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Biomedical subjects

V Znojil

Publications and source records attributed to V Znojil.

At least 19 recordsLinked to original sources
PubMed2003

Elevation of extracellular adenosine mobilizes haematopoietic progenitor cells and granulocytes into peripheral blood and enhances the mobilizing effects of granulocyte colony-stimulating factor.

We tested the capabilities of drugs elevating extracellular adenosine and of granulocyte colony-stimulating factor (G-CSF), given alone or in combination, to mobilize haematopoietic progenitor cells for granulocytes and macrophages (GM-CFC) and granulocytes into peripheral blood. Elevation of extracellular adenosine was induced by joint administration of dipyridamole (DP), a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP) serving as an adenosine prodrug. DP + AMP, G-CSF or all these drugs in combination were administered either singly or repeatedly in a 4-d treatment regimen. Elevation of extracellular adenosine was found to mobilize significantly both GM-CFC and granulocytes after both single and repeated administration of DP + AMP. These results show that the elevation of extracellular adenosine presents a potent mechanism for mobilization of GM-CFC and granulocytes into the blood. When the combination of DP + AMP + G-CSF was given under the 4-d regimen, the mobilizing effects of its administration were additive when compared with those of DP + AMP alone or G-CSF alone. The observed ability of the drugs elevating extracellular adenosine to enhance the mobilizing action of G-CSF points out possible practical utilization of the findings presented here. This conclusion is further supported by the results of an additional experiment which indicate that blocking of haemodynamic side effects of drugs elevating extracellular adenosine by noradrenaline does not suppress their mobilizing effects.

Adenosine↗
PubMed2002

Plasminogen-activator-inhibitor-1 promoter polymorphism as a risk factor for adult periodontitis in non-smokers.

Periodontal diseases belong to the most common chronic disorders affecting mankind. Smoking and impaired plasminogen activation with hypercoagulation and fibrinolysis inhibition have been proposed as having a role in predisposition to these diseases. We investigated relationships among adult periodontitis, smoking, and a variation in the deletion/insertion (4G/5G) promoter polymorphism of the plasminogen-activator-inhibitor-1 (PAI-1) gene in 304 Caucasian subjects. An association was detected between the deletion (4G) allele (and 4G/4G genotype) and periodontitis (P = 0.0022, P(corr) < 0.01; P = 0.014, P(corr) < 0.05). A stronger association occurred in non-smokers (P = 0.00021, P(corr) < 0.01; P = 0.0024, P(corr) < 0.05) where the presence of the PAI-1 gene 4G allele appears to be one of the risk factors for periodontitis.

Adult↗
PubMed2002

Prevalence of endothelial nitric oxide synthase gene polymorphisms in patients with atopic asthma.

BACKGROUND: Asthma is a common multifactorial disease, the aetiology of which is attributable to both environmental and genetic factors. The endothelial nitric oxide synthase (NOS3) gene has been implicated in asthma pathogenesis. OBJECTIVE: This study investigated associations of 27 base-pair tandem repeat polymorphism in intron 4 and the Glu298Asp (G894T) variant of the NOS3 gene with atopic asthma in a Czech population. METHODS: Polymerase chain reaction was used to determine the NOS3 genotypes in subjects with atopic asthma (n = 163) and random controls (n = 209). RESULTS: The NOS3 allele or genotype distributions did not differ significantly between the control and asthma groups. However, the common genotype (bb) of the NOS3 polymorphism in intron 4 was found to be significantly associated with total IgE levels (P = 0.006), specific IgE levels for feathers (P = 0.0002) and a positive skin prick test for hay (P = 0.004). In one atopic patient, we identified an additional 27-bp repeat in the NOS3 gene (NOS3c), which occurred in heterozygous combination with the NOS3b allele (NOS3b/c genotype). In addition, we describe a new polymorphism (A5495G) in the NOS3 gene, which was in almost complete linkage disequilibrium with the NOS3 repeat polymorphism in intron 4. The Glu298Asp variant was not associated with asthma and/or related atopic phenotypes in our study. CONCLUSION: Neither the NOS3 'b' allele nor the NOS3 'b/b' genotype showed any general association with atopic asthma, but they were associated with atopy-related phenotypes. We conclude that the NOS3 gene polymorphisms may act as disease modifiers in atopic asthma phenotype in our population.

Adolescent↗
PubMed2001

Methylenetetrahydrofolate reductase polymorphism, type II diabetes mellitus, coronary artery disease, and essential hypertension in the Czech population.

Increased plasma concentrations of homocysteine have been found in patients with coronary artery disease (CAD) and essential hypertension (EH) and in patients with diabetic complications. The 677C/T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism is related to the MTHFR enzyme activity and to the plasma homocysteine concentration. This study was designed to investigate an association of this polymorphism with CAD, EH, and type II diabetes mellitus in the Czech population. The MTHFR genotypes were assessed by the polymerase chain reaction-based methodology in a sample of 1199 unrelated Caucasian subjects with CAD, EH, type II diabetes, or a combination of these diseases, and in healthy subjects. Allele frequencies of the MTHFR polymorphism differed considerably between women with and without type II diabetes mellitus (P = 0.00069), with a higher frequency of the C allele in the diabetic women. In addition, the MTHFR T allele frequency was significantly higher in normotensive subjects with CAD compared with normotensive subjects without this disease (P = 0.020). Both associations were confirmed by multiple logistic regressions. In conclusion, while the C allele of the 677C/T MTHFR polymorphism is associated with type II diabetes mellitus in women, the T allele is associated with CAD only in normotensive subjects of Czech origin.

Aged↗
PubMed2001

The C766T low-density lipoprotein receptor related protein polymorphism and coronary artery disease, plasma lipoproteins, and longevity in the Czech population.

Low-density lipoprotein receptor related protein (LRP) is a multifunctional endocytic receptor involved in various biological processes including the regulation of the coagulation-fibrinolysis balance, the lipoprotein metabolism, and cellular migration, all of which relate to the development of atherosclerosis. Polymorphisms affecting the function or expression of LRP may thus influence the individual risk of atherosclerosis development. This study investigated the association between the C766T LRP polymorphism, coronary artery disease (CAD), and plasma lipoprotein levels in a large sample of Caucasian subjects of Czech nationality. In addition, the 4G/5G promoter polymorphism of the gene coding for plasminogen activator inhibitor 1 (PAI-1), the known ligand of LRP with strong antifibrinolytic potential, was ascertained to investigate its possible association with CAD. Both polymorphisms were studied using polymerase chain reaction analysis in 654 patients with angiographically confirmed CAD and in 525 controls. No statistically significant differences in allele frequencies of the polymorphisms studied were detected between patients and controls, even when men, women, hypertonic, and type II diabetic subjects were compared separately. However, the frequency of the T allele of the LRP polymorphism was significantly higher in patients than controls when only subjects with the 5G/5G PAI-1 genotype were analyzed. In addition, the T LRP allele frequency was significantly lower in subjects aged 60 years or over than in those who were younger in both groups. No significant association was observed between the LRP or PAI-1 polymorphisms and plasma lipoprotein levels in the CAD patients. Our results demonstrate that the T allele of the C766T LRP polymorphism is negatively related to longevity, and that it increases the risk of CAD development in subjects with the 5G/5G PAI-1 genotype.

Aged↗
PubMed2001

Relationship of age and the body mass index to selected hypertensive complications in pregnancy.

OBJECTIVES: Older maternal age is considered to be a risk factor for a number of pregnancy-associated pathologies. Average weight increases with age. The aim of this study is to assess the effects of maternal age on selected disorders of pregnancy independently from the influence of maternal weight. METHODS: The retrospective study included 910 women. The following parameters were evaluated: age, p-BMI (body mass index before pregnancy), hypertension, severe hypertension, pre-eclampsia, proteinuria, severe proteinuria, thromboembolic diseases, pregnancy duration and fetal growth restriction. RESULTS: The correlation between the p-BMI and age and BMI was confirmed (P<0.001). After filtering away the mutual influence of age and p-BMI applying logistic regression we proved a statistically significant effect of p-BMI on the incidence of hypertension, severe hypertension, proteinuria and pre-eclampsia (P<0.001). The maternal age (cleared of the p-BMI) effects only hypertension. CONCLUSIONS: Age alone proved to be a risk factor for severe hypertension or severe hypertension of the pregnant subjects. Increased risk for proteinuria, hypertension and pre-eclampsia is directly associated with p-BMI of the pregnant women, and only indirectly with their age.

Adult↗
PubMed2001

Drugs elevating extracellular adenosine enhance cell cycling of hematopoietic progenitor cells as inferred from the cytotoxic effects of 5-fluorouracil.

OBJECTIVE: Our previous studies showed that the combined administration of drugs elevating extracellular adenosine, i.e., dipyridamole and adenosine monophosphate (AMP), enhanced hematopoiesis in normal mice and increased hematopoietic recovery in irradiated mice. In the present study, we have examined the possibility that these effects are due to the adenosine-induced cycling of the hematopoietic progenitor cells. MATERIALS AND METHODS: Experiments were performed under in vivo conditions using B10CBAF1 mice. The cycling status of hematopoietic progenitor cells (CFU-S(day 10), CFC-GM, and BFU-E) was determined on the basis of their sensitivity to 5-fluorouracil (5-FU), a cycle-specific cytotoxic agent. RESULTS: Pretreatment of mice with dipyridamole + AMP enhanced the cytotoxic effects of a single bolus of 5-FU at a dose of 3 mg per mouse. Sensitizing effects of drugs occurred after a delay of several hours and attained a maximum of about 40-60% reduction of the progenitor cells surviving after 5-FU alone. The period of maximum sensitization of CFU-S by the combination of dipyridamole + AMP was shifted to later time intervals as compared with the effects on CFC-GM and BFU-E. Pretreatment of mice with the drugs also aggravated the 5-FU-induced lethality. Reduction of survival was found in mice exposed to two cycles of 3 mg of 5-FU following the pretreatment with dipyridamole + AMP at a time period characterized by the highest fraction of CFU-S in the S phase. CONCLUSIONS: The results suggest that adenosine receptor signaling, induced by the administration of drugs elevating extracellular adenosine, enhances cycling of the hematopoietic progenitor cells. These effects might have pharmacological implications in the therapy of blood disorders.

Adenosine↗
PubMed2001

The interaction of the polymorphisms in transporter of antigen peptides (TAP) and lymphotoxin alpha (LT-alpha) genes and atopic diseases in the Czech population.

BACKGROUND: Transporter antigen peptide gene (TAP) products are involved in antigen processing. These genes, inducible by interferon gamma, as well as lymphotoxin alpha (LT-alpha), are located in the HLA region. Their involvement in immune response regulation makes them candidate atopy susceptibility genes. OBJECTIVE: This study investigates a possible association between previously identified polymorphisms within the TAP-1 and LT-alpha genes and clinically manifested atopic diseases in the Czech population. METHODS: Caucasian subjects of Czech nationality (n = 427) were included in our study. We examined 184 healthy controls and 243 patients with histories of atopic asthma, allergic rhinitis and atopic dermatitis or their combinations. We used the amplification refractory mutation system polymerase chain reaction to determine TAP-1 gene polymorphisms. LT-alpha genotypes were determined by PCR and restriction analysis by NcoI. RESULTS: No significant differences were found in allele or genotype frequencies of the LT-alpha gene, as well as in polymorphisms for Val-->Ile at codon 333 and Gly-->Asp at codon 637 in the TAP-1 gene between controls and patients. However, analysis of the concurrence of the double genotypes of the TAP-1 polymorphism at codon 333 and the LT-alpha genes showed differences between controls and atopic patients (P < 0.02). CONCLUSION: Several reports have indicated that different HLA products and genes may be risk factors for or protective factors against the development of atopy. We report no association between polymorphisms in the LT-alpha and TAP-1 genes alone and atopic diseases in the central Europe Caucasian (Czech) population, but there was an interesting interaction between the TAP333 and LT-alpha polymorphisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Polymorphisms 1704G/T and 2184A/G in the RAGE gene are associated with antioxidant status.

