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Biomedical subjects

K Huber

Publications and source records attributed to K Huber.

At least 19 recordsLinked to original sources
PubMed1992

Determination of plasma urokinase-type plasminogen activator antigen in patients with primary liver cancer: characterization as tumor-associated antigen and comparison with alpha-fetoprotein.

We determined the plasma levels of urokinase-type plasminogen activator (u-PA) antigen and alpha-fetoprotein (AFP) in 44 patients with different stages of liver cirrhosis and in 29 patients with liver cirrhosis-based primary liver cancer at the time of first clinical detection of the malignant disease. Sensitivity values of u-PA and AFP in detecting primary liver cancer were 57 and 62%, respectively, and specificity values were 95 and 86%, respectively. A combination of both markers led to a significant increase of sensitivity to 89.7%. The specificity of the combination of both markers was 97.3%. In tumor patients with unilocular disease and tumor patients with multicentric disease and/or metastatic spread, similar sensitivity values could be obtained with both markers. Therefore, a combination of u-PA and AFP can increase the accuracy of detection of primary liver cancer, especially in chronic liver diseases known to be predisposing for primary liver cancer, e.g., liver cirrhosis of long duration.

Antigens, Neoplasm↗
PubMed1992

A decrease in plasminogen activator inhibitor-1 activity after successful percutaneous transluminal coronary angioplasty is associated with a significantly reduced risk for coronary restenosis.

To determine a possible relation of changes in plasma levels of plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) to the development of coronary restenosis after successful coronary angioplasty (PTCA), we followed 104 patients with a low grade residual stenosis after PTCA (less than 30%) for a period of 12 months. PAI-1 plasma levels (functional activity) and t-PA antigen were determined 1 day before PTCA and 3 days, 3 months and 6 months thereafter. Thirty-four patients (32.69%) developed angiographically proven coronary restenosis (group A) within a time range of 4-48 weeks (median 12.5 weeks) after PTCA while the remaining patients (group B) had neither clinical signs nor angiographic evidence of restenosis after 6 months. No significant differences could be demonstrated in t-PA antigen or PAI-1 activity (plasma levels between the two groups of patients the day before PTCA). During the whole observation period t-PA plasma levels were not significantly different between the two groups; however, PAI-1 plasma levels were significantly higher at 3 months and 6 months after PTCA in patients of group A (p less than 0.005). When the pattern of PAI-1 plasma levels over time (increase or decrease between two consecutive time points of blood collection) was used to discriminate between the two study groups only 3.5-18% of patients with a decrease in PAI-1 developed coronary restenosis within the following observation period in contrast to 25-58% of patients with an increase in PAI-1 plasma levels (p less than 0.05 to p less than 0.0005).

Aged↗
PubMed1991

Hepatic synthesis and clearance of components of the fibrinolytic system in healthy volunteers and in patients with different stages of liver cirrhosis.

We determined plasma levels of tissue-type plasminogen activator (t-PA) antigen, urokinase-type plasminogen activator (u-PA) antigen, and activity of the fast acting inhibitor of plasminogen activator (PAI-1) in patients with different stages of liver cirrhosis (Child A, B, and C) and in age and sex-matched healthy controls to investigate the contribution of the liver to the metabolism of these main components of the fibrinolytic system. For control purposes routine clotting parameters were also determined. In patients with the most severe form of liver cirrhosis (Child C) t-PA antigen levels were significantly elevated as compared to patients with Child A or Child B (p less than 0.05) or to controls (p less than 0.01). Furthermore, Child C patients exhibited significantly decreased PAI-1 plasma levels (p less than 0.05) as compared to controls. We were not able to demonstrate, however, any significant correlation between liver function and u-PA plasma levels. Furthermore, t-PA antigen and albumin plasma levels were negatively correlated (r = 0.48; p = 0.0015) and t-PA antigen and bilirubin were positively correlated (r = 0.46; p = 0.0022) thus indicating that the liver is mainly involved in the clearance of t-PA antigen. PAI-1 activity, however, seems to depend partially on synthesis by the liver as demonstrated by a positive correlation between PAI-1 and albumin (r = 0.33; p = 0.037). These physiologic liver functions are both progressively attenuated in severe liver damage and an increase of t-PA plasma levels and a decrease of PAI-1 might contribute to the higher fibrinolytic tendency observed in those patients.

