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Biomedical subjects

C Mannhalter

Publications and source records attributed to C Mannhalter.

At least 145 records · Page 8Linked to original sources
PubMed1993

[Factor XII (Hageman factor) deficiency: a risk factor for development of thromboembolism. Incidence of factor XII deficiency in patients after recurrent venous or arterial thromboembolism and myocardial infarction].

103 patients suffering from recurrent venous thrombosis, recurrent arterial thromboembolism and/or recurrent myocardial infarction and 50 healthy subjects were tested for Hageman factor (F XII) coagulant activity and antigen. Among the 103 patients we identified 15 subjects with F XII deficiency (15%), 3 with protein C deficiency (3%) and 3 with protein S deficiency (3%). Combined F XII and protein C, protein S or antithrombin III deficiency was not observed. The 103 patients were divided into subgroups according to the type of thrombotic complication. Among patients with exclusively recurrent venous thromboembolism 8% (p = 0.153) were deficient in F XII. Among patients suffering from recurrent arterial thromboembolism and/or myocardial infarction, the incidence of F XII deficiency was significantly higher (20%, p < 0.003). In 67% of the patients with F XII deficiency a positive family history of thrombosis could be established. In contrast, only 32% (p = 0.043) of all venous and 28% (p = 0.019) of all arterial thrombosis patients had a positive family history. We believe that reduced levels of F XII should be considered as a risk factor in the development of thromboembolism. Consequently, more attention should be payed to the measurement of F XII when evaluating thromboembolic risk factors especially in cases of recurrent arterial thromboembolism and/or myocardial infarction.

Adult↗
PubMed1992

The prevalence of factor XII deficiency in 103 orally anticoagulated outpatients suffering from recurrent venous and/or arterial thromboembolism.

One hundred and three patients suffering from recurrent venous thrombosis, recurrent arterial thromboembolism and/or recurrent myocardial infarction and 50 healthy subjects were tested for Hageman factor (FXII) coagulant activity and antigen. Among the 103 patients we identified 15 subjects with FXII deficiency (15%), 3 with protein C deficiency (3%) and 3 with protein S deficiency (3%). Combined FXII and protein C, protein S or antithrombin III deficiency was not observed. The 103 patients were divided into subgroups according to the type of thrombotic complication. Among patients with exclusively recurrent venous thromboembolism 8% (p = 0.153) were deficient in FXII. Among patients suffering from recurrent arterial thromboembolism and/or myocardial infarction, the incidence of FXII deficiency was significantly higher (20%, p less than 0.003). In 67% of the patients with FXII deficiency a positive family history of thrombosis could be established. In contrast, only 32% of all venous and 28% of all arterial thrombosis patients had a positive family history. We believe that reduced levels of FXII should be considered as a risk factor in the development of thromboembolism. Consequently, more attention should be payed to the measurement of FXII when evaluating thromboembolic risk factors especially in cases of recurrent arterial thromboembolism and/or myocardial infarction.

Acenocoumarol↗
PubMed1992

Relationship of myc protein expression to the phenotype and to the growth potential of HOC-7 ovarian cancer cells.

In this investigation we demonstrate expression of myc oncoproteins in HOC-7 ovarian adenocarcinoma cells. The cells were exposed to differentiation inducing agents such as dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), retinoic acid (RA) and transforming growth factor-beta 1 (TGF-beta 1). Myc protein expression in treated cells was then compared with that in control cultures and in monoclonal HOC-7 sublines, which are characterised by distinct phenotypes. Cells exposed to DMSO and DMF became markedly enlarged and flattened and developed cytoplasmic extensions. They looked similar to a subline, which revealed a less malignant and more differentiated cell phenotype. All four inducers prolonged the cell doubling time and reduced the saturation density to levels, normally found in the more differentiated subline. Furthermore, all inducers except RA elevated extracellular fibronectin, which is characteristic for less malignant epithelial cell phenotypes. All four agents inhibited myc oncoprotein expression reversibly (1% DMSO greater than 0.5% DMF greater than 10 microM RA greater than 10 ng ml-1 TGF-beta 1) and in time-dependent manner. Down-regulation of myc protein expression is, therefore, closely related to inducer-dependent growth reduction of HOC-7 cells and to the development of a less malignant cell phenotype.

