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Biomedical subjects

E A Beck

Publications and source records attributed to E A Beck.

At least 91 records · Page 5Linked to original sources
PubMed1976

Bleeding disorder with abnormal wound healing, acid-soluble clots and normal factor XIII.

An unusual bleeding disorder clinically resembling factor XIII deficiency is presented. The only detectable coagulation abnormality was rapid clot dissolution in 1% monochloroacetic acid. This abnormality was ascribed to the sustained increase of a pepsin-like plasma protease which is activated at low pH. Asystematic search for similar phenomena revealed that massive blood transfusion may also enhance plasma-clot solubility in acid, possibly by release of a red cell protease. We conclude that the acid clot solubility test is not a specific indicator of factor XIII deficiency, but this simple assay is recommended for further studies of acid plasma protease activity. The diagnostic relevance and pathophysiologic importance of increased pepsin-like activity in plasma remain to be elucidated.

Acetates↗
PubMed1976

Clottability and cross-linking reactivity of fibrin(ogen) following differential release of fibrinopeptides A and B.

Human fibrinogen was treated at pH 6.0, 7.3 and 9.0 with thrombin, batroxobin (thrombin-like fraction of Bothrops atrox venom) or an extract of the venom from Ancistrodon contortrix contortrix. These three enzymes released the NH2-terminal fibrinopeptides A and B at different rates. Thrombin-free, preactivated factor XIII (factor XIIIa) was added to incubation mixtures to stabilize resulting fibrin(ogen) aggregates. Cross-linking of gamma-chains and the size of covalently linked fibrin-fibrinogen oligomers were studied in an early stage of fibrinopeptide cleavage using polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. Batroxobin (pH 7.3) and thrombin (pH 6.0) preferentially released fibrinopeptide A, and resulting fibrin aggregates became rapidly insoluble. However, when fibrinopeptide B was removed with the contortrix enzyme, soluble cross-linked oligomers appeared initially. The opaque fibrin clots, produced by thrombin (pH 6.0) or contortrix procoagulant fraction (pH 7.3), were found to be devoid of alpha-polymers even after prolonged incubation with factor XIIIa. Our data suggest that the solubility and opacity of fibrin networks are not primarily related to the type of the cross-link (gamma-gamma versus alpha-alpha interactions).

Blood Coagulation↗
PubMed1976

[Structural model of factor VIII complex].

Gel filtration patterns on Sepharose CL-2B of functional subunits (procoagulant, ristocetin cofactor, antigen) derived from highly purified human factor VIII indicate that the native, intact complex is reproducibly eluted in the void volume. The complex is, however, degraded by proteolytic (and possibly other) enzymes contaminating the purified material during dialysis at room temperature. Resulting degradation products were fractionated by gel filtration and characterized by SDS-polyacrylamide electrophoresis. Our results suggest that factor VIII consists of identical subunits (mol. wt. about 500 000) which might be linked together by hydrophobic bonds. Only native high molecular weight aggregates posses ristocetin cofactor activity.

Factor VIII↗
PubMed1976

Reactivity of fibrinogen crosslinking sites in the absence of thrombin.

The reactivity of fibrinogen crosslinking sites with thrombin-free, preactivated factor XIII (F. XIIIa) was investigated under different conditions such as increased ionic strength, presence of urea, protamine sulfate (PS) or of varying concentrations of monodansylcadaverine (MDC). Crosslinking and incorporation of MDC into fibrinogen or fibrin gamma- and alpha-chains were evaluated by SDS-polyacrylamide gel electrophoresis. According to our results, rates of crosslinking of, and of MDC incorporation into, both gamma- and alpha-chains of fibrinogen were low under physiological conditions; they were not significantly influenced by the presence of either 1.0 M NaCl or 1.0 M urea. In contrast, 0.01% PS precipitated fibrinogen, and, simultaneously, significantly increased the rates of crosslinking and of MDC incorporation into both gamma- and alpha-chains. MDC, at concentrations above approximately 6 mM, also precipitated fibrinogen, and, up to a concentration of about 9 mM, markedly enhanced the reactivity of acceptor crosslinking sites. Our results suggest that solubility of fibrinogen and the conformational arrangement of its subunit chains are closely interdependent; the reactivity of crosslinking sites with F. XIIIa seems to be a function of this conformational state.

