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Biomedical subjects

H Ida

Publications and source records attributed to H Ida.

At least 37 records · Page 2Linked to original sources
PubMed2001

Quantitative analysis of mRNA expression of TIMPs in the periprosthetic interface tissue of loose hips by real-time PCR system.

Matrix metalloproteinases (MMPs) and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs), have been reported to play a critical role in extracellular degradation around artificial hip joints. Although messenger ribonucleic acid (mRNA) expression patterns of several MMPs and TIMPs were reported, there is no report of quantitative mRNA analysis of TIMPs in periprosthetic tissues. In this study, mRNA expression of four different types of TIMPs in periprosthetic interface tissue of loose hips was analyzed by a quantitative polymerase chain reaction system. The mRNA expression level of TIMP-1, -2, and -3 in periprosthetic interface tissue was significantly higher than that in control. In contrast, the mRNA expression level of TIMP-4 in the periprosthetic interface tissue was lower. This study suggested that increased levels of TIMP-1, -2, and -3, and decreased levels of TIMP-4 may contribute to pathologic extracellular matrix degradation in combination with MMPs, thus leading to prosthetic loosening and osteolysis around artificial total hip joints.

Aged↗
PubMed2001

Effects of enzyme replacement therapy in thirteen Japanese paediatric patients with Gaucher disease.

UNLABELLED: To determine treatment effects in the unique and previously internationally unreported Japanese paediatric patient population with Gaucher disease (GD), we analysed six response parameters among 13 patients given enzyme replacement therapy (ERT). Also to obtain insights into optimising maintenance dosing, through subgroup analysis we retrospectively examined effects of three ERT dose reduction schedules from a starting regimen of 60 U/kg of body weight every 2 weeks. Our patients included 11 males and two females, 11 individuals with possible type 1 and two individuals with type 3b GD, six individuals with the L444P/F2131 genotype and five with the L444P/L444P genotype, and five who had been splenectomised. Despite different mutation prevalence, Japanese patients with GD, like their counterparts from other ethnic groups, generally benefitted from ERT. However, early and marked ERT dose reduction (from 60 U/kg to 30 or 15 U/ kg every 2 weeks within < or =6 months) was associated with insufficient improvement of mean haemoglobin level and relative height and with insufficient improvement or worsening of platelet count. Only the subgroup given 60 U/kg of ERT every 2 weeks for 36 months had significant improvement in mean haemoglobin, platelet count, angiotensin-converting enzyme and acid phosphatase levels and relative height at 36 months. CONCLUSION: These data suggest that long-term high dose enzyme replacement therapy may be required to obtain sufficient improvement to maintain health among paediatric patients with severe Gaucher disease.

Asian People↗
PubMed2001

Staging of idiopathic choroidal neovascularization by optical coherence tomography.

PURPOSE: To assess the clinical course of idiopathic choroidal neovascularization (ICNV) by optical coherence tomography (OCT). METHODS: Thirty-two patients with a clinical diagnosis of ICNV were examined between December 1995 and October 1999. The ages of the patients ranged from 18 to 53 (mean 35.9) years, and the mean period of observation was 5.8 months. Color fundus photography, fluorescein angiography, Indocyanine green angiography, and OCT were performed. The stage of the ICNV was classified as active, intermediate, or cicatricial, based on past history, fundus findings, and fluorescein angiography (FAG). The characteristic OCT images at these three stages were determined. RESULTS: OCT revealed that there were characteristic tomographic images of the choroidal neovascularization (CNV) at each stage. In the active stage, OCT revealed the CNV as a highly reflective, multi-layered area protruding into the subretinal space. In the intermediate stage, the reflectivity of the CNV became stronger and its margin in the subretinal space became smooth. With regression of the ICNV, the lesions consisted of two different areas: a most reflective area corresponding to the fibrotic changes of the CNV (imaged white in OCT images), and a reddish highly reflective area representing a compound protrusion of the CNV. In the cicatricial stage, the ICNV was observed as a moderately high reflective area covered by a dome-shaped highly reflective layer corresponding to the retinal pigment epithelium. CONCLUSION: These findings demonstrated clearly the changes in the OCT images during the development and regression of ICNV. OCT was useful for following the clinical course and understanding the mechanism of the CNV regression.