Actins↗
PubMed1991

C1-esterase inhibitor in uncomplicated pregnancy and mild and moderate preeclampsia.

Routine coagulation tests and measurement of the plasma levels of C1-esterase inhibitor (C1-INH) and antithrombin III were performed in 17 women with mild preeclampsia, 10 women with moderate preeclampsia and 20 women with uncomplicated pregnancy. All pregnant probands were within the third trimester of pregnancy. 20 non-pregnant women were used as controls. The groups were matched in age and the pregnant ones were also matched in gestational age. C1-INH activity and antigen were significantly reduced (p less than 0.002) in normally pregnant women as compared with non-pregnant ones. Further, C1-INH activity was lower in women with mild preeclampsia and significantly lower in women with moderate preeclampsia (p less than 0.05) as compared with normally pregnant women. None of the plasmatic coagulation tests was indicative of a consumption reaction. We conclude that C1-INH activity and antigen reductions are commonly associated with pregnancy. Furthermore, as markedly lower values can be found in mild and moderate preeclampsia, measurement of the C1-INH activity in pregnant women within the third trimester might proof useful to establish the diagnosis of a preeclamptic condition.

Adult↗
PubMed1991

A rapid method for the isolation of genomic DNA from citrated whole blood.

We have developed a DNA isolation method which allows the isolation of high quality DNA from frozen citrated blood and cell lines within 90 min. The procedure avoids the use of toxic organic reagents and tedious extraction steps. DNA prepared by this method is very well suited for restriction fragment length polymorphism and polymerase chain reaction analysis.

Blood Chemical Analysis↗
PubMed1991

Detection of engraftment and mixed chimerism following bone marrow transplantation using PCR amplification of a highly variable region-variable number of tandem repeats (VNTR) in the von Willebrand factor gene.

Detection of host cells in peripheral blood and/or bone marrow (mixed chimerism) of patients who have undergone bone marrow transplantation (BMT) is possible using either immunological methods or cytogenetic or molecular genetic analysis. We shall report a new method for the detection of mixed chimerism, which makes use of the fact, that the von Willebrand factor (vWF) gene has a highly variable region-variable number of tandem repeats (VNTR)--within intron 40. vWF-VNTR amplification by the polymerase chain reaction (PCR) was performed as described by Peake et al. We have studied 185 peripheral blood and/or bone marrow samples of 26 patients. Median time after BMT was 14 months (range 1-83 months). Of the 11 patients who were studied sequentially during the first 100 days following BMT, mixed chimerism was detected in four, but only transiently. None of these patients has relapsed so far. Of 18 patients who were studied more than 100 days after BMT mixed chimerism was found in three; two of these patients have subsequently relapsed. The advantages of this new method are: (a) it is informative in a high percentage of patients; (b) it requires only small amounts (200 microliters) of peripheral blood; (c) reliable results can be obtained at leukocyte counts of even less than 50 per microliters. The clinical relevance and sensitivity of the method compared with established methods for detection of mixed chimerism remain to be determined.

Bone Marrow↗
PubMed1990

[Molecular genetic studies in the von Willebrand's syndrome].

The successful cloning of the von Willebrand (vW) gene in 1985 and the production of gene probes stimulated a number of molecular genetic patient studies. It turned out that even in the case of patients with severe vW syndrome gross delections were only rarely found. We could not identify a deletion in the eight severe vW patients studied. Thus, at the moment it is not possible to directly demonstrate the genetic defect in vW patients. However, a number of restriction fragment length polymorphisms (RFLPs) within the vW gene were identified. They cosegregate with the gene and can be used for segregation analysis of the disease. These RFLPs should help to achieve better diagnosis of the vW syndrome in the future. This paper shows the data obtained in two families. They demonstrate the usefulness of RFLP analysis for diagnosis of carriers of the vW syndrome.

Adult↗
PubMed1990

Diagnosis of carriers of haemophilia A by RFLP analysis: Austrian results.

