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Biomedical subjects

K Morikawa

Publications and source records attributed to K Morikawa.

At least 307 records · Page 17Linked to original sources
PubMed1986

Possible participation of tumoricidal macrophages in the therapeutic effect of bleomycin on a transplantable rat fibrosarcoma.

When bleomycin (BLM) (5 mg/kg/day) was administered i.p. to WKA rats for 5 days from the eighth day after KMT-17 implantation, the therapeutic effects of BLM were demonstrated by complete tumor regression in 50% of the cases and prolongation of the mean survival time of the remainder [survival days, 44.3 +/- 13.6 (SD)]. The combined administration of an antimacrophage agent, carrageenan, with BLM significantly inhibited the therapeutic effects of BLM (cure rate, 33%; survival days, 29.8 +/- 5.8). By means of a Winn assay, the tumor neutralizing activity of both spleen cells and peritoneal cells (PC) against KMT-17 cells was found to be augmented in BLM-treated tumor bearing rats as compared with that in nontreated tumor bearing rats. The enhanced tumor neutralizing activity of spleen cells was not abolished by an anti-rat T-cell serum plus complement treatment and was present in an adherent macrophage enriched population. Similarly, an in vitro [125I]iododeoxyuridine release test enabled us to observe the enhancement of the cytotoxic activity of adherent spleen cells and adherent PC in BLM-treated rats. The cytotoxic activity of the PC of BLM-treated rats was not specific to KMT-17 cells alone but was also observed to operate against antigenically different tumor cells such as WFT-2N, KST-20, and K562 cells. An in vitro carrageenan treatment of PC taken from BLM-treated rats reduced their cytotoxic activity. At the same time, the combined administration of carrageenan and BLM also reduced the cytotoxic activity of PC. These results suggest that the tumoricidal activity of macrophages in tumor bearing rats is augmented after BLM therapy and that the activated tumoricidal macrophages may participate in the host-mediated antitumor effects of BLM.

Animals↗
PubMed1986

Calcium-dependent and -independent tumoricidal activities of polymorphonuclear leukocytes induced by a linear beta-1,3-D-glucan and phorbol myristate acetate in mice.

Some antitumor immunomodulators, such as a linear beta-1,3-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140 (TAK), induce potent tumoricidal activity of polymorphonuclear leukocytes (PMNs). In the present study we investigated the role of calcium on the tumoricidal activity of PMNs induced by immunomodulators, especially TAK. The calcium chelator ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) almost completely inhibited TAK-induced PMN cytotoxicity and this inhibition was restored by Ca2+ but not by Mg2+. In Ca2+- and Mg2+-free medium, PMN cytotoxicity induced by TAK was recovered by the addition of Ca2+ provided that Mg2+ was also present. By scopoletin assay, hydrogen peroxide released from PMNs by TAK was also observed in the presence of Ca2+ but not in its absence. The PMN cytotoxicities induced by the other immunomodulators, Propionibacterium acnes, Bacillus Calmette-Guérin, zymosan A, and Nocardia cell wall skeletons were also Ca2+ dependent, judging from studies with EGTA and measurement of hydrogen peroxide release in the presence and absence of Ca2+. The Ca2+ dependency of these PMN cytotoxicities suggests that Ca2+ influx is involved in the cytolytic process, but PMN cytotoxicity was not induced by simple addition of the calcium ionophore A23187. Like TAK, phorbol myristate acetate induced PMN cytotoxicity but this cytotoxicity was not Ca2+ dependent. The present report demonstrates the difference in Ca2+ dependency of these PMN cytotoxicities; i.e., extracellular calcium was required for immunomodulator-induced PMN cytotoxicity, but not for phorbol myristate acetate-induced PMN cytotoxicity. This suggests that the processes of induction of PMN cytotoxicity by the two types of activators are not identical.

Adjuvants, Immunologic↗
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

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

Influence of chronic hyperprolactinemia induced by sulpiride on the hypothalamo-pituitary-testicular axis in normal men.

