Biomedical subjects

T Ochi

Publications and source records attributed to T Ochi.

At least 73 records · Page 4Linked to original sources

PubMed2000

Different role of IL-4 in the onset of hapten-induced contact hypersensitivity in BALB/c and C57BL/6 mice.

1. To study the role of interleukin (IL)-4 in the onset of contact hypersensitivity (CH) in mice, the effect of IL-4 gene-depletion and anti-IL-4 monoclonal antibody treatment on dinitrofluorobenzene (DNFB)-induced CH was examined. Simultaneously, to clarify the effect of background gene, DNFB-induced CH in BALB/c and C57BL/6 mice was compared. 2. Five repeated topical applications of DNFB to the ears of mice resulted in CH of the ears in terms of increases in ear thickness and histopathological changes. The magnitude of ear thickness increase in BALB/c mice was almost three times greater than that in C57BL/6 mice. 3. The CH in BALB/c mice was significantly suppressed by IL-4 gene-depletion and anti-IL-4 monoclonal antibody treatment. In contrast, the symptoms of dermatitis in C57BL/6 mice were slightly affected by the same treatment. These changes corresponded well to the production of specific IgE antibody. 4. Total IgE antibody production and the expression of productive Cepsilon mRNA were dramatically suppressed by IL-4 gene-depletion and anti-IL-4 treatment in BALB/c and C57BL/6 mice. Neither total IgG nor IgM levels in either strain of mice was altered by depletion of IL-4. 5. The expression of IFN-gamma in the skin lesion was dramatically suppressed by IL-4 gene-depletion in BALB/c mice, but not in C57BL/6 mice. 6. These findings indicate that IL-4 plays an important role in the onset of DNFB-induced CH in BALB/c mice, but not in C57BL/6 mice.

Animals↗

PubMed2000

IL-6 inhibits the proliferation of fibroblastic synovial cells from rheumatoid arthritis patients in the presence of soluble IL-6 receptor.

IL-6 and tumor necrosis factor (TNF)-alpha have been proven to play an important role in the development of rheumatoid arthritis (RA). It is well known that TNF-alpha induces IL-6 production from synovial cells as well as their proliferation. The effect of IL-6 on synovial cells, however, is not clear. An in vitrostudy was performed to determine the effect of IL-6 on the proliferation of synovial cells. Fibroblastic synovial cells isolated from the synovial tissues of eight RA patients were employed after the third to sixth passages. IL-6 in the presence of soluble IL-6 receptor (sIL-6R) inhibited the proliferation of synovial cells in a dose-dependent manner in seven cases without increasing the number of necrotic or apoptotic cells, while TNF-alpha increased synovial cell proliferation in all cases. The inhibitory effect of IL-6 was observed only in the presence of sIL-6R although small amounts of IL-6R were detected in these cells by RT-PCR analysis. However, anti-IL-6R or anti-gp130 mAb treatment increased spontaneous growth of synovial cells in all eight cases, suggesting that endogenous IL-6 and a small amount of IL-6R expressed in synovial cells suppressed their growth without exogenous IL-6 or sIL-6R. In addition, the IL-6-sIL-6R complex reduced the TNF-alpha-induced proliferation of synovial cells while TNF-alpha induced their IL-6 production. These data suggest that IL-6 may act as a negative feedback factor for TNF-alpha-induced synovial cell growth.

Arthritis, Rheumatoid↗

PubMed2000

Involvement of multinucleated giant cells synthesizing cathepsin K in calcified tendinitis of the rotator cuff tendons.

OBJECTIVES: Calcified tendinitis of the shoulder joint is a common painful condition. Resorption of the calcium deposits is one of the key events in the pathogenesis of this disease. The aim of this study was to examine whether the multinucleated giant cells that appear in this condition have osteoclast phenotypes. METHODS: Immunohistochemical and RNA in situ hybridization analysis of cathepsin K, a marker for osteoclasts, was performed in human surgical samples. RESULTS: The multinucleated cells located near the calcium deposits were positive for cathepsin K protein and mRNA. Reverse transcription-polymerase chain reaction using human cathepsin K-specific oligonucleotide primers confirmed that synthesis of cathepsin K mRNA occurs in the tissues of calcified rotator cuffs. CONCLUSION: The multinucleated giant cells which appear in the resorption area of calcium deposits in calcified tendinitis have the osteoclast phenotype.

Arthrography↗

PubMed2000

Transcription factor decoy for NFkappaB inhibits cytokine and adhesion molecule expressions in synovial cells derived from rheumatoid arthritis.

OBJECTIVE: Numerous cytokines are expressed in lesions of synovial hyperplasia of patients with rheumatoid arthritis (RA), and their pathophysiological contributions have been the subject of speculation. These genes are regulated by the transcription factor NFkappaB which in turn is activated by tumour necrosis factor-alpha (TNF-alpha) and cytokines. In this study we examined the inhibition of the production of pro-inflammatory cytokines, adhesion molecule and matrix metalloproteinase (MMP) from synovial tissue of patients with RA by the introduction of synthetic double-stranded DNA with high affinity for the NFkappaB binding site. METHOD: NFkappaB decoy oligonucleotides (ODN) were introduced with the aid of the haemagglutinating virus of Japan (HVJ)-liposome method into synovial tissue or synovial cells derived from patients with RA. The levels of interleukin-1beta (IL-1beta), IL-6, TNF-alpha, intercellular adhesion molecule-1 (ICAM-1) and MMP-1 were determined by means of enzyme-linked immunosorbent assay (ELISA) and Northern blotting analysis. A cell counting kit was used to study the effect of NFkappaB decoy ODN on synovial cell proliferation. RESULTS: The production of these mediators was significantly inhibited by the introduction of NFkappaB decoy ODN compared with the effect of scrambled decoy ODN. Transfection of NFkappaB decoy ODN resulted in a significant inhibition of synovial cell proliferation as compared with that of scrambled decoy ODN. CONCLUSION: The results demonstrated in this study suggest the potential usefulness of NFkappaB decoy ODN for gene therapy of inflammatory synovitis of RA.

Arthritis, Rheumatoid↗

PubMed2000

A long-term follow-up study of cervical lesions in rheumatoid arthritis.

To determine the natural history of cervical lesions in rheumatoid arthritis, 161 patients who had been followed for a minimum of 5 years were enrolled in this study. The average follow-up period was 10.2 years (range, 5 to 20 years). The severity of the rheumatoid arthritis was classified into three types based on the multiplicity of peripheral joint rheumatoid involvement: a least erosive subset, a more erosive subset, and a mutilating disease subset. Ninety-two patients (57%) had upper cervical involvement, which progressed in the order of anterior atlantoaxial subluxation, anterior atlantoaxial subluxation combined with vertical subluxation, and vertical subluxation alone. Subaxial subluxation was found in 18 patients (11%). In 17 of these 18 patients, upper cervical lesions were also noted. The incidence of cervical involvement in each disease subset was 39% in the least erosive group, 83% in the more erosive group, and 100% in the mutilating disease group. Fifty percent of the patients with cervical involvement had neck pain, and the remaining patients were asymptomatic. Neural involvement occurred in 10 patients. In 7 of these 10 patients, vertical subluxation of the atlas was responsible for the neural deficit. Six patients required surgical intervention because of progressive myelopathy.

Adolescent↗

PubMed2000

Effect of Am-80, a retinoid derivative, on 2, 4-dinitrofluorobenzene-induced contact dermatitis in mice.

Retinoids have many pharmacological activities, including anti-inflammatory action and antiangiogenesis, effected through the regulation of various gene transcriptions. In this study, we investigated the effect of Am-80, one of the retinoic acid derivatives, on hapten-induced contact hypersensitivity in BALB/c mice. After application of 2,4-dinitrofluorobenzene (DNFB) to the ears of the mice, severe contact hypersensitivity with marked infiltration of inflammatory cells and hypertrophy of the epidermis was caused. The thickness of the ears increased biphasically and reached a peak 3 and 24 h after the DNFB challenge. Am-80 significantly inhibited ear thickness in the late-(24 h), but not the early-phase (3 h) reaction in a dose-dependent manner. In a histopathological study, obvious depression of edema and infiltration of inflammatory cells was observed in the ears of mice treated with Am-80. Am-80 inhibited the levels of expression in mice ears of interferon-gamma (IFN-gamma) and interleukin-6 (IL-6), but not tumor necrosis factor-alpha (TNF-alpha) or interleukin-4 (IL-4). Furthermore, Am-80 inhibited the antigen-induced production of some cytokines, including IFN-gamma and IL-6, but not IL-4, in vitro. Therefore, Am-80 inhibited hapten-induced contact hypersensitivity through the direct inhibition of inflammatory cytokines such as IFN-gamma and IL-6.

Animals↗

PubMed2000

Novel mutations of the cathepsin K gene in patients with pycnodysostosis and their characterization.

Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, osteosclerosis, acroosteolysis, bone fragility, and skull deformities. Recently, mutations in the gene encoding cathepsin K (CK), a lysosomal cysteine protease localized exclusively in osteoclasts, were found to be responsible for this disease. We analyzed genomic DNA from four unrelated Japanese patients with this disorder and identified three different mutations of their CK genes: a previously reported missense mutation (A277 V), a novel single base deletion mutation (531 del T) causing a frame shift from codon 142 that results in a premature termination codon, and a novel missense mutation (L9P) in the signal peptide region. To investigate whether the L9P mutation disrupts signal peptide function and decreases protein synthesis, mutant and wild-type CK complementary DNAs driven by the cytomegalovirus promoter were transfected into COS-7 cells, and their gene products were detected by immunohistochemistry and Western blotting. Expression of the mutant protein was markedly reduced, suggesting decreased mature CK production in this patient, which may have been due to dysfunction of the signal peptide. These results provide evidence that a structural change in the signal peptide of the CK protein was involved in the pathogenesis of pycnodysostosis.

Adult↗

PubMed2000

Anti-inflammatory effect of FR140423, a novel selective cyclo-oxygenase-2 inhibitor, in rat adjuvant arthritis without gastrointestinal side effects.

We investigated the effect of FR140423 (3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulphinyl)phen yl]pyrazole), a novel and selective cyclo-oxygenase (COX)-2 inhibitor, in rat adjuvant arthritis. The results were compared with that of indomethacin. We tested the inhibitory effects of FR140423 on paw oedema and the formation of the arachidonic acid metabolites prostaglandin (PG) E2 and leukotriene (LT) B4 in inflamed paws immunized with heat-killed and dried Mycobacterium tuberculosis. Oral administration of FR140423 showed a dose-dependent anti-inflammatory effect. This effect was two- to threefold more potent than that of indomethacin. The increase of PGE2 and LTB4 in inflamed paws was associated with the development of paw swelling. FR140423 and indomethacin dose-dependently suppressed the level of PGE2 but not LTB4 in arthritic paws. Unlike indomethacin, FR140423 did not induce gastric lesions even at doses up to 10 mgkg(-1) in arthritic rats. FR140423 has a potent anti-inflammatory effect mediated by inhibition of PGE2 produced by COX-2 in inflamed tissues. The safety profile of FR140423 appears to be an improvement on the safety profile of indomethacin.

Animals↗

PubMed2000

Clinical characteristics of female patients with coronary spastic angina: comparison with male patients.

There are many patients with vasospastic angina who have minor atherosclerosis, and in Japan the majority of them are male. No data exist concerning sex differences in patients with coronary spastic angina, so the present study sought to clarify the clinical characteristics between male and female patients with vasospastic angina. Between April 1991 and June 1998, 204 consecutive patients were diagnosed with vasospastic angina and of these, 26 (12.7%) were female. An acetylcholine test was performed with incremental doses of 20, 50, and 80 microg injected into the right coronary artery and 20, 50, and 100 microg into the left coronary artery. Ergonovine was injected in a total dose of 40 microg into the right coronary artery and 64 microg into the left coronary artery. Coronary spasm was defined as 99% or more luminal narrowing accompanied by ischemic changes on ECG. Compared with male patients, female patients had less organic stenosis (12 vs 33%, p<0.05), less history of smoking (15 vs 85%, p<0.01), and fewer focal spasms (31 vs 64%, p<0.01). There were no other differences between the 2 groups. In conclusion, Japanese female patients with vasospastic angina had the characteristics of diffuse provoked spasm, less organic stenosis, and less history of smoking, but only 1 in 10 of all patients with vasospastic angina are female.

