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Biomedical subjects

S Kishimoto

Publications and source records attributed to S Kishimoto.

At least 379 records · Page 21Linked to original sources
PubMed1985

Immune responses to polyethylene glycol modified L-asparaginase in mice.

Suppression of anti-L-asparaginase (anti-A-ase) IgG and IgE antibody responses was achieved in Balb/c mice with polyethylene glycol (PEG, MW, 5,000) conjugated Escherichia coli A-ase. Following the administration of the mixture of A-ase and PEG-A-ase, antibody production to A-ase was reduced. PEG-A-ase administration prior to A-ase suppressed the primary and secondary responses to A-ase antibody. The suppression could be transferred to normal mice with spleen cells from A-ase tolerant mice. The cell transfer experiment showed that the suppression was caused by suppressor T cells. Since PEG-A-ase administration failed to suppress antibody response to ovalbumin, the suppression seemed to be A-ase specific. PEG-A-ase administration also suppressed the delayed type hypersensitivity reaction. IgG and IgE antibodies to PEG or PEG-A-ase were not detected in mice immunized with PEG or PEG-A-ase in the presence of Freund's complete adjuvant or A1(OH)3, respectively.

Animals↗
PubMed1985

Spontaneous immunoglobulin A secretion and lack of mitogen-responsive B cells in systemic lupus erythematosus.

In an analysis of lymphocyte functions of systemic lupus erythematosus (SLE) patients, B cell abnormalities such as a lack of mitogen-responsive B cells and a predominance of spontaneous IgA-secreting cells (SC) were found. Lymphocyte functions of 20 SLE patients were studied. Impaired proliferative response to B cell mitogen, Staphylococcus aureus strain Cowan I (Cowan I), was observed, whereas the response to T cell mitogen phytohemagglutinin was normal. High levels of spontaneous IgA-SC were observed in SLE patients (greater than 10(2) cells/10(4) peripheral blood mononuclear cells [PBMC]), whereas spontaneous IgM-, IgG-, or IgE-SC were not proportionately increased. The number of spontaneous IgA-SC decreased with time in culture and became undetectable by day 5 of culture. In contrast, spontaneous immunoglobulin- (IgM, IgG, and IgA) SC were not observed in healthy volunteers (less than 10 cells/10(4) PBMC). Moreover, in SLE patients failure of induction of immunoglobulin-secreting cells (ISC) was observed when B cells were stimulated by Cowan I and B cell differentiation factor at any day tested, whereas ISC were induced in healthy volunteers on day 6 of culture. Depletion of T cells or macrophages did not affect the results obtained. These results suggest that the abnormalities observed in SLE B cells are not due to the in vitro direct effects of suppressor macrophages or suppressor T cells, and that the condition of the predominance of spontaneous IgA-SC and the unresponsiveness to exogenous stimulation may be emblematic of hyperactive B cells in SLE.

Antibody-Producing Cells↗
PubMed1985

Chemical modification of sulfazecin. Synthesis of 4-(substituted methyl)-2-azetidinone-1-sulfonic acid derivatives.

In expectation of improving the antibacterial activity of sulfazecin by chemical modification at the 3- and 4-positions, a number of 3-[2-(2-aminothiazol-4-yl)-(Z)-2-(substituted oxyimino)-acetamido]-4-(substituted methyl)-2-azetidinone-1-sulfonic acids were synthesized. Among various 4-substituents explored, the carbamoyloxymethyl group was found to provide a good effect to the antibacterial activity of these 2-azetidinone derivatives. An extensive study of structure-activity relationships led to selecting (3S,4S)-3-[2-(2-aminothiazol-4-yl)-(Z)-2-carboxymethoxyiminoace tamido]-4- carbamoyloxymethyl-2-azetidinone-1-sulfonic acid, AMA-1080 (Ro 17-2301), which has highly potent antibacterial activity against Gram-negative bacteria including Pseudomonas aeruginosa, for further biological and subsequent clinical evaluation.

Anti-Bacterial Agents↗
PubMed1985

Induction of persistent autoimmune haemolytic anaemia in mice by combined use of rat erythrocyte preimmunization and chronic GVHR.

Female F1 mice (BDF1: C57BL/6 x DBA/2, BCF1: C57BL/6 x C3H/HeN, BBF1: C57BL/6 x BALB/c) were preimmunized with rat erythrocytes and then received splenic T cells from parental female C57BL/6 mice injected with hydrocortisone acetate before killing. In BDF1 and BCF1 mice, direct Coombs' test (DCT) positivity persisted for more than 4 months in almost all mice. They also showed haematological sign of anaemia, and the survival of infused 51Cr-labelled parental C57BL/6 erythrocytes was reduced. In BBF1 mice, DCT positivity returned to negative within 2 months. Autoantibodies were eluted from DCT-positive erythrocytes and their specificities were examined. They were capable of binding equally well to erythrocytes from all strains of mice tested, including the donor mice. They also cross-reacted with rat erythrocytes but not with sheep, rabbit or human erythrocytes. Isotypes of the autoantibodies eluted were also examined. Interestingly, isotypes of the autoantibodies obtained from individual mice were confined to one or other subclass of IgG isotype: IgG1, IgG2a or IgG2b.

Anemia, Hemolytic, Autoimmune↗
PubMed1985

Murine tumor cell lysis by antibody-dependent macrophage-mediated cytotoxicity using syngeneic monoclonal antibodies.

Four monoclonal antibodies to MH134 murine syngeneic hepatoma cells, 3H1, 7C2, 11G2, and 12A2, were produced by hybridomas constructed by fusing P3-X63-Ag8-U1 murine myeloma cells with spleen cells of a C3H/HeN mouse immunized with the syngeneic tumor cells. Immunodiffusion analysis with rabbit anti-mouse immunoglobulin antisera showed that 3H1, 7C2, 11G2, and 12A2 are IgG2a, IgM, IgG1, and IgG2a, respectively. Enzyme-linked immunosorbent assay using cells of five syngeneic tumor lines, MH134, MM102, MM46, MM48, and X5563, and lymph node cells of C3H/HeN and C57BL/6 mice showed that 3H1 specifically bound to MH134 tumor cells, whereas 7C2, 11G2, and 12A2 reacted not only with MH134 but also with MM102 and MM46 tumor cells. None of these monoclonal antibodies bound either to cells of MM48 or X5563 tumor lines or to normal lymph node cells. These results strongly suggest that MH134 tumor cells display at least two kinds of tumor-associated antigens on their cell surfaces: one is expressed uniquely by MH134 tumor cells, which are recognized by 3H1; the other is commonly shared by MH134, MM102, and MM46 tumor cells, which are determined by the other three antibodies. 3H1, 11G2, and 12A2 but not 7C2 were found to be able to induce antibody-dependent cellular cytotoxicity (ADCC) against MH134 tumor cells. Target specificity of ADCC induced by these monoclonal antibodies was identical with that seen in enzyme-linked immunosorbent assay. 3H1, 7C2, and 12A2 but not 11G2 exhibited complement-dependent cytotoxicity, showing the same specificity in target cell lysis as that seen in enzyme-linked immunosorbent assay or ADCC. Pretreatment of MH134 tumor cells with 7C2 inhibited ADCC of both 11G2 and 12A2. Pretreatment of the tumor cells with 11G2 inhibited complement-dependent cytotoxicity of both 7C2 and 12A2. Neither ADCC nor complement-dependent cytotoxicity of 3H1 was inhibited by the pretreatment of the cells with 7C2 or 11G2. These results strongly suggest that tumor-associated antigens recognized by 3H1 are located apart from that recognized by 7C2, 11G2, and 12A2 and that the binding sites of the latter three antibodies are closely associated with, or identical with, each other in the tumor-associated antigen. The ability of 12A2 to induce ADCC against MH134 tumor cells was significantly stronger than that of 3H1 or 11G2.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Effector mechanism in concomitant immunity potentiated by intratumoral injection of Nocardia rubra cell wall skeleton.

