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Biomedical subjects

M Utsuyama

Publications and source records attributed to M Utsuyama.

At least 55 records · Page 3Linked to original sources
PubMed1993

Effects of a protein-free diet or food restriction on the immune system of Wistar and Buffalo rats at different ages.

The effects of a protein-free diet or food restriction on the immune system were examined in two rat strains, Wistar and Buffalo, in different age-groups. Unlike Wistar rats, Buffalo rats have an unusually hyperplastic thymus and a large number of peripheral T cells. The protein-free diet (PFD) in rats resulted in marked thymic involution together with a reduction of splenic T cells, both in number and in antibody response to sheep red blood cells. The depressive effect of the PFD on the immune system was more serious in young immature rats than in older rats, but less serious in Buffalo rats having enhanced T cell functions regardless of age. Thymic involution was also accelerated in both strains of rats by feeding them a restricted amount of the control diet containing well-balanced nutrients (food restriction, FR). In the FR experiment, no significant change was observed in immune functions of Wistar rats. A slight reduction was observed in the immune functions of Buffalo rats with FR, but absolute levels were distinctly higher in Buffalo rats than in Wistar rats even after FR. These results suggested (1) that the thymic function is sensitive to protein deficiency; (2) that a well-balanced dietary condition is necessary for immunological maturation in the early stage of life and preservation of immune functions at older age; (3) that animals having higher immune functions are more resistant to malnutrition than ordinary ones.

Aging↗
PubMed1993

Differential effect of host microenvironment and systemic humoral factors on the implantation and the growth rate of metastatic tumor in parabiotic mice constructed between young and old mice.

B16 melanoma cells were injected into the tail vein of young mice, old mice and parabiotic mice constructed between young and old mice, and the number and shape of pulmonary metastases were compared among three experimental groups. In unpaired mice, the number of metastatic colonies in the lungs was 10-fold larger in young than in old mice. In parabiotic mice, the number in young mice was almost comparable with that of unpaired young mice, but the number in old mice approached the level of young mice. Metastatic colonies on the pulmonary surface of young mice were mostly nodular in shape, while those of old mice were flat in shape. The shape of colonies reflecting the tumor growth rate did not change in parabiotic old mice in spite of an increase in number. In young parabiotic mice, the large and intermediate colonies decreased with a concomitant increase of small ones as compared with unpaired young mice. These results suggest that the implantation of metastatic colonies in the lung is mainly dependent on systemic humoral factors and their growth is mainly dependent on the host local factors in the microenvironment, and distinct age changes of both factors greatly influence the metastatic mode of tumors, respectively.

Aging↗
PubMed1993

Monoclonal antibody to beta peptide, recognizing amyloid deposits, neuronal cells and lipofuscin pigments in systemic organs.

A monoclonal antibody (AmT-1) produced against synthetic amyloid beta peptide (1-28 residues) was revealed to be reactive with amyloid beta peptide blotted on nitrocellulose membrane, but not with that dissolved in sodium dodecyl sulfate and electrophoresed. AmT-1 immunostained senile plaques of typical, primitive and diffuse type, as well as amyloid deposits in cerebral vessels. It also reacted with neuronal and glial cells of normal and Alzheimer's disease (AD) brains. In addition, AmT-1 was also reactive strongly with lipofuscin pigments of adrenal reticular cells, and weakly with those of eccrine glands and liver cells. A rat neural cell line (PC12h) was reactive with AmT-1. By immunoelectron microscopy, a positive reaction was seen in ribosomes along the rough endoplasmic reticulum of nerve cells and PC12h cells. By immunoprecipitation, AmT1 reacted with a band at 36 kDa in the brain homogenates from Ad patients as well as from normal aged subjects. By immunoblotting analysis, AmT1 reacted with a band at 36 kDa in the cytosolic fraction of PC12 cells, and three bands (12-17 kDa) in the lipopigment fraction of the adrenal gland. These findings suggest that the cerebral amyloid deposits contain substance(s) having an epitope common to neuronal cells and lipofuscin pigments. The possible relationship between cerebral amyloid deposits and lipofuscin pigments in systemic organs is discussed.

