Autoantibodies in scleroderma and tightskin mice

There is much evidence to suggest that scleroderma in human patients is caused by a fundamental defect in the immune system. In tightskin mice, the scleroderma syndrome is associated with autoimmunity, particularly autoantibodies interacting with scleroderma target antigens.     

Histochemical study of mitochondrial enzymes in cerebellar cortex of macular mutant mouse,a model of Menkes kinky hair disease

The cerebellar Purkinje cells in the hemizygote of the macular mutant mouse contain numerous abnormal mitochondria which show a marked decrease in cytochrome c oxidase activity. Using histochemical methods we studied the activity of other mitochondrial enzymes, such as NADH diaphorase and succinic dehydrogenase, in the cerebellar cortex of this mutant mouse. Such activities were markedly increased in the Purkinje cells, especially in the soma and stem dendrite, from 10 days after birth in the hemizygote as compared with findings in normal littermates. These results were considered to be due to an increased number of abnormal mitochondria.Supported by the Research Grants nos. 2A-5-03 and 3B-1-04 for Nervous and Mental Disorders from the Ministry of Health and Welfare, and by Grant no. 04670492 of the Ministry of Education of Japanese Government     

Effect of FK-506 on xenografted human Graves' thyroid tissue in severe combined immunodeficient mice

OBJECTIVE We studied the macrolide antibiotic FK-506, an immunosuppressive agent, in an attempt to ameliorate the lesion of autoimmune thyroid disease in human thyroid tissue xenografted into severe combined immunodeficient (SCID) mice. It was not felt appropriate to employ this agent directly in patients with autoimmune thyroid disease because adequate therapeutic modalities are available and the introduction of new, experimental agents could not be justified. Moreover, the study of the tissue before and after treatment could not have been undertaken directly in patients. DESIGN Human thyroid xenografts from four patients with Graves' disease and two normal persons were xenografted into SCID mice. Two weeks after xenograft-ing, human immunoglobulin G (IgG) was detectable in all SCID mice xenografted with Graves' thyroid tissue. Mice were divided into two groups with human IgG levels similar to each other. Mice in the first group were treated with FK-506 daily for 6 weeks; mice in the second (similar) group were given phosphate-buffered saline (PBS) only (control group). MEASUREMENTS Blood samples were taken every 2 weeks from the tail veins for human IgG, thyroid stimulating antibody, thyroperoxidase antibodies, thyroglobulin antibodies, and interferon-gamma (IFN-7). After 8 weeks treatment, animals were sacrificed; thyroid tissue was examined histologically and for thyrocyte HLA-DR expression. FK-506 was also added to thyrocytes in in-vitro tissue culture conditions. RESULTS After 4–6 weeks of FK-506 therapy, human IgG, all thyroid antibodies and IFN-7 were suppressed, while the levels remained elevated in the control group. Lymphocytic infiltration virtually disappeared in the human thyroid tissue of the FK-506-treated mice and thyrocyte HLA-DR expression markedly declined; in the control mice, lymphocytic infiltration remained heavy and HLA-DR expression remained high. On the other hand, FK-506 added directly to thyrocytes in vitro (without lymphocytes) did not reduce thyrocyte HLA-DR expression. CONCLUSIONS FK-506 appears to suppress the activation of intrathyroidal lymphocytes, but not thyrocytes. From these observations, it is concluded that this agent, by its action on intrathyroidal lymphocytes, is able to ameliorate the immunologically mediated histological and serological disturbance in human autoimmune thyroid disease, at least under these circumstances.     

Curative resection of gastric cancer: Limitation of peritoneal lavage cytology in predicting the outcome

Patients with stage T3N0～2M0 gastric carcinoma (n = 108) were studied for relevant prognostic factors. Peritoneal lavage cytology (PLC) was performed in all. In univariate analysis, 5-year survival rates were better with smaller serosal invasion (diameter <3.0 cm vs. ≥3.0 cm, 61% vs. 37%, P < 0.05) and fewer metastatic nodes (≤5 vs. ≥6, 57% vs. 29%, P < 0.05). In multivariate analyses, only these two factors were significant. The predictive value of PLC was not shown in both univariate and multivariate analyses. Peritoneal recurrence occured in 14 (22%) of 77 patients with negative PLC, and in 3 (18%) of 17 with positive PLC, the difference being not significant. Our results indicate that PLC is insensitive in predicting the development of peritoneal recurrence. Its role in the estimation of survival is limited, as many will die of visceral or locoregional recurrence if not of peritoneal dissemination.     

ENDOSCOPIC SUBMUCOSAL DISSECTION FOR RECURRENT GASTRIC TUMORS

Endoscopic resection has been accepted as the standard treatment for intramucosal gastric tumors of differentiated type. However, the indication was limited to small tumors to achieve en bloc resection and prevent local recurrence in cases of conventional endoscopic mucosal resection (EMR) such as the strip biopsy and the cap technique. To avoid multi‐fragmental resection, we have developed endoscopic submucosal dissection (ESD) as a new endoscopic resection technique. ESD is a remarkable technique, because we make it possible to remove the lesions en bloc regardless of size, shape, coexisting ulcer, and location. However, it is difficult or impossible to resect recurrent tumors en bloc in conventional EMR owing to hard fibrosis, and some patients need laparotomy. Using ESD, we can dissect the submucosal layer as we directly look at the submucosa, and remove the lesion safely and reliably even in cases of hard fibrosis. The key to treatment of recurrent tumors in ESD are as follows: (i) using enough submucosal injection solution (we use a mixture of Glyceol and 1% 1900 kDa hyaluronic acid preparation); (ii) incising the mucosa without fibrosis; (iii) understanding characteristics of various cutting devices, and changing other devices in difficult situations. In these ways we can remove the majority of the recurrent tumors en bloc. Hence, we consider that ESD is a very effective treatment which achieves excellent en bloc and complete resection rates and enables patients with intramucosal gastric tumors to a recurrent‐free survival even in recurrent tumors.     

Natural history of vascular calcification in dialysis and transplant patients

Nephrol Dial Transplant 2004; 19:     

Health-related quality of life among persons living in Japan with a permanent colostomy.

OBJECTIVE: To compare the health-related quality of life (HRQOL) of persons with a permanent colostomy to that of the general Japanese population and explore the factors influencing HRQOL. DESIGN: A cross-sectional survey. SETTING AND SUBJECTS: A total of 255 persons with an ostomy who attended a meeting of the Japan Ostomy Association in the Kanto region of Japan. INSTRUMENTS: The HRQOL was assessed using Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), Japanese version 1.2. Factors potentially influencing the HRQOL were age, sex, marital status, employment status, number of people in the household, time since colostomy, and diagnosis. METHODS: Questionnaires were distributed to the subjects and SF-36 scores were determined and compared with the corresponding national-norm data by Wilcoxon signed rank sum test. A logistic regression analysis was used to explore the influencing factors. RESULTS: The questionnaire response rate was 66.7%. Subjects with a urostomy or an ileostomy and those with missing data were excluded. Data from 102 subjects with a permanent colostomy were analyzed. The subjects' scores were significantly lower than the national-norm scores in the role-physical and social functioning scales. Being employed was associated with significantly lower scores or associated with a tendency toward lower scores. CONCLUSIONS: Scores in two scales in these subjects were lower than those of national-norm scores. Being employed had a negative impact on the HRQOL of subjects with a permanent colostomy. The results of this study provide reference data for future research and underscore the importance of support for persons with a colostomy.     

Maintenance of Androgen-, Glucocorticoid- or Estrogen-responsive Growth in Shionogi Carcinoma 115 Subline Sustained in Castrated Mice with High Dose of Estrogen for 30 Generations (3 Years)

Shionogi carcinoma 115 (SC115), an androgen-dependent mouse mammary tumor, rapidly loses its androgen responsiveness after androgen withdrawal. The growth of this tumor can also be stimulated by high doses of estrogen or glucocorticoid. In the present study, the maintenance of hormone-responsive growth of SC115 tumors with a high dose of estrogen was examined in castrated male mice using an SCI 15 subline obtained by serial transplantations of SCI 15 tumors in estrogen-treated castrated mice for 3 years (30 generations) (subline E₂). Seed tumors from both SC115 and subline E₂ could rapidly grow in castrated mice given daily injections of testosterone propionate (TP), 17β-estradiol (E₂), or dexamethasone (Dex) (100 μg/mouse/day) but not in those given vehicle alone. Although SCI 15 and subline-E₂ tumors grown with TP or Dex showed temporary regression after steroid withdrawal, the tumors grown with E₂ did not show such temporary regression. The TP-, E₂-, or Dex-induced growth of subline-E₂ tumors was almost the same as that of the original SCI 15 tumors. However, responsiveness to androgen, estrogen or glucocorticoid of both tumors disappeared within one passage in steroid-depleted castrated mice. The present findings demonstrate that the loss of responsiveness to androgen as well as to high doses of estrogen or glucocorticoid of SCI 15 tumors can be prevented in castrated mice not only with androgen but also with high doses of estrogen.     

Transfer of occupational health problems from a developed to a developing country: Lessons from the Japan–South Korea experience

Many corporations move their manufacturing facilities or technologies from developed to developing countries. Stringent regulations have made it costly for industries to operate in developed, industrialized countries. In addition, labor costs are high in these countries, and there is increasing awareness among the general public of the health risks associated with industry. The relocation of hazardous industries to developing countries is driven by economic considerations: high unemployment, a cheaper labor force, lack of regulation, and poor enforcement of any existing regulations make certain countries attractive to business. The transfer of certain industries from Japan to Korea has also brought both documented occupational diseases and a new occupational disease caused by chemicals without established toxicities. Typical examples of documented occupational diseases are carbon disulfide poisoning in the rayon manufacturing industry, bladder cancer in the benzidine industry, and mesothelioma in the asbestos industry. A new occupational disease due to a chemical without established toxicities is 2‐bromopropane poisoning. These examples suggest that counter‐measures are needed to prevent the transfer of occupational health problems from a developed to a developing country. Corporate social responsibility should be emphasized, close inter‐governmental collaboration is necessary and cooperation among non‐governmental organizations is helpful. Am. J. Ind. Med. 52:625–632, 2009. © 2009 Wiley‐Liss, Inc.