Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0155339 (Brown)
 12,436 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemorrhagic diathesis was observed in patients with renal insufficiency after carbenicillin at serum levels greater than 300 mug/ml. Normal coagulation factors (F. I, II, V, VII, VIII, X), normal PTT, normal platelet counts, negative ethanol gelation test (fibrin monomers) were found as well as a prolongation of thromboplastin time (Quick), thrombin time, reptilase time and thrombin coagulase time. Platelet function was disturbed. In addition, the plasmatic system was involved: inhibition of fibrinogen-fibrin conversion (Belitser assay) and enhanced antithrombin III activity; in vivo the latter was ascribed to a heparin-like activity. In vitro, abnormal III was seen: however an enhanced antithrombin III activity in vitro was not found with carbenicillin and various penicillin derivatives. This study demonstrates that carbenicillin, in addition to its known effect on platelet function, also disturbs the plasmatic coagulation system. This additional effect of carbenicillin is clinically important since protamin chloride effectively blocks bleeding without interfering with antibacterial activity. Both penicillin and penicillin derivatives have been shown to interfere with hemostasis and to cause clinically manifest hemorrhagic diathesis (Fleming and Fish 1947, Lurie et al. 1970a, b, McClure et al. 1970, Yudis et al. 1972, Demos 1971, Waisbren et al. 1971). Carbenicillin interferes with ADP-, collagen- or thrombin-induced platelet aggregation and with the release reaction both in vivo (McClure et al. 1970, Cazenae et al. 1973) and in vitro (McClure et al. 1970, Cazenave et al. 1973). In addition Lurie and colleagues (1970b) concluded that an inhibition of the conversion of fibrinogen to fibrin is involved although no experimental details were given. Later Brown and colleagues (1974) concluded that carbenicillin at usual dose levels "only affects the platelet component of hemostasis and has little effect on fibrin formation or other phases of coagulation in patients with normal renal function".
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PMID:Bleeding in uremic patients after carbenicillin. 103

The cardiovascular and haematological effects of purified prothrombin activator derived from the venom of the Australian Common Brown Snake (Pseudonaja textilis) were studied in anaesthetised, mechanically ventilated dogs. Severe depression of systemic blood pressure and cardiac output and a rise in central venous pressure were observed. Thrombocytopenia, prolongation of both prothrombin time and activated partial thromboplastin time and a reduction in serum fibrinogen were also observed. All of these observed effects were prevented by the prior administration of heparin--a naturally occurring anticoagulant. We conclude that the prothrombin activator in Pseudonaja textilis venom may cause cardiovascular depression due to myocardial dysfunction secondary to disseminated intravascular coagulation.
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PMID:The cardiovascular and haematological effects of purified prothrombin activator from the common brown snake (Pseudonaja textilis) and their antagonism with heparin. 160 37

The haematological effects of Brown Snake (Pseudonaja) species (textilis, affinis, nuchalis) were studied in anaesthetised, mechanically ventilated dogs. Marked thrombocytopenia, depletion of serum fibrinogen and prolonged prothrombin and activated partial thromboplastin time, were recorded at 5 to 10 and 30 to 40 minutes after intravenous envenomation. Fibrin degradation products were not elevated. Because these haematological effects occurred simultaneously with cardiovascular depression (previously reported), we postulate that hypotension sometimes observed in human envenomation may be due to intravascular coagulation with myocardial ischaemia.
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PMID:Studies on Australian snake venoms, Part II: The haematological effects of brown snake (Pseudonaja) species in the dog. 176 99

A deficiency in the plasma kallikrein-kinin system of Brown Norway rat mutant Katholiek strain (B/N-Ka), first reported by Damas et al. was further characterized. The prolonged activated partial thromboplastin time (APTT) of B/N-Ka rat plasma was corrected by an addition of rat HMW-kininogen, indicating B/N-Ka rat is deficient in HMW kininogen. The study of kinin-release of plasmas of the three strains of rat (B/N-Ka, B/N Ki and SD) by several kininogenases expressed that B/N-Ka rat is deficient in LMW kininogen, in addition to HMW kininogen deficiency. The plasmas of the three strains of rat were gel-filtered through Sephacryl S-200 gel and profiles of kinin-release of the fractions were examined by several kininogenases. The result demonstrated that normal rat plasma contains three kinds of kininogen (HMW and LMW kininogens, and T-kininogen), and B/N-Ka plasma contains only T-kininogen. B/N-Ka rat plasma demonstrated T-kininogen antigen but no HMW kininogen by the study of immunodiffusion using their antisera raised in rabbits.
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PMID:Characterization of kininogen deficiency of Brown Norway rat mutant Katholiek strain. 310 13

To study the participation of the Hageman factor-related contact system of plasma in the pathogenesis of glomerulonephritis (GN), an anti-BM GN was induced in a group of 10 normal Brown Norway rats and another of seven Brown Norway BN/Mai Pfd f rats. The latter strain is characterized by a congenital deficiency of plasma prekallikrein and of high-molecular weight kininogen, with lengthening of the activated partial thromboplastin time. In the deficient group, one animal developed crescents in less than 25% of glomeruli, five in 25-50% and one in 50-75%. In the group of normal rats, extracapillary proliferation was of greater severity: one animal showed crescents in less than 25% of glomeruli, two in 50-75% and five in more than 75% of glomeruli. Although in both groups intense glomerular fibrin deposition was documented, the intensity of these deposits was less severe in the deficient animals. These data suggest, in the first place, that functional integrity of the contact system is not a necessary requirement for glomerular fibrinogenesis, other mechanisms being implicated in this phenomenon. On the other hand, this functional deficit has exerted a protective effect on crescent formation, which suggests that the contact system can play a role as a mediator of injury in glomerulonephritis, perhaps through the release of contact system-dependent mediators of inflammation.
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PMID:Role of the plasma contact system in the pathogenesis of experimental anti-GBM glomerulonephritis. 339 22

We compared the major changes induced by ellagic acid (EA), a Hageman factor activator, in normal rats and in kininogen-deficient Brown Norway rats. In normal rats, large doses of EA induced a congestion of lymph nodes, spleen and liver, a prolongation of activated partial thromboplastin time, the consumption of prekallikrein, high molecular weight kininogen and fibrinogen, as well as the stimulation of platelets with their accumulation in lungs, liver and spleen. A systemic hypotension of long duration was also observed. The fibrinogen consumption, the thrombocytopenia and the lengthening of activated partial thromboplastin time were dose-dependent. In kininogen-deficient rats, EA induced only a minimal congestion of lymphoid tissues, the accumulation of platelets in lungs, a decrease of plasma fibrinogen and a short-lasting hypotension. It is concluded that the vascular changes induced by blood coagulation with ellagic acid resulted mainly from kinin formation.
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PMID:Studies on the vascular and hematological changes induced by ellagic acid in rats. 344 21

The mechanism involved in glomerular fibrin deposition was investigated during mercuric chloride (HgCl2)-induced autoimmune glomerulonephritis in the Brown Norway rat. To ascertain whether the local hemostatic system was activated secondarily to the immunological conflict, the ability of glomerular lysates to induce coagulation in vitro was assessed in treated and control rats. Glomerular procoagulant activity (PCA) of HgCl2-injected rats was measured on day 12 (latent phase of the disease), day 20 (acme), and days 32 and 42 (recovery phase) after the first mercury injection. PCA rose 3-fold (p less than 0.02) at day 20 and then almost returned to control values. Proteinuria, PCA, and the incidence of glomerular fibrin deposits peaked concomitantly at day 20. Glomerular PCA was characterized as thromboplastin. The number of Ia positive cells detected by monoclonal OX-6 antibody was not different from the control number at any phase of the disease; the number of macrophages per glomerular section detected by electron microscopy at day 20 in HgCl2-injected rats was 1.80 +/- 0.60, versus 0.30 +/- 0.11 in the controls. No correlation was found between glomerular PCA and either the number of monocytes/macrophages or of Ia-positive cells present in the glomeruli. Since glomerular PCA was maximal at the onset of fibrin formation in the glomeruli and then decreased toward its basal level, and since the fibrin disappeared, it is concluded that increased production of thromboplastin by glomeruli, with activation of the extrinsic coagulation pathway, may contribute to intraglomerular fibrin deposition in HgCl2-induced glomerulonephritis.
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PMID:Enhanced glomerular procoagulant activity and fibrin deposition in rats with mercuric chloride-induced autoimmune nephritis. 347 99

High-molecular-weight kininogen has been isolated from rat plasma in three steps in a relatively high yield. The purified preparation gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the absence and presence of 2-mercaptoethanol, and the apparent Mr was estimated as 100,000. On incubation with rat plasma kallikrein, rat high Mr kininogen yielded a kinin-free protein consisting of a heavy chain (Mr = 64,000) and a light chain (Mr = 46,000), liberating bradykinin. The kinin-free protein was S-alkylated, and its heavy and light chains were separated by a zinc-chelating Sepharose 6B column. The amino acid compositions of rat high Mr kininogen and its heavy and light chains were very similar to those of bovine high Mr kininogen and its heavy and fragment 1.2-light chains, respectively. A high histidine content in the light chain of rat high Mr kininogen indicated the presence of a histidine-rich region in this protein as in bovine high Mr kininogen, although this region was not cleaved by rat plasma kallikrein. Rat high Mr kininogen corrected to normal values the prolonged activated partial thromboplastin time of Brown-Norway Katholiek rat plasma known to be deficient in high Mr kininogen and of Fitzgerald trait plasma. The kinin-free protein had the same correcting activity as intact high Mr kininogen. Rat high Mr kininogen also accelerated approximately 10-fold the surface-dependent activation of rat factor XII and prekallikrein, which was mediated with kaolin, amylose sulfate, and sulfatide. These results indicate that rat high Mr kininogen is quite similar to human and bovine high Mr kininogens in terms of biochemical and functional properties.
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PMID:Rat plasma high-molecular-weight kininogen. A simple method for purification and its characterization. 384 94

Activated partial thromboplastin time (APTT) was examined in Brown Norway (B/N) Katholiek rat, which was previously reported as high molecular weight kininogen deficient. APTT of B/N Katholiek was prolonged to 35 sec in comparison with B/N Kitasato and SD rat, showing APTT of 22-24 sec. The mixture of B/N Katholiek plasma and B/N Kitasato plasma (1:1) showed normal APTT value. B/N Katholiek plasma corrected the abnormally prolonged human coagulation factor deficient plasmas, such as XI, XII and prekallikrein deficient plasmas, while it did not correct the APTT of HMW kininogen deficient, Fitzgerald plasma. Intravenous injection of bromelain, which was previously reported to produce prolonged hypotension through the activation of factor XII to release bradykinin, induced slight effect in Katholiek rat, while in Kitasato rat it showed prolonged hypotension in similar degree as SD rat. Contents of coagulation factors in B/N Katholiek thus measured as well as the values of prekallikrein and HMW kininogen previously reported were summarized and suggested that B/N Katholiek rat could be similar deficiency as Fitzgerald trait.
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PMID:Prolonged activated partial thromboplastin time and deficiency of high molecular weight kininogen in brown Norway rat mutant (Katholiek strain). 671 Apr 38

Protein C is a major regulatory protein critical to physiologic anticoagulation. When activated, it selectively degrades the activated forms of factors V and VIII, thereby, down-regulating blood coagulation. Using an activated partial thromboplastin time (APTT) assay, Dahlback et al. recently reported that some individuals with thrombophilia show a poor in vitro anticoagulant response to activated protein C (APC-Resistance). Subsequent studies identified a point mutation in the gene for factor V as the underlying cause of APC-Resistance. The incidence of APC-Resistance in patients with recurrent thromboembolic events approaches 50%. The APC-Resistance phenotype is also present in approximately 5% of normal Caucasian subjects. In an attempt to develop a more sensitive and specific test system, we evaluated an assay based on Textarin(Pentapharm, Basel, Switzerland). Textarin, a protein fraction of Pseudonaja textilis venom (Australian Eastern Brown Snake) activates prothrombin in the presence of phospholipid (PL), factor V and calcium ions. Based on Textarin's requirement for factor V, we developed a Textarin time assay to test for APC-Resistance. We evaluated this test system in normal subjects and the following patient populations: stable orally anticoagulated, previously diagnosed factor V Leiden, and therapeutically heparinized samples. We found the Textarin assay to be a sensitive and specific test system to identify APC-Resistance. The phenotypic Textarin APC-Resistance test correlated more closely with the genotypic abnormality of factor VR506Q than the APTT-APC-Resistance test.
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PMID:APC-resistance as measured by a Textarin time assay: comparison to the APTT-based method. 887 45


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