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BACKGROUND: The prognostic significance of cardiac magnetic resonance (CMR)-based left atrial ejection fraction (LAEF) is not well defined in the ischemic cardiomyopathy (ICM) cohort. OBJECTIVES: The authors sought to assess the prognostic impact of LAEF, when adjusted for left ventricular remodeling, myocardial infarct size (MIS), left atrial volume index, and functional mitral regurgitation (FMR), on outcomes in patients with advanced ICM. METHODS: ICM patients who underwent CMR were retrospectively evaluated (April 2001-December 2019). LAEF, left atrial volume index, MIS, left ventricular remodeling, and FMR were derived from CMR. The primary clinical endpoint was a composite of all-cause mortality and cardiac transplant. A baseline multivariable Cox proportional hazards regression model was constructed to assess prognostic power of LAEF. RESULTS: There were 718 patients (416 primary events) evaluated, with a median duration of follow-up of 1,763 days (4.8 years) and a mean LAEF of 36% ± 15%. On multivariable analysis, higher LAEF was independently associated with reduced risk (HR: 0.24, 95% CI: 0.12-0.48, P < 0.001), even after adjusting for FMR and MIS. The highest adjusted risk was observed in patients with an LAEF <20% and an MIS of >30% (HR: 3.20, 95% CI: 1.73-5.93). The lowest risk was in patients within the comparator group with an LAEF of >50% and a MIS of <15% (HR: 1.07, 95% CI: 0.81-1.42). CONCLUSIONS: Reduced LAEF is independently associated with increased mortality in ICM. Risk associated with declining LAEF is continuous and incremental to other risk factors for adverse outcomes in patients with ICM even after adjusting for MIS and FMR severity.
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BACKGROUND: Sodium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). Sodium handling is fine-tuned in the distal nephron, were eplerenone exhibits some of its pleotropic effects. Little is known about the effect of eplerenone on serum sodium and the prognostic relevance of sodium alterations in patients with MI complicated with LVSD and/or HF. METHODS: The EPHESUS trial randomized 6632 patients to either eplerenone or placebo. Hyponatremia and hypernatremia were defined as sodium < 135 mmol/L or > 145 mmol/L, respectively. Linear mixed models and time updated Cox regression analysis were used to determine the effect of eplerenone on sodium changes and the prognostic importance of sodium changes, respectively. The primary outcomes were all-cause mortality and a composite of cardiovascular (CV) mortality and CV-hospitalization. RESULTS: A total of 6221 patients had a post-baseline sodium measurement, 797 patients developed hyponatremia (mean of 0.2 events/per patient) and 1476 developed hypernatremia (mean of 0.4 events/per patient). Patients assigned to eplerenone had a lower mean serum sodium over the follow-up (140 vs 141 mmol/L; p < 0.0001) and more often developed hyponatremia episodes (15 vs 11% p = 0.0001) and less often hypernatremia episodes (22 vs. 26% p = 0.0003). Hyponatremia, but not hypernatremia was associated with adverse outcome for all outcome endpoints in the placebo group but not in the eplerenone group (interaction p value < 0.05 for all). Baseline sodium values did not influence the treatment effect of eplerenone in reducing the various endpoints (interaction p value > 0.05 for all). Development of new-onset hyponatremia following eplerenone initiation did not diminish the beneficial eplerenone treatment effect. CONCLUSION: Eplerenone induces minor reductions in serum sodium. The beneficial effect of eplerenone was maintained regardless of the baseline serum sodium or the development of hyponatremia. Sodium alterations should not refrain clinicians from prescribing eplerenone to patients who had an MI complicated with LVSD and/or HF. TRAIL REGISTRY: ClinicalTrials.gov identifier: NCT00232180. Serum sodium and eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.
