New diagnostic tests for pulmonary embolism.

In 1990, the multicenter Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED), sponsored by the National Institutes of Health, compared the diagnostic value of the radioisotopic ventilation-perfusion lung scan (V/Q scan) with that of pulmonary angiography for the diagnosis of pulmonary embolism (PE). Despite the endurance of the radioisotopic V/Q scan as the most widely used test for evaluation of pulmonary embolism (PE), a better screening tool is clearly needed for use in the emergency department. During the past decade, several new modalities have emerged for evaluation of patients with suspected PE. We evaluate the diagnostic utility of the D-dimer test and the alveolar dead space determination as potential screening tests and of spiral computed tomography, magnetic resonance imaging, transthoracic echocardiography, and transesophageal echocardiography as potential confirmatory tests for PE. For comparison, recent data on the diagnostic utility of the alveolar-arterial oxygen gradient and the V/Q scan are included. The potential application of these new tests to a hypothetical ED population is described.

Preliminary crystallographic analysis of a Fab specific for P-glycoprotein with and without bound peptide.

The antigen-binding fragment (Fab) of anti-peptide monoclonal antibody C219 raised against the multidrug resistance associated P-glycoprotein has been crystallized with and without bound peptide. The crystals of the Fab in the absence and presence of peptide belong to space groups P2(1) and P2(1)2(1)2(1), respectively. The volumes of both crystal forms are consistent with the presence of four Fab molecules per asymmetric unit. Diffraction data to 3.2 A resolution have been collected on a San Diego Multiwire Area Detector system from both crystal forms. Determination of the molecular replacement solutions is underway.

Comparative molecular modeling and crystallization of P-30 protein: a novel antitumor protein of Rana pipiens oocytes and early embryos.

The P-30 protein (Onconase) of Rana pipiens oocytes and early embryos is homologous to members of the pancreatic ribonuclease superfamily and exhibits an antitumor activity in vitro and in vivo. It appears that the ribonucleolytic activity of P-30 protein may be required for its antitumor effects. A comparative molecular model of P-30 protein has been constructed based upon the known three-dimensional structure of bovine pancreatic RNase A in order to provide structural information. Functionally, these enzymes hydrolyze oligoribonucleotides to pyrimidine-3'-phosphate monoesters and 5'-OH ribonucleotides. In the modeling procedure, automated sequence alignments were revised based upon the inspection of the RNase A structure before the amino acids of the P-30 protein were assigned the coordinates of the RNase A template. The inevitable intermolecular steric clashes that result were relieved on an interactive graphics device through the adjustment of side chain torsion angles. This process was followed by energy minimization of the model, which served to optimize stereochemical geometry and to relieve any remaining unacceptably close contacts. The resulting model retains the essential features of RNase A as sequence insertions and deletions are almost exclusively found in exposed surface loops. The all atom superposition of active site residues of the P-30 protein model and an identically minimized RNase A structure has a root mean square deviation of 0.52 A. Though tentative, the model is consistent with a pyrimidine specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Stability of the amino acid content of nerve endings after administration of gamma-aminobutyrate agonists and antagonists.

The administration of GABA agonists or antagonists to mice resulted in unchanged levels of aspartate, glutamate, GABA and taurine in nerve endings (synaptosomes). On the other hand, agonist-induced increases in the levels of some of the amino acids occurred in locations other than the nerve endings. The GABA agonist SL75102 inhibited in vitro uptake of D-aspartate into synaptosomes, thereby raising the possibility that a similar phenomenon may cause an in vivo redistribution of glutamate and aspartate in brain tissue.