Masashi Kataoka

ADAM family proteins in the immune system

CD156 is a member of a family proteins characterized by a disintegrin and a metalloprotease domain (ADAM). These molecules are phylogenically conserved but have individual roles in a variety of cells. Here, Shunsuke Yamamoto and colleagues discuss data suggesting that ADAM family proteins have important roles in the immune system.

Primary structure of rat CD14 and characteristics of rat CD14, cytokine, and NO synthase mRNA expression in mononuclear phagocyte system cells in response to LPS.

Rat CD14 cDNA clones were isolated. The predicted protein sequence exhibits 82,61.6, and 64% identity with the mouse, rabbit, and human CD14, respectively. The levels of rat CD14 mRNA expression in resident peritoneal macrophages (PM), alveolar macrophages (AM), and peripheral blood monocytes (BM) were constitutively high, whereas that in Kupffer cells (KC) was low. On intravenous injection with lipopolysaccharide (LPS), the expression of rat CD14 mRNA in KC increased markedly, whereas the increases in PM, AM, and BM were mild. Similar features of expression of rat CD14 in these cells were observed after stimulation with LPS in vitro. The level of tumor necrosis factor α (TNF‐α) mRNA expression in KC after stimulation with LPS in vivo was comparable to that in PM, AM, and BM, whereas that of TNF‐α mRNA expression in KC and PM after stimulation with LPS in vitro was lower than that in AM and BM. Interleukin (IL)‐1β and iNOS mRNA expressions in KC after stimulation with LPS in vivo and in vitro were low, whereas those in PM, AM, and BM were high. Little or no expression of IL‐6 was observed in KC after stimulation with LPS in vivo and in vitro, whereas higher expression was observed in PM, AM, and BM than in KC. J. Leukoc. Biol. 61: 736–744; 1997.

Structure of the Murine CD156 Gene, Characterization of Its Promoter, and Chromosomal Location

The murine cell surface antigen mCD156 is a glycoprotein that is expressed in monocytic cell lines and consists of a metalloprotease domain, a disintegrin domain, a cysteine-rich domain, and an epidermal growth factor-like domain in the extracellular region. The mCD156 gene is composed of 24 exons and 23 introns and spans approximately 14 kilobases. The first exon encodes most of the signal peptide sequence, and the transmembrane region is encoded by a single exon (19). In contrast, the other regions are composed of multiple exons. Of these, exons 7–12 and 12–15 encode a metalloprotease domain and a disintegrin domain, respectively. Sequence analysis of the 5′-flanking DNA revealed many potential regulatory motifs. Chloramphenicol acetyltransferase analysis demonstrated that nucleotides at positions −183, −334, and −623 containedcis-acting enhancing elements in a mouse monocytic cell line, aHINS-B3. Nucleotides at positions −183 and −390 contained elements responsible for lipopolysaccharide (LPS) inducibility, although several other 5′-flanking regions were also involved in LPS responsiveness. Regions −202, −507, and −659 play a role in interferon-γ inducibility. Some of the potential regulatory motifs and other unknown cis elements may be involved in the constitutive expression, and LPS and interferon-γ inducibilities. The mCD156 gene was mapped to chromosome 7, region F3-F4.

Manipulation of the anabolic and catabolic responses with BMP-2 and zoledronic acid in a rat femoral fracture model

Bone repair involves a complex set of regulated signaling pathways that control the formation of new bone matrix and the resorption of damaged bone matrix at the fracture site. It has been reported that the optimal time point for single-dose zoledronic acid (ZA) administration systemically increased the strength of bone morphogenetic protein (BMP)-7-mediated callus. However, its repair mechanism during bone fracture healing remains unknown. We aimed to investigate the synergic effect of recombinant human (rh) BMP-2 and ZA in a rat femoral fracture model. Fifty-eight rats were divided into 4 groups. Group I (n=14) animals were implanted with a carrier alone. Group II (n=15) animals were implanted with a carrier containing 1-μg rhBMP-2. Group III (n=14) animals were implanted with a carrier and a subcutaneous systemic ZA injection 2 weeks after surgery. Group IV (n=15) animals were implanted with a carrier containing 1-μg rhBMP-2 and ZA subcutaneous injection 2 weeks after surgery. The rats were euthanized after 6 weeks and their fractured femurs were explanted and assessed by manual palpation, radiographs, and high-resolution micro-computerized tomography (micro-CT) and were subjected to biomechanical and histological analysis. The fusion rates in Group IV (93.3%) were considerably higher than those in Groups I (28.6%), II (53.3%), and III (57.1%). Additionally, the radiographic scores of Group IV were higher than those in Groups I, II, and III. In micro-CT analysis, the tissue volume (TV) of the callus was higher in Group IV than in Groups I and II (p<0.05). New bone volume (BV) and trabecular spacing (Tb.Sp) also showed essentially the same trend as that of TV. The ratio of BV to TV (BV/TV), the trabecular number (Tb.N), and the trabecular thickness (Tb.Th) was higher in Groups III and IV than in Groups I and II (p<0.05). In biomechanical analysis, the ultimate loads at failure and stiffness in Groups III and IV were on average higher than those in Groups I and II (p<0.05), while the energy absorption of Group IV was higher than those of Groups I and II (p<0.05). The synergic effect of rhBMP-2 and ZA given systemically as a single dose at the optimal time was efficacious for fracture repair and significantly enhanced bone fusion. Our results suggest that this combination facilitates bone healing and has potential clinical application.

Expression of scavenger receptor class A and CD14 in lipopolysaccharide-induced lung injury

CD14 and macrophage scavenger receptor class A type I and II (MSR‐A) are receptors for lipopolysaccharide (LPS). In this study, the expressions of both receptors in the lung after administration of LPS in aerosol to mice with a nebulizer were observed. Bronchiolar epithelial cells and alveolar macrophages immediately incorporated LPS and expressed CD14. CD14‐positive neutrophils then appeared in the alveolar space followed by the appearance of MSR‐A‐expressing cells in the vascular lumen, pulmonary interstitium, and alveolar space. Numbers of apoptotic cells increased after 1 day, and MSR‐A‐expressing macrophages actively incorporated apoptotic bodies. Daily administration of macrophage colony stimulating factor (M‐CSF) to the mice resulted in increased levels of MSR‐A expression and reduced levels of CD14 as well as several cytokine expressions, leading to shortening of the inflammatory process. The numbers of apoptotic cells were reduced in M‐CSF injected mice. These findings imply that CD14 acts as an immediate expressing receptor for LPS and MSR‐A exerts a protective function by scavenging LPS and apoptotic cells in LPS‐induced lung injury.

Role of multinuclear cells in granulation tissue in osteomyelitis Immunohistochemistry in 66 patients

We investigated the origin of multinuclear cells (MNCs) in the granulation tissue in osteomyelitis by immunohistochemical techniques in 66 patients. 12 samples were analyzed for the presence of CD68, cathepsin K, CD11b and tartrate-resistant acid phosphatase (TRAP) activity. Many MNCs were present in the granulation tissue adjacent to a sequestrum. MNCs in contact with the sequestrum were also noted, however, no osteoblasts were found. Immunohistochemically, CD68, cathepsin K and TRAP were strongly expressed in most of the MNCs, while CD11b positive cells were not found. MNCs remote from and in contact with the sequestrum showed the same immunohistochemical features which are characteristic of osteoclasts. Further, MNCs in contact with the sequestrum had originally developed in the granulation tissue and directly infiltrated towards the sequestrum without cellto-cell interaction with osteoblasts.

Subchondral cyst of the tibia secondary to Wilson disease

We present the case of a 40-year-old male patient who had been suffering from Wilson disease for over 20 years, whose knee was diagnosed as osteoarthritis combined with subchondral cyst of the tibia. Preoperative examinations (X-ray, CT and MRI) confirmed the diagnosis. The microscopic examination detected thickening of the synovial membrane, and histopathological findings revealed that lymphoid cells and plasma cells were infiltrated at the synovial membrane. On copper-specific staining, no copper pigmentation was identified. However, the energy-dispersive X-ray (EDX) microanalysis revealed copper pigmentation in high concentration. These findings may contribute to our better comprehension of the development process of the arthropathy in patients with Wilson disease. The combination of subchondral cyst with Wilson disease is extremely rare, as only about 16 such cases have been reported in the English literature.

An Assessment of Histopathological Criteria for Infection in Joint Arthroplasty in Rheumatoid Synovium

Abstract: Intraoperative frozen section is reported to be a reliable means of identifying occult infection for preoperative evaluation of arthroplasty. The aim of this study was to determine whether the reported histopathological criteria – the existence of more than 10 polymorphonuclear cells (PMN) per high-power field – is valuable for determination of infection during the arthroplasty of patients with rheumatoid arthritis (RA). The permanent histological sections of RA synovium were analysed to study the degree of infiltration of PMNs. Furthermore, in order to examine the penetrative distribution of PMNs within the synovial tissues, immunohistochemical staining of PMNs was performed. In addition, the clinical history, from the postoperative period to the present, was investigated in 46 patients (60 joints). The presence of early- and/or late-stage postoperative infection, the development of postoperative fever, the progression of erythrocyte sedimentation rate (ESR) (more than 30 mm per hour) and the changes in CRP (more than 10 mg per litre) were further examined and compared with the histopathological tissue analyses and findings. The results demonstrated the presence of more than five PMNs per high-power field, excluding surface fibrin and inflammatory exudate in at least five separate microscopic fields in 10 joints (16.7%) of nine patients, out of 60 joints of 46 patients, in which no postoperative infection was evident. As to the magnitude of penetrative distribution of PMNs in 10 joints, there was a trend of deepening infiltration among the patients with intensive PMN infiltration. In addition, no development of postoperative fever, CRP or continuous indications of high ESR values were evident in this group. As the existence of more than 10 PMN per high-power field was not absolutely indicative of occult infection, investigation of frozen section during arthroplasty should be carefully managed.

Iliopsoas bursa of the rheumatoid hip joint. A case report and review of the literature

SummaryPresented is the case of a 63-year-old woman, with a 30-year history of rheumatoid arthritis, whose hip was completely destroyed and accompanied with enlargement of the iliopsoas bursa. Preoperative diagnosis was confirmed by computed tomography, magnetic resonance (MR) imaging and arthrography. She was treated by resection of the iliopsoas bursa and total prosthetic replacement of the hip joint. The pathogenesis is uncertain. In the literature, enlargement of the iliopsoas bursa with rheumatoid arthritis, osteoarthritis, pigmented villonodular synovitis, and synovial chondromatosis had been reported. Nevertheless, a correct preoperative diagnosis of the enlargement of the iliopsoas bursa is very difficult. MR imaging with enhanced Gadolinium-DTPA (Gd-DTPA) is proposed as the most useful examination for preoperative diagnosis.

Idiopathic Heterotopic Ossification Within the Tibial Nerve

Heterotopic ossification has been reported to occur following burns, musculoskeletal trauma, and tetanus and in association with metabolic and neurologic disorders. Heterotopic ossification is found most commonly in the muscles, and histopathologically identical lesions have been described in tendons, subcutaneous fat, ligaments, fasciae, aponeuroses, and joint capsules1. Heterotopic ossification can also cause clinically relevant peripheral nerve entrapment2-4. Heterotopic ossification or calcification within a peripheral nerve is a rare lesion and may arise in association with neurofibroma5, leprosy6, CREST syndrome (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia)7, diabetic neuropathy8-10, and chronic renal failure11. In a recent review of the literature, we found only two cases of idiopathic intraneural heterotopic ossification12,13. We describe here an unusual case of a painful ossifying lesion arising from the tibial nerve in a man. The radiographic and histopathologic findings were similar to those of myositis ossificans. A forty-two-year-old male truck driver had persistent discomfort in the right popliteal fossa for four months. Previously, he had been healthy and he had no history of trauma. He reported the gradual onset of severe pain and tenderness and had noticed swelling in the right popliteal fossa and calf with paresthesias and decreased sensation in the right leg. He was referred to our hospital in January 2000. Physical examination disclosed a hard, …