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Biomedical subjects

F Bachmann

Publications and source records attributed to F Bachmann.

At least 55 records · Page 3Linked to original sources
PubMed1987

Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors.

During pregnancy the plasma concentration of two different inhibitors of plasminogen activators (PAIs) increases. The only one found in the plasma of nonpregnant women (PAI1) is immunologically related to a PAI of endothelial cells; its plasma activity, as deduced from the inhibition of single-chain tissue-type plasminogen activator (t-PA), increased from 3.4 +/- 2.3 U/mL (mean +/- 95% confidence limits) in the plasma of nonpregnant women to 29 +/- 7 U/mL at term, and its antigen level, measured by a radioimmunoassay, increased from 54 +/- 17 ng/mL to 144 +/- 25 ng/mL. In pregnancy plasma a second PAI (PAI 2) related to a PAI found in placenta extracts was observed. Its level, quantified with a radioimmunoassay, increased from below the detection limit (approximately 10 ng/mL) in normal plasma to 260 ng/mL at term. One hour after delivery, PAI 1 activities and antigen decreased sharply, but the PAI 2 antigen levels remained constant. Three days later, the PAI 1 antigen levels had fallen to normal levels, but the PAI 2 antigen levels were still at least eightfold above the nonpregnant values. During pregnancy, the t-PA and prourokinase (u-PA) antigen concentrations increased 50% and 200%, respectively, whereas the plasminogen and alpha 2-antiplasmin levels remained constant. Despite the large variations in the levels of PAs and PAIs, the overall fibrinolytic activity as measured in diluted plasma by a radioiodinated fibrin plate assay did not change significantly. Just after delivery, a great increase in the t-PA antigen levels was observed. Three to five days after delivery most parameters of the fibrinolytic system were normal again. Our results demonstrate that during pregnancy and in the puerperium profound alterations of the fibrinolytic system occur that are characterized by increases in PAs and their inhibitors, but these alterations do not affect the overall fibrinolytic activity.

Adult↗
PubMed1987

Plasminogen activator inhibitor 1: development of a radioimmunoassay and observations on its plasma concentration during venous occlusion and after platelet aggregation.

To study the effect of plasminogen activator inhibitors (PAI) on fibrinolysis it is essential to be able to specifically measure these proteins in plasma. To this end PAI-1 was purified from cortisol-stimulated HT 1080 fibrosarcoma cells and antisera raised in rabbits. The immunologic relationship of the purified inhibitor to PAI-1 in plasma and platelet extracts was established by immunoblotting and regular and reverse fibrin zymography. Furthermore, the purified product could be immunoprecipitated with antibodies to human or bovine endothelial cell-derived PAI-1. A radioimmunoassay was developed that measures both free and tissue-type plasminogen activator (t-PA)-bound PAI-1 in plasma and has an effective range of 8 to 250 ng/mL. PAI-1 antigen levels showed a twofold increase after 20 minutes of venous occlusion, partially due to hemoconcentration. Approximately one quarter of PAI-1 before and after venous occlusion is derived from platelets. After correction for hemoconcentration and the contribution of platelets to plasma PAI-1 levels, a still significant increase in PAI-1 levels was noted during venous occlusion, which suggests that the local vascular bed releases PAI-1. Concomitant with PAI-1, t-PA antigen levels increased eightfold and fibrinolytic activity 18-fold after 20 minutes of venous occlusion. PAI-1 and t-PA levels tend to augment with age: in a group of older healthy volunteers (mean age, 53 years) PAI-1 levels were twice and t-PA levels 1.7 times higher than those in a group with a mean age of 29 years. Determination of PAI-1 antigen levels before and after platelet aggregation demonstrated that 85% of PAI-1 in platelet-rich plasma is associated with platelets. The average amount of PAI-1 per platelet was 0.3 fg/platelet, ie, 4,000 molecules per platelet.

Adult↗
PubMed1986

High-affinity binding sites for human Glu-plasminogen unveiled by limited plasmic degradation of human fibrin.