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Insuficiência Cardíaca , Infarto do Miocárdio , Disfunção Ventricular Esquerda , Eplerenona/uso terapêutico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Sódio , Resultado do TratamentoRESUMO
BACKGROUND: We undertook the present analysis to examine the shifting influence of prognostic factors in HIV-positive patients diagnosed with aggressive non-Hodgkin lymphoma (NHL) over the last two decades. PATIENTS AND METHODS: We carried out a pooled analysis from an existing database of patients with AIDS-related lymphoma. Individual patient data had been obtained prior from prospective phase II or III clinical trials carried out between 1990 until 2010 in North America and Europe that studied chemo(immuno)therapy in HIV-positive patients diagnosed with AIDS-related lymphomas. Studies had been identified by a systematic review. We analyzed patient-level data for 1546 patients with AIDS-related lymphomas using logistic regression and Cox proportional hazard models to identify the association of patient-, lymphoma-, and HIV-specific variables with the outcomes complete response (CR), progression-free survival, and overall survival (OS) in different eras: pre-cART (1989-1995), early cART (1996-2000), recent cART (2001-2004), and contemporary cART era (2005-2010). RESULTS: Outcomes for patients with AIDS-related diffuse large B-cell lymphoma and Burkitt lymphoma improved significantly over time, irrespective of baseline CD4 count or age-adjusted International Prognostic Index (IPI) risk category. Two-year OS was best in the contemporary era: 67% and 75% compared with 24% and 37% in the pre-cART era (P < 0.001). While the age-adjusted IPI was a significant predictor of outcome in all time periods, the influence of other factors waxed and waned. Individual HIV-related factors such as low CD4 counts (<50/mm(3)) and prior history of AIDS were no longer associated with poor outcomes in the contemporary era. CONCLUSIONS: Our results demonstrate a significant improvement of CR rate and survival for all patients with AIDS-related lymphomas. Effective HIV-directed therapies reduce the impact of HIV-related prognostic factors on outcomes and allow curative antilymphoma therapy for the majority of patients with aggressive NHL.
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Fármacos Anti-HIV/uso terapêutico , Antineoplásicos/uso terapêutico , Infecções por HIV/terapia , Imunoterapia/métodos , Linfoma Relacionado a AIDS/terapia , Linfoma não Hodgkin/terapia , Adolescente , Adulto , Idoso , Fármacos Anti-HIV/efeitos adversos , Antineoplásicos/efeitos adversos , Distribuição de Qui-Quadrado , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Bases de Dados Factuais , Progressão da Doença , Intervalo Livre de Doença , Europa (Continente) , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/imunologia , Infecções por HIV/mortalidade , Humanos , Imunoterapia/efeitos adversos , Estimativa de Kaplan-Meier , Modelos Logísticos , Linfoma Relacionado a AIDS/diagnóstico , Linfoma Relacionado a AIDS/imunologia , Linfoma Relacionado a AIDS/mortalidade , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , América do Norte , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The long-term durability and prognostic significance of improvement in renal function after mechanical circulatory support (MCS) has yet to be characterized in a large multicenter population. The primary goals of this analysis were to describe serial post-MCS changes in estimated glomerular filtration rate (eGFR) and determine their association with all-cause mortality. METHODS AND RESULTS: Adult patients enrolled in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) with serial creatinine levels available (n=3363) were studied. Early post-MCS, eGFR improved substantially (median improvement, 48.9%; P<0.001) with 22.3% of the population improving their eGFR by ≥100% within the first few weeks. However, in the majority of patients, this improvement was transient, and by 1 year, eGFR was only 6.7% above the pre-MCS value (P<0.001). This pattern of early improvement followed by deterioration in eGFR was observed with both pulsatile and continuous-flow devices. Interestingly, poor survival was associated with both marked improvement (adjusted hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.19-2.26; P=0.002) and worsening in eGFR (adjusted HR, 1.63; 95% CI, 1.15-2.13; P=0.004). CONCLUSIONS: Post-MCS, early improvement in renal function is common but seems to be largely transient and not necessarily indicative of an improved prognosis. This pattern was observed with both pulsatile and continuous-flow devices. Additional research is necessary to better understand the mechanistic basis for these complex post-MCS changes in renal function and their associated survival disadvantage. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00119834.
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Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Coração Auxiliar , Rim/fisiopatologia , Idoso , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Although there is evidence linking smoking and heart failure (HF), the association between lifetime smoking exposure and HF in older adults and the strength of this association among current and past smokers is not well known. METHODS: We examined the association between smoking status, pack-years of exposure, and incident HF risk in 2,125 participants of the Health, Aging, and Body Composition Study (age 73.6 ± 2.9 years, 69.7% women, 54.2% whites) using proportional hazard models. RESULTS: At inception, 54.8% of participants were nonsmokers, 34.8% were past smokers, and 10.4% were current smokers. During follow-up (median 9.4 years), HF incidence was 11.4 per 1,000 person-years in nonsmokers, 15.2 in past smokers (hazard ratio [HR] vs nonsmokers 1.33, 95% CI 1.01-1.76, P = .045), and 21.9 in current smokers (HR 1.93, 95% CI 1.30-2.84, P = .001). After adjusting for HF risk factors, incident coronary events, and competing risk for death, a dose-effect association between pack-years of exposure and HF risk was observed (HR 1.09, 95% CI 1.05-1.14, P < .001 per 10 pack-years). Heart failure risk was not modulated by pack-years of exposure in current smokers. In past smokers, HR for HF was 1.05 (95% CI 0.64-1.72) for 1 to 11 pack-years, 1.23 (95% CI 0.82-1.83) for 12 to 35 pack-years, and 1.64 (95% CI 1.11-2.42) for >35 pack-years of exposure in fully adjusted models (P < .001 for trend) compared with nonsmokers. CONCLUSIONS: In older adults, both current and past cigarette smoking increase HF risk. In current smokers, this risk is high irrespective of pack-years of exposure, whereas in past smokers, there was a dose-effect association.
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Insuficiência Cardíaca/epidemiologia , Fumar/epidemiologia , Idoso , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Incidência , Masculino , Modelos de Riscos Proporcionais , Fatores de Risco , Fumar/efeitos adversos , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To test three theories of hypercortisolemia in depression-hypothalamic overdrive, impaired glucocorticoid feedback, or autonomous cortisol production. METHOD: We applied an overnight low-cortisol feedback strategy by administering metyrapone to hypercortisolemic depressed in-patients and control subjects. RESULTS: Under metyrapone, the increases of plasma adrenocorticotropic hormone (ACTH) concentrations and of basal and pulsatile ACTH secretion were not exaggerated in hypercortisolemic depressed patients compared with control subjects. ACTH approximate entropy (ApEn) did not differ at baseline or under metyrapone. Thus, neither hypothalamic overdrive nor irregular ACTH secretion was seen. We did not detect impaired cortisol feedback: the ACTH response was not reduced, and ApEn measures that are sensitive to feedback changes were comparable in both groups. Metyrapone disrupted cortisol secretory regularity in depressed and control subjects. On the baseline day, basal cortisol secretion was significantly increased and was highly irregular (high ApEn), and ACTH-cortisol cross-ApEn was markedly elevated in high-cortisol patients. CONCLUSION: Classical feed-forward overdrive and impaired feedback theories of hypercortisolemia in depression were not supported. Depressive hypercortisolemia may result from alternative pathophysiological mechanisms involving irregular basal hypersecretion of cortisol, associated with adrenal enlargement, possibly through splanchnic sympathetic activation of the adrenal cortex.
