T helper cell IL-4 drives intestinal Th2 priming to oral peanut antigen, under the control of OX40L and independent of innate-like lymphocytes.

Intestinal T helper type 2 (Th2) immunity in food allergy results in IgG1 and IgE production, and antigen re-exposure elicits responses such as anaphylaxis and eosinophilic inflammation. Although interleukin-4 (IL-4) is critically required for allergic sensitization, the source and control of IL-4 during the initiation of Th2 immunity in vivo remains unclear. Non-intestinal and non-food allergy systems have suggested that natural killer-like T (NKT) or γδ T-cell innate lymphocytes can supply the IL-4 required to induce Th2 polarization. Group 2 innate lymphoid cells (ILCs) are a novel IL-4-competent population, but their contribution to initiating adaptive Th2 immunity is unclear. There are also reports of IL-4-independent Th2 responses. Here, we show that IL-4-dependent peanut allergic Th2 responses are completely intact in NKT-deficient, γδ T-deficient or ILC-deficient mice, including antigen-specific IgG1/IgE production, anaphylaxis, and cytokine production. Instead, IL-4 solely from CD4(+) Th cells induces full Th2 immunity. Further, CD4(+) Th cell production of IL-4 in vivo is dependent on OX40L, a costimulatory molecule on dendritic cells (DCs) required for intestinal allergic priming. However, both Th2 cells and ILCs orchestrated IL-13-dependent eosinophilic inflammation. Thus, intestinal Th2 priming is initiated by an autocrine/paracrine acting CD4(+) Th cell-intrinsic IL-4 program that is controlled by DC OX40L, and not by NKT, γδ T, or ILC cells.

Pulmonary M. tuberculosis infection delays Th1 immunity via immunoadaptor DAP12-regulated IRAK-M and IL-10 expression in antigen-presenting cells.

Interaction of mycobacteria with the host leads to retarded expression of T helper cell type 1 (Th1) immunity in the lung. However, the immune mechanisms remain poorly understood. Using in vivo and in vitro models of Mycobacterium tuberculosis (M. tb) infection, we find the immunoadaptor DAP12 (DNAX-activating protein of 12 kDa) in antigen-presenting cells (APCs) to be critically involved in this process. Upon infection of APCs, DAP12 is required for IRAK-M (interleukin-1 receptor-associated kinase M) expression, which in turn induces interleukin-10 (IL-10) and an immune-suppressed phenotype of APCs, thus leading to suppressed Th1 cell activation. Lack of DAP12 reduces APC IL-10 production and increases their Th1 cell-activating capability, resulting in expedited Th1 responses and enhanced protection. On the other hand, adoptively transferred DAP12-competent APCs suppress Th1 cell activation within DAP12-deficient hosts, and blockade of IL-10 aborts the ability of DAP12-competent APCs to suppress Th1 activation. Our study identifies the DAP12/IRAK-M/IL-10 to be a novel molecular pathway in APCs exploited by mycobacterial pathogens, allowing infection a foothold in the lung.

Interleukin-15 treatment improves glucose homeostasis and insulin sensitivity in obese mice.

The prevalence of metabolic diseases associated with obesity, such as type 2 diabetes, continues to rise along with obesity rates. Recently, obesity has been described as an inflammatory condition, suggesting a link between the dysregulation in proinflammatory cytokine production and the aetiology of these metabolic diseases. While known as an immunomodulatory cytokine, Interleukin-15 (IL-15) has been shown to have effects on adipose tissue and induce weight loss in diet-induced obese mice. As weight loss improves glucose homeostasis, the goal of this study was to determine whether IL-15 impacts glucose regulation in a mouse model of diet-induced obesity. Our data demonstrate that IL-15 treatment significantly improves insulin sensitivity and glucose and insulin responses to an oral glucose challenge compared to obese counterparts and/or lean controls. These results show that IL-15 may be a novel therapeutic target for the treatment of obesity and its associated abnormal glucose regulation.

Expressing human interleukin-15 from oncolytic vesicular stomatitis virus improves survival in a murine metastatic colon adenocarcinoma model through the enhancement of anti-tumor immunity.

In this study, we sought to enhance the potency of an oncolytic virus, vesicular stomatitis virus (VSV), by inserting a transgene encoding a highly secreted version of human interleukin-15 (IL-15). IL-15 has shown promise as an immunotherapeutic cytokine, as it is able to enhance both natural killer (NK) and T-cell responses, but it has not yet been tested as a therapeutic transgene in the context of viral oncolysis. The transgene was modified to ensure enhanced secretion of IL-15 from infected cells, leading to strong localized expression from infected CT-26 tumors in vivo. This localized expression in the tumor microenvironment led to a clear enhancement to anti-tumoral T-cell responses and enhanced survival, while additional IL-15 administration systemically failed to further enhance the therapy. Overall, the transient localized expression of IL-15 in the tumour by an oncolytic virus was able to induce stronger anti-tumoral immunity in a murine model of colon carcinoma.

