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Biomedical subjects

J Mares

Publications and source records attributed to J Mares.

At least 19 recordsLinked to original sources
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↗
PubMed1996

The use of kinetic children's drawings to explore the pain experiences of children in hospital.

Under the influence of D. Armstrong, R. Burns, S. Kaufman, author proposed his own method of verbal-graphic diagnostics of children's experience with painful interventions in hospital. Child or adolescent characterizes actual and ideal psychosocial environment during painful interventions by kinetic drawing and writing comments. Children's drawings were analyzed by means quantitative and qualitative indicators set. Research sample consisted of 13 children and adolescents (median 12 years) hospitalized at the Pediatric Clinic of University Hospital. Results indicate that for an ill child apparently is not so stressing the painful intervention itself as the circumstances under which it is performed (inadequate preparation of the child, impersonal environment, absence of significant others and social support).

Adolescent↗
PubMed1995

Comparison of mRNA contents of interleukin-1 beta and nitric oxide synthase in pancreatic islets isolated from female and male nonobese diabetic mice.

Interleukin-1 beta (IL-1 beta) has been suggested to mediate beta-cell destruction in insulin-dependent diabetes mellitus (IDDM) by inducing nitric oxide production. In this study, we assessed the levels of IL-1 beta and the inducible form of nitric oxide synthase (iNOS), using a semi-quantitative polymerase chain reaction assay, and performed determinations of nitrite accumulation and IL-1 beta bioactivity, on pancreatic islets isolated from 5- and 16-week-old female and male nonobese diabetic (NOD) mice and from nondiabetes prone NMRI mice. NOD mouse islets contained notable amounts of IL-1 beta mRNA. At 5 weeks of age, but not at 16 weeks, the values were higher in islets isolated from NOD females compared to males. The IL-1 beta bioactivity showed differences roughly reflecting the mRNA levels in the NOD mouse islets. In the NMRI mouse islets the IL-1 beta bioactivity was very low. The expression of iNOS mRNA increased in both male and female islets between 5 and 16 weeks of age. Immunocytochemistry of pancreatic sections indicated the presence of macrophages especially in the peri-insular area of the NOD mice which suggests that IL-1 beta was produced by macrophages. The levels of IL-1 beta activity and mRNA in freshly isolated islets from NOD 5-weeks-old females did not correlate to the iNOS mRNA content or to the nitrite production. However, after incubation with IL-1 beta in vitro, both NOD and NMRI islets responded with a marked increase in nitric oxide production.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1995

[Models of focal hypoxia of the central nervous system].

Vascular disease and focal cerebral ischemia still represent the major cause of neurological morbidity and mortality. Mechanisms of hypoxic changes are associated with energy depletion and impairment of biological membranes. Reperfusion after the stroke plays an important role in the development of morphological and functional changes of the nervous tissue. In experiments, different models of focal cerebral ischemia based on the middle cerebral artery occlusion (MCAO) are used. Four main categories of such models are most frequently employed: 1. Temporary intraluminal occlusion of part of the circle of Willis (via internal carotid artery), 2. Abluminal application of the vasoconstrictor peptide (endothelin-1) to the MCA, 3. Tromboembolic models, 4. Microclips. Reliable quantification of morphological changes is also possible. Discussed models are used for testing different types of treatment of the cerebral ischemia, including pharmacological stimulation and blocking of individual membrane receptor systems.

Animals↗