The binding of human 125I-Glu-plasminogen to human plasmin-degraded fibrin was studied. Treatment of preformed and polymerized fibrin with 0.01 IU plasmin/ml resulted in an increased binding of 125I-Glu-plasminogen depending upon the length of time of preincubation of fibrin with plasmin. Binding reached a plateau of 30% of total added radioactivity after 60 min. At this time, less than 10% of fibrin had been digested. Polyacrylamide/urea/acetic acid gel electrophoresis revealed that the radioiodinated plasminogen bound to plasmin-degraded fibrin was of the Glu form. Computerized non-linear regression analysis of the binding experiments revealed that limited plasmic degradation of fibrin progressively generates high-affinity binding sites (Kd approximately equal to 0.3 microM) for Glu-plasminogen. At the time of maximal Glu-plasminogen binding approximately 5 high-affinity binding sites per 100 molecules of fibrin had been generated. The low-affinity type of binding sites were also identified. These observations describe a new mechanism which exquisitely modulates the plasmic breakdown of fibrin by a continuous renewal of high-affinity binding sites for Glu-plasminogen on the surface of the fibrin gel during the fibrinolytic process.

Binding Sites↗
PubMed1986

Purification and characterization of a plasminogen activator inhibitor from the histiocytic lymphoma cell line U-937.

We report the production, purification, characterization, and partial amino acid sequence of a plasminogen inhibitor (PA-I). The starting material is culture fluid from phorbol myristate 13-acetate-treated U-937 cells and the isolation steps consist of preparative isoelectric focusing followed by affinity chromatography on Cibacron Blue-Sepharose. PA-I migrates as a closely spaced doublet of 47-kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and forms covalent complexes with urokinase and two-chain tissue-type plasminogen activator, displaying second order rate constants of 0.9 X 10(6) M-1 s-1 and 0.2 X 10(6) M-1 s-1, respectively. Upon treatment with 1 M NH4OH, the covalent complexes were hydrolyzed, yielding a 35-kDa inhibitor fragment. A partial amino acid sequence of PA-I showed that it belongs to the antithrombin III family of inhibitors. PA-I is immunologically related to a PA-inhibitor from human placenta. mRNA from phorbol myristate 13-acetate-treated U-937 cells directed, in a rabbit reticulocyte derived cell-free system, the biosynthesis of only one 47-kDa protein that could be immunoprecipitated with anti-PA-I IgG, indicating that the two molecular forms of PA-I are the products of post-translational processing.

Amino Acid Sequence↗
PubMed1986

Studies on the release of a plasminogen activator inhibitor by human platelets.

The relative contribution of platelets to plasminogen activator inhibitor (PA-inhibitor) activity in blood was investigated. From the difference in PA-inhibitor levels in platelet-poor plasmas of 12 donors (3 +/- 1 U/ml, mean +/- 95% confidence limits) and in the corresponding platelet-rich plasmas after induction of platelet aggregation by collagen, ADP or epinephrine (7 +/- 1 U/ml), it may be concluded that a greater amount of PA-inhibitor in blood is associated with platelets than with plasma. In collagen-stimulated platelets maximal release of PA-inhibitor and of beta-thromboglobulin (beta-TG) was attained within fifteen seconds, whereas in ADP-stimulated platelets the release of both factors was slower. In platelet-poor plasma no correlation was found between the level of PA-inhibitor and that of beta-TG. Thus, the PA-inhibitor found in plasma is not derived from platelets that had been stimulated after blood collection. The rate of complex formation and the Mr of the principal complexes of radioiodinated tissue-type plasminogen activator (t-PA) or urokinase (UK), in platelet-poor plasma, in platelet-rich plasma after platelet aggregation or in an extract of washed platelets was the same. Moreover, complexes of UK or t-PA with plasmatic PA-inhibitor or with the PA-inhibitor(s) from platelets bound to immobilized antibodies against bovine endothelial cell-derived PA-inhibitor. These results show that the PA-inhibitors in plasma and in platelets are very similar or identical.

Adenosine Diphosphate↗
PubMed1986

The fast-acting inhibitor of tissue-type plasminogen activator in plasma is also the primary plasma inhibitor of urokinase.

