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C Kurashima

Publications and source records attributed to C Kurashima.

At least 19 recordsLinked to original sources
PubMed2000

Measurement of anti-thyroglobulin and anti-thyroid peroxidase antibodies using highly sensitive radioimmunoassay: an effective method for detecting asymptomatic focal lymphocytic thyroiditis in the elderly.

Subclinical thyroiditis or thyroid dysfunction is relatively common in the elderly. To estimate the effectiveness of measurement of serum levels of anti-thyroglobulin and anti-microsomal or thyroid peroxidase antibodies for detecting focal lymphocytic thyroiditis (FLT) in the elderly, we examined the relationships between antibody titer and postmortem histological finding of the thyroid gland in 180 consecutive autopsies (69 women and 111 men) over 60 years of age without any overt clinical thyroid or collagen diseases. FLT was found in 25 cases (13.9%) with female predominance (21.7% in female vs. 9.0% in male). Measurements of serum levels of anti-thyroglobulin and anti-thyroid peroxidase antibodies by radioimmunoassay (TgAb and TPOAb, respectively) were compared with the measurements of anti-thyroglobulin and anti-microsomal antibodies by a hemagglutination technique (TGHA and MCHA, respectively), using sera from 25 patients with FLT and age- and sex-matched 51 patients without FLT. Among 25 cases with FLT, TgAb and TPOAb were positive in 17 (68%) and 12 (48%), respectively. There was a close relationship between degree of FLT and serum level of TgAb or TPOAb (P<0.0001). On the other hand, TGHA and MCHA were positive only in 8 (32%) and 10 (40%), respectively. TgAb and TPOAb were more sensitive than TGHA (68% vs. 32%, P<0.05) and MCHA (48% vs. 40%) to detect FLT. Positive findings in either TgAb or TPOAb significantly improved sensitivity (76%) compared with that of TGHA or MCHA (44%) (P<0.05). Specificities of combined measurements of TgAb and TPOAb (90%) were not significantly different from those of TGHA and MCHA (100%). These findings indicate that TgAb is a more sensitive method for detecting FLT and that its diagnostic sensitivity for FLT increases by using it in combination with TPOAb. Therefore, in the elderly without clinically or biochemically overt thyroid dysfunction, positive TgAb and/or TPOAb could imply presence of FLT, and their titers might reflect degree of inflammation.

Aged↗
PubMed1998

Histological evidence for cell proliferation activity in cystic tumor (endodermal heterotopia) of the atrioventricular node.

Cystic tumor (endodermal heterotopia) of the atrioventricular (AV) node in a 95-year-old female is described. Electrocardiograms showed complete AV blockage with a narrow QRS morphology resulting from the long-standing first degree of AV blockage since age 61. A cardiac pacemaker was implanted at age 83. The patient died of pneumonia at age 95. Autopsy demonstrated a normal heart weight (320 g), normal coronary artery and normal myocardium. Histological examination of the conduction system revealed a marked fibrotic sinoatrial (SA) node and a cystic lesion in the lower right atrium, including the approaches to the AV node. The bundle of His and its branches were completely intact. Cellular nests and cystically dilated tubules were scattered within a loose tissue stroma, which measured 18 x 12 x 5 mm. There were several mitotic figures among the tubules, as well as nuclear fragments similar to apoptotic bodies and exfoliation of the tumor cells. Immunohistochemical studies demonstrated a positive reaction for epithelial membrane antigen, carcinoembryonic antigen, CA19-9, cytokeratin and secretory component in the tubular cells, and a negative reaction for thrombomodulin. Endocrine cells among the tubules were positive only for calcitonin and serotonin. Ultrastructurally, sparse microvilli and desmosome-like structures between the tumor cells were observed. These findings support that this lesion originates from the endoderm. Moreover, it is likely that progression in the degree of AV block may be explained by the cell proliferation activity of the tumor.

Aged↗
PubMed1997

Age-related changes of cytokine production by murine helper T cell subpopulations.

