Adhesion molecules play important roles in immune reactions and inflammatory processes and may constitute attractive targets for immunomodulatory approaches. In this study, blocking mAbs against a series of adhesion molecules were tested for their therapeutic effect on developing arthritis in a mouse model. MAbs were given for a period of 4 weeks at the time of exspected incidence of visible disease symptoms, i.e. 4 weeks after priming with collagen type II. A significant reduction of incidence down to values of 13% and 29% of the controls was obtained with mAbs against CD44 and alpha 4-integrin, respectively, during an observation time of 13 weeks. MAbs against CD4 and LFA-1 resulted only in weaker, non-significant effects or a delay in the incidence. MAbs against other molecules including L-selectin, ICAM-1 or VCAM-1 were not effective. The development of antibodies against collagen type II, collagen type I, proteoglycans and the immunogen, bovine collagen type II was affected by mAb treatment to a different extent. In this case, the anti CD4 mAb was the most effective, followed by the anti alpha 4-antibodies in most cases, whereas anti CD44 showed less clear effects on the development of humoral responses. In a skin delayed type hypersensitivity model analyzed for comparison, mAbs against LFA-1/ICAM-1 and alpha 4-integrin showed the largest effects on ear swelling. These data show that mAbs against several adhesion molecules are able to block selectively distinct aspects of immune reactions, and that CD44 and alpha 4-integrins could be promising targets for an immunotherapy of rheumatoid arthritis with receptor-interfering agents.
Background: Radiation therapy to the mediastinum and breast can be associated with cardiac complications. Cardiac damage may manifest early during radiation therapy or occur late, years after radiation therapy has been finished. Hypothesis: Myocardial damage is associated with the release of both troponin I (TnI) and brain natriuretic peptide (BNP). The current study sought to determine whether radiation treatment to the mediastinum and breast leads to the release of cardiac biomarkers. Methods: The study comprised 23 patients: 18 with lung cancer and 5 with breast cancer. Radiation therapy was performed for up to 6 weeks. Total radiation dose was >45 Gy in each patient with a dose of 1.8 Gy per fraction. Blood samples to determine TnI and BNP were taken before and once a week during radiation therapy. Echocardiography was done before and after radiation had been finished. Results: Two patients died during the study. Both TnI and BNP levels increased significantly during the study (log10 scale); however, absolute and mean values remained on a relatively low level (mean preradiation and postradiation TnI: 0.007 ± 0.008, 0.014 ± 0.01 ng/ml; mean preradiation and postradiation BNP: 123 ± 147, 159 ± 184 pg/ml). Conclusion: Radiation therapy leads to cardiac cell damage and changes in the left ventricular loading conditions as suggested by a significant increase of the cardiac biomarkers TnI and BNP. Determination of serum levels seems to be superior to echocardiography in detecting radiation-induced cardiac damage. Serial measurements of cardiac biomarkers may facilitate the management of patients undergoing radiation therapy and may help to define subgroups at high risk of developing heart failure.
DNA-content and size of the nuclear areas in different zones of malignant melanomas of different histological types and in dysplastic naevi were measured in order to provide information on the histogenesis and proliferative behaviour of human malignant melanoma. The results were compared with those from normal epidermis, common naevi, and reactive melanocytic hyperplasias. The mitotic index of melanomas--divided into different topographic zones in an analogous way--was also determined. The DNA-histographs of all naevi and reactive melanocytic hyperplasias showed a diploid maximum, but the dysplastic naevi had a larger proportion of nuclei with hyperdiploid and tetraploid DNA-content, indicating an increased proliferative activity. The mean values (X) of nuclear areas in dysplastic naevi (DN) were about the same as in common naevi (CN) and slightly lower than in superficial spreading melanomas (SSM). The coefficient of variability (cv) as an indicator of anisokaryosis was markedly higher in DN (27.8) and SSM (29.3) than in CN (20.2). In DNA-content we found similar results: almost no difference in mean values, but DN taking an intermediate position between CN and SSM with respect to cv (CN: 12.3; DN: 21.0; SSM: 36.6). There was no unequivocal evidence in these data for DN being a precancerous stage. Superficial melanomas with a nodular component ("SSM/NM") differed from SSM and NM by increased DNA-content and greater variability of nuclear areas and showed the clearest features of malignancy in their DNA-histographs. The mitotic indices had rather low values in SSM and intraepidermal marginal zones of "SSM/NM" on one hand and markedly higher values in NM and nodular parts of "SSM/NM" on the other. The highest mitotic counts were found in the three investigated metastases.
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