Matise M.P.,Johnson University
Wiley Interdisciplinary Reviews: Developmental Biology | Year: 2013
The generation of neuronal diversity in the ventral spinal cord during development is a multistep process that occurs with precise and reproducible spatiotemporal order. The proper functioning of the central nervous system requires that this be carried out with extraordinary precision from the outset. Extrinsic influences such as the secreted Sonic hedgehog (SHH) protein provide positional cues that are read out genetically as specific patterns of gene expression in subsets of dividing progenitors, which is the first overt indication that they have begun to embark upon cell-type-specific differentiation programs. Cells generated from these segregated domains will ultimately share similar properties and functions. Recent work illustrates that SHH, which regulates target genes via the GLI transcription factors, directly controls a subset of progenitor fate determinant genes and that both derepression and activation play a role in shaping the differential response to this morphogen. © 2012 Wiley Periodicals, Inc.
Check J.H.,Johnson University
American Journal of Reproductive Immunology | Year: 2012
Recommendations for the use of heparin for preventing miscarriage are recently rapidly changing based on evidenced based prospective studies. At present either heparin or low molecular weight heparin (LMWH) is recommended for the antiphospholipid syndrome (APS). However criteria for diagnosing APS have become much stricter. The exact timing of the heparin is still being evaluated since it is not clear if the main therapeutic effect is in inhibition of thrombosis when the heparin could be started at the time in the first trimester when the platelets become thrombophilic or does its main role in improving implantation in which it would be started shortly before or shortly after ovulation. Possibly heparin is superior to LMWH in improving the implantation process though more studies are needed to corroborate or refute this suggestion. At present inherited thrombophilias are not considered a cause of first trimester miscarriage and thus measuring these factors are not recommended. There is no evidence that heparin has any benefit in preventing miscarriage from unexplained causes. Heparin is effective alone and there does not appear to be any extra benefit from adding aspirin (or even aspirin may negate some of its benefits). © 2012 John Wiley & Sons A/S.
White E.,Cancer Institute of New Jersey |
White E.,Johnson University |
White E.,Rutgers University
Nature Reviews Cancer | Year: 2012
Autophagy (also known as macroautophagy) captures intracellular components in autophagosomes and delivers them to lysosomes, where they are degraded and recycled. Autophagy can have two functions in cancer. It can be tumour suppressive through the elimination of oncogenic protein substrates, toxic unfolded proteins and damaged organelles. Alternatively, it can be tumour promoting in established cancers through autophagy-mediated intracellular recycling that provides substrates for metabolism and that maintains the functional pool of mitochondria. Therefore, defining the context-specific role for autophagy in cancer and the mechanisms involved will be important to guide autophagy-based therapeutic intervention. © 2012 Macmillan Publishers Limited. All rights reserved.
Hollenberg S.M.,Johnson University
American Journal of Respiratory and Critical Care Medicine | Year: 2011
Shock occurs when failure of the cardiovascular systemcompromises tissue perfusion. When fluid administration fails to restore adequate arterial pressure and organ perfusion in patients with shock, therapy with vasoactive agents should be initiated. The key to selecting among vasoactive agents is to make the choice in the context of the goals of therapy. The ultimate goals of hemodynamic therapy in shock are to restore effective tissue perfusion and to normalize cellular metabolism. The clinician needs to consider ways of achieving those goals and the mechanisms of action of potential therapies. Armed with this knowledge, it becomes easier to match the mechanism of action of a particular agent to the goals of therapy. When this is done, differences among various agents are seen primarily as differences in mechanisms of action, and discussions about which agent is "best" are transformed into consideration of which agent is best suited to implement the therapeutic strategy that has been selected in a given clinical context. Despite the complex pathophysiology of shock, use of vasoactive agents for hemodynamic support of patients with shock can be guided by an underlying approach in which clinicians define specific goals and end points, titrate therapies to those end points, and evaluate the results of their interventions on an ongoing basis. Copyright © 2011 American Thoracic Society.
Karantza V.,Johnson University |
Karantza V.,Cancer Institute of New Jersey
Oncogene | Year: 2011
Keratins are the intermediate filament (IF)-forming proteins of epithelial cells. Since their initial characterization almost 30 years ago, the total number of mammalian keratins has increased to 54, including 28 type I and 26 type II keratins. Keratins are obligate heteropolymers and, similarly to other IFs, they contain a dimeric central α-helical rod domain that is flanked by non-helical head and tail domains. The 10-nm keratin filaments participate in the formation of a proteinaceous structural framework within the cellular cytoplasm and, as such, serve an important role in epithelial cell protection from mechanical and non-mechanical stressors, a property extensively substantiated by the discovery of human keratin mutations predisposing to tissue-specific injury and by studies in keratin knockout and transgenic mice. More recently, keratins have also been recognized as regulators of other cellular properties and functions, including apico-basal polarization, motility, cell size, protein synthesis and membrane traffic and signaling. In cancer, keratins are extensively used as diagnostic tumor markers, as epithelial malignancies largely maintain the specific keratin patterns associated with their respective cells of origin, and, in many occasions, full-length or cleaved keratin expression (or lack there of) in tumors and/or peripheral blood carries prognostic significance for cancer patients. Quite intriguingly, several studies have provided evidence for active keratin involvement in cancer cell invasion and metastasis, as well as in treatment responsiveness, and have set the foundation for further exploration of the role of keratins as multifunctional regulators of epithelial tumorigenesis. © 2011 Macmillan Publishers Limited All rights reserved.