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1.
PLoS Negl Trop Dis ; 15(6): e0009494, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34133422

RESUMO

We report the identification of two orthobunyaviruses, Melao virus (MELV) and Oropouche virus (OROV), in plasma specimens from Haitian children with acute febrile illness who presented during outbreaks caused by alpha- and flaviviruses in 2014. Heretofore not described as a human pathogen, MELV was isolated in cell culture from the plasma of five case patients. OROV RNA was detected in the plasma of an additional child, using an unbiased sequencing approach, with phylogenetic inference suggesting a close relationship with strains from Brazil. Abdominal pain was reported by four case patients with MELV infections, with lymphadenopathy noted in two cases. Our findings document the occurrence of these orthobunyaviruses within the Caribbean region and highlight the critical importance of surveillance with viral genome sequence analyses to identify outbreaks caused by these and other emerging viruses.


Assuntos
Infecções por Bunyaviridae/epidemiologia , Orthobunyavirus/isolamento & purificação , Dor Abdominal , Adolescente , Infecções por Bunyaviridae/sangue , Infecções por Bunyaviridae/diagnóstico , Criança , Pré-Escolar , Doenças Transmissíveis Emergentes/virologia , Feminino , Genoma Viral , Haiti/epidemiologia , Humanos , Linfadenopatia , Masculino , Orthobunyavirus/classificação , Orthobunyavirus/genética , Filogenia , RNA Viral/genética
2.
J Biol Chem ; 290(10): 6670-8, 2015 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-25586187

RESUMO

Subclinical super-low-dose endotoxin LPS is a risk factor for the establishment of low-grade inflammation during the pathogenesis and progression of chronic diseases. However, the underlying mechanisms are not well understood. At the cellular level, a disruption of lysosome fusion with endosomes or autophagosomes may contribute to the potentiation of low-grade inflammation. In this study, we identified that subclinical super-low-dose endotoxin LPS can potently inhibit the process of endosome acidification and lysosome fusion with endosomes or autophagosomes in primary macrophages. Super-low-dose LPS induced the inhibitory phosphorylation of VPS34, thus leading to the disruption of endosome-lysosome fusion. This effect may depend upon the clearance and relocation of Tollip in macrophages by super-low-dose LPS. Consistent with this notion, Tollip-deficient macrophages had constitutively elevated levels of VPS34 inhibitory phosphorylation and constitutive disruption of endosome-lysosome fusion. By employing a skin excision wound-healing model, we observed that Tollip-deficient mice had significantly elevated levels of cell stress and reduced wound repair. This study reveals a novel mechanism responsible for the modulation of endosome-lysosome fusion and low-grade inflammation in innate macrophages.


Assuntos
Autofagia/imunologia , Imunidade Inata , Inflamação/imunologia , Lipopolissacarídeos/toxicidade , Lisossomos/imunologia , Animais , Endossomos/efeitos dos fármacos , Endossomos/imunologia , Humanos , Inflamação/induzido quimicamente , Inflamação/patologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lisossomos/efeitos dos fármacos , Lisossomos/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Knockout
3.
Stroke ; 41(4): 700-6, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20185777

RESUMO

BACKGROUND AND PURPOSE: Microembolic signals (MES) found on transcranial Doppler range from harmless air bubbles to large, solid, particulate emboli from the heart and large vessels. The presence of MES is not always associated with poor clinical outcome. The purpose of our study was to determine whether the relative energy index of MES measured by power M-mode Doppler can distinguish malignant from benign MES and to identify patients with worse prognosis. METHODS: We prospectively collected transcranial Doppler emboli monitoring data from patients with symptomatic carotid stenosis presenting with TIA or ischemic stroke. For each patient, we calculated the relative energy index of MES and categorized those >1.0 as malignant MES. We compared the clinical characteristics, number, and volume of diffusion-weighted imaging lesions, and degree of stenosis and plaque characteristics on CT angiogram of patients with malignant and benign MES. RESULTS: We enrolled 92 patients, 29 with TIA and 63 with stroke, within 48 hours of symptom onset. Twenty-six patients had a total of 319 MES; of these, 82.4% were benign and were 17.6% malignant. Malignant MES traveled further within intracranial vessels than benign MES. The 9 patients with >1 malignant MES had significantly larger baseline diffusion-weighted imaging lesion volume, had a higher prevalence of intraluminal thrombus on CT angiogram of the neck and plaque ulceration, and were more likely to have a poor clinical outcome (modified Rankin Score > or = 2) than those with benign MES (OR, 6.5; 95% CI, 1.47-28.68). The presence of malignant MES led to the institution of more aggressive secondary prevention measures. CONCLUSIONS: Power M-mode transcranial Doppler identifies a subgroup of patients with malignant MES. These signals are more frequent in longer arterial trajectory. Patients with malignant MES have larger baseline infarcts, a higher prevalence of intraluminal thrombus or ulcerated plaque in the carotid artery, and worse clinical outcome.


Assuntos
Embolia/diagnóstico por imagem , Embolia/patologia , Ultrassonografia Doppler Transcraniana , Idoso , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/patologia , Embolia/etiologia , Humanos , Ataque Isquêmico Transitório/diagnóstico por imagem , Ataque Isquêmico Transitório/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia
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