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Biomedical subjects

S Kotake

Publications and source records attributed to S Kotake.

At least 19 recordsLinked to original sources
PubMed2001

Activated human T cells directly induce osteoclastogenesis from human monocytes: possible role of T cells in bone destruction in rheumatoid arthritis patients.

OBJECTIVE: To elucidate the direct role of human T cells in the induction of osteoclastogenesis in rheumatoid arthritis (RA), by studying human monocytes and the pathogenetic roles of receptor activator of nuclear factor kappaB ligand (RANKL), RANK, and osteoprotegerin (OPG). METHODS: Synovial tissue obtained at total knee replacement was stained immunohistologically using anti-RANKL, CD3, and CD4 antibodies. Synovial fluid was obtained from patients with RA, osteoarthritis (OA), gout, or trauma. Concentrations of the soluble form of RANKL (sRANKL) and OPG in the synovial fluid were measured by enzyme-linked immunosorbent assay. Activated T cells from peripheral blood mononuclear cells (PBMC) of healthy volunteers were cultured with human monocytes from PBMC. RESULTS: Immunostaining of the synovial tissue of RA patients demonstrated that RANKL-positive cells were detected in a subset of fibroblast-like synoviocytes and infiltrating mononuclear cells. Double immunostaining revealed that RANKL-positive cells were detected in a subset of CD3+ cells and CD4+ cells. An increased concentration of sRANKL and a decreased concentration of OPG were detected in synovial fluid from RA patients. The ratio of the concentration of sRANKL to that of OPG was significantly higher in synovial fluid of RA patients than in synovial fluid of patients with OA or gout. The activated T cells expressing RANKL induced osteoclastogenesis from autologous peripheral monocytes. The role of RANKL in this osteoclastogenetic process was confirmed by dose-dependent inhibition by OPG. CONCLUSION: The present study is the first to demonstrate osteoclastogenesis using human-derived T cells and monocytes. In addition, the present findings suggest that excess production of RANKL by activated T cells increases the level of sRANKL in synovial fluid and may contribute to osteoclastic bone resorption in RA patients.

Antibodies↗
PubMed2001

Osteoprotegerin inhibits in vitro mouse osteoclast formation induced by joint fluid from failed total hip arthroplasty.

Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis. We investigated the presence of OPG and bone-resorbing cytokines, the potential of osteoclastic differentiation in joint fluid from failed total hip arthroplasty (THA), and the inhibitory effect of OPG on osteoclast formation in vitro induced by the joint fluid. The study was aimed to clarify one important step in the cascade of periprosthetic osteolysis in the process of implant loosening. OPG levels in failed THA joint fluid of 20 cases were significantly lower than osteoarthritis (OA) joint fluid of 15 cases (p < 0.001). The levels of bone-resorbing cytokines, interleukin (IL)-1beta, and IL-6 were significantly higher in failed THA joint fluid than OA fluid (p < 0.001 and p = 0.001, respectively). Marked osteoclast formation was observed in the presence of failed THA joint fluid in the mouse coculture system, when compared to OA fluid (p < 0.001). The addition of 100 ng/mL OPG to the mouse coculture system completely inhibited osteoclast formation in the presence of failed THA joint fluid (p < 0.001). The data suggest that low levels of OPG combined with higher IL-1beta and IL-6 levels represent the potential of osteoclast differentiation and its activation in failed THA joint fluid. Inhibition of osteoclastogenesis in vitro by OPG suggests that a low level of OPG with elevated bone resorbing cytokines contributes to periprosthetic osteolysis via osteolytic joint fluid, thus leading to THA prosthesis loosening.

Animals↗
PubMed2001

Pancytopenia and colitis with Clostridium difficile in a rheumatoid arthritis patient taking methotrexate, antibiotics and non-steroidal anti-inflammatory drugs.

Methotrexate (MTX) is widely used despite its side-effects. We describe a rheumatoid arthritis (RA) patient taking low-dose MTX who developed severe pancytopenia and colitis with Clostridium difficile after the administration of antibiotics for acute pyelonephritis. Our case suggests that low-dose MTX may seriously interact with antibiotics and that these side-effects should always be considered when RA patients are treated with MTX and antibiotics.

Aged↗
PubMed2001

Stromal cell activity in bone marrow from the tibia and iliac crest of patients with rheumatoid arthritis.

Bone marrow aspirates were obtained from the iliac crest and tibial epiphysis in 23 patients with rheumatoid arthritis (RA) who were undergoing total knee arthroplasty. The number of fibroblast colony-forming units (CFU-F), which contain osteogenic precursor cells, and alkaline phosphatase (ALP) activity, as a marker of the osteoblastic phenotype. were compared between the iliac and tibial marrow for each patient. The prevalence of CFU-F in tibial marrow was similar to that in iliac marrow (96% vs 100%, respectively). However, the average number of CFU-F per 4 x 10(5) bone marrow mononuclear cells was significantly lower in tibial marrow than in iliac marrow (8.2 vs 28.1, respectively; P < 0.01). Although ALP activity was detected in all iliac and tibial marrow specimens, it was significantly lower in tibial marrow compared with iliac marrow (3.7 vs 11.9 nmol/min/mg protein, respectively; P < 0.01). In addition, there was a significant correlation between the patient's age and the number of CFU-F in iliac marrow (r = -0.547; P < 0.01), although there was no correlation in tibial marrow. These results demonstrate that the osteogenic activity of bone marrow varies at different sites in patients with RA. The data may also contribute to further investigation into the differential effects of various disease processes on systemic as well as local stromal cell activity in bone marrow.

Adult↗
PubMed2001

Cricoarytenoid arthritis with rheumatoid arthritis and systemic lupus erythematosus.

A 56-year-old woman with rheumatoid arthritis (RA) suddenly developed severe respiratory distress and laryngeal stridor, which required endotracheal intubation. She had had RA for 12 years, which had been controlled well with prednisolone (3 mg/day) at the orthopedic clinic. Laryngoscopy revealed cricoarytenoid arthritis. She was finally diagnosed as having overlap syndrome with RA and systemic lupus erythematosus. She was given high dose corticosteroids that improved her clinical symptoms and laryngoscopic findings. She represents the first patient with overlap syndrome who developed an acute airway obstruction due to cricoarytenoid arthritis.

Arthritis, Rheumatoid↗
PubMed2000

Amelioration of experimental autoimmune uveoretinitis by pretreatment with a pathogenic peptide in liposome and anti-CD40 ligand monoclonal antibody.

We have defined a peptide K2 (ADKDVVVLTSSRTGGV) that corresponds to residues 201-216 of bovine interphotoreceptor retinoid-binding protein and induces experimental autoimmune uveoretinitis (EAU)4 in H-2Ak-carrying mice (H-2Ak mice). In this study, we attempted to ameliorate EAU in the H-2Ak mice without nonspecific suppression of T cell responses. Preceding s.c. administration of liposomes including K2 (liposomal K2) specifically inhibited subsequent generation of T cell response to K2. The same result was obtained with a combination of OVA323-339 peptide and the OVA-specific TCR-transgenic T cells. It was suggested that the inhibition was mainly attributed to peripheral anergy induction of T cells specific for the peptide Ag, although specific cell death might also be involved in the inhibition. Pretreatment with liposomal K2 also considerably abolished IFN-gamma production but not IL-4 production. The specific inhibitory effect of the pretreatment with liposomal peptide was augmented by a simultaneous administration of anti-CD40 ligand (anti-CD40L) mAb. Moreover, it was shown that the pretreatment with liposomal K2 reduced both the incidence and severity of the subsequent K2-induced EAU, and the simultaneous administration of anti-CD40L mAb augmented this preventive effect by liposomal K2. Our findings demonstrate that the s.c. administration of liposomal pathogenic peptide and anti-CD40L mAb can be applied to preventing autoimmune diseases without detrimental nonspecific suppression of T cell responses.

Amino Acid Sequence↗
PubMed2000

Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction.

Osteoclast differentiation factor (ODF, also called RANKL/TRANCE/OPGL) stimulates the differentiation of osteoclast progenitors of the monocyte/macrophage lineage into osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF, also called CSF-1). When mouse bone marrow cells were cultured with M-CSF, M-CSF-dependent bone marrow macrophages (M-BMM phi) appeared within 3 d. Tartrate-resistant acid phosphatase-positive osteoclasts were also formed when M-BMM phi were further cultured for 3 d with mouse tumor necrosis factor alpha (TNF-alpha) in the presence of M-CSF. Osteoclast formation induced by TNF-alpha was inhibited by the addition of respective antibodies against TNF receptor 1 (TNFR1) or TNFR2, but not by osteoclastogenesis inhibitory factor (OCIF, also called OPG, a decoy receptor of ODF/RANKL), nor the Fab fragment of anti-RANK (ODF/RANKL receptor) antibody. Experiments using M-BMM phi prepared from TNFR1- or TNFR2-deficient mice showed that both TNFR1- and TNFR2-induced signals were important for osteoclast formation induced by TNF-alpha. Osteoclasts induced by TNF-alpha formed resorption pits on dentine slices only in the presence of IL-1alpha. These results demonstrate that TNF-alpha stimulates osteoclast differentiation in the presence of M-CSF through a mechanism independent of the ODF/RANKL-RANK system. TNF-alpha together with IL-1alpha may play an important role in bone resorption of inflammatory bone diseases.

Acid Phosphatase↗
PubMed2000

An integrated genetic linkage map with 1,137 markers constructed from five F2 crosses of autoimmune disease-prone and -resistant inbred rat strains.

The rat (Rattus norvegicus) is an important experimental model for many human diseases including arthritis, diabetes, and other autoimmune and chronic inflammatory diseases. The rat genetic linkage map, however, is less well developed than those of mouse and human. Integrated rat genetic linkage maps have been previously reported by Pravenec et al. (1996, Mamm. Genome 7: 117-127) (500 markers mapped in one cross), Bihoreau et al. (1997, Genome Res. 7: 434-440) (767 markers mapped in three crosses), Wei et al. (1998, Mamm. Genome 9: 1002-1007) (562 markers mapped in two crosses), Brown et al. (1998, Mamm. Genome 9: 521-530) (678 markers mapped in four crosses), and Nordquist et al. (1999, Rat Genome 5: 15-20) (330 markers mapped in two crosses). The densest linkage map combined with a radiation hybrid map, reported by Steen et al. (1999, Genome Res. 9: AP1-AP8), includes 4736 markers mapped in two crosses. Here, we present an integrated linkage map with 1137 markers. We have constructed this map by genotyping F2 progeny of five crosses: F344/NHsd x LEW/NHsd (673 markers), DA/Bkl x F344/NHsd (531 markers), BN/SsN x LEW/N (714 markers), DA/Bkl x BN/SsNHsd (194 markers), and DA/Bkl x ACI/SegHsd (245 markers). These inbred rat strains vary in susceptibility/resistance to multiple autoimmune diseases and are used extensively for many types of investigation. The integrated map includes 360 loci mapped in three or more crosses. The map contains 196 new SSLP markers developed by our group, as well as many SSLP markers developed by other groups. Two hundred forty genes are incorporated in the map. This integrated map should allow comparison of rat genetic maps from different groups and thereby facilitate genetic studies of rat autoimmune and related disease models.

Animals↗
PubMed2000

Different influence of macrophage migration inhibitory factor (MIF) in signal transduction pathway of various T cell subsets.

It has been shown that macrophage migration inhibitory factor (MIF) modulates not only macrophage functions, but also T cell functions. However, detailed analysis of the MIF function on responses of various T cell subpopulations remained to be elucidated. In this report, using a neutralizing anti-MIF monoclonal antibody (mAb) we examined MIF functions on various T cell lineages. It was shown that anti-MIF mAb inhibited antigen-specific responses of both IFN-gamma producing and IL-4 producing T cells. The inhibition appeared to be related to blockade of the signal pathway via T cell receptor (TCR) but not that via IL-2 receptor (IL-2R). However, the anti-MIF mAb showed no inhibitory effect on NK-T cell responses stimulated through TCR. These results suggest that MIF is involved in the signal pathway via TCR in mainstream T cells but not in NK-T cells.

Amino Acid Sequence↗
PubMed2000

High-dose corticosteroid administration induces increase of serum macrophage migration inhibitory factor in patients with Vogt-Koyanagi-Harada's disease.

To investigate the influence of corticosteroid administration on the serum level of macrophage migration inhibitory factor (MIF), sera obtained from 9 patients with Vogt-Koyanagi-Harada's disease who had been treated with high-dose corticosteroid were analyzed. The serum MIF levels of most patients were prominently increased on day 7 and/or day 14 after corticosteroid treatment. No TNF-alpha was detected in the sera. The average serum MIF level of nine patients at the highest stages after corticosteroid administration was significantly higher than that before the corticosteroid treatment. It seems that MIF is a unique cytokine and acts together with corticosteroid to regulate inflammation and immunity.

Administration, Oral↗
PubMed2000

Increase of macrophage migration inhibitory factor in sera of patients with iridocyclitis.

AIMS: To determine whether macrophage migration inhibitory factor (MIF) levels were increased in sera of the patients with iridocyclitis. METHODS: Sera were obtained from 41 patients with acute iridocyclitis, 13 patients with chronic iridocyclitis, and 44 healthy control subjects. MIF levels were determined by a human MIF ELISA. RESULTS: The average levels of MIF in the sera of patients with both acute and chronic iridocyclitis were significantly higher than that of healthy subjects. CONCLUSION: Uveitis induces the elevation of serum MIF, which may affect various inflammatory symptoms in uveitis.

Acute Disease↗
PubMed2000

Systemic lupus erythematosus with myocardial dysfunction due to microvasculopathy.

A 25-year-old Japanese woman with systemic lupus erythematosus (SLE) had myocardial dysfunction. Heart catheterization showed normal coronary anatomy. Left ventricular cineangiography demonstrated hypokinesis in the anterior and posterior segments. Myocardial scintigraphy revealed patchy defects in the regions unrelated to coronary arteries. These data suggested that the myocardial dysfunction was due to microvasculopthy. In addition, it was speculated that the microvasculopathy was caused by vasculitis but not by thrombi, since she did not have antiphospholipid syndrome. In support of this speculation, corticosteroid therapy without any thrombolytic agents was effective. This report represents the first live patient with SLE in whom myocardial dysfunction due to microvasculopathy has been demonstrated.

Adult↗
PubMed2000

Inhibition of experimental autoimmune uveoretinitis with anti-macrophage migration inhibitory factor antibodies.

PURPOSE: The role of macrophage migration inhibitory factor (MIF) in the regulation of ocular autoimmune disease was studied in experimental autoimmune uveoretinitis (EAU) in rats following immunization with a retinal antigen (Ag), interphotoreceptor retinoid-binding protein (IRBP). METHODS: LEW rats were immunized with a single injection of IRBP derived peptide, R16(ADGSSWEGVGVVPDV). A neutralizing monoclonal antibody (mAb, IgM) to MIF was injected intraperitoneally every second day from day 0 to day 6 (group A), or from day 8 to day 14 (group B). Control rats were treated with unrelated mouse IgM or PBS. T cell proliferative responses were measured 12 days after immunization. The occurrence and severity of EAU were observed and compared among experimental and control groups. RESULTS: T cell proliferative responses against R16 were inhibited in rats treated with anti-MIF mAb compared with the control rats. The development of EAU was delayed in the rats of group A in comparison with those of group B and the control group. The mean histological EAU score on day 18 in group A was 1.11 +/- 0. 11 and significantly lower than those of the group B (1.29 +/- 0.19) and the control (1.67 +/- 0.19). CONCLUSIONS: The present result suggests that MIF plays an important role in induction of EAU.

Amino Acid Sequence↗