Expression of major histocompatibility complex class I and class II antigens in canine masticatory muscle myositis

Studies in human immune-mediated inflammatory myopathies have documented expression of major histocompatibility complex class I (MHC class I) and class II (MHC class II) antigens on muscle fiber membranes in the presence or absence of cellular infiltration. Here we evaluate the presence and distribution of these antigens in canine masticatory muscle myositis, an immune-mediated inflammatory myopathy. Twelve samples of temporalis and masseter muscles from dogs with a clinical diagnosis of canine masticatory muscle myositis were examined by immunohistochemistry and double-immunofluorescence confocal microscopy. MHC class I and class II antigens were expressed in muscle fibers independent of inflammatory cell infiltration. Furthermore MHC class I and class II antigens were expressed on the sarcolemma and co-localized with dystrophin. Our results suggest that MHC class I and class II expression in canine masticatory muscle myositis may play a role in the initiation and maintenance of the pathological condition, rather than just a consequence of a preceding local inflammation.     

The HER2 World: Better Treatment Selection for Better Outcome

Understanding the mechanisms of trastuzumab efficacy and resistance is a step toward optimizing treatment outcome in HER2-positive breast carcinoma patients. Preclinical studies have indicated different trastuzumab antitumor mechanisms, that is, cytostatic inhibition of tumor proliferation, antibody-dependent cell cytotoxicity, and inhibition of HER2-mediated DNA repair. Clinical studies point to the clinical setting dependence of these mechanisms, with antibody-dependent cell cytotoxicity predominating when trastuzumab is used as monotherapy in neoadjuvant and metastatic settings, whereas inhibition of DNA repair predominates in neoadjuvant and adjuvant settings involving concomitant trastuzumab and chemotherapy; in sequential protocols, the antibody appears to act primarily through cytostatic activity by inhibiting HER2-mediated cell proliferation. Because the mechanisms of resistance to trastuzumab likely depend directly on those of its antitumor activity, resistance mechanisms must also be considered with respect to the different clinical settings. Moreover, the response to this reagent should be assessed according to its ability to induce tumor cytotoxic or cytostatic activity.     

Regulation of breast cancer response to chemotherapy by fibulin-1

Doxorubicin treatment was found to augment the expression of the extracellular matrix (ECM) protein fibulin-1 in cultured human breast cancer cell lines and in MDA-MB-361 tumors grown in athymic mice. Doxorubicin was also found to augment tumor expression of the fibulin-1-binding proteins fibronectin and laminin-1. Growth of breast cancer cell lines on Matrigel, an ECM extract containing fibulin-1 and laminin-1, resulted in lower levels of doxorubicin-induced apoptosis as compared with controls. Moreover, tumors formed by injection of athymic mice with MDA-MB-361 cells mixed with Matrigel were significantly more doxorubicin resistant and displayed lower levels of apoptosis compared with those that formed in the absence of Matrigel. Monoclonal antibodies against fibulin-1 reversed Matrigel-dependent doxorubicin resistance. Furthermore, small interfering RNA-mediated suppression of fibulin-1 expression in breast cancer cells resulted in a 10-fold increase in doxorubicin sensitivity as compared with control cells. Together, these findings point to a role for fibulin-1 in breast cancer chemoresistance.     

Being informed,demanding and responsible consumers of assistive technology: an educational issue

Purpose : Awareness and knowledge of Assistive Technology (AT) are key factors in supporting empowerment of people with disabilities. They also greatly contribute to the success of AT solutions. Based on the findings of the EUSTAT study--an international project within the Telematics Application Programme of the European Commission--this paper offers a synthesis of the guidelines developed for those who organize educational activities on AT addressed towards end-users. Results : The educational process is looked at within an empowerment perspective rather that as a mere transmission of notions. The effectiveness of education should be evaluated in relation to the increased ability of end users to make use of AT knowledge for improving their quality of life, and becoming informed, demanding and responsible consumers of AT products and services. Conclusion : To such end a number of critical factors are identified, and ways to address them are discussed. Finally, a case study is reported as an example of an effective AT educational curriculum for end-users.     

CABG in patients with left ventricular dysfunction: indications,techniques and outcomes

Ischemic chronic heart failure (CHF) represents one of the cardiovascular diseases with the worst degree of morbidity and mortality in the western world, and with the highest health care costs. Despite several studies demonstrated that surgical revascularization (CABG), especially in the presence of viable myocardium, improve heart function, and therefore, survival, the matter remains unclear and controversial. In the late 1970s, the Coronary Artery Surgery Study showed that a subgroup of patients with coronary artery disease, angina, and reduce LV function had a significant survival benefit after CABG compared to those treated medically. The key concept behind this observation was the presence of viable myocardium, which can resume function following revascularization. In contrary, the surgical treatment for ischemic heart failure (STICH) trial, which randomized patients with CAD and LV dysfunction to evidence-based medical therapy or CABG plus medical therapy, failed to demonstrate at a median follow-up of 56 months a significant difference between the CABG group and the medical therapy group in the rate of death from any cause. However, the results of the STICH extension study (STICHES) at 10 years follow-up demonstrated that CABG is associated with a significant reduction in all-cause mortality, cardiovascular mortality, and readmission for heart compared to optimal medical therapy (OMT) in patients with severe ischemic LV dysfunction. Therefore, this review discusses the available evidences in literature, from observational studies to randomized trials, including operative techniques and controversial issues, in order to better clarify the role of CABG in the current management of ischemic patients with LVD.