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Biomedical subjects

S Kurashige

Publications and source records attributed to S Kurashige.

At least 55 records · Page 3Linked to original sources

Enhancing effects of mini-cells prepared from Salmonella typhimurium on anti-tumor immunity in sarcoma 180-bearing mice.

The enhancing effect of mini-cells of Salmonella typhimurium which do not contain chromosomal DNA on anti-tumor immunity in mice was studied. The growth of sarcoma 180 cells which were subcutaneously transplanted into ICR mice was significantly retarded in mice treated with Salmonella mini-cells at the same time or 7 days after S180 transplantation, while no or only a little growth inhibition was observed in mice treated 7 days prior to S180 transplantation. Treatment with mini-cells inoculation alone did not increase the survival time of mice that had received intraperitoneal transplants of S180 cells. However, a statistically significant increase of survival time was observed in mice treated with a combination of mini-cells and surgical resection of subcutaneous tumors when S180 cells were injected 7 days after the surgical resection. The injection of mini-cells restored macrophage chemotaxis in S180-bearing mice in which macrophage chemotaxis was greatly retarded but lymphocyte activity was not.

Animals↗

Purine metabolic enzymes in lymphocytes. I. Adenosine deaminase and purine nucleoside phosphorylase activities in mouse lymphocyte subpopulations.

The distribution of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities in lymphoid organs and lymphocyte subpopulations in mice, and the effect of phytohemagglutinin P (PHA-P) and concanavalin A (Con A) on the enzyme activities were studied. ADA activity was distributed equally in cells from all organs used and no mouse strain differences were observed. In contrast, PNP activity varied with the mouse strain, being highest in C57BL/6 mice and lowest in BALB/c mice, and with the organ in ICR mice, being high in peripheral blood lymphocytes and spleen lymphocytes, low in mesenteric lymph node cells and absent or very weak in thymus cells. T and B lymphocytes were prepared from spleen of ICR mice. High ADA activity was found in both T and B lymphocytes, whereas PNP activity in the T lymphocytes was about one-third of that in the B lymphocytes. PNP activity in thymus cells was increased to the normal level of T lymphocytes in the spleens by cultivation without stimulant. The development of PNP activity in thymus cells was partially inhibited by Con A but was not affected by PHA-P. ADA activity in thymus cells was enhanced by in vitro stimulation with PHA-P but not with Con A. In contrast, in spleen lymphocytes the development of ADA activity was enhanced by stimulation with PHA-P and Con A, and that of PNP activity was enhanced by PHA-P but not by Con A.

Adenosine Deaminase↗

Purine metabolic enzymes in lymphocytes. II. Adenosine deaminase and purine nucleoside phosphorylase activities in the immune response.

ICR mice were immunized with sheep red blood cells (sRBC). Both adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities in spleen lymphocytes increased faster than the serum antibody titer and reached a peak one week after the immunization. ADA activity increased significantly in T lymphocytes but not in B lymphocytes collected from the spleens of the immunized mice. A statistically significant increase in PNP activity was found in both T and B lymphocytes from the spleens of the immunized mice. Spleen lymphocytes collected from ICR mice which had been immunized with mitomycin C-treated sarcoma 180 (S180) cells one week earlier showed cytotoxic activity against viable S180 cells. Both ADA and PNP activities in spleen lymphocytes of S180-immunized mice increased significantly, and both activities increased in T lymphocytes prepared from spleen of immunized mice. In contrast, an increase was found in PNP activity but not in ADA activity in B lymphocytes. These results suggest that an increase in both ADA and PNP activities may by necessary for the T-cell response in both humoral and cellular immune responses, and that an increase in PNP activity may be necessary for the B-cell response.

Adenosine Deaminase↗

Macrophage activities in sarcoma 180-bearing mice and EL4-bearing mice.

Four types of macrophage activities were studied in sarcoma 180-bearing ICR mice and EL4-bearing C57BL mice. Sarcoma 180 cells grow very slowly and do not metastasize, while EL4 cells grow very rapidly and metastasize rapidly to the liver. Chemotactic activity of macrophages was significantly reduced from an early stage in both sarcoma 180-bearing ICR mice and EL4-bearing C57BL mice as compared with that in normal mice. Digestive activity, which was determined by following O2- production by chemiluminescence measurements was also reduced from an early stage in tumor-bearing mice, whereas no reduction of engulfment activity of microorganisms was observed until an advanced stage in both sarcoma 180-bearing mice and EL4-bearing mice. In contrast enhancement activity of macrophages in the blastogenic response of spleen lymphocytes to bacterial lipopolysaccharide was retained at the normal level at the early stage of the tumor graft and was reduced in later stages. These results suggest that activities of Ia-negative macrophages were at first depressed generally in tumor-bearing hosts and later the activities of Ia-positive macrophages were depressed by factor(s) which might be produced by tumor cells.

