Biomedical subjects

T Ochi

Publications and source records attributed to T Ochi.

At least 181 records · Page 10Linked to original sources

PubMed1997

The relationship between HLA-DRB1 alleles and disease subsets of rheumatoid arthritis in Japanese.

To assess the association between HLA-DRB1 and the pathogenesis of rheumatoid arthritis (RA) in the Japanese population, we typed for HLA-DRB1 alleles in 852 Japanese patients. An analysis of HLA-DRB1 allele associations was performed on the overall group and in three disease subsets of adult-onset RA, classified according to the extent of joint destruction evident on plain radiograms, i.e. least erosive subset (LES), more erosive subset (MES) and most erosive subset with mutilating disease (MUD). The Japanese RA patients with positively associated with DRB1*0101 and *0405, and negatively associated with DRB1*0701, *0802, *1302 and *1405. DRB1*0101 was associated more strongly with a milder disease subset and the relative risk (RR) was 1.9, 1.5 and 1.2 for LES, MES and MUD, respectively. On the other hand, DRB1*0405 was associated more strongly with a more severe disease subset, the RR being 1.8, 4.0 and 4.3 for LES, MES and MUD, respectively. These findings suggest that RA is a heterogeneous disease, not only clinically, but also in terms of its immunogenetic background, and that HLA-DRB1 can be a useful prognostic factor for RA.

Adolescent↗

PubMed1997

Longitudinal evaluation of time related bone remodeling after cementless total hip arthroplasty.

Bone remodeling after cementless total hip arthroplasty was evaluated by dual energy x-ray absorptiometry in a longitudinal study of 32 hips. After insertion of a fully porous surface anatomic stem made of cobalt chromium, bone mineral density was analyzed until at least 2 years postoperatively. Bone remodeling was evaluated in terms of regional bone density changes in the seven adjacent periprosthetic zones as well as the global change in bone density distribution over the entire periprosthetic area. At 12 months after the operation, the averaged regional bone mineral density in all seven zones showed a rapid decrease, ranging from 9% to 24% of the bone mineral density present at 2 weeks postoperatively. Thereafter, the bone density change appeared to be stabilized. The global change in the bone density distribution was expressed as two summarizing statistical indexes derived from principal component analysis: the first index represents the change of average bone mineral density over the entire periprosthetic area, and the second represents the severity of bone mineral density decrease in the proximal area versus the distal area. The second index proved that more bone density reduction occurred in the proximal area, but this was variable among patients and correlated significantly with the stem size and the initial bone mineral density in the distal part of the periprosthetic area. This longitudinal dual energy x-ray absorptiometry study suggests that a large part of the bone remodeling after cementless hip arthroplasty ceases within 1 year postoperatively, and stem size and the initial bone density around the distal portion are important considerations for predicting the proximal bone density decrease during the early rapid remodeling period.

Absorptiometry, Photon↗

PubMed1997

Three-dimensional endoscopic mode for observation of laryngeal structures by helical computed tomography.

We produced high-quality three-dimensional (3D) endoscopic images of the larynx using helical scanning computed tomography. Subjects included two normal volunteers and 10 patients: five with laryngeal cancer, four with unilateral recurrent laryngeal nerve (RLN) palsy, and one with atrophied vocal folds. Two vertically split hemilaryngeal images were displayed together with the oral and tracheal views. Although motion artifacts were seen in four patients, laryngeal structures including the vocal fold, ventricular fold, and ventricle were clearly identified in all subjects. In the patients with cancer, axial images showing the extent of the tumor in each patient provided more information than 3D endoscopic images. In the patients with RLN palsy and atrophied vocal fold, combination of 3D endoscopic and cross-sectional images offered more diagnostic information than axial images alone.

Adult↗

PubMed1997

Studies on anti-inflammatory agents. V. Synthesis and pharmacological properties of 3-(difluoromethyl)-1-(4-methoxyphenyl)-5- [4-(methylsulfinyl)phenyl]pyrazole and related compounds.

A series of novel 1,5-diphenylpyrazole derivatives bearing hydrophilic substituents was prepared. The anti-inflammatory and analgesic activities of these compounds were evaluated by using the adjuvant arthritis and Randall-Selitto assays in rats, and the structure-activity relationships were studied. The optimal compound was 3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyraz ole (10) with oral ED50 values of 0.31 and 2.6 mg/kg on adjuvant-induced arthritis and carrageenin-induced foot edema, respectively. Compound 10 showed analgesic activities not only toward inflamed paw but also toward normal paw (ED30 = 0.55 and 1.8 mg/kg, respectively) in the Randall-Selitto assay, and moreover, 10 was effective in the tail-pinch assay (ED50 = 21 mg/kg) similarly to morphine. The asymmetric synthesis and pharmacological properties of the enantiomers of 10 are also reported.

