Kaposi's sarcoma-associated herpesvirus inhibits expression and function of endothelial cell major histocompatibility complex class II via suppressor of cytokine signaling 3.

Endothelial cells (EC) can present antigen to either CD8(+) T lymphocytes through constitutively expressed major histocompatibility complex class I (MHC-I) or CD4(+) T lymphocytes through gamma interferon (IFN-γ)-induced MHC-II. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), an EC neoplasm characterized by dysregulated angiogenesis and a substantial inflammatory infiltrate. KSHV is understood to have evolved strategies to inhibit MHC-I expression on EC and MHC-II expression on primary effusion lymphoma cells, but its effects on EC MHC-II expression are unknown. Here, we report that the KSHV infection of human primary EC inhibits IFN-γ-induced expression of the MHC-II molecule HLA-DR at the transcriptional level. The effect is functionally significant, since recognition by an HLA-DR-restricted CD4(+) T-cell clone in response to cognate antigen presented by KSHV-infected EC was attenuated. Inhibition of HLA-DR expression was also achieved by exposing EC to supernatant from KSHV-inoculated EC before IFN-γ treatment, revealing a role for soluble mediators. IFN-γ-induced phosphorylation of STAT-1 and transcription of CIITA were suppressed in KSHV-inoculated EC via a mechanism involving SOCS3 (suppressor of cytokine signaling 3). Thus, KSHV infection resulted in transcriptional upregulation of SOCS3, and treatment with RNA interference against SOCS3 relieved virus-induced inhibition of IFN-γ-induced STAT-1 phosphorylation. Since cell surface MHC-II molecules present peptide antigens to CD4(+) T lymphocytes that can function either as direct cytolytic effectors or to initiate and regulate adaptive immune responses, inhibition of this antigen-presenting pathway would provide a survival advantage to the virus.

Kaposi's sarcoma-associated herpesvirus infection of endothelial cells inhibits neutrophil recruitment through an interleukin-6-dependent mechanism: a new paradigm for viral immune evasion.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), an endothelial cell (EC) neoplasm characterized by dysregulated angiogenesis and inflammation. KSHV infection of EC causes production of proinflammatory mediators, regarded as possible initiators of the substantial mononuclear leukocyte recruitment seen in KS. Conversely, KSHV immune evasion strategies exist, such as degradation of EC leukocyte adhesion receptors by viral proteins. Here, we report the effects of KSHV infection of primary EC on recruitment of flowing leukocytes. Infection did not initiate adhesion of any leukocyte subset per se. However, on cytokine-stimulated EC, KSHV specifically inhibited neutrophil, but not PBL or monocyte, transmigration, an observation consistent with the inflammatory cell profile found in KS lesions in vivo. This inhibition could be recapitulated on uninfected EC using supernatant from infected cultures. These supernatants contained elevated levels of human interleukin 6 (hIL-6), and both the KSHV- and the supernatant-induced inhibitions of neutrophil transmigration were abrogated in the presence of a hIL-6 neutralizing antibody. Furthermore, preconditioning of EC with hIL-6 mimicked the effect of KSHV. Using RNA interference (RNAi), we show that upregulation of suppressor of cytokine signaling 3 (SOCS3) was necessary for this effect of hIL-6. These studies reveal a novel paracrine mode of KSHV immune evasion, resulting in reduced recruitment of neutrophils, a cell type whose antiviral and antitumor roles are becoming increasingly appreciated. Moreover, the findings have implications for our understanding of the contribution of hIL-6 to the pathogenesis of other inflammatory disorders and tumors in which this cytokine is abundant.

Positive bowel contrast agent for MR imaging of the abdomen: phase II and III clinical trials.

PURPOSE: To evaluate the efficacy and safety of two dose levels of an orally administered ferric ammonium citrate-based contrast agent for bowel enhancement on T1-weighted spin-echo magnetic resonance (MR) images in 222 patients with known or suspected abnormality of the upper abdomen. MATERIALS AND METHODS: Adverse reactions were graded for intensity, frequency, duration, and relationship to the contrast agent. Twelve unblinded readers compared enhanced with unenhanced images; all MR images were evaluated by two independent offsite radiologists in a blinded review. RESULTS: No statistically significant changes in mean vital signs or laboratory values were seen. Forty-eight of 220 patients (22%) reported minor side effects. The readers found increased intraluminal signal intensity and improved contrast enhancement of the gastrointestinal tract and distention and improved signal homogeneity in 101-107 cases (89%-98%) after ingestion; the blinded reviewers' findings were similar. CONCLUSION: The contrast agent provided new or additional radiologic information in 142 patients (64%), specific additional information in a detected abnormality in 46 of 142 patients (32%), and information that changed diagnosis, management, or surgical approach in 22 of 142 patients (15%).

Digital processing of film radiographs.

Initial clinical experience with a system for the digitization, processing, and display of film radiographs is described. Film is digitized using a high-intensity laser scanner; the recorded image data may then be subjected to a wide variety of processing options, with display of processed images on television monitors. The possibilities of clinical applications to processing and display of chest radiographs and film mammograms are described. A comparison of conventional analog subtraction and digitized film subtraction angiography indicated equivalent diagnostic capability, with the advantage of flexible, interactive image processing with the digital technique. A specially designed, energy-selective cassette permits dual-energy imaging from two films effectively exposed to different x-ray energy spectra. Dual-energy imaging may be capable of the characterization of body materials, including lung nodules, and useful for eliminating obscuring radiographic shadows overlying regions of interest.