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M Kakinuma

Publications and source records attributed to M Kakinuma.

At least 73 records · Page 4Linked to original sources
PubMed1987

A transforming gene, hst, found in NIH 3T3 cells transformed with DNA from three stomach cancers and a colon cancer.

DNA samples from 5 out of 15 stomach cancers and from 5 out of 15 colon cancers showed transforming activity in NIH 3T3 cells upon transfection. A transforming gene from an NIH 3T3 transformant induced by transfection of DNA from a stomach cancer was cloned, and showed transforming activity amounting to 120 focus-forming units/micrograms. The transforming gene was identified as hst. The hst gene was also responsible for acquisition of the transforming activity in DNA samples from 2 other stomach cancers and one colon cancer.

Animals↗
PubMed1986

Parallelism between superoxide production of peritoneal exudate cells and lung granulomatous response in mice vaccinated with BCG cell walls.

Since peritoneal macrophages are reported to be different from alveolar macrophages in their activated states, we examined whether O-2 production, one of the parameters of macrophage activation, in mouse peritoneal exudate cells (PEC) is enhanced under the condition in which lung granuloma, the accumulation of activated macrophages, is produced with Bacillus Calmette-Guérin (BCG) cell wall (CW). As a result, we observed the enhanced O-2 production of PEC that occurs in parallel with lung granuloma formation; high responders, C56BL/6 mice, showed high O-2 production of PEC whereas low responders, C3H/He and DBA/1 mice showed low O-2 production of PEC, suggesting that enhanced O-2 production of PEC as well as lung granuloma formation is genetically controlled. Results from T cell-depleted mice and allogeneic bone marrow chimeric mice also showed the occurrence of this parallelism. From these findings, we presumed that circulating macrophage activating factor and other lymphokines produced by BCG CW-sensitized T cells may activate both peritoneal macrophages and lung macrophages.

Animals↗
PubMed1986

Analysis of synthetic sites of fourth and fifth components of serum complement system in allogeneic bone marrow chimaeras.

Synthetic tissue sites for the fourth and fifth components of complement (C4 and C5) have been investigated using allogeneic bone marrow chimaeras in mice. One group of chimaeric mice was prepared by transplanting bone marrow cells from C5-sufficient donor mice into irradiated C5-deficient recipients or vice versa, and another group was prepared by transplanting marrow cells from mice that produce high levels of C4 into irradiated recipients that are characterized by having low levels of C4 or vice versa. In such chimaeras, lymphoid cells and serum immunoglobulin allotypes were shown to be exclusively of donor origin. However, haemolytic activities of sera from the chimaeras were consistently identical with those of normal mice of the recipient strain. Similar results were obtained when the complement component levels of the sera were evaluated by double diffusion assays. C4 or C5 antigens were detected in sera of the chimaeras only when recipients were strains that are characterized by having high C4 level or were C5-sufficient mice, respectively. These findings indicate that circulating C4 or C5 complement components present in the blood are not synthesized primarily by cells that are descendants of bone marrow cells in these chimaeric mice.

Animals↗
PubMed1985

Analyses of H-2 restriction specificity of helper T cells in fully allogeneic bone marrow chimera in mice.

Using irradiation bone marrow chimeras to analyze restriction specificity of helper T cells, we found that recipient H-2 type dictated the H-2 type which the T cells recognize as self (adaptive differentiation). T cells from (H-2b----H-2k) chimeras cooperate with non-T cells bearing Iak to generate a vigorous PFC response to sheep erythrocytes (SRBC) in vitro, but not with genetically identical H-2b cells. However, when T cells from the chimeras and H-2b non-T cells were adoptively transferred into irradiated (donor X recipient) F1 mice with SRBC, marked responses were seen in recipient spleens where radio-resistant F1 macrophages might exist and act as antigen presenting cells (APC). From these in vitro and in vivo observations, we considered that in the primary antibody response to a T dependent antigen such as SRBC, only T cell-macrophage (APC) matching is required. In contrast, when T cells from H-2 incompatible chimeras which had been primed with SRBC in vivo were analyzed in vitro, these cells cooperated also with H-2b non-T cells. These findings indicate that there may be two separate stages of T cell differentiation during which the self restriction specificity is acquired: one appears to be responsive to intrathymic influences and is not associated with antigenic stimuli, and the other shows signs of being responsive to post-thymic stimuli and of involving antigenic presentation. Moreover, the latter appears to utilize the influence of donor type macrophages.

Animals↗
PubMed1985

Analyses of Ia restriction specificity of helper T cells in H-2 subregion compatible bone marrow chimera in mice.

Using irradiation bone marrow chimeras which had partial compatibility in H-2 subregions between donor and recipient mice, we found that H-2I matching was sufficient for the chimeras to generate anti-sheep erythrocyte plaque-forming cell (PFC) responses. In such chimeras, T cells appeared to encounter appropriate partner cells bearing the same Ia antigens as those which they had learned to recognize as self in the recipient micro-environment. Furthermore, the PFC number seen in I-A compatible chimeras was only about half of that seen in I-A, I-E compatible chimeras, suggesting the existence of two independent subpopulations of helper T cells. When incompatibility of donor and recipient mice existed on the left side of the H-2I region, the responses were very weak. However, even in such chimeras, marked responses were observed for both IgM and IgG type PFC following a sufficient period after immunization. This observation appears to indicate the existence of a minor subpopulation of helper T cells which can expand and interact effectively with antigen presenting cells of donor type.

Animals↗
PubMed1985

Involvement of suppressor cells induced with membrane fractions of trypanosomes in immunosuppression of trypanosomiasis.

We showed that infection with Trypanosoma congolense in mice led to suppression of listeria-induced delayed type hypersensitivity (DTH). Mice were pre-treated with irradiated T. evansi, which caused rapid and effective suppression of DTH. A membrane fraction obtained by homogenizing T. evansi variant in a hypotonic buffer solution and centrifuging it at 150,000g produced suppression of listeria-induced DTH when injected i.p. into mice as early as 1 day before listeria immunization. Furthermore, we demonstrated by an adoptive transfer system that the suppressor cells involved in this suppression had developed in the spleen and that the activity of the splenic suppressor cells was due to the presence of a macrophage population.

Animals↗
PubMed1985

c-myc Gene amplification in primary stomach cancer.

Fourteen human primary stomach cancer tissues were screened by Southern blot hybridization using six oncogene probes (myc, myb, H-ras, K-ras, abl, mos), and an amplification of c-myc oncogene was found in one tissue. This is the first report of c-onc amplification in primary stomach cancer tissue.

Adenocarcinoma↗
PubMed1985

Strain differences in lung granuloma formation in response to a BCG cell-wall vaccine in mice. Demonstration of two types of low responders.

It is known that C57BL/6, C57BL/10 and SJL mice are high responders to intravenously injected BCG cell-wall vaccine or oil-treated BCG organisms, whereas C3H, DBA/1 and DBA/2 mice are low responders. In a previous study, we found that C3H mice produced extensive lung granuloma when they were primed subcutaneously with BCG cell-wall vaccine and later rechallenged intravenously with the same vaccine. Now, we report that DBA/1 mice, but not DBA/2 mice, did not respond to intravenously challenged BCG cell-wall vaccine, even if this priming-rechallenging protocol is used. Thus, the low responders to the BCG cell-wall vaccine are divided into two groups. Breeding experiments using DBA/1 mouse as a parent suggest that an X-linked gene might control the responsiveness to BCG cell-wall vaccine in vivo.

Animals↗
PubMed1983

Strain differences in lung granuloma formation in response to a BCG cell-wall vaccine in mice. Failure of antigen presentation by low-responder macrophages.

C57BL/6 (B6) mice are high responders whereas C3H/He (C3H) mice are low responders of lung granuloma response to a BCG cell-wall vaccine (BCG CW). Studies with allogeneic bone-marrow chimaeras and tetraparental bone-marrow chimaeras demonstrated clearly that the response is dependent on the cells derived from B6 bone marrow. Cell transfer experiments on these chimaeric mice as well as on T cell-depleted mice indicated that macrophages of C3H origin were responsible for the low responsiveness observed. Alveolar macrophages collected from tetraparental bone-marrow chimaeras which had received intravenously BCG CW 4 weeks before showed the same H-2b/H-2k ratio as that of spleen lymphocytes, thus it was proved that efferent phase of lung granuloma response was not impaired in C3H mice. In addition, C3H mice did produce extensive lung granuloma when BCG CW was first injected subcutaneously and rechallenged intravenously. These results strongly suggest that impairment of antigen presentation, when BCG CW was injected intravenously, caused reduced lung granuloma response in C3H mice.