The formation of advanced glycation end products (AGEs) and oxidative stress are supposed to play an important role in the development of diabetic late complications. AGEs can bind to several binding sites including receptor of advanced glycation end products (RAGE). AGE-RAGE interaction results in free radical generation. The aim of the present study was to investigate the impact of previously described polymorphisms in the RAGE gene (G82S, 1704G/T, 2184A/G, and 2245G/A) on the glycoxidation status in non-insulin-dependent diabetes mellitus (NIDDM). A total of 371 unrelated caucasian subjects were enrolled in the study. The NIDDM group consisted of 202 subjects, and the presence of late diabetic complications in 5 particular localizations was expressed as an index (I(compl)). The nondiabetic group included 169 subjects. Glycated hemoglobin (HbA(1c)), glycated stratum corneum proteins (Amadori, AGE), total carotenoids, alpha- and beta -carotene, gamma-tocopherol, lutein, lycopene, and alpha-tocopherol were measured in each subject. Statistically significant differences in allele frequencies between the NIDDM and the nondiabetic groups were observed for the G82S and 2245G/A polymorphisms (P =.047 and .032, respectively). HbA(1c), Amadori, and AGE did not reveal any significant association with any of the polymorphisms analyzed. However, significant differences between subjects bearing "wild-type majority" genotypes 1704GG+2184AA and subjects with "mutated" genotypes were found for total carotenoids (P =.001), alpha-carotene (P =.046), beta-carotene (P =.028), lutein (P =.001), lycopene (P =.006), and alpha-tocopherol (P =.047). I(compl) significantly correlated with the plasma levels of all antioxidants (all P <.01), while no correlation of I(compl) with glycation variables was observed. The newly identified intron polymorphisms in the RAGE gene were proved to be associated with the antioxidant status in NIDDM subjects. The extent of diabetic vascular disease is related to the plasma levels of antioxidants.

Alleles↗
PubMed2001

Interactions of lymphotoxin alpha (TNF-beta), angiotensin-converting enzyme (ACE), and endothelin-1 (ET-1) gene polymorphisms in adult periodontitis.

BACKGROUND: Adult periodontitis is a complex multifactorial disease whose etiology is not well defined. To investigate whether the genes encoded within the HLA class III region may confer susceptibility to periodontitis, polymorphisms in the ET-1 and TNF-beta genes were analyzed together with the I/D polymorphism of the ACE gene. METHODS: We determined allele and genotype frequencies of the NcoI bi-allelic polymorphism of the TNF-beta gene, the I/D (insertion/deletion) polymorphism of the ACE gene, and the TaqI polymorphism of the ET-1 gene in 63 Caucasian patients with adult periodontitis and 95 orally healthy controls. RESULTS: We found a significant difference in a 3 locus combination of genotypes between patients and controls (P<0.05). In the next analyses, no significant differences were found in allele frequencies of single genes, but we did find a significant difference in the genotype distribution between cases and controls for TNF-beta (P<0.03). Differences were also observed for 2 locus combinations of ACE and TNF-beta genotypes (P<0.03), and the ET-1 and TNF-beta (P<0.05) genes. Evidence of deviation from Hardy-Weinberg equilibrium was observed in the periodontitis group for TNF-beta, with an absence of the B1B1 homozygotes in patients. CONCLUSIONS: This study is of an exploratory nature. Considering the number of significant results, however, at least a part of the observed associations may obviously be real and our findings suggest that interactions of the TNF-beta, ET-1, and ACE genes may be involved in susceptibility to adult periodontitis.

Adult↗
PubMed2001

Distribution of the receptor for advanced glycation end products gene polymorphisms in patients with chronic periodontitis: a preliminary study.