RFLP analysis with extragenic and intragenic probes was performed in 25 Austrian families with haemophilia A for the purpose of carrier diagnosis. Diagnosis could be established in 22 families, in 7 families with intragenic and extragenic probes, in 15 families with extragenic probes only. The remaining 3 families were not informative. During routine diagnosis we found three interesting cases which are described in the following paper. Firstly, we identified one deletion with Bcl I/p 114.12. Secondly, we observed an additional polymorphic band (5.2 kb) with Xba I/probe A. Thirdly, we saw one case where Bcl I/p 114.12 and Bgl I/1.8 were not in linkage disequilibrium.

Austria↗
PubMed1989

Identification of the target platelet glycoprotein in autoimmune thrombocytopenia occurring after allogeneic bone marrow transplantation.

We report the case of a patient who developed autoimmune thrombocytopenia after allogeneic bone marrow transplantation from her HLA-identical sister. An IgG autoantibody was detected that bound to the platelet glycoprotein IIb/IIIa and to the HLA class I proteins. Immunoprecipitation studies with radiolabeled platelets revealed additional antibody binding sites on proteins of 214 kDa molecular weight under nonreduced conditions and 65 and 56 kDa molecular weight under reduced conditions.

Adult↗
PubMed1989

Effects of 3-azidothymidine on platelet counts, indium-111-labelled platelet kinetics, and antiplatelet antibodies.

Treatment of the acquired immunodeficiency syndrome with 3-azidothymidine (zidovudine; AZT) can induce severe neutropenia and anemia, while platelet counts increase. In order to understand the mechanism by which this favorable effect on platelets is induced, we prospectively studied platelet kinetics and platelet serology in 8 hemophiliacs receiving the drug. All patients underwent a second investigation after 3 months of treatment. Four patients were thrombocytopenic before treatment. Platelet counts increased significantly already after 1 week of treatment (p = 0.03), when only 3 patients remained thrombocytopenic. In these latter patients a further increase of platelet counts was noticed during the following 3 months. Platelet life-span was shortened in all patients at the initial investigation and a significant prolongation was measurable at the second evaluation (p = 0.015). Platelet-associated immunoglobulin G was increased in 3 patients at the first investigation and in 4 patients at the follow-up. Platelet-associated complement (PAC3d) was elevated in all subjects at the first determination. It decreased in 6, but increased in 2 patients thereafter; thus these changes did not become significant (p = 0.078). Immunofluorescence studies revealed antiplatelet antibodies in 7 patients' sera before treatment, and in 5 sera during drug therapy. At both investigations, the antibodies bound to the platelet glycoprotein IIIa as was demonstrated by immunoprecipitation of radiolabeled platelet proteins. We conclude, that AZT treatment improves platelet counts in HIV-infected hemophiliacs primarily by a prolongation of platelet survival without having a significant influence on antiplatelet antibody binding.

Autoantibodies↗
PubMed1988

Commercial immunodepleted deficient plasmas contain cleaved high molecular weight kininogen (HK).

Comparative analysis of high molecular weight kininogen (HK) in various commercial congenital and immunodepleted deficiency plasmas was performed by immunoblotting of HK. It was found, that some artificially depleted deficiency plasmas contained proteolytically cleaved, kinin-free kininogen. In contrast, in all congenitally deficient plasmas, HK was present in the intact, single chain form. Thus, cleavage of kininogen could have been triggered by or during the immunodepletion procedure. It was seen, that the degree of proteolytic cleavage and degradation of HK in depleted plasmas differed among various manufacturers. E.g. depleted products of one company contained only trace amounts of cleaved HK, in contrast to products of another one, in which HK was completely degraded. The immunoblot analysis of HK reflects the occurrence of proteolytic events during the production of artificially deficient plasmas and can therefore serve as a quality control method.

Blood Coagulation Tests↗
PubMed1988

Purification of plasma protein.

The purification of coagulation proteins from plasma milieu is a complex and sometimes difficult task. Most clotting factors are present in plasma in trace amounts. They are sensitive to proteolytic degradation and adsorption to surfaces. Thus for most coagulation proteins it was not until the seventies that highly purified preparations were available. Nowadays, most coagulation proteins are isolated from plasma using combinations of ion exchange, molecular sieve and affinity chromatographies. Sometimes, e.g. for Vitamin K dependent factors, specific adsorption properties are utilized. During affinity chromatography, proteins may be bound to specific immobilized receptors, antibodies, substrates, or inhibitors. An example for the latter is the use of bezamidine-Sepharose for the purification of thrombin. Immunoadsorption to immobilized monoclonal antibodies allowed the isolation of highly purified factor VIII:C. For factor XI and prekallikrein the binding of these proteins to the immobilized cofactor high molecular weight kininogen is utilized for an effective separation of contaminations. Antithrombin III can be isolated by linkage to its cofactor, heparin, on heparin-Sepharose. Using affinity chromatography on lysine-Sepharose it is possible to isolate plasminogen from plasma, serum or urine in a one step procedure with high yield and quality. This, of course, is an ideal situation, where the goal of a purification, namely the separation of a highly purified, biologically active product with high yield can be accomplished in a simple, fast procedure.