Animals↗
PubMed1982

Specific elimination of the T lineage cells: effect of in vitro treatment with anti-Thy 1 serum without complement on the adoptive cell transfer system.

Thymocytes from C57BL/6(B6) mice treated with anti-Thy 1 antiserum without complement in vitro were transferred to lethally irradiated AKR mice. Five days following transfer, the proportion of Thy 1.2(+) cells recovered from the recipient spleen was significantly lower (7%) than that from the control mice which had received untreated cells (64%). the B6 spleen cells were treated in the same manner and transferred with SRBC (T-dependent antigen) or DNP-Ficoll (T-independent antigen) to irradiated syngeneic recipients. The recipients developed a response to SRBC which was significantly lower than that observed in control mice, but showed the same number of plaque-forming cell (PFC) against TNP-SRBC as the control group of mice which had received untreated B6 spleen cells. These results clearly show that in vitro pretreatment of lymphocytes with anti-Thy 1 serum without complement specifically resulted in elimination or inactivation of the T lineage cells in the host environment. The mechanisms of the elimination are discussed in this study.

Animals↗
PubMed1982

Cellular regulation of lung granuloma formation and delayed- type hypersensitivity induced with BCG cell walls. Further evidence of involvement of cellular immunity in lung granuloma formation.

We have previously showed several evidences in which cellular immunity is involved in lung granuloma formation induced with oil-associated BCG cell wall (CW) vaccine. In the present study, we examined in mice the effects of thymectomy, splenectomy and the administration of cyclophosphamide on lung granuloma formation as well as BCG CW-induced footpad reactions to PPD, a prototype of delayed-type hypersensitivity (DTH). The results presented herein provide further evidence that cellular immunoregulatory mechanisms control the development of lung granuloma and DTH, and that lung granuloma formation is thymus- and spleen-dependent.

Animals↗
PubMed1982

Further study on relationship of anti-tuberculous protection to lung granulomata produced by intravenous injections of synthetic 6-0-mycoloyl-N-acetyl-muramyl-L-alanyl-D-isoglutamine with or without specific antigens.

The synthetic adjuvant, 6-0-mycoloyl-n-acetylmuramyl-L-alanyl-D-isoglutamine (mycol-MDP), is know to have a similar activity to the adjuvant moiety which resides in BCG cell walls (CW). Mycol-MDP plus a specific antigen, PPD, produced lung granulomata followed by anti-tuberculous protection in BCG CW high responder C57BL/6 (B6) mice, but not in low responder C3H/HeMs) (C3H) mice when a granuloma assay and an aerosol challenge with Mycobacterium bovis, Ravenel were carried out 4 weeks after the injection. However, when the granuloma assay and mycobacterial infection were performed 1 week after the injection, both B6 and C3H mice showed slight but definite lung granuloma formation accompanied by detectable protection. This suggested that the early development of granuloma was elicited by direct activation of macrophages with mycol-MDP. This possibility was confirmed since T-cell-deprived (B) mice produced lung granulomata 1 week after injection with mycol-MDP alone. However, contrary to our expectation, these B mice did not show anti-tuberculous protection. The role of T cells for anti-tuberculous immunity is discussed in relation to the adjuvant activity of mycol-MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1981

Restricted antibody formation to sheep erythrocytes of allogeneic bone marrow chimeras histoincompatible at the K end of the H-2 complex.

Employing a new method for allogeneic bone marrow transplantation, irradiation chimeras constructed from various combinations of marrow cells from B10 H-2 recombinant mice and AKR recipients were prepared. Though these chimeras had well-developed populations of T and B cells, they showed strikingly different patterns of responses in the primary antibody formation to sheep erythrocytes (SRBC), a T dependent antigen. These are (a) AKR mice treated with C57BL/10 cells, [B10 leads to AKR] fully H-2 incompatible, and AKR mice treated with B10.A (5R) cells, [5R leads to AKR] I-J,E compatible chimeras that were almost completely unresponsive to SRBC; (b) AKR mice treated with B10.BR cells [BR leads to AKR] fully H-2 compatible, and AKR mice treated with B10 AKM cells, [AKM leads to AKR] chimeras where donor and recipient differed only at H-2D, showed the same number of plaque-forming cells (PFC) as B10 control mice; (c) AKR mice treated with B10.A cells, [B10 leads to AKR] chimeras, where donor and recipient were matched at H-2K-I-E region, showed about one-half the number of PFC as the control mice. From these results we conclude that in allogeneic bone marrow chimeras primary antibody response to T-dependent antigen, such as SRBC, is generated when at least the K end of the H-2 complex is compatible between donor and recipient.

