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1.
Artigo em Russo | MEDLINE | ID: mdl-37490669

RESUMO

OBJECTIVE: To reveal the relationships between antipsychotic and anticholinergic drugs and cognitive functions in patients with schizophrenia. MATERIAL AND METHODS: The observational prospective study was conducted at the Bekhterev National Medical Center of Psychiatry and Neurology. The study involved 41 patients (22 men and 19 women) with paranoid schizophrenia, according to ICD 10 criteria, aged 30.12±8.24 years on stable antipsychotic monotherapy or in combination with anticholinergic drug (trihexiphenidyl). Cognitive functions were assessed using the «Brief Assessment of Cognitive Function in Patients with Schizophrenia¼ (BACS) scale, severity of mental state and extrapyramidal disturbances were measured using the «Positive and Negative Syndrome Scale (PANSS) and the Simpson-Angus Scale for Assessment of Extrapyramidal Side Effects (SAS). All examination procedures were performed twice at weeks 2 and 8 of therapy. Patients were divided into 2 groups according to the type of antipsychotic therapy. Twelve patients received first generation antipsychotics (FGAs) (group 1), 29 patients received second generation antipsychotics (SGAs) (group 2). RESULTS: Patients receiving SGAs had a significant decrease in the overall SAS score at week 8 of therapy compared with data at week 2, and there was an improvement in cognitive function, unlike patients receiving FGAs. There were also changes on BACS tests the digit sequencing (V=51.5, p=0.007), token motor task (V=75.5, p=0.007) and Tower of London (V=52, p=0.027) only in patients of group 2. CONCLUSION: The improved tolerance to the drug, as well as cognitive measures, was shown in patients taking SGAs by week 8. Our study confirms the importance of adhering to the minimum effective dose of antipsychotic drugs for the treatment of schizophrenia to prevent cognitive impairment, and to give preference to SGAs in the choice of treatment.


Assuntos
Antipsicóticos , Feminino , Humanos , Masculino , Antipsicóticos/efeitos adversos , Cognição , Quimioterapia Combinada , Estudos Prospectivos , Esquizofrenia Paranoide/tratamento farmacológico
2.
Vestn Oftalmol ; 138(5): 80-86, 2022.
Artigo em Russo | MEDLINE | ID: mdl-36288421

RESUMO

Gyrate chorioretinal atrophy (GCA) is a rare hereditary disease with certain complications; one extremely rare complication of GCA is foveoschisis. For the first time in Russian ophthalmology, a 10-year-old female child has been described to have genetically verified GCA associated with the OAT gene in combination with ornithinemia and foveoschisis. The diagnosis was made on the basis of fundus examination, perimetry data, autofluorescence, optical coherence tomography, fluorescence angiography, electroretinography, mass spectrometry with confirmation by molecular genetic research. The presented clinical case illustrates the need for an interdisciplinary approach to the diagnosis of GCA with diagnostic algorithm involving various examination methods and doctors of different specialties.


Assuntos
Atrofia Girata , Retinosquise , Criança , Feminino , Humanos , Atrofia Girata/etiologia , Atrofia Girata/complicações , Corioide/patologia , Retina/diagnóstico por imagem , Retina/patologia , Angiofluoresceinografia , Retinosquise/etiologia , Retinosquise/complicações , Atrofia
3.
Vestn Oftalmol ; 138(4): 48-57, 2022.
Artigo em Russo | MEDLINE | ID: mdl-36004591

