial peptidoglycans, such as disaccharide peptides which were N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D-isoglutaminyl-meso-diaminopimelyl-D-alanine and N-acetylglucosaminyl-6,o-acetyl-N-acetylmuramyl-L-alanyl-D-isoglutaminyl-meso-diaminopimelyl-D-alanine, also produced polyarthritis with low incidence in Difco oil but not in the other mineral oils described above. MDP and bacterial disaccharide peptides were able to produce the disease even in the latter mineral oil only when the concentration of Arlacel A was increased from 15% to 20 to 30% in the oil. We concluded that one of the minimal essential structures responsible for development of this disease is MDP, although the role of the oil vehicle remained uncertain, and there is no direct correlation between granulona formation and arthritogenicity of MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1980

Lipophilic derivative of muramyl dipeptide is more active than muramyl dipeptide in priming macrophages to release superoxide anion.

Mouse peritoneal macrophages, when treated with a lipophilic derivative of muramyl dipeptide either in vitro or in vivo by intraperitoneal injection, showed a more than fivefold increase in their ability to generate superoxide anion after stimulation of the macrophages with phorbol myristate acetate. This response was more than twice that observed with the parent molecule, muramyl dipeptide (MDP). Unlike MDP, which has a systemic effect, the lipophilic derivative, [B30]-MDP, did not alter the response of peritoneal macrophages when given subcutaneously in the flank, suggesting that [B30]-MDP remains localized at the site of injection. The enhanced effect of [B30]-MDP over MDP appeared to be due to the inherent lipophilicity of the molecule, and was probably not due to either stimulation of T lymphocytes or activation of the alternative pathway of complement.

Acetylmuramyl-Alanyl-Isoglutamine↗