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Y Shigeyama

Publications and source records attributed to Y Shigeyama.

At least 19 recordsLinked to original sources
PubMed2001

Have the new drugs relieved the burden of the orthopedic surgeon?

Rheumatoid arthritis (RA) represents a chronic joint inflammation that leads to destructive lesions of joint cartilage and periarticular bone. Increased understanding of the molecular and cellular mechanisms of RA and recent advantages in molecular technology have resulted in new antirheumatic drugs such as tumor necrosis factor-alpha blockers, inhibitors of interleukin-1, and novel disease-modifying antirheumatic drugs such as leflunomide. This review summarizes the important effects of the novel antirheumatic drugs and their potential impact on the work of orthopedic surgeons. The ability of these agents not only to improve the clinical signs and symptoms of RA but also to prevent progressive joint damage promises support to the work of orthopedic surgeons and to the interdisciplinary treatment of RA patients. The challenge, however, will be to conduct studies that show the concrete way in which the single drugs may best relieve the burden of the orthopedic surgeon.

Animals↗
PubMed2000

Expression of sentrin, a novel antiapoptotic molecule, at sites of synovial invasion in rheumatoid arthritis.

OBJECTIVE: Sentrin, a novel antiapoptotic molecule, has been shown to interact with the signal-competent form of Fas/APO-1 and tumor necrosis factor receptor I (TNFRI), and thereby, to protect cells against anti-Fas/APO-1- and TNF-induced cell death. Since reduced apoptosis in the synovial lining is supposed to contribute to synovial hyperplasia in rheumatoid arthritis (RA), we searched for the expression of sentrin-1 messenger RNA (mRNA) in synovium from patients with RA. METHODS: The expression of sentrin-1 mRNA was examined by in situ hybridization on snap-frozen sections of normal and RA synovial tissues as well as on paraffin-embedded RA synovial specimens, including the interface of cartilage-bone and invading synovium. Immunohistochemical double labeling after in situ hybridization was performed to further characterize sentrin-1 mRNA-expressing cells. In addition, quantitative analysis of sentrin-1 mRNA expression in RA synovial fibroblasts (RASF), osteoarthritis synovial fibroblasts (OASF), and normal fibroblasts was performed by quantitative real-time polymerase chain reaction. Expression levels were standardized to the expression of GAPDH. The in vivo maintenance of sentrin expression in RASF aggressively invading human cartilage was explored in the SCID mouse model of RA. RESULTS: A marked expression of sentrin-1 mRNA could be seen in all RA synovial specimens, predominantly in SF of the lining layer and at sites of invasion of RA synovium into cartilage. In normal synovial tissues, no sentrin-1 mRNA was detectable. RASF showed a maximum 32.5-fold (mean +/- SD 14.9 +/- 11.6) increase of sentrin-1 mRNA expression compared with normal fibroblasts and a maximum 31.4-fold (mean +/-SD 14.3 +/- 10.9) increase compared with OASF. When coimplanted with normal human cartilage in the SCID mouse model, invading RASF maintained their sentrin-1 mRNA expression for at least 60 days in vivo. CONCLUSION: The marked expression of sentrin in rheumatoid synovial tissue, but not in normal or OA synovial tissue, may contribute to the modulation of Fas- and TNFR-mediated apoptosis in RA synovium, and thereby extend the lifespan of invasive, cartilage-destructive SF.

Animals↗
PubMed2000

Differential expression pattern of membrane-type matrix metalloproteinases in rheumatoid arthritis.

