Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 73
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Bull Exp Biol Med ; 156(6): 756-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24824689

RESUMO

Proteolytically inactive recombinant forms of urokinase (uPAHQ and amino-terminal fragment) inhibit spontaneous migration of endothelial cells; amino-terminal fragment also suppresses angiogenesis stimulated by basic fibroblast growth factor in vitro. These findings suggest the possibility of using synthesized proteolytically inactive recombinant forms of urokinase for the regulation of endothelial cell migration and suppression of neoangiogenesis.


Assuntos
Movimento Celular/efeitos dos fármacos , Células Endoteliais/metabolismo , Neovascularização Patológica/prevenção & controle , Proteínas Recombinantes/farmacologia , Ativador de Plasminogênio Tipo Uroquinase/farmacologia , Células Cultivadas , Endotélio Vascular/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos
2.
Bioorg Khim ; 39(6): 658-70, 2013.
Artigo em Russo | MEDLINE | ID: mdl-25696928

RESUMO

By means of computer simulation has been built polypeptide antigen conformational structure that imitates the immunodominant epitope of the 2nd extracellular loop of ß1-adrenoreceptor. A linear 25-membered peptide corresponding to calculated sequence was synthesized by means of solid-phase methoyd using Fmoc-technology, then directed by the closure ofdisulfide bridges was obtained original bicyclic polypeptide corresponding to the proposed structure of the conformational antigen. With the help of high-resolution NMR spectroscopy 3D structure of synthetic conformational antigen was investigated. It was shown that the structure of the bicyclic polypeptide similar to that of building computer model. Bicyclic conformational antigen was suitable for the detection of autoantibodies in the blood serum of patients with rhythm and conductivity violation without evidence of organic disease of the cardiovascular system.


Assuntos
Epitopos Imunodominantes/imunologia , Peptídeos/química , Conformação Proteica , Receptores Adrenérgicos beta 1/imunologia , Antígenos/imunologia , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/imunologia , Simulação por Computador , Humanos , Epitopos Imunodominantes/química , Espectroscopia de Ressonância Magnética , Peptídeos/imunologia , Receptores Adrenérgicos beta 1/química
3.
Kardiologiia ; 49(9): 27-38, 2009.
Artigo em Russo | MEDLINE | ID: mdl-19772500

RESUMO

One of the major cardiovascular risk factor which predisposes to and accelerates atherosclerosis is arterial hypertension (AH). To determine the molecular basis of the crosslink between AH and atherosclerosis for the development of new treatment strategies large-scale transcriptome analysis of the cells implicated in atherogenesis is needed. We used cDNA microarray technique for simultaneous analysis of gene expression in human abdominal aorta normal sites and atherosclerotic lesions of different histological types, as well as in peripheral blood leukocytes from patients with essential hypertension (EH) and donors. The microarray data were verified by quantitative RT-PCR (reverse transcription coupled with polymerase chain reaction) and immunohistochemical analysis. Differential expression of 40 genes has been found, among which twenty two genes demonstrated up-regulation and 18 genes demonstrated down-regulation in atherosclerotic aorta compared with normal vessel. New gene-candidates, implicated in atherogenesis, have been identified - FPRL2, CD37, CD53, RGS1, LCP1, SPI1, CTSA, EPAS1, FHL1, GEM, RHOB, SPARCL1, ITGA8, PLN, and COL14A1. These genes participate in cell migration and adhesion, phenotypic changes of smooth muscle cells, immune and inflammatory reactions, oxidative processes and extracellular matrix remodeling. We have found increased expression levels of CD53, SPI1, FPRL2, SPP1, CTSD, ACP5, LCP1, CTSA and LIPA genes in peripheral blood leukocytes from EH patients and in atherosclerotic lesions of human aorta. The majority of these genes significantly (p<0.005) positively (r>0.5) correlated with AH stage as well as with histological grading of atherosclerotic lesions.


Assuntos
Aorta Abdominal/metabolismo , Aterosclerose/genética , DNA Complementar/análise , Perfilação da Expressão Gênica/métodos , Expressão Gênica , Hipertensão/complicações , Leucócitos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta Abdominal/patologia , Aterosclerose/etiologia , Aterosclerose/metabolismo , Biomarcadores , Feminino , Humanos , Hipertensão/genética , Hipertensão/metabolismo , Imuno-Histoquímica , Leucócitos/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
4.
Zh Vopr Neirokhir Im N N Burdenko ; (3): 14-9; discussion 19-20, 2008.
Artigo em Russo | MEDLINE | ID: mdl-19062590

RESUMO

Authors presented the results of experimental and clinical studies of effects of recombinant prourokinase on brain tissue, its toxicity and safety in intracerebral administration for lysis of hypertensive intracerebral hematomas. Experiments were performed in 64 rabbits. Histological specimens were examined in different periods after injection of prourokinase into white matter and into experimental hematoma. It is revealed that dose of 615 mg/kg causes minimal changes in cerebral tissue. Clinical study was based on analysis of puncture aspiration of intracerebral hematomas with local fibrinolysis performed in 275 patients with hemorrhagic stroke. Dynamics of MRI, clinical and laboratory parameters, coagulation, analysis of aspirated products of lysis were assessed. Authors showed that recombinant prourokinase and the drug "Puroplazan" are effective for local fibrinolysis. The drugs are non-toxic and non-allergenic and do not cause cerebral edema.


Assuntos
Fibrinolíticos/uso terapêutico , Hematoma/terapia , Hemorragia Intracraniana Hipertensiva/terapia , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Adulto , Idoso , Animais , Fibrinolíticos/administração & dosagem , Fibrinolíticos/efeitos adversos , Hematoma/diagnóstico , Hematoma/diagnóstico por imagem , Hematoma/cirurgia , Humanos , Hemorragia Intracraniana Hipertensiva/diagnóstico , Hemorragia Intracraniana Hipertensiva/diagnóstico por imagem , Hemorragia Intracraniana Hipertensiva/cirurgia , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Radiografia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Sucção , Resultado do Tratamento , Ativador de Plasminogênio Tipo Uroquinase/administração & dosagem , Ativador de Plasminogênio Tipo Uroquinase/efeitos adversos
5.
Kardiologiia ; 48(9): 34-42, 2008.
Artigo em Russo | MEDLINE | ID: mdl-18991818

RESUMO

Gene expression level of 2900 genes was studied by cDNA microarray in patients with atrial fibril-lation (AF) or sinus rhythm. Gene transcripts were analysed in samples of right atrial appendages from 47 patients undergoing surgery for valve repair or coronary artery bypass. Standard correlation analysis and two dimensional hierarchical clustering were used for study of differentially expressed genes in patient groups. A highly positive correlation of gene expression with AF was shown for cardiac muscle LIM domain protein (CSRP3), cardiac muscle myosin heavy chain beta isoform (MYH7), calmodulin (CALMS) and homeobox protein (PKNOXl) genes (r > 0.77, p < 0.007). In contrast, metallothionein (MT1/2), mitochondrial aldehyde dehydrogenase 2 (ALDH2), ras-related protein (RaplA) and guanine nucleotide binding protein G (GNAL) genes revealed highly negative correlation with AF (r < -0.75, p < 0.002). Alterations of gene activity were more evident at permanent as compared with paroxysmal AF. In addition, genes overexpressed in AF patients demonstrated underexpression in coronary artery disease patients (r=-0.8, p=0.0002) and conversely. Genes correlating with AF belong to different functional categories, including sarcomere organization, contraction, Ca2+ homeostasis, signaling and transcription regulation, extracellular matrix interactions and oxidative stress. Downregulation of MT1/2 and ALDH2 genes, known protectors against oxidative stress, may contribute to maintenance of oxidative stress in myocardial tissues of AF patients. The identification of novel genes - participants of pathological process in AF may open new perspective for search of therapeutic agents.


Assuntos
Apêndice Atrial/metabolismo , Fibrilação Atrial/genética , DNA Complementar/genética , Expressão Gênica , Proteínas Musculares/genética , Miócitos Cardíacos/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Adulto , Idoso , Apêndice Atrial/patologia , Fibrilação Atrial/metabolismo , Fibrilação Atrial/patologia , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/biossíntese , Miócitos Cardíacos/patologia , Reprodutibilidade dos Testes
6.
Arkh Patol ; 70(2): 31-6, 2008.
Artigo em Russo | MEDLINE | ID: mdl-18540439

RESUMO

Phospholipase A2, group IIA, gene expression has been analyzed in primary heart tumors. High expression has been demonstrated through several ways: reverse-transcriptase chain polymerase chain, Northern blotting hybridization at the RNA level and immunoblotting, immunohistochemical assay at the protein level. Human cardiac myxoma exhibits highly positive phospholipase A2, group IIA, immunophenotype (100% positive cases). The immunophenotype is unique among human primary cardiac tumors. Phospholipase A2, group IIA, can be proposed as a tissue marker for pathological examination after heart tumor resection.


