PASylation technology improves recombinant interferon-β1b solubility, stability, and biological activity.

Recombinant interferon-β1b (IFN-β1b) is an effective remedy against multiple sclerosis and other diseases. However, use of small polypeptide (molecular weight is around 18.5 kDa) is limited due to poor solubility, stability, and short half-life in systemic circulation.

[Value of allele gene polymorphism of the inflammation system for prognosis of patients with myocardial infarction].

In recent years levels of a number of inflammatory markers namely C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF) etc. are measured for the purpose of postinfarction risk evaluation. Dynamics of inflammatory markers concentrations can reflect processes occurring in atherosclerotic plaque and coronary arteries.

Family Analysis of Linkage and Association of HLA-DRB1, CTLA4, TGFB1, IL4, CCR5, RANTES, MMP9 and TIMP1 Gene Polymorphisms with Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS). Proteins of the immune system, as well as proteins that are involved in the infiltration of activated immune cells in the CNS, play an important role in the pathogenesis of MS. We investigated the association and linkage with MS of the following immune-system genes polymorphisms: HLA-DRB1,CTLA4,TGFB1,IL4,CCR5 andRANTES, as well as of the matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase  1 (TIMP1) genes polymorphisms.

[Polymorphism C1444T of C-reactive protein gene and C-reactive protein concentration in blood serum of healthy people and patients with myocardial infarction].

Unlabelled: CRP level is a risk factor of development of ischemic heart disease (IHD) and acute myocardial infarction (MI) in healthy people, while in patients with cardiovascular diseases it is a marker of unfavorable prognosis. It has been shown in recent investigations that individual variations of plasma CRP levels to a great extent are genetically determined. These data constitute a basis for the study of associations of polymorphic variants of the CRP gene with risk of MI in healthy people as well as with unfavorable prognosis in IHD patients.

[Analysis of linkage and association of alleles of proinflammatory cytokines genes IL-6, IFNg and TNF with multiple sclerosis using transmission disequilibrium test (TDT)].

Proinflammatory cytokines Interleukin-6 (IL-6), Interferon-gamma (IFNg) and Tumor necrosis factor (TNF) are known as participants of inflammation and play an important role in pathogenesis of multiple sclerosis (MS). Based on literature data about influence of SNPs G(-308)A of TNF gene, A(+874)T of IFNG gene and G(-174)C of IL-6 gene on production of these cytokines, we investigated association of these polymorphic sites with MS. Linkage and association of alleles of these genes with MS was analyzed by transmission disequilibrium test (TDT).

[Complex analsis of association of inflammation genes with myocardial infarction].

Carriage frequencies of alleles and genotypes of functionally important polymorphous loci of some inflammation genes: proinflammatory cytokines genes IL-6, LTA and TNF, anti-inflammatory cytokine gene TGFB1 and CC chemokine receptor 5 gene CCR5 were analyzed in the patients with myocardial infarction (MI) of Russian ethnic descent (199 cases) and in the control group of the same ethnic descent (142 controls). Complex analysis using APSampler algorithm revealed MI association with carriage of all polymorphous variants studied, as individual risk factors (insertion/deletion polymorphism of CCR5 and SNP G252A LTA) or only in combination with other alleles/genotypes. Carriage of bi- or triallelic combinations was associated with MI more significantly than carriage of any their subsets: single alleles or allele pairs.

[Complex analysis of genetic predisposition to ischemic stroke in Russians].

Carriage frequencies of alleles and genotypes of 10 functionally important single nucleotide polymorphisms that are located in genes FGA, FGB, APOE, LPL, ACE and CMA1 were analyzed in the ischemic stroke (IS) patients of Russian ethnic descent and in the control group of the same ethnic descent and of similar gender and age. Comparison between patients and control group revealed no significant differences in frequencies of individual alleles and genotypes for all the polymorphic loci studied. However, complex analysis of genetic predisposition using APSampler algorithm revealed carriage of allele (-491A) APOE as a predisposing factor for IS (p = 0.

[Genetic predisposition to multiple sclerosis as a polygenic autoimmune disease].

Unrelated patients with definite multiple sclerosis (MS) and healthy controls of Russian descent were genotyped at 16 polymorphic loci of the DRB1, TNF, LTa, TGFb1, CCR5 and CTLA4 genes and TNFa and TNFb microsatellites. The association of allelic variants with MS (p<0,01) was studied using the case-control method with the PSampler algorithm recently developed by our group. The previously described DRB1*15(2) allele, the TNFa9 allele and the biallelic combination (CCR5d32,DRB1*04) were reidentified as MS-associated in Russians.

[Polymorphism of APOE gene and risk of development of the multiple sclerosis at ethnic Russians].

The multiple sclerosis is a complex disease of the central nervous system with the pronounced hereditary predisposition. The purpose of our research consisted in acknowledgement of the assumption on importance of apolipoprotein E gene (APOE) polymorphism in exon 4 in development of the multiple sclerosis in ethnic Russians. Research was lead on the samples independently collected in Moscow (106 patients and 189 persons of control group), Sverdlovsk area (54 and 109, accordingly) and republic Bashkortostan (119 and 285, accordingly).

[Comparative genetic analysis of different forms of low-renin arterial hypertension].

High level of clinical and genetic heterogeneity is a characteristic of arterial hypertension (AH) that is one of the most wide-spread cardiovascular diseases. In most cases (excluding a few monogenic forms), AH is a polygenic disease and genes of renin-angiotensin-aldosterone system play an important role in AH predisposition. 20-25% AH cases occur during low activity of renin in blood plasma (low-renin form of AH) while aldosterone production can be increased (hyperaldosteronism, HA) or normal.

[Contribution of CYP11B2, REN and AGT genes in genetic predisposition to arterial hypertension associated with hyperaldosteronism].

We carried out comparison of distribution of alleles and genotypes of polymorphic loci of renin-angiotensin-aldosterone system genes: CYP11B2 (C-344T), AGT (Thr174Met) and REN (C-5434T, C-5312T, and A BglI G) and their combinations in two groups of patients with low renin forms of arterial hypertension (AH). Group 1 included 59 patients with low renin hyperaldosteronism (HA) at the background of glomerular zone adenoma and hyperplasia of adrenal cortex. Group 2 included 28 patients with low renin hypertensive disease characterized by normal level of aldosterone.

[The beta-fibrinogen gene polymorphism, fibrinogen level and platelet aggregation in patients with ischemic stroke].

We examined an association of the C-148T beta-fibrinogen gene polymorphism with fibrinogen level and platelet aggregation in patients with ischemic stroke and in people with vascular risk factors but no ischemic stroke. Among stroke patients, carriers of an -148T allele had significantly higher plasma fibrinogen level and platelet aggregation to norepinephrin compared to the C/C homozygotes. No significant differences in frequencies of a C-148 allele between stroke patients and controls were observed.

Polymorphism of apolipoprotein E (APOE) and lipoprotein lipase (LPL) genes and ischaemic stroke in individuals of Yakut ethnicity.

There is evidence that most forms of ischaemic stroke (IS) result from synergistic effects of the modifiable predisposing factors and multiple genes. In the present work, we report results of case-control study of IS association with apolipoprotein E gene (APOE) (promoter and coding polymorphisms) and lipoprotein lipase gene (LPL) (presence/absence of a HindIII cutting site). We studied 107 unrelated patients of Yakut ethnicity (69 men and 38 women, mean age 58.

Three allele combinations associated with multiple sclerosis.

Background: Multiple sclerosis (MS) is an immune-mediated disease of polygenic etiology. Dissection of its genetic background is a complex problem, because of the combinatorial possibilities of gene-gene interactions. As genotyping methods improve throughput, approaches that can explore multigene interactions appropriately should lead to improved understanding of MS.

[Association of polymorphisms in SULT1A1 and UGT1A1 Genes with breast cancer risk and phenotypes in Russian women].

Estrogens are critical for breast cancer initiation and development. Sulfotransferase 1A1 (SULT1A1) and UDP-glucuronosyltransferase 1A1 (UGT1A1) conjugate and inactivate both estrogens and their metabolites, thus preventing estrogen-mediated mitosis and mutagenesis. SULT1A1 and UGT1A1 genes are both polymorphic, and different alleles encode functionally different allozymes.

A Markov chain Monte Carlo technique for identification of combinations of allelic variants underlying complex diseases in humans.

In recent years, the number of studies focusing on the genetic basis of common disorders with a complex mode of inheritance, in which multiple genes of small effect are involved, has been steadily increasing. An improved methodology to identify the cumulative contribution of several polymorphous genes would accelerate our understanding of their importance in disease susceptibility and our ability to develop new treatments. A critical bottleneck is the inability of standard statistical approaches, developed for relatively modest predictor sets, to achieve power in the face of the enormous growth in our knowledge of genomics.

[Extent and location of lesions in aorta and its main branches in patients with nonspecific aortoarteritis with various genotypes in the region of major histocompatibility complex].

Aim: To elucidate associations between location and extent of lesions of arterial vascular bed in patients with nonspecific aortoarteritis and presence of various alleles of DRB1 gene of HLA class II in patients of Russian ethnicity.

Material And Methods: Ultrasonography, magnetic resonance imaging and computed tomography were used for examination of arteries in 25 patients aged 22-69 years. Genotyping of HLA-DRB1 locus was carried out in all patients and in a group of practically healthy subjects of the same ethnic group (controls).

Prevention of experimental autoimmune encephalomyelitis in DA rats by grafting primary skin fibroblasts engineered to express transforming growth factor-beta1.

To determine whether primary fibroblasts producing latent transforming growth factor beta1 (TGF-beta1) are capable of down-regulating experimental autoimmune encephalomyelitis (EAE), a retroviral vector TGF-beta1-pBabe-neo (-5'UTR) was used for efficient gene transfer into primary skin fibroblasts of DA rats. After heat activation, conditioned medium from the transduced fibroblasts was found to inhibit significantly in vitro proliferation of lymphocytes from lymph nodes of DA rats with EAE. Intraperitoneal administration of TGF-beta1-transduced fibroblasts into DA rats during the priming phase of EAE resulted in a significant reduction in mortality and in the mean clinical and EAE scores versus the control immunized animals treated with non-transduced fibroblasts.

A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC) system.

Background: Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others.

Results: In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs.

[Polymorphism of length of tetranucleotide repeat from the 5'-side from the myelin basic protein gene in multiple sclerosis in Russians].

The myelin basic protein gene (MBP) can confer the susceptibility to multiple sclerosis, because its protein product is the main protein component of myelin of the central nervous system and a potential autoimmune antigen in the disease. A possible association of multiple sclerosis with alleles and genotypes of a microsatellite repeat (TGGA)n, located to the 5' side from the first exon of MBP in ethnic Russians (126 patients with reliable multiple sclerosis and 142 healthy controls from Central Russia) was analyzed using the case-control method. Upon separation of the tetranucleotide repeat site amplification products in 1.

Myelin basic protein gene is associated with MS in DR4- and DR5-positive Italians and Russians.

Background: The myelin basic protein (MBP) gene may confer genetic susceptibility to multiple sclerosis (MS). The association of MS with alleles of the (TGGA)n variable number tandem repeat (VNTR) 5' to the MBP gene is the subject of conflicting reports.

Objective: To study possible MS association with VNTR alleles of MBP gene in ethnic Italians and ethnic Russians.

[Immunogenetics of optic neuritis in children with multiple sclerosis].

The aim of the work was to study immunogenetic peculiarities of optic neuritis in children with MS. Using PCR-SSP technique genomic typing was performed on HLA DRB1 gene (chromosome 6p21) of 56 unrelated children with ON registered at least once in clinically verified MS. 264 adult MS patients and 328 healthy controls from the same stratum of population were also genotyped.

The chemokine receptor CCR5 deletion mutation is associated with MS in HLA-DR4-positive Russians.

The authors studied the possible association between the presence of a 32-base pair deletion allele in CC chemokine receptor 5 gene [3p21] (CCR5 Delta 32 allele) and the occurrence of MS. The presence of CCR5 Delta 32 homozygotes among patients with MS indicates that the absence of CCR5 did not protect against MS. Moreover, the CCR5 Delta 32 mutation was associated with MS in HLA-DR4-positive Russians (p(corr) < 0.