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1.
Environ Sci Technol ; 48(9): 4707-15, 2014 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-24624890

RESUMO

Oil and natural gas production in the Western United States has grown rapidly in recent years, and with this industrial expansion, growing environmental concerns have arisen regarding impacts on water supplies and air quality. Recent studies have revealed highly enhanced atmospheric levels of volatile organic compounds (VOCs) from primary emissions in regions of heavy oil and gas development and associated rapid photochemical production of ozone during winter. Here, we present surface and vertical profile observations of VOC from the Uintah Basin Winter Ozone Studies conducted in January-February of 2012 and 2013. These measurements identify highly elevated levels of atmospheric alkane hydrocarbons with enhanced rates of C2-C5 nonmethane hydrocarbon (NMHC) mean mole fractions during temperature inversion events in 2013 at 200-300 times above the regional and seasonal background. Elevated atmospheric NMHC mole fractions coincided with build-up of ambient 1-h ozone to levels exceeding 150 ppbv (parts per billion by volume). The total annual mass flux of C2-C7 VOC was estimated at 194 ± 56 × 10(6) kg yr(-1), equivalent to the annual VOC emissions of a fleet of ∼100 million automobiles. Total annual fugitive emission of the aromatic compounds benzene and toluene, considered air toxics, were estimated at 1.6 ± 0.4 × 10(6) and 2.0 ± 0.5 × 10(6) kg yr(-1), respectively. These observations reveal a strong causal link between oil and gas emissions, accumulation of air toxics, and significant production of ozone in the atmospheric surface layer.


Assuntos
Poluentes Atmosféricos/análise , Atmosfera/química , Compostos Orgânicos Voláteis/análise , Monitoramento Ambiental/métodos , Hidrocarbonetos/análise , Ozônio/análise , Espectrofotometria Ultravioleta , Utah
2.
Circulation ; 122(13): 1319-27, 2010 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-20837893

RESUMO

BACKGROUND: Although short- and medium-term outcomes after transcatheter aortic valve implantation are encouraging, long-term data on valve function and clinical outcomes are limited. METHODS AND RESULTS: Consecutive high-risk patients who had been declined as surgical candidates because of comorbidities but who underwent successful transcatheter aortic valve implantation with a balloon-expandable valve between January 2005 and December 2006 and survived past 30 days were assessed. Clinical, echocardiographic, and computed tomographic follow-up examinations were performed. Seventy patients who underwent successful procedures and survived longer than 30 days were evaluated at a minimum follow-up of 3 years. At a median follow-up of 3.7 years (interquartile range 3.4 to 4.3 years), survival was 57%. Survival at 1, 2, and 3 years was 81%, 74%, and 61%, respectively. Freedom from reoperation was 98.5% (1 patient with endocarditis). During this early procedural experience, 11 patients died within 30 days, and 8 procedures were unsuccessful. When these patients were included, overall survival was 51%. Transaortic pressure gradients increased from 10.0 mm Hg (interquartile range 8.0 to 12.0 mm Hg) immediately after the procedure to 12.1 mm Hg (interquartile range 8.6 to 16.0 mm Hg) after 3 years (P=0.03). Bioprosthetic valve area decreased from a mean of 1.7±0.4 cm(2) after the procedure to 1.4±0.3 cm(2) after 3 years (P<0.01). Aortic incompetence after implantation was trivial or mild in 84% of cases and remained unchanged or improved over time. There were no cases of structural valvular deterioration, stent fracture, deformation, or valve migration. CONCLUSIONS: Transcatheter aortic valve implantation demonstrates good medium- to long-term durability and preserved hemodynamic function, with no evidence of structural failure. The procedure appears to offer an adequate and lasting resolution of aortic stenosis in selected patients.


Assuntos
Estenose da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca , Hemodinâmica , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/mortalidade , Estudos de Coortes , Seguimentos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Taxa de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
3.
J Evol Biol ; 23(8): 1664-71, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20546090

RESUMO

When individuals interact, phenotypic variation can be partitioned into direct genetic effects (DGEs) of the individuals' own genotypes, indirect genetic effects (IGEs) of their social partners' genotypes and epistatic interactions between the genotypes of interacting individuals ('genotype-by-genotype (GxG) epistasis'). These components can all play important roles in evolutionary processes, but few empirical studies have examined their importance. The social amoeba Dictyostelium discoideum provides an ideal system to measure these effects during social interactions and development. When starved, free-living amoebae aggregate and differentiate into a multicellular fruiting body with a dead stalk that holds aloft viable spores. By measuring interactions among a set of natural strains, we quantify DGEs, IGEs and GxG epistasis affecting spore formation. We find that DGEs explain most of the phenotypic variance (57.6%) whereas IGEs explain a smaller (13.3%) but highly significant component. Interestingly, GxG epistasis explains nearly a quarter of the variance (23.0%), highlighting the complex nature of genotype interactions. These results demonstrate the large impact that social interactions can have on development and suggest that social effects should play an important role in developmental evolution in this system.


Assuntos
Dictyostelium/fisiologia , Modelos Genéticos , Dictyostelium/genética , Dictyostelium/crescimento & desenvolvimento , Genótipo , Fenótipo , Esporos de Protozoários/fisiologia
4.
Science ; 208(4441): 313-4, 1980 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-7367862

RESUMO

The language barrier of the chimpanzee Lana, previously described by Rumbaugh (1977), can be simulated by a computer model in which the animal selects, depending upon context, one of six stock sentences with fixed and variable elements.


Assuntos
Comunicação Animal , Comportamento Animal/fisiologia , Idioma , Pan troglodytes/fisiologia , Animais , Aprendizagem/fisiologia
5.
J Vasc Res ; 45(4): 357-62, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18332634

RESUMO

Dysregulation of matrix metalloproteinase (MMP)-2 in the vasculature has been suggested to be associated with increased prevalence of cardiovascular disease and renal injury. In this descriptive study, we hypothesized that arterial MMP-2 activity is elevated in the presence of cardiovascular risk factors such as diabetes, hypertension, smoking and ageing, and that it correlates with the degree of kidney function. MMP-2 activity in internal mammary arteries (n = 37) was measured using gelatinolytic zymography, and cutoffs were determined using sample-derived medians. Patient demographics and clinical data were analyzed, and the estimated glomerular filtration rate (eGFR) was calculated. High MMP-2 activity (>60,000 units) was associated with age, hypertension and diabetes (p = 0.0034, 0.06 and 0.0034, respectively). Multivariate analysis showed that age and diabetes were independent predictors of high MMP-2 activity. There is a trend towards increased MMP-2 activity and reduced eGFR (p = 0.010). The current exploratory work describes that the activity of MMP-2 in the internal mammary artery is correlated with age, hypertension, diabetes and eGFR. It is the first report suggesting that MMP-2 in the arterial vasculature could be the possible mediator crucial in linking the progression of kidney function to cardiovascular disease.


Assuntos
Envelhecimento , Diabetes Mellitus Tipo 2 , Hipertensão , Nefropatias , Artéria Torácica Interna/enzimologia , Metaloproteinase 2 da Matriz/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Taxa de Filtração Glomerular , Humanos , Pessoa de Meia-Idade
6.
Mol Cell Biol ; 14(6): 4020-31, 1994 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8196641

RESUMO

We have mapped the regions in the Drosophila melanogaster tissue-specific transcription factor Grainyhead that are required for DNA binding and dimerization. These functional domains correspond to regions conserved between Grainyhead and the vertebrate transcription factor CP2, which we show has similar activities. The identified DNA-binding domain is large (263 amino acids) but contains a smaller core that is able to interact with DNA at approximately 400-fold lower affinity. The major dimerization domain is located in a separate region of the protein and is required to stabilize the interactions with DNA. Our data also suggest that Grainyhead activity can be modulated by an N-terminal inhibitory domain.


Assuntos
Sequência Conservada , Proteínas de Ligação a DNA/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Fatores de Transcrição/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Primers do DNA , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Proteínas de Ligação a RNA , Mapeamento por Restrição , Homologia de Sequência de Aminoácidos , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Vertebrados
7.
J Appl Physiol (1985) ; 100(2): 685-9, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16239613

RESUMO

The curvilinearity of the atrial pressure-volume curve implies that atrial compliance decreases progressively with increasing left atrial (LA) pressure (LAP). We predicted that reduced LA compliance leads to more rapid deceleration of systolic pulmonary venous (PV) flow. With this rationale, we investigated whether the deceleration time (t dec) of PV systolic flow velocity reflects mean LAP. In eight patients during coronary surgery, before extracorporeal circulation, PV flow by ultrasonic transit time and invasive LAP were recorded during stepwise volume loading. The t dec was calculated using two methods: by drawing a tangent through peak deceleration and by drawing a line from peak systolic flow through the nadir between the systolic and early diastolic flow waves. LA compliance was calculated as the systolic PV flow integral divided by LAP increment. Volume loading increased mean LAP from 11 +/- 3 to 20 +/- 5 mmHg (P < 0.001) (n = 40), reduced LA compliance from 1.16 +/- 0.42 to 0.72 +/- 0.40 ml/mmHg (P < 0.004) (n = 40), and reduced t dec from 320 +/- 50 to 170 +/- 40 ms (P < 0.0005) (n = 40). Mean LAP correlated well with t dec (r = 0.84, P < 0.0005) (n = 40) and LA compliance (r = 0.79, P < 0.0005) (n = 40). Elevated LAP caused a decrease in LA compliance and therefore more rapid deceleration of systolic PV flow. The t dec has potential to become a semiquantitative marker of LAP and an index of LA passive elastic properties.


Assuntos
Função do Átrio Esquerdo/fisiologia , Veias Pulmonares/fisiologia , Velocidade do Fluxo Sanguíneo , Complacência (Medida de Distensibilidade) , Ecocardiografia Doppler , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão , Circulação Pulmonar/fisiologia , Veias Pulmonares/diagnóstico por imagem , Análise de Regressão , Sístole , Fatores de Tempo
8.
Circulation ; 100(11): 1236-41, 1999 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-10484546

RESUMO

BACKGROUND: Patients with inflammatory heart muscle diseases would benefit from a safe, convenient, rapidly performed diagnostic technique with real-time results not involving tissue removal. We have performed a detailed evaluation of detection of heart allograft rejection by autofluorescence in a heterotopic abdominal rat heart allograft model ex vivo. METHODS AND RESULTS: Recipient rats with allograft (Lewis to Fisher 344; n=71) and isograft (Lewis to Lewis; n=33) hearts, treated with cyclosporine or untreated, were killed at days 2, 4, 7, 14, 21, 28, and 56 after transplant. Nontransplant controls with (n=24) or without (n=24) immunosuppressive therapy were also studied. When the rats were killed, autofluorescence spectra were acquired under blue-light excitation from midtransverse ventricular sections of native and transplanted hearts. Corresponding sections were then evaluated pathologically by a modified International Society for Heart and Lung Transplantation (ISHLT) grading schema. The spectral differences between rejecting and nonrejecting hearts were quantified by linear discriminant functions, producing scores that decreased progressively with increasing severity of tissue rejection. Mean+/-SD discriminant function scores were 2.9+/-1.6, 1.8+/-2.2, -0.1+/-2.8, -1.2+/-2.3, and -2.3+/-3.0 for isografts and allograft ISHLT grades 0, I, II, and III, respectively (Spearman rank-order correlation -0.6; P<0.001, test for trend). Cyclosporine had no detectable effect on the spectra. CONCLUSIONS: The correlation between changes in autofluorescence spectra and ISHLT rejection grade strongly supports the possibility of catheter-based, fluorescence-guided surveillance of rejection.


Assuntos
Rejeição de Enxerto/diagnóstico , Transplante de Coração , Espectrometria de Fluorescência , Animais , Ciclosporina/farmacologia , Rejeição de Enxerto/patologia , Imunossupressores/farmacologia , Ratos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Sensibilidade e Especificidade , Transplante Heterólogo , Transplante Homólogo , Transplante Isogênico
9.
J Am Coll Cardiol ; 37(8): 2025-30, 2001 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-11419882

RESUMO

OBJECTIVES: This study compared a prediction of mean left atrial pressure (P(LA)) ascertained by Doppler echocardiography of pulmonary venous flow (PVF), with predicted P(LA) using the pulmonary artery occlusion pressure (P(PAO)). BACKGROUND: In select patient groups, PVF variables correlate with P(PAO)) an indirect measure of P(LA). METHODS: In 93 patients undergoing cardiac surgery, we recorded with transesophageal echocardiography mitral valve early (E) and late (A) wave velocities, deceleration time (DT) of E (DT(E)), and pulmonary vein systolic (S) and diastolic (D) wave velocities, DT of D (DT(D)) and systolic fraction. The P(PAO) was measured using a pulmonary artery catheter zeroed to midaxillary level. A further catheter was held at midatrial level to zero a transducer and was then inserted into the left atrium. A prediction rule for P(LA) from DT(D) was developed in 50 patients and applied prospectively to estimate P(LA) in 43 patients. RESULTS: A close correlation (r = -0.92) was found between P(LA) and DT(D). Systolic fraction (r = -0.63), DT(E) (r = -0.61), D wave (r = 0.57), E wave (r = 0.52), and E/A ratio (r = 0.13) correlated less closely with P(LA). The mean difference between predicted and measured P(LA) was 0.58 mm Hg for DT(D) method and 1.72 mm Hg for P(PAO), with limits of agreement (mean +/- 2 SE) of -2.94 to 4.10 mm Hg and -2.48 to 5.92 mm Hg, respectively. A DT(D)) of <175 ms had 100% sensitivity and 94% specificity for a P(LA) of >17 mm Hg. CONCLUSIONS: Deceleration time of pulmonary vein diastolic wave is more accurate than P(PAO) in estimating left atrial pressure in cardiac surgical patients.


Assuntos
Função do Átrio Esquerdo , Veias Pulmonares/fisiologia , Idoso , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Artéria Pulmonar/fisiologia , Veias Pulmonares/diagnóstico por imagem , Fluxo Sanguíneo Regional , Reprodutibilidade dos Testes , Ultrassonografia Doppler
10.
J Am Coll Cardiol ; 27(1): 155-60, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8522690

RESUMO

OBJECTIVES: This study sought to investigate whether right atrial pressure could be used to estimate pericardial pressure during positive end-expiratory pressure (PEEP). BACKGROUND: Because of elevated intrathoracic pressure during PEEP, pulmonary capillary wedge pressure may not accurately reflect left ventricular preload. An estimate of pericardial pressure during PEEP would allow assessment of transmural filling pressure. METHODS: In eight patients, at the start of cardiac surgery, pericardial and pleural pressures were recorded by balloon transducers placed over the anterolateral left ventricular wall. We also recorded intravascular pressures and left ventricular short-axis area by transesophageal echocardiography. RESULTS: A stepwise increase in PEEP from 0 to 15 cm H2O caused a linear increase in pleural pressure from 0.3 +/- 0.6 (mean +/- SEM) to 6.1 +/- 0.8 mm Hg (p < 0.01). Pericardial pressure increased from 2.3 +/- 0.5 to 5.9 +/- 0.6 mm Hg (p < 0.01). The correlation between right atrial (Pra) and pericardial pressure (Pperic) was good: Pra = 0.85 x Pperic + 1.8, r = 0.77. The correlation between changes in right atrial pressure and in pericardial pressure was better: delta Pra = 0.96 x delta Pperic -0.2, r = 0.97. Pulmonary capillary wedge pressure increased with PEEP (p < 0.05), whereas left ventricular area decreased (p < 0.05). However, there was a progressive reduction in transmural pressure, calculated as wedge pressure minus pericardial pressure (p < 0.05), and in transmural pressure, estimated as wedge pressure minus right atrial pressure (p < 0.05). The estimated transmural filling pressure correlated (r = 0.86) with end-diastolic area. CONCLUSIONS: The present observations suggest that right atrial pressure may be used to estimate changes in pericardial pressure with PEEP and that pulmonary capillary wedge pressure minus right atrial pressure is a potentially clinically useful approximation of transmural filling pressure.


Assuntos
Respiração com Pressão Positiva/métodos , Função Ventricular Esquerda/fisiologia , Pressão Ventricular , Adulto , Idoso , Análise de Variância , Função Atrial , Pressão Sanguínea , Ponte de Artéria Coronária , Ecocardiografia Transesofagiana , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Pressão Propulsora Pulmonar , Análise de Regressão
11.
J Am Coll Cardiol ; 23(3): 753-8, 1994 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-8113561

RESUMO

OBJECTIVES: This study was conducted to measure the cardiac constraining effect of the lungs during positive end-expiratory pressure and relate extracardiac pleural pressure (radial stress) to airway pressure, right atrial pressure and left ventricular filling. BACKGROUND: During positive end-expiratory pressure ventilation, the extracardiac pressure is elevated, and therefore intracavitary filling pressure does not reflect ventricular preload. Estimates of this pressure might be useful clinically to assess left ventricular preload. METHODS: In eight patients who had undergone coronary or valvular surgery and whose pericardium was left widely open, a flat pleural balloon transducer was placed over the anterolateral left ventricular wall. We recorded pulmonary capillary wedge pressure, right atrial pressure and left ventricular short-axis end-diastolic area by transesophageal echocardiography. Incremental positive end-expiratory pressure was applied. RESULTS: Extracardiac pleural pressure increased (p < 0.01) from 0.6 +/- 1.8 (+/- SD) to 2.4 +/- 1.8, 5.3 +/- 1.5 and 8.2 +/- 1.5 mm Hg at a positive end-expiratory pressure of 5, 10 and 15 cm H2O, respectively. The slope relating extracardiac pleural pressure to positive end-expiratory pressure (in mm Hg) was 0.70 +/- 0.10, and the intercept was zero. Increasing extracardiac pleural pressure was associated with a progressive increase in pulmonary capillary wedge pressure and a decrease in left ventricular end-diastolic area. Consequently, although pulmonary capillary wedge pressure and left ventricular area changed in opposite directions, the value of pulmonary capillary wedge pressure minus extracardiac pleural pressure correlated positively with left ventricular area (r = 0.95, p < 0.001). Changes in right atrial pressure (Pra) correlated with changes in extracardiac pleural pressure (Ppleural): delta Pra = -0.3 + 0.56. delta Ppleural (r = 0.89, p < 0.001). CONCLUSIONS: In postoperative patients with open pericardium, pulmonary capillary wedge pressure minus extracardiac pleural pressure predicts left ventricular end-diastolic area during positive end-expiratory pressure. Further studies should be done to determine whether the observed relations between airway pressure and extracardiac pleural pressure and between right atrial pressure and extracardiac pleural pressure may give clinically useful estimates of left ventricular preload during positive end-expiratory pressure.


Assuntos
Ponte de Artéria Coronária , Pleura/fisiologia , Respiração com Pressão Positiva , Volume Sistólico , Idoso , Função do Átrio Direito/fisiologia , Cateterismo , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Pericardiectomia , Pressão , Pressão Propulsora Pulmonar/fisiologia , Função Ventricular Esquerda/fisiologia
12.
J Am Coll Cardiol ; 34(3): 802-9, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10483963

RESUMO

OBJECTIVES: The purpose of this study was to determine the origin of the pulmonary venous systolic flow pulse using wave-intensity analysis to separate forward- and backward-going waves. BACKGROUND: The mechanism of the pulmonary venous systolic flow pulse is unclear and could be a "suction effect" due to a fall in atrial pressure (backward-going wave) or a "pushing effect" due to forward-propagation of right ventricular (RV) pressure (forward-going wave). METHODS: In eight patients during coronary surgery, pulmonary venous flow (flow probe), velocity (microsensor) and pressure (micromanometer) were recorded. We calculated wave intensity (dP x dU) as change in pulmonary venous pressure (dP) times change in velocity (dU) at 5 ms intervals. When dP x dU > 0 there is a net forward-going wave and when dP x dU < 0 there is a net backward-going wave. RESULTS: Systolic pulmonary venous flow was biphasic. When flow accelerated in early systole (S1), pulmonary venous pressure was falling, and, therefore, dP x dU was negative, -0.6 +/- 0.2 (x +/- SE) W/m2, indicating a net backward-going wave. When flow accelerated in late systole (S2), pressure was rising, and, therefore, dP x dU was positive, 0.3 +/- 0.1 W/m2, indicating a net forward-going wave. CONCLUSIONS: Pulmonary venous flow acceleration in S1 was attributed to a net backward-going wave secondary to a fall in atrial pressure. However, flow acceleration in S2 was attributed to a net forward-going wave, consistent with propagation of the RV systolic pressure pulse across the lungs. Pulmonary vein systolic flow pattern, therefore, appears to be determined by right- as well as left-sided cardiac events.


Assuntos
Função do Átrio Esquerdo/fisiologia , Pressão Sanguínea/fisiologia , Veias Pulmonares/fisiologia , Fluxo Pulsátil/fisiologia , Idoso , Velocidade do Fluxo Sanguíneo/fisiologia , Ponte de Artéria Coronária , Doença das Coronárias/fisiopatologia , Doença das Coronárias/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Monitorização Intraoperatória/estatística & dados numéricos , Análise de Regressão , Sístole/fisiologia
13.
J Am Coll Cardiol ; 36(3 Suppl A): 1104-9, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10985712

