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Biomedical subjects

M Nobunaga

Publications and source records attributed to M Nobunaga.

At least 37 records · Page 2Linked to original sources
PubMed1994

Additive two DMARD therapy of the patients with rheumatoid arthritis.

From the beginning of 1987 to the end of 1989, 72 rheumatoid arthritis patients (RA) whose disease could not be controlled by a single disease modifying antirheumatic drug (DMARD) were selected for the trial treatment. They continued the DMARD treatment used initially at its regular dose, and then started another DMARD regimen at 1/3 to 1/2 of the regular dose as an additive DMARD treatment, which we have designated as Additive Two DMARD Therapy (ATDT). The patients were followed until the end of 1992. In the 3 months of ATDT, the effectiveness of ATDT was obtained in 42 (58.3%) patients who showed more than a 30% decrease in the initial Lansbury's activity index (AI). The rate of side effects at 3 months were 5.6%. Tiopronin, bucillamine or salazopirine added to gold sodium thiomalate or tiopronin were suggested as the recommended DMARD combinations for ATDT. The suppressive effects on AI, ESR, CRP and rheumatoid factor continued for as long as 18 to 24 months. The mean period of ATDT was 21.7 months and that at which ATDT proved useful was 31.9 months. A discontinuation of the first DMARD treatment without any following disease aggravation was obtained in 10 of 15 patients whose disease activity had been sufficiently suppressed for longer than a year. In conclusion, ATDT was suggested to be a useful way of treating RA patients whose disease activity could not be controlled by a single DMARD treatment, as well as a way of evaluating the next DMARD while the ongoing DMARD was observed to gradually lose its initial drug effect.

Adult↗
PubMed1994

Methotrexate for steroid-resistant systemic lupus erythematosus.

We here report two patients with steroid-resistant systemic lupus erythematosus (SLE) who were successfully treated with methotrexate (MTX). In both cases, a steroid resistant high fever, associated with mild myositis and pancytopenia were the main common findings, and all these symptoms were alleviated within a few days either by 7.5 mg or 5 mg MTX per week. The number of CD4+ cells increased along with the clinical improvement, whereas the number of CD20+ cells and HLA-DR expressing cells also decreased. Taking into account the side effects of high dose corticosteroids and cyclophosphamides, treatment with a weekly low dose of MTX is known to contribute to an improvement in the long-term prognosis for patients with refractory SLE.

Adult↗
PubMed1994

Effects of cytokines on alkaline phosphatase and osteocalcin production, calcification and calcium release by human osteoblastic cells.

We examined the effect of TNF-alpha, IL-1 beta and IL-6 on alkaline phosphatase (ALP) and osteocalcin (OC) production, calcification and calcium (Ca) release in human osteoblastic cell cultures obtained from human periosteum. The cells were cultured with varying concentrations of cytokines for 3 days. TNF-alpha and IL-1 beta significantly inhibited ALP production, decreased cellular Ca content, and significantly enhanced 45Ca release in human osteoblastic cells. IL-6, on the other hand, significantly suppressed 45Ca release by osteoblastic cells. These cytokines did not influence the production of OC by osteoblastic cells. The results obtained suggest that TNF-alpha and IL-1 beta may inhibit bone formation and calcification and that the effects of IL-6 on osteoblastic cells may be different from those of TNF-alpha or IL-1 beta. These effects on osteoblastic cells may be one of the mechanisms by which bone loss occurs in patients with RA.

Alkaline Phosphatase↗
PubMed1994

Effect of cytokine-induced soluble ICAM-1 from human synovial cells on synovial cell-lymphocyte adhesion.

