[Cellular mechanisms of bone resorption in rheumatoid arthritis].
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Animals↗
Biomedical subjects
Y Fujikawa
Publications and source records attributed to Y Fujikawa.
Pathogenicity and vaccine efficacy of a thymidine kinase-deficient mutant of feline herpesvirus type 1 in cats.
We constructed a recombinant feline herpesvirus type 1 (FHV-1) which was deleted in a defined region (450 bp) within the thymidine kinase (TK) gene (C7301dlTK) [Yokoyama et al. (1995) J Vet Med Sci 57: 709-714]. In this report, we carried out two experiments to assess the pathogenicity and vaccine efficacy of the recombinant C7301dlTK in cats. The first experiment showed that, following multiple inoculation of the recombinant C7301dlTK by intraocular, intranasal and oral routes, the virus was sufficiently attenuated in cats, although a high titer of the virus was recovered from target organs (eye, nose, and mouth). In the second experiment, two intramuscular vaccinations with the recombinant C7301dlTK protected cats to a significant degree against subsequent challenge with the parent FHV-1 strain C7301 at 4 weeks after the last vaccination. These results demonstrate that the recombinant C7301dlTK is effective as a live attenuated vaccine with a clear genetic marker.
Alphaherpesvirinae↗
Human monoclonal rheumatoid factors augment arthritis in mice by the activation of T cells.
In order to investigate the in vivo role of rheumatoid factor (RF), the effects of the administration of human monoclonal (m) IgM-RF and IgG-RF on the development of arthritis in mice were examined. The administration of human mRFs into mice immunized with type II collagen (CII) markedly enhanced the clinical score and paw swelling. The severity of arthritic joint disease with a marked infiltration of lymphoid cells, proliferation of synovial membrane, pannus formation and destruction of articular cartilage was significantly enhanced in both groups receiving RF (RF-enhanced arthritis). Skin ulcers were also observed in some of these RF-enhanced arthritis mice, whereas no such signs were observed in CII-immunized mice without mRFs. Both IgM-RF and IgG-RF increased CII-specific IgG antibodies in circulation, and the severity of arthritis correlated with the production of high titres of anti-CII antibodies. In vivo treatment of RF-enhanced arthritis mice with an anti-CD4 MoAb or an anti-CD8 MoAb inhibited the induction and progression of arthritis in these mice. Administration of RF to severe combined immunodeficient (SCID) mice with arthritis developed by the transfer of spleen cells from CII-immunized mice, prolonged the arthritis and enhanced the severity. This murine model of RF-enhanced arthritis may provide a useful tool for analysing the pathogenesis of rheumatoid arthritis in RF-positive patients.
Adoptive Transfer↗
Bone resorption by tartrate-resistant acid phosphatase-positive multinuclear cells isolated from rheumatoid synovium.
Inflammatory reactions in rheumatoid arthritis (RA) often cause severe joint destruction. However, the mechanism of bone destruction is still a matter of controversy. To determine whether multinuclear cells found in the rheumatoid synovium can resorb bone, isolated synovial cells were assessed for tartrate-resistant acid phosphatase (TRAP) staining and the ability to resorb bone in a dentine resorption assay. TRAP-positive multinuclear cells were found in six out of 10 samples. These six samples showed resorption pit formation on dentine slices. The other four samples did not form resorption pits. The results of this study demonstrate that TRAP-positive multinuclear cells isolated from the rheumatoid synovium form resorption pits on dentine slices. Our results suggest that inflamed synovial cells in rheumatoid joints might participate in bone destruction.
Acid Phosphatase↗
Human osteoclast formation and bone resorption by monocytes and synovial macrophages in rheumatoid arthritis.
OBJECTIVE: To determine whether synovial macrophages and monocytes isolated from patients with rheumatoid arthritis patients are capable of differentiating into osteoclastic bone resorbing cells; and the cellular and humoral conditions required for this to occur. METHODS: Macrophages isolated from the synovium and monocytes from the peripheral blood of rheumatoid arthritis patients were cultured on bone slices and coverslips, in the presence and absence of UMR 106 rat osteoblast-like cells, 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) and macrophage colony stimulating factor (M-CSF), and assessed for cytochemical and functional evidence of osteoclast differentiation. RESULTS: Isolated calcitonin receptor (CTR), tartrate resistant acid phosphatase (TRAP), and vitronectin receptor (VNR) negative, CD11b and CD14 positive monocytes and macrophages differentiated into CTR, TRAP, and VNR positive multinucleated cells capable of extensive lacunar bone resorption when co-cultured for 14 d with UMR 106 cells in the presence 1,25(OH)2D3 and M-CSF. CONCLUSIONS: Mononuclear phagocytes (monocytes and macrophages) from rheumatoid arthritis patients are capable of differentiating into multinucleated cells showing all the cytochemical and functional criteria of mature osteoclasts. Synovial macrophage-osteoclast differentiation may represent an important cellular mechanism in the bone destruction associated with rheumatoid arthritis.
Aged↗
The human osteoclast precursor circulates in the monocyte fraction.
The osteoclast is known to be formed by fusion of circulating mononuclear precursor cells of haematopoietic origin. The precise nature of these circulating cells and, in particular, their relation to monocytes is unknown. We have developed an in vitro system of human osteoclast formation whereby human monocytes [CD14, CD11a, CD11b and HLA-DR positive, and tartrate-resistant acid phosphatase (TRAP), calcitonin receptor (CTR), vitronectin receptor (VNR) negative] were isolated and cocultured for up to 21 days with UMR106 rat osteoblast-like cells or ST2 mouse preadipocytic bone marrow stromal cells in the presence of 1 alpha, 25 dihydroxyvitamin D3 (1,25(OH)2D3) and macrophage colony stimulating factor (M-CSF). Numerous TRAP, VNR and CTR positive multinucleated cells, capable of extensive lacunar bone resorption, formed in these cocultures; the absolute requirements for this to occur were contact with the above bone stromal cells, 1,25(OH)2D3, and M-CSF. These results show that the human mononuclear osteoclast precursor circulates in the monocyte fraction and exhibits a monocyte phenotype, acquiring osteoclast phenotypic features in the process of differentiation into mature functional osteoclasts.
Acid Phosphatase↗
Increased osteoclastic differentiation by PMMA particle-associated macrophages. Inhibitory effect by interleukin 4 and leukemia inhibitory factor.
To determine the influence of polymethylmethacrylate (PMMA) wear particles on macrophage-osteoclast differentiation, PMMA particles were added to mouse monocytes which were cocultured with UMR 106 osteoblast-like cells in the presence of 1,25 dihydroxy vitamin D3[1,25(OH)2D3] for up to 7 days on glass coverslips and for up to 14 days on human cortical bone slices. An increase in osteoclast differentiation, as evidenced by the expression of the osteoclast-associated enzyme tartrate-resistant acid phosphatase (TRAP) and the extent of lacunar bone resorption, was observed in monocyte cultures to which PMMA had been added. Interleukin 4 (IL-4) and Leukemia Inhibitory Factor (LIF) added to these cocultures caused considerably less expression of TRAP and significant inhibition of lacunar bone resorption. This inhibitory effect was reversed by the addition of specific neutralizing antibodies to LIF and IL-4. These findings show that PMMA-wear particle-associated macrophages exhibit an enhanced capacity for differentiation to osteoclastic bone-resorbing cells.
Acid Phosphatase↗
Grafted bone used in acetabular reconstruction: assessment by SPECT scintigraphy.
OBJECTIVE: To investigate incorporation of the grafted bone used for acetabular reconstruction. DESIGN: Single photon emission computed tomography (SPECT) was carried out at the 1st, 6th, and 12th month after the operation and the uptakes on serial SPECT scintigrams were normalized. The horizontal histogram of scintigraphic activity at the level of the central grafted bone in the coronal image was designated the profile curve. PATIENTS: Seven patients who had undergone bipolar hip arthroplasty for osteoarthritis of the hip were randomly selected. RESULTS AND CONCLUSION: Five of seven profile curves obtained at the 1st month demonstrated a single peak at the host-graft junction. The profile curve obtained at the 6th month showed two peaks at the host-graft junction and the periphery of the grafted bone in all patients. The profile curve at the 12th month showed slightly increased activity in the center of the grafted bone. This preliminary study demonstrates that comparison of the serial profile curves on SPECT is valuable in evaluating the progress of incorporation of the grafted bone in hip arthroplasty.
Acetabulum↗
Increased IL-1 receptor antagonist (IL-1ra) production and decreased IL-1 beta/IL-1ra ratio in mononuclear cells from rheumatoid arthritis patients.
In order to investigate the possible role of IL-1 receptor antagonist (IL-1ra) in patients with rheumatoid arthritis (RA), this study was undertaken to measure the amounts of IL-1ra and interleukin-1 beta (IL-1 beta) protein produced by mononuclear cells (MNC) and to investigate the relationship between production of these cytokines and clinical parameters. The MNC were cultured for 24 h and the supernatants were measured for IL-1ra and IL-1 beta by ELISA kits. MNC from peripheral blood (PB) and synovial fluid of RA patients produced significantly higher amounts of IL-1ra than normal PBMNC (P < 0.01 and P < 0.05, respectively). When the IL-1 beta/IL-1ra ratio was calculated, IL-1 beta/IL-1ra ratios of RA PBMNC were significantly lower than those of normal PBMNC (P < 0.001). The IL-1 beta/IL-1ra ratio of RA PBMNC was significantly higher in active RA patients than in RA patients in remission (P < 0.02). The amounts of IL-1ra produced by stimulated RA PBMNC positively correlated with the joint score (P < 0.05), serum CRP levels (P < 0.05) and the amounts of IL-1 beta produced (P < 0.01). The amounts of IL-1ra produced by unstimulated RA PBMNC did not correlate with any of the clinical parameters studied. Gold sodium thiomalate (GST), but not auranofin, increased IL-1ra production in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Interleukin-1 receptor antagonist production in cultured synovial cells from patients with rheumatoid arthritis and osteoarthritis.
OBJECTIVE: To measure the amounts of interleukin-1 receptor antagonist (IL-1ra) protein produced by cultured synovial cells obtained from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial cells obtained from patients with either RA or OA were cultured and the supernatants were measured for IL-1ra by enzyme linked immunosorbent assay. RESULTS: The synovial cells obtained from patients with RA produced significantly smaller amounts of IL-1ra than did those obtained from patients with OA, in a late passage (third to fifth) without stimulation and a first passage both with and without stimulation (p < 0.025, respectively). In addition, when the patients with RA were divided into two groups according to the maximum number of lining cell layers, the amounts of IL-1ra produced by the proliferative type were smaller than those produced by the less proliferative type (p < 0.025). CONCLUSIONS: The above findings suggest that IL-1ra production in RA synovial cells is suppressed, and that reduced IL-1ra protein production is one of the causes which leads to the proliferation of lining cells and persistent joint inflammation.
Arthritis, Rheumatoid↗
Bipolar hip arthroplasty without acetabular bone-grafting for dysplastic osteoarthritis. Results after 6-9 years.
The authors report the clinical and radiographic results of 36 bipolar hip arthroplasties after performing excavation of the steep and shallow acetabulum without acetabular bone-grafting for dysplastic osteoarthritis. The procedures were carried out between 1981 and 1985. Survivorship analysis showed that 84.6 of the bipolar hip arthroplasties were retained for 8 years. Twenty-nine patients, which were followed for 6-9 years after surgery, were reviewed. Severity of acetabular dysplasia was classified according to the method of Crowe. Class 1 included 17 hips and class 2 included 12 hips. The average preoperative clinical score was 49 points. The average postoperative clinical hip score improved to 87 points after 6 years. Twenty-seven of the 29 hips assessed were classified as either excellent or good by Charnley's function score. Stress fracture, due to excessive acetabular excavation at the time of surgery, and femoral component loosening were major symptomatic complications. The cessation of radiographic evidence of migration of the bipolar socket was recognized in 25 of 29 procedures at 6 years after surgery (86.2%). Cineradiographic study demonstrated that the abduction motion under standing position for 20 of 24 hip joints functioned dominantly at the inner-bearing and metallic-stem interface.
Acetabulum↗
[Stromelysin-1 (MMP-3) level in the sera from patients with rheumatoid arthritis and other connective tissue diseases--clinical significances in early onset rheumatoid arthritis].
Stromelysin-1 (MMP-3) is a metalloproteinase that degrades articular cartilage matrix in patients with rheumatoid arthritis (RA). We measured MMP-3 in the sera from patients with RA and other connective tissue diseases using specific sandwich EIA and studied its clinical significance in early onset RA. MMP-3 level in healthy control (n = 170) was significantly higher in male than in female. The level of MMP-3 in RA was significantly and dramatically higher than in healthy control, osteoarthritis, systemic lupus erythematosus, progressive systemic sclerosis, primary sjogren's syndrome, mixed connective tissue disease, gouty arthritis and traumatic arthritis. Serum MMP-3 significantly correlated with serum BUN or serum creatinine levels in SLE patients but not in RA patients. In early onset RA, serum MMP-3 level was significantly elevated. Furthermore, when the relationship between the serum MMP-3 level and X-ray findings of the joints in RA was studied, it was found that MMP-3 level was elevated even in stage I or II and that there was no statistical differences between stage I or II and stage III or IV, suggesting that serum MMP-3 level is elevated in the early stage of initial inflammatory process when only mild cartilage degradation is seen. These results suggest that measurements of serum MMP-3 is an important tool for establishing diagnosis of early onset RA, and that serum MMP-3 level may be a marker of cartilage destruction and of estimating therapeutic efficacy in early onset RA.
Aged↗
Effect of oxytocin and indomethacin on the estrous cycle of goats.
The effect of oxytocin and indomethacin on luteal function during the estrous cycle in goats was investigated. Daily subcutaneous administration of oxytocin given on days 12-15 of the estrous cycle had no effect on length of the cycle or concentrations of progesterone and estradiol-17 beta. Oxytocin given on days 3-6 shortened the cycle and decreased concentrations of progesterone, but increased the estradiol-17 beta to levels similar to seen at estrus. These changes caused by oxytocin were prevented by indomethacin, a prostaglandin synthetase inhibitor, although indomethacin given alone did not affect luteal function. These results suggest that luteal function affected by prostaglandin in the early luteal phase of goats may be different from that in cattle.
Animals↗
Differential inhibition of T and B cell responses to individual antigenic determinants in orally tolerized mice.
Immunological tolerance of systemic immunity can be induced by the oral administration of an exogenous antigen, which is termed oral tolerance. We examined whether there was a difference in the degree of tolerance between individual antigenic determinants in oral tolerance. Feeding bovine alpha s1-casein, a major protein in cow's milk, as a constituent of the diet induces oral tolerance in mice. However, a weak antibody response can be elicited in the alpha s1-casein-fed animals by subsequent immunization with the antigen. We examined the fine specificity of such anti-alpha s1-casein antibodies produced in alpha s1-casein-fed mice. The results demonstrated that there was a difference in the inhibition of antibody response between different B cell determinants. Differential inhibition could also be observed for T cell responses. T cells specific for dominant determinants were preferentially tolerized, while those for cryptic determinants escaped oral tolerance. Our results imply the importance of antigen presentation for this differential inhibition of antigenic determinants. We suggest that orally administered antigen does not induce tolerance to some of the B and T lymphocyte repertoire which could potentially induce harmful food hypersensitivity.
Administration, Oral↗
Association of HLA-DR and HLA-DQ antigens with congenital dislocation and dysplastic osteoarthritis of the hip joints in Japanese people.
OBJECTIVE: To investigate the frequency of HLA-DR and DQ antigens among patients with congenital dislocation of the hip joint or dysplastic osteoarthritis (OA) and to determine whether tissue typing might contribute to better understanding of these disorders. METHODS: HLA-DR and DQ typing was undertaken in 18 patients with congenital dislocation of the hip joints, 65 patients with dysplastic OA of the hip, 42 patients with primary OA of the knee, and 40 normal controls. Typing for HLA-D antigens was performed using the standard microlymphocytotoxicity method. RESULTS: The frequency of HLA-DR4 in patients with congenital dislocation of the hip joint (61.1%) and patients with dysplastic OA of the hip (58.5%) was significantly increased compared with normal controls (27.5%) (Pcorr < 0.05 and P < 0.01, respectively). The relative risk for HLA-DR4 was 4.1428 and 3.7104, respectively, in these 2 disease groups. The frequency of HLA-DR4 in the patients with primary OA of the knee (35.7%) did not differ significantly from that in normal controls. CONCLUSION: The results strongly indicate that development of congenital dislocation of the hip joint and progression of dysplastic OA of the hip are associated with genes of the HLA-D region.
Aged↗
Estimation of xyloglucan in vegetables by enzyme-linked immunosorbent assay.
We prepared the antibody specific against plant xyloglucan and applied it to enzyme-linked immunosorbent assay in order to estimate xyloglucan contents in several vegetables. In this experiment, xyloglucan was detected in the 24% aqueous potassium hydroxide-soluble fractions of tomato, cabbage, lettuce, and eggplant. The xyloglucan contents of these vegetables were estimated to be 1.4 mg, 54 micrograms, 14 micrograms, and 4 micrograms per one hundred grams of their edible portions, respectively, using tamarind xyloglucan as a standard xyloglucan.
Chemical Fractionation↗
Nootropic candidates inhibit head-twitches induced by mescaline in mice.
The effects of various nootropic candidates on mescaline-induced head-twitches were studied in mice. The number of head-twitches induced by mescaline (100 mg/kg, s.c.) was significantly reduced by idebenone (32 and 100 mg/kg, i.p.), minaprine (0.32-10 mg/kg, p.o.) and nebracetam (100 mg/kg, p.o.). Cholinesterase inhibitors such as tetrahydroaminoacridine (1 and 10 mg/kg, p.o.), NIK-247 (10 and 18 mg/kg, p.o.) and physostigmine (0.32 mg/kg, i.p.) also suppressed the head-twitch response to mescaline. These results suggest that the direct or indirect cholinergic-activating effects of these drugs may be involved in inhibiting mescaline-induced head-twitches.
Animals↗
Reversal of MRI lesion with relapse and remission of partial motor seizures in epilepsia partialis continua.
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Adolescent↗