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Biomedical subjects

J R Wall

Publications and source records attributed to J R Wall.

At least 109 records · Page 6Linked to original sources
PubMed1982

Nature of thyrotropin displacement activity in subacute thyroiditis.

Using a radioreceptor assay and serum immunoglobulin (Ig) prepared by ammonium sulfate precipitation, significant TSH displacement activity (TDA) was demonstrated in 5 of 15 patients with subacute thyroiditis tested during the acute phase. Using a cAMP generation assay, adenyl cyclase stimulation by Ig from patients with subacute thyroiditis was not demonstrated. The nature of the TDA demonstrated in subacute thyroiditis was investigated to determine whether the factor measured was TSH receptor antibody, as is found in Graves' hyperthyroidism, or thyroglobulin, which is know to give false positive responses in the radioreceptor assay. When Ig was prepared by DEAE+-Sephadex chromatography, mean TSH displacement indices were similar to those given by ammonium sulfate-prepared Ig for both Graves' disease and subacute thyroiditis. On the other hand, when Ig was prepared by DEAE+-cellulose chromatography, which isolates highly purified IgG, mean indices were significantly less than for ammonium sulfate-prepared Ig for both Graves' hyperthyroidism and subacute thyroiditis. Thyroglobulin was not detected in Ig prepared by any of the 3 methods. Although high concentrations of crude thyroid-soluble fraction and purified thyroglobulin gave strongly positive responses in the radioreceptor assay, concentrations of thyroglobulin over the range found in the sera of patients with subacute thyroiditis could not be shown to give positive responses. Moreover, TSH displacement indices did not correlate with serum thyroglobulin levels. As determined by species cross-reactivity and dose-responses studies, the TDAs demonstrated in subacute thyroiditis and Graves' hyperthyroidism were similar. It was concluded that the TDA demonstrated in subacute thyroiditis represents antibody which binds to, but does not stimulate, the TSH receptor.

Adolescent↗
PubMed1981

Graves' ophthalmopathy.

Graves' ophthalmopathy usually occurs in association with hyperthyroidism. Its occasional occurrence in the absence of thyroid disease suggests, however, that it may be a separate autoimmune disorder. While the evidence supporting an autoimmune pathogenesis is considerable for the ophthalmopathy, it is not so impressive as that for Graves' hyperthyroidism: orbital antibodies have not been convincingly demonstrated and autoantigens have not been identified. On the other hand, in patients with Graves' ophthalmopathy the orbital tissues and eye muscle membranes are infiltrated with lymphoid cells and show evidence of cell-mediated immune reactions. Although there is some evidence that binding of thyroid stimulating hormone fragments and thyroglobulin-antithyroglobulin immune complexes to eye muscle membranes may be important in the pathogenesis of the ophthalmopathy, this needs to be confirmed. The mechanism for the association of hyperthyroidism and ophthalmopathy is unknown, but the association likely reflects an influence of thyroid hormones on the immune system. In view of the autoimmune pathogenesis the logical treatment of Graves' ophthalmopathy appears to be immunosuppression.

Autoantibodies↗
PubMed1981

Failure of haemagglutination and immunofluorescence methods to detect serum orbital antibodies in patients with Graves' ophthalmopathy.

Serum antibodies against human, bovine, and guinea-pig, orbital antigens were tested for in patients with Graves' ophthalmopathy using haemagglutination and immunofluorescence techniques. Although low titres of antibodies were demonstrated in a small proportion of patients with Graves' ophthalmopathy, the prevalence was similar to that for normal subjects using both tests. The significance of these findings and the evidence for a role of autoantibodies in the pathogenesis of Graves' ophthalmopathy are discussed.

Adult↗
PubMed1981

Immunoreactivity in vitro to human testis in patients with lepromatous leprosy.

Patients with lepromatous leprosy and tuberculoid leprosy, together with normal aged matched controls, were tested for in vitro immunoreactivity against a panel of soluble extracts prepared from normal human tissues. The panel consisted of a soluble homogenate of human testis as well as two partially purified fractions of this extract, and control extracts from other human tissues. Immunoreactivity was assessed by extract induced peripheral blood lymphocyte (PBL) transformation, leucocyte migration inhibition (LMI) and leucocyte adherence inhibition (LAI). Although no difference in PBL transformation, LMI, or LAI was obtained between the groups with the control tissue extracts, significant reactivity was obtained for the patients with lepromatous leprosy in at least one of the in vitro tests, when one of the testis extracts was used (Mann-Whitney test). No such reactivity to the testis extracts was obtained in the patients with tuberculoid leprosy or the normal control subjects. Of the twenty-two patients studied with lepromatous leprosy, thirteen had clinical evidence of testicular disease and nine of these patients had raised PBL transformation and LAI reactivity to the testis extracts. This finding of immunoreactivity against testicular extracts in a significant number of patients with lepromatous leprosy by at least one of the vitro tests used, suggests that the associated in vivo testicular atrophy that occurs in these patients may have an auto-immune basis.

Adolescent↗
PubMed1981

Effects of experimental hyper- and hypothyroidism on numbers of blood mononuclear cells and immune function in rats and guinea-pigs.

