The HIV-1 envelope protein gp120 impairs B cell proliferation by inducing TGF-ß1 production and FcRL4 expression.

The humoral immune response after acute infection with HIV-1 is delayed and ineffective. The HIV-1 envelope protein gp120 binds to and signals through integrin α4ß7 on T cells. We found that gp120 also bound to and signaled through α4ß7 on naive B cells, which resulted in an abortive proliferative response. In primary B cells, signaling by gp120 through α4ß7 resulted in increased expression of the immunosuppressive cytokine TGF-ß1 and FcRL4, an inhibitory receptor expressed on B cells. Coculture of B cells with HIV-1-infected autologous CD4(+) T cells also increased the expression of FcRL4 by B cells. Our findings indicated that in addition to mediating chronic activation of the immune system, viral proteins contributed directly to HIV-1-associated B cell dysfunction. Our studies identify a mechanism whereby the virus may subvert the early HIV-1-specific humoral immune response.

Higher obesity class is associated with more severe esophageal symptoms and reflux burden but not altered motor function or contractile reserve.

BACKGROUND: Patients with obesity often report esophageal symptoms, with abnormal reflux and esophageal motility suggested as potential mechanisms. However, prior studies showed varying results, often limited by study design/size and esophageal function/symptom measures utilized. We aimed to examine the relationship between obesity and objective esophageal function testing and patient-reported outcomes, utilizing prospective symptom, manometric and reflux monitoring data with impedance. METHODS: Adults referred for high-resolution impedance-manometry (HRiM) and multichannel intraluminal impedance-pH monitoring (MII-pH) to evaluate esophageal symptoms were enrolled. Validated symptom and health-related quality of life (HR-QOL) instruments were prospectively collected: GERDQ, reflux symptoms index (RSI), dominant symptom intensity (DSI, multiplied 5-point Likert scales for symptom frequency/severity), global symptom severity (GSS, 100-point visual analog scale), and Short Form-12 (SF-12) for HR-QOL. Esophageal function testing measures were compared across body mass index (BMI) categories and correlated with patient-reported outcomes. KEY RESULTS: Seven hundred and fifty four patients were included (Normal:281/Overweight:253/Class I obesity:137/Class II/III obesity:83). Reflux burden measures on MII-pH (acid exposure time, total reflux episodes, bolus exposure time), conclusive pathologic reflux (Lyon), and hiatal hernia were increased in higher obesity classes compared to normal BMI. Class II/III obesity was associated with more normal/hypercontractile swallows, less ineffective swallows, and better bolus transit on HRiM. BMI correlated positively with GERDQ/RSI/DSI/GSS, and negatively with physical component score (SF-12). Esophageal symptom severity and HR-QOL correlated strongly with MII-pH findings, but not HRiM measures. CONCLUSIONS/INFERENCES: Obesity is associated with increased esophageal symptom burden and worse physical HR-QOL, which correlate with higher acid/bolus reflux burden but not altered esophageal motility/transit/contractile reserve.

Sorting out the Relationship Between Esophageal and Pulmonary Disease.

The aim of this review is to explore the relationship between esophageal syndromes and pulmonary diseases considering the most recent data available. Prior studies have shown a close relationship between lung diseases such as asthma, chronic obstructive pulmonary disorders (COPD), Idiopathic pulmonary fibrosis (IPF), and lung transplant rejection and esophageal dysfunction. Although the association has long been demonstrated, the exact relationship remains unclear. Clinical experience has shown a bidirectional relationship where esophageal disease may influence the outcomes of pulmonary disease and vice versa. The impact of esophageal dysfunction on pulmonary disorders may also be related to 2 different mechanisms: the reflux pathway leading to microaspiration and the reflex pathway triggering vagally mediated airway reactions. The aim of this review is to further explore these relationships and pathophysiologic mechanisms. Specifically, we discuss the proposed hypotheses for the relationship between the 2 diseases, as well as the pathophysiology and new developments in clinical management.

Detoxification of phenanthrene in Arabidopsis thaliana involves a Dioxygenase For Auxin Oxidation 1 (AtDAO1).

Polycyclic aromatic hydrocarbon (PAH) contamination has a negative impact on ecosystems. PAHs are a large group of toxins with two or more benzene rings that are persistent in the environment. Some PAHs can be cytotoxic, teratogenic, and/or carcinogenic. In the bacterium Pseudomonas, PAHs can be modified by dioxygenases, which increase the reactivity of PAHs. We hypothesize that some plant dioxygenases are capable of PAH biodegradation. Herein, we investigate the involvement of Arabidopsis thaliana At1g14130 in the degradation of phenanthrene, our model PAH. The At1g14130 gene encodes Dioxygenase For Auxin Oxidation 1 (AtDAO1), an enzyme involved in the oxidative inactivation of the hormone auxin. Expression analysis using a ß-glucuronidase (GUS) reporter revealed that At1g14130 is prominently expressed in new leaves of plants exposed to media with phenanthrene. Analysis of the oxidative state of gain-of-function mutants showed elevated levels of H2O2 after phenanthrene treatments, probably due to an increase in the oxidation of phenanthrene by AtDAO1. Biochemical assays with purified AtDAO1 and phenanthrene suggest an enzymatic activity towards the PAH. Thus, data presented in this study support the hypothesis that an auxin dioxygenase, AtDAO1, from Arabidopsis thaliana contributes to the degradation of phenanthrene and that there is possible toxic metabolite accumulation after PAH exposure.