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1.
J Clin Invest ; 126(8): 3117-29, 2016 08 01.
Article in English | MEDLINE | ID: mdl-27454292

ABSTRACT

A rare subset of HIV-1-infected individuals is able to maintain plasma viral load (VL) at low levels without antiretroviral treatment. Identifying the mechanisms underlying this atypical response to infection may lead to therapeutic advances for treating HIV-1. Here, we developed a proteomic analysis to compare peripheral blood cell proteomes in 20 HIV-1-infected individuals who maintained either high or low VL with the aim of identifying host factors that impact HIV-1 replication. We determined that the levels of multiple histone proteins were markedly decreased in cohorts of individuals with high VL. This reduction was correlated with lower levels of stem-loop binding protein (SLBP), which is known to control histone metabolism. Depletion of cellular SLBP increased promoter engagement with the chromatin structures of the host gene high mobility group protein A1 (HMGA1) and viral long terminal repeat (LTR), which led to higher levels of HIV-1 genomic integration and proviral transcription. Further, we determined that TNF-α regulates expression of SLBP and observed that plasma TNF-α levels in HIV-1-infected individuals correlated directly with VL levels and inversely with cellular SLBP levels. Our findings identify SLBP as a potentially important cellular regulator of HIV-1, thereby establishing a link between histone metabolism, inflammation, and HIV-1 infection.


Subject(s)
HIV Infections/metabolism , Nuclear Proteins/metabolism , Viral Load , Virus Replication , mRNA Cleavage and Polyadenylation Factors/metabolism , Cell Cycle , Chromatin/metabolism , HIV-1/physiology , HMGA1a Protein/metabolism , HeLa Cells , Histones/metabolism , Humans , Inflammation , Leukocytes, Mononuclear/metabolism , Promoter Regions, Genetic , Protein Domains , Proteome , Tumor Necrosis Factor-alpha/metabolism
2.
J Neuroimaging ; 13(1): 79-82, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12593136

ABSTRACT

The authors describe 2 patients with new-onset, refractory status epilepticus and serological evidence for Bartonella infection. Brain magnetic resonance imaging (MRI) in patient 1 showed transient diffusion abnormalities in the posterior (pulvinar) thalami. In patient 2, brain MRI showed several enhancing cortical lesions, of which one lesion was bright on diffusion-weighted imaging (DWI). In patients with unexplained, refractory seizures, the presence of DWI abnormalities warrants a search for unusual infectious or inflammatory disorders, like Bartonella encephalitis.


Subject(s)
Bartonella Infections/pathology , Encephalitis/pathology , Magnetic Resonance Imaging , Status Epilepticus/pathology , Adult , Aged , Bartonella Infections/complications , Female , Humans , Status Epilepticus/complications
3.
SAGE Open Med ; 2: 2050312114554673, 2014.
Article in English | MEDLINE | ID: mdl-26770744

ABSTRACT

BACKGROUND: Legionella pneumonia has long been recognized as an important cause of community-acquired pneumonia associated with significant morbidity and mortality; however, the description of the incidence of this disease is restricted to sporadic cases in the literature. With the advent of an inexpensive and rapid urine antigen test, routine testing has become more common. We report findings of a retrospective review of 266 patients who were admitted with a clinical diagnosis of community-acquired pneumonia over a 12-month period and were tested for Legionella pneumophila serogroup 1, reporting the prevalence and determinants of Legionella infection. METHODS: Chart reviews of 266 patients admitted for community-acquired pneumonia and who underwent urine antigen testing for Legionella pneumophila during a 1-year time period were conducted, looking at demographic information as well as clinical and laboratory presentation, reporting on the prevalence and determinants of urine antigen positivity using multivariate logistic regression analysis. RESULTS: Legionella pneumophila serogroup 1 was found in 2.3% of cases of community-acquired pneumonia. We also found that altered mental status, diarrhea, history of lung disease, and alcohol intake were significantly associated with pneumonia associated with Legionella. The presence of these four factors had a low sensitivity in predicting Legionella infection (33%); however, they had a positive predictive value of 98%, with a specificity of 100. All the Legionella-infected patients in our study required admission to the intensive care unit, and one of them developed Guillain-Barré syndrome, which to our knowledge represents the only reported case of this syndrome related to Legionella infection in an adult in the English scientific literature. CONCLUSION: Legionella pneumophila serogroup 1 is a common cause of sporadic cases of community-acquired pneumonia associated with a high morbidity and protean manifestations. Clinical features have a poor sensitivity in identifying cases, and routine urine antigen testing in patients with suggestive clinical symptoms appears to be a rational approach in the evaluation of community-acquired pneumonia.

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