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Biomedical subjects

K Iwabuchi

Publications and source records attributed to K Iwabuchi.

At least 235 records · Page 13Linked to original sources
PubMed1986

Generation of cytotoxic T lymphocyte responses to allo-H-2 antigens in allogeneic bone marrow chimeras histocompatible at the H-2 subregions.

The present study was performed to determine whether H-2 matching is required for full cytotoxic T lymphocyte (CTL) responses to allo-H-2 antigens in allogeneic bone marrow chimeric mice. A number of irradiated, bone marrow-reconstituted chimeras constructed from various combinations of marrow cells from B10 H-2 recombinant strains and AKR recipient mice were prepared. Spleen cells obtained from such chimeras and normal control mice were activated in vitro by culturing them with irradiated stimulator cells. It was shown that spleen cells from [4R----AKR], [(4R X 3R)F1----AKR] or [AQR----AKR] chimeras, which were histocompatible on the left hand-side of the H-21 subregion between donor and recipient mice, generated greater CTL activities than those that were seen with spleen cells of [3R----AKR] or [5R----AKR] chimeras, which were histoincompatible in this region. We were unable to demonstrate suppressor cell activity of the spleen cells of [3R----AKR] chimeras cultured with stimulator cells. Although spleen cells from [3R----AKR] chimeras showed substantial proliferative responses to stimulator cells (MLR) and to Con A and LPS, IL2 activities of supernatants from Con A-activated spleen cells (Con A SN) of the chimeras were significantly lower than those of [4R----AKR] or [(4R X 3R)F1----AKR] chimeras. Furthermore, vigorous CTL activities were obtained with either spleen cells or thymocytes from [3R----AKR] chimeras when rat Con A SN was added to the MLR cultures. These observations suggest that the numbers of precursor CTLs in the cells from [3R----AKR] chimeras are at the same level as those of [(4R X 3R)F1----AKR] or normal mice and that the low CTL activities generated by spleen cells of [3R----AKR] chimeras compared to H-2I-matched chimeras are due in large measure to deficiency in IL2 production by the splenic T cells of the [3R----AKR] chimeras.

Animals↗
PubMed1986

A study on location of synthetic site which mainly synthesizes and delivers fifth component of complement system in vivo.

Tissue sites for synthesis of the fifth component of complement (C5) in vivo have been investigated by using allogeneic bone marrow chimeras and bone marrow chimeras which were transplanted in addition with hepatocytes. Our prior studies have demonstrated that bone marrow chimeras which had been prepared by transplanting marrow cells from C5-sufficient donor mice into irradiated C5-deficient recipients lacked detectable levels of C5 in the sera. However, when such potentially C5-deficient [C5(+)---C5(-)] chimeras were introduced into their spleens by means of injections of fully dispersed single cell suspensions of hepatocytes isolated from the C5-sufficient donor strain, they accepted the transplantation of hepatocytes for prolonged periods and developed a measurable amount of C5 in the sera. These results indicate that C5 protein in sera is not synthesized in significant amount by cells that are descendants of bone marrow cells but rather that this complement component is synthesized and delivered to the blood in vivo by somatic cells including liver cells that are not derivatives of the bone marrow.

Animals↗
PubMed1986

A monoclonal antibody (1B7) specific for polymorphic determinant on mouse I-A antigens recognizes monomorphic epitope shared by most of RT-1 haplotypes in rats.

A monoclonal antibody, 1B7, which was established by immunizing C57BL/10 mice with splenocytes from B10.BR, was investigated by serological, immunochemical and functional analyses in mouse, rat, guinea pig and human systems. 1B7 recognized a polymorphic determinant on class II antigens in the mouse system. In the rat system, however, this antibody appeared to recognize a monomorphic epitope shared by all RT-1 haplotypes. 1B7 showed no reactivity in the human and guinea pig strains tested.

Animals↗
PubMed1986

Potent platelet antiaggregant action of an antiarrhythmic peptide (AAP).