Assuntos
Biomarcadores Tumorais/metabolismo , Fosfolipases A2 do Grupo II/metabolismo , Neoplasias Cardíacas/enzimologia , Neoplasias Cardíacas/patologia , Mixoma/enzimologia , Mixoma/patologia , Adolescente , Adulto , Idoso , Biomarcadores Tumorais/imunologia , Criança , Feminino , Fosfolipases A2 do Grupo II/imunologia , Neoplasias Cardíacas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Mixoma/imunologia
7.
Mol Biol (Mosk) ; 40(1): 90-9, 2006.
Artigo em Russo | MEDLINE | ID: mdl-16523696

RESUMO

Association of RNA molecules forming a two-component B:LS trans-analog of antigenomic HDV ribozyme was studied. From previously synthesized trans-ribozymes the B:LS ribozyme differs by length and sequence of its RNA molecules (33 and 34 bp, respectively), topology of functional parts and the absence of very short reaction product. The ribozyme displays a biphasic kinetics of self-cleavage similar to that of cis-ribozyme. Our original kinetic scheme for the B:LS trans-ribozyme self-cleavage (www.cardio.ru\labgen\RZ_e.html)describes a possible cause of biphasic nature of the reaction curve, namely, variation of the rate-limiting stage in the series of successive conformational transformations which coincide with the ribozyme self-cleavage. Interactions between the molecules involved in the reaction, i.e., "multimerization" of entire ribozyme and its components can be regarded as another cause of the biphasic kinetics. B:LS trans-ribozyme is a convenient model for the investigation of this process, since the binding of LS and B allows the formation of complexes with 1B:2LS or 2B:1LS stoichiometry and complexes with the cleavage products. We examined the factors determining dissociation-association of the ribozyme components using a series of electrophoreses under nondenaturing conditions. The possibility of interaction between cis- and transribozyme components was confirmed experimentally. In the presence of LS excess over B the ribozyme can form multimeres. These findings suggest the involvement of intermolecular interactions in native cis-ribozyme self-cleavage.


Assuntos
Genoma Viral , Vírus Delta da Hepatite/genética , RNA Catalítico/química , RNA Viral/genética , Pareamento de Bases , Sequência de Bases , Cinética , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Relação Estrutura-Atividade
8.
Mol Biol (Mosk) ; 38(6): 1050-8, 2004.
Artigo em Russo | MEDLINE | ID: mdl-15612593

RESUMO

B : LS ribozyme, a trans-variant of naturally occurring HDV ribozyme, has been constructed. The ribozyme consists of a substrate-containing LS chain and an enzyme B chain and differs from previously constructed trans-ribozymes in the length and nucleotide sequence of its oligonucleotide chains (34 and 33 bp, respectively). The chains readily associate with each other at a room temperature while the LS cleavage reaction at this temperature is negligible slow, which allowed us to investigate the association of the intact chains. At the same time the self-cleavage rate constant for the trans-ribozyme B : LS at 50 degrees C is close to those for the previously studied permuted cis-ribozymes, especially LSB variant. In addition, the dependence on the reaction conditions (Mg2+ concentration, pH, temperature) of the trans-ribozyme was similar to that of cis-ribozyme. Similar to other trans-ribozymes, B : LS ribozyme demonstrates the ability for multiple use of the enzyme B-chain with an excess of the substrate LS chain. The kinetics model of self-cleavage reaction for B : LS is presented in http://www.cardio.ru/labgen/RZ_r.html. Taken together, our results show that the original trans-variant of HDV ribozyme can be used as a model for the investigation of self-cleavage process of HDV ribozymes.


Assuntos
Genoma Viral , Vírus Delta da Hepatite/genética , RNA Catalítico/metabolismo , Sequência de Bases , Concentração de Íons de Hidrogênio , Cinética , Magnésio/química , Conformação de Ácido Nucleico , RNA Catalítico/química , Temperatura Ambiente
9.
Kardiologiia ; 43(7): 77-82, 2003.
Artigo em Russo | MEDLINE | ID: mdl-12891303

RESUMO

Carney complex is an autosomic dominant disorder initially described as the association of cardiac myxomas, spotty skin pigmentation and endocrine overactivity and considered as a multiple neoplasia and lentiginosis syndrome. Mutations in the tumor suppressor gene PRKAR1A, coding for the type 1-alpha regulatory subunit of cAMP-depended protein kinase A have been previously identified in about half of the Carney complex kindreds. In this paper we report identification of the molecular defect in PRKARIA gene in two Carney complex patients. A new mutation (403delAC) located in a 3rd exon of PRKARIA gene has been observed in one case, and a previously described mutation in exon 7 (847delTC) in the second case.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/genética , Neoplasias Cardíacas/genética , Neoplasia Endócrina Múltipla/genética , Mixoma/genética , Transtornos da Pigmentação/genética , Adolescente , Adulto , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico , Genes Supressores de Tumor , Humanos , Masculino , Mutação , Linhagem , Síndrome
10.
Mol Biol (Mosk) ; 35(5): 879-99, 2001.
Artigo em Russo | MEDLINE | ID: mdl-11605542

RESUMO

The kinetic characteristics have been studied for noncircularly permuted variants of the human hepatitis delta virus (HDV) antigenomic ribozyme to find out the cause of the two-phase kinetics of the self-cleavage reaction. Different ways of reaction initiation, suboptimal conditions, and jumpwise changes of reaction conditions have been used, and the temperature dependences have been studied. A correlation has been shown between the apparent kinetic constant of the first reaction phase and the portion of the ribozyme molecules that self-cleaved during the first phase. Partial restoration of the initial reaction characteristics has been shown by the reinitiation of reaction being stopped after completing the first phase. On the basis of all the data obtained, a scheme of the self-cleavage reaction has been proposed including: (i) activation of the ribozyme with energy of 40-50 kcal/mol and a characteristic time of several deciminutes under optimal reaction conditions; (ii) fast and reversible reaction of the phosphodiester bond cleavage; (iii) reaction leading to isomerization of the 3',5'-phosphodiester bond to the 2',5' bond in the self-cleavage site with a characteristic activation time of tens of minutes; and (iv) practically irreversible conformational change leading to fixation of the cleavage by immobilization of the 5'-terminal nucleotide of the product in the center of the formed structure and displacement of the 3'-terminal nucleotide to the periphery. The latter process has a characteristic time of tens of minutes and a low activation energy.


Assuntos
Vírus Delta da Hepatite/genética , Modelos Químicos , RNA Catalítico/química , RNA Viral/química , Sequência de Bases , Genoma Viral , Cinética , Dados de Sequência Molecular
16.
Vestn Oftalmol ; 115(1): 16-8, 1999.
Artigo em Russo | MEDLINE | ID: mdl-10207313

RESUMO

Heparin inhalations combined with intravenous laser exposure of the blood are effective in patients with nonproliferative, preproliferative, and proliferative diabetic retinopathy. Clinical effect consisted in decrease of edema in the macular area, partial resolution of hemorrhages, a tendency to decrease in the caliber of veins, improvement of visual acuity, and extension of visual field. Immunological studies revealed immunomodulating effect of heparin inhalations and intravenous laser exposure of the blood, manifesting by decreased levels of pathological circulating immune complexes and increased concentrations of immunoglobulins, mainly IgG and IgM. Diabetic hemophthalmia is to be treated by subtenon implantation of a collagen system with injection of a prourokinase thrombolytic in combination with preoperative preparation including heparin inhalations, intravenous laser exposure of the blood, and parabulbar administration of 0.5 ml 1% emoxipin for 5 days in order to normalize immune hemostatic and redox processes and create conditions for effective action of the thrombolytic.


Assuntos
Sangue/efeitos da radiação , Retinopatia Diabética/terapia , Fibrinolíticos/administração & dosagem , Heparina/administração & dosagem , Terapia a Laser , Administração por Inalação , Idoso , Feminino , Fibrinolíticos/uso terapêutico , Seguimentos , Heparina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Acuidade Visual , Campos Visuais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA