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Biomedical subjects

M Shingu

Publications and source records attributed to M Shingu.

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

Production of soluble ICAM-1 by mononuclear cells from patients with rheumatoid arthritis patients.

The present study was designed to quantify the level of the soluble form of ICAM-1 (sICAM-1) produced by mononuclear cells (MNC) of rheumatoid arthritis (RA) patients, and to correlate these levels with the disease activity and with the amounts of cytokines or rheumatoid factors (RF) produced by MNC. Unstimulated synovial fluid (SF) MNC produced higher amounts of sICAM-1 than peripheral blood (PB) MNC in RA patients (P < 0.01). sICAM-1 production by PHA-stimulated MNC was higher in RA SF MNC than RA or normal PB MNC (P < 0.01). The amounts of SICAM-1 produced correlated with the amounts of soluble IL-2 receptor produced (P < 0.02) but not with IL-1B or the Lansbury activity index in RA PB MNC. sICAM-1 correlated with the amounts of soluble CD23 and IL-4 produced by normal PB MNC (P < 0.01). The amounts of sICAM-1 correlated with IgG-RF (P < 0.02) and IgM-RF (P < 0.01) produced by unstimulated MNC obtained from the bone marrow (BM) of RA patients. ICAM-1 expression of T-lymphocyte subsets, B lymphocytes, and monocytes obtained from RA PB and RA BM assayed by two-color flow cytometry ranged from 0.1 to 6%, which was not appreciably different from that of normal controls. The monocyte fraction of RA PB MNC produced significantly higher amounts of sICAM-1 than lymphocyte fraction. These results suggest that sICAM-1 produced by MNC may be a marker of cell activation in T and B lymphocytes, in contrast to the transient increase of ICAM-1 expression.

Adult↗
PubMed1994

Role of oxygen radicals and IL-6 in IL-1-dependent cartilage matrix degradation.

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. In the present study, the effects of IL-6 and oxygen radical scavengers on cartilage matrix degradation were studied. Superoxide dismutase, catalase, or methionine all significantly inhibited cartilage matrix degradation both in IL-1 beta-stimulated and unstimulated experimental conditions. Both 10 mM EDTA and 100 nM tissue inhibitor of metalloproteinase (TIMP) significantly inhibited cartilage matrix degradation. The addition of methionine significantly inhibited collagenase activity produced in the culture supernatants of chondrocytes stimulated with IL-1 beta. IL-6 significantly suppressed cartilage matrix degradation produced spontaneously or by IL-1 beta stimulation in chondrocytes. IL-6 inhibited superoxide production by chondrocytes both in IL-1 beta-stimulated or unstimulated conditions. These results suggest that oxygen radicals are involved in cartilage matrix degradation mediated by both paracrine and autocrine IL-1 mechanisms and that oxygen radical-mediated activation of collagenase in chondrocytes may explain the mechanisms of how oxygen radicals are involved in cartilage matrix degradation. IL-6 inhibited superoxide production in chondrocytes and thus inhibited cartilage matrix degradation.

Arthritis, Rheumatoid↗
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

Functional oligomerization of purified human papillomavirus types 16 and 6b E7 proteins expressed in Escherichia coli.

Purified non-fused soluble human papillomavirus type 16 and 6b E7 proteins expressed in Escherichia coli were found to form oligomers. For both proteins, several degrees of oligomerization were demonstrated by gel filtration, dynamic laser light scattering and scanning electron microscopy. Oligomerization was dependent on the concentration of E7 protein. Oligomerized E7 proteins were able to bind the retinoblastoma gene product pRB and stimulated DNA synthesis when introduced into cells.

Base Sequence↗
PubMed1994

Detection and typing of human rotavirus in reference to repeated acute gastroenteritis in infants.

Stool specimens from infants who visited a clinic because of acute gastroenteritis were tested for the presence of human rotavirus. Among the samples obtained were specimens taken from seven patients who had visited the clinic at two different times. In six of these seven children, human rotavirus (HRV) was detected in only one of the specimens taken (i.e. during only one of the two visits). One patient was shown to have excreted HRV twice; in both cases the HRV was serotyped to be type 1. The present results indicate that the symptomatic reinfection of HRV was not a widely occurring phenomenon in the group of infants tested.

Acute Disease↗
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

Engraftment of HTLV-I-transformed human T-cell line into SCID mice with NK cell function.

HTLV-I-transformed human T-cell line, MT-2, has been reported to successfully proliferate in only the SCID mice with depletion of NK cell function. However, MT-2 cells could be engrafted into SCID mice possessing normal NK cell function in this study. MT-2 cells (5-7 x 10(7) cells) were intraperitoneally injected into SCID mice without the deletion of NK cell function. The SCID mice developed tumors in the peritoneal cavities 3 months after the inoculation of MT-2 cells. All tumors reacted to anti-HTLV-I p19 and anti-HLA-DR monoclonal antibodies by immunofluorescence assay and were also positive for the HTLV-I gene by PCR assay. DNA obtained from main organs in group of mice with or without tumors showed a high incidence of positive signals for HTLV-I gene by PCR assay.

Animals↗
PubMed1994

Transformation assays of the cell mitotic and proliferation activities of purified oncogene products.

Using two direct introduction methods, DNA synthesis or cell proliferation activities of three purified proteins from E. coli, namely, human papillomavirus (HPV) E7 proteins of type 16, a mutant type 16 (24 C-G) (transformation defective) and type 6b, were measured in mouse fibroblast, C127 cells. By a microinjection method, the order of the cell mitotic indexes for the three E7 proteins as determined by 5-bromo-2'-deoxy-uridine (BrdU) staining was type 16, 6b and 16 (24 C-G). By the osmotic shock method, the 3H-TdR incorporation and coloration by (3-carboxymethoxy phenyl)-2-(4-sulfophenyl)-2H-tetolazorium (MTS) for the three proteins correlated with the pRb binding and focus forming activities previously reported (Munger et al. 1991). These results indicate that the simple osmotic shock method for direct protein introduction may be generally useful for transformation assays of oncoproteins.

Animals↗
PubMed1994

Therapeutic effects of bovine enterovirus infections on autochthonous rat ovarian carcinomas induced by 7,12-dimethylbenz (a) anthracene (DMBA).

It has been previously reported that infection by a bovine enterovirus (MZ-468), which does not infect normal human cells, was remarkably effective for the therapy of adult T cell leukemia (ATL) in experimental rabbit models (Shingu et al. 1991). Therapeutic treatment studies were performed twice on 30 and 20 autochthonous rat ovarian carcinomas induced by DMBA. The average tumor size of the virus treatment group was significantly smaller than the control group when analyzed by a nonparametric Mann-Whitney method (p < 0.06 and 0.002 for the 1st and 2nd experiments, respectively). These results indicate that an enterovirus infection may be clinically useful for the therapy of human ovarian cancers with bad prognoses.

9,10-Dimethyl-1,2-benzanthracene↗
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↗
PubMed1993

Association of RNA with human papillomavirus E7 protein of type 16 but not type 6b.

Nonfused human papillomavirus (HPV) type 16 and 6b E7 proteins were expressed in E. coli and fractionated by ion exchange and gel filtration chromatography. The E7 protein of type 6b was purified, but that of type 16 was found to be associated with RNA molecules which could not be excluded by repeated chromatography. The type 16 E7 protein in CaSki cells was also associated with RNA molecules of the same size.

Animals↗
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↗