Induction of Autoimmunity in a Bleomycin-Induced Murine Model of Experimental Systemic Sclerosis: An Important Role for CD4+ T Cells

Systemic sclerosis (SSc) is an autoimmune disease characterized by the excessive deposition of collagen in the skin or other organs and the production of specific antinuclear antibodies (ANAs). Recently, bleomycin (BLM)-induced experimental scleroderma was reported in a murine model. Here, we present further development of this model and suggest that it is appropriate for the analysis of human diffuse type SSc. BLM was injected into the shaved backs of C3H or BALB/c mice (100μg/mouse) 5 days per week for 3 weeks. Skin fibrosis was confirmed and pathological changes were seen in the lower part of the esophagus and stomach similar to those seen in SSc. The sera from these mice had autoantibodies specific to the damaged tissues and ANAs. Transfer of CD4+ T cells from BLM-treated BALB/c mice induced the same pathological changes and antibody production in untreated-BALB/c nude mice. Hence, tissue fibrosis and the production of ANAs are probably associated with CD4+ T-cell activity in this model. In conclusion, this model will be valuable for investigating the relationship between tissue fibrosis and abnormalities of the immune system

A Simple Enzymatic Method for Production of a Wide Variety of D-Amino Acids Using L-Amino Acid Oxidase from Rhodococcus sp. AIU Z-35-1

A simple enzymatic method for production of a wide variety of D-amino acids was developed by kinetic resolution of DL-amino acids using L-amino acid oxidase (L-AAO) with broad substrate specificity from Rhodococcus sp. AIU Z-35-1. The optimum pH of the L-AAO reaction was classified into three groups depending on the L-amino acids as substrate, and their respective activities between pH 5.5 and 8.5 accounted for more than 60% of the optimum activity. The enzyme was stable in the range from pH 6.0 to 8.0, and approximately 80% of the enzyme activity remained after incubation at 40°C for 60 min at pH 7.0. D-Amino acids such as D-citrulline, D-glutamine, D-homoserine or D-arginine, which are not produced by D-aminoacylases or D-hydantoinases, were produced from the racemic mixture within a 24-hr reaction at 30°C and pH 7.0. Thus, the present method using L-AAO was versatile for production of a wide variety of D-amino acids

Preoperative radiographic and histopathologic evaluation of central chondrosarcoma

Distinguishing grade 1 chondrosarcoma from grade 2 chondrosarcoma is critical both for planning the surgical procedure and for predicting the outcome. We aimed to review the preoperative radiographic and histologic findings, and to evaluate the reliability of preoperative grading. We retrospectively reviewed the medical records of 17 patients diagnosed with central chondrosarcoma at our institution between 1996 and 2011. In these cases, we compared the preoperative and postoperative histologic grades, and evaluated the reliability of the preoperative histologic grading. We also assessed the preoperative radiographic findings obtained using plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI). Preoperative histologic grade was 1 in 12 patients, 2 in 4 patients, and 3 in 1 patient. However, 6 of the 12 cases classified as grade 1 before surgery were re-classified as grade 2 postoperatively. In the radiographic evaluation, grade 1 was suspected by the presence of a ring-and-arc pattern of calcification on plain radiography and CT and entrapped fat and ring-and-arc enhancement on MRI. Grades 2 and 3 were suspected by the absence of calcification and the presence of cortical penetration and endosteal scalloping on plain radiography and CT, as well as soft-tissue mass formation on MRI. Although the combination of radiographic interpretation and histologic findings may improve the accuracy of preoperative grading in chondrosarcoma, the establishment of a standard evaluation system with the histologic and radiographic findings and/or the development of new biologic markers are necessary for preoperative discrimination of low-grade chondrosarcoma from high-grade chondrosarcoma.ArticleARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY. 133(9):1225-1231 (2013)journal articl

Metastatic Carcinoma to Subcutaneous Tissue and Skeletal Muscle: Clinicopathological Features in 11 Cases

Objective: Metastatic carcinoma to subcutaneous tissue or skeletal muscle is relatively rare. The present study aimed to clarify the clinicopathological features for confirming the diagnosis as soft tissue metastasis and determining the primary site. Methods: We reviewed records of 11 patients with soft tissue metastasis who were in our institution from 1996 to 2009. Results: In 9 of 10 patients who underwent magnetic resonance imaging, findings consisted of poorly circumscribed high-intensity lesions around the tumor on T2-weighted images, irregular peritumoral enhancement and poorly enhanced lesions at the center of the tumor on T1-weighted images. Systematic immunohistochemical examination was more valuable for diagnosing as soft tissue metastasis and confirming the primary site. The expression patterns of cytokeratins 7 and 20 and tissue-specific antibodies such as thyroid transcription factor-1, MUC5AC and CDX2 were useful diagnostic markers. The primary site could be determined in five patients with cytokeratin 7/20 immunophenotype and positivity for tissue-specific antibodies. In four cases, determination of the primary site finally became possible by comparison with the histological findings of operative specimens in past carcinoma and/or in consideration of radiological findings and the results of cytokeratin 7/20 phenotyping. Conclusions: Systematic immunohistochemical examination is helpful for confirmation of the primary origin in soft tissue metastasis of carcinoma in addition to clinical information such as the history and condition of past carcinoma, radiological findings and comparison between the histology of biopsy specimens and past carcinoma.ArticleJAPANESE JOURNAL OF CLINICAL ONCOLOGY. 41(3):358-364 (2011)journal articl

Multifocal Periosteal Chondromas in the Ring Finger of an Adolescent Boy: Case Report

We describe an unusual case of a 12-year-old boy who presented with a loss of motion in the ring finger caused by 2 separate periosteal chondromas involving the proximal and middle phalanges. Range of motion improved and recurrence did not occur at the 5-year follow-up after marginal excision of both lesions. (J Hand Surg 2011;36A:101-105.ArticleJOURNAL OF HAND SURGERY-AMERICAN VOLUME. 36A(1):101-105 (2011)journal articl

Comparative Angiogenic Activities of Induced Pluripotent Stem Cells Derived from Young and Old Mice

Advanced age is associated with decreased stem cell activity. However, the effect of aging on the differentiation capacity of induced pluripotent stem (iPS) cells into cardiovascular cells has not been fully clarified. We investigated whether iPS cells derived from young and old mice are equally capable of differentiating into vascular progenitor cells, and whether these cells regulate vascular responses in vivo. iPS cells from mouse embryonic fibroblasts (young) or 21 month-old mouse bone marrow (old) were used. Fetal liver kinase-1 positive (Flk-1+) cells, as a vascular progenitor marker, were induced after 3 to 4 days of culture from iPS cells derived from young and old mice. These Flk-1+ cells were sorted and shown to differentiate into VE-cadherin+ endothelial cells and α-SMA+ smooth muscle cells. Tube-like formation was also successfully induced in both young and old murine Flk-1+ cells. Next, hindlimb ischemia was surgically induced, and purified Flk-1+ cells were directly injected into ischemic hindlimbs of nude mice. Revascularization of the ischemic hindlimb was significantly accelerated in mice transplanted with Flk-1+ cells derived from iPS cells from either young or old mice, as compared to control mice as evaluated by laser Doppler blood flowmetry. The degree of revascularization was similar in the two groups of ischemic mice injected with iPS cell-derived Flk-1+ cells from young or old mice. Transplantation of Flk-1+ cells from both young and old murine iPS cells also increased the expression of VEGF, HGF and IGF mRNA in ischemic tissue as compared to controls. iPS cell-derived Flk-1+ cells differentiated into vascular progenitor cells, and regulated angiogenic vascular responses both in vitro and in vivo. These properties of iPS cells derived from old mice are essentially the same as those of iPS cells from young mice, suggesting the functionality of generated iPS cells themselves to be unaffected by aging

Multifocal Periosteal Chondromas in the Ring Finger of an Adolescent Boy: Case Report

We describe an unusual case of a 12-year-old boy who presented with a loss of motion in the ring finger caused by 2 separate periosteal chondromas involving the proximal and middle phalanges. Range of motion improved and recurrence did not occur at the 5-year follow-up after marginal excision of both lesions. (J Hand Surg 2011;36A:101-105.ArticleJOURNAL OF HAND SURGERY-AMERICAN VOLUME. 36A(1):101-105 (2011)journal articl

Preoperative radiographic and histopathologic evaluation of central chondrosarcoma

BACKGROUND: Distinguishing grade 1 chondrosarcoma from grade 2 chondrosarcoma is critical both for planning the surgical procedure and for predicting the outcome. We aimed to review the preoperative radiographic and histologic findings, and to evaluate the reliability of preoperative grading. METHODS: We retrospectively reviewed the medical records of 17 patients diagnosed with central chondrosarcoma at our institution between 1996 and 2011. In these cases, we compared the preoperative and postoperative histologic grades, and evaluated the reliability of the preoperative histologic grading. We also assessed the preoperative radiographic findings obtained using plain radiography, computed tomography (CT), and magnetic resonance imaging (MRI). RESULTS: Preoperative histologic grade was 1 in 12 patients, 2 in 4 patients, and 3 in 1 patient. However, 6 of the 12 cases classified as grade 1 before surgery were re-classified as grade 2 postoperatively. In the radiographic evaluation, grade 1 was suspected by the presence of a ring-and-arc pattern of calcification on plain radiography and CT and entrapped fat and ring-and-arc enhancement on MRI. Grades 2 and 3 were suspected by the absence of calcification and the presence of cortical penetration and endosteal scalloping on plain radiography and CT, as well as soft-tissue mass formation on MRI. CONCLUSION: Although the combination of radiographic interpretation and histologic findings may improve the accuracy of preoperative grading in chondrosarcoma, the establishment of a standard evaluation system with the histologic and radiographic findings and/or the development of new biologic markers are necessary for preoperative discrimination of low-grade chondrosarcoma from high-grade chondrosarcoma