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Biomedical subjects

Y Ueki

Publications and source records attributed to Y Ueki.

At least 91 records · Page 5Linked to original sources

Increased accumulation of cytosine arabinoside in human leukemic cells and enhancement of its cell-killing activity by uridine.

The effects of uridine(UR) on the cell-killing activity of cytosine arabinoside(ara-C) against human leukemic cells, MOLT-4, and on ara-C accumulation in cells were studied. The 50% lethal dose(LD50) of ara-C as determined by clonogenic assay was decreased to 5.0 x 10(-8) mol from 9.0 x 10(-7) mol after 3 days exposure to 10(-3) mol of UR. The accumulation of 3H-ara-C at 24 and 48 h was significantly increased in culture medium containing 10(-8) mol of 3H-ara-C and 10(-3) mol of UR (5,129 +/- 123.5 vs 2,554 +/- 115.5 cpm/10(5) cells at 24 h, p less than 0.01, and 5,772 +/- 123.2 vs 1,372 +/- 51.8 cpm/10(5) cells at 48 h, p less than 0.01). It is noteworthy that cell-killing activity of ara-C against human leukemic cells was enhanced by the combination with a nucleoside(UR), but not with antileukemic agents.

Cell Survival↗

Phenotypic characterization of lymphocytes infiltrating synovial tissue from patients with rheumatoid arthritis: analysis of lymphocytes isolated from minced synovial tissue by dual immunofluorescent staining.

The phenotypic markers of mononuclear cells in synovial tissue from 19 patients with active rheumatoid arthritis (RA) were identified by a dual immunofluorescent method. The mononuclear cells were isolated from synovial tissue by mechanical disaggregation and an enzymatic digestion technique. The results revealed a marked reduction in CD4+2H4+ cells (suppressor inducer T cells) and an increment in CD4+4B4+ cells (helper T cells) among CD4+ cells in synovial tissue. The percentage of CD8+CD11b+ cells (suppressor effector T cells) was significantly lower in synovial tissue than in peripheral blood from patients with RA, resulting in an increased percentage of CD8+CD11b-- cells (cytotoxic T cells). The synovial tissue had higher percentages of pan B cells (B1+ cells), differentiated B cells (B1+B2-- cells) and plasma cells (PCA-1+ cells). These findings suggest that a combination of the increment in helper T cells, the reduction in suppressor T cells, and the increment in differentiated B cells may lead to excessive production of autoantibodies.

Adult↗

Inhibitory effects of gold sodium thiomalate on the proliferation and interferon-gamma induced HLA-DR expression in human endothelial cells.

Our study was undertaken to investigate the effects of gold sodium thiomalate (GSTM) on the proliferation and HLA-DR antigen expression of human umbilical vein endothelial cells (EC). The proliferation of the EC was determined by 3H-thymidine incorporation into the EC. The expression of HLA-DR antigen on the surface of the EC was detected by an indirect immunofluorescent method using a fluorescent flow cytometer. When GSTM was added at the start of the EC culture, GSTM at a low concentration could inhibit the proliferative response of the EC to endothelial cell growth supplement. Furthermore, when the EC were cultured with recombinant interferon-gamma (rIFN-gamma) and GSTM, GSTM was also able to suppress the HLA-DR antigen expression on the surface of EC induced by rIFN-gamma. On the time-kinetic study of the effects of GSTM on the HLA-DR antigen expression induced by rIFN-gamma, the pretreatment of GSTM was able to suppress the HLA-DR antigen expression, whereas GSTM did not affect the HLA-DR antigen expression already induced by rIFN-gamma. Our findings suggest that the therapeutic effects of gold compounds in patients with rheumatoid arthritis may be attributed to the interference of the proliferation and HLA-DR antigen expression of the EC.

Antigens, Surface↗

[A case of early gastric carcinoma which disappeared with treatment of low dose 5-FU].

A 60-year-old male with early gastric carcinoma of Ha type, had received colectomy for his carcinoma in transverse colon. He was treated after operation with 5-Fluorouracil (5-FU) orally at 200 mg per day. One and a half month after operation at a total dose 8.4 g 5-FU, the patient was examined on his stomach by endoscope and barium enema. The polypoid tumor in the stomach was not recognized there. No lesion has been noticed in his stomach endoscopically in the following 1 year.

Administration, Oral↗

Increment in the Ta1+ cells in the peripheral blood and thyroid tissue of patients with Graves' disease.

The present study utilized the anti-Ta1 mAb to characterize the cell surface phenotypes of peripheral blood and intrathyroidal lymphocytes in patients with Graves' disease. We found an increase in PBL bearing the Ta1 Ag in untreated patients. The euthyroid patients in remission, induced by antithyroidal drugs, radioisotope therapy, and subtotal thyroidectomy, had lower percentages of Ta1+ cells than did untreated patients. An increased percentage of Ta1+ cells in untreated patients was found in both CD4+ cells and CD8+ cells. The ratio of CD4+Ta1+ cells to CD8+Ta1+ cells in untreated patients was significantly higher than that of normal subjects. There was a positive correlation between the percentage of Ta1+ cells and the level of anti-TSH receptor antibody. In this prospective study, the proportion of Ta1+ cells was decreased in parallel with the reduction in anti-TSH receptor antibody and free T3 levels. In the chronically treated patients, the proportion of Ta1+ cells in the thyroid tissue was, yet similar to that in the peripheral blood, markedly increased in comparison to that of normal subjects. In contrast to Ta1+ cells, the thyroid tissue had a significantly higher percentage of HLA-DR+ T cells than did the paired peripheral blood. The proliferative responses of the Ta1+ cell-enriched population isolated from untreated patients toward thyroglobulin and microsomal Ag were markedly higher than those in a Ta1+ cell-depleted population, but both populations were able to respond equally to PHA. These results suggest that the Ta1+ cells may include Ag-triggered memory cells that are reactive with thyroid-specific Ag. Furthermore, monitoring such cells may provide an objective measure of abnormal immunologic activity.

Adolescent↗

Characterization of HTLV-I in a T-cell line established from a patient with myelopathy.

We have established an interleukin 2-dependent, OKT4-positive T-cell line, named HCT-1, from cells in the cerebrospinal fluid obtained from a patient with human T-cell lymphotropic virus type I (HTLV-1)-associated myelopathy. Antigens for HTLV-I were detected in HCT-1 cells by indirect immunofluorescence and Western blot testing, and type C virus particles were detected by electron microscopy. Southern blot analysis of HCT-1 cellular DNA, using an HTLV-I probe, revealed that the integrated provirus genome could not be distinguished from the HTLV-I genome in adult patients with T-cell leukemia.

Blotting, Southern↗

Cerebral ischemia: changes in monoamines are independent of energy metabolism.

The relationship of neurotransmitters and neuroeffectors to the energy state of the brain was examined in the gerbil model of ischemia after 5 and 15 min of bilateral common carotid artery occlusion only or with 1 hr of reperfusion. The gerbil brains were fixed by microwave irradiation and a total of 15 metabolites were measured from a single piece of tissue from either the hippocampus or the striatum. The rapid alterations in energy-related compounds and cyclic nucleotides appeared to be directly related both to the loss of oxygen and glucose during ischemia and the resupply of these nutrients during reflow. Significant reduction in the level of monoamines occurred principally during reflow, at a time when the energy-related metabolites were restored. It is proposed that the changes in monoamines were triggered by other ischemic-induced events unrelated to energy depletion.

Adenosine Triphosphate↗

Alignment of protein sequences using the hydrophobic core scores.

Making an alignment of the amino acid sequences is an essential step in the prediction of an unknown protein structure by model building from the known structure of a protein of the same family. To improve the accuracy of the alignments, we introduced the concept of hydrophobic core scores, which restrains putting insertions/deletions in the hydrophobic core regions of the protein. Eight pairs of protein sequences were aligned by this method, and the quality of the alignments were assessed by reference to those obtained by the structural superposition. The introduction of the hydrophobic core scores derived from the knowledge of the tertiary structure of one of each pair resulted in an improvement of the accuracy of the alignments. The quality of the alignment was found to depend on the homology of the protein sequences.

Amino Acid Sequence↗

Interleukin-1 production and action in thyroid tissue.

This study was undertaken to determine the effects of interleukin-1 (IL-1) on human thyroid epithelial cells (thyrocytes) and whether thyrocytes produce IL-1. The supernatants of cultured peripheral blood monocytes stimulated with lipopolysaccharide (LPS) increased [3H]thymidine incorporation into thyrocytes from normal subjects and patients with Grave's disease. The IL-1 levels of cultured supernatants of monocytes were measured by a thymocyte costimulation assay and a solid phase sandwich immunoenzymometric assay. The supernatants of monocyte cultures stimulated with LPS contained significant amounts of IL-1 bioactivity and IL-1 alpha and IL-1 beta immunoactivity. Recombinant IL-1 beta (rIL-1 beta) also stimulated [3H]thymidine incorporation into thyrocytes from normal subjects and patients with Graves' disease, and it increased the proportion of thyrocytes in the S phase of the cell cycle. Furthermore, thyrocytes stimulated with rIL-1 beta for 24 h produced significant amounts of prostaglandin E2. Indomethacin inhibited completely the rIL-1 beta-stimulated prostaglandin E2 production and increased markedly [3H]thymidine incorporation. IL-1-like activity also was detected in the cultured supernatants of lipopolysaccharide (LPS)-stimulated thyrocytes from Graves' and normal thyroid glands, but the amount of IL-1-like activity secreted by thyrocytes was significantly less than that secreted by circulating monocytes. The kinetics of the release of IL-1-like activity by thyrocytes were similar to those of its production by circulating monocytes. Pretreatment of thyrocytes with interferon-gamma failed to enhance the release of IL-1-like activity. Moreover, IL-1 alpha or IL-1 beta immunoreactivity could not be detected in the supernatants of LPS-stimulated thyrocytes, despite the presence of IL-1-like bioactivity. No IL-1 alpha mRNA was detected in unstimulated thyrocytes or thyrocytes stimulated with LPS and phorbol myristate acid. These findings demonstrate that thyrocytes produce an IL-1-like substance(s), but not IL-1, when stimulated by LPS. We conclude that IL-1 may regulate the proliferation of thyrocytes and that local production of IL-1 by infiltrating monocytes may contribute to the development of goiter in patients with autoimmune thyroid diseases.

Biological Availability↗

Abnormal B lymphocyte function in thyroid glands from patients with Graves' disease.

Thyroid-infiltrating B lymphocytes from patients with Graves' disease were investigated in regard to their phenotypic profiles, cell size, cell cycle status, proliferative response to Staphylococcus aureus Cowan 1 (SAC), and spontaneous production of immunoglobulin G (IgG) and antithyroidal autoantibodies. Thyroid tissues and peripheral blood were obtained at the time of subtotal thyroidectomy of 27 Graves' patients who had been treated with thionamide drugs and iodide before operation. Two intrathyroidal mononuclear cell populations were obtained from these thyroid tissues. One cell population was isolated from the supernatants after mechanical disaggregation of the tissues and was defined as TG-1 cells. Another cell population, defined as TG-2 cells, was isolated from the supernatants of overnight cultures of the thyroid debris after enzymatic digestion. The percentages of B lymphocytes bearing activated markers and plasma cells (CD20+CD21-, IgM+IgD-, CD20+ transferrin receptor+, PCA-1+) were significantly higher in the TG-1 and TG-2 cell populations than in peripheral blood from Graves' disease patients and normal subjects. These phenotypic changes were accompanied by increased thyroid gland B lymphocyte cell size from patients with Graves' disease. The proliferative response of B lymphocytes to SAC was markedly lower in TG-1 and TG-2 cell populations than in peripheral blood cells from Graves' disease patients and normal subjects. B lymphocytes isolated from thyroid glands secreted significantly more IgG and antithyroidal autoantibodies than those from peripheral blood. Based on the findings of abnormalities in thyroid-infiltrating B lymphocytes, we suggest that activated B lymphocytes may induce the excessive production of antithyroidal autoantibodies in thyroid glands from patients with Graves' disease.

Adult↗

Cytotoxic activity of interleukin-2 (IL-2) activated killer cells toward thyroid epithelial cells.

We investigated the sensitivity of thyroid epithelial cells (thyrocytes) to IL-2 activated killer cells. The thyrocytes were lysed by autologous and allogeneic IL-2-activated killer cells; there were no differences in sensitivity to the killer cells between normal thyrocytes and thyrocytes from patients with Graves' disease. When thyrocytes were pretreated with recombinant interferon (rIFN) gamma or alpha, the IL-2-activated killer cell-mediated cytotoxicity was depressed and varied inversely with the cell surface expression of class I HLA gene products. The rIFN-gamma pretreatment did not alter the kinetics of thyrocytes lysis by IL-2-activated killer cells. Using cold target competition analysis, rIFN-gamma-pretreated thyrocytes clearly competed less effectively than did untreated cells for lysis of untreated target cells. These results suggest that rIFN-gamma or IFN-alpha pretreatment of thyrocytes may reduce their ability to be recognized by effector cells. These findings suggest that destruction of thyrocytes in autoimmune thyroiditis may be, in part, due to IL-2-activated killer cells and may be regulated by IFN.

