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Biomedical subjects

J Mares

Publications and source records attributed to J Mares.

At least 19 recordsLinked to original sources
PubMed2001

[Molecular genetics of Wilms' tumor].

Molecular genetics of the Wilms' tumor plays an important role in the elucidation of the genetic etiology of the tumor disease generally. Contrary to the genesis of retinoblastoma, where a single gene is inactivated by two hits, the biological signalling pathways determining the origin of the Wilms' tumor are more complex and several genes in several loci may participate. Formation of the Wilms' tumor is accompanied with the most frequent genetic alteration, which is the loss of heterozygosity on the short arm of chromosome 11. It indicates inactivation of one or several tumor suppressor genes located at 11p region. The most studied gene of the Wilms' tumor is WT1 gene, which has been cloned and sequenced. Biological function of WT1 protein is complex one and it requires probably an interaction with other proteins, DNA and also RNA. The development of the tumor determines not only the genetic changes, but also epigenetic changes, e.g., hypermethylation of promoter and genome imprinting.

Chromosome Mapping↗
PubMed2001

Methylation changes in promoter and enhancer regions of the WT1 gene in Wilms' tumours.

Although the WT1 gene has been implicated in the aetiology of Wilms' tumour, mutations in WT1 are found only in minority of the tumours. DNA methylation of regulatory elements represents another possibility of modulation of gene expression. We studied methylation in the promoter and enhancer regions of the WT1 gene in 34 Wilms' tumour patients by the polymerase chain reaction on HpaII-digested DNA and by the bisulphite method. No methylation was detected in the promoter region in either tumour or normal kidney or blood DNA samples. In contrast, a HpaII site in the enhancer region was at least partially methylated in normal kidney and blood DNA samples and in about one-third of the tumours, while the majority of tumours showed no methylation. The differential methylation in the enhancer region of the WT1 gene may indicate that methylation of this element can play a role in the regulation of this gene.

Adolescent↗
PubMed2000

[DNA methylation and neoplasms].

DNA methylation and acetylation of histone proteins represent two global mechanisms controlling the gene expression. DNA methylation profiles alter during the development of the organism and during progression of neoplasia. Three types of alterations of the DNA methylation profiles were observed in the tumor cells: hypomethylation, hypermethylation and the loss of imprinting. Beside the intra-gene mutation and the heterozygosity absence, DNA methylation can be understood as the third mechanism of tumor-suppressor gene inactivation in the genesis of neoplasia. Our review article brings recent findings and hypotheses on the role of DNA methylation in the carcinogenesis and its possible application in the diagnostics and therapy of the malignant proliferation.

DNA Methylation↗
PubMed2000

Use and evaluation of the Czech version of the SF-36 questionnaire self-reported health status of medical students.

SF-36 questionnaires were completed by 231 medical students of the Faculty of Medicine in Hradec Králové (1997, 1998). Results of measurements of eight health dimensions are presented here. Significantly lower values for bodily pain were found in the group of overweight students. Students with some reported cured diseases have significantly lower values for bodily pain and general health dimensions in comparison with students without any reported disease. In our sample a high rate of non-smokers (86.4% men and 93.6% women) and low rate of students with BMI > 25 (18.4% men and 3.8% women) were found. About 30% of respondents reported one or more cured diseases. In addition to the SF-36 questionnaire, students in 1998 completed also a special one-page form (3). The one-page form enabled direct estimates of the eight dimensions of the health status on a scale from 0% to 100%. This study compares the results of measurement of the health status for both instruments. Differences found here are compared and discussed with similar comparisons in an American study (3). Results in both studies are similar but not the same. An indirect measurement of health status with specific questions in the SF-36 is more objective than a direct measurement with the one-page form. Nevertheless, the SF-36 is limited in the number of possible answers for some dimensions (RP, RE). In that case, our results indicate that a percentage scale from the one-page form seems better. Additionally this study compares the results of the SF-36 in Czech medical students with comparable samples from other three European countries. On average, the health dimensions of SF-36 in Czech medical students achieved the worst values in comparison with samples from Switzerland, Germany and Great Britain.

Activities of Daily Living↗
PubMed2000

[Lower urinary tract function and its disorders].

The lower urinary tract provides two modes of operation--storage and elimination of urine. The normal function results in the coordination of contraction and relaxation of muscles of the urinary bladder and urethral sphincters. Disorders of these activities or their interaction lead to the development of lower urinary tract dysfunctions. The nervous system plays an essential role in the regulation of the functions. The control of micturition is coordinated by several regious of the central nervous system. Afferents and efferents of the peripheral nervous system carry signals from and to the lower urinary tract. The reflex circuitry controlling micturition consists of five components: spinal efferent neurons, peripheral efferent neurons, primary afferent neurons, spinal interneurons and neurons in the brain. Preganglionic neurons located in the sacral parasympathetic nucleus and lumbar sympathetic nucleus excite the peripheral efferent neurons innervating smooth muscles of the urinary bladder and urethra. Motoneurons of sacral Onuf's nucleus excite the striated muscle of the external urethral sphincter. Myelinated and unmyelinated afferent axons transmit information from the lower urinary tract to the lumbosacral spinal cord. Three receptor types of the lower urinary tract are present: tension receptors, volume receptors and "silent receptors", which become nociceptors following the sensitization. Afferent pathways terminate on spinal interneurons. Spinal interneurons relay information to the brain or to other regions of the spinal cord. Because micturition reflexes are mediated by disynaptic or polysynaptic pathways, interneuronal mechanisms are of crucial importance in the regulation of lower urinary tract. Central pathways involved in micturition reflexes are located in spinal and supraspinal areas. Micturition reflexes can be modulated at the level of the spinal cord by viscero--bladder and somato--bladder reflexes. Supraspinal areas have a more complicated organization: critical component of the micturition reflex is the pontine micturition center and the periaqueductal gray. Inhibitory and excitatory areas in the pontomedullary and hypothalamic systems and the brain play an important role in the regulation of micturition reflexes.

Humans↗
PubMed1999

[Regeneration and transplantation of nerve tissue].

Initial experimental transplantations and attempts to induce regeneration in the nerve tissue were done during the last decades of the 19th century. Though experiments were partly successful, the Cajal's doctrine about the unchanging adult nervous system overbalanced those promising findings for long period thereafter. Only during the last thirty years requirements of clinicians moved neuroscientists to study the problems of regeneration and transplantation in the CNS again. The possibility of transferring nerve cells from a donor to the host CNS, their survival, and formation of functional contacts has been fully established. Recent findings has shown that techniques of molecular biology can overcome some of the essential problems of transplantation, e.g. the glial scar. It is evident that the key role in plastic processes accompanying integration of the transplanted cells have neurotrophic factors produced both by the host and the graft. The entire microenvironment within the transplanted tissue is altered. Some specific features of the graft may be also significant. As the implant is mostly an embryonic tissue, processes of differentiation have to be considered. Accordingly, transplantation can be used as a model in the studies of neuroontogeny. In our experiments structural association of neurones transplanted as a suspension of embryonic cells into the dorsal blade of the dentate gyrus where granule cells were eliminated was described. Differentiation and signs of synapse formation were observed. Using Timm staining method, changes in the distribution of mossy fibres were identified. In thirty-day-old grafts, high number of NADPH-d positive neurones was found. Some nitric oxide producing neurones formed long processes extending into the host tissue. Such long fibres also produced nitric oxide synthase. In order to influence the process of the graft integration we induced extreme hyperfunction by a metrazol kindling. In kindled animals, more neurones survived, however, the density of apoptotic cells was similar to control animals. Our findings may be related to the hyperfunction or to the effect of metrazol on the nerve cells of both the host and the graft. They may result from microenvironmental changes or from the activation of genes participating on the mechanism of priming.

Animals↗
PubMed1998

Allele loss in Wilms tumors of chromosome arms 11q, 16q, and 22q correlate with clinicopathological parameters.