Blood Coagulation Factors↗
PubMed1987

Identification of a defective factor XI cross-reacting material in a factor XI-deficient patient.

A homozygous factor XI-deficient girl, who appeared to be positive for cross-reacting material (CRM+) was studied for clarification. Factor XI antigen (F XI:Ag) was measured by radial immunodiffusion using monospecific, heterologous anti-factor XI antibodies. Factor XI coagulant activity (F XI:C) was determined in a modified activated partial thromboplastin time (APTT) test. The ratio of F XI:C to F XI:Ag was 0.04 for the proposita, as compared with 0.7 to 0.74 in the other family members. In contrast, 12 normal individuals had ratios of F XI:C to F XI:Ag of 1.04 +/- 0.15. F XI esterolytic activity was clearly higher than F XI:C in the proband, but not in her relatives. Immunoblotting studies demonstrated F XI CRM in the patient's plasma. Chromatography on diethylaminoethanol (DEAE)-Sephadex at pH 8.4 led to an almost complete removal of F XI from the plasma. The defective F XI was not bound to a negatively charged kaolin surface due to an abnormal interaction with high-mol-wt kininogen (HMWK).

Antigens↗
PubMed1985

Clotting activities and antigen concentrations of contact factors in kidney disease.

Factor XII, prekallikrein (PK) and high molecular weight kininogen (HMWK) clotting activities and antigen concentrations in kidney disease patients were studied. Chronic hemodialysis led to a reduction of F XII, PK and HMWK clotting activities. F XII and PK antigen levels were also low. In contrast, the HMWK antigen was normal with respect to concentration as well as electrophoretic migration behaviour on 2 D-immunelectrophoresis. In kidney transplant recipients more than three month after the transplantation, we found an increased of F XII and PK clotting activities, which appeared to depend on the time elapsed since the operation. However, the antigen levels remained normal. The group of chronic kidney disease patients not requiring hemodialysis exhibited normal mean values of all three clotting activities as well as normal F XII and HMWK antigen levels. The PK antigen was reduced. However, a separate evaluation of F XII clotting activities (F XII:C) in patients with glomerular nephritis showed elevated F XII:C which correlated with the BUN values. During acute processes of the kidney disease we observed very high PK clotting activities, which normalized with stabilization of the patients. Our results show that the contact phase coagulation factors behave abnormally in certain kidney disease patients.

Blood Coagulation↗
PubMed1985

High levels of plasma protein C in nephrotic syndrome.

In patients with severe nephrotic syndrome determinations of plasma protein C: Ag levels (8 patients: 5 adults, 3 children) and protein C activity (3 out of 8 patients) revealed significantly elevated plasma protein C concentrations. Furthermore we observed a significant inverse correlation of protein C: Ag to AT III: Ag levels. No protein C: Ag could be detected in the urine of two patients studied. We conclude from our data, that changes of plasma protein C do not contribute to the high thrombotic tendency in nephrotic syndrome.

Adolescent↗
PubMed1985

Combined dys-form of homozygous factor XI deficiency and heterozygous factor XII deficiency.

A 12-year-old girl with lifelong hemorrhagic episodes was found to have both a dys-form of homozygous factor XI deficiency and heterozygous factor XII deficiency. The heredity of the coagulation defects was confirmed by family studies. Severe bleeding after dental surgery occurred in spite of replacement therapy and local measures including fibrin glue. Our findings suggest that the risk of bleeding in patients with homozygous factor XI deficiency must not be underestimated and that the most effective measure is the transfusion of sufficient amounts of fresh frozen plasma until at least the 5th postoperative day.

Blood Transfusion↗