Primary growth of AMC 60 fibrosarcoma inoculated into the hind leg of ACI/N rats resulted in occasional generation of concomitant resistance to growth of a second graft of the same tumor cells in the peritoneal or pleural cavity. Using this syngeneic tumor-host system, experiments were carried out to elucidate the effect of intratumoral injections of an immunomodulator, Nocardia rubra cell wall skeleton (N-CWS), on concomitant immunity. Rats bearing a solid tumor into which N-CWS was repeatedly injected showed a significant inhibitory effect on the proliferation of the tumor cells inoculated secondarily into the peritoneal cavity, i.e., concomitant immunity, as compared to control groups of normal, N-CWS-treated and solid tumor-bearing rats. Peritoneal macrophages, when harvested after i.p. tumor inoculation into the N-CWS treated solid tumor-bearing rats, were found to be significantly potentiated for tumoricidal activity against [5-125I]iodo-2'-deoxyuridine-labeled AMC tumor cells. These potentiated macrophages were induced tumor specifically by i.p. inoculation of AMC tumor cells but not by unrelated syngeneic reticulosarcoma SL 1 tumor cells; nevertheless their tumoricidal activity was observed tumor nonspecifically for the SL 1 tumor cells. Additional experiments revealed that nonadherent peritoneal cells were only weakly tumoricidal and that the macrophage tumoricidal activity was completely abolished in the presence of carrageenan. Thus in the model presented here, it is possible to conclude that the augmentation of concomitant immunity by injection of N-CWS into a primary solid tumor is mainly due to potentiation of the tumoricidal activity of tumor-associated macrophages in the peritoneal cavity. Although the underlying mechanism by which concomitant resistance can be augmented by intratumoral injection of N-CWS remains undetermined, the existence of a tumor-specific trigger for induction of potentiated tumoricidal macrophages may indicate that N-CWS when injected repeatedly into the tumor tissue plays an important role in augmenting a pre-existing, weak, tumor-specific cell-mediated immune response leading to activation of macrophages.

Animals↗
PubMed1984

Estrogen induces secretary proteins in transformed mouse Leydig cell in vivo, but not in vitro.

The estrogen-induced proteins were analyzed in one of estrogen responsive mouse Leydig tumors. The incubation of cells freshly prepared from solid tumors with [35S] methionine resulted in the demonstration of estrogen-induced secretary protein with a molecular weight of 34,000. The additional minor estrogen-induced secretary protein (36,000) was also identified. An exposure of these cells to the culture condition for 48 hr caused the loss of their ability to synthesize these secretary proteins even in the presence of estrogen. In contrast, minced tumor tissue was observed to sustain the ability to synthesize these proteins at least for 48 hr. These results would suggest that some cellular arrangement is required for the synthesis of estrogen-induced proteins.

Animals↗
PubMed1984

Enhanced suppression of myocardial slow action potentials during hypoxia by free fatty acids.

Effects of free fatty acids (palmitate and linoleate) on myocardial contractility and slow action potentials (APs) were examined in Langendorff-perfused chick hearts. To study the slow APs exclusively, the fast Na+ channels were voltage-inactivated in elevated K+ (25 mM), and the concentration of Ca2+ ion was increased to 5.4 mM in order to induce slow APs. Palmitate (0.18, 0.54 or 0.72 mM) along with albumin (0.12 mM) was added to the perfusate. Albumin by itself did not affect contractility or the slow APs during normoxia and hypoxia. Under well oxygenated conditions, palmitate had no effect on contractility or the slow APs. However, palmitate accelerated the decline of contractility during hypoxia in a dose-dependent fashion. Hypoxia suppressed the slow APs, and palmitate and linoleate further exacerbated the suppression of slow APs produced by hypoxia. Nevertheless, palmitate and linoleate did not enhance the hypoxic reduction of the tissue high energy phosphate level. The present results suggest that free fatty acids elicit cardio-depressant effects on hearts through their direct action on the myocardial cell membrane (slow channels) rather than through any metabolic effects.

Adenosine Triphosphate↗