Animals↗
PubMed1976

[The clinical significance of granulocyte colonies in bone marrow cultures].

The culture system for in vitro evaluation of "colony forming units - culture (CFU-c)" is briefly outlined. This method offers a new approach to studies of proliferation and differentiation of hemopoietic progenitor cells, especially in disorders of granulopoiesis. From available published data it is evident that quantitation of CFU-c is also an indicator of diagnostic and prognostic value for assessment of various types of leukemia. The CFU-c assay has furthermore been introduced to test the viability and proliferating capacity of cryopreserved bone marrow, especially with a view to possible transfusion of stored autologous bone marrow as an adjuvant to cytostatic therapy.

Bone Marrow↗
PubMed1976

Importance of protease inhibition in studies on purified factor VIII (antihaemophilic factor).

According to some authors factor VIII procoagulant activity may be dissociable from carrier protein (MW approximately 2 X 10(6) by agarose gel filtration, e.g. at high ionic strength. We were able to reproduce this phenomenon. However, addition of protease inhibitor (Trasylol) prevented the appearance of low molecular weight peak of factor VIII procoagulant activity both at high ionic strength and elevated temperature (37 degrees C). We conclude from our results that procoagulant activity and carrier protein (von Willebrand factor, factor VIII antigen) are closely associated functional sites of native factor VIII macromolecule. Consequently, proteolytic degradation should be avoided in functional and structural studies on factor VIII and especially in preparing factor VIII concentrate for therapeutic use.

Antigens↗
PubMed1975

[Blood damage due to chloramphenicol and thiamphenicol].

Dose-related blood dyscrasias during treatment with either chloramphenicol or thiamphenicol chiefly include erythroid suppression and may be recognized at an early stage by observation of reticulocytopenia and an increased serum iron concentration. Ferrokinetic studies show the typical features of sideroblastic anemia. Whilst chloramphenicol is conjugated with glucuronic acid in the liver, thiamphenicol is predominantly eliminated by the kidney in its unmodified form. Sensitization against both drugs has been described and may, following reexposure, lead to dangerous granulocytopenia. Potentially the most dangerous late complication after chloramphenicol treatment, i.e. aplastic anemia, has not thus far been observed in patients treated with thiamphenicol.

Anemia, Aplastic↗
PubMed1975

[Diagnostic significance of the demonstration of fibrin and fibrinogen degradation products in the urine].

The concentration of fibrin/fibrinogen degradation products in urine (FDPu) was measured in samples obtained from 114 patients and 63 clinically healthy volunteers, once or repeatedly. The FDP titers measured by the hemagglutination inhibition (HI) method corresponded to less than 2.6 mug/ml FDP in all samples from healthy controls. Slightly elevated FDP concentrations were found in urine obtained from a few patients with disorders not primarily involving the urinary tract. The clinical importance of these isolated findings remains unclear. Urinary tract infections were not frequently accompanied by elevated FDPu concentrations. In patients with glomerulonephritis FDP excretion correlated somewhat better with severity of the renal affection. A further group of patients showed an unequivocal correlation between FDP excretion in the urine and postoperative complications following renal transplantation. However, the clinical diagnosis of acute rejection crisis was usually established at the same time or even before an increase in FDPu was found. Our results suggest that among diagnostic procedures the measurement of FDPu contributes little specific information for the evaluation of urinary tract disease. FDPu measurements in the immediate postoperative phase following renal transplantation may however be important for prognostic evaluation and, in individual cases, predict transplant rejection. We also attempted to define the FDPu qualitatively by simultaneous measurements using HI and the staphylococcal clumping test (SCT). Immunoelectrophoresis confirmed the well-known fact that the SCT detects only high-molecular FDP; this limits its clinical usefulness, despite its high sensitivity.

Female↗
PubMed1975

Plasmic degradation of human fibrinogen. III. Molecular model of the plasmin-resistant disulfide knot in monomeric fragment D.