BACKGROUND: Periodontal diseases are viewed today as multifactorial problems initiated and sustained by bacteria but significantly modified by the body's response to bacterial plaque. A recent study suggested that receptor for advanced glycation end products (RAGE) could be involved in the pathophysiology of periodontitis. The aim of this study was to investigate a possible association of 3 common polymorphisms in the RAGE gene with chronic periodontitis. METHODS: We studied 101 Caucasian patients with chronic periodontitis together with 162 orally healthy subjects. Three polymorphisms, one in intron 7 (1704G/T), second in intron 8 (2184A/G), and the third in exon 3 (G82S) of the RAGE gene, were investigated by polymerase chain reaction methods (PCR) with subsequent enzymatic restriction with Bfal, BsmFI, or Alu Il, respectively. RESULTS: A statistically significant difference in allele frequencies between patients and the reference group was found for intron variant 1704G/T (P= 0.02, Pcorr >0.05). There was no significant difference in genotype or allele frequency distributions between groups for intron variant 2184A/G or for the exon variant exchanging amino acid Gly for Ser at position 82 (G82S). CONCLUSIONS: We can speculate that susceptibility to the development of chronic periodontitis could be influenced by the 1704G/T polymorphism of the RAGE gene, independently of diabetes.

Adult↗
PubMed2001

Combination of drugs elevating extracellular adenosine with granulocyte colony-stimulating factor promotes granulopoietic recovery in the murine bone marrow after 5-fluorouracil treatment.

Combined administration of drugs elevating extracellular adenosine, namely dipyridamole and adenosine monophosphate, together with granulocyte colony-stimulating factor was shown to enhance granulopoietic recovery in the bone marrow of mice treated with 5-fluorouracil. Enhanced regeneration was found both at the level of hematopoietic progenitor cells for granulocytes and macrophages and in the compartment of morphologically recognizable granulocyte precursors. The results might have positive clinical impact. The adjunct use of drugs elevating extracellular adenosine might reduce the cost expenditure of therapy with granulocyte colony-stimulating factor.

Adenosine↗
PubMed2001

[Polymorphism of angiotensin converting enzyme (ACE) and TNF-beta genes in men with disorders of spermatogenesis--pilot study].

INTRODUCTION: The presence of components of the renin angiotensin system and tumour necrosis factor in a male reproductive tract supports the hypothesis that these substances may influence reproductive functions. It was proved that angiotensin II as a product of ACE has influence on sperm capacitation and motility. TNF-beta is released from T-lymphocytes and has the regulatory effect on steroidogenesis and spermatogenesis. Aberrations of these agents can result in infertility. OBJECTIVE: The aim of this study was to determine the allele frequency of ACE and TNF-beta genes in men with pathological sperm count and men with normal fertility. We examined the insertion/deletion (I/D) ACE and B1/B2 TNF-beta gene polymorphic alleles and analyzed their frequency in patients and fertile men. DESIGN: A pilot study. SETTING: 1st Clinic of Gynaecology and Obstetrics and Institute of Pathologic Physiology, Masaryk University, Brno, CR. MATERIAL AND METHODS: The genomic DNA was isolated from peripheral blood leukocytes by a standard method according to Sambrook in a group of 46 patients (33.4 +/- 7.2 years) with pathological sperm count (9 azoospermia, 21 severe oligoasthenospermia, 16 moderate oligoasthenospermia) and in a control group of 88 healthy men (31.2 +/- 9.3 years) with normal fertility. Polymerase chain reaction (PCR) was used for genom analysis. The method according to Rigat was used for the I/D ACE polymorphism. B1/B2 TNF-beta genotype of each patient was determined after Nco I digestion of the amplified product and subsequent agrose gel electrophoresis. Fisher's exact test and chi square test were used for statistical analysis. RESULTS: In the study we found these differences of allel frequency and their combination: 1. Combinations of the genotype II (ACE) + B1B2 (TNF-beta) and genotype II (ACE) + B2B2 (TNF-beta) were less frequent in patients (8.7%) than in fertile men (28.4%), this difference was statistically significant (p = 0.021). 2. Allele B1 (TNF-beta) was more frequent among patients (40.2%) than in the control group (29.5%), this difference was near to the point of statistical significance (p = 0.05). 3. Allele D (ACE) frequency was higher in men with pathological sperm count (52.2%) than in fertile men (44.9%), this difference was not statistically significant (p = 0.15). CONCLUSION: The study has found different allele frequency of I/D ACE and B1/B2 TNF-beta genes polymorphism in men with pathological sperm count compared to men with normal fertility. These results could contribute to elucidate the genetic background of a male infertility.

Adult↗
PubMed2001

Variants of endothelin-1 gene in atopic diseases.

BACKGROUND: Several studies suggest that the vasoactive peptide endothelin-1 (ET-1) could be involved in the pathophysiology of atopic asthma and allergic rhinitis. However, a possible involvement of polymorphisms of the corresponding gene in the origin of these conditions has so far not been subjected to a more comprehensive study. OBJECTIVE: This study investigates a possible association of two common polymorphisms in the ET-1 gene (TaqI in intron4 and BsiYI in position 138) with clinically manifested atopic diseases. The genetic linkage of these polymorphisms with the underlying phenotypes of asthma or parameters of atopy including total IgE level was examined, too. METHODS: The study included 456 subjects-270 Czech patients (Caucasians, Central Europe) with clinically manifested atopic diseases and 186 unrelated referent subjects with negative familial history of asthma/atopy. ET-1 genotypes were determined by PCR and restriction analysis by TaqI and BsiYI, respectively. RESULTS: No significant differences were found for the two polymorphisms between atopic patients and healthy subjects, or between subselected asthmatic patients and controls. However, the insertion exonic variant of ET-1 gene showed a significant association with signs of atopy, especially with total serum IgE levels (total IgE levels < or = 150 IU/ml turned out to be associated with DD genotypes, total IgE > 150 IU/ml with II and ID genotypes [OR = 3.76 (95% CI: 1.52-9.34), p = 0.003, Pc = 0.0061). CONCLUSIONS: These findings suggest that ET-1 may participate in the pathogenesis of high total serum IgE level in clinically manifested atopic diseases in our population.

Adult↗
PubMed2000

Single effects of apolipoprotein B, (a), and E polymorphisms and interaction between plasminogen activator inhibitor-1 and apolipoprotein(a) genotypes and the risk of coronary artery disease in Czech male caucasians.

To evaluate whether polymorphisms in genes whose products are involved in lipid metabolism and fibrinolysis alter the risk of coronary artery disease (CAD), allele frequencies of four genetic polymorphisms were ascertained by PCR-based methods in 175 Czech male patients with coronary artery disease and in 222 Czech men with no symptoms of CAD. The following polymorphisms were studied: apolipoprotein B (apo B) signal peptide insertion/deletion polymorphism, 5' apolipoprotein(a) [apo(a)] TTTTA repeat polymorphism, apolipoprotein E (apo E) varepsilon2, varepsilon3, varepsilon4 polymorphism, and plasminogen activator inhibitor-1 (PAI-1) 4G/5G promoter polymorphism. Apo B and apo(a) allele frequencies differed significantly between the CAD and the control groups (P<0.01 each), with higher frequencies of apo B deletion and apo(a) shorter repeat alleles in the CAD group. We did not observe any differences in allele frequencies of either PAI-1 or apo E polymorphisms but the genotype frequencies of apo E were slightly different between the two groups (P<0.05). In addition, we observed a gene-gene interaction between the PAI-1 and apo(a) polymorphisms with respect to the risk of CAD. None of the polymorphisms studied were associated with the severity of CAD or a history of myocardial infarction. Our findings support the idea that several polymorphisms in apolipoprotein genes may by themselves and/or in interaction with other polymorphisms contribute to risk factors for CAD in men.

Adult↗