An extended analysis for loss of heterozygosity (LOH) on eight chromosomes was conducted in a series of 82 Wilms tumors. Observed rates of allele loss were: 9.5% (1p), 5% (4q), 6% (6p), 3% (7p), 9.8% (11q), 28% (11p15), 13.4% (16q), 8.8% (18p), and 13.8% (22q). Known regions of frequent allele loss on chromosome arms 1p, 11p15, and 16q were analyzed with a series of markers, but their size could not be narrowed down to smaller intervals, making any positional cloning effort difficult. In contrast to most previous studies, several tumors exhibited allele loss for multiple chromosomes, suggesting an important role for genome instability in a subset of tumors. Comparison with clinical data revealed a possible prognostic significance, especially for LOH on chromosome arms 11q and 22q with high frequencies of anaplastic tumors, tumor recurrence, and fatal outcome. Similarly, LOH 16q was associated with anaplastic and recurrent tumors. These markers may be helpful in the future for selecting high-risk tumors for modified therapeutic regimens.

Alleles↗
PubMed1998

Two Li-Fraumeni syndrome families with novel germline p53 mutations: loss of the wild-type p53 allele in only 50% of tumours.

We describe two Li-Fraumeni syndrome families. Family A was remarkable for two early childhood cases of adrenocortical tumours, family B for a high incidence of many characteristic cancers, including a childhood case of choroid plexus tumour. Using direct sequencing, we analysed exons 5-9 of the p53 gene in constitutional DNA of individuals from both families and found two novel germline mutations in exon 5. In family A, we detected a point substitution in codon 138 (GCC to CCC), which resulted in the replacement of the alanine by a proline residue. Family B harboured a single-base pair deletion in codon 178 (CAC to -AC), resulting in a frameshift and premature chain termination. Three out of six tumours examined from both families, a renal cell carcinoma, a rhabdomyosarcoma and a breast cancer, showed loss of heterozygosity and contained only the mutant p53 allele. The remaining three neoplasms, both adrenocortical tumours and the choroid plexus tumour retained heterozygosity. Immunohistochemistry with anti-p53 antibody confirmed accumulation of p53 protein in tumours with loss of heterozygosity, while the remaining tumours were p53 negative. These results support the view that complete loss of activity of the wild-type p53 need not be the initial event in the formation of all tumours in Li-Fraumeni individuals.

Adolescent↗
PubMed1998

[Postictal depression in 12-day-old animals].

Postictal depression systematically follows epileptic after-discharges (AD) evoked from many different regions of the brain of adult animals. In presented experiments we tested by evoking ADs from sensorimotor cortex whether the susceptibility to undergo postictal depression is age-dependent and whether it correlates with the individual duration of ADs. Groups of 12-, 18- and 25-day-old male rats were used (freely moving animals--semichronic preparations; six trains of rhythmic electrical stimulations in one min. intervals after the end of previous seizure; EEG recordings; durations of ADs were measured). In the whole group of the 25-day-old animals the mean duration of ADs after individual stimulations illustrated the inhibitory influence of the first seizure on the duration of all subsequent ADs. In 18-day-old animals the depression was less pronounced and in 12-day-old it seemed to be not present. Analysis of results in individual animals in the group of youngest animals showed, that duration of pairs of subsequent seizures was related to the duration of the first of them. Also in this age group long seizures caused postictal depression. Duration of seizures seems to vary individually and it strongly influences the mean results of the whole group. The differences between the groups could be explained on the basis of the different pattern of ADs in young and older animals. In young animals the total "output" of seizure is low and it could also cause not so intensive and long posttetanic depression based on changes of intracellular Ca2+, because this form of synaptic plasticity seems to involve the activation of Ca(2+)-dependent protein kinases. Synaptic energy consumption also may play some role in postictal depression occurrence.

Age Factors↗
PubMed1998

Oncogene amplification and expression in pediatric solid tumors.

Oncogene amplification and expression and their mutual relationship was analyzed in 92 pediatric tumors by Southern and Northern blot hybridization with N-MYC, ERB A, ERB B, N-RAS and Shb probes. Amplification and overexpression was associated with more advanced clinical stages of tumor, especially in neuroblastomas, rhabdomyosarcomas and ganglioneuroblastomas. The most frequent alteration observed was N-MYC amplification together with overexpression. N-RAS amplification was not detected, while the overexpression of this oncogene was found in 3 cases. Neither amplification nor overexpression was revealed in any specimen of hepatoblastoma or hepatocellular carcinoma. We suggest that oncogenes overexpression provides more accurate prognostic information than amplification.

Child↗
PubMed1997

[Tumor suppressor genes].

The main role of tumour suppressor genes is the inhibition of cell proliferation. Somatic mutations in these genes are found frequently in sporadic tumors. Germ line mutations in tumour suppressor genes are responsible for hereditary cancer syndromes. In a carrier of such a germ line mutation, a somatic mutation or loss of the remaining functional copy of the gene is sufficient for the complete loss of function of the tumour suppressor. Therefore the carriers of germ line mutations have a high risk of developing malignancies. Many tumour suppressor genes have been cloned and characterized recently and many others are intensively searched for. Protein products of these genes serve different cellular functions and many of them directly participate in the cell cycle control. The characterization of tumour suppressor genes is important both for the understanding of processes of carcinogenesis and for practical use in the diagnostics, prognostics and therapy of tumours.

Animals↗
PubMed1997

[Postoperative pain in children].

The authors present their experience with the follow up and influencing of postoperative pain in 65 children aged 6-18 years operated and hospitalised at the department of paediatric surgery of the Faculty Hospital in Hradec Králové. The authors investigated in operated children with different diagnoses the topology, quality, intensity, development and treatment of postoperative pain. As to selected ways of monitoring of different dimensions of pain they selected those which take into account age and possible communication with the child. For the treatment of postoperative pain they used in 96% analgesics and in 4% anaesthetics.

Adolescent↗
PubMed1997

Children pain during dental treatment.

This research work was done on the set of 69 children and adolescents 6-14 years old at the children's department of the dental clinic, university hospital in Hradec Králové. We found their expectancy of dental pain inadequate to reality: 67% children overestimated expected pain, 12% underestimated it. It does not see that children feelings prior to very performance would signalize in advance how much unpleasant or painful the dental procedure is going to be. We have not found any significant difference in either understanding the instruction or sticking to them, or general cooperation of children. The average time interval of dental procedures fluctuated between 18 and 40 minutes, children were not given any anesthetics (with exception of two cases of extractions) which could be one of the causes of distress. From all the children 35% experienced pain in the dental chair and were able to assess it by VAS and verbally characterize its quality. According to the view of children assessing the subjectively experienced pain intensity there exist two types of dental procedures: the first type being represented by painless but demanding patience procedures, the second group of painful treatment (making fillings or extractions). There were no statistical difference between girls and boys in their experiencing pain but there was some difference between girls and boys as went for an approach of health workers: these much more often tried to support girls.

Adolescent↗
PubMed1996

[A method for detection of germinal mutations in the p53 tumor suppressor gene].

BACKGROUND: The tumour suppressor gene p53 is exhibits somatic mutations in a high proportion of human tumours. In addition, there are cancer families suffering from the Li-Fraumeni syndrome, the members of which carry germ line mutations in this gene. The carriers of the p53 germ line mutations have a high risk of developing tumours. The genetic diagnosis of carriership of the mutation in the tumour family members is important for preventive measures and for eventual tumour therapy modification. METHODS AND RESULTS: We have developed a method for the detection of germ line mutations in the p53 gene based on non-radioactive SSCP and direct sequencing of PCR products. We have proved the efficiency of the method by finding known mutations in eight tumour cell lines. In our collection of tumour families we have detected polymorphisms in exons 4 and 6 of the p53 gene. In one family which conformed to the criteria of the Li-Fraumem syndrome we have found a novel germ line mutation in exon 5. CONCLUSIONS: The method developed by us is very simple and sensitive. The germ line mutations in the p53 gene are very rare.

Female↗
PubMed1996

[Amplification of oncogenes in solid tumors in children].

BACKGROUND: The objective of the work was detection of amplification of oncogenes N-MYC, N-RAS, C-ERB A, C-ERB B and adaptor tyrosine kinase Shb in a group of 92 child age tumours in an attempt to reveal clinical and histopathological associations. METHODS AND RESULTS: Amplifications of oncogenes were detected by means of Southern's transfer, hybridization with labelled probes and densitometric evaluation. Amplification of the N-MYC oncogene in child tumours can be considered a manifestation of progression of the disease with an adverse prognosis, in particular in neuroblastomas, where it corresponds also with the adverse histological finding. In a group of sarcomas N-MYC amplification was detected in advanced clinical stages, while in malignant lymphogranulomas of the Hodgkin type it was not found. In Wilms tumour it was detected sporadically. Amplifications of oncogenes ERB A and ERB B are rare, amplifications of the oncogene RAS were not observed. Coamplifications characterized progression of the disease, in case of neuroblastoma even very short survival. In hepatic malignancies oncogene amplification was not found even in advanced stages. CONCLUSIONS: Oncogene amplification characterizes progression in a number of child tumours and its application in clinical oncology is prognostically useful.

Child↗
PubMed1996

[Oncogenes and the malignancy process].

An important group of genes for the development of neoplastic diseases are, in addition to tumour suppressor genes, protooncogenes. The latter are highly preserved genes present in a similar sequence in the cell genomes of different species (yeasts - man). They encode components of biochemical signalling pathways by which external mitotic signals stimulate cell proliferation and products which inhibit cell differentiation. The result of activation of protooncogenes into oncogenes (mutations, chromosomal rearrangements, amplifications, viral insertions, insertion mutagenesis) is in particular hyperstimulation of cells resulting in uncontrolled proliferation. Mutations are of the dominant type, elimination of one allele leads to the transformation of a protooncogene into an oncogene. Oncogenes are classified with regard to the transmission level of the mitogenic signal on which they act. Originally they were detected in the genome of oncogenic viruses. However, they do not form their constant and specific constituent, the virus acts as a vector which transmits cellular protooncogenes (or oncogenes) during the reproductive cycle from one cell to another. The activity of various types of oncogenes is the necessary prerequisite for the genesis and development of various neoplastic diseases. Detection of oncogene alterations provides in some instances important diagnostic, prognostic and therapeutic findings.

Gene Expression Regulation, Neoplastic↗
PubMed1996

Control of SHB gene expression by protein phosphorylation.

To increase our understanding of the role of the Src homology 2 (SH2) domain-containing protein Shb in the mitogenic signal transduction, Shb mRNA contents were determined in the fibroblast-like NIH3T3 cells and the insulin producing beta TC-1 cells under various conditions. In NIH3T3 cells, the serine/ threonine phosphatase inhibitor okadaic acid and the tyrosine kinase inhibitor genistein increased Shb mRNA contents, the protein kinase C activating phorbol ester 12-O-tetradecanoyl 13-acetate (TPA) decreased the Shb mRNA content, whereas the tyrosine kinase inhibitor tyrphostin 25 and the mitogen platelet-derived growth factor (PDGF-BB) had no effect. In beta TC-1 cells, okadaic acid and genistein increased the Shb mRNA content, whereas tyrphostin 25 and serum were without effect. Okadaic acid and genistein decreased the rates of beta TC-1 cell DNA synthesis. It is concluded that expression of the SHB gene is under a complex mode of regulation involving at least three different protein kinases. As a consequence of this, it is likely that SHB gene expression is significantly modulated by conditions of specific activation of certain pathways, whereas its expression appears little influenced by serum and a mitogen.

3T3 Cells↗