Amir-houshang Shemirani | University of Debrecen (original) (raw)

Papers by Amir-houshang Shemirani

Research paper thumbnail of Influence of preanalytical factors on the mean platelet volume

European Archives of Oto-Rhino-Laryngology, 2016

Research paper thumbnail of The lack of aspirin resistance in patients with coronary artery disease

Journal of translational medicine, Jan 15, 2016

Aspirin resistance established by different laboratory methods is still a debated problem. Using ... more Aspirin resistance established by different laboratory methods is still a debated problem. Using COX1 specific methods no aspirin resistance was detected among healthy volunteers. Here we tested the effect of chronic aspirin treatment on platelets from patients with stable coronary artery disease. The expression of COX2 mRNA in platelets and its influences on the effect of aspirin was also investigated. One hundred and forty four patients were enrolled in the study. The direct measurement of COX1 acetylation was carried out by monoclonal antibodies specific to acetylated and non-acetylated COX1 (acCOX1 and nacCOX1) using Western blotting technique. Arachidonic acid (AA) induced TXB2 production by platelets was measured by competitive immunoassay. AA induced platelet aggregation, ATP secretion and VerifyNow Aspirin Assay were also performed. COX2 and COX1 mRNA expression in platelets were measured in 56 patients by RT-qPCR. In 138 patients only acCOX1 was detected, in the remaining s...

Research paper thumbnail of A kataláz enzim génje polimorfizmusának hatása az enzim expressziójára= Association of catalase gene and catalase protein expression

A VÉZETT MUKKA ÉS A MUNKATERV MEGVALÓSTÁSA ÉVENKÉNTI BONTÁSBAN 2008 1. Beteg minták gyűjtése: meg... more A VÉZETT MUKKA ÉS A MUNKATERV MEGVALÓSTÁSA ÉVENKÉNTI BONTÁSBAN 2008 1. Beteg minták gyűjtése: megkezdődött a. 264 kontroll egyén, b. 105 feltehetően beta-thalassemiás, c. 76 vitiligos, d. 560 diabeteses beteg 2. Ezen mintákból l történt kataláz aktivitás mérés, DNS extrakció. 3. A kataláz gén 5' végén taláható-262C>T mutáció analízishez a LNA (Locked Nucleic Acid) próbák tervezése, szintetizáltatása megtörtént. 2009 1. 61 betegnél detektáltunk 50%-nál kisebb kataláz aktivitást. Ezeknél a veleszületett kataláz hiány ismert mutációinak vizsgálata a. heteroduplex eljárással történt a 2-es exon esetében b. a 3 exon, 4 exon, 4 intron, 7 intron mutációk vizsgálatára Light Cycler próbákat terveztettünk és szintetizáltatunk. A reakció optimalizálása/primerek nem volt sikeres, mivel nagyszámban (mintegy 25 %)-ban kaptunk mutációra utaló görbéket. Ezeknek a verifikálása a költséges nukleotid szekvencia analízissel nem volt betervezve. Ezért ezen vizsgálatokat a további exonokra már nem végeztük el. c. az exon 9 mutációk analízise az általunk kifejlesztett és szabadalomban rögzített eljárásunkkal végezzük (P 07 00560). Mutációs jel esetén szekvencia analízis készül. 2. 3 (BSc) hallgató (Kujbus Rita, Kocsordi Krisztina, Szabó Enikő) befejezte és sikeresen megvédte a kataláz enzim polimorfizmusának vizsgálatával foglakozó diploma dolgozatát 2010 1.További beteg minták gyűjtése az OEC Egységei révén: a. Belgyógyászat: diabetes mellitus (1-és 2-es típus): 548, b. Klinikai Biokémiai és Molekuláris Patológiai Intézet: betathalassemia megerősítés HPLC (HbA2 és HbF)-vel 123, c. Foglakozás Egészségügyi Szolgálat: kontroll: 312 d. Bőrgyógyászati klinika: vitiligo 76 (előzetesen) 2. Ezen már véglegesnek tűnő mintabankból megtörtént a vér kataláz aktivitás mérés, és a genomiális DNS szeparálás. 3. Megkezdődött az átlagos vér kataláz aktivitás 50%-ánál kisebb kataláz aktivitású minták vizsgálata a lehetséges genetikai okok felderítésére. 4. Elsőként polimorfizmus szűrést végeztünk SSCP és heteroduplex eljárásokkal. Ezek után történt a polimorfizmus/mutáció megerősítése DNS szekvencia analízissel. CORE Metadata, citation and similar papers at core.ac.uk

Research paper thumbnail of Újszülöttek in Utero Kialakult Thrombosisa: Örökletes Thrombophilia?

