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Biomedical subjects

J A Simpson

Publications and source records attributed to J A Simpson.

16 recordsLinked to original sources

Long-lived reactive species on free-radical-damaged proteins.

We have demonstrated two novel reactive species on radical-modified proteins which are relatively long-lived, one oxidizing and one reducing. The two species are reactive with critical biological components, and so may be of physiological and pathological importance. The oxidizing species, which have been identified as protein hydroperoxides, can consume key cellular reductants, such as ascorbate and glutathione. The reducing species can act on both free and metalloprotein forms of copper and iron ions, which participate in radical generation. These findings suggest that proteins may act as traps for the chemical energy released by free radicals, with the capacity to pass it on to other molecules. The long-lived nature of both the reactive moieties indicates that they may be able to diffuse and transfer damaging reactions to distant sites.

Amino Acids

Hypothesis: a damaging role in aging for reactive protein oxidation products?

This paper discusses our knowledge of protein oxidation and its relationship to aging. It also outlines new observations from our laboratories concerning reactive species produced during protein oxidation, and proposes that these may inflict damage on other molecules, and hence contribute to the progression of aging. Whereas it has previously been difficult to see how relatively inert protein oxidation products could possibly have any causal role in aging, the detection of these novel reactive species implies a potentially significant role.

Aging

Differential accuracy in person perception across traits: examination of a functional hypothesis.

Although strangers can assess certain traits of unacquainted others with moderate validity, overall validity is low. Differential validity across traits may be due to (a) the extent to which targets display valid cues or (b) the extent to which perceivers validly use cues. A functionalist perspective suggests that valid cue utilization should vary with how important the consequences of accurate trait assessment are. It was predicted from this perspective that perceivers would judge strangers' sociosexuality more accurately than 3 other traits--social potency, social closeness, and stress reaction. Perceivers viewed 1-min videotaped segments of targets being interviewed and rated them on the 4 traits. Ratings were correlated with target-reported trait measures. As predicted, perceivers' ratings of male sociosexuality agreed relatively well with self-reports. This effect was moderated by sex of target and sex of perceiver.

Adult

Plasma-exchange combined with immunosuppressive therapy in myasthenia gravis.

Twenty-one patients with myasthenia gravis underwent a course of plasma exchange combined with immunosuppressive therapy. In fifteen there was dramatic clinical improvement which has been maintained for periods up to 19 months. Nine of these patients now take no anticholinesterase drugs. Six patients had a recurrence 3--9 months after the first course but in the three given a second course remissions were again obtained.

Adult

Solanum torvum as a causative agent of enzootic calcinosis in Papua, New Guinea.

Inclusion of dried powdered leaves of Solanum torvum Swartz (collected in Papua, New Guinea) in the diet of rats induced hypercalcaemai rapidly and hyperphosphataemia more slowly; soft tissue calcification was most evident in the kidney and lung. Solanum torvum may be a causative agent of enzootic calcinosis in cattle in Papua, New Guinea.

Animals

Penicillamine-associated myasthenia gravis, antiacetylcholine receptor and antistriational antibodies.

Myasthenia gravis with thymic hyperplasia developed in a patient with Wilson's disease after eight years of penicillamine treatment. Four months prior to the onset of myasthenia, penicillin hypersensitivity was observed. Immunofluorescence on the excised thymus revealed immunoglobulin and complement deposition, but the myasthenia persisted after thymectomy and continuation of penicillamine therapy. Increased antiacetylcholine receptor antibody was demonstrable throughout. This patient subsequently became pregnant, enabling studies to be performed on the transplacental transfer of the immunoglobulin G (IgG) class antiacetylcholine receptor antibody. Eleven cases of rheumatoid arthritis with penicillamine-associated antistriational antibodies have also been observed; in three of these cases there was evidence of myasthenia gravis. These observations extend earlier reports of the association of penicillamine with myasthenia gravis and suggest that antistriational antibody, antiacetylcholine receptor antibody and thymic hyperplasia may be independent effects of penicillamine therapy.

Acetylcholine

Studies on the nature of autoimmunity in myasthenia gravis. Evidence for an immunodeficiency type.

Clinical and laboratory data continue to support the concept of a genetically determined breakdown of immunological tolerance in myasthenia gravis with immunological damage to the motor end plates. The demonstration of impaired function of thymus-derived lymphocytes and of IgA deficiency correlate well with the clinical data in which there is an increase incidence of autoimmune diseases associated with anergy. Whilst the exact pathogenesis of myasthenia gravis is unknown, the available data support the concept of an immune deficiency disorder.

Antibody Formation

Absence of cellular hypersensitivity to muscle and thymic antigens in myasthenia gravis.

Humoral antibodies to skeletal muscle and its components and to thymus have been demonstrated in the sera of patients with myasthenia gravis. A role for cellular hypersensitivity to similar antigens in the pathogenesis of the disease has been suggested by some reports of the presence of cellular immunity. A detailed immunological study using muscle and thymic antigens, including those prepared from the patients' own tissues, failed to confirm these findings. It is suggested that previous reports of cellular hypersensitivity represent the demonstration of an epiphenomenon.

Cell Migration Inhibition

Myasthenia gravis: a personal view of pathogenesis and mechanism, part 1.

A review of our current knowledge of the etiology and pathogenesis of myasthenia gravis is presented, with particular emphasis on the immunological aspects of the disease. Part 1, published in this issue, deals with the clinical and genetic features of myasthenia gravis which led to the autoimmune theory of the etiology of this disease. Various theories in this field are reviewed, and recent advances in our knowledge of the acetylcholine receptor protein, and its immunology, are examined. Part 2, which will appear in the March/April issue, provides a review of the dysfunction of physiology, pharmacology, and structure of the neuromuscular junction in myasthenia gravis, and the part played by the autoimmune process.

Adult

Myasthenia gravis: a personal view of pathogenesis and mechanism, part 2.

A review of our current knowledge of the etiology and pathogenesis of myasthenia gravis is presented, with particular emphasis on the immunological aspects of the disease. Part 1, published in the January/February issue of MUSCLE & NERVE, dealt with the clinical and genetic features of myasthenia gravis which led to the autoimmune theory of the etiology of the disease. Part 2, which appears in this issue, provides a review of the dysfunction of physiology, pharmacology, and structure of the neuromuscular junction in myasthenia gravis, and the part played by the autoimmune process.

Autoimmune Diseases