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Biomedical subjects

O O Favorova

Publications and source records attributed to O O Favorova.

At least 19 recordsLinked to original sources
PubMed2005

[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). RESULTS AND CONCLUSION: Patients compared with controls had significantly higher frequency of class II alleles of HLA-DRB1 gene which corresponded to serological specificity DR1. Subgroup of patients carriers of DR1 allele had significantly less extensive involvement of arterial vasculature compared with subgroup of carriers of other alleles. The revealed clinical-genetic relationship reflects special features of aortoarteritis in Russian population and evidence for genetic heterogeneity of this disease.

Adult↗
PubMed2003

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. METHODS: Two hundred sixty-nine unrelated patients with definite MS and 385 unrelated healthy control subjects from Italy and Russia were genotyped for the MBP VNTR region and for the human leukocyte antigen (HLA) class II DRB1 gene. The phenotype, allele, and genotype frequencies for two groups of MBP alleles were determined. Patients and control subjects were stratified according to HLA-DRB1 phenotypes. RESULTS: The distribution of MBP alleles and genotypes in the two ethnic groups, including both MS patients and control subjects, was very similar. When MS patients and healthy control subjects were stratified according to HLA-DRB1 phenotypes, a significant association of MS with MBP alleles was found only in the DR4- and DR5-positive subgroups. A significant association with MBP alleles was also observed in the nonstratified groups, owing mainly to the contribution of the DR4- and DR5-positive individuals. CONCLUSION: Polymorphism of the MBP or another gene in its vicinity appears to contribute to the etiology of MS for the subgroups of DR4- and DR5-positive Italians and Russians.

Adolescent↗
PubMed2003

[Association between DNA antibodies levels in the blood of patients with multiple sclerosis and clinical presentation of the disease].

Multiple sclerosis (MS) as an autoimmune disease is characterized by occurrence of high titres of antibodies (AB) to cell structures and autoantigens. Various AB-mediated effector mechanisms can participate directly in the pathogenesis of demyelinisation damaging myelin, oligodendrocytes and nervous fibres. Antinuclear AB, including anti-DNA AB are an example of activation of humoral immunity in MS. Pathogenetic and clinical value of these AB is investigated insufficiently. The aim of this study was estimation of the AB titers in MS patients from two populations of Russia in relation to clinical features of MS. Results of examination of 83 patients with definite MS from Novosibirsk and Moscow (49 and 34 patients) are analyzed. Groups of comparison consisted of healthy donors and patients with SLE of the same age. Use of identical methods in the analysis of the data received in two various populations made the data objective as much as possible and revealed the strongest clinico-biochemical associations. Levels of AB to both native and denaturated DNA were studied. Comparison of several test-systems showed that the system produced by "Specialized scientific Labs" Company has the best sensitivity. In two populations of MS patients the levels of AB in plasma were similar and associated between each other, higher than in donors, but lower than in SLE patients. In both groups MS patients with secondary progressive MS had higher percent of samples of plasma with average and high levels of AB. In the Novosibirsk group associations of levels of AB with parameters of disease severety (EDSS and a number of FS scales) were seen. In the Moscow group levels of AB to DNA were significantly associated with time from the disease onset to certain level of disability (EDSS 3); both the analysis of average values and the correlation analysis showed a weak association of AB to DNA level and MS duration. The data testify that AB to DNA play a more important role in MS pathogenesis than was considered earlier. Catalytic AB as a part of anti-DNA AB may play a special role.

Adult↗
PubMed2002

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) < 0.001, odds ratio [OR] = 25.0). The (CCR5 Delta 32,DR4)-positive phenotype was negatively associated with early MS onset (at ages < or = 18 years) (p = 0.0115, OR = 0.1).

Adult↗
PubMed2002

Association and linkage of juvenile MS with HLA-DR2(15) in Russians.

The aim of this study was to determine the role of the HLA-DRB1 gene [6p21] in susceptibility to juvenile MS (JMS) (age at onset < or =15 years) of children of Russian descent. Association of DR2(15) with JMS has been found by the comparison of patients with JMS with both unrelated and affected family-based healthy controls. The linkage of DR2(15) with JMS was shown by transmission disequilibrium test. There were no significant differences in the frequencies of DRB1 alleles and genotypes between 56 patients with JMS and 234 patients with MS with age at onset > or =16 years.

Adolescent↗
PubMed2002

[Multiple sclerosis with early onset: pathogenesis, clinical characteristics, possibilities in the treatment of its pathogenesis].