Orvosi Hetilap, 2009

Thromboembolic events are relatively uncommon in childhood. It involves mainly children under one... more Thromboembolic events are relatively uncommon in childhood. It involves mainly children under one year of age and adolescents, with an incidence is 5.1/10000 live births. Authors present a course of disease of seven cases with neonatal thromboembolic events (2.5/admissions), diagnosed and treated at the Neonatal Division of Department of Pediatrics. In three of seven cases thrombosis proved to be of intrauterine origin. In each of the latter cases, inherited thrombophilia of the mothers was detected. Additional risk factors including infection could be revealed only in one case. Using in vivo and post mortem DNA analysis, mother-like-thrombophilia could not be confirmed in any of the newborns. Based on their experiences, authors suppose that undetected predisposing factors added to maternal thrombophilia can be considered as etiological factor. Authors suggest the intensive follow-up of pregnant women with thrombophilia and also their fetuses.

Research paper thumbnail of Factor XIII deficiency: complete phenotypic characterization of two cases with novel causative mutations

Haemophilia, 2013

Coagulation factor XIII (FXIII) exists as heterotetramer (FXIII-A 2 B 2) in the plasma and as dim... more Coagulation factor XIII (FXIII) exists as heterotetramer (FXIII-A 2 B 2) in the plasma and as dimer (FXIII-A 2) in cells. Activated FXIII mechanically stabilizes fibrin and protects it from fibrinolysis by cross-linking fibrin chains and a 2plasmin inhibitor to fibrin. FXIII is essential to maintaining haemostasis, and its deficiency causes severe bleeding diathesis. Due to improper laboratory practices, FXIII deficiency is considered the most under-diagnosed bleeding disorder. The aim of this study was to demonstrate in two cases how FXIII deficiency is properly diagnosed and classified, and to compare results of laboratory analysis and clinical symptoms. FXIII activity from plasma and platelets was measured by a modified ammonia release assay, while FXIII-A 2 B 2 , FXIII-A and FXIII-B antigens were determined by ELISA. The exon-intron boundaries and the promoter region of F13A1 gene were amplified by PCR and the amplified products were analysed by direct fluorescent sequencing. FXIII-A mRNA in platelets was determined by RT-qPCR. Two children with severe bleeding symptoms were investigated. In both cases FXIII activity and FXIII-A antigen were undetectable in the plasma and platelet lysate. In the plasma no FXIII-A 2 B 2 antigen was found, while FXIII-B antigen was >30% in both cases. Proband1 was a compound heterozygote possessing a known missense mutation (c.980G>A, p.Arg326Gln) and a novel splice-site mutation (c.1112+2T>C). Proband2 was homozygote for a novel single nucleotide deletion (c.212delA) leading to early stop codon. The discovered mutations explain the severity of clinical symptoms and the laboratory data. Methods precise in the low activity/antigen range are required to draw valid conclusion on phenotypegenotype relationship.

Research paper thumbnail of A Novel Catalase Mutation (a GA Insertion) Causes the Hungarian Type of Acatalasemia

Blood Cells, Molecules, and Diseases, 2000

ABSTRACT Acatalasemia, a deficiency of enzyme catalase, is an autosomal recessive syndrome with a... more ABSTRACT Acatalasemia, a deficiency of enzyme catalase, is an autosomal recessive syndrome with an incidence of 5:106 in Hungary. We have examined the first Hungarian acatalasemic family for the disease-causing mutation. All exons of the catalase gene were screened by PCR-SSCP, PCR-heteroduplex, and nucleotide sequence analysis. The heteroduplex formation detected in exon 2 was verified by nucleotide sequence analysis. We found a GA insertion at nucleotide position 138, increasing the GA repeat number from 4 to 5. This GA insertion caused a frameshift in the amino acid sequence from position 68 to 133 and generated a TGA terminating codon at amino acid position 134. This truncated protein lacks the essential amino acid (histidine 74) in the active center. This finding can explain the decreased blood catalase activity in the Hungarian acatalasemic family.

Research paper thumbnail of The Prognostic Role of CYP Enzyme in Kidney Transplantation: A Single Centre Experience

Transplantation Proceedings

Research paper thumbnail of The Effect of Activated FXIII, a Transglutaminase, on Vascular Smooth Muscle Cells

International Journal of Molecular Sciences

Plasma factor XIII (pFXIII) is a heterotetramer of FXIII-A and FXIII-B subunits. The cellular for... more Plasma factor XIII (pFXIII) is a heterotetramer of FXIII-A and FXIII-B subunits. The cellular form (cFXIII), a dimer of FXIII-A, is present in a number of cell types. Activated FXIII (FXIIIa), a transglutaminase, plays an important role in clot stabilization, wound healing, angiogenesis and maintenance of pregnancy. It has a direct effect on vascular endothelial cells and fibroblasts, which have been implicated in the development of atherosclerotic plaques. Our aim was to explore the effect of FXIIIa on human aortic smooth muscle cells (HAoSMCs), another major cell type in the atherosclerotic plaque. Osteoblastic transformation induced by Pi and Ca2+ failed to elicit the expression of cFXIII in HAoSMCs. EZ4U, CCK-8 and CytoSelect Wound Healing assays were used to investigate cell proliferation and migration. The Sircol Collagen Assay Kit was used to monitor collagen secretion. Thrombospondin-1 (TSP-1) levels were measured by ELISA. Cell-associated TSP-1 was detected by the immunoflu...

