Icahn School of Medicine at Mount Sinai

About: Icahn School of Medicine at Mount Sinai is a education organization based out in New York, New York, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 37488 authors who have published 76057 publications receiving 3704104 citations. The organization is also known as: Mount Sinai School of Medicine.

Von Hippel–Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma

Abstract: Von Hippel-Lindau disease (VHL) is an autosomal dominant disorder with inherited susceptibility to various forms of cancer, including hemangioblastomas of the central nervous system, phaeochromocytomas, pancreatic malignancies, and renal cell carcinomas. Renal cell carcinomas constitute a particularly frequent cause of death in this disorder, occurring as bilateral and multifocal tumours, and presenting at an earlier age than in sporadic, non-familial cases of this tumour type. We report here that the VHL gene is linked to the locus encoding the human homologoue of the RAF1 oncogene, which maps to chromosome 3p25 (ref. 4). Crossovers with the VHL locus suggest that the defect responsible for the VHL phenotype is not a mutation in the RAF1 gene itself. An alternative or prior event to oncogene activation in tumour formation may be the inactivation of a putative 'tumour suppressor' which can be associated with both the inherited and sporadic forms of the cancer. Sporadic renal cell carcinomas have previously been associated with the loss of regions on chromosome 3p (refs 5, 6). Consequently, sporadic and VHL-associated forms of renal cell carcinoma might both result from alterations causing loss of function of the same 'tumour suppressor' gene on this chromosome.

Essential Role of the Histone Methyltransferase G9a in Cocaine-induced Plasticity

Abstract: Cocaine-induced alterations in gene expression cause changes in neuronal morphology and behavior that may underlie cocaine addiction. In mice, we identified an essential role for histone 3 lysine 9 (H3K9) dimethylation and the lysine dimethyltransferase G9a in cocaine-induced structural and behavioral plasticity. Repeated cocaine administration reduced global levels of H3K9 dimethylation in the nucleus accumbens. This reduction in histone methylation was mediated through the repression of G9a in this brain region, which was regulated by the cocaine-induced transcription factor DeltaFosB. Using conditional mutagenesis and viral-mediated gene transfer, we found that G9a down-regulation increased the dendritic spine plasticity of nucleus accumbens neurons and enhanced the preference for cocaine, thereby establishing a crucial role for histone methylation in the long-term actions of cocaine.

The Inner Life of Physicians and Care of the Seriously Ill

Abstract: Seriously ill persons are emotionally vulnerable during the typically protracted course of an illness. Physicians respond to such patients’ needs and emotions with emotions of their own, which may reflect a need to rescue the patient, a sense of failure and frustration when the patient’s illness progresses, feelings of powerlessness against illness and its associated losses, grief, fear of becoming ill oneself, or a desire to separate from and avoid patients to escape these feelings. These emotions can affect both the quality of medical care and the physician’s own sense of well-being, since unexamined emotions may also lead to physician distress, disengagement, burnout, and poor judgment. In this article, which is intended for the practicing, nonpsychiatric clinician, we describe a model for increasing physician selfawareness, which includes identifying and working with emotions that may affect patient care. Our approach is based on the standard medical model of risk factors, signs and symptoms, differential diagnosis, and intervention. Although it is normal to have feelings arising from the care of patients, physicians should take an active role in identifying and controlling those emotions.

Complexity in Biological Signaling Systems

Abstract: Biological signaling pathways interact with one another to form complex networks. Complexity arises from the large number of components, many with isoforms that have partially overlapping functions; from the connections among components; and from the spatial relationship between components. The origins of the complex behavior of signaling networks and analytical approaches to deal with the emergent complexity are discussed here.

APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline

Abstract: Vascular contributions to dementia and Alzheimer's disease are increasingly recognized1-6. Recent studies have suggested that breakdown of the blood-brain barrier (BBB) is an early biomarker of human cognitive dysfunction7, including the early clinical stages of Alzheimer's disease5,8-10. The E4 variant of apolipoprotein E (APOE4), the main susceptibility gene for Alzheimer's disease11-14, leads to accelerated breakdown of the BBB and degeneration of brain capillary pericytes15-19, which maintain BBB integrity20-22. It is unclear, however, whether the cerebrovascular effects of APOE4 contribute to cognitive impairment. Here we show that individuals bearing APOE4 (with the e3/e4 or e4/e4 alleles) are distinguished from those without APOE4 (e3/e3) by breakdown of the BBB in the hippocampus and medial temporal lobe. This finding is apparent in cognitively unimpaired APOE4 carriers and more severe in those with cognitive impairment, but is not related to amyloid-β or tau pathology measured in cerebrospinal fluid or by positron emission tomography23. High baseline levels of the BBB pericyte injury biomarker soluble PDGFRβ7,8 in the cerebrospinal fluid predicted future cognitive decline in APOE4 carriers but not in non-carriers, even after controlling for amyloid-β and tau status, and were correlated with increased activity of the BBB-degrading cyclophilin A-matrix metalloproteinase-9 pathway19 in cerebrospinal fluid. Our findings suggest that breakdown of the BBB contributes to APOE4-associated cognitive decline independently of Alzheimer's disease pathology, and might be a therapeutic target in APOE4 carriers.