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Biomedical subjects

H Ida

Publications and source records attributed to H Ida.

At least 55 records · Page 3Linked to original sources
PubMed2000

Regulation of rheumatoid synovial cell growth by ceramide.

Overgrowth of rheumatoid synoviocytes, which results in joint destruction, is due to impaired balance between cell proliferation and cell death (apoptosis). Ceramide is an important lipid messenger involved in mediating a variety of cell functions including apoptosis. We investigated the effects of ceramide on growth-promoting anti-apoptotic signals in rheumatoid synovial cells. Human synovial cells isolated from patients with rheumatoid arthritis (RA) were stimulated with platelet-derived growth factor (PDGF) in the presence or absence of C2-ceramide. The kinase activity of Akt, MEK, and ERK1/2 was analyzed in PDGF-stimulated synovial cells by Western blot analysis. Pretreatment with C2-ceramide completely inhibited PDGF-induced cell cycle progression of rheumatoid synovial cells. PDGF stimulation induced phosphorylation and activation of Akt, MEK, and ERK1/2 in rheumatoid synovial cells. C2-ceramide inhibited the activation of Akt, MEK and ERK1/2 in PDGF-stimulated synovial cells. Our data demonstrated that inhibition of anti-apoptotic kinases, such as Akt and ERK1/2, may play an important role in ceramide-mediated apoptosis of rheumatoid synovial cells.

Apoptosis↗
PubMed2000

Induction of COX-2 expression by nitric oxide in rheumatoid synovial cells.

Prostaglandins formed by cyclooxygenase (COX) enzymes are important mediators of inflammation. The contribution of inducible COX-2 in the rheumatoid synovium is well documented. In this study, we evaluated the contribution of nitric oxide (NO) to COX-2 expression in rheumatoid synovial cells. Exposure of rheumatoid synovial cells to a NO donor, SNAP, induced COX-2 protein expression in a dose-dependent manner. RT-PCR analysis also demonstrated that COX-2 mRNA was induced in SNAP-treated synovial cells. Dexamethasone at therapeutic concentrations markedly inhibited this NO-mediated COX-2 expression in synovial cells. In contrast to its effect on COX-2 expression, SNAP did not affect the constitutive expression of COX-1 in rheumatoid synovial cells. Our findings suggest that NO is an important modulator of COX-2 expression and that glucocorticoids exert their anti-inflammatory action in rheumatoid synovium, at least in part, by suppression of COX-2 induction.

Arthritis, Rheumatoid↗
PubMed2000

Perlecan (heparan sulfate proteoglycan) gene expression reflected in the characteristic histological architecture of salivary adenoid cystic carcinoma.

In order to determine the role of the basement membrane-type heparan sulfate proteoglycan (HSPG), known as perlecan, in the formation of the characteristic cribriform 'structures of salivary adenoid cystic carcinomas, the mode of expression of mRNA for the core protein of HSPG was investigated by using in situ hybridization (ISH) both in surgical specimens and in a cell system (ACC3) of adenoid cystic carcinomas. In the surgical specimens, the mRNA for the HSPG core was more intensely expressed in solid tumor cell nests, especially in smaller ones. Within the nests, the signals were detected almost exclusively in cuboidal cells forming small pseudocysts. In contrast, signals were absent in flat cells forming large pseudocysts or in carcinoma cell nests attaching to the peripheral nerves or blood vessels. In normal salivary gland tissues, myoepithelial cells expressed the mRNA at a high level, but acinar and duct epithelial cells did not. In the time-course experiment of ACC3 cells, signals for HSPG core increased with time and reached the maximum on day 4, decreasing thereafter in a culture condition in which cells reached confluence in a week. The results indicate that HSPG is biosynthesized by adenoid cystic carcinoma cells which are in the proliferation phase, and that tumor cells producing HSPG tend to form initial structures of stromal pseudocysts.

Carcinoma, Adenoid Cystic↗
PubMed2000

Communicating hydrocephalus in a patient with Gaucher's disease type 3.

The case of a 3-year-old male with type 3 Gaucher's disease, whose genotype for the beta-glucosidase gene was D409H/unknown mutation, is presented. After the onset of visceral and neurologic signs during infancy, a radiologic investigation at 3 years of age revealed communicating hydrocephalus, an unusual complication of Gaucher's disease. A ventriculoperitoneal shunt operation led to clinical and radiologic improvement. The possibility of this complication should be considered in the treatment of patients with Gaucher's disease.

Child, Preschool↗
PubMed2000

FK506 augments glucocorticoid-mediated cyclooxygenase-2 down-regulation in human rheumatoid synovial fibroblasts.

Prostaglandins (PG) formed by cyclooxygenase (COX) enzymes are important mediators of inflammation in rheumatoid arthritis. The contribution of the inducible COX-2 to inflammation in the rheumatoid synovium is well documented. We examined the regulation of COX-2 mRNA and protein expression in response to both glucocorticoids (GC) and FK506 using rheumatoid synovial fibroblasts. Combined treatment of FK506 and a low concentration of dexamethasone (DEX) (10(-9) M) down-regulated synovial COX-2 mRNA and protein expression. In contrast, neither FK506 nor DEX (10(-9) M) alone influenced COX-2 expression. Immunocytochemical studies showed that pretreatment with FK506 enhanced the nuclear translocation of the glucocorticoid receptor (GR) in synovial fibroblasts in the presence of low concentrations of DEX (10(-9) M). Transient transfection experiments showed that treatment of cells with FK506 enhanced the expression of glucocorticoid-responsive gene reporter in the presence of DEX (10(-9) M). NF-kappaB is known to mediate the transcriptional activation of the COX-2 gene. Electrophoretic mobility shift assay demonstrated that DNA-binding activity of NF-KB was suppressed more profoundly by FK506 plus DEX (10(-9) M) treatment with those of DEX (10(-9)M) alone in IL-1beta-stimulated synovial cells. Our results indicated that FK506-induced potentiation of GR-mediated repression of synovial COX-2 gene transcription is the result of increased translocation of GR to the nucleus and subsequent repression of NF-kappaB transactivation. Our results also suggest that FK506 may exert anti-inflammatory effects in the rheumatoid synovium by potentiating GR-mediated signal transduction.

Arthritis, Rheumatoid↗
PubMed2000

Nuclear factor-kappaB and caspases co-operatively regulate the activation and apoptosis of human macrophages.

Accumulating evidence suggests that macrophages function as major effector cells in the pathological process of various human diseases. We examined here the role of nuclear factor-kappaB (NF-kappaB) and caspases in the regulation of activation and apoptosis of macrophages. Activation of the human monoblastic leukaemia cell line, U937, by phorbol 12-myristate 13-acetate (PMA) increased the expression of CD14/CD86, and cytokine production. PMA stimulation also increased the expression of both pro-caspase-8 and pro-caspase-3 in U937, but not apoptosis or intracellular caspase-3 activity. PMA also increased the expression of X-chromosome-linked inhibitor of apoptosis protein (XIAP) in U937, suggesting an inhibitory action for XIAP on the caspase cascade in PMA-stimulated U937. Electrophoretic mobility shift assay (EMSA) showed a significant increase of nuclear NF-kappaB activity in PMA-stimulated U937. When a potent NF-kappaB inhibitor, pyrrolidine dithiocarbamate (PDTC), was added to U937 cell culture in the presence of PMA, apoptosis was triggered by activation of caspase-3, which was induced by caspase-8 activation. XIAP expression was markedly suppressed in PMA-treated U937 in the presence of PDTC. The inhibitors of caspase-8 and caspase-3 mostly inhibited apoptosis of U937 treated with PMA in the presence of PDTC. Furthermore, a phenotype of U937 treated with PMA and PDTC in the presence of caspase inhibitor was almost identical to that of unstimulated U937. Our results suggest that the signalling pathways involved in the activation and apoptosis of human macrophages could be co-operatively regulated by the use of NF-kappaB and caspase inhibitors, thus enabling the control of macrophage function and number.

Apoptosis↗
PubMed2000

Histopathologic retinal changes with intravitreous fluorosilicone oil in rabbit eyes.

BACKGROUND: Fluorosilicone oil (FSiO, 1,000-10,000 centistokes), which has a higher density (1.29 g/cm3) than vitreous gel, is useful as an operative tool and a tamponade for the inferior retina during difficult retinal detachment surgery. The occurrence of histopathologic retinal changes after injection of FSiO into the vitreous cavity is controversial. METHODS: Retinas obtained from 18 rabbits were evaluated histopathologically within 8 weeks of injection into the vitreous cavity of purified FSiO or balanced salt solution as control in phakic eyes. The histopathologic retinal changes caused by FSiO were compared with those of previously reported high-density hydrophobic vitreous substitutes, such as silicone-fluorosilicone copolymer oil (SiFO) and perfluorocarbon liquids. RESULTS: By light and electron microscopy, all retinas injected with FSiO were the same as control retinas within 2 weeks of the injection, but the outer plexiform layer disappeared from the inferior retina 4 weeks after injection. The receptor cell nuclei migrated to the photoreceptor layer in the inferior retina 8 weeks after injection. However, no preretinal membrane, including foam cells, was found in any eye injected with FSiO. CONCLUSION: FSiO may be useful as a temporary vitreous substitute in difficult inferior retinal detachments.

Animals↗
PubMed2000

In vivo NMR micro-imaging of kidney and liver of mouse at 9.4 T.

NMR micro-images of the kidney and liver were measured at 9.4 T in intact mouse, schistosoma Mansoni-infected mouse, and lupus nephritis in an MRL/lpr mouse. High-field NMR imaging has the advantages of sensitivity, spatial resolution, and tissue contrasts based on longitudinal and transverse relaxations, magnetic susceptibility differences and blood flow.

Animals↗
PubMed2000

High macrophage-colony stimulating factor levels in synovial fluid of loose artificial hip joints.

OBJECTIVE: To clarify a macrophage-colony stimulating factor (M-CSF) related mechanism of aseptic loosening of artificial hip joints. METHODS: Synovium-like interface tissues between bone and prosthesis, regenerated pseudocapsular tissues, and synovial fluid (SF) were collected from 9 patients with loose artificial hip joint at revision surgery. Tissue distribution, production site, and SF level of M-CSF in loose hip joints were investigated by immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and ELISA, respectively. For a comparative assessment of the M-CSF level in loose hip joints, SF of active rheumatoid arthritis (RA) and mild osteoarthritis (OA) also were analyzed by ELISA. RESULTS: Immunohistochemical analysis showed the presence of M-CSF immunoreactive cells mainly in the interface tissues between bone and prosthesis and inner pseudocapsular tissues, both of which were in contact with joint fluid. RT-PCR analysis confirmed the local production of M-CSF in these periprosthetic tissues. Significantly higher M-CSF level in loose hip joint fluid than in active RA and mild OA fluid was revealed by ELISA. CONCLUSION: High M-CSF level in loose hip joint fluid suggests transportation of M-CSF from production sites to joint fluid. This indicates that not only polyethylene wear particles (reported to induce foreign body reaction at the bone-prosthesis interface), but also M-CSF, abundant in joint fluid, are transported to and affect the interface. Thus, M-CSF is locally produced in periprosthetic tissues of loose hip joints and possibly contributes to periprosthetic weakening and osteolysis via joint fluid, leading to prosthetic loosening.

Aged↗
PubMed1999

Inhibition of caspase cascade by HTLV-I tax through induction of NF-kappaB nuclear translocation.

NF-kappaB is required for prevention of apoptosis. We examined the importance of human T-cell leukemia virus-I (HTLV-I) Tax protein to stimulate NF-kappaB nuclear translocation, thus preventing apoptosis. Jurkat cells and JPX-9 cells in which the inducible Tax expression plasmid vector was stably transfected were used in the present study. Both Jurkat and Tax(-) JPX-9 cells had small amounts of basal nuclear NF-kappaB activity. The addition of NF-kappaB inhibitors suppressed NF-kappaB nuclear translocation of the cells, thus inducing apoptosis. Sequential activation of caspases from caspase-8 to caspase-3 was shown during this process. NF-kappaB nuclear translocation in JPX-9 cells was stimulated through Tax expression, and both the activation of caspases and apoptosis induced by NF-kappaB inhibitors were significantly suppressed in the Tax(+) JPX-9 cells. The expression of Bcl-2, Bax, and Bcl-x was not changed among Jurkat, Tax(-) JPX-9, and Tax(+) JPX-9 cells in the presence or absence of NF-kappaB inhibitors. X-chromosome-linked inhibitor of apoptosis (XIAP) protein expression in Tax(-) JPX-9 cells was significantly suppressed by NF-kappaB inhibitors, however, its expression in Tax(+) JPX-9 cells was maintained even by the addition of NF-kappaB inhibitors. Our results suggest that the activation of NF-kappaB via Tax protein in HTLV-I infected cells renders the cells resistant to apoptosis. The expression of anti-apoptotic gene products such as XIAP to suppress caspase cascade, results in an increase of cytokine production and cell proliferation; one of the proposed mechanisms that promotes autoimmune disorders such as Sjögren's syndrome and rheumatoid arthritis found in HTLV-I seropositive subjects.

Apoptosis↗
PubMed1999

Vascular cell adhesion molecule-1-mediated matrix metalloproteinase-2 induction in peripheral blood T cells is up-regulated in patients with HTLV-I-associated myelopathy.

We investigated whether matrix metalloproteinase-2 (MMP-2) is induced in peripheral blood T cells after their contact with tumor necrosis factor-alpha (TNF-alpha)-stimulated glioblastoma cell line (T98G), expressing vascular cell adhesion molecule-1 (VCAM-1), in patients with HTLV-I-associated myelopathy (HAM) compared to control patients with other neurological disorders (OND). Gelatin zymography revealed that the incremental ratio of gelatinolytic activity of MMP-2 in culture supernatants derived from T cells cocultured with TNF-alpha-stimulated T98G to that of supernatants derived from cultures of T cells alone was significantly higher in HAM patients than in control patients with OND. Immunoblot analysis of immunoprecipitates of culture supernatant showed that increased gelatinolytic activity of MMP-2 was due to increased production of MMP-2 protein in T cells. Increased gelatinolytic activity of MMP-2 in T cells of HAM patients was blocked by pretreatment of TNF-alpha-stimulated T98G with anti-VCAM-1 antibody before coculture with T cells, indicating that MMP-2 induction was VCAM-1-mediated. Although no significant differences were noted in the percentage of VLA-4-positive cells in cultured T cells between HAM patients and control patients with OND, our results indicate that VCAM-1-mediated MMP-2 induction is up-regulated in T cells of HAM patients.

Adult↗
PubMed1999

FK506 markedly enhances apoptosis of antigen-stimulated peripheral T cells by down-regulation of Bcl-xL.

BACKGROUND: FK506 is a clinically effective immunosuppressive agent and promoter of immunologic tolerance. However, limited information is available about the mechanism of FK506-induced immunosuppression. METHODS: In the present study, we investigated the molecular mechanism of FK506-mediated enhancement of apoptosis using in vivo activated T lymphocytes. We examined the effects of FK506 on apoptosis-related proteins in superantigen-stimulated peripheral T cells. RESULTS: Injection of staphylococcal enterotoxin B (SEB) into BALB/c mice resulted in a selective apoptosis of splenic Vbeta8-positive T cells after 48 hr. Injection of FK506 within 36 hr of SEB injection resulted in a marked enhancement of DNA fragmentation of splenic Vbeta8+ T cells. FK506 did not affect the expression of Fas antigen on SEB-activated Vbeta8+ T cells. As Bcl-2-related proteins are involved in apoptotic process, we also evaluated their role by examining the expression of Bcl-2, Bcl-X(L), and Bax on SEB-FK506-treated murine splenic T cells. Although SEB injection slightly increased the expressions of Bcl-2 and Bax on V138+ T cells, FK506 did not modulate Bcl-2 or Bax expression in these cells. In contrast, the expression of Bcl-x(L) on Vgamma8+ T cells, which was markedly induced by SEB, was abrogated by FK506. CONCLUSIONS: Our findings indicate FK506-induced enhancement of apoptosis of activated T cells is mediated by down-regulation of Bcl-X(L) expression on these cells. Our results also suggest that Bcl-x(L) is a critical determinant of apoptosis of activated T cell and may represent a potential target for new therapies designed to achieve immunological tolerance.

Animals↗
PubMed1999

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in joint fluid of the patients with loose artificial hip joints.

The pseudojoint cavity formed in patients undergoing total hip arthroplasty (THA) is later remodeled to synovial membrane-like tissue, which produces pseudosynovial fluid. This pseudosynovium also is an important source of matrix metalloproteinases (MMPs). As it is widely speculated that synovial fluid MMPs may contribute to local tissue degradation in rheumatoid arthritis (RA) and osteoarthritis (OA), we hypothesize that locally produced MMPs are found in the pseudosynovial fluid, via which they have access to the implant-host interface, and that if they retain their proteolytic potential, they might contribute to aseptic loosening. Enzyme-linked immunosorbent assay (ELISA), immunoblotting, and zymography were used to analyze MMPs and tissue inhibitors of metalloproteinases (TIMPs) in synovial fluid in aseptic loosening, which was compared to RA and OA. Pseudosynovial THA fluid was characterized using low levels of MMP-1 but moderate levels of MMP-13 and MT1-MMP (MMP-14). Due to the lack of an appropriate assay, MMP-13 and MT1-MMP were not similarly assessed, but the immunoblotting indicated that they were in the 56 kD intermediate proteolytically processed forms. The MMP-9 level was intermediate between RA and OA. MMP-2 was on a significant level, but there were no differences among study groups. The THA group also was characterized using relatively high levels of TIMP-1 and TIMP-2. Accordingly, MMP-9 and MMP-2 were found to occur in the 92 kD and 72 kD proenzyme form, respectively, with full activity retained in all study groups. The data suggest that proMMP-2-TIMP-2 and proMMP-9-TIMP-1 complexes are formed in the pseudosynovial fluid due to the excess of TIMPs over MMPs in aseptic loosening of THA. TIMP-complexed MMPs are resistant to MMP-mediated proteolytic activation, which may explain their latency and proenzyme zymogen form. Thus, formation of stabilizing proMMP-TIMP complexes enable transportation of proMMPs far from their original site of production. Due to motion-associated cyclic changes of the intra-articular pressure, fluid-phase MMPs stabilized by TIMPs might be absorbed to implant surfaces and interface tissues and help to dissect the implant/cement-to-bone interface in situ. Consequently, they may contribute to local proteolytic/tissue destructive events and aseptic loosening.

Aged↗
PubMed1999

Regulation of synovial cell apoptosis by proteasome inhibitor.

OBJECTIVE: Recent studies have shown the importance of proteasome function in the regulation of apoptosis. This study examined whether inhibition of proteasome function mediates apoptosis of synovial cells, and whether cytokines modulate this process. METHODS: Type B synovial cells (fibroblast-like synovial cells) were cultured with tumor necrosis factor alpha (TNF alpha) or transforming growth factor beta1 (TGFbeta1), and further incubated in the presence of variable concentrations of Z-Leu-Leu-Leu-aldehyde (LLL-CHO), a proteasome inhibitor. During this process, apoptosis of synovial cells was determined by Hoechst 33258 dye staining and 51Cr release assay. The involvement of caspase cascade was examined using enzyme activity assay and blocking experiments by peptide inhibitors. The expression of pro-caspases, Bcl-2-related proteins, and X chromosome-linked inhibitor of apoptosis (XIAP) in synovial cells was examined by Western blot analysis. RESULTS: Apoptosis of cultured synovial cells was induced in a dose-dependent manner by LLL-CHO. Activation of caspase cascade through caspase-8 to caspase-3 was essential during this process. Pretreatment of synovial cells with TNF alpha significantly augmented both the activation of caspases and the proportion of apoptosis in synovial cells induced by LLL-CHO, whereas TGFbeta1 pretreatment markedly suppressed these phenomena. The ratio of the expression of Bcl-2 to Bax or Bcl-xL to Bax, and XIAP expression in synovial cells may not be directly associated with the susceptibility of synovial cells to apoptosis by LLL-CHO. CONCLUSION: Apoptosis of synovial cells was induced by inhibition of proteasome function through the activation of caspase cascade, and this process was clearly modulated by cytokines. These data provide new insight into the regulatory mechanisms controlling synovial cells in rheumatoid synovitis by proteasome inhibitors, and might be useful for the design of new therapeutic strategies in rheumatoid arthritis.

Apoptosis↗
PubMed1999

Clinical and molecular analysis of Japanese patients with neuronal ceroid lipofuscinosis.

Neuronal ceroid lipofuscinosis (NCL) is one of the most common inherited neurological diseases in childhood. It occurs every 12,500 births in northern-European populations. Mental retardation, visual impairment, and seizures are common symptoms. The prevalence of NCL is variable depending upon the races or countries. Although a wealth information is available in Caucasian populations, there is little information about NCL in Asian people. Because a nationwide survey in Japanese patients with NCL has never been performed, we pursued an epidemiological survey. We identified 36 NCL patients in Japan. Patients with infantile, late infantile, juvenile, and adult type accounted for 2, 15, 15, and 4 cases, respectively. Seizures were a major initial symptom in the late infantile type. In the juvenile type, visual failure was present in 73% at onset. Recently, the juvenile NCL (Batten disease) gene has been isolated. Studies of the mutations in this gene demonstrated that a 1.02-kb deletion was the most prevalent mutation among Caucasian patients, accounting for 81% of total alleles. To determine the prevalence of this 1.02-kb deletion in Japanese patients, we performed a rapid allele-specific polymerase chain reaction test. No 1.02-kb major deletion was detected in 5 Japanese juvenile NCL cases. These data suggest that the distribution of NCL and clinical findings are similar to those of Caucasian subjects; however, prevalence of mutations in Japanese patients with NCL would be distinct from that observed in Caucasians.

Adolescent↗
PubMed1999

Severity of upper limb injuries in snowboarding.

A retrospective survey of 1,445 snowboarders and 10,152 skiers was undertaken to determine the incidence, pattern and severity of both snowboarding and skiing injuries. The incidence of snowboarding injury (0.33%) was higher than that of skiing injury (0.11%, P < 0. 01). Also, in showboarding there was frequent involvement of the arms (51.3%) when compared with skiing (25.9%, P < 0.001). In the arms, fracture (45.7%) was frequently observed in snowboarding, vs 31.3% in skiing. The wrist was the most affected site (18.7%, P < 0. 01) in snowboarding (skiing 2.3%), and the fracture rate was significantly high (71.6%, P < 0.001). The rate of dislocation of the elbow (27.7%) was also higher in snowboarding than in skiing (13. 5%, P < 0.001). Regarding arm injuries, 57.9% of injured snowboarders were beginners whose experience was shorter than 1 year, and 91.5% was caused by falling down. These results indicate that a snowboarding injury involving the upper limb region is a severe accident, with a frequent risk of fracture in the wrist and dislocation of the elbow. The severity of arm injuries in snowboarding seems to be caused by direct force on the wrist and elbow, which receive the full impact of a fall. These data suggest that beginners should have appropriate lessons of basic skills including safe falling. The development of a safety system also appears sensible to prevent such severe injuries in snowboarding.

Accidental Falls↗