Biomedical subjects
Publications and source records attributed to T Shiba.
Ancovenin, an inhibitor of angiotensin I converting enzyme isolated from the culture broth of a Streptomyces species, is a dialysable peptide composed of sixteen amino acid residues containing unusual amino acids such as threo-beta-methyllanthionine, meso-lanthionine, and dehydroalanine.
Palmitoyltuberactinamine N (Pal-Tua N) and di-beta-lysylcapreomycin IIA (di-beta-Lys-Cpm IIA), which are synthetic derivatives of the antituberculous agent tuberactinomycin (Tum) and capreomycin (Cpm) respectively, were tested for anti-bacterial activity. Pal-Tua N inhibited not only tuberactinomycin-resistant Mycobacterium smegmatis but also Escherichia coli, Corynebacterium diphtheriae, Staphylococcus aureus, Streptococcus pyogenes, although it has lost activity against Mycobacterium tuberculosis. Di-beta-Lys-Cpm IIA inhibited the growth of laboratory-derived Tum-resistant M. smegmatis and M. tuberculosis as well as Tum-resistant M. tuberculosis from patients with one exceptional case.
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The prophylactic and chemotherapeutic efficacy of PMPC against infections after TUR-P has been investigated. Bacteriological evaluation: PMPC , 200-300 mg/day for 2-12 weeks, was administered to 49 patients, who had over 10(3)CFU/ml of microorganisms after CET or CEC treatment for 3-7 days. The eradication rate of microorganisms was 40.8% after 2 weeks, 52.2% after 4 weeks, 64.1% after 6 weeks, 65.0% after 8 weeks and 70.6% after 12 weeks. Effectiveness on pyuria : The improvement rate of pyuria against 59 patients who had over 10(5)/hpf of pyuria , was 15.3% after 2 weeks, 16.4% after 4 weeks, 25.4% after 6 weeks, 58.5% after 8 weeks, 72.7% after 10 weeks and 75.0% after 12 weeks. Overall clinical efficacy on PMPC was examined in 26 patients. The results of efficacy were 27.3% after 2 weeks, 48.0% after 4 weeks, 50.0% after 6 weeks, 69.2% after 8 weeks, 75.0% after 10 weeks and 77.0% after 12 weeks. The clinical response was evaluated according to a criterion for clinical evaluation of antimicrobial agent on chronic complicated UTI proposed by UTI committee in Japan. No severe adverse effect including allergic reaction was found. Following administration of PMPC , three patients experienced adverse gastric reactions, and drug administration was discontinued at week 6 or 8. PMPC was effective as a prophylactic chemotherapeutic drug against infections after TUR-P and prostatectomy.
The records of 27 cases of disseminated intravascular coagulation with burn, trauma, perforated peritonitis or leakage of gastrointestinal anastomoses at the Second Department of Surgery and Intensive Care Unite, Toho University Hospital from 1977 to 1982 were reviewed. In this series, multiple organ failure (MOF) occurred in 20 cases and single organ failure occurred in 4 cases. Lung failure occurred in 20 out of 27 cases. Renal failure occurred in 18 out of 27 cases. Then, correlation was observed between decrease in platelet count and decrease in PaO2/FiO2. Serum creatinine level and total bilirubin level were elevated according to the progress of DIC. Twenty death cases with DIC out of 21 had MOF. However, 3 survived cases out of 6 cases had only single organ failure and other 3 survived cases out of 6 cases had not organ failure. Therefore, close correlation was observed between DIC and MOF in the prognosis of DIC. Earlier and active support of organ failure was important for clinical management of DIC.
The adjuvant effect of synthetic analogues of lipid A was investigated in mice in vivo. Two of the five synthetic lipid A analogues showed adjuvant activity when they were incorporated into dipalmitoylglycerophosphocholine-cholesterol-dipalmitoylglycerophosphate liposomes sensitized with trinitrophenylaminocaproylglycerophosphoethanolamine. The minimum structure for an adjuvant effect in the liposomal immunogen system was 1-monophosphate of 6-0-(2-deoxy-2-tetradecanoylamino-6-0-tetradecanoyl-D-glucopyranosyl)-2-deoxy-2 -tetradecanoyl-amino-3,4-di-O-tetradecanoyl-D-glucopyranose.
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Cell walls isolated from four bacterial species (Streptococcus pyogenes, Lactobacillus plantarum, Streptomyces gardneri, and Nocardia corynebacteriodes), which exhibited the adjuvant effect of stimulating cellular and humoral immune responses against ovalbumin in guinea pigs, caused the slow-starting and long-lasting contraction of guinea pig ileal strips suspended in Tyrode solution. In contrast to these cell walls active in immunoadjuvancy, those isolated from five bacterial species (Micrococcus lysodeikticus, Staphylococcus epidermidis, Arthrobacter atrocyaneus, Corynebacterium insidiosum, and Ampullariella regularis), which lacked immunoadjuvancy at least in intact walls, caused no or very weak contraction of the ileal strips. Further study demonstrated that both a monomer and a polymer of disaccharide-stem peptides, which were obtained by enzymatic degradation of S. epidermis cell wall peptidoglycans, displayed similar contractile effects. It was finally revealed that guinea pig ileum strips showed a definite contractile response to N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and 6-O-stearoyl- and 6-O-(2-tetradecylhexadecanoyl)-MDPs, but not to their analogs, whose C-terminal amino acid was L-isoglutamine or D-isoasparagine in place of D-isoglutamine and which lacked adjuvancy. 6-O-(3-Hydroxy-2-docosylhexacosanoyl)-MDP, on the other hand, caused a slow and lasting relaxation of the ileum strips, but its L-isoglutamine and D-isoasparagine analogs did not.
