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 & Cancer. The organization has 44277 authors who have published 79222 publications receiving 4788882 citations.

New uses for old drugs

Abstract: It takes too long and costs too much to bring new drugs to market. So let's beef up efforts to screen existing drugs for new uses, argue Curtis R. Chong and David J. Sullivan Jr. Drug rediscovery is becoming big business. It is so costly to bring a new drug to market that drug companies are looking at their back catalogues and patent expirations with a new eye. As Curtis R. Chong and David J. Sullivan Jr explain, the screening of existing drugs for new activities is a valuable short-cut between the lab and the clinic. And a comprehensive screening campaign could be particularly useful in uncovering treatments for neglected diseases.

Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons.

Abstract: PURPOSE. To compare the number of retinal ganglion cells (RGCs) topographically mapped with specific visual field threshold test data in the same eyes among glaucoma patients. METHODS. Seventeen eyes of 13 persons with well-documented glaucoma histories and Humphrey threshold visual field tests (San Leandro, CA) were obtained from eye banks. RGC number was estimated by histologic counts of retinal sections and by counts of remaining axons in the optic nerves. The locations of the retinal samples corresponded to specific test points in the visual field. The data for glaucoma patients were compared with 17 eyes of 17 persons who were group matched for age, had no ocular history, and had normal eyes by histologic examination. RESULTS. The mean RGC loss for the entire retina averaged 10.2%, indicating that many eyes had early glaucoma damage. RGC body loss averaged 35.7% in eyes with corrected pattern SD probability less than 0.5%. When upper to lower retina RGC counts were compared with their corresponding visual field data within each eye, a 5-dB loss in sensitivity was associated with 25% RGC loss. For individual points that were abnormal at a probability less than 0.5%, the mean RGC loss was 29%. In control eyes, the loss of RGCs with age was estimated as 7205 cells per year in persons between 55 and 95 years of age. In optic nerves from glaucoma subjects, smaller axons were significantly more likely to be present than larger axons (R 2 = 0.78, P < 0.001). CONCLUSIONS. At least 25% to 35% RGC loss is associated with statistical abnormalities in automated visual field testing. In addition, these data corroborate previous findings that RGCs with larger diameter axons preferentially die in glaucoma.

Executive Summary: 2013 IDSA Clinical Practice Guideline for Vaccination of the Immunocompromised Host

Abstract: An international panel of experts prepared an evidenced-based guideline for vaccination of immunocompromised adults and children. These guidelines are intended for use by primary care and subspecialty providers who care for immunocompromised patients. Evidence was often limited. Areas that warrant future investigation are highlighted.

Oncogenic forms of p53 inhibit p53-regulated gene expression

Abstract: Mutant forms of the gene encoding the tumor suppressor p53 are found in numerous human malignancies, but the physiologic function of p53 and the effects of mutations on this function are unknown. The p53 protein binds DNA in a sequence-specific manner and thus may regulate gene transcription. Cotransfection experiments showed that wild-type p53 activated the expression of genes adjacent to a p53 DNA binding site. The level of activation correlated with DNA binding in vitro. Oncogenic forms of p53 lost this activity. Moreover, all mutants inhibited the activity of coexpressed wild-type p53, providing a basis for the selection of such mutants during tumorigenesis.

Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice

Abstract: To determine the role of brain-derived neurotrophic factor (BDNF) in the enhancement of hippocampal neurogenesis resulting from dietary restriction (DR), heterozygous BDNF knockout (BDNF +/-) mice and wild-type mice were maintained for 3 months on DR or ad libitum (AL) diets Mice were then injected with bromodeoxyuridine (BrdU) and killed either 1 day or 4 weeks later Levels of BDNF protein in neurons throughout the hippocampus were decreased in BDNF +/- mice, but were increased by DR in wild-type mice and to a lesser amount in BDNF +/- mice One day after BrdU injection the number of BrdU-labeled cells in the dentate gyrus of the hippocampus was significantly decreased in BDNF +/- mice maintained on the AL diet, suggesting that BDNF signaling is important for proliferation of neural stem cells DR had no effect on the proliferation of neural stem cells in wild-type or BDNF +/- mice Four weeks after BrdU injection, numbers of surviving labeled cells were decreased in BDNF +/- mice maintained on either AL or DR diets DR significantly improved survival of newly generated cells in wild-type mice, and also improved their survival in BDNF +/- mice, albeit to a lesser extent The majority of BrdU-labeled cells in the dentate gyrus exhibited a neuronal phenotype at the 4-week time point The reduced neurogenesis in BDNF +/- mice was associated with a significant reduction in the volume of the dentate gyrus These findings suggest that BDNF plays an important role in the regulation of the basal level of neurogenesis in dentate gyrus of adult mice, and that by promoting the survival of newly generated neurons BDNF contributes to the enhancement of neurogenesis induced by DR