Early onset multiple sclerosis (MS) has some peculiarities in the disease course. 56 patients with definite MS with the onset at the age under 15 years were included in this clinical, immunogenetical and neurophisiological study. The analyses of the relations between different clinical characteristics of MS in children has shown, that patients with onset under 10 years, had rare relapses, but more progressive development of disability in contrast to the patients with MS onset at the age of 11-15 years. Duration of the first remission was associated with the time to sustained disability in children with MS. The number and volume of MRI T2-positive lesions in the white matter of the brain was associated with the age of onset, duration of the disease and with the number of relapses. In several cases the phenomena of clinical-MRI dissociation was observed. Generic HLA-DRB1 genomic typing was performed in all the patients. High frequency of DR2(15) genotype in MS-affected children in comparison with the group of healthy controls was more expressed as compared with MS-affected adults. The comparison of frequencies of DRB1 alleles in transmitted, i.e. appeared in the affected child haplotypes and in non-transmitted haplotypes confirmed results of the case-control study showing the very significant association of MS with DR2 alleles and extremely significant--with its DR15 subtype in children. The data of transmission/disequilibrium test (TDT) analysis provide strong evidence for linkage of DR15 alleles and susceptibility to sporadic MS in patients with disease onset before 15 years. The positive experience of management (beta-interferon-1a) was shown in MS-affected children in three cases.

Adjuvants, Immunologic↗
PubMed2001

Catalytic heterogeneity of polyclonal DNA-hydrolyzing antibodies from the sera of patients with multiple sclerosis.

Various catalytic antibodies or abzymes have been detected recently in the sera of patients with several autoimmune pathologies, where their presence is most probably associated with autoimmunization. Recently we have shown that DNase activity is associated with IgGs from the sera of patients with multiple sclerosis (MS) but not with those from the sera of normal humans. Here we present evidence showing that MS IgG, its F(ab) fragments, and separated L-chains catalyze DNA hydrolysis. The properties of the DNase activity of these polyclonal IgGs distinguish them from other known human DNases. In addition, their specific activities with different oligonucleotide substrates and the range of optimal pHs, apparent K(M) values and substrate specificities varied widely for different patients. The findings speak in favor of the generation by the immune systems of individual patients of a variety of polyclonal catalytic IgG pools, from relatively small to extremely large ones.

Antibodies, Catalytic↗
PubMed2001

Randomized study of antibodies to IFN-gamma and TNF-alpha in secondary progressive multiple sclerosis.

Studies of cytokines in multiple sclerosis (MS) have shown that immune mechanisms connected with disturbance of the synthesis of cytokines probably play critical roles in the initiation and prolongation of MS. In a double-blind, placebo-controlled trial, 45 patients with active secondary progressive MS were randomized to three groups of 15 patients, each receiving a short course of antibodies to IFN-gamma, to tumor necrosis factor (TNF)-alpha, or a placebo. After 12 months with analysis of disability (Expanded Disability Status Scale scores), accompanied by interval determinations of lymphocyte subpopulations, cytokine production levels, MRI, and evoked potentials, it was found that only patients who received antibodies to IFN-gamma showed statistically significant improvement compared to the placebo group--a significant increase in the number of patients without confirmed disability progression. This was supported by MRI data (a decrease in the number of active lesions) and systemic changes in cytokine status (a decrease in IL-1beta, TNF-alpha, and IFN-gamma concentrations in supernatants of actvated blood cells of these MS patients and an increase in TGF-beta production). Neutralization of IFN-gamma could be a new approach to treating secondary progressive MS. Long-term administration of humanized monoclonal antibodies to IFN-gamma and simultaneous use of antibodies to IFN-gamma together with IFN-beta products are planned.

Animals↗
PubMed2000

Clinico-immunogenetic characteristics of multiple sclerosis with optic neuritis in children.

The frequency of multiple sclerosis (MS) with clinical onset before 16 years of age in different regions of Russia fluctuates from 2 to 10% of all MS patients. One of the most frequent signs of MS manifestation and/or exacerbation at this age is optic neuritis (ON). Forty-seven children with MS were observed in Moscow. Diagnosis of MS in every case was clinically definite and proved by serial MRI. Clinico-tomographic dissociation was noticed: numerous large lesions, typical for MS on T2 images were often seen in children with mild or moderate residual neurological symptoms. All patients had relapsing/remitting MS course, mean EDSS was 2.24+/-0.26. Thirty-eight children (80%) had ON at least once, ten (21.3%) - twice or more times. In several cases ON had subclinical course or might be missed and the damage of the optic nerve with partial atrophy was found only after complex ophthalmological investigation including visual evoked potentials. Thus, the clinical course of MS and ON have some peculiarities in children and may be genetically based. Analyses of allelic polymorphisms of HLA-DR and TNF loci on chromosome 6 was performed. Data from children with MS were compared with data from their parents, healthy controls and other MS patients from the same ethnic group. Children with MS had increased frequency of DR2(15) and TNF-a11, but not TNF-a9 as adult MS patients from the same ethnic group. The presence of TNF-a7, rare in adult patients, could be proposed as a marker of early MS onset.

Adolescent↗
PubMed1999

[The risk factors for the development of multiple sclerosis in the Moscow population. II. The combination of exogenous and hereditary factors].

Simultaneous study of both external and hereditary risk factors of the development of multiple sclerosis (MS) was carried out in Moscow population. As a result of the genotyping of HLA-DR locus on the chromosome 6, there were found markers of the predisposition to MS: by HLA-DR: DR2(15) way, especially, in homozygous heredity and in the absence of such specificity--alleles of DR3 group. The data were confirmed concerning both the elevation of frequency of the alleles of tumor necrosis factor (TNF)a1 and alpha 2 and the decrease of frequency of TNF-alpha 7 allele in MS. There was also confirmed association of the disease with the external factors, such as "predominance of the meat nutrition at the age under 15 years" and "tonsillitis at the age under 15 years". There were two combinations of the external and hereditary factors, when the power of the association increased significantly: "predominance of meat nutrition at the age under 15 years" and DR2(15) and "tonsillitis at the age under 15 years" and DR3. When genetic factors were excluded, the relation of MS with the external factors was considerably reduced; when the external factors were excluded, the association of MS with genetic markers became statistically insignificant. A combination of these external factors, which were the sources for the additional antigenic immunostimulation, with certain genetic factors in DR region suggested the presence of the genetically determined peculiarities of the composition of antigen presentation HLA-DR in the individuals with DR2(15) and DR3. There was no statistically confirmed presence of a combination of the external factors with TNF-alpha alleles which increased additionally MS risk. The presence of immunostimulating antigen-containing external factors may be significant for the influence of TNF-alpha in less degree than for the realization of predisposition in form of the certain composition of HLA molecules.

Adolescent↗
PubMed1998

Polyclonal antibodies from blood and cerebrospinal fluid of patients with multiple sclerosis effectively hydrolyze DNA and RNA.

It is known that in the blood of patients with some autoimmune diseases catalytically active antibodies hydrolyzing proteins, DNA, and RNA may be detected. In the present work homogeneous preparations of IgG antibodies (Ab) possessing high affinity for nucleic acids (NA) were obtained for the first time from blood and cerebrospinal fluid of patients with multiple sclerosis (MS). The fraction of IgG Ab as well as its Fab fragments and isolated light chains of both kappa- and lambda-types were shown to catalyze effectively the hydrolysis of DNA and RNA. It is shown by different methods that the capability for nucleic acid hydrolysis is an intrinsic property of the polyclonal Ab. NA-hydrolyzing Ab were detected in the blood of 69 of 72 and in the cerebrospinal fluid of 5 of 5 examined MS patients, while they were not detected in the blood of any of 50 healthy donors examined. Comparison of relative rates of RNA hydrolysis and of the substrate specificity in hydrolysis of various model RNAs--cCMP, poly(U), poly(A), and poly(C)--revealed pronounced differences of MS antibodies from ribonucleases of human blood, ribonuclease A, and all earlier described abzymes. The abzymes are usually characterized by relatively low specific activities in comparison with that of normal enzymes catalyzing analogous reactions. Ab from the blood of MS patients are the first example of autoabzymes whose specific activity in RNA hydrolysis is comparable or even higher than that of pancreatic ribonuclease A--one of the most active RNA-hydrolyzing enzymes.

Antibodies, Catalytic↗
PubMed1997

[Genetic predisposition factors for multiple sclerosis (based on the data from genotyping patients of the Russian ethnic group)].

Patients' genotyping of Russian ethnic group with multiple sclerosis (MS) was performed for the first time in two loci of the main complex of histocompatibility: in DR HLA class II (gene DRB1) and in the locus of tumor necrosis factors (TNF). There was no difference in the incidence of alleles groups which correlated with some specificity of DR. Meanwhile TNF-a1 and TNF-a9 alleles were encountered significantly more frequently in patients and TNF-a7 in control group. When all the patients and controls examined were divided into groups in dependence on combination of DR and TNF it was found that relations observed between MS and TNF-a7 and TNF-a9 alleles were displayed much more in individuals which carried alleles of gene DRB1, corresponding to DR15 specificity. These are alleles which are known as the main risk factor of MS in Caucasians. The patients with "protective" TNF-a7 allele were characterized by more favorable course of the disease. Thus highly significant genetic markers were revealed for the first time in region of TNF genes which were associated with increased or decreased risk of MS development at least in Russian ethnic group. There was also possibility of their interaction with group of DR15 alleles of DRB1 gene. One of the markers revealed (TNF-a7) occurred to be bound both with decreased risk of MS and with favorable clinical course, which was observed for genetic markers of MS for the first time. Manifestation of one or another property of TNF-a7 marker depends on the presence of alleles of DRB1 gene which corresponds to DR15 specificity.

