TRACP Influences Th1 pathways by affecting dendritic cell function.

TRACP, a marker of osteoclasts, is also expressed by cells of the immune system. We identified a novel function for TRACP in the dendritic cell. DCs from TRACP knockout mice have impaired maturation and trigger reduced Th1 responses in vivo. We postulate that TRACP has an important role in the presentation of antigens to T cells. INTRODUCTION: TRACP is highly expressed by osteoclasts, activated macrophages, and dendritic cells (DCs). Knockout mice lacking TRACP have an intrinsic defect in osteoclastic resorption and macrophages that display abnormal immunomodulatory responses and cytokine secretion profiles. Our aim in this study was to investigate the significance of TRACP in the inductive phase of the immune response by examining dendritic cells from TRACP(-/-) mice. MATERIALS AND METHODS: Maturational state and function of leukocyte subsets in mice was assessed by flow cytometry. The ability of the immune system to respond to nonspecific activation and to specific antigen was assessed by delayed type hypersensitivity and the presence of isotype-specific serum antibody in vivo and T-cell proliferation and cytokine production in vitro. RESULTS: The ability of lipopolysaccharide (LPS) to upregulate MHC II and CD80 in DCs from TRACP(-/-) mice was reduced compared with wildtype mice, although production of IL-10 by DCs from TRACP-deficient animals was increased. T- and B-cell responses not involving antigen presentation (anti-CD3, TNP-ficoll) were normal in TRACP(-/-) mice, but responses to T-dependent antigens were impaired. Specifically, TRACP(-/-) mice had defective delayed hypersensitivity responses to picryl chloride and reduced proliferative responses to ovalbumin compared with wildtype mice. In response to ovalbumin, but not anti-CD3, T cells from TRACP(-/-) mice produced less interferon-gamma (IFN-gamma), but there was no difference in IL-4 production: TRACP(-/-) mice also produced less ovalbumin (OVA)-specific IgG2a after immunization. CONCLUSIONS: The finding that DCs from TRACP(-/-) mice have impaired maturation and defective Th1 responses shows that TRACP is important for polarizing responses in na?ve T cells to antigen-presented dendritic cells.     

Developing an integrated public health information system for Missouri.

The Missouri Department of Health realized it had a problem with 67 different information systems that ran on different platforms and could not communicate with one another. A new, integrated information system, the Missouri Health Strategic Architectures and Information Cooperative (MOHSAIC) is being developed based on information engineering (IE). This article describes IE, the process of developing MOHSAIC, and some key lessons learned in developing the system. Some of the lessons learned include the importance of executive sponsorship, tension between efficiency and program accountability, importance of confidentiality, and difficulties of funding an integrated system. The article stresses how integrated information systems will be important for the viability of public health under health care reform.     

The treatment of diffuse lewy body disease: A pilot study

Single case studies may provide useful information and generate hypotheses for later testing in group studies. The effect of anti-Parkinsonian medication is reported in five individual cases of diffuse Lewy body disease. The problems caused by the variability in congnitive function and psychiatric symptoms in these cases are outlined together with suggested strategies for future research.     

Axial rotation component of thoracic scoliosis

The axial rotation (rotation about a vertical axis) of the vertebrae, of the ribs, and of the back surface are components of the deformity recognized clinically as the "rib hump" in thoracic scoliosis. Relationships of these rotations to the lateral deviation and lateral curvature of the spine were studied in 40 patients with idiopathic scoliosis. Stereoradiographs of the spine and rib cage were used to measure three components of axial rotation: rotation of the vertebrae, of the rib cage, and of the plane of maximum curvature of the spine. Stereotopographs of the back surface were digitized to measure the axial rotation of the back surface. In individual patients, there were high correlations of all components of axial rotation at each spinal level with the corresponding vertebral lateral deviation from the spinal axis. By regression analyses of the maximum values of each rotation in each curve, the rotation of the apex vertebra was found to be generally of lesser magnitude than the rotation of the plane of maximum curvature of the spine and in an opposite sense in kyphotic curves. The rib cage rotation was generally of lesser magnitude than the vertebra rotation, and the back surface rotation was less than both of these skeletal rotations. Vertebra rotation correlated most closely with lateral deviation of the spine. Simple segmental coupling of axial rotation and lateral bending could not be responsible for this axial rotation.     

CD1a and antitumour immune response

Primary immune response is based on the capacity of local professional antigen-presenting cells (whose prototype is represented by dendritic cells, DCs) to take up and present antigens to selected clones of T cells, but also to non-specific effector cells such as macrophages or natural killer cells. The four CD1 proteins, all of which share a limited homology to class I MHC proteins, are differently expressed in various cell types, of both mesenchymal and, as recently described, epithelial lineage. Regarding the role of CD1 molecules in the anti-tumour response, it has been reported that CD1+ dendritic cells are involved in the first steps of the primary immune response in a number of malignancies. Moreover, the presence of a high number of DCs in the tumoral or peritumoral area, as well as in the draining lymph nodes, has been shown to correlate with a better prognosis. A recent report on the presence of CD1a in metaplastic epithelial cells of Barrett esophagus introduced new questions about CD1a expression patterns. Moreover, the strong correlation between the lack of CD1a+ cells and the malignant evolution of the lesion may indicate a possible role of non-professional APCs in mediating and/or potentiating immune responses to tumours.