Aged↗
PubMed1993

Influence of age on the signal transduction of T cells in mice.

A 5- to 10-fold decline was observed in the proliferative activity of T cells stimulated with anti-CD3 mAb between young and old mice. However, the number of CD3 molecules on the T cell surface was almost comparable between young and old T cells. The formation of the second messenger such as inositol triphosphate (IP3) and diacylglycerol (DAG) after mitogenic stimulation decreased in old T cells as compared with young ones. The activity of phospholipase C (PLC), which is responsible for the liberation of IP3 and DAG from phosphatidylinositol-4,5-bisphosphate (PIP2) was not different between young and old T cells. The content of PIP2 in the membrane was also comparable between young and old T cells. These findings have suggested that the age-related decline in the proliferative activity of T cells could be due to impairment of intracellular signal transduction, probably in the pathway somewhere between TCR and PLC.

Aging↗
PubMed1992

Salvage of infarcted myocardium by angiogenic action of basic fibroblast growth factor.

Coronary collateral vessels reduce damage to ischemic myocardium after coronary obstruction. Factors that stimulate collateral formation are expected to have ameliorating effects on myocardial infarction. In a canine experimental myocardial infarct model, intracoronary injection of basic fibroblast growth factor (bFGF) improved cardiac systolic function and reduced infarct size. Treatment with bFGF increased the number of arterioles and capillaries in the infarct. Thus, the angiogenic action of bFGF might lead to a reduction in infarct size. The application of bFGF might bring about a therapeutic modality for the salvage of infarcted myocardium.

Animals↗
PubMed1992

Differential age-change in the numbers of CD4+CD45RA+ and CD4+CD29+ T cell subsets in human peripheral blood.

Peripheral blood mononuclear cells were obtained from people ranging in age from newborn to 102 years old and analyzed by dual color flow cytometer in terms of number and percentage of various subsets of T cells, B cells and natural killer cells (CD3, 4, 5, 8, 11b, 19, 20, 21, 25, 29, 45RA and 56). Numbers of T cells (CD3+ or CD5+ cells) significantly declined at the 3rd decade as compared with those of younger people, stayed at a relatively constant level between the 3rd and the 7th decade and gradually declined thereafter. In T cell subsets, both CD4 and CD8 positive positive cells decreased with age, but a decrease was more pronounced in the latter, showing an age-related increase of CD4/CD8 ratio. The most interesting finding was a contrasting age-change in two subsets of CD4+ T cells; i.e. a subset of suppressor inducer T cells (CD4+CD45RA+ naive cells) decreased with age, while a subset of helper inducer T cells (CD4+CD29+ memory cells) increased with age. CD20+ B cells also decreased with age in a manner similar to that observed in T cells. Natural killer cells (CD56) showed an increase in numbers with age. The relationship between these changes in various subsets of peripheral blood leukocytes and the age-related decline in immune functions has been discussed.

Adolescent↗
PubMed1992

Aging and immunity.

The function of the immune system peaks at around puberty and gradually declines thereafter with advance in age. The age-related decline of immunological function primarily occurs in the T cell-dependent immune system and is generally associated with increase in susceptibility to infections as well as in incidence of autoimmune phenomena in the elderly. The age-related change in T cell-dependent immune functions can be ascribed to the physiological thymic atrophy which starts in an early stage of life. Emigration of T cells from the thymus to the periphery mainly takes place in the late fetal and newborn stage, and dramatically declines after puberty. In other words, the thymic capacity to promote T cell differentiation starts to change in the early stage of life in terms of quantity and quality of T cells. Thus, the composition of T cell-subsets in the periphery gradually changes with age, resulting in the alteration of T cell functions in the elderly. The restoration of immunological functions of the aged individuals is possible and might be beneficial for them to cope with various diseases associated with aging. Physiological thymic atrophy is controlled by both extrathymic and intrathymic factors, and is not a totally irreversible process. The process of thymic atrophy might be explained by further understanding of the relationship between the neuroendocrine and the immune systems.

