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Biomedical subjects

T Makinodan

Publications and source records attributed to T Makinodan.

At least 55 records · Page 3Linked to original sources
PubMed1985

Comparison of the radiosensitivity of interleukin-2 production between species, between tissues, and between young and old individuals.

The radiosensitivity of interleukin-2 (IL-2) production was assessed of (a) peripheral blood mononuclear cells (PBMC) of young humans, dogs, and mice (C57BL/6); (b) PBMC and splenic cells of young mice; and (c) PBMC of young and old humans and the splenic cells of young and old mice. The results indicate that (a) large differences in radiosensitivity exist between the PBMC of humans, dogs, and mice (e.g., the radiation doses which resulted in 37% remaining IL-2 activity (D37) of human, dog, and mouse PBMC were 3771, greater than 10,000, and 1398 rads, respectively); (b) only a small difference exists between the PBMC and splenic cells of mice; and (c) no difference exists between the PBMC of young and old humans and between splenic cells of young and old mice. Topological abnormalities, as judged by scanning electron microscopic analysis, could not be detected in dog PBMC after their exposure to 1800 rads, but could be detected in mouse PBMC after their exposure to 400 rads.

Adult↗
PubMed1985

Age-related changes in immunologic and hormonal activities.

The immune system has been a focus of intensive gerontological research, because it appears to be involved in many deleterious diseases associated with ageing, including cancer, and because the likelihood of successful therapeutic strategies for altered immune functions in the elderly is high. Research efforts have been centred on two levels of biological complexity--the cell and the organism. At the cellular level, emphasis has been on the nature of the alteration in immune functions with age, and, at the level of the organism, whether the diseases associated with immunological dysfunction of elderly individuals can be controlled by immunomodulation. We discuss age-related changes at the cellular level with emphasis on qualitative changes in the antigen/mitogen responsive cells with respect to production of and response to hormones. We then consider whether ageing 'hot spots' exist along the differentiation vector of antigen/mitogen responsive cells; i.e., whether immune cells are vulnerable to ageing only at certain stages of their differentiation processes. We conclude by considering the use of tissue grafting and chemical treatment, the two most encouraging methods of immunopotentiation at the level of the organism, as an option in modulating resistance of old individuals to cancer.

Aging↗
PubMed1985

Change in the metastatic mode of B16 malignant melanoma in C57BL/6 mice with ageing and sex.

An attempt has been made to determine whether changes in the host environment due to ageing or sex differences can influence the metastatic mode of malignant tumours. B16-F10 melanoma cells with a high pulmonary metastasizing potential were injected into the outer ear of C57BL/6 mice; the growth of primary tumour and metastasis of the cervical node were assessed every two days, and the number of lung compared; and in the second young male and female mice were used. The rate of growth of primary tumours was found to be comparable between young and ole mice. Metastasis in the cervical lymph node occurred earlier in old than in young mice. Lung metastases occurred earlier in old than in young mice, but their growth was slower in old than in young mice. Metastasis in the cervical node occurred earlier in males than in females. More lung metastases were found in male than in female mice.

Aging↗
PubMed1985

Influence of age on the production and regulation of interleukin-1 in mice.

The decrease in T-cell proliferation with age is due, in part, to the decline in the production of IL-2. Since IL-1 is needed to trigger IL-2 production, we determined the IL-1 producing capacity of peritoneal macrophages of young (2-4 months) and old (24-26 months) BALB/c and C57BL/6 mice. Mice were stimulated with LPS, and their peritoneal macrophages were obtained 3 days later, purified, and assessed for IL-1 production by coculturing them with splenic T cells at a ratio of 1:5 in the presence of LPS. Supernatants were obtained 4 days later when the PGE2 and IL-2 activities were minimal and IL-1 activity maximal. IL-1 activity was assessed for their ability to augment the proliferative activity of indicator thymocytes in their response to PHA stimulation. The results revealed that (i) IL-1 production by cells of old BALB/c and C57BL/6 mice is reduced to about 40% and 30% that of young mice, respectively; (ii) indomethacin enhances IL-1 production by cells of both young and old mice to the same extent; and (iii) reduction in the IL-1 producing capacity by cells of old mice results from altered activities of both the IL-1 producing peritoneal macrophages and the augmenting T cells.

