Nuclear factor of activated T cells is associated with a mast cell interleukin 4 transcription complex.

Interleukin 4 (IL-4), an immunoregulatory cytokine, is produced only by a subset of activated T cells and cells of the mast cell-basophil lineage. The production of IL-4 by mast cells likely represents a significant source of this protein in local immune-inflammatory responses in the skin, brain, gastrointestinal, and respiratory tracts, in which mast cells are prevalent. In the present study, the cis- and trans-acting elements that control inducible mast cell IL-4 gene transcription were examined and compared with those that function in T cells. We demonstrate that, as in T cells, sequences between bp -87 and -70 are critical for protein association and activation-dependent gene transcription and that this region (termed the activation-responsive element region) is the target of an inducible, cyclosporin A-sensitive, DNA-protein interaction. When assessed by electrophoretic mobility shift assays and UV cross-linking analyses, multiple proteins in both T- and mast cell nuclear extracts associate with the activation-responsive element in vitro, and some of these appear identical. However, distinct proteins are associated with each of the complexes as well. AP-1 family members are unique to the T-cell-stimulation-dependent complex, whereas mast cell complexes contain factors that are reactive with anti-nuclear factor of activated T cells p (NF-ATp) and anti-NF-ATc antibodies but have distinct molecular masses compared with those of T-cell-derived NF-AT. Furthermore, an anti-NF-ATp-reactive factor with a molecular mass of approximately 41 kDa is present in the nuclei of unstimulated cells and binds independently of cell activation, unlike the previously described NF-AT family members. These data support the idea that there are uniquely regulated, cell lineage-specific transcription factors related to T-cell-derived NF-AT that mediate inducible IL-4 transcription in mast cells. These differences likely reflect the distinct cell surface signaling requirements for IL-4 production in T and mast cells.

CT features of plexiform neurofibroma of the submandibular gland.

Plexiform neurofibroma of the submandibular gland is an extremely rare tumor. We report the CT findings in a 6-year-old girl with type 1 neurofibromatosis who had a histopathologically proven submandibular gland plexiform neurofibroma. A "branching" hypodense mass was noted on the CT scan infiltrating the submandibular gland and the adjacent spaces of the neck. CT could be extremely valuable in suggesting the diagnosis.

Influence of electrophysiological heterogeneity on electrical stimulation in healthy and failing human hearts.

The application of strong electrical stimuli is a common method used for terminating irregular cardiac behaviour. The study presents the influence of electrophysiological heterogeneity on the response of human hearts to electrical stimulation. The human electrophysiology was simulated using the ten Tusscher-Noble-Noble-Panfilov cell model. The anisotropic propagation of depolarisation in three-dimensional virtual myocardial preparations was calculated using bidomain equations. The research was carried out on different types of virtual cardiac wedge. The selection of the modelling parameters emphasises the influence of cellular electrophysiology on the response of the human myocardium to electrical stimulation. The simulations were initially performed on a virtual cardiac control model characterised by electrophysiological homogeneity. The second preparation incorporated the transmural electrophysiological heterogeneity characteristic of the healthy human heart. In the third model type, the normal electrophysiological heterogeneity was modified by the conditions of heart failure. The main currents responsible for repolarisation (Ito, IKs and IKI) were reduced by 25%. Successively, [Na+]i was increased by the regulation of the Na+-Ca2+ exchange function, and fibrosis was represented by decreasing electrical conductivity. Various electrical stimulation configurations were used to investigate the differences in the responses of the three different models. Monophasic and biphasic electrical stimuli were applied through rectangular paddles and needle electrodes. A whole systolic period was simulated. The distribution of the transmembrane voltage indicated that the modification of electrophysiological heterogeneity induced drastic changes during the repolarisation phase. The results illustrated that each of the heart failure conditions amplifies the modification of the response of the myocardium to electrical stimulation. Therefore a theoretical model of the failing human heart must incorporate all the characteristic features.

Comparison of outcome after stenting for de novo versus restenotic narrowings in native coronary arteries.

Intracoronary stenting of de novo narrowings results in a lower restenosis rate when compared with percutaneous transluminal coronary angioplasty. We sought to determine whether intracoronary stenting for restenotic narrowings is associated with a worse outcome when compared with stenting for de novo narrowings. A total of 114 consecutive patients with 124 narrowings were retrospectively identified. Stents were deployed in 46 de novo (37%) and in 78 restenotic (63%) narrowings. The 2 groups were similar with respect to variables known to affect restenosis. Follow-up angiograms were available in 88% of patients at a mean of 6.3 +/- 3.3 months after stent implantation. At follow-up angiography, a significantly higher restenosis rate in the restenotic group was observed (p = 0.05). Restenosis risk could not be predicted from variables known at the time of stent implantation. However, the presence of angina at the time of follow-up was significantly associated with restenosis (p = 0.01). Kaplan-Meier survival curves for freedom from repeat target-site revascularization demonstrated a significant difference in the need for target-site revascularization between the de novo and restenotic groups over the first-year post-stent implantation (p = 0.01; relative risk = 1.94). Multivariate analysis identified restenosis as the indication for stenting (p <0.01), postprocedure percent stenosis (p = 0.01), and narrowing length (p = 0.01) as independent predictors for repeat target-site revascularization. When compared with de novo narrowings, restenotic narrowings have a worse outcome after stenting. A prospective, randomized trial comparing outcome after percutaneous transluminal coronary angioplasty and stents for restenotic narrowings would be useful.

Rheumatoid arthritis: an immune disease in search of an etiology.

The current knowledge of the immunologic and etiologic factors which play a role in rheumatoid arthritis is reviewed and extrapolated to the systemic effects of rheumatoid disease. The disease process is viewed as the incidental result of an atypical immuno-inflammatory mechanism initiated by an unidentified antigenic stimulus.

Acute bacterial arthritis.

Analysis of 29 consecutive cases of acute bacterial arthritis requiring hospitalization reveals the importance of local and systemic immunologic states or conditions which reduce the efficacy of immune responses in the establishment of joint infections. The complications of trauma and surgery are considered as interfering with the normal local immune response.

Morphometric study of emphysema: an hypothesis on the evolution of the anatomic damage of the disease.

Mathematical analysis of morphometric studies on the destruction of pulmonary tissue in cases of centrilobular emphysema has been used to identify degrees and localization of structural damage. From the data, an hypothesis of sequential, cumulative, individual destructive events has been developed to explain the distributive and progressive parenchymal changes in the lungs.