Biomedical subjects
Publications and source records attributed to T Tanigawa.
In vitro quantitative biosynthetic studies were carried out on bone marrow cells obtained from an eleventh case with gamma heavy chain disease. The findings indicate that neither cytoplasmic nor extracellular degradation was responsible for the presence of the gamma heavy chain fragment in serum. The absence of a covalent-bound light chain was also confirmed.
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Recently, we reported that intraportal (IP) injection of donor spleen cells (SPCs) before transplantation as well as at the time of transplantation significantly prolongs cardiac allograft survival in rats (7). Long-term establishment of chimerism induced by intraportal administration of SPCs could be a part of this prolongation. In this study, we examined the effect of irradiation of SPCs as a source of donor antigens on cardiac allograft survival. Experiments were carried out using DA (RT1a) as the donor and BUF (RT1b) as the recipient strain. Fifty million irradiated or nonirradiated SPCs were injected either intravenously (i.v.) or intraportally (i.p.) on day -10 or day 0, the day of cardiac allografting. Untreated animals rejected allografts within a mean survival time (MST) of 7.2 +/- 0.8 days (n = 5). Injection (i.p.) of SPCs on both day -10 (n = 4) and day 0 (n = 6) induced significant prolongation of MST over the control (19.0 +/- 4.7, 14.2 +/- 2.1 days; p < 0.001 vs. control), while i.v. injection of SPCs on either day -10 (n = 4) or day 0 (n = 4) failed to do so (9.2 +/- 1.0, 8.5 +/- 0.6 days). Significant prolongation was still observed when irradiated SPCs were injected on day -10 (n = 4; MST: 19.0 +/- 5.4 days, p < 0.002 vs. control), but not when injected on day 0 (n = 5; MST: 9.4 +/- 2.1 days). These data suggest that the immunosuppressive effect of i.p. injection of donor SPCs could be induced by differential mechanisms according to the timing of inoculation of donor antigens.
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The authors examined the effects of organic solvents on lymphocyte subpopulations in blood. Natural killer and T-lymphocyte subpopulations and B (CD19+) -lymphocytes were measured with flow cytometry in 16 male rotogravure printers on a Friday and on the following Monday. Numbers of all 3 subpopulations of natural killer cells (i.e., CD57+ CD16+, CD57- CD16+, and CD57+ CD16- cells), 2 subpopulations of T lymphocytes (CD4+ CD45RA+ and total CD8+ cells), and total lymphocytes on Friday were significantly fewer than those found on the following Monday. Conversely, the number of B lymphocytes on Friday was significantly larger than the number on Monday. The number of B lymphocytes was significantly correlated with blood toluene levels on Friday. The alteration in the number of CD57+ CD16+ NK cells from Friday to the following Monday was correlated inversely with the corresponding change in exposure level of toluene on Friday. The authors suggest that the effects of mixed organic solvents (primarily toluene) are recoverable decreases of natural killer cells and T lymphocytes and increases in B lymphocytes.
T lymphocyte subpopulations (CD4+, CD8+, and CD3+ cells), Leu 11a-(CD16) positive lymphocytes, and total lymphocytes in peripheral blood in 52 male dyestuff workers were analyzed to determine the effects of benzidine and beta-naphthylamine on the human immune system. The workers had been exposed prior to 1972 to benzidine and beta-naphthylamine (aromatic amines) at a chemical plant. The dyestuff workers included 27 workers who had engaged in production of aromatic amines (i.e., high-exposure group) and 25 workers who had handled dyestuff at their job (low-exposure group). The total and relative numbers of CD4+ and CD3+ T lymphocytes in the high-exposure group were significantly lower than those found in the control (no-exposure) group (p < .01). Relative--but not total--number of CD16+ lymphocytes in the high-exposure group was significantly higher than in the control group (p < .05). However, there were no significant differences between the low-exposure group and control group with respect to all T lymphocyte subpopulations, CD16+, and total lymphocytes. Perhaps the number of circulating CD4+ T lymphocytes decreases in workers exposed to aromatic amines. It is concluded that measurement of CD4+ lymphocytes provides a useful biological marker of past exposure to aromatic amines.