Aged↗
PubMed1991

[Side effects of percutaneous radiotherapy in the area of the thorax: cardiac toxicity of mantle field irradiation].

Radiation-induced cardiotoxicity is a factor not to be neglected, especially after mediastinal irradiation in Hodgkin's disease and Non-Hodgkin-Lymphoma. Caused by primary and secondary radiation lesions, cardiopathy may develop up to several years after treatment. Clinically, acute pericarditis is prevalent. To reduce cardiac long-term side effects, adequate radiation technique is crucial. Diagnosis and therapy in radiation-induced cardiopathy are presented.

Heart↗
PubMed1990

Activation of coagulation and fibrinolysis in patients with arteriosclerosis: relation to localization of vessel disease and risk factors.

Activation markers of blood coagulation and fibrinolysis and several fibrinolytic parameters were determined in arteriosclerotic patients to investigate the relation between extension and main localization of vessel disease, risk factors and disturbances within the blood coagulation and the fibrinolytic system. Indications of an increased intravascular fibrin formation and subsequent fibrinolysis were found in peripheral artery disease (PAD) patients but not in coronary artery disease (CAD) patients. Compared with healthy controls PAD patients had elevated TAT (median: 3.2 ng/ml, 1.5-70 vs. 2.1, 1.2-4.7, p less than 0.005) and D-Dimer (median: 365 ng/ml, range 85-2000 vs. 185, 79-360; p less than 0.0001) plasma levels, whereas TAT (2.4, 1.2-13) and D-Dimer (190, 58-1000) levels of CAD patients were in the normal range. No associations were detected between risk factors of arteriosclerosis (hyperlipidemia, diabetes mellitus, cigarette smoking, hypertension) and the plasma levels of the activation markers TAT and D-Dimer. Independent from risk factors PAD and CAD patients had elevated plasma plasminogen activator inhibitor capacity (PAI cap). Our results provide evidence that 1) increased plasma levels of blood coagulation and fibrinolysis activation markers are not related to risk factors of arteriosclerosis but seem to be unspecifically caused by activation processes on arteriosclerotic vessel wall defects, 2) increased plasma PAI cap found in arteriosclerotic patients is a relatively unspecific phenomenon associated with arterial vessel disease.

Antithrombin III↗
PubMed1990

Plasminogen activator inhibitor-1 levels in patients with chronic angina pectoris with or without angiographic evidence of coronary sclerosis.

Increased plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been shown to exist in 40 to 60% of patients with stable coronary artery disease and have been suggested to be responsible for the development of coronary thrombotic complications. However, it is also discussed whether PAI-1 elevation might mainly be due to variables like increased age or to reactive mechanisms caused e.g. by the chest pain itself. To exclude age dependent or pain related influences, age-matched patients with stable angina pectoris (NHYA II) and angiographically proven coronary artery disease (CAD, n = 16) or without evidence for coronary sclerosis (variant angina, n = 10; angina-like syndrome with normal coronary angiogram, n = 5; non-CAD, n = 15) have been investigated for their plasma PAI-1 activity and t-PA antigen levels. The mean PAI activity in CAD patients (17.5 U/ml) was significantly higher than in non-CAD patients (9.6 U/ml) (p less than 0.0001). In the CAD patients no significant variation in plasma PAI-1 values could be demonstrated when related to the extent of the disease or to a history of previous myocardial infarction. t-PA antigen was also elevated in CAD patients as compared to the non-CAD group (p less than 0.02). The results suggest therefore a strong correlation between coronary artery disease itself and elevated levels of components of the plasma fibrinolytic system.

