Structural elucidation of high‐molecular‐weight alkaline degradation products of hexoses

1. Native DNA from two strains of Bacillus subtilis was chromatographed by stepwise elution from MAK (methylated albumin on kieselguhr). 2. Transforming activity was confined to two out of the three main fractions, activity being distributed between the two peaks differently for DNA from the different strains. 3. Fractionation of DNA from both strains on 2% agarose gel gave two components. Approx. 75% of the material was eluted within the void volume of the column. Approx. 25% of the material consisted of degradation products of lower molecular weight. 4. Chromatography on MAK of the material of high molecular weight eluted from agarose gel gave a number of peaks differing in molecular weight, indicating that degradation of the DNA takes place during chromatography on MAK. 5. The distribution of transforming activity among the fractions from MAK suggests that degradation occurs preferentially in certain regions of the DNA.

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Activated Thrombin-activatable Fibrinolysis Inhibitor Reduces the Ability of High Molecular Weight Fibrin Degradation Products to Protect Plasmin from Antiplasmin

Journal of Biological Chemistry ◽

10.1074/jbc.m313211200 ◽

2004 ◽

Vol 279 (14) ◽

pp. 13340-13345 ◽

Cited By ~ 23

Author(s):

Mark Schneider ◽

Nicole Brufatto ◽

Erin Neill ◽

Michael Nesheim

Keyword(s):

Molecular Weight ◽

High Molecular Weight ◽

Degradation Products ◽

Thrombin Activatable Fibrinolysis Inhibitor ◽

Fibrin Degradation Products ◽

Fibrinolysis Inhibitor

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The Fibrin Assay Comparison Trial (FACT)

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615652 ◽

2001 ◽

Vol 85 (04) ◽

pp. 671-678 ◽

Cited By ~ 82

Author(s):

Sybille Zips ◽

Hanimsah Ergül ◽

Dieter Heene ◽

Carl-Erik Dempfle ◽

Keyword(s):

Molecular Weight ◽

High Molecular Weight ◽

Degradation Products ◽

Plasma Samples ◽

Fibrin Degradation Products ◽

Comparison Trial ◽

Clinical Conditions ◽

D Dimer

SummaryAlthough D-dimer has gained widespread clinical use as a parameter for detection of in vivo fibrin formation, the issue of standardization of D-dimer assays remains to be resolved. The FACT study was performed to generate basic data for development of calibrators and standard preparations.A set of 86 samples, including plasma samples from patients with DIC, DVT, and other clinical conditions, serial dilutions of pooled plasma samples, and plasma samples containing fibrinogen- and fibrin derivatives, were distributed to 12 manufacturers of D-dimer assays.D-dimer assays differ concerning specificity for crosslinked fibrin, and preference for either high molecular weight fibrin complexes, or low molecular weight fibrin degradation products. Terminal plasmin digests of fibrin clots for calibration produce aberrant results in some assays, especially those with preference for high molecular weight crosslinked fibrin derivatives. The best conformity is achieved by the use of pooled plasma samples from patients with high levels of D-dimer antigen in plasma. In vitro preparations containing a comparable composition of fibrin derivatives to clinical plasma samples may also serve as reference material.

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Characterization of Chlorinated Aromatic Structures in High Molecular Weight BKME-Materials and in Fulvic Acids from Industrially Unpolluted Waters

Water Science & Technology ◽

10.2166/wst.1994.0704 ◽

1994 ◽

Vol 29 (5-6) ◽

pp. 81-91 ◽

Cited By ~ 6

Author(s):

O. Dahlman ◽

A. Reimann ◽

P. Ljungquist ◽

R. Mörck ◽

C. Johansson ◽

...

Keyword(s):

Molecular Weight ◽

High Molecular Weight ◽

Organic Materials ◽

Degradation Products ◽

Methyl Esters ◽

Acid Methyl Ester ◽

Fulvic Acids ◽

Gas Chromatography Mass Spectrometry ◽

Degraded Samples

This paper presents the results of a comprehensive characterization of chlorinated aromatic structures in high molecular weight organic material from bleached kraft mill effluents (BKME) and industrially unpolluted surface waters and groundwaters. After oxidative degradation (permanganate) of the organic materials and derivatization (diazomethane) of the degradation products obtained, the occurrence of chlorinated aromatic degradation products was investigated using gas chromatography/mass spectrometry. About twenty chlorinated methyl esters of aromatic carboxylic acids were identified in degraded samples of both industrial and natural origin. The identified compounds originated from chlorinated 4-hydroxyphenyl, 3,4-dihydroxyphenyl, guaiacyl, “condensed” guaiacyl, syringyl and veratryl units present as structural elements in the high molecular weight organic materials studied. Degradation products originating from mono- and dichlorinated 4-hydroxyphenyl units dominated in the degraded samples from unpolluted environments, whereas degradation products originating from chlorinated guaiacyl and syringyl units were most abundant in the degraded softwood and hardwood BKME samples. A special study of the monochlorinated isomers of 4-ethoxy-3-methoxybenzoic acid methyl ester showed that the 6-chloro isomer dominated in the degraded BKME samples whereas about equal amounts of the 5-chloro and 6-chloro isomers were found in degraded fulvic acids isolated from unpolluted waters.

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Fibrin Degradation Products and Vascular Permeability

10.1055/s-0039-1680689 ◽

1977 ◽

Author(s):

Bengt Gerdin ◽

Herman Högstorp ◽

Olle Lindquist ◽

Tom Saldeen ◽

Erik Svensjö

Keyword(s):

Molecular Weight ◽

Vascular Permeability ◽

High Molecular Weight ◽

Degradation Products ◽

Cheek Pouch ◽

Low Molecular Weight ◽

Hamster Cheek Pouch ◽

Fibrin Degradation Products ◽

Lymphatic Duct ◽

Fibrin Clots

Increased vascular permeability plays an important role in the pathogenesis of the delayed microembolism syndrome. Fibrin degradation products (FDP) may play a role for this permeability disturbance. Fractions of lymph from the cannulated right lymphatic duct in dogs with induced microembolism syndrome and lysate from fibrin clots obtained by gel chromatography were used. The effect on vascular permeability was determined in the hamster cheek pouch and in the dorsal skin of the rat. Increased permeability was determined by leakage of fluorescein labelled dextran in the first model and by use of isotope labelled albumin in the second model. Lymph from the lymphatic duct and fractions of lysate from fibrin clots caused an increased vascular permeability of the same character in both models, the effect being partly due to high molecular weight products and partly due to low molecular weight products. The effect of high molecular weight products may possibly be due to their continous cleavage releasing low molecular weight vasoactive FDP. The effect of FDP on vascular permeability was enhanced by pretreatment with the β-adrenergic inhibitor propranolol and inhibited by the β2-adrenergie stimulator terbutaline. Bredykinin and PGE1 both increased macromolecular leakage in the hamster cheek pouch. This increase was also counteracted by terbutaline. The FDP effect on permeability might be due to contraction of the endothelial cells.

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High molecular weight kininogen inhibits fibrinogen binding to cytoadhesins of neutrophils and platelets.

The Journal of Cell Biology ◽

10.1083/jcb.109.1.377 ◽

1989 ◽

Vol 109 (1) ◽

pp. 377-387 ◽

Cited By ~ 64

Author(s):

E J Gustafson ◽

H Lukasiewicz ◽

Y T Wachtfogel ◽

K J Norton ◽

A H Schmaier ◽

...

Keyword(s):

Molecular Weight ◽

High Molecular Weight ◽

Degradation Products ◽

Platelet Glycoprotein ◽

Human Neutrophils ◽

Human Neutrophil Elastase ◽

Factor Xii ◽

High Molecular Weight Kininogen ◽

Gamma Chain ◽

Fibrinogen Binding

Fibrinogen inhibited 125I-high molecular weight kininogen (HMWK) binding and displaced bound 125I-HMWK from neutrophils. Studies were performed to determine whether fibrinogen could bind to human neutrophils and to describe the HMWK-fibrinogen interaction on cellular surfaces. At 4 degrees C, the binding of 125I-fibrinogen to neutrophils reached a plateau by 30 min and did not decrease. At 23 and 37 degrees C, the amount of 125I-fibrinogen bound peaked by 4 min and then decreased over time because of proteolysis of fibrinogen by human neutrophil elastase (HNE). Zn++ (50 microM) was required for binding of 125I-fibrinogen to neutrophils at 4 degrees C and the addition of Ca++ (2 mM) increased the binding twofold. Excess unlabeled fibrinogen or HMWK completely inhibited binding of 125I-fibrinogen. Fibronectin degradation products (FNDP) partially inhibited binding, but prekallikrein and factor XII did not. The binding of 125I-fibrinogen at 4 degrees C was reversible with a 50-fold molar excess of fibrinogen or HMWK. Binding of 125I-fibrinogen, at a concentration range of 5-200 micrograms/ml of added radioligand, was saturable with an apparent Kd of 0.17 microM and 140,000 sites/cell. The binding of 125I-fibrinogen to neutrophils was not inhibited by the peptide RGDS derived from the alpha chain of fibrinogen or by the mAb 10E5 to the platelet glycoprotein IIb/IIIa heterodimer. Fibrinogen binding was inhibited by a gamma-chain peptide CYGHHLGGAKQAGDV and by mAb OKM1 but was not inhibited by OKM10, an mAb to a different domain of the adhesion glycoprotein Mac-1 (complement receptor type 3 [CR3]). HMWK binding to neutrophils was not inhibited by OKM1. These observations were consistent with a further finding that fibrinogen is a noncompetitive inhibitor of 125I-HMWK binding to neutrophils. Fibrinogen binding to ADP-stimulated platelets was increased twofold by Zn++ (50 microM) and was inhibited by HMWK. These studies indicate that fibrinogen specifically binds to the C3R receptor on the neutrophil surface through the carboxy terminal of the gamma-chain and that HMWK interferes with the binding of fibrinogen to integrins on both neutrophils and activated platelets.

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Plasmic degradation of crosslinked fibrin. I. Structural analysis of the particulate clot and identification of new macromolecular-soluble complexes

Blood ◽

10.1182/blood.v56.3.456.456 ◽

1980 ◽

Vol 56 (3) ◽

pp. 456-464 ◽

Cited By ~ 53

Author(s):

CW Francis ◽

VJ Marder ◽

SE Martin

Keyword(s):

Molecular Weight ◽

Structural Analysis ◽

High Molecular Weight ◽

Polypeptide Chain ◽

Degradation Products ◽

Fibrin Clot ◽

Proteolytic Cleavages ◽

Soluble Complexes ◽

Covalently Bound

Abstract Plasmic degradation of crosslinked fibrin has been studied to identify the proteolytic cleavages that convert the clot into a soluble lysate and also to identify the derivatives that are likely to circulate during clot dissolution. Initial polypeptide chain cleavages do not disrupt the solid clot matrix. With continued exposure to plasmin, high molecular weight derivatives are produced that remain attached to the clot by noncovalent forces. Further degradation then results in the liberation into solution of several large, noncovalently bound complexes. Progressive degradation of the largest, initially liberated complexes to the terminal derivatives, DD/E, DD, and E, occurs in solution after their release from the clot. As the fibrin clot is exposed to plasmin for longer intervals, progressive dissolution occurs, but the structure of the covalently bound insoluble fibrin core, the noncovalently attached derivatives, and the liberated complexes remains constant. Since much of the initially liberated protein is in complexes larger than DD/E, these derivatives probably represent the more prevalent plasmic degradation products of crosslinked fibrin in vivo.

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