We have compared the ability of a plasminogen activator inhibitor (PA-inhibitor) in human plasma, to form complexes with radioiodinated tissue-type plasminogen activator (t-PA) and high molecular weight urokinase (HMr-UK). Addition of 125I-t-PA (final concentration 10 IU/ml) or of 125I-HMr-UK (2 IU/ml) to a plasma containing 33 U/ml of PA-inhibitor resulted in the rapid formation of a 110,000 Mr complex of 125I-t-PA or a 95,000 Mr complex of 125I-HMr-UK with PA-inhibitor. Upon prolonged incubation of the plasma with 125I-HMr-UK a secondary complex of a Mr of 88,000 was observed, which probably derives from limited degradation of the 95,000 complex. Preincubation of the plasma with unlabelled t-PA, HMr-UK or LMr-UK at higher concentrations prevented the subsequent formation of complexes between radiolabelled PAs and the PA-inhibitor. These results thus demonstrate that t-PA and UK form complexes with the same PA-inhibitor. The rate of complex formation of 125I-t-PA or of 125I-HMr-UK with the plasma PA-inhibitor was similar (second order rate constant of association with PA-inhibitor in the order of 10(7) M-1s-1).

Glycoproteins↗
PubMed1986

Human primary colon carcinomas xenografted into nude mice. I. Characterization of plasminogen activators expressed by primary tumors and their xenografts.

Analysis was made of plasminogen activator (PA) activities present in 0.125% Triton X-100 extracts of human primary colon carcinomas and of their respective serial subcutaneous xenografts in nude mice. A correlation between tumor invasiveness and PA expression was observed in that primary tumors exhibiting clearly invasive growth patterns demonstrated high concentrations of PAs while subcutaneous xenografts, exhibiting noninvasive pseudobenign growth, contained very low levels of PA activity. The decrease in fibrinolytic activity observed in subcutaneous xenografts was not due to an increase in inhibitors of fibrinolytic activity. Immunologic characterization of PAs in tumor extracts showed that over 90% of human PA activity was of the urokinase type. Furthermore, tumor-derived urokinase was shown to be present in a proenzyme form. It was resistant to diisopropyl fluorophosphate (DFP) and was not inhibited by purified PA inhibitor. However, after its activation into urokinase by plasmin, it was completely inhibited by DFP and PA inhibitor.

Adenocarcinoma↗
PubMed1986

Human primary colon carcinomas xenografted into nude mice. II. Modulation of tumor plasminogen activator activity by the host tissue environment.

The characterization and quantitation of plasminogen activators (PAs) expressed by human colon carcinoma cell lines and primary colon carcinomas inoculated into nude outbred (nu/nu) mice, either as subcutaneous or gut-implanted (GI) xenografts, were discussed. The two colon carcinoma cell lines used in this study, Col 112 (moderately differentiated) and Col 115 (poorly differentiated), differ in their PA expression, the former being a urinary-type PA and the latter being a tissue-type PA producer. Both cell lines demonstrate a positive correlation between tumor invasiveness and measured PA activity; subcutaneous xenografts growing as noninvasive pseudobenign tumor masses were associated with low levels of PA activity, whereas GI xenografts exhibiting invasive growth expressed higher PA activity. Furthermore, coinoculation of Col 115 tumor cells sc and GI in the same host induced high levels of PA activity in subcutaneous xenografts, suggesting a stimulatory effect of the GI xenograft on subcutaneous xenograft PA expression. Also, purified murine plasminogen was demonstrated to represent an efficient substrate for tumor-secreted human PA.

Animals↗
PubMed1979

[Acquired von Willebrand's syndrome associated with malignant lymphoma].

The sudden development of multiple bleeding episodes in a 63-year-old patient with malignant lymphoma was shown to be due to the presence of an acquired von Willebrand syndrome, characterized by a prolonged bleeding time and low levels of the factors VIII: C, VIIR:Ag and VIII:Rcof. Crossed immunoelectrophoresis demonstrated diminution of the factor VIII portion with least anodic mobility. Mixing experiments of the patient's and normal plasma revealed a weak (T/2: 4.5 hours) inhibitory activity against the factors VIII:C, VIIIR:Ag and VIII:Rcof. After infusion of 800 units of cryoprecipitate there was rapid destruction (T/2: less than 1 hour) of infused factors VIII: C and VIIIR:Ag and no correction of the bleeding time. Chemotherapy resulted in disappearance of the lymphoma and the hemostatic defect, and its discontinuation in their reappearance. The weak inhibitory activity of the patient's plasma does not fully account for the factor VIII levels observed and other pathophysiological mechanisms, such as adsorption of factor VIII to the malignant lymphocytes, must be considered.

