Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diisopropyl methylphosphonate (DIMP), and dicyclopentadiene [3a,4,7,7a-tetrahydro-4,7-methyanoindene] (DCPD), were found as contaminants of groundwater in Colorado. Since there was a potential for cattle to be exposed to these chemicals by drinking well water, a study of their effects was initiated. Eight-to-ten week old calves were given a single dose of either DIMP at 62.5, 125, 250, 500 and 1000 mg/kg of body weight (b.w.) or DCPD at 250, 500, 1000 or 2000 mg/kg of b.w. The calves given DIMP developed tympanitis and ataxia, followed by depression, prostration, and death within two hr after dosing. A slight but significant increase in activated partial thromboplastin time was the only change observed in any of the clinical pathologic parameters. The only gross pathologic changes were acute gastroenteritis with hemorrhages in calves given 1000 mg/kg of b.w. Mild signs of intoxication, ataxia and excess salivation, were observed in calves given 250 mg of DCPD/kg of b.w. At higher doses, these signs were intensified; in addition, calves fell and, while prostrate, exhibited running movements and tonic, clonic spasms. The severity of the signs observed increased as the dose of DCPD increased. All calves given 2000 mg/kg of b.w. and one calf given 1000 mg/kg of b.w. died before seven days after dosing. The only clinical pathologic changes found were increased serum levels of creating phosphokinase, glutamic-oxalacetic transaminase, and glutamic pyruvic transaminase. The only consistent gross pathologic change was congestion in a variety of tissues in calves given 2000 mg/kg of b.w. A variety of histologic changes were observed in tissues from calves treated with both chemicals. However, these changes were not consistent for any one dose level and were not dose dependent. DIMP was slightly toxic for calves, since no signs of intoxication were observed at doses less than 1000 mg/kg of b.w. DCPD exerted detrimental effects on calves at 250 mg/kg of b.w. and was classified as moderately toxic.
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PMID:Toxicologic evaluation of diisopropyl methylphosphonate and dicyclopentadiene in cattle. 730 51

The generation of prothrombin-activator (thromboplastin) in water snake (Natrix piscator) is clearly delayed, compared to a mammalian system, but the final activity is well comparable to that in man, when homologous sources of "phospholipid" (erythrocyte-lysate) and of substrate plasma are employed in one stage "thromboplastin generation test". The use of heterologous source of either of the above reagents resulted in significantly longer clotting times; hence the need for homologous source of above reagents in the test is emphasized for comparative studies on animal haemostasis.
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PMID:Prothrombin-activator (thromboplastin) generation in the blood of water snake (Natrix piscator). 733 Aug 28

The possibility that anticoagulation with warfarin might inhibit the development of spontaneous metastases from intestinal carcinomas induced by azoxymethane (AOM) was tested in Sprague-Dawley rats with and without 60% distal small-bowel resection (DSBR). Warfarin (0.5 mg/l) was added to the drinking water from 1 week or 12 weeks postoperatively, and thromboplastin times were measured thereafter. AOM was given by 12 weekly s.c. injections (10 mg/kg/week), starting 1 week after DSBR. Besides increasing the sensitivity of rats to warfarin, DSBR itself caused partial anticoagulation, probably because of vitamin K malabsorption: at 30 weeks faecal fat was 59-93% higher, while serum B12 was 40% lower (> 0.05 P > 0.005). Adaptive growth of the jejunum and caecum after DSBR was manifested by 22-76% increases in segmental weight and surface area (P < 0.001). DSBR produced a 4-fold increase in duodenojejunal tumours at 15-25 weeks (P = 0.025) and a 76% increase in colorectal tumours at 25-35 weeks (P < 0.005). Eight of 20 control rats dying after 15 weeks had lymphatic metastases, compared with 0 of 15 rats with DSBR plus warfarin from week 1 (P = 0.005). The overall prevalence of metastases was reduced by both DSBR and warfarin, when assessed independently. Intestinal carcinogenesis induced by AOM is enhanced by the adaptive response to DSBR, but anticoagulation inhibits spontaneous metastases in this model.
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PMID:Effects of anticoagulation and ileal resection on the development and spread of experimental intestinal carcinomas. 742 32

The energetic contribution of protein solvation-desolvation reactions to generation of coagulation activated factor X (FXa) by the extrinsic pathway protease complex was determined using the technique of osmotic stress. The initial rate of FXa generation by limited proteolysis of human FX was measured in reaction mixtures with human tissue factor (TF) and factor VIIa (FVIIa) assembled either in aqueous phase or on phospholipid membranes. Osmotic stress was induced on the surface of reacting proteins with either polyethylene glycol, or dextran of 6000 and 500,000 molecular weight, respectively. These inert polymers are sterically excluded from the solvation shells of proteins and thus increase the water activity in the excluded spaces. The volume of water transferred either to or from the excluded spaces during formation of reaction intermediates was calculated from the ratio of change in free energy of activation with change in osmotic pressure, delta G*/delta II. For aqueous phase-assembled reactions, delta G* values decreased with delta II at ratios of -2.36 +/- 0.38 and -2.26 +/- 0.26 kcal/mol/atm for polyethylene glycol and dextran, respectively. These values correspond to 5488 +/- 883 and 5255 +/- 604 mol of water transferred from the reacting protein surfaces per mol of FXa generated. At a physiologic osmotic pressure of 7 atm the work of transfer corresponded to 16 kcal/mol, approximately 70% of delta G*. The observed osmotic effects were independent of the viscosity, temperature, and ionic strength of solutions. For reactions assembled on phospholipid membranes, delta G* increased with delta II at a ratio of 0.35 +/- 0.05 kcal/mol/atm, corresponding to 814 +/- 116 mol of water tansferred from bulk solution to protein surfaces. At physiologic osmotic pressure the work of transfer is 2.45 kcal/mol, approximately 12% of delta G*. Results indicate that for factor Xa generation in aqueous phase the work of desolvation is a significant component of the free energy of activation. Results also suggest that phospholipid membranes catalyze the reaction by reducing the desolvation component of the free energy of activation.
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PMID:Protein hydration during generation of coagulation factor Xa in aqueous phase and on phospholipid membranes. 754 Oct 37

Purified heparin, dermatan sulfate, and chondroitin sulfate in mixtures were fractionated by sequential precipitation with increasing volumes of acetone and analyzed by agarose-gel electrophoresis and for M(r), charge density, constituent disaccharides, and anticoagulant activity (for heparin). Purified glycosaminoglycans are generally utilized for pharmaceutical purposes and show physicochemical properties of glycosaminoglycans used as drugs. Heparin is the first glycosaminoglycan to precipitate at low percentages of acetone. The relative amount of slow moving and fast moving components, the M(r) and charge density, and the disaccharide pattern of fractionated heparin depend on the percentage of solvent. The activated partial thromboplastin time activity of fractions composed of heparin decreases with the charge density and M(r). Dermatan sulfate is precipitated by acetone over a narrow range (0.6-0.7 vol, 37-41%), and one of these fractions is constituted by 100% of this polysaccharide. These species of dermatan sulfate have different percentages of constituent disaccharides compared to the native polysaccharide. Nonsulfated disaccharide and disaccharide-6-sulfate are enriched. The dermatan sulfate species precipitated by acetone are also enriched in disaccharide-4,6-disulfated. Chondroitin sulfate is the most soluble glycosaminoglycan in mixed acetone/water solvent. It begins to precipitate at 0.8 vol (44%) of acetone. Different species of chondroitin sulfate can be recovered by precipitation at different percentages of solvent, and they show a decrease in M(r) and charge density depending on the percentage of acetone. The chondroitin sulfate species fractionated are also enriched in disulfated disaccharides compared to native polysaccharide. A different distribution of the three disulfated disaccharides can be pointed out in the fractionated chondroitin sulfate. Sequential precipitation performed by carefully increasing acetone percentages can help obtain purified species of glycosaminoglycan with desired properties from a mixture and tissue extracts, and achieve savings in time.
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PMID:Fractionation of heparin, dermatan sulfate, and chondroitin sulfate by sequential precipitation: a method to purify a single glycosaminoglycan species from a mixture. 807 97

Dysbaric osteonecrosis (DON) can occur in humans and sheep after a single hyperbaric air exposure with inadequate decompression. The authors hypothesize that DON does not result from primary embolic or compressive effects of nitrogen bubbles on the osseous vasculature, but by secondary injury to the marrow adipose tissue by rapidly expanding nitrogen gas that triggers local, and possibly systemic, intravascular coagulation. A 28-year-old scallop diver remained at a depth of 92 feet in sea water for 4.5 hours on surface-supplied compressed air. Decompression sickness occurred after a no-stop ascent to the surface, and he died 70 minutes later. Autopsy showed multiple gas bubbles, not only within the great vessels, but in the fatty marrow of his femoral and humeral heads. Lipid and platelet aggregates were found on the surface of marrow bubbles. Fibrin-platelet thrombi were detected within dilated venous sinusoids adjacent to bubbles, and in veins, capillaries, and arterioles. Since pulmonary, renal, and intraosseous (subchondral) fat embolism and fibrin thromboses were observed, it is suggested that injured marrow adipocytes can release liquid fat, thromboplastin, and other vasoactive substances, which conceivably can also play a systemic procoagulant role in triggering disseminated intravascular coagulation and additional DON.
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PMID:The pathophysiologic role of fat in dysbaric osteonecrosis. 822 35

This study investigates the influence of a high protein intake on normal hemostasis, fluid balance and organ growth. Adult rats were fed semipurified diets that contained either 18 or 56 g/100 g casein-lactalbumin for 2 wk, and the following functions were measured: food and water intake, weight gain, blood pressure, bleeding and clotting time, ADP-stimulated platelet aggregation, thrombin time, prothrombin time and partial thromboplastin time. Although food intake was depressed by the high protein diet, weight gain was not affected by the regimen. Water consumption, 24-h urine excretion and kidney weight were significantly greater in rats fed the high protein diet than in controls. High protein intake resulted in shorter barbiturate-induced sleeping time. Bleeding time and clotting time were significantly lower in rats fed the high protein diet for 7 d. However, heart rate, mean arterial pressure, plasma protein and osmolarity, platelet aggregation, prothrombin time, partial thromboplastin time and thrombin time did not differ significantly. Because a high protein intake caused rapid coagulation of blood in rats without affecting the activity of clotting factors, we suggest that this diet sensitized rats to factors that initiate clotting in vivo.
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PMID:High casein-lactalbumin diet accelerates blood coagulation in rats. 850 60

The mechanism by which intracerebral hemorrhage leads to the formation of brain edema is unknown. This study assesses the components of blood to determine if any are toxic to surrounding brain. Various solutions were infused stereotactically into the right basal ganglia of rats. The animals were sacrificed 24 hours later; brain edema and ion contents were measured. Whole blood caused an increase in brain water content and ion changes consistent with brain edema. Concentrated blood cells, serum from clotted blood, and plasma from unclotted blood all failed to provoke edema formation when infused directly into the brain. On the other hand, activation of the coagulation cascade by adding prothrombinase to plasma did produce brain edema. The edema response to whole blood could be prevented by adding a specific thrombin inhibitor, hirudin, to the injected blood. This study indicates that thrombin plays an important role in edema formation from an intracerebral blood clot.
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PMID:Edema from intracerebral hemorrhage: the role of thrombin. 861 42

We determined whether antithrombin (AT III) or hirudin (a specific thrombin inhibitor) reduce both the accumulation of fibrinogen in lung parenchyma and the procoagulant activity of bronchoalveolar lavage (BAL) fluid during acute lung injury induced by pulmonary overdistention. Newborn piglets were randomized to six-hourly infusions of AT III concentrate, a continuous infusion of recombinant hirudin, or no anticoagulant therapy. All animals were subjected to 24 h of identical mechanical ventilation at high peak pressures (3.9 kPa or 40 cm H2O). Tidal volumes were raised to a mean of 69 mL/kg in all three groups. Mean AT III levels in supplemented piglets (n = 22) were increased to 1.46 (SD 0.24) U/mL at 24 h, compared with 0.67 (SD 0.16) U/mL in controls (n = 23). The median activated partial thromboplastin time in animals receiving hirudin (n = 18) was prolonged to 53 s versus 34 s in untreated animals. The intrapulmonary accumulation of i.v. administered 125I-fibrinogen was reduced by AT III concentrate or hirudin, compared with untreated littermates (p = 0.003). The procoagulant activity of BAL fluid was also decreased by both thrombin inhibitors (p = 0.001). Intrapulmonary accumulation of fibrinogen and the procoagulant activity of BAL fluid were reduced by AT III or hirudin during lung injury caused by pulmonary overdistention. Future investigations should determine whether tangible clinical benefits result from this reduced potential for fibrin deposition in the injured lung.
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PMID:Thrombin inhibitors reduce intrapulmonary accumulation of fibrinogen and procoagulant activity of bronchoalveolar lavage fluid during acute lung injury induced by pulmonary overdistention in newborn piglets. 872 31

Bacteriorhodopsin (bR) is a light-driven proton pump from Halobacterium salinarium and is a model system for studying membrane protein folding, stability, function, and structure. bR is composed of bacterio-opsin (bO), the 248-amino acid apo protein, and all-trans retinal, which is linked to lysine 216 via a protonated Schiff base. A bO gene (sbOd) possessing 29 unique restriction sites and a carboxyl-terminal purification epitope (1D4, nine amino acids) has been designed and synthesized. Overexpression of bO was achieved by fusion to the carboxyl terminus of maltose binding protein (MBP). The expressed fusion protein (MBP-sbO-1D4) formed inclusion bodies in Escherichia coli and, following solubilization with urea and removal of the urea by dialysis, approximately 170 mg of approximately 75% pure MBP-sbO-1D4 was obtained from 1 L of culture. MBP-sbO-1D4 formed high molecular weight (> or = 2,000 kDa) oligomers that were water-soluble. The synthetic bO with the 1D4 tag (sbO-1D4) was separated from MBP by trypsin cleavage at the factor Xa site between the MBP and sbO-1D4 domains. Selective trypsin cleavage at the factor Xa site, instead of at the 14 other potential trypsin sites within bO, was accomplished by optimization of the digestion conditions. Both MBP-sbO-1D4 and sbO-1D4 were regenerated with all-trans retinal and purified to homogeneity. In general, 6-10 mg of sbR-1D4 and 52 mg of MBP-sbR-1D4 were obtained from 1 L of cell culture. No significant differences in terms of UV/vis light absorbance, light/dark adaptation, and photocycle properties were observed among sbR-1D4, MBP-sbR-1D4, and bR from H. salinarium.
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PMID:Overexpression of bacterio-opsin in Escherichia coli as a water-soluble fusion to maltose binding protein: efficient regeneration of the fusion protein and selective cleavage with trypsin. 886 82


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