Mouse CD4+ T cells were subdivided into two subsets by cell surface markers: CD44loCD45RBhi (naive) and CD44hiCD45RBlo (memory) T cells. We have reported that CD44loCD45RBhi T cells, which are predominant in young mice, decreased with age, while CD44hiCD45RBlo T cells increased. Among T cells of the same phenotype, however, it remains to be solved whether or not there is a functional difference between young and old. Therefore, we compared old with young T cells by a cytokine production assay (IL-2, IFN-gamma, IL-4 and IL-10). We employed the negative selection method by cell affinity column instead of flow cytometry as it was important to use T cells not reacted with antibodies in the cytokine production assay and as the method is quick enough to preserve the viability of the cells. Then the divided T cells were stimulated with immobilized anti-CD3 epsilon monoclonal antibody (mAb). Young CD4+ T cells produced more IL-2 and IL-4 than aged CD4+ T cells, while aged CD4+ T cells produced more IL-10 than young cells. There was no distinct age-related change in IFN-gamma production. As concerns purified CD4+ T cell subpopulations, young CD44loCD45RBhi T cells produced more IL-2 (5.3-fold higher) than young CD44hiCD45RBlo T cells and much more IL-2 (> 10-fold higher) than both groups of aged T cells. Dramatic IFN-gamma production was found in young and old CD44hiCD45RBlo T cells and young CD44loCD45RBhi T cells; however, IFN-gamma production of old CD44loCD45RBhi T cells was much lower (1/16-1/20) than that of other cell groups. IL-4 production was mainly observed in the CD44hiCD45RBlo T cell group in both young and old mice, although the former produced more IL-4 (5.2-fold higher) than the latter. There was no remarkable difference between young and old mice in the pattern of IL-10 production. These phenomena could reveal functional heterogeneity of aged CD4+ T cell subpopulations under natural conditions. Even if the surface marker is the same, the pattern of cytokine production is different between young and old cells.

Aging↗
PubMed1997

[Two cases of papillary adenocarcinoma of the thyroid gland associated with chylothorax].

Case 1. An 85-year-old woman had a papillary adenocarcinoma of the thyroid gland and a pleural effusion. The pleural effusion appeared to be a chylous exudate and it did not re-accumulate after thoracenthesis. Thoracic imaging indicated that the chylothorax was caused by direct invasion of the thoracic duct by the thyroid carcinoma. Case 2. A 53-year-old woman had a 20-year history of recurrent chylothorax. She died due to sepsis one year after the third admission for dyspnea and chylothorax. The autopsy findings included papillary adenocarcinoma of the thyroid gland with metastasis to the left supraclavicular lymph nodes. The thoracic duct was inflamed, fibrotic, and completely obstructed. Invasion by the carcinoma may have compressed and destroyed the thoracic duct, and caused chylothorax. Recurrent inflammatory granulation caused total obstruction of the thoracic duct. Reports of chylothorax associated with carcinoma of the thyroid gland are rare.

Adenocarcinoma, Papillary↗
PubMed1995

Expression of ZAP-70 gene in the developing thymus and various nonlymphoid tissues of embryonic and adult mice.

The full length of cDNA encoding murine ZAP-70 was obtained from a cDNA library of embryonic mouse thymus. Northern blot analysis indicated that the expression of ZAP-70 mRNA was most pronounced in the thymus and spleen and also slightly in the brain. Analysis by in situ hybridization revealed that the mRNA was expressed not only in T cells in the thymus and spleen, but also in nerve cells of the brain. In the thymus, the distribution of positive cells was different between newborn and young adult mice. In the newborn thymus, positive signal in thymocytes was localized in the subcapsular layer as well as in the medulla, while in the young adult thymus, it was localized exclusively in the medulla. Furthermore, the in situ hybridization revealed that positive signal was also seen in the liver, intestine, and lung of embryonic mice. These findings have suggested that ZAP-70 plays an important role in growth, differentiation, and function of not only T cells but also nerve cells and several embryonic tissues.

Amino Acid Sequence↗
PubMed1995

Differential expression of protein tyrosine kinases in the cortical and medullary thymic epithelial cell lines.

Expression of protein tyrosine kinase (PTK) was evaluated and compared between cortical and medullary thymic epithelial cell (TEC) lines, TEC 14C18 and TEC1C6, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) methods using degenerate primers for conserved sequence in catalytic domain of PTK revealed the expression of 13 kinds of PTKs in these cell lines. These PTKs included 6 receptor and 7 non-receptor types. In the next step, we compared the intensity of mRNA expression level of these kinases between cortical and medullary TEC lines. Tyrosine kinases of receptor type were differentially expressed between cortical and medullary TEC lines; e.g., mRNA expression of flg was observed more intensively in the cortical TEC line than in the medullary one, while mRNA expression of bek, met and sky was vice versa. On the other hand, expression of non-receptor tyrosine kinases, including four JAK-tyk family members, are comparable in both lines. These results suggested that these PTKs, especially of receptor type, might play an important role in the development of the thymic microenvironment.

Amino Acid Sequence↗
PubMed1995

The role of thymus in the aging of Th cell subpopulations and age-associated alteration of cytokine production by these cells.

