Allospecific Memory B Cell Responses Are Dependent on Autophagy.

Long-lived, donor-reactive memory B cells (Bmems) can produce alloantibodies that mediate transplant injury. Autophagy, an intrinsic mechanism of cell organelle/component recycling, is required for Bmem survival in infectious and model antigen systems, but whether autophagy affects alloreactive Bmem is unknown. We studied mice with an inducible yellow fluorescent protein (YFP) reporter expressed under the activation-induced cytidine deaminase (AID) promoter active in B cells undergoing germinal center reactions. Up to 12 months after allogeneic sensitization, splenic YFP+ B cells were predominantly IgD- IgM- IgG+ and expressed CD73, CD80, and PD-L2, consistent with Bmems. Labeled cells contained significantly more cells with autophagosomes and more autophagosomes per cell than unlabeled, naïve B cells. To test for a functional link, we quantified alloantibody formation in mice with B cells conditionally deficient in the requisite autophagy gene ATG7. These experiments revealed absent B cell ATG7 (1) prevented B cell autophagy, (2) inhibited secondary alloantibody responses without altering primary alloantibody formation, and (3) diminished frequencies of alloreactive Bmems. Pharmacological autophagy inhibition with 3-methyladenine had similar effects on wild-type mice. Together with new documentation of increased autophagosomes within human Bmems, our data indicate that targeting autophagy has potential for eliminating donor-reactive Bmems in transplant recipients.

Model of influenza A virus infection: dynamics of viral antagonism and innate immune response.

Viral antagonism of host responses is an essential component of virus pathogenicity. The study of the interplay between immune response and viral antagonism is challenging due to the involvement of many processes acting at multiple time scales. Here we develop an ordinary differential equation model to investigate the early, experimentally measured, responses of human monocyte-derived dendritic cells to infection by two H1N1 influenza A viruses of different clinical outcomes: pandemic A/California/4/2009 and seasonal A/New Caledonia/20/1999. Our results reveal how the strength of virus antagonism, and the time scale over which it acts to thwart the innate immune response, differs significantly between the two viruses, as is made clear by their impact on the temporal behavior of a number of measured genes. The model thus sheds light on the mechanisms that underlie the variability of innate immune responses to different H1N1 viruses.

Clinical value of thin collimation in the diagnostic workup of pulmonary embolism.

OBJECTIVE: We report our experience with thin-collimation helical CT in a population of patients suspected of having pulmonary embolism. CONCLUSION: Thin-collimation helical CT provided technically acceptable examinations for pulmonary embolism in 360 patients (97%). In this population, CT revealed pulmonary embolism in 104 patients (29%), negative findings in 217 patients (59%), indeterminate findings in 39 patients (10%), and alternative diagnoses in 65% of patients with negative or inconclusive findings. Ventilation-perfusion scanning and Doppler sonography of the lower extremities were performed in 158 (44%) and 133 patients (37%), respectively, whereas pulmonary angiography was performed in 27 patients (7.5%). The estimated false-negative rate of helical CT was 5%.

[The respective role and limitations of pulmonary angiography, thoracic computed tomography, and MRI in the diagnosis of pulmonary embolism]. / Places respectives et limites de l'angiographie pulmonaire, de la tomodensitométrie thoracique, et de l'IRM dans le diagnostic de l'embolie pulmonaire.

Spiral or helical angioscanography for the positive or differential diagnosis of pulmonary emboli has become an emerging technique but remains poorly practised and has been little assessed scientifically. The optimal conditions to perform the test should be understood. The physician should appreciate in view of a large choice of parameters, the diagnostic value of the result and its reliability proximally and distally. Pulmonary angiography is only indicated when the angioscanography is negative according to the degree of clinical and paraclinical suspicion. Angiography magnetic resonance imaging is a diagnostic test full of promise which does not yet have its place in routine practice.

Spiral CT of pulmonary embolism: diagnostic approach, interpretive pitfalls and current indications.

The introduction of spiral CT has recently modified the diagnostic work-up of pulmonary embolism, because it is possible to depict noninvasively endoluminal clots in second-to-fourth-division pulmonary arteries. If this technique is currently considered a powerful imaging alternative for the detection of acute central emboli, it is mainly related to the possibility to obtain a uniform and high degree of arterial enhancement of pulmonary arteries down to 2-3 mm in diameter. Minimal experience in spiral CT angiography is necessary to achieve this goal and requires familiarity with both data acquisition and contrast medium injection. Numerous interpretive pitfalls exist in assessing spiral CT images, and certain caveats have to be heeded. However, their recognition becomes increasingly less problematic as the radiologist gains experience with spiral CT of the pulmonary vasculature. Therefore, the purpose of this article is to review the diagnostic approach to pulmonary embolism with spiral CT, with special emphasis on protocol parameters and scan interpretation.

Volume rendering of the tracheobronchial tree: clinical evaluation of bronchographic images.

