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.

Clinical Response to Aminoglycoside Therapy: Importance of the Ratio of Peak Concentration to Minimal Inhibitory Concentration

Abstract: In an examination of the relationships among plasma aminoglycoside concentrations, the minimal inhibitory concentration (MIC) for the infecting organism, and therapeutic outcome, data were analyzed from 236 patients with gram-negative bacterial infections who were participants in four clinical trials of gentamicin, tobramycin, and amikacin. Clinical response to therapy occurred in 188 (80%) patients. Elevated maximal and mean peak aminoglycoside concentration/MIC ratios were strongly associated with clinical response (P less than .00001 and P less than .0001, respectively). A graded dose-response effect was found between an increasing maximal peak concentration/MIC ratio and clinical response. By logistic regression the peak concentration/MIC ratios were associated significantly with clinical response after adjustment for underlying severity of illness and other factors correlated with response. These results demonstrate that a high peak concentration relative to the MIC for the infecting organism is a major determinant of the clinical response to aminoglycoside therapy.

Trinucleotide repeat length instability and age of onset in Huntington's disease

Abstract: The initial observation of an expanded and unstable trinucleotide repeat in the Huntington's disease gene has now been confirmed and extended in 150 independent Huntington's disease families. HD chromosomes contained 37-86 repeat units, whereas normal chromosomes displayed 11-34 repeats. The HD repeat length was inversely correlated with the age of onset of the disorder. The HD repeat was unstable in more than 80% of meiotic transmissions showing both increases and decreases in size with the largest increases occurring in paternal transmissions. The targeting of spermatogenesis as a particular source of repeat instability is reflected in the repeat distribution of HD sperm DNA. The analysis of the length and instability of individual repeats in members of these families has profound implications for presymptomatic diagnosis.

Homer: a protein that selectively binds metabotropic glutamate receptors.

Abstract: Spatial localization and clustering of membrane proteins is critical to neuronal development and synaptic plasticity. Recent studies have identified a family of proteins, the PDZ proteins, that contain modular PDZ domains and interact with synaptic ionotropic glutamate receptors and ion channels. PDZ proteins are thought to have a role in defining the cellular distribution of the proteins that interact with them. Here we report a novel dendritic protein, Homer, that contains a single, PDZ-like domain and binds specifically to the carboxy terminus of phosphoinositide-linked metabotropic glutamate receptors. Homer is highly divergent from known PDZ proteins and seems to represent a novel family. The Homer gene is also distinct from members of the PDZ family in that its expression is regulated as an immediate early gene and is dynamically responsive to physiological synaptic activity, particularly during cortical development. This dynamic transcriptional control suggests that Homer mediates a novel cellular mechanism that regulates metabotropic glutamate signalling.