Previously, we reported a decrease of CD4+ T lymphocytes in workers exposed to benzidine and beta-naphthylamine, which are aromatic amines. In the present study, CD4+ T lymphocyte subpopulations (i.e., CD4+CD45RA+ and CD4+CD29+ cells), total CD4+ T lymphocytes, and CD8+ T lymphocytes were measured in 78 male dyestuff workers who had been exposed to aromatic amines. The aromatic amine workers consisted of 40 individuals who had engaged in production of aromatic amines (high-exposure group) and 38 workers who had handled only dyestuff in their job (low-exposure group). The control group consisted of 30 healthy male volunteers who were working at the same factory and who did not have a history of occupational exposure to aromatic amines or to other hazardous chemicals. The absolute and relative numbers of CD4+CD45RA+ (suppressor-inducer) T lymphocytes in the high-exposure group of aromatic amine workers were significantly lower than those in the control group, after controlling for the effects of age by the analysis of covariance. Similarly, the relative, but not absolute, number of total CD4+ T lymphocytes in the high-exposure group of aromatic amine workers was significantly lower than that found in the control group. It is suggested that the CD4+CD45RA+ T lymphocyte is a major site of the effects of aromatic amines on lymphocyte subpopulations.
To examine the effects of smoking on lymphocyte subpopulations, we measured the following cell subpopulations: CD4+ T-cell subpopulations (i.e., CD4+CD29+, CD4+ CD45RO+, and CD4+CD45RA+ cells); CD8+ T-cell subpopulations (i.e., CD8+CD11a+ and CD8+CD11b+ cells); and natural killer cell subpopulations (i.e., CD16+CD57-, CD16+CD57+, and CD16-CD57+ cells). We measured these subpopulations, together with total CD4+ T, total CD8+ T, total CD3+ T, B (CD19+), and total lymphocytes, in 10 male heavy smokers, 38 male light-to-moderate smokers, and 33 male nonsmokers. The mean ages were 30 y, 31 y, and 32 y, respectively, and ages did not vary significantly among the smokers. CD4+CD29+ and CD4+CD45RO+ (memory T) cells in heavy smokers were significantly more numerous than those in light-to-moderate smokers and nonsmokers. Also, these memory T-cell subpopulations were significantly more numerous in light-to-moderate smokers than in nonsmokers. The number of CD4+CD45RA+ (naive T) cells was significantly larger in heavy smokers than nonsmokers; numbers of CD4+CD45RO+ T and CD4+CD29+ T cells (memory T cells) were significantly correlated with daily cigarette consumption. Numbers of CD3+ T, CD4+ T, CD19+ B, and total lymphocytes in heavy smokers were significantly larger than in nonsmokers. There were significantly more CD3+ T, CD4+ T, and total lymphocytes in light-to-moderate smokers than in nonsmokers. The numbers of CD4+ T lymphocytes in heavy smokers were significantly larger than in light-to-moderate smokers. Perhaps CD4+ T cell subpopulations, especially memory T cells, are most susceptible to the effects of smoking on lymphocyte subpopulations.
Approximately 10-30% of the Japanese population suffer from Japanese cedar (Cryptomeria japonica) pollinosis in the spring. To date, the effects of this pollinosis on lymphocyte subpopulations have not been examined epidemiologically. To examine the effects of smoking and Japanese cedar pollinosis on lymphocyte subpopulations, we used flow cytometry to measure CD4+ and CD8+ T-lymphocyte subpopulations, natural-killer cell subpopulations, B(CD19+) lymphocytes, and total lymphocytes in 61 smokers and 51 nonsmokers. Some of these individuals had histories of pollinosis during November 1993-an off-season for Japanese cedar pollination. Our findings suggested that (a) CD4+ T-lymphocyte subpopulations (i.e., CD4+CD29+, CD4+CD45RA+, and CD4+ CD45RO+ cells) together with total CD4+ T, total T, and total lymphocytes, were increased by the effects of smoking; (b) CD8dim+CD11a+T, and CD8+CD11bt, and CD57+CD16+ natural killer cells, together with total CD8+CD11 a+ T and total CD8+ T lymphocytes, were increased by the effects of pollinosis on smokers, even though no lymphocyte subpopulations were increased by only the pollinosis effects; (c) CD4+CD29+T and CD8dimCD11a+ T lymphocytes were increased by the effects of smoking on pollinosis, and (d) CD4+CD29+ T and CD4+CD45RO+ T lymphocytes, CD8dim+CD11 a+ T, and CD8+CD11b+ T lymphocytes and CD57+CD16+ natural killer cells, together with total CD4+ T, total T (CD3+), total CD8+CD11a+, total CD8+ T, and total lymphocytes, were increased by the combined effects of smoking and pollinosis.
The localization of endothelin (ET)-1/big ET-1, ET-3/big ET-3, ET-A and ET-B receptor was immunohistochemically examined in human adrenal glands composed of 36 normal cases, nine hyperplasia, 70 adenomas and seven carcinomas of cortical cells. In normal adrenals, ET-1/big ET-1 and ET-B receptor were regularly detected in the cortical cells, especially in the zona fasciculata for ET-1 and zona glomerulosa for ET-B receptor but not in the medulla, while ET-A receptor localized occasionally in endothelial cells or rarely in cortical cells and ET-3/big ET-3 was very limited in the cortical cells. In hyperplasia, adenoma and carcinoma, ET-1/big ET-1 and ET-B receptor showed frequent localization, although focal distribution of the ET-B receptor was rather predominant in these groups. ET-A receptor and ET-3/big ET-3 were very infrequently expressed. Functioning versus non-functioning and hypertensive versus normotensive cases revealed no significant differences in the frequency of positive cells for ET-1/big ET-1, ET-3/big ET-3, ET-A receptor or ET-B receptor. Alternatively, the frequency of immunoreactivity to ET-1/big ET-1 or ET-B receptor significantly decreased in hyperplasia, adenoma and carcinoma, when compared with that of normal adrenal cortex. The present study, therefore, indicates that ET-1/big ET-1 and ET-B receptor are a prevalent ligand-receptor system in normal and hyperplastic/neoplastic adrenocortical cells, even with a malignant profile, and may contribute in maintaining adrenocortical cell function or cell viability but not cell growth or systemic hypertension.
To examine the effects of uncontrollable and controllable electric shocks on the immune system in rats, the proportion of CD4+, CD8+ or CD25+ T lymphocytes to total lymphocytes was measured in the peripheral blood, spleen, and thymus. The rats were given either controllable shocks, identical uncontrollable shocks, or no shocks, and then small shocks 24 h later (reinstating shocks). The proportion of CD4+ T lymphocytes relative to total lymphocytes in both the peripheral blood and spleen of uncontrollable rats (URs) was significantly smaller than was found in no-shock rats (NRs). Similarly, the proportion of CD4+ T lymphocytes in the thymus of controllable rats (CRs) was significantly smaller than in NRs. In contrast, the proportion of CD8+ T lymphocytes in the thymus of URs was significantly larger than in NRs and CRs. The CD4+ to CD8+ T lymphocyte ratios (CD4+/CD8+ ratios) in the peripheral blood, spleen and thymus of URs were significantly smaller than in NRs; also, the ratios in the peripheral blood and spleen of URs were significantly smaller than in CRs. The white blood cell (WBC) count of URs was significantly smaller than those of NRs and CRs, and the WBC count of CRs was significantly smaller than those of NRs and CRs, and the WBC count of CRs was significantly smaller than that of NRs. These results suggest that decreases in CD4+ T lymphocytes (and/or an increase of CD8+ T lymphocytes) in the peripheral blood, spleen, and thymus are caused by uncontrollable stress followed by a reinstating stress condition, leading to the decrease of WBC in the peripheral blood and decreases in the CD4+/CD8+ ratios in these tissues.
To find the most susceptible lymphocyte subpopulation with exposure to various occupational hazardous substances, we reanalyzed our previous data. We measured T, B and natural killer NK cell subpopulations by means of flowcytometry among workers who were exposed to aromatic amines, chromate, mercury lead and organic-solvents. The exposed/non-exposed ratio was defined as the mean value of the absolute number of lymphocyte subpopulations in the exposed workers divided by the corresponding value of the non-exposed control group in 5 studies reported previously by us. The ratio of CD4+CD45RA+ T cells in all the exposed groups examined in this study was less than 1.0, and the mean of these ratio was 0.77, which was the lowest among lymphocyte subpopulations examined. The mean ratio was 1.06 for CD4+CD29+ T cells, 0.91 for CD4+ T cells, 0.99 for CD8+ T cells, 0.93 for CD3+ T cells, 0.99 for CD19+B cells, 0.96 for CD57-CD16+ NK cells, 0.82 for CD57+CD16+ NK cells, 1.25 for CD57+CD16- NK cells and 0.89 for total lymphocytes. With regard to the difference between exposed and non-exposed workers the estimated overall difference in the mean absolute number of CD4+CD45RA+ T cell subpopulation between exposed and non-exposed workers among five studies was -135 ((% confidence interval, CI: (-194,-75)) cells/mm3 (p<0.01). In conclusion, naïve (CD4+CD45RA+) T cell subpopulation was the most susceptible to the effects of various toxic substances as compared with other lymphocyte subpopulations. This lympohocyte subpopulation may be useful for monitoring immune system of workers exposed to various types of substances in the workplace.