Adolescent↗
PubMed2001

Impaired degradation of serum amyloid A (SAA) protein by cytokine-stimulated monocytes.

Secondary amyloidosis (AA amyloidosis) is a systemic disease characterized by the extracellular tissue deposition of insoluble amyloid A (AA) protein. Aberrant metabolism of serum amyloid A (SAA) by macrophages is only one of many putative mechanisms which may be important in AA amyloidogenesis. In this study, we investigated the effects of cytokines on human monocyte-mediated SAA proteolysis. Human peripheral blood mononuclear cells (PBMC) or CD14(+) monocytes were cultured with SAA, and the culture supernatants were then subjected to anti-SAA immunoblot. CD14(+) monocytes degraded SAA completely. Whereas, when CD14(+) monocytes were pretreated with IL-1 beta or IFN-gamma, increasing amounts of SAA-related derivatives were detected in culture supernatants. These findings suggest that activation of monocytes by IL-1 beta or IFN-gamma hampers the proteolysis of a precursor protein and leads to a partial degradation of SAA. This down-regulated proteolysis of SAA protein by cytokine-stimulated monocytes may play a role in the mechanism of AA amyloid formation as well as its removal.

Amyloidosis↗
PubMed2001

Expression of membrane-type 1 matrix metalloproteinase in rheumatoid synovial cells.

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is thought to be a putative regulator of pro-gelatinase A (MMP-2) in the rheumatoid synovium. In this study, we examined the effects of IL-1beta, one of the inflammatory cytokines, on the expression of MT1-MMP and the activation of pro-MMP-2 using rheumatoid synovial cells. We also studied the effects of KE-298 (2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid), a new disease-modifying anti-rheumatic drug (DMARD), on MT1-MMP expression of rheumatoid synovial cells. Type B synovial cells (fibroblast-like synovial cells) were cultured with KE-298 (25-100 microg/ml) in the presence of IL-1beta for 48 h. Activation of pro-MMP-2 secreted from synovial cells was analysed by gelatin zymography. Reverse transcription-polymerase chain reaction (RT-PCR) methods were used to detect MT1-MMP mRNA. MT1-MMP protein expression on synovial cells was examined by anti-MT1-MMP immunoblot. An active form of MMP-2 was demonstrated in the culture media conditioned by IL-1beta-stimulated synovial cells. In addition, MT1-MMP mRNA and protein expression of rheumatoid synovial cells were increased by IL-1beta treatment. KE-298 blocked this IL-1beta-induced pro-MMP-2 activation and MT1-MMP expression, but did not affect IL-1beta-induced tissue inhibitor of metalloproteinase-2 (TIMP-2) secretion from rheumatoid synovial cells. These findings indicate that activation of rheumatoid synovial cells by IL-1beta results in the induction of MT1-MMP expression. Given that MT1-MMP promotes matrix degradation by activating pro-MMP-2, these results suggest a novel mechanism whereby cytokine may contribute to articular destruction in rheumatoid arthritis (RA). KE-298 may prevent this process by down-regulating MT1-MMP expression.

Antirheumatic Agents↗
PubMed2001

Regulation of rheumatoid synoviocyte proliferation by endogenous p53 induction.

The p53 tumour suppressor protein protects cells from tumorigenic alterations by inducing either cell growth arrest or apoptosis. In the present study, we investigated the role of endogenous p53 expressed in rheumatoid arthritis synovial fibroblasts which show transformed-appearing phenotypes. Type B synovial cells (fibroblast-like synovial cells) were exposed to a proteasome inhibitor, carbobenzoxyl-leucinyl-leucinyl-leucinal (MG-132). During this process, the expressions of p53 and p21 were examined by Western blot. Cell cycle analysis of the synovial cells was determined by DNA staining using propidium iodide (PI). Inhibition of proteasome resulted in the accumulation of p53 which was followed by an increase in the amount of a cyclin-dependent kinase (CDK)-inhibitor, p21. As a consequence, the retinoblastoma gene product, Rb, remained in the hypophosphorylated state, thus preventing PDGF-stimulated synovial cells from progressing into S-phase. This study shows that endogenous p53, which is inducible in rheumatoid synovial cells, is functionally active based on the findings that its expression blocks the G1/S transition by inhibiting the CDK-mediated phosphorylation of Rb via p21 induction. Thus the induction of p53 using proteasome inhibitor may provide a new approach in the treatment of RA.

