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Biomedical subjects

V Znojil

Publications and source records attributed to V Znojil.

At least 55 records · Page 3Linked to original sources
PubMed1999

Association analysis of 24-h blood pressure records with I/D ACE gene polymorphism and ABO blood group system.

The purpose of this study was to analyze the association between 24-h blood pressure parameters, insertion/deletion polymorphism of the angiotensin I converting enzyme gene and the ABO blood group system in a sample of the general Czech population. Fourteen parameters describing the 24-h blood pressure readings were obtained by analyzing blood pressure records in 243 volunteers, 119 men and 124 women. These parameters were adjusted for sex and body mass index (BMI) by means of multiple regression test. All subjects were genotyped for the insertion/deletion polymorphism of angiotensin I converting enzyme (I/D ACE) gene and routinely examined for the blood group phenotype in the ABO system. An association was found between the interaction of I/D ACE gene polymorphism and ABO blood group system on the one hand and mean values of systolic (p=0.016) or mean arterial (p=0.027) blood pressures and the phase shift of 24-h BP rhythm (p=0.036) on the other hand. Among three I/D ACE variants the DD genotype was associated with the highest values of mean blood pressure in blood group A and AB carriers. The same genotype was associated with the lowest blood pressures in blood group B and O carriers. In subjects with the DD genotype, the earlier daily position of the maximum of 24-h BP rhythm was found in blood group B, AB and O carriers. On the contrary, blood group A was associated with the latest position of maximum of the 24-h BP rhythm in the DD genotypes.

ABO Blood-Group System↗
PubMed1999

[Emergency ERCP and acute biliary pancreatitis].

In the period from 1992 to 1997, a total of 130 urgent therapeutic ERCPs were performed at the 2nd Department of Surgery of the Faculty of Medicine in Brno. The examination was indicated because of acute pancreatitis, acute septic cholangitis, and papillary ileus. Fifty nine patients with proven acute biliary pancreatitis and successful endoscopic papillosphincterotomy were followed up subsequently. Information on 44 patients could be retrieved (75%). The results were evaluated and compared with a group of patients treated for acute biliary pancreatitis at the 2nd Department of Surgery in Brno before introduction of urgent therapeutic ERCPs. In addition to lower mortality, in the group of patients who underwent endoscopy a decrease in the percentage of surgical revisions needed was reached, and in the group with conservative treatment, statistically significant reduction of hospitalization was duration achieved. (Tab. 3, Fig. 1, Ref. 14.)

Acute Disease↗
PubMed1998

Change in lateralization of the P22/N30 cortical component of median nerve somatosensory evoked potentials in patients with cervical dystonia after successful treatment with botulinum toxin A.

The precentral P22/N30 cortical component of the median nerve somatosensory evoked potentials (SEPs) was recorded in 16 patients (11 women and five men) suffering from cervical dystonia before and after botulinum toxin therapy. Cervical dystonia was diagnosed as idiopathic in all patients: 13 patients suffered from right-sided torticollis, and three suffered from left-sided torticollis. The amplitude of the P22/N30 component and the side-to-side ratio of amplitude values were measured. Normal values were obtained by acquiring measurements in two groups of healthy volunteers (n1 = 20 and n2 = 20). The recordings in the first control group were done with the patient's head in a normal position, whereas, in the second control group, the patient kept the head intentionally rotated 60 degrees to the right. Patients were treated with local injections of botulinum toxin A (BTX-A). The mean duration of treatment was 8.3 months, and the mean total amount of BTX injected was 295 U. The P22/N30 precentral component was repeatedly recorded in patients after head posture had been corrected to the normal plane by BTX-A treatment. The recordings showed that the amplitude of the P22/N30 precentral component recorded contralaterally to the direction of head deviation was significantly higher in patients before treatment than after treatment. Contralateral pretreatment amplitudes were also significantly higher (p < 0.01 and p < 0.05, respectively) than amplitudes in both groups of healthy volunteers. The mean side-to-side ratio of precentral P22/N30 component amplitudes was significantly higher in patients before treatment compared with after treatment and also compared with both control groups. These changes in dystonic patients probably reflect the direction of head rotation, the muscle pattern of torticollis, and the change in force of dystonic contraction after the treatment. The changes presumably could be the result of higher excitability of the precentral cortex contralateral to head rotation in patients with cervical dystonia and its change after successful BTX-A treatment.