RESUMO

PURPOSE: To present the main aspects of interdisciplinary diagnostics of patients with hereditary retinal diseases and the first results of the follow-up of patients with inherited retinal dystrophies (IRD) caused by biallelic mutations in the gene RPE65 after gene replacement therapy in Russia. MATERIAL AND METHODS: The cohort of patients consisted of six children (5-15 years old) with the diagnosis of Leber amaurosis type 2. All patients underwent a multi-disciplinary examination using conventional clinical, instrumental and molecular-genetic methods. Genetic diagnosis was established based on the results of two-stage DNA diagnostics using high-performance parallel sequencing of a custom panel and family segregation analysis by Sanger sequencing. RESULTS: In the Research Centre for Medical Genetics the first group of Russian patients with an orphan inherited retinal disease was verified, they underwent subretinal injection of the gene replacement drug Voretigene neparvovec (12 eyes) in the Helmholtz National Medical Research Center of Eye Diseases. According to the regulated terms of monitoring gene therapy patients, they were examined in the Research Centre for Medical Genetics after 1, 3, 6 and 12 months, and then once per year. Thus, the available data allows us to analyze the first results 3 months after the treatment. CONCLUSION: The presented data on inherited retinal dystrophies caused by biallelic mutations in the RPE65 gene emphasize the need to change the diagnostic algorithm in the ophthalmic practice. The use of clinical instrumental and molecular genetic diagnostic methods makes it possible to apply etiotropic treatment to patients with a disabling disease that was previously considered untreatable. The gene replacement drug Voretigene neparvovec registered in Russia showed irrefutable first positive results in all targeted patients.


Assuntos
Amaurose Congênita de Leber , Distrofias Retinianas , Adolescente , Criança , Pré-Escolar , Terapia Genética/métodos , Humanos , Amaurose Congênita de Leber/diagnóstico , Amaurose Congênita de Leber/genética , Amaurose Congênita de Leber/terapia , Mutação , Retina , Distrofias Retinianas/diagnóstico , Distrofias Retinianas/genética , Distrofias Retinianas/terapia , cis-trans-Isomerases/genética
4.
Sci Rep ; 9(1): 14412, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594988

RESUMO

Hereditary spastic paraplegia (HSP) comprises a heterogeneous group of neurodegenerative disorders, it share common symptom - of progressive lower spastic paraparesis. The most common autosomal dominant (AD) forms of HSP are SPG4 (SPAST gene) and SPG3 (ATL1 gene). In the current research we investigated for the first time the distribution of pathogenic mutations in SPAST and ATL1 genes within a large cohort of Russian HSP patients (122 probands; 69 famillial cases). We determined the frequencies of genetic abnormalities using Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and Next Generation Sequencing (NGS) of targeted gene panels. As a result, SPG4 was diagnosed in 30.3% (37/122) of HSP cases, where the familial cases represented 37.7% (26/69) of SPG4. In total 31 pathogenic and likely pathogenic variants were detected in SPAST, with 14 new mutations. Among all detected SPAST variants, 29% were gross deletions and duplications. The proportion of SPG3 variants in Russian cohort was 8.2% (10/122) that were all familial cases. All 10 detected ATL1 mutations were missense substitutions, most of which were in the mutational hot spots of 4, 7, 8, 12 exons, with 2 novel mutations. This work will be helpful for the populational genetics of HSP understanding.


Assuntos
Proteínas de Ligação ao GTP/genética , Predisposição Genética para Doença , Proteínas de Membrana/genética , Paraplegia Espástica Hereditária/genética , Espastina/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Éxons , Feminino , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Mutação/genética , Linhagem , Federação Russa/epidemiologia , Paraplegia Espástica Hereditária/epidemiologia , Paraplegia Espástica Hereditária/patologia , Adulto Jovem
6.
Klin Lab Diagn ; 63(1): 44-50, 2018.
Artigo em Russo | MEDLINE | ID: mdl-30550091

