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Y Kawabe

Publications and source records attributed to Y Kawabe.

At least 145 records · Page 8Linked to original sources
PubMed1994

The histidine interruption of an alpha-helical coiled coil allosterically mediates a pH-dependent ligand dissociation from macrophage scavenger receptors.

Macrophage scavenger receptors uptake modified low density lipoproteins (LDLs) through receptor-mediated endocytosis. In the alpha-helical coiled coil domain, 2 histidines (His168 and His260) disrupt leucine or isoleucine heptad repeats. Substitution of His168 or/and His260 to leucine had no effect on AcLDL binding activities. However, the His260-replaced receptors had their ligand degradation activities diminished. Cell surface ligand release experiments under acidic pH clarified that His260 mutants lost their ligand dissociation activities at 37 degrees C. Furthermore, immunoelectron microscopic experiments using anti-scavenger receptor antibody showed that the His260 replaced receptors were not able to release gold-labeled AcLDL in endosomes. Here we propose an allosterical ligand dissociation mechanism by His260 in macrophage scavenger receptors.

Allosteric Regulation↗
PubMed1994

Sterol mediated regulation of SREBP-1a,1b,1c and SREBP-2 in cultured human cells.

Under conditions of cholesterol depletion and SREBP-1 accumulation, changes in the levels of sterol regulatory element binding protein(s) (SREBPs) and sterol regulated gene mRNA were studied in Hep G2 cells by RNase protection assay. Cholesterol depletion increased the expression of mRNAs for cholesterol biosynthetic enzymes and low density lipoprotein (LDL) receptor. mRNAs levels for SREBP-1c and SREBP-2 were also increased by the cholesterol depletion. In contrast, levels for SREBP-1a and 1b (1a/b) mRNA increased transiently and then decreased. To examine the effect of SREBP-1 accumulation, Hep G2 cells were incubated with a SREBP-1 degradation inhibitor, N-acetyl-leucyl-leucyl-norleucinal (ALLN). The ALLN treatment increased the LDL receptor mRNA significantly, and also increased mRNA levels for HMG-CoA reductase, SREBP-1a/b and SREBP-2. The mRNA level for squalene synthase was not changed, and for SREBP-1c was decreased by the treatment. In conclusion, the regulation of differential expression of SREBP mRNA may be involved in sterol mediated regulation of gene expression. Moreover, the regulation of the SREBP-1 level may be a critical step in the regulation of sterol mediated LDL receptor expression.

Amino Acid Sequence↗
PubMed1994

Oxidation-induced aggregation of rabbit low-density lipoprotein by azo initiator.

Oxidation of low-density lipoprotein (LDL) has been considered as an important step in the early pathogenesis of atherosclerosis. We investigated the oxidative modification of LDL by a water-soluble azo-initiator AAPH (2,2,-azo-bis(2-amidinopropane).2HCl) and analyzed the uptake of AAPH-oxidized LDL with mouse peritoneal macrophages. Oxidative modification of LDL by AAPH was similar to the modification induced by copper in regard to the degree of oxidation and formation of aggregated LDL. The aggregated oxidized (AO-) LDL was fractionated by gel permeation chromatography and compared with the monomeric oxidized (MO-) LDL to make clear their characterization. The results of binding, cell association, and degradation with macrophages indicated that both AO- and MO-LDL were bound and endocytosed by macrophages. The cross competition experiment showed that nonreciprocal competition existed among MO-LDL, AO-LDL, and monomeric acetylated (MAc-) LDL. By the sterol accumulation experiment in macrophages with the various types of modified LDL, the cellular sterol accumulation was shown as the following order, AO-LDL > MAc-LDL > MO-LDL. These results indicated that the oxidation by AAPH can induce the aggregation of LDL and that the AO-LDL contribute to lipid accumulation into macrophages more than the MO-LDL.

Acetylation↗
PubMed1994

Expression of adhesion molecule ICAM-1 (CD54) in thyroid papillary adenocarcinoma.

The expression of adhesion molecules in thyroid specimens from 10 cases of papillary adenocarcinoma, 5 cases of follicular adenoma and 3 normal thyroid specimens was examined by an immunohistochemical method. Thyroid epithelial cells from all cases of papillary adenocarcinoma expressed the intercellular adhesion molecule 1 (ICAM-1, CD54). The ICAM-1-positive staining in these was detected predominantly on the apical site of malignant thyroid epithelial cells. However, no ICAM-1 expression was detected on thyrocytes of adenoma, and normal thyroid tissues. Furthermore, thyroid epithelial cells in patients with thyroid tumor and normal thyroid tissue did not react with anti-LFA-1, anti-VLA-4, anti-VCAM-1 and anti-ELAM-1 monoclonal antibodies. It is speculated that ICAM-1 expression in thyroid papillary adenocarcinoma may have a functional significance.

Adenocarcinoma, Follicular↗
PubMed1994

Mechanism of inhibitory effect of dextran sulfate and heparin on human T-cell lymphotropic virus type I (HTLV-I)-induced syncytium formation in vitro: role of cell-to-cell contact.

Cell-to-cell contact is usually essential for syncytium formation by HTLV-I-infected cell lines. The present study was undertaken to determine the inhibitory effect of polyanionic compounds, dextran sulfate and heparin, on HTLV-I-induced syncytium formation, as demonstrated by the fusion of HTLV-I-infected cells with target cells. These two compounds almost completely blocked syncytium formation in the early phase of the reaction at a concentration of 125 micrograms/ml, but dextran, as a control, did not inhibit it at concentrations up to 625 micrograms/ml. 50% inhibition of syncytium formation was detected at a concentration of 2 micrograms/ml of dextran sulfate 5000, 3 micrograms/ml of dextran sulfate 8000 and 8 micrograms/ml of heparin. The binding of radiolabeled HTLV-I-infected cells (HCT-1) to the target cells was inhibited by addition of dextran sulfate and heparin, and the inhibitory effects were concentration-dependent. No marked changes were detected in the expression of adhesion molecules on the virus-infected cells and target cells, and in the expression of envelope proteins on the virus-infected cells after exposing them to the polyanionic compounds. These results suggest that the blocking of cell-to-cell contact by polyanionic compounds, probably independent of surface adhesion molecules, is important for their inhibitory effect on HTLV-I-induced syncytium formation.

Antibodies, Monoclonal↗
PubMed1994

The expression of adhesion molecules in thyroid glands from patients with Graves' disease.

We studied the potential role of adhesion molecules in the pathogenesis of Graves' disease. Thyroid specimens of Graves' thyroid glands and control thyroid glands were stained with monoclonal antibodies against adhesion molecules by an immunohistologic method. Thyroid tissues obtained from patients with Graves' disease had an enhanced expression of intercellular adhesion molecule-1 (ICAM-1) on capillary endothelial cells around the thyroid follicles and on postcapillary endothelial cells in lesions with aggregates of mononuclear cells. Positive staining for ICAM-1, lymphocyte function-associated antigen-1 (LFA-1), and very late antigen-4 (VLA-4) was found on the infiltrating mononuclear cells. The postcapillary vascular endothelial cells expressed increased endothelial-leukocyte adhesion molecule-1 (ELAM-1), but not vascular cell adhesion molecule-1 (VCAM-1). VCAM-1 and ELAM-1 were detected on the dendritic-like cells in the germinal centers of lymphoid follicle-like areas. No significant expression of these adhesion molecules was detected on normal thyroid glands. These results suggest that the LFA-1/ICAM-1 and ELAM-1 pathways may be responsible for the migration of mononuclear cells into the thyroid glands of patients with Graves' disease, and that the VLA-4/VCAM-1 pathway plays a critical role in the cellular interactions that lead to the formation of B-memory cells and the excess production of antibodies.

Adult↗
PubMed1994

Expression of basic fibroblast growth factor in synovial tissues from patients with rheumatoid arthritis: detection by immunohistological staining and in situ hybridisation.

OBJECTIVE: The distribution and production of basic fibroblast growth factor (bFGF) was examined on the synovium from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: The localisation of bFGF was determined by an immunohistochemical staining procedure using anti-bFGF monoclonal antibody. The expression of bFGF mRNA was detected by nonradioactive in situ hybridisation using bFGF antisense oligo DNA. RESULTS: The bFGF was found in the synovial lining cell, sublining stromal fibroblast-like cells, and vascular endothelial cells from patients with RA and OA. Little or no bFGF was found in non-inflamed synovium. Immunostaining of bFGF in the synovial cells was more extensive and intense in synovium of patients with RA than that of patients with OA. The nuclei of the synovial lining cell layer were also immunostained. These nuclear staining were more intense in the lining cell layer from RA patients with moderate or severe proliferation of synovial cells than in RA patients with mild proliferation. The bFGF mRNA was also detected in the synovial lining cell layer of the inflamed synovium. CONCLUSION: The synovial lining cells produced bFGF. The proliferation of synovial cells in the inflamed joints may be the results of stimulation by the bFGF in autocrine manner.

Aged↗
PubMed1994

Interleukin 4 increases human synovial cell expression of VCAM-1 and T cell binding.

OBJECTIVE: The effects were studied of interleukin 4 (IL-4) on T cell-synovial cell adhesion and on the expression of adhesion molecules on the surface of synovial fibroblast-like cells. METHODS: The adhesion of T cells toward the synovial cells were measured by 51chromium-labelled adhesion assay. The expression of adhesion molecules on synovial cells were analysed by flowcytometry. RESULTS: Stimulation of synovial cells with IL-4 increased T cell-synovial cells adhesion in a time- and dose-dependent manner. IL-4 considerably enhanced the expression of VCAM-1 on the surface of synovial cells, but not the expression of ICAM-1 and ELAM-1. The combination of IL-1 beta and IL-4 had no effect on the expression of ICAM-1 or VCAM-1 on the surface of synovial cells. The increased adhesion of T cells to IL-4 stimulated synovial cells was inhibited significantly by adding anti-VCAM-1 or anti-CD29 monoclonal antibody. Furthermore, anti-VLA-4 alpha or the combination of anti-VLA-4 alpha and anti-VCAM-1 antibodies blocked completely T-cell binding to IL-4 stimulated synovial cells. CONCLUSIONS: These results suggest that the increased adhesion of T cells to IL-4-stimulated synovial cells is mediated by VLA-4/VCAM-1 pathway.

Adult↗
PubMed1994

Characterization of aggregated low density lipoproteins induced by copper-catalyzed oxidation.

Oxidation of low density lipoproteins (LDL) has been shown to lead to enhanced uptake by macrophages mediated by the scavenger receptor. In the present study, changes in LDL induced by copper-catalyzed oxidation were investigated using gel permeation chromatography (GPC), and the results were compared with several parameters of oxidized LDL (ox-LDL). When LDL at 200 micrograms/ml was oxidized with 10 microM Cu2+ at 37 degrees C for up to 24 hours, increases in thiobarbituric acid-reactive substances and electrophoretic mobility were first observed within 3 hours. An increase in fluorescence and a decrease in intact apolipoprotein B (apoB) were than observed in parallel with an increase in 125I-LDL degradation by macrophages after 6 hours. Finally, LDL aggregation separated by liquid chromatography was observed after 24 hours. The aggregated and monomeric fractions of ox-LDL were analyzed and the results compared with the monomeric fraction of native LDL. Both fractions of ox-LDL contained hardly any intact apoB and showed an intense fluorescence. The electrophoretic mobility increment of aggregated ox-LDL was almost half that of monomeric ox-LDL, yet the lysine residues of aggregated ox-LDL were more extensively decreased than those of monomeric ox-LDL. Degradation of aggregated ox-LDL by macrophages showed a slightly greater increase than that of monomeric ox-LDL. GPC analysis is a useful method to estimate the LDL aggregation, and these results provide a basis to investigate the formation of aggregated LDL.

Animals↗
PubMed1994

[Regulation of gene expression by cholesterol and macrophage scavenger receptor].

Cellular cholesterol level is strictly regulated by the synthesis and the incorporation of cholesterol. Cholesterol synthetic enzymes and lipoprotein receptors are regulated mainly at the transcriptional level. Recently, sterol regulatory element binding proteins (SREBPs) which induce LDL receptor expression, were cloned and the mechanism of sterol-mediated gene regulation was proposed. Cholesterol synthesizing enzymes such as HMG-CoA reductase, farnesyl pyrophosphate synthase and squalene synthase are also regulated by the cellular cholesterol level, but it is suggested that SREBPs are not play critical role in their regulation. Scavenger receptors also uptake cholesterol into macrophage, but the receptors are not regulated by the cellular cholesterol level and this leads to the abnormal accumulation of cholesterol in macrophages.

Alkyl and Aryl Transferases↗
PubMed1994

[Collagen diseases complicated with myelodysplastic syndrome (MDS)--report of three cases].

We presented three cases of collagen diseases complicated with myelodysplastic syndrome (MDS). To our knowledge, MDS following collagen disease is very rare, and only seven cases have been reported previously. First case (a 40-years old woman) had suffered from rheumatoid arthritis, systemic lupus erythematosus and Sjögren's syndrome for 16 years. Second case (a 65-years old woman) had suffered from rheumatoid arthritis for 15-years. Third case (a 63-years old woman) had suffered from progressive systemic sclerosis for 16 years. These patients developed MDS. After onset of MDS, cytopenia progressed rapidly within half a year. In the types of MDS, case 1 and case 2 had refractory anemia and case 3 had refractory anemia with excess of blasts and a preleukemic state. Case 2 had a clonal abnormality of haemopoietic stem cells. It is unlikely that MDS in our cases are caused by mutant agents or irradiation. These results suggest MDS may be contributed to long-term immunodysfunction found in these collagen diseases.

Adult↗
PubMed1993

Charged collagen structure mediates the recognition of negatively charged macromolecules by macrophage scavenger receptors.

Macrophage scavenger receptors mediate the recognition of a wide range of negatively charged macromolecules including modified low density lipoproteins (LDL). Truncated bovine receptors lacking residues 330-342, which include the conserved lysine cluster of a collagen-like domain, were unable to degrade modified LDL in spite of their expression on the cell surface. Substitution of lysine 337 into alanine abolished the acetyl-LDL degradation and binding at 37 degrees C, but did not abolish the 4 degrees C binding. In contrast, substitution of more than 2 lysines in this region are needed to abolish the oxidized LDL degradation and 37 degrees C binding. Based on computational modeling of this domain, we propose that a "charged collagen" structure containing a lysine cluster forms a positively charged groove which specifically interacts with negatively charged ligands.

Amino Acid Sequence↗
PubMed1993

Infection of human synovial cells by human T cell lymphotropic virus type I. Proliferation and granulocyte/macrophage colony-stimulating factor production by synovial cells.

The present study was performed to clarify the relationship between human T cell lymphotropic virus type I (HTLV-I) infection and chronic inflammatory arthropathy. To determine the ability of HTLV-I to infect synovial cells and the effect on synovial cell proliferation, synovial cells were cocultured with the HTLV-I-producing T cell lines (MT-2 or HCT-1). After coculture with HTLV-I-infected T cells, the synovial cells expressed HTLV-I-specific core antigens, and HTLV-I proviral DNA was detected from the synovial cells by polymerase chain reaction. These cocultured synovial cells with HTLV-I-infected T cells proliferated more actively than the synovial cells cocultured with uninfected T cells. This stimulatory effect of HTLV-I-infected T cells on synovial cell proliferation seems necessary to contact each other. After being cocultured with MT-2 cells, synovial cells proliferated more actively than control cells even after several passages. Furthermore, HTLV-I-infected synovial cells produced significant amounts of granulocyte/macrophage colony-stimulating factor. These results suggest that HTLV-I can infect synovial cells, resulting their active proliferation and may be involved in the pathogenesis of proliferative synovitis similar to that found in rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1993

Stimulation of mitogenesis in human thyroid epithelial cells by endothelin.

We investigated whether a potent vasoconstrictor, endothelin, stimulated the proliferation of human thyroid epithelial cells (thyrocytes). [3H]-thymidine incorporation into normal thyrocytes and thyrocytes from patients with Graves' disease was significantly increased at 10(-9) mol/l endothelin, reaching a plateau at 10(-8) mol/l. The proliferative responses of the thyrocytes obtained from patients with Graves' disease were similar to those of normal thyrocytes. Furthermore, the cell number of thyrocytes stimulated by endothelin was increased as compared with that of unstimulated thyrocytes. Neither indomethacin nor heparin affected this endothelin-stimulated thyrocyte proliferation. When thyrocytes were cultured with both endothelin and recombinant interleukin 1 beta, there was an additive effect on thyrocyte proliferation. The Ca2+ entry blocker, verapamil, inhibited both the proliferative responses of thyrocytes to endothelin and the additive effect of endothelin and recombinant interleukin 1 beta on thyrocyte proliferation. These results suggest that endothelin functions as a growth-promoting factor for human thyrocytes, presumably through intracellular calcium influx.

Calcium↗
PubMed1993

[Clinical features of intestinal tuberculosis].

We had tuberculosis infection cases of gastrointestinal tract diagnosed histopathologically during January 1980 to December 1991 in Tokyo National Chest Hospital. There were 12 cases (male 8, female 4) from 24 y.o. to 88 y.o. (mean 50 y.o.). We got histopathological specimen by operation (6 cases), biopsy (4), and section (2). Pulmonary tuberculosis was complicated in 8 cases, 7 cases had cavity formation and another case was miliary tuberculosis. Distribution of tuberculous lesion was colon (7 cases), small intestines (5), cecum (2), rectum (1) and esophagus (1). First symptom was mainly abdominal symptom such as abdominal pain and diarrhea. There were a perforative peritonitis and a intestinal obstruction during chemotherapy. Three died cases complicated low albuminemia. We suppose that serum albumin is one of the useful marker of patient's prognosis.

Adult↗
PubMed1992

Interferon-alpha and dexamethasone inhibit adhesion of T cells to endothelial cells and synovial cells.

We investigated whether interferon-gamma (IFN-gamma), interferon-alpha (IFN-alpha) and glucocorticoids affected the adhesion of T cells to human umbilical endothelial cells or human synovial cells. About 30% of peripheral blood T cells could bind to unstimulated endothelial cells, but only a few T cells could bind to unstimulated synovial cells. When both endothelial cells and synovial cells were cultured with recombinant IFN-gamma (rIFN-gamma), the percentage of T cell binding to both types of cells increased in a dose-dependent manner. rIFN-alpha and dexamethasone blocked the T cell binding to unstimulated endothelial cells. Furthermore, rIFN-alpha and dexamethasone suppressed T cell binding to both endothelial cells and synovial cells stimulated by IFN-gamma, and also inhibited intercellular adhesion molecule-1 (ICAM-1) expression on both endothelial cells and synovial cells stimulated by IFN-gamma. These results suggest that IFN-alpha and glucocorticoids may inhibit T cell binding to endothelial cells or synovial cells by modulating adhesion molecule expression on these cells.

Arthritis, Rheumatoid↗
PubMed1992

Primary Sjögren's syndrome with antibodies to HTLV-I: clinical and laboratory features.

The prevalence of antibodies to human T lymphotropic virus type I (HTLV-I) was studied in patients with primary Sjögren's syndrome. Thirteen of 36 serum samples were positive by enzyme linked immunosorbent assay (ELISA) and particle agglutination assay for antibodies to HTLV-I and were confirmed by western blotting. The presence of antibodies to HTLV-I may signify an HTLV-I carrier state. These patients had a high occurrence of extraglandular manifestations such as uveitis, myopathy, and recurrent high fever compared with patients who did not have antibodies to HTLV-I. Patients with antibodies to HTLV-I had an increased spontaneous proliferation of peripheral blood mononuclear cells compared with those without the antibodies. The proportions of activated and memory T cells (HLA-DR+ CD3+, CD25+ CD3+, and CD29+ CD4+ cells) were higher in HTLV-I carriers than in non-carriers. The presence of antibodies to HTLV-I in some patients with primary Sjögren's syndrome suggests that HTLV-I may cause primary Sjögren's syndrome or its extraglandular manifestations, or both.

Adult↗