University of Medicine and Dentistry of New Jersey

About: University of Medicine and Dentistry of New Jersey is a based out in . It is known for research contribution in the topics: Population & Poison control. The organization has 14634 authors who have published 19610 publications receiving 1041794 citations.

Activation of Mst1 causes dilated cardiomyopathy by stimulating apoptosis without compensatory ventricular myocyte hypertrophy.

Abstract: Activation of mammalian sterile 20-like kinase 1 (Mst1) by genotoxic compounds is known to stimulate apoptosis in some cell types. The importance of Mst1 in cell death caused by clinically relevant pathologic stimuli is unknown, however. In this study, we show that Mst1 is a prominent myelin basic protein kinase activated by proapoptotic stimuli in cardiac myocytes and that Mst1 causes cardiac myocyte apoptosis in vitro in a kinase activity-dependent manner. In vivo, cardiac-specific overexpression of Mst1 in transgenic mice results in activation of caspases, increased apoptosis, and dilated cardiomyopathy. Surprisingly, however, Mst1 prevents compensatory cardiac myocyte elongation or hypertrophy despite increased wall stress, thereby obscuring the use of the Frank-Starling mechanism, a fundamental mechanism by which the heart maintains cardiac output in response to increased mechanical load at the single myocyte level. Furthermore, Mst1 is activated by ischemia/reperfusion in the mouse heart in vivo. Suppression of endogenous Mst1 by cardiac-specific overexpression of dominant-negative Mst1 in transgenic mice prevents myocyte death by pathologic insults. These results show that Mst1 works as both an essential initiator of apoptosis and an inhibitor of hypertrophy in cardiac myocytes, resulting in a previously unrecognized form of cardiomyopathy.

Representation of African-Americans, Hispanics, and Whites in National Cancer Institute Cancer Treatment Trials

Abstract: Background : The National Cancer Institute (NCI)-sponsored clinical trials cooperative groups place more than 25 000 American patients in treatment trials every year. Equal access and proportional representation of all races/ethnicities is desired. Purpose : Our objectives were to evaluate the inclusion of African-Americans, Hispanics, and non-Hispanic whites in NCI-sponsored treatment trials and to determine if there is proportional racial/ethnic representation. Methods : During the period of January 1, 1991, through June 30, 1994, 99 495 cancer patients were enrolled in clinical trials and declared themselves as non-Hispanic black, non-Hispanic white, or Hispanic (of any race). In the analysis, participants in NCI treatment trials were subdivided into three age groups : birth to 19 years, 20-49 years, and 50 or more years. The racial/ethnic composition of each of these age groups was compared with the racial/ethnic makeup of the American population with cancer. Estimates of the number of incident cancer cases per year were made for each racial/ethnic group within each age group using data from the Surveillance, Epidemiology, and End Results (SEER) Program and the 1990 Census. The percentage of all cancer patients who were in each racial/ethnic group were compared with the population that entered clinical trials. Comparisons are also made separately for patients with leukemia and breast, colorectal, lung, and prostate cancers. Results : Among patients 0-19 years old, 20-49 years old, and 50 years old or older there is relatively proportional representation of non-Hispanic blacks, Hispanics, and non-Hispanic whites in trials. It is noted that more than 70% of cancer patients aged 0-19 years are estimated to enter cooperative group clinical trials compared with 4.0% of cancer patients aged 20-49 years and 1.5% of patients aged 50 years or older. Conclusions : Accrual of American cancer patients to NCI-sponsored treatment trials generally parallels the incident burden of disease among non-Hispanic African-Americans, Hispanics, and non-Hispanic whites. Implications : This study shows that the NCI clinical trials are, as a whole, racially/ethnically representative of the American population and suggests that there is equal access to NCI clinical trials.

Exacerbation of Damage and Altered NF-κB Activation in Mice Lacking Tumor Necrosis Factor Receptors after Traumatic Brain Injury

Abstract: Tumor necrosis factor α (TNFα) is widely expressed in both neurons and glia and has been shown to be upregulated after traumatic brain injury (TBI). TNFα receptor activation results in activation of the transcription factor nuclear factor κB (NF-κB), which may serve an antiapoptotic role via the induction of target genes manganese superoxide dismutase (MnSOD) and/or calbindin. In the present study, we used a controlled cortical impact model of TBI with pertinent lines of transgenic mice to combine both morphological characterization and molecular analysis to elucidate the role of TNFα after TBI. Measurements of both the lesion volume and the blood–brain barrier breach indicated exacerbations in mice rendered genetically deficient in both the p55 and p75 TNFα receptors (TNFR-KO) compared with wild-type animals. Additionally, animals genetically altered to overexpress MnSOD showed a significant decrease in lesion volume compared with that of control littermates, whereas no alterations were observed in mice lacking the calcium-binding protein calbindin D28k. Analysis of NF-κB activation and relative levels of MnSOD revealed delayed responses in the injured cortex of TNFR-KO animals compared with wild-type animals, implying that endogenous TNFα may be neuroprotective after TBI.

Invited review: Physiological and pathophysiological responses to intermittent hypoxia.

Abstract: This mini-review summarizes the physiological adaptations to and pathophysiological consequences of intermittent hypoxia with special emphasis given to the pathophysiology associated with obstructive sleep apnea. Intermittent hypoxia is an effective stimulus for evoking the respiratory, cardiovascular, and metabolic adaptations normally associated with continuous chronic hypoxia. These adaptations are thought by some to be beneficial in that they may provide protection against disease as well as improve exercise performance in athletes. The long-term consequences of chronic intermittent hypoxia may have detrimental effects, including hypertension, cerebral and coronary vascular problems, developmental and neurocognitive deficits, and neurodegeneration due to the cumulative effects of persistent bouts of hypoxia. Emphasis is placed on reviewing the available data on intermittent hypoxia, making extensions from applicable information from acute and chronic hypoxia studies, and pointing out major gaps in information linking the genomic and cellular responses to intermittent hypoxia with physiological or pathophysiological responses.