RESUMO

The purpose of study is to establish features of autoimmune reaction of children with Crohn's disease. The sampling included 62 patients aged from 2 to 17 years with diagnosis of Crohn's disease. The evaluation was carried out concerning concentration in blood serum of immunoglobulins IgA, IgM, IgG, IgЕ, antibodies to Saccharomyces cerevisiae (ASCA) classes IgA, IgG и IgЕ, antibodies to Candida albicans classes IgA, IgM, IgG и IgЕ, anti-neutrophilic cytoplasmic antibodies (ANCA) to myeloperoxidase (MPO), to proteinase 3 (PR3), anti-nuclear antibodies (ANA), antibodies to DNAds, DNAss (to double-helical and single-stranded DNA), antibodies to antigens of small and large intestines, pancreas, circulating immune complexes. The hyperimmunoglobulinemia was diagnosed in 47 (75.8%) out of 62 patients with Crohn's disease. The increased level of IgM in blood was detected in 29 patients (46.8%). The hyperimmunoglobulinemia У was established in 19 (30.6%) out of 62 children. The hypoimmunoglobulinemia was detected in 22 (35.5%) of patients and in 17 (77.3%) out of them the disimmunoglobulinemia type IV (isolated decreasing of concentration of IgA). The evaluation of rate of occurrence of specifc antibodies in blood serum demonstrated that in patients most frequently was detected presence of specifc IgE to Saccharomyces cerevisiae (70.9%). The increased level of ASCA (IgA, IgG) was detected in 22 (35.5%) patients. The concentration of antibodies to DNAds, DNAss in blood exceeded standard value in 4.8% and 16.1% patients correspondingly. The increased level of circulating immune complex was established in 20 (32.3%) patients. The concentration of ANA corresponded to standard values in all 62 (100%) patients. The evaluation of results of correlation analysis established a strong positive correlation of concentration in blood of antibodies to antigens of small and large intestines; average positive correlation of level of antibodies to antigens of small intestine and IgM, ANCA PR3, ASCA IgE, antibodies to Candida albicans classes IgM, IgG, IgE, antibodies to antigens of pancreas; average degree of positive correlation between concentration of antibodies to antigens of large intestine and IgA, IgM, circulating immune complex, ANCA PR3, DNAss, ASCA IgE, antibodies to antigens of pancreas; strong positive correlation between concentrations of IgA to Candida albicans and ANA. The detection of auto-to antibodies Saccharomyces cerevisiae, Candida albicans, ANCA, antigens of small and large intestines, pancreas and expressed degree of correlation of many indices of autoimmune reaction indicate to intensity of immune pathological process under Crohn's disease. Under Crohn's disease, the formation of antibodies to ASCA is a prognostically unfavorable sign. The immune diagnostic under Crohn's disease is necessary for evaluating severity of course of disease, differential diagnostic, establishment of prognosis and selection of individual immune correcting therapy.


Assuntos
Doença de Crohn , Adolescente , Anticorpos Anticitoplasma de Neutrófilos , Anticorpos Antifúngicos , Biomarcadores , Criança , Pré-Escolar , Humanos , Imunoglobulina A , Imunoglobulina G
7.
Acta Naturae ; 9(3): 71-80, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29104778

RESUMO

Induction of donor specific tolerance (DST) by the introduction of donor cells into a recipient's portal vein is one of the approaches used to solve the problem of transplant engraftment. However, the mechanism of DST development remains unclear to this moment. In the present work, we first studied the change in the content of immunoproteasomes and macrophages of the liver at early stages of the development of allospecific portal tolerance in rats by Western blotting and flow cytofluorimetry. On the basis of the data obtained, we can conclude that the induction of DST is an active process characterized by two phases during which the level of the proteasome immune subunits LMP2 and LMP7 in liver mononuclear cells, including Kupffer cells, and the number of Kupffer cells change. The first phase lasts up to 5 days after the beginning of DST induction; the second phase - from 5 to 14 days. In both phases, the level of the subunits LMP2 and LMP7 in the total pool of mononuclear cells and Kupffer cells increases, with maximum values on days 1 and 7. In addition, the total number of Kupffer cells increases in both phases with a shift in several days. The most noticeable changes take place in the second phase. The third day is characterized by a lower content of mononuclear cells expressing immunoproteasomes compared to the control value in native animals. Presumably, at this time point a "window of opportunity" appears for subsequent filling of an empty niche with cells of different subpopulations and, depending on this fact, the development of tolerance or rejection. The results obtained raise the new tasks of finding ways to influence the cellular composition in the liver and the expression of immunoproteasomes on the third day after the beginning of DST induction to block the development of rejection.