Adult↗
PubMed1998

Angiotensin I-converting enzyme and angiotensinogen gene interaction and prediction of essential hypertension.

To prove whether the interaction between insertion/deletion (I/D) angiotensin I converting enzyme (ACE) and M235T angiotensinogen (AGT) gene polymorphic alleles could contribute to causing essential hypertension, we examined subjects from the Czech Republic (365 Caucasians total; 202 normotensives and 163 hypertensives). Subjects were genotyped for insertion/deletion polymorphism of ACE (I/D ACE, intron 16) and for M235T polymorphism of angiotensinogen gene (AGT, exon 2) by means of the polymerase chain reaction (PCR) method. The case-control approach was used. Fisher's exact test followed by Holmes's test to overcome the problem of multiple comparisons were used for the statistical analysis of data. No association of single gene allelic variants with essential hypertension was found in our population. Having compared only double homozygote combinations, the association of the DDMM genotype with essential hypertension was proven (P = 0.0081). To the contrary, IITT (P = 0.0086) was found more frequently in normotensive subjects. We conclude that the interaction of the I/D ACE and M235T AGT polymorphic alleles can contribute to essential hypertension, despite the absence of single gene associations with the condition.

Adult↗
PubMed1998

Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice.

The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of 60Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multilineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive states induced by radiation exposure.

Adenosine↗
PubMed1997

Serum IgD levels in children under investigation for and with defined immunodeficiency.

BACKGROUND: The function and regulation of circulating IgD are unclear. Serum IgD levels were increased in a wide range of immunological diseases but these associations did not give a clue to the regulation of serum IgD production. METHODS: Serum IgD levels in 131 children with various non-HIV-related immunodeficiency diseases were investigated to examine their relationship with immunoglobulin or antibody production and activation of the immune system. Data from a group of 109 nonimmunodeficient children were also available for comparison. RESULTS: There was a bimodal distribution of serum IgD levels. In 87 patients IgD levels fell below the limit of detection of 5 IU/ml, while the remainder showed an approximately normal distribution skewed to the right after log transformation. The proportion of children with undetectable IgD levels (< 5 IU/ml) was significantly increased in immunodeficient children (87/131 vs. 28/109, p < 0.001). No difference in the occurrence of immunoglobulin or antibody deficiencies was demonstrated in immunodeficient children with detectable and nondetectable IgD levels. There was a positive correlation of serum IgD with age, serum IgA and IgE, white blood count and CD4+CD25+ lymphocytes but not with other immunoglobulin isotypes or immune activation markers. CONCLUSION: Determination of serum IgD levels did not seem to be of particular clinical benefit in the investigation of HIV-negative immunodeficient children and serum IgD levels were not associated with the general picture of immune activation. Observed distribution patterns and associations may have implications for the regulation of serum IgD production.

Age Factors↗
PubMed1997

Enhancement of haemopoietic spleen colony formation by drugs elevating extracellular adenosine: effects of repeated in vivo treatment.

The potential role of adenosine receptor signalling in the amplification of haemopoietic stem cells in vivo was investigated. Elevation of extracellular adenosine in mice was induced by the joint administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate, an adenosine prodrug. The response of haemopoietic stem cells to the drug treatment was measured by endogenous spleen colony-forming assay in sublethally gamma-irradiated animals. The combination of drugs was administered before irradiation either singly or repeatedly at 24 h intervals. The results demonstrated the possibility of enhancing the spleen colony formation by the drug treatment. The highest stimulatory effect on spleen colony counts and on the colony sizes occurred after 3-4 injections of the drugs. Higher spleen colony responses were observed under injection regimens terminated 3 h before irradiation, as compared to those terminated 24 h before the radiation exposure. The results are interpreted as an evidence of the expansion of the stem cell pool. A tolerance to this stimulatory action developed after more than 3 injections of the drugs.

Adenosine↗
PubMed1996

Angiotensin I-converting enzyme (ACE) polymorphism and ABO blood groups as factors codetermining plasma ACE activity.

The activity of serum angiotensin I-converting enzyme (ACE) was measured in 197 unrelated healthy Caucasian subjects. Plasma ACE activity was correlated with sex, ABO blood groups, and ACE insertion/deletion (I/D) polymorphism. Marked differences in plasma ACE activity levels were observed both among the blood groups and among ACE phenotypes. The corresponding ACE activities were as follows: blood group A, 19.45+/-0.96 (mean+/-SE); O, 20.74+/-1.58; B, 26.17+/-1.40; AB, 24.77+/-1.93 (U/mL: F=4.173; p=0.006983). With ACE genotypes: II, 16.96+/-1.33; ID, 24.25+/-1.05; DD, 27.14+/-1.20 (U/mL; F=6.359; p=0.002165). No difference was observed between men and women. The I/D polymorphism and the ABO system turned out to be two independent (additive) factors influencing plasma ACE activity. Together, they are responsible for 9.56% of the phenotypic variability of ACE. We discuss the role of the ABO system in the known effects of glycosylation of proteins.

ABO Blood-Group System↗
PubMed1996

Morphometric characteristics of cardiac hypertrophy induced by long-term inhibition of NO synthase.

Morphometry of cardiomyocytes and capillary domains in the left ventricle myocardium was performed in control rats and in rats treated with nitro-L-arginine methyl ester 50 mg/kg/day p.o. for a period of 8 weeks. The myocardial hypertrophy accompanying the NO-deficient hypertension induced by chronic inhibition of NO synthase is characterized by an increase in thickness of myocardial fibres and by relative rarefaction of the capillary bed, e.g. an alteration in myocardial structure which is typical for pressure overload hypertrophy.

Animals↗
PubMed1995

Synergistic effect of granulocyte colony-stimulating factor and drugs elevating extracellular adenosine on neutrophil production in mice.

Experimental evidence suggests that the activation of purinoceptors by extracellular adenosine can modulate proliferation and/or differentiation of hematopoietic cells. The present study was undertaken to investigate the potential interactions of this system of intercellular signaling with the effects of granulocyte colony-stimulating factor (G-CSF) on granulopoiesis in vivo. Elevation of extracellular adenosine in normal mice was induced by the joined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole, AMP, and G-CSF, administered either alone or in combinations, were evaluated. The agents were injected to mice in a 4-day regimen, and the hematologic endpoints were determined 24 hours after the completion of the treatment. It was shown that the effects of G-CSF, ie, increases in peripheral blood neutrophils, granulocyte-macrophage progenitor cells (GM-CFC), and morphologically determined granulocytic cells in femoral marrow and a decrease in the marrow erythroid cells, can be enhanced by the combination of dipyridamole plus AMP administered 30 minutes before G-CSF. Furthermore, it was ascertained that the stimulatory action of dipyridamole plus AMP was expressed particularly at lower doses of G-CSF (1.5, 3, and 4.5 micrograms/d). At higher doses of G-CSF (6 and 9 micrograms/d), the interactions were no more evident. When combining dipyridamole, AMP, and 3 micrograms of G-CSF, peripheral neutrophils increased approximately 3.9- to 4.5-fold compared with an approximate 2.2-fold increase induced by G-CSF alone. The results indicate the possible therapeutic potential of combination therapy with G-CSF and drugs increasing extracellular adenosine.

Adenosine↗
PubMed1995

Radioprotection of mouse hemopoiesis by dipyridamole and adenosine monophosphate in fractionated treatment.

The purpose of the studies reported here was to investigate the ability of the combined administration of dipyridamole and adenosine monophosphate, drugs known to elevate extracellular adenosine, to protect mice undergoing treatment with fractionated irradiation (five doses of 2 or 3 Gy each) given at 24-h intervals. Based on observations of hemopoietic recovery (endogenous hemopoietic spleen colony formation, marrow granulocyte-macrophage colony-forming cells, peripheral blood cells) after the completion of fractionated irradiation and on survival studies, it was demonstrated that the repeated administration of the drugs 60 min before each of the radiation fractions mitigates the hemopoietic injury and enhances the survival of mice irradiated with an additional "top-up" dose. It could be deduced that the single protective actions of the drugs retain their efficacy in repeated treatment and enhance the sparing effect of dose fractionation on hemopoiesis. Interestingly, the toxic side effects of the drugs tend to decrease when they are administered repeatedly, probably due to the development of tolerance to their cardiovascular action. This reduction in toxicity offers benefit with respect to the potential use of these hemopoiesis-protecting drugs in clinical radiotherapy.

Adenosine Monophosphate↗
PubMed1995

Radioprotective efficacy of dipyridamole and AMP combination in fractionated radiation regimen, and its dependence on the time of administration of the drugs prior to irradiation.

We have recently demonstrated that the combined administration of dipyridamole and adenosine monophospate to mice induces radioprotective effects in terms of postirradiation haemopoietic recovery in animals irradiated with a single dose. The aim of the present experiments was to investigate the radioprotective ability of the drug combination under conditions of fractionated radiation treatment. It has been shown that administration of drugs either 15 or 60 min before each of the five daily 3-Gy doses of gamma-radiation enhances haemopoietic recovery and survival of mice exposed to an additional "top-up" dose of 3.5 Gy. Furthermore, it has been ascertained that the regimen using administration of the drugs 60 min prior to irradiation is more effective than administration of the drugs 15 min prior to irradiation. Due to the evidence that administration of the drugs 15 min prior to irradiation protects the organism mainly via mechanisms of systemic hypoxia while the pretreatment 60 min before irradiation avoids the role of hypoxia and mainly induces cell proliferation effects, our results suggest a more effective protective role of mechanisms stimulating haemopoiesis under conditions of fractionated radiation. The data may provide a basis for more rational use of radioprotection in fractionated radiation regimens.

Adenosine Monophosphate↗
PubMed1994

Microcytic anemia and changes in ferrokinetics as late after-effects of glucan administration in murine hepatitis virus-infected C57BL/10ScSnPh mice.

Mild microcytic anemia (without changes in mean corpuscular hemoglobin concentration, MCHC) was discovered 6-14 weeks after a single s.c. administration of 4 mg of particulate glucan to C57BL/10ScSnPh mice serologically positive for murine hepatitis (MHV). The anemia was associated with granulocytosis, decreased body weight and spleen hypertrophy. The overall intensity of erythropoiesis was measured by 59Fe-incorporation into the heme of erythropoietic organs. The localization of erythropoiesis became markedly redistributed--heme production was suppressed in the bone marrow while a several-fold increase was recorded for the spleen. A new steady state was also discovered in ferrokinetics: an iron pool localized away from the blood, erythropoietic organs and the liver was significantly elevated, and hypoferremia was detected. Anemia and wasting of mice were not observed in the same mouse strain free of MHV. A single administration of particulate glucan resulted in late impairment of red blood cell formation in the C57BL/10ScSnPh mouse strain infected with the mouse hepatitis virus. The anemia shares a number of features with those observed for the anemia of chronic diseases.

Adjuvants, Immunologic↗
PubMed1993

On control of the hematopoietic cell proliferation.

Hematopoietic cells, detected as spleen colony forming units (CFU-S), vary in their proliferation rate, and this can be investigated in vivo by determining the fraction of CFU-S synthesizing DNA. A large number of measurements of CFU-S number and the fraction synthesizing DNA has been obtained under standardized conditions in normal mice and after a single dose of arabinosyl cytosine (ara-C). These data are analyzed with respect to the correlation between the number of CFU-S and their DNA-synthesizing fraction since, in the past, it has been maintained that the CFU-S proliferation rate responds sensitively to changes in CFU-S numbers. The present analysis does not support this traditional view--it instead demonstrates that natural variations in CFU-S numbers occurring in the same range as those following ara-C do not trigger CFU-S proliferation. On the other hand, administration of ara-C triggers most of the surviving CFU-S into the cell cycle, while decreasing CFU-S numbers by only about 40%. Data are also presented showing changes of CFU-S numbers and their DNA-synthesizing fraction in mice given a single dose of cyclophosphamide (CY). CY reduces CFU-S numbers, but the fraction synthesizing DNA can be either increased or decreased depending on time after treatment. Both these experimental situations argue against a close relationship between CFU-S numbers and their proliferation rate and suggest a different or a more complex regulation.

Animals↗
PubMed1991

Hematopoietic stem cells in +/+, nu/+, and nu/nu C57Bl/10 mice.

Mice with the nu mutation have been shown to have a reduced incidence of spleen colony-forming units (CFU-S), with a higher variability between individual mice compared to +/+ mice. The presence of these defects also in nu/+ mice indicates that this mutation is a codominant trait and that the hematopoietic changes may not be solely caused by thymus dysgenesis. The proportion of CFU-S synthesizing DNA (approximately 40%) has not been significantly different between +/+, nu/+, and nu/nu mice.

Animals↗
PubMed1990

Ferrokinetics and erythropoiesis in mice after long-term inhalation of benzene.

Ferrokinetics and erythropoiesis were examined in mice exposed for 6 or 7 weeks to an airborne concentration of 300 ppm of benzene, for 6 h per day, and 5 days per week. Ferrokinetic indicators showed only a slightly enhanced production of haeme and erythrocytes in the spleen (133% +/- 18% and 122% +/- 17%, respectively). Production did not change in the femoral marrow; a decline of CFU-C, BFU-E and especially CFU-E (34% +/- 8%) took place there and a shift of cellularity into less mature developmental classes in the erythroblast compartment, without this compartment as a whole being damaged. The erythrocytes produced have an enhanced MCV (109% +/- 0%) and MCH (109% +/- 1%) with an unchanged MCHC; their concentration in blood sank to 87% +/- 1%. The absolute reticulocyte count rose to 160% +/- 16%. 59Fe incorporation into the liver declined far below the level attributable to decreased accessibility of the tracer (84% +/- 4%). A shortening of the life span of late erythroblasts and circulating erythrocytes was deduced from these findings and methodological problems related to some of the seemingly controversial findings are discussed.

Administration, Inhalation↗
PubMed1990

Haemopoietic stem cells: spleen colony-forming cells are normally actively proliferating.

The haemopoietic stem cells forming spleen colonies (CFU-S) had on average 30 to 40% of cells engaged in the DNA synthesis in normal mice continuously over 4 years. A majority of experiments aimed at the suppression of the CFU-S proliferation, which included suppression of the T-lymphocytes by means of cyclosporin A or by adult thymectomy, administration of antibacterial and antifungal agents and maintainance of mice in a sterile environment, suppression of antibody-producing cells by a successive administration of the bacterial lipopolysaccharide and cyclophosphamide and attempts to increase the total number of CFU-S in the body through massive transfusions of bone marrow cells or by grafting plugs of the bone marrow under the kidney capsulae, have not been sufficiently effective. A transient suppression of CFU-S proliferation occurred during recovery of the haemopoietic tissue from damage caused by cyclophosphamide. The results support the view that changes in CFU-S numbers and in the proportion of them in DNA synthesis may be positively correlated when CFU-S numbers fluctuate physiologically about their normal values. The failure to manipulate the CFU-S proliferation rate easily suggests that proliferation of these cells may not be under a strong 'switch on - switch off' control.

Animals↗