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Biomedical subjects

Y Kawabe

Publications and source records attributed to Y Kawabe.

At least 127 records · Page 7Linked to original sources
PubMed1996

[Home oxygen therapy (HOT) in patients with pulmonary tuberculosis sequelae--comparison between patients medically treated and those surgically treated].

In Japan there are about 40,000 patients under home oxygen therapy (HOT), of whom about 30 to 40% are pulmonary tuberculosis sequelae (TBS). These patients can be divided into three groups depending on the treatments they had, Group 1: those who had medical treatments only, Group 2: those who had artificial pneumothorax, and Group 3: those who had thoracoplasties or other surgical treatments. The purpose of this study was to observe the distributions and possible differences in the survival rates among these groups. The study included 1537 patients with TBS under HOT followed at National Hospitals and Sanatoriums nationwide in Japan. In 819 patients the treatments were specified and of those 354 were in Group 1, 29 in Group 2, and 436 in Group 3, so that the proportion of surgically treated patients in PTS was estimated between 28.4% (436/ 1537) to 53.2% (436/819). The ages at the onset of tuberculosis, at the start of HOT and the intervals in between were 36.6, 66.2 and 29.8 in Group 1, and 26.8, 65.5, and 38.1 in Group 3 respectively. Though the ages at the start of HOT were the same, those at the onset of tuberculosis were about ten years younger in Group 3 than in Group 1. Comparing Group 1 and 3, the survival rates after the initiation of HOT (Kaplan-Meier method) was better in Group 2 (surgically treated) than in Group 1 (medically treated). It is speculated that the reason could be a better preservation of the function of the remaining lung in the surgically treated and a higher incidence of obstructive impairments in the medically treated patients.

Adolescent↗
PubMed1996

Increased population of high fluorescence 1F7 (CD26) antigen on T cells in synovial fluid of patients with rheumatoid arthritis.

OBJECTIVE: To investigate the activation of T cells in peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis (RA). METHODS: The expression of CD26 (Ta1 and 1F7) antigen on T cells was analyzed in 7 women with RA and 7 healthy control subjects by immunofluorescence. RESULTS: The percentage of CD3+ CD26+ cells was significantly higher in PB of patients with RA compared with healthy subjects. The IF7+ cell population was divided into high (1F7+high cells) and low fluorescence populations (1F7+low cells), based on 1F7 antigen density. The percentage of 1F7+high cells in SF of RA was markedly increased compared with PB of patients and healthy subjects. However, RA SF contained lower percentages of whole 1F7+ cells compared with PB. CONCLUSION: Our results indicate that SF of patients with RA contains activated T cells, and suggest that T cells with high levels of CD26 antigen may preferentially migrate into the rheumatoid synovium to induce inflammation and tissue destruction.

Adult↗
PubMed1995

Defective TCR-mediated signaling in anergic T cells.

Extrathymic T cell tolerance to Ags can be achieved through clonal deletion by activation-induced programmed cell death as well as by functional unresponsiveness (anergy) of Ag reactive-T cells. Previous studies demonstrated that in vivo administration of staphylococcal enterotoxin B (SEB) induces SEB-specific T cell anergy. To investigate the molecular mechanisms of T cell anergy, we analyzed the TCR-mediated signal transduction in normal and anergic T cells. Anergic T cells exhibited impaired protein tyrosine phosphorylation on TCR-mediated stimulation. The altered tyrosine phosphorylation in anergic T cells may be caused by a defect in tyrosine phosphorylation of TCR zeta-chain and its subsequent association with ZAP-70 tyrosine kinase. Our data demonstrated that TCR zeta-chain phosphorylation and its sequential interaction with ZAP-70 are essential for the initiation of TCR-mediated signal transduction.

Animals↗
PubMed1995

Macrophage scavenger receptor mediates the endocytic uptake and degradation of advanced glycation end products of the Maillard reaction.

Modification of proteins by long-term incubation with glucose leads to the formation of advanced glycation end products (AGE). Recent immunological demonstration of the presence of AGE proteins in several human tissues suggests that they may be involved in aging, diabetic complications and atherosclerosis. AGE proteins are taken up by macrophages via the AGE receptor, which is similar to the macrophage scavenger receptor (MSR). In the present study, we examined whether MSR could mediate the endocytic uptake of AGE proteins by using Chinese hamster ovary (CHO) cells overexpressing bovine type II MSR (CHO-SRII). 125I-labelled AGE bovine serum albumin (125I-AGE-BSA) as well as 125I-acetylated low-density lipoprotein (125I-acetyl-LDL) underwent endocytic degradation by CHO-SRII cells, but not by control CHO cells. Endocytic degradation of 125I-acetyl-LDL and 125I-AGE-BSA by CHO-SRII cells was significantly inhibited by unlabeled AGE-BSA, as well as by acetyl-LDL. Immunoelectron microscopic studies using both AGE-BSA conjugated with gold particles and anti-(bovine MSR) antibody (D2) revealed co-localization of gold particles and the reactive sites for the antibody at coated pits of plasma membranes as well as in endosomes. These results clearly show that MSR mediates the endocytic uptake and degradation of AGE proteins, suggesting a new role of MSR in biological recognition of AGE in vivo.

Animals↗
PubMed1995

The role of protein kinase in human synovial fibroblast growth.

The histological features of rheumatoid arthritis (RA) consist of overgrowth of synovial cells. Several growth factors that cause synovial hyperplasia have been identified in RA synovium. The basic-fibroblast growth factor (b-FGF), representing one of these growth factors, may play an important role in the pathogenesis of RA. We examined the b-FGF-mediated intracellular signal pathway involved in synovial cell growth. b-FGF-induced synovial cell growth was inhibited by protein tyrosine kinase (PTK) inhibitors, herbimycin A and genistein, but not by H7 that inhibits protein kinase C (PKC). Stimulation of synovial cells with b-FGF resulted in tyrosine phosphorylation of cellular proteins and MAP kinase activation. Our results also demonstrated that b-FGF-mediated activation of MAP kinase was inhibited by herbimycin A indicating that protein tyrosine kinase may be involved in the activation of MAP kinase in human synovial cells. However, inhibition of b-FGF-mediated MAP kinase activation by PKC downregulation did not occur.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Transforming growth factor beta 1 induces apoptotic cell death in cultured human umbilical vein endothelial cells with down-regulated expression of bcl-2.

Transforming growth factor beta 1 (TGF-beta 1) is a potent growth inhibitor of human umbilical vein endothelial cells (HUVEC). We investigated whether apoptosis is involved in the TGF-beta 1 mediated HUVEC growth inhibition. Using immunofluorescence microscopy and staining by propidium iodide, we showed HUVEC treated with TGF-beta 1 contained characteristic apoptotic nuclei with condensation of chromatin. FACS analysis demonstrated that the number of cells with hypodiploid DNA contents were increased in HUVEC treated with TGF-beta 1. The DNA fragmentation assay exhibited typical ladder formation in TGF-beta 1-treated HUVEC. Using Western blot analysis, the expression of bcl-2 on HUVEC was down-regulated by TGF-beta 1-treatment. These findings suggest that TGF-beta 1 regulates the growth of HUVEC by inducing apoptosis accompanied with down-regulation of bcl-2 expression.

Apoptosis↗
PubMed1995

The molecular mechanism of the induction of the low density lipoprotein receptor by chenodeoxycholic acid in cultured human cells.

In a cultured human hepatoblastoma cell line, Hep G2, chenodeoxycholic acid (CDCA) induced LDL receptor mRNA levels approximately 4 fold and mRNA levels for HMG-CoA reductase and HMG-CoA synthase two fold. In contrast, the mRNA levels for mevalonate kinase, farnesyl pyrophosphate synthase and squalene synthase were not changed significantly. The pattern of the induction of the sterol-sensitive genes was similar to the induction by N-acetyl-leucyl-leucyl-norleucinal (ALLN), an SREBP degradation inhibitor, suggesting that CDCA may increase mature SREBPs. CDCA could inhibit the 25-hydroxycholesterol mediated inactivation of SREBP without affecting mRNA levels of SREBPs. These results suggest that CDCA can affect sterol metabolism by a novel mechanism involving the inhibition of the oxysterol-mediated inactivation of SREBP.

Alkyl and Aryl Transferases↗
PubMed1995

Localization of advanced glycation end products of Maillard reaction in bovine tissues and their endocytosis by macrophage scavenger receptors.

In aged bovines, the accumulation of advanced glycation end-products (AGEs) in macrophages, endothelial cells, adventitial cells, or pericytes; epithelial or parenchymal cells of some organs such as the liver, adrenals, and kidneys; neuronal cells in the brain; and extracellular matrix was demonstrated by immunohistochemistry using anti-AGE monoclonal antibody 6D12. Immunoelectron microscopy demonstrated the localization of AGEs in the endosomal and lysosomal compartments of various types of cell and in the extracellular matrix. By biochemical characterization of the interaction of AGEs with bovine alveolar macrophages using [125I]AGE-bovine serum albumin (BSA), the cell association and subsequent endocytic degradation of [125I]AGE-BSA were confirmed. To investigate the possible participation of scavenger receptors in the endocytosis of AGEs, these cells were incubated with AGE-BSA conjugated with colloidal gold particles (AGE-BSA-Au particles) and examined by immunoelectron microscopy with a monoclonal antibody for bovine macrophage scavenger receptors, D2. In these macrophages, AGE-BSA-Au particles were bound to the D2-positive scavenger receptors on the surface membrane, endocytosed, and directed to secondary lysosomes. The scavenger receptors were dissociated from the ligands in late endosomes and recycled via a trans-Golgi system to the cell surface membrane. These data suggest that scavenger receptors participate in the endocytic process of AGEs by macrophages.

Aging↗
PubMed1995

Serum cytokines in patients with rheumatoid arthritis. Correlation of interferon gamma and tumor necrosis factor alpha with the characteristics of peripheral blood mononuclear cells.

Serum cytokines such as interleukin 1 beta (IL-1 beta), interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF alpha) were measured in 40 patients with rheumatoid arthritis (RA). In the 40 patients studied, serum IL-1 beta was detected in 5 patients, IFN-gamma in 10 patients, and TNF alpha in 20 patients. The IL-1 beta-positive group showed increased values of activity indices compared to the IL-1 beta-negative group. Values of serum IFN-gamma correlated well with the number of peripheral blood lymphocytes and CD3+ cells and with the percentage of CD3+ CD26+ cells. Values of serum TNF alpha correlated positively with the number of peripheral blood monocytes and the percentage of CD3+ HLA-DR+ and CD3+ CD25+ cells. These results indicated that serum IL-1 beta in RA patients reflects the activity of RA, while the serum IFN-gamma and TNF alpha in RA patients may be related to circulating activated lymphocytes and monocytes, respectively.

Adult↗
PubMed1995

Synovial cells are potent antigen-presenting cells for superantigen, staphylococcal enterotoxin B (SEB).

There is ample evidence suggesting that superantigens may act as a triggering factor in the pathogenesis of rheumatoid arthritis (RA). We investigated whether superantigen could activate T cells in the presence of synovial cells. T cells were cultured with SEB in the presence of interferon-gamma (IFN-gamma)-treated synovial cells. T cell proliferation and activation were assessed by 3H-thymidine incorporation and IL-2 production. The expression of HLA class II antigens and adhesion molecules on synovial cells was detected by flow cytometer. In the presence of IFN-gamma-treated synovial cells, T cells proliferated vigorously and produced IL-2 in response to SEB. A low SEB-induced T cell response was noticed in the presence of untreated synovial cells. Allogeneic as well as autologous IFN-gamma-treated synovial cells markedly enhanced SEB-induced T cell proliferation. IFN-gamma-treated synovial cells had increased expression of HLA class II antigens and intercellular adhesion molecule-1 (ICAM-1) adhesion molecules. MoAbs towards these antigens markedly inhibited the SEB-induced T cell response. These results indicate that activated synovial cells are potent antigen-presenting cells for SEB to T cells, and that superantigens may play a critical role in the pathogenesis of RA through activated synovial cells.

Antibodies, Monoclonal↗
PubMed1995

Increased levels of serum IgM antibody to staphylococcal enterotoxin B in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the role of superantigen in rheumatoid arthritis (RA) by assaying the serum levels of staphylococcal enterotoxin B (SEB) antibodies. METHODS: Serum IgG and IgM SEB antibodies were measured using an enzyme linked immunosorbent assay (ELISA), and confirmed by Western blot analysis. The T cell receptor V beta (TCR V beta) repertoire was analysed using the reverse transcriptase polymerase chain reaction. RESULTS: RA patients had increased levels of serum IgM SEB antibody compared with normal subjects, patients with systemic lupus erythematosus, Sjögren's syndrome, and Behçet's disease. The titres of rheumatoid factor (RF) showed no correlation with the levels of IgM SEB antibodies, and the levels of SEB antibodies were not inhibited by the addition of human immunoglobulin, or after absorption of RF. RA patients whose disease duration was less than 10 years had greater levels of serum IgM SEB antibodies than those with disease duration more than 10 years. The levels of IgM and IgG SEB antibodies in synovial fluid from RA patients were correlated with those in their sera. Western blot analysis detected IgM and IgG SEB antibodies as a band of approximately 30 kDa molecular size. The percentage of TCR V beta 2, V beta 5.2, and V beta 12 in phytohaemagglutinin stimulated peripheral T cells correlated significantly with the levels of serum IgM SEB antibody in RA patients. CONCLUSION: These results suggest that SEB, one of the superantigens, may have a critical role in the pathogenesis of RA.

Adult↗
PubMed1995

FK506 augments activation-induced programmed cell death of T lymphocytes in vivo.

FK506 is an immunosuppressive drug that inhibits T cell receptor-mediated signal transduction. This drug can induce immunological tolerance in allograft recipients. In this study, we investigated the in vivo effects of FK506 on T cell receptor-mediated apoptosis induction. Injection of anti-CD3 antibody (Ab) in mice resulted in the elimination of CD4+ CD8+ thymocytes by DNA fragmentation. FK506 treatment significantly augmented thymic apoptosis induced by in vivo anti-CD3 Ab administration. Increased thymic apoptosis resulted in the disappearance of CD4+ CD8+ thymocytes after anti-CD3 Ab/FK506 treatment. DNA fragmentation triggered by FK506 was induced exclusively in antigen-stimulated T cells, since enhanced DNA fragmentation induced by in vivo staphylococcal enterotoxin B (SEB) injection was confirmed in SEB-reactive V beta 8+ thymocytes but not in SEB-nonreactive V beta 6+ thymocytes. In addition to thymocytes, mature peripheral T cells also die by activation-induced programmed cell death. A similar effect of FK506 on activation-induced programmed cell death was observed in SEB-activated peripheral spleen T cells. In contrast, cyclosporin A treatment did not enhance activation-induced programmed cell death of thymocytes and peripheral T cells. Apoptosis is required for the generation and maintenance of self-tolerance in the immune system. Our findings suggest that FK506-triggered apoptosis after elimination of antigen-activated T cells may represent a potential mechanism of the immunological tolerance achieved by FK506 treatment.

Animals↗
PubMed1995

Tyrosine phosphorylation participates in peripheral T-cell activation and programmed cell death in vivo.

T-cell antigen receptor (TCR), which is not itself a protein tyrosine kinase (PTK), is thought to be associated with at least two SRC-like PTKs, P59fyn and ZAP-70. Activation of these PTKs is required for T-cell signal transduction. The aim of the present study was to determine the roles of PTKs in peripheral T-cell activation, induced by in vivo bacterial superantigen administration. We demonstrated that in vivo staphylococcal enterotoxin B (SEB) administration induced an enhanced tyrosine phosphorylation in peripheral spleen T cells undergoing a programmed cell death. In vitro immunecomplex kinase assay using antibody against P59fyn showed increased fyn kinase activity in SEB-stimulated spleen T cells. We examined the effect of PTK-specific inhibitors on DNA fragmentation and programmed cell death of V beta 8 positive T cells following in vitro culture of SEB-primed spleen T cells. Our results indicated that pretreatment of SEB-activated T cells with PTK inhibitors reduced DNA fragmentation and programmed cell death of V beta 8 positive T cells. These findings suggest that PTK plays an important role in activation and apoptosis of peripheral T cells induced by in vivo SEB administration.

Animals↗
PubMed1995

[Association of active pulmonary tuberculosis and malignant diseases: a clinical study].

The association of pulmonary tuberculosis and bronchogenic carcinoma has been reported by many authors, however, there are rather few studies about the association of pulmonary tuberculosis and other malignant diseases and how the latter affects the outcome of the former. Between 1980 and 1993, we had in our hospital 104 patients who had both active pulmonary tuberculosis and malignant diseases. Pulmonary tuberculosis was diagnosed at the time or after the diagnosis of malignant diseases in 74 patients, of whom 92% (68 patients) were males and 42% (31 patients) were over the age of 70. There were 23 stomach cancer (31%), and 15 lung cancer (20%). In 11 patients tuberculosis developed after the initiation of radiation and/or chemotherapy. 67 patients could be followed up for more than 6 months after the initiation of chemotherapy for tuberculosis and the negative conversion rate was as high as 95.5% at 3 months. The fact indicates that the association of malignant diseases does not influence the course of tuberculosis and that these patients could be treated safely in general hospitals, provided the diagnosis is made properly without unnecessary delay.

Adult↗
PubMed1995

[Long-term study of patients with sequelae of pulmonary tuberculosis after pneumonectomy--obstructive impairment and its causes].

Changes in pulmonary function, chest X-ray films, and CT were retrospectively studied in patients with sequeae of pulmonary tuberculosis 30 years after pneumonectomy (PNX). Over more than 10 years, VC and FEV1% changed at a rate of 23.2 +/- 8.8 ml and 0.683 +/- 0.688% per year, respectively. In the patients studied 30 years after PNX (N = 30), VC was 900 +/- 210 ml, %VC 31.6 +/- 8.1%, and FEV1% was 67.2 +/- 6.8%. About half of these patients had mild airway obstruction. FEV1% was negatively related to the distance from the hilum to the diaphragm on the mid-clavicular line (on the chest films) divided by body height (r = -0.607). Therefore, we think that the airway obstruction may be due to overextension of the bronchi of middle and lower lobes. Emphysema was not found in 18 patients who had no sign of hyperinflation or herniation of the remaining lung to the PNX side on their CT, but it was found in one patient with these signs.

Adult↗
PubMed1995

Determination of mRNA levels of cholesterol biosynthesis enzymes and LDL receptor using ribonuclease protection assay.

We designed a rapid method for determining mRNA content of cholesterol biosynthesis enzymes and LDL receptor (LDLR) using a ribonuclease protection assay (RPA). 32P-labeled cRNA fragments for genes of human LDLR and the enzymes HMG-CoA synthase (HMGS), HMG-CoA reductase (HMGR), mevalonate kinase (MK), farnesyl pyrophosphate synthase (FPPS), and squalene synthase (SQS) were prepared by in vitro transcription. Total RNA prepared from HepG2 cells was hybridized with the cRNA probe and the hybridized mRNA was determined under protection from RNase digestion. Probe content used in this assay was excess in determining the desired mRNA in total RNA, and surplus probes were completely digested using RNase under standard conditions. When cells were cultured in DMEM supplemented with 10% fetal calf serum (FCS), mRNA levels of FPPS, SQS, and LDLR were about 4- to 7-fold higher than those of HMGS, HMGR, and MK. On incubation with DMEM supplemented with 10% lipoprotein-deficient serum (LPDS) for 8 h, all messenger RNA levels increased 1.5- to 3.5-fold. In addition, when the HMG-CoA reductase inhibitor compactin was added to 10% LPDS-DMEM, these levels increased even further and the change in mRNA level seemed to differ between the enzymes and LDLR. From these results, we conclude that RPA is a useful method for determining the very small amount of mRNA level of cholesterol biosynthesis enzymes and LDLR in the cell.

Base Sequence↗
PubMed1994

Prevention of anti-CD3 monoclonal antibody-induced thymic apoptosis by protein tyrosine kinase inhibitors.

The thymus gland is crucial for the formation of thymocytes of diverse TCR specificity. Recent studies have demonstrated that deletion (negative selection) of autoreactive thymocytes occurs through the process of apoptosis in which TCR activates cell death by DNA fragmentation. In addition, in vitro stimulation of thymocytes with anti-CD3 mAb, calcium ionophore, or glucocorticoids results in DNA fragmentation followed by cell death. The availability of various substances capable of inhibiting activation-induced programmed cell death of thymocytes may be used as a tool to help identify several important events occurring during the process of apoptosis. We investigated the effect of protein tyrosine kinase (PTK) inhibitors, herbimycin A and genistein, on thymocyte apoptosis induced by stimulation of anti-CD3 mAb or glucocorticoid. Anti-CD3 mAb stimulation resulted in removal of CD4+CD8+ thymocytes by DNA fragmentation. However, in PTK inhibitor-pretreated thymocytes, there was a minimal deletion of double positive thymocytes. In contrast, PTK inhibitors did not prevent glucocorticoid-induced thymic apoptosis. Our results suggest that anti-CD3 mAb-induced thymic apoptosis depends on PTK activation via TCR, and that glucocorticoid-induced thymic apoptosis is PTK-independent.

Animals↗