Arthritis, Rheumatoid↗
PubMed2001

Nitric oxide protects cultured rheumatoid synovial cells from Fas-induced apoptosis by inhibiting caspase-3.

Nitric oxide (NO) is elevated in the synovial fluids and sera of patients with rheumatoid arthritis (RA) and is thought to be an important proinflammatory mediator in the rheumatoid synovium. To test the hypothesis that NO might modulate the apoptosis-inducing signal pathway, we investigated the effects of NO on rheumatoid synovial-cell apoptosis induced by Fas ligation with anti-Fas antibody. Pretreatment of synovial cells with the NO donor S-nitro-N-acetylpenicillamine (SNAP) prevented the Fas-mediated induction of apoptosis. The activation of caspase-3 was required to mediate Fas-induced synovial cell apoptosis. The NO donor SNAP inhibited Fas-induced caspase-3 activation in rheumatoid synovial cells. However, NO did not interrupt Fas-induced caspase-8 cleavage or subsequent cytochrome c release into the cytosol in rheumatoid synovial cells. These data indicate that NO prevents apoptosis in rheumatoid synovial cells by directly inhibiting caspase-3 activation. Thus, we propose that NO interferes with cell death signal transduction and may contribute to rheumatoid synovial cell proliferation by inhibiting induction of apoptosis.

Apoptosis↗
PubMed2001

Enhanced expression of basement-membrane-type heparan sulfate proteoglycan in tumor fibro-myxoid stroma of intrahepatic cholangiocarcinoma.

To investigate the molecular mechanism for enhanced fibrous stroma formation in intrahepatic cholangiocarcinoma (ICC), we surveyed the expression pattern of basement-membrane-type heparan sulfate proteoglycan (HSPG; also known as perlecan) at the core protein and the mRNA level in ICC as well as in other liver neoplasms and reactive hepatic diseases. Immunohistochemistry of paraffin-embedded liver sections with hyaluronidase pretreatment showed that HSPG was present in small amounts in normal liver around the bile ducts and the blood vessels within the portal area. There was no evident expression within the hepatic lobules. Intense immunoexpression of HSPG was seen in the tumor-specific fibro-myxoid stroma of ICC and metastatic liver cancer originating from the colon. However, tumor-specific stroma of hepatocellular carcinomas showed little or no expression of HSPG. At the mRNA level, signals for HSPG were found in tumor cells of cholangiocarcinoma and metastatic colonic carcinomas, and in myofibroblasts in the tumor fibro-myxoid-specific stroma. From immunoprecipitation and reverse transcription-polymerase chain reaction (RT-PCR) analyses, a cultured human intrahepatic cholangiocarcinoma cell line (CCKS1), was found to express high levels of HSPG core protein and mRNA. These findings suggest that biliary and metastatic colon carcinoma cells as well as stromal myofibroblasts have a potential for HSPG production. In order to investigate the growth, invasion and metastatic ability of ICC, further study of the 'self-made' stromal component of ICC may provide a new approach.

Adult↗
PubMed2001

Establishment and characterization of immortalized Schwann cells from murine model of Niemann-Pick disease type C (spm/spm).

Niemann-Pick disease type C (NPC) is characterized by an accumulation of unesterified cholesterol in the endosomal/lysosomal (E/L) system, resulting in progressive neurodegeneration and death during early childhood. To investigate the cellular pathomechanism of nervous system involvement in NPC, continuous neural cell lines are desirable. In this study, we obtained neuronal and Schwann cell cultures and established spontaneously immortalized Schwann cell lines from dorsal root ganglia and peripheral nerves of NPC model mouse (spm/spm). One of the cell lines, designated SPMS9, had distinct Schwann cell phenotypes and was maintained over 10 months without phenotypic alterations. The level of Npc1 mRNA was markedly decreased, and NPC1 protein was not detectable in SPMS9 cells. These cells contained intracytoplasmic granules positive for filipin cholesterol staining and immunoreactive for GM2 ganglioside. Electron-microscopically, intracytoplasmic polymorphous membranous inclusions and vacuoles were demonstrated in SPMS9 cells. The treatment with an inhibitor of ceramide-specific glucosyltransferase, N-butyldeoxynojirimysin (NB-DNJ) markedly reduced the intracytoplasmic granular immunofluorescence for GM2 ganglioside in SPMS9 cells, whereas the amount of filipin-positive granules remained unchanged. The SPMS9 cells retained vesicular fluorescence of cationic dye acriflavine 16-24 hours after loading, indicating the defect of transmembrane efflux pump activity of NPC1 in the E/L compartment in these cells. These immortalized Schwann cells can be useful in studies on the nervous system lesions in NPC.

Animals↗
PubMed2001

New disease-modifying antirheumatic drug 2 acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298) selectively augments activation-induced T cell death.

We examined in this study whether the newly developed disease-modifying antirheumatic drug (DMARD) 2-acetylthiomethyl-4-(4-methylphenyl)-4-oxobutanoic acid (KE-298) augments activation-induced T cell death. Peripheral blood (PB) T cells, isolated from healthy donors, were activated by incubation with interleukin-2 (IL-2) followed by further culture with 12-0-tetradecanoyl phorbol 13-acetate (PMA) and ionomycin in the presence or absence of KE-298. The apoptosis of activated T cells was examined by flow cytometric determination of hypodiploid DNA. Fas expression and caspase-3 activity in activated T cells were also examined by flow cytometry, and expression of Fas ligand (FasL), Bcl-2-related proteins, and X chromosome-linked inhibitor of apoptosis protein (XIAP) was determined by Western blot analysis. Apoptosis was not obvious in resting T cells and was not augmented by KE-298. In contrast, apoptosis was clearly detected in activated T cells (activation-induced T cell death) with the increment of caspase-3 activity, and incubation of these cells with KE-298 further enhanced apoptosis. Treatment of activated T cells with KE-298 increased Bax expression but decreased XIAP expression without affecting the expression of Fas/FasL. Thus caspase-3 activity in activated T cells appeared to be increased by KE-298. Our results suggest that the newly developed DMARD, KE-298, selectively augmented activation-induced T cell death. This finding may contribute to the therapeutic efficacy of KE-298 in rheumatoid arthritis (RA) patients and provide new insight into the pharmacologic action of DMARDs.

Antirheumatic Agents↗
PubMed2001

A new variant neuropathic type of Gaucher's disease characterized by hydrocephalus, corneal opacities, deformed toes, and fibrous thickening of spleen and liver capsules.

We report a new variant type of Gaucher's disease characterized by hydrocephalus, corneal opacities, deformed toes, gastroesophageal reflux, and fibrous thickening of splenic and hepatic capsules. This patient had 1 D409H allele. He differed from other reported cases with a 1342G to C (D409H) homozygous mutation (onset at 4 months, no cardiac involvement until the age of 12 years, and massive hepatosplenomegaly with fibrous thickening of spleen and liver capsules). Enzyme replacement therapy was given for 4 years, resulting in an improvement of visceral and hematologic abnormalities but no neurologic improvement.

Biopsy↗
PubMed2001

Type II Gaucher disease: compound heterozygote with RecNciI and L444P mutations.

We report the phenotype and genotype of an Indonesian Chinese boy with type II Gaucher disease. He had a unique presentation of recurrent cyanosis from laryngospasm. He was compound heterozygous for L444P/L444P + A456P + V460V. There have been few reports of this heterozygosity and its phenoptype. This genotype-phenotype correlation will be important for physicians in genetic counselling. Type II Gaucher disease in Southeast Asia may not be as rare as was perceived, but may be a condition that is under-reported. The success of our technique together with the results have made it possible for us to perform prenatal diagnosis and carrier detection for the family.

Alleles↗
PubMed2001

Geranylgeraniol, an intermediate product in mevalonate pathway, induces apoptotic cell death in human hepatoma cells: death receptor-independent activation of caspase-8 with down-regulation of Bcl-xL expression.

Geranylgeraniol (GGOH), an intermediate of mevalonate metabolism, is known to induce apoptosis in various lines of cancer cells. The present study was undertaken to clarify the signaling pathways of apoptosis induced by GGOH in human hepatoma cells. HuH-7 human hepatoma cells were incubated in the absence or presence of GGOH. Activation of caspase-8 /-9 /-3 in HuH-7 cells was found after 8 h treatment with GGOH, at which time DNA fragmentation and loss of mitochondrial transmembrane potential (Deltaphim) occurred. HuH-7 cells do not express Bcl-2; however, down-regulation of Bcl-xL expression preceded activation of the caspase cascade in GGOH-treated HuH-7 cells, while Bax expression was not changed by GGOH treatment. Addition of caspase inhibitors restored the decreased cell viability of HuH-7 cells by GGOH, including Deltaphim, to the baseline level, which indicated that caspase triggers mitochondria-dependent apoptotic pathways in GGOH-treated HuH-7 cells. Similarly, GGOH-mediated apoptosis of HuH-7 cells was clearly prevented by coadministration of ursodeoxycholic acid (UDCA), which led to restoration of the level of Bcl-xL expression. Activation of caspase-8 /-9 /-3, as well as Deltaphim, by GGOH treatment was suppressed by addition of UDCA. Our results indicate that activation of the caspase cascade initiating from caspase-8, which could be accelerated by down-regulation of Bcl-xL expression, plays a key role in an apoptotic process induced by GGOH in human hepatoma cells.

Apoptosis↗
PubMed2001

Importance of NF-kappaB in rheumatoid synovial tissues: in situ NF-kappaB expression and in vitro study using cultured synovial cells.

OBJECTIVES: To examine whether inhibition of NF-kappaB induces apoptosis of human synovial cells stimulated by tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), and anti-Fas monoclonal antibody (mAb). METHODS: The expression of proliferating cell nuclear antigen (PCNA), NF-kappaB, and the presence of apoptotic synovial cells were determined in synovial tissues. Apoptosis of cultured synovial cells was induced by inhibition of NF-kappaB nuclear translocation by Z-Leu-Leu-Leu-aldehyde (LLL-CHO). The activation of caspase-3 and expression of XIAP and cIAP2 in synovial cells in LLL-CHO induced apoptosis was also examined. RESULTS: Abundant PCNA+ synovial cells were found in rheumatoid arthritis (RA) synovial tissue, though a few apoptotic synovial cells were also detected in the RA synovial tissues. Nuclear NF-kappaB was expressed in RA synovial cells. Electrophoretic mobility shift assay showed that treatment of cells with TNFalpha or IL1beta significantly stimulated nuclear NF-kappaB activity. A small number of apoptotic synovial cells expressing intracellular active caspase-3 were found after treatment of cells with LLL-CHO. Although treatment of RA synovial cells with TNFalpha or IL1beta alone did not induce apoptosis, apoptosis induced by LLL-CHO and caspase-3 activation were clearly enhanced in TNFalpha or IL1beta stimulated synovial cells compared with unstimulated synovial cells. Furthermore, induction of apoptosis of synovial cells with caspase-3 activation by anti-Fas mAb was clearly increased by LLL-CHO. The expression of cIAP2 and XIAP in synovial cells may not directly influence the sensitivity of synovial cells to apoptosis induced by LLL-CHO. CONCLUSION: The results suggest that NF-kappaB inhibition may be a potentially important therapeutic approach for RA by correcting the imbalance between apoptosis and proliferation of synovial cells in RA synovial tissue.

Antibodies, Monoclonal↗
PubMed2001

High-turnover periprosthetic bone remodeling and immature bone formation around loose cemented total hip joints.

Aseptic loosening and periprosthetic osteolysis are the major problems awaiting solution in total hip surgery. The clinical investigation focused on the analysis of periprosthetic bone remodeling to clarify one important key event in the cascade of periprosthetic connective tissue weakening and osteolysis around loose artificial hip joints. Twelve acetabular bone samples adjacent to granulomatous synovial-like membrane of loose hip prosthesis were retrieved at revision surgery and processed for Villanueva bone staining for morphological observation and bone histomorphometric analysis. Eight well-fixed bony samples were used as control. Although osteoclastic surface and eroded surface by osteoclasts were evident in the periprosthetic bone from loose hip joints (p = 0.003 and p = 0.027), increased osteoid/low-mineralized bone matrix (p < 0.001) and osteoid width (p < 0.001) also were significant findings in structural analysis. In addition, not only elevated mineral apposition rate (MAR; p = 0.044) but also increased mineralizing surface (p = 0.044) and bone formation rate (BFR; p = 0.002) in loose periprosthetic bones were shown in dynamic data analysis. These results were confirmed by precise morphological observation by confocal laser scanning microscopy. Active coupling of bone formation and resorption and increased osteocytes with abundant bone canalicular projections were found in combined with the presence of immature bone matrices (osteoid and low-mineralized bone areas) in periprosthetic bones from loose hip joints. These results indicated that active osteoclastic bone resorption and/or defective bone formation are coupled with monocyte/macrophage-mediated foreign body-type granuloma in the synovial-like interface membrane of loose hip joints. Thus, this unique high-turnover periprosthetic bone remodeling with bad bone quality probably is caused by the result of cellular host response combined with inappropriate cyclic mechanical loading. The fragile periprosthetic bone may contribute to hip prosthesis loosening.

Aged↗
PubMed2001

Initiation of enzyme replacement therapy for an adult patient with asymptomatic type 1 Gaucher's disease.

A 27-year-old woman was admitted for further examination of thrombocytopenia. Symptoms were absent, but physical examination demonstrated hepatosplenomegaly without neurological abnormalities. Bone marrow examination revealed many Gaucher cells, and glucocerebrosidase activity from cultured skin fibroblasts was markedly reduced. A 1448C (L444P) mutation was detected on one allele of the glucocerebrosidase gene. Because magnetic resonance imaging (MRI) of the femora indicated severe infiltration of Gaucher cells into bone marrow, enzyme replacement therapy was initiated despite the absence of skeletal symptoms. Hematologic abnormalities, visceral and bone involvement have been improving. In cases of thrombocytopenia or hepatosplenomegaly, Gaucher's disease should be suspected.

Adult↗
PubMed2000

Messenger ribonucleic acid expression of 16 matrix metalloproteinases in bone-implant interface tissues of loose artificial hip joints.

Matrix metalloproteinases (MMPs) have been reported to be the major factors responsible for aseptic loosening of artificial hip joints. So far, messenger ribonucleic acid (mRNA) expression patterns of seven MMPs have been reported, but that of many other MMPs which have been newly discovered or recently considered to be responsible for prosthetic loosening is still unknown. In this study, mRNA expression pattern of 16 different types of MMPs were analyzed to evaluate which MMPs were locally produced and contributed to prosthetic loosening. Synovium-like interface tissues between bone and prosthesis were collected from 18 cases of aseptic loose artificial hip joint at revision surgery. Six cases of normal synovium were used as controls. Total RNA was extracted by single-step acid guanidinium-thiocyanate-phenol-chloroform procedure. mRNA expression of MMPs was analyzed by semiquantitative reverse transcription-polymerase chain reaction. Based on local expression pattern of MMPs at the mRNA level, aseptic loose artificial hip joint was characterized by elevated expression of MMP-1, MMP-9, MMP-10, MMP-12, and MMP-13; moderate expression of MMP-2, MMP-7, MMP-8, MMP-11, membrane type (MT)1-MMP (MMP-14), MT2-MMP (MMP-15), MT3-MMP (MMP-16), MT4-MMP (MMP-17), and MMP-19; lower expression of MMP-3; and little significance of MMP-20. The MMPs detected in this study can potentially degrade almost all components of the periprosthetic extracellular matrix. Thus, many MMP type enzymes possibly contribute to prosthetic loosening and osteolysis through pathologic extracellular matrix degradation and connective tissue/bone remodeling around prostheses.

Aged↗