A possible effect of thyroid hormones on numbers of mononuclear cells and immune reactivity has been studied in hyperthyroid and hypothyroid guinea-pigs and rats. There were no major changes in populations of blood mononuclear cells in hyperthyroid or hypothyroid animals compared with populations in euthyroid animals. Although there was some evidence for depressed cell-mediated responses to an extract of Candida (monilia) albicans in hyperthyroid rats as assessed by skin tests, this was minor, and responses in tuberculin purified protein derivative (PPD) were normal in all groups, whilst production of macrophage migration inhibition factor in response to PPD and Candida was similar in the three groups of animals. Antibody responses to sheep red blood cells, a thymic-dependent antigen, tended to be depressed in hyperthyroid and hypothyroid rats and increased in hyperthyroid and hypothyroid guinea-pigs, although this was significant only for hyper-thyroid guinea-pigs 16 days after immunization. Responses to trinitrophenol-Ficoll, a thymic-independent antigen, were similar to the three groups of guinea-pigs. Thus, a major effect of excess or deficiency of thyroid hormone on immune responses to foreign antigens has not been demonstrated, although it is possible that immune reactions against thyroid antigens may be more sensitive to the effect of thyroid hormones than responses to foreign antigens.

Animals↗
PubMed1981

Blood mononuclear cells with suppressor activity in patients with thyroid disorders: increased levels of T gamma cells in subacute thyroiditis.

Blood T lymphocytes with suppressor activity [stable T cells, low affinity T cells and T cells with Fc receptors for IgG (T gamma cells)] were enumerated, using rosette tests, in patients with Graves' hyperthyroidism, Hashimoto's thyroiditis, silent thyroiditis, primary hypothyroidism, Graves' ophthalmopathy and subacute thyroiditis. General suppressor function, assessed as inhibition of pokeweed mitogen induced plasma cell generation by concanavalin-A stimulated T cells was measured in patients with Graves' hyperthyroidism, Hashimoto's thyroiditis and subacute thyroiditis. Suppressor T cell numbers were found to be essentially normal in patients with Graves' hyperthyroidism, Hashimoto's thyroiditis, Graves' ophthalmopathy, silent thyroiditis and hypothyroidism, although % T gamma cells were increased in 5 of the 7 patients with subacute thyroiditis tested. Suppressor cell function was normal in patients with graves' hyperthyroidism, Hashimoto's thyroiditis and subacute thyroiditis. It is likely that the putative deficiency of suppressor T cells in thyroid autoimmunity is restricted to a few clones of cells allowing retention of thyroid directed effector cells. The mechanism for increased T gamma cells in subacute thyroiditis is unclear although likely to reflect either a physiological response to sensitization following thyroid antigen release or a non-specific effect of the viral infection.

Adolescent↗
PubMed1981

Natural cytotoxicity of blood mononuclear cells from normal subjects and patients with Hashimoto's thyroiditis against normal thyroid cells.

Natural cytotoxicity of human blood mononuclear cells against dog thyroid cells grown in monolayer was investigated. Cytotoxicity was assessed as specific release of 51Cr from Na51CrO4 labelled thyroid cells. The effector cells were unfractionated blood mononuclear cells prepared by Hypaque-Ficoll gradient centrifugation. Killing of dog thyroid cells by peripheral blood mononuclear cells from normal subjects was demonstrated. This was time and effector: target cell ratio dependent. Killing by peripheral blood mononuclear cells from patients with Hashimoto's thyroiditis was similar to that for normal subjects although increased killing was demonstrated in 2 patients and decreased killing in 2 patients. A possible role of natural cytotoxicity against thyroid cells in thyroid autoimmunity is discussed.

Adult↗
PubMed1980

Production of migration inhibitory factor in response to bacterial and fungal antigens in patients with untreated Graves' disease.

Tests for the production of migration inhibitory factor by peripheral blood leukocytes in response to ubiquitous bacterial and fungal antigens were carried out in patients with untreated Graves' disease and in healthy control subjects. Dose-response studies, tests for the production of this factor after 72 hours' stimulation with phytohemagglutinin as a test for reserve, and tests before and after 24 hours' preculture to deplete suppressor cells were also performed in some patients. The antigens used were Candida, Trichophyton-Oidiomyces-Epidermophyton, mumps live attenuated virus and purified protein derivative of tuberculin. The production of migration inhibitory factor was measured by the agarose microdroplet method.The production of migration inhibitory factor in response to all the antigens except mumps virus was slightly greater in the patients than in the control subjects, although the differences were not significant. The dose-response characteristics and the production of migration inhibitory factor after stimulation with phytohemagglutinin were similar in the two groups. The production of migration inhibitory factor in response to suboptimal concentrations of Candida, Trichophyton-Oidiomyces-Epidermophyton and mumps virus was not enhanced in either group after 24 hours' preculture apart from a slight increase in response to mumps virus in the patients.These results fail to support the suggestion that patients with Graves' disease have a deficiency of suppressor cells.

Adult↗
PubMed1980

Fc receptor-bearing blood mononuclear cells in thyroid disorders: increased levels in patients with subacute thyroiditis.

Blood mononuclear cells bearing Fc receptors for immunoglobulin G were measured in patients with thyroid disorders as the percentage of EA rosette-forming cells (% EA-RFC). Levels were normal in patients with untreated Graves' hyperthyroidism, Graves' ophthalmopathy, and Hashimoto's thyroiditis. On the other hand, the % EA-RFC was increased in eight of nine patients with subacute thyroiditis (SAT) tested during the acute phase, returning to normal during recovery. Levels were normal in all five patