[The effectiveness of rinorin introduced in the combined treatment of chronic adenoiditis in the children].

This study was designed to analyse the effectiveness of combined treatment of chronic adenoiditis in the children with the use of rinorin (Orion, Finland) in comparison with the traditional methods for the management of this condition either combined with irrigation therapy or without it. The results of the study indicate that the application of rinorin enhance the effectiveness of the treatment due to the substantial reduction of the manifestation of clinical symptoms and the frequency of relapses. The patients describe rinorin as a modern convenient-to-use preparation superior to the traditional medicines for the treatment of adenoiditis which improved medication compliance.

Divergent clinical and neuropathological phenotype in a Gerstmann-Sträussler-Scheinker P102L family.

OBJECTIVES: Gerstmann-Sträussler-Scheinker syndrome belongs to the genetic prion diseases being associated with mutations in the prion protein gene (PRNP). The most common is the point mutation at codon 102, leading to the substitution of proline to leucine (P102L). Previous reports have indicated a phenotypic heterogeneity among individuals with this mutation. Here, we describe the clinical and pathological phenotype in members of the first Finnish kindred with the P102L mutation in the PNRP gene. MATERIALS AND METHODS: Genetic and clinical information was available in five members of a family, while a systematic histologic and immunohistochemical assessment of the post-mortem brain was carried out in three. RESULTS: Clinical presentation, disease duration and the clinical phenotype (ataxia vs dementia) varied between patients. There was a significant correlation between clinical symptoms and the neuroanatomical distribution of prion protein-immunoreactive aggregates, i.e. subtentorial predominance in ataxia vs cortical predominance in dementia. A significant concomitant Alzheimer is disease-related pathology was observed in the brain of one patient with dementia as onset symptom. CONCLUSIONS: This is the first Scandinavian family carrying the P102L mutation in the PRNP gene. Gerstmann-Sträussler-Scheinker syndrome should be considered in the differential diagnosis when handling with patients with ataxia and/or dementia of unclear aetiology.

The alpha11beta1 integrin has a mechanistic role in control of interstitial fluid pressure and edema formation in inflammation.

OBJECTIVE: Collagen-binding integrins may be involved in controlling interstitial fluid pressure (Pif), transcapillary fluid flux, and tissue fluid volume. Our aim was to explore whether the newly discovered collagen binding alpha11beta1 integrin has a mechanistic role in inflammatory edema formation. METHODS AND RESULTS: In collagen matrices seeded with a mixture of mast cells and fibroblasts, fibroblasts lacking the alpha11 integrin subunit (alpha11(-/-)) contracted collagen gels less efficiently than control fibroblasts, suggesting that the alpha11beta1 integrin is able to mediate tensile force in connective tissues. In alpha11(-/-) mice, control Pif in skin did not differ from the pressure found in wild-type mice. Whereas a reduction in Pif was found in control mice after inducing inflammation, thereby contributing to fluid extravasation and edema formation, such a reduction was not seen in alpha11(-/-) mice. That this effect is mediated through the extracellular compartment is suggested by a similar plasma protein extravasation ratio in alpha11(-/-) and wild-type mice. CONCLUSIONS: Our data suggest that alpha11beta1 integrins on dermal fibroblasts mediate collagen lattice remodeling and have a mechanistic role in controlling Pif in inflammation and thereby fluid extravasation and edema formation in vivo.

Physiology and pathology of collagen receptors.

Just before the transition from pre-genomic to the post-genomic era, the two latest members of the mammalian integrin family were identified. These integrins, which were named alpha10beta1 and alpha11beta1, are both collagen receptors and are related. Rather than being twins, they can be regarded as close cousins. They both belong to the subfamily of integrins that contain an I-domain in the alpha subunit. This domain is also the part that endows these integrins with the capacity to bind the GFOGER sequence in collagens. In the current review, we summarize and update the current knowledge about the in vitro and in vivo functions of these integrins.

[Effects of ACE inhibitor fosinopril on a 24-h profile of arterial pressure in hypertensive patients with obesity and hypercholesterolemia].

AIM: To study effects of fosinopril on a 24-h profile of blood pressure (BP) in hypertensive patients with obesity and hypercholesterolemia. MATERIAL AND METHODS: A randomized comparative trial enrolled 96 patients aged 30-50 years with arterial hypertension (AH) of the first and second degree. The patients were randomized into 2 groups by age, gender, AH duration, office AP, body mass index, cholesterol level. The patients of group 1 received fosinopril (monopril) in a single daily dose 10 mg with further rise to 20 mg. The patients of group 2 were given metoprolol twice a day in a dose 25 mg with further rise to 75 mg. Examination of the patients was made before the treatment and after 16 weeks of therapy with fosinopril and metoprolol. RESULTS: A 16-week therapy with fosinopril resulted in lowering of office BP, mean day systolic, diastolic, pulse BP. The profile of SBP improved: the number of "dippers" with an adequate day profile of BP rose. Fosinopril significantly reduced left ventricular myocardial mass (LVMM) and myocardial mass index. Metoprolol had the same hypotensive action but had no effect on mean 24-h pulse and mean BP, LVMM, LVMM index. CONCLUSION: Fosinopril is more effective than metoprolol in relation to a 24-h profile of BP and LVMM reduction.

[Analysis of deletion mutations in the PARK2 gene in idiopathic Parkinson's disease]. / Analiz deletsionnykh mutatsii v gene PARK2 u bol'nykh idiopaticheskoi formoi bolezni Parkinsona.

A method for analysis of deletions and duplications of individual exons and groups of exons in the parkin gene (PARK2) in both homozygous and heterozygous states has been developed. The method is based on semiquantitative polymerase chain reaction (PCR). The method has been used for analysis of the frequency of deletions in gene PARK2 in patients with idiopathic Parkinson's disease from Bashkortostan. Two unrelated patients have been found to carry a deletion of the 12th (last) exon of gene PARK2. Possibly, this deletion has caused the disease in the given patients.

[Analysis of the allele polymorphism of (CTG)n and (GAG)n triplet repeats in DM, DRPLA, and SCA1 genes in various populations of Russia]. / Analiz allel'nogo polimorfizma tripletnykh povtorov (CTG)n i (GAG)n v genakh DM, DRPLA i SCA1 v razlichnykh populiatsiiakh Rossii.

Polymorphism of highly polymorphic triplet repeats CTG of the 3'-untranslated region of the myotonin protein kinase gene and CAG of the genes associated with dentatorobral-pallidoluysian atrophy (DRPLA, or Hew River syndrome) and spinocerebellar ataxia type 1 (SCA1) was analyzed in several ethnic populations of Russia. A difference in allele spectra of the three genes was demonstrated for populations differing in ethnic origin.

[CTG-repeat analysis of myotonin protein kinase gene in Bashkortostan patients with myotonic dystrophy]. / Analiz CTG-povtorov gena miotoninproteinkinazy u bol'nykh miotonicheskoi distrofiei iz Bashkortostana.

A DNA analysis of 72 patients from Bashkortostan clinically diagnosed with myotonic dystrophy and 54 their family members was conducted. CTG-repeat expansion in the myotonin proteinkinase gene was found in 67 (92%) patients and 12 their relatives without clinical symptoms of the disease at the moment of examination. A correlation between the most distinct clinical symptoms and CTG-repeat number has been studied. A CTG-repeat expansion in generations was compared to that in sib pairs with myotonic dystrophy. In 17.6% of the cases, CTG-repeat number decreased in the following generations and in 11.7% it did not change, the percentages being higher than those described elsewhere. In general, anticipation phenomenon was confirmed for CTG-repeat in myotonin proteinkinase gene.

[Polymorphism of glutathione S-transferases M1 and T1 in several populations of Russia]. / Polimorfizm glutation-S-transferaz M1 i T1 v riade populiatsii Rossii.

Frequencies of the wild-type and null genotypes of the GSTM1 and GSTT1 genes were established in healthy donors from several Russian populations (ethnic Russians from the towns of Oshevensk and Kholmogory, Arkhangel'sk oblast; ethnic Khants; ethnic Kalmyks; and ethnic Buryats) in order to identify the ethnic group with the maximal frequency of the null genotype. The highest frequency of individuals with the null genotype of both genes was observed in the Kalmyk and Buryat populations. The results may be used to study the effect of climatic and ecological conditions on multifactorial disease incidence in populations.

Polymorphism of trinucleotide repeats in loci DM, DRPLA and SCA1 in East European populations.

A normal polymorphism at three triplet repeat loci (myotonic dystrophy (DM), dentatorubral-pallidoluysian atrophy (DRPLA) and spinocerebellar ataxia type 1 (SCA1)) were examined in healthy unrelated individuals from the Siberian Yakut (Mongoloid) population, the Adygei (Caucasian) population and nine East European populations: populations from Russia (Holmogory, Oshevensk, Kursk, Novgorod, Udmurts, Bashkir), two Ukrainian populations (Lviv and Alchevsk) and one Belarussian. The distribution of alleles for DRPLA and SCA1 were similar for all East-European populations. For the DM locus, East European populations had typical allele distribution profiles with two modes, (CTG)5 and (CTG)11-14, but some differences were found for the Bashkir population where alleles containing 11-14 CTG repeats had relatively higher frequency. The Yakut population had different allele spectra for all types of repeats studied. Higher heterozygosity levels and insignificant differences between expected and observed heterozygosity were found for all tested loci. The latter led us to suggest that the trinucleotide repeat loci analysed are not influenced by selection factors and could be useful for genetic relationship investigations in different populations.

[Expansion and mutation rate in CTG repeats in the myotonic dystrophy gene]. / Izuchenie ékspansii i chastoty mutirovania CTG-povtorov gena miotonicheskoi distrofii.

The CTG repeat of the myotonic dystrophy (MD) gene was analyzed in 62 MD patients and 54 healthy members of their families. A CTG repeat expansion was revealed in 57 (92%) patients and in 12 relatives who did not express clinical signs of MD. Family analysis showed that the CTG repeat number increased, which was associated with anticipation, decreased, or remained the same (17.6%) in alleles transmitted from parents to their children. The spontaneous mutation rate of the CTG repeat was estimated at 4 x 10(-2). Instability was characteristic of alleles with more than 19 repeated units.

[Molecular-genetic analysis of torsion dystonia in Russia]. / Molekuliarno-geneticheskii analiz torsionnoi distonii v Rossii

For the first time in Russia, analysis of the GCH-I and DYT1 genes was carried out for the purpose of direct DNA diagnostics in families with various forms of hereditary torsion dystonia (TD). Four new missense mutations (Met102Lys, Thr94Lys, Cys141Trp, and Ser176Thr) in the GCH-I gene were found in patients with dopa-responsive dystonia (DRD), testifying to a genetic heterogeneity of this clinical form of TD. The distribution of the major del GAG mutation in exon 5 of the DYT1 gene was studied in patients with non-dopa-responsive dystonia (NDRD). In total, the mutation was found in 68% of the patients. The frequency of this mutation in Ashkenazi Jews with NDRD was 100% (twice higher than in Slavonic families), suggesting the founder effect reported for NDRD in this ethnic group. Mutations of the GCH-I and DYT1 genes were also found in patients with atypical and questionable cases of TD, which are difficult to diagnose with methods other than DNA analysis. The data obtained made it possible to extend the spectrum of clinical signs of DRD and NDRD and to revise the views on true penetrance of the corresponding mutant genes, which is important for medical genetic counseling in affected families.

[Normal polymorphism of the (CTG)n repeat in the myotonin protein kinase (DM) gene on chromosome 19q13.3 in Western European populations]. / Normal'nyi polimorfizm povtora (CTG)n v gene miotoninproteinkinazy (DM) na khromosome 19q13.3 v populiatsiiakh vostochnoi evropy.

Polymorphism of a highly polymorphic CTG repeat in the 3'-untranslated region of the myotonin protein kinase gene was analyzed in healthy people from several Eastern European populations (Russians, Moldovans, Belarussians, Komis, Chuvashes, Udmurts, Bashkirs, Tatars, Maris, and Mordovians). In total, 26 alleles of the CTG repeat were found, the repeat number ranging from 5 to 33 (alleles with six and seven repeats were not detected). The heterozygosity of individual populations varied from 61 to 91%. In the total sample combining all populations, the observed and expected heterozygosities did not differ (fixation index -0.0022) suggesting selective neutrality of the normal polymorphism of the CTG repeat in the myotonin protein kinase gene.

[Analysis of expansion of the triplet repeat (CTG)n in myotonic dystrophy patients from Bashkir]. / Analiz ékspansii tripletnogo povtora (CTG)n u bol'nykh miotonicheskoi distrofiei iz Bashkiri.

A method was elaborated for simple and rapid diagnosis of myotonic dystrophy (MD). The method consists in estimating expansion of the CTG repeat in the myotonin protein kinase gene by means of PCR amplification of a gene fragment from genomic DNA and Southern hybridization of the amplified fragments with probe (CTG)9. Bashkir patients with Rossolimo-Steinert-Batten-Kurshmann MD were examined with this method.

[Analysis of polymorphism of CTG repetitive sequences in the gene of myotonic dystrophy in human populations of the Volga-Ural region]. / Analiz polimorfizma CTG-povtorov v gene miotonicheskoi distrofii v populiatsiiakh narodov Volgo-Ural'skogo regiona.

Distribution of CTG repetitive sequences in the myotonic dystrophy (MD) gene was analyzed in ten populations of the Volga-Ural region, including Tatars, Chuvashes, Maris, Udmurts, Mordovians, Komis, and four ethnogeographical groups of Bashkirs. A total of 25 alleles were found (9 to 14 in individual populations), with each allele containing 5 to 34 trinucleotide repeats. The allele frequency distribution had two peaks corresponding to alleles with 5 and 11-14 CTG repeats. The frequency of the (CTG)5 allele varied from 0.23 to 0.47 in Maris and Mordovians, respectively. Regarding the (CTG)11-14 alleles, those containing 13 and 12 trinucleotides were most frequent in all populations; their frequencies varied from 0.15 in Mordovians to 0.24 in Maris and Bashkirs from the Abzelilovskii raion (district). Alleles with large numbers of repeats (more than 30) were only found in Tatars and Bashkirs from the Abzelilovskii raion, where their frequency was 0.01. The data obtained were compared with those on other human populations from various regions of the world. In general, the populations of the Volga-Ural region took an intermediate position between European and Asian populations (although were somewhat more similar to the latter ones) with respect to the distribution of allelic frequencies of the CTG repetitive sequences. In individual populations, the number of genotypes varied from 13 to 27 in Mordovians and Bashkirs from the Ilishevskii raion, respectively. The observed heterozygosity was the highest (91%) in Udmurts and the lowest (58%) in Mordovians; the average heterozygosity was 81%. Such a high heterozygosity, as well as the revealed differentiation of the populations with respect to the distribution of the allelic frequencies of CTG repetitive sequences in the MD gene, allow this polymorphic DNA locus to be considered a highly informative genetic marker of populations.

[Polymorphism of the (CTG)n repeat in the myotonin protein kinase (DM) gene in Belarussian populations: analysis of interethnic heterogeneity]. / Polimorfizm povtora (CTG)n v gene miotoninproteinkinazy (DM) v populiatsiiakh belorusov: analiz vnutriétnicheskoi geterogennosti.

The highly polymorphic CTG triplet repeat in the 3'-nontranscribed region of the myotonin protein kinase (DM) gene was studied in healthy people from three rural populations (Grodnenskii, Khoinikskii, and Nesvizhskii raions) and the town Bobruisk, Belarus. The allele frequency distribution of this repeat proved to be similar in all the regional groups of Belarussians.

A novel mutation in the GTP cyclohydrolase I gene associated with a broad range of clinical presentations in a family with autosomal dominant dopa-responsive dystonia.

We examined a large family of Ashkenazi Jewish origin with autosomal dominant dopa-responsive dystonia (DRD). Mutation analysis of the GTP cyclohydrolase I gene revealed in affected members a novel point mutation (a C/A change in exon 1) resulting in a threonine-to-lysine substitution at residue 94. The mutation was characterized by variable expressivity and was associated with either a 'classical' DRD phenotype or various atypical phenotypes, such as subtle transitory equinovarus postures of the feet or isolated hand tremor. This observation demonstrates the significance of the molecular testing in establishing the clinical diagnosis of DRD.

[PCR analysis of microsatellite DNA markers: possibility of erroneous determination of genotypes]. / PTsR-analiz mikrosatellitnykh DNK markerov: vozmozhnost' oshibochnogo opredeleniia genotipov.

A comparative study of two techniques for the PCR genotyping of highly polymorphic tandem repeats was carried out by the example of a triplet repeat in the myotonin protein kinase gene. Sequencing denaturing gels were shown to yield more precise results in the analysis of amplification products.

The GTP cyclohydrolase I gene in Russian families with dopa-responsive dystonia.

OBJECTIVE: To search for mutations in the GTP cyclohydrolase I (GCH-I) gene in a set of Russian families with dopa-responsive dystonia (DRD). DESIGN: Six large families with 54 affected family members and 2 patients with sporadic DRD were examined. Mutation screening was performed using single-strand conformation polymorphism analysis followed by direct sequencing of the presumably mutated exons, in patients whose results showed a normal pattern on single-strand conformation polymorphism analysis, the entire coding region of the GCH-I gene was sequenced. RESULTS: Three new heterozygote point mutations located within exons 1, 2, and 4 of the GCH-I gene were identified in 3 families with autosomal-dominant inheritance. All these mutations are predicted to cause amino acid changes in the highly conserved regions of the gene. In patients from 3 other families and in both patients with sporadic DRD, no alterations in the translated portion of the GCH-I gene were observed. CONCLUSIONS: Mutations in the coding region of the GCH-I gene account for a significant fraction (up to half) of the patients with a typical clinical picture of DRD. None of the mutations in the GCH-I gene described so far were detected more than once, which precludes the possibility of creating simple DNA testing procedures for routine clinical practice.