The present study was designed to establish (i) the effects of cytokines on soluble ICAM-1 (sICAM-1) production by human synovial cells (SC) and ICAM-1 expression on these cells, and (ii) the effects of sICAM-1 on lymphocyte-SC adhesion. sICAM-1 production was enhanced in parallel with ICAM-1 expression by IL-1 beta, TNF-alpha and IFN-gamma. IL-4 showed no effects on ICAM-1 expression. In contrast with the transient elevation of cell-associated ICAM-1 by IL-1 beta, which peaked 36 h after stimulation and declined thereafter, sICAM-1 continued to accumulate in culture supernatants even after 48 h. Purified sICAM-1 was obtained from a 48 h culture synovial cell supernatant by affinity chromatography using ICAM-1 monoclonal antibody. The purified sICAM-1 significantly inhibited adhesion of lymphocytes and monocytes to cytokine-stimulated synovial cells. These results suggest that sICAM-1 may modulate chronic synovitis by inhibiting ICAM-1-mediated cell-to-cell adhesion.

Cell Adhesion↗
PubMed1994

Trilineage response to rhG-CSF with subsequent clonal hematopoiesis in a patient with severe bone marrow aplasia.

We treated a patient with severe aplastic anemia with long-term administration of recombinant human granulocyte-colony stimulating factor (rhG-CSF). When a trilineage response of hematopoiesis was obtained after the first treatment, a chromosomal change [45XX, -7] was observed in 20 of the 20 metaphases examined. Later, we were able to show a monoclonal X inactivation pattern in the phosphoglycerate kinase (PGK) gene in the peripheral blood polymorphonuclear leukocytes and mononuclear cells, indicating the presence of clonal hematopoiesis regardless of the disappearance of the karyotype abnormality. We suggest that it is important to pay close attention to the appearance of clonal hematopoiesis during the administration of G-CSF to patients with idiopathic severe bone marrow aplasia.

Adult↗
PubMed1994

Analysis of the genes encoding the variable regions of human IgG rheumatoid factor.

OBJECTIVE: To better understand the immunoglobulin variable (V) region repertoire of rheumatoid factors (RF). METHODS: We characterized the heavy (H) and light (L) chain gene segments utilized in a monospecific IgG RF secreting hybridoma (AEE111F) which were derived from a patient with rheumatoid arthritis (RA). The hybridoma was established by fusion of a mouse myeloma cell line with bone marrow derived mononuclear cells from a patient with RA. First strand complementary DNA (cDNA) was generated and used for a polymerase chain reaction amplification of the H and L chain V domains. The amplified V domains were sequenced and compared with an extensive database of germline and cDNA V gene segments. RESULTS: The VH sequence was found to be 96% homologous to a previously described fetal VH3 cDNA (60P2). The VL sequence was also highly homologous to the previously described V lambda II gene (96%) derived from a patient with systemic lupus erythematosus which correlated with an 8.12 idiotype (Id), and to an antibacterial antibody against the Haemophilus influenzae type b capsular polysaccharide (94.7%). CONCLUSION: The overlap among this RF VL gene and the 2 reported V lambda sequences of antibodies that expressed anti-DNA related Id and an environmental pathogen specificity suggests that a part of the IgG RF isolated from patients with RA may thus be derived from the physiological natural antibody repertoire during an abnormal immune response and then develop high affinity, monospecific RF by the selection of an antigen driven mechanism.

Amino Acid Sequence↗
PubMed1994

[Cytokines and vasculitis].

Humoral and cellular immune mechanisms are thought to be involved in various forms of vasculitis and glomerulonephritis. Recent clinical and experimental results point to a role of cytokines in ANCA-positive vasculitides. In patients with malignant rheumatoid arthritis (MRA) which is characteristically induced by vasculitis in extra-articular lesions, serum soluble IL-2 receptor level was significantly higher than in rheumatoid arthritis patients without vasculitis. In Wegener's granulomatosis, TNF-alpha, IL-1 beta and IL-2 receptor positive infiltrating cells were observed in the kidneys of these patients, and in these patients, plasma levels of TNF-alpha and soluble IL-2 receptor were markedly increased. These results suggest that in ANCA-positive vasculitis TNF-alpha and IL-1 beta are produced in situ by activated infiltrating mononuclear cells and resident renal cells. In patients with giant cell arteritis and Kawasaki disease, increased levels of leukaemic inhibitory factor (LIF) and TNF-alpha were observed, respectively. These inflammatory cytokines increased in the vascular tissues and circulation may be a result of increased production by infiltrated cells or vascular cells such as endothelial cells or may be a result of endothelial cell lysis.

Arthritis, Rheumatoid↗
PubMed1994

Possible mechanism of vascular damage in pre-eclampsia.

To clarify the pathophysiological changes of pre-eclampsia, we investigated the injurious effect of sera from women with pre-eclampsia on cultured endothelial cells, vascular smooth muscle cells and fibroblasts. We obtained serum samples from 32 Japanese women, including 10 healthy nonpregnant women, 12 normal pregnant women and 10 women with pre-eclampsia. Cell injury was measured by the release of radiolabelled chromium from the cells into the culture medium. The mean values +/- SD of percentage chromium release from endothelial cells in normal nonpregnant, normal pregnant and pre-eclamptic subjects were 8.5 +/- 2.4, 8.8 +/- 2.1 and 19.7 +/- 3.6%, respectively. Sera from women with pre-eclampsia demonstrated significantly greater endothelial cell injury than did sera from normal pregnant and nonpregnant subjects. However, normal pregnant and pre-eclamptic subjects did not differ with respect to both vascular smooth muscle cell injury and fibroblast injury. These results indicate that a serum cytotoxic to endothelial cells is present in pre-eclampsia and that this activity has a cellular specificity for endothelial cells.

Adult↗
PubMed1994

[The comparison of clinical features between early rheumatoid arthritis and established rheumatoid arthritis].

Clinical features between 69 early RA patients (within a year duration) and 79 established RA patients (more than 3 years duration) were compared retrospectively. There were no significant differences about frequencies of morning stiffness (68.2% vs 54.4%) and rheumatoid nodules (20.2% vs 15.2%) between early RA and established RA. There were also no significant differences between two groups about elevation of ESR (92.8% vs 97.4%), positivity of CRP (97.1% vs 94.9%) and rheumatoid factor (RF) (82.6% vs 93.7%), and Lansbury activity index (AI) (mean 68.8% vs 78.8%). After hospitalization and treatment, all clinical indices (ESR, CRP, RF, AI) improved significantly in both groups. There, however, were clinically more "marked improvement" (39.1% vs 16.4%) and "remission" (8.7% vs none) in early RA group. We conclude that by hospitalization and treatment, clinical improvement can be expected in both early and established RA, but to secure satisfactory improvement, early detection and intervention of RA would be recommended.

Adult↗
PubMed1994

The association of myasthenia gravis and connective tissue diseases--the role of Sjøgren's syndrome.

The symptoms of myasthenia gravis (MG) reflect the loss of neuromuscular transmission due to the functional loss of the acetylcholine receptor. We reviewed the reported association of MG and connective tissue diseases including rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis (PSS), polymyositis and dermatomyositis, mixed connective tissue disease (MCTD) and Sjøgren's syndrome (SjS). We found that the association of MG and MCTD or PSS is rare. We also reviewed the role of D-penicillamine, thymus abnormalities and the coexistence of SjS as one of the underlying pathological conditions for the association of MG and various connective tissue diseases.

Connective Tissue Diseases↗
PubMed1993

Plasma concentration of human atrial natriuretic hormone in patients with connective tissue diseases.

Atrial natriuretic peptide (ANP), a peptide released from the cardiac atria, compensates blood volume expansion by its diuretic, natriuretic and vasoactive properties. We measured human plasma ANP(hANP) levels in patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and progressive systemic sclerosis (PSS) and found that their values were higher than those of healthy controls. In SLE patients, hANP levels correlated with serum creatinine concentration and the patients with proteinuria showed high levels of hANP. Administration of large amount of corticosteroid as a remission induction of the patients with SLE caused high levels of hANP. In patients with PSS, %FEV1 showed strong inverse correlations between hANP levels, and the patients with an enlarged second curvature of the heart had high levels of hANP. In patients with RA, no significant correlation was found between hANP levels and clinical variables including patients' age.

Adult↗
PubMed1993

The effects of cytokines on metalloproteinase inhibitors (TIMP) and collagenase production by human chondrocytes and TIMP production by synovial cells and endothelial cells.

It has been suggested that IL-1 produces cartilage matrix degradation by metalloproteinases such as collagenase, and that such degradation is regulated by metalloproteinase inhibitors (TIMP). Therefore, the balance between collagenase and TIMP is an important factor for tissue destruction in inflammatory joints. In the present study the effects of cytokines on collagenase and TIMP production in chondrocytes as well as the effects of cytokines on TIMP production in connective tissue cells were studied. IL-1 beta inhibited TIMP production in endothelial cells while enhancing TIMP production in synovial cells and chondrocytes. In addition, tumour necrosis factor-alpha (TNF-alpha) significantly inhibited and IL-6 significantly enhanced TIMP production in endothelial cells, synovial cells and chondrocytes. In the chondrocyte supernatant, collagenase activity/TIMP ratio was significantly elevated by the addition of either IL-1 beta or TNF-alpha to the cells, whereas the ratio was significantly decreased by IL-6. These results suggest that the cytokine effects on TIMP production are different among the different cell types, and that either IL-1 beta or TNF-alpha induce cartilage matrix degradation by disrupting the collagenase/TIMP balance, while, on the other hand, IL-6 protects the tissue through an opposite effect.

Cartilage↗
PubMed1993

Mixed connective tissue disease presenting myasthenia gravis.

We herein describe a 41-year-old female patient with an association of myasthenia gravis (MG) with anti-acetylcholine receptor (AcR) antibody, mixed connective tissue disease (MCTD) and Sjögren's syndrome (SjS). We reviewed the reported association of MG and MCTD, systemic lupus erythematosus, progressive systemic sclerosis, polymyositis and dermatomyositis, and SjS. Since we could find only two patients who fulfilled the diagnostic criteria for MCTD in the previous literature, we concluded that the association of MG and MCTD is rare. We also discuss the coexistence of SjS as one of the underlying pathological conditions for the association of MG and various connective tissue diseases including MCTD.

Adult↗
PubMed1993

In vitro IgM rheumatoid factor production by peripheral blood mononuclear cells from patients with seronegative rheumatoid arthritis.

OBJECTIVE: We investigated whether mononuclear cells (MNC) from patients with seronegative rheumatoid arthritis (SNRA) are able to produce rheumatoid factor (RF) in response to lectin stimulation, Staphylococcus aureus Cowan I (SAC) or pokeweed mitogen (PWM), and also we investigated the role of CD5+ B cells in the pathogenesis of in vitro IgM RF production. METHODS: IgM RF production was measured by enzyme linked immunosorbent assay and CD5+ B cells by flow cytometry. Also, the effects of monocyte depletion and the inhibition of prostaglandin (PG) were compared in SNRA, seropositive RA (SPRA) and healthy controls. RESULTS: Peripheral blood MNC of patients with SNRA were able to produce the same amount of IgM RF as patients with SPRA following stimulation and SAC. CD5+ B cells also increased in patients with SNRA as well as patients with SPRA compared to healthy controls. However, a definite contribution of the CD5+ B cells to SAC-induced IgM RF production could not be demonstrated. The role of macrophage and PG on in vitro IgM RF synthesis were insignificant. CONCLUSION: MNC of patients with SNRA were able to produce IgM and IgG RF in response to SAC stimulation as well as that of the healthy controls. However, we could not find a significant role of CD5+ B cells and monocytes on in vitro IgM RF synthesis by MNC of patients with SNRA.

Adult↗