Expression of CD10 in malignant müllerian mixed tumors and adenosarcomas: an immunohistochemical study.

CD10 has been demonstrated to be positive in endometrial stromal sarcoma (ESS) and thus is useful in establishing the diagnosis, but its expression in malignant müllerian mixed tumor (MMMT) and müllerian adenosarcoma remains to be clarified. In this study, 12 cases of MMMT (9 uterine, 2 tubal, and 1 metastatic), 6 cases of müllerian adenosarcoma (three corporeal, two cervical, and one tubal), and 7 cases of primary uterine sarcomas had their tissues examined immunohistochemically for expression of CD10, desmin, myoglobin, alpha-smooth muscle actin (SMA), and cytokeratin. Of the primary uterine sarcomas, two were primary rhabdomyosarcomas (one cervical and one corporeal), two were ESSs, two were high-grade leiomyosarcomas, and one was a high-grade endometrial sarcoma. Sarcomatous components in all cases of MMMT and müllerian adenosarcoma, as well as all uterine sarcomas, were positive for CD10, showing moderate to marked staining intensity with varying distribution except in one MMMT, which showed weak and very focal staining. In four MMMTs, three adenosarcomas, and one rhabdomyosarcoma, myoglobin- and/or desmin-positive rhabdomyoblastic cells were positive for CD10. The immunoreactivity for CD10 showed the same distribution for alpha-SMA and myoglobin in three and two MMMTs, respectively. In five cases of MMMT, carcinomatous components were focally positive for CD10, and in two cases small populations of round or short spindle cells in sarcomatous components were positive for CD10, alpha-SMA, and cytokeratin (CAM5.2). These results indicate that CD10 expression is not restricted to ESS but can be positive in MMMT and müllerian adenosarcoma as well as in a variety of uterine tumors including high-grade leiomyosarcoma and rhabdomyosarcoma. CD10 expression might be one of the characteristics of müllerian system-derived neoplastic mesenchymal cells.     

Distinct roles of Smad pathways and p38 pathways in cartilage-specific gene expression in synovial fibroblasts

The role of TGF-beta/bone morphogenetic protein signaling in the chondrogenic differentiation of human synovial fibroblasts (SFs) was examined with the adenovirus vector-mediated gene transduction system. Expression of constitutively active activin receptor-like kinase 3 (ALK3CA) induced chondrocyte-specific gene expression in SFs cultured in pellets or in SF pellets transplanted into nude mice, in which both the Smad and p38 pathways are essential. To analyze downstream cascades of ALK3 signaling, we utilized adenovirus vectors carrying either Smad1 to stimulate Smad pathways or constitutively active MKK6 (MKK6CA) to activate p38 pathways. Smad1 expression had a synergistic effect on ALK3CA, while activation of p38 MAP kinase pathways alone by transduction of MKK6CA accelerated terminal chondrocytic differentiation, leading to type X collagen expression and enhanced mineralization. Overexpression of Smad1 prevented MKK6CA-induced type X collagen expression and maintained type II collagen expression. In a mouse model of osteoarthritis, activated p38 expression as well as type X collagen staining was detected in osteochondrophytes and marginal synovial cells. These results suggest that SFs can be differentiated into chondrocytes via ALK3 activation and that stimulating Smad pathways and controlling p38 activation at the proper level can be a good therapeutic strategy for maintaining the healthy joint homeostasis and treating degenerative joint disorders.     

Detection of IgM antibody to Epstein-Barr virus, 1999-2006: analysis of data collected at a commercial diagnostic laboratory in Japan

The status of infectious mononucleosis in Japanese youth has been little studied. To gain more information, we analyzed data from tests for Epstein-Barr virus-specific IgM in about 180,000 serum specimens sent to a commercial diagnostic laboratory from clinics nationwide between 1999 and 2006. The IgM antibody to the viral capsid antigen (VCA) was assayed by indirect immunofluorescence with P3HR-1 cells. In an age-distribution graph of IgM positive specimens, two peaks were found both in young children and youth. Boys outnumbered girls in the group of children aged 0 to 3, and vice versa in the group of youth aged 15 to 25. IgM-positive specimens increased from spring to autumn only in the youth group, suggesting that infectious mononucleosis in this group occurs more during this time. Infectious mononucleosis symptoms are more severe in youth, and further epidemiological studies are needed to clarify the disease status in young Japanese adults.     