Angina Pectoris↗
PubMed1989

Heparin induced increase of t-PA antigen plasma levels in patients with unstable angina: no evidence for clinical benefit of heparinization during the initial phase of treatment.

Patients with unstable coronary artery disease were randomly treated either with a combination therapy consisting of nitrates and calcium-channel blockers without or with addition of clinical grade heparin administered subcutaneously; in order to evaluate the effect of heparin treatment on the fibrinolytic system, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) plasma levels were related to the clinical course of the disease. In heparinized patients thrombin time was prolonged more than 3-fold the normal range indicating effective heparin treatment. Heparinization led to a significant increase in t-PA antigen plasma levels (p less than 0.0001) within approximately four hours while PAI-1 activities remained unaltered. However, the measurable increase of the anticoagulant and pro-fibrinolytic activities of heparin did not result in a short-term benefit for the heparinized patients because the number of further ischemic attacks per patient during the observation period of three days was not different between the two study groups.

Aged↗
PubMed1989

Complex formation between urokinase and plasma protein C inhibitor in vitro and in vivo.

Protein C inhibitor (PCI) and plasminogen activator inhibitor 3 (PAI-3; urinary urokinase inhibitor) are immunologically identical. The role of PCI for urokinase (uPA) inhibition in vivo was investigated. We therefore developed an enzyme-linked immunosorbent assay (ELISA) specific for uPA-PCI complexes: Rabbit anti-PCI IgG was immobilized on a microtiter plate and following incubation with uPA-PCI complex-containing samples, bound uPA-PCI complexes were quantified with a horseradish-peroxidase-linked monoclonal antibody (MoAb) to uPA. Using this assay, time, dose, and heparin-dependent complexes were detected when uPA was incubated with normal plasma or purified urinary PCI, whereas no complexes were measurable using PCI-immunodepleted plasma. Plasma samples (containing 20 mmol/L benzamidine to prevent complex formation ex vivo) from patients undergoing systemic urokinase therapy (1 x 10(6) IU/60 min intravenously [IV]) after myocardial infarction were also studied. uPA present in these plasma samples (up to 1,200 ng/mL) had only 43% to 70% of the specific activity of purified 2-chain uPA, suggesting that a major portion of uPA is complexed to inhibitors. In these plasma samples uPA-PCI complexes were present in a concentration corresponding to 21% to 25% of inactive uPA antigen. These data suggest that at high uPA concentrations, such as during uPA therapy, plasma PCI might contribute significantly to uPA inhibition in vivo.

Enzyme-Linked Immunosorbent Assay↗
PubMed1989

Evaluation of fibrinolytic capacity in plasma during thrombolytic therapy with single (scu-PA) or two-chain urokinase type plasminogen activator (tcu-PA) by a combined assay system for urokinase type plasminogen activator antigen and function.

A combined assay for urokinase type plasminogen activator (u-PA) activity and antigen determination in plasma samples is described. This assay is based on binding of u-PA to an antibody immobilized on a microtiter plate followed by determination of the enzymatic activity of the bound u-PA. Thereafter bound u-PA antigen can be quantified by means of a specific peroxidase labelled monoclonal antibody against u-PA. By use of this assay system u-PA activity and antigen can be determined with lower detection limits of 0.08 IU/ml and 1.0 ng/ml, respectively, and intraassay as well as interassay coefficients of variation of 10% and 12% for activity and 5% and 7% for antigen determinations, respectively. Normal plasma levels of u-PA antigen could be determined to be 1.88 ng/ml +/- 0.61. Furthermore, this assay system allows specific quantification of u-PA antigen and activity during thrombolytic therapy.

Antigens↗
PubMed1988

Circadian fluctuations of plasminogen activator inhibitor and tissue plasminogen activator levels in plasma of patients with unstable coronary artery disease and acute myocardial infarction.