RESUMO

OBJECTIVES: Our objective was to define the outcomes of patients with cardiogenic shock (CS) due to severe mitral regurgitation (MR) complicating acute myocardial infarction (AMI). BACKGROUND: Methods for early identification and optimal treatment of such patients have not been defined. METHODS: The SHOCK Trial Registry enrolled 1,190 patients with CS complicating AMI. We compared 1) the cohort with severe mitral regurgitation (MR, n = 98) to the cohort with predominant left ventricular failure (LVF, n = 879), and 2) the MR patients who underwent valve surgery (n = 43) to those who did not (n = 51). RESULTS: Shock developed early after MI in both the MR (median 12.8 h) and LVF (median 6.2 h) cohorts. The MR patients were more often female (52% vs. 37%, p = 0.004) and less likely to have ST elevation at shock diagnosis (41% vs. 63%, p < 0.001). The MR index MI was more frequently inferior (55% vs. 44%, p = 0.039) or posterior (32% vs. 17%, p = 0.002) than that of LVF and much less frequently anterior (34% vs. 59%, p < 0.001). Despite having higher mean LVEF (0.37 vs. 0.30, p = 0.001) the MR cohort had similar in-hospital mortality (55% vs. 61%, p = 0.277). The majority of MR patients did not undergo mitral valve surgery. Those undergoing surgery exhibited higher mean LVEF than those not undergoing surgery; nevertheless, 39% died in hospital. CONCLUSIONS: The data highlight opportunities for early identification and intervention to potentially decrease the devastating mortality and morbidity of severe post-myocardial infarction MR.


Assuntos
Insuficiência da Valva Mitral/complicações , Sistema de Registros , Choque Cardiogênico/etiologia , Idoso , Cateterismo , Angiografia Coronária , Feminino , Implante de Prótese de Valva Cardíaca , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/terapia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Revascularização Miocárdica , Razão de Chances , Estudos Prospectivos , Choque Cardiogênico/mortalidade , Choque Cardiogênico/fisiopatologia , Choque Cardiogênico/terapia , Volume Sistólico , Taxa de Sobrevida
14.
J Mol Biol ; 304(4): 657-68, 2000 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-11099387

RESUMO

Citrate synthases from Thermoplasma acidophilum (optimal growth at 55 degrees C) and Pyrococcus furiosus (100 degrees C) are homo-dimeric enzymes that show a high degree of structural homology with each other, and thermostabilities commensurate with the environmental temperatures in which their host cells are found. A comparison of their atomic structures with citrate synthases from mesophilic and psychrophilic organisms has indicated the potential importance of inter-subunit contacts for thermostability, and here we report the construction and analysis of site-directed mutants of the two citrate synthases to investigate the contribution of these interactions. Three sets of mutants were made: (a) chimeric mutants where the large (inter-subunit contact) and small (catalytic) domains of the T. acidophilum and P. furiosus enzymes were swapped; (b) mutants of the P. furiosus citrate synthase where the inter-subunit ionic network is disrupted; and (c) P. furiosus citrate synthase mutants in which the C-terminal arms that wrap around their partner subunits have been deleted. All three sets of mutant enzymes were expressed as recombinant proteins in Escherichia coli and were found to be catalytically active. Kinetic parameters and the dependence of catalytic activity on temperature were determined, and the stability of each enzyme was analysed by irreversible thermal inactivation experiments. The chimeric mutants indicate that the thermostability of the whole enzyme is largely determined by the origin of the large, inter-subunit domain, whereas the dependence of catalytic activity on temperature is a function of the small domain. Disruption of the inter-subunit ionic network and prevention of the C-terminal interactions both generated enzymes that were substantially less thermostable. Taken together, these data demonstrate the crucial importance of the subunit contacts to the stability of these oligomeric enzymes. Additionally, they also provide a clear distinction between thermostability and thermoactivity, showing that stability is necessary for, but does not guarantee, catalytic activity at elevated temperatures.


Assuntos
Citrato (si)-Sintase/química , Citrato (si)-Sintase/metabolismo , Pyrococcus furiosus/enzimologia , Thermoplasma/enzimologia , Citrato (si)-Sintase/genética , Citrato (si)-Sintase/isolamento & purificação , Estabilidade Enzimática/genética , Escherichia coli/genética , Cinética , Modelos Moleculares , Mutação/genética , Estrutura Quaternária de Proteína , Subunidades Proteicas , Pyrococcus furiosus/genética , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Eletricidade Estática , Temperatura , Termodinâmica , Thermoplasma/genética
15.
Cell Death Dis ; 6: e1666, 2015 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-25719250

RESUMO

Withanolide E, a steroidal lactone from Physalis peruviana, was found to be highly active for sensitizing renal carcinoma cells and a number of other human cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Withanolide E, the most potent and least toxic of five TRAIL-sensitizing withanolides identified, enhanced death receptor-mediated apoptotic signaling by a rapid decline in the levels of cFLIP proteins. Other mechanisms by which TRAIL sensitizers have been reported to work: generation of reactive oxygen species (ROS), changes in pro-and antiapoptotic protein expression, death receptor upregulation, activation of intrinsic (mitochondrial) apoptotic pathways, ER stress, and proteasomal inhibition proved to be irrelevant to withanolide E activity. Loss of cFLIP proteins was not due to changes in expression, but rather destabilization and/or aggregation, suggesting impairment of chaperone proteins leading to degradation. Indeed, withanolide E treatment altered the stability of a number of HSP90 client proteins, but with greater apparent specificity than the well-known HSP90 inhibitor geldanamycin. As cFLIP has been reported to be an HSP90 client, this provides a potentially novel mechanism for sensitizing cells to TRAIL. Sensitization of human renal carcinoma cells to TRAIL-induced apoptosis by withanolide E and its lack of toxicity were confirmed in animal studies. Owing to its novel activity, withanolide E is a promising reagent for the analysis of mechanisms of TRAIL resistance, for understanding HSP90 function, and for further therapeutic development. In marked contrast to bortezomib, among the best currently available TRAIL sensitizers, withanolide E's more specific mechanism of action suggests minimal toxic side effects.


Assuntos
Apoptose/efeitos dos fármacos , Carcinoma de Células Renais/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Vitanolídeos/farmacologia , Animais , Western Blotting , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Imunoprecipitação , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/farmacologia
16.
Neurology ; 56(9): 1222-4, 2001 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-11342693

RESUMO

A retrospective review of 29 consecutive unselected patients referred for neuro-ophthalmic evaluation after the diagnosis of neurofibromatosis type 2 (NF2) showed that four of them had a monocular elevator paresis. In two of the four MRI demonstrated lesions, presumed to be schwannomas, of the third nerve. These findings indicate that monocular elevator paresis is a common neuro-ophthalmic finding in NF2, which the authors suspect is probably a sign of third nerve infiltration or compression by a schwannoma.


Assuntos
Neurofibromatose 2/complicações , Neurofibromatose 2/patologia , Transtornos da Motilidade Ocular/complicações , Transtornos da Motilidade Ocular/patologia , Paresia/complicações , Paresia/patologia , Adolescente , Adulto , Neoplasias dos Nervos Cranianos/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neurilemoma/patologia , Estudos Retrospectivos
17.
Am J Cardiol ; 82(7): 912-4, 1998 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-9781979

RESUMO

Long-term resistance training as performed by elite female resistance-trained athletes appears to be an insufficient stimulus to alter left ventricular cavity size, wall thickness, or estimated mass.


Assuntos
Hipertrofia Ventricular Esquerda/etiologia , Levantamento de Peso/fisiologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Manobra de Valsalva
18.
Am J Cardiol ; 63(13): 912-6, 1989 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-2648791

RESUMO

The determinants of myocardial salvage after thrombolytic therapy during acute myocardial infarction (AMI) have not been clearly defined. In 1984, a prospective randomized trial was undertaken to define the relations between delay to treatment and effectiveness of perfusion to salvage of myocardium. Patients presenting within 2 hours of symptom onset received intravenous streptokinase immediately (group 1, 20 patients) or 5 hours after symptom onset (group 2, 16 patients). Effective perfusion (less than or equal to 90% residual stenosis with rapid distal runoff) occurred in 63% of patients in both groups. Five patients, all in group 1, had recurrent AMI; 4 of the 5 had effective perfusion. There was no group difference in left ventricular ejection fraction at baseline or before discharge. However, group 1 patients with effective perfusion tended to have a greater predischarge mean ejection fraction than those in group 1 with ineffective perfusion (53 +/- 13 vs 44 +/- 16%, p less than 0.10) and had a greater mean value than those in group 2 with ineffective perfusion (53 +/- 13 vs 38 +/- 17%, p less than 0.03). The ejection fraction did not change significantly between admission and discharge in either group, but it increased significantly in group 1 patients with effective perfusion and no recurrent AMI (delta EF = +6 +/- 8%, p less than 0.04). Group 1 patients with ineffective perfusion had a significant decrease in ejection fraction (delta EF = -4 +/- 4%, p less than 0.04). In group 2 patients the ejection fraction did not change, regardless of the state of perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Infarto do Miocárdio/tratamento farmacológico , Reperfusão Miocárdica , Idoso , Ensaios Clínicos como Assunto , Creatina Quinase/sangue , Feminino , Humanos , Isoenzimas , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/fisiopatologia , Distribuição Aleatória , Estreptoquinase/uso terapêutico , Volume Sistólico , Fatores de Tempo
19.
Am J Cardiol ; 61(1): 16-20, 1988 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-3337005

RESUMO

To test the hypothesis that scans with technetium-99m pyrophosphate (Tc-99m-PPi) are positive when performed early after successful thrombolytic therapy for acute myocardial infarction (AMI), 16 consecutive patients with AMI who received thrombolytic therapy within 5 hours after the onset of chest pain were studied. Patients were included if chest pain lasted for greater than 30 minutes, was unresponsive to sublingual nitroglycerin and was associated with at least 0.2 mV ST-segment elevation in at least 2 contiguous electrocardiographic leads. All patients received 1.5 million IU of streptokinase intravenously, a mean of 195 +/- 99 minutes after onset of chest pain. Tc-99m-PPi scans and coronary cineangiograms were recorded 491 +/- 156 minutes and 518 +/- 202 minutes, respectively, after the onset of symptoms. Effective reperfusion was present in 10 patients, 6 of whom had positive Tc-99m-PPi scans (sensitivity of 60% to detect reperfusion). Of the 6 patients without effective reperfusion, 3 had positive Tc-99m-PPi scans (specificity of 50%, p greater than 0.05). Analysis of the data using various definitions of effective reperfusion or artery patency yielded similar results. Thus, our findings indicate that early AMI scanning with Tc-99m-PPi does not accurately detect the presence or absence of reperfusion in patients with AMI after treatment with intravenous streptokinase. At this time, coronary cineangiography is the only reliable method to detect reperfusion promptly after thrombolytic therapy.


Assuntos
Infarto do Miocárdio/tratamento farmacológico , Polifosfatos , Estreptoquinase/uso terapêutico , Pirofosfato de Tecnécio Tc 99m , Tecnécio , Polifosfatos de Estanho , Idoso , Cineangiografia , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Perfusão
20.
Am J Kidney Dis ; 34(1): 125-34, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10401026

RESUMO

Cardiovascular disease occurs in patients with progressive renal disease both before and after the initiation of dialysis. Left ventricular hypertrophy (LVH) is an independent predictor of morbidity and mortality in dialysis populations and is common in the renal insufficiency population. LVH is associated with numerous modifiable risk factors, but little is known about LV growth (LVG) in mild-to-moderate renal insufficiency. This prospective multicenter Canadian cohort study identifies factors associated with LVG, measured using two-dimensional-targeted M-mode echocardiography. Eight centers enrolled 446 patients, 318 of whom had protocol-mandated clinical, laboratory, and echocardiographic measurements recorded. We report 246 patients with assessable echocardiograms at both baseline and 12 months with an overall prevalence of LVH of 36%. LV mass index (LVMI) increased significantly (>20% of baseline or >20 g/m2) from baseline to 12 months in 25% of the population. Other than baseline LVMI, no differences in baseline variables were noted between patients with and without LVG. However, there were significant differences in decline of Hgb level (-0.854 v -0.108 g/dL; P = 0.0001) and change in systolic blood pressure (+6.50 v -1.09 mm Hg; P = 0.03) between the groups with and without LVG. Multivariate analysis showed the independent contribution of decrease in Hgb level (odds ratio [OR], 1.32 for each 0.5-g/dL decrease; P = 0.004), increase in systolic blood pressure (OR, 1.11 for each 5-mm Hg increase; P = 0.01), and lower baseline LVMI (OR, 0.85 for each 10-g/m2; P = 0.011) in predicting LVG. Thus, after adjusting for baseline LVMI, Hgb level and systolic blood pressure remain independently important predictors of LVG. We defined the important modifiable risk factors. There remains a critical need to establish optimal therapeutic strategies and targets to improve clinical outcomes.


Assuntos
Anemia/epidemiologia , Hemoglobinas/metabolismo , Hipertrofia Ventricular Esquerda/epidemiologia , Insuficiência Renal/complicações , Anemia/etiologia , Pressão Sanguínea/fisiologia , Estudos de Coortes , Ecocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/etiologia , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo
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