Mouse CD4+ T cells were subdivided into two subpopulations, naive (CD44low CD45RBhigh) and memory (CD44high CD45RBlow) T cells, by flow cytometric analysis. Examination of spleen and peripheral blood of C57BL/6 mice of various ages revealed that there was a reciprocal age-associated change in these two subpopulations, i.e. naive T cells predominant in young mice decreased with age, while memory T cells increased. In order to investigate the role of the thymus in the age change of naive and memory T cells, we employed two experimental systems: radiation bone marrow chimeras constructed between young and old mice, and grafting of young or old thymus into nude mice. Data from these two experiments suggested that the young thymus has a greater ability to provide naive T cells than the old thymus, while the old thymus favors the maintenance of memory T cells rather than naive T cells. In reference to cytokine production by enriched naive and memory T cells, young naive T cells produced mainly IL-2 and young memory T cells mainly IL-4. On the other hand, in old mice, memory T cells produced twice as much IL-2 than naive T cells, although the level was significantly lower than that of young mice. In addition, old naive T cells produced twice as much IL-4 than old memory T cells. These results suggested a distinct age change in the profile of cytokine production and functional heterogeneity of two Th cell subpopulations.

Age Factors↗
PubMed1994

Understanding the mechanism of the age-change of thymic function to promote T cell differentiation.

Immunological functions peak at around puberty and gradually decline thereafter with advancing age. The immunological decline mainly occurs in the T cell-dependent immune system and is generally associated with an increase in not only susceptibility to infections but also incidence of autoimmune phenomena. The age-related changes in T-cell dependent immune functions can be mainly ascribed to the physiological thymic involution which starts in the early phase of life. The age-related thymic involution can be ascribed to either extrinsic or intrinsic factors. Bone marrow stem cells can be one of the extrinsic factors for the thymic involution, but their role is estimated to be marginal as compared with alteration of the thymic microenvironment. With advancing age, the thymic capacity to promote T-cell differentiation declines together with a change in the composition of T-cell subsets produced. Such an alteration of the thymic environment is responsible for the age-related change in peripheral T cells in number and in composition. Age change is observed in several intrinsic factors in the thymic environment which influence proliferation of thymocytes. These thymic intrinsic factors can either promote or inhibit proliferation of thymocytes, and promoting factors generally decrease with age with a concomitant increase in inhibitory factors. Various endocrine hormones are important extrinsic factors influencing the thymic function. In fact, physiological thymic involution can be intervened by manipulation of the endocrine system, sometimes resulting in rejuvenation of immune functions to a certain extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Epithelial class II MHC antigen normally expressed by submandibular glands of elderly people.

Immunohistochemical studies were made on 81 submandibular glands obtained from over 60-year-old autopsy cases. Those patients who had had either sialolithiasis or autoimmune diseases were not included in this study. HLA-DR expression was observed in the great majority (95.1%) of the aged submandibular glands, especially on the serous acinar cells and the intercalated duct cells, regardless of the appearance of focal lymphocytic infiltration. The incidence of HLA-DP expression was slightly lower (85.2%) and HLA-DQ was much lower (42.0%) than that of HLA-DR. These data support the proposal that epithelial expression of class II antigens in aged glands is a focal sign of age-related immunological disorders.

Aged↗
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

Restricted expression of transgenic HLA-DRA gene in thymic epithelial cells and its role in acquisition of T cell tolerance to self-superantigens and processed DR alpha-derived peptide.

We have established a set of transgenic mouse lines in which the HLA-DRA gene was expressed in different cell types. In one line (DR alpha-24), DR alpha E beta b molecules were expressed on thymic medullary and cortical epithelial cells and all lineages of bone marrow-derived antigen-presenting cells (APC) except for thymic macrophages. By contrast, expression of the molecules in another line (DR alpha-30) was found on thymic medullary and cortical epithelial cells but not on bone marrow-derived APC in the thymus and periphery. To evaluate the role of thymic epithelial cells in acquisition of T cell tolerance, comparative analysis of DR alpha-24 and DR alpha-30 was performed. In DR alpha-30, T cells expressing TcR V beta 5 and V beta 11 were eliminated to comparable levels to those in DR alpha-24, suggesting that expression of the DR alpha E beta b molecules on thymic epithelial cells are sufficient for clonal deletion of the self-superantigen-reactive T cells. In addition, CD4+ T cells from DR alpha-30 as well as those from DR alpha-24 were tolerant to DR alpha-derived peptide/I-Ab complex expressed on spleen cells from DR alpha-24 even in the presence of exogenous interleukin-2. These observations suggest that expression of the DR alpha chain in thymic epithelial cells could induce T cell tolerance directed toward naturally processed DR alpha-derived peptide bound to I-Ab molecules, probably via clonal deletion of the self-reactive T cells.

Animals↗
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↗
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↗
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↗