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M Hosono

Publications and source records attributed to M Hosono.

At least 163 records · Page 9Linked to original sources
PubMed1989

Studies on B-cell memory. IV. Effects of lipopolysaccharide on primary and secondary antibody responses to T-independent type-2 (TI-2) antigen in mice.

Effects of LPS on primary and secondary antibody responses to typical TI-2 antigens were investigated in mice. Simultaneous injection of LPS with a TI-2 antigen showed only little adjuvant effect on the following primary antibody response to the antigen. In contrast, either a single or multiple injections of LPS, prior to the immunization with a TI-2 antigen, significantly augmented the following primary antibody response to the antigen. LPS, however, inhibited the development of B-cell memory to a TI-2 antigen when administered together with the antigen. Moreover, an injection of LPS in mice, which had strong IgM and IgG B-cell memories to a TI-2 antigen, caused disappearance or profound reduction of the memories. The results suggest that LPS produced by gram-negative bacteria exerts inhibitory effects on the development and continuation of B-cell memory to bacterial infections.

Adjuvants, Immunologic↗
PubMed1989

Enhanced adrenergic response of the cerebral vasculature in alloxan-induced diabetic rats.

The influence of alloxan-induced diabetes on the adrenergic constriction of the rat cerebral vasculature was investigated in the in situ perfused brain preparation. The preparation was perfused with an artificial medium at a constant flow rate and the change in perfusion pressure was measured. Norepinephrine (NE) and serotonin produced a dose-dependent increase in the perfusion pressure, but only the effect of NE was significantly enhanced in the diabetic rats. Such an enhancement of NE-induced vasoconstriction was not observed in the perfused hindquarter preparations from the diabetic rats. Propranolol (1 microM) potentiated the cerebrovascular constriction by NE and abolished the difference between diabetic and control rats at low doses of NE. However, vasoconstriction by the higher doses of NE in the diabetic rats was still enhanced even in the presence of propranolol. The cerebrovascular constriction by phenylephrine was also enhanced in the diabetic rats, while the vasoconstricting effects of clonidine, xylazine and oxymetazoline were not affected by diabetes. These results suggest that the enhanced cerebrovascular constriction by NE may be due to either the reduced response through beta-adrenoceptors or the enhanced response through alpha 1-adrenoceptors. The enhanced adrenergic constriction of the cerebral vasculature might be concerned with the high incidence of neurological deficit in stroke patients with diabetes.

Animals↗
PubMed1989

Immune responses in newly developed short-lived SAM mice. III. Genetic control of defective helper T-cell activity in in vitro primary antibody response.

Immune activities of newly developed, short-lived SAM-P/1 mice declined sharply after a few months of age. As early as 2 months of age, the activity of T-helper (Th) cells ('Th2'-like) in the in vitro primary antibody response was profoundly impaired, in contrast to normal activity of Th cells ('Th1'-like) engaged in cell-mediated immune responses. Thus, young SAM-P/1 mice show a functional heterogeneity of Th cells. To determine how such a 'Th2' abnormality is inherited in SAM-P/1 mice, immune activities of their hybrids and backcrosses between MHC-identical, high responder B10.BR mice were statistically assessed. The distribution of responses did not support the Mendelian single-gene determination for low responsiveness. Moreover, involvement of a single gene which exhibits incomplete dominance was ruled out because of a continuous distribution pattern of antibody response in the F2 generation. Such an analysis strongly suggests that the impaired 'Th2'-like activity of SAM-P/1 mice is under control of two genes, based on the proportion of low responders in F2 hybrids (29 out of 267, 10.8%) and on calculation according to Wright's formula (n = 1.72). Further linkage analyses suggest that one of the genes is closely linked to albino coat-colour (c) locus on chromosome 7. The putative two genes are likely to control 'differentiation' or 'maturation' of Th2-like cells defectively, but the defect is not refractory, because in vivo-primed Th cells function in vitro as do those in ordinary strains of mice. Possible mechanisms and biological significance in relation to loss of immune activity with ageing are discussed.

Aging↗
PubMed1988

T-1583 and forskolin are similar in their cardiac effects and dissimilar in their vascular effects.

The cardiac and coronary vascular effects of T-1583, a selective beta 1-adrenoceptor full agonist, and forskolin, a direct activator of adenylate cyclase, were compared in isolated, blood-perfused papillary muscle, sinoatrial node, and atrioventricular (AV) node preparations of dogs. Both agents were injected intra-arterially. The two agents increased the force of contraction of the paced papillary muscle and the unpaced one, and the rate of automaticity of the latter. They increased sinus rate and accelerated AV nodal conduction. In producing these effects T-1583 was 50 to 80 times more potent than forskolin, indicating that both agents have similar cardiac profiles. At the doses that produced a 50% increase in the force of contraction of the papillary muscle, both agents produced about a 20% increase in sinus rate. Such degrees of force-rate separation were close to those obtained with most new positive inotropic agents with an inhibitory action on cyclic AMP phosphodiesterase. T-1583 differed distinctly from forskolin in that the former increased only slightly coronary blood flow, whereas the latter increased it greatly. Thus, forskolin is more coronary vasodilatory than positively inotropic, and more positively inotropic than positively chronotropic. T-1583 is a more positively inotropic than positively chronotropic and more positively chronotropic than coronary vasodilatory.

Adrenergic beta-Antagonists↗
PubMed1988

Strain differences of age-dependent changes in the responsiveness to a T-independent type-2 antigen in mice.

We have assessed age-associated early changes in antibody response to a T-independent type-2 (TI-2) antigen, dinitrophenylated ficoll (DNP-Ficoll). Mice of most strains, including long-lived and autoimmune-prone strains, give a high response when approximately 2 months old; thereafter the response declines sharply to the 3rd-4th month of age and continues to do so, more gradually, up to the age of 6 months. Age-related changes in the response of C57BL/6 mice follows a different course: the response remains unchanged up to the first year of life, i.e. to middle age. The in vitro anti-DNP-Ficoll antibody response of B cells could be increased by the addition of young syngeneic T cells. The augmenting activity of splenic T cells of C3H/He mice declines clearly as a function of age. In contrast, splenic T cells of C57BL/6 mice have low augmenting activity whether the T cells are obtained from young or middle-aged donors. Unlike the augmenting capacity of T cells, B-cell responsiveness to DNP-Ficoll increases until middle age in all strains examined. We conclude that early age-associated changes in antibody response to the TI-2 antigen is polymorphic and that the early age-related decline in in vivo responsiveness is attributable to an age-associated decline in augmenting T helper cell activity.

Aging↗
PubMed1988

Unidirectional responses to Mls determinants in vivo. Polyclonal T-cell responses to a single common determinant of Mls in different efficiencies?

Polyclonal anti-Mls responses of peripheral (mature) and thymic (immature) lymphocytes were studied in vivo in terms of local host-versus-graft and graft-versus-host reactions. The level of stimulatory activity differed between the various types of Mls antigens, with Mlsa and Mlsd having the highest levels. Mlsc a lower level, and Mlsb the lowest level. The immunogenicity of Mlsa and Mlsd may not be identical, since Mlsd mice responded to the Mlsa determinant, while Mlsa mice did not react with the Mlsd determinants. This suggests that the anti-Mls response is unidirectional. The fact that Mlsb mice made tolerant at birth to Mlsd (Mlsa) antigens behave like Mlsd (Mlsa) mice when responding to Mls antigens supports this suggestion. Furthermore, thymus cells from the Mlsa-tolerized BALB/c (Mlsb) mice were unresponsive to both Mlsa and Mlsd antigens, while those made tolerant to Mlsd were responsive to Mlsa. These results indicate that the polyclonal response to the strongly immunogenic Mlsa,d antigens is unidirectional, and that the immunogenicity of Mlsa and Mlsd is not identical. Based on the results of tolerance experiments and data on T-cell clones, we suggest that the difference in immunogenicity between Mlsa,b,d antigens is due to different efficiencies of the responding T-cell populations, probably because of a quantitative difference in a single common antigenic determinant expressed in each Mls haplotype, which results in different levels of stimulation of T cells according to the avidity for the determinant.

Animals↗
PubMed1988

Improvement of pentobarbital-induced heart failure by MCI-154, a novel and potent cardiotonic agent, in the dog heart-lung preparation.

The efficacy of MCI-154, a new pyridazinone cardiotonic agent, in improving heart failure was assessed in dog heart-lung preparations in which cardiac function had been severely depressed by pentobarbital. MCI-154 in doses of 10-100 micrograms improved the cardiac function curve and restored it to the control level at 100 micrograms. At this dose, MCI-154 neither produced an increase in heart rate beyond the control value nor induced arrhythmias. The effects of MCI-154 were not affected by atenolol, a cardioselective beta 1-blocker. These results indicate that MCI-154 would be of potential use in the treatment of heart failure.

Animals↗
PubMed1988

Generation of self-macrophage-toxic non-T cells in the MHC-homozygous F1 spleen cells co-cultured with parental cells: possible involvements of host cells in impaired immunity in GVH disease.

Simplified-in vitro system was developed to examine the contribution of host's cells in graft-versus-host (GVH)-disease-associated immunodeficiencies. In analogy with major histocompatibility complex (MHC)-matched GVH-reaction, (BALB/c x DBA/2)F1 (H-2d) hybrid spleen cells were co-cultured with irradiated BALB/c (H-2d) spleen cells, so that cellular activities to be generated are ascribable to F1 cells. In vitro development of anti-allo-specific cytotoxic T cells of the F1 origin was dramatically suppressed by coexistence of the irradiated parental cells and by the addition of F1 cells precultured once with the parental cells, suggesting the generation of suppressor cells in the F1 (host) cells activated by the parental cells. Thus generated suppressor cells are Thy.1-, weakly or nonadherent and radiosensitive. Interestingly, in the same reactions there also developed Thy.1- cytotoxic cells for autologous macrophage targets. An involvement in immunodeficiencies in GVH disease of the host-derived cytotoxic and/or immunosuppressive, non-T cells was discussed.

Animals↗
PubMed1987

Neonatal tolerance induction in the thymus to MHC-class II-associated antigens. III. Significance of hemopoietic stem cells for induction and maintenance of Mls tolerance by continuous supply of tolerance-inducing nonlymphocytes.

The role of hemopoietic stem cells and other cell types in the induction and maintenance of immunologic tolerance in the thymus was investigated by intravenous injection of Mls-semi-allogeneic cells into newborn mice less than 24 hr after birth. Mls-specific tolerance was induced by inoculation of peritoneal cells and thymus cells, and the tolerant state was compared with that induced by bone marrow cells which had hemopoietic stem cell activity and were able to create a stable chimera in both central and peripheral lymphoid organs. When peritoneal or thymus cells were injected, the level of tolerance attained was proportional to the number of cells injected, though peritoneal cells were 20 times as effective as thymus cells. In vivo functions of tolerance-inducing cells and their immediate precursors were radiosensitive and belonged to a Thy-1-, nylon-wool-nonadherent (probably non-B), weakly Sephadex G-10-adherent cell population. Tolerance induced by peritoneal cell injections was transient, starting to terminate within the first 2 weeks of life, while tolerance caused by bone marrow cell injections persisted through more than 6 weeks. Such transient tolerance induced by the former became long-lasting when followed by an additional injection of bone marrow cells, which did not cause thymic lymphocyte chimerism. All data indicated that bone marrow stem cells were engaged in tolerance induction and maintenance by continuously supplying tolerance-inducing nonlymphocytes.

Animals↗
PubMed1987

Coronary vasodilator versus cardiac effects of MCI-176, a novel quinazolinone calcium antagonist, in the dog heart.

We compared the coronary vasodilator and cardiac effects of MCI-176, a novel quinazolinone calcium antagonist, in isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. The drug was administered intraarterially. In SA node preparations MCI-176 reduced sinus rate and produced atrial standstill in large doses. In AV node preparations MCI-176 prolonged AV conduction time and produced second- or third-degree AV block in large doses only when administered into the artery supplying the AV node, but failed to affect AV conduction when administered into the artery supplying the His-Purkinje-ventricular system. In paced papillary muscle preparations MCI-176 reduced the force of contraction. In spontaneously beating papillary muscles MCI-176 failed to change the beating rate. MCI-176 increased blood flow in all preparations. The dose that doubled blood flow was slightly larger than the dose that produced a 15% increase in AV conduction time, but about one-third the dose that produced a 15% decrease in sinus rate. The dose estimated to reduce the force of contraction by half was more than approximately 10 times the dose that doubled blood flow. The results indicate that MCI-176 can be classified as a nonvasoselective calcium antagonist but that it differs from others.

Animals↗
PubMed1987

Effect of DHP-218, a novel dihydropyridine phosphonate, on atrioventricular nodal conductivity compared with its vascular effect in dogs.

The effect of DHP-218, a dihydropyridine phosphonate Ca2+ channel blocker, on atrioventricular (AV) nodal conductivity was compared with its vascular effect in dogs. In isolated, blood-perfused AV node preparations, a long-lasting increase in AV conduction time which culminated in second- or third-degree AV block at large doses occurred when DHP-218 was injected into the AV node artery, but not when injected into the artery that supplies the His-Purkinje-ventricular system. However, with DHP-218, a far longer-lasting increase in blood flow through both arteries occurred, and at smaller doses it occurred with little effect on AV conduction. In anesthetized, open-chest dogs of which heart rate was controlled at 150 beats/min, intravenous DHP-218 produced an initially rather quick and later very slowly developing and long-lasting fall in blood pressure. AV conduction time was prolonged only after the largest dose. The functional refractory period of the AV conduction system was rather shortened in all doses examined except for the largest dose. A marked increase in AV conduction time which culminated in third-degree AV block was seen in one of six dogs, only under conditions in which the heart was deprived of central neural control. These results indicate appreciable selectivity of DHP-218 for vasculature versus the AV node.

Animals↗
PubMed1987

Cardiac and coronary vasodilator effects of the novel cardiotonic agent, MCI-154, assessed in isolated, blood-perfused dog heart preparations.

MCI-154 is a potent nonglycoside and non-sympathomimetic cardiotonic agent with a pyridazinone structure. We assessed its cardiac and coronary vasodilator effects by use of isolated, blood-perfused papillary muscle, sinoatrial (SA) node, and atrioventricular (AV) node preparations of dogs. The drug (1-100 nmol) was injected intraarterially. MCI-154 increased the force of contraction of paced and unpaced papillary muscles but failed to affect the rate of automaticity of the latter. It increased sinus rate and shortened AV conduction time by accelerating AV nodal conduction, but in all doses examined it produced no arrhythmias. In all preparations, it increased blood flow. All the effects were long-lasting (1-2 h). MCI-154, however, was not homogeneously effective on these cardiovascular variables. The drug was nearly equieffective in producing a positive inotropic effect and coronary vasodilatation, but less effective in producing positive chronotropic and dromotropic effects. In having such a cardiovascular profile, MCI-154 most resembles milrinone among new cardiotonic agents, although unlike milrinone, its main mechanism of cardiotonic action is believed to be the sensitization of the contractile proteins to Ca2+. Whatever mechanisms are involved, the revealed cardiovascular profile of MCI-154 justifies its clinical trial in the treatment of heart failure.

Animals↗
PubMed1987

Immune responses in newly developed short-lived SAM mice. Selectively impaired T-helper cell activity in in vitro antibody response.

New short-lived strains of mice (SAM-P), which have been developed by Takeda et al. (1981), shows a defective antibody response to T dependent (TD) antigen in vitro, as demonstrated in the accompanying paper (see page 419). In the present study, we investigated the cellular site of the defect, using a cell culture system. In this paper, it is demonstrated that T-helper (Th) cell activity for the antibody response to TD antigen is impaired, while other cellular immune responses, e.g. mixed leucocyte reaction, cytotoxic T-lymphocyte response, and delayed-type hypersensitivity reaction, are normal. These results suggest that the defect in T-helper subset is limited in helper function for the antibody response, and that the helper function for the cell-mediated immune responses is intact. These two functions of the T-helper subset are apparently regulated in a different manner. The SAM-P strains of mice may thus serve as an appropriate model for studying functional heterogeneity in T-helper/inducer cell subsets.

Aging↗
PubMed1987

Immune responses in newly developed short-lived SAM mice. I. Age-associated early decline in immune activities of cultured spleen cells.

