CD11b+Ly-6Chi cells, including inflammatory monocytes (IMCs) and inflammatory dendritic cells (IDCs), are important in infectious, autoimmune, and tumor models. However, their role in T cell regulation is controversial. Here we show that T cell regulation by IMCs and IDCs is determined by their activation state, and is plastic during an immune response. Non-activated IMCs and IDCs function as antigen-presenting cells (APCs), but activated IMCs and IDCs suppress T cells through nitric oxide (NO) production. Suppressive IMCs are induced by IFN-γ , GM-CSF, TNF-α and CD154 derived from activated T cells during their interaction. In experimental autoimmune encephalomyelitis (EAE), CD11b+Ly-6Chi cells in the central nervous system (CNS) are increasingly activated from disease onset to peak, and switch their function from antigen presentation to T cell suppression. Furthermore, transfer of activated IMCs or IDCs enhances T cell apoptosis in the CNS and suppresses EAE. These data highlight the interplay between innate and adaptive immunity: immunization leads to the expansion of Ly-6Chi myeloid cells initially promoting T cell function. As T cells become highly activated in the target tissue, they induce activation and NO production in Ly-6Chi myeloid cells, which in turn suppress T cells and lead to the contraction of local immune response.
Inflammation and angiogenesis play major roles in carotid plaque vulnerability. The purpose of this study was to determine if grayscale features of carotid plaques are associated with histological markers for inflammation. Thirty-eight individuals completed a dedicated research carotid ultrasound exam prior to carotid endarterectomy. Grayscale analysis was performed on plaque images to measure plaque echogenicity (grayscale median [GSM] pixel brightness), plaque area, presence of discrete white areas [DWAs], and the percent of black area near the lumen on any one component of the plaque. Plaques with higher ultrasound GSM had greater percent calcification (p=0.013) on histopathology. Presence of an ultrasound DWA was associated with more plaque hemosiderin (p=0.0005) and inflammation (p=0.019) on histopathology examination. The percent of plaque black area in any one component was associated with a higher score for macroscopic ulceration (p=0.028). Ultrasound plaque characteristics (GSM, DWAs and Black areas) represent histopathological markers associated with plaque vulnerability.
Parasitic infections frequently lead to immune deviation or suppression. However, the application of specific parasitic molecules in regulating autoimmune responses remain to be explored. Here we report on the immune modulatory function of Lacto-N-fucopentaose III (LNFPIII), a schistosome glycan, in an animal model for multiple sclerosis. We found that LNFPIII treatment significantly reduced the severity of experimental autoimmune encephalomyelitis (EAE) and CNS inflammation, and skewed peripheral immune response to a Th2 dominant profile. Inflammatory monocytes (IMCs) purified from LNFPIII-treated mice had increased expression of nitric oxide synthase 2, and mediated T cell suppression. LNFPIII treatment also significantly increased expression of arginase-1, aldehyde dehydrogenase 1, indoleamine 2,3-dioxygenase and heme oxygenase 1 in splenic IMCs. Furthermore, LNFPIII treatment significantly reduced trafficking of dendritic cells across brain endothelium in vitro. In summary, our study demonstrates that LNFPIII glycan treatment suppresses EAE by modulating both innate and T cell immune response.
Object The angioarchitectural features of an AVM provide key information regarding natural history and treatment planning. Because of rapid filling and vascular overlap, 2D and 3D-DSA are often suboptimal for evaluation of these features. We have developed an algorithm that derives a series of fully time resolved 3D-DSA volumes (4D-DSA) at up to 30frames/sec from a conventional 3D-DSA. The temporal/spatial resolution of 4D reconstructions is significantly higher than that provided by current MRA and CTA techniques. 4D reconstruction allows viewing of an AVM from any angle at any time during its opacification. This feasibility study investigated the potential of 4DDSA to improve the ability to analyze angioarchitectural features as compared to conventional 2D and 3D-DSA. Methods 2D, 3D and 4D-DSA reconstructions of angiographic studies of 6 AVMs were evaluated by 3 cerebrovascular neurosurgeons and 1 interventional neuroradiologist. These observers evaluated the ability of each modality to visualize the angioarchitectural features of the AVMs. They also compared the information provided using the combination of 2D and 3D-DSA with that provided by a 4D-DSA reconstruction. Results By consensus, 4D-DSA provided the best ability to visualize the internal features of the AVM including intranidal aneurysms, fistula, venous obstructions and sequence of filling and draining. 2D and 3D images in comparison were limited because of overlap of the vasculature. Conclusion In this small series 4D-DSA provided better ability to visualize an AVM’s angioarchitecture than did conventional methods. Further experience is required to determine the ultimate utility of this technique.
The role played by vessel disease in stroke-related cognition dysfunction is unclear. We assessed the impact of significant atherosclerotic disease on cognition-even in patients asymptomatic for stroke. We hypothesized that patients would perform poorly relative to controls, but that symptomatic/asymptomatic status (history of stroke/transient ischemic attack) would have no effect. Fifty-two carotid endarterectomy candidates with >60% carotid stenosis and 17 controls underwent a 60-min neuropsychological test protocol. Symptomatic and asymptomatic patients showed deficits in executive function, delayed verbal recall, and general knowledge. Patients symptomatic for stroke also performed worse on tests of language and motor/visuomotor ability. Symptomatic and asymptomatic patients differed in working memory and language task performance. Although all patients showed deficits in executive function and memory, only symptomatic patients showed additional deficits in language and motor function. Cognitive abnormalities in patients viewed as "asymptomatic" for stroke underscore the need for early identification and treatment.
Background and Purpose 4D DSA is a time resolved technique providing allows viewing of a contrast bolus at any time and from any desired viewing angle. Our hypothesis was that the information content in a 4D DSA reconstruction was essentially equivalent to that in a combination of 2D acquisitions and a 3D DSA reconstruction. Materials and Methods 26 consecutive patients who had both 2D and 3D DSA acquisitions were included in the study. The angiography report was used to obtain diagnosis and characteristics of abnormalities. Diagnosis included AVM/AFS, aneurysms, stenosis and normal. 4D DSA reconstructions were independently reviewed by 3 experienced observers who had no part in the clinical care. Using an electronic evaluation form these observers recorded their assessments based only on the 4D reconstructions. The clinical evaluations were then compared with the 4D evaluations as to diagnosis and lesion characteristics. Results Results showed both Interrater and interclass agreements (κ 0.813 and 0.858). Comparing the 4D diagnosis with the clinical diagnosis for the 3 observers yielded Kappa values of (0.906, 0.912, 0.906). The κ for agreement between the 3 observers as to type of abnormality were 0.949, 0.845, 0.895. Complete agreement on the presence of an abnormality between the clinical and 4D DSA was complete in 23/26 cases. In 2 cases there was conflicting opinions. Conclusion In this study, the information content of 4D DSA reconstructions was largely equivalent to that of the combined 2D/3D studies. Availability of 4D DSA should reduce the requirement for 2D DSA acquisitions.
BACKGROUND AND PURPOSE: 4D DSA allows viewing of 3D DSA as a series of time-resolved volumes of a contrast bolus. There is no comparison of the accuracy of the anatomic information provided by 4D DSA with that available from conventional 2D and 3D DSA. Our purpose was to make this comparison by using a canine model.
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