Antigens↗
PubMed1978

The hemostatic mechanism after open-heart surgery. III. Correlation between the appearance of an abnormal protein demonstrated by gel electrophoresis and of an inhibitor of the extrinsic coagulation system (PEC).

A prospective study in 13 patients undergoing open-heart surgery with extracorporeal circulation revealed a marked decrease of the mean one-stage prothrombin time activity from 88% to 54% (p less than 0.005) but lesser decreases of factors I, II, V, VII and X. This apparent discrepancy was due to the appearance of an inhibitor of the extrinsic coagulation system, termed PEC (Protein after Extracorporeal Circulation). The mean plasma PEC level rose from 0.05 U/ml pre-surgery to 0.65 U/ml post-surgery (p less than 0.0005), and was accompanied by the appearance of additional proteins as evidenced by disc polyacrylamide gel electrophoresis of plasma fractions (p less than 0.0005). The observed increases of PEC, appearance of abnormal protein bands and concomitant increases of LDH and SGOT suggest that the release of an inhibitor of the coagulation system (similar or identical to PIVKA) may be due to hypoxic liver damage during extracorporeal circulation.

Aspartate Aminotransferases↗
PubMed1976

[Intermittent pneumatic compression of leg and thigh: a new successful method for the prevention of postoperative thrombosis].

In a prospective study, 54 patients undergoing joint-replacement operations were randomized into a control and a treatment group. In the treatment group low pressure intermittent compression (Phlebo-Dynastat) to calves and thighs was started on the day of operation and continued until patients were fully mobilized. In 34 evaluable patients undergoing total hip arthroplasty the incidence of deep vein thrombosis (DVT) as determined by venography was 43% in the control group and 22% in the treatment group (p = 0.18). In 17 patients undergoing total knee replacement, DVT occurred postoperatively in 70% of the control group but in none of the treatment group (p = 0.002). The difference between the control and Phlebo-Dynastat group when comparing all patients was highly significant (p less than 0.005). Low pressure intermittent venous compression offers a welcome alternative method of thrombosis prophylaxis in patients with increased risk of bleeding.

Air Pressure↗
PubMed1976

Spectrophotometric assays for warfarin sodium and dicumarol. Use in rapid detection of patients suspected of drug intoxication or surreptitious noningestion.

The usefulness of assays for the rapid identification and determination of quantitative plasma levels of warfarin sodium and dicumarol is documented by the case histories of five patients: a man who accidentally took dicumarol for several weeks and developed an acute condition within the abdomen, a man who ingested 500 mg of warfarin sodium in a suicide attempt, a malingering nurse who surreptitiously took dicumarol, a nurse with warfarin intoxication who did not follow dosage prescription because of fear of developing thrombosis, and a woman with calf vein thrombosis who did not ingest the administered warfin sodium becausing of fear of developing bleeding. In every patient, the diagnosis of surreptitious ingestion or noningestion was suspected on the basis of the coagulation profile pattern. Confirmation of the disorder by the spectrophotometric assay enable the clinician to choose the appropriate course of action with speed and purpose.

Accidents, Home↗
PubMed1976

Thromboembolic disease in patients undergoing total knee replacement.

In a prospective study fo the incidence of deep-vein thrombosis in thirty patients undergoing total knee replacement, all patients had clinical examinations and 125I fibrinogen scanning, while those suspected of having deep venous thrombosis also had confirmatory venography. Sixteen (53 per cent) of the thirty patients had thromboembolic disease; nine had thrombi only in the limb operated on; four had bilateral deep venous thrombi; and three had pulmonary embolism. In nine patients who took aspirin regularly the incidence of thromboembolism was 11 per cent, while in the eight who did not take aspirin or any other antiplatelet drug the incidence was 88 per cent, a difference which was highly significant (p = 0.003).

Aged↗