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Biomedical subjects

W R Bell

Publications and source records attributed to W R Bell.

At least 91 records · Page 5Linked to original sources
PubMed1985

Disorganization of cultured vascular endothelial cell monolayers by fibrinogen fragment D.

Fibrinogen fragment D, which is heterogeneous, has several important biological functions. Human fibrinogen fragments D94 (molecular weight, 94,000), D78 (78,000), and E (52,000) were purified. Fragments D78 and D94 but not purified fibrinogen or fragment E specifically caused disorganization of bovine aortic endothelial cells cultured as monolayers. Within 2 hours of exposure to pathophysiological concentrations of fragment D, the confluent endothelial cells retracted from each other and projected pseudopodia. These disturbed cells subsequently became rounded and detached from the substrate. The actin present in stress fibers in stationary monolayer cells was diffusely redistributed in cells with fragment D-induced alterations in morphology. This effect was not observed in monolayers of kidney epithelial cells. The results demonstrate a specific effect of fibrinogen fragment D on the disorganization of cultured vascular endothelial cell monolayers and suggest that fragment D plays a role in the pathogenesis of syndromes with vascular endothelial damage.

Actins↗
PubMed1985

Histidine-rich glycoprotein and changes in the components of the fibrinolytic system after streptokinase therapy in patients with pulmonary thromboembolism.

Although the biological function of histidine-rich glycoprotein (HRG) is unknown, it may serve as an antifibrinolytic agent by interfering with the binding of plasminogen to fibrin. To define the role of HRG, plasma titers were measured by single radial immunodiffusion in eleven patients with thromboembolism before and after streptokinase (SK) therapy and were found unchanged (84.7 +/- 6.2%, M +/- SEM before, and 99.5 +/- 6.3% after 12 hr of SK therapy). The HRG peaks on crossed immunoelectrophoresis before and after SK infusion were also unchanged. Alpha 2-plasmin inhibitor fell during SK infusion as measured immunologically (102.0 +/- 15.0% before and 28.0 +/- 1.6% after 12 hr of therapy) and fibrinogen-fibrin degradative products appeared (mean titer of 1:2,048 after 12 hr of therapy), indicating that the infused SK was biologically active. Plasminogen levels before therapy were normal, as measured functionally and immunologically (105.4 +/- 4.9% and 96.0 +/- 5.6%, respectively), and both decreased after 12 hr of SK therapy (15.2 +/- 5.6% and 50.8 +/- 4.3%). No changes in functional antithrombin III titer, Hageman factor antigen level, or fibrinogen concentration, as measured turbidimetrically, were observed. Thus, although these data do not allow one to make any firm conclusions regarding the physiologic role of this protein in fibrinolysis, they do not exclude its increased catabolism, compensated by increased production, in patients undergoing fibrinolytic therapy.

Blood Proteins↗
PubMed1985

Trousseau's syndrome. Devastating coagulopathy in the absence of heparin.

Two patients with Trousseau's syndrome experienced frequently recurring concomitant arterial and venous thrombotic events that resulted in sequential amputation and loss of the lower extremities. Serial examination of the blood in the patients demonstrated that these devastating thrombotic events were preceded by severe disseminated intravascular coagulopathy that occurred within an interval of a few hours. Warfarin therapy was without effect in preventing the occurrence of these events. Both patients demonstrated the absolute need for intravenous heparin, which effectively prevented the thrombotic events; when it was discontinued, the immediate consequences were disastrous and resulted in death. Techniques for long-term outpatient heparin therapy are discussed.

Blood Coagulation Tests↗
PubMed1985

Metastatic intravagal paraganglioma. Case report and review of the literature.

Intravagal paragangliomas are rare tumors of neural crest origin. These tumors are usually benign with few reports of metastases or aggressive behavior. One case of intravagal paraganglioma metastatic to a regional lymph node is described and the diagnosis and management of these tumors are discussed. The reports of 14 other cases with regional or distal metastases are reviewed.

Adult↗
PubMed1985

Novel factor X deficiency. Normal partial thromboplastin time and associated spindle cell thymoma.

