Single repeat deletion in ApoA-I blocks cholesterol esterification and results in rapid catabolism of delta6 and wild-type ApoA-I in transgenic mice.

The deletion mutation Delta6 apolipoprotein A-I lacks residues 143-164 or repeat 6 in the mature apoA-I protein. In vitro studies show this mutation dramatically reduces the rate of lecithin:cholesterol acyltransferase (LCAT) catalyzed cholesterol esterification. The present study was initiated to investigate the effect of this mutation on in vivo high density lipoprotein (HDL) cholesterol esterification and metabolism.

Understanding variability in physician ratings of the appropriateness of coronary angiography after acute myocardial infarction.

We examined variability in ratings of the appropriateness of coronary angiography for 890 clinical scenarios (indications) after an acute myocardial infarction (AMI) from a nine-member multispecialty panel as a function of panel characteristics and the attributes of the clinical indications. We documented a substantial degree of reliability in the ratings. However, key differences among the experts in terms of both their overall propensity to score high and their beliefs regarding the impact of clinical factors on appropriateness were identified.

Applying Bayesian ideas to the development of medical guidelines.

Measurements of the quality of health care, in particular the underuse and overuse of medical therapies and diagnostic tests, often involve employment of medical practice guidelines to assess the appropriateness of treatments. This paper presents a case study of a Bayesian analysis for the development of medical guidelines based on expert opinion, using ordinal categorical rater data. We develop guidelines for the use of coronary angiography following an acute myocardial infarction (AMI) for 890 clinical indications using statistical models fit to appropriateness ratings obtained from a nine-member expert panel.

Rating the appropriateness of coronary angiography--do practicing physicians agree with an expert panel and with each other?

Background: Evaluations of the appropriateness of medical care are important to monitor the quality of care and to contain costs and enhance safety by reducing inappropriate care. Experts' views are usually incorporated into evaluations of appropriateness. However, practicing physicians may not concur with these views, and physicians' clinical backgrounds may influence their beliefs.

The hydrophobic face orientation of apolipoprotein A-I amphipathic helix domain 143-164 regulates lecithin:cholesterol acyltransferase activation.

Apolipoprotein A-I (apoA-I) activates the plasma enzyme lecithin:cholesterol acyltransferase (LCAT), catalyzing the rapid conversion of lipoprotein cholesterol to cholesterol ester. Structural mutants of apoA-I have been used to study the details of apoA-I-LCAT-catalyzed cholesterol ester formation. Several studies have shown that the alpha-helical segments corresponding to amino acids 143-164 and 165-186 (repeats 6 and 7) are essential for LCAT activation.

Recombinant adeno-associated virus (AAV-CFTR) vectors do not integrate in a site-specific fashion in an immortalized epithelial cell line.

Adeno-associated virus-2 (AAV) can integrate in a site-specific manner to human chromosome 19 and is currently in phase I clinical trials for cystic fibrosis (CF) at Johns Hopkins Hospital. The goal of this study was to determine the fate of recombinant AAV containing the CFTR cDNA (AAV-CFTR) in an immortalized pseudotetraploid CF bronchial epithelial cell line (IB3-1) established from a patient with CF. Fluorescence in situ hybridization (FISH) and Southern blotting of DNA from IB3-1 cells infected with wild-type (wt) or recombinant AAV-CFTR were performed.