Jewish Hospital

About: Jewish Hospital is a healthcare organization based out in Cincinnati, Ohio, United States. It is known for research contribution in the topics: Antigen & Population. The organization has 3881 authors who have published 3414 publications receiving 123044 citations.

Association of antithrombotic factor deficiencies and hypofibrinolysis with Legg-Perthes disease.

Abstract: Thirty-three (75 per cent) of forty-four unselected children who had Legg-Perthes disease were found to have coagulation abnormalities. Twenty-three children had thrombophilia (a deficiency in antithrombotic factor C or S, with an increased tendency toward thrombosis); nineteen of the twenty-three children had protein-C deficiency and four had protein-S deficiency. Seven children had a high level (0.25 gram per liter or more) of lipoprotein(a), a thrombogenic, atherogenic lipoprotein associated with osteonecrosis in adults. Three children had hypofibrinolysis (a reduced ability to lyse clots). The mean age of the children when the Legg-Perthes disease was first diagnosed was 5.8 ± 2.7 years, and the mean age at the time of the present study was 10.1 ± 4.4 years. At least one of the first-degree relatives of eleven of the nineteen probands who had a low protein-C level had a low protein-C level as well; all of these low levels represented previously undiagnosed familial protein-C deficiency. The eleven probands who had familial protein-C deficiency were more likely to have early onset of Legg-Perthes disease (at or before the age of five years) than the eleven children who had normal levels of protein C, protein S, and lipoprotein(a) as well as normal fibrinolytic activity (chi-square = 6.6; p = 0.01). At least one first-degree relative of one of the four probands who had a low protein-S level had a low protein-S level and previously undiagnosed familial protein-S deficiency. At least one first-degree relative of six of the seven probands who had a high level of lipoprotein(a) had a familial high level of lipoprotein(a). Six of the seven children who had a high level of lipoprotein(a) also had a low level of stimulated tissue-plasminogen activator activity, the major initiator of fibrinolysis. At least one first-degree relative of one of the three probands who had normal levels of protein C, protein S, and lipoprotein(a) but low stimulated tissue-plasminogen activator activity also had low stimulated tissue-plasminogen activator activity (familial hypofibrinolysis). Legg-Perthes disease, thrombophlebitis, premature myocardial infarction, and stroke, which are ramifications of the familial thrombophilic-hypofibrinolytic disorders, were common in the first and second-degree relatives of the thirty-three children with Legg-Perthes disease who also had thrombophilic-hypofibrinolytic disorders. CLINICAL RELEVANCE: Protein-C or S deficiency, hypofibrinolysis, or a high level of lipoprotein(a) may result in thrombotic venous occlusion of the femur, which leads to the venous hypertension and osteonecrosis of the femoral head characteristic of Legg-Perthes disease. When Legg-Perthes disease develops in a child, the levels of proteins C and S, lipoprotein(a), and stimulated fibrinolysis should be measured. Early diagnosis of protein-C or S deficiency, hypofibrinolysis, or a high level of lipoprotein(a) in such children may open avenues for pharmacological preventive therapy to reduce thrombophilia, stimulate fibrinolysis, or lower the level of lipoprotein(a), potentially ameliorating the Legg-Perthes disease process.

Inhibition of Membrane Transport in Streptococcus faecalis by Uncouplers of Oxidative Phosphorylation and Its Relationship to Proton Conduction

Abstract: We studied the effect of compounds that uncouple oxidative phosphorylation on membrane function in Streptoccocus faecalis, an organism which relies upon glycolysis for the generation of metabolic energy. At low concentrations (ranging from 10−7 to 10−4m), tetrachlorosalicylanilide, tetramethyldipicrylamine, carbonylcyanide m-chlorophenylhydrazone, pentachlorophenol, and dicoumarol strongly inhibited energy-dependent transport of rubidium, phosphate, and certain amino acids. However, these compounds had little effect on the generation of adenosine triphosphate via glycolysis or on its utilization for the synthesis of macromolecules. They also did not seriously inhibit uptake of those monosaccharides and amino acids which do not require concurrent metabolism. It is proposed that the uncouplers interfere with the utilization of metabolic energy for membrane transport. The uncouplers accelerated the translocation of protons across the cytoplasmic membrane. It appears that a proton-impermeable membrane is required for transport, perhaps, because a proton gradient is involved in the coupling of metabolic energy to the translocation of substrates across the membrane.