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I Raskó

Publications and source records attributed to I Raskó.

At least 19 recordsLinked to original sources
PubMed2001

UVB irradiation-induced apoptosis increased in lymphocytes of Huntington's disease patients.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansion in the IT-15 gene coding for huntingtin. The mechanism of neuronal degeneration induced by the mutant huntingtin is not known. Apoptosis may play a role in it. Huntingtin is widely expressed in the cells, so abnormalities can be expected also in non-neural tissue. We examined the susceptibility of lymphocytes from HD patients, asymptomatic carriers and normal individuals to UVB irradiation-induced apoptosis. Lymphocytes from eight HD patients and two asymptomatic carriers showed increased apoptotic cell death compared to controls. Our results suggests that sensitivity of HD cells to induced apoptosis is not restricted to neurons.

Adult↗
PubMed2000

A simple and efficient method for PCR amplifiable DNA extraction from ancient bones.

A simple and effective modified ethanol precipitation-based protocol is described for the preparation of DNA from ancient human bones. This method is fast and requires neither hazardous chemicals nor special devices. After the powdering and incubating of the bone samples Dextran Blue was added as a carrier for removing the PCR inhibitors with selective ethanol precipitation. This method could eliminate the time-consuming separate decalcification step, dialysis, application of centrifugation-driven microconcentrators and the second consecutive PCR amplification. The efficiency of this procedure was demonstrated on ten 500-1200-year-old human bones from four different Hungarian burial sites. A mitochondrial specific primer pair was used to obtain sequence information from the purified ancient DNA. The PCR amplification, after our DNA extraction protocol, was successful from each of the 10 bone samples investigated. The results demonstrate that extraction of DNA from ancient bone samples with this new approach increases the success rate of PCR amplification.

Adolescent↗
PubMed2000

Mammalian S-phase checkpoint integrity is dependent on transformation status and purine deoxyribonucleosides.

In eukaryotic cells arrested in S-phase, checkpoint controls normally restrain mitosis until after replication. We have identified an array of previously unsuspected factors that modulate this restraint, using transformed hamster cells in which cycle controls are known to be altered in S-phase arrest. Arrested cells accumulate cyclin B, the regulatory partner of the mitotic p34(cdc2) kinase, which is normally not abundant until late G(2) phase; treatment of arrested cells with caffeine produces rapid S-phase condensation. We show here that such S-phase checkpoint slippage, as visualised through caffeine-dependent S-phase condensation, correlates with rodent origin and transformed status, is opposed by reverse transformation, and is favoured by c-src and opposed by wnt1 overexpression. Slippage is also dependent on a prolonged replicative arrest, and is favoured by arrest with hydroxyurea, which inhibits ribonucleotide reductase. This last is a key enzyme in deoxyribonucleotide synthesis, recently identified as a determinant of malignancy. Addition of deoxyribonucleosides shows that rapid S-phase condensation is suppressed by a novel checkpoint mechanism: purine (but not pyrimidine) deoxyribonucleosides, like reverse transformation, suppress cyclin B/p34(cdc2) activation by caffeine, but not cyclin B accumulation. Thus, ribonucleotide reductase has an unexpectedly complex role in mammalian cell cycle regulation: not only is it regulated in response to cycle progression, but its products can also reciprocally influence cell cycle control kinase activation.

Animals↗
PubMed1999

Chemical reverse transformation of CHO-K1 cells induces changes in expression of a candidate tumour suppressor and of a gene not previously characterised as transformation related.

Chemical reverse transformation of CHO-K1 and other cells is a well-established phenomenon, in which oncogenically transformed cells re-acquire fibroblastoid morphology, contact inhibition and anchorage-dependent growth, in response to cyclic AMP and other agents. A limited number of changes in gene transcription and enzyme activity have been demonstrated to coincide with these morphological and physiological changes. We have used a partial differential display to identify four genes that are transcriptionally modulated in reverse transformation. One of these, encoding ribosomal protein S18, is transcriptionally suppressed, probably as a result of the detransforming process. Three others are transcriptionally activated. One has homology to NADH-ubiquinone oxidoreductase chain 4 protein, and is also probably changed as a result of the detransforming process. Another is homologous to a human sequence which encodes a 27 kDa protein, p27(BBP/eIF6), that is involved in the biogenesis of 60S ribosomal subunit, and in cell lines of epithelial origin binds to beta integrin. This has not previously been described as transformation-related, and could have a causative role in reverse transformation. The third has homology, with transcriptional or processing variations, to a human genomic sequence, a positional candidate for a tumour suppressor gene, encoding the Krit1 protein which interacts with the Ras-family GTPase Krev-1.

Animals↗
PubMed1999

Deletion patterns of dystrophin gene in Hungarian patients with Duchenne/Becker muscular dystrophies.

Deletion pattern analysis of the dystrophin gene was performed in 159 Hungarian patients with Duchenne/Becker muscular dystrophy. In 116 cases (73% of total patients), exon deletions were detected by PCR amplification. In 37 patients (31.9% of patients with a deletion) one exon was deleted, while five or more exons were missing in 40 children (34.4%). With respect to the proximal-distal distribution of the deletions, 90 children (77.6%) had deletions exclusively at the 3' end of the gene, 21 deletions (18.1%) affected only the 5' end, and in five patients (4.3%) large-scale deletions were detected, which affected both regions. Analysis of the breakpoint distribution pattern in the dystrophin gene showed that, similarly to that observed in several Western European populations, intron 44 was involved most frequently (n = 35, 15.1%) as a starting breakpoint. In the Hungarian population introns 50 and 52 were the second (n = 30, 12.9%) and third (n = 29, 12.5%) most frequently observed hot spots at the 3' end; these seem to be characteristic for the Hungarian patients. At the 5' end the breakpoint peak (n = 6, 2.58%) was in intron two. As it was proposed by previous national studies, our findings also suggest that certain intronic sequences, characteristic for a population, probably determine the development of a preferential breakpoint profile in this disease.

Child↗
PubMed1999

Analysis of CAG repeat expansion in Huntington's disease gene (IT 15) in a Hungarian population.

Huntington's disease (HD) is a neurodegenerative disorder with autosomal dominant inheritance. The genetic defect is a CAG trinucleotide repeat expansion at the 5' end of the IT 15 gene on chromosome 4. This gene has not been analyzed in the Hungarian population yet. To obtain data DNA from 26 HD patients, 18 members of their families and 70 normal controls was amplified in the involved region by polymerase chain reaction. The CAG repeat numbers varied from 37 to 70 (median: 43) in HD patients and asymptomatic carriers, while individuals of the normal control group had 10-36 CAG repeat numbers (median: 18). The length of CAG repeat expansion in Hungarian HD patients was similar to that reported from other countries. The group of normal controls had the same CAG repeat expansion as populations reported from Western European countries. It is a useful piece of data for population genetics to prove that the population of Hungary is a mélange of different nations that influenced the history of the country in the last 11 centuries. As opposed to this, the only closely related nation, the Finnish, was genetically more isolated during this time, so the frequency of HD (and also the number of CAG repeats in normal individuals) proved to be exceptionally low.

Adult↗
PubMed1998

No mitochondrial haplotype was found to increase risk for Alzheimer's disease.

BACKGROUND: Seventy Alzheimer's disease (AD) patients and 80 age- and sex-matched controls were analyzed for mitochondrial mutations T4336C and A3397G, reported to be associated with AD, and for mutations T4216C/G13708A characteristic for a normal human haplotype associated with increased frequency of occurrence of some hereditary diseases. The distribution of apolipoprotein E (apoE) alleles was also analyzed. METHODS: Mitochondrial DNA was amplified by polymerase chain reaction, and the presence of mutations was detected by digestion with approximately chosen restriction endonucleases (restriction fragment length polymorphism). RESULTS: One patient and 2 controls were found to belong to the T4336C/T1630C haplotype. No A3397G mutant was detected. The T4216C/G13708A haplotype occurred at 5/70 and 5/80 frequency in the two groups. Prevalence of the apoE4 allele was significantly higher in AD patients (25%) than in the control group (8.1%). CONCLUSIONS: The T4336C/T16304C mutations were not found to associated with AD, and no predisposing mitochondrial haplotypes were found.

Aged↗
PubMed1998

[The DNA-chip, a new tool for medical genetics].

