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Biomedical subjects

U Christensen

Publications and source records attributed to U Christensen.

At least 55 records · Page 3Linked to original sources

Comparison of splenoportography and transhepatic portography in the diagnosis of portal vein thrombosis.

Accurate diagnosis and localization of thrombosis in the portal venous system is essential for proper surgical treatment. We compared the results of percutaneous transhepatic portography and splenoportography in 66 patients with cirrhosis of the liver. The two methods agreed on absence of thrombosis in 48, and in presence of thrombosis (verified later by surgery/autopsy) in four patients. In 12 patients an apparent thrombosis diagnosed by splenoportography was disproved by transhepatic portography, and vice versa in two patients. Free portal pressure and splenic pulp pressure did not differ significantly irrespective of the 'diagnosis' of thrombosis. We conclude, that transhepatic portography is better than splenoportography in making the diagnosis of thrombosis in the portal venous system although failure to visualize the splenic vein may indicate splenoportography.

Female↗

C-terminal lysine residues of fibrinogen fragments essential for binding to plasminogen.

Experiments involving affinity chromatography on immobilized plasminogen columns and the concomitant use of plasmin and carboxypeptidase B indicate that the COOH-terminal lysine residues formed by plasmin-catalyzed cleavage of fibrinogen are essential for the high-affinity binding of the resulting cleavage products to plasminogen.

Chromatography, Affinity↗

Different inhibition of one and two chain tissue plasminogen activator by a placental inhibitor studied with two tripeptide-p-nitroanilide substrates.

The interaction of tissue plasminogen activator derived from a melanoma cell line with a specific plasminogen activator inhibitor from placental tissue, which inhibits urokinase and tissue plasminogen activator but not plasmin, was studied. Tissue plasminogen activator exists in two forms, a one chain and a two chain molecule. It was found that the two enzyme species each form 1:1 complexes with the inhibitor and that the two chain enzyme binds the inhibitor very strongly, Ki = 3 X 10(-10) mol/l, whereas the one chain enzyme forms a much weaker complex, Ki is approximately 10(-7) to 10(-8) mol/l. Substrate hydrolysis is much more efficiently catalysed by the two chain plasminogen activator than by the one chain activator.

Anilides↗

Interactions of Streptomyces subtilisin inhibitor with Streptomyces griseus proteases A and B. Enzyme kinetic and computer simulation studies.

Streptomyces subtilisin inhibitor (SSI), a dimeric protein that strongly inhibits subtilisins, was shown to form tight inhibitory complexes with Streptomyces griseus proteases A and B (SGPA and SGPB). The apparent dissociation constants of the SGPA-SSI and SGPB-SSI complexes were found to be orders of magnitude less than those of subtilisin-SSI complexes. Using the known atomic coordinates for SGPA and SSI, the highly complementary nature of the surface geometries of the two proteins was confirmed by a computer graphics study, which led to a proposed structure for the SGPA-SSI complex. Kinetic studies further suggested that the SSI dimer can bind two molecules of either SGPA or SGPB, and the 2:1-complexes (consisting of one inhibitor dimer and one enzyme molecule) apparently possess lower intrinsic dissociation constants than the 2:2-complexes. It was also shown that both of SGPA and SGPB are inhibited by both soybean trypsin inhibitor (Kunitz) and bovine pancreatic trypsin inhibitor (Kunitz), but far less strongly than by SSI.

Aspartic Acid Endopeptidases↗

Does a portal-systemic shunt increase the risk of primary hepatic carcinoma in cirrhosis of the liver?

To test the relative risk (RR) of primary hepatic carcinoma (PHC) in portal-systemic-shunted patients with cirrhosis of the liver, two autopsy materials were studied, 201 shunted and 378 non-shunted patients with histologically verified cirrhosis. Of these 579 patients, 55 had PHC (cases) and 524 were without PHC (controls). Cases and controls were divided into subgroups in accordance with sex, age, and alcohol consumption habits. Shunted patients with a postoperative survival of more than 6 months were studied separately. For shunted men alive more than 6 months postoperatively, after adjustment for difference in age and presence of large alcohol consumption, a high risk of PHC was found (RR, 3.28; 95% confidence intervals, 1.52-7.45). The presence of HBsAg was probably without importance for the relative risk of PHC in these patients, since liver tissue HBsAg was only found in 2 of all 19 shunted patients with PHC.

Carcinoma↗

Mechanism of alpha 2-macroglobulin-proteinase interactions. Studies with trypsin and plasmin.