Aging↗
PubMed1984

Different metastatic modes of malignant melanoma implanted in the ear of young and old mice.

An attempt has been made to determine (a) whether aging plays an important role in resistance against metastasis and (b) whether dithiothreitol, an effective in vitro mitogenic potentiator of splenic cells of young and old mice, can modulate the occurrence of pulmonary metastasis. B16-F10 melanoma cells were injected into the outer ear of young and old female C57BL/6 mice; and the growth of the primary tumor, the palpable size of the cervical lymph node, and the number of lung metastases were then determined at various intervals. The ear was amputated when the primary tumor reached 4 mm in mean diameter. The following results were obtained. (a) The growth rate of the primary tumor in young mice is comparable to that in old mice. (b) Enlargement of the cervical lymph node occurs earlier in old than in young mice. (c) Old mice are more vulnerable to pulmonary metastases, but small metastasized pulmonary colonies are more prominent in old than in young mice. (d) Dithiothreitol (100 micrograms) injected every 2 days after the inoculation of tumor cells is effective in reducing the incidence of pulmonary metastases in old mice.

Aging↗
PubMed1984

Influence of age on the ability of thymic adherent cells to produce factors in vitro which modulate immune responses of thymocytes.

Thymic adherent cells from BALB/c mice ranging in age from 1 day to 20 months were cultured in vitro for 1 month. The supernatants, collected at weekly intervals, were assessed for their ability to augment the antigen/mitogen responses of thymocytes from 2- or 4-week-old BALB/c mice and spleen cells from 3-month-old nude BALB/c mice. The results indicate that (a) the ability of thymic adherent cells to produce an augmenting factor(s) declines sharply between 2.5 and 5 months of age; (b) thymic adherent cells of 1-day-old mice synthesize an inhibitory factor(s) in addition to the augmenting factor, while those of young adult mice synthesize only the augmenting factor, and those of 20-month-old mice synthesize primarily the inhibitory factor; (c) supernatants containing the augmenting factor can be neutralized by mixing them with supernatants containing the inhibitory factor; (d) thymocytes which are responsive to the augmenting factor are immature as judged by their sensitivity to dexamethasone and by their ability to bind macrophages; and (e) spleen cells of normal and nude mice are not responsive to either the augmenting or the inhibitory factor of the supernatant.

Aging↗
PubMed1984

Differential effects of age on mitotically active and inactive bone marrow stem cells and splenic T cells in mice.

Young and old BALB/c mice and thymectomized young mice were subjected to continuous exposure of 6-thioguanine (6-TG), and the numbers of their bone marrow spleen colony-forming units (CFU-S) and in vitro culture colony-forming units (CFU-C) and the number and mitogen-induced proliferative activity of their splenic T cells were determined at various time intervals. The results indicated that (a) old mice have seven times more 6-TG-resistant (6-TGr) CFU-S than young mice, (b) the mitogen-induced proliferative activity of 6-TGr T cells is comparable to that of 6-TG-sensitive (6-TGs) T cells of both young and old mice, and (c) 6-TGr CFU-S and T cells are resistant to 6-TG because they are mitotically inactive and not because they are drug-resistant mutants.

Aging↗
PubMed1984

Immunologic basis for susceptibility to infection in the aged.

Age-related immune dysfunction contributes to the vulnerability of old individuals to infection, e.g., animal model studies demonstrate the association between age-related decline in T cell-dependent immunologic responses and the decline in resistance against viral, bacterial, and parasitic infections. This review briefly describes age-related changes in the immune system at the systemic, tissue and cellular levels. At the systemic level, emphasis is on polymorphic effects of aging; at the tissue level, emphasis is on the vulnerability of primary tissues engaged in the generation of antigen-responsive cells and on the difference in the onset and rate of changes between different peripheral tissues of the system; and at the cellular level, emphasis is on the qualitative changes at the surface receptor, cytoplasmic and nuclear levels.

Aged↗
PubMed1984

Influence of conditioned psychological stress on immunological recovery in mice exposed to low-dose X irradiation.

A study was initiated to determine the effects of psychological stress on the immune response in BALB/c mice recovering from exposure to a low dose of ionizing radiation. Mice were first subjected to conditioning training for 12 days, then exposed to 200 R, subjected to psychological stress for 14 days, and assessed for peak anti-sheep RBC response. The seven treatment groups included two unirradiated groups and five irradiated groups. Mice exposed to 200 R and then subjected to conditioned psychological stress responded less vigorously to antigenic stimulation than those of the other irradiated groups. The psychological stress imposed upon these mice did not influence the antibody-forming capacity of unirradiated mice. These results indicate that a psychological stress which did not affect the immunological activity of unirradiated mice can curtail the immunological recovery of mice exposed to low doses of ionizing radiation.

Animals↗
PubMed1983

Natural cell-mediated cytotoxicity among A-bomb survivors residing in the United States.

Natural cell-mediated cytotoxicity (NCMC) by lymphocytes from Japanese atomic bomb survivors now living in the United States was measured. Seventy-one individuals were exposed to an estimated '0.00' Gy ('0 rads') (S0 group) and 58 to greater than '0.00 Gy' (S+ group) at the time of the bomb. Of this 58, 51 (88 per cent) received less than 0.50 Gy and 30 (52 per cent) received less than 0.10 Gy. NCMC was measured against 51Cr-labelled K562 target cells. Activity by lymphocytes from S+ group donors was significantly greater than that for the S0 group (p = 0.028 by the stratified Wilcoxon rank-sum test). This difference between the S+ and S0 populations was detected 35 years after exposure to the bomb. It is therefore feasible and important to examine appropriate biologic parameters to elucidate the effects of low doses of radiation in humans.

Aged↗
PubMed1983

Immune function in aging atomic bomb survivors residing in the United States.

Immunologic parameters were studied among survivors of the 1945 atomic bombs who now reside in the United States. Of all known survivors living in the U.S., about 40% (n = 189) participated in this study. Of those survivors on whom radiation exposure information was available (n = 168), 96% were exposed to less than 50 rad at the time of the bomb (ATB). Survivors were divided into two groups; those exposed to varying low doses of radiation (S+ group, exposed at less than or equal to 2500 m from the hypocenter) were compared with those exposed to "O rad" (S0 group, exposed at greater than 2500 m from the hypocenter). Of the former group, 92% were exposed to less than 100 rad and 89% to less than 50 rad ATB. Cellular immune responses, including natural cell-mediated cytotoxicity (NCMC), interferon production, and the mitogenic response to PHA, tended to be higher among S+ individuals, although only the difference for NCMC was statistically significant. This was suggestive of a trend which was consistent with the higher serum interferon levels and lower frequencies of detectable immune complexes and antimitochondrial antibodies among the S+ group, although these differences were not statistically significant. Other immunologic parameters which showed no trend included frequency of antinuclear antibodies, rheumatoid factor, levels of serum immunoglobulins, levels of isoantibodies and heteroantibodies, and the magnitude of the mixed lymphocyte reaction.

Adolescent↗
PubMed1982

Requirement of 2-mercaptoethanol for in vitro growth factor production by T cells and vulnerability of the response to age.

The effects of 2-mercaptoethanol and age on spleen cells derived from young (3-4 months) and old (24-months) C57BL/6 mice were measured with respect to T cell growth factor or Interleukin 2 production. It was shown that: (A) 2-mercaptoethanol (or some homologue) is absolutely required for T cell growth factor production in vitro by murine cells (the optimum concentration is 5 X 10(-5) M for both young and old cells); (B) old cells are less responsive to suboptimum concentrations than young cells but their responses are not reduced to the same degree as young cells by supraoptimum toxic doses of 2-mercaptoethanol; and (C) at optimum 2-mercaptoethanol concentrations young and old cells have similar kinetic responses for T cell growth factor production and the accumulation of the T cell growth factor reaches a maximum between 18 and 24 hours. Considerations are presented of 2-mercaptoethanol (or some homologue) in its role as an important reactant in the production of T cell growth factor and in its susceptibility to aging.

Aging↗
PubMed1982

Restoration of impaired immune functions in aging animals. VI. Differential potentiating effect of 2-mercaptoethanol on young and old murine spleen cells.

The differential effect of 2-mercaptoethanol (2-ME) on spleen and bone marrow cells of young and old mice was determined in vitro. Both the ability of spleen cells to proliferate and to generate Ig-secreting cells and the capacity of bone marrow cells to generate myeloid colonies were assessed. All three activities assessed in both young and old mice were enhanced by the presence of 2-ME, but a differential effect with respect to age was noted in only one. This was the polyclonal activating antibody response to bacterial lipopolysaccharide (LPS) in which 2-ME enhanced young spleen cells to a greater extent than old spleen cells, although their mitogenic responses to LPS were enhanced to the same extent. The ability of 2-ME to enhance old spleen B cells to proliferate but not differentiate in their response to LPS would suggest that aging alters certain subpopulations of spleen cells, some of which are sensitive and others insensitive to the potentiation effects of 2-ME. The enhancing action of 2-ME on the proliferative activity of LPS-stimulated young spleen cells was reduced drastically by decreasing the number of T cells by prior treatment of spleen cells with anti-T cell reagent. The proliferative activity was then brought back to normal pretreatment level by adding enriched T cells. Therefore it would appear that regulatory T cells are the target of the enhancing action of 2-ME. The failure of old spleen cells to respond vigorously to the polyclonal activating action of LPS and 2-ME individually and in combination would indicate that age-related alterations may be taking place in the B cells and/or the regulatory cells. Young-old spleen cell mixture study indicates that there are regulatory cells in old spleen cells which can inhibit B cell differentiation but not B cell proliferation.

Adjuvants, Immunologic↗
PubMed1982

Role of T cells and adherent cells in age-related decline in murine interleukin 2 production.

Spleen and lymph node cells from young (3 to 4 months) and old (24 to 36 months) mice of two inbred lines and one hybrid stock were assessed for the effect of age on IL 2 production. The results revealed that the production of IL 2 by old spleen and lymph node cells is reduced to 42% that of young cells. Cell counting, IL 2 inhibition and absorption, and cell mixture studies were then performed to determine the basis for the reduced IL 2 production. Cell counting studies revealed that the reduced IL 2 production by old cells cannot be caused by a decrease with age in the total number of Lyt 1+ T helper cells or by an increase with age in Lyt 2+ T suppressor cells. IL 2 inhibition, IL 2 absorption, and young-old spleen cells mixture studies revealed that the decrease in the level of IL 2 activity with age is caused neither by the formation of excessive amounts of soluble IL 2 inhibitors, by the generation of excessive numbers of IL 2 responsive blast cells, nor by an increase in suppressor cells. Further cell mixture studies revealed a decrease in IL 2 production by young T cells in presence of old adherent cells, which did not approach that of the old T cell-old adherent cell mixture, and an increase in IL 2 production by old T cells in the presence of young adherent cells, which did not approach that of the young T cell-young adherent cell mixture. These results would indicate that the decline in activity of both the T cells and adherent cells involved in IL 2 production are responsible for the reduction. Finally, it was found that the reduced proliferative activity of Con A-stimulated old spleen cells can be enhanced to the same extent as that of young spleen cells by exposing them to exogenous IL 2.

Age Factors↗
PubMed1981

Cellular and molecular aspects of immune system aging.

We begin with a brief discussion of the importance and advantages of immune studies to the problem of aging. This is followed by a short over-view of immune system aging at the systemic level. The major portion of the article is a review of observation, both at the cellular and molecular level, of changes in aging immune cells, with sections on intercellular communication, membrane phenomena, cyclic nucleotides, and molecular genetic changes.

Adolescent↗