Research paper thumbnail of N‐glycosylation of blood coagulation factor XIII subunit B and its functional consequence

Journal of Thrombosis and Haemostasis, 2020

This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmer... more This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Research paper thumbnail of Platelet count and mean volume in acute stroke: a systematic review and meta-analysis

Research paper thumbnail of Characteristics of platelet count and size and diagnostic accuracy of mean platelet volume in patients with venous thromboembolism. A systematic review and meta-analysis

Platelets, Jan 18, 2017

The purpose of this study was to evaluate the association between platelet (PLT) count and mean p... more The purpose of this study was to evaluate the association between platelet (PLT) count and mean platelet volume (MPV) and venous thromboembolism (VTE). Thus, this study reviewed and performed a quantitative synthesis on data from the literature. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 18 studies were included in this paper. A random-effect meta-analysis was conducted for the assessment of heterogeneity using thrombosis place, type of analyzer, type of anticoagulant and incubation time of samples as covariates. A mixed-effect meta-regression was performed based on the subgroup for the whole samples using thrombosis place and method of measurement as moderators for MPV and PLT, respectively. The cumulative estimates and 95% confidence interval (95%CI) of specificity, sensitivity, area under the receiver operator characteristic curve (AUC) and diagnostic odds ratio (DOR) for MPV were...

Research paper thumbnail of The clinical significance of pneumatic tube transport system on platelet indices: EDTA or citrate anticoagulant?

International Journal of Laboratory Hematology, 2017

Research paper thumbnail of A véralvadás XIII-as faktora: strukturális és funkcionális vonatkozások, jelentősége különböző kórképekben= Blood coagulation FXIII: structural, functional aspects, its involvement in various pathological conditions

Research paper thumbnail of Decreased factor XIII levels in factor XIII A subunit Leu34 homozygous patients with coronary artery disease

Thrombosis Research, 2008

Introduction: The effect of factor XIII A subunit (FXIII-A) Val34Leu polymorphism on the risk of ... more Introduction: The effect of factor XIII A subunit (FXIII-A) Val34Leu polymorphism on the risk of coronary artery disease (CAD) has been extensively studied. In this study we investigated how FXIII-A Val34Leu genotypes influence plasma factor XIII levels in patients with coronary sclerosis (CS) and myocardial infarction (MI) and how fibrinogen level modulates this effect. Patients and methods: 955 consecutive patients admitted for coronary angiography were categorized according to the presence or absence of significant CS and the history of MI. The frequency of FXIII-A Val34Leu polymorphism, fibrinogen, FXIII activity and antigen levels were determined. Results and conclusions: CS or MI decreased FXIII levels in patients homozygous for FXIII-A Leu34 allele, but not in heterozygous or wild type patients. In the subgroup of patients with CS, but without the history of MI no significant effect was detected, which suggests that MI has a more prominent role. The specific activity of plasma FXIII was independent of FXIII-A Val34Leu genotype. FXIII and fibrinogen levels significantly correlated in CS+ and MI+ patients. In MI+ patients of Leu/Val or Leu/Leu genotypes and with fibrinogen levels in the lowest quartile, FXIII levels were lower than in the

Research paper thumbnail of Association of von Willebrand factor and fibrinogen plasma levels with primary Raynaud’s phenomenon in male and female patients

Rheumatology International, 2011

Research paper thumbnail of Increased mean platelet volume in primary Raynaud's phenomenon

Platelets, 2011

We hypothesized that mean platelet volume (MPV), a reliable marker of platelet activation, might ... more We hypothesized that mean platelet volume (MPV), a reliable marker of platelet activation, might be elevated in primary Raynaud's phenomenon (PRP) even if there was no thrombotic complication in our subjects. In this retrospective-cohort study, we examined the clinical value of MPV in 200 patients with PRP and 116 clinical controls, and measured MPV and platelet P-selectin (CD62P) in all study participants. We also evaluated the effect of age, gender, and disease duration on these platelet activation markers in PRP. MPV and CD62 positivities were significantly (p<0.001) elevated in patients with PRP compared with controls. These differences retained when patients and controls were analyzed according to age, gender, and the disease duration. In logistic regression analysis, MPV (OR: 15.8, 95% CI: 8.14-30.64, p<0.001) and CD62P (OR: 11.3, 95% CI: 4.85-26.12, p<0.001) were found to be independently associated with PRP. In conclusion, increased MPV is independently related to PRP, and its level was not influenced by age, gender, and the duration of PRP.