Aged↗

PubMed2000

New combined spasm provocation test in patients with rest angina: intracoronary injection of acetylcholine after intracoronary administration of ergonovine.

The incidence of provoked coronary spasm with the standard single spasm provocation test has been relatively low in patients with rest angina. The present study examined the clinical usefulness of a newly designed spasm provocation test, an intracoronary injection of acetylcholine (ACh) following an ergonovine (ER) test, in patients with rest angina who demonstrated low disease activity and atypical chest pain. Triple sequential spasm provocation tests were performed in 24 patients with atypical chest pain who had no ischemia and in 40 patients with rest angina who had distinct ischemia. Initially, an ACh test (20-100 microg) and then an ER test (40-64 microg) were performed and then, if no spasm was provoked, an intracoronary injection of ACh was given after the ER test to evaluate coronary spasm. Coronary spasm was defined as total or subtotal occlusion. In the 24 patients with atypical chest pain, no spasm was provoked by intracoronary injection of either ACh or ER, but coronary spasms were induced in 2 patients using the new method, with the remaining 22 not experiencing spasm (specificity of new method, 92%). In the 40 patients with rest angina, intracoronary injection of ACh induced coronary spasm in 22 patients (group I) and 6 (group II) demonstrated spasm with intracoronary injection of ER. Coronary spasm was not induced by either the ACh test or the ER test in 12 patients (group III). The intracoronary administration of ACh after the ER test provoked spasm in 11 of 12 patients. Diffuse spasms were provoked in 10 of 11 patients. In patients with rest angina, the frequency of chest pain attacks in 1 month experienced by patients in group III (0.8+/-0.8) was significantly lower than that of patients in group I (7.0+/-5.3, p<0.01) or II (3.5+/-2.3, p<0.05). No serious or irreversible complications related to this new combined method were observed. In conclusion, this method was safe and reliable for the induction of coronary spasm in patients with rest angina who may have low disease activity.

Acetylcholine↗

PubMed2000

Pulmonary edema after cardioversion for paroxysmal atrial flutter: left ventricular diastolic dysfunction induced by direct current shock.

This report describes a patient with the pulmonary edema after cardioversion for paroxysmal atrial flutter without organic heart disease. A 68-year-old man was admitted to hospital for paroxysmal atrial flutter. Antiarrhythmic agents were not effective, and direct current cardioversion was performed on the 4th hospital day. Three hours after cardioversion, the patient complained of dyspnea, and a chest X-ray showed pulmonary edema. He responded to oxygen, intravenous furosemide and drip infusion of nitroglycerine. During tapering of the medication, his condition remained stable. The patient was discharged on the 7th day after admission. Echocardiographic findings indicated that transient left ventricular diastolic dysfunction due to direct current shock was the most likely cause of the lung edema.

Aged↗

PubMed2000

Reconstruction of the lateral ligaments of the ankle using solvent-dried and gamma-irradiated allogeneic fascia lata.

We have described a method of anatomical reconstruction of the lateral ligaments of the ankles with instability using allogeneic fascia lata dried with solvents and sterilised with gamma irradiation. Twenty ankles of 20 patients were assessed objectively and subjectively after a mean follow-up of 4.2 years (3.1 to 10). The result was excellent in 12 (60%), good in seven (35%) and fair in one (5%); none had a poor result. Stress radiography showed that the angle of talar tilt improved from 12.3+/-4.2 degrees (mean +/- SD) to 5.9+/-3.0 degrees and that the anterior drawer distance decreased from 9.2+/-3.9 mm to 4.4+/-2.5 mm. Neither infection nor limitation of movement occurred after operation. Fascia lata allografts provide a good alternative to autogenous grafts such as the peroneus brevis tendon.

Adolescent↗

PubMed2000

Scintigraphic assessment of the rotated femoral head after transtrochanteric rotational osteotomy for osteonecrosis.

