Assuntos
Cloreto de Sódio na Dieta/efeitos adversos , Animais , População Negra , Pressão Sanguínea/efeitos dos fármacos , Cultura , Dieta Hipossódica , Conservação de Alimentos , História do Século XVIII , História do Século XIX , História do Século XX , História Antiga , História Medieval , Humanos , Hipertensão/induzido quimicamente , Hipertensão/etnologia , Hipertensão/terapia , Cloreto de Sódio na Dieta/administração & dosagem , Cloreto de Sódio na Dieta/história , Estados UnidosRESUMO
Decorin binding protein A (DbpA) has been shown by several laboratories to be a protective antigen for the prevention of experimental Borrelia burgdorferi infection in the mouse model of Lyme borreliosis. However, different recombinant forms of the antigen having either lipidated amino termini, approximating the natural secretion and posttranslational processing, or nonprocessed cytosolic forms have elicited disparate levels of protection in the mouse model. We have now used the unique functional properties of this molecule to investigate the structural requirements needed to elicit a protective immune response. Genetic and physicochemical alterations to DbpA showed that the ability to bind to the ligand decorin is indicative of a potent immunogen but is not conclusive. By mutating the two carboxy-terminal nonconserved cysteines of DbpA from B. burgdorferi strain N40, we have determined that the stability afforded by the putative disulfide bond is essential for the generation of protective antibodies. This mutated protein was more sensitive to thermal denaturation and proteolysis, suggesting that it is in a less ordered state. Immunization with DbpA that was thermally denatured and functionally inactivated stimulated an immune response that was not protective and lacked bactericidal antibodies. Antibodies against conformationally altered forms of DbpA also failed to kill heterologous B. garinii and B. afzelii strains. Additionally, nonsecreted recombinant forms of DbpA(N40) were found to be inferior to secreted lipoprotein DbpA(N40) in terms of functional activity and antigenic potency. These data suggest that elicitation of a bactericidal and protective immune response to DbpA requires a properly folded conformation for the production of functional antibodies.
Assuntos
Adesinas Bacterianas , Anticorpos Antibacterianos/biossíntese , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas de Bactérias , Grupo Borrelia Burgdorferi/imunologia , Proteínas de Transporte/imunologia , Epitopos de Linfócito B/química , Epitopos de Linfócito B/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/química , Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Transporte/química , Proteínas de Transporte/genética , Reações Cruzadas , Modelos Animais de Doenças , Feminino , Doença de Lyme/prevenção & controle , Vacinas contra Doença de Lyme/imunologia , Camundongos , Camundongos Endogâmicos C3H , Dados de Sequência Molecular , Conformação Proteica , Vacinação , Vacinas Sintéticas/imunologiaAssuntos
Amiloidose/patologia , Cardiomiopatias/patologia , Idoso , Idoso de 80 Anos ou mais , Humanos , MasculinoRESUMO
Primary cardiac tumors involving the heart may be either benign or malignant. Most of the benign tumors are myxomas, which are most commonly located in the left atrium. Primary malignant neoplasms usually involve the myocardium and the interior of the cardiac cavities, whereas neoplasms metastatic to the heart most commonly involve pericardium, and pericardial effusion and constriction are the most common consequences. Computed tomography and magnetic resonance imaging are becoming the most useful instruments of precision for the diagnosis of cardiac tumors. Pericardial cysts, teratomas, lipomatous hypertrophy of the atrial septum, papillary fibroelastomas, thrombi, and sarcoid are frequently mistaken for cardiac neoplasms. There are a number of cardiac consequences of malignancy, including radiation heart disease, cardiac hemorrhages, cardiac infection, cardiac adiposity or the corticosteroid-treated heart, cardiac hemosiderosis, and toxicity due to anthracycline chemotherapy.
RESUMO
In comparing the cause of death and other cardiac morphologic findings among 60 women and 40 men aged >75 years who died of acute myocardial infarction, we found that women died more often from mechanical complications than left ventricular pump failure. Women had cardiomegaly, nonanterior location of acute myocardial infarction, healed myocardial infarcts, and dilated left ventricular cavity less often than men.
Assuntos
Causas de Morte , Morte Súbita Cardíaca , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/patologia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Autopsia , Distribuição de Qui-Quadrado , Feminino , Humanos , Incidência , Masculino , Probabilidade , Fatores de Risco , Distribuição por SexoRESUMO
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a primary cardiac disease with a diverse clinical spectrum, in which many of the abnormal structural and pathophysiologic features are consequences of inappropriate left ventricular hypertrophy. METHODS: We analyzed the amount, distribution and structure of the cardiac collagen network in transmural sections of the ventricular septum (thickness 17 to 40 mm, mean 25 mm) in 16 previously asymptomatic children and young adults with HCM (11 to 31 years of age, mean 20 years) who died suddenly. The morphologic appearance and volume fractions of interstitial (matrix) and perivascular (adventitial) collagen were analyzed with polarization microscopy and computerized videodensitometry in picrosirius red-stained sections. Findings were compared with 16 structurally normal hearts, 5 with systemic hypertension and 6 infants who died of HCM. RESULTS: Adults and young children with HCM had an eightfold greater amount of matrix collagen compared with normal controls (14.1 +/- 8.8% vs. 1.8 +/- 1% of the tissue section; p < 0.0001), and a threefold increase compared with patients with systemic hypertension (4.5 +/- 1.3%; p < 0.001) and infants with HCM (4.0 +/- 2.4%; p < 0.001). Compared with normal controls and hypertensives, adults and young children (and infants) with HCM showed increased numbers and thickness of each collagen fiber component of the matrix (perimysial coils, pericellular weaves and struts), which were often arranged in disorganized patterns. In HCM patients, the amount of collagen was not a consequence of other clinical, demographic and morphologic disease variables. CONCLUSIONS: Left ventricular collagen matrix in young, previously asymptomatic patients with HCM who died suddenly is morphologically abnormal and substantially increased in size. The enlarged matrix collagen compartment is present in HCM at an early age, further expands during growth, is partially responsible for increased ventricular septal thickness and likely represents a primary morphologic abnormality in this disease. These findings support the view that the complex HCM disease process is not confined to sarcomere protein abnormalities, but also involves connective tissue elements.