Research paper thumbnail of The effect of metoprolol alone and combined metoprolol–felodipin on the digital microcirculation of patients with primary Raynaud's syndrome

Microvascular Research, 2011

Calcium channel inhibitors have beneficial impact on microcirculation, but beta-blocker effect is... more Calcium channel inhibitors have beneficial impact on microcirculation, but beta-blocker effect is controversial. Clinicians still do not agree on beta-blocker combination with other treatments in the management of impaired microcirculation. The aim of the present study was to describe the effects of beta-blocker metoprolol monotherapy and combined with calcium channel inhibitor felodipin on digital microcirculation in primary Raynaud's syndrome. Methods: We enrolled in this study 46 patients suffering from both hypertension and primary Raynaud's syndrome. Fifteen patients were treated with beta-blocker monotherapy (metoprolol), 13 received combined beta-blocker and calcium channel blocker therapy (felodipin and metoprolol), while 18 patients without any medications served as controls. Measurement of digital microcirculation was carried out with laser Doppler scanner. Results and conclusions: Our investigation concludes that the concurrent administration of beta-blockers with calcium channel inhibitors positively reduces symptoms in patients suffering from Raynaud's syndrome.

Research paper thumbnail of Correlations between Clinicopathological Parameters and Molecular Signatures of Primary Tumors for Patients with Stage T3n0 Colorectal Adenocarcinomas: A Single Center Retrospective Study on 100 Cases

Hepatogastroenterology, 2012

To examine the clinical and protein expression characteristics of tumor tissues for prediction of... more To examine the clinical and protein expression characteristics of tumor tissues for prediction of prognosis in colorectal cancer (CRC). We retrospectively analyzed the clinicopathological data of patients with stage T3N0 CRC, operated between 1997-2003 and the surgical materials for the relation between disease prognosis and p53, p21, p16, β-catenin, E-cadherin, EGFR, hMLH1, hMSH2 and TS protein expressions. A significantly shorter 3-year disease free survival was observed in patients under the age of 50. The worst 5-year overall survival (OS) observed for patients over 70. Tumor localization and number of processed lymph nodes significantly affected prognosis. The EGFR, hMSH2 and TS expressions and the 5-fluorouracyl treatment were not found to be of prognostic value; p53 and p21 positivity had significantly worse survival. When β-catenin membrane expression disappeared on tumor cells, the 5-year OS rate decreased and time to metastasis shortened significantly. Membrane β-catenin expression, processed lymph nodes number and age were detected as independent prognostic markers. These results suggest that the evaluation of a clinicopathological profile, based on age, tumor localization, number of examined lymph nodes, p53, p21 and E-cadherin β-catenin expression appears to be useful in identifying high risk patients.

Research paper thumbnail of Factor XIII-A subunit Val34Leu polymorphism in fatal atherothrombotic ischemic stroke

Blood Coagulation & Fibrinolysis, 2014

Factor XIII (FXIII) is a regulator of fibrinolysis and clot firmness. Val34Leu polymorphism of it... more Factor XIII (FXIII) is a regulator of fibrinolysis and clot firmness. Val34Leu polymorphism of its potentially active A subunit (FXIII-A) leads to faster activation of FXIII, influences clot structure and provides a moderate protection against coronary artery disease. The effect of FXIII-A Val34Leu polymorphism on the risk of atherothrombotic ischemic stroke (AIS) has been investigated in a few studies with contradictory results. In all previous studies, only patients surviving AIS were enrolled and sex-specific effects were not explored. In this retrospective multicenter cohort, we investigated the effect of FXIII-A Val34Leu polymorphism on the risk of fatal AIS in women and men. DNA isolation and genetic determinations in the case of 316 patients who died of AIS were carried out on paraffin-embedded tissue specimens. Genetic analyses for population controls, patients with history of AIS and sex-matched controls were performed on extracted genomic DNA from peripheral blood leukocytes. The prevalence of homozygous wild-type, and heterozygous genotypes, Leu34 carriers and Leu34 allele was not different significantly between the patients with fatal AIS and their respective controls. Logistic regression analysis with age as co-variant demonstrated that in women, homozygous presentation of Leu34 allele represented a more than three-fold increased risk of AIS with fatal outcome. The results demonstrate that FXIII-A Val34Leu polymorphism does not influence the occurrence of AIS, but has an effect on the severity of its outcome. This effect is sex-specific and in homozygous women, the prothrombotic/antifibrinolytic effects of FXIII-A Val34Leu polymorphism seem to prevail.

