Biomedical subjects

S Halfon

Publications and source records attributed to S Halfon.

11 recordsLinked to original sources

PubMed2002

Effect of anticoagulants and antiplatelet agents on platelet-mediated thrombin generation.

The present study was designed to determine the mechanism by which and extent to which antagonists of glycoprotein IIbIIIa (GPIIbIIIa or alpha beta ) or activated factor X (FXa) activity block tissue factor-initiated thrombin generation by prothrombinase complexes assembled on the surface of activated platelets. In the presence of high concentrations of GPIIbIIIa antagonists, which eliminate platelet aggregation but not activation, there is still a substantial amount of thrombin produced. In contrast, specific antagonists of the coagulation cascade lead to abolition of both thrombin generation and platelet aggregation. In addition, inhibitors with similar inhibitory activity (Ki) against purified human FXa require a much broader range of concentrations (a variation of 10 000-fold or more) to reduce the amount of thrombin produced in a platelet-rich plasma assay. At the doses tested, inhibitors with greater potency in prevention of thrombin production in the platelet-rich plasma assay were effective in vivo antithrombotics in an animal model system, whereas a lower potency compound did not reduce thrombus mass. Therefore, inhibition of FXa within platelet bound prothrombinase rather than inhibition of purified FXa in solution may be a better predictor of antithrombotic efficacy. In addition, all the studied anticoagulants fared better than the antiplatelet agents in reducing thrombin generation.

Animals↗

PubMed1998

Autocatalytic activation of human legumain at aspartic acid residues.

Human legumain was characterized following overexpression in a murine cell line as the C-terminal Ig-fusion protein. Upon acid treatment, the prolegumain autoproteolyzed distal to two aspartic acid residues to yield a highly active form. The ability of mature legumain to cleave after aspartic acid residues was confirmed with a small peptide substrate. Substitution of alanine for the putative catalytic cysteine, or for either of two strictly conserved histidine residues, partly or wholly eliminated autoactivation but not the ability of wild-type legumain to correctly process the variants to the properly sized proteins.

Amino Acid Sequence↗

PubMed1998

Leukocystatin, a new Class II cystatin expressed selectively by hematopoietic cells.

We describe a new cystatin in both mice and humans, which we termed leukocystatin. This protein has all the features of a Class II secreted inhibitory cystatin but contains lysine residues in the normally hydrophobic binding regions. As determined by cDNA library Southern blots, this cystatin is expressed selectively in hematopoietic cells, although fine details of the distribution among these cell types differ between the human and mouse mRNAs. In addition, we have determined the genomic organization of mouse leukocystatin, and we found that in contrast to most cystatins, the leukocystatin gene contains three introns. The recombinant proteins corresponding to these cystatins were expressed in Escherichia coli as N-terminal glutathione S-transferase or FLAGTM fusions, and studies showed that they inhibited papain and cathepsin L but with affinities lower than other cystatins. The unique features of leukocystatin suggests that this cystatin plays a role in immune regulation through inhibition of a unique target in the hematopoietic system.

Amino Acid Sequence↗

PubMed1992

Quantitative effects of antihydrophobic agents on binding constants and solubilities in water.

The effects of urea and of guanidinium chloride on binding constants in water for 6-(4-tert-butylanilino)-naphthalene-2-sulfonate and of bis(p-tert-butylphenyl) phosphate binding to beta-cyclodextrin and to N,N'-bis(6-beta-cyclo-dextrinyl)imidazolium ion have been determined. Their effects on the water solubility of p-tert-butylbenzyl alcohol and p-methylbenzyl alcohol have also been examined. Quantitative correlations show that the effects of these additives, which diminish hydrophobic effects, are similar for release of a tert-butylphenyl group from a cyclodextrin cavity into water or for solubilizing such a group from a second phase. The effects of these agents on the binding constants for double-ended substrates binding to the bis(cyclodextrin) host are much larger than for a simple substrate binding to monomeric cyclodextrin, consistent with additivity of free-energy perturbations. Ethanol also decreases binding in these systems, and increases solubilities, but the quantitative correlations are less straightforward.

Alcohols↗

PubMed1986

The association of dyslipoproteinemia with corneal arcus and xanthelasma. The Lipid Research Clinics Program Prevalence Study.

The prevalence rates of xanthelasma and corneal arcus were computed for normolipidemic and dyslipoproteinemic participants in the Lipid Research Clinics population surveys. The prevalence of both xanthelasma and corneal arcus increased with age, was highest in persons with type II phenotype, and usually low in those with type IV phenotype. The relative effects of age and use of gonadal hormones were different in the two lesions. Both xanthelasma and corneal arcus were associated with increased levels of plasma cholesterol and low-density lipoprotein cholesterol (LDL-C), especially in young males. In general, persons with either lesion had increased odds of having type IIa dyslipoproteinemia but decreased odds of having type IV. Xanthelasma and corneal arcus were highly associated with each other, especially in young people. There was no consistent univariate association of xanthelasma and corneal arcus with smoking, alcohol consumption, blood pressure, obesity, sedentary lifestyle, family history of ischemic heart disease, or glucose and uric acid plasma concentrations. Adjusted odds ratios for ischemic heart disease in participants with xanthelasma and corneal arcus were generally increased, except in older female nonusers of gonadal hormones, in whom they were significantly decreased. Neither xanthelasma nor corneal arcus showed a consistent association with manifestations of peripheral arterial disease. Thus the clinical findings of xanthelasma or corneal arcus, especially in young people, seem to identify persons with plasma lipoprotein abnormalities.

Adult↗

PubMed1973