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Hormônio Adrenocorticotrópico/sangue , Síndrome de Cushing/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Retroalimentação Fisiológica , Hidrocortisona/sangue , Sistema Hipófise-Suprarrenal/fisiopatologia , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Estudos de Casos e Controles , Síndrome de Cushing/complicações , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/complicações , Inibidores Enzimáticos , Feminino , Glucocorticoides , Humanos , Hidrocortisona/metabolismo , Masculino , Metirapona , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/metabolismoRESUMO
AIMS: Although left ventricular (LV) relaxation is well recognized as a predictor of mitral annulus (MA) early diastolic (E') velocity, its significance relative to other predictors of E' is less well understood. METHODS AND RESULTS: We assessed 40 healthy volunteers, 43 patients with acutely decompensated chronic systolic heart failure (HF), and 36 patients with hypertrophic obstructive cardiomyopathy (HOCM) using echocardiography and right or left heart catheterization. Data were obtained at baseline. In addition, in healthy volunteers haemodynamics were varied by graded saline infusion and low body negative pressure, while in HF patients it was varied by vasoactive drug treatment. E- and A-wave velocity (E/A) ratio of the mitral valve inflow, systolic MA velocity integral (s' integral) and E' and late velocity (A') of lateral and septal MA pulsed wave velocities were assessed by echocardiography. Time constant of isovolumic pressure decay τ(0)) was calculated from isovolumic relaxation time/[ln(aortic dicrotic notch pressure) - ln(LV filling pressure)]. In all three groups, s' integral was the strongest predictor of E' (partial r= 0.53-0.79; 0.81 for three groups combined), followed by E/A ratio (partial r= 0.10-0.78; 0.26 for all groups combined) and τ(0) (partial r= -0.1 to 0.023; -0.21 for all groups combined). CONCLUSION: In healthy adults, patients with systolic HF, or patients with HOCM, E' is related to LV long-axis function and E/A ratio, a global marker of LV filling. E' appears less sensitive to LV relaxation.
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Cardiomiopatia Hipertrófica/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico por imagem , Valva Mitral/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Adulto , Idoso , Cateterismo Cardíaco , Cardiomiopatia Hipertrófica/fisiopatologia , Estudos de Casos e Controles , Diástole , Ecocardiografia Doppler , Feminino , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/fisiopatologia , Valor Preditivo dos Testes , Sístole , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).
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Dispneia/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Natriuréticos/uso terapêutico , Peptídeo Natriurético Encefálico/uso terapêutico , Readmissão do Paciente/estatística & dados numéricos , Doença Aguda , Idoso , Método Duplo-Cego , Dispneia/etiologia , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/mortalidade , Humanos , Hipotensão/induzido quimicamente , Análise de Intenção de Tratamento , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Natriuréticos/efeitos adversos , Peptídeo Natriurético Encefálico/efeitos adversos , RecidivaRESUMO
BACKGROUND: How serum albumin levels are associated with risk for heart failure (HF) in the elderly is unclear. METHODS: We evaluated 2,907 participants without HF (age 73.6 +/- 2.9 years, 48.0% male, 58.7% white) from the community-based Health ABC Study. The association between baseline albumin and incident HF was assessed with standard and competing risks proportional hazards models controlling for HF predictors, inflammatory markers, and incident coronary events. RESULTS: During a median follow-up of 9.4 years, 342 (11.8%) participants developed HF. Albumin was a time-dependent predictor of HF, with significance retained for up to 6 years (baseline hazard ratio [HR] per -1 g/L 1.14, 95% CI 1.06-1.22, P < .001; annual rate of HR decline 2.1%, 95% CI 0.8%-3.3%, P = .001). This association persisted in models controlling for HF predictors, inflammatory markers, and incident coronary events (baseline HR per -1 g/L 1.13, 95% CI 1.05-1.22, P = .001; annual rate of HR decline 1.8%, 95% CI 0.5%-3.0%, P = .008) and when mortality was accounted for in adjusted competing risks models (baseline HR per -1 g/L 1.13, 95% CI 1.05-1.21, P = .001; annual rate of HR decline 1.9%, 95% CI 0.7%-3.1%, P = .002). The association of albumin with HF risk was similar in men (HR per -1 g/L 1.13, 95% CI 1.05-1.23, P = .002) and women (HR per -1 g/L 1.12, 95% CI 1.04-1.22, P = .005) and in whites and blacks (HR per -1 g/L 1.13, 95% CI 1.04-1.22, P< .01 for both races) in adjusted models. CONCLUSIONS: Low serum albumin levels are associated with increased risk for HF in the elderly in a time-dependent manner independent of inflammation and incident coronary events.
