Thomsonians: the people's doctors.
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Biomedical subjects
Publications and source records attributed to D J Wallace.
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Immune complex mediated damage, still incompletely understood, is a frequent and important pathogenetic mechanism in several major rheumatic diseases. Injury by circulating immune complexes seems to be related mainly to the size of the complexes and their ability to activate the complement system. The more circulating immune complexes are looked for to assess the nature of an activity of diseases, the more clinicians are faced with difficulties in interpretation. This is partly because of rapidly increasing number and types of immune complex assays and the conflicting data obtained. An understanding of the principles behind the commonly used immune complex assays allows the clinician to appreciate their advantages and weak points and to apply them correctly in investigating the clinicopathological aspects of immune complex mediated rheumatic diseases.
A 73-year-old woman with Felty's syndrome and arthritis mutilans of long duration presented with tophaceous gout. The 7 previously reported cases of coexistent gout and rheumatoid arthritis (RA) are critically reviewed. Possible explanations for the rare coexistence of RA and gout are discussed: if uric acid is an inhibitor of the immune response, then hyperuricemia and gout could protect against development of RA. Conversely, crystalline protein binding may be a critical factor in the pathogenesis of gout, and the presence of abnormal proteins in RA could protect against gout.
We have demonstrated the efficacy of therapeutic pheresis in a number of rheumatic diseases, especially rheumatoid arthritis (RA). Ten of 12 patients with RA went into remissions averaging 4 months. These patients were pheresed 20 times over 11 weeks in a tapering fashion on a Haemonetics Model 30 Blood Processor. Clinical remissions were sustained even though serologies, immunoglobulins, immune functions, sedimentation rates, and circulating immune complexes returned to their pre-pheresis baseline by pheresis number 20. All these patients were taking gold or D-penicillamine concurrently, but neither of the 2 patients who failed to respond was on these agents. Plasmapheresis was just as effective as lymphoplasmapheresis. It is theorized that removal of a plasma factor that modulates lymphocyte or neutrophil function produces remissions in RA and that long-acting drugs (e.g., gold or penicillamine) are able to prevent its continued production and produce a sustained remission.
This article is a comprehensive overview of the biology of aging. The largely unproductive history of research on aging is presented, to lay the groundwork for a discussion of why such research is performed and what aging levels and human models are employed. The anatomic, biochemical, physiologic and behavioral measures used in such studies are delineated. Some of the most promising theories of aging (genetic, autoimmune, viral, free radical) are discussed, as are factors that could prolong the lifespan if optimally employed. Philosophic considerations are emphasized.
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Modifications are described to a previously published technique for quantitative determination of mite populations in animal feedingstuffs. In the modified method, the oil phase is kerosene instead of a mixture of kerosene and tetralin (1 + 1), and aqueous industrial methylated spirit is substituted for aqueous ethanol in the aqueous phase. Emulsion formation at the interface is considerably reduced by incorporating a pre-extraction stage. Examination of mites on the filter paper is made easier and quicker by staining them with Phloxin B. Trials carried out with known numbers of mites in samples of dairy feed concentrates indicate mean recoveries of 84-96% throughout the range tested. The results show that the accuracy of the technique is not affected by the level of infestation.
Although cumulative evidence suggests that a genetic predisposition plays a major role in the development of systemic lupus erythematosus (SLE), the susceptibility genes are mostly unknown. The difficulty in identifying susceptibility genes is due in part to the inherent nature of this polygenic complex disease and the diverse genetic backgrounds of human populations. Murine SLE models that have homogenous genetic backgrounds are less complex for genetic dissection. Genome-wide linkage studies of murine SLE have mapped the position of a number of susceptibility loci. Recently, several of these major murine loci have been shown to link to different clinical and laboratory features of lupus-like phenotypes. In addition, evidence for additional genetic contributions via interaction between murine loci has been reported. In human SLE, many polymorphic genes (which have potential roles in SLE, as suggested by their known functions) have been associated with SLE or SLE subsets by population-based case-control or within-case studies. Because more compelling genetic evidence includes linkage analysis, our group has used the identified murine susceptibility loci as a guide and conducted linkage analysis of genetic markers located within a specific, possibly syntenic human chromosomal region. Evidence for linkage of a chromosome 1q41-42 region was observed in SLE-affected sibling pairs from multiple ethnic groups. This article summarizes recent developments and outlines possible future directions in delineating the genetic basis of SLE.