Research paper thumbnail of The effect of FXIII-A Val34Leu genotype on the risk of peripheral arterial disease

Blood Coagulation & Fibrinolysis, 2013

Research paper thumbnail of Influence of preanalytical factors on the mean platelet volume

European Archives of Oto-Rhino-Laryngology, 2016

Research paper thumbnail of The lack of aspirin resistance in patients with coronary artery disease

Journal of translational medicine, Jan 15, 2016

Aspirin resistance established by different laboratory methods is still a debated problem. Using ... more Aspirin resistance established by different laboratory methods is still a debated problem. Using COX1 specific methods no aspirin resistance was detected among healthy volunteers. Here we tested the effect of chronic aspirin treatment on platelets from patients with stable coronary artery disease. The expression of COX2 mRNA in platelets and its influences on the effect of aspirin was also investigated. One hundred and forty four patients were enrolled in the study. The direct measurement of COX1 acetylation was carried out by monoclonal antibodies specific to acetylated and non-acetylated COX1 (acCOX1 and nacCOX1) using Western blotting technique. Arachidonic acid (AA) induced TXB2 production by platelets was measured by competitive immunoassay. AA induced platelet aggregation, ATP secretion and VerifyNow Aspirin Assay were also performed. COX2 and COX1 mRNA expression in platelets were measured in 56 patients by RT-qPCR. In 138 patients only acCOX1 was detected, in the remaining s...

Research paper thumbnail of A kataláz enzim génje polimorfizmusának hatása az enzim expressziójára= Association of catalase gene and catalase protein expression

A VÉZETT MUKKA ÉS A MUNKATERV MEGVALÓSTÁSA ÉVENKÉNTI BONTÁSBAN 2008 1. Beteg minták gyűjtése: meg... more A VÉZETT MUKKA ÉS A MUNKATERV MEGVALÓSTÁSA ÉVENKÉNTI BONTÁSBAN 2008 1. Beteg minták gyűjtése: megkezdődött a. 264 kontroll egyén, b. 105 feltehetően beta-thalassemiás, c. 76 vitiligos, d. 560 diabeteses beteg 2. Ezen mintákból l történt kataláz aktivitás mérés, DNS extrakció. 3. A kataláz gén 5' végén taláható-262C>T mutáció analízishez a LNA (Locked Nucleic Acid) próbák tervezése, szintetizáltatása megtörtént. 2009 1. 61 betegnél detektáltunk 50%-nál kisebb kataláz aktivitást. Ezeknél a veleszületett kataláz hiány ismert mutációinak vizsgálata a. heteroduplex eljárással történt a 2-es exon esetében b. a 3 exon, 4 exon, 4 intron, 7 intron mutációk vizsgálatára Light Cycler próbákat terveztettünk és szintetizáltatunk. A reakció optimalizálása/primerek nem volt sikeres, mivel nagyszámban (mintegy 25 %)-ban kaptunk mutációra utaló görbéket. Ezeknek a verifikálása a költséges nukleotid szekvencia analízissel nem volt betervezve. Ezért ezen vizsgálatokat a további exonokra már nem végeztük el. c. az exon 9 mutációk analízise az általunk kifejlesztett és szabadalomban rögzített eljárásunkkal végezzük (P 07 00560). Mutációs jel esetén szekvencia analízis készül. 2. 3 (BSc) hallgató (Kujbus Rita, Kocsordi Krisztina, Szabó Enikő) befejezte és sikeresen megvédte a kataláz enzim polimorfizmusának vizsgálatával foglakozó diploma dolgozatát 2010 1.További beteg minták gyűjtése az OEC Egységei révén: a. Belgyógyászat: diabetes mellitus (1-és 2-es típus): 548, b. Klinikai Biokémiai és Molekuláris Patológiai Intézet: betathalassemia megerősítés HPLC (HbA2 és HbF)-vel 123, c. Foglakozás Egészségügyi Szolgálat: kontroll: 312 d. Bőrgyógyászati klinika: vitiligo 76 (előzetesen) 2. Ezen már véglegesnek tűnő mintabankból megtörtént a vér kataláz aktivitás mérés, és a genomiális DNS szeparálás. 3. Megkezdődött az átlagos vér kataláz aktivitás 50%-ánál kisebb kataláz aktivitású minták vizsgálata a lehetséges genetikai okok felderítésére. 4. Elsőként polimorfizmus szűrést végeztünk SSCP és heteroduplex eljárásokkal. Ezek után történt a polimorfizmus/mutáció megerősítése DNS szekvencia analízissel. CORE Metadata, citation and similar papers at core.ac.uk

Research paper thumbnail of Újszülöttek in Utero Kialakult Thrombosisa: Örökletes Thrombophilia?

Orvosi Hetilap, 2009

Thromboembolic events are relatively uncommon in childhood. It involves mainly children under one... more Thromboembolic events are relatively uncommon in childhood. It involves mainly children under one year of age and adolescents, with an incidence is 5.1/10000 live births. Authors present a course of disease of seven cases with neonatal thromboembolic events (2.5/admissions), diagnosed and treated at the Neonatal Division of Department of Pediatrics. In three of seven cases thrombosis proved to be of intrauterine origin. In each of the latter cases, inherited thrombophilia of the mothers was detected. Additional risk factors including infection could be revealed only in one case. Using in vivo and post mortem DNA analysis, mother-like-thrombophilia could not be confirmed in any of the newborns. Based on their experiences, authors suppose that undetected predisposing factors added to maternal thrombophilia can be considered as etiological factor. Authors suggest the intensive follow-up of pregnant women with thrombophilia and also their fetuses.

Research paper thumbnail of Factor XIII deficiency: complete phenotypic characterization of two cases with novel causative mutations

Haemophilia, 2013

Coagulation factor XIII (FXIII) exists as heterotetramer (FXIII-A 2 B 2) in the plasma and as dim... more Coagulation factor XIII (FXIII) exists as heterotetramer (FXIII-A 2 B 2) in the plasma and as dimer (FXIII-A 2) in cells. Activated FXIII mechanically stabilizes fibrin and protects it from fibrinolysis by cross-linking fibrin chains and a 2plasmin inhibitor to fibrin. FXIII is essential to maintaining haemostasis, and its deficiency causes severe bleeding diathesis. Due to improper laboratory practices, FXIII deficiency is considered the most under-diagnosed bleeding disorder. The aim of this study was to demonstrate in two cases how FXIII deficiency is properly diagnosed and classified, and to compare results of laboratory analysis and clinical symptoms. FXIII activity from plasma and platelets was measured by a modified ammonia release assay, while FXIII-A 2 B 2 , FXIII-A and FXIII-B antigens were determined by ELISA. The exon-intron boundaries and the promoter region of F13A1 gene were amplified by PCR and the amplified products were analysed by direct fluorescent sequencing. FXIII-A mRNA in platelets was determined by RT-qPCR. Two children with severe bleeding symptoms were investigated. In both cases FXIII activity and FXIII-A antigen were undetectable in the plasma and platelet lysate. In the plasma no FXIII-A 2 B 2 antigen was found, while FXIII-B antigen was >30% in both cases. Proband1 was a compound heterozygote possessing a known missense mutation (c.980G>A, p.Arg326Gln) and a novel splice-site mutation (c.1112+2T>C). Proband2 was homozygote for a novel single nucleotide deletion (c.212delA) leading to early stop codon. The discovered mutations explain the severity of clinical symptoms and the laboratory data. Methods precise in the low activity/antigen range are required to draw valid conclusion on phenotypegenotype relationship.

Research paper thumbnail of A Novel Catalase Mutation (a GA Insertion) Causes the Hungarian Type of Acatalasemia

Blood Cells, Molecules, and Diseases, 2000

ABSTRACT Acatalasemia, a deficiency of enzyme catalase, is an autosomal recessive syndrome with a... more ABSTRACT Acatalasemia, a deficiency of enzyme catalase, is an autosomal recessive syndrome with an incidence of 5:106 in Hungary. We have examined the first Hungarian acatalasemic family for the disease-causing mutation. All exons of the catalase gene were screened by PCR-SSCP, PCR-heteroduplex, and nucleotide sequence analysis. The heteroduplex formation detected in exon 2 was verified by nucleotide sequence analysis. We found a GA insertion at nucleotide position 138, increasing the GA repeat number from 4 to 5. This GA insertion caused a frameshift in the amino acid sequence from position 68 to 133 and generated a TGA terminating codon at amino acid position 134. This truncated protein lacks the essential amino acid (histidine 74) in the active center. This finding can explain the decreased blood catalase activity in the Hungarian acatalasemic family.

Research paper thumbnail of The Prognostic Role of CYP Enzyme in Kidney Transplantation: A Single Centre Experience

Transplantation Proceedings

Research paper thumbnail of The Effect of Activated FXIII, a Transglutaminase, on Vascular Smooth Muscle Cells

International Journal of Molecular Sciences

Plasma factor XIII (pFXIII) is a heterotetramer of FXIII-A and FXIII-B subunits. The cellular for... more Plasma factor XIII (pFXIII) is a heterotetramer of FXIII-A and FXIII-B subunits. The cellular form (cFXIII), a dimer of FXIII-A, is present in a number of cell types. Activated FXIII (FXIIIa), a transglutaminase, plays an important role in clot stabilization, wound healing, angiogenesis and maintenance of pregnancy. It has a direct effect on vascular endothelial cells and fibroblasts, which have been implicated in the development of atherosclerotic plaques. Our aim was to explore the effect of FXIIIa on human aortic smooth muscle cells (HAoSMCs), another major cell type in the atherosclerotic plaque. Osteoblastic transformation induced by Pi and Ca2+ failed to elicit the expression of cFXIII in HAoSMCs. EZ4U, CCK-8 and CytoSelect Wound Healing assays were used to investigate cell proliferation and migration. The Sircol Collagen Assay Kit was used to monitor collagen secretion. Thrombospondin-1 (TSP-1) levels were measured by ELISA. Cell-associated TSP-1 was detected by the immunoflu...

Research paper thumbnail of N‐glycosylation of blood coagulation factor XIII subunit B and its functional consequence

Journal of Thrombosis and Haemostasis, 2020

This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmer... more This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Research paper thumbnail of Platelet count and mean volume in acute stroke: a systematic review and meta-analysis

Research paper thumbnail of Characteristics of platelet count and size and diagnostic accuracy of mean platelet volume in patients with venous thromboembolism. A systematic review and meta-analysis

Platelets, Jan 18, 2017

The purpose of this study was to evaluate the association between platelet (PLT) count and mean p... more The purpose of this study was to evaluate the association between platelet (PLT) count and mean platelet volume (MPV) and venous thromboembolism (VTE). Thus, this study reviewed and performed a quantitative synthesis on data from the literature. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 18 studies were included in this paper. A random-effect meta-analysis was conducted for the assessment of heterogeneity using thrombosis place, type of analyzer, type of anticoagulant and incubation time of samples as covariates. A mixed-effect meta-regression was performed based on the subgroup for the whole samples using thrombosis place and method of measurement as moderators for MPV and PLT, respectively. The cumulative estimates and 95% confidence interval (95%CI) of specificity, sensitivity, area under the receiver operator characteristic curve (AUC) and diagnostic odds ratio (DOR) for MPV were...

Research paper thumbnail of The clinical significance of pneumatic tube transport system on platelet indices: EDTA or citrate anticoagulant?

International Journal of Laboratory Hematology, 2017

Research paper thumbnail of A véralvadás XIII-as faktora: strukturális és funkcionális vonatkozások, jelentősége különböző kórképekben= Blood coagulation FXIII: structural, functional aspects, its involvement in various pathological conditions

Research paper thumbnail of Decreased factor XIII levels in factor XIII A subunit Leu34 homozygous patients with coronary artery disease

Thrombosis Research, 2008

Introduction: The effect of factor XIII A subunit (FXIII-A) Val34Leu polymorphism on the risk of ... more Introduction: The effect of factor XIII A subunit (FXIII-A) Val34Leu polymorphism on the risk of coronary artery disease (CAD) has been extensively studied. In this study we investigated how FXIII-A Val34Leu genotypes influence plasma factor XIII levels in patients with coronary sclerosis (CS) and myocardial infarction (MI) and how fibrinogen level modulates this effect. Patients and methods: 955 consecutive patients admitted for coronary angiography were categorized according to the presence or absence of significant CS and the history of MI. The frequency of FXIII-A Val34Leu polymorphism, fibrinogen, FXIII activity and antigen levels were determined. Results and conclusions: CS or MI decreased FXIII levels in patients homozygous for FXIII-A Leu34 allele, but not in heterozygous or wild type patients. In the subgroup of patients with CS, but without the history of MI no significant effect was detected, which suggests that MI has a more prominent role. The specific activity of plasma FXIII was independent of FXIII-A Val34Leu genotype. FXIII and fibrinogen levels significantly correlated in CS+ and MI+ patients. In MI+ patients of Leu/Val or Leu/Leu genotypes and with fibrinogen levels in the lowest quartile, FXIII levels were lower than in the

Research paper thumbnail of Association of von Willebrand factor and fibrinogen plasma levels with primary Raynaud’s phenomenon in male and female patients

Rheumatology International, 2011

Research paper thumbnail of Increased mean platelet volume in primary Raynaud's phenomenon

Platelets, 2011

We hypothesized that mean platelet volume (MPV), a reliable marker of platelet activation, might ... more We hypothesized that mean platelet volume (MPV), a reliable marker of platelet activation, might be elevated in primary Raynaud's phenomenon (PRP) even if there was no thrombotic complication in our subjects. In this retrospective-cohort study, we examined the clinical value of MPV in 200 patients with PRP and 116 clinical controls, and measured MPV and platelet P-selectin (CD62P) in all study participants. We also evaluated the effect of age, gender, and disease duration on these platelet activation markers in PRP. MPV and CD62 positivities were significantly (p<0.001) elevated in patients with PRP compared with controls. These differences retained when patients and controls were analyzed according to age, gender, and the disease duration. In logistic regression analysis, MPV (OR: 15.8, 95% CI: 8.14-30.64, p<0.001) and CD62P (OR: 11.3, 95% CI: 4.85-26.12, p<0.001) were found to be independently associated with PRP. In conclusion, increased MPV is independently related to PRP, and its level was not influenced by age, gender, and the duration of PRP.

Research paper thumbnail of The effect of metoprolol alone and combined metoprolol–felodipin on the digital microcirculation of patients with primary Raynaud's syndrome

Microvascular Research, 2011

Calcium channel inhibitors have beneficial impact on microcirculation, but beta-blocker effect is... more Calcium channel inhibitors have beneficial impact on microcirculation, but beta-blocker effect is controversial. Clinicians still do not agree on beta-blocker combination with other treatments in the management of impaired microcirculation. The aim of the present study was to describe the effects of beta-blocker metoprolol monotherapy and combined with calcium channel inhibitor felodipin on digital microcirculation in primary Raynaud's syndrome. Methods: We enrolled in this study 46 patients suffering from both hypertension and primary Raynaud's syndrome. Fifteen patients were treated with beta-blocker monotherapy (metoprolol), 13 received combined beta-blocker and calcium channel blocker therapy (felodipin and metoprolol), while 18 patients without any medications served as controls. Measurement of digital microcirculation was carried out with laser Doppler scanner. Results and conclusions: Our investigation concludes that the concurrent administration of beta-blockers with calcium channel inhibitors positively reduces symptoms in patients suffering from Raynaud's syndrome.

Research paper thumbnail of Correlations between Clinicopathological Parameters and Molecular Signatures of Primary Tumors for Patients with Stage T3n0 Colorectal Adenocarcinomas: A Single Center Retrospective Study on 100 Cases

Hepatogastroenterology, 2012

To examine the clinical and protein expression characteristics of tumor tissues for prediction of... more To examine the clinical and protein expression characteristics of tumor tissues for prediction of prognosis in colorectal cancer (CRC). We retrospectively analyzed the clinicopathological data of patients with stage T3N0 CRC, operated between 1997-2003 and the surgical materials for the relation between disease prognosis and p53, p21, p16, β-catenin, E-cadherin, EGFR, hMLH1, hMSH2 and TS protein expressions. A significantly shorter 3-year disease free survival was observed in patients under the age of 50. The worst 5-year overall survival (OS) observed for patients over 70. Tumor localization and number of processed lymph nodes significantly affected prognosis. The EGFR, hMSH2 and TS expressions and the 5-fluorouracyl treatment were not found to be of prognostic value; p53 and p21 positivity had significantly worse survival. When β-catenin membrane expression disappeared on tumor cells, the 5-year OS rate decreased and time to metastasis shortened significantly. Membrane β-catenin expression, processed lymph nodes number and age were detected as independent prognostic markers. These results suggest that the evaluation of a clinicopathological profile, based on age, tumor localization, number of examined lymph nodes, p53, p21 and E-cadherin β-catenin expression appears to be useful in identifying high risk patients.

Research paper thumbnail of Factor XIII-A subunit Val34Leu polymorphism in fatal atherothrombotic ischemic stroke

Blood Coagulation & Fibrinolysis, 2014

Factor XIII (FXIII) is a regulator of fibrinolysis and clot firmness. Val34Leu polymorphism of it... more Factor XIII (FXIII) is a regulator of fibrinolysis and clot firmness. Val34Leu polymorphism of its potentially active A subunit (FXIII-A) leads to faster activation of FXIII, influences clot structure and provides a moderate protection against coronary artery disease. The effect of FXIII-A Val34Leu polymorphism on the risk of atherothrombotic ischemic stroke (AIS) has been investigated in a few studies with contradictory results. In all previous studies, only patients surviving AIS were enrolled and sex-specific effects were not explored. In this retrospective multicenter cohort, we investigated the effect of FXIII-A Val34Leu polymorphism on the risk of fatal AIS in women and men. DNA isolation and genetic determinations in the case of 316 patients who died of AIS were carried out on paraffin-embedded tissue specimens. Genetic analyses for population controls, patients with history of AIS and sex-matched controls were performed on extracted genomic DNA from peripheral blood leukocytes. The prevalence of homozygous wild-type, and heterozygous genotypes, Leu34 carriers and Leu34 allele was not different significantly between the patients with fatal AIS and their respective controls. Logistic regression analysis with age as co-variant demonstrated that in women, homozygous presentation of Leu34 allele represented a more than three-fold increased risk of AIS with fatal outcome. The results demonstrate that FXIII-A Val34Leu polymorphism does not influence the occurrence of AIS, but has an effect on the severity of its outcome. This effect is sex-specific and in homozygous women, the prothrombotic/antifibrinolytic effects of FXIII-A Val34Leu polymorphism seem to prevail.

Research paper thumbnail of The effect of FXIII-A Val34Leu genotype on the risk of peripheral arterial disease

Blood Coagulation & Fibrinolysis, 2013