PubMed Health⌕ Search

Biomedical subjects

G C White

Publications and source records attributed to G C White.

At least 19 recordsLinked to original sources
PubMed1992

Affinity chromatography of platelets on immobilized thrombin: retention of catalytic activity by platelet-bound thrombin.

Radioactivity from I125-labeled human platelets was measured to estimate the extent of binding of platelet surface proteins to immobilized thrombin. 1-3% of the radioactivity was bound with 10-20% of this amount apparently irreversibly bound to the thrombin matrix. Site-specific chemical modification of thrombin with pyridoxal-5'-phosphate, N-bromosuccinimide or tetranitromethane resulted in a variable reduction of the amount of radiolabel bound. When thrombin modified with H-D-PheProArg-chloromethyl ketone (PPACK) was coupled to the matrix, there was no difference in the binding of platelet membrane proteins when compared to a control thrombin preparation while thrombin modified with tosyl-Lys-chloromethyl ketone (TLCK) coupled to the matrix did not bind radiolabel any more effectively than albumin which served as the control. However, when thrombin was modified with PPACK after coupling to the agarose matrix, ability to bind radiolabel was lost. Thrombin bound to platelets remained catalytically active when assayed with a peptide nitroanilide substrate. These results suggest tight binding between thrombin and platelets that is not only not dependent on active site integrity but leaves the bound thrombin catalytically competent.

Amino Acid Chloromethyl Ketones↗
PubMed1992

Purified factor IX using monoclonal immunoaffinity technique: clinical trials in hemophilia B and comparison to prothrombin complex concentrates.

Replacement therapy for hemophilia B (factor IX deficiency) using prothrombin complex concentrate (PCC) has been associated with serious complications of thromboembolic events and transmission of viral infections. Monoclonal antibody-purified factor IX (Mononine) provides a highly purified factor IX concentrate, while eliminating other vitamin K-dependent factors (II, VII, and X). Mononine was evaluated for in vivo recovery, half-life, and for its safety and efficacy in 10 patients with hemophilia B. The in vivo recovery of factor IX with Mononine was a 0.67 +/- 0.14 U/dL (mean +/- SD) increase per 1U/kg of infused factor IX, and the biologic half-life (t1/2), determined using the terminal phase of elimination, was 22.6 +/- 8.1 hours. Comparison of in vivo recovery of other vitamin K-dependent factors following a single infusion of either Mononine or PCC showed that, whereas Mononine infusion caused no changes in other vitamin K-dependent factors or in prothrombin activation fragment (F1+2), PCC infusion was associated with significant increases of factors II (2.7 U/dL per 1 U/dL of IX increase) and X (2.2 U/dL for 1 U/dL for 1 U/dL of IX). Patients who used Mononine as their sole therapeutic material during the 12-month period showed an excellent response in hemostasis for their bleeding episodes. Their experience with long-term use of Mononine was at least equivalent to their previous experience with PCC in the frequency and amount of factor usage. No patients developed antibody against mouse IgG or an increase in IX inhibitor during the 12-month period. These results indicate that monoclonal antibody-purified factor IX concentrate provides hemostatically effective factor IX replacement while avoiding extraneous thrombogenic substances.

Antibodies, Monoclonal↗
PubMed1979

Glanzmann's thrombasthenia. Report of two oral surgical cases using a new microfibrillar collagen preparation and EACA for hemostasis.

Glanzmann's thromboasthenia is a rare congenital platelet disorder characterized by a prolonged bleeding time, a qualitative platelet defect, and severe hemorrhagic episodes. Patients with this disorder have been managed by administration of blood and blood components (most recently, platelet-rich plasma and platelet concentrates) to control hemorrhage resulting from trauma or surgical procedures. The two case reports presented here illustrate the use of a local hemostatic agent (microfibrillar bovine collagen, Avitene) and a systemic fibrinolytic inhibitor (epsilon aminocaproic acid, Amicar) to control postoperative hemorrhage secondary to elective extraction of teeth. The clinical results demonstrate excellent postoperative hemostasis and support recent in vitro observation of platelet adherence to the collagen preparation. This provides an alternate therapeutic modality in the management of patients with Glanzmann's disease and possibly other disorders of platelet function.

Abscess↗
PubMed1978

Thrombin binding to thrombasthenic platelets.

Platelets from two patients with Glanzmann's thrombasthenia showed decreased iodination of surface glycoproteins GPIIb and GPIII. Despite these changes, the binding of [125I] alpha-thrombin to the thrombasthenic platelets was normal. Binding was linear up to a thrombin concentration of 0.1 to 0.2 U/ml, at which point a change in the slope of the binding curve was observed. At lower concentrations of thrombin, 1,000 to 2,000 molecules of thrombin were bound per platelet, with an apparent Kdiss of 0.1 to 0.3 U/ml. With high concentrations of thrombin, thrombasthenic platelets bound 30,000 to 65,000 molecules of thrombin per platelet at saturation, with an apparent Kdiss of 5 to 10 U/ml. The release of [14C]serotonin by thrombasthenic platelets as a function of thrombin concentration was also similar to release by normal platelets. These studies indicate that the receptor(s) for thrombin on the plasma membrane of platelets from patients with Glanzmann's disease are intact and that membrane glycoproteins GPIIb and GPIII play little or no role in either the initial binding of thrombin to platelets or the transmission of this surface stimulus to release-inducing mechanisms.

Adult↗
PubMed1977

Structure-function relationships in the interaction of alpha-thrombin with blood platelets.