Animals↗

PubMed1997

Studies on anti-inflammatory agents. IV. Synthesis and pharmacological properties of 1,5-diarylpyrazoles and related derivatives.

A series of novel 1,5-diarylpyrazole derivatives was synthesized and tested for anti-inflammatory and analgesic activities to develop anti-inflammatory agents with fewer side effects than existing nonsteroidal anti-inflammatory drugs. The structure-activity relationships in this series were extensively studied. Electron-withdrawing substituents such as CN and CF3 were optimal at the 3-position of the pyrazole ring. Replacement of these substituents with bulky ones gave less active compounds. The 4-(methylsulfonyl)phenyl group seemed to be the optimal group at the 5-position of the pyrazole ring. The most potent compound was 1-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-pyrazole-3-carbonitrile (19a), with oral ED50 value of 0.030 and 0.47 mg/kg on adjuvant-induced arthritis and collagen-induced arthritis, respectively, and an ED30 value of 7.4 mg/kg in the yeast-induced hyperalgesia (Randall-Selitto) assay. Compound 19a also showed potent inducible cyclooxygenase (COX-2)-inhibitory activity (IC50 = 0.24 microM) with no COX-1 inhibition even at 100 microM.

Anilides↗

PubMed1997

Acetabular osteolysis and migration in bipolar arthroplasty of the hip: five- to 13-year follow-up study.

We have reviewed 65 bipolar arthroplasties of the hip in 55 patients with osteoarthritis secondary to dysplasia. The mean age at operation was 56 years (42 to 79) and the mean period of follow-up was 7.2 years (5.0 to 13.0). The average Merle d'Aubigné and Postel score before operation was 10.3 and at final follow-up 15.0. There were excellent or good results in 42 hips (65%). Migration of the outer head was observed in 50 hips (77%), most often in the group with a centre-edge angle of less than 0 degrees, an acetabular head index of less than 60%, coverage of the outer head by the original acetabulum of less than +10 degrees and after bone grafting of the acetabulum. This migration was progressive in 31 (62%) of the 50 hips, with massive osteolysis of the acetabulum in eight. The extent and progression of migration were closely associated with this osteolysis. Four hips required revision for extensive migration of the outer head with destruction of the acetabulum or severe acetabular osteolysis, and nine hips are awaiting revision for failure of the bipolar prosthetic head. The overall failure rate was 18%. We report major problems after bipolar hip arthroplasty for osteoarthritis secondary to hip dysplasia with progressive migration of the outer head and massive acetabular osteolysis at five years or more after operation.

Acetabulum↗

PubMed1997

Early deterioration after modified rotational acetabular osteotomy for the dysplastic hip.

We performed a modified, rotational acetabular osteotomy through a lateral transtrochanteric approach on 19 hips in 18 patients with a dysplastic joint. Six hips in six patients were operated on using the original approach. The mean age at operation was 28 years (14 to 54) and the mean period of follow-up 2.3 years (1 to 4.4). Clinical evaluation using the Merle d'Aubigne score showed excellent or good results in 76%. Radiologically, 15 hips showed good acetabular remodelling and no signs of progressive osteoarthritis. In ten hips (40%) there was chondrolysis and collapse of the transferred acetabulum or both within one year, although this gave only mild pain in some patients. Factors which were significantly associated with the grade of outcome included age at the time of operation, the thickness of the transferred acetabulum, failure to use a bone graft, and a transtrochanteric approach.

Acetabulum↗

PubMed1997

Skeletal metastases from soft-tissue sarcomas. Incidence, patterns, and radiological features.

We reviewed 277 patients with soft-tissue sarcoma (STS) treated between 1975 and 1995 to study the incidence, distribution, time of appearance, and radiological findings of skeletal metastases. Of these, 28 (10.1%) had metastases within a mean period of 18.6 months after admission. The incidence of skeletal metastases differed among the histological subtypes of sarcoma; alveolar soft-part sarcoma, dedifferentiated liposarcoma, angiosarcoma, and rhabdomyosarcoma tended to show higher incidences. The regional bones close to the primary tumour were affected in 13 (46.4%) of the 28 patients, and the axial bones in 18 (64.3%). Radiologically, the metastatic bony lesions predominantly showed osteolytic changes, and there were pathological fractures in 21 of 44 lesions.

Adolescent↗

PubMed1997

Three modes of ossification during distraction osteogenesis in the rat.

We developed a rat model of limb lengthening to study the basic mechanism of distraction osteogenesis, using a small monolateral external fixator. In 11-week-old male rats we performed a subperiosteal osteotomy in the midshaft of the femur with distraction at 0.25 mm every 12 hours from seven days after operation. Radiological and histological examinations showed a growth zone of constant thickness in the middle of the lengthened segment, with formation of new bone at its proximal and distal ends. Osteogenic cells were arranged longitudinally along the tension vector showing the origin and the fate of individual cells in a single section. Typical endochondral bone formation was prominent in the early stage of distraction, but intramembraneous bone formation became the predominant mechanism of ossification at later stages. We also showed a third mechanism of ossification, 'transchondroid bone formation'. Chondroid bone, a tissue intermediate between bone and cartilage, was formed directly by chondrocyte-like cells, with transition from fibrous tissue to bone occurring gradually and consecutively without capillary invasion. In situ hybridisation using digoxigenin-11-UTP-labelled complementary RNAs showed that the chondroid bone cells temporarily expressed type-II collagen mRNA. They did not show the classical morphological characteristics of chondrocytes, but were assumed to be young chondrocytes undergoing further differentiation into bone-forming cells. We found at least three different modes of ossification during bone lengthening by distraction osteogenesis. We believe that this is the first report of such a rat model, and have shown the validity of in situ hybridisation techniques for the study of the cellular and molecular mechanisms involved in distraction osteogenesis.

Animals↗

PubMed1997

Hepatocyte growth factor facilitates cartilage repair. Full thickness articular cartilage defect studied in rabbit knees.

Hepatocyte growth factor (HGF) is a multifunctional factor which promotes proliferation, motility and morphogenesis in epithelial cells. In addition, it has been found to play an important role in cartilage metabolism. To investigate articular cartilage repair using HGF in vivo, we injected HGF into rabbit knee joints, where 4 mm diameter osteochondral defects had been made, and observed the animals for 6 months. We found that HGF effectively repaired osteochondral defects. The repair process of the articular cartilage defects using HGF was shown to be much better than saline injection on all macroscopic and histologic examinations. Although the observation period in our study was short, HGF is one of the most promising candidates for repairing articular cartilage defects clinically.

Animals↗

PubMed1997

Enhanced expression of CD14 antigen on myeloid lineage cells derived from the bone marrow of patients with severe rheumatoid arthritis.

OBJECTIVE: We previously reported the accumulation of abnormal myeloid cell populations reacting with CD14 (MY4) monoclonal antibody in the iliac and epiphyseal bone marrow of patients with severe rheumatoid arthritis (RA). Therefore, we investigated in vitro production and modulation of CD14+ myeloid cells from iliac bone marrow cells. METHODS: Mononuclear cells were prepared from iliac bone marrow aspirates from patients with RA. The presence of unusual myeloid cells was assessed by 2 color flow cytometry of cells cultured under various conditions. RESULTS: Cultured iliac bone marrow cells of patients with severe RA produced 14.7% of CD14+ CD15+ cells on average. Cultures derived from healthy donors and from patients with a milder form of RA produced fewer CD14+ CD15+ cells (< 10%). The production of CD14+ CD15+ cells was enhanced by granulocyte macrophage colony stimulating factor and interleukin 1beta, but inhibited by T lymphocytes. CONCLUSION: Production and modulation of CD14+ myeloid cells were observed in iliac bone marrow of patients with severe RA.

Adult↗

PubMed1997

Natural history of upper cervical lesions in rheumatoid arthritis.

The natural history of the upper cervical lesions in rheumatoid arthritis (RA) was investigated, based on a follow-up study of 79 patients. At the beginning of this study, anterior atlantoaxial subluxation (AAS) was found in 35 patients, AAS combined with vertical subluxation (VS) in 34, and VS alone in 10. During the follow-up period (mean, 6.4 years), these lesions deteriorated in 30 of the 79 patients. To evaluate the occipitoatlantoaxial relation, the angles between occiput and atlas (C0/C1 angle) and between atlas and axis (C1/C2 angle) were measured, and the correlation between these angles and deterioration of the lesions was investigated. The severity of RA was classified according to the "disease subset" advocated by one of us (T.O.): the least erosive subset (LES), the more erosive subset (MES), and the mutilating subset (MUD). There was a significant positive correlation between the C1/C2 angle and atlantodental interval (ADI) and a significant negative correlation between the C0/C1 angle and the ADI. This indicates that the atlas not only shifts forward but also slips down and forward at an incline from the axis. With an increase of the atlantal inclination, the anterior arch of atlas displaces in an anteroinferior direction, and VS combines with AAS. The development of associated VS lessens the amount of the ADI. At the advanced stage of the natural course, AAS is concealed, and VS alone is demonstrated. We concluded that the upper cervical lesion deteriorated in the order of AAS, AAS + VS, and VS alone. In patients classified as the LES subset, only AAS was found, and VS was never combined with AAS at the terminal stage. In patients in the MES, VS frequently combined with AAS. All patients who deteriorated to VS alone were ranked as MUD.

Adult↗

PubMed1997

Osteoclastogenesis in iliac bone marrow of patients with rheumatoid arthritis.

OBJECTIVE: To investigate osteoclastogenesis in bone marrow cells from patients with various pathogenic backgrounds known to induce osteoporosis, to identify specific factors that may cause generalized osteoporosis in patients with rheumatoid arthritis (RA). METHODS: Bone marrow blood was obtained from 59 women, 36 with RA and 23 without RA. Patients with RA were classified as severe (26) and mild RA (10: 5 patients with and 5 without corticosteroid therapy). The non-RA subjects were divided into 3 groups, premenopausal (7), menopausal (8), and elderly (8). As a marker of bone resorption, the pyridinoline crosslinked telopeptide domain of type I collagen (ICTP) concentration in the bone marrow supernatant was measured by radioimmunoassay. The bone marrow cells were cultured 14 days in the presence or absence of autologous bone marrow supernatant; then the number of tartrate resistant acid phosphatase positive multinucleated cells (TRAP positive MNC) was counted as an indicator of osteoclastogenesis. RESULTS: ICTP concentration of the bone marrow supernatant and the number of TRAP positive MNC showed remarkable enhancement in some patients with severe RA, but these features were not observed in the 3 control groups. CONCLUSION: Increased bone resorption and enhanced osteoclastogenesis were specifically observed in the iliac bone marrow of patients with RA, especially those with severe RA. These phenomena can be considered to accompany generalized osteoporosis in RA.

Adult↗

PubMed1997

Lengthening of the lower limbs in patients with achondroplasia and hypochondroplasia.

Ten years of experience in lower limb lengthening achieved in 35 patients with achondroplasia and seven patients with hypochondroplasia is reported. A uniform method of callus distraction (callotasis) was used in all cases, although the order of lengthening of each bone differed among the cases. The mean age of the patients at the time of first operation was 14.5 years; at followup, the mean age was 18.8 years. The mean lengthening achieved in the femur was 7.2 cm (range, 4.5-12 cm) and in the tibia 7.1 cm (range, 4.5-13 cm). More lengthening was achieved in the more recent cases. The function of lengthened limbs, evaluated by physical strength tests, was better at followup than before lengthening in the growing children, although the mechanical axes of the lengthened bones were not necessarily in correct alignment.

Achilles Tendon↗

PubMed1997

Mechanisms of KE298, 2-acetylthiomethyl-3-(4-methylbenzoyl) propionic acid, to suppress abnormal synovial cell functions in patients with rheumatoid arthritis.

OBJECTIVE: 2-Acetylthiomethyl-3-(4-methylbenzoyl) propionic acid, KE298, a derivative or propionic acid developed in Japan has been shown to be effective for suppressing disease activity of rheumatoid arthritis (RA) in clinical trials in Japan. It is thus a candidate as a new disease modifying antirheumatic drug (DMARD). We analyzed effects of KE298 on synovial fibroblast-like cells in patients with RA to obtain insight into the clinical application of this medication. METHODS: RA synovial fibroblast-like cells were co-cultured with KE298 at 10(-4)-10(-5) M in the presence or absence of tumor necrosis factor-alpha 2 ng/ml, and their subsequent proliferative responses and proinflammatory cytokine and matrix metalloproteinase (MMP) production at the mRNA and protein levels were measured. Effects of KE298 on MMP-1 gene transcription and AP-1 transcription factor expression of RA synovial cells were studied by chloramphenicol acetyltransferase assay and gel shift assay, respectively. RESULTS: KE298 inhibited proliferation of RA synovial cells, proinflammatory cytokine production, and MMP-1 production mainly by reducing their transcription via downmodulation of AP-1 transcription factor. CONCLUSION: KE298 inhibits aberrant synovial cell functions of patients with RA by downregulating gene transcription, suggesting clinical application and usefulness of this new DMARD.

Antirheumatic Agents↗

PubMed1996

A cDNA cloning of human AEBP1 from primary cultured osteoblasts and its expression in a differentiating osteoblastic cell line.

By comparing lists of 3'-directed partial cDNA sequences (gene signatures) randomly collected from various tissues, genes uniquely expressed in individual tissue can be identified. A full length cDNA clone, corresponding to one such gene signature, unique to human osteoblast and adipose tissue, was isolated. This cDNA clone encodes a 845-amino acid protein that is almost identical to the mouse adipocyte transcription factor AEBP1 except that it has additional 105 amino acids in the N terminus. A northern hybridization showed that in the differentiating murine osteoblastic cell line, AEBP1 is also expressed but that it is shut off in the final calcification phase, suggesting a transcriptional repressive effect on genes for bone formation.

3T3 Cells↗

PubMed1996

Induction of chromosomal aberrations in cultured human fibroblasts by inorganic and organic arsenic compounds and the different roles of glutathione in such induction.

Clastogenic effects of a variety of arsenic compounds were examined on cultured human fibroblasts. The following compounds were tested: inorganic arsenicals (arsenite and arsenate), the major metabolites of inorganic arsenicals in human and experimental animals [methylarsonic acid (MAA), dimethylarsinic acid (DMAA) and trimethylarsine oxide (TMAO)], and water-soluble organoarsenic derivatives [2', 3'-dihydroxypropyl-5-deoxy-5-dimethylarsinoyl-beta-D-riboside (arsenosugar), arsenocholine, arsenobetaine and tetramethylarsonium iodide] found in marine organisms. Arsenic compounds induced mainly chromatid gaps and chromatid breaks. The rank order of compounds in terms of clastogenic potency was arsenite > arsenate > DMAA > MAA > TMAO. DMAA was very potent and caused chromosome pulverizations in most metaphases when present at doses higher than 7 x 10(-3) M. Arsenosugar, arsenocholine, arsenobetaine and tetramethylarsonium iodide were less effective. Depletion of cellular glutathione (GSH) with L-buthionine-SR-sulfoximine (BSO), increased the incidence of chromosomal aberrations induced by arsenite, arsenate and MAA, and markedly suppressed the clastogenic effects of DMAA. DMAA was highly clastogenic even in GSH-depleted cells when the cells were incubated with DMAA in the presence of GSH (5 and 10 mM). These results suggest that GSH might play a role in protecting cells against the clastogenic effects of arsenite, arsenate and MAA. GSH might be involved in the expression of clastogenic actions of DMAA.

Arsenicals↗

PubMed1996

Menadione causes increases in the level of glutathione and in the activity of gamma-glutamylcysteine synthetase in cultured Chinese hamster V79 cells.

Incubation of cultured Chinese hamster V79 cells with menadione (2-methyl-1,4-naphthoquinone), a generator of superoxide anion radicals, caused a rapid increase in the level of glutathione disulfide (GSSG) and a decrease in the level of glutathione (GSH), which followed a 1.5- to 2-fold increase in the level of GSH during post-treatment incubation. Menadione also caused a concentration- and time-dependent increase in the activity of gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme in the synthesis of GSH. These results suggested that the increase in level of GSH after treatment with menadione was due to the increase in the activity of gamma-GCS. Dicoumarol, an inhibitor of DT-diaphorase, did not influence the increase in the activity of gamma-GCS caused by menadione but it did enhance the cytotoxicity and the increase in the level GSSG caused by menadione. This result suggested that neither the DT-diaphorase-mediated metabolism of menadione nor the increase in level of GSSG caused by menadione was associated with the increase in the activity of gamma-GCS. Chelators of divalent iron and copper (I), and cycloheximide did not influence the increase in the activity of gamma-GCS caused by menadione. Thus, it appeared that reactive oxygen radicals, generated from hydrogen peroxide by an iron- or copper-catalyzed Fenton reaction, were not responsible for the increase in the activity of gamma-GCS and that the increase was not an inducible phenomenon.

Animals↗