Management of primary antibody deficiency by consultant immunologists in the United Kingdom: a paradigm for other rare diseases.
Variation in clinical practice and its effect on outcome is little known for rare diseases such as primary antibody deficiency. As part of a national audit a survey of all 30 consultant immunologists in the United Kingdom dealing with primary antibody deficiency syndromes in adults and children was carried out in 1993 to ascertain their practices in diagnosis and management. Consensus guidelines were published after the survey was completed. Comparison of the survey results of clinical practice at the time the guidelines were published with the standards identified highlighted that the practice of a minority of specialists was at variance with their peers and with the consensus document, particularly in the use of intramuscular immunoglobulin, the dose and frequency of intravenous immunoglobulin, and target trough immunoglobulin G concentration, which has implications for the quality of patient care. However, much closer agreement existed in the key areas of management, such as diagnosis and selection of intravenous immunoglobulin. The approach and the problems identified are relevant to the management of other rare diseases, in which diagnosis and management is complex and there are few specialists with the necessary knowledge to undertake such care. This survey, the first attempted audit of practice, shows that within a motivated group of specialists highly significant differences in practice may exist and the authors emphasise the importance of setting clear guidelines against which care can be assessed. (+info)
Burnet Oration: living in the Burnet lineage.
Scientific discoveries are not made in isolation. Innovation depends on resources, both intellectual and physical. A primary requirement is the development and maintenance of appropriate institutions. Such structures do not emerge by chance, but arise from opportunity, political will and the continued efforts and commitment of many people over long periods. Suitable buildings, laboratories and state-of-the-art equipment are obviously necessary, but hardware alone is of little value in the absence of a vibrant research culture. The key characteristics of the latter are intellectual foment, open debate and a body of wisdom and knowledge about the particular subject area. Rolf Zinkernagel and 1 played a part in triggering a paradigm shift in the understanding of T cell recognition, a contribution recognized by the 1996 Nobel Prize for Physiology or Medicine. In our Nobel lectures, we both discussed briefly why it was that the John Curtin School of Medical Research (JCSMR) of 1973-75 provided a milieu that facilitated the emergence of the underlying experiments and ideas. My intention here is to discuss in more detail the scientific lineages that put this physical and intellectual environment in place, focusing particularly on the influence of Sir Frank Macfarlane (Sir Mac) Burnet as we celebrate his centenary year. (+info)
The discovery of T cell help for B cell antibody formation: a perspective from the 30th anniversary of this discovery.
Thirty years ago, Miller and Mitchell described the bone-marrow origin of antibody-forming cells and the thymic origin of the help needed to activate the bone-marrow-derived antibody formation. Since then, there has been a continuous stream of discovery in Australia, from Zinkernagel and Doherty's description of MHC-restricted antigen recognition to Goodnow's dissection of the maturation and tolerization of antigen-specific B cells. All of these discoveries, and many more described in the text, contribute to the modern synthesis in immunology. (+info)
Introduction to immunology and autoimmunity.
Autoimmune disease occurs when the immune system attacks self-molecules as a result of a breakdown of immunologic tolerance to autoreactive immune cells. Many autoimmune disorders have been strongly associated with genetic, infectious, and/or environmental predisposing factors. Comprising multiple disorders and symptoms ranging from organ-specific to systemic, autoimmune diseases include insulin-dependent diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, thyroiditis, and multiple sclerosis. There are also implications of autoimmune pathology in such common health problems as arteriosclerosis, inflammatory bowel disease, schizophrenia, and certain types of infertility. Largely of unknown etiology, autoimmune disorders affect approximately 3% of the North American and European populations, > 75% of those affected being women. This discussion provides a brief introduction to the immune system and tolerance maintenance, an overview of selected autoimmune diseases and possible mechanisms of immune autoreactivity, and a review of experimental autoimmune models. (+info)
Progress in standardization: 4 immunological reagents.
The need for material standards in the field of clinical immunology, together with the mode of operation of the combined World Health Organization/International Union of Immunological Societies programme for the provision of such standards, are discussed. Attention is drawn to the importance of the use of International Units in reporting concentrations of complex constituents, e.g., immunoglobulins in body fluids, and to the availability of standard materials against which such components can be calibrated. The necessity for the standardization of nomenclature is also emphasized. (+info)
Transplantation and its biology: from fantasy to routine.
The replacement of diseased organs and tissues by the healthy ones of others has been a unique milestone in modern medicine. For centuries, transplantation remained a theme of fantasy in literature and the arts. Within the past five decades, however, it has developed from a few isolated attempts to salvage occasional individuals with end-stage organ failure to a routine treatment for many patients. In parallel with the progressive improvements in clinical results has come an explosion in immunology, transplantation biology, immunogenetics, cell and molecular biology, pharmacology, and other relevant biosciences, with knowledge burgeoning at a rate not dreamed of by the original pioneers. Indeed, there have been few other instances in modern medicine in which so many scientific disciplines have contributed in concert toward understanding and treating such a complex clinical problem as the failure of vital organs. The field has been a dramatic example of evolution from an imagined process to an accepted form of therapy. (+info)
Provision of allergy care for optimal outcome in the UK.
Allergy is common and the prevalence has increased substantially in the last 2-3 decades. There has been a particular increase in severe allergic disease, including anaphylaxis, food, drug and latex rubber allergy. Provision of allergy services in the NHS is extremely poor and there is a huge unmet need. Allergy is a full speciality, but there are few consultants and few trainees. Whilst other specialists have a role in the management of allergy, it is no longer adequate to devolve most of allergy care to them. Provision of allergy care must be lead by allergy specialists so that adequate standards of care can be achieved. The lack of care leads to morbidity, mortality and substantial cost to the NHS, much of which is avoidable. There is an urgent need for the creation of more consultant posts in allergy and this requires recognition by Trust Managers, Regional Commissioners and the Department of Health. (+info)
Identification of the enzymatic active site of tobacco caffeoyl-coenzyme A O-methyltransferase by site-directed mutagenesis.
Animal catechol O-methyltransferases and plant caffeoyl-coenzyme A O-methyltransferases share about 20% sequence identity and display common structural features. The crystallographic structure of rat liver catechol O-methyltransferase was used as a template to construct a homology model for tobacco caffeoyl-coenzyme A O-methyltransferase. Integrating substrate specificity data, the three-dimensional model identified several amino acid residues putatively involved in substrate binding. These residues were mutated by a polymerase chain reaction method and wild-type and mutant enzymes were each expressed in Escherichia coli and purified. Substitution of Arg-220 with Thr resulted in the total loss of enzyme activity, thus indicating that Arg-220 is involved in the electrostatic interaction with the coenzyme A moiety of the substrate. Changes of Asp-58 to Ala and Gln-61 to Ser were shown to increase K(m) values for caffeoyl coenzyme A and to decrease catalytic activity. Deletions of two amino acid sequences specific for plant enzymes abolished activity. The secondary structures of the mutants, as measured by circular dichroism, were essentially unperturbed as compared with the wild type. Similar changes in circular dichroism spectra were observed after addition of caffeoyl coenzyme A to the wild-type enzyme and the substitution mutants but not in the case of deletion mutants, thus revealing the importance of these sequences in substrate-enzyme interactions. (+info)