Faculty Profiles - NISHIDA Keiichiro

Papers - NISHIDA Keiichiro

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Carpal tunnel syndrome grading system in rheumatoid arthritis

Junko Shinoda, Hiroyuki Hashizume, Cherie McCown, Masuo Senda, Keiichiro Nishida, Takeshi Doi, Hajime Inoue

Journal of Orthopaedic Science 7 ( 2 ) 188 - 193 2002

Language：English Publishing type：Research paper (scientific journal)

The grading system of Hashizume and Hirooka for carpal tunnel syndrome (CTS) was modified to refine the system for surgical treatment selection for specific subsets of CTS in patients with rheumatoid arthritis (RA). The grading system uses clinical signs and symptoms of CTS, including pain indications, to identify surgical subsets of patients to facilitate treatment selection. Retrospective analysis of the system included radiographic and electromyographic findings. Twenty-nine hands of 21 adult patients with CTS in RA were graded in the current study. Eight hands with mild synovitis received conservative treatment only. Endoscopic carpal tunnel release (ECTR), using Okutsu's universal subcutaneous endoscopic system with a clear cannula, was performed in 11 hands with moderate synovitis. Open carpal tunnel release (OCTR) combined with flexor tenosynovectomy was performed in 9 hands with severe synovitis. One more hand required OCTR after ECTR when malignant RA was diagnosed. Clinical results, evaluated using Kelly's criteria, were: excellent in 19 hands, good in 5, fair in 4, and poor in the 1 patient with malignant RA. Clinical symptoms of CTS improved in all but the latter patient. Although the sample size in the current study is small, the results appear to warrant further study to determine the clinical utility of the grading system.

DOI： 10.1007/s007760200032

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Evidence of oncotic cell death and DNA fragmentation in human hypertropic chondrocytes in chondro-osteophyte

Doi, T., Nishida, K., Matsuo, M., Yoshida, A., Murakami, T., Inoue, H.

Osteoarthritis and Cartilage 10 ( 4 ) 2002

Expression of caspase-3 and-9 relevant to cartilage destruction and chondrocyte apoptosis in human osteoarthritic cartilage

M Matsuo, K Nishida, A Yoshida, T Murakami, H Inoue

ACTA MEDICA OKAYAMA 55 ( 6 ) 333 - 340 2001.12

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

To clarify the involvement of the caspase family in the pathway of NO-induced chondrocyte apoptosis, osteoarthritis (OA) cartilage obtained from 8 patients undergoing total hip arthroplasty were used for histopathological study. Cartilage samples taken from non-fibrillated areas of femoral head resected during surgery for femoral neck fracture were used for comparison. DNA fragmentation of chondrocytes was detected by the nick end-labeling (TUNEL) method. Apoptosis was further confirmed by transmission electron microscopy. The distributions of nitrotyrosine (NT), caspase-3, and -9 were examined immunohistochemically. The populations of apoptotic as wen as NT-, caspase-3-, and -9-positive cells were quantified by counting the number of cells in the superficial, middle, and deep layers, respectively. The TUNEL-positive cells were observed primarily in superficial proliferating chondrocytes, clustering chondrocytes, and deep-layer chondrocytes of OA cartilage. Few positive cells were seen in the proliferating chondrocytes in the middle layer. Positive reactions for caspase-3 and -9 were observed in chondrocytes in similar areas. Histological OA grade showed significant correlations with the mean populations of apoptotic chondrocytes (% apoptosis) over the 3 areas. The populations of NT-positive cells (% NT) over the same areas also showed significant correlation with OA grade. Positivity for caspase-3 closely correlated with the OA grade, % apoptosis and %NT. It was concluded that caspase-3 and -9 could play a role in NO-induced chondrocyte apoptosis in OA cartilage.

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Involvement of nitric oxide in chondrocyte cell death in chondro-osteophyte formation

K Nishida, T Doi, M Matsuo, Y Ishiwari, H Tsujigiwa, A Yoshida, M Shibahara, H Inoue

OSTEOARTHRITIS AND CARTILAGE 9 ( 3 ) 232 - 237 2001.4

Language：English Publishing type：Research paper (scientific journal) Publisher：W B SAUNDERS CO LTD

Objective: To examine the nitric oxide (NO) production relevant to chondrocyte cell death in order to elucidate the mechanism of chondro-osteophyte formation in osteoarthrotic joints.
Design: Human chondra-osteophytes were obtained during total hip arthroplasty. Expression of inducible nitric oxide synthase (iNOS) mRNA was determined by in-situ hybridization. Localization of iNOS and nitrotyrosine at protein level were examined by immunohistochemistry. Cell death of chondrocytes were confirmed by both TUNEL method and transmission electron microscopy.
Results: The various populations of proliferative and hypertrophic chondrocytes expressed iNOS mRNA and iNOS as well as nitrotyrosine protein. Approximately 30% at hypertrophic chondrocytes forming chondro-osteophyte showed positive reaction to TUNEL staining. Electron microscopy confirmed both disintegrated and apoptotic chondrocytes in these zones. In the deep hypertrophic zone calcification was seen around each of the matrix vesicles and some masses of cell debris.
Conclusion: Chondro-osteophyte formation involves NO production by chondrocytes. The expression and localization of iNOS and nitrotyrosine in chondro-osteophytes suggest the significant role of NO in chondrocyte hypertrophy and apoptosis. (C) 2001 OsteoArthritis Research Society international.

DOI： 10.1053/joca.2000.0380

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Reconstruction using clavicle afre resection of arcoma of the proximal humerus.

Ozaki T, Hashizume H, Nishida K, Kawai A, Inoue H

Clin Orthop 2001

Reconstruction of the proximal humerus with the clavicle after tumor resection: A case report

Ozaki, T., Hashizume, H., Kunisada, T., Kawai, A., Nishida, K., Sugihara, S., Inoue, H.

Clinical Orthopaedics and Related Research ( 385 ) 2001

Expression of connective tissue growth factor in cartilaginous tumors

Toshihiko Shakunaga, Toshifumi Ozaki, Nobuya Ohara, Koji Asaumi, Takeshi Doi, Keiichiro Nishida, Akira Kawai, Tohru Nakanishi, Masaharu Takigawa, Hajime Inoue

Cancer 89 ( 7 ) 1466 - 1473 2000.10

Language：English Publishing type：Research paper (international conference proceedings) Publisher：FREUND PUBL HOUSE LTD

BACKGROUND. Connective tissue growth factor (CTGF) predominantly is expressed in hypertrophic chondrocytes and its specific receptors are demonstrated on chondrocytic cells. Therefore, CTGF may be involved in the proliferation and/or differentiation of cartilage cells. In the current study, CTGF expression was examined both in chondrosarcoma and enchondroma to clarify the relation between the expression of CTGF and the grade of malignancy. METHODS. The expression of CTGF and proliferating cell nuclear antigen (PCNA) were analyzed immunohistochemically in 34 cartilaginous tumor specimens. Eighteen tumors were determined to be chondrosarcoma including 8 Grade 1 tumors, 6 Grade 2 tumors, and 4 Grade 3 tumors. The percentage of CTGF positive and PCNA positive cells was quantified using at least 500 cells. RESULTS. CTGF was expressed in 70.1% of enchondroma cells, 84.0% of Grade 1 chondrosarcoma cells, 53.7% of Grade 2 tumor cells, and 26.8% of Grade 3 tumor cells (ρ = -0.501
P = 0.0053). In chondrosarcoma cases, CTGF expression was correlated closely with tumor grade (ρ = -0.920
P = 0.0001). There was a strong correlation between PCNA expression and tumor grade (ρ = 0.907
P &lt
0.0001) and a strong negative correlation between CTGF and PCNA expression (ρ = -0.493
P = 0.0061). In chondrosarcoma cases, patients with high expression of CTGF (≥ 30%) showed higher overall survival compared with those with low expression (&lt
30%) (P = 0.004). CONCLUSIONS. The current study revealed a correlation between the histologic grade of chondrosarcoma and prognosis, and the concomitant association between CTGF immunostaining and tumor grade and prognosis. Therefore, immunohistochemical staining with CTGF is a useful procedure for assessing the tumor grade anti clinical course in patients with chondrosarcoma. (C) 2000 American Cancer Society.

DOI： 10.1002/1097-0142(20001001)89:7<1466::AID-CNCR8>3.0.CO;2-G

CD44 expression in soft tissue sarcomas

N Kahara, T Ozaki, T Doi, K Nishida, A Kawai, M Shibahara, H Inoue

VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY 436 ( 6 ) 574 - 578 2000.6

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER VERLAG

Recent studies have shown that expression of alternatively splicing variants of CD44 is correlated with prognosis for several kinds of malignant tumors. However, little is known about the expression of CD44 standard and variant isoforms in soft tissue sarcomas. In this study 47 cases of soft tissue sarcoma [18 malignant fibrous histiocytomas (MFHs), 13 synovial sarcomas (SSs), 7 malignant schwannomas (MSs), and 9 liposarcomas (LSs)] were examined immunohistochemically. The monoclonal antibodies to the standard form of CD44 (CD44H) and variant exons of CD44v3, 4, 5, 6, 7, 9, and v10 were used. We analyzed the membranous expression pattern of CD44H and CD44 variant exons and assessed the relation between expression of CD44s and metastasis-free survival rates (MFSR) of patients with soft tissue sarcoma. A few sarcomas expressed CD44v3 (2/47) and v7 (2/47), but none of the sarcomas expressed CD44v10. CD44v4 (5/47), v5 (4/47), v6 (10/47), and v9 (9/47) are relatively common types of variant isoforms in soft tissue sarcomas. Expression of CD44v6 is more frequently detected in high-grade than in low-grade tumors. CD44v6 or CD44v9 expression was correlated with metastasis-free survival of patients with soft tissue sarcomas.

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Increased osteocyte apoptosis during the development of femoral head osteonecrosis in spontaneously hypertensive rats

M Shibahara, K Nishida, H Asahara, T Yoshikawa, S Mitani, Y Kondo, H Inoue

ACTA MEDICA OKAYAMA 54 ( 2 ) 67 - 74 2000.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

We investigated the presence of osteocyte apoptosis in the necrotic trabeculae of the femoral head of spontaneously hypertensive rat (SHR) using the in situ nick end labeling (TUNEL) method and transmission electron microscopy. The occurrence of osteonecrosis and ossification disturbance was significantly higher in SHR compared with Wistar Kyoto (WKY) rats, and Wistar (WT) rats used as control animals (P < 0.01). A high population of TUNEL positive osteocytes was detected mainly in 10- and 15-week-old SHRs. Sectioned examination of the femoral head of SHRs and WKY rats by electron microscopy revealed apoptotic cell appearances such as aggregation of chromatin particles and lipid formation. In contrast, a positive reaction was significantly lower in osteocytes in the femoral heads of WT rats (P < 0.01). Our results indicate that apoptosis forms an important component of the global pathologic process affecting the femoral head of SHR, which leads to osteonecrosis in this region.

DOI： 10.18926/AMO/32287

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The role of nitric oxide in arthritic joints: A therapeutic target?

K. Nishida, T. Doi, H. Inoue

Modern Rheumatology 10 ( 2 ) 63 - 67 2000.1

Language：English

Nitric oxide (NO) is produced by many cell types in the joint, and its expression is delicately regulated. Depending on its concentration and cellular origin, NO appears to have both pro- and anti-inflammatory potential in the joint. Constitutively expressed nitric oxide synthase (NOS) produces small amounts of NO, which is essential for normal physiological homeostasis. However, inflammatory stimuli such as endotoxins, cytokines, and growth factors promote inducible NOS (iNOS) expression, initially as an anti-inflammatory response, and catalyse a high output of NO. Excessive NO can amplify inflammatory pathways and contribute to the development and maintenance of arthritis. Consequently, proper regulation of NO synthesis can lead to a novel therapeutic approach for inflammatory joint diseases. Further careful study will be necessary to develop new drugs to regulate the NO pathway and to determine the dosage, timing of administration, and duration of treatment in order to avoid both undesirable immunostimulatory effects and immunosuppressive effects. © 2000, The Japan Rheumatism Association and Springer-Verlag Tokyo. All rights reserved.

DOI： 10.3109/s101650050001

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Simultaneous fracture-dislocations of the distal and proximal interphalangeal joints

K Nakago, H Hashizume, M Senda, K Nishida, S Masaoka, H Inoue

JOURNAL OF HAND SURGERY-BRITISH AND EUROPEAN VOLUME 24B ( 6 ) 699 - 702 1999.12

Language：English Publishing type：Research paper (scientific journal) Publisher：CHURCHILL LIVINGSTONE

Sixteen cases of simultaneous fracture-dislocations of both the distal interphalangeal (DIP) and proximal interphalangeal (PIP) joints in the same finger that were treated during the past 10 years were classified into three types: the swan-neck injury (dorsal fragment of the base of the distal phalanx at the DIP joint and palmar fragment of the base of the middle phalanx at the PIP joint); the double-hyperextension injury (palmar fragments at the DIP and PIP joints); and the straight-finger injury (with dorsal and palmar bone fragments at the DIP joint). The results of treatment were more satisfactory in PIP joints than in DIP joints.

DOI： 10.1054/jhsb.1999.0228

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Ultrasonographic analysis of shoulder rotator cuff tears

S Masaoka, H Hashizume, M Senda, K Nishida, M Nagoshi, H Inoue

ACTA MEDICA OKAYAMA 53 ( 2 ) 81 - 89 1999.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

Seventy-nine shoulders suspected of rotator cuff tears were examined by ultrasonography (US) and forty-three received surgery. Long and short axis scans were performed and findings of each were separately classified according to a five-grade system, and the results were correlated with the actual extent of tear observed during surgery. Internal echogenicity and subacromial impingement were analyzed before and after surgery. A accuracy of US in detecting rotator cuff tears was analyzed. In addition, the correlation between cuff shape observed by US before surgery and actual shape observed during surgery was assessed. It was noted that cuff thinning and abnormalities in shape did not recover to normal after surgery. However, in the cases of discontinuities observed by US before surgery, US findings indicated that the torn cuff was anchored to the greater tuberosity and functional during active motion. Although post-operative US findings were not normal, clinical results were good in most cases. Sensitivity of US for detecting rotator cuff tear was 100% and specificity 94%. US is non-invasive, cost effective and allows the physician to examine the joint while it is in motion. Therefore, at this time, we use US as a screening method for detecting rotator cuff tears. Furthermore, US allows us to check for re-tears while the joint is in motion, which is essential for accurate diagnosis.

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Expression of CD44 variants in osteosarcoma

M. Kuryu, T. Ozaki, K. Nishida, M. Shibahara, A. Kawai, H. Inoue

Journal of Cancer Research and Clinical Oncology 125 ( 11 ) 646 - 652 1999

Language：English Publishing type：Research paper (scientific journal)

The standard form of CD44 (CD44H) is a transmembranous glycoprotein, widely distributed on a variety of human lymphoid cells, epithelial cells and tumours. CD44 has many variant forms, which are generated by alternative splicing. In recent years, CD44 has been reported to be related to the degree of tumour differentiation, tumour cell invasion, and metastasis. We investigated 44 tumour specimens in 39 patients with osteosarcoma immunochemically to analyze the expression of CD44 standard (CD44H) and variant exon-encoded gene products (CD44v3, v4, v5, v6, v7, v9, and v10). Furthermore, the relationship between CD44 expression and the clinical outcome of patients with osteosarcoma was analyzed. Membrane accentuation and exclusive cytoplasmic reactivity were analyzed as separate staining patterns. Tumour cells and some multinucleated giant cells were markedly stained. CD44H, v3, v4, v5, v6, v7, v9, and v10 were expressed in 85%, 49%, 54%, 59%, 46%, 5%, 28%, and 10% of the specimens respectively. The cumulative 5-year metastasis-free survival was 58% in CD44v6-negative cases and 24% in CD44v6-positive cases (P = 0.046). However, the cumulative 5-year metastasis-free survival was not significantly different between cases positive and negative for other variants of CD44. Multivariate analysis (Cox proportional-hazard model) with CD44v6 expression (positive or negative), chemotherapy (intensive or non-intensive), tumour site (proximal or distal), and age (at least 30 years or less than 30 years) showed that expression of CD44v6 and chemotherapy were important prognostic factors in patients with osteosarcoma. Overexpression of CD44 isoforms containing variant v6 is correlated with poor prognosis in patients with osteosarcoma.

DOI： 10.1007/s004320050329

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Ultrasonographic analysis of shoulder cuff tearsUltrasonographic analysis of shoulder cuff tears

Masaoka S, Hashizume H, Senda M, Nishida K

Acta MEd Okayama 1999

Integrin-regulated sevreton of interleukin 4: A novel pathway of mechanotransduction in human articular chondrocytes

145 183 - 189 1999

Evaluation of Rheumatoid Arthritis Using a Scoring System Devised from Magnetic Resonance Imaging of Rheumatoid Knees

Takeuchi Kazuhiro, Inoue Hajime, Yokoyama Yoshiki, Senda Masuo, Ota Yusuke, Abe Nobuhiro, Nishida Keiichiro

Acta Medica Okayama 52 ( 4 ) 211 - 224 1998.8

Fibrous structure and connection surrounding the metacarpophalangeal joint

H Takagoshi, H Hashizume, K Nishida, S Masaoka, H Asahara, H Inoue

ACTA MEDICA OKAYAMA 52 ( 1 ) 19 - 26 1998.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

The fibrous components of the metacarpophalangeal (MP) joint including the palmar plate, the collateral ligament and the dorsal plate were studied with particular attention paid to the fibrous structure of the fibrous tendon sheath and the deep transverse metacarpal ligament. The tough fibrillar structure around the MP joint, especially the force nucleus, consisted of three types of mixed fibers: the fibrous tendon sheath of the A, pulley, the deep transverse metacarpal ligament, and the palmar plate. The tendon sheath was located on the ulnar side in the index and middle fingers, on the central position in the ring finger, and on the radial side in the little finger. These fibrous connections among the fingers formed a transverse arch in the hand. The palmar plate of the MP joint was relatively rigid and appears to function as a cushion when flexed. A fold-like protrusion of the synovial layer of the palmar plate of the MP joint had a meniscoid function, which was larger than that of the proximal interphalangeal joint. The capsule of the MP joint was thicker at the dorsal area, forming a dorsal plate, which is a sliding floor of the extensor mechanism and has a meniscoid function for joint congruity. The main lateral stabilizer consisted of collateral ligaments and accessory collateral ligaments anchored to the palmar plate. These structures act together as a "phalangeal cuff", connecting the proximal phalanx to the metacarpal head and stabilizing the MP joint.

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Mast cells in osteoarthritic and rheumatoid arthritic synovial tissues of the human knee

J Pu, K Nishida, H Inoue, H Asahara, A Ohtsuka, T Murakami

ACTA MEDICA OKAYAMA 52 ( 1 ) 35 - 39 1998.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

The distribution and density of mast cells in the normal and diseased synovial membranes were investigated. The mast cell count (MCC) in the osteoarthritic (OA) synovium (36.9 +/- 26.9 cells/mm(2)) was significantly higher than that in the rheumatoid arthritic (RA) synovium (18 +/- 12.3 cells/mm(2)). There was a marked positive correlation between the MCC and the volume of joint fluid in OA (r = 0.544). There was a marked negative correlation between the MCC and the volume of joint fluid in RA (r = -0.478). The synovial inflammatory score had a poor correlation with the MCC in OA (r = 0.377) and RA (r = 0.305). No correlation was noted between MCC and age, sex, roentgenographic grades, disease duration, C-reactive protein or leucocyte number in synovial fluid. Our data suggests, thus, that mast cells could be involved in the pathogenesis of inflammatory diseases of the synovium, especially in the mechanism of hydroarthrosis.

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A Pathogenic role for IL-12 in maintaining Th1 immuneresponses in rheumatoid arthritis.

Morita Y, Yamamura M*, Nishida K, Harada S, Okamoto H, Inoue H, Ohmoto Y, Modlin RL, Makino H

Arthritis Rheum 41 306 - 314 1998

慢性関節リウマチの手指屈筋腱腱鞘炎

太田裕介, 井上一, 橋詰博行, 西田圭一郎, 浅原弘嗣, 臼井正明, 阿部信寛

岡山県立大学短期大学部研究紀要 ( 5 ) 37 - 44 1998

Language：Japanese Publisher：岡山県立大学短期大学部

［概要］慢性関節リウマチ（RA）において手指屈筋腱腱鞘炎（腱鞘炎）を起こす例をしばしば認めるため，横断調査を行った。［対象，方法］岡山大学整形外科リウマチ外来に通院している52例（男６例，女46例）で平均年齢59.5歳（24～85歳），平均罹病期間9.2年（2～30年）を対象とし，視診および触診にて腱鞘炎，弾発現象，ロッキングの有無，および弾発現象の既往につき調査した。調査期間は平成９年４月～５月の２ヵ月間であった。［結果］腱鞘炎を25例（48％）63指に認めた。全63指中，母指～小指が各々4，12，14，19，14指と環指に多かった。１指発生が10例と最も多かったが８指発生も２例あり，うち１例は両手指廃用であった。弾発現象を９例（17％）11指に認め，中指２指，環指５指，小指４指と環指に多い傾向を認めた。ロッキングは４例（８％）５指に認め，手指基節掌側に３例，母指基節掌側に１例認めたが，痛みはなく，日常生活動作の障害はわずかであった。弾発現象の既往のある25例中２例が手術を受けていたが９例（17％）が放置にて治癒していた。また４例はRAの初発症状として弾発現象を認めた。［考察］弾発現象は放置しても自然に消失することが多いので，短期的には経過観察でもよいが，腱断裂を起こす例もあるので，注意が必要と思われた。［まとめ］日常診療において手指屈筋腱腱鞘炎の存在に留意し，腱鞘内注射が有効でない場合は手術的治療も考慮すべきと思われた。

DOI： 10.15009/00000959

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Other Link： http://id.nii.ac.jp/1212/00000959/

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