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C Mannhalter

Publications and source records attributed to C Mannhalter.

156 records · Page 9Linked to original sources
PubMed1984

Phospholipids accelerate factor IX activation by surface bound factor XIa.

Activation of bovine factor IX by surface bound factor XIa which was generated either by activation of human citrated factor IX deficient plasma or a mixture of purified human factors XII, high molecular weight kininogen (HMWK) and XI in glass tubes, is accelerated by cephalin. Human brain cephalin in dilutions ranging from 1:5 to 1:500 was studied for its effect on the activation of factor IX in concentrations of 1.0 u/ml and 16 u/ml. Cephalin dilutions from 1:5 to 1:30 accelerated the activation of the concentrated factor IX sample two- to threefold. Protein cleavage of this factor IX sample in the presence of 1:30 cephalin occurred twice as fast as in the absence of cephalin. Activation of the dilute factor IX sample (1.0 u/ml) was most effectively accelerated by cephalin in dilutions from 1:30 to 1:250. In all experiments the presence of phospholipid led to an increased factor IX cleavage concomitantly with faster generation of factor IXa activity. The results demonstrate that phospholipids actively participate in blood coagulation at an earlier stage than previously described.

Animals↗
PubMed1984

CRM+ severe Fletcher factor deficiency associated with Graves' disease.

A 59-year-old male patient with Graves' disease and severe hereditary Fletcher factor deficiency is described. PKK clotting activity as well as the activity by a chromogenic substrate method (Chromozym PK) was less then 0.01 U/ml. In contrast to functional tests, the immunological assay (Laurell method) showed a PKK antigen concentration of 0.25 U/ml, indicating the presence of an abnormal nonfunctional PKK molecule (CRM+ variant). An inhibitor was excluded since the patient plasma did not inactivate partially purified PKK. Investigation of 11 family members revealed a reduction of the PKK clotting activity in 9 relatives of the patient. Since Graves' disease is considered an autoimmune disease, our case represents an example of an association of a severe hereditary deficiency of a contact factor and an autoimmune disease.

Cross Reactions↗
PubMed1983

Prekallikrein, HMW-kininogen and factor XII in various disease states.

The behaviour of prekallikrein (PKK), factor XII, high molecular weight kininogen (HMWK) and kallikrein-inhibitor (KK-I) in 367 patients with various diseases is described. Malignancies lead to elevation of factor XII and KK-I, and reduction of PKK. The effect is more pronounced in patients with metastases. In renal diseases also one or more of the above mentioned parameters are abnormal. Defects requiring dialysis treatment significantly impair the contact factors. In this group low levels of PKK, Factor XII and HMWK and increased KK-I are common. In chronic renal disease patients, only F XII and KK-I are elevated, whereas PKK and HMWK are normal. Kidney transplantation leads to a rise in KK-I and reduction of PKK and HMWK. The values almost normalize few days after the operation. Factor XII, slightly increased immediately after transplantation, remains high in long term transplant recipients, whereas HMWK falls below normal. In liver disease patients, acute and chronic hepatitis, cirrhosis of the liver and coma, PKK is reduced. In cases with acute hepatitis PKK raises with recovery. Cirrhosis and coma lead to low HMWK and factor XII concentrations. KK-I is mostly affected during acute hepatitis, and is then highly increased. Our results clearly demonstrate that the biologic activity of one or more of contact factors is affected in many diseases.

Factor XII↗
PubMed1982

Surface adsorption of factor XI. II. Evidence that different mechanisms are involved in binding to glass and plastic materials.

Blood coagulation factors XI and XIa possess binding site(s) for glass and plastics, located in the heavy chain of the molecule. To elucidate the nature of binding, adsorption and desorption properties of factor XI and XIa to different surfaces have been studied. Desorption experiments with high salt (2.4 M NaC1) suggest participation of ionic forces in the binding to glass. This is consistent with the decreased adsorption of factor XI (pI-9.0) to glass with increasing pH. The non-ionic detergent Triton X-100, which splits hydrophobic bonds, desorbs factor XI very well from plastics and partially from glass. The anionic detergent SDS, which will split hydrophobic as well as ionic bonds, is the most effective agent tested for the elution of factor XI from glass. We, therefore infer, that the binding of factor XI to glass is the combined effect of ionic and hydrophobic binding, whereas the adsorption of factor XI to plastics is primarily hydrophobic.

Adsorption↗
PubMed1981

Contact activation of factor XI.

Factor XI is a circulating trace plasma protein composed of two similar or identical chains of about 80 000 daltons which upon activation undergo proteolytic cleavage. Recently, we have shown that trypsin activation leads to an active factor XI (factor XIa) which, on reduction, yields three chains of 46 000, 37 000 and 26 000 daltons. Herein, we re-evaluate the effect of contact activation of factor XI at an activating surface both in normal human plasma and in a mixture of purified factors XI, XII, and high molecular weight kininogen (HMWK). Mixtures were analysed by coagulant activity and by reduced sodium dodecyl sulphate polyacrylamide gel electrophoresis using [125I]factor XI. In the purified system, fully activated factor XI on reduction yielded chains of 46 000, 37 000 and 23 000 daltons. In contrast, factor XI activated by surface contact in plasma yielded on reduction only chains of 46 000 and 37 000 daltons in addition to some uncleaved 80 000 chain. We propose that factor XIa containing only 46 000 and 37 000 chains be designated factor XIa alpha, and that factor XIa containing the third chain of 23 000 daltons be designated factor XI a beta. Sequential elution of contact activated plasma factor XI revealed that factor XIa was attached to the glass surface through the 46 000 dalton chain.