The DNA (chip) technology, emerged in the last two years, provides an incredible technical development in rapid and automatised performance of genetic identification. The principle of procedure is, that by series of photolitographic and chemical steps on solid-phase of a small surface relatively dense oligonucleotide arrays can be generated. The oligonucleotides produced by the computer-directed in-situ microfabrication may bind complementary fluorescent-labeled DNA fragments from the unknown sample. After scanning, the registered position of positive signals provide information on the identity of DNA fragments. By this novel approach not only DNA sequencing can be performed, but genetic errors of known genes, presence of infectious organisms and the typing of genetic markers (such as HLA) used for transplantation and forensic medicine can be determined. The DNA-chip technology is a revolutionary new milestone in genetic diagnose.

DNA↗
PubMed1998

Carrier detection by microsatellite analysis of Duchenne/Becker muscular dystrophy in Hungarian families.

Duchenne and Becker muscular dystrophies are among the most severe and frequent inherited disorders. Being still incurable, medical treatment is concentrated on the carrier diagnosis of the members of the affected families. Here we report the results of the studies of 151 members of 41 Hungarian families, obtained with multiplex PCR amplification of 18 exons as well as the muscle specific promoter region, and haplotype analysis of two polymorphic (CA)n repeat microsatellite loci in introns 45 and 49 of the dystrophin gene. The analysis of 15 deletion-type families revealed a frequency of new mutations not differing significantly from that in the other regions of Europe. We also compared the allele distributions of the two microsatellites in randomly selected normal individuals and affected family members. The allele distribution of STRP45 shows interesting differences between the two populations.

Alleles↗
PubMed1998

Increased apolipoprotein E4 allele frequency is associated with vascular dementia in the Hungarian population.

INTRODUCTION: The regulatory role of apolipoprotein E in lipid transport and metabolism was utilized to investigate the allelic association between the apolipoprotein E4 (apoE4) allele and vascular dementia (VD) in a selected sample of Hungarian patients with multiple deep subcortical infarcts and leukoaraiosis. MATERIAL AND METHODS: Thirty-four Caucasian VD cases and 79 healthy control probands were involved in this study according to the criteria of ICD-10 and NINDS-AIREN International Workshop Diagnostic Criteria. The genomic DNA was isolated from whole blood and the apoE alleles were determined by polymerase chain reaction. RESULTS: The E2, E3 and E4 allele frequencies in the VD group were 5%, 76%, and 19%, respectively; and significant (P<0.03) differences were found in comparison with the data on the healthy controls (E2, 6%; E3, 87%; E4, 8%). The apoE4 allele frequency was intermediate between HC and Alzheimer's dementia group (28%). CONCLUSION: These results indicate that the apoE4 allele could be a risk factor not only for certain primary degenerative, but also for vascular dementias.

Aged↗
PubMed1997

Apolipoprotein E allele frequencies in patients with late-onset sporadic Alzheimer's dementia in Hungary.

INTRODUCTION: The presence of the apolipoprotein E4 allele (apoE4) has been recognized as a risk factor for the development of presenile and senile forms of Alzheimer's dementia (AD). MATERIAL AND METHODS: The apoE alleles frequency of 71 normal controls (NC), 60 demented controls (DC) and 50 senile type AD subjects was determined by polymerase chain reaction in order to get data about the apoE polymorphism of the Hungarian AD population. RESULTS: The apoE3/3 genotype was the most common in all groups. The apoE4 frequency was significantly higher (28%) in the AD group than that was (7% and 9%) in the NC and DC populations, respectively. No apoE4 homozygotes were found in the DC group and the number of heterozygotes was lower in the DC than in the AD group. CONCLUSION: The results are in good agreement with others in the literature and support the occurrence of an increased apoE4 allele frequency in Hungarian senile AD population.

Age of Onset↗
PubMed1997

Changes in alkylation damage removal during in vitro neuronal differentiation.

Mouse teratocarcinoma cell lines allow the analysis of very early commitment and differentiation events, that are likely to be similar to those operating in the early mouse embryo. We have previously characterised the excision repair capabilities of these cells after ultraviolet light irradiation and found that differentiation is accompanied by reduction of excision repair. In the present study we examine the operation of an other DNA repair pathway participating in the removal of alkylation damage. O6-alkylguanine-DNA alkyltransferase (ATase) activity was determined in undifferentiated and differentiated mouse P19 teratocarcinoma cell line. To obtain more information about regulation of ATase we transfected P19 cells with constructs harbouring a human ATase cDNA driven by a housekeeping promoter.

Alkylation↗
PubMed1997

Molecular genetic studies in monogenic and polygenic human diseases.

The main goal of this study was to determine and characterise the types of mutations in two monogenic human disorders: cystic fibrosis (CF) and Duchenne/Becker muscular dystrophy (DMD, BMD) and the susceptibility allele frequency in a polygenic disease: type I insulin-dependent diabetes mellitus (IDDM). After analysing 220 chromosomes for mutations in the CF (Cystic Fibrosis Transmembrane Conductance Regulator = CFTR) gene, delta F508 mutation was most abundant (41%) and out of the non-delta F508 CF mutations 5% was identified as G542X, G551D, R553X, N1303K and W1282X. The CF haplotype analysis by using linked markers to the CFTR gene revealed that the CF "B" haplotype occurred in 66.7% of patients, and this haplotype was 57.2% in patients carrying the delta F508 mutation. Prenatal genetic diagnosis for CF was performed in 10 fetuses: 3 were affected, 6 were carriers, and 1 without any CF mutation. Fifty % of 66 patients with DMB/BMD muscular dystrophy had one or more exon deletions in the dystrophin gene. Eighty-five % of the deletions occurred at the 3' and 15% at the 5' end of the gene. Out of the three prenatal diagnosis in one case DMD was substantiated. Thirty-six % of 50 patients with IDDM possessed four, 44% three and 20% two susceptibility markers in the HLA-DQA1, -DQB1 region. The onset of the disease correlated with the number of susceptibility alleles.

Alleles↗
PubMed1994

[A variant of xeroderma pigmentosum: two cases of pigmented xerodermoid].

Two patients (sister and brother) of pigmented xerodermoid are presented: the character of clinical signs (phothosensitivity, poikilodermia, keratoses and keratomas, furthermore in the brother the squamous cell epithelioma of left thigh), according to them the case history (appearance of precancerous conditions and carcinoma in early adult life) made the disease suspicious to a variant of xeroderma pigmentosum. A DNA reparation test was also carried out, which confirmed the above clinical diagnosis in both patients.

Adult↗
PubMed1994

[Gene deletion analysis in molecular diagnosis of Duchenne-Becker muscular dystrophy].

Deletion analysis of the dystrophin gene (Xp21) was carried out by examinations of the most frequently deleted 18 exons (3., 4., 6., 8., 12., 13., 17., 19., 43., 44., 45., 47., 48., 49., 50., 51., 52. and 60. exon) and the muscle specific promoter in 42 Duchenne and Becker muscular dystrophy (DMD/BMD) affected patients with multiple polymerase chain reaction (PCR). 22 (52%) of 42 patients were found to have one or more exon deletions. 9% BMD patients (milder allelic form) were found in the deletion group versus 35% in the non deletion group. This method seems to be useful for prenatal genetic diagnosis in the family of deletion patients.

Adolescent↗
PubMed1993

DR beta-RFLP analysis of serologically DRw6 compatible kidney donor/recipient pairs.

HLA-DR beta-RFLP analysis of serologically 1 or 2 DR-antigen compatible renal allograft donors and recipients (D/R), selected for DRw6 antigen (study group), or for other DR antigens (control group) and its correlation with the graft outcome revealed that: 1. In the study group where donors and recipients were selected for matching in DRw6 antigen, 8 out of ten D/R pairs turned out to be incorrectly classified due to a number of mismatches in the HLA-DR locus RFLP analysis. In the control group, only 2 out of ten patients matched poorly by means of RFLP. The difference between the two groups was significant. 2. A significantly higher incidence of rejection episodes was seen in the study group (2.7 +/- 1.5) than in the controls (1.4 +/- 0.5). 3. The total dose of methylprednisolone necessary for suppressing the rejection episodes was higher in the study group (6.0 +/- 2.9 g) than in the control one (4.07 +/- 2.77 g), but the difference was not significant. 4. The graft survival 2 years after transplantation was 30% in the study group and 70% in the control group.

Graft Rejection↗