Biomedical subjects
J R Wall
Publications and source records attributed to J R Wall.
Leucine aminopeptidase polymorphism in Phaseolus and differential elimination of the donor parent genotype in interspecific backcrosses.
Explore the source record for details and available documents.
Luekocyte adherence inhibition in response to human orbital and lacrimal extracts in patients with Graves' ophthalmopathy.
Leukocyte adherence inhibition (LAI) may be a test for cell-mediated immunity or cytophilic antibodies. LAI tests were carried out on patients with Graves' ophthalmopathy, using normal human lacrimal gland, orbital fat, and eye muscle extracts as antigens. The results were expressed as % LAI. The percentage leukocyte adherence inhibition in tests from patients and normal subjects were not significantly different for any preparation (Mann-Whitney tests). Taking the upper limit of normal as the mean % LAI + 2SD for normal subjects, tests were positive, to eye muscle extract, in only one patient whilst borderline inhibition, in response to eye muscle and fat extracts respectively, was demonstrated in two patients. All three had active disease. LAI tests may be positive only during the acute stage of Graves' ophthalmopathy. The significance of these findings in respect to the pathogenesis of Graves' ophthalmopathy is discussed.
In vitro production of thyroid-binding antibodies by peripheral blood lymphocytes from patients with Graves' disease: nonspecific responses associated with culture supernatant proteins.
Peripheral blood lymphocytes from patients with Graves' disease were cultured for 7 days with mitogens (phytohemagglutinin, Concanavalin A, protein A), or specific antigen (thyroid membranes), in an attempt to produce thyroid-binding antibodies (TBAb) in vitro. TBAb was measured in culture supernatants using a sensitive radioreceptor assay. Mean TBAb indices of mitogen or antigen-stimulated cultures did not differ significantly from those of unstimulated cultures for either patients or normal subjects. Although TBAb indices of less than 0.70, which are generally considered positive for serum TBAb, were demonstrated in a small proportion of individual tests of supernatants from patients with Graves' disease, low indices were also found in tests from normal subjects. One cause of such nonspecific responses was found to be culture infection. The factor associated with positive responses in infected cultures was unlikely to be an immunoglobulin since TBAb-like activity was not detected in globulins isolated by DEAE + -Sephadex chromatography, which isolates only IgG and IgA, and the activity was not neutralized by anti-IgG serum. The possible ways of improving the culture system for in vitro TBAb production and the significance of nonspecific responses in the radioreceptor assay are discussed.
Isolation and characterization of mononuclear cells from various thyroid tissue specimens.
Extensive studies of humoral and cell mediated autoimmune responses to thyroid antigens have been performed in order to understand the underlying mechanisms of autoimmune thyroid disorders. Very little is known, however, about the nature of the lymphocyte subpopulations in the thyroid gland and their possible involvement in the pathogenesis of thyroid diseases. We have developed a Percoll gradient technique to separate mononuclear cells from thyroid cells of resected thyroid glands. Thyroid tissue was minced, incubated with Dispase and passed through a tissue sieve. The filtrate was layered onto a four step discontinuous Percoll gradient (densities 1.140, 1.077, 1.061, 1.030 g/ml). Thyroid cells appeared in band II and mononuclear cells in band III. Mononuclear cells were characterized using the monoclonal antibodies OKT-3, OKT-8, OKI-a and OKM-1, and the levels of these populations in peripheral blood and thyroid tissue compared. Patients have been classified by conventional clinical, immunological and histological criteria. The studies involved thyroid tissues from 8 patients with euthyroid nodular goitre, 7 patients with Graves' disease and 1 with Hashimoto's thyroiditis. In the thyroid tissue of non-autoimmune thyroid diseases we find significantly less OKT-3+ cells compared to peripheral blood. In thyroid tissue of autoimmune thyroid diseases there are significantly less OKT-8+ cells compared to peripheral blood. These preliminary results might be linked to the hypothesis of decreased suppressor T-cell activity in autoimmune thyroid disease.
Natural cytotoxicity of peripheral blood leukocytes from normal subjects and patients with Hashimoto's thyroiditis against human adult and fetal thyroid cells.
Natural cytotoxicity of human peripheral blood leukocytes against fetal and adult human thyroid cells was investigated in vitro. Natural killer (NK) cell activity was determined at various effector: target cell ratios in a standard 51Cr release assay with human thyroid cells as targets. The effector cells were unfractionated peripheral blood mononuclear cells obtained by Hypaque-Ficoll gradient centrifugation. We have demonstrated that peripheral blood leukocytes from normal subjects and patients with Hashimoto's thyroiditis exhibit natural cytotoxicity against both human fetal and adult thyroid cells. This was effector: target cell ratio and incubation time dependent. Although there was a tendency for increased killing of fetal thyroid cells by peripheral blood leukocytes from patients with Hashimoto's thyroiditis compared to age/sex matched normal subjects this was not significant and there were no significant differences between the two groups for killing of adult thyroid cells. A possible role for natural cytotoxicity in progressive thyroid tissue destruction in Hashimoto's thyroiditis is discussed.
Role of eye muscle antibody measurement in diagnosis of thyroid-associated ophthalmopathy: a laboratory update.