This report presents a heretofore undescribed laboratory variant of congenital factor X deficiency, seen in conjunction with a relatively rare tumor. The patient had a history of bleeding, a prolonged prothrombin time, and a factor X value of 4.2 percent of normal activity, but the partial thromboplastin time and Russell's viper venom clotting time were normal. Management of this case required unusual measures to treat the patient's coagulopathy.

Blood Coagulation Tests↗
PubMed1985

Assay of human fibrinopeptides by high-performance liquid chromatography.

Fibrinopeptides A, AP, and B, desarginine fibrinopeptide B, and a previously unknown peptide corresponding to B beta 3-14 were resolved within 10 min by an HPLC technique using an isocratic solvent system (22% acetonitrile in 0.1% trifluoroacetic acid) and a 0.46 X 10-cm Spherisorb ODS-2 (3-micron) octadecylsilane column. Fibrinopeptides A and AY eluted in the same peptide peak. The method was used to evaluate a carboxypeptidase which converts fibrinopeptide B into its desarginine form. Fifty percent inhibition of this activity occurred at 1.7 mM epsilon-aminocaproic acid (EACA). At saturating substrate concentrations the rates of total fibrinopeptides A and B release were unaffected by 125 mM EACA, a concentration at which the carboxypeptidase activity is completely inhibited.

Amino Acid Sequence↗
PubMed1985

A model of the heterogeneity of red cell hemoglobin concentration.

A model of red cell hemoglobin concentration has been developed and computer stimulations performed to investigate quantitatively the relationship among the intraindividual heterogeneities of cell hemoglobin content, volume, and hemoglobin concentration. In the model, the cell volume and hemoglobin content frequency distributions and their joint distributions are described by Gaussian probability distributions. The frequency distributions of cell hemoglobin concentration are determined from the joint probability distributions by summing the joint probabilities of the variate pairs the ratios of which equal the specified concentration. For the parameter values considered, the mean cell hemoglobin concentration closely approximates the average (i.e., statistical mean) concentration. The heterogeneity of cell hemoglobin concentration increases with increasing coefficients of variation of cell hemoglobin content and cell volume and with decreasing correlation coefficients. When the correlation coefficient is greater than 0.7, cell hemoglobin concentration shows less relative dispersion than the component indices.

Erythrocyte Indices↗
PubMed1985

Microwave technology for the rapid thawing of frozen blood components.

Based on a continuing need to provide a more rapid response to requests for thawed fresh frozen plasma, the authors evaluated plasma thawing with the use of a microwave oven and compared it with conventional 37 degrees C waterbath thawing methods. Their results indicate that microwave-thawed plasma contains precipitated denatured protein (mainly albumin and fibrinogen) and that there is a significant reduction of coagulation Factors IX, X, XI, and fibrinogen compared with fresh plasma. They also measured levels of di-ethyl hexyl phthalate after microwave thawing and found its rate of accumulation similar to that of the 37 degrees C waterbath. More importantly, fundamental principles of microwave heating preclude uniform temperatures being maintained throughout the thawing of plasma; hence, the denaturation of plasma proteins is expected to occur under even low heating conditions.

Blood Preservation↗
PubMed1985

Thrombolytic therapy for inferior vena cava thrombosis in paroxysmal nocturnal hemoglobinuria.

Two patients with paroxysmal nocturnal hemoglobinuria had increasing abdominal girth and ascites. The Budd-Chiari syndrome or inferior vena cava thrombosis was shown by angiography. After thrombolytic therapy, both patients improved, and thrombolysis was shown by radiography. Neither patient had induction of hemolysis secondary to these agents. These studies suggest that both streptokinase and urokinase are safe and effective in the treatment of intra-abdominal venous thromboses associated with paroxysmal nocturnal hemoglobinuria.

Abdomen↗
PubMed1985

Coronary thrombolysis with recombinant tissue-type plasminogen activator. A hematologic and pharmacologic study.

The blood of 30 patients who received recombinant tissue-type plasminogen activator for lysis of acute coronary thrombosis was examined to identify the effects of this enzyme on the fibrinolytic and coagulation systems. Doses ranged from 20 to 80 mg and duration of infusion ranged from 15 minutes to 4.5 hours. Doses of 60 mg or less and duration of infusion of 2 hours or less caused only mild fibrinogenolysis, a 28% drop from baseline plasma fibrinogen concentrations to nadir. In contrast, higher doses or longer infusion periods led to significantly lower fibrinogen levels, a 61% decrease of fibrinogen levels at nadir (p less than 0.01), and this effect was sustained. Dosing by weight led to less appreciable fibrinogen breakdown. A strong negative correlation was seen between plasma plasminogen activator and fibrinogen levels (r = -0.83, p less than 0.001) during the infusion. In-vitro studies showed the enzyme to deplete fibrinogen rapidly, and this activation was blocked with a protease inhibitor.

Adult↗
PubMed1984

Evidence that less replacement therapy is required for dental extractions in hemophiliacs.

The requirements for factor VIII (AHF) or factor IX (PTC) of hemophilic patients undergoing dental extractions were evaluated to determine the minimum effective regimen. Sixteen patients underwent 19 operative procedures. The mean total dose of factor VIII or IX was 45.8 U/kg for 11 procedures with preoperative replacement therapy and 34.5 U/kg for the 8 without. Four patients received no replacement therapy at all. Our results compared favorably to published studies employing factor replacement alone or in combination with antifibrinolytic agents such as epsilon-amino-caproic acid (EACA), with respect to blood products utilized and duration of hospitalization. However, our patients received less factor replacement than usually suggested. General anesthesia with intubation, a common recommendation, was not required in any patients. Dental extractions can be carried out in hemophiliacs using less replacement therapy than currently recommended. In some circumstances, no replacement therapy may be necessary. The reported efficacy of antifibrinolytic agents in reducing the requirement for replacement therapy is difficult to assess because of the relatively large amount of prophylactic factor replacement used in conjunction with these agents.

Factor IX↗
PubMed1984

Distribution of antithrombin III and glucosylceramide in human plasma lipoproteins and lipoprotein deficient plasma.

We have investigated the distribution of antithrombin-III and glucosylceramide (Glc-Cer) in human plasma, plasma lipoproteins and lipoprotein-deficient plasma. Antithrombin III activity was measured employing immunochemical and biological assays. Glc-Cer was quantified by gas liquid chromatography (GLC). Whole plasma contained 145 micrograms antithrombin III/ml plasma, all of which was associated with the lipoprotein-deficient plasma (d greater than 1.25 g/ml). Whereas, most if not all the plasma GlcCer was associated with plasma low density lipoproteins (LDL) (d-1.022-1.055 g/ml) and high density lipoproteins (HDL) (d-1.063-1.25). GlcCer was not found in the lipoprotein-deficient plasma. We conclude that GlcCer on lipoproteins does not contribute to antithrombin III activity. Moreover, the absence of GlcCer in lipoprotein-deficient plasma does not impair antithrombin-III activity.

Antithrombin III↗
PubMed1984

The fibrinolytic system in man.

The existence of a system in the human body capable of inducing the dissolution of endogenous pathologically formed thrombi was appreciated in ancient times. Considered in detail in this article are the data that have elucidated the physiologic regulation of which plasmin formation is dependent on, the plasma concentration of plasminogen, availability of activators of plasminogen in the plasma and surrounding tissue environment, the concentration of naturally present inhibitors, and the existence of fibrin in the circulation. Important in this rapidly progressive scientific discipline is consideration of the factors which control the synthesis of the components of this proteolytic enzyme system. Recently abundant information has indicated that this plasminogen-plasmin proteolytic enzyme system can be utilized therapeutically. Knowledge of the mechanisms of this system has permitted identification of agents that can be exogenously administered to releave thrombotic obstruction to blood flow in the venous (pulmonary emboli, deep vein thrombosis) and arterial (peripheral and central vessels) circulatory systems. Particularly important is the demonstration that thrombolytic agents can directly attack and alleviate the immediate cause of acute myocardial infarction. As a result of the innovations in the present decade, it is evident that the plasminogen system can be advantageously employed to reverse the pathologic effects of all thrombotic diseases.

Antifibrinolytic Agents↗