For elucidation of the effects of hyperprolactinemia on the hypothalamic-pituitary-testicular axis, five healthy men were exposed to sulpiride (300 mg/day by mouth); four among the five maintained hyperprolactinemia (71.6 to 95.3 ng/ml) for 78 days. Clomiphene citrate (CC), luteinizing hormone (LH)-releasing hormone, and human chorionic gonadotropin tests were performed before and after sulpiride treatment. The CC test, given as a measure of hypothalamic function, was carried out in each of the five volunteers before sulpiride treatment (control) and on days 14 (2 weeks) and 60 (2 months) of sulpiride administration. Each value of plasma LH stimulated by CC was integrated and expressed as a ratio of the integrated value obtained after administering CC at 2 weeks and 2 months to that from each control experiment. The mean ratio in the four subjects at 2 months (mean +/- standard deviation, 0.769 +/- 0.121) was significantly lower than that at 2 weeks (0.942 +/- 0.073; P less than 0.05) and before sulpiride treatment (1.000; P less than 0.01). Impairment of LH responses to CC by 2-month long sulpiride-induced hyperprolactinemia suggests that chronic hyperprolactinemia in men partly suppresses LH secretion by its inhibitory action on the hypothalamus.

Adult↗
PubMed1985

Sequential changes of the T lymphocytes following ER rosette formation in guinea pigs. I. Expression of Fc and complement receptors.

Changes in proportions of the Fc and complement receptor (FcR, CR) positive T lymphocytes from guinea pigs following their interaction with rabbit erythrocytes (ER) were studied using EA and EAC rosette forming assays. Significant increases in the percentages of EA and EAC rosette forming cell (RFC) were observed when thymocytes or lymph node cells were assayed after ER rosette formation. Furthermore, T-enriched fraction by the ER monolayer adherence technique also showed similar or somewhat higher increases in the proportions of both EA and EAC RFC than those of unfractionated cells after contact with ER. The double rosette assay by ER with EA or EAC showed that 50-80% of the Fc and/or complement receptor positive lymphocytes bound rabbit erythrocytes simultaneously. These findings strongly suggest that at least a subset of the guinea pig T cells is altered to express Fc and/or complement receptors on their surfaces following the interaction with ER.

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

Bacterial examination of serous otitis media and experimental tubal stenosis.

Involvement of bacteria in serous otitis media was studied in man and by animal experimentation (using rabbits). Bacteria from the middle ear fluid, the skin of the external ear canal and the epipharynx of 100 human ears were cultured. Bacteria were also cultured from 50 ears of rabbits with serous otitis media induced experimentally by tubal stenosis, in the same way as those taken from human ears. Bacteria were detected in the middle ear fluid of 61 human ears (61%), and in 48 human ears (48%) except for those with contamination. The bacteria detected in the middle ear fluid were the same as those detected in the epipharynx in 40 of the 50 rabbit ears during the period from the start of treatment to the 30th day. In ears which were treated for more than 30 days, the bacteria detected in the middle ear fluid tended not to be the same as those detected in the epipharynx. From these results it was inferred that inflammation of the epipharynx spread over the middle ear cavity through the auditory tube.

Adolescent↗
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

[Pharmacological studies of N-(2-mercapto-2-methylpropionyl)-L-cysteine (SA 96). VI. Effects on vitamin B6, metals and skin collagen in rats].

N-(2-Mercapto-2-methylpropionyl)-L-cysteine (SA 96), an antirheumatic agent, and the main metabolite of SA 96, N-[2-methyl-2-(methylthio)propionyl]-L-cysteine (SA 679), were investigated for the effects on vitamin B6 (VB6), metals and skin collagen in rats in comparison with D-penicillamine (D-Pc). SA 96 had no effect on VB6 amount in serum and liver at doses of 30 mg/kg and 150 mg/kg, p.o., for 28 days, but SA 96 as well as SA 679 lowered the level in the liver slightly at a dose of 600 mg/kg. On the other hand, D-Pc lowered the VB6 level markedly both in serum and liver at doses of 150 mg/kg and 600 mg/kg, p.o., for 28 days. SA 96, SA 679 or D-Pc had no effect on urinary VB6 excretion. The degree of complexing of SA 96 as well as SA 679 with pyridoxal-5-phosphate in vitro was very slight as compared with D-Pc. SA 96 and D-Pc increased Cu and Zn excretion in urine, decreased Cu level both in serum and liver, and increased Zn level in serum. However, the degree of these effects of SA 96 on the metals was very slight as compared with D-Pc. SA 96 or SA 679 had no effect on skin collagen, neither soluble nor insoluble collagen, but D-Pc increased soluble collagen markedly. In addition, at a dose of 600 mg/kg, D-Pc decreased insoluble collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