Aging↗
PubMed1992

Ontogeny and development of extrathymic T cells in mouse liver.

We previously demonstrated that the liver may be a major site of extrathymic T-cell differentiation in mice. In the present study, the ontogeny and subsequent development of such T cells in the liver and other organs were investigated. This study was possible because these T cells have T-cell receptors (TcR) of intermediate intensity (i.e. intermediate TcR cells) and constitutively express a high level of interleukin-2 receptor beta chain (IL-2R beta). Therefore the two-colour staining for CD3 (or alpha beta TcR) and IL-2R beta identifies even a small proportion of intermediate TcR cells. The total numbers of mononuclear cells obtained from the liver, thymus and spleen varied from foetal to adult life. Especially in the liver, many haematopoietic cells were present in the parenchymal space at the foetal stage. There were no lymphocytes in the sinusoidal lumen at this period. In contrast, lymphocytes appeared in the hepatic sinusoids after birth and increased with ageing. Phenotypic analysis revealed that intermediate TcR cells appeared in the liver and spleen on Day 4 after birth. Bright TcR cells of thymic origin were also present in the peripheral organs on Day 4. Thereafter, intermediate TcR cells increased in the liver, whereas bright TcR cells increased in the periphery as a function of age. Similarly, thymectomized and congenitally athymic mice had mainly intermediate TcR cells in the liver and, to some extent, periphery. It is concluded that intermediate TcR cells, possibly of extrathymic origin, are generated only after birth and expand with ageing.

Aging↗
PubMed1991

Production of a monoclonal antibody strongly reacting with immature thymic T lymphocytes and its immunohistological application.

A monoclonal antibody Th-5 has been produced against mouse immature thymic lymphocytes and employed to study the process of T cell differentiation in the thymus. Immunohistologically, Th-5 positive thymic T lymphocytes were first found at Day 12 of gestation. They increased in number as well as staining intensity until Day 18 of gestation and decreased thereafter. Th-5 antigen expression was not seen in lymphoid cells in the fetal liver. In the newborn thymus, lymphocytes in the subcapsular layer were still strongly positive, while other cortical lymphocytes became moderately positive for Th-5. Th-5 positiveness was more pronounced in the medulla than in the cortex in the thymus of young adult mice. The staining pattern of Th-5 in the thymus was apparently different from those with other T cell markers (Thy-1, CD3, CD4, CD5, CD8) including J11d, Pgp-1, IL-2R, and 3A10 (TCR gamma delta). Flow cytometric analyses showed that the expression of Th-5 was mostly associated with the Thy-1 antigen. However, the fluorescent intensity of Th-5 gradually declined with ontogenic development of the thymus, and the molecular size of the antigen was approximately 100 kDa, which is different from Thy-1 antigen (25-30 kDa). Considering these findings, the strong expression of Th-5 could be one of the markers of immature thymic T lymphocytes in the early phase of the ontogenic development.

Animals↗
PubMed1991

Age influence on the thymic capacity to promote differentiation of T cells: induction of different composition of T cell subsets by aging thymus.

Three kinds of experiments were performed to see the differential effect of aging thymus on T cell differentiation in nude mice and thymectomized mice. In the experiment of thymus grafting into nude mice, the thymic capacity to promote T cell differentiation was the highest at newborn stage, and declined to 80% of the peak level at as early as 1 week of age. The level at 4 weeks of age was 50-60% of the peak level and did not greatly change thereafter with advancing age of thymus donors, up to 24 months of age. However, composition of T cell subsets differed with age of thymus graft; i.e. L3T4(CD4)+ T cells were more easily induced than Lyt-2(CD8)+ T cells by aging thymus, resulting in an increase of the ratio of L3T4+/Lyt-2+ T cells with advancing age of thymus donors. The decreased number of T cells and their subsets in the mice thymectomized at 4 weeks of age could be almost totally recovered by the grafting of newborn thymus, but less efficiently by the grafting of 24-month-old thymus. In the latter case again, L3T4+ T cells were more easily induced than Lyt-2+ T cells, resulting in an increase of the ratio of L3T4+/Lyt-2+ T cells by the grafting of the old thymus. In neonatal mice thymectomized 3 days after the birth, Lyt-2+ T cells were more severely affected than L3T4+ cells, resulting in high ratio of L3T4+/Lyt-2+ T cells. It was suggested that the capacity of the thymus to induce T cells started to decline as early as 1 week of age and did not greatly change between 4 weeks and 24 months of age. However, the composition of T cell subsets induced by the thymus changed with age, with preference for L3T4+ T cells over Lyt-2+ T cells.

Aging↗
PubMed1991

Determination of interleukin 2 receptor number of Con A stimulated human lymphocytes with aging.

Defective proliferative responses of lymphocytes from elderly donors to various mitogens have been reported in numerous studies. The aim of the present work was to monitor the kinetic response of lymphocytes obtained from elderly and young individuals regarding the Con A stimulated proliferative response and IL-2 receptor expression. The studies were performed by flow cytometric analysis using FITC conjugated anti-IL-2 receptor monoclonal antibody. The data obtained show that beside a detectable decrease in the proliferative capacity of peripheral blood lymphocytes from elderly subjects, the mean IL-2 receptor number/cell did not decrease, but even slightly increased under ConA stimulation. The pattern of distribution of IL-2 receptor positive lymphocytes is different in young and elderly individuals. These data suggest that the decreased proliferative response observed with aging is not due to the decrease of IL-2 receptor number, but most probably to an altered post-receptorial signal transduction mechanism, coupled to changes in responsive cell populations.

Adult↗
PubMed1990

Immunohistological study of senile brains by using a monoclonal antibody recognizing beta amyloid precursor protein: significance of granular deposits in relation with senile plaques.

Immunochemical analyses revealed that a monoclonal antibody Am-3 recognized beta amyloid precursor protein (beta APP) in senile plaques extracted from Alzheimer's brain, but did not recognize beta amyloid protein. Immunohistochemically, however, the staining pattern of Am-3 in frozen section of Alzheimer's brain was almost the same with that of rabbit polyclonal antibody to beta amyloid peptide which could recognize both beta amyloid protein and beta APP. In other words, beta APP was present in senile plaques of various types, cerebrovascular amyloid and granular deposits. The granular deposits were 5-10 microns in size and laminarily distributed in the 1st, 3rd and 4th layers of cerebral cortex. They were especially abundant in 1st and 4th layers where senile plaques were usually fewer in number. Although the distribution in the cerebral cortex was different between the senile plaques and the granular deposits, the number of the granular deposits was well correlated with that of senile plaques. The granular deposits were negative in Congo-red birefringence, but contained beta amyloid protein as well as beta APP fragment judging from positive staining by both Am-3 and polyclonal antibody to synthetic beta amyloid peptide. Thus, they could be regarded as "pre-amyloid".

Aged↗
PubMed1990

Age-related hyperplasia of the thymus and T-cell system in the Buffalo rat. Immunological and immunohistological studies.

