Search PubMed⌕ Search

Biomedical subjects

D L Aronson

Publications and source records attributed to D L Aronson.

At least 37 records · Page 2Linked to original sources
PubMed1988

Turnover of tPA in rabbits: influence of carbohydrate moieties.

The turnover of tissue plasminogen activator (tPA) was studied in rabbits using a double-label technique which allowed the comparison of various tPA derivatives with a standard tPA in individual animals. Purified recombinant tPA (Alteplase) was labelled with 125I and used as a standard for each experiment. Various tPA preparations which lacked specific carbohydrate structures were labelled with 131I (in separate experiments) and injected along with the 125I-tPA standard into rabbits. The clearance of standard tPA was biphasic with an average T 1/2 alpha and T 1/2 beta of 0.85 min and 12 min respectively. Type II tPA which lacks a portion of carbohydrate associated with Type I tPA as well as desialated tPA demonstrated a longer T 1/2 beta than standard tPA.

Animals↗
PubMed1988

Cause of death in hemophilia A patients in the United States from 1968 to 1979.

Death data on 949 hemophiliacs for the years 1968-1979 have been analyzed. The median age at death has increased from 33 to 55 years. There was no evidence of new diseases caused by the more intensive therapy during this time interval. The leading infectious disease was hepatitis, accounting for eight deaths. Only one acute hepatitis death was listed after 1974, when sensitive tests for hepatitis B antigen screening of plasma were implemented. Cirrhosis was a primary or associated cause of death in 76 cases (8%) and pneumonia was a primary or associated cause of death in 62 deaths (6.5%). The types of malignancies in hemophiliacs were similar to those in the male US population with no evidence of excessive retrovirus malignancies prior to infection with HIV-1.

Adolescent↗
PubMed1987

Thrombogenicity of factor IX complex: in vivo investigation.

Factor IX Complex therapy has been associated with thrombosis when used in patients with liver disease, hemophilia B and hemophilia A with inhibitors to Factor VIII when administered repetitively and in high doses. Three mechanisms for inducing thrombogenicity have been proposed: activated coagulants, coagulant-active phospholipid content and/or the high zymogen level attained in recipients. A new animal model using Russel Viper Venom (RVV) as an in vivo stimulus of coagulation has been used to investigate the role of high levels of zymogens in the induction of thrombosis. The quantity of RVV tolerated by rabbits infused with Factor IX Complex is reduced 100-fold. Infusion of Factor X or prothrombin also reduces the lethal dose of RVV. In contrast, Coagulation Factor IX devoid of other coagulants has little effect. However other animal data indicate that the amount of activated coagulants can play a role in the in vivo thrombogenicity of Factor IX Complex.

Animals↗
PubMed1986

Turnover of human tissue plasminogen activator (tPA) in rabbits.

The turnover of purified tissue plasminogen activator (tPA) from two different manufacturers was compared in rabbits. The first was melanoma derived one-chain tPA and the second was recombinant two-chain tPA. No differences were noted between the two products. A biphasic disappearance curve was observed for the protein (125Iodine labelled). The first phase was extremely rapid with a T1/2 of 0.59-0.89 min; the secondary phase had a T1/2 of 10-12 min. tPA accumulated rapidly in the liver (44% at twenty min) and appeared to be degraded as demonstrated by the increase in plasma of low molecular weight material which was also TCA soluble. Fractionation of purified recombinant two-chain tPA on a Dupont GF-250 column yielded two peaks of protein (Peak 1 and Peak 2) and the turnover of each in rabbits was compared.

Animals↗
PubMed1985

Experimental studies on venous thrombosis: effect of coagulants, procoagulants and vessel contusion.

We have examined the relative contribution of stasis, activated coagulants, procoagulants and vessel wall damage in the pathogenesis of experimental venous thrombosis. Using a Wessler stasis model in rabbits, we found an inverse correlation between duration of stasis and the amount of Contact Factor and Factor Xa required to produce a stasis thrombus. However, the slope of the dose-response curve for producing thrombi was different with these two coagulants. The infusion of Factor IX complex was also thrombogenic in this model despite prolonged circulation prior to stasis, implying that high levels of multiple procoagulants may be thrombogenic. In contrast, Factor VIII concentrates or a purified Factor IX preparation did not give thrombi under these conditions. When the vessel wall was crushed mechanically, followed by restored blood flow and subsequent stasis, there was essentially no formation of thrombi over the time course of the experiments. Scanning electron microscopy demonstrated that although the endothelium was swollen and damaged, there was usually no exposure of sub-endothelium and no adherence platelets. Where there was definite disruption of the endothelium, activated platelets could be seen adhering to the vessel wall. However, the blood in the segments remained fluid over a period of 30 min, despite the presence of adherent platelets. Our experiments demonstrated that the combination of vessel wall damage and stasis was relatively ineffective in producing venous thrombosis. In contrast, high levels of zymogens or small amounts of activated clotting factors, combined with local stasis, is a very effective thrombogenic stimulus in the venous system.

Animals↗
PubMed1985

Measures to inactivate viral contaminants of pooled plasma products.

In order to produce safer plasma products all possible methods of virus inactivation and reduction must be investigated systematically. Since the number and types of viruses are unknown and could change with time, a general viricidal approach is necessary. While heating has been the standard, a variety of methods are available for reducing the transmission of virus infection by blood products. Satisfactory development of these methods is limited by the cumbersome, expensive and imprecise experimental tools being used, i.e., the chimpanzee or human clinical trials.

Animals↗
PubMed1984

The use of prothrombin activating snake venoms to measure human prethrombin 2: absence of prethrombin 2 in serum.

The activation of the prothrombin intermediate, Prethrombin 2, has been studied in order to establish test systems that would enable identification of Prethrombin 2 in serum and Factor IX concentrates. While activation of Prethrombin 2 by Taipan Snake Venom (TSV) was slow and incomplete, inclusion of approximately molar amounts of prothrombin fragments F1 or F1.2 markedly enhanced the amount of thrombin formed by TSV. This effect could also be obtained by the inclusion of serum. Neither normal serum nor Factor V deficient serum contain any identifiable Prethrombin 2. On the other hand substantial amounts of Prethrombin 2 are present in Factor IX concentrates used for the treatment of Christmas Disease (Hemophilia B).

Chromatography, DEAE-Cellulose↗
PubMed1981

Uptake of ornithine by rat liver mitochondria.

Uptake of [14C]-L-ornithine by rat liver mitochondria has been measured by using the silicone sampling technique. The uptake of ornithine measured after 20-45 s of incubation exhibits stereospecificity, pH dependence, and a lack of dependence on respiratory energy. A slower subsequent increase in [14C]-L-ornithine counts associated with the mitochondria, which is blocked by the transaminase inhibitor aminooxyacetate, is attributed to metabolism of the labeled ornithine. Each of the reagents N-ethylmaleimide, Tris (HCl) buffer, Tl2+SO42(-), Mg2+SO42(-), and choline chloride inhibits ornithine accumulation. A lack of inhibition by mersalyl is interpreted as indicating that ornithine uptake does not require transmembrane Pi flux. Uptake of ornithine to levels in excess of the concentration in the medium can largely be accounted for by an osmotically insensitive fraction of the ornithine taken up, which is assumed to be adsorbed to solid structures of the mitochondria.

Aminooxyacetic Acid↗