What you should know about PR3-ANCA: An introduction

Anti-neutrophil cytoplasmic antibodies (ANCA) have become important diagnostic markers of small vessel vasculitides characterized by focal necrotizing lesions of vessel walls and accumulation of lymphocytes and macrophages around the affected vessels. IgG class ANCA directed to proteinase 3 (PR3) of neutrophils and monocytes seem to be directly involved in the pathophysiology of vascular damage by causing excessive neutrophil activation and vessel wall destruction. PR3 and elastase are important players in the mechanisms of vascular necrosis. Methods of detecting ANCA have now been defined but are not uniformly used, even though clinical decisions heavily depend on correct ANCA results.     

What you should know about PR3-ANCA: Conformational requirements of proteinase 3 (PR3) for enzymatic activity and recognition by PR3-ANCA

The neutrophil azurophil granule constituent proteinase 3 (PR3) is the principal antigen for anti-neutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis. The conformation of the mature PR3 enzyme results from intracellular post-translational processing. The nascent molecule undergoes proteolytic cleavage of the amino-terminal signal peptide and activation dipeptide and of a carboxy-terminal peptide extension. The conformation of PR3 is stabilized by four disulfide bonds and, to a lesser extent, by asparagine-linked glycosylation. Most anti-neutrophil cytoplasmic antibodies directed against proteinase 3 (PR3-ANCA) recognize conformational epitopes. The expression of recombinant PR3 has provided a better understanding of the significance of the various intracellular processing steps for enzymatic activity and recognition by PR3-ANCA.     

What you should know about PR3-ANCA. Evidence for the role of T cells in the pathogenesis of systemic vasculitis

The pathogenesis of systemic vasculitis is complex and is likely to involve many mechanisms. There is a growing body of evidence that T cells may contribute to the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Predominantly, T cells and monocytes are found in inflammatory infiltrates in patients with Wegener's granulomatosis (WG). The production of ANCA appears to be T-cell-dependent. T lymphocytes from the peripheral blood of patients with ANCA-associated vasculitis have been shown to proliferate in response to proteinase 3 (PR3). These and other findings outlined in this review indicate T-cell involvement, although further studies are still needed to elucidate the exact contribution of T cells to the pathogenesis of systemic vasculitis.     

What you should know about PR3-ANCA: Evidence for the role of T cells in the pathogenesis of systemic vasculitis

The pathogenesis of systemic vasculitis is complex and is likely to involve many mechanisms. There is a growing body of evidence that T cells may contribute to the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Predominantly, T cells and monocytes are found in inflammatory infiltrates in patients with Wegener's granulomatosis (WG). The production of ANCA appears to be T-cell-dependent. T lymphocytes from the peripheral blood of patients with ANCA-associated vasculitis have been shown to proliferate in response to proteinase 3 (PR3). These and other findings outlined in this review indicate T-cell involvement, although further studies are still needed to elucidate the exact contribution of T cells to the pathogenesis of systemic vasculitis.     

What many transgender activists don't want you to know: and why you should know it anyway

Currently the predominant cultural understanding of male-to-female transsexualism is that all male-to-female (MtF) transsexuals are, essentially, women trapped in men's bodies. This understanding has little scientific basis, however, and is inconsistent with clinical observations. Ray Blanchard has shown that there are two distinct subtypes of MtF transsexuals. Members of one subtype, homosexual transsexuals, are best understood as a type of homosexual male. The other subtype, autogynephilic transsexuals, are motivated by the erotic desire to become women. The persistence of the predominant cultural understanding, while explicable, is damaging to science and to many transsexuals.     

What tissue bankers should know about the use of allograft heart valves

Heart valve allografts (usually referred to as ‘homografts’) have been used in cardiac surgery for over 45 years when they were amongst the first valves ever used. Today they remain an important part of valve replacement and reconstructive surgery, particularly in the field of congenital heart disease. There are currently seven tissue banks on the UK and Eire that procure, prepare and store these homografts for surgical implantation, currently providing around 700 grafts per year. This article reviews the history and applications of homografts and compares their performance and outcomes with current prosthetic alternatives. It also describes the processes of valve procurement and storage and describes their clinical applications, hopefully providing tissue bankers with the surgeon’s insight into what is required. Homograft degeneration and the natural history of these tissues is discussed, together with future expectations and developments in homograft valve technology.     

What tissue bankers should know about the use of allograft blood vessels

Vascular allografts have been used by surgeons with varying levels of enthusiasm over the last 100 years, to treat a wide variety of vascular conditions. This article reviews the history of vascular allografts, the current indications for use, and the background to current retrieval, processing and cryopreservation techniques.     

What tissue bankers should know about the use of allograft meniscus in orthopaedics

The menisci of the knee are two crescent shaped cartilage shock absorbers sitting between the femur and the tibia, which act as load sharers and shock absorbers. Loss of a meniscus leads to a significant increase in the risk of developing arthritis in the knee. Replacement of a missing meniscus with allograft tissue can reduce symptoms and may potentially reduce the risk of future arthritis. Meniscal allograft transplantation is a complex surgical procedure with many outstanding issues, including ‘what techniques should be used for processing and storing grafts?’, ‘how should the allografts be sized?’ and ‘what surgical implantation techniques might be most appropriate?’ Further clinical research is needed and close collaboration between the users (surgeons) and the suppliers (tissue banks) is essential. This review explores the above subject in detail.     

All you wanted to know about SELEX

In vitro selection, or SELEX, is a technique that allows the simultaneous screening of highly diverse pools of different RNA or DNA (dsDNA or ssDNA) molecules for a particular feature. Different examples from a great variety of applications ofin vitro selection experiments are described and a detailed overview of the method and its variations will be given. Some especially conclusivein vitro selection experiments are discussed in detail to illustrate the potential power and diversity of this method. Potential restrictions of the methods and possible ways to overcome them are pointed out.