PURPOSE: To evaluate the application of the volume-rendering technique to airway disease. MATERIAL AND METHODS: Seventy-four spiral computed tomographic (CT) examination (1- to 5-mm section thickness; pitch, 1.7-20.0) were performed for known or suspected abnormality of the airways, including (a) benign tracheobronchial stenosis (group 1, n = 47), (b) complex airway lesions (group 2, n = 15), and (c) bronchiectasis (group 3, n - 12). Two radiologists independently compared overlapping transverse CT scans and volume-rendered bronchographic images for detection of airway abnormalities and identification of lesion morphology and extent, with bronchoscopic correlation. RESULTS: Bronchographic image quality was graded as excellent (73%) or good (24%), whereas motion-related artifacts led to poor image quality in 3% of cases (trapezoid parameters included window width of -700 to -350 HU, triangular trapezoid shape, parenchymal opacification of 70%, unshaded algorithm). Compared with transverse CT scans, volume-rendered images (a) provided supplemental group 3, even, seven), (b) improved confidence in the interpretation of congenital airway abnormalities in six cases (8%) (all from group 2), and (c) corrected interpretive errors in four cases (5%) (group 1, two cases; group 2, two). CONCLUSION: Volume-rendered images improved the recognition of mild changes in airway caliber and the understand of complex tracheobronchial anomalies.

Tracheobronchial tree: assessment with volume rendering--technical aspects.

A volume-rendering technique was applied at the level of normal airways. Two spiral computed tomographic data sets (central and peripheral bronchi) were selected to evaluate the influence of the technique parameters. Optimal bronchogram-like images were obtained with a continuous rim of peripheral voxels, a 70% opacity value, and the unshaded algorithm. Volume rendering allows creation of airway reconstructions that are very similar to conventional bronchograms.

Multiplanar and three-dimensional reconstruction techniques in CT: impact on chest diseases.

The purpose of this review is to capture the current state-of-the art of the technical aspects of multiplanar and three-dimensional (3D) images and their thoracic applications. Planimetric and volumetric analysis resulting from volumetric data acquisitions obviates the limitations of segmented transverse images. Among the 3D reconstruction techniques currently available, the most recently introduced technique, i. e., volume rendering, has to be evaluated in comparison with 3D shaded surface display and maximum or minimum intensity projection. Slabs are useful in detecting and localizing micronodular or microtubular patterns and in analyzing mild forms of uneven attenuation of the lungs. Three-dimensional angiography is helpful in the pretherapeutic evaluation and posttreatment follow-up of pulmonary arteriovenous malformations, in the comprehension of the postoperative reorientation of the pulmonary vessels, in the surgical planning of pulmonary tumors, and in the diagnosis of marginated thrombi. The systemic supply to the lung and superior vena cava syndromes are also relevant to these techniques. In acquired or congenital tracheobronchial diseases including stenosis, extraluminal air and complex airway anatomy, multiplanar and 3D reformations have a complementary role to both transaxial images and endoscopy. New developments are also expected in various topics such as 3D conformal radiation therapy, planning of intraluminal bronchoscopic therapy, virtual endoscopy, and functional imaging of the bronchial tree. Miscellaneous clinical applications are promising in the analysis of diaphragmatic morphology and pathophysiology, in the volumetric quantification of the lung parenchyma, and in the vascular components of the thoracic outlet syndromes.

Functional anatomy of the thoracic outlet: evaluation with spiral CT.

PURPOSE: To determine the anatomic characteristics of the thoracic outlet before and after dynamically induced modifications. MATERIALS AND METHODS: Fifty-two volunteers (24 women; 28 men; mean age, 42 years) with no clinical or radiographic indications of thoracic outlet syndrome underwent spiral computed tomography (CT) of the apexes at full inspiration with the arms alongside the body and then with the dominant arm in hyperabduction, with a contralateral rotation of the head. RESULTS: After elevation of the dominant arm, (a) no statistically significant difference was found in median value of the costosubclavian and costoclavicular distances; (b) the median distance between the posterior border of the smaller pectoral muscle and the anterosuperior chest wall was 12 mm in all subjects; (c) the subclavian artery in 18 (75%) women and in 20 (71%) men and/or the subclavian vein in three (12%) women and in three (11%) men were identified in the costoclavicular space. The median angles of rotation, retraction, and upward displacement of the clavicle were 22 degrees, 32 degrees, and 7 degrees, respectively, in women and 25 degrees, 31 degrees, and 11 degrees, respectively, in men. CONCLUSION: Spiral CT is expected to be useful for determining the complex pathophysiologic processes that underlie thoracic outlet syndrome.

Spiral CT of pulmonary embolism: technical considerations and interpretive pitfalls.

The diagnostic work-up of pulmonary embolism has been recently modified by the introduction of spiral computed tomography (CT), which enables noninvasive depiction of endoluminal clots in second-to fourth-division pulmonary arteries. If this technique is currently considered a powerful imaging alternative for the detection of acute central emboli, it is mainly related to the possibility to obtain a uniform and high degree of arterial enhancement of pulmonary arteries down to 2-3 mm in diameter. Minimal experience in spiral CT angiography is necessary to achieve this goal and requires familiarity with both data acquisition and contrast medium injection. A number of interpretive pitfalls exist in assessing spiral CT images, and certain caveats have to be heeded. However, it is important to keep in mind that their recognition becomes less and less problematic as the radiologist gains experience with spiral CT of the pulmonary vasculature. Therefore, the purpose of this article is to review the diagnostic approach to pulmonary embolism with spiral CT, with special emphasis on protocol parameters and scan interpretation.