A mixture of fragments D, derived from fibrinogen by plasmic degradation, was S-reduced and carboxymethylated. Individual chains were separated by gel filtration on Sephadex G-100 and characterized by peptide mapping, N-terminal amino acid analysis, polyacrylamide electrophoresis in sodium dodecyl sulfate, and amino acid composition. It was demonstrated that all D species contain the same alpha- and beta-chain remnants, having mol. wts of 10 000 and 45 000, respectively. Their heterogeneity was shown to be caused by the gradual degradation of the gamma-chain at its C-terminal end. Denatured fragment D was further degraded with plasmin in the presence of 2 M urea. One beta- (mol. wt 17 000) and two gamma-fragments (mol. wts 5000 and 6000) were split from fragment D, in addition to non-characterized small peptides, leaving behind a plasmin-resistant core, designated as fragment d. Fragment d was in turn reduced and carboxymethylated, and the resulting constituent chains were isolated by chromatography on carboxymethyl-cellulose and Sephadex G-100. The reduced alpha-, beta- and gamma-chain remnants of fragment d were found to have been derived from the N-terminal portion of fragment D and have estimated mol. wts of 9000, 24 000 and 13 000, respectively. A tentative scheme for the conversion of an early fragment D into the core fragment d is proposed. Our results conclusively support the model of asymmetric degradation of fibrinogen, according to which 2 mol of monomeric fragment D are produced from 1 mol of fibrinogen.

Amino Acid Sequence↗
PubMed1975

Plasmic degradation of human fibrinogen. IV. Identification of subunit chain remnants in fragment Y.

A method is presented for detection of cross-linking acceptor sites on fibrinogen chains, using monodansyl-cadaverine labeling in the presence of activated fibrin stabilizing factor, and polyacrylamide electrophoresis in the presence of sodium dodecyl sulfate. Fluorescent gamma-chain monomers and dimers were produced at a considerably faster rate than the labeled alpha-chain derivative. Purified fragments X, Y and D were prepared all from the same plasmic digest of fibrinogen. Following incubation with fibrin stabilizing factor, thrombin and monodansyl-cadaverine, they were reduced with beta-mercaptoethanol and examined by sodium dodecyl sulfate/acrylamide electrophoresis. Three gamma-chains (mol. wts 49 000, 42 000 and 39 000) had reacted with dansyl-cadaverine while no alpha-chain remnant took up the label. Additional protein and carbohydrate staining further facilitated identification of the individual subunit chains. At least three critical peptide bonds, located on alpha, beta- and gamma-chain remnants, must be broken during conversion of fragment Y into D and E. Sequential cleavage results in heterogeneous appearance of reduced subunit chains. As a consequence, there exist several molecular entities of fragment Y, all of which may have the same molecular weight though they represent various products of progressive plasmic digestion. Our results are compatible with the model of asymmetric degradation of fibrinogen, according to which fragment X produces 1 mol of fragment E e and 2 mol of the monomeric fragment D.

Amino Acid Sequence↗
PubMed1975

[Unexpected hemorrhage in surgery].

Unexpected hemorrhage in surgery may be avoided whenever preoperative examinations have not detected a defect of hemostasis. A prospective study conducted before oral surgery demonstrated that a simple preoperative screening program was suitable for specific detection of patients with bleeding tendencies and to indicate the need for a more detailed evaluation of hemostasis. The screening program includes a detailed history with the aim of detecting congenital defects of hemostasis or bleeding tendencies due to prolonged, acquired disorders. The thromboplastin time (Quick test) should be performed to evaluate asymptomatic, acquired coagulation defects, especially liver disease, whereas the semiquantitative determination of platelets on blood smears is necessary to rule out thrombocytopenia. A dramatic complication of massive bleeding is the so-called "dilution syndrome" caused by simultaneous blood loss and transfusion of stored blood (or red cells alone), leading to a progressive reduction of clotting factors and platelets. Therapeutic and organizational measures which are necessary in this exceptional situation are briefly discussed.

Blood Coagulation Tests↗