Highly purified alpha-thrombin has been chemically modified in an attempt to determine which features of the molecule are important for normal platelet-thrombin interactions. Modifying agents included diisopropylphosphorofluoridate and 1-chloro-3-tosylamido-7-amino-L-2-heptanone, which modify serine and histidine, respectively, at the catalytic site, as well as N-bromosuccinimide and 2-hydroxy-5-nitrobenzyl bromide, which modify a single tryptophan at or near the fibrinogen-binding site. Active site-directed modification did not appreciably affect the binding characteristics, but prevented platelet activation. In contrast, modification of tryptophan at the macromolecular substrate-binding site resulted in the loss of high affinity binding of thrombin to platelets, while low affinity binding was apparently unaffected. This modification altered but did not abolish the ability of thrombin to effect platelet aggregation and release of [14C]serotonin. These results suggest that residues at the catalytic site are not involved in binding and that the macromolecular substrate-binding site of alpha-thrombin participates in high affinity binding to platelets. These data are also consistent with the existence of at least two types of binding sites for thrombin on the platelet surface as well as more than one platelet-binding region on the thrombin molecule.

2-Hydroxy-5-nitrobenzyl Bromide↗
PubMed1977

Treatment of anti-factor VIII antibodies.

Bleeding episodes in patients with hemophilia A with anti-factor VII antibodies are frequently difficult to treat. Factor VIII concentrates administered by continuous infusion or prothrombin complex concentrates (PCC) have been used for treatment. Hemophilia A patients with inhibitors who respond to factor VIII concentrates generally have low to moderate inhibitor titers (generally less than 20 Bethesda units). Those patients who receive PCC are quite difficult to evaluate but promising clinical responses have clearly been observed. This paper describes our experience with both modalities of therapy and will offer specific guidelines for such therapy.

Adult↗
PubMed1977

Prothrombin complex concentrates: potentially thrombogenic materials and clues to the mechanism of thrombosis in vivo.

Factors affecting the coagulant activity of two different prothrombin complex concentrates have been investigated using a sensitive in vitro assay developed in this laboratory. One concentrate contained substantial amounts of potentially thrombogenic material, while the other, which was deliberately fortified with antithrombin III and heparin during production, was judged to be relatively nonthrombogenic. The coagulant activity of the thrombogenic concentrate has been partially identified and was due largely to the presence of coagulation factos IXa and Xa. Neither concentrate contained detectable thrombin. However, after incubation with calcium or various polyamines, large amounts of additional coagulant material, including thrombin, appeared. Heparin and antithrombin III not only neutralized the thrombogenic materials present in the thrombogenic concentrate, but also inhibited the de novo generation of coagulant enzymes during incubation with calcium. The implication of these studies on the preparation of prothrombin complex concentrates and on host susceptibility to thrombosis during the clinical use of these concentrates is discussed.

Antithrombins↗
PubMed1977

Estimation and testing of parameters in Richards growth model for western grebes.

Growth rate coefficients for dark- and light-phase western grebes (Aechmophorus occidentalis) are compared with the Richards' growth model. The statistical assumptions necessary to estimate and test parameters are carefully scrutinized. Autocorrelations of the residuals are removed with an autoregressive model, and heterogeneity of variance of the residuals is corrected with weighted least squares. A model allowing random variation in the process of growth is also suggested as being a more realistic representation of the process. No differences were detected between dark- and light-phase growth rate coefficients.

Animals↗
PubMed1976

Bladder cancer in rubber workers. Do screening and doctors' awareness distort the statistics?

The use of recognised carcinogens in the rubber industry before 1950 led to the introduction of screening progammes offering urinary cytology to workers who had been exposed. Publicity given to the introduction of these programmes and to individual claims for compensation have increased medical practitioners' awareness of a relationship between work and the industry and the subsequent development of bladder cancer. In this study 27 rubber workers and 88 controls registered in 1966 and 1967 with bladder cancer have been followed. A comparison of their death-rates and of the relative frequency of bladder cancer recorded on the death certificates should indicate whether cytological screening or doctors' awareness might explain a recent rise in the bladder-cancer death-rate in this industry. Since the proportions of rubber workers and controls who died before 1976 were similar (74% and 73% respectively) and bladder cancer was mentioned with similar frequence on their death certificates (80% and 83% respectively) neither screening nor doctor's awareness would appear to have an important influence.

Adenocarcinoma↗
PubMed1976

Distribution of survival times of 12,000 head and neck cancer patients who died with their disease.

The lognormal parametric statistical model can provide, for groups of carcinoma cervix patients, good estimates of long-term survival fractions several years earlier than would otherwise be possible. The present paper extends this model work to head and neck cancer by using a minimum chi-squared test for goodness of fit (P greater than 0-05), to study the distribution of survival times of patients who died with their cancer present. Some 12,000 case histories were available from 7 hospital registries, 4 regional cancer registries and one national registry (the OPCS). All histories were followed up for at least 10 years subsequent to treatment and could be grouped into one of 8 cancer sites: antrum, floor of mouth, larynx, nasopharynx, pyriform fossa, post cricoid, tonsil and tongue. The theoretical distributions investigated were the lognormal, negative exponential and skew exponential. The results showed that the lognormal provided the best overall fit to the data, although the range of optimum values for the lognormal parameter, S, differed with cancer site. The optimum range did, however, usually include the value S=0-45. These results will now permit the second stage of validation of the lognormal model to proceed for head and neck cancers.

England↗