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Biomedical subjects

M J Griffith

Publications and source records attributed to M J Griffith.

At least 109 records · Page 6Linked to original sources
PubMed1981

Dissociation of antithrombin III--thrombin complex. Formation of active and inactive antithrombin III.

Dissociation of the complexes formed during the reaction of thrombin with antithrombin III was studied by determining the kinetics of release of thrombin and active antithrombin III from the complexes. The rate of thrombin release increased gradually between pH 7.0 and 8.5 and then sharply increased at pH 9.0. The rate of active antithrombin III release did not change significantly over the same pH range. The results suggested that thrombin is released after reaction with antithrombin III via two pathways which are differentially affected by the pH of the solution. At pH 7.0 thrombin is released predominantly by dissociation of a non-acylated enzyme--inhibitor complex since active antithrombin III was released in relatively low amounts. The results suggested that thrombin inhibition by antithrombin III does not require the formation of an acyl bond between the active-site serine of thrombin and a carbonyl carbon of antithrombin III. The release of thrombin by acylation--deacylation appeared to be limited by the rate of enzyme acylation which was favored by more alkaline pH. This further suggests that acyl bond formation is a secondary reaction that can occur during thrombin inhibition by antithrombin III but is not necessary for thrombin inhibition.

Antithrombin III↗
PubMed1981

Membership duration and utilization rates in a prepaid group practice.

The relationship between utilization rates and duration of membership in prepaid group practices can have important implications for national policy and HMO administration. The results of this study demonstrate a substantial reduction in utilization rates with increasing duration of membership over a 5-year period in a developing prepaid group practice (PGP) located in urban St. Louis. This "start-up effect" is strongly evident across different socioeconomic subgroupings of the study population (sex, race, income, education and age) and for different employers and cohorts. The implications of widespread start-ups for health care financing policy and for important PGP management decisions are discussed, and suggestions are made for future study of the start-up phenomenon.

Adolescent↗
PubMed1981

Characterization of the defect in activation of factor IX Chapel Hill by human factor XIa.

Factor IXChapel Hill (Factor IXCH), an abnormal Factor IX molecule isolated from the plasma of a patient with mild hemophilia B, has previously been shown to exhibit delayed activation by Factor XIa and calcium. In this study, we have found that Factor IXCH is cleaved upon incubation with human Factor XIa and calcium; however, cleavage of this protein is not observed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis under nonreducing conditions. Under reducing conditions, the rate of disappearance of the zymogen parallels both the appearance of the heavy chain and the generation of clotting activity. In addition, a protein band that migrates with an apparent molecular weight of 45,000 also increases in parallel with clotting activity. Factor IXCH and normal Factor IX (Factor IXN), after incubation with Factor XIa and calcium, were subjected to amino terminal sequence analysis. Activated Factor IXN is cleaved at an arginine-alanine (Arg-Ala) bond and an arginine-valine (Arg-Val) bond as demonstrated by formation of the three amino terminal sequences corresponding to the amino terminal of the light chain, heavy chain, and activation peptide. However, activated Factor IXCH has only two amino terminal sequences, corresponding to the original amino terminal sequence and the heavy chain (formed by cleavage at the Arg-Val bond). It is concluded that the major defect in Factor IXCH is the inability of Factor XIa to cleave the Arg-Ala bond at a significant rate. The rate of formation of clotting activity of Factor IXCH is approximately 60% of the rate of formation of clotting activity of Factor IXN. The specific clotting activity of activated Factor IXCH is between 20 and 33% of activated Factor IXN.

Amino Acid Sequence↗
PubMed1979

Acetate kinase from Veillonella alcalescens. Regulation by succinate and substrates.

The kinetic properties of acetate kinase from Veillonella alcalescens were investigated. In the presence of high concentrations of nucleotide both forward and reverse reactions were observed. In the presence of succinate the degree of cooperativity between subunits of the homodimer decreased, i.e. the Hill coefficient, n, decreased from 2.5 to 1.4 for acetyl phosphate in the presence of succinate. At low substrate concentrations hyperbolic kinetic data were observed with succinate. We have proposed a modified version of the concerted symmetry model to describe the kinetics observed with this enzyme. The primary differentiating feature of the proposed model is the requirement for activator ligand binding for catalysis. In the absence of succinate, the substrate (acetate or acetyl phosphate) also functions as an activating ligand.

Acetate Kinase↗
PubMed1979

Acetate kinase from Veillonella alcalescens. Purification and physical properties.

Acetate kinase (ATP:phosphotransferase E.C.2.7.2.1) has been purified to a high state of purity from Veillonella alcalescens. The native enzyme had a molecular weight of 88,000, as determined by Sephadex G-150 gel filtration. The molecular weight of the monomeric enzyme, estimated from sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was 42,000. The enzyme was determined to be a homodimer from the amino acid composition and the results of trypsin digestion and cyanogen bromide cleavage. Two moles of phosphate were incorporated into the dimer upon incubation of the enzyme with ATP and acetate. These results support the conclusion that each subunit of the dimeric enzyme consists of a single active catalytic center. Succinate enhanced the rate of ATP-ADP phosphoryl group exchange 20-fold and the binding of ATP 10-fold. These results are considered in light of data from previous reports (Pelroy, R. A., and Whiteley, H. R. (1971) J. Bacteriol. 105, 259-267; Bowman, C. M., Valdez, R. O., and Nishimura, J. S. (1976) J. Biol. Chem 251, 3117-3121).

Acetate Kinase↗
PubMed1976

Slipping of the capital femoral epiphysis.

Experimental and clinical studies have shown that the capital femoral epiphysis slips by rotating backwards and downwards around the curved surface of the metaphysis and remains in a plane that lies posteriorly at right angles to the anteversion plane of the neck of the femur. The relevance of these findings to the diagnosis and treatment of the condition is discussed. A geometric flexion osteotomy designed to correct the deformity is described.

Bone Nails↗