Adult↗
PubMed1991

[Immunochemical study of tryptophanyl-tRNA-synthetase].

The immunochemical approach used extensively in medicine and in some fields of biology has not yet been systematically applied to enzymology, in particular, to the study of a large, functionally significant group of enzymes, such as aminoacyl-tRNA synthetases (EC 6.1.1). The present investigation was aimed at the analysis of applicability of polyclonal and monoclonal antibodies against bovine tryptophanyl-tRNA synthetase in the study of functional properties of this enzyme as well as of its distribution inside the cell and among organs and tissues of various animals. The general conclusions one may draw from these data are as follows. i) Tryptophanyl-tRNA synthetase of eukaryotes, eubacteria and archaebacteria share one common structural element (antigenic determinant) that is not essential for the catalytic activity. The evolutionary conservative nature of this element suggests that the enzyme may implement functions other than catalysis of tryptophanyl-tRNA formation. ii) Tryptophanyl-tRNA synthetase shows an anomalous distribution among mammalian organs: its content is far greater in the exocrine part of the ruminant animal pancreas in comparison with their other organs (liver) or with other mammalian orders. This finding suggests that the enzyme or its fragments may play a role in the digestive function of ruminant animals. iii) Tryptophanyl-tRNA synthetase was found in considerable quantities in diffuse chromatin of mammalian cell nuclei. This fact indicates that the enzyme may participate in such processes in the nucleus as transcription, processing, transport, etc. It may thus be concluded that tryptophanyl-tRNA synthetase of higher organisms, besides catalyzing the formation of aminoacyl-tRNAs can exert some other, yet unknown, noncanonical functions.

Animals↗
PubMed1990

Expression of c-myc gene in human ovary carcinoma cells treated with vanadate.

The widely accepted hypothesis of vanadate action on cells postulates that this ion inhibits protein phosphatase(s) that dephosphorylates protein phosphotyrosine residues. This inhibition causes tyrosine hyperphosphorylation of cell proteins followed by changes in physiological action of phosphoproteins resulting in stimulation of cell proliferation, expression of protooncogenes, and transient cell transformation. We have found that treatment of human ovary carcinoma (CaOv) cells with vanadate causes the increase in total protein phosphorylation from 1.5- to 2.0-fold whereas the ratio between phosphoserine, phosphothreonine, and phosphotyrosine content remains unchanged. At the same time, enhancement of c-myc gene expression (not c-fos) was observed. Hence, the increase in the ratio of phosphotyrosine to phosphoserine and phosphothreonine is not an obligatory intermediate stage before vanadate-dependent activation of c-myc expression.

Cell Transformation, Neoplastic↗
PubMed1990

[A peptide, containing the universal antigenic determinant of tryptophanyl-tRNA-synthetase].

Among clostripain hydrolysate peptides of beef pancreas tryptophanyl-tRNA synthetase the peptide Ile-Ser-Phe-Pro-Ala-Ile-Asn-Gln-Phe-Ala-Ala-Pro-Ser-Gln-Phe-Ser-Ile-Arg was revealed which contains the continuous antigenic determinant for monoclonal antibody Am1. This antibody specifically cross-reacts with tryptophanyl-tRNA synthetases of procaryotes, eucaryotes and archebacteriae. The synthetic peptide with identical amino acid sequence plus N-terminal Arg residue (S-peptide), being immobilized on enzyme immunoassay (EIA) microtitration plate, also binds with Am1. Am1 affinity constant (M-1) measured by non-competitive EIA was (3.0 +/- 0.3).10(7) for S peptide and (1.4 +/- 0.3).10(9) for the native enzyme. The sequence of immunoreactive peptide adopts with high probability the secondary structure including beta-turn(s) and antiparallel beta-sheet composed of inverted repeats. At the same time, the analysis of circular dichroism spectrum (in the far UV) of the peptide dissolved in water comes closest to 16% beta-turn and only 8% beta-sheet. The binding of Am1 with peptide was not observed in aqueous solution.

Amino Acid Sequence↗