A potent platelet antiaggregant action of an antiarrhythmic peptide (AAP) was demonstrated to be a cause of the antithrombotic effect. AAP (10, 20 or 40 mg/kg, i.v.) inhibited ex vivo platelet aggregation induced by collagen in a dose-dependent manner. AAP also inhibited the platelet aggregation of platelet-rich plasma (PRP) induced by collagen, Ca-ionophore A-23187, adenosine diphosphate (ADP), thrombin or arachidonic acid in vitro. The IC50 was 2.5 mM for collagen, 1.7 mM for A-23187, 5 mM for ADP, 0.4 mM for thrombin and 0.15 mM for arachidonic acid. The aggregation inhibitory activity of the peptide on washed platelet (WP), in a Ca2+-free medium, was stronger than on PRP. The IC50 was 1 mM for collagen and 20 microM for A-23187. No significant difference was found between antiaggregant activities of platelet-free plasma (PFP) from AAP-treated rats and PFP from normal rats supplemented with AAP. The direct action of AAP on platelets was also supported by the incorporation of AAP into platelet cytoplasma which caused a decrease of Ca2+-dependent 3':5'-cyclic nucleotide phosphodiesterase (Ca-PDE) activity. It was considered that AAP showed its platelet aggregation inhibitory activity by decreasing intracellular Ca2+ concentration through the inhibition of Ca-PDE activity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Response of immunoreactive antiarrhythmic peptide (IR-AAP) level associated with experimental arrhythmia in rats.

The change in endogenous antiarrhythmic peptide (AAP) levels in serum, heart and kidney from rats under several drug-induced arrhythmias was investigated using a sensitive and specific radioimmunoassay. The extracts from serum, heart and kidney were fractionated by Sephadex G-25 chromatography to obtain a fraction which was found at the same position as that of synthetic AAP. In serum, the immunoreactive (IR)-AAP level increased about threefold under CaCl2-, aconitine- and epinephrine-induced arrhythmias. In heart, the IR-AAP level was doubled by CaCl2, increased 1.4 times by aconitine and decreased by one third by epinephrine. The levels in serum and heart were slightly increased by ADP. The kidney IR-AAP level was not changed under these drug-induced arrhythmias. Considering the previous result that AAP could protect against CaCl2- and aconitine-induced arrhythmias but not against epinephrine-induced arrhythmia, the change in the IR-AAP level in heart coincided with the effect of AAP given to animals under arrhythmia. Quinidine, propranolol and verapamil had no effect on serum IR-AAP level. These results suggested that endogenous AAP in heart worked to suppress certain arrhythmia.

Aconitine↗
PubMed1986

[Percutaneous chronic toxicity study of 10% nitroglycerin (NT-1 ointment) in rabbits].

A chronic toxicity test of 10% nitroglycerin (NT-1 ointment) was carried out in male NZW rabbits. NT-1 ointment was applied to the back skin for 26 weeks at daily doses of 15, 60 and 240 mg/kg as nitroglycerin itself, and 5-week withdrawal period was followed. Topical dermal responses to NT-1: Macroscopically, erythema, edema, scales, papules and dermal thickening were observed in response to NT-1 ointment. In the withdrawal period, however, all of them disappeared. Histopathologically, thickening of epidermis and cell infiltration were observed in response to NT-1 ointment. In addition, elongation of rete ridges and Touton giant cells were found only in 60 and 240 mg/kg groups, and hyperkeratosis only in 240 mg/kg group. At the end of withdrawal period, Touton giant cells were still found in 60 and 240 mg/kg groups, although the other dermal reactions disappeared. Systemic responses to NT-1 ointment: A slight increase in the excretion of loose or mucous feces was observed in 240 mg/kg group. The weights of right and left kidneys were increased by the administration of 240 mg/kg NT-1 ointment, and a similar trend was seen also in the weight of heart, although there found no such among-group differences at the end of withdrawal period. White blood cells, especially neutrophils, and gamma-globulin fraction were increased in response to 240 mg/kg NT-1 ointment. In conclusion, a no-toxic effect dose of NT-1 ointment as nitroglycerin itself was considered to be 15 mg/kg/day for the skin and 60 mg/kg/day for the general somatic system.