BACKGROUND: The purpose of this study was to assess the usefulness of bone scintigraphy in predicting progressive collapse of the femoral head after transtrochanteric rotational osteotomy for the treatment of osteonecrosis of the femoral head. METHODS: We studied thirty-three hips in thirty patients with osteonecrosis of the femoral head who had undergone transtrochanteric rotational osteotomy. There were twenty male and ten female patients, with a mean age of 34.4 years at the time of the operation. The mean duration of follow-up was 10.0 years. According to the staging system of Ficat and Arlet, there were nineteen stage-2 hips and fourteen stage-3 hips at the time of the operation. Conventional anteroposterior and lateral radiographs were assessed. In addition, bone scans were performed at three weeks after the operation to predict the outcome with regard to the rotated femoral head. On the basis of the location of low scan activity within the femoral head, the scintigraphic findings were classified into one of two categories: type A if there was no low scan activity in the weight-bearing area of the femoral head or type B if low scan activity occupied the entire weight-bearing area. Six hips with collapse were studied histologically. RESULTS: Postoperative scintiscans revealed sixteen type-A hips and seventeen type-B hips. Of the type-A hips, only three exhibited progressive collapse of the femoral head after the osteotomy, whereas fourteen of the type-B hips exhibited progressive collapse. A significant association was found between the postoperative scintigraphic findings and the final radiographic result (p < 0.01). CONCLUSIONS: Bone scintiscans made three weeks after transtrochanteric rotational osteotomy were useful for predicting the final clinical result.

Adult↗

PubMed2000

Evaluation of periprosthetic bone-remodeling after cementless total hip arthroplasty. The influence of the extent of porous coating.

BACKGROUND: Total hip arthroplasty changes the levels of stress within the proximal part of the femur, and the femur remodels adjacent to the prosthesis. The stem size and the initial bone-mineral density around the distal portion of the stem affect postoperative bone-remodeling after the insertion of a fully porous-coated metal-cancellous prosthesis. The purpose of this study was to evaluate the influence of the extent of porous coating of this prosthesis on femoral bone-remodeling. METHODS: A longitudinal examination of sixty-one hips in fifty-four patients was performed. Thirty-one hips in twenty-seven patients with a fully porous-coated stem (Group A) and thirty hips in twenty-seven patients with a proximally porous-coated stem (Group B) were followed for twenty-four to thirty months. Periprosthetic bone-mineral density was measured with dual-energy x-ray absorptiometry at specific intervals after the operation. RESULTS: In both groups, the greatest loss of bone-mineral density, compared with the initial (three-week) value, was approximately 20 percent in zone 7 at twelve to eighteen months. In other zones, bone-remodeling appeared to cease by twelve months. At the last follow-up evaluation, the loss of bone-mineral density in the distal and middle regions in Group A was significantly greater than that in Group B (p < 0.01 for zone 3 and p < 0.05 for zone 6). In contrast, with the numbers available, there were no significant differences in loss of bone-mineral density in the proximal regions (zones 1 and 7) between the two groups at any follow-up period. CONCLUSIONS: The extent of porous coating affects bone-remodeling in the distal periprosthetic region rather than in the proximal region. The results in the present report are specific to the particular implants that were studied.

Absorptiometry, Photon↗

PubMed2000

Levels of serum and synovial fluid pyridinium crosslinks in patients with rheumatoid arthritis.

OBJECTIVE: To elucidate the major source of pyridinium crosslinks in rheumatoid arthritis (RA). METHODS: Serum samples were collected from 75 patients with RA and 41 healthy controls, and synovial fluid (SF) samples were collected from 20 patients with RA and 13 with osteoarthritis (OA). Paired samples of serum and SF were collected at the same time from 26 patients with RA. Levels of pyridinium crosslinks were determined by a recently developed high sensitivity assay method using high pressure liquid chromatography. RESULTS: The levels of serum pyridinoline (PYD) and serum deoxypyridinoline (DPD) were significantly higher in patients with RA than in healthy controls, and significantly correlated with laboratory variables indicating disease activity and severity. The levels of SF DPD, but not SF PYD, were significantly higher in patients with RA than in patients with OA. The levels of SF PYD and SF DPD both showed a significantly positive correlation with those of either SF interleukin 1beta or SF interleukin 6 in patients with RA. Finally, the levels of PYD, but not DPD, were higher in SF than in serum in all paired RA samples collected at the same time, with significant correlation between the members of each pair. CONCLUSION: These observations suggest than an increase of PYD in RA serum may originate mostly from affected joints and that an increase of DPD in RA serum may be influenced more by systemic bone resorption.