Animals↗

Immunopotentiating activity of whole cells and mini-cells of Salmonella typhimurium.

Salmonella typhimurium strain 9 produces mini-cells during cell proliferation. Mini-cells are viable but cannot proliferate since they do not contain chromosomal DNA. Effects of whole cells and mini-cells of S. typhimurium on the immune responses were investigated, with the following results. Phagocytosis of peritoneal macrophages was enhanced by in vivo stimulation of both whole cells and mini-cells. Cellular immunity against L1210 cells (mouse leukemia cells) and Sarcoma 180 cells was also enhanced by both whole cells and mini-cells. Mini-cells slightly stimulated in vitro blast cell transformation of normal mouse lymphocytes. Whole cells of S. typhimurium induced antibody-forming cells to produce IgG of higher affinity but mini-cells did not. Mini-cells were not directly cytotoxic for normal lymphocytes or L1210 cells.

Adjuvants, Immunologic↗

Spontaneously induced suppressor cells in vitro: nonspecific suppression of in vitro antibody formation.

Nonspecific suppressor cells were induced during in vitro culture of normal mouse spleen cells (SPC) using the Marbrook culture system. The suppressor cells inhibited both the primary and secondary antibody-formation responses antigen nonspecifically in vitro, and both IgM- and IgG-responses were inhibited. The supernatants from suppressive precultured cells were not suppressive. The suppressor cells also inhibited the response of allogeneic SPC beyond H-2 compatibility. The induction of the suppressor cells did not require the presence of antigen but required fetal calf serum (FCS) or both FCS and 2-mercaptoethanol (2-ME). The suppressor cells were generated from the nylon-wool adherent, radiation-sensitive T cell population. On the other hand, the suppressor cells were nylon-wool nonadherent, relatively radiation-sensitive T cells. Actively antibody-producing cells were not affected by the suppressor cells. The suppressor cells inhibited the mitogenic responses of normal SPC to phytohemagglutinin-P (PHA), bacterial lipopolysaccharide (LPS) and concanavalin A (Con A). The suppressor cells themselves inhibited the growth of EL4 cells (T-cell leukemia of C57BL/6 mouse origin) and MOPCll cells (B cells, plasmacytoma of BALB/c mouse origin) even at a low effector-to target cell ratio (E:T ratio = 1:1), but did not kill these tumor cells. These results indicate that the target cells of the suppressor cells are both T and B cells, and that the mechanism of action of the suppression is either inhibition of proliferation or inhibition of early events in the course of the immune response.

Animals↗

Acceleration of allogeneic antitumor immunity with immune RNA in vitro and T-cell suppression by L1210 tumor bearer spleen cells.

RNA fractions extracted from the spleens of immunized animals prepared against L1210 leukemia cells can transfer allospecific cell-mediated immunity both in vitro and in vivo. Both preculture of nonsensitized lymphocytes prior to the treatment with immune RNA and additional culture of lymphocytes after 1-hr treatment with immune RNA enhance the growth-inhibitory activity of immune RNA-treated lymphocytes. Preculture for 5 hr and additional culture for 24 hr are sufficient for maximal enhancement of the growth-inhibitory activity. There is no significant difference in inhibition between lymphocytes treated with immune RNA for 1 hr and 24 hr. The growth inhibition by lymphocytes is augmented proportionally to the increase in the dose of immune RNA in vitro but not in vivo. In mice given i.p. injections of immune RNA-treated syngeneic spleen cells (before or after inoculation with L1210 cells), a significant prolongation of the mean survival time [27.0 +/- 5.4 (S.D.) days, 0.05 < p < 0.1] was not achieved when compared with control mice (21.4 +/- 1.6 days). Evidence is presented that suppressor cells in the spleens of L1210-bearing mice are involved in preventing effector cell function in vivo. The present study revealed that 8 X 10(3) and 5 X 10(5) suppressor cells were sufficient to inhibit completely the activity of immune RNA-treated effector cells in vitro and in vivo, respectively. Suppressive activity was abolished by treatment with anti-Thy 1.2 serum and complement and partially abolished with irradiation (1500 R). The suppressor cells belonged to a radiation-sensitive T-cell population. The limited activity of immune RNA in vivo is probably due to the destruction of immune RNA by RNase present in the host plasma and tissues and the acquisition of suppressor cells which inhibits nonadherent peritoneal exudate cell activity in the animal.

Animals↗

Induction of IgM memory with RNA from the spleens of immunized mice.