Administration, Cutaneous↗
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↗
PubMed1986

[A study of proliferative responses to host Ia antigens in fully allogeneic bone marrow chimeras in mice--sequential analysis of the reactivity and characterization of the cells involved in the response].

Irradiation bone marrow chimeras were established by reconstitution of lethally irradiated AKR mice with C57BL/10 marrow cells which had pretreated with anti-Thy-1 serum. Mixed lymphocyte reactions (MLR) were carried out serially to analyze developing reactivities of lymphocytes from such chimeras, [B10----AKR], against donor, host or third party antigens. Spleen cells of [B10----AKR] chimeras 8 weeks after reconstitution regularly showed proliferative responses when stimulated with spleen cells of the strain of the irradiated recipient (AKR). However, the responsiveness was consistently lower than that generated against third party antigens. The stimulator cells were Ia positive in both anti-recipient and anti-third party responses, and the responding splenocytes were of donor origin and showed Thy-1+, Ly-1+2-, and L3T4+ phenotypes, although a minor population of Ly-2+ and L3T4- T cells might be involved in anti-third party response. Further, we found that substantial proliferative responses to Ia antigens of the recipient strain and also to third party antigens are generated by the thymocytes obtained from the irradiation chimeras at an early stage following bone marrow reconstitution. Majority of the responding thymocytes had surface traits of PNA-, donor type Thy-1+, and L3T4+ in both anti-recipient and anti-third party MLRs. However, as for the Ly-2 antigen, Ly-2+ thymocytes seemed to be, at least partially, involved in anti-host responses. This capacity of thymus cells to mount a response to antigens of the recipient strain declined shortly thereafter. The spleen cells at the same time developed a more durable capability to exhibit anti-host reactivities. Awareness of the sequence of development of these cellular reactivities and capacities to respond to host and third party alloantigens may be crucial to understanding the underlying molecular mechanisms involved in generating a T cell repertoire one component of which is restricted to Ia antigens of the recipient strain.

Animals↗
PubMed1985

Characteristics of macrophages in irradiation chimeras in mice reconstituted with allogeneic bone marrow cells.

Biological and immunological characteristics of the reticuloendothelial system of irradiation bone marrow chimeric mice and macrophages collected from various tissue sources of the mice were studied. The chimeras showed comparable activities in carbon clearance to those of normal donor or recipient mice. The macrophages from spleen, lymph node, bone marrow, peripheral blood, liver, peritoneal cavity, and lung were demonstrated to be of donor marrow origin. They showed almost the same enzyme activities and phagocytic capability of sheep erythrocytes (SRBC, E), SRBC sensitized with anti-SRBC IgG (EA), and SRBC sensitized with anti-SRBC IgM and coated with complement (EAC) as those of normal mice. Proportions of Fc receptor and complement receptor-positive cells are also in normal range. In addition, the antigen-presenting capability of the chimeric macrophages for in vitro primary antibody response to SRBC was intact. These observations suggest that the reticuloendothelial system and macrophages of allogeneic bone marrow chimeras where donor and recipient differ at the major histocompatibility complex have no defect so far as could be ascertained by the present study.

Animals↗
PubMed1985

Studies on neurotransmitter markers and striatal neuronal cell density in Huntington's disease and dentatorubropallidoluysian atrophy.