Animals↗
PubMed1981

Suppression of BCG cell wall induced delayed-type hypersensitivity by BCG pre-treatment. I. Induction of adherent suppressor cells by live BCG injection and their characterization.

Previous injections of live Bacillus Calmette-Guérin (BCG) in mice produced a suppression of delayed-type hypersensitivity (DTH) induced by oil-treated BCG cell walls (CW). This phenomenon was analysed by the macrophage migration inhibition (MI) test in which peritoneal exudate cells (PEC) from live BCG-injected mice were mixed with PEC from BCG CW-immunized mice, with the result that the former cells suppressed the MI activity in the latter. We considered the Mi test to be a reliable method for demonstrating the existence of suppressor cells induced by the injection of live BCG. Moreover, we found that the adherent cells of PEC possessed a suppressive effect which was retained even after treatment with either anti-mouse Ig or anti-brain associated theta (BA theta) antigen; that the PEC from mice injected with live BCG on at least the 12th day before cell harvesting showed the suppression; and that the suppression operated across the H-2 barrier.

Animals↗
PubMed1981

Failure of C3H mice to develop lung granuloma after intravenous injection of BCG cell wall vaccine. Demonstration of a defect in lymphoid cells.

C57Bl/6 (B6) mice produced highly developed granulomata in the lung 3 or 4 weeks after intravenous injection with oil-associated BCG cell walls (CW), but C3H/He (C3H) mice did not. The potential to develop granulomata is genetically controlled (Yamamoto & Kakinuma, 1978). It is probable that the genes control only T-cell mediated granuloma and not non-specific inflammation prior to onset of immunopathological response. The retention of an FITC-labelled BCG CW preparation in the lungs of B6 and C3H mice did not differ until 10 days after injection, although 24 hr uptake of 125 I-labelled BCG CW in B6 lung was twice as much as that in C3H lung. Furthermore, C3H mice did not show a secondary type granuloma response in the lungs after subsequent injections of BCG CW. In experiments using radiation chimaeras, B6 mice reconstituted with C3H bone marrow cells were unable to produce a granulomatous response to BCG CW. In contrast, C3H mice reconstituted with B6 bone marrow cells showed a good granulomatous response. These results suggest that the C3H mice possessed a deficiency within their lympho-haematopoietic cells.

Animals↗
PubMed1980

Relationship of anti-tuberculous protection to lung granuloma produced by intravenous injection of synthetic 6-O-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine with or without specific antigens.

Intravenous administration of 6-O-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine (mycol-MDP) together with a specific antigen, PPD, in a water-in-oil emulsion was found to produce lung granuloma and to provide a low but significant grade of protection in mice against tuberculous infection within 4 weeks. However, these products, when given in an oil-in-water emulsion did not produce granuloma. Mycol-MDP alone produced comparable lung granuloma in both C57Bl/6 mice, high responders to BCG cell walls (CW), and C3H/He mice, low responders, 1 week after the injection, and when challenged at this time by aerosol containing virulent bovine tubercle bacilli, they showed significantly increased resistance. The present results confirmed the close relationship between lung granuloma and protection against aerosol challenge with Ravenel and revealed that the extent of lung granuloma at the time of aerosol challenge is crucial for the development of protection in mice immunized with mycol-MDP plus PPD as it is in mice immunized with BCG CW. However, these findings are not always the case for lung granuloma induced with mycol-MDP alone.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1979

Intrathymic injection of antigen: a potent procedure for the induction of suppressor T cells.

Immunological tolerance is induced in mice by intrathymic injection of HSA. The tolerance thus induced is mediated by suppressor T cells. Strong tolerance persists more than 56 days after the induction, and the high efficiency of the tolerance thus induced is accounted for in terms of the number or the potentiality of suppressor cells. Possible mechanisms of suppressor T cell induction by iT injection of the antigen are discussed briefly.

Animals↗