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Biomedical subjects

D M McCord

Publications and source records attributed to D M McCord.

6 recordsLinked to original sources
PubMed1999

Measuring social competence with the Wechsler Picture Arrangement and Comprehension subtests.

Authors tested the traditional assumption that the WAIS-R and WISC-R Picture Arrangement and Comprehension subtests are interpretable as measures of social competence. Although this assumption has existed for over 50 years, there is a lack of empirical evidence to support this contention. Performance on Picture Arrangement and Comprehension were correlated with Personality Inventory for Children (PIC) FACTOR II: Social Incompetence and Social Skills Scale scores for 136 males and 64 females ranging from 6 to 20 years of age. Correlations between Picture Arrangement and Comprehension scaled scores and PIC measures of social deficiencies were not significant for either the WISC-R or WAIS-R. However, ipsative scatter analyses revealed that participants with relatively strong Comprehension performance were rated as experiencing fewer social problems than other participants. Interpreting Picture Arrangement and Comprehension subtests as indicators of social competence is cautioned.

Adolescent↗
PubMed1990

Characterization of the functional defect in factor IX Alabama. Evidence for a conformational change due to high affinity calcium binding in the first epidermal growth factor domain.

Factor IX Alabama is a factor IX variant in which a glycine has been substituted for Asp47 in the first epidermal growth factor (EGF) domain. The structural defect in factor IX Alabama results in a molecule with 10% of normal coagulant activity. The interactions of immunoaffinity-purified factor IX Alabama with its activator, cofactors, and substrate have been investigated to determine the functional defect in the variant. Factor IX Alabama is activated by factor XIa/calcium at near normal rates. Calcium fluorescence-quenching experiments indicate that high affinity calcium binding in the first EGF domain is not altered in factor IX Alabama. The active site of factor IXa Alabama is fully competent to activate factor X in the absence of calcium when using polylysine as a surface to catalyze the reaction. Factor IXa Alabama has only 64% of normal factor IXa activity in the presence of 300 microM CaCl2 in the polylysine-catalyzed system although apparent high affinity calcium binding constants are similar. Factor IXa Alabama has 52-60% of normal activity in a calcium/phospholipid vesicle system. The addition of factor VIIIa to the phospholipid vesicle system decreases the relative rate of factor IXa Alabama to 18-19% of normal. Three-dimensional computer-aided models of the first EGF domain of normal factor IX and factor IX Alabama indicate no major structural alterations resulting from the glycine substitution for Asp47. The model of the first EGF domain of normal factor IX predicts a calcium-binding site involving Asp47, Asp49, Asp64, and Asp65. Our binding data, however, indicate that Asp47 is not necessary to form the high affinity binding site. We conclude that Asp47 in normal factor IX coordinates to the bound calcium, inducing a conformational change in the molecule essential for proper interaction with factor X and factor VIIIa.

Binding Sites↗
PubMed1989

Mechanism by which recombinant factor VIIa shortens the aPTT: activation of factor X in the absence of tissue factor.

Clinical trials have recently begun using high concentrations of activated recombinant factor VII (rFVIIa) for the treatment of hemophilic patients with inhibitors. Unexpectedly, the activated partial thromboplastin time (aPTT) was observed to be significantly shortened during infusion of the rFVIIa. To determine the mechanism for this shortening, the effect of rFVIIa on both the prothrombin time (PT) and the aPTT of normal and various factor-deficient plasmas was examined. rFVIIa shortened the PT of all plasmas tested except FX and FV deficient plasmas. rFVIIa also shortened the aPTT of all plasmas tested except FX and FV deficient plasmas. Since there is no added tissue factor (TF) in aPTT reagents, rFVIIa appeared to shorten the aPTT in the absence of TF. To investigate this possibility, the activity of rFVIIa in a purified system containing only FX, phospholipid vesicles (1:1 PS:PC), and calcium was examined. In this system, rFVIIa activated factor X in the absence of TF. If any component of the purified system was omitted, there was no detectable activation of FX. Thus it appears that calcium and phospholipids are required for the activation of FX by rFVIIa in the absence of TF. Increasing the concentration of rFVIIa increased the rate of FX activation, but the rate of activation was always much lower than that observed with even trace amounts of tissue factor. We conclude that high concentrations of rFVIIa, in the presence of calcium and phospholipid, can directly activate FX in the absence of TF and hence account for the shortening of the aPTT in inhibitor patients treated with rFVIIa.

Blood Coagulation Tests↗
PubMed1989

Functional consequences of an arginine180 to glutamine mutation in factor IX Hilo.

Factor IX Hilo is a variant factor IX molecule that has no detectable coagulant activity. The defect in factor IX Hilo arises from a point mutation in the gene such that in the protein Arg180 is converted to a Gln. Activation of factor IX Hilo by factor Xla was monitored using the fluorescent active site probe p-aminobenzamidine. Normal factor IX showed complete activation in one hour as determined by measuring the increase in fluorescence when p-aminobenzamidine bound to activated factor IX. Factor IX Hilo showed no increase in fluorescence even after 24 hours, indicating that the active site was not exposed. Polyacrylamide gel electrophoresis showed that factor IX Hilo was cleaved to a light chain plus a larger peptide with a molecular weight equivalent to a heavy chain covalently linked to an activation peptide. Amino terminal amino acid sequencing of factor IX Hilo cleaved by factor Xla showed cleavage only at Arg145-Ala146, indicating that the Gln180-Val181 bond was not cleaved and that the active site was thus not exposed. The presence of factor IX Hilo in patient plasma was responsible for the patient having a very long ox brain prothrombin time characteristic of severe hemophilia Bm. Patient plasma had an ox brain prothrombin time of 100 seconds using a Thrombotest kit, significantly prolonged over the normal control value of 45 seconds. When factor IX Hilo was depleted from patient plasma using an immunoaffinity column, the ox brain prothrombin time decreased to 41 seconds. When factor IX Hilo was added back to depleted patient plasma, to normal plasma depleted of factor IX by the same affinity column, or to plasma from a CRM- hemophilia B patient, the ox brain prothrombin time was significantly prolonged. We conclude that the Arg180 to Gln mutation in factor IX Hilo results in a molecule that cannot be activated by factor Xla. Further, our data suggest that the mutation results in a molecule that interacts with components of the extrinsic pathway to give a prolonged ox brain prothrombin time.

Amino Acid Sequence↗
PubMed1989

Do redundant visual and auditory target variables facilitate control behavior?

The compensatory tracking paradigm has been used extensively in pioneering work on Control Theory, a cybernetic model of behavior. In most studies subjects have been asked to control or maintain at a steady state a single variable or aspect of the stimulus display. The present study utilized three groups of subjects, comparing their performance effectiveness in controlling: (1) a visual stimulus (cursor) versus (2) an auditory stimulus (tone) versus (3) a combined, redundant-cue condition employing both cursor and tone. Freshman volunteers responded to a computer display using a joystick controller; their task was to keep stationary a stimulus that was subject to a smoothed, quasirandom disturbance. Contrary to predictions, subjects in the cursor-alone group performed more effectively than subjects in the combined cursor-tone group. While speculative interpretations are offered, further research is needed to clarify these results.

Adolescent↗