Overexpression of gamma-glutamyltransferase in transgenic mice accelerates bone resorption and causes osteoporosis

We previously identified gamma-glutamyltransferase (GGT) by expression cloning as a factor inducing osteoclast formation in vitro. To examine its pathogenic role in vivo, we generated transgenic mice that overexpressed GGT in a tissue-specific manner utilizing the Cre-loxP recombination system. Systemic as well as local production of GGT accelerated osteoclast development and bone resorption in vivo by increasing the sensitivity of bone marrow macrophages to receptor activator of nuclear factor-kappaB ligand, an essential cytokine for osteoclastogenesis. Mutated GGT devoid of enzyme activity was as potent as the wild-type molecule in inducing osteoclast formation, suggesting that GGT acts not as an enzyme but as a cytokine. Recombinant GGT protein increased receptor activator of nuclear factor-kappaB ligand expression in marrow stromal cells and also stimulated osteoclastogenesis from bone marrow macrophages at lower concentrations. Thus, GGT is implicated as being involved in diseases characterized by accelerated osteoclast development and bone destruction and provides a new target for therapeutic intervention.     

Correlation between adiponectin and reduction of cell adhesion molecules after pitavastatin treatment in hyperlipidemic patients with type 2 diabetes mellitus

The aim of this study was to determine whether pitavastatin may prevent the progression of atherosclerotic changes in hyperlipidemic patients. Seventy-five hyperlipidemic patients with and without type 2 diabetes were enrolled to receive pitavastatin 2 mg daily. Cell adhesion molecules (sCD40L, sP-selectin, sE-selectin, and sL-selectin), chemokines (MCP-1 and RANTES) and adiponectin were measured at baseline and after 3 and 6 months of pitavastatin treatment. Adiponectin levels prior to pitavastatin treatment in hyperlipidemic patients with and without diabetes were lower than levels in normolipidemic controls. Both total cholesterol and the LDL-cholesterol (LDL-C) decreased significantly after pitavastatin administration. Additionally, hyperlipidemic patients with type 2 diabetes exhibited a significant increase in adiponectin levels after pitavastatin treatment (before vs. 3 months, 6 months, 2.81 ± 0.95 vs. 3.84 ± 0.84 μg/ml (p < 0.01), 4.61 ± 1.15 μg/ml (p < 0.001)). Furthermore, hyperlipidemic diabetics exhibited significant decreases in sE-selectin and sL-selectin levels after 6 months of pitavastatin treatment (sE-selectin, before vs. 6 months, 74 ± 21 vs. 51 ± 10 ng/ml, p < 0.05; sL-selectin, before vs. 6 months, 896 ± 141 vs. 814 ± 129 ng/ml, p < 0.05). In addition, adiponectin showed significant correlation with sE-selectin and sL-selectin in diabetic hyperlipidemia. However, MCP-1, RANTES and sCD40L did not exhibit any differences before or after pitavastatin administration. These results suggest that pitavastatin possesses an adiponectin-dependent anti-atherosclerotic effect in hyperlipidemic patients with type 2 diabetes in addition to its lowering effects on total cholesterol and LDL-C.     

Radial head dislocation with ulnar plastic deformation in children: an osteotomy within the middle third of the ulna

This retrospective study includes 6 patients (average age, 8.7 years) with a dislocation of the radial head and ulnar plastic deformation. All were Monteggia fractures, Bado type I equivalents. The maximum ulnar bow was near the midulna. Five patients underwent an ulnar osteotomy, with elongation and reduction of the angulation within the middle third of the ulna, and open reduction of the radial head. One patient underwent an ulnar osteotomy with only elongation. The osteotomy sites were stabilized by a plate and screws or Kirschner wires. Mean follow-up was 3.4 years. Postoperatively, the average elbow range of motion was extension to 0 degrees, flexion to 138 degrees, forearm supination to 90 degrees, and forearm pronation to 88 degrees. Results in all patients were rated as excellent. One nonunion occurred. An osteotomy performed within the middle third of the ulna, combined with open reduction of the radial head, resulted in excellent clinical outcomes.