Neurotransmitter abnormalities in the basal ganglia of individual "choreic" patients (9 cases of Huntington's disease-HD and 3 cases of dentatorubropallidoluysian atrophy-DRPLA) and 14 normal controls were investigated. Choline acetyltransferase activity in the striatum was decreased in approximately half the "choreic" patients. GABA concentration in the substantia nigra or in the globus pallidus was decreased in all "choreic" cases except one case of DRPLA. Substance P concentration was also reduced in the same nuclei as GABA except in one case of HD. These findings imply: cholinergic, GABAergic or substance P-related markers found in the basal ganglia of HD are not disease-specific but also found in the other "choreic" disorder, i.e. DRPLA; most prominent biochemical changes in HD would be a decrease of GABA in the basal ganglia. Correlation analysis of the markers in the basal ganglia and the striatal neurone densities of "choreic" patients (5 cases of HD and 3 cases of DRPLA) and 7 normal controls yielded positive correlation between GABA concentration in the substantia nigra and the globus pallidus, and the neuronal cell density in "small" cells in the striatum of normal control and HD. Positive correlation between substance P concentration and the striatal neurone density was only found in the substantia nigra. Choline acetyltransferase activity in the striatum was found to be positively correlated with the density of "large" cells in the striatum rather than that of "small" cells. In DRPLA there was no direct correlation between the values of the markers in the basal ganglia and the striatal neurone density. The decrease of transmitter markers without striatal cell loss in this particular choreic disorder could be regarded as a sequence of "biochemical degeneration" of striatal neurones. Based on these findings, the underlying mechanisms of choreic involuntary movements were briefly discussed.

Adult↗
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

H-2-incompatible bone marrow chimeras produce donor-H-2-restricted Ly-2 suppressor T-cell factor(s).

To study adaptive-differentiation phenomena of T lymphocytes, suppressor T-cell factors (TsF) produced by Ly-2+ splenic T cells from fully allogeneic mouse bone marrow chimeras were analyzed. AKR mice irradiated and reconstituted with B10 marrow cells (B10----AKR chimeras) produced an Ly-2+ TsF after hyperimmunization with sheep erythrocytes. The TsF suppressed primary antibody responses (to sheep erythrocytes) generated with spleen cells of mice of H-2b haplotype but not those of H-2k haplotype. Thus, this suppressor factor was donor-H-2-restricted. The immunoglobulin heavy chain variable region gene (Igh-V)-restricting element was not involved in this form of suppression. Similar results were obtained when TsF from B6----BALB/c and BALB/c----B6 chimeras were analyzed. The TsF from B10----AKR chimeras suppressed responses of B10.A(3R) and B10.A(5R) mice but not those of B10.A(4R). This finding showed that identity between the factor-producing cells and target spleen cells is required on the left-hand side of the E beta locus of the H-2 region and that the putative I-Jb locus is not involved in this form of suppression. The present results support the postulate that post-thymic differentiation in the presence of continued or repeated stimulation with antigen and donor-derived antigen-presenting cells generates donor-H-2-restricted T-cell clones that may predominate within the repertoire of the specific antigen being presented.

Alleles↗
PubMed1985

Recipient micro-environment does not dictate the Igh-V restriction specificity of T cell suppressor inducer factor (TsiF) from allogeneic bone marrow chimera in mice.

We have ascertained previously from a study of fully allogeneic irradiation chimeras in mice that the H-2 restriction of the suppressor factor (Ly-2 T suppressor factor) is determined by the post-thymic environment protected by the donor cells, rather than by the thymic environment of the recipient. In the present study, we analyzed differentiation influences that determine the Igh restriction specificities of the suppressor inducer T cell factor(s) (TsiF) that are produced by Ly-1+ splenic T cells in fully allogeneic bone marrow chimeras in mice. AKR mice that had been lethally irradiated and reconstituted with B10 marrow cells, [B10----AKR] chimeras, produced Ly-1 TsiF after hyper-immunization with sheep erythrocytes (SRBC) which suppressed antigen--specifically the primary antibody responses to SRBC that were generated in cells of the same Igh-Vb haplotype of donor strain and not those generated in cells of the recipient Igh-Va type. Similar results were obtained when Ly-1 TsiF from [B6----BALB/c] and [BALB/c----B6] chimeras were analyzed. Furthermore, the Ly-1 TsiF from [BALB/c----B6] chimeras suppressed the primary antibody responses of both BALB/c [H-2d, Igh-Va, Igh-Ca] and BAB-14 (H-2d, Igh-Va, Igh-Cb), but not those of CAL-20 (H-2d, Igh-Vd, Igh-Cd). These results demonstrate clearly that the Ly-1 TsiF from allogeneic bone marrow chimeras are donor Igh-V-restricted and are not influenced by the recipient micro-environment, presumably that provided by the thymuses of the recipient mice.

Animals↗