Ribonucleic acid (immune RNA, iRNA), extracted from the spleens of mice immunized with sheep red blood cells (SRBC), induced specific immunological memory. The humoral immune responses of iRNA-treated animals were compared with in vivo and in vitro primary and secondary responses, using the haemolytic plaque-forming cell (PFC) assay. IgM antibody formation was markedly higher in iRNA-treated than in any other mice. The effect of iRNA was antigen-specific and similar materials from non-immunized mice had no activity.

Animals↗

In vitro and in vivo antibacterial activity of KW1070, a new aminoglycoside antibiotic.

KW1070, a new aminoglycoside antibiotic with the novel aminocyclitol, fortamine, has a broad spectrum of activity in vitro and in vivo against gram-positive and gram-negative bacteria. The minimum inhibitory concentrations of KW1070 are similar to those of kanamycin against aminoglycoside-susceptible strains, slightly less than those of gentamicin or 3',4'-dideoxykanamycin B. Minimal bactericidal concentrations were found to be near minimal inhibitory concentrations. KW1070 was active in vitro against many aminoglycoside-resistant bacterial strains that possess aminoglycoside-inactivating enzymes, particularly AAC(6'), AAC(2'), AAD(2''), and APH(3'). The activities of KW1070 in mice infected with Staphylococcus aureus, Escherichia coli, Proteus sp., and Serratia marcescens compared favorably with the activities of amikacin and kanamycin; KW1070 was also singificantly active in mice infected with resistant strains bearing the aminoglycoside-inactivating enzymes listed above.

Acetylation↗

In vitro and in vivo antibacterial activity of AB206, a new naphthyridine derivative.

AB206 (5,8-dihydro-5-methoxy-8-oxo-2H-1,3-dioxolo-4,5-g quinoline 7-carboxylic acid) is a novel antibacterial agent structurally related to nalidixic acid. AB206 has potent antibacterial activity against clinical isolates of gram-negative bacteria and is 4 to 18 times more active than nalidixic acid. AB206 inhibited the growth of Staphylococcus aureus and Pseudomonas aeruginosa, which were resistnat to nalidixic acid. Cross-resistance was not observed between AB206 and various antibiotics, and most bacterial strains resistant to nalidixic acid were susceptible to AB206. AB206 showed bactericidal activity against Escherichia coli, Proteus, Klebsiella pneumoniae, and P. aeruginosa. Chemotherapeutic effects after oral administration of AB206 in mice experimentally infected with E. coli, K. pneumoniae, and Proteus morganii showed that AB206 was two to four times more potent than nalidixic acid.

4-Quinolones↗

Cefroxadine (CGP-9000), an orally active cephalosporin.

Cefroxadine (GCP-9000; CXD), 7 beta[D-2-amino-2-(1,4-cyclohexadienyl)-acetamido]-3-methoxy-ceph-3-em-carboxylic acid, is a new orally active cephalosporin derivative. The spectrum of antibacterial activity of CXD is identical with that of cephalexin (CEX), but CXD was twofold more effective than CEX against Escherichia coli and Klebsiella pneumoniae, CXD was as stable to penicillinase as CEX, but it was hydrolyzed by cephalosporinase, with a relative rate of hydrolysis similar to that of CEX. The affinities of CXD and CEX to penicillin-binding proteins of E. coli were estimated; the affinity of CXD to penicillin-binding protein 1Bs was higher than that of CEX. Consistent with this, CXD had more intensive lytic activity than CEX. In vivo antibacterial activities of CXD and CEX were compared using systemic infections of mice with E. coli and K. pneumoniae; CXD was consistently more active than CEX.

Administration, Oral↗

Effects of levamisole administration on treatment with 6-mercaptopurine riboside of mice bearing L1210 leukemia cells.

DBA/3 mice and BALB/c X DBA/2 F1 mice were inoculated i.p. with 1 X 10(5) L1210 leukemia cells on Day 0. Beginning with Day 1 following inoculation, the animals were given injections of 6-mercaptopurine riboside (200 mg/kg i.p.) once daily for 5 consecutive days in combination with a single s.c. injection of levamisole (LMS) (10 mg/kg). In DBA/2 mice, a marked decrease in the total peritoneal cell count was achieved when LMS was given on any day from Day -2 to 3 as compared with therapy using 6-mercaptopurine riboside alone, although the survival time was not prolonged in these mice. When LMS was given on Day 1 or 3, a decrease was observed in the in vitro growth rate of the L1210 cells obtained on Day 11 from the peritoneal cavity. In BALB/c X DBA/2 F1 mice, no significant changes were observed in either the total peritoneal cell count or the in vitro growth rate when LMS was injected on Day 3 or daily from Day 3 to 5. Daily injection of LMS from Day 1 to 3 resulted in a conspicuous inhibition of the in vitro growth rate, although no significant changes were observed in the total peritoneal cell count. It seems reasonable to conclude from these results that LMS has a potentiating effect on the antitumor activity of 6-mercaptopurine riboside.

Animals↗

Ribonucleic acid in the immune response.

In the studies of experimental salmonellosis, immunization of mice with a live vaccine SER of S. enteritidis was found to be effective against further infection with virulent S. enteritidis 116--54. Macrophages obtained from the peritoneal cavity, subcutaneous tissue or liver of immunized mice inhibited intracellular growth of bacteria and resisted cell degeneration caused by engulfment of virulent 116--54 bacteria. This immunity was called cellular immunity. We discovered by chance in 1961 a transfer agent of immunity (TA) from the culture fluid of immunized macrophages. This agent is RNA in nature and can be extracted from the spleen, peritoneal exudate cells or the lymph node of immunized animals and is called immune (i) RNA. We could demonstrate antibody activity in macrophages treated in vitro or in vivo with iRNA by the immune adherence hemagglutination technique. Cellulr immunity against tumor cells could be transferred in vitro or in vivo to lymphocytes through iRNA prepared from the spleen cells of syngeneic, allogeneic and xenogeneic animals immunized with the tumor cells. We prepared iRNA against antigens capable of inducing humoral antibody production in animals, i.e., RBCs, bacterial toxin, bacterial flagella and hapten-protein conjugates. Serum antibody was not demonstrated in recipient animals of iRNA's by single or repeated injections of these agents. However, in these animals an increase in the number of specific antibody-carrying cells was found as rosette-formers. It was found further that prior injection of iRNA could induce immunologic memory and produced a high titer of humoral antibody after a boosting stimulation with a small dose of the corresponding antigen. The required interval between the first iRNA and the second antigenic stimulation, and the minimal effective doses of iRNA and antigen are described. We studied the interaction of iRNA with either T- or B-cells and with both cells using adoptive transfer system, athymic nude mice and neonatally thymectomized (NT) mice. Immune rna's against T-dependent and T-independent antigens could not induce the proliferation of antibody-carrying cells in cyclophosphamide-treated (B-cell depleted) mice. But these agents could induce the proliferation of rosette-formers, implying that iRNA's can replace some role of T-cells even against T dependent antigens. B-cells can be directly activated by treatment with iRNA against both T-dependent and T-independnet antigens, and they differentiated into rosette-formers. Passive transfers of iRNA were successful in establishing immunity against infection with S. enteritidis, or immunity to Salmonella flagella, RBCs and hapten-protein conjugates. The ability of iRNA to confer a secondary response of antibody formation is serially and passively transmissible in recipient animals. These facts suggest the presence of some mechanism that is responsible for the amplification of antigenic stimulation in the immune response...

Animals↗

Antibacterial activity of apalcillin (PC-904) against gram-negative bacilli, especially ampicillin-, carbenicillin-, and gentamicin-resistant clinical isolates.

Apalcillin (PC-904) is active against carbenicillin- and ampicillin-resistant strains of gram-negative bacilli. Among Pseudomonas aeruginosa strains highly resistant to carbenicillin (>/=3,200 mug/ml), half of them were susceptible to PC-904 at a concentration of 50 to 1,600 mug/ml. The minimal inhibitory concentration of PC-904 against P. aeruginosa strains resistant to carbenicillin (400 to 1,600 mug/ml) ranged from 3.1 to 25 mug/ml. Ampicillin- and carbenicillin-resistant Enterobacteriaceae strains were similarly susceptible to PC-904. However, drug resistance to PC-904 was already apparent among some strains of P. aeruginosa, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, P. vulgaris, and P. morganii, recently isolated in Japan; i.e., 4, 35, 32, 4, 6, and 14% of strains isolated were resistant. PC-904 was more active, on the other hand, than ampicillin and carbenicillin against antibiotic-susceptible Enterobacteriaceae and also showed high activity against most species of Pseudomonadaceae, especially P. cepacia and P. aeruginosa. The minimum inhibitory concentrations of PC-904 were greatly affected by inoculum size when the organisms tested were strains producing large amounts of beta-lactamase.

Ampicillin↗

Determination of the ID50 values of antibacterial agents in agar.

Microorganisms were plated on agar plates containing various concentrations of an antimicrobial drug and inhibition of growth was determined at each drug concentration. The ID50 value and the gradient of the line were calculated by the least square method. When 200 approximately 800 bacterial cells were inoculated on an agar plate, growth inhibition corresponded linearly with the log concentration of a drug within range of 5 approximately 95% inhibition. The ID50 value and the gradient obtained were reproducible and reliable using microorganisms at stationary phase of growth with all tested bacterial species and all tested antimicrobial agents. It was found that the ID50 values of drugs were more reproducible and may be more reliable than the MIC (minimum inhibitory concentration) values of the drugs.

Agar↗