Autoradiography↗
PubMed1980

Surface adsorption of factor XI. Association of adsorption sites with the heavy chain of activated factor XI.

These experiments study surface adsorption of native and activated factor XI using purified radiolabelled human factor XI and trypsin activated factor XI. Both forms of factor XI adsorb not only to glass but also to polypropylene, polyethylene and polystyrene. Albumin (10 mg/ml) markedly reduces adsorption to plastics but not to glass. Sodium dodecyl sulfate prevents adsorption to all surfaces tested. Reduction of 125I-activated factor XI in the presence of sodium dodecyl sulfate yields labelled chains of molecular weight of about 46,000 (heavy chain), 37,000 (light chain) and a further breakdown product of about 26,000. Reduction of activated factor XI in glass or plastic in the absence of sodium dodecyl sulfate yields only light chain and breakdown product in solution; heavy chain is removed by adsorption. Therefore, we conclude that the adsorption site (s) in trypsin activated factor XI and presumably also in native factor XI is (are) located in the heavy chain subunit of the molecule.

Adsorption↗
PubMed1980

Trypsin activation of human factor XI.

Human factor XI circulates as a zymogen composed of two similar or identical chains of Mr = 80,000. Upon activation either by trypsin or by blood-clotting proteins involving clotting factors XII and high molecular weight kininogen, it undergoes proteolytic cleavage in which the Mr = 80,000 chain reportedly is cleaved to a heavy and light chain of Mr of about 48,000 and 33,000, respectively. In these studies, we have reinvestigated trypsin activation of factor XI and demonstrate that trypsin-activated factor XI contains three chains of apparent Mr = 46,000, 37,000, and 26,000. Kinetic studies lead to the conclusion that the parent chain of Mr = 80,000 is cleaved into chains of Mr = 46,000 and 37,000. This cleavage is followed by a second nondestructive cleavage, most probably of the chain of Mr = 46,000, to yield the third product which migrates as a band of Mr = 26,000.

Enzyme Activation↗
PubMedDate not supplied

Common IgE-epitopes of recombinant Phl p I, the major timothy grass pollen allergen and natural group I grass pollen isoallergens.

Grass pollen allergens are potent elicitors of Type I allergy. More than 95% of grass pollen allergic patients display IgE-cross-reactivity to group I grass pollen allergens of different grass species. A cDNA coding for the major timothy grass pollen allergen, Phl p I, was isolated previously. To investigate the presence of common IgE-epitopes among naturally occurring group I grass pollen isoallergens, Phl p I was expressed in Escherichia coli and used for IgE-absorption experiments. Recombinant Phl p I was able to inhibit IgE-binding to most of group I isoallergens from seven grass species as identified by two dimensional electrophoresis. When tested in competitive ELISA experiments, recombinant Phl p I bound a high percentage of grass pollen specific IgE. The results indicate that recombinant Phl p I shares many of the IgE-epitopes with natural group I grass pollen allergens and hence may represent a useful tool for specific diagnosis and therapy of grass pollen allergy.

Allergens↗
PubMedDate not supplied

Prospective monitoring of minimal residual disease in acute myeloid leukemia with inversion(16) by CBFbeta/MYH11 RT-PCR: implications for a monitoring schedule and for treatment decisions.

Minimal residual disease in patients with acute myeloid leukemia (AML) with inversion(16) can be monitored by CBFbeta/MYH11 RT-PCR. While the association between molecular remission (MR) in bone marrow (BM) and peripheral blood (PB) and long-term clinical remission (CR) seems to be established, there are insufficient data on the kinetics of CBFbeta/MYH11. We have performed a prospective study in order to generate a reasonable and sufficient schedule for PCR-monitoring. 11 patients with AML and inversion (16) in complete hematological remission have been prospectively monitored by CBFbeta/MYH11 RT-PCR in their BM and PB during an observation period of 7 to 67 months (median 32 months). Patients were followed during consolidation chemotherapy with repetitive cycles of high-dose Ara-C and after autologous or allogeneic stem cell transplantation in 2nd CR or refractory AML. MR never coincided with achievement of CR but occurred between 2 and 8 months after hematological remission. All patients in continuous CR were PCR-negative after 1-8 (median 4) months. Two patients relapsed despite MR for 10 to 15 months. Molecular relapse preceded hematological relapse by 3 to 5 months. Three out of four patients who were not in MR after 8 months relapsed. Allogeneic stem cell transplantation was able to eradicate minimal residual disease in 4/4 patients. In 2 patients a temporary reconversion to PCR-positivity was reversed by reduction of immunosuppression. 1 patient did not become PCR-negative until compete withdrawal of immunosuppression. We suggest that BM and PB should be examined after the last consolidation treatment. In case of MR, PB should be examined every 1 to 2 months and BM examination should be done only in case of PCR-positivity in PB in order to confirm the molecular relapse and to identify an impending cytogenetic and/or hematological relapse. CBFbeta/MYH11 RT-PCR monitoring is able to predict relapse 3 to 5 months prior to overt hematological relapse, offers a window of opportunity for preemptive therapy of molecular relapse and confers implications for immunotherapy in the setting of allografting.

Acute Disease↗