Search

The aim of this study was to examine association between IFNL4 gene ss469415590 and treatment efficiency in group of Ukrainian PEG-interferon/ribavirin-treated chronic hepatitis C patients. Study group consisted of 92 unrelated hepatitis C virus genotype 1 mono-infected patients: case group - 29 patients with late or absent virological response; control group - 63 patients with sustained virological response. Study material was genomic DNA. Genotyping was performed using amplification-refractory mutation system PCR. Statistical analysis was performed using GenePop and OpenEpi statistical packages. Obtained results show that ss469415590 ΔG/ΔG genotype is associated with poor virological response (OR = 3.62; CI 95%: 1.12-11.67) in PEG-interferon/ribavirin-treated chronic hepatitis C patients from Ukraine.

In the article the data on the distribution of CYP21A2 gene mutations (gene deletion/conversion, c.290-13C>A/G, E110Vfs, I172N, cluster of mutations I236N, V237E, M239K, V281L, Q318X, R356W) among Ukrainian patients with congenital adrenal hyperplasia of different clinical phenotypes are presented. The most common mutation in the studied group (n = 27) is the CYP21A2 gene deletion/conversion. Possible patterns of the studied mutations distribution in different populations of the world and the patients’ genotype – phenotype association are discussed.

Background: Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder with the frequency of carriers in a number of ethnical groups ranging from 1/50 to 1/25. However, the prevalence of SMA for population of Ukraine remains to be established., Methods: For the analysis of deletion in exon 7 SMN1 gene in SYBR Green Real-Time qPCR assay specific for the single nucleotide change in exon 7 (cd 840 C >T) was used., Results: Using SYBR Green qPCR assay, the incidence of the exon 7 SMN1 deletion was established among 370 unrelated individuals without family history of SMA. The carrier frequency for this group of Ukrainians was estimated as 3.24% (1/31)., Conclusions: The results of our study showing the high prevalence of carriers warrant the importance of population screening for SMA in Ukraine.

The comparative analysis of the associations between G20210A polymorphism of F2 gene, G1691A polymorphism of F5 gene, -5T/C polymorphism of gene GP1BA, I/D polymorphism of gene ACE and the risk of development of the stroke in two ethnical samplings--Russian and Ukrainian populations--was conducted. It was shown that the patients of the Russian population with genotype DD have a higher level of the risk of ischemic stroke development (OR = 1.4, 95% CI [1.05; 1.78], p = 0.02), whereas genotypes I/I and I/D are associated with the lower level of risk of ischemic stroke (OR = 0.7, 95% CI [0.56; 0.95], p = 0.02). In the Ukrainian ethnical sampling, differences in distribution of genotypes and alleles frequencies between patients with stroke and healthy persons upon given polymorphic locus are not significant, and I/D polymorphism of gene ACE is not associated with the risk of development of the stroke (OR = 0.8, 95% CI [0.48; 1.32], p = 0.45). The G20210A polymorphism of gene F2, G1691A polymorphism of gene F5, -5T/C polymorphism of gene GP1BA are not associated with the risk of stroke in two ethnical samplings.

The frequency of heterozygote carriers of (risk zone, alleles of FMR1 gene (40-47 CGG-repeats) was significantly higher in group of patients with ovarian dysfunction than in control group I. The tendency for higher frequency of those alleles was observed in patients with "poor response" to superovulation induction in IVF cycles. The average number of oocytes and follicles, which was obtained after stimulation of superovulation, was significantly decreased in FMR1 gene "risk zone" alleles carriers compared to patients with normal alleles of FMR1 gene. The average general dosage of exogenous gonadotrophin, necessary for superovulation induction was significantly higher in heterozygote carriers of FMR1 gene "risk zone" alleles than in patients with normal genotype. Thereby, the FMR1 gene "risk zone" alleles can be one of the hereditary susceptibility factors of impairment nature and stimulated ovulation.

The number of CAG repeats of exon 1 of AR gene was determined in a group of 228 infertile males with azoospermia (n = 68) and oligozoospermia (n = 160) as well as in control group (124 proven fathers) by fluorescent polymerase chain reaction amplification followed by fragment analysis on automated fluorescent analyzer "A.L.F-express". The frequency of alleles with GAG-repeats < or = 18 was significantly higher (P < 0,01) in the group of patients with azoospermia (17,7%) comparing with the control group (2,4%) as well as in the group of patients with oligozoospermia (12,5%) comparing with the control group (2,4%). The frequency of alleles with CAG-repeats > or = 28 significantly differed (P < 0,01) between the group of patients with oligozoospermia (12,5%) and the control group (2,4%). Our data suggest an association between CAG repeats number and impaired spermatogenesis in azoospermic and oligozoospermic males.

Mutations Arg124Cys, Thr538Arg, Arg555Thr, Arg555Gln, Leu558Pro, and His626Arg in TGFBI gene were analyzed by polymerase chain reaction and restriction in 84 patients with various forms of corneal stromal dystrophies from 49 unrelated families and 29 clinically healthy relatives of these patients. A new mutation in TGFBI gene, Leu558Pro, was identified in the patients with atypical lattice dystrophy. The haplotypes of four microsatellite markers surrounding TGFBI gene region were analyzed in 22 families. The data on association of genotype and phenotype suggest that the analysis of TGFBI gene mutations is important for differential diagnostics of corneal dystrophies.

The methylation status of the FMR1 gene promotor was studied in 8 patients with detected CGG-expansion or negative PCR analysis (CGG-expansion or deletion). In all these causes the methylation status was detected. The modified PCR protocol of Hin6.I-restricted DNA has been proposed for performing diagnosis, postnatal and prenatal diagnostics and for screening patients with mental retardation and newborn boys.

Allelic polymorphism of five microsatellite loci of the human Y chromosome (DYS19, DYS390, DYS391, DYS392, and DYS393) was analyzed in samples of male populations from Ukraine, Russia, and Belarus (152 subjects in total). The allelic diversity indices (Dg) were determined for all loci; they varied from 0.23 to 0.72. The mean values of this parameter in the Ukrainian, Russian, and Belarussian populations were 0.45, 0.47, and 0.52, respectively. A total of 53 different haplotypes were found in 152 subjects from three populations. The most frequent haplotype was found in 14.5% of the subjects, whereas 35 haplotypes (23%) were each found in only one person. The haplotypic diversity index (Dhp) was 0.94. The genetic distances between the populations studied and some populations of Western and Central Europe were estimated. These data were used to construct a phylogram (tree) of genetic similarity between the populations, which demonstrated that the three Eastern Slavic populations are genetically close to one another and remote from Western European populations.

The results of molecular-genetic analysis of 12 mini- and microsatellite loci in populations of different regions of Ukraine (Kiev, Kremenchug, L'vov, Lugansk, and in Crimea tatars) were presented. Allele frequencies for each locus were determined and genetic distances between analyzed populations were calculated. The results of the analysis were applied for investigation of genetic heterogeneity and biological history of populations from different regions of Ukraine.

Results of phenotypical, patho-psychological and molecular-genetic analysis of the 53 probands with clinical features of the fragile X syndrome and 10 female carriers are presented. The clinical heterogeneity, diagnostic criteria, methods of genetic risk estimation, perspectives of prevention of this disease are discussed.

Results of analysis of chimeric SMN genes among some high SMA-risk families from Ukraine using the EcoRV and DdeI restriction enzyme hydrolysis of PCR products is presented. Chimeric cen/telSMN gene was detected in probands with homozygous deletions of telSMN exon 7 only, as well in proband with absent of homozygous deletion of exons 7 and/or 8 of the SMN gene. Effectivity of approach of detection of chimeric SMN genes based on the EcoRV and DdeI restriction enzyme analysis of PCR products and mechanisms of formation of chimeric SMN genes are discussed.

The clinical and genetical characteristics of patients with phenylketonuria in the Crimean population is done in the present work. The comparison of clinical peculiarities of 28 patients, revealed by means of neonatal screening and that of 24 patients, the treatment of which was started late is presented. The prenatal diagnostics of 4 families with high phenylketonuria risk is conducted.

DNA-analysis of some mutation of SMN, dystrophin, FMR1 and PAH genes was performed among 149 high risk families of SMA, DMD, fragile X syndrome and PKU from different regions of Ukraine. The results of analysis of: deletions in the 7th and 8th exons of SMN gene; deletions in muscle-specific promoter region and 15 exons of dystrophin gene; R408W and IVS10nt546 mutations in PAH gene; GGG-expansions in FMR1 gene are presented.

The results of DNA analysis of deletion in exons 7 and 8 of SMN gene, and exon 5 of NAIP gene in 24 SMA-families from Ukraine are presented. Deletions of SMN exons 7 and 8, or 7 were found in 46 (97.9%) of 47 SMA-chromosomes. A homozygous deletion of NAIP exon 5 was demonstrated in 4 (19%) of 21 SMA-families. The authors have demonstrated that in 2 SMA patients with homozygous deletion SMN exon 7 only, the remaining SMN exon 8 was a part of a chimeric CBCD41/SMN gene.

The spontaneous deletion in FMR1 gene in a patient with the typical Fragile X phenotype was described. It was assumed that this deletion is located around CGG region in Pst1 fragment of the gene. The alleles with normal range of CGG copies and corresponding to premutation and full mutation ranges were revealed in mother-mosaic of proband. The possible mechanisms of trinucleotide repeat sequence instability are discussed.

The allelic variation of the hypervariable locus from 3'-untranslated region of apolipoprotein B gene in healthy volunteers from different regions of Ukraine was analysed. Among 396 DNA samples studied, 13 allelic variants were identified with the number of repeats ranging from 29 to 53. The frequency of alleles varied from 0.0013 to 0.3575 with the mean heterozygosity index 77.9%. The investigation of the genetic differences between 4 populations of different regions of Ukraine has been performed. A high level of the polymorphism and a heterozygosity index of APOB locus allow to recommend this polymorphic system as an informative marker for study of genetic structure population and to forensic medical analysis.

Seven mutations in CFTR gene have been screened in patients with cystic fibrosis from Ukraine. The frequency of major mutation delF508 among patients and healthy donors from different regions was studied. Data of age, origin and possible ways of spreading of this mutation in Ukraine have been discussing.

The genetic heterogeneity of populations of different regions of Ukraine was studied using four polymorphic LNA sequences (GTAA-tandem repeats from the 3'-untranslated region of the dystrophin gene, the polymorphic systems pERT87-15--BamHI, pERT8718--TaqI, and pERT87-15--XmnI of the pERT locus of human chromosome X). We analyzed 500 DNA samples of healthy donors from the Kiev, Lvov, Poltava, and Lugansk regions. The above-mentioned polymorphic DNA sequences were used as markers to determine genetic distances between the regional populations of Ukraine. The data obtained indicate the existence of significant genetic differences among the regional populations of Ukraine. DNA polymorphism in the pERT87-8--TaqI system contributes the most significantly to these differences.

Mutations in the CFTR gene have been screened in 110 families from Ukraine with high risk of cystic fibrosis. Deletion F508 was found in 121 (55%) of 220 CF alleles. Among the rest mutant alleles (with the absence of delta F508) six other mutations occurring in the 7th, 10th, 11th exons of the CFTR gene were screened. In this way, 5 CF alleles may be characterized: 1 allele with R334W (the 7th exon) 1 with 1677 delTa (the 10th exon), 1 allele with G551D and 2 alleles with R553X (the 11th exon). We have screened 865 healthy donors for F508 from different regions of Ukraine. The frequency of heterozygous carriers in different regions ranged from 1:28 to 1:170. Strong linkage imbalance was found between polymorphic markers of 4 bp tandem repeats from the 3'-end of the sixth intron in the CFTR gene and deletion F508.

DNA analysis of deletions within 14 exons and promoter region of dystrophin gene was performed in 34 Ukrainian families with high risk of muscular Duchenne dystrophy. The presence of dystrophin gene deletions in different exons was found clustering near central part of dystrophin gene. The necessity of DNA analysis of mutations in dystrophin gene and its use for screening and prenatal diagnosis of muscular Duchenne dystrophy is under discussion.

The results of comparative RFLP analysis in some DNA loci of chromosome 7 in the populations of different Ukrainian regions are presented. Significant differences in RFLP-genotype distributions among regional populations are found. The role of different genetical processes which take place in the populations of different regions of the Ukraine is under discussion.

RELP analysis of DNA loci MET, D7S8 and D7S23 was carried out in Leningrad population and partially in populations of Moscow, Azerbaijan, Ukraine, Buryatia as well as in individuals from high risk families and in cystic fibrosis (CF) patients by means of blot hybridization and polymerase chain reaction. Allelic polymorphism of all loci studied in these three groups was found to be quite similar to that in the North-Western Europe and in whites of the North America. Linkage disequilibrium of the alleles studied with the CF gene was especially pronounced for alleles of the D7S23 locus and gradually decreases from KM-19 through CS-7 to XV-2c DNA probes. The data witness genetic homogeneity of the CF mutation in European populations of the USSR and its similarity to this mutation in Western Europe. The significance of these data for potential diagnosis of CF and for heterozygous carrier detection is discussed.

The purpose of the study was to evaluate the effectiveness of RF-hyperthermia and regional intraarterial hyperglycemia as adjuvant radiotherapy vs conventional radiotherapy of advanced head and neck cancers. Altogether 115 patients with advanced T3-T-4 carcinoma of the tongue, oral cavity and oropharynx underwent external radiotherapy (Co-60). An RF capacitative heating device operating at 40.68 MHz was employed twice a week, a total of 4 sessions per patient. Intratumor temperature was 41.5-43 degrees C. Hyperglycemia was performed via the branches of the carotid artery, a total of 3 sessions per patient. There were 4 groups (1-31 patients on conventional radiotherapy; 2-24 patients on thermoradiotherapy; 3-30 patients on radiotherapy plus regional hyperglycemia; 4-30 patients underwent combined radio-modification). A complete response was 29% for conventional radiotherapy, 67% for thermoradiotherapy, 60% for radiotherapy plus hyperglycemia, and 77% for combined radio-modification. A 2-year local control was found to be 13% for radiotherapy, 37% for thermoradiotherapy, 17% for radiotherapy plus hyperglycemia, and 35% for combined radio-modification. Only hyperthermia was found to improve a 2-year local control of advanced oropharyngeal cancer.

The method of specific DNA amplification was used to study the polymorphism of the length of restriction fragment in the system CS-7 and KM-19 locus D7S23 in the family C. It is shown that cohesion of alleles A2 and B2 with mutation of mucoviscidosis and presence of a mucoviscidosis gene occurred in a healthy sibling. The family C, is prospective for prenatal diagnosis of mucoviscidosis by the method of specific DNA amplification in the system KM-19 restrictase Pst-1 and CS-7-Hinf-6-1.

The authors had 41 patients with chronic pain syndromes which had formed after injuries or diseases of the nervous system. Previously conducted nonoperative treatment and operations on the focus of affection and the peripheral sensory neuron failed to produce the desirable pain-relieving effect. Sixty-five surgical interventions were carried out on the pain-conducting tracts of the spinal cord by an open or closed approach (uni- and bilateral chordotomy, commissurotomy, posterior longitudinal myelotomy, coagulation of the posterior root entry zones, percutaneous chordotomy, percutaneous rhizotomy). Microsurgical techniques, stereotaxic manipulations, refined instruments were used. With strict consideration for the indications for the operation and their differentiated fulfillment favourable results were produced in most cases, in 83% in the immediate postoperative period and in 75% of cases in the long-term period.

A trauma of the brain has been found to be regularly attended by the development of anticerebral antibodies. The frequency with which the anticerebral autoantibodies circulating in the blood stream are detected and their titre depend upon the extent to which the brain matter has been damaged. Positive reactions with the cerebral antigen become apparent habitually by the end of the 1st post-traumatic week and continue to be present in the majority of patients till their discharge from the hospital and in cases of more severe injuries-even for a much longer time. Earlier and more distinct formation of anticerebral antibodies found in patients with a repeated cerebro-cranial injury bears evidence to sensitization of the organism with the cerebral tissue antigens.

An allogeneic cerebral dura mater prepared under nonsterile conditions will become fully sterilized after 48 hours of storage in a 0.75% formalin solution. The long-term (up to 3 years) conservation of this tissue in the above mentioned solution preserves it in a condition permitting transplantation. The experimental transplantation of such tissue results in making the subdural space airtight. This occurs primarily because of the adhesion of the edges of the donor and recipients dura mater in the area of the defect as a result of aseptic inflammation with subsequent resolution and replacement of the transplant with the connective tissue of a similar structure with the dura mater.

ECG changes after a session of regional intraarterial hyperglycemia (RIH) in 13 patients (the mean age of 49 years) with locally advanced cancer of the tongue, oral mucosa and oropharynx were presented. The time course of ECG resulted from a noticeable decrease in the T wave amplitude or a shift of the ST-T segment below the isoline. The results of quantitative ECG changes were the following. The area of the R, AVR, AVF wave and QRS, AVR, AVF complex was decreased. Besides, a significant diversity of changes of the area of ST-T segment, its increase in AVR and AVF and decrease in the V2 leads were noted in this group of patients. Taking into account the mean age of patients and the negative ECG time course after a RIH session, the necessity of patients' examination (including ECG after a RIH session and, when indicated, a consultation by a cardiologist) was emphasized.