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Insuficiência Cardíaca/sangue , Albumina Sérica/análise , Idoso , Composição Corporal , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Medição de Risco , Volume SistólicoRESUMO
The family Phycodnaviridae encompasses a diverse and rapidly expanding collection of large icosahedral, dsDNA viruses that infect algae. These lytic and lysogenic viruses have genomes ranging from 160 to 560 kb. The family consists of six genera based initially on host range and supported by sequence comparisons. The family is monophyletic with branches for each genus, but the phycodnaviruses have evolutionary roots that connect them with several other families of large DNA viruses, referred to as the nucleocytoplasmic large DNA viruses (NCLDV). The phycodnaviruses have diverse genome structures, some with large regions of noncoding sequence and others with regions of ssDNA. The genomes of members in three genera in the Phycodnaviridae have been sequenced. The genome analyses have revealed more than 1000 unique genes, with only 14 homologous genes in common among the three genera of phycodnaviruses sequenced to date. Thus, their gene diversity far exceeds the number of so-called core genes. Not much is known about the replication of these viruses, but the consequences of these infections on phytoplankton have global affects, including influencing geochemical cycling and weather patterns.
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Eucariotos/virologia , Phycodnaviridae/fisiologia , Genoma Viral , Phycodnaviridae/genética , Phycodnaviridae/ultraestruturaRESUMO
BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear. METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group. RESULTS: A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density. CONCLUSIONS: Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment.
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Perfilação da Expressão Gênica , Expressão Gênica , Linfoma Difuso de Grandes Células B/genética , Células Estromais/metabolismo , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Progressão da Doença , Doxorrubicina , Matriz Extracelular/genética , Regulação Neoplásica da Expressão Gênica , Genes MHC da Classe II , Centro Germinativo , Humanos , Fatores Imunológicos/administração & dosagem , Estimativa de Kaplan-Meier , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Pessoa de Meia-Idade , Análise Multivariada , Neovascularização Patológica/genética , Prednisona , Prognóstico , Rituximab , Células Estromais/patologia , VincristinaRESUMO
OBJECTIVE: The mechanisms mediating hypercortisolemia in depression remain controversial. Adopting the biomarker strategy, we studied adrenocorticotropin (ACTH) and cortisol dynamics in hypercortisolemic and non-hypercortisolemic depressed in-patients, and in normal volunteers. METHOD: Deconvolution analysis of 24-h pulsatile secretion, approximate entropy (ApEn) estimation of secretory regularity, cross-ApEn quantitation of forward and reverse ACTH-cortisol synchrony, and cosine regression of 24-h rhythmicity. RESULTS: Hypercortisolemia was strongly associated with melancholic and psychotic depressive subtypes. Hypercortisolemic patients had elevated ACTH and cortisol secretion, mediated chiefly by increased burst masses. Basal ACTH secretion was increased, ACTH half-life was reduced, and mean 24-h ACTH concentration was normal. Cortisol secretion was increased in a highly irregular pattern (high ApEn), with high ACTH --> cortisol cross-ApEn (impaired feedforward coupling). Cortisol-mediated feedback on the secretory pattern of ACTH was normal. Hypercortisolemic depressed patients had normal programming of the central hypothalamo-pituitary-adrenal (HPA) axis pulse generator: ACTH pulse frequency, cortisol pulse frequency, circadian acrophases, and ApEn of ACTH secretion were normal. Responsiveness of the adrenal cortex to endogenous ACTH was normal. Non-hypercortisolemic patients resembled hypercortisolemic patients on ACTH regulatory parameters but had low total cortisol secretion. CONCLUSION: Increased ACTH secretion occurs in depressed in-patients regardless of cortisolemic status, confirming central HPA axis overdrive in severe depression. Depressive hypercortisolemia results from an additional change in the adrenal cortex that causes ACTH-independent, disorderly basal cortisol release, a sign of physiological stress in melancholic/psychotic depression.
