Moderate expression of prostate-specific membrane antigen, a tissue differentiation antigen and folate hydrolase, facilitates prostate carcinogenesis

Increased expression of PSMA, a differentiation antigen with folate hydrolase activity, is an independent marker of prostate cancer progression. Mice expressing moderate levels of human PSMA in their prostate develop PIN-like lesions by 9 months. The aim of this study was to determine whether PSMA is involved in prostate carcinogenesis and progression and, if so, the possible mechanism by which PSMA may exert its effects. Using prostates from PSMA-transgenic mice, we developed a tissue recombinant model that exhibits small atypical glands with features of adenocarcinoma. This was not observed in tissue recombinants that were composed of prostate tissues from the wild-type siblings. Cells from PSMA-transgenic tissue recombinants have the ability to form colonies in semisolid agar. PSMA may facilitate this phenotype by increasing the invasive ability of cells. Ectopic PSMA expression on PC-3 cells increased the invasive capacity of cells in in vitro invasion assays, which could be competed out by folic acid. These results suggest PSMA facilitates the development of prostate cancer, and the invasive ability of these cells may be modulated by folate levels. These findings show a novel mechanism that may contribute to the known role of folate in cancer prevention, and may lead to the use of PSMA inhibitors as novel chemopreventive agents for prostate cancer. Moreover, our model should prove useful for further dissecting pathways involved in prostate carcinogenesis and progression.     

Optimal heart failure therapy and successful cardioversion in heart failure patients with atrial fibrillation

BACKGROUND: Effectiveness, safety, and other factors associated with success of cardioversion (CV) of atrial fibrillation (AF) have not yet been evaluated in patients with reduced left ventricular ejection fraction. We studied 148 consecutive patients with left ventricular dysfunction (ejection fraction < or = 45%), who underwent electrical CV for AF in our department. The patients had New York Heart Association heart failure ranging from class II to IV. The overall CV success rate was 71%. We relied on univariate and multivariate regression and sought variables influencing success rate. Conversion success did not correlate with New York Heart Association class. Instead, we found that the greatest predictor was the degree of heart failure treatment. Patients receiving beta-blockers, angiotensin-converting enzyme inhibitors or angiotension receptor blockers, plus mineralocorticoid receptor blockers had the greatest chance for conversion success. Success was more likely in patients with coronary artery disease (91%) than in patients with nonischemic cardiomyopathy. CONCLUSIONS: Cardioversion is a safe and effective method for the restoration of sinus rhythm in patients with AF and reduced left ventricular ejection fraction. Our findings underscore the value of aggressive heart failure treatment before CV in patients with AF.     

Synergistic action of calcium ionophore A23187 and phorbol ester TPA on B-chronic lymphocytic leukemia cells

The peripheral blood mononuclear cells from 16 patients with B-chronic lymphocytic leukemia (B-CLL, n = 13), B-prolymphocytic leukemia (B-PLL, n = 2) or hairy cell leukemia (n = 1) were incubated in the presence of the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) and the calcium ionophore A23187. A synergy between these inducers was found with respect to morphological changes and B cell proliferation and differentiation. A23187 used alone did not activate the cells. B-CLL cells treated with the double stimulus acquired a plasmacytoid morphology, showed significantly higher incorporation of 3H-thymidine and 3H-uridine, and produced significantly higher amounts of monoclonal immunoglobulin compared with the same cells exposed to either of the inducers alone. These results indicate that phorbol ester and calcium ionophore act synergistically on B-CLL cells to induce proliferation and differentiation. B-PLL cells responded more vigorously to the signals provided by TPA and A23187. Previous studies showed that TPA and A23187 can mimic the two physiological second messengers diacylglycerol and inositol trisphosphate in the transduction of signals leading to cell activation, proliferation, and differentiation in normal B cells. The present findings suggest that the capacity of B- CLL and B-PLL cells to differentiate in response to signals of the second messenger pathway is intact.     

Digital Pathology Consultations—a New Era in Digital Imaging, Challenges and Practical Applications

Digital pathology has grown dramatically in the last 10 years and has created opportunities to not only support the triaging of difficult cases among specialists within an organization, but also enable remote pathology consultations with external organizations across the world. This study investigated one organization's need for a vendor agnostic Digital Pathology Consultation workflow solution that overcomes the challenges associated with the transfer of large studies across a local area network or across the Internet. The organization investigated is a large multifacility healthcare organization that consists of 20 hospitals spread across a wide geographical area. The organization has one of the largest academic pathology departments in the USA, with more than 100 diagnostic anatomic pathologists. This organization developed a set of web-based tools to support the workflow of digital pathology consultations and allow the viewing of whole slide images. The challenges and practical implementations of two different use cases are addressed: the occasional end user (professional or patient) requesting a second opinion and the external laboratory or hospital looking for an established consultative relationship with a large volume of cases. The solution presented in this study addresses the challenges associated with the distribution of large images and the lack of established imaging standards, while providing for a convenient and secure portal for pathologist report entry and distribution.     

Salivary nitric oxide levels in inflammatory periodontal disease - a case-control and interventional study

To cite this article: Int J Dent Hygiene 10 , 2012; 67–73
DOI: 10.1111/j.1601‐5037.2011.00508.x
Parwani SR, Chitnis PJ, Parwani RN. Salivary nitric oxide levels in inflammatory periodontal disease – A case‐control and interventional study. Abstract: Background: Biochemical markers of inflammatory periodontal disease present in saliva can partially determine the extent of periodontal disease. Furthermore, collection of salivary constituents is a simple and non‐invasive procedure. Nitric oxide (NO) has been linked to etiopathogenesis of inflammatory periodontal disease and is expressed in saliva. This study was conducted with the objective of estimating salivary NO levels in inflammatory periodontal diseases (gingivitis and periodontitis) and comparing these levels with control subjects. A re‐assessment of these levels was also made after providing appropriate treatment with a view to ascertain its diagnostic and prognostic values. Methods: This was a case–control as well as an interventional study including a total of 90 (30 control, 30 gingivitis and 30 periodontitis) subjects. Saliva samples were collected from each subject, and NO levels were assayed by Griess reaction. Results: NO levels were increased significantly in gingivitis and periodontitis subjects as compared with controls. There was a statistically significant decrease in the NO levels in each study group after the healing period (corresponding to the reduced clinical signs of inflammation). Our study also correlated probing pocket depths with salivary NO levels in periodontitis group where we found a positive correlation between the two. Conclusion: Salivary NO levels can be utilized as a good indicator of the inflammatory status of the periodontium, and evaluating its levels in saliva by Griess reaction on a photoelectric colorimeter is a reliable, accurate and faster method to estimate the level of inflammation in periodontal tissues.