Immunoglobulin-A distribution in glomerular disease: Analysis of immunofluorescence localization and pathogenetic significance

Immunoglobulin-A distribution in glomerular disease. Analysis of immunofluorescence localization and pathogenetic significance. Renal biopsies from 470 patients with various glomemlonephropathies were studied for patterns and frequency of glomerular bound IgA. Correlations of IgA with IgG, IgM, C3, and C4 were made. Glomerular deposits of IgA were observed in five of six cases of Henoch-Schoenlein anaphylactoid nephritis (83%), stalk proliferative glomerulonephritis (73%), lupus nephritis (60%), and focal proliferative glomerulonephritis (57 %). In addition, IgA was less frequently observed in diffuse (acute) proliferative (33%), membranoproliferative (42%), membranous (32%), focal sclerosing (25%) crescentic (26%), and chronic glomerulonephritides (23%) as well as malignant arterionephrosclerosis, amyloidosis, and a group of patients with minimal glomerular alteration and no determinable diagnosis (40%). IgA was not specifically associated with IgG or IgM in any one diagnostic category but was often present with both. Deposits containing C3 and C4 most closely paralleled those of IgG and/or IgM. Presence of IgA appeared to correlate with variable degrees of increased glomerular mesangial cellularity in “minimal”, stalk proliferative, and focal-segmental glomerular lesions. The cause and immunopathogenetic significance of mesangial or peripheral glomerular capillary localization of IgA is unknown. Though a number of apparent examples of what has been referred to as IgA-IgG nephropathy were observed in this study, this entity, characterized by mesangial deposits of IgA, IgG, and C3, could not always be specifically identified or differentiated on histopathologic criteria alone from a variety of other glomerulopathies in which variable proportions of IgA, IgG, IgM, C3, and C4 globulins were localized

Developing and applying a gene functional association network for anti-angiogenic kinase inhibitor activity assessment in an angiogenesis co-culture model

<p>Abstract</p> <p>Background</p> <p>Tumor angiogenesis is a highly regulated process involving intercellular communication as well as the interactions of multiple downstream signal transduction pathways. Disrupting one or even a few angiogenesis pathways is often insufficient to achieve sustained therapeutic benefits due to the complexity of angiogenesis. Targeting multiple angiogenic pathways has been increasingly recognized as a viable strategy. However, translation of the polypharmacology of a given compound to its antiangiogenic efficacy remains a major technical challenge. Developing a global functional association network among angiogenesis-related genes is much needed to facilitate holistic understanding of angiogenesis and to aid the development of more effective anti-angiogenesis therapeutics.</p> <p>Results</p> <p>We constructed a comprehensive gene functional association network or interactome by transcript profiling an in vitro angiogenesis model, in which human umbilical vein endothelial cells (HUVECs) formed capillary structures when co-cultured with normal human dermal fibroblasts (NHDFs). HUVEC competence and NHDF supportiveness of cord formation were found to be highly cell-passage dependent. An enrichment test of Biological Processes (BP) of differentially expressed genes (DEG) revealed that angiogenesis related BP categories significantly changed with cell passages. Built upon 2012 DEGs identified from two microarray studies, the resulting interactome captured 17226 functional gene associations and displayed characteristics of a scale-free network. The interactome includes the involvement of oncogenes and tumor suppressor genes in angiogenesis. We developed a network walking algorithm to extract connectivity information from the interactome and applied it to simulate the level of network perturbation by three multi-targeted anti-angiogenic kinase inhibitors. Simulated network perturbation correlated with observed anti-angiogenesis activity in a cord formation bioassay.</p> <p>Conclusion</p> <p>We established a comprehensive gene functional association network to model in vitro angiogenesis regulation. The present study provided a proof-of-concept pilot of applying network perturbation analysis to drug phenotypic activity assessment.</p

Yielded to Christ or conformed to this world? Postwar Mennonite responses to labour activism

This is the accepted version of the manuscript.The urbanization of North American Mennonites after the Second World War necessitated a reconsideration of Mennonite religious beliefs. Post-war concerns for social justice led to a greater emphasis on non-violence and agape at the expense of Gelassenheit. The tenor of Mennonite church conference resolutions regarding labour union membership changed; while skepticism remained regarding the wisdom of union involvement, the door was left open for participation in unions. The labour militancy of the 1970s led Manitoba Mennonites to re-examine their engagement with the labour movement, a process that has continued to the present day. Without further research on Mennonite workplaces, it cannot be known exactly how the change in religious emphases has affected Mennonite identity.https://journals.sagepub.com/doi/abs/10.1177/00084298070360020