8.
Tumour Biol ; 39(2): 1010428317691010, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28215104

RESUMO

Recent research indicates that the C-terminal Eps15 homology domain 1 is associated with epithelial growth factor receptor-mediated endocytosis recycling in non-small-cell lung cancer. The aim of this study was to determine the clinical significance of Eps15 homology domain 1 gene expression in relation to phosphorylation of epithelial growth factor receptor expression in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Eps15 homology domain 1, RAB11FIP3, and phosphorylation of epithelial growth factor receptor expression via immunohistochemistry. The clinical significance was assessed via a multivariate Cox regression analysis, Kaplan-Meier curves, and the log-rank test. Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor were upregulated in 60.46% (185/306) and 53.92% (165/306) of tumor tissues, respectively, as assessed by immunohistochemistry. The statistical correlation analysis indicated that Eps15 homology domain 1 overexpression was positively correlated with the increases in phosphorylation of epithelial growth factor receptor ( r = 0.242, p < 0.001) and RAB11FIP3 ( r = 0.165, p = 0.005) expression. The multivariate Cox proportional hazard model analysis demonstrated that the expression of Eps15 homology domain 1 alone is a significant prognostic marker of breast cancer for the overall survival in the total, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. However, the use of combined expression of Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor markers is more effective for the disease-free survival in the overall population, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. Moreover, the combined markers are also significant prognostic markers of breast cancer in the human epidermal growth factor receptor 2 (+), estrogen receptor (+), and estrogen receptor (-) groups. Eps15 homology domain 1 has a tumor suppressor function, and the combined marker of Eps15 homology domain 1/phosphorylation of epithelial growth factor receptor expression was identified as a better prognostic marker in breast cancer diagnosis. Furthermore, RAB11FIP3 combines with Eps15 homology domain 1 to promote the endocytosis recycling of phosphorylation of epithelial growth factor receptor.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias da Mama/metabolismo , Proteínas de Transporte/metabolismo , Receptores ErbB/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Inclusão em Parafina
9.
Dokl Biochem Biophys ; 468(1): 200-2, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27417720

RESUMO

Native structure of active forms of rat liver immune proteasomes has been studied by two-dimensional electrophoresis method modified for analysis of unpurified protein fractions. The developed method allowed revealing the proteasome immune subunits LMP7 and LMP2 in 20S subparticles and in the structures bound to one or two PA28αß activators, but not to the PA700 activator, which is involved in the hydrolysis of ubiquitinated proteins. The results obtained indicate the participation of the immune proteasomes in delicate regulatory mechanisms based on the production of biologically active peptides and exclude their participation in processes of crude degradation of "rotated" ubiquitinated proteins.


Assuntos
Cisteína Endopeptidases/metabolismo , Fígado/enzimologia , Fígado/imunologia , Complexo de Endopeptidases do Proteassoma/química , Complexo de Endopeptidases do Proteassoma/metabolismo , Western Blotting , Proteínas de Ciclo Celular , Cisteína Endopeptidases/química , Eletroforese em Gel Bidimensional/métodos , Conformação Proteica , Proteínas/química , Proteínas/metabolismo
10.
Genetika ; 52(2): 231-41, 2016 Feb.
Artigo em Russo | MEDLINE | ID: mdl-27215038

RESUMO

A study of Russian cystic fibrosis (CF) patient DNA was conducted to assess the incidence frequency of 19 mutations, namely CFTRdele2,3(21kb), F508del, I507del, 1677delTA, 2143delT, 2184insA, 394delTT, 3821delT, L138ins, 604insA, 3944delGT, G542X, W128X, N1303K, R334W, and 3849+10kbC>T, S1196X, 621+1g>t, and E92K of the CFTR gene. We also sought to determine the estimated CF frequency in Russian Federation. In addition, we determined the total information content of the approach for 19 common mutations registration in the CFTR gene, 84.6%, and the allelic frequencies of the examined mutations: three mutations were observed with a frequency exceeding 5% (F508del, 53.98%, E92K, 6.47%, CFTRdele2,3(21kb), 5.35%); other mutations were observed with frequencies ranging from 0.13% to 3.0%. The CF population carrier frequency was 1 in 38 subjects, while the predicted CF frequency was 1 in 5776 newborns.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Mutação/genética , Fibrose Cística/epidemiologia , Fibrose Cística/patologia , Análise Mutacional de DNA , Feminino , Frequência do Gene , Heterozigoto , Humanos , Recém-Nascido , Masculino , Federação Russa
11.
Arkh Patol ; 76(5): 3-12, 2014.
Artigo em Russo | MEDLINE | ID: mdl-25543402