Growth, CO2 consumption and H2 production of Anabaena variabilis ATCC 29413-U under different irradiances and CO2 concentrations.

AIMS: The objective of this study is to develop kinetic models based on batch experiments describing the growth, CO(2) consumption, and H(2) production of Anabaena variabilis ATCC 29413-U(TM) as functions of irradiance and CO(2) concentration. METHODS AND RESULTS: A parametric experimental study is performed for irradiances from 1120 to 16100 lux and for initial CO(2) mole fractions from 0.03 to 0.20 in argon at pH 7.0 +/- 0.4 with nitrate in the medium. Kinetic models are successfully developed based on the Monod model and on a novel scaling analysis employing the CO(2) consumption half-time as the time scale. CONCLUSIONS: Monod models predict the growth, CO(2) consumption and O(2) production within 30%. Moreover, the CO(2) consumption half-time is an appropriate time scale for analysing all experimental data. In addition, the optimum initial CO(2) mole fraction is 0.05 for maximum growth and CO(2) consumption rates. Finally, the saturation irradiance is determined to be 5170 lux for CO(2) consumption and growth whereas, the maximum H(2) production rate occurs around 10,000 lux. SIGNIFICANCE AND IMPACT OF THE STUDY: The study presents kinetic models predicting the growth, CO(2) consumption and H(2) production of A. variabilis. The experimental and scaling analysis methods can be generalized to other micro-organisms.

[Hospital management of atrial fibrillation. Epidemiologic data and therapeutic strategy. Report of 100 consecutive patients]. / Prise en charge hospitalière de la fibrillation auriculaire. Données épidémiologiques et stratégie thérapeutique. A propos de 100 patients consécutifs.

Despite recent large scale trials, the management of atrial fibrillation remains very variable. The authors report the results of a prospective study of the management of atrial fibrillation in their department. One hundred consecutive patients admitted for atrial fibrillation were included in the study. The epidemiological and clinical data and the results of the therapeutic strategy were recorded prospectively. Three embolic complications occurred before hospital admission. The hospital stay was marked by spontaneous reduction of atrial fibrillation in 14 cases in the 6 hours following admission. The therapeutic strategy was the following: 40 arrhythmias were respected (well tolerated, > 1 year or with a left atrium 60 mm). Oral amiodarone (30 mg/Kg and 15 mg/Kg the next day) was given to 22 patients. Only 9 patients (41%) were converted (average delay of 12 hours). Four patients received intravenous amiodarone, reducing two arrhythmias. Twenty patients were treated by external electrical cardioversion of first intent and 14 after failure of pharmacological reduction. All of these procedures, early (after 48 hours anticoagulation and transoesophageal echocardiography), or late (after 1 month of anticoagulation), restored sinus rhythm without complications, especially embolic. This register showed a relatively low efficacy of oral amiodarone in the reduction of atrial fibrillation and underlines the efficacy and safety of external electrical cardioversion, even when performed early.

His-Purkinje system reentry as a proarrhythmic effect of flecainide.

We report a case of tachycardia due to reentry within the His-Purkinje system (HPS) occurring after introduction of flecainide. The patient presented with a mild mitral regurgitation and normal left ventricular function. He had incomplete left bundle branch block with left-axis deviation. At the electrophysiology study, a prolonged HV interval was observed at baseline, and the tachycardia could be reproduced after ajmaline infusion. Six months after interruption of flecainide, the patient remains free of arrhythmia recurrence. The authors emphasize that proarrhythmic effects of flecainide may include reentry within the HPS in patients with underlying HPS disease.

[Hygroma of the posterior cranial fossa. Case report]. / Igroma della fossa cranica posteriore. Relazione di un caso.

Posterior fossa hygroma is a rare entity. In a series of 553 cases of surgically treated traumatic subdural lesions, reported by Jamieson and Yelland, only 14 were in the posterior fossa; of these 7 were hygromas and 7 haematomas, giving an incidence of only 1,4% of all subdural haematomas. This report describes a case of a posterior fossa hygroma, that occurred in a 16-years-old boy, 4 days after an occipital head injury.

[Intradural rupture of an intervertebral disk]. / Rottura intradurale del disco intervertebrale.

Since the first description of ruptured lumbar disc, erosion of a fragment of disc through the dura mater has been mentioned only rarely. The authros report two cases occurred among 1,078 herniated discs surgically treated in their department over a period of 8 years, from January 1st., 1970 through March 31st., 1978. Various factors that might contribute to this relatively rare complication of disc disease are mentioned, and literature on the subject is summarized.