Adult↗

PubMed2000

Foot deformities in rheumatoid arthritis and relevance of disease severity.

OBJECTIVE: To investigate foot deformities in rheumatoid arthritis (RA) in relation to the disease severity. METHODS: Radiographs of 100 weight bearing feet of 50 patients who had had RA for >10 years (mean 13.5 years) were studied. The patients were classified into 2 study groups according to the severity of disease. We measured hallux valgus angle (HVA), intermetatarsal angle between first and 2nd (M1/2), and intermetatarsal angle between first and 5th (M1/5) on anteroposterior (AP) radiographs, as well as calcaneal pitch (CP) and first metatarsal pitch (MP) on lateral radiographs. The differences in these angles between the 2 groups (Inter-group study) and the correlations among angles within each group (Intra-group study) were examined. RESULTS: Inter-group study showed significant differences between the 2 groups for all variables. Intra-group study, on the other hand, showed no correlation between variables of the 2 deformities, i.e., splaying of forefoot (M1/2 and M1/5) and flattening of longitudinal arch (CP and MP). Only HVA correlated with the splaying (M1/2 and M1/5) in both study groups. CONCLUSION: Disease severity is related to the progression of foot deformities in RA, but the flattening and the splaying are not correlated with each other. We believe that foot deformities should be treated properly and early, especially for patients who are expected to have severe disease.

Adult↗

PubMed2000

Interleukin-1beta induces elevation of spermidine/spermine N1-acetyltransferase activity and an increase in the amount of putrescine in synovial adherent cells from patients with rheumatoid arthritis.

OBJECTIVE: To investigate polyamine metabolism in rheumatoid synovial adherent cells stimulated by interleukin- 1beta (IL-1beta). METHODS: Synovial adherent cells obtained from patients with rheumatoid arthritis (RA) were cultured and incubated in the presence or absence of human recombinant IL-1beta at a concentration of 10 ng/ml for 24 h. The cellular contents of polyamines as well as the activities of spermidine/spermine N1-acetyltransferase (SAT) and ornithine decarboxylase (ODC) were measured. RESULTS: Polyamines in synovial adherent cells decreased significantly after 24 h incubation in the absence of IL-1beta. However, in the presence of IL-Ibeta, putrescine and N'-acetylspermidine increased significantly. No significant difference was observed between the amount of spermidine in synovial adherent cells incubated with and without IL-1beta. Spermine and N8-acetylspermidine in synovial adherent cells incubated with IL-1beta decreased significantly more than in synovial adherent cells incubated without. SAT activity reached a peak 12 h after the addition of IL-1beta and then decreased, while the ODC activity did not increase. SAT activity was elevated by the addition of IL-1beta in a dose dependent manner. CONCLUSION: An increase in the putrescine level in rheumatoid synovial adherent cells as a result of the elevation of SAT activity induced by IL-1beta may play a role in RA.

Acetyltransferases↗

PubMed1999

Induction of multiple microtubule-organizing centers, multipolar spindles and multipolar division in cultured V79 cells exposed to diethylstilbestrol, estradiol-17beta and bisphenol A.

Inducibility of multipolar spindles and multipolar division by diethylstilbestrol (DES) and estradiol-17beta (E2) was investigated in terms of the mechanism of induction of aneuploidy by the estrogens. DES, E2 and bisphenol A (Bp-A), a structural analogue of DES, caused mitotic arrest and aberrant spindles, such as tripolar and multipolar spindles, in a concentration-dependent manner. Gamma-tubulin, a well-characterized component of microtubule-organizing centers (MTOCs), was co-localized with the aberrant spindles induced by estrogens and Bp-A. The number of gamma-tubulin signals in the mitotic cells coincided with that of the aberrant spindles and rose with an increasing concentration of the chemicals. The incidence and location of gamma-tubulin in interphase cells were not influenced by the chemicals. These results suggest that multiple MT nucleating sites were induced by the estrogens and Bp-A during the transition from interphase to the mitotic phase. DES, E2 and Bp-A induced multipolar division in a concentration-dependent process associated with the induction of aneuploidy.

Aneuploidy↗