The time course of the interactions of alpha 2-macroglobulin with trypsin and with plasmin was studied by measuring the generation of thiol groups, the concentration of alpha 2-macroglobulin subunits cleaved at the bait regions, and the change in intrinsic protein fluorescence of alpha 2-macroglobulin-enzyme reaction mixtures as functions of time. The interaction of alpha 2-macroglobulin with trypsin was found to be very fast but could be studied in the presence of benzamidine, a rather strong competitive inhibitor of trypsin. The results obtained indicate that alpha 2-macroglobulin-proteinase reactions, known to involve specific limited proteolysis of the bait regions, gross conformational changes, and cleavage of the internal beta-cysteinyl-gamma-glutamyl thiol esters of native alpha 2-macroglobulin, may proceed via at least two different reaction pathways determined by the nature of or the concentration of the reacting proteinase. After initial cleavage of one bait region at high proteinase activity the next step presumably is a fast cleavage of a second bait region before any substantial rearrangements leading to generation of thiol groups and the final incorporation of the proteinase occur. At low proteinase activity no further bait region cleavages occur and only the two thiol groups of half of the alpha 2-macroglobulin molecule are generated in the final 1:1 complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of cimetidine on upper gastrointestinal bleeding after renal transplantation: a prospective study.

In 97 consecutive patients undergoing renal transplantation the incidence of upper gastrointestinal bleeding was registered over 180 days after allocation to treatment with either cimetidine or placebo. Bleeding episodes occurred in 12 patients, 11 of whom were receiving placebo and only one cimetidine (p less than 0.01). All bleeding episodes occurred during the first month after allotransplantation. Treatment with cimetidine did not lead to an increased incidence of rejection of the allograft. It is concluded that cimetidine is effective and safe in protecting against upper gastrointestinal bleeding after renal transplantation.

Cimetidine↗

The AH-site of plasminogen and two C-terminal fragments. A weak lysine-binding site preferring ligands not carrying a free carboxylate function.

Glu-plasminogen [native plasminogen (Glu-1-Asn-790)], Lys-plasminogen [plasmin-cleaved fragment of plasminogen (Lys-77-Asn-790)] and miniplasminogen [fragment of plasminogen (Val-440-Asn-790)] were all found to interact specifically with immobilized 6-aminohexyl ligands. The interactions apparently are mediated by a single weak lysine-binding site, termed the AH-site, as seen from the patterns of inhibition obtained from frontal-quantitative-affinity-chromatography experiments with 6-aminohexanoic acid and alpha-N-acetyl-L-lysine methyl ester as competing ligands. The AH-site, in contrast with the strong lysine-binding site of Glu-plasminogen and Lys-plasminogen, may prefer ligands not carrying a free carboxylate function and therefore may interact with lysine side chains of proteins. In Glu-plasminogen the AH-site is present, but is apparently only partially free to react. It is suggested that it participates in an intramolecular complex and that an equilibrium state between two Glu-plasminogen forms exists. It is further suggested that binding of the plasminogens to fibrin is mainly determined by the AH-site.

Aminocaproates↗

Colostomy irrigation with prostaglandin E2 and bisacodyl. A double-blind cross-over study.

The emptying of the colon and the side-effects after intraluminal application of prostaglandin E2 and of bisacodyl in 14 patients was studied by employing colostomy irrigation. The design was double-blind with cross-over, the irrigation was one litre of tap water to which was added in randomized sequence placebo, prostaglandin *2 (350, 700 and 1400 micrograms) or bisacodyl (1.25, 2.5 and 5 mg). Neither prostaglandin E2 nor bisacodyl had any significant effect.

Adult↗

Enzymatic properties of alpha 2-macroglobulin-proteinase complexes. Apparent discrimination between covalently and noncovalently bound trypsin by reaction with soybean trypsin inhibitor.

The binding of trypsin to alpha 2-macroglobulin, the appearance of free beta-cysteinyl thiol groups of the formed complexes, the steady-state kinetics of their enzymic hydrolysis of carbobenzoxy-L-valyl-glycyl-L-arginyl-4-nitroanilide and finally their reactions with soybean trypsin inhibitor leading to the formation of ternary alpha 2-macroglobulin-trypsin-soybean trypsin inhibitor complexes were investigated. Each alpha 2-macroglobulin molecule binds two trypsin tightly; the dissociation constants were found to be unmeasureably small, but the extent of formation of 1:1 and 1:2 complexes at different molar ratios of alpha 2-macroglobulin to trypsin as determined from the appearance of thiol groups clearly indicated that binding of trypsin to alpha 2-macroglobulin shows negative cooperativity. Binding of the first trypsin makes the access of the second less easy. The kinetic results showed a decrease of the kc/Km value of hydrolysis of the tripeptide substrate by approx. 4-fold compared to that of free trypsin for each alpha 2-macroglobulin-bound trypsin. Here no differences were seen between the bound trypsins. The analysis of the reactions between the alpha 2-macroglobulin-trypsin complexes and soybean trypsin inhibitor shows that ternary complexes do form, although slowly, and that two processes occur, not only when 1:2 complexes but also when 1:1 complexes react with soybean trypsin inhibitor. Soybean trypsin inhibitor apparently discriminates between two distinct binding modes of trypsin to alpha 2-macroglobulin, the covalently and the noncovalently alpha 2-macroglobulin-bound trypsins.

Animals↗

Risk of early death in extremely overweight young men.

The effect of pronounced obesity in youth on later mortality was studied in 1239 men with extreme overweight, defined as a weight/height 2 greater than or equal to 31 kg/m2, in the population of 331 919 men liable for military service in the Copenhagen area during the period 1943-1977. A random sample of 2948 drawn from the remaining study population served as a control group. All men were followed up until November 1980, by which time 33 deaths had occurred among the extremely overweight subjects compared with 89 in the control group. This gave a mortality ratio (observed to expected number of deaths) of 1.14 (95% confidence limit 0.91-1.40) for controls with a significantly greater mortality of 1.73 (95% confidence limit 1.20-2.41) for obese subjects. The relative risk, estimated from the survival time distributions, was fairly constant around 1.6 throughout the 37 years of observation. Taking into account age at and year of entry in a regression analysis did not change the relative mortality risk. The proportion of natural death was significantly higher in the obese group than in the control group until the age of 30 but not thereafter. Pronounced obesity in youth is a health hazard, manifesting itself particularly in a distinct increase in mortality from natural causes in early adulthood.

Adolescent↗

The free portal pressure in awake patients with and without cirrhosis of the liver.

The free portal pressure was measured by percutaneous transhepatic catheterization of the portal vein in 106 patients with cirrhosis of the liver and in 19 patients without liver disease and with normal portography. Patients with cirrhosis had a median portal pressure of 38 cmH2O and patients without liver disease had a median portal pressure of 16 cmH2O. Among the cirrhotic patients the free portal pressure showed no relationship to etiology of cirrhosis, ascites, variceal bleedings or extrahepatic shunting. The median portal pressure was significantly higher in patients with (40 cmH2O) than without (30 cmH2O) gastroesophageal varices (p less than 0.01). The pressure was not related to the size of the varices.

Adult↗

Comparison of the diagnosis of oesophageal varices by oesophagoscopy and transhepatic portography.

We compared the diagnosis of oesophageal varices obtained by oesophagoscopy and percutaneous transhepatic portography in 78 patients with hepatic cirrhosis who were suspected of having oesophageal varices because of ascites and/or preceding upper gastrointestinal haemorrhage. Portograms were evaluated independently of the clinical and endoscopical findings. Endoscopy showed varices in 59 patients and portography in 54 patients. The two methods agreed on the presence of varices only in 46 patients (59%), on the absence of varices in 11 patients (14%), and disagreed in 21 patients (27%). Among the patients showing varices by endoscopy, portography agreed on the diagnosis in 78%, and among patients without endoscopical varices, portography agreed in 58%. The corresponding rates of agreement expected by chance alone are 69% and 31%, respectively. The free portal pressure was lowest in patients with no varices according to both techniques, highest in patients with varices by both techniques and intermediate in patients in whom there was disagreement on the diagnosis. Modification of the criteria for endoscopical and portographical diagnosis of varices and distinction between patients with and without ascites and preceding haemorrhage had no appreciable effect on the agreement. We conclude that endoscopy and portography show only moderate agreement in the diagnosis of oesophageal varices.

Adult↗

Kinetics of the reaction between urokinase and an inhibitor of fibrinolysis from placental tissue.

The interaction of urokinase (EC 3.4.21.31) and a protein proteinase inhibitor of fibrinolysis partially purified from placental tissue, which inhibits urokinase but not plasmin, was investigated. The preparations of the inhibitor contained no other known proteinase inhibitors. It was found that a 1:1 complex is formed and that the reaction proceeds as a second order, one step process, the association rate constant of which is 4.5 10(6) M-1 S-1 at pH 8.4, 37 degrees C and 3.0 10(6) M-1 S-1 at pH 7.3, 37 degrees C. The binding is very tight, the dissociation constant of the inhibitor-urokinase complex was estimated to be Ki less than or equal to 10(-11) M.

Blood Proteins↗