We treated 414 new patients with stage pTa, grades 1 and 2 bladder tumors by transurethral resection between 1970 and 1982. All of the patients with grade 3 or previous upper tract tumors, or who had been treated at some stage with intravesical chemotherapy were excluded. Followup for 5 or more years was available in 188 of the patients. There was a low increase in T stage (6 per cent). Of the patients followed for 5 or more years 46 per cent remained free of tumor. Only 16 per cent of the patients had multiple tumors at presentation and 20 per cent had tumors of 10 gm. or more. These factors were associated with a worse prognosis. Patients free of tumor at 3 months had an 80 per cent chance of having no further recurrences and this rate remained the same up to 2 years from the start of the disease. Patients with a recurrence at 3 months were much less likely to remain free of tumor, and had a higher chance of recurrence at every future visit.

A hallmark of autoimmunity in murine models of lupus is the formation of germinal centers (GCs) in lymphoid tissues where self-reactive B cells expand and differentiate. In the host response to foreign antigens, follicular dendritic cells (FDCs) maintain GCs through the uptake and cycling of complement-opsonized immune complexes. Here, we examined whether FDCs retain self-antigens and the impact of this process in autoantibody secretion in lupus. We found that FDCs took up and retained self-immune complexes composed of ribonucleotide proteins, autoantibody, and complement. This uptake, mediated through CD21, triggered endosomal TLR7 and led to the secretion of interferon (IFN) α via an IRF5-dependent pathway. Blocking of FDC secretion of IFN-α restored B cell tolerance and reduced the amount of GCs and pathogenic autoantibody. Thus, FDCs are a critical source of the IFN-α driving autoimmunity in this lupus model. This pathway is conserved in humans, suggesting that it may be a viable therapeutic target in systemic lupus erythematosus.

Neutrophils and complement are key members of innate immunity. The alternative pathway (AP) of complement consists of C3, factor B, factor D and properdin, which amplifies AP activation. AP has been implicated in many neutrophil-mediated diseases, such as anti-neutrophil cytoplasmic antibody-associated vasculitis. The exact mechanism by which the AP and neutrophils interact remains largely unstudied. We investigated the ability of the AP to interact with neutrophil components which can be exposed and released upon activation. Our studies focused on neutrophil enzymes, including myeloperoxidase (MPO), proteinase 3 (PR3), azurocidin, elastase, lysozyme and cathepsin G. All enzymes except for azurocidin were able to bind properdin. However, only MPO could induce C3 activation. MPO mediated AP complement activation in the presence of MgEGTA compared to the EDTA control. This activation resulted in C3 deposition and required properdin to occur. Furthermore, we could show that MPO binds properdin directly, which then serves as a focus for AP activation. In summary, properdin can directly interact with neutrophil components. MPO demonstrates the ability to activate the AP which is dependent on properdin. Finally, MPO is capable of inducing properdin-initiated C3 and C5b-9 deposition in vitro.

A follow-up of 406 traumatic spinal cord injuries admitted from 1967 to 1982 is presented. Forty patients died, only two (5% of deaths and 0.5% of the series) from renal complications. Twenty-seven died from pulmonary or cardiovascular causes, complete and cervical lesions being the most significant factors in mortality. Early and continued active urological treatment aimed at the provision of low pressure bladder drainage to protect the upper tract. The management and results are critically discussed.

Dendritic cells (DCs) and complement are both key members of the innate and adaptive immune response. Recent experimental mouse models have shown that production of alternative pathway (AP) components by DCs strongly affects their ability to activate and regulate T‐cell responses. In this study we investigated the production and regulation of properdin (fP) and factor H (fH) both integral regulators of the AP, by DCs and tolerogenic DCs (tolDCs). Both fP and fH were produced by DCs, with significantly higher levels of both AP components produced by tolDCs. Upon activation with IFN‐γ both cells increased fH production, while simultaneously decreasing production of fP. IL‐27, a member of the IL‐12 family, increased fH, but production of fP remained unaffected. The functional capacity of fP and fH produced by DCs and tolDCs was confirmed by their ability to bind C3b. Inhibition of fH production by DCs resulted in a greater ability to induce allogenic CD4+ T‐cell proliferation. In contrast, inhibition of fP production led to a significantly reduced allostimulatory capacity. In summary, this study shows that production of fP and fH by DCs, differentially regulates their immunogenicity, and that the local cytokine environment can profoundly affect the production of fP and fH.