A study was made on the activity of various bacterial cell walls and peptidoglycans to liberate serotonin from rabbit blood platelets. All of the test cell walls or peptidoglycans prepared from 27 strains of 21 bacterial species were shown to cause a marked release of serotonin, regardless of differences in types of peptidoglycan and non-peptidoglycan moieties and in some biological properties. The assay made with the water-soluble "digests" of Staphylococcus epidermidis cell wall peptidoglycans, which were prepared by use of appropriate enzymes, revealed that a polymer of peptidoglycan subunits (a disaccharide-stempeptide) was definitely active in the release of serotonin, but a structural unit monomer was inactive. Among a variety of synthetic muramylpeptides and their 6-O-acyl derivatives, only 6-O-(3-hydroxy-2-docosylhexacosanoyl)-N-acetylmuramyl-L-alanyl-D-isoglutaminyl- L-lysyl-D-alanine was found to hold a strong serotonin-liberating activity.
Bacterial cell walls, water-soluble fragments of the wall peptidoglycan, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), and 6-O-acyl derivatives of MDP were examined for migration-stimulating activity on human peripheral blood monocytes by using a multiwell chemotaxis assembly. Cell walls isolated from 11 bacterial species caused a definite increase in monocyte migration, but the walls of Micrococcus lysodeikticus were scarely active. The migration-enhancing activity of Staphylococcus epidermidis cell walls was retained by a monomer as well as a polymer of disaccharide peptides which were prepared by digestion of the peptidoglycan with enzymes. It was finally revealed that the migration of monocytes was enhanced by MDP. 6-O-Octadecanoyl-MDP, 6-O-(2-tetradecylhexadecanoyl)-MDP, and 6-O-(3-hydroxy-2-docosylhexacosanoyl)-N-acetylmuramyl-L-seryl-D-isoglutamine were active, but to a lesser extent. A checkerboard assay demonstrated that the increased monocyte migration caused by S. epidermidis cell walls was directed toward a positive stimulus (chemotaxis).
It has been known that CA change during physical exercises and associate with dynamic aspects of the coagulation fibrinolysis system of the blood. Therefore, we studied fibrin and fibrinogen degradation products (FDP) under physical exercises together with LDH, CPK, LA, CRE, Na, K and P. 1) College students of Department of Education majoring in sciences of physical education significantly increased activities of CPK and LDH during the training for volleyball games compared with the pre-training values. This increment was remarkable for those who exercised hard, that is, who were loaded with large physical stress. 2) Changes in LA were included in the range of its normal values. Freshmen who had not been trained much and consequently whose adaptability for physical stress was insufficient increased the LA level significantly relative to the pre-training level. 3) Although changes in P were included in the range of its normal values, significant increase was observed by physical stress. Examinations by individual disclosed that a tendency of changes in P was similar to that in CPK and FDP. 4) The tendency of changes in FDP agreed with that in CPK and P and an increase was observed for those who were loaded with large physical stress. It was further observed that especially for those who were loaded with large mental stress together with physical stress the increase in FDP was evident. Therefore, it has been suggested that FDP can be used as an index of biotic effects of not only physical stress but also mental stress.
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The site of interaction of phage MS2 A protein on MS2 RNA was determined by analysing the base sequence of the RNA fragment which was released from the RNAase-resistant complex prepared by RNAase digestion of RNA-A protein complex. The result showed that there were two types of RNA fragment: one had a sequence which corresponded to the sequence of the 5'-side maturation region of MS2 RNA and the other corresponded to the sequence of the 3'-side untranslated region. These results were confirmed by a competition experiment in in vitro reconstitution system using f2 defective RNA, lacking about 30% of the 5'-side, and MS2 5FUra (5-fluorouracil) RNA, lacking about 35% of the 3'-side, as competitors. These results seem to indicate that the A protein is bound to at least two sites on MS2 RNA.
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The possible involvement of cell-mediated immune response to liver specific lipoprotein (LSP) in the pathogenesis of liver injury was investigated. The subjects were consisted of one patient with acute hepatitis, five cases with chronic active hepatitis and one case with chronic failure inactive hepatitis. When peripheral blood lymphocytes from these patients were cultured in the presence of LSP and lymphocyte transformation was determined by measuring the uptake of [3H]-thymidine into the acid-insoluble materials, positive blastogenesis was seen in three cases with chronic active hepatitis. Furthermore, when peripheral blood lymphocytes from halothane-induced cholestatic hepatitis were cultured with offending drug in the presence of LSP and lymphocyte transformation was determined, a positive blastogenesis was seen. The factor which activated Kupffer cells (KCAF), a kind of lymphokine, was also detectable in the culture medium of activated lymphocytes from four patients who showed positive blastogenesis by estimating [3H]-glucosamine incorporation into Kupffer cells. The macrophage activating factor (MAF) was detectable in culture medium of activated lymphocytes from three patients who showed positive blastogenesis by estimating [3H]-glucosamine incorporation into macrophages. Furthermore, the KCAF-activated Kupffer cells and MAF-activated macrophages were shown to be cytotoxic for the isolated liver cells causing marked inhibition of albumin synthesis. The observations suggest that Kupffer cell-mediated cytotoxicity and macrophage-mediated cytotoxicity play a role in the pathogenesis of liver disease.