Hideo Imamura

Interleukin 1β and stromelysin (MMP3) activity of synovial fluid as possible markers of osteoarthritis in the temporomandibular joint

PURPOSE This study investigated the early signs of synovitis and cartilage degradation by means of synovial fluid analysis in temporomandibular joints (TMJs) with internal derangement (closed lock) or osteoarthritis (OA). PATIENTS AND METHODS Synovial fluid was obtained from 25 TMJs in 22 patients diagnosed with closed lock and from 15 asymptomatic TMJs of 12 normal controls. IL-1 beta concentrations were measured using enzyme-linked immunosorbent assay (ELISA), and proteinase activity was detected by means of gelatin enzymography. RESULTS Nine of the 25 TMJs with closed lock (CL group) exhibited osteolytic changes on the surface of the condyle. TMJs in the normal control group did not show any bony changes. Mean IL-1 beta concentration in the synovial fluid (SF) protein in the CL group was 330.1 +/- 347.7 pg per 100 micrograms protein, which was significantly higher than in the normal control (76.7 +/- 95.3 pg/100 micrograms SF-protein). Synovial fluid from the TMJs with osteolytic changes contained higher levels of IL-1 beta (531.8 +/- 379.6 pg/100 micrograms SF-protein) than those without bony changes (216.7 +/- 280.1 pg/100 micrograms SF-protein). Matrix metalloproteinase (MMP) activity with a molecular weight of 50 kd (stromelysin or MMP3) was detected in a highly augmented form in two synovial fluid samples of seven closed lock patients. CONCLUSION The results suggest that IL-1 beta levels in synovial fluid of the TMJ have a positive correlation with OA change. The MMP3 activity detected was greatly increased in patients with cartilage degradation. These findings suggest that both changes may be important markers of early bone deterioration in TMJs that are undetectable by radiograph imaging.

Clear cell odontogenic carcinoma. A case report with massive invasion of neighboring organs and lymph node metastasis.

Clear cell odontogenic carcinoma is a rare and unusual tumor that occurs in the jaws. This tumor is generally considered to be of a low grade of malignancy. We describe a patient with a huge clear cell odontogenic carcinoma that originated in the mandible and exhibited massive invasion into the adjacent tissues and metastases to the submandibular lymph nodes. The ultrastructural and immunohistochemical details are described.

Tumoricidal effect of human PBMC following stimulation with OK-432 and its application for locoregional immunotherapy in head and neck cancer patients.

Both cell-mediated and cytokine-mediated antitumor activities were induced in peripheral blood mononuclear cells (PBMC) in short-term culture with streptococcal preparation, OK-432. Kinetic analysis of OK-432-activated killer activity (OKAK) showed that it reached a plateau level much faster (by 48 h of culture) than that detected in PBMC stimulated with recombinant interleukin 2 (rIL-2) (lymphokine-activated killer: LAK). We also found that the tumor growth inhibitory factor (TGIF) activity was produced in the culture supernatant (CSN) of the OK-432-activated PBMC (OK-MC) and the activity synchronously increased with augmentation of OKAK activity. The TGIF activity was rarely found in the CSN of rIL-2-stimulated PBMC. The TGIF activity detected in CSN of OK-MC was further characterized as derived from a cytokine different from interferon gamma (IFN gamma), tumor necrosis factor (TNF), or lymphotoxin (LT) by a neutralization test using monoclonal antibodies to these cytokines. These 48-h-cultured-OK-MC were adoptively transferred (adoptive immunotherapy: AIT) into 19 head and neck cancer patients either alone or in combination with chemotherapy and/or radiation therapy, and their therapeutic effects were examined. AIT was performed by intra-arterial or intratumoral administration of OK-MC. There were no significant side effects observed in this treatment. In these patients, approximately 1-10 x 10(7) cells were transferred into the tumor burden. Of the 19 patients, 17 had primary cancer, and in 6 (6/17;35%) of them complete remission (CR) of the tumor was obtained. Partial remission (PR) was attained in 9 of the 17 patients (9/17; 53%), giving the overall response rate of 88%.(ABSTRACT TRUNCATED AT 250 WORDS)

Effective Induction of Human NK Cells with OK-432 and Further Augmentation of Their Cytolytic Function by rIL-2

Low concentrations of exogenously added recombinant interleukin 2 (rIL‐2) were able to augment OK‐432‐induced natural killer (NK) cell activity. This kind of augmenting effect depended on the dose of rIL‐2 and manifested itself only in PBMC stimulated with OK‐432 (OK‐MC) followed by rIL‐2; augmentation did not happen in the reverse order. The existence of CD16+/CD25+ (IL‐2 receptor positive; IL‐2R+) and CD57+/CD25+ double positive cells which possess NK cell surface markers in OK‐MC markedly increased in a long‐term culture (12 days). A strong positive correlation was observed between the IL‐2‐dependent augmentation of NK activity and the quantitative changes in cell populations that possessed NK cell phenotypes. Treatment of the day‐12‐OK‐MC with monoclonal anti‐CD56 antibody plus complement could almost completely abrogate the augmented NK cytotoxicity. Furthermore, this augmenting effect was detectable within 4 hr after addition of rIL‐2 at single cell level, suggesting that the effect did not require NK cells DNA synthesis. Thus it was suggested that OK‐432 could promote and upregulate the expression of IL‐2 receptor (CD25) on CD56+ NK cell populations. Moreover, it was considered that the interaction of low concentration rIL‐2 with IL‐2 receptors on OK‐432‐activated NK cells could augment their lytic function.

Locoregional immunotherapy of head and neck cancers utilizing allogeneic spleen cells — a report of 2 cases

Frozen-stored human spleen cells (SC) cultured with streptococcus preparation OK-432 acquired direct cytotoxicity to autologous as well as allogeneic tumor cells. The activated cells started to produce cytocidal cytokine TGIF, which is distinct from previously known cytokines.We examined the possibility of allogeneic adoptive immunotherapy (AIT) using these OK-432-stimulated spleen cells (OK-SC) in two cancer patients. Rapid necrosis of cancer tissue and remarkable decreases of tumor markers in tumor effusion were observed. There were no severe side effects.

Clinicopathological study on three cases of cemento-ossifying fibroma.

セメント質骨形成線維腫3例について臨床病理学的に検討した。性別は, 3例すべて男性で, 初診時年齢は14歳, 43歳, 47歳 (平均年齢: 34.7歳) であった。3例とも下顎臼歯部に発生していた。X線所見では, すべて境界明瞭な病変で, X線透過像とX線不透過像の混在例であった。治療法は, 3例すべてに対し腫瘍摘出術を行い, 自家腸骨海綿骨移植を追加施行した。術後経過はすべて良好で, 再発例は認めていない。摘出した腫瘍は被膜を欠いており, 線維性組織中に種々の成熟度を示すセメント質様ないし骨様組織の形成が認められた。

Clinicostatistical analysis of 56 cases of odontogenic tumors.

1981年10月から2002年6月までの20年8か月間に, 奈良県立医科大学口腔外科において経験した135例の歯原性腫瘍について, 1992年のWHO分類に基づき臨床統計的検討を行った。組織型別ではエナメル上皮腫が56例と最も多く, 続いて集合性歯牙腫が41例, 複雑性歯牙腫が18例であり, 残り良性腫瘍が17例, 悪性腫瘍が3例であった。初診時年齢は5歳から77歳で平均年齢は29.8歳であった。性別では, 男性71例, 女性64例で, 男女比は1.1: 1であった。部位別は上顎が45例, 下顎が90例であった。エナメル上皮腫, 集合性歯牙腫, 複雑性歯牙腫の好発部位は, それぞれ下顎臼歯部, 上顎前歯部, 下顎臼歯部であった。主訴の大部分が精査依頼であったが, エナメル上皮腫においては腫脹が最も多かった。エナメル上皮腫におけるX線所見は, 多房性が22例, 単房性が14例, 蜂巣状が3例であった。関連埋伏歯は全症例中39例みられた。隣在歯の歯根吸収はエナメル上皮腫に24例みられた。治療法は摘出が90例, 開窓が16例, 下顎区域切除が12例, 下顎辺縁切除が3例, 上顎部分切除が3例であった。再発は一次症例ではエナメル上皮腫に3例, 二次症例ではエナメル上皮腫に3例, 歯原性粘液腫に1例と悪性エナメル上皮腫に1例に認められた。