Osteoprotegerin (OPG), identical with osteoclastogenesis inhibitory factor, is a member of a subgroup of the tumor necrosis factor (TNF)-receptor superfamily, which functions as a soluble decoy receptor. It has been reported that OPG expression is associated with bone metastasis of cancer of the breast and prostate. In the present study, we examined the expression of OPG in gastric carcinomas using immunohistochemistry and reverse-transcription polymerase chain reaction methods, and compared with clinicopathological parameters. The expression of OPG mRNA was confirmed in a gastric carcinoma cell line (MKN-7) and gastric carcinoma tissues. Immunohistochemically, strongly positive staining of OPG was found in 65% (67/103) of gastric carcinomas, whereas OPG protein was not detected in non-neoplastic mucosal epithelia. The expression of OPG protein in gastric carcinoma tissues correlates significantly with depth of tumor invasion, nodal metastases and advanced tumor stage. Furthermore, the prognosis of the cases with strong OPG expression was significantly worse than those with weak or no expression of OPG. These results suggest that OPG may participate in stomach carcinogenesis, invasion and metastasis, and may serve as a novel molecular marker for aggressive gastric cancer.

Active oxygen species are reported to cause organ damage. This study was therefore designed to determine the behaviour of antioxidants and free radical scavengers so as to reveal changes in animals in the hyper- and hypothyroid state. Levels of antioxidant factors (i.e. coenzyme Q (CoQ)10, CoQ9 and vitamin E) and free radical scavengers (catalase, glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD)) were measured in the heart muscles of rats rendered hyper- or hypothyroid by 4 weeks of thyroxine (T4) or methimazol treatment. Serum levels of CoQ9 and total SOD were also measured. A significant reduction in CoQ9 levels was observed in the heart muscles of both hyper- and hypothyroid rats when compared with control hearts. There was no difference in serum CoQ9 levels in thyroid dysfunction when compared with control animals. Levels of vitamin E in the heart muscles of hyperthyroid rats were significantly increased, and there was no reduction in vitamin E levels in hypothyroid rats when compared with control hearts. GSH-PX levels in the heart muscle were reduced in hyperthyroid rats and increased in hypothyroid rats when compared with control hearts. However, there were no differences in catalase levels in heart muscle between hyper- and hypothyroid rats. The concentration of SOD in heart muscle was increased in hyperthyroid rats and was not decreased in hypothyroid rats compared with control rats, suggesting the induction of SOD by excessive production of O2-. These data suggest that the changes in these scavengers have some role in cardiac dysfunction in the hyper- and hypothyroid state in the rat.

IntroductionAdenosine deaminase (ADA) is an enzyme of the purine salvage pathway that catalyses the deamination of adenosine and 2Ј-deoxyadenosine to inosine and 2Ј-deoxyinosine, respectively. Inherited deficiency of ADA was serendipitously found to result in one of the autosomal recessive forms of severe combined immunodeficiency (SCID). 1 Evaluation of a genotype-phenotype relationship revealed a deficiency of ADA results in varied impairment of immune status as well as clinical course. 2 Residual ADA enzyme activity of each mutant correlated closely with biochemical and clinical phenotypes of patients. 3 In 1990, the first clinical trial of gene therapy was performed in a patient with ADA deficiency. 4 Since then, more than 10 patients with ADA deficiency have been treated by gene therapy. Although beneficial effects of the gene therapy were reported in some cases, 4,5 complete cure of the disease by stem cell gene therapy has not yet been realized. [6][7][8] Such results may suggest that inevitable ADA enzyme replacement interferes with growth advantage of gene-introduced cells compared with recent successful gene therapy of X-SCID patients. 9 Here we report data on 2 patients with ADA deficiency from different families, in whom possible reverse mutation had occurred as reported previously. 10 We detected the reversion in the patients' T-cell lines, and at least one of them seemed to possess the revertant cells in vivo; however, mutant cells might overcome the revertant after receiving ADA enzyme replacement therapy. Study design PatientsPatient 1, now a 13-month-old girl, is the first child of a healthy unrelated couple. She had an episode of respiratory infection at age 15 days, and after 5 days, she was admitted to a hospital with progressive respiratory distress and failure to thrive. Because the number of her peripheral blood lymphocytes was very low (200/L), she was suspected to have SCID, and screening of ADA enzyme activity revealed a trace level of ADA. The patient is now being treated with ADA polyethylene glycol-modified bovine ADA (PEG-ADA).Patient 2, now an 11-month-old girl, is the second child of a healthy couple without consanguinity. When she was 1 month old, she had a bacterial skin infection on her thigh. The episode was temporally controlled; however, she was hospitalized after a few days because the infection recurred. Laboratory examination revealed a very low number of white blood cells (700-1700/L) and hypogammaglobulinemia (IgG, 162 mg/dL; IgA, Ͻ6.0 mg/dL; IgM, 13.5 mg/dL). Her red blood cells (RBC) were examined by ADA screening assay, and the results showed a trace level of the enzyme activity. During this study, she received bone marrow transplantation from her healthy brother when she was 5 months old. Cell linesThe T-cell lines from the patients were established using herpesvirus saimiri as described elsewhere. 11 B-cell lines were also established with EpsteinBarr virus. Because of the low number of peripheral lymphocytes, it took 2 to 3 months to establish both the patients' l...