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Biomedical subjects

G C White

Publications and source records attributed to G C White.

At least 127 records · Page 7Linked to original sources

The effect of platelet inhibitors on glycoprotein V hydrolysis by thrombin.

Platelet membrane glycoprotein V ( GPV ) is hydrolyzed during thrombin-induced platelet aggregation. The present studies were undertaken to determine whether cleavage of GPV was a direct result of thrombin action or was secondary to platelet activation. Acetylsalicylic acid or vincristine had little or no effect on platelet activation or cleavage of GPV by thrombin. Prostacyclin or antimycin A and 2-deoxyglucose inhibited platelet activation but had no effect on hydrolysis of GPV . These findings suggest that the hydrolysis of GPV occurs independently of the biochemical and morphological changes associated with platelet activation and is therefore a direct effect of thrombin.

Antimycin A↗

Effect of 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine on calcium fluxes by human platelet microsomes.

Under conditions where optimal concentrations of arachidonic acid, phosphatidic acid, or the calcium ionophore A23187 caused release of 50-95% of calcium from preloaded platelet microsomes, basophil platelet activating factor (1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine, AGEPC) did not cause the release of calcium at concentrations as high as 2 X 10(-5) M. The failure to stimulate calcium release was not due to metabolism or inactivation of AGEPC. These results show that AGEPC is not a calcium ionophore and is unable to directly effect the release of calcium from microsomes by mechanisms other than ionophoric action. The increase in intracellular levels that occurs during AGEPC-induced platelet aggregation must be an indirect effect of the AGEPC.

Arachidonic Acid↗

Phenotypic modification of the reactivity in human serum of Escherichia coli K1 isolates.

Three Escherichia coli strains producing the K1 antigen and shown to be resistant to the complement-mediated bactericidal action of human serum when grown in batch culture, were cultivated in the chemostat under conditions of carbon-, nitrogen-, magnesium- and phosphate-limitation. All strains were fully serum resistant when grown under carbon-limiting conditions but became phenotypically serum sensitive when limited by magnesium. One strain, belonging to serogroup O7:K1, also displayed serum sensitivity when nitrogen limited and showed an intermediate serum response when phosphate was used as the limiting nutrient.

Antigens, Bacterial↗

Rainsplash as a mechanism for soil contamination of plant surfaces.

We characterized the physical transport of soil, and therefore contaminants attached to the soil, onto vegetative surfaces due to rainsplash. Soil accumulation by tomato plants (Lycopersicon esculentum) was investigated as a function of soil particle size, rainstorm characteristics, foliage height, surface area and canopy cover of the plants. No soil particles greater than 105 micron in diameter were detected on the plants. Most of the soil was splashed no higher than 40 cm above the ground surface. Linear relationships were observed for concentrations of less than 53 micron soil on vegetation and certain rainfall characteristics. Data from this study, as well as ancillary calculations, provide evidence that a significant fraction of surficial contamination of foliage may be attributed to the rainsplash mechanism.

Food Contamination, Radioactive↗

High resolution electrophoretic analysis of human fibrinogen and its crosslinked intermediates.

Heterogeneity in human fibrinogen was examined using an improved two-dimensional isoelectric focusing-SDS polyacrylamide gel electrophoretic procedure. Four different preparations of fibrinogen were compared: single donor fibrinogen prepared from plasma by precipitation with ammonium sulfate or by affinity chromatography on fibrin-monomer Sepharose, fraction 1-4 prepared from Cohn fraction I paste, and Kabi grade L. The subunit A alpha, B beta, and gamma chains in all preparations had marked charge heterogeneity. The three chains were clearly separated from each other and a range of isoelectric points for each chain could be assigned. Minor variations in the subunit heterogeneity of the different preparations were found. Intermediates in the transition from fibrinogen to crosslinked fibrin were also examined. A striking increase in the heterogeneity of the beta chain was observed during crosslinking.

Chemical Phenomena↗

An evaluation of soil sampling for 137Cs using various field-sampling volumes.

The sediments from a liquid effluent receiving area at the Los Alamos National Laboratory and soils from an intensive study area in the fallout pathway of Trinity were sampled for 137Cs using 25-, 500-, 2500- and 12,500-cm3 field sampling volumes. A highly replicated sampling program was used to determine mean concentrations and inventories of 137Cs at each site, as well as estimates of spatial, aliquoting, and counting variance components of the radionuclide data. The sampling methods were also analyzed as a function of soil size fractions collected in each field sampling volume and of the total cost of the program for a given variation in the radionuclide survey results. Coefficients of variation (CV) of 137Cs inventory estimates ranged from 0.063 to 0.14 for Mortandad Canyon sediments, whereas CV values for Trinity soils were observed from 0.38 to 0.57. Spatial variance components of 137Cs concentration data were usually found to be larger than either the aliquoting or counting variance estimates and were inversely related to field sampling volume at the Trinity intensive site. Subsequent optimization studies of the sampling schemes demonstrated that each aliquot should be counted once, and that only 2-4 aliquots out of as many as 30 collected need be assayed for 137Cs. The optimization studies showed that as sample costs increased to 45 man-hours of labor per sample, the variance of the mean 137Cs concentration decreased dramatically, but decreased very little with additional labor.

Cesium Radioisotopes↗

Biological elimination rates of radioisotopes by mallards contaminated at a liquid radioactive waste disposal area.

The biological elimination of nine gamma-emitting radioisotopes was studied in mallards (Anas platyrhynchos) which were released onto liquid radioactive waste pounds in southeastern Idaho. After 68, 75 or 145 days, the ducks were removed from the contaminated environment and placed in metabolic cages. Whole-body and feces-urine counts were made for 51 days and then the ducks were sacrificed and dissected for tissue analyses. The biological elimination of radioisotopes were fit to two compartment models using non-linear least squares estimation. Fecal-urine data substantiated two-compartment elimination of all radionuclides. Biological half-lives in mallards were 10 days (131I), 22 days (140Ba), 86 days (51Cr), 32 days (58Co), 26 days (75Se), 67 days (65Zn), 10 days (134Cs), 67 days (60Co) and 11 days (137Cs). Body burdens in ducks were at 90% of equilibrium with the radioactive waste pond water at the time of removal from the waste ponds. Tissue distribution of radionuclides on the day of removal from the ponds showed gut to have the highest concentrations followed by feather, liver and muscle. After 51 days in metabolic cages, feather had the greatest radionuclide concentrations followed by liver, muscle and gut. Liver contained the greatest variety of radionuclides and muscle the smallest. Biological elimination rates for the major dose-contributing nuclides (134Cs and 137Cs) to humans consuming contaminated waterfowl tissue indicate that the dose to man could be reduced substantially due to the rapid elimination of these radionuclides by mallards. Contaminated waterfowl would receive most of the internal dose in the first month after leaving the contaminated environment indicating that long-term doses would be inconsequential.

Animals↗

Morphological study of early phases of platelet adhesion to foreign surfaces: effect of calcium.

The role of calcium in the interfacial reactions occurring during the early phases of blood contact with glass surfaces has been studied using a rheologic technique that permits enumeration of adherent platelets as well as ultrastructural visualization of the blood-glass interface by both transmission and scanning electron microscopy . In the presence of calcium, platelets adhere to the glass surface at a rapid rate. Within 4 minutes, most of the adherent platelets have lost their normal discoid shape and show pseudopod formation and cytoplasmic spreading. These platelets conform with the glass surface and show central apposition of platelet organelles similar to that seen in activated platelets. Fibrin strands and platelet aggregates are also seen. Chelation of calcium using sodium citrate or EDTA results in decreased platelet adhesion or retention to glass. Platelets that are adherent to glass in the presence of citrate and EDTA retain their discoid shape, although an occasional platelet may show pseudopod formation and centralization of organelles. Calcium appears to be an important factor governing the adhesion of platelets to glass and appears to exert this effect on the platelets themselves in their plasma milieu and not on the preceding adsorption of plasma proteins.

Blood Platelets↗

Heparin cofactor activities in a family with hereditary antithrombin III deficiency: evidence for a second heparin cofactor in human plasma.

Plasma levels of antithrombin-heparin cofactor, determined by heparin-dependent antithrombin assay, and antithrombin III antigen were measured in 22 members of a large kindred predisposed to venous thrombosis. While 11 members had reduced plasma levels of both antithrombin-heparin cofactor and antithrombin III antigen, the levels of antithrombin-heparin cofactor were always greater than the levels of antithrombin III antigen: 66% (+/- 7%) and 49% (+/- 5%) of normal plasma, respectively. Pooled normal plasma and plasma from one of the affected family members (60% antithrombin-heparin cofactor and 47% antithrombin III antigen) were fractionated by heparin-agarose affinity chromatography. Antithrombin-heparin cofactor, which eluted from heparin-agarose with buffer containing 0.4 M NaCl and did not cross-react with antibody specific for antithrombin III and did not inhibit factor Xa at an appreciable rate in the presence of heparin, was designated heparin cofactor A. Antithrombin-heparin cofactor, which eluted from heparin-agarose with buffer containing 2.0 M NaCl, was functionally and antigenically identified as antithrombin III. The concentrations of heparin cofactor A in normal and patient plasma were similar (4.5 x 10(-7) M), while the concentration of antithrombin III in patient plasma (8.0 x 10(-7) M) was only 50% of normal (1.6 x 10(-6) M). The functional properties of both heparin cofactor A and antithrombin III obtained from patient plasma were normal. From the results of the present study it would appear that the antithrombin-heparin cofactor concentrating measured in patient plasma reflects the combined concentrations of heparin cofactor A and antithrombin III. Since heparin cofactor A does not cross-react with antibody to antithrombin III, the concentration of antithrombin III antigen in patient plasma is thus lower than the concentration of antithrombin-heparin cofactor.

Antithrombin III↗

Treatment of a high titer anti-factor-VIII antibody by continuous factor VIII administration: report of a case.

Daily administration of large doses of factor VIII concentrate in a hemophiliac with a high titer factor VIII inhibitor resulted in marked reduction in the titer and response of the inhibitor to factor VIII administration and made possible elbow and bilateral knee replacements under conventional factor VIII coverage. Studies performed during the course of treatment indicated that the reduction in the inhibitor was the result of specific tolerance to factor VIII.

Adult↗

Autoplex versus proplex: a controlled, double-blind study of effectiveness in acute hemarthroses in hemophiliacs with inhibitors to factor VIII.

In view of uncontrolled observations and anecdotal reports suggesting that the activated PCC, Autoplex, was much more effective than standard (non-activated) PCC in controlling bleeding in hemophiliacs with inhibitors, a controlled double-blind study was designed to compare the effectiveness of Autoplex and Proplex. Acute hemarthrosis was chosen for study as this common but non-life-threatening lesion lends itself well to controlled study. A single dose of "unknown" product (Autoplex 75 FECU/kg; Autoplex 50 FECU/kg; or Proplex 75 FIX U/kg) was given, and effectiveness was judged at 6 hr. By all criteria of efficacy, there were no significant differences between the products. It is noteworthy that a single dose of PCC was judged effective in 50% of episodes, a figure that is consistent with other published clinical trials. In this model, no additional benefit was derived from using the activated PCC, Autoplex, in either dosage.

Blood Coagulation Factors↗

The management of musculoskeletal problems in hemophilia. Part I. Principles of medical management of hemophilia.

Musculoskeletal bleeding in general and arthropathy in particular are the central problems among many in the two major forms of hemophilia: classic hemophilia, caused by factor VIII deficiency, and Christmas disease, caused by factor IX deficiency. Currently available replacement therapy, if properly used in a multidisciplinary setting, should provide significant benefit to hemophilic patients despite its cost and occasional complications.

Anemia, Hemolytic↗

Factor VIII inhibitors: a clinical overview.

There is much evidence to indicate that inhibitors to Factor VIII in patients with classical hemophilia are the result of an immunological response to exposure to material (VIII:C or VIII:CAg) that is absent or present in reduced amounts in these patients. The inhibitor is an antibody that is usually restricted in immunochemical composition and in many instances contains predominantly or exclusively gamma G3 or gamma G4 heavy chains. Exposure to Factor VIII in many inhibitor patients leads to typical anamnestic responses with marked increases in the level of the inhibitor. The tendency to develop inhibitors and the clinical characteristics of the inhibitor may be affected by genetic factors, basal levels of Factor VIII:C and/or VIII:CAg, and the nature and amount of the "immunizing" material. Currently accepted therapeutic modalities are aimed primarily at the management of acute bleeding episodes.

Adolescent↗

Hydrolysis of human platelet membrane glycoproteins with a Serratia marcescens metalloprotease: effect on response to thrombin and von Willebrand factor.

Metalloproteases from at least two Gram-negative organisms selectively hydrolyze the surface of human fixed washed platelets. The protease-treated platelets lose their ability to aggregate with bovine von Willebrand factor and human von Willebrand factor plus ristocetin. The present study reports the membrane glycoprotein alterations and loss of platelet function that occur after incubation of fresh washed human platelets with a purified protease produced by Serratia marcescens. The studies were undertaken in order to examine, using the Serratia protease as an enzymatic probe, the relationship between externally oriented glycoproteins and two known aggregating agents, bovine von Willebrand factor and thrombin. Platelet membrane glycoproteins were analyzed after discontinuous NaDodSO(4)/polyacrylamide gel electrophoresis using both staining with periodic acid-Schiff reagent and autoradiography of (3)H-labeled platelets. Both methods of detection demonstrated that at Serratia protease concentrations above 0.6 mug/ml there was hydrolysis within 3 min of a membrane glycoprotein (M(r) 185,000) corresponding to GPIb in control platelets. The loss of GPIb was accompanied by the appearance in the platelet supernatant of a glycopeptide (M(r) 156,000). Under reducing conditions, the hydrolyzed membrane glycopeptide in the supernatant had a consistently faster migration (M(r) 149,000). Platelets treated with Serratia protease at concentrations sufficient to give maximal cleavage of GPIb were unresponsive to bovine von Willebrand factor and did not aggregate or release [(14)C]serotonin at doses of von Willebrand factor up to 0.33 unit/ml. On the other hand, the response to bovine alpha-thrombin was only minimally impaired by treatment with Serratia protease. These results implicate GPIb in the response by platelets to bovine von Willebrand factor but suggest that surface components other than GPIb play a major role in the response by platelets to thrombin.

Blood Coagulation Factors↗