RESUMO

OBJECTIVE: To determine the genetic forms of follicular cell thyroid carcinoma (FCTC) (papillary and follicular thyroid carcinoma (PTC and FTC)), to identify criteria to individually predict the development of the same disease for relatives, and to assess the role of molecular markers in the diagnosis, prognosis, and treatment of this disease. SUBJECTS AND METHODS: One hundred and ninety adult patients aged 20 to 84 years with histologically verified PTC and FTC and 20 children (12 patients with PTC and 8 with benign thyroid tumors) aged 2 to 16 years were examined. To assess the role of the BRAF gene as a molecular marker for thyroid carcinoma, DNA was isolated from the thyroid tumor tissue of 29 patients, which had been obtained by fine-needle aspiration biopsy (FNAB) and scraping and swabbing the cytological specimen previously showing an area containing tumor cells. A BRAF c.1799T>A (p.V600E) mutation in the FNAB specimens was tested by allele-specific ligation, followed by PCR amplification. RESULTS: The examinees' families were found to have a segregation of benign thyroid tumor and nontumor diseases (13.6%). Neoplasias of different sites were observed in 15% of the patients' relatives. Multiple primary tumors were detected in 6.1% of the patients and in 25% of the examined children (3/12). PTC was ascertained to accumulate as two clinical forms in the families. One form belongs to familial PTC (FPTC) in which two or three generations of relatives in the family are afflicted by only PTC and have a more severe phenotype of the disease. The other includes an association of FPTC with papillary kidney cancer. Furthermore, FPTC and PTC may be a component of multitumor syndromes, such as multiple endocrine neoplasia type 1, Cowden syndrome, and familial adenomatous polyposis. The familial hereditary forms of FCTC were generally revealed in 4.2% of the patients. BRAF v600E mutations were found in only 3 patients with Stages II and III PTC and were not in all the 12 children with PTC. CONCLUSION: The found clinical manifestation of the hereditary forms of FCTC permits the identification of people at high risk for this disease. No correlation between somatic BRAF mutations with a less favorable course in PTC can be noticed because there are few observations. Analysis of published data on the role of molecular markers in FCTC has shown that the existing specific somatic changes complement information in the differential cytological diagnosis when examining FNAB specimens.


Assuntos
Adenocarcinoma Folicular/genética , Carcinoma/genética , Patologia Molecular , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Carcinoma/diagnóstico , Carcinoma/patologia , Carcinoma Papilar , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Linhagem , Mutação Puntual , Polimorfismo de Nucleotídeo Único , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia
12.
Bioorg Khim ; 40(1): 42-54, 2014.
Artigo em Russo | MEDLINE | ID: mdl-25898722

RESUMO

The proteasomes in the liver of August rats (RT1C) were investigated 30 days after the allotransplantation of Wistar rat (RT1u) thyroid tissue under renal capsule with/without induction of donor specific tolerance by donor splenocyte intraportal administration. The level of the total proteasome pool, immune proteasomes containing the LMP2 and/or LMP7 subunits, proteasome 19S- and 11S-regulators was defined. The intact and sham-operated August rats were used as control groups. The level of all immune proteasome forms and 11S regulator increased while the level of the total proteasome pool and 19S regulator decreased in the liver of experimental animals compared to the control groups that indicated changes of liver functional state after transplantation. The 19S/11S ratio increased in the liver of non-tolerated rats compared to tolerated animals. In the liver of tolerated rats with survived transplants, the quantity of mononuclear cells, expressing the immune subunit LMP2, greatly increased in comparison with control and non-tolerated animals. Study of the survived transplants showed the increase of the ratio of LMP2/LMP7 immune subunits and 19S/11S regulators in them compared to the tissue replacing the rejected transplants. In the control intact thyroid tissue, the immune proteasomes were almost not revealed, while 19S/11S ratio was maximal. Thus, the development of the immune reaction or its suppression is accompanied by change of the balance between different proteasome forms. The immune subunit LMP7 and 11S regulator are connected with the response against donor tissue. On the contrary, the immune subunit LMP2 and 19S regulator are likely to be important for the immune tolerance development and survived tissue functioning. The low content of the immune proteasomes in the follicle cells was found by immunofluorescence assay. The formation of antigens for major histocompatibility complex class I molecules was impaired by low immune proteasome content that led to immunological tolerance to hormone-producing follicle cells.


Assuntos
Complexo de Endopeptidases do Proteassoma/metabolismo , Glândula Tireoide/enzimologia , Glândula Tireoide/transplante , Tolerância ao Transplante/fisiologia , Transplante Homólogo , Animais , Cisteína Endopeptidases , Feminino , Fígado/enzimologia , Ratos Wistar , Tolerância ao Transplante/imunologia
13.
Gig Sanit ; (4): 65-73, 2013.
Artigo em Russo | MEDLINE | ID: mdl-24340605

RESUMO

In the paper there are presented the results of a study of anxiety and balance ofparts of autonomous nervous system in healthy children 5-7 years old, residing in different parts of Magnitogorsk. It is shown that state of heightened and high alert was shown to be more common among children living on the left bank of the Urals river around the Magnitogorsk Metallurgical Integrated Plant. In these children an imbalance in the work of the parts of the autonomic nervous system was detected more frequently, at that shifts were observed mainly in the direction to ergotropic tone. At the same time balanced work of the parts of the autonomic nervous system was observed more frequently in children living on the right bank of the Urals river. Discovered psychosomatic features of examined children turned out to be associated with both the social characteristics of family lifestyle and the emotional stress of parents, and the contents of some organic compounds in total snow samples collected in the territories of kindergartens which they attended. One ofthe most significant results ofthe work we consider the detection of a correlation relationship between emotional stress of parents and activity of key enzymes in their children, reflecting the protective and adaptive reactions of the organism. On the basis of these and previously obtained data, we suggest that social and psychological factors of the family are not only a potential source of maladaptation of the child, but, probably, can have an impact on the stability and sensitivity of the genome of children.


Assuntos
Poluentes Atmosféricos , Ansiedade/psicologia , Sistema Nervoso Autônomo/fisiologia , Metalurgia , Adaptação Fisiológica , Adaptação Psicológica , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Ansiedade/genética , Ansiedade/fisiopatologia , Sistema Nervoso Autônomo/efeitos dos fármacos , Estudos de Casos e Controles , Criança , Pré-Escolar , Monitoramento Ambiental , Instabilidade Genômica , Humanos , Federação Russa , Fatores Socioeconômicos
14.
Bioorg Khim ; 39(4): 400-10, 2013.
Artigo em Russo | MEDLINE | ID: mdl-24707720

RESUMO

The dynamics of the expression of LMP7 and LMP2 proteasome subunits in embryonic and early postnatal development of rat spleen and liver is investigated in comparison with the dynamics of chymotrypsin-like and caspase-like proteasome activities and expression of MHC (major histocompatibility complex) class I molecules. The immune subunits LMP7 and LMP2 distribution in spleen and liver cells in the development process is also studied. A mutual for both organs tendency to the increase of the expression of both LMP7 subunit and LMP2 one on P21 (the 21st postnatal day) as compared to the embryonic period is discovered. However, the total proteasome level is shown to be constant. At definite development stages, the dynamics of immune subunits expression in the spleen and liver was different. In the spleen gradual enhancement of both immune subunits level being detected on P1, P18 and P21, in the liver gradual enhancement periods on E16 (the 16th embryonic day) and E18 changed to the stage of the shrink of immune subunits level on P5. This level did not reliably change till P18 and was augmented on P21. The alterations revealed were accompanied by chymotrypsin-like activity raise and caspase-like activity drop in spleen by P21 as compared with the embryonic period, which proves the enlargement of proteasome ability to form antigenic epitopes for MHC class I molecules. In the liver, both activities increased by P21 in comparison with the embryonic period. Such dynamics of caspase-like activity can be explained not only by the change of proteolytic constitutive and immune subunits, but also by additional regulatory mechanisms. Besides, it is discovered that the increment of immune subunits expression in the early spleen development is connected with the process of successive forming the white pulp by B- and T-lymphocytes enriched by immune subunits. In the liver, the growth of immune subunits level by P21 was accompanied by their expression expansion in hepatocytes, while their plunge by P5 may be related to the loss of liver function of a primary lymphoid organ of the immune system by this stage and disappearance of B-lymphocytes enriched by immune proteasomes in it. In the spleen and liver, MHC class I molecules were revealed at the periods of the raise of proteasome immune subunits level. On E21 , the liver was enriched by neuronal NO-synthase, its level decreased after birth and enhanced to P18. This fact indicates the possibility of the induction of the immune subunits LMP7 [character: see text] LMP2 expression in hepatocytes in signal way with neuronal NO-synthase participation. The results obtained prove that T-cell immune response with spleen participation as regards rat liver cells is possible starting with P19-P21 stage. First, at this period, white pulp T-area is formed in the spleen. Second, enhanced immune proteasomes and MHC class I molecules levels in hepatocytes can procure antigenic epitopes formation from foreign proteins and their delivery to cell surface for their subsequent presentation for cytotoxic T-lymphocytes.


Assuntos
Cisteína Endopeptidases/biossíntese , Sistema Imunitário/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Cisteína Endopeptidases/imunologia , Epitopos/imunologia , Regulação da Expressão Gênica no Desenvolvimento , Sistema Imunitário/crescimento & desenvolvimento , Fígado/crescimento & desenvolvimento , Fígado/imunologia , Fígado/metabolismo , Complexo Principal de Histocompatibilidade , Óxido Nítrico Sintase/metabolismo , Complexo de Endopeptidases do Proteassoma/biossíntese , Complexo de Endopeptidases do Proteassoma/imunologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Ratos , Baço/crescimento & desenvolvimento , Baço/imunologia , Baço/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo
15.
Genetika ; 48(7): 863-71, 2012 Jul.
Artigo em Russo | MEDLINE | ID: mdl-22988772

RESUMO

Molecular genetic study of the CFTR gene in cystic fibrosis patients from the Chuvash Republic is presented. We found linkage disequilibrium of the disease with 22-7-16-13 haplotype using intragenic markers. Major mutation p.E92K was revealed in chromosomes carrying this haplotype. The frequency of this mutation in Chuvash patients was 66.6%. Population study of the distribution of two mutations (p.E92K and F508del) of the CFTR gene revealed that their population frequency in heterozygous carriers was one per 37 subjects while calculated cystic fibrosis frequency in Chuvashia is one per 5420 newborns.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Mutação , Fibrose Cística/epidemiologia , Etnicidade/genética , Frequência do Gene , Genética Populacional , Humanos , Federação Russa
16.
Izv Akad Nauk Ser Biol ; (3): 296-302, 2012.
Artigo em Russo | MEDLINE | ID: mdl-22834313

RESUMO

Induction of donor-specific tolerance in a recipient is one of the methods for enhancing acceptance of the grafts of endocrine glands in the absence of immunodepressants, which interfere with hormone production. This paper describes changes in the proteasome pool in the rat liver, spleen, and graft during the development of donor-specific tolerance after intraportally infusing the recipient with donor splenocytes with subsequent allografting of ovarian tissue into the renal capsule. It has been demonstrated that the shift in the balance in the liver and graft proteasome pools towards the variants with the LMP2 subunit determines the development of immunological tolerance and graft retention. On the contrary, an increase in the forms with the LMP7 subunit induces the immune response and graft rejection.


Assuntos
Tolerância Imunológica/fisiologia , Ovário/transplante , Complexo de Endopeptidases do Proteassoma/metabolismo , Transplante Homólogo/imunologia , Animais , Cisteína Endopeptidases/metabolismo , Estradiol/sangue , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Fígado/metabolismo , Ovariectomia , Progesterona/sangue , Complexo de Endopeptidases do Proteassoma/imunologia , Ratos , Ratos Wistar , Baço/imunologia , Baço/metabolismo
17.
Genetika ; 46(6): 844-52, 2010 Jun.
Artigo em Russo | MEDLINE | ID: mdl-20734777

RESUMO

The frequency and spectrum of mutations and the IVS8- T polymorphism of the CFTR gene have been studied in a sample of 963 in Russian infertile men. Mutations have been found in 48 out of 1926 analyzed chromosomes (2.5%) in the heterozygous state (n = 46) and in the compound heterozygote L138ins/N1303K (n = 1/n = 1). A CFTR gene mutation was combined with the 5T allele (mutCFTR/5T) in 11 patients. The following mutations have been found: F508del (n = 18), CFTRdele2,3 (21kb) (n = 9), W1282X (n = 7), 2143delT (n = 4), 3849+10kbC>T (n = 2), L138ins (n = 2), 1677delTA (n = 1), 2184insA (n = 1), 3821delT (n = 1), G542X (n = 1), N1303K (n = 1), and R334W (n = 1). The F508del mutation is the most frequent; it has been detected in 37.5% of the affected chromosomes. The total proportion of four mutations (F508del, CFTRdele2,3 (21kb), W1282X, and 2143delT) is about 79% of all mutations found. The 5T allele has been found in 10.9% infertile men and 4.8% of control men. Significant differences in the frequency of the IVS8-5T variant of the CFTR gene have been found between these groups (p = 0.005), as well as between infertile patients without mutations and control men (p = 0.019). In total, the mutations and/or 5T allele have been found in 14.6% of the patients examined. These data indicate increased frequencies of the mutations of the CFTR gene and its allele variant IVS8-5T in Russian infertile men.


Assuntos
Alelos , Cromossomos Humanos/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Frequência do Gene/genética , Infertilidade Masculina/genética , Mutação , Polimorfismo Genético , Humanos , Masculino , Federação Russa
18.
Radiats Biol Radioecol ; 50(3): 345-51, 2010.
Artigo em Russo | MEDLINE | ID: mdl-20734808

RESUMO

The spontaneous level of cytogenetic damage in three plant species (Achyrophorus maculatus (Scop.) L., Plantago lanceolata L., Plantago media L.) growing at the territory of East Ural radioactive trace was studied. The radiation resistance of plants from radioactive and control nonpolluted sites was determined. The effects of additional fractionated irradiation by different doses and the role of antioxidant systems in the formation of radioprotector effect were examined. It was shown that the level of mutation process in the plant populations growing at the radiation polluted sites is increased compared to the control populations from the pure territory. The additional acute gamma-irradiation of seeds collected from the polluted and pure territories showed the improved radiation resistance of the plants from the polluted territory. In the control population of A. maculatus in the versions with a one-hour interval between fractions, the radiation effect follows the additivity principle; in the same time, at a one-day interval between fractions, a highly significant radioprotective effect manifested most clearly in the experimental population is induced. For higher plants, the enhanced effectiveness of the functioning of antioxidant systems in plants growing at radiation polluted territories was first shown. Thus, the radioprotector mechanisms of low-dose chronic and preliminary irradiation are similar and one of these mechanisms is the activation of antioxidant systems in plants growing under conditions of chronic low-intensity irradiation for long periods of time.


Assuntos
Aberrações Cromossômicas , Raios gama , Plantas/efeitos da radiação , Liberação Nociva de Radioativos , Sementes/efeitos da radiação , Cromossomos de Plantas/genética , Cromossomos de Plantas/efeitos da radiação , Relação Dose-Resposta à Radiação , Monitoramento Ambiental , Plantas/genética , Tolerância a Radiação/efeitos da radiação , Federação Russa , Sementes/genética
20.
Vestn Khir Im I I Grek ; 134(1): 99-100, 1985 Jan.
Artigo em Russo | MEDLINE | ID: mdl-3992817

RESUMO

Results of the experimental use of Dimiphen blue for determination of viability of tissues are presented. Experiments were made in 23 rabbits with standard contusion-crush skin-muscle wounds. the results have shown that the method is good for diagnosis and may be recommended for clinical use.


Assuntos
Corantes , Desbridamento/métodos , Músculos/lesões , Compostos Orgânicos , Pele/lesões , Ferimentos e Lesões/fisiopatologia , Animais , Músculos/patologia , Coelhos , Pele/patologia , Ferimentos e Lesões/patologia , Ferimentos e Lesões/cirurgia
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