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.

Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease.

Abstract: Recent epidemiological and clinical data suggest that persons with low folic acid levels and elevated homocysteine levels are at increased risk of Alzheimer's disease (AD), but the underlying mechanism is unknown. We tested the hypothesis that impaired one-carbon metabolism resulting from folic acid deficiency and high homocysteine levels promotes accumulation of DNA damage and sensitizes neurons to amyloid β-peptide (Aβ) toxicity. Incubation of hippocampal cultures in folic acid-deficient medium or in the presence of methotrexate (an inhibitor of folic acid metabolism) or homocysteine induced cell death and rendered neurons vulnerable to death induced by Aβ. Methyl donor deficiency caused uracil misincorporation and DNA damage and greatly potentiated Aβ toxicity as the result of reduced repair of Aβ-induced oxidative modification of DNA bases. When maintained on a folic acid-deficient diet, amyloid precursor protein (APP) mutant transgenic mice, but not wild-type mice, exhibited increased cellular DNA damage and hippocampal neurodegeneration. Levels of Aβ were unchanged in the brains of folate-deficient APP mutant mice. Our data suggest that folic acid deficiency and homocysteine impair DNA repair in neurons, which sensitizes them to oxidative damage induced by Aβ.

Regulation of Adipocyte Development

Abstract: INTRODUCTION . . . • . . . . . . • . . . . . . . . . . . . . . . . . . . . . . . . . • • . . . . . . . . • . • . . . . . . • 99 CELL CULTURE MODELS FOR ADIPOCYTE DEVELOPMENT . • • . . . . . . • . • . . . . 101 Multipotent Stem-Cell Lines . • • • . • . • • • • • . • . • . • • • • • • . • • • • • • • • • . • . • • • • • . • • . 101 Preadipocyte Cell Lines . . . . . . . . • . . . . . . . . • . . . . . • • . • . . . • • • • • . . . . . • . • . . . . . . 102 EXTERNAL MODULATORS OF PREADIPOCYTE DIFFERENTIATION . . • • . • • . • 105 TIlE DEVELOPMENT PROGRAM . . . . • . . . . . . . • . . . . . . . . . . . . . . . . • • . . . . . . . • . . 106 Determination . • . • . • • • . • • . • . • . • • . . • . • . • • • . • . • • • • • • • • • • • . • • • • • • . • • • • . . • • 106 CelVCell Contact at Confluence . . . . • . . . . . . . . . . . . . . . • . . . . . . . . . • . . . . . . • . . • . 107 Induction 0/ Diff erentiation . . . . . . . . . . . . . . . . . . . . . . . . . • . . . . . . • . . . . . . . . • . . . . 107 Terminal Diff erentiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . • . 108 TRANSCRIPTIONAL CONTROL OF ADIPOCYTE GENES DURING DIFFERENTIATION . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 Trans-Acting Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . • . . . . • • . . . . . . . . • . • . . . . . 109 Expression o/Transcription Factors During Development . . . . . . . . . . . . . . . . . . . . ll8

Human hallucinogen research: guidelines for safety.

Abstract: There has recently been a renewal of human research with classical hallucinogens (psychedelics). This paper first briefly discusses the unique history of human hallucinogen research, and then reviews the risks of hallucinogen administration and safeguards for minimizing these risks. Although hallucinogens are relatively safe physiologically and are not considered drugs of dependence, their administration involves unique psychological risks. The most likely risk is overwhelming distress during drug action ('bad trip'), which could lead to potentially dangerous behaviour such as leaving the study site. Less common are prolonged psychoses triggered by hallucinogens. Safeguards against these risks include the exclusion of volunteers with personal or family history of psychotic disorders or other severe psychiatric disorders, establishing trust and rapport between session monitors and volunteer before the session, careful volunteer preparation, a safe physical session environment and interpersonal support from at least two study monitors during the session. Investigators should probe for the relatively rare hallucinogen persisting perception disorder in follow-up contact. Persisting adverse reactions are rare when research is conducted along these guidelines. Incautious research may jeopardize participant safety and future research. However, carefully conducted research may inform the treatment of psychiatric disorders, and may lead to advances in basic science.

Activity-dependent regulation of dendritic growth and patterning.

Abstract: One of the most remarkable features of the developing brain is its ability to undergo structural change in response to experience. Among the cellular elements that show this kind of plasticity are dendrites, which are the components that receive and process synaptic information. Recent observations indicate that calcium signalling in neurons can regulate dendritic growth and remodelling by several mechanisms, and these mechanisms are likely to be key mediators of structural plasticity in the developing brain.