Johns Hopkins University School of Medicine

About: Johns Hopkins University School of Medicine is a healthcare organization based out in Baltimore, Maryland, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 44277 authors who have published 79222 publications receiving 4788882 citations.

Inactivation of LKB1/STK11 Is a Common Event in Adenocarcinomas of the Lung

Abstract: Frequent losses of chromosome 19p have recently been observed in sporadic lung adenocarcinomas, targeting the location of a critical tumor suppressor gene. Here we performed fine mapping of the short arm of chromosome 19 and found that the LKB1/STK11 gene mapped in the minimal-deleted region. Because germ-line mutations at LKB1/STK11 result in the Peutz-Jeghers syndrome and an increased risk of cancer, we performed a detailed genetic screen of the LKB1/STK11 gene in lung tumors. We detected a high frequency of somatic alterations (mainly nonsense mutations) in primary lung adenocarcinomas and in lung cancer cell lines. Thus, our findings demonstrate for the first time that LKB1/STK11 inactivation is a very common event and may be integrally involved in the development of sporadic lung adenocarcinoma.

Cyclic GMP-Activated Conductance of Retinal Photoreceptor Cells

Abstract: This review examines the ionic conductance that generates the electrical response to light in rods and cones of the vertebrate retina. In visual physiology this conductance is commonly referred to as the light-regulated or light-sensitive conductance. The designation cGMP-activated con­ ductance is perhaps preferable because it is now known to be controlled by guanosine 3',5'-cyclic monophosphate (abbreviated here as cGMP); light modulates the conductance solely by changing the intracellular con­ centration of cGMP. We shall use the different terms for the conductance interchangeably. A review on this channel seems timely in view of the speed of recent progress in understanding its nature and function. The conductance is interesting for several reasons. First, it has physio­ logical properties that are beautifully suited for its role in visual trans­ duction. Second, it is the first ionic channel found whose gating is directly controlled by a cyclic nucleotide. Third, there are indications that the conductance may belong to a new family of ion channels involved in signal

Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures

Abstract: Tumor-infiltrating immune cells have been linked to prognosis and response to immunotherapy; however, the levels of distinct immune cell subsets and the signals that draw them into a tumor, such as the expression of antigen presenting machinery genes, remain poorly characterized. Here, we employ a gene expression-based computational method to profile the infiltration levels of 24 immune cell populations in 19 cancer types. We compare cancer types using an immune infiltration score and a T cell infiltration score and find that clear cell renal cell carcinoma (ccRCC) is among the highest for both scores. Using immune infiltration profiles as well as transcriptomic and proteomic datasets, we characterize three groups of ccRCC tumors: T cell enriched, heterogeneously infiltrated, and non-infiltrated. We observe that the immunogenicity of ccRCC tumors cannot be explained by mutation load or neo-antigen load, but is highly correlated with MHC class I antigen presenting machinery expression (APM). We explore the prognostic value of distinct T cell subsets and show in two cohorts that Th17 cells and CD8+ T/Treg ratio are associated with improved survival, whereas Th2 cells and Tregs are associated with negative outcomes. Investigation of the association of immune infiltration patterns with the subclonal architecture of tumors shows that both APM and T cell levels are negatively associated with subclone number. Our analysis sheds light on the immune infiltration patterns of 19 human cancers and unravels mRNA signatures with prognostic utility and immunotherapeutic biomarker potential in ccRCC.

A Comparison of Levomethadyl Acetate, Buprenorphine, and Methadone for Opioid Dependence

Abstract: Background Opioid dependence is a chronic, relapsing disorder with important public health implications. Methods In a 17-week randomized study of 220 patients, we compared levomethadyl acetate (75 to 115 mg), buprenorphine (16 to 32 mg), and high-dose (60 to 100 mg) and low-dose (20 mg) methadone as treatments for opioid dependence. Levomethadyl acetate and buprenorphine were administered three times a week. Methadone was administered daily. Doses were individualized except in the group assigned to low-dose methadone. Patients with poor responses to treatment were switched to methadone. Results There were 55 patients in each group; 51 percent completed the trial. The mean (±SE) number of days that a patient remained in the study was significantly higher for those receiving levomethadyl acetate (89±6), buprenorphine (96±4), and high-dose methadone (105±4) than for those receiving low-dose methadone (70±4, P<0.001). Continued participation in the study was also significantly more frequent among patients rec...