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Biomedical subjects

M Hosono

Publications and source records attributed to M Hosono.

At least 181 records · Page 10Linked to original sources
PubMed1986

Age-related change of spleen cells participating in MHC-homozygous F1 anti-parent mixed lymphocyte reactions.

The stimulatory activity of spleen cells of BALB/c (H-2d) mice in the in vitro proliferative response of spleen cells from the major histocompatibility complex (MHC)-syngeneic (BALB/c x DBA/2)F1 (CDF1) mice increased gradually with the age of the BALB/c mice used, although that for MHC-allogeneic C57BL/6 (H-2b) spleen cells scarcely changed. Cell fractionation experiments indicated that adherent cells and T cells in the F1 responder and in the stimulator, respectively, were requisite for the response. Genetic studies with H-2d-homozygous F1 cells as responders and H-2d-allogeneic and parental cells as stimulators indicated that the response was controlled by an autosomal gene(s), probably by the Mls gene. Then, CDF1 (MLsb/a) anti-BALB/c (Mlsb) response was considered to be the result of Mlsb-T cell response of the irradiated 'stimulator' against Mlsa determinants on adherent cells of the Mlsb/a hybrid mice, or mediated by so-called 'back stimulation'. Thus, the degree of proliferative response in CDF1 anti-BALB/c was well correlated with that in BALB/c anti-CDF1, and increased with age of the BALB/c mice, indicating an age-related increase of T cell response to non-MHC antigens probably in association with self-MHC class II antigens. On the other hand, the anti-allo-MHC class II activity scarcely changed during adult life. These results indicate that self- and allo-class II reactive T cell compartments fluctuate under different mechanisms in terms of T cell repertoire in aging animals.

Aging↗
PubMed1985

On the degradation of dermorphin and D-Arg2-dermorphin analogs by a soluble rat brain extract.

Degradation of dermorphin, [D-Arg2]dermorphin and [D-Arg2, Gly3, Phe4]dermorphin in a soluble rat brain extract was examined. The former two heptapeptides were degraded in a similar fashion to produce corresponding N-terminal tetrapeptide as the main degradation product along with the parallel release of Tyr5, Pro6 and Ser7-NH2. Tyr-D-Arg-Phe-Gly showed a good enzymatic stability. When captopril, an angiotensin-converting enzyme inhibitor, was present in the incubation mixture, hydrolysis of the Gly4-Tyr5 bond was markedly suppressed and resulted in release of the corresponding N-terminal hexapeptide as the main degradation product. Combined use of captopril and amastatin, an aminopeptidase inhibitor, markedly suppressed the hydrolysis of these peptides. On the other hand, [D-Arg2, Gly3, Phe4]dermorphin was hydrolyzed easier than the other two heptapeptides and considerable amounts of Tyr1 and Phe4 were released after 20 hr incubation while the N-terminal tetrapeptide, Tyr-D-Arg-Gly-Phe, showed a good enzymatic stability. On the basis of these results, possible degradation pathways of these heptapeptides were discussed.

Amino Acids↗
PubMed1985

The analgesic activity of D-Arg2-dermorphin and its N-terminal tetrapeptide analogs after subcutaneous administration in mice.

D-Arg2-dermorphin and its nineteen N-terminal tetrapeptide analogs were prepared, and their analgesic activities after subcutaneous administration in mice and the stability of a D-Arg2-dermorphin tetrapeptide to enzymatic degradation were examined. The analgesic effect was assessed by the tail pressure test. D-Arg2-dermorphin was found to have analgesic potency equal to or slightly greater than that of dermorphin. In a series of tetrapeptide analogs, a very pronounced activity greater than that of morphine was observed for analogs of the following structure, H-Tyr-D-Arg-Phe-X-OH (X = Gly, sarcosine and D-Ala) or its esters. Replacement of D-Arg2 by D-Arg(NO2), D-homoarginine or D-Lys resulted in a decrease in potency, suggesting that the guanidino group and side chain length of D-Arg2 are of great importance for a higher activity. D-Arg2-tetrapeptide (H-Tyr-D-Arg-Phe-Gly-OH) was found to be more stable than the parent tetrapeptide (H-Tyr-D-Ala-Phe-Gly-OH) to cleavage both by aminopeptidase M and by carboxypeptidase Y.

Analgesics, Opioid↗
PubMed1985

Ontogeny of 'macrophage' function. V. Differential effect of prostaglandin E2 on the activation of newborn and adult mouse macrophages.

Our previous papers indicate that peritoneal exudate macrophages (PM) of newborn mice are strongly suppressive for the tumor cell growth in comparison with those of adult mice. Neither newborn PM nor adult PM are cytolytic, but they both can be activated to be cytolytic by being cultured overnight either with a high concentration of bacterial lipopolysaccharide (LPS) or with a low concentration of LPS plus lymphokine. This paper shows that the activation of adult PM was inhibited by prostaglandin E2 (PGE2) added simultaneously with LPS, though that of newborn PM was not affected by PGE2. Adult PM, however, acquired the resistance to PGE2 by the preculture with LPS and/or lymphokine for 4 hr so as to be activated by LPS in the presence of PGE2. These results indicate that newborn PM are more activated than adult PM to a state which adult PM attain after moderate activation with LPS or lymphokine.

Age Factors↗
PubMed1985

Antinociceptive properties of a new tetrapeptide, Asn-Ala-Gly-Ala, in mice.

The effect of intracerebroventricularly (i.c.v.) administered Asn-Ala-Gly-Ala (NAGA), a partial sequence of beta-lipotropin, was investigated using the tail-pressure, hot-plate and phenylbenzoquinone (PBQ)-induced writhing tests in mice. I.c.v. administration of NAGA produced a dose-dependent inhibition of responses as measured by the three different assays. The ED50 of NAGA on the tail-pressure test did not differ from that obtained on the hot-plate test. NAGA showed a prominent reduction in activity on the PBQ writhing as compared with the hot-plate and tail-pressure tests. A low dose of naloxone (0.1-1.0 mg/kg, s.c.) resulted in a dose-dependent antagonism of the effect of NAGA in all assays. These data suggest that the antinociceptive effect induced by NAGA may involve the endogenous opioid system in mice.

Analgesics↗
PubMed1984

Autostimulatory lymphoid cells in aging mice: induction of syngeneic host-versus-graft reaction by radioresistant adherent cells in normal recipients.

When young (6-week-old) BALB/c and also young C57BL/6 mice were inoculated into footpads with spleen cells from normal, syngeneic, aged donors, their response to the inoculum resulted in the enlargement of popliteal lymph nodes (PLN). The degree of PLN enlargement increased as the age of donor mice increased up to age one year. Spleen and lymph node cell populations were highly effective in eliciting the PLN enlargement. Thymus cells and bone marrow cells were moderately effective, but erythrocytes were ineffective. Resident peritoneal exudate cells and spleen adherent cells were much more effective than a whole spleen cell population. The syngeneic response seems to be attributable to a host-versus-graft reaction, since the PLN response was not affected by 2000 rad irradiation of inoculum cells and since the nylon wool-passed spleen T cell population was ineffective as the stimulator. The response was significantly reduced 3 weeks after thymectomy of recipients. PLN enlargement was also observed in older (7-month-old) mice which received spleen cells of younger mice. In this case, however, the response is ascribable to a graft-versus-host reaction, since the inoculation of radiosensitive spleen T cells into footpads resulted in the PLN enlargement. On the other hand, such a stimulatory activity was not found in either lymph node cells or thymus cells. These results suggest that the antigenicity of adherent cells changes with age and that the change is discernible by spleen-locating and short-lived T cells of young mice.

Aging↗
PubMed1984

Autostimulatory adherent cells in the spleen of aging mice: characterization in the syngeneic host-versus-graft reaction.

Enlargement of the popliteal lymph node (PLN) of 6-week-old mice were elicited by the footpad injection of spleen cells of sex-matched, syngeneic, older mice, but not of 6-week-old mice, in a fashion of host-vs.-graft reaction. Effective stimulating cells in the inoculum seem to be Ia-bearing adherent cells. On the other hand, neither B and T cells nor immunoglobulin-secreting cells were effective for host T cell stimulation. Among nonlymphocytic adherent cells, only those attached to plastic dishes after a 24 h-incubation, enriched in macrophages, showed the stimulatory activity for the young recipients, while cells which had adhered once but detached and became non-adherent during a 24 h-incubation or a crude non-macrophage fraction did not induce the PLN response. Thus, the age-related antigenic change may occur on macrophages but not on dendritic cells. The effective cells should be alive, heat-killed cells being impotent to elicite the response. Such spleen adherent cells of aged mice were found to be also stimulative for age-matched recipients, when they are older than 3 months. Autostimulation by macrophages might be responsible, at least in part, for the age-related change of immune functions.

Aging↗
PubMed1984

Distinctive effect of angiotensin II on prostaglandin production in dog renal and femoral arteries.

The effect of angiotensin II (Ang II) on prostaglandin (PG) production in dog renal and femoral vasculature was examined in vivo and in vitro. In pentobarbital anesthetized dogs, the reduction of blood flow induced by intra-arterial infusion of Ang II was potentiated by pre-treatment with indomethacin (5 mg/kg) in the renal but not the femoral vasculature. Isolated renal and femoral arterial strips were incubated and the release of PGE2 and PGI2 (as 6-keto-PGF1 alpha) into the medium was measured by radioimmunoassay. Basal PGE2 and PGI2 production by renal and femoral arterial strips was approximately the same. PGI2 production was predominant for both strips. Ang II stimulated PG production in renal but not femoral arteries. In the renal artery, Ang II-induced PG production was inhibited by indomethacin (10(-6) M), mepacrine (10(-4) M) and saralasin (10(-6) M). These results suggest that Ang II stimulates PG production by the renal artery per se and the Ang II receptor is linked to phospholipase A2 in the renal but not the femoral artery.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Differential distribution of tolerogenic bovine gamma-globulin in lymphoid tissues.

Deaggregated, tolerogenic bovine gamma-globulin was traced after intravenous injection into DDD mice. Amount of organ-distributed tolerogen varied among lymphoid organs such as spleen, thymus, axillary lymph node and femur bone marrow, probably depending on the amount of blood supply. On the other hand, the tolerogen elimination rate (TER) in these organs was almost the same as TER in blood, the half life being 2.6 days. Although the TER of tissue-associated tolerogen and of cell-associated tolerogen were also almost the same as that in blood, relative amount of cell-associated tolerogen differed among organs, the antigen amounts being 77 times higher in lymph node cells and 4 times higher in spleen and bone marrow cells than in thymus cells. These results are discussed in relation to the difference in the tolerance inducibility among lymphoid organs reported previously.

Animals↗
PubMed1984

Ontogeny of antigen-presenting activity of haptenized cells in mice: early development of syngeneic T cell-stimulatory cells in thymus.

Trinitrophenyl (TNP)-modified thymus cells stimulated the proliferation of syngeneic spleen T cells in in-vitro culture supplemented with syngeneic normal mouse serum. The stimulatory activity of the TNP-adult thymus cells was about a half of that of TNP-adult spleen cells. Neither thymus cells depleted of adherent cells before haptenization nor TNP-thymus cells treated with anti-Ia antiserum served as stimulators. TNP-thymus cells, but not TNP-spleen cells, prepared from cells of newborn mice within one week after birth were almost as competent as adult TNP-thymus cells. TNP-spleen cells first became effective when spleen cells were obtained from mice at the age of 3 weeks. Ineffectiveness of the newborn spleen cells is not due to immunosuppressive function. These results indicate that Ia-bearing antigen-presenting cells appear earlier in the thymus than in the spleen. The intrathymic Ia+ adherent cells, however, seem not to be autonomously potent for accessory cell function, since haptenized thymus cells were not able to stimulate T cells if adherent cells were removed from the responder cells. This suggests that the second type of adherent cells residing in spleen but not in thymus is required for the activation of T cells in response to TNP-thymic adherent cells.

Aging↗
PubMed1982

The use of phagocytic peritoneal exudate cells as targets for the estimation of cytotoxic T cell activity.

A new method for measuring cytotoxic T lymphocyte (CTL) activity has been developed with peritoneal exudate cells (PECs) as target. A monolayer of target PECs was labelled with Indian ink and exposed to CTL. After incubation, detached or damaged PECs were rinsed out of the target monolayer, and the remaining phagocytes were fragmented and dissolved by the addition of 2 N NaOH. The number of undamaged target cells was estimated by colorimetric reading of the amount of Indian ink in the phagocytes surviving CTL attack. In studies with several strains of mice, only PECs from the same strain as the stimulator cell donors used for CTL induction were damaged by CTL effectors. When CTLs generated against TNP-modified syngeneic stimulators were used as effectors TNP syngeneic PECs, but neither unmodified syngeneic PECs nor allogeneic TNP-PECs, were damaged. These results demonstrate the antigen specificity of immunolysis of PECs. Macrophage target cells were stable and showed no tendency to spontaneous cell damage during 24 h incubation without effector cells.

Animals↗
PubMed1980

Plasmid-controlled mercury biotransformation by Clostridium cochlearium T-2.

A strain of Clostridium cochlearium having methylmercury-decomposing ability was isolated. The ability was cured by the treatment with acridine dye and recovered by the conjugation of the cured strain with the parent strain. The cured strain then showed the activity to methylate mercuric ion as previously reported (M. Yamada and K. Tonomura, J. Ferment. Technol. 50:159-166, 1971). These results and the agarose gel electrophoretic pattern of the deoxyribonucleic acids from the lysates indicate a possible role of plasmids in controlling the mercury biotransformation of the two opposite directions in a single bacterial strain: methylation in the absence of the plasmid and demethylation in the presence of it. A possible mechanism for mercury resistance involving hydrogen sulfide is discussed.

Biotransformation↗