Using a cell culture system, age-associated changes in immune activities were investigated in newly developed, short-lived mouse strains. These SAM-P strains of mice (H-2k), which have a remarkably short life span (around 9 months) under conventional breeding conditions, showed an age-associated early decline in several immune functions, as compared to ordinary strains of AKR/J (H-2k) and C3H/He (H-2k) mice. Their antibody-forming capacity to T-independent antigen, DNP-Ficoll, and natural killer (NK) cell activity showed a markedly early onset of regression and a sharp decline from the level of control mice at 2 months of age. SAM-P strains of mice have a profound defect in antibody response to a T-dependent (TD) antigen, such as sheep red blood cells (SRBC), thus there was only a feeble antibody response to SRBC as early as the age of 2 months, and a negligible response at a later age. In contrast, the allo-specific cytotoxic T lymphocyte (CTL) response of the mice was as high as that of control mouse strains at 2 months of age and declined little until at least 6 months of age. The early age-related functional decline in the immune system of SAM-P mice suggests that these new inbred strains are appropriate models for investigating the age-related appearance of immune dysfunctions.

Aging↗
PubMed1986

Neonatal tolerance induction in the thymus to MHC-class II-associated antigens. I. Preferential induction of tolerance to Mls antigens and resistance to allo-MHC antigens.

Neonatal tolerance inducibility of self-major histocompatibility complex (MHC)-class II-associated antigens was compared with that of allo-class II antigens. BALB/c (H-2d, Mlsb) mice, less than 24 hr after birth, were intravenously injected with bone marrow cells of either (BALB/c X DBA/2)F1 (H-2d, Mlsb/a, semiallogeneic at the Mls locus) or (BALB/c X B10.BR)F1 (H-2d/k, Mlsb; semiallogeneic at the MHC), as antigens. The mice were tested for in vivo immune activity of class II-reactive T cells by means of the popliteal lymph node-swelling assay. They developed tolerance, irrespective of type of antigens, showing profoundly suppressed host-versus-graft reaction, and those tolerized to the allo-MHC antigens accepted skin grafts of the corresponding allogeneic mice. In the thymus and spleen of the Mls-tolerant mice, antigen-specific class II-reactive T-cell activity was completely abolished, without the apparent involvement of suppressor cells. In contrast, the activity in allo-MHC-tolerant mice was not reduced in either thymus or peripheral lymphoid organs, suggesting that systemic hyporesponsiveness is attributable to reversible suppression of immune competent cells. The resistance for cell-level tolerance induction to allo-class II antigens may not be ascribed to the active participation of allo-MHC antigens in prevention of or in escape from tolerance induction or both, since an injection of bone marrow cells of both Mls and H-2-semiallogeneic (DBA/2 X B10.BR)F1 (H-2d/k, Mlsa/b) mice could induce tolerance to Mlsa-H-2d antigens in newborn thymus cells.

Animals↗
PubMed1986

Neonatal tolerance induction in the thymus to MHC-class II-associated antigens. II. Significance of MHC antigens in anti-Mls tolerance.

Specificity of anti-Mlsa tolerance induced in BALB/c (H-2d, Mlsb) neonates was investigated by a popliteal lymph node (PLN)-swelling assay for the local graft-versus-host (GVH) reaction by injecting tolerant thymus cells into the footpads of several types of F1 hybrid mice. When thymus cells were obtained from 1-week-old normal BALB/c, they evoked enlargement of PLNs of (BALB/c X DBA/2)F1 (H-2d, Mlsb/a) [CDF1] recipients and of other hybrid recipients, heterozygous in Mlsa,c,d alleles, irrespective of the major histocompatibility complex (MHC) haplotypes. The same thymus cells did not cause the response in MHC-heterozygous F1 hybrids when the hybrids were homozygous in Mlsb, identical with BALB/c mice. Therefore, the PLN response to Mls antigens, known to be closely associated with MHC-class II antigens, was not directed to the class II antigens themselves. This enabled us to examine the effects of MHC on tolerance induction to the Mls antigens. When BALB/c neonates were injected with CDF1 bone marrow cells, complete tolerance to Mlsa-H-2d antigens of CDF1 cells was induced in the thymus, while responsiveness to Mlsa antigens in the context of H-2k and H-2b antigens, was not affected. This indicates MHC-restriction of neonatal tolerance to Mls antigens. Furthermore, when Mls and H-2-heterozygous (BALB/c X AKR)F1 (H-2d/k, Mlsb/a) bone marrow cells served as the tolerogen, thymus cells of BALB/c neonates were also tolerized to Mlsa-H-2k antigens as well as to Mlsa-H-2d antigens, which suggests the involvement of MHC, probably class II antigens of tolerance-inducing cells.

Animals↗