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Síndrome de Cushing/epidemiologia , Síndrome de Cushing/fisiopatologia , Transtorno Depressivo Maior/epidemiologia , Adolescente , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Ritmo Circadiano/fisiologia , Síndrome de Cushing/sangue , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Eletroencefalografia , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/fisiopatologiaRESUMO
CD307 is a differentiation antigen expressed in B-lineage cells. One soluble and two membrane-bound forms have been predicted and an enzyme-linked immunosorbent assay (ELISA) for soluble CD307 established. Our goal was to determine if CD307 is expressed on the surface of cells from patients with multiple myeloma (MM), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and other B-cell malignancies and if soluble CD307 levels are elevated in the blood of patients with these B-cell malignancies. Cells and blood were collected from patients. Expression of CD307 was measured by flow cytometry and blood levels of soluble CD307 by ELISA. High soluble CD307 levels were detected in 21/43 (49%) of patients with MM, 36/46 (78%) with CLL and 9/24 (38%) with MCL. Soluble CD307 levels correlated with plasma cell percentages in bone marrow aspirates in MM and total white blood cells in CLL. CD307 on the cell membrane was detected by flow cytometry in 8/8 MM, 23/29 CLL and 4/5 MCL samples. Because CD307 is present on malignant cells from patients with MM, CLL and MCL, CD307 may be a useful therapeutic target for the treatment of these diseases.
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Biomarcadores Tumorais , Leucemia Linfocítica Crônica de Células B/sangue , Linfoma de Célula do Manto/sangue , Mieloma Múltiplo/sangue , Receptores de Superfície Celular/metabolismo , Adolescente , Adulto , Idoso , Linfócitos B/metabolismo , Linfócitos B/patologia , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Receptores FcRESUMO
The potential role of viruses in coral disease has only recently begun to receive attention. Here we describe our attempts to determine whether viruses are present in thermally stressed corals Pavona danai, Acropora formosa and Stylophora pistillata and zoanthids Zoanthus sp., and their zooxanthellae. Heat-shocked P. danai, A. formosa and Zoanthus sp. all produced numerous virus-like particles (VLPs) that were evident in the animal tissue, zooxanthellae and the surrounding seawater; VLPs were also seen around heat-shocked freshly isolated zooxanthellae (FIZ) from P. danai and S. pistillata. The most commonly seen VLPs were tail-less, hexagonal and about 40 to 50 nm in diameter, though a diverse range of other VLP morphotypes (e.g. rounded, rod-shaped, droplet-shaped, filamentous) were also present around corals. When VLPs around heat-shocked FIZ from S. pistillata were added to non-stressed FIZ from this coral, they resulted in cell lysis, suggesting that an infectious agent was present; however, analysis with transmission electron microscopy provided no clear evidence of viral infection. The release of diverse VLPs was again apparent when flow cytometry was used to enumerate release by heat-stressed A. formosa nubbins. Our data support the infection of reef corals by viruses, though we cannot yet determine the precise origin (i.e. coral, zooxanthellae and/or surface microbes) of the VLPs seen. Furthermore, genome sequence data are required to establish the presence of viruses unequivocally.
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Antozoários/virologia , Vírion/isolamento & purificação , Animais , Citometria de Fluxo/métodos , Microscopia Eletrônica de Transmissão/métodos , Vírion/patogenicidade , Vírion/ultraestruturaRESUMO
EhV-86 is a large double stranded DNA virus with a 407,339 base pair circular genome that infects the globally important microalga Emiliania huxleyi. It belongs to a new genus of viruses termed the Coccolithoviridae within the algal virus family Phycodnaviridae. By plotting the EhV-86 genome against itself in a dot-plot analysis we revealed three families of distinctly different repeat sequences throughout its genome, designated Family A, B and C. Family A repeats are non-coding, found immediately upstream of 86 predicted coding sequences (CDSs) and are likely to play a crucial role in controlling the expression of the associated CDSs. Family B repeats are GC rich, coding and correspond to possible calcium binding sites in 22 proline-rich domains found in the protein products of eight predicted EhV-86 CDSs. Family C repeats are AT-rich, non-coding and are likely to form part of the origin of replication. We suggest that these repeat regions are of fundamental importance during virus propagation being involved with transcriptional control (Family A), virus adsorption/release (Family B) and DNA replication (Family C).
