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Biomedical subjects

M Utsuyama

Publications and source records attributed to M Utsuyama.

At least 73 records · Page 4Linked to original sources
PubMed1989

Hypertrophy of the thymus and restoration of immune functions in mice and rats by gonadectomy.

Hypertrophy of the thymus was observed in aging C57BL/6 mice, ranging in age from 4 to 20 months, which had been gonadectomized 2 months before the sacrifice, and the magnitude of thymic regeneration was more pronounced in male than in female. However, enhancement of anti-SRBC antibody response was observed only in female, but not in male mice regardless of age. Gonadectomy brought about not only thymic hypertrophy but also an increase in T cells and B cells in the spleen. An increase in T cell subpopulations was proportional in female mice, but disproportional in male. The disproportional increase of T cell subpopulations could account for the failure to enhance the anti-SRBC antibody response in male mice. Gonadectomy also resulted in the thymic hypertrophy in male and female young Wistar rats, but not in those which had been previously hypophysectomized.

Aging↗
PubMed1989

Combined grafting of bone marrow and thymus, and sequential multiple thymus graftings in various strains of mice. The effect on immune functions and life span.

The combined grafting of young bone marrow and newborn thymus performed in old mice was effective in restoring the impaired immune functions, but the same treatment performed in middle-aged adult mice had no effect on the life span of C3H/MTV female mice. Sequential multiple newborn thymus graftings starting at young adult age were effective in enhancing immunological functions, delaying the onset of tumor and extending the survival rate to certain degree in the first half of the experimental course in both C3H/MTV as well as C57BL/6 mice, but these effects were not observed in the latter half of the experimental course. It was suggested that multiple newborn thymuses sequentially implanted into the peritoneal cavity underwent atrophy and these atrophic thymuses had a suppressive effect on the host immune system. In autoimmune prone B/WF1 mice, however, the combined grafting of young bone marrow and newborn thymus resulted in suppression of antibody formation to SRBC, and single grafting of either young bone marrow or newborn thymus resulted in a trend of increase in the antibody formation to SRBC. The sequential multiple newborn thymus graftings in B/WF1 mice brought about aggravation of kidney diseases and shortening of the mean life span. On the contrary, administration of thymosin in B/WF1 mice resulted in amelioration of kidney disease and elongation of the mean life span.

Animals↗
PubMed1989

Spontaneous development of organ-specific autoimmune lesions in aged C57BL/6 mice.

We have shown that spontaneously occurring, organ-specific autoimmune lesions develop in aged C57BL/6 mice of both sexes, especially in 24-month-old senescent mice. The inflammatory lesions were found in the multiple organs such as salivary gland, kidney, pancreas, lung, and liver, associated with ageing process. Organ-specific autoimmune lesions first appeared in 6-month-old C57BL/6 mice, and were aggravated with advancing age. In contrast, significant inflammatory changes did not develop in the thyroid, stomach, testis, ovary, and prostate in aged C57BL/6 mice. The incidence and severity of organ-specific autoimmune lesions in this strain of non-autoimmune mice increase with advance of age. The most severely affected lesion was sialadenitis developed in the submandibular salivary gland of aged mice, and a significant difference between male and female mice was noted only in the salivary gland. The infiltrating cells within the lesions of multiple organs consisted mainly of Thy 1.2+ and L3T4+ cells. Autoantibodies were detected in the sera of the mice with each corresponding organ-specific autoimmune lesions.

Aging↗
PubMed1988

Immunohistochemical studies in human thymomas. Localization of thymosin and various cell marker.

Forty five human thymomas were studied immunohistochemically using antibodies to thymosin x-1, thymosin beta-3, cortical epithelium of human thymus (UH-1), mouse thymic nurse cells (Th-3) and Leu-7. Most thymomas were found to contain thymosin x-1 (80%) and thymosin beta-3 (89%). Also used in the study were a new monoclonal antibody (UH-1), which reacts with the epithelial cells forming a meshwork in the cortex of the normal newborn thymus and Leu 7, which reacts with subcapsular epithelial cells in the outer thymic cortex. The combined use of UH-1 and Leu-7 was found to identify neoplastic epithelial cells of thymic cortical origin in thymomas. Approximately 80% (37/45) of the thymomas in the present study reacted with Leu-7, UH-1 or both antibodies, and were thus considered to be derived from cortical thymic epithelium. Of the eight thymomas which were negative with both Leu-7 and UH-1, four were histologically of mixed type characterized by the formation of epithelial cell islands. All four of these thymomas were positive with thymosin and were therefore considered to be of medullary origin. Ten of the thymoma were associated with myasthenia gravis; all were positive with UH-1 and were consider to be of cortical origin.

Antibodies, Monoclonal↗
PubMed1988

Decline in the production of interleukin-3 with age in mice.

Previously, we and others have found that the ability to produce interleukin-1 (IL-1) and interleukin-2 (IL-2) declines with age in mice. The purpose of this study was to determine the influence of age on the capacity of mice to produce interleukin-3 (IL-3). Splenic cells (5 X 10(6)/ml) from young (3-4 months) and old (24-32 months) C57BL/6 mice were first assessed for their IL-3-producing capacities in response to varying doses of concanavalin A (Con A; 2-20 micrograms/ml) in a time-dependent manner. The results showed that the production of IL-3 by both young and old C57BL/6 mice was maximal on Days 3 and 4 in response to 20 micrograms/ml of Con A, and that of IL-2 was minimal (activity was less than 0.1 unit) on Day 4. Consequently, Day 4, was selected to assess the effect of age on IL-3 production by splenic cells. The results showed a twofold reduction in IL-3 production with age (P less than 0.05). Young-old splenic cell mixture experiments at ratios of 1:0, 3:1, 1:1, 1:3, and 0:1 indicated that the decrease in IL-3 production with age was not due to an increase in suppressor cell activity. Experiments based on mixtures of nylon wool-enriched splenic T-cell and adherent cells and on anti-MAC-1 plus complement-treated spleen cells indicated that (a) adherent cells are not required for T-cell production of IL-3, unlike IL-2 production, and (b) the decrease in IL-3 production with age is due solely to alteration in IL-3-producing T cells. Finally, a strong correlation was demonstrated between the production of IL-2 and IL-3 by spleen cells of individual young and old mice (r = 0.92, P less than 0.01). That production of both IL-2 and IL-3 is affected in a similar manner by age would suggest that a single class of helper T cells may be responsible for production of both lymphokines.

Aging↗
PubMed1988

Spontaneous development of autoimmune sialadenitis in aging BDF1 mice.

This study reports that spontaneous autoimmune sialadenitis developed in aging female, rather than male, BDF1 mice. The lesions first appeared in 6-month-old female BDF1 mice and were aggravated with advancing age, especially in 24-month-old and 30-month-old senescent mice. In contrast, significant inflammatory changes did not develop in aging male BDF1 mice. The presence of antisalivary duct antibody was found in sera from mice with sialadenitis. The infiltrating cells in the lesions of submandibular salivary glands were mainly composed of T cells, especially Lyt 1+ and L3T4+ cells. Moreover, mild inflammatory lesions were observed in parotid, sublingual salivary glands, pancreas, or kidneys in some mice that developed spontaneously occurring sialadenitis.

Aging↗
PubMed1988

Influence of age on the proliferation and peripheralization of thymic T cells.

Bone marrow cells obtained from B10.Thy-1.1 mice (H-2b, Thy-1.1) were injected directly into the thymus of C57BL/6 mice (H-2b,Thy 1.2) of various ages. Thymocyte precursors in the injected donor-bone marrow cells could proliferate in the thymic microenvironment in the following manner: first, preferentially proliferating into the subcapsular cortex; and second, spreading to the whole layer of the cortex, a portion of them gradually moving into the medulla. The proliferation of donor-type thymocytes was most pronounced when intrathymic injection of bone marrow cells (ITB) was performed in newborn mice and especially prominent in week-old mice; it took approximately ten weeks for donor-type thymocytes to finish the whole course of proliferation, differentiation, and emigration to the periphery. When ITB was performed in mice 4 weeks of age and older, the proliferation of donor-type thymocytes was retarded at onset, less pronounced in magnitude, and disappeared earlier. Emigration of donor-type T cells from the thymus to the peripheral lymphoid tissues occurred most rapidly when ITB was performed in newborn mice, and these T cells continued to reside thereafter in the peripheral lymphoid tissues. However, when ITB was performed in mice 4 weeks of age and older, the number of emigrated T cells in the spleen decreased (about a tenth of that in newborn mice) and, moreover, these T cells resided only transiently in the spleen. It was suggested that T cells emigrating from the thymus of mice from newborn to 2 weeks of age are long-lived, whereas those from the thymus in mice 4 weeks of age and older are short-lived. However, when 4-week-old young adult mice were treated by irradiation or hydrocortisone, the thymic capacity was enhanced in terms of proliferation and peripheralization of thymocytes, and emigrated T cells became long-lived.

Adrenal Cortex Hormones↗
PubMed1987

Age-related changes of splenic T cells in mice--a flow cytometric analysis.

