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1.
Clin Infect Dis ; 66(9): 1435-1441, 2018 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-29145631

RESUMEN

Background: Campylobacter species are a leading cause of diarrheal disease globally with significant morbidity. Primary prevention efforts have yielded limited results. Rifaximin chemoprophylaxis decreases rates of travelers' diarrhea and may be suitable for high-risk persons. We assessed the efficacy of rifaximin in the controlled human infection model for Campylobacter jejuni. Methods: Twenty-eight subjects were admitted to an inpatient facility and randomized to a twice-daily dose of 550 mg rifaximin or placebo. The following day, subjects ingested 1.7 × 105 colony-forming units of C. jejuni strain CG8421. Subjects continued prophylaxis for 3 additional days, were followed for campylobacteriosis for 144 hours, and were subsequently treated with azithromycin and ciprofloxacin. Samples were collected to assess immunologic responses to CG8421. Results: There was no difference (P = 1.0) in the frequency of campylobacteriosis in those receiving rifaximin (86.7%) or placebo (84.6%). Additionally, there were no differences in the clinical signs and symptoms of C. jejuni infection to include abdominal pain/cramps (P = 1.0), nausea (P = 1.0), vomiting (P = .2), or fever (P = 1.0) across study groups. Immune responses to the CG8421 strain were comparable across treatment groups. Conclusions: Rifaximin did not prevent campylobacteriosis in this controlled human infection model. Given the morbidity associated with Campylobacter infection, primary prevention efforts remain a significant need. Clinical Trials Registration: NCT02280044.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones por Campylobacter/prevención & control , Quimioprevención , Rifaximina/uso terapéutico , Adulto , Antibacterianos/administración & dosificación , Azitromicina/uso terapéutico , Campylobacter jejuni , Ciprofloxacina/uso terapéutico , Diarrea/prevención & control , Método Doble Ciego , Femenino , Voluntarios Sanos , Experimentación Humana , Humanos , Masculino , Rifaximina/administración & dosificación , Adulto Joven
2.
Immunogenetics ; 66(1): 1-8, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24096970

RESUMEN

Leukocyte immunoglobulin-like receptor (LILR)B3 and LILRA6 represent a pair of inhibitory/activating receptors with identical extracellular domains and unknown ligands. LILRB3 can mediate inhibitory signaling via immunoreceptor tyrosine-based inhibition motifs in its cytoplasmic tail whereas LILRA6 can signal through association with an activating adaptor molecule, FcRγ, which bears a cytoplasmic tail with an immunoreceptor tyrosine-based activation motif. The receptors are encoded by two highly polymorphic neighboring genes within the leukocyte receptor complex on human chromosome 19. Here, we report that the two genes display similar levels of single nucleotide polymorphisms with the majority of polymorphic sites being identical. In addition, the LILRA6 gene exhibits copy number variation (CNV) whereas LILRB3 does not. A screen of healthy Caucasians indicated that 32 % of the subjects possessed more than two copies of LILRA6, whereas 4 % have only one copy of the gene per diploid genome. Analysis of mRNA expression in the major fractions of PBMCs showed that LILRA6 is primarily expressed in monocytes, similarly to LILRB3, and its expression level correlates with copy number of the gene. We suggest that the LILRA6 CNV may influence the level of the activating receptor on the cell surface, potentially affecting signaling upon LILRB3/A6 ligation.


Asunto(s)
Antígenos CD/genética , Variaciones en el Número de Copia de ADN/genética , Polimorfismo de Nucleótido Simple/genética , Receptores Inmunológicos/genética , Niño , Estudios de Cohortes , ADN/análisis , ADN/genética , Familia , Femenino , Humanos , Masculino , Linaje , ARN Mensajero/genética
3.
Transcription ; 13(1-3): 70-81, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36047906

RESUMEN

Transcription elongation by RNA polymerase II (Pol II) has emerged as a regulatory hub in gene expression. A key control point occurs during early transcription elongation when Pol II pauses in the promoter-proximal region at the majority of genes in mammalian cells and at a large set of genes in Drosophila. An increasing number of trans-acting factors have been linked to promoter-proximal pausing. Some factors help to establish the pause, whereas others are required for the release of Pol II into productive elongation. A dysfunction of this elongation control point leads to aberrant gene expression and can contribute to disease development. The BET bromodomain protein BRD4 has been implicated in elongation control. However, only recently direct BRD4-specific functions in Pol II transcription elongation have been uncovered. This mainly became possible with technological advances that allow selective and rapid ablation of BRD4 in cells along with the availability of approaches that capture the immediate consequences on nascent transcription. This review sheds light on the experimental breakthroughs that led to the emerging view of BRD4 as a general regulator of transcription elongation.


Asunto(s)
Proteínas Nucleares , Factores de Transcripción , Animales , Drosophila/genética , Mamíferos/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Regiones Promotoras Genéticas , ARN Polimerasa II/genética , ARN Polimerasa II/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Transcripción Genética
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