A decrease in the fibrinolytic potential, mainly due to an elevation of plasminogen activator inhibitor (PAI), has been described in patients with stable coronary artery disease and a previous myocardial infarction. We investigated plasma levels of PAI and tissue plasminogen activator (t-PA) and their possible circadian variations in patients with unstable coronary artery disease (CAD). Sixty-three patients were studied for at least 2 consecutive days during their stay at the coronary care unit (CCU). Diurnal plasma fluctuations in PAI and t-PA and onset of further myocardial ischemic episodes were monitored. As controls we used 22 age-matched patients submitted to the clinic because of non cardiac chest pain or valvular disease who revealed no evidence of CAD. PAI levels were significantly elevated in patients with unstable CAD (p less than 0.0001) but were not influenced by the extent of underlying CAD, history of previous myocardial infarction, known risk factors for CAD, or by extent of myocardial damage. The circadian variation of PAI levels with peak values between midnight and 6 A.M. found in controls was still present in patients but at a higher level. Preservation of circadian pattern in PAI plasma levels despite myocardial ischemic attacks indicates that elevation of PAI is rather not caused by a reactive phenomenon. On the other hand, elevated PAI levels and episodes of severe myocardial ischemia exhibiting a median time of onset at 10 A.M. seem to be closely related.

Aged↗
PubMed1988

[Persistent changes in tissue-type plasminogen activator and plasminogen activator inhibitor fibrinolytic parameters in patients following juvenile ischemic cerebral infarct].

In diseases associated with thrombotic or thromboembolic complications, a reduction in the fibrinolytic potential may contribute to the risk to develop thrombosis. To investigate whether juvenile cerebral infarction is associated with a permanent defect of the fibrinolytic system we measured the main components of the fibrinolytic system, tissue plasminogen activator (t-PA) and its fast acting inhibitor (PAI) in plasma samples of 21 patients (aged 21-44 years) 3-24 months after the acute event. The data obtained were compared to those from thirteen healthy young volunteers (22-46 years). A direct effect of known risk factors on the fibrinolytic system could be excluded because patients avoided their risk factors immediately after the ischemic cerebral attack. Hypertension and the combination of oral contraceptives and smoking had been the most striking original risk factors. Levels of t-PA antigen and t-PA activity before and after venous occlusion, or PAI activity were not different between patients and controls suggesting that at least a permanent decrease in the activity of the fibrinolytic system does not exist in these patients. However, our findings do not exclude that a temporary defect in fibrinolysis might have contributed to the acute onset of the thrombotic cerebral event possibly induced by the risk factors originally present.

Adult↗
PubMed1988

Plasminogen activators and plasminogen activator inhibitor in malignant and non-malignant ascitic fluid.

Ascitic fluid from tumour patients (hepatoma, gastric cancer, gallbladder cancer, colorectal cancer, ovarian cancer) and from non-malignant diseases (liver cirrhosis, congestive heart failure) were compared with respect to their content of determinants of the fibrinolytic system, tissue-type plasminogen activator antigen (t-PAag) and activity (t-PAact), urokinase-type plasminogen activator antigen (u-PA) and plasminogen activator inhibitor activity (PAI). Furthermore, SDS-polyacrylamide slab-gel electrophoresis (SDS-PAGE) was performed to evaluate molecular weight distribution of the detectable fibrinolytic parameters. In malignant ascites, PAI activity was three to four times higher, and increased complex formation of PAI with t-PA could be demonstrated, compared with non-malignant ascitic fluid. Tissue-type plasminogen activator antigen and activity showed a similar concentration in ascites of both study groups. Urokinase-type plasminogen activator antigen was detectable neither in ascites of malignant nor in ascites of non-malignant origin. It is concluded that t-PA is the physiological plasminogen activator in ascites and that increased PAI levels followed by increased complex formation between t-PA and PAI might reflect a reaction of the peritoneum.

Adult↗
PubMed1988

The primary structure of the hemoglobin of the Rock-Hopper penguin (Eudyptes crestatus, Sphenisciformes).

The blood of the Rock-Hopper Penguin contains only one hemoglobin component, corresponding to the Hb A of other birds. The primary structures of the alpha- and beta-chains are presented. The chains were separated by high-performance liquid chromatography and cleaved either enzymatically (alpha) or both enzymatically and chemically (beta). Both the native chains and their peptides were sequenced using liquid and gas phase sequenators. The peptides were aligned using their homology to the sequence of human hemoglobin and other bird hemoglobins. As compared to human hemoglobin, 44 amino-acid replacements are found in the alpha-chains (68% homology) and 47 in the beta-chains (67.8% homology). These exchanges involve seven alpha 1/beta 1 and one alpha 1/beta 2 contact in the alpha-chains, whereas in the beta-chains eight alpha 1/beta 1, one alpha 1/beta 2 and one hem contact are substituted. The influence of these replacements on the structure-function relationships in hemoglobin, as well as their importance for the diving ability of penguins, are discussed.

Amino Acid Sequence↗
PubMed1988

The primary structure of the hemoglobin of the Cormorant (Phalacrocorax carbo, Pelecaniformes).

The erythrocytes of the adult Cormorant contain two hemoglobin components in a ratio of 83% Hb A to 17% Hb D. The primary structures of the alpha A-, alpha D- and beta-chains are presented. The globin chains were separated by high-performance liquid chromatography and cleaved enzymatically and/or chemically. The native chains and their fragments were sequenced using liquid- or gas-phase sequencers, and the peptides aligned using the homology to human and to avian hemoglobin sequences. Compared to human hemoglobin, there are 46 amino-acid replacements in the alpha A-chains (67.4% homology), 65 replacements in the alpha D-chains (53.9% homology) and 45 replacements in the beta-chains (69.2% homology). In the functionally important regions, the percentage of amino-acid substitutions, as compared to human hemoglobin, is 13.2% in the alpha A-, 19.0% in the alpha D - and 16.0% in the beta-chains. The importance of the replacement beta 135 arginine (other birds)----glycine (Cormorant) in the phosphate-binding pocket and its effect on phosphate binding will be discussed.

Amino Acid Sequence↗
PubMed1988

Levels of plasminogen activator inhibitor in patients with angina pectoris.

Levels of plasminogen activator inhibitor type 1 (PAI) were measured in 180 patients with angina pectoris (148 males and 32 females, age range 29 to 70 years). An age-matched normal population served as a control. PAI was determined by a functional titration assay, its activity was expressed as arbitrary units (AU). PAI levels were significantly (P less than 0.005) higher in patients with angina (24.3 +/- 10.3 AU/ml) than in normals (20.4 +/- 4.6 AU/ml). PAI levels were unrelated to sex or age in both the patient and the control groups. Plasma triglyceride levels were correlated to PAI in patients and in normals. Patients with a history of previous myocardial infarction (n = 114) had similar PAI levels as patients without infarction (24.2 +/- 11.1 AU/ml as compared to 24.4 +/- AU/ml). It is concluded that PAI levels are elevated in patients with coronary heart disease, whether myocardial infarction has taken place or not.

Adult↗
PubMed1987

Nomograms for the prediction of patient's plasma volume in plasma exchange therapy from height, weight, and hematocrit.

The knowledge of plasma volume (PV) is a basic requirement for the standardization of plasma exchange therapy. PV has to be determined by calculation, as the measurement of PV before every plasma exchange is too cost- and time consuming. A known correlation with measured values results from calculation of plasma volume by means of patient's height and weight. But the present equations are only reliable at normal hematocrit. For this reason we modified the Retzlaff-equations and compared the validity of plasma volume predictions, calculated by these and own equations, with plasma volume measured by the 51Cr-method in 59 patients with pathological hematocrit. The correlation coefficient was 0.82 for men and 0.81 for women (2 0.001) with the modified Retzlaff-equations. On the average the relative error was -1.5% for all and 2.8% for fat and thin men. No significant improvement of accuracy was achieved with other equations. Thus, plasma volume can accurately be calculated from height, weight, and hematocrit with our modified Retzlaff-equations in patients with pathological hematocrit, even if they are very fat or thin. Nomograms for men and women were constructed in order to facilitate the calculation.

Blood Volume Determination↗