Splenic T cells of C57BL/6 mice, ranging in age from newborn to 24 months old, were examined by two-colour flow cytometry using monoclonal antibodies (moAbs) to Thy-1, Lyt-1, Lyt-2 and L3T4. Thy-1+ cells in the spleen increased gradually after the birth, and reached a plateau around at 3 months of age, but did not show a significant age-related decline even at 24 months of age. Lyt subpopulations of T cells (Lyt-1+2+, Lyt-1+2-, Lyt-1-2+) showed a proportional increase until 1 month of age, but the onset of their imbalance was observed as early as 3 months of age. The percentage of L3T4+ subpopulation stayed at a relatively constant level throughout life (approx. 55%). At the individual cell level, Lyt-2 antigen was most vulnerable to aging and its membrane surface density showed a prominent decrease in 24-month-old T cells. An apparent decline was observed in the mitogen reactivity and cell-mediated cytolytic T lymphocyte (CTL) activity of old T cells or their subpopulations which were purified by the cell sorter.

Aging↗
PubMed1987

Aluminum accumulation in tangle-bearing neurons of Alzheimer's disease with Balint's syndrome in a long-term aluminum refiner.

Progressive dementia had developed since the age of 55 in a male patient, who had worked as an aluminum refiner for 30 years. Balint's syndrome was observed from at 60 and he died of bronchopneumonia at 65. Neuropathological examination revealed characteristic features of Alzheimer's disease with marked atrophy of the occipito-temporal lobes and senile plaques of the cerebellum. Wavelength-dispersive X-ray microanalysis disclosed focal aluminum accumulation within the nucleus and cytoplasm of the tangle-bearing neurons. Microanalysis by the same method failed to disclose aluminum accumulation in the tangle-bearing neurons in a case of senile dementia of Alzheimer's type who had no possible inhalation of aluminum.

Adolescent↗
PubMed1986

Age-related change in the potential of bone marrow cells to repopulate the thymus and splenic T cells in mice.

Bone marrow chimeras were produced between various combinations of young and old mice using either C57BL/6 mice only or a combination of C57BL/6 and B10.Thy-1.1 mice. The wet weight of the thymus and the number of thymocytes and splenic T cells of donor origin were assessed at appropriate intervals after the bone marrow transplantation. It was revealed that the old bone marrow was inferior to young in terms of the capacity to repopulate the thymus and splenic T cells. Moreover, some age-related qualitative changes appeared to occur in the thymocyte progenitors, as the composition of Lyt phenotype of donor-type T cells in the spleen was different between chimeras produced with young bone marrow and those with old.

Aging↗
PubMed1986

Contrasting feature in the repopulation of host-type T cells in the spleens of F1----P and P----F1 radiation bone marrow chimeras.

The regeneration and persistence of host- and donor-derived T cells were examined in the thymus as well as the spleen of mouse radiation bone marrow chimeras of two semiallogeneic combinations (F1----P, P----F1) with different Thy-1 markers on T cells of donor and host origins. An unexpectedly large number of host-type T cells were recovered from the spleens of F1----P chimeras, amounting to as high as 45 and 25% of total T cells at 6 and 14 weeks after bone marrow transplantation (BMT), respectively. To the contrary, the residual host-type T cells in the spleens of P----F1 chimeras disappeared quickly, resulting in less than 0.1% of total T cells at 6 weeks after BMT. It was also revealed that the number of host-type T cells in the spleens of F1----P chimeras decreased in proportion to increase of radiation dose given to the recipients.

Animals↗
PubMed1986

Analysis of the thymic microenvironment by monoclonal antibodies with special reference to thymic nurse cells.

Two hybridoma cell lines secreting monoclonal antibodies against stromal tissues of mouse thymus were produced using the spleen cells of BALB/C mice immunized with newborn thymic homogenate of C57BL/6 mice emulsified in Freund's complete adjuvant. The monoclonal antibody Th-3 reacted with stromal cells in the thymic cortex and the monoclonal antibody Th-4 reacted with stromal cells in the thymic medulla. The stromal cells revealed by Th-3 showed a meshwork structure in the cortex, and formed a monolayered border at the cortical surface and around the vasculature. Each mesh of this structure was connected to each other, forming a complex labyrinth and being open toward the medullary area. Neither lymphoid cells nor any cells in any other organs were reacted with this Th-3 antibody. However, the reactivity of Th-3 with the thymic cortical stromal cells was observed not only in C57BL/6 mice which had been used as source of antigen, but also in other strains of mice such as C3H and BALB/C. Immunoelectron microscopy revealed that Th-3 monoclonal antibody was reactive with some component, diffusely present in the cytoplasm of cortical epithelial cells. The pattern of Th-3 positive meshwork in the thymic cortex was quite similar to that stained by either anti-IA or anti-IE antibody, but the Th-3 positive reaction was not inhibited by these anti-IA and anti-IE antibodies. Thymic nurse cells prepared by the method of Wekerle were positive for Th-3 antibody. On the contrary, Th-4 reacted only with epithelial cells in the thymic medulla. It was suggested that Th-3 monoclonal antibody detected some antigen specific to so called thymic nurse cells.

Animals↗
PubMed1985

Intrathymic T cell differentiation in radiation bone marrow chimeras and its role in T cell emigration to the spleen. An immunohistochemical study.

Immunohistochemical studies were made on the regeneration of T cells of host- and donor-type in the thymus and spleen of radiation bone marrow chimeras by using B10- and B10.BR-Thy-1 congenic mice. Both the thymic cortex and the medulla were first repopulated with thymocytes of irradiated host origin, restoring the normal histologic appearance by days 11 to 14, regardless of the H-2 compatibility between the donor and the host. In Thy-1 congenic chimeras, thymocytes of donor bone marrow origin, less than 100 cells in one thymic lobe, were first recognized at day 7, when the thymus involuted to the smallest size after the irradiation. The thymocytes of donor-type then proliferated exponentially, showing a slightly faster rate when higher doses of bone marrow cells were used for reconstitution, reaching a level of 100 million by day 17 and completely replacing the cortical thymocytes of host origin by day 21. The replacement of cortical thymocytes started from the subcapsular layer in a sporadic manner. The replacement of medullary thymocytes from host- to donor-type occurred gradually between days 21 and 35, after the replacement in the cortex was completed. In the spleen, about 1 million survived cells were recovered at day 3 after the irradiation, and approximately 60% of them were shown to be host-type T cells that were observed in the white pulp areas. The host-type T cells in the spleen increased gradually after day 10, due to the influx of host-type T cells from the regenerating thymus. Thus a pronounced increase of T cells of host-type was immunohistochemically observed in the splenic white pulp between days 21 and 28, when thymocytes of host-type were present mainly in the thymic medulla. These host-type T cells were shown to persist in the spleen for a long time, as long as 420 days after the treatment. Phenotypically, they were predominantly Lyt-1+2+ when examined at day 28, but 5 mo later, they were about 50% Lyt-1+2+ and 50% Lyt-1+2-. Donor-type T cells in the spleen began to appear at about day 14 in chimeras that were transplanted with a larger dose of bone marrow cells, whereas this was slightly delayed in those grafted with a smaller dose of bone marrow cells, starting at about day 28.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

The effect of sequential multiple grafting of syngeneic newborn thymus on the immune functions and life expectancy of aging mice.

Enhancement of the immune functions and extension of the mean life expectancy were successfully performed in aging mice by sequential multiple grafting of syngeneic newborn thymus. In the first experiment, 2-month-old female C57BL/6 mice were grafted with either syngeneic newborn thymus or newborn spleen every 2 months, 5 or 6 times. A significant enhancement of T cell dependent immune functions were observed in the group sequentially grafted with newborn thymus, in comparison to that grafted with multiple sequential newborn spleen or with a single newborn thymus and that without a graft. In the second experiment, the same sequential grafting protocol was performed in middle aged mice at monthly interval for 4-5 consecutive months and the immune functions and survival rate were compared between the experimental and control groups. The immune functions were only partially rejuvenated, but an extension of the mean remaining life expectancy was observed in the experimental group (312 +/- 38 days) as compared with control (214 +/- 42 days), although maximal life-span was the same in both groups (1100 days).

Aging↗
PubMed1984

Differential rate of age-related decline in immune functions in genetically defined mice with different tumor incidence and life span.

Immunological studies were performed in aging C57BL/6 and BDF1 mice. In C57BL/6 mice the incidence of malignant tumor was high and their mean life span was 665 days in males and 649 days in females. In BDF1 mice, the incidence of malignant tumors was significantly lower, and their mean life span was 954 days in males and 846 days in females. Immunologically, either the onset of decline occurred earlier, the rate of the age-related decline in activity was more rapid, and/or the magnitude of decline was greater in the shorter-lived C57BL/6 than in the longer-lived BDF1 mice. The close relationship between (a) the susceptibility especially to malignant lymphoma; (b) the onset, rate and magnitude of age-related decline in T-cell-dependent immunologic activities, and (c) the life span would suggest that T-cell immunity may be playing an important role in the resistance against life-shortening malignant lymphoma in C57BL/6 mice.

Aging↗