OBJECTIVE: To review the current role of measurement of serum eye muscle antibodies in thyroid-associated ophthalmopathy (TAO). METHODS: We conducted laboratory studies to determine the prevalences of serum autoantibodies reactive with eye muscle antigens in patients with active and inactive TAO, Graves' hyperthyroidism, and Hashimoto's thyroiditis as well as in normal subjects. RESULTS: The two antigens most often recognized in immunoblotting with crude human or porcine eye muscle membranes by serum autoantibodies in patients with TAO are eye muscle membrane proteins of 55 and 64 kd. One 64-kd eye muscle protein has recently been cloned by screening a human eye muscle expression library with two different antibody probes and identified from a computer gene bank search as the calcium-binding protein calsequestrin. A fragment of a 220-kd eye muscle protein, called G2s, has also been cloned by screening the eye muscle library with affinity-purified antibodies reactive with a 55-kd eye muscle membrane protein. The prevalences of autoantibodies reactive with these two antigens in our study groups were as follows. Antibodies against calsequestrin were detected in 38% of patients with TAO for <1 year, in 17% of those with TAO for >3 years, in 17% of patients with Graves' hyperthyroidism without ophthalmopathy, in 12% of patients with Hashimoto's thyroiditis without ophthalmopathy, and in 21% of normal subjects. Antibodies reactive with the 64-kd protein were demonstrated in 62% of patients with recent-onset active TAO, in 33% with eye disease for >3 years, in 39% of patients with Graves' hyperthyroidism without ophthalmopathy, in 25% of patients with Hashimoto's thyroiditis, and in 16% of normal control subjects. Antibodies reactive with G2s fusion protein were detected in 67% of patients with recent-onset active TAO, in 46% of patients with Graves' hyperthyroidism, and in 20% of normal subjects. Antibodies reactive with the parent protein, of which G2s is a fragment, may be markers of early eye muscle swelling and inflammation, whereas those reactive with the 64-kd protein and, less often, calsequestrin are associated with established eye disease. CONCLUSION: Measurement of serum eye muscle antibodies is recommended as an aid to the early diagnosis of ophthalmopathy in predisposed patients and first-degree relatives of patients with TAO as well as to monitor active or progressive eye disease.
Interleukin-2 receptor beta and CD57 expression in orbital tissues from patients with chronic, stable thyroid-associated ophthalmopathy.
In order to determine whether components of the interleukin-2 receptor (IL-2R) and lymphoid cells are present in extra ocular and periocular tissues from patients with chronic, stable thyroid-associated ophthalmopathy (TAO) we studied 16 specimens of extra ocular muscle and periorbital connective tissue from 14 patients with chronic, stable, TAO using an immunohistochemical assay and a panel of murine monoclonal antibodies reactive with IL-2R alpha and beta components and lymphoid cell surface markers. As controls we studied orbital tissues from 11 patients undergoing surgery for unrelated orbital disorders. All extra ocular muscle specimens from patients with TAO exhibited IL-2R beta expression primarily on the perimysium and endomysium surrounding the ocular muscle fasciculi and fibers of which nine specimens stained intensely. The Natural Killer (NK) cell marker CD57 was the most common cell surface antigen detected, in seven of nine specimens, whose localization often corresponded to that of IL-2R beta distribution. No IL-2R alpha expression was detected in any specimen. Seven of the 11 control specimens were positive for IL-2R beta but in a less intense fashion than in TAO specimens while no CD57 staining was detected. T cell, B cell, and cells of granulocyte and monocyte lineage were only occasionally found in both TAO and control specimens. The aberrant expression of IL-2R beta and CD57 which may be representative of NK cell presence in extra ocular muscle tissues from patients with stable, chronic TAO may play a role in the pathogenesis of the ophthalmopathy.(ABSTRACT TRUNCATED AT 250 WORDS)
Significance of tissue specific and tissue non specific autoimmune reactions of Graves' disease.
The relationship between the many immunologic abnormalities demonstrated in the peripheral blood of patients with Graves' disease (GD) and the broad spectrum of clinical features with which patients may present has not yet been addressed in detail. In this review we examine the evidence to support the notion that GD could be considered a multi-system autoimmune disorder in which tissue damage is restricted to the thyroid gland, connective tissue of the skin and orbit, extra-ocular and other skeletal muscles and, possibly, the lacrimal glands. Apart from the well recognized reactions of autoantibodies and sensitized T lymphocytes with epitopes on the thyroid specific TSH receptor, thyroid peroxidase and thyroglobulin, in patients with hyperthyroidism, there is also good evidence for autoantibody and, to a lesser extent, T lymphocyte reactivity with several eye muscle, other skeletal muscle and connective tissue, antigens in patients with ophthalmopathy, systemic myopathy, dermopathy and acropachy. There is also some evidence for immunoreactivity against lacrimal gland antigens in patients with ophthalmopathy associated with other features of GD. There are, in addition, a variety of organ non-specific reactions in GD; antinuclear antibodies are detected in serum from about one-third of patients with hyperthyroidism and ophthalmopathy, while from 5% to 10% have antibodies reactive with several other ubiquitous tissue proteins. Cloned proteins which are autoantigenic in some patients with hyperthyroidism or Hashimoto's thyroiditis and ophthalmopathy include collagen XIII, nebulin, the calcium binding protein calmitine, and the Mac-II antigen. All antibodies reactive with eye muscle antigens, except the 64 kDa protein which is also expressed in the thyroid, cross react with the same, or a related, protein in other skeletal muscle. Future research should focus on the underlying mechanisms for this broad loss of tolerance to self antigens and the effect of environmental factors such as stress, radioiodine and viral infection of the thyroid gland and other target tissues, in precipitating disease.
Treatment of a habitual smoker using nicotine gum: a case report.
Explore the source record for details and available documents.