Biomedical subjects

Y Kawabe

Publications and source records attributed to Y Kawabe.

At least 91 records · Page 5Linked to original sources

PubMed1998

[Report of national survey on death due to tuberculosis in 1994 in national hospitals and the treatment and prognosis of tuberculous patients with mechanical ventilation].

1. National survey on died patients with active tuberculosis (tbc) or tbc sequelae had been held in national hospitals every five year from 1959 (3433 cases) to 1994 (688 cases). In 1994, 330 patients died due to pulmonary tbc. Recent study revealed the decreased rate of death due to operation, or far advanced cavitary cases, and the increased rate of nontuberculous death, aged people (> 60 yrs), and nontuberculous complications. Main causes of death in pulmonary tbc were lung insufficiency (about half) and general weakness (almost one fifth) in any survey. Rapid progression of pulmonary tbc had been increased cause of death (20.9% in 1994). Main attributable factors of death in 1994 in pulmonary tbc cases were severe condition on admission (38.4%), disturbed lung function (31.2%) and old age (33.2%). Delayed treatment (13.9%) and complications (12.1%) were increasing factors. Early death within 3 months from onset in 1994 was seen in patients < 60 yrs as well as in patients > 80 yrs. Severity due to delayed treatment and rapid progression were supposed to the causes of early death. 2. During 1994 to 1997, mechanical ventilation (MV; > 24 hours) was applied to 18 patients with active pulmonary tuberculosis; 10 acute respiratory failure (ARF), 5 chronic respiratory failure (CRF), 2 central nervous system tbc and 1 hemoptysis. Only one ARF case and three CRF ones survived. ARF cases had low PaO2/FIO2 (about 100), low albuminemia, short MV period (7 cases: < 7 days) and steroid therapy (9 cases). CRF cases had higher PaO2/FIO2 (294), longer MV period (4 cases: > 30 days) and all CO2 narcosis. 3. Noninvasive positive pressure ventilation (NIPPV) was applied to 23 patients with pulmonary tbc sequelae. In 13 patients with stable chronic respiratory failure (mean PaO2 91 mmHg, PaCO2 82 mmHg) 10 continued NIPPV and started home mechanical ventilation (HMV). In 10 patients with acute on chronic respiratory failure (mean PaO2 61 mmHg, PaCO2 92 mmHg) 2 patients fell into tracheal intermittent positive pressure ventilation (TIPPV). Eight patients recovered with NIPPV and 5 started HMV. NIPPV is supposed to be very effective to treat severe chronic hypercapmic respiratory failure.

Adult↗

PubMed1998

[The levels of FDP, FDP-E and D-dimer in patients with rheumatoid arthritis].

We studied the relationship of FDP and D-dimer levels of rheumatoid arthritis (RA) patients with their activities of RA. We evaluated FDP/D-dimer levels of thirty-six RA patients. And we also evaluated FDP/D-dimer levels of 14 patients with systemic lupus erythematosus (SLE) and 12 patients with other rheumatic diseases as control. RA patients were divided into two groups according to their activities. Nineteen patients, who fulfilled at least three of four activities criteria, were classified as active group [RA (A) group], and other 17 patients were classified as not-active group [RA (B) group]. FDP and D-dimer levels of RA patients were higher than those of SLE or other patients group significantly (P < 0.01). Furthermore, in RA patients, high levels of FDP and D-dimer were observed in RA (A) group compared to RA (B) group. In some RA patients, decrease of FDP and D-dimer levels were observed according to their RA activities. FDP and D-dimer levels were not correlated with the level of rheumatoid factor (RF). These results show that the FDP and D-dimer levels were elevated according to RA activity in RA patients.

Adult↗

PubMed1998

Serum amyloid A protein induces production of matrix metalloproteinases by human synovial fibroblasts.

Serum amyloid A (SAA) is a precursor protein for amyloid A, which is a constituent for amyloid fibrils in secondary amyloidosis. To determine the role of SAA in the articular destruction in patients with rheumatoid arthritis (RA), we investigated the effects of SAA on the production of matrix metalloproteinases (MMPs) by rheumatoid synovial fibroblasts. SAA stimulated rheumatoid synovial fibroblasts to produce MMP-2 and MMP-3 in a dose-dependent manner. Pretreatment of synovial fibroblasts with cycloheximide prevented SAA-mediated MMP-2 and MMP-3 secretion. When SAA-containing media were immunodepleted by anti-SAA-specific antibody, SAA-mediated MMP secretion was also abrogated. The level of MMP-3 mRNA was increased in SAA-stimulated synovial fibroblasts compared with that of control cells. Our data indicate that SAA is a potent inducer of MMPs in the RA synovium and may play a critical role in the degradation of extracellular matrix in the rheumatoid joint.

Arthritis, Rheumatoid↗

PubMed1998

[Clinical review of 74 cases with miliary tuberculosis].

Seventy-four cases of miliary tuberculosis were studied retrospectively. The mean age of the patients was 45.3 years. Twenty-two patients suffered from another underlying diseases. Six were infected with human immunodeficiency virus. Twelve had been treated with corticosteroids. Fever was present in 97.3 per cent of patients. Elevation of serum alkaline phosphatase was found in 67.6 per cent of cases. The skin reaction to tuberculin was positive in 61.2 per cent. Nodular shadows were found in the chest X-ray in 98.6 per cent of cases. The nodules were smaller than 2 mm in diameter in 52.7 per cent of cases. Other findings were enlargement of mediastinal lymph node (17.6%), cavities (23.0%), pleural effusion (27.0%), and consolidation (35.1%). Sputum cultures and urine cultures were positive for Mycobacterium tuberculosis in 76.8 per cent and 58.6 per cent of cases respectively. The diagnosis was confirmed by histopathological findings in some cases. The rate of positive biopsies was 61.5 per cent by bone marrow aspiration, 83.3 per cent by lymph node biopsy, 100 per cent by liver and lung biopsy. Antituberculosis therapy was successful in most of the patients. Seven patients died of miliary tuberculosis, 4 of them had adult respiratory distress syndrome.

Adolescent↗

PubMed1998

[Lung cancer in patients with sequelae of tuberculosis].

To clarify features of lung cancer in patients with tuberculosis sequelae, we analyzed data on 15 cases (5.1%) who were diagnosed with lung cancer before death among 294 deceased cases with tuberculosis sequelae at our hospital. There were 12 men and 3 women, with a mean age of 64 years. Most of the 15 patients had pulmonary dysfunction, and 4 had received home oxygen therapy. All 12 men had a history of smoking, and 10 of them had squamous cell carcinoma of the lung. There was no definite correlation between the locations of the tuberculosis lesion and those of lung cancer lesion on chest X-rays. Twelve patients had had thoracoplasty for tuberculosis, and in 6 of these patients the lung cancer occurred in the same lung. Lung cancer was apt to be diagnosed in an advanced stage. However, in patients who received home oxygen therapy, diagnosis had been made at an early stage because of the frequent chest X-ray follow-up. We conclude that lung cancer is an important complication in patients with tuberculosis sequelae, and early diagnosis of lung cancer by careful follow-up is essential in the care of cases with tuberculosis sequelae who have poor pulmonary function and/or systemic conditions.

Aged↗

PubMed1997

FK506 potentiates steroid-induced T-cell apoptosis.

BACKGROUND: FK506 and glucocorticoids are used for allograft rejection, graft-versus-host disease, and autoimmune diseases. MATERIALS: We investigated the combined effect of FK506 and glucocorticoids on T-cell apoptosis. RESULTS: Dexamethasone injection in mice reduced the number of CD4+CD8+ thymocytes by increasing DNA fragmentation. Pretreatment with FK506 significantly augmented thymocyte DNA fragmentation induced by dexamethasone injection. Increased thymic apoptosis resulted in the disappearance of CD4+CD8+ thymocytes after FK506/dexamethasone injection. In addition to thymocytes, mature human peripheral blood T cells undergo apoptosis by exposure to dexamethasone in vitro. FK506 synergistically enhanced dexamethasone-mediated apoptosis of human peripheral blood T cells. CONCLUSIONS: Thus, our results showed that FK506 enhanced dexamethasone-induced apoptosis of T cells in vivo and in vitro. This interaction may enhance the therapeutic immunosuppression achieved by these two drugs.

Adult↗

PubMed1997

Fas/Fas ligand interaction regulates cytotoxicity of CD4+ T cells against staphylococcal enterotoxin B-pulsed endothelial cells.

Infiltration of activated CD4+ T cells and apoptosis of endothelial cells are present in the synovium of rheumatoid arthritis (RA). Using staphylococcal enterotoxin B (SEB) as an antigen, we examined the possible role of antigen (Ag)-dependent activation of CD4+ T cells by endothelial cells, in inducing endothelial cell apoptosis. The human endothelial cell line, EA.hy926 cells, was cultured with or without interferon-gamma (IFN-gamma) and further incubated with CD4+ T cells in the presence or absence of SEB. After this cocultivation, the cytotoxicity and Fas ligand (FasL) expression of CD4+ T cells were examined. A small percentage of EA.hy926 cells expressed HLA-DR and -DQ, and this expression was significantly augmented after IFN-gamma stimulation. Anti-Fas IgM-induced apoptosis was exhibited by both unstimulated and IFN-gamma-stimulated EA.hy926 cells. Cytotoxicity of CD4+ T cells toward SEB-pulsed unstimulated EA.hy926 cells was detected. Furthermore, when CD4+ T cells were incubated with IFN-gamma-stimulated, SEB-pulsed EA.hy926 cells with augmented HLA-DR and -DQ expression, this cytotoxicity was more significant. The addition of anti-HLA-DR and -DQ monoclonal antibodies (mAbs) or human Fas chimeric protein (hFas-Fc) reduced the cytotoxicity. FasL expression was induced in CD4+ T cells cocultured with SEB-pulsed EA.hy926 cells, especially when the EA.hy926 cells were IFN-gamma-stimulated. Furthermore, the addition of mAbs against CD54 and CD58 inhibited both the cytotoxicity and FasL expression of CD4+ T cells induced by SEB-pulsed EA.hy926 cells, indicating the importance of costimulatory molecules on EA.hy926 cells in activating CD4+ T cells. Our results suggest that CD4+ T cells are activated by endothelial cells in an Ag-dependent manner and subsequently express FasL, which induces Fas-mediated apoptosis of endothelial cells. This phenomenon may counteract the growth of RA synovium by inhibiting the proliferation of endothelial cells.

Antibodies, Monoclonal↗

PubMed1997

Beta 2-microglobulin induces stromelysin production by human synovial fibroblasts.

beta 2-Microglobulin (beta 2-m) is a major constituent of amyloid fibrils in hemodialysis-associated amyloidosis (HAA), a serious complication in patients on long-term hemodialysis. The most distinctive pathological feature of HAA is the deposition of amyloid fibrils with subsequent articular inflammation and destruction. However, the pathological role of beta 2-m is not well known at present. We investigated the effects of beta 2-m on the production of proteinases from synovial fibroblasts isolated from patients with rheumatoid arthritis. beta 2-m stimulated synovial fibroblasts to produce stromelysin, a neutral matrix metalloproteinase (MMP-3). The production of MMP-2 and of a tissue inhibitor of metalloproteinase-1 (TIMP-1) were not enhanced by beta 2-m-treated synovial fibroblasts. Stromelysin is capable of degrading several components of the extracellular matrix and believed to be the key enzyme causing articular destruction in inflammatory joint diseases. Our results suggest a novel role for beta 2-m in articular inflammation and destruction mediated by stromelysin in HAA.

Cells, Cultured↗

PubMed1997

An alternative form of nucleolysin binds to a T-cluster DNA in the silencer element of platelet factor 4 gene.

The cDNA of a T-cluster binding protein (TCBP) has been cloned using the Southwestern method. The cDNA sequence of TCBP reveals that it has 78% homology to that of nucleolysin, a factor involved in apoptosis in cytolytic lymphocyte target cells. In particular, the 0.8kb sequences of the 5'-half of both cDNAs were identical. However, nucleolysin has a lysosome-targeting motif at the carboxy terminus, while TCBP has a hydrophobic sequence instead. Southern blot experiments have revealed that both cDNA sequences existed in the same YAC clone derived from chromosome 10. This strongly suggests that the TCBP cDNA is an alternatively spliced product of the nucleolysin/TCBP gene. The TCBP mRNA is ubiquitously expressed, not only in megakaryocytic cells but also in other hematopoietic cells. However, when HEL cells were induced to differentiate to megakaryocytes by DMSO, TCBP mRNA was reduced, while PF4 gene expression increased simultaneously. Gel mobility shift analysis demonstrated that recombinant TCBP specifically bound to the T-cluster and the proximal T-rich region of the PF4 promoter. Co-transfection experiments showed that TCBP reduced the gene expression from the PF4 promoter. On the other hand, TCBP did not affect expression from the PF4 promoter in which the T-cluster and the T-rich region had been removed. These results indicate that TCBP may participate in the regulation of PF4 gene expression by binding to the T-cluster and the T-rich sequence.