Assuntos
Eucariotos/virologia , Phycodnaviridae/genética , Composição de Bases , Sequência de Bases , DNA Viral/química , DNA Viral/genética , Genoma Viral , Dados de Sequência Molecular , Phycodnaviridae/classificação , Phycodnaviridae/patogenicidade , Phycodnaviridae/fisiologia , Sequências Repetitivas de Ácido Nucleico , Homologia de Sequência do Ácido NucleicoRESUMO
Emiliania huxleyi-specific viruses ( EhV) were isolated from E. huxleyi blooms off the coast of Plymouth, UK, in July 1999 and July/August 2001, and from an E. huxleyi bloom induced during a mesocosm experiment in a fjord off Bergen, Norway, during June 2000. Transmission electron microscopy revealed that all 10 virus isolates are 170-200 nm in diameter with an icosahedral symmetry. Their density is approximately 1.2 in CsCl gradients and they have large double stranded DNA genomes approximately 410 kb in size. Phylogenetic analysis of the DNA polymerase genes of these viruses suggests that EhV belongs to a new genus within the family of algal viruses, Phycodnaviridae. We propose to name this new virus genus Coccolithovirus. Differences within members of the Coccolithovirus were elucidated by host range analysis of the virus isolates and sequence analysis of a gene fragment encoding part of their putative major capsid protein. All 10 virus isolates within this new genus only infected E. huxleyi strains that have previously been shown to exhibit low dimethylsulphoniopropionate lyase (DMSP-lyase) activity (CCMP1516, CCMP374 and L), while E. huxleyi strains with high DMSP-lyase activity (CCMP373 and CCMP379) were resistant to infection.
Assuntos
Eucariotos/virologia , Phycodnaviridae/classificação , Sequência de Bases , Capsídeo/genética , DNA Polimerase Dirigida por DNA/genética , Dados de Sequência Molecular , Phycodnaviridae/genética , Phycodnaviridae/ultraestrutura , FilogeniaRESUMO
Here, we describe the application of an isothermal nucleic acid amplification assay, signal-mediated amplification of RNA technology (SMART), to detect DNA extracted from marine cyanophages known to infect unicellular cyanobacteria from the genus Synechococcus. The SMART assay is based on the target-dependent production of multiple copies of an RNA signal, which is measured by an enzyme-linked oligosorbent assay. SMART was able to detect both synthetic oligonucleotide targets and genomic cyanophage DNA using probes designed against the portal vertex gene (g20). Specific signals were obtained for each cyanophage strain (S-PM2 and S-BnMI). Nonspecific genomic DNA did not produce false signals or inhibit the detection of a specific target. In addition, we found that extensive purification of target DNA may not be required since signals were obtained from crude cyanophage lysates. This is the first report of the SMART assay being used to discriminate between two similar target sequences.
Assuntos
Bacteriófagos/genética , Cianobactérias/virologia , DNA Viral/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Sequência de Bases , DNA Viral/genética , Dados de Sequência Molecular , Sondas de Oligonucleotídeos/genética , Sensibilidade e Especificidade , Transcrição Gênica/genéticaRESUMO
The most common human leukemia is B cell chronic lymphocytic leukemia (CLL), a malignancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression "signature," irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and/or cell of origin. Nonetheless, the expression of hundreds of other genes correlated with the Ig mutational status, including many genes that are modulated in expression during mitogenic B cell receptor signaling. These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease.