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H A Cooper

Publications and source records attributed to H A Cooper.

53 records · Page 3Linked to original sources

The defect in hemophilic and von Willebrand's disease plasmas studied by a recombination technique.

Factor VIII in preparations from normal plasma is a large glycoprotein of greater than 2 million molecular weight which elutes in the exclusion volume of 4% agarose gels at an ionic strength of 0.15. Recent studies have demonstrated that the factor VIII in canine and bovine plasma is a macromolecular complex composed of a large inert carrier protein and a noncovalently bound small fragment which contains the procoagulant active site. This complex is dissociable in 0.25 M CaCl(2), and conditions for its recombination have been reported. The present study reports the dissociation characteristics of normal human factor VIII preparations in 0.25 M CaCl(2) and the ability to achieve quantitative recombination of the dissociated fragments of normal human and bovine factor VIII after the removal of Ca(2+). The recombination technique was used to characterize further the defect in hemophilia and von Willebrand's disease. Void volume preparations from human hemophilia A(-), canine hemophilia A, and human von Willebrand's plasma, with no factor VIII procoagulant activity, were mixed with the small active fragment prepared from the normal plasma of their respective species. Chromatography of the three mixtures in agarose gel showed that the fractions from the human hemophilic plasmas contained a molecule that bound the small active normal fragment, but neither the fractions from canine hemophilia A plasmas nor the fractions from the human von Willebrand's plasmas demonstrated evidence of such material. These data suggest that there is present in human hemophilia A plasma a normal functional carrier molecule which is absent or nonfunctional in the plasma of hemophilic dogs and humans with von Willebrand's disease.

Animals↗

Plasma aggregating factor (bovine) for human platelets: a marker for study of antihemophilic and von Willebrand Factors.

The human-platelet aggregating factor in preparations of bovine plasma and bovine antihemophilic factor has been reported to be an activity of bovine antihemophilic factor. However, we show that activities of aggregating factor and antihemophilic factor are present in varying proportion in different preparations of antihemophilic factor. Aggregating factor activity is more stable on storage than is antihemophilic factor activity and can be selectively adsorbed by human platelets. Further, antihemophilic factor activity free of aggregating activity was eluted from DEAE-Sephadex. The factors were also separated during agarose chromatography in 0.25 M CaCl(2), which yields a small-molecular-weight moiety with antihemophilic factor activity; aggregating factor activity continued to elute in the void volume. Thus, aggregating factor activity is clearly separable from antihemophilic factor activity. The usual physiologic platelet-aggregating reactions require fresh platelets. Fresh, aged, and sonicated platelets, but not platelets that have been frozen and thawed, react with aggregating factor, indicating that the platelet "receptor sites" for the aggregating factor are unusually stable.

Animals↗

Factor VIII recombination after dissociation by CaCl12.

Factor VIII is a large protein molecule of molecular weight 2,000,000 or larger that elutes in the void volume on agarose gel chromatography. It has been shown previously that high concentrations of alkali halides and, more specifically, 0.25 M Ca(2+) dissociate the molecule into a large carrier protein and a small fragment that retains the factor VIII activity. Factor VIII was prepared from normal canine plasma collected in sodium oxalate and heparin and adsorbed with BaSO(4). Results with Ca(2+) dissociation were the same as those obtained with fraction prepared from canine plasma collected in sodium citrate. The addition of 0.1 M epsilon-aminocaproic acid in the dissociation step had no effect. Fractionation of canine hemophilic plasma produced preparations without activity, and no activity was found when these inert preparations were dissociated with Ca(2+). These results indicate that the Ca(2+) dissociation is a true dissociation and not caused by enzymatic degradation by plasmin, thrombin, or activated factors VII, IX, or X. The apparent molecular weight of the small active fragment of factor VIII determined by gel chromatography was about 100,000. Finally, when the large carrier protein and the small active fragment of factor VIII were separated by gel chromatography, mixed, and dialyzed free of Ca(2+), they recombined to form a large active molecule that appeared in the void volume on agarose gel chromatography.

Aminocaproates↗

Fetal hemoglobin.

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Adolescent↗

Central venous catheter use and the risk of infection in children with acute lymphoblastic leukemia: a report from the Children's Cancer Group.

PURPOSE: To describe patterns of central venous catheter (CVC) use and determine the risk of infection associated with a catheter in children with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Children with ALL (n = 1934), participating in Children's Cancer Group studies for good-prognosis ALL (CCG-1881) and intermediate-risk ALL (CCG-1891) were evaluated in a retrospective case-control study. The presence of a catheter and the occurrence of infectious complications were recorded after each treatment phase. RESULTS: Young age and enrollment in the intermediate-risk study were associated with higher rates of catheter use. During each of the first four phases of therapy, the adjusted risk of infection was two- to fourfold higher when a catheter was in place. The proportion of patients with infection during the first four phases of therapy was 2.6 times higher with a CVC (14.4% versus 5.7%). Catheter use was associated with significantly increased hospitalization rates during induction, consolidation, and interim maintenance, but not during delayed intensification. A catheter did not significantly increase the risk of fever during neutropenia. CONCLUSION: The presence of a CVC increases the risk of infection during the early phases of low-intensity therapy for ALL.

Antineoplastic Agents↗

Activated recombinant human coagulation factor VII therapy for intracranial hemorrhage in patients with hemophilia A or B with inhibitors. Results of the novoseven emergency-use program.

Activated recombinant human coagulation factor VII (rFVIIa) is a promising new therapeutic agent for patients with hemophilia A or B with inhibitors who experience serious bleeding episodes or who need coverage during surgical procedures. This open-label, uncontrolled, emergency-use study evaluated the efficacy and safety of rFVIIa in 11 hemophiliac patients and 1 FVII-deficient patient with life-threatening intracranial hemorrhage previously unresponsive to one or more alternative therapies. rFVIIa effectively controlled intracranial hemorrhage in 10 of the 12 patients. Patients with hemophilia A or B received an average of 96.9 rFVIIa injections over 14.7 days with a mean total administration of 153.3 mg, corresponding to 8.1 mg/kg. Most reported adverse events were considered to be unrelated to rFVIIa therapy. These findings suggest that rFVIIa is an effective and well-tolerated therapeutic option in the management of central nervous system bleeding in patients with hemophilia A or B with inhibitors.

Adult↗