Cells, Cultured↗

Increment of Tal positive cells in peripheral blood from patients with rheumatoid arthritis.

Recently it was demonstrated that the Tal antigen is a marker for activated T cells and the population of Tal+ cells includes memory T cells. Our study was undertaken to analyze Tal+ cells in peripheral blood from patients with rheumatoid arthritis (RA) and examine the correlation between the proportion of Tal+ cells and disease activity. Using a dual immunofluorescent method, T cell subsets were analyzed in peripheral blood from 46 patients with RA, 10 patients with osteoarthritis (OA) and 10 healthy subjects. Patients with RA had a significantly higher percentage of T cells bearing the Tal antigen than patients with OA and healthy subjects. Furthermore, the percentage of CD3+Tal+ cells in peripheral blood from patients with RA was significantly correlated with disease activity including erythrocyte sedimentation rate, morning stiffness and the Lansbury index, whereas CD3+ HLA-DR+ cells did not correlate. In serial observations in patients with RA, the percentage of CD3+ Tal+ cells decreased in accordance with the improvement of disease activity. Thus, we suggest that the percentage of Tal+ cells may be a marker of the disease activity in patients with RA.

Aged↗

Elevation of a tumor associated antigen CA 19-9 levels in patients with rheumatic diseases.

We investigated the incidence and characteristics of an elevated tumor associated antigen CA 19-9 in patients with rheumatic diseases. Serum concentration of CA 19-9 was increased in 13 of 39 patients (33.3%) with definite or classical rheumatoid arthritis (RA), in 6 of 19 patients (31.6%) with systemic lupus erythematosus (SLE), in 3 of 9 patients (33.3%) with progressive systemic sclerosis (PSS) and in 9 of the other 35 patients (25.7%). Malignant neoplasm was not detected in any of the patients with rheumatic diseases. Pretreatment of mouse serum with patients' sera did not reduce the measured CA 19-9 values obtained by the conventional assay. The CA 19-9 antigen found in sera from patients with RA was present in a non-IgG fraction, and had the same molecular weight as that in one patient with pancreatic cancer, as determined by gel filtration. These results demonstrated that serum CA 19-9 levels were increased in some patients with rheumatic diseases.

Adult↗

[A case of progressive systemic sclerosis accompanied with rheumatoid arthritis].

A 37-year old man was suffered from Raynaud's phenomenon, sclerodactyly, and polyarthritis involving knees, shoulders, and hands. Recurrent skin ulcers were present in finger tips. Laboratory studies showed positive RA test, antinuclear antibody (nucleolar type), and anti-Scl 70 antibody. So diagnosis of progressive systemic sclerosis (PSS) was made. Progressed destructive arthritis with rheumatoid nodules developed in the patient. The joint destruction was severe and he was satisfied with the criteria of the American Rheumatism Association (ARA). This patient appears to be an overlapping case of PSS and rheumatoid arthritis (RA).

Adult↗

[Combination chemo-endocrine therapy of metastatic and stage IV breast cancer with cyclophosphamide, adriamycin, prednisolone and tamoxifen (CAPT)--with special reference to management of brain and liver metastasis].

Sixty-three evaluable patients with metastatic and stage IV breast cancer who had not previously undergone chemo-endocrine therapy were treated with a combination chemoendocrine therapy regimen consisting of cyclophosphamide 100 mg p.o. every day, adriamycin 10 mg i.v. on day 1 to 5, prednisolone 10 mg or 20 mg (20 mg was given on day 1 to 5) p.o. every day, and tamoxifen 20 mg p.o. every day. Adriamycin on day 1 to 5 was repeated three times every two weeks. After a total dose of 150 mg of adriamycin, the patients were changed to maintenance therapy consisting of cyclophosphamide 100 mg p.o., prednisolone 10 mg p.o. and tamoxifen 20 mg p.o. every day. After 72 months of the treatment there were 61 patients good for evaluation, 13 patients achieved a complete response (21.3%) with a median survival of 30.5 months and 18 patients had a partial response (29.5%) with a median survival of 21.0 months, and 30 patients failed to respond (49.2%) with a median survival of 8.5 months. There was a significant difference in survival time between responders (CR + PR) and non-responders (NC + PD) (p less than 0.001). Responses by site were seen in lung 10/18 (55.6%), liver 3/6 (50.0%), brain 2/4 (50.0%), bone 6/17 (35.3%) and soft tissue 14/24 (56.3%). A Satisfactory response for brain and liver metastasis, which are usually viewed as a sign of grim prognosis, was obtained similar to other sites of metastasis. Retreatment with CAPT, which was attempted in patients with secondary brain metastasis who responded to CAPT for initial brain metastasis, was uniformly effective. High ration of androgen to corticosteroid, positive estrogen receptors, long disease-free survival (over two years), premenopausal, high Broca' index (above 110) resulted from the chemo-endocrine therapy regimen CAPT. Toxicity was minimal and consisted of nausea, vomiting, alopecia and leucopenia.

Adult↗

Probing the normal and autoimmune B cell repertoire with Epstein-Barr virus. Frequency of B cells producing monoreactive high affinity autoantibodies in patients with Hashimoto's disease and systemic lupus erythematosus.

The frequency of cell precursors producing Ig of different classes and Ag-binding activities were determined, using EBV-infection and limiting dilution assays, in healthy subjects and patients with autoimmune disease. A large proportion of circulating B cells from healthy subjects were committed to the production of IgM antibodies that were polyreactive and bound a variety of self- and exogenous Ag, i.e., IgG Fc fragment, ssDNA, thyroglobulin, thyroid microsomal Ag, insulin, and tetanus toxoid. Similar frequencies of these polyreactive antibody-producing cells were found in patients with Hashimoto's disease and SLE. In contrast, significantly higher frequencies of cell precursors producing monoreactive IgG autoantibodies to thyroid Ag (thyroglobulin and thyroid microsomal Ag) and ssDNA were found in Hashimoto's disease and SLE patients, respectively. Calculation of the Kd revealed that monoclonal polyreactive antibodies were in general low affinity (Kd, 10(-3) to 10(-7) mol/liter), whereas monoclonal monoreactive autoantibodies were high affinity (Kd, 10(-9) to 10(-11) mol/liter). The detected frequency and high affinity of the monoreactive autoantibodies in Hashimoto's disease and SLE patients were comparable to those of anti-tetanus toxoid and anti-insulin IgG mAb produced by B cell clones from vaccinated healthy subjects and insulin-treated patients with insulin-dependent diabetes mellitus, respectively. These findings support the hypothesis that the autoimmune B cell repertoire in patients with organ-specific and systemic autoimmunity is shaped by Ag-driven responses rather than merely reflecting a polyclonal B cell activation.

Antibodies, Monoclonal↗

Effect of ischemia on noradrenergic and energy-related metabolites in the cerebral cortex of young and adult gerbils.

Relationships between ischemic changes in the cerebral cortical content of energy and noradrenergic metabolites were evaluated in young and adult gerbils. Groups of 3-week- and 3-month-old gerbils were subjected to 5 or 15 min of bilateral carotid artery occlusion alone or with 1 hr of release. Ischemia of 5 and 15 min depleted energy-related metabolites but did not affect the content of either norepinephrine or homovanillic acid in young and adult gerbils. At 1 h of reflow, after 5 and 15 min of ischemia, the levels of norepinephrine significantly decreased, while those of homovanillic acid increased in the adult but not in the young gerbils. At this time a complete recovery of energy reserves was seen in both the young and the adult gerbils. These results indicate that the ischemic change in homeostasis of energy metabolism is not directly associated with that of the noradrenergic system in young and adult cerebral cortex.

Aging↗

Delayed hypometabolism induced by bilateral ischemia in the gerbil: regional metabolic thresholds.

The common carotid arteries were occluded in gerbils for 5 min and the metabolic rate was estimated by measuring the loss of high-energy phosphate equivalents at 4 days of reperfusion in the cerebral cortex, hippocampus, and striatum. Metabolites values at 4 days of reperfusion were not different from those of controls with the exception of glycogen, which was significantly elevated in the hippocampus. The metabolic rate, as determined by the "closed-box" method at 4 days of reflow, was decreased by more than 50% in all three regions after 5 min of bilateral ischemia. The ischemic time necessary to elicit the hypometabolic response at 4 days of reflow was 2, 3 and 4 min for the striatum, hippocampus, and cortex, respectively. It is suggested that delayed postischemic hypometabolism may be a component of an adaptive process which counteracts, to varying degrees, the deleterious effects of ischemia depending on the region examined.

Adenosine Triphosphate↗