RESUMO
Proliferating Ki-67+ cardiomyocytes were detected in the interventricular septum myocardium of adult patients with hypertrophic cardiomyopathy. In the same patients, the severity of hypertrophy and the degree of cardiomyocyte differentiation were assessed by the content of myofibrils, ultrastructural morphology, and the pattern of connexin 43-containing gap junction distribution. Adult Ki-67+ cardiomyocytes containing sarcomeric α-actin (sarc α-act+) in the sarcoplasm (diameter 23.9±6.9 µ) were detected in the myocardium of patients with hypertrophic cardiomyopathy; their relative content varied from 2 to 3084 cells per 1 million cardiomyocytes. Small early differentiating Ki-67+/sarc α-act+ cardiomyocytes with a thin cytoplasm layer (diameter 5.9±1.7 µ) constituted from 3 to 2262 cells per 1 million cardiomyocytes. These cells were found in the myocardium with the most pronounced structural changes: hypertrophy of cardiomyocytes with signs of their partial dedifferentiation.
Assuntos
Cardiomiopatia Hipertrófica/patologia , Ventrículos do Coração/patologia , Miocárdio/patologia , Miócitos Cardíacos/patologia , Sarcômeros/patologia , Remodelação Ventricular , Actinas/genética , Actinas/metabolismo , Adolescente , Adulto , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/metabolismo , Contagem de Células , Diferenciação Celular , Proliferação de Células , Conexina 43/genética , Conexina 43/metabolismo , Feminino , Expressão Gênica , Ventrículos do Coração/metabolismo , Ventrículos do Coração/ultraestrutura , Humanos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/ultraestrutura , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/ultraestrutura , Sarcômeros/metabolismo , Sarcômeros/ultraestruturaRESUMO
The myocardium of the right and left atrial appendages (auricles) in patients with paroxysmal, persistent, and permanent forms of atrial fibrillation was examined by histological methods and electron microscopy. Isolated atrial amyloidosis was detected in the left (50.0-56.3% patients) and in the right (45.0-55.6% patients) atrial appendages. In all cases, immunohistochemistry revealed atrial natriuretic peptide in fibrillary amyloid deposits. Ultrastructurally, amyloid masses formed clusters of myofibrils 8-10 nm in diameter. They were chaotically located in the extracellular space along the sarcolemma as well as in membrane invaginations, dilated tubules of cardiomyocyte T-tubular system, and vascular walls. Amyloidosis was predominantly observed in women; its degree positively correlated with age of patients and duration of atrial fibrillation but negatively correlated with atrial fibrosis. The study revealed positive (in permanent atrial fibrillation) and negative (in paroxysmal atrial fibrillation) correlation of amyloidosis with myofibril content in atrial cardiomyocytes.
Assuntos
Amiloidose/patologia , Fibrilação Atrial/patologia , Átrios do Coração/patologia , Adulto , Idoso , Amiloide/metabolismo , Amiloidose/metabolismo , Fibrilação Atrial/metabolismo , Fator Natriurético Atrial/metabolismo , Feminino , Átrios do Coração/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , Adulto JovemRESUMO
Endomyocardial biopsy samples of the interventricular septum from patients with hypertrophic cardiomyopathy isolated during myectomy were examined. We revealed significant variability of cardiomyocyte ploidy (from 2.9c to 13.5c) that directly correlated with myocyte size; the maximum ploidy was found in young patients. Ultrastructural signs of increased contractile and synthetic activity of cells were observed in patients with high DNA content in cardiomyocytes.
Assuntos
Cardiomiopatia Hipertrófica/patologia , Miocárdio/patologia , Miócitos Cardíacos/patologia , Ploidias , Septo Interventricular/patologia , Adolescente , Adulto , Fatores Etários , Envelhecimento , Biópsia , DNA/genética , Humanos , Pessoa de Meia-Idade , Miócitos Cardíacos/citologia , Adulto JovemRESUMO
Interventricular septum myocardium was studied in 40 patients with obstructive hypertrophic cardiomyopathy. Immunohistochemical assay revealed c-kit-positive resident cardiac stem cells in 82.5% patients. The content of the connective tissue and myofibrillar disarray zones and the degree of cardiomyocyte hypertrophy and myolysis were determined. In 30% cases, cardiomyocytes containing atrial natriuretic peptide were detected in the interventricular septum myocardium. The data were compared with clinical and functional parameters of patients. It was found that cardiac stem cells are present in patients, whose myocardium was characterized by increased density of the connective tissue, hypertrophy of mature cardiomyocytes, medium degree of myolysis in them, and accumulation of natriuretic peptide, a cardiac failure marker, in cardiomyocytes.