OBJECTIVE: To study the expression of messenger RNA (mRNA) for different membrane-type matrix metalloproteinases (MT-MMPs) and compare their expression pattern in rheumatoid arthritis (RA) and normal synovium. METHODS: Polymerase chain reaction (PCR) with specific primers was performed to analyze the presence of MT1-, MT2-, MT3-, and MT4-MMP in synovial tissue and synovial fibroblasts from 10 patients with RA and 4 subjects without arthritis. In addition, in situ hybridization with digoxigenin-labeled RNA probes was used to investigate the expression pattern of MT-MMPs in the synovium of these subjects. MT-MMP-expressing cells were characterized by immunohistochemical double labeling with anti-CD68 monoclonal antibodies. RESULTS: Reverse transcription-PCR revealed the expression of MT1-, MT2-, MT3-, and MT4-MMP mRNA in all tissues and cell cultures examined. However, in situ hybridization showed considerable differences in the expression pattern of the different MT-MMPs in RA synovium. MT1- and MT3-MMP mRNA were highly expressed in both the lining and the sublining layer, with more intense staining in the lining. Immunohistochemical double labeling demonstrated the presence of mRNA for MT1-MMP in fibroblasts and macrophages, as well as in osteoclast-like cells at sites of bone resorption. Expression of MT3-MMP mRNA was seen in fibroblasts and some macrophages. Expression of MT2- and MT4-MMP was characterized by staining of only a few CD68-negative fibroblasts, and no differences could be found between the lining and sublining. Normal synovial samples showed only limited staining for all MT-MMPs. CONCLUSION: Our results indicate a role for MT1-MMP not only in the matrix degradation by fibroblasts, but also in osteoclast-mediated bone resorption in RA. Given the ability of MT1-MMP to activate MMP-2 and MMP-13, the findings also point to a cooperation between fibroblasts and macrophages in degrading cartilage and bone. While MT3-MMP is also intensely expressed in RA synovium, MT2- and MT4-MMP appear not to be involved in rheumatoid joint destruction.

Arthritis, Rheumatoid↗
PubMed2000

Expression of osteoclast differentiation factor in rheumatoid arthritis.

OBJECTIVE: To analyze the expression pattern of osteoclast differentiation factor (ODF) and its contribution to osteoclastogenesis in rheumatoid arthritis (RA). METHODS: The expression of ODF was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) in RA synovial fibroblasts (RASF) isolated from 7 RA patients and in normal skin fibroblasts. Using RNA probes specific for ODF, in situ hybridization was performed. Immunohistochemical double labeling for CD68 was applied to characterize the ODF-expressing cells. ODF protein and messenger RNA (mRNA) expression by RASF with or without 1,25(OH)2D3 was studied by Western blot analysis and quantitative real-time PCR. In addition, we performed coculture experiments with RASF and normal peripheral blood mononuclear cells with or without 1,25(OH)2D3. RESULTS: By RT-PCR, ODF mRNA expression was found in all RASF investigated, but not in normal skin fibroblasts. In situ hybridization revealed that in RA synovial tissues, ODF mRNA was expressed mainly in the lining layer and at sites where synovium was attached to bone. Immunohistochemical double labeling demonstrated ODF mRNA expression mainly in CD68-fibroblast-like synoviocytes and CD68+ multinucleated osteoclast-like cells. By Western blotting, all RASF expressed ODF protein. However, different levels of ODF expression were found in the RASF from different patients. Interestingly, RASF expressing higher levels of ODF induced a larger number of osteoclast-like cells than did RASF expressing only low levels of ODF. Although 1,25(OH)2D3 did not alter the levels of ODF expression in RASF on either Western blot or quantitative real-time PCR, osteoclastogenesis required the presence of 1,25(OH)2D3. CONCLUSION: The present results suggest that activated RASF, by expressing ODF, play an important role in rheumatoid bone destruction. Moreover, the data provide evidence that RASF not only activate osteoclasts, but also contribute directly to osteoclastogenesis.

Arthritis, Rheumatoid↗
PubMed1998

Expression of type I and XII collagen during development of the periodontal ligament in the mouse.

The purpose (of this study) was to determine the temporal and spatial pattern of type XII collagen expression during murine tooth/root development. Using in situ hybridization techniques, expression of type XII collagen was compared with that of type I collagen, the most abundant collagen in periodontal tissues. Mouse first mandibular molars were examined at the following developmental periods: pre-root formation, early root formation, initial alignment of the periodontal ligament (PDL) fibres, and PDL maturation as the tooth erupted and attained occlusal function. Transcripts for type I collagen were identified in bone cells and odontoblasts at all times but not in the dental follicle before root formation. As root formation progressed, type I collagen expression became apparent within cells of the dental follicle and forming PDL. During early stages of tooth development, signal for type XII collagen was not observed in any cells/tissues. Type XII collagen expression was first detected in the dental follicle/PDL region during tooth eruption and increased in the PDL as the molar tooth erupted into the mouth and achieved occlusal contact. These findings suggest that type XII expression is timed with the alignment and organization of PDL fibres and is limited in tooth development to cells within the periodontal ligament.

Animals↗
PubMed1997

Guyon's canal syndrome. A different clinical presentation caused by an atypical fibrous band.

An atypical case of Guyon's canal syndrome is reported. A 40-year-old woman with hypoaesthesia and claw-finger deformity of the little finger, hypothenar muscle atrophy but no first dorsal interosseous muscle atrophy, underwent release of a fibrous band to decompress the ulnar nerve at the deep branch just proximal to the branch to the abductor digiti minimi muscle. The claw-finger deformity recovered 1 week after surgery.

Adult↗
PubMed1997

Histopathology and clinical results of carpal tunnel syndrome in idiopathic cases and hemodialysis patients.

The results of the histological examinations of specimens of the tenosynovium of the flexor tendon, the epineurium and the transverse carpal ligament from two groups of Japanese patients with carpal tunnel syndrome (idiopathic and hemodialysis) were compared. Amyloid deposits, positively identified as beta 2-microglobulin, appeared in all patients in the long-term hemodialysis group, but in no patients in the idiopathic group. Although the pathogenesis differed between the two groups, both resulted in nerve compression in the carpal tunnel. Therefore, surgical release is considered beneficial for both groups.

Aged↗
PubMed1997

Endoscopic carpal tunnel pressure measurement: a reliable technique for complete release.

Carpal tunnel syndrome is diagnosed by clinical symptoms, Tinel's sign, Phalen's test and electromyography. Carpal tunnel pressure measurement can also aid in the precise identification of excessive pressure sites that indicate locations for release. In this study, pressure measurements made during endoscopic carpal tunnel release at 5 points were significantly higher anywhere in the carpal tunnel than outside the tunnel and decreased markedly after release. We concluded that our measurement technique can improve the reliability of endoscopic carpal tunnel release by decreasing the likelihood of missing any nerve entrapment sites.

Adult↗
PubMed1997

Muscle strength in rheumatoid elbow: quantitative measurement and comparison to Larsen's X-ray grade.

Accurate assessment of elbow function is important to determine the total ability of the arm. The purpose of this study was to clarify the relationship between isometric muscle strength of the elbows of patients with rheumatoid arthritis (RA) and Larsen's X-ray evaluation. Fifty-six elbows of 45 RA patients aged 47 to 77 years (mean age, 63 years) were tested. Muscle strength was measured with an isometric torque-cell dynamometer. Test-retest reliability of the dynamometer was proven by measuring 12 elbows of 6 healthy young men. In RA patients, elbow flexion and extension strength decreased in proportion to increases in the severity of Larsen's grades from Grade 1 to 4. However, Grade 5 elbows had greater muscle strength than those in Grade 4. Forearm pronation and supination strength also decreased in proportion to increases in the severity of Larsen's grades from Grade 1 to 5. This quantitative study made it clear that the muscle strength of RA patients' elbows almost completely correlates to X-ray finding according to the grade of Larsen's evaluation based on X-rays. With regard to muscle strength of postoperative elbows, both flexion strength and supination strength after total elbow replacement (TER) were about two times greater than before TER, and after synovectomy it was as great as those in non-operative RA patients of Grade 2.

Adult↗
PubMed1996

Partial cDNA sequencing of mouse dentine sialoprotein and detection of its specific expression by odontoblasts.

Dentine sialoprotein (DSP), a 53-kDa acidic glycoprotein, is expressed by odontoblasts and secreted into the dentine extracellular matrix. Although little is known about its biological function, it might play a part in dentinogenesis. Because DSP has only been shown to occur in rat dentine, it is important to demonstrate its existence in another species. Here, the presence of DSP gene in the mouse genome, and the cloning of a mouse DSP cDNA coding for about one-fifth of the molecule with a nucleotide sequence similar to that for rat cDNA, are reported. Using in-situ hybridization, DSP mRNA was uniquely detected in mouse odontoblasts.

Animals↗
PubMed1996

Expression of adhesion molecules during tooth resorption in feline teeth: a model system for aggressive osteoclastic activity.

Tooth resorption, a common feline dental problem, is often initiated at the cemento-enamel junction and hence is called cat 'neck' lesion. Studies have demonstrated that osteoclasts/odontoclasts are increased and activated at resorption sites, and that areas of resorption are partly repaired by formation of tissues resembling bone, cementum, and possibly dentin. However, the cellular/molecular mechanisms/factors involved in resorption and repair are unknown. In this study of tissues from cats with 'neck' lesions, we used specific antibodies and immunohistochemical analyses to examine adhesion molecules associated with mineralized tissues, bone sialoprotein (BSP) and osteopontin (OPN), and a cell-surface receptor linked with these molecules, alpha v beta 3, for their localization in these lesions. In addition, to determine general cellular activity during repair, we performed in situ hybridization using a type I collagen riboprobe. Results showed OPN localized to resorption fronts and reversal lines, while BSP was localized to reversal lines. However, some osteoclasts and odontoblasts "sat" on mineralized surfaces not associated with OPN. The cell-surface receptor, alpha v beta 3, was localized to surfaces of osteoclasts/odontoclasts. Type I collagen mRNA was expressed where osteoblasts attempted to repair mineralized tissue. In contrast, odontoblasts did not express mRNA for type I collagen. This study suggests that osteoclastic resorption is the predominant activity in 'neck' lesions and that this activity was accompanied, at least in part, by increased concentrations of OPN and an associated integrin, alpha v beta 3, at resorption sites. Lack of collagen expression by odontoblasts indicates that odontoblasts do not play an active role in attempts at repair.

Animals↗
PubMed1996

Non-traumatic paralysis of the posterior interosseous nerve.

We treated 31 patients with non-traumatic paralysis of the posterior interosseous nerve over 15 years. There were 10 men and 21 women of mean age 40.3 years (17 to 71). Six were managed conservatively, and 25 by operation. In 14 patients entrapment occurred at the supinator, including three who had double compression at both the entrance and exit from the muscle. In four it was caused by a ganglion, in one by a lipoma, in one by a dislocated radial head and in two by a marked constriction in the nerve of unknown cause. The remaining three patients were retrospectively diagnosed as having neuralgic amyotrophy, the only observable change at operation being slight oedema of the nerve. Paralysis recovered in 24 out of the 25 patients at between 2 to 18 months (mean 5.6) after operation, and the one failure was treated later by tendon transfer.

Adolescent↗
PubMed1995

Site-directed mutagenesis of the arginine-glycine-aspartic acid sequence in osteopontin destroys cell adhesion and migration functions.

Osteopontin (OPN) is a secreted calcium-binding phosphoprotein produced in a variety of normal and pathological contexts, including tissue mineralization and cancer. OPN contains a conserved RGD (arg-gly-asp) amino acid sequence that has been implicated in binding of OPN to cell surface integrins. To determine whether the RGD sequence in OPN is required for adhesive and chemotactic functions, we have introduced two site-directed mutations in the RGD site of the mouse OPN cDNA, in which the RGD sequence was either deleted or mutated to RGE (arg-gly-glu). In order to test the effect of these mutations on OPN function, we expressed control and mutated mouse OPN in E. coli as recombinant glutathione-S-transferase (GST)-OPN fusion proteins. Control mouse GST-OPN was functional in cell adhesion assays, supporting attachment and spreading of mouse (malignant PAP2 ras-transformed NIH 3T3, and, to a lesser extent, normal NIH 3T3 fibroblasts) and human (MDA-MB-435 breast cancer, and normal gingival fibroblast) cells. In contrast, neither of the RGD-mutated OPN proteins ("delRGD" or "RGE") supported adhesion of any of the cell lines, even when used at high concentrations or for long assay times. GRGDS (gly-arg-gly-asp-ser) peptides inhibited cell adhesion to intact GST-OPN, as well as to fibronectin and vitronectin. In chemotaxis assays, GST-OPN promoted directed cell migration of both malignant (PAP2, MDA-MB-435) and normal (gingival fibroblast, and NIH 3T3) cells, while RGD-mutated OPN proteins did not. Together these results suggest that the conserved RGD sequence in OPN is required for the majority of the protein's cell attachment and migration-stimulating functions.

3T3 Cells↗
PubMed1995

Commercially-prepared allograft material has biological activity in vitro.

The well-established finding that implantation of demineralized bone matrix at non-skeletal sites results in formation of cartilage and bone has been attributed to bone morphogenetic proteins/factors. Commercially-available demineralized bone allograft materials are being used currently to reconstruct/regenerate bone. The studies described here focused on establishing biological activity of protein extracts prepared from commercially obtained bone graft material in vitro. Furthermore, the biological activity of these protein extracts in vitro was compared with similar extracts prepared from freshly obtained human bone. Biological activities of bone matrix proteins examined included their ability to promote proliferation, attachment, and migration of gingival fibroblasts using an in vitro system. Guanidine followed by guanidine/EDTA was used to separate bone matrix proteins into proteins associated with soft tissues of bone and proteins retained within the mineral compartment, respectively. Two preparations of each starting material were tested and the biological activity of each preparation was evaluated in triplicate at least three times. Slot blot analysis revealed that commercially-prepared material contained type I collagen; fibronectin; BSP; and BMP-2, 4, and 7. However, the freshly prepared bone extracts appeared to have higher BMP concentrations. The ability of commercial extracts to promote cell proliferation, while significant, was limited and significantly less when compared with similar extracts prepared from freshly obtained bone. All extracts promoted cell attachment significantly, while none of the extracts promoted cell migration. Thus, commercially-prepared material retained proteins having the capacity to influence cell behavior in vivo. However, some biological activity as measured in vitro was lost as a result of tissue processing.

Blotting, Western↗
PubMed1993

Chemotactic response of fibroblasts to root surface components in wound healing following flap surgery.

The purpose of this study was two-fold; first to investigate the chemotactic response of periodontal cells to root surface components during wound healing following flap surgery; second, to investigate the chemoattractive effect of the root components on cell migration. Cells were obtained by culturing cells from monkey periodontal tissues and rat calvarial cells. Root surface components were obtained from teeth extracted at 4, 7, 10 and 14 days after flap surgery. The chemotactic response of the isolated cells to root surface components was quantitated by an in vitro assay using a 48 well microchemotaxis chamber. The effect of root components or other growth factors on the cell migration was evaluated using a three-dimensional gel system. Cemental components produced a strong chemotactic response for gingival fibroblasts, alveolar bone cells and rat calvarial cells. Kinetics of the chemotactic potential of cementum was characterized by an initial increase (up to 7 days after surgery), a transient decline (at 10 days after surgery) and a second increase (at 14 days after surgery). Cemental components obtained 7 days after surgery most profoundly facilitated invasion of gingival fibroblasts with comparable effects induced by PDGF and TGF-beta. These results suggest that cemental components influence the chemotactic migration of gingival fibroblasts at the initial stage of wound healing, and therefore, cementum plays an important role in periodontal regeneration.

Alveolar Process↗
PubMed1991

An ultrastructural study comparing new gingival tissue attachment on chemically exposed fibrils and retained periodontal ligament.

Successful periodontal healing has been demonstrated in animals following application of citric acid to exposed root surface. However, we have been unable to achieve comparable results on clinical patients. Accordingly, the present study, using monkeys, was designed to re-evaluate the degree of interdigitation of newly-formed gingival fibrils with ones exposed to citric acid compared to normal attachment tissues of the retained periodontal ligament. We found that superficial collagen fibrils in both cases suffer degradation following normal inflammation and healing secondary to flap surgery. On retained periodontal ligament tissues, this change was limited to superficial levels and newly-formed collagen fibrils were linked immediately with old ones. In contrast, when exposed collagen fibrils were conditioned by exposure to citric acid, the degradative change occurred more deeply, and healing was delayed. Thus, the citric acid may not be the best choice of root treatments in terms of promoting better gingival tissue attachment. Furthermore, the results indicated that fibrils preserved on the root should not be curetted as possible during flap surgery as they offer an improved chance for optimal reattachment.

Animals↗