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Clinical and Experimental Immunology Jul 1979Recent studies in experimental crescentic glomerulonephritis, using the technique of glomerular culture, have shown that the macrophage is a major cell type present...
Recent studies in experimental crescentic glomerulonephritis, using the technique of glomerular culture, have shown that the macrophage is a major cell type present within the glomeruli and developing crescents. It has been suggested that their accumulation is a consequence of glomerular fibrin deposition. The effect of defibrination with ancrod on the cellular events occurring in experimental crescentic glomerulonephritis in the rabbit was therefore assessed in this disease using the techniques of culture of isolated glomeruli, electronmicroscopy or renal tissue, and light microscopy. Defibrinated animals developed only minimal renal impairment, virtually no fibrin deposition in Bowman's Space and only a mild degree of crescent formation, in contrast to the severe renal failure, fibrin deposition and crescent formation that occurred in the untreated animals. The culture of isolated glomeruli and electronmicroscopy of intact renal tissue demonstrated large numbers of macrophages within and emerging from glomeruli of both defibrinated and untreated animals. However, only in untreated animals were macrophages seen to migrate into Bowman's Space, phagocytose fibrin, transform into epithelioid cells and accumulate to form crescents. These studies suggest that fibrin deposition in Bowman's Space is the major stimulus to the macrophage migration from capillary loops and accumulation in Bowman's Space. However, fibrin deposition does not appear to be the stimulus to macrophage accumulation within capillary loops as this event was not affected by defibrination.
Topics: Animals; Culture Techniques; Female; Fibrin; Glomerulonephritis; Kidney Glomerulus; Macrophages; Microscopy, Electron; Rabbits
PubMed: 487657
DOI: No ID Found -
British Journal of Experimental... Apr 1979Injection of bacterial lipopolysaccharide into pregnant mice resulted in fibrinogen accumulation, thrombosis and haemorrhage in the placental tissue and foetal death....
Injection of bacterial lipopolysaccharide into pregnant mice resulted in fibrinogen accumulation, thrombosis and haemorrhage in the placental tissue and foetal death. Depletion of circulating fibrinogen by a thrombin-like enzyme from the venom of Malayan pit viper, Arvin, prevents foetal death. Foetal protection was also obtained by treating the mothers with a preparation of phospholipase C from Bacillus cereus known to inactivate tissue thromboplastin. It is suggested the lipopolysaccharide causes foetal death by inducing thrombosis as a consequence of activation of placental thromboplastin.
Topics: Ancrod; Animals; Female; Fetal Death; Fibrinogen; Lipopolysaccharides; Mice; Phospholipases; Placenta; Pregnancy; Thrombosis
PubMed: 444421
DOI: No ID Found -
The Journal of Biological Chemistry Apr 1978The potential cross-link acceptor sites of fibrin were specifically labeled with the fluorescent, substitute cross-link donor monodansyl cadaverine (MDC). Several...
The potential cross-link acceptor sites of fibrin were specifically labeled with the fluorescent, substitute cross-link donor monodansyl cadaverine (MDC). Several fluorescent alpha-chain peptides generated from enzymatic and cyanogen bromide (CNBr) cleavage of the labeled fibrin were identified by sodium dodecyl sulfate disc gel electrophoresis; they were isolated and then characterized by amino acid analysis, NH2-terminal sequence analysis, and chromatographic and electrophoretic analyses of their digestion products. Ancrod cleavage of MDC-labeled fibrin produced a series of six alpha-chain peptides of molecular weights 34,000 to 12,000, each of which contained an MDC-labeled acceptor site, and an NH2-terminal alpha-chain derivative of molecular weight 37,500. The latter remains disulfide bound in the residual fibrin and has two MDC-labeled sit-s which are separable by CNBr cleavage. Mild plasmin digestion of MDC-labeled fibrin generated fluorescent alpha-chain peptides of molecular weights 45,000, 42,000, 35,000, 23,000, 21,000, and 2,500 in the supernatant and a nonfluorescent NH2-terminal alpha-chain derivative of molecular weight 25,000 which remained in the insoluble residual fibrin. The alignment of these plasmic supernatant peptides was determined from NH2-terminal sequence analyses which indicated that an MDC acceptor site was located at approximately residue 255 of the Aalpha-chain. Cleavage of the MDC-labeled alpha-chain by CNBr, however, localized most of its fluorescence (approximately 80%) to a fragment of molecular weight 29,000 which had the same NH2-terminal sequence as the labeled plasmic peptide of molecular weight 21,000. Both peptides were cleaved by ancrod into two acceptor site-containing peptides of approximately equal fluorescence. The preliminary NH2-terminal sequence analyses of these peptides, when combined with the above findings, indicated that these two other cross-link acceptor sites are in a peptide segment which comprises the middle 17% of the Aalpha-chain.
Topics: Amino Acids; Binding Sites; Cadaverine; Dansyl Compounds; Fibrin; Fibrinogen; Humans; Macromolecular Substances; Molecular Weight; Protein Binding
PubMed: 632262
DOI: No ID Found -
Blood Oct 1977The polymerization of thrombin and ancrod fibrin monomers was studied with a standardized technique that evaluated turbidity changes and protein incorporation into the... (Comparative Study)
Comparative Study
The polymerization of thrombin and ancrod fibrin monomers was studied with a standardized technique that evaluated turbidity changes and protein incorporation into the clot. Ancrod fibrin monomers were found to polymerize more slowly and form less turbid clots (at identical protein concentrations). Changes in ionic strength and pH influences ancrod fibrin monomer polymerization to a greater extent than thrombin fibrin monomer polymerization. Benzyltriethylammonium chloride was shown to be a potent inhibitor of fibrin monomer polymerization, with a greater inhibitory effect on ancrod fibrin monomers than on thrombin fibrin monomers. The differences between ancrod and thrombin fibrin may play a role in the infrequent thrombotic complications reported with ancrod therapy.
Topics: Ancrod; Chemical Phenomena; Chemistry; Electrophoresis, Polyacrylamide Gel; Fibrin; Humans; Hydrogen-Ion Concentration; Osmolar Concentration; Polymers; Thrombin
PubMed: 20184
DOI: No ID Found -
British Journal of Cancer Jun 1977
Topics: Ancrod; Animals; Coumarins; Diet; Lung Neoplasms; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms, Experimental; Transplantation, Isogeneic; Vitamin K Deficiency
PubMed: 871374
DOI: 10.1038/bjc.1977.135 -
British Medical Journal Feb 1977
Topics: Ancrod; Drug Resistance; Endopeptidases; Humans; Thromboembolism
PubMed: 837184
DOI: 10.1136/bmj.1.6059.508-c -
British Medical Journal Jan 1977
Topics: Adult; Ancrod; Antibody Formation; Endopeptidases; Female; Humans; Hydrocortisone; Thromboembolism
PubMed: 837082
DOI: 10.1136/bmj.1.6056.290-c -
Annals of the Royal College of Surgeons... Nov 1976The plasma fibrinogen concentration is directly related to blood viscosity, which in turn is inversely related to blood flow. The way in which the plasma fibrinogen...
The plasma fibrinogen concentration is directly related to blood viscosity, which in turn is inversely related to blood flow. The way in which the plasma fibrinogen level affects the clinical status of patients with peripheral vascular disease is discussed with reference to both retrospective and prospective studies of patients undergoing major arterial surgery. Animal experiments are described in which the effect of reducing the plasma fibrinogen level with oral clofibrate and parenteral Arvin (ancrod) on the patency of Dacron arterial grafts was studied.
Topics: Ancrod; Animals; Blood Flow Velocity; Blood Vessels; Blood Viscosity; Body Temperature; Clofibrate; Depression, Chemical; Fibrinogen; Hematocrit; Humans; Intermittent Claudication; Postoperative Complications; Rabbits; Vascular Surgical Procedures
PubMed: 984690
DOI: No ID Found -
Kidney International Nov 1976Defibrination with ancrod in nephrotoxic nephritis in rabbits. In rabbits with nephrotoxic nephritis, defibrination with ancrod provided protection when administered...
Defibrination with ancrod in nephrotoxic nephritis in rabbits. In rabbits with nephrotoxic nephritis, defibrination with ancrod provided protection when administered during the autologous phase, after extensive glomerular fibrin deposition had occurred and crescents and renal failure were developing. When further glomerular fibrin deposition was prevented by defibrination, deposited fibrin was rapidly removed, indicating that glomerular fibrin-clearing mechanisms are retained in crescentic nephritis. Defibrination had no effect on the extent of glomerular C3 deposition or on the amount of proteinuria.
Topics: Ancrod; Animals; Basement Membrane; Complement C3; Creatinine; Disease Models, Animal; Endopeptidases; Fibrin; Fibrinolysis; Fluorescent Antibody Technique; Immune Sera; Immunoglobulin G; Kidney Glomerulus; Male; Nephritis; Rabbits
PubMed: 794557
DOI: 10.1038/ki.1976.120 -
British Journal of Experimental... Aug 1976It is shown that after a single i.v. dose of [131I]-polyvinylpyrrolidone ([131I]-PVP) the total body and plasma radioactivities of rabbits decrease at distinctly...
It is shown that after a single i.v. dose of [131I]-polyvinylpyrrolidone ([131I]-PVP) the total body and plasma radioactivities of rabbits decrease at distinctly different rates. The difference between these two rates is utilized to calculate the phagocytic rate of [131I]-PVP by reticuloendothelial cells.A number of experimental conditions are reported in which enhanced reticuloendothelial uptake of [131I]-PVP is readily demonstrable. They include the injection of small quantities of heterologous plasma, certain proteolytic fragments of the fibrinogen molecule, the clearance of antigen-antibody complexes, and the acute phase reaction (inflammatory response) as brought about by serum sickness, sterile abscess and vaccination. Based on these observations it is suggested that [131I]-PVP may provide a convenient technique for the long-term monitoring of the activity of reticuloendothelial cells, presumably mainly that of the histiocytes. The pronounced polydispersity of commercially available [131I]-PVP is a serious problem in this respect which can be largely overcome, but not completely abolished, by the screening techniques described herein. Post-mortem analyses of rabbit tissues showed most of the [131I]-PVP to be present in the skin (20%), followed by the liver (14%), bone marrow (10%), muscle (7%) and kidney (5%). Gel filtration studies with [131]-PVP in the presence and in the absence of plasma proteins failed to demonstrate any association between PVP and the proteins. [131I]-PVP kept at physiological pH and 37 degrees C lost less than 5% of its radioactivity over one month due to spontaneous deiodination.
Topics: Ancrod; Animals; Antigen-Antibody Complex; Chromatography, Gel; Fibrinogen; Iodine Radioisotopes; Mononuclear Phagocyte System; Phagocytosis; Povidone; Rabbits; Rats; Vaccines
PubMed: 971408
DOI: No ID Found