Assuntos
Cardiomiopatia Hipertrófica/patologia , Miocárdio/citologia , Miócitos Cardíacos/citologia , Células-Tronco/citologia , Septo Interventricular/citologia , Adolescente , Adulto , Fator Natriurético Atrial/metabolismo , Cardiomiopatia Hipertrófica/cirurgia , Ecocardiografia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-kit/metabolismo , Estatísticas não Paramétricas , Células-Tronco/metabolismoRESUMO
We studied the content of resident myocardial stem cells, cardiomyocyte precursors, in myocardial biopsy specimens from the right ventricular outflow tract of patients of the first two years of life with tetralogy of Fallot. Myocardial resident stem cells were detected by the method of confocal immunohistochemistry using antibodies to c-kit and sarcomeric α-actin. The diameter of right ventricular cardiomyocytes was measured; the presence of myolysis zones was semiquantitatively evaluated. Electron microscopic analysis of right ventricular cardiomyocytes was performed. The data on the content of resident myocardial stem cells were compared with clinical and functional parameters of the patients and morphological peculiarities of the myocardium. C-kit-positive resident myocardial stem cells were detected in the right ventricle of 17.4% patients with tetralogy of Fallot. The content of resident myocardial stem cells in these patients varied from 4 to 45 (median 11) per 1 mln cardiomyocytes; this parameter was higher in patients with high content of small cardiomyocytes (diameter <10 µ) and cardiomyocytes with incomplete myofibril assembly in the right ventricular myocardium.
Assuntos
Ventrículos do Coração/citologia , Miócitos Cardíacos/citologia , Células-Tronco/citologia , Tetralogia de Fallot/patologia , Actinas/análise , Actinas/imunologia , Pré-Escolar , Humanos , Lactente , Miocárdio/patologia , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-kit/análise , Proteínas Proto-Oncogênicas c-kit/imunologiaRESUMO
Understanding the molecular basis and cell mechanisms, clinical course, and treatment of hypertrophic cardiomyopathy (HCMP) has progressed substantially in the last decade. The majority of genetic mutations associated with HCMP occur in genes encoding sarcomeric proteins, which are expressed only in cardiomyocytes. The spectrum of morphological features of HCMP includes: hypertrophy of myocardium, myocardial disarray, interstitial fibrosis, mitral valve abnormalities, and microvascular remodeling, is indicative of the involvement of other cell lineages. The link between sarcomeric gene defects and these HCM phenotypes remains elusive. Based on novel insights provided by cardiac developmental biology we can create new effective methods of treatment of this complex disease.
Assuntos
Cardiomiopatia Hipertrófica , Circulação Coronária/fisiologia , Miocárdio/patologia , Remodelação Ventricular/fisiologia , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/etiologia , Cardiomiopatia Hipertrófica/fisiopatologia , Progressão da Doença , Fibrose , HumanosRESUMO
We present the results of treatment of chronic ischemia of the lower extremities (distal form) with angiogenesis stimulators, autologous endothelioblast precursors (CD133+) and gene preparation of vascular endothelial growth factor VEGF165 (angiostimulin). Good clinical effect was attained in all patients, which was confirmed instrumentally 1, 3, and 6 months after administration of the stimulant: transcutaneous oxygen tension on the foot, index of malleolar pressure, and walking duration increased, parameters of microcirculation improved, the number of newly formed collateral arteries increased (angiography findings), quality of life improved (SF 36 questionnaire), and parameters of coagulogram also improved. The maximum positive dynamics was observed by month 3 of the study.
Assuntos
Indutores da Angiogênese/uso terapêutico , Terapia Baseada em Transplante de Células e Tecidos/métodos , Terapia Genética/métodos , Isquemia/tratamento farmacológico , Perna (Membro)/irrigação sanguínea , Antígeno AC133 , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia , Antígenos CD/uso terapêutico , Doença Crônica , Feminino , Glicoproteínas/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/uso terapêuticoRESUMO
The paper presents the first results of therapeutic angiogenesis in clinical cardiosurgery: human VEGF(165) gene transplantation to coronary patients. The use of this therapeutic method is particularly effective in patients with inoperable cardiovascular injuries, i.e. patients with the most severe condition, in whom treatment remains little effective at the modern level of cardiosurgery development.
Assuntos
Doença das Coronárias/tratamento farmacológico , Vasos Coronários/efeitos dos fármacos , Fator 2 de Crescimento de Fibroblastos/uso terapêutico , Terapia Genética/métodos , Isquemia/tratamento farmacológico , Neovascularização Fisiológica/fisiologia , Plasmídeos/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Animais , Doença das Coronárias/cirurgia , Vasos Coronários/fisiologia , Relação Dose-Resposta a Droga , Ecocardiografia , Eletrocardiografia , Fator 2 de Crescimento de Fibroblastos/genética , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/irrigação sanguínea , Revascularização Miocárdica , Plasmídeos/genética , Tomografia por Emissão de Pósitrons , Qualidade de Vida , Ratos , Tomografia Computadorizada de Emissão de Fóton Único , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
AIM: To evaluate the results of surgical treatment of patients with ischemic heart disease in combination with intraoperative intramyocardial introduction of the human gene VEGF165 (angiostimulin). MATERIAL AND METHODS: Twenty four patients enrolled in the study were examined using 12-lead ECG, echocardiography, treadmill exercise test, single-photon emission computed tomography of the myocardium with Tc-99m-tetrophosmine, fluorodesoxyglucose (FDG) positron-emission tomography of the myocardium, selective coronarography. Out of 24 patients, 10 patients have been reexamined so far. The effect of the treatment was assessed by the data obtained at the treadmill test, transthoracic echocardiography, myocardial scintigraphy and FDG. RESULTS: All the patients demonstrated a clinical response. The class of effort angina improved, the dose of the prescribed nitric drugs was decreased, exercise tolerance and total stress time rose, quality of life improved. Myocardial scintigraphy registered reduction of the total area and better accumulation of the radiopharmaceutical under load and at rest 3 and 6 months after the operation including myocardial areas which had not been revacularised at coronary artery bypass grafting but had been treated with the preparation of the human gene VEGF165. CONCLUSION: The results of the study suggest that therapeutic angiogenesis may be an alternative impact on those myocardial areas which are supplied by the affected but ineligible for bypass grafting coronary arteries.
Assuntos
Circulação Colateral/efeitos dos fármacos , Isquemia Miocárdica/terapia , Revascularização Miocárdica , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Terapia Combinada , Angiografia Coronária , Ecocardiografia , Eletrocardiografia , Teste de Esforço , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/cirurgia , Compostos Organofosforados , Compostos de Organotecnécio , Qualidade de Vida , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/administração & dosagemAssuntos
Feto/metabolismo , Lipoproteínas HDL/metabolismo , Fígado/metabolismo , Receptores de Superfície Celular/metabolismo , Células Cultivadas , Eletroforese em Gel de Poliacrilamida , Humanos , Técnicas In Vitro , Ligantes , Fígado/citologia , Microscopia de Contraste de Fase , Peso Molecular , Receptores de Superfície Celular/químicaAssuntos
Complexo Antígeno-Anticorpo/sangue , Aortite/imunologia , Arterite/imunologia , Proteínas de Fase Aguda/análise , Adolescente , Adulto , Aorta Abdominal , Doença Crônica , Proteínas do Sistema Complemento/análise , Feminino , Humanos , Imunoglobulinas/sangue , Masculino , Pessoa de Meia-Idade , Artéria RenalRESUMO
Sixty patients with systemic lupus erythematosus (SLE) were examined: 40 patients with cryoglobulinemia and 20 patients without it. Cryoglobulinemia was observed in patients with SLE, as a rule, in the acute course of the disease ending in renal affection. Cryoglobulinemia in SLE was accompanied by the phenomenon of generalized vasculitis in the form of skin and mucosa lesions with ulcero-necrotic changes and affections of the central and peripheral nervous system and the kidneys. The clinical picture of SLE accompanied by cryoglobulinemia was characterized by a polysyndrome phenomenon and infrequent presence of the ARA criteria. Cryoglobulinemia was accompanied by high titres of anti-DNA. Thus, cryoglobulinemia can be regarded as one of the important factors of immunocomplex damage in SLE.
Assuntos
Anticorpos Antinucleares/análise , Complexo Antígeno-Anticorpo/análise , Doenças Autoimunes/diagnóstico , Crioglobulinas/análise , Doenças do Complexo Imune/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Adolescente , Adulto , Doenças Autoimunes/imunologia , DNA/imunologia , Feminino , Humanos , Doenças do Complexo Imune/imunologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
EIA was used to measure the concentration of fibronectin in plasma and cryoprecipitates of 37 patients suffering from systemic lupus erythematosus coupled with cryoglobulinemia. A definite relationship was discovered between the level of cryoglobulins and the activity of SLE, the concentration of fibronectin in plasma and liver damage. A tendency was revealed towards increase of the fibronectin content in plasma of patients with a high level of antibodies to native DNA and CIC as was a significant correlation between the concentration of cryoglobulin protein and the concentration of fibronectin in cryoprecipitates.
Assuntos
Crioglobulinemia/imunologia , Fibronectinas/sangue , Lúpus Eritematoso Sistêmico/imunologia , Adolescente , Adulto , Anticorpos/sangue , Cardiolipinas/imunologia , Doença Crônica , Complemento C1q/análise , Crioglobulinas/análise , DNA/imunologia , Feminino , Humanos , Imunoglobulinas/análise , Nefrite Lúpica/imunologia , Masculino , Pessoa de Meia-Idade , Fator Reumatoide/sangueRESUMO
The authors provide the results of studying the methodologic characteristics and of the clinical trial of the C1q-ELISA for detection of the circulating immune complexes. The C1q-ELISA is shown to have a high sensitivity and to make it possible to identify 3 micrograms/ml and more of aggregated gamma-globulin. The method can use for detection of CIC E (ab')2-fragments of antibodies to IgG of man and protein A labeled with peroxidase. Using the method, the circulating immune complexes were identified in the sera of 50% of patients with systemic lupus erythematosus, of 30% of patients with dilated cardiomyopathy and of 53% of patients with nonspecific aortoarteritis. It is concluded that the C1q-ELISA can be used in clinical practice for detecting the circulating immune complexes in different diseases of man.
Assuntos
Complexo Antígeno-Anticorpo/análise , Complemento C1q/análise , Lúpus Eritematoso Sistêmico/imunologia , Cardiomiopatia Dilatada/imunologia , Ensaio de Imunoadsorção Enzimática , Fator VIII/análise , Humanos , Imunoglobulina G/análise , Arterite de Takayasu/imunologia , gama-Globulinas/análiseRESUMO
A considerable imbalance in humoral and cellular factors of immunity characterized by high B-cell activity associated with a relative T-cell deficiency has been revealed in patients with coronary heart disease. Immunological imbalance is characteristic for all the clinically pronounced forms of coronary heart disease, forming long before obvious lesions of the coronary arteries. This makes it possible to regard patients without coronarographically documented atherosclerosis as having functional form of the process pathogenetically identical to atherosclerosis according to immunological criteria.
Assuntos
Doença da Artéria Coronariana/imunologia , Sistema Imunitário/imunologia , Adulto , Idoso , Complexo Antígeno-Anticorpo/análise , Proteína C-Reativa/análise , Proteínas do Sistema Complemento/análise , Doença das Coronárias/imunologia , Humanos , Imunoglobulinas/análise , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Fagocitose , Formação de RosetaRESUMO
Levels of circulating immune complexes (CIC) and apolipoproteins (apo-A and apo-B) were compared and correlated with the severity of atherosclerotic affection of heart vessels in coronary patients with coronarographically-verified coronary arterial atherosclerosis. An inverse correlation between blood CIC and apo-A levels, and a direct correlation between the CIC level and the apo-B/apo-A index were demonstrated. The variation of CIC levels in patients with atherosclerotic lesions of varying severity corresponded to that of the apo-B/apo-A index. The correlation of these parameters was particularly significant in coronary patients with 2 coronary vessels affected.
Assuntos
Complexo Antígeno-Anticorpo/análise , Apolipoproteínas A/sangue , Apolipoproteínas B/sangue , Doença das Coronárias/sangue , Adulto , Doença das Coronárias/etiologia , Doença das Coronárias/imunologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The coagglutination test was used to identify Shigella boydii and Shigella dysenteriae. A trial was carried out with 13 native rabbit antisera to S. boydii and 10 antisera to S. dysenteriae, as well as with coagglutinating reagents prepared from these antisera. The use of coagglutinating reagents was shown to ensure the complete specificity of the results, to prevent the adsorption of diagnostic antisera and to decrease their consumption 50 times. The importance of the coagglutination test for the identification of shigellae is discussed.