Amino Acid Sequence↗

PubMed1997

A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection.

Macrophage type-I and type-II class-A scavenger receptors (MSR-A) are implicated in the pathological deposition of cholesterol during atherogenesis as a result of receptor-mediated uptake of modified low-density lipoproteins (mLDL). MSR-A can bind an extraordinarily wide range of ligands, including bacterial pathogens, and also mediates cation-independent macrophage adhesion in vitro. Here we show that targeted disruption of the MSR-A gene in mice results in a reduction in the size of atherosclerotic lesions in an animal deficient in apolipoprotein E. Macrophages from MSR-A-deficient mice show a marked decrease in mLDL uptake in vitro, whereas mLDL clearance from plasma occurs at a normal rate, indicating that there may be alternative mechanisms for removing mLDL from the circulation. In addition, MSR-A-knockout mice show an increased susceptibility to infection with Listeria monocytogenes or herpes simplex virus type-1, indicating that MSR-A may play a part in host defence against pathogens.

Animals↗

PubMed1997

Apoptosis induction in human peripheral blood T lymphocytes by high-dose steroid therapy.

High-dose steroid pulse therapy is effective in transplant rejection and severe autoimmune diseases. Our goal was to identify the mechanism by which high-dose steroid exerts specific immunosuppressive actions. In this study, we investigated the in vivo effects of high-dose (1 g) methylprednisolone infusion on peripheral blood T lymphocyte apoptosis induction in 15 patients with severe autoimmune diseases. DNA fragmentation was detected in peripheral blood T cells isolated from these patients after 2 and 4 hr of steroid infusion. In contrast, T cells isolated from the same patients before or 8 or more hours after infusion did not show DNA fragmentation. DNA fragmentation was more significant in CD4+ than CD8+ T cells. The susceptibility of CD4+ T cells to apoptosis was associated with a lower expression of Bcl-2 in these cells compared with that on CD8+ T cells. To support the T-cell apoptosis induction by pulse therapy, peripheral blood T cells from normal subjects underwent DNA fragmentation after in vitro exposure to 2.5-10 microg/ml of methylprednisolone for 30 min. Our results indicate that induction of peripheral blood T-cell apoptosis is an important mechanism contributing to the immunosuppression observed after high-dose steroid therapy.

Adult↗

PubMed1997

Superantigen-induced stromelysin production from rheumatoid synovial cells.

Superantigens activate a large number of T cells in a V beta-restricted manner after binding to MHC class II molecules on the antigen presenting cells (APC). Superantigens also activate APC directly by interacting with their ligands, MHC class II molecules. In the present study, we examined the effects of superantigens on matrix metalloproteinases (MMPs) secretion from rheumatoid synovial fibroblasts. We demonstrated that stimulation of interferon (IFN)-gamma-treated synovial fibroblasts with staphylococcal enterotoxin A (SEA) selectively induced the secretion of stromelysin, a neutral MMP, from synovial fibroblasts. Pretreatment of synovial fibroblasts with cycloheximide, an inhibitor of protein synthesis, prevented MMP-3 secretion from rheumatoid synovial cells suggesting that protein synthesis was required for SEA-induced MMP-3 secretion after SEA binding to MHC class II molecules. Our data suggest that in the synovium, bacterial superantigens are potent inducers of stromelysin which plays a critical role in articular destruction observed in inflammatory joint disease.

Arthritis, Rheumatoid↗

PubMed1997

A case of cytophagic histiocytic panniculitis: successful treatment of recurrent attacks with steroid pulse therapy and oral cyclosporin A.

We report a 35-year-old man, who had been diagnosed with Weber-Christian disease, presented with acute onset of high fever, malaise, jaundice and hepatosplenomegaly with subcutaneous nodules. Laboratory tests showed elevated serum ferritin and liver enzymes, especially lactate dehydrogenase (LDH), with pancytopenia and coagulation abnormalities. Peripheral blood and bone marrow examinations showed erythro-, leuko- and thrombo-phagocytic histiocytes and macrophages. The patient developed the same clinical features seven years ago. Based on diagnosis of cytophagic histiocytic panniculitis, the patient was treated with steroid pulse therapy and oral cyclosporin A. The combination therapy caused a marked improvement in the clinical condition.

Adult↗

PubMed1997

Modulation of Fas-mediated apoptosis of human thyroid epithelial cells by IgG from patients with Graves' disease (GD) and idiopathic myxoedema.

The expression of two autoimmune thyroid diseases. GD and idiopathic myxoedema, is associated with antibodies to the thyroid-stimulating hormone (TSH) receptor. Thyroid stimulating antibodies (TSAb) in GD are TSH agonists and cause hyperthyroidism as well as goitre, whereas thyroid stimulation blocking antibodies (TSBAb) in idiopathic myxoedema are TSH antagonists and cause hypothyroidism and thyroid atrophy. We investigated the effect of antibodies to TSH receptor on Fas-mediated apoptosis of thyroid epithelial cells (thyrocytes). Human IgG was isolated from healthy donors, patients with GD and idiopathic myxoedema. Human thyrocytes were obtained from surgical specimens. Thyrocytes were cultured in the presence or absence of human IgG with or without interferon-gamma (IFN-gamma) or IL-1beta for a specified time. After incubation, we examined the level of cAMP in cultured supernatants and both Fas and Bcl-2 expression on thyrocytes. In addition, we examined anti-Fas-mediated apoptosis of thyrocytes. Fas expression on thyrocytes was significantly down-regulated by Graves' IgG and TSH, although idiopathic myxoedema IgG did not affect Fas expression on thyrocytes. Idiopathic myxoedema IgG abrogated the effect of TSH on both cAMP production and inhibition of Fas expression on thyrocytes. Treatment of thyrocytes with IL-1beta or IFN-gamma caused a marked augmentation of Fas expression on thyrocytes. The increase of Fas expression of thyrocytes induced by IL-1beta or IFN-gamma was significantly suppressed in the presence of TSH or Graves' IgG. Anti-Fas-induced apoptosis of thyrocytes was observed in thyrocytes treated with IL-1beta or IFN-gamma, but was markedly inhibited in the presence of TSH or Graves' IgG. Furthermore, idiopathic myxoedema IgG abrogated most of the inhibitory effect of TSH on Fas-mediated apoptosis of thyrocytes treated with IL-1beta or IFN-gamma. Bcl-2 expression of thyrocytes did not change after stimulation with TSH, Graves' IgG, idiopathic myxoedema IgG, IL-1beta or IFN-gamma. These results suggest that TSAb found in Graves' patients may be potentially involved in the development of goitre by inhibition of Fas-mediated apoptosis of thyrocytes. In addition, TSBAb inhibit the action of TSH and increase the sensitivity toward Fas-mediated apoptosis of thyrocytes, inducing thyroid atrophy seen in patients with idiopathic myxoedema.

Apoptosis↗

PubMed1997

Effects of rapamycin on apoptosis of rheumatoid synovial cells.

In the present study, we investigated the effects of an immunosuppressant, rapamycin, on bcl-2 expression and the susceptibility of human rheumatoid synovial fibroblasts to Fas-mediated apoptosis. Rapamycin treatment down-regulated bcl-2 expression on rheumatoid synovial cells in a dose-dependent manner. In contrast, Fas antigen expression was not influenced by rapamycin treatment. Rapamycin treatment also enhanced the susceptibility of rheumatoid synovial cells to anti-Fas monoclonal antibody-mediated apoptosis. Our results suggest that rapamycin augments the sensitivity of rheumatoid synovial fibroblasts to apoptosis by down-regulating bcl-2 expression. This pharmacological alteration of sensitivity to apoptosis in the rheumatoid synovium may represent a new therapeutic approach for rheumatoid arthritis.

Adult↗

PubMed1997

Inhibitory effects of interleukin-10 on synovial cells of rheumatoid arthritis.

This paper describes the immunoregulatory effects of interleukin-10 (IL-10) on synovial cells in vitro. Synovial cells were cultured with IL-10 in the presence or absence of various cytokines. Following incubation, the costimulatory molecule expression on synovial cells and cytokine production in culture supernatants were analysed by an indirect immunofluorescence method and enzyme-linked immunosorbent assay, respectively. We also examined the effect of IL-10 on the function of synovial cells as antigen-presenting cells (APC). Synovial cells spontaneously express several kinds of costimulatory molecule and produce various kinds of cytokines. Stimulation of synovial cells with interferon-gamma (IFN-gamma), IL-1 beta, or 12-O-tetradecanoyl phorbol 13-acetate (TPA) markedly enhanced the expression of costimulatory molecules and cytokine production of these cells. Both spontaneous and up-regulated costimulatory molecule expression and cytokine production were significantly suppressed by the addition of IL-10. Autologous T-cell proliferation was stimulated by purified protein derivative (PPD) in IFN-gamma-treated synovial cells and treatment of these synovial cells with IL-10 also suppressed T-cell proliferation. Our results suggest that IL-10 has an inhibitory effect on synovial cells and is an important immunoregulatory component of the cytokine network in rheumatoid arthritis.

Arthritis, Rheumatoid↗

PubMed1997

High prevalence of Sjögren's syndrome in patients with HTLV-I associated myelopathy.

OBJECTIVE: A high seroprevalence of HTLV-I in female Sjögren's syndrome (SS) patients has been reported in Nagasaki, Japan, an area that is heavily endemic for HTLV-I infection. Salivary IgA class antibodies to HTLV-I were common among HTLV-I seropositive patients with SS. This study was undertaken to elucidate the pathogenesis of SS caused by HTLV-I infection. METHODS: The clinical features and histological findings of SS and the prevalence of serum autoantibodies in 10 patients with HTLV-I associated myelopathy (HAM) who were consecutively admitted into Nagasaki University School of Medicine, were compared with those of 20 HTLV-I seropositive and 20 HTLV-I seronegative patients with SS. RESULTS: Ocular and oral manifestations of SS were commonly detected in HAM patients. These patients also had extraglandular manifestations including recurrent uveitis, arthropathy, interstitial pneumonitis, Raynaud's phenomenon, and inflammatory bowel disease. All patients with HAM histologically showed a mononuclear cell infiltration in the labial salivary glands. Six of 10 patients had a mononuclear cell infiltration with a focus score of 1 or greater. According to the preliminary criteria for SS proposed by the European Community, definitive SS was diagnosed in six patients and probable SS in two patients. Serum gamma globulin and IgG values were increased in HAM patients. Patients with HAM had lower prevalence of rheumatoid factor, antinuclear antibody, and anti-SS-A (Ro) antibody than those of HTLV-I seropositive and HTLV-I seronegative SS patients. However, there was no significant difference in the prevalence of these antibodies among HAM patients with definitive SS, HTLV-I seropositive and HTLV-I seronegative SS patients. The CD3+CD4+ T cells preferentially infiltrated into the salivary glands in HAM patients as well as the salivary glands of patients with HTLV-I seropositive and seronegative patients. It seems probable that peripheral blood mononuclear cells from HAM patients preferentially infiltrated into the salivary glands, and that these cells produced the autoantibodies as well as anti-HTLV-I antibody. CONCLUSION: The results strongly support the idea that HTLV-I is involved in the pathogenesis of the disease in a subset of patients with SS in endemic areas.

Adult↗

PubMed1997

Analysis of the hypervariable region of hepatitis C virus E2/NS1 gene in an infant infected by blood transfusion.

We investigated the sequential change in the hypervariable region 1 (HVR 1) of hepatitis C virus (HCV) E2/NS1 gene in an infant. He was transfused with 160 mL of blood containing the HCV (0.7 Meq/mL) on the 6th d after birth and subsequently developed chronic viremia. At 16 mo, the HVR1 amino acid sequences of HCV observed in the infant's sera were very similar to those from the donor (his maternal grandfather) on the day of transfusion. However, highly variable amino acid sequences of HVR1 were observed throughout infancy. These results demonstrate that an adaptive response of HCV to evade host immunity seems to occur, as in adult cases, even in early infancy when the ability to produce humoral immunoglobulin is thought to be low.

Amino Acid Sequence↗