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Biomedical subjects

E Tsuda

Publications and source records attributed to E Tsuda.

At least 19 recordsLinked to original sources
PubMed2005

Dilated coronary arterial lesions in the late period after Kawasaki disease.

OBJECTIVES: There are two types of late coronary dilated lesions after Kawasaki disease: new aneurysms and expanding aneurysms. The development of coronary dilated lesions late after Kawasaki disease was investigated. METHODS: Between 1978 and 2003, 562 patients with coronary arterial lesions underwent selective coronary angiography on at least two occasions. RESULTS: Of the 562 patients studied, 17 new dilated or expanding lesions were found in 15 patients (3%, 11 boys, four girls). The time of detection of new aneurysms after Kawasaki disease ranged from 1.9-19.2 years (median 11.4 years) and their diameters ranged from 2.0-6.5 mm (median 4.4 mm). Thirteen new aneurysms occurred in vessels in which previous aneurysms had regressed and all new aneurysms were associated with localised stenosis. A new aneurysm at the bifurcation or in the branches was seen in 14 (93%) and 13 were eccentric (87%). Of two expanding aneurysms, one involved the right coronary artery in one patient and the other the left anterior descending coronary artery. One expanding aneurysm increased from 4.4 mm to 19.5 mm over 17 years, and the other expanding aneurysm increased from 10 mm to 15 mm in one year. CONCLUSIONS: Neither new nor expanding aneurysms have caused cardiac events. New aneurysms often develop as a pre-stenotic or post-stenotic dilatation secondary to localised stenosis. New and expanding aneurysms may be caused by haemodynamic factors in addition to the abnormality of the coronary arterial wall after severe acute vasculitis. Coronary arterial wall abnormalities were stenosis as well as, rarely, dilatation of the vessels in the late period. It is important to recognise that the changes of the coronary arterial wall persist late after regression of a large aneurysm.

Adolescent↗
PubMed2004

Osteoclastogenesis inhibitory factor/osteoprotegerin reduced bone loss induced by mechanical unloading.

Skeletal unloading resulting from space flight and prolonged immobilization causes bone loss. Such bone loss ostensibly results from a rapid increase in bone resorption and subsequent sustained reduction in bone formation, but this mechanism remains unclear. Osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG) is a recently identified potent inhibitor of osteoclast formation. We studied effects of OPG administration on tail-suspended growing rats to explore the therapeutic potential of OPG in the treatment and prevention of bone loss during mechanical unloading, such as that which occurs during space flight. Treatment with OPG in tail suspension increased the total bone mineral content (BMC g) of the tibia and femur and the total bone mineral density (BMD g/cm2) of the tibia. Moreover, treatment with OPG prevented reduction not only of BMC and BMD, but also of bone strength occurring through femoral diaphysis. Treatment with OPG in tail-suspended rats improved BMC, BMD and bone strength to levels of normally loaded rats treated with vehicle. Treatment with OPG in normally loaded rats significantly decreased urinary excretion of deoxypyridinoline, but the effect of OPG in tail suspension was unclear. These results indicate that OPG may be useful in inhibiting bone loss-engendered mechanical unloading.

Amino Acids↗
PubMed2002

Coronary artery dilatation exceeding 4.0 mm during acute Kawasaki disease predicts a high probability of subsequent late intima-medial thickening.

We used intravascular ultrasound (IVUS) to compare the degree of coronary artery dilatation during the acute phase of Kawasaki disease with the extent of intima-medial thickening more than 10 years later. We wanted to determine if there was a threshold degree of dilatation that was highly predictive of later thickening. Twenty-eight patients with a mean age of 17.3 +/- 1.7 years were studied; the mean interval from the initial selective coronary angiography to the IVUS study was 15.0 +/- 1.6 years. We measured the maximum intima medial thickness of selected coronary arterial segments in IVUS images and measured the largest diameters of the corresponding coronary arterial segments in the initial coronary angiograms. A significant correlation was found between the initial diameters of the coronary arteries and the intima medial thickness more than 10 years later in the right coronary, the left anterior descending coronary, and the left circumflex arteries. The coefficient of correlation was 0.77 (n = 120, p < 0.0001), and for the bifurcation of the left coronary artery it was 0.50 (n = 26, p < 0.01). For this study, abnormal intima medial thickness was defined as more than 0.40 mm. When the initial coronary arterial dilatation exceeded 4.0 mm, the sensitivity was 28/31 (90%) and the specificity was 87/89 (98%) in the right coronary, the left anterior descending coronary, and the left circumflex arteries. For the bifurcation of the left coronary artery, the sensitivity was 14/21 (67%) and the specificity was 5/5 (100%).

Adolescent↗
PubMed2002

Changes in osteoprotegerin and markers of bone metabolism during glucocorticoid treatment in patients with chronic glomerulonephritis.

It is well known that long-term glucocorticoid treatment causes osteoporosis, but the precise mechanism remains unclear. Recently, osteoprotegerin (OPG) has been identified as a cytokine that inhibits osteoclast differentiation. We have previously demonstrated that serum OPG is suppressed by glucocorticoids. Therefore, the present study was carried out to clarify the interrelationships between OPG and other markers of bone metabolism during glucocorticoid treatment. Thirteen patients (7 men, 6 women; 44.1 +/- 5.9 years old) with chronic glomerulonephritis who were to be treated with glucocorticoids for the first time were chosen for this study. Markers of bone metabolism, including serum OPG, osteocalcin (OC), bone-specific alkaline phosphatase activity (bAP), parathyroid hormone (PTH), tartrate-resistant acid phosphatase (TRAP), and bone mineral density (BMD), were measured before and during the treatment period. Glucocorticoids significantly reduced BMD of the lumbar spine in the 6 month treatment period (p < 0.01). Serum OPG was decreased significantly by glucocorticoids within 2 weeks (p < 0.001), and serum TRAP, a marker of bone resorption, was markedly increased (p < 0.001). On the other hand, there were no remarkable changes in serum PTH. Serum OC and bAP, markers of bone formation, were transiently reduced during the treatment period (p < 0.01). Furthermore, only serum OPG was positively and independently correlated with percentage BMD of age-matched reference (%AMR). These findings imply that glucocorticoid-induced bone loss develops rapidly via enhanced bone resorption and suppressed bone formation. Moreover, the increased bone resorption caused by glucocorticoids may be, at least in part, mediated by inhibition of OPG, not increment of PTH.

Adult↗
PubMed2001

Immunological study on circulating murine osteoprotegerin/osteoclastogenesis inhibitory factor (OPG/OCIF): possible role of OPG/OCIF in the prevention of osteoporosis in pregnancy.

Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) is a soluble member of the tumor necrosis factor receptor family and plays a crucial role in the negative regulation of osteoclastic bone resorption. We have immunized OPG/OCIF knockout mice with murine rOPG/rOCIF and established a panel of hybridomas producing monoclonal antibodies (mAbs) to murine rOPG/rOCIF. Utilizing the mAbs, we developed enzyme-linked immunosorbent assay (ELISA) systems: one detecting both homodimeric and monomeric forms of murine OPG/OCIF and the other detecting only dimeric form of murine OPG/OCIF. With the aid of these ELISA systems we showed that OPG/OCIF is present mainly as a monomer in murine blood. The concentration of OPG/OCIF in normal mouse sera was approximately 500 pg/ml and there was no statistical difference in the serum concentration of OPG/OCIF among genders, age, and strains. Interestingly, the concentration of circulating OPG/OCIF in mouse markedly increased during pregnancy. The result indicated that circulating OPG/OCIF plays an important role in the protection of bone from excess resorption during pregnancy in mammals.

Animals↗
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

Synovial cells from a patient with rheumatoid arthritis produce osteoclastogenesis inhibitory factor/osteoprotegerin: reciprocal regulation of the production by inflammatory cytokines and basic fibroblast growth factor.

To understand the involvement of osteoclastogenesis inhibitory factor (OCIF), also called osteoprotegerin (OPG), in the pathogenesis of bone destruction in rheumatoid arthritis (RA), we investigated the cytokine network involved in the production of OCIF by human fibroblast-like synovial (HFLS) cells from a patient with RA. Inflammatory cytokines, such as interleukin (IL)-1beta, IL-6 plus soluble IL-6 receptor (sIL-6R), IL-17, and tumor necrosis factor (TNF)-alpha, which are elevated in synovial fluid in RA, upregulated the production of OCIF to a level (5-20 ng/ml) sufficient to inhibit osteoclastogenesis in vitro. These inflammatory cytokines (except for IL-6 plus sIL-6R) stimulate OCIF production directly or indirectly through stimulation of prostaglandin E2 (PGE2) synthesis. In contrast to the findings with inflammatory cytokines, basic fibroblast growth factor (bFGF) inhibited the production of OCIF by the cells in a dose-dependent manner. While bFGF enhanced both the inflammatory cytokine-mediated release of PGE2 and the PGE2-mediated OCIF production, it significantly suppressed OCIF production by negating the direct stimulatory effect of the inflammatory cytokines. These findings suggest that bFGF in the synovial fluid of patients with RA may lead to severe joint destruction by suppressing the production of OCIF by HFLS cells.

Arthritis, Rheumatoid↗
PubMed2001

Periodontal ligament cells secrete the factor that inhibits osteoclastic differentiation and function: the factor is osteoprotegerin/osteoclastogenesis inhibitory factor.

The periodontal ligament, a highly specialized connective tissue situated between the tooth and the alveolar bone of the tooth socket, has been thought to influence the remodeling of the alveolar bone. The effects of two human periodontal ligament fibroblastic cell populations (HPLFs) on osteoclast-like cell (OCL) formation and the function of authentic osteoclasts were examined. The addition of the conditioned media (CM) from both HPLF cultures (HPLF-CMs) to mouse bone marrow culture inhibited OCL formation in spite of the presence of 10(-8)M 1alpha, 25 dihydroxyvitamin D3 (1alpha,25(OH)2D3). This inhibitory effect was most remarkable when both CMs were added during day 6 to day 9 following bone marrow culture, just at the late stage of OCL differentiation. HPLF-CMs also induced a significant decrease in the pit area and the pit number formed by authentic osteoclasts on ivory slices. The administration of neutralizing monoclonal antibody (OI-1) against human osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) with HPLF-CMs to mouse bone marrow culture almost completely blocked the inhibitory effect of these CMs on OCL formation. Immunofluorescent examination of HPLF with OI-1 revealed intense positive reactivity in the cytoplasm. Western blot analysis of HPLF-CM using anti-human OPG/OCIF polyclonal antibody resulted in the detection of bands of 60 kDa and 120 kDa which were consistent with those of OPG/OCIF. These results suggest that HPLF cells produce and secrete OPG/OCIF, and that this factor from HPLF prevents the differentiation of the late preosteoclast and the function of the mature osteoclasts.

Adolescent↗
PubMed2001

Guidelines for catheter intervention in coronary artery lesion in Kawasaki disease.

The Research Committee of Ministry of Health, Labour and Welfare 'Study of treatment and long-term management in Kawasaki disease' reported the guidelines for catheter intervention in coronary artery lesion in Kawasaki disease in this paper. The contents include: (i) background and natural history of coronary artery lesion in Kawasaki disease; (ii) indication of catheter intervention; (iii) types of procedure, and their indication and care; (iv) institute and backup system; (v) the management after procedure, evaluation and follow up; and (vi) prospects, especially in relation to bypass surgery.

Angioplasty, Balloon, Coronary↗
PubMed2001

Glucocorticoid decreases circulating osteoprotegerin (OPG): possible mechanism for glucocorticoid induced osteoporosis.

BACKGROUND: Osteoporosis is a well known side-effect of long-term treatment with glucocorticoids. However, the precise mechanism of this disorder is unclear. Recently, osteoprotegerin (OPG) [osteoclastogenesis inhibitory factor (OCIF)] has been identified as a novel cytokine, which inhibits differentiation and activation of osteoclast. In the present study, in order to clarify the roles of OPG in the development of glucocorticoid-induced osteoporosis, we measured circulating OPG before and after glucocorticoid therapy. METHODS: The study subjects were 12 patients (five males, seven females, 53.4 +/- 4.8 [SE] years) with various renal diseases that required glucocorticoid therapy. All patients received glucocorticoids for the first time. Treatment was initiated at an average dose of 32.5 +/- 3.0 mg per day. Serum OPG was measured using enzyme-linked immunosorbent assay (ELISA). Laboratory data, markers of bone metabolism and circulating OPG were compared before and after treatment for 4 weeks. RESULTS: Serum OPG prior to glucocorticoid therapy was positively and independently correlated with serum creatinine. Serum OPG decreased significantly (P: < 0.0001) from 1.03 +/- 0.14 to 0.77 +/- 0.12 ng/ml after short-term administration of glucocorticoids. Furthermore, serum osteocalcin as a marker of bone formation was also reduced markedly (P: = 0.001). On the other hand, there were no remarkable changes in serum calcium, total alkaline phosphatases, creatinine and intact parathyroid hormone in response to glucocorticoid administration. CONCLUSION: These findings indicate that short-term administration of glucocorticoids significantly suppresses serum OPG and osteocalcin. It might participate in the development of glucocorticoid-induced osteoporosis via an enhancement of bone resorption and suppression of bone formation.

Female↗
PubMed2001

Reversal of multidrug resistance by novel nitrophenyl pyrones, SNF4435C and D.

SNF4435C and D, novel immunosuppressants produced by a strain of Streptomyces spectabilis, were examined for their reversing effects in vitro on various multidrug-resistant (MDR) tumor cells overexpressing P-glycoprotein. These two compounds in the range of 3-10 microM completely reversed the resistance of MDR variant cells, mouse leukemia P388 cells [vincristine (VCR)-resistant P388/VCR and adriamycin (ADM)-resistant P388/ADM], human myelogenous leukemia K562 cells (VCR-resistant K562/VCR and ADM-resistant K562/ADM) and human ovarian cancer A2780 cells (ADM-resistant AD(10)), against VCR. Both compounds moderately potentiated the sensitivity of the MDR cells to ADM but the reversal was not complete. SNF4435C and D significantly increased the intracellular accumulation of VCR in AD(10) cells as potently as verapamil, cyclosporin A (CysA) and FK506, whereas the compounds exerted no effect on the accumulation of VCR in the drug-sensitive parent cells. Moreover, SNF4435C improved the chemotherapeutic efficacy of VCR in the treatment of P388/VCR-bearing mice. When 10 mg/kg SNF4435C was administered intraperitoneally to the mice concurrently with 0.2 mg/kg VCR for every 5 days, a treated/control (T/C) value of 143% was obtained. These results suggest that the compounds are useful candidates or tools for MDR modification in cancer chemotherapy.

Animals↗
PubMed2001

SNF4435C and D, novel immunosuppressants produced by a strain of Streptomyces spectabilis. I. Taxonomy, fermentation, isolation and biological activities.

SNF4435C and D, novel nitrophenyl pyrones, have been isolated from the culture broth of an actinomycete strain SNF4435. The strain was identified as Streptomyces spectabilis from its morphological and cultural characteristics. SNF4435C and D showed a potent immunosuppressive activity in vitro and selectively suppressed B-cell proliferation induced by LPS versus T-cell proliferation induced by Con A.

Animals↗
PubMed2001

SNF4435C and D, novel immunosuppressants produced by a strain of Streptomyces spectabilis. II. Structure elucidation.

SNF4435C and D are new immunosuppressants isolated from the culture broth of a strain of Streptomyces spectabilis. Their molecular formulas were determined as C28H31NO6 based on the HRFAB-MS analyses. The structures of SNF4435C and D were elucidated to be novel nitrophenyl pyrones having an intriguing tricyclic ring system and diastereoisomers of each other by spectroscopic analyses including various NMR measurements.

Fermentation↗
PubMed2001

SW-163C and E, novel antitumor depsipeptides produced by Streptomyces sp. I. Taxonomy, fermentation, isolation and biological activities.

Novel depsipeptides, SW-163C and E were isolated from the culture broth of an actinomycete strain. The producing organism, designated as SNA15896, was identified as a member of Streptomyces from its morphological and cultural characteristics. SW-163C and E exhibited potent antitumor activities against various tumor cell lines in vitro and against murine leukemia P388 in vivo. The compounds also showed antimicrobial activities.

Animals↗
PubMed2001

SW-163A and B, novel immunosuppressants produced by Streptomyces sp.

SW-163A and B, novel immunosuppressants, were isolated from the culture broth of Streptomyces sp. SNA15896. The molecular formulas of SW-163A and B were determined as C34H42N2O12 and C33H40N2O12 based on the HRFAB-MS analysis, respectively. Both compounds were elucidated to be a large ring ester structure through spectroscopic analyses including various NMR measurements. SW-163A and B showed immunosuppressive and antimicrobial activities in vitro.

Amino Acids↗