118 research outputs found
Increased plasma von Willebrand factor antigen levels but normal von Willebrand factor cleaving protease (ADAMTS13) activity in preeclampsia.
The activity of ADAMTS13, the von Willebrand factor (VWF) cleaving protease is low in several conditions, including HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome. As HELLP syndrome develops in most cases on the basis of preeclampsia, our aim was to determine whether plasma ADAMTS13 activity is decreased in preeclampsia. Sixty-seven preeclamptic patients, 70 healthy pregnant women and 59 healthy non-pregnant women were involved in this case-control study. Plasma ADAMTS13 activity was determined with the FRETS-VWF73 assay, while VWF antigen (VWF:Ag) levels with an enzyme-linked immunosorbent assay. The multimeric pattern of VWF was analyzed by SDS-agarose gel electrophoresis. There was no significant difference in plasma ADAMTS13 activity between the preeclamptic and the healthy pregnant and non-pregnant groups (median [25-75 percentile]: 98.8 [76.5-112.8] %, 96.3 [85.6-116.2] % and 91.6 [78.5-104.4] %, respectively; p > 0.05). However, plasma VWF:Ag levels were significantly higher in preeclamptic patients than in healthy pregnant and non-pregnant women (187.1 [145.6-243.1] % versus 129.3 [105.1-182.8] % and 70.0 [60.2-87.3] %, respectively; p < 0.001). The multimeric pattern of VWF was normal in each group. Primiparas had lower plasma ADAMTS13 activity than multi-paras (92.6 [75.8-110.6] % versus 104.2 [92.1-120.8] %; p = 0.011). No other relationship was found between clinical characteristics, laboratory parameters and plasma ADAMTS13 activity in either study group. In conclusion, plasma ADAMTS13 activity is normal in preeclampsia despite the increased VWF:Ag levels. However, further studies are needed to determine whether a decrease in plasma ADAMTS13 activity could predispose preeclamptic patients to develop HELLP syndrome
A diabeteshez társuló angiopathia hajlam és kockázat korai felmérése és prospektív követő vizsgálata vasculáris haematológiai módszerekkel = Early risk assessment of diabetic angiopathy using vascular haematological parameters, a prospective follow-up study
Több, mint 400 diabeteses beteg haptoglobin fenotípus vizsgálatát elvégeztük. A megoszlás hasonló más orszégokéhoz, az érszövődmények 5 éves periódusa lezártakor az eredményeket közleményekben publikáljuk. Gyulladásos bélbetegségben a legfontosabb eredmények: Crohn betegségben a haptoglobin I-1 fenotípus gyakorisága nagy, colitis ulcerosában a megosztás az átlagos lakosságéhoz hasonló. A betegség lefolyása összefüggést mutat a haptoglobin típussal, a primer sclerotizáló chollangitis II-2 fenotípus mellett gyakori. Coeliakilában végzett nagyszmámú vizsgálat azt jelzi, hogy a II-1 típus a várhatónál jóval gyakoribb és itt is összefüggés található a klinikai lefolyással. A haptoglobin fenotípus és a bélbetegségek közötti összefüggéseket elsőként ismertük fel. Hasonlóan ígéretesnek látszik az első 60 beteg vizsgálata alapján krónikus lymphoid leukémiában induló felmérésnek. | Haptoglobin phenotypic analysis have been performed in more than 400 diabetic patients, the distrubution is similar to other popoulationb reports, finishing the five year vascular followup rusts will be published. Haptoglobin phenotype seems to correlate with type and clinical course of inflammatory bowel diseases (based upon large series of measurements), i.e. 1-1 type seems to be common in Crohns disease, whereas primary sclerotising cholangitis is linked to 2-2 phenotype cases. In celiac disease the prevalent phenotype is 2-1, and our data suports that the haptoglobin phenotype seems to influence the clinicalk course. These result are clearly new informations, their publication had been done or some of theme are submitted for publication more recently. Promising data (60 cases) weere gained in chronic lymphocytic leukemia in our recently launched survey, as well
Evaluation of Mannose-Binding Lectin is a Useful Approach to Predict the Risk of Infectious Complications Following Autologous Hematopoietic Stem Cell Transplantation
Interaction of factor XIII subunits
Coagulation factor XIII (FXIII) is a heterotetramer consisting of 2 catalytic A subunits (FXIII-A2) and 2 protective/inhibitory B subunits (FXIII-B2). FXIII-B, a mosaic protein consisting of 10 sushi domains, significantly prolongs the lifespan of catalytic subunits in the circulation and prevents their slow progressive activation in plasmatic conditions. In this study, the biochemistry of the interaction between the 2 FXIII subunits was investigated. Using a surface plasmon resonance technique and an enzyme-linked immunosorbent assay-type binding assay, the equilibrium dissociation constant (Kd) for the interaction was established in the range of 10(-10) M. Based on the measured Kd, it was calculated that in plasma approximately 1% of FXIII-A2 should be in free form. This value was confirmed experimentally by measuring FXIII-A2 in plasma samples immunodepleted of FXIII-A2B2. Free plasma FXIII-A2 is functionally active, and when activated by thrombin and Ca(2+), it can cross-link fibrin. In cerebrospinal fluid and tears with much lower FXIII subunit concentrations, >80% of FXIII-A2 existed in free form. A monoclonal anti-FXIII-B antibody that prevented the interaction between the 2 subunits reacted with the recombinant combined first and second sushi domains of FXIII-B, and its epitope was localized to the peptide spanning positions 96 to 103 in the second sushi domain
A Von Willebrand Faktor multimer- és konformáció függő aktivitása és a vascularis haematologia = The structure and conformation dependent activity of VWF and its implications on vascular haematology
A von Willebrand faktor (VWF) egy nagy molekulatömegű azonos alegységekből felépülő glikoprotein, mely alegységenként kollagén és thrombocyták számára szolgáló kötőhellyel is rendelkezik. A VWF és a thrombocyták jelen vannak a keringésben azonban összekapcsolódásuk csak akkor következik be, ha a VWF kapcsolatba lép a szubendotheliummal és/vagy nagy áramlási nyíróerők lépnek fel. 1. Vizsgáltuk a szabályozás hátterében feltételezhető konformációváltozást, ehhez a. tisztított VWF-ot, és thrombocytákat modellező GPIb-vel fedett polisztirol gyöngyöket hoztunk létre. Utóbbiakról igazoltuk, hogy aktív konformációjú GPIb található a felszínükön és képesek VWF kötésére. b. Fág technológiával kerestük a VWF konformáció függő, thrombocyta adhézióban szerepet játszó epitópjait. Három szelekciós kör után olyan peptid szekvenciát sikerült azonosítanunk, amely gátolja a VWF-kollagén kölcsönhatást. 2. A VWF adhezív funkciója függ az oligomerek méretétől, ezért a. a VWF polimerizáltságának mértékét leíró módszert hoztunk létre, amely továbbfejlesztett SDS-agaróz elektroforézist követő denzitometriás adatok általunk kifejlesztett számítógépes analízisén alapul b. A VWF kollagén kötő aktivitása ugyancsak függ a multimerek méretétől. Vizsgáltuk a különböző típusú humán kollagének (I és III) VWF kötő tulajdonságait. Az ezt mérő módszert alkalmassá tettük magas VWF antigén szint esetén is a mérésre. Folyamatban van módszereket nagy klinikai beteganyagon való alkalmazása. Közlemények száma: 11 | Von Willebrand factor (VWF) is one of the key proteins of platelet adhesion. The high molecular weight homooligomer, with a collagen and a platelet binding site in each subunit. It is circulating in the bloodstream together with platelets, however, the VWF-platelet reaction does not occur, unless VWF is attached to the subendothelial collagen and/or fluid shear forces are present. 1. We studied the hypothesized conformational changes responsible for the regulation a. We developed a method to purify VWF and created GPIb coated polystyrene beads to model platelets, and demonstrated that GPIb is immobilized in an active conformation and capable of binding VWF. b. We used phage technology to identify the conformation dependent platelet binding epitopes of VWF and a peptide sequence which is capable of inhibiting the VWF-collagen interaction found. 2. Adhesion activity of VWF is dependent on the size of oligomers, therefore: a. We developed a method to describe the extent of polymerization of VWF, which is based on our computational method applied to the densitometric curves of our improved SDS-agarose gelelectophoresis technique. b. The collagen binding of VWF is also dependent on the size of VWF oligomers. We evaluated the collagen binding properties of different human collagen types (I and III), and improved the present methods, to enable measurements in the high VWF antigen range. Application of the methods in clinical studies is going on. Number of publications: 1
Evaluation of Mannose-Binding Lectin is a Useful Approach to Predict the Risk of Infectious Complications Following Autologous Hematopoietic Stem Cell Transplantation
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