Isolation of an abnormal protein C molecule from the plasma of a patient with thrombotic diathesis

Protein C has been purified from the plasma of a patient with thrombotic diathesis. Both before and after isolation, the protein showed reduced capacity to hydrolyze synthetic substrates and to anticoagulate plasma. Proteolysis with the soluble thrombin- thrombomodulin complex proceeded normally and to completion as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. Approximately one-third of the protein is functional, indicating a heterozygous defect. Indirect studies suggest that the abnormal component can bind to protein S and phospholipids. Both forms of activated protein C can also incorporate radiolabeled diisopropylfluorophosphate.     

Quadrilateral space syndrome: a rare cause of shoulder pain

The authors report a case of quadrilateral space syndrome in a baseball pitcher. The diagnosis was made by means of subclavian arteriography performed with the arm in abduction and external rotation. This entity is a rare cause of shoulder pain caused by occlusion of the posterior humeral circumflex artery in the quadrilateral space.     

Lung lesions: correlation between viewing time and detection

The influence of viewing time on the detectability of subtle and obvious lung cancers was studied. Frontal chest radiographs of 40 patients with subtle cancers, 40 patients with obvious cancers, and 40 healthy control subjects were shown to four observers for four different viewing times (0.25 second, 1 second, 4 seconds, and unlimited time). Receiver operating characteristic analysis was used to compare the detectability of lesions. Performance was degraded as viewing time decreased. The true-positive fractions for subtle and obvious cancers were 30% and 70% at 0.25 second and 74% and 98% at unlimited viewing time, respectively, for a given false-positive fraction of 20%. Thus, even with unlimited viewing time, the false-negative fraction for subtle cancers was 26%. The difference in detectability between subtle and obvious lung cancers was exaggerated at 1.0 second compared with 4 seconds and unlimited viewing time. The following conclusions were reached: (a) a substantial proportion of subtle lung lesions are missed, even with unlimited viewing time; (b) a large proportion of obvious lung cancers are detected with flash viewing; (c) the detectability of lesions decreases considerably as viewing time becomes less than 4 seconds; and (d) differences in detectability are exaggerated by short viewing times.     

Intrahepatic bile duct and portal vein anatomy revisited

Seventeen normal cadaver livers were studied to assess the anatomic relationship of bile ducts to portal veins. The common bile duct, main portal vein, and hepatic artery were cannulated and injected with air, dilute contrast medium, and mineral oil, respectively. The livers were placed in anatomic position and examined with computed tomography. In the lateral segment of the left hepatic lobe, the bile ducts were anterior to the portal vein in seven cases, posterior in seven, and tortuous (ie, both anterior and posterior) in three. In the medial segment of the left lobe, the bile ducts were anterior in four cases, posterior in four, tortuous in three, and not seen in six. In the right lobe, the bile ducts were anterior in nine cases, posterior in five, tortuous in one, and not seen in two. In the porta hepatis, the bile ducts were anterior in ten cases, posterior in one, tortuous in five, and not seen in one. Histologic findings confirmed the anterior and posterior location of the bile ducts relative to the portal veins. These findings contradict the commonly held view of intrahepatic bile ducts being anterior to the portal vein and are clinically significant for techniques such as bile duct drainage.     

5-substituted 2′-deoxyuridines: Correlation between inhibition of tumor cell growth and inhibition of thymidine kinase and thymidylate synthetase

A large variety of 5-substituted 2′-deoxyuridines (dUrds) and 2′-deoxyuridylates (dUMPs) have been evaluated for their inhibitory effects on the thymidine (dThd) kinase or thymidylate (dTMP) synthetase isolated from mouse leukemia L1210 cells. The most potent inhibitors of dThd kinase were 5-chloro-, 5-bromo- and 5-iodo-dUrd. Their K_i/K_m values ranged from 0.57 to 0.82. All dUrd analogs tested showed competitive kinetics with respect to dThd. However, there was little, if any, correlation between the inhibitory effects of the compounds on L1210 cell growth and their inhibitory activities against dThd kinase (r = 0.16). The most potent inhibitors of dTMP synthetase were (in order of decreasing activity): 5-nitro-dUMP > 5-formyl-dUMP > 5-fluro-dUMP > 5-oxime of 5-formyl-dUMP > 5-azidomethyl-dUMP > (E)-5-(2-bromovinyl)-dUMP. The k_i/K_m values for these compounds ranged from 0.001 to 0.665. All dUMP analogs tested showed competitive kinetics with respect to dUMP (if not preincubated with the enzyme at 37°). There was a strong correlation (r = 0.833) between the inhibitory effects of these compounds on L1210 cell growth and their inhibitory activities against dTMP synthetase. Thus, the suppressive action of 5-substituted dUrd derivatives on tumor cell growth would involve prior conversion of the nucleoside analogs to the corresponding 5′-monophosphates followed by an inhibition of dTMP synthetase.