Faculty Bibliography

We have examined the differential binding of Hck and Fyn to HIV-1 Nef to elucidate the structural basis of SH3 binding affinity and specificity. Full-length Nef bound to Hck SH3 with the highest affinity reported for an SH3-mediated interaction (KD 250 nM). In contrast to Hck, affinity of the highly homologous Fyn SH3 for Nef was too weak (KD > 20 microM) to be accurately determined. We show that this distinct specificity lies in a variable loop, the 'RT loop', positioned close to conserved SH3 residues implicated in the binding of proline-rich (PxxP) motifs. A mutant Fyn SH3 with a single amino acid substitution (R96I) in its RT loop had an affinity (KD 380 nM) for Nef comparable with that of Hck SH3. Based on additional mutagenesis studies we propose that the selective recognition of Nef by Hck SH3 is determined by hydrophobic interactions involving an isoleucine residue in its RT loop. Although Nef contains a PxxP motif which is necessary for the interaction with Hck SH3, high affinity binding was only observed for intact Nef protein. The binding of a peptide containing the Nef PxxP motif showed > 300-fold weaker affinity for Hck SH3 than full-length Nef.

We began implementation of a medical decision support system (MDSS) at the Columbia-Presbyterian Medical Center (CPMC) using the Arden Syntax in 1992. The Clinical Event Monitor which executes the Medical Logic Modules (MLMs) runs on a mainframe computer. Data are stored in a relational database and accessed via PL/I programs known as Data Access Modules (DAMs). Currently we have 18 clinical, 12 research and 10 administrative MLMs. On average, the clinical MLMs generate 50357 simple interpretations of laboratory data and 1080 alerts each month. The number of alerts actually read varies by subject of the MLM from 32.4% to 73.5%. Most simple interpretations are not read at all. A significant problem of MLMs is maintenance, and changes in laboratory testing and message output can impair MLM execution significantly. We are now using relational database technology and coded MLM output to study the process outcome of our MDSS.

David Oshinsky reviews the biography "Man of the People: A Life of Harry S. Truman" by Alonzo L. Hamby

David Oshinsky reviews the book "The Populist Persuasion: An American History" by Michael Kazin

Not Without Honor: The History of American Anti-Communism by Richard Gid Powers

Depression is common and treatable, but the burden of awareness is the patient's. It is the physical symptoms of depression that bring people into a doctor's office