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Biomedical subjects

V Znojil

Publications and source records attributed to V Znojil.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2000

Influence of the joint treatment with granulocyte colony-stimulating factor and drugs elevating extracellular adenosine on erythropoietic recovery following 5-fluorouracil-induced haematotoxicity in mice.

The presented data address the problem of pleiotropic effects of granulocyte colony-stimulating factor (G-CSF) and suggest the ability of drugs increasing the level of extracellular adenosine to activate erythropoiesis when given jointly with G-CSF. To demonstrate these interactions, the effects of the drugs on the recovery from erythropoietic damage induced in mice by a single dose of 5-fluorouracil (5-FU) were investigated. Elevation of extracellular adenosine and thus activation of adenosine receptors was induced by joint administration of dipyridamole (DP), a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The drugs were injected in a 4-d treatment regimen starting 2 h after 5-FU injection. Both DP+AMP and G-CSF alone induced only weak effects. However, the combination of the three drugs produced significant elevation of erythrocytes in the peripheral blood which pertained in the posttreatment period. Stimulation of proliferation of erythroid progenitor cells (BFU-E) in femoral bone marrow and increased levels of reticulocytes in the peripheral blood were observed in the course of the 4-d treatment regimen. In addition, significantly decreased mean cell haemoglobin accompanying the elevated numbers of erythrocytes in the combination-treated mice was found. This effect could be interpreted as the result of a sublethal 5-FU-induced damage to erythroid progenitor and precursor cells forced to proliferate intensively by the combination therapy. The observed additivity and synergism of G-CSF with elevated extracellular adenosine in terms of erythropoiesis is an interesting finding with potential implications in clinical practice.

Adenosine↗
PubMed2000

Radioprotective action of extracellular adenosine on bone marrow cells in mice exposed to gamma rays as assayed by the micronucleus test.

The frequency of micronucleated polychromatic erythrocytes (PCEs) in mouse bone marrow was assessed after administration of dipyridamole and/or adenosine monophosphate (AMP) to nonirradiated mice or to mice irradiated 15 min later with a sublethal dose of 6.5 Gy gamma rays. In nonirradiated mice, the administration of the drugs increased the frequency of micronucleated PCEs significantly (by 108%). In contrast, in irradiated mice, the number of radiation-induced micronucleated PCEs was significantly decreased if the mice had been pretreated with dipyridamole or AMP alone (by 24% after administration of each of the compounds) and in particular after administration of the drugs in combination (by 36%).

Adenosine Monophosphate↗
PubMed1999

Lateralization of the P22/N30 precentral cortical component of the median nerve somatosensory evoked potentials is different in patients with a tonic or tremulous form of cervical dystonia.

Somatosensory evoked potentials (SEPs) of the median nerve were recorded in 40 patients with the tonic and tremulous form of torticollis and in 40 healthy volunteers. Polymyographic recordings of the activity of cervical muscles were performed in all patients with cervical dystonia to determine the dystonic and antagonistic muscles. Patient SEPs were recorded during abnormal head movement. SEPs in 20 healthy volunteers were recorded with the head in the middle position. SEPs in another 20 healthy volunteers were recorded with the head rotated 60 degrees to the right. The mean peak-to-peak amplitude values of the precentral P22/N30 and the postcentral N20/P25 complexes and their mean side-to-side ratios were calculated in the F3 (F4), C3' (C4'), and C3+ (C4+) electrode positions in all four groups. In patients with the tonic form of torticollis (group I), an apparent mean P22/N30 amplitude increase was found above the hemisphere contralateral to the direction of head deviation in both precentral electrode positions, F3(4) and C3(4)'. A statistically significant difference was observed between group I and other patient and control groups. In patients with the tremulous form of torticollis (group II), an increase in the mean P22/N30 amplitude was found above both hemispheres in both precentral electrode positions F3(4) and C3(4)'; a significant difference was found between group II and both control groups. Lateralization of the P22/N30 component was found only in patients with the tonic form of torticollis. The mean side-to-side ratio of the precentral P22/N30 component amplitude was significantly different when group I was compared with either group II or control groups. No significant difference between group II and either control group was found. No significant abnormalities in the postcentral N20/P25 component were found in either the dystonic patients or in healthy control subjects. These results might indicate a different pattern of cortex excitability in patients with tonic versus tremulous forms of torticollis and therefore may implicate different underlying pathophysiological mechanisms in these two forms of disorder.

Adult↗
PubMed1999

Association of 3 gene polymorphisms with atopic diseases.

BACKGROUND: Various peptidases, including angiotensin-converting enzyme (ACE), inactivate some inflammatory peptides that are considered to influence the pathogenesis of atopic diseases. This enzyme is also involved in the conversion or activation of 2 bronchoconstriction mediators: angiotensin II from angiotensinogen and endothelin (ET), respectively. OBJECTIVE: We tested a hypothesis that asthma or other atopic diseases are associated with insertion/deletion ACE, M235T angiotensinogen, and TaqI ET-1 gene polymorphisms. METHODS: A case-control approach was used in the study. Healthy subjects (141 persons) were used as control subjects, and 231 patients with histories of atopic asthma, allergic rhinitis, atopic dermatitis, or a combination thereof were studied. ACE genotype was determined by PCR, angiotensinogen M235T and ET-1 by PCR, and restriction analysis by AspI and TaqI, respectively. RESULTS: We found the significant association of the insertion/deletion polymorphism of the ACE, as well as that of M235T polymorphism of the angiotensinogen genes, with the group of patients with atopic diseases ( P =.0025 and P =.0204, respectively). No difference was proved for the intron 4 (position 8000) polymorphism in the ET-1 gene when comparing the atopic patients with the control group (P =.1774). A significant difference was found between groups of patients with both asthma and rhinitis and patients without both respiratory atopic diseases (P =.0033). CONCLUSION: It follows that the examined polymorphisms in the genes for ACE, angiotensinogen, and ET-1 could participate in the etiopathogenesis of atopic diseases.

Adolescent↗
PubMed1999

Pretreatment with granulocyte colony-stimulating factor reduces myelopoiesis in irradiated mice.

The purpose of this study was to investigate effects of the treatment prior to irradiation with granulocyte colony-stimulating factor (G-CSF) on hematopoiesis in B10CBAF1 mice exposed to a sublethal dose of 6.5 Gy of 60Co gamma radiation. G-CSF was administered in a 4-day regimen (3 microg/day); irradiation followed 3 h after the last injection of G-CSF. Such a treatment was found to stimulate granulopoiesis, as shown by increased counts of granulocyte-macrophage progenitor cells (GM-CFC) and of granulocytic cells in the femoral marrow and spleen at the time of irradiation. However, postirradiation counts of GM-CFC and granulocytic cells in the marrow of mice pretreated with G-CSF were reduced up to day 18 after irradiation. Interestingly, the D0 values for marrow GM-CFC determined 1 h after in vivo irradiation were 1.98 Gy for controls and 2.47 Gy for mice pretreated with G-CSF, indicating a decreased radiosensitivity of these cells after drug treatment. The inhibitory effects of the pretreatment with G-CSF on the postirradiation granulopoiesis could be attributed to the phenomenon of "rebound quiescence" which can occur after cessation of the treatment with growth factors. Postirradiation recovery of erythropoiesis in the spleen of mice pretreated with G-CSF exhibited a dramatic increase and compensated for the decreased erythropoiesis in the marrow at the time of irradiation. This complexity of the hematopoietic response should be taken into account when administering G-CSF in preirradiation regimens.

Animals↗
PubMed1999

Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine act additively to enhance the hemopoietic spleen colony formation in irradiated mice.

The effects of combined administration of two drugs elevating extracellular adenosine, namely dipyridamole (DP) and adenosine monophosphate (AMP), and granulocyte colony-stimulating factor (G-CSF) on hemopoietic stem cells in vivo were investigated. The experiments were performed on mice using the endogenous spleen colony formation in gamma-irradiated animals as an endpoint. The results have shown that DP and AMP act additively with G-CSF to enhance spleen colony formation and thus the erythroid repopulation of the spleen. These findings indicate that the signaling pathways of G-CSF and drugs elevating extracellular adenosine can interact at the level of primitive hemopoietic stem cells. The enhancement of hemopoiesis-stimulating effects of G-CSF by DP and AMP, which are low-priced and clinically available drugs, could improve the cost-effectiveness of the therapy with G-CSF.

Adenosine↗