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M Sanak

Publications and source records attributed to M Sanak.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Molecular studies in a population of children with bronchial asthma. I. Polymorphism in the promotor region of gene CD14].

UNLABELLED: Allergic asthma is associated with the recruitment of the inflammatory cells into the bronchial mucosa. Surface expression of CD14, a marker of activation and differentiation of macrophages/monocytes, was suggested to protect against Th-2 response. OBJECTIVE: To investigate clinical effects of genetic polymorphism of CD14 promoter in asthmatic children. METHODS: In ISAAC survey, 50 children with asthma were identified (wheezing in the last year, serum IgE level > 150 kIU/l, positive bronchial challenge test with aerolized hypertonic saline) and 73 children without the above signs. Age range of surveyed children was 13-14 years. Genotypic pattern of CD14 promoter -159 C to T transition was assessed by RFLP method. RESULTS: There was no difference in the allelic (0.36 vs. 0.38 for -159T) or genotype frequencies (0.12 vs. 0.15 for -159TT) of CD14 polymorphism between allergic asthmatics and controls. Moreover, there was no relationship between CD14 genotype and serum IgE level or bronchial hyper-responsiveness. CONCLUSION: Our results do not confirm the association of CD14 polymorphism (promoter -159 C to T transition) with asthma in Polish children.

Adolescent↗
PubMed2000

Frequency data on the loci vWA, FES/FPS, F13A01, TH01, TPOX and CSF1P0 in a population from South Poland.

Allele and genotype frequencies for six short tandem repeat (STR) loci were determined in a sample of 124 inhabitants from South Poland with commercial PCR-based typing kits. No deviations from Hardy-Weinberg expectations were found. The combined power of discrimination for the six loci was 0.9999982. There was no genotypic disequilibrium between the loci except for vWA and F13A01. The set of PCR loci was validated as useful for paternity testing and individual identification in the Polish population.

Alleles↗
PubMed2000

Aspirin-tolerant asthmatics generate more lipoxins than aspirin-intolerant asthmatics.

Asthma is characterized by chronic airway inflammation resulting from overproduction of pro-inflammatory mediators, such as leukotrienes (LT). The authors questioned the biosynthetic capacity of asthmatic patients for lipoxins (LX) and 15-epimer lipoxins (15-epi-LX), endogenous regulators of inflammatory responses that inhibit pro-inflammatory events. Levels of LXA4, 15-epi-LXA4 and LTC4 were determined in 14 clinically characterized aspirin-intolerant asthmatics (AIA), 11 aspirin-tolerant asthmatics (ATA) and eight healthy volunteers using a stimulated whole blood protocol. Both LXA4 and 15-epi-LXA4 were generated in whole blood activated by the divalent cation ionophore, A23187. Higher levels of LXA4 were produced in ATA than either AIA or healthy volunteers. Exposure of AIA whole blood to interleukin-3 prior to A23187 did not elevate their reduced capacity to generate LXA4. Generation of a bronchoconstrictor, LTC4, was similar in both AIA and ATA. Consequently, the ratio of LXA4:LTC4 quantitatively favoured the bronchoconstrictor for AIA and differed from both ATA and healthy subjects. In addition, the capacity for 15-epi-LXA4 generation was also diminished in AIA, since whole blood stimulated in the presence of aspirin gave increased levels only in samples from ATA. The present results indicate that asthmatics possess the capacity to generate both lipoxins and 15-epimer-lipoxins, but aspirin-intolerant asthmatics display a lower biosynthetic capacity than aspirin-tolerant asthmatics for these potentially protective lipid mediators. This previously unappreciated, diminished capacity for lipoxin formation by aspirin-intolerant asthmatic patients may contribute to their more severe clinical phenotype, and represents a novel paradigm for the development of chronic inflammatory disorders.

Adult↗
PubMed2000

Relationship between bleeding time, aspirin and the PlA1/A2 polymorphism of platelet glycoprotein IIIa.

A single nucleotide T to C transition of the gene encoding glycoprotein IIIa leads to a common diallelic polymorphism Leu-33-->Pro (PLA1/A2). We studied the relationship between the PlA1/A2 polymorphism and platelet function in 80 healthy men, aged 20-25 years. Before aspirin ingestion, bleeding time (BT) was shorter in carriers of the PlA2 than in carriers of the PlA1/A1 allele. At 4 h after ingestion of 300 mg of aspirin, BT became prolonged, and the intergroup difference was enhanced. In seven out of 26 PLA2 allele carriers, aspirin shortened BT on average by 30 s, compared with only one among 54 subjects with the PlA1/A1 genotype. Thus, BT both at baseline and after aspirin depends on the PlA1/A2 polymorphism of glycoprotein IIIa. Carriers of the PlA2 allele appear to be more resistant to the antithrombotic action of aspirin.

Adult↗
PubMed2000

A moderate and unspecific release of cysteinyl leukotrienes by aspirin from peripheral blood leucocytes precludes its value for aspirin sensitivity testing in asthma.

Aspirin-induced asthma (AIA) is a clinical syndrome related to cysteinyl leukotriene overproduction in airways. The confirmation of the diagnosis requires inconvenient provocation tests with acetyl salicylic acid (ASA). A study was performed to evaluate whether measurement in vitro of cysteinyl leukotrienes (cys-LTs) release by isolated peripheral blood leucocytes, stimulated with ASA, can be of use for diagnosis of AIA. A cellular allergen stimulation test, CAST, was adapted to measure leukotriene release from leucocytes of 32 aspirin-tolerant and 26 aspirin-intolerant asthmatics. The cells were stimulated with Lys-ASA, N-formyl-methionyl-leucyl-phenylalanine (fMLP), or both fMLP and Lys-ASA, in a buffer containing IL-3, and results compared with human leukaemia cell line (Hl-60) response to Lys-ASA. Cys-LTs were measured in cell supernatant fluids by ELISA. ASA had a rather week stimulatory effect on cys-LTs release in both groups of patients. Contrary to some previous studies, no significant differences were found between cys-LTs release by leucocytes from AIA and ATA, or by differentiated Hl-60 cells. Measurement of cysteinyl-leukotriene release by peripheral blood leucocytes pre-treated with aspirin has no value for diagnosis of AIA.

Adult↗
PubMed2000

Enhanced expression of the leukotriene C(4) synthase due to overactive transcription of an allelic variant associated with aspirin-intolerant asthma.

Aspirin-intolerant asthma (AIA), a distinct clinical syndrome affecting about 10% of adult asthmatics, appears to be unusually dependent on cysteine leukotriene (cys-LT) overproduction by pulmonary eosinophils. The gene coding for leukotriene (LT) C(4) synthase (LTC(4)S), the enzyme controlling cys-LT biosynthesis, exists as two common alleles distinguished by an A to C transversion at a site 444 nucleotides upstream of the translation start. We tested the hypothesis that this single nucleotide polymorphism (SNP) affects binding of transcription factors and influences the transcription rate, predisposing to AIA. Gel shift assay studies revealed that the (-444)C allele, conferring an activator protein-2 binding sequence, is an additional target for a transcription factor of histone H4 consensus. Introduction of the H4TF-2 decoy oligonucleotide into LTC(4)S-positive, differentiated HL-60 cells decreased accumulation of LTC(4) to 68%. Transfection of COS-7 with promoter construct increased expression of beta-galactosidase reporter for the (-444)C variant. The (-444)C allelic frequency was significantly higher in AIA patients (n = 76) as compared with matched aspirin-tolerant asthmatics (n = 110) and healthy controls (n = 75). Patients with AIA had also upregulated LTC(4)S messenger RNA expression in peripheral blood eosinophils. An inhaled provocation test with lysine-aspirin led to an increase in urinary output of LTE(4), which reached statistical significance only in carriers of the (-444)C allele. Our results suggest that a transcription factor, present in dividing and bone marrow resident progenitors of eosinophils, triggers LTC(4)S transcription in carriers of a common (-444)C allele due to binding with the histone H4 promoter element of the gene. Genetic predisposition to cys-LT pathway upregulation, a hallmark of AIA, can be related to overactive expression of the LTC(4)S (-444)C allele.

Adult↗
PubMed1999

[Factor V leiden and venous thromboembolism in a woman taking second generation oral contraceptives: a case report].

The most common cause of thrombophilia is a point mutation in factor V gene (G1691A), leading to factor V Leiden synthesis, which is resistant to the inhibition by activated protein C. Administration of oral contraceptives is associated with an increased risk of venous thromboembolism in carriers of factor V Leiden mutation. We describe here a case of 44-year-old woman who developed right popliteal and superficial deep vein thrombosis after a 2-month use of a contraceptive which consists of 0.15 mg levonorgestrel and 0.03 mg ethynylestradiol. The mutation G1691A of factor V gene was detected with the polymerase chain reaction. No other inherited or acquired risk factors for thrombosis was found in this patient. Treatment with low molecular weight heparin and subsequently, oral anticoagulation was effective. Women with factor V Leiden should be discouraged from taking oral contraceptives. Screening for factor V Leiden in these women appears to be useful and contribute to the prevention of thrombosis in risk situations.

Adult↗
PubMed1999

[Coincidence of 20210A prothrombin variant and factor V Leiden predisposing to venous thromboembolism].

Coexistence of inherited and environmental risks leads to the high hazard of venous thromboembolism. In such cases, there might be difficulties in the diagnosis and treatment of recurrent episodes. The importance of Factor V Leiden and prothrombin variant 20210A in the pathogenesis of venous thromboembolic disease, is widely accepted, but the carriership of thrombophilic genes' variants is usually not sufficient for the development of the disease. We report two cases of familial thrombophilia with concurrent presence of prothrombin variant 20210A and factor V Leiden. In a 28-year-old woman: pregnancy, immobilization, obstetric intervention appeared to precipitate the thromboembolic complication. In the second patient, the genetic studies revealed both thrombophilic mutations which could predispose to the recurrent venous thromboembolism, previously thought to be idiopathic. We discuss diagnostic and therapeutic difficulties in such patients.

Adult↗
PubMed1998

Data on the loci LDLR, GYPA, HBGG, D7S8 and GC in a south Polish population.

Allele and genotype frequencies were determined in a sample of 102 inhabitants from South Poland with a commercial PCR based typing kit. No deviations from Hardy-Weinberg expectations were found. The combined power of discrimination for the five loci was 0.994. The systems did not show any allelic association between loci. The polymarker set was validated as useful for paternity testing and individual identification in a Polish population.

Alleles↗
PubMed1995

D1S80 VNTR locus genotypes in population of south Poland; meta-analysis pointer to genetic disequilibrium of human populations.

A highly variable number of tandem repeats (VNTRs) in a human locus D1S80 can prove to be useful for forensic science purposes. As with other genetic polymorphisms, a database of a local population allelic frequencies is needed to ensure that no departure from genetic equilibrium exists. DNA from the locus D1S80 was amplified by polymerase chain reaction (PCR) and analyzed by horizontal PAGE followed by silver staining. Samples from 133 unrelated inhabitants of Southern Poland were examined. The amplified fragment length polymorphism (AMP-FLP) analysis of the D1S80 locus demonstrated 21 alleles and heterozygosity of 0.85%. Out of the 231 possible genotypes, 47 were observed. The results were compared to the published D1S80 population studies and a meta-analysis of the genotype frequencies was performed. The G statistics revealed a deviation from genetic equilibrium in the Spanish population. Replicated goodness of fit tests showed highly significant heterogeneity of genotype distribution between tested populations. Therefore, interpretation of the casework on the basis of D1S80 locus typing may be biased by interpopulation differences.

Adult↗