This report describes the development of hyperplasia of both the thymus and the peripheral T-cell system with advancing age in the Buffalo rat. Buffalo/Mna rats do not show age-related thymic involution, but rather develop thymic hyperplasia with advancing age. This thymic growth is expansile and there is no infiltration of the surrounding tissues. Because the enlarging thymus occupies the thoracic cavity, most of the rats die of respiratory failure by the age of 24 months. Thymic enlargement is due to primary hyperplasia of cortical epithelial cells and the large number of proliferating lymphocytes. The hyperplastic epithelial cells are bizarre in shape and strongly positive when stained with Th-3 monoclonal antibody (MoAb), anti-thymosin antibody and anti-EGF antibody, but negative with Th-4 MoAb. The patterns of distribution of CD-5+, CD-4+ and CD-8+ lymphocytes within the hyperplastic thymus are similar to those seen in young rats of other species. The high level of T-cell emigration from the thymus to the periphery appears to persist throughout life, since the percentage of normal splenic T-cells also increase with advancing age and exceed 70% of the total by 24 months of age. This thymic enlargement with abnormal hyperplasia of cortical epithelial cells can be prevented by hypophysectomy.

Aging↗
PubMed1989

Changes in serum levels of Forssman-like antibody in patients with gastric cancer.

Because Forssman antigen, one of the most well-known heteroantigens, has been noted in certain cancerous tissues, it would seem that the serum levels of the Forssman antibody of patients with these cancers would be low, owing to the absorption of the naturally occurring antibody by the Forssman antigen-containing cancerous tissues. This hypothesis was tested by researchers assessing the serum hemolysin titers of 174 patients with cancer (gastric cancer, 100; colonic cancer, 40; and other cancers, 45) and of 856 age-matched, sex-matched, and blood type-matched healthy individuals against the serum levels of sheep red blood cells. Serum levels of the hemolysin of patients with gastric cancer tend to be lower than those of patients with other types of cancer and also lower than those of age-matched and sex-matched controls. The decrease was especially prominent in patients with moderately differentiated adenocarcinoma of the stomach. Preoperative and postoperative serum samples of 40 patients with gastric cancer were analyzed therefore to determine the effect of surgically removing the cancer on the serum level of the hemolysin. The results showed that the serum levels of the hemolysin antibody increased in all 40 patients after the successful surgical removal of the cancer. However, in patients with recurrence of the cancer, the serum levels of hemolysin decreased again in 11 of 11 patients. These results indicate that the serum levels of the Forssman-like hemolysin could be used as an index of recurrence in patients with gastric cancer after surgical removal of the cancer.

Adenocarcinoma↗
PubMed1989

Establishment of a monoclonal antibody against senile plaques and its application for immunohistological and immunoelectron microscopical studies in the brain of the elderly.

A monoclonal antibody (Am-3) was produced against senile plaques in the brain of a patient with Alzheimer's disease. Am-3 was reactive with senile plaques of typical, primitive and diffuse type not only in the brain used as immunogen, but also those in the brain of 15 out of 25 autopsy cases of the aged people. Moreover, Am-3 was also reactive with granular materials of various sizes scattered in the 1st, 3rd and 4th layers of the cerebral cortices of the cases with severe dementia. Am-3 was also reactive with vessel wall of the congophilic angiopathy. By immunoelectron microscopic examination, Am-3 was positive with amyloid fibril in the core and crown of senile plaques, and in the congophilic angiopathy.

Aged↗
PubMed1989

Immunohistological analysis of immigration of thymocyte-precursors into the thymus: evidence for immigration of peripheral T cells into the thymic medulla.

The immigration route of thymocyte precursors into the thymic microenvironment was examined in various experiments using two strains of mice (B10.Thy-1.1 and C57BL/6) that were identical in H-2 and different in Thy-1 locus. The experiment of thymus grafting revealed that there were two types of thymocyte precursors; one immigrated into the cortex and vigorously proliferated and the other directly immigrated into the medulla. Such a direct immigration of host-type cells into the medulla of the grafted thymus was not observed, when thymus was grafted into young adult nude mice having no T cells. When bone marrow cells were iv injected into intact mice, the direct immigration of donor-type cells was observed only in the cortex, not in the medulla. In parabiotic mice, the immigration of partner's cells into the medulla was observed independently before the proliferation of partner's cell in the cortex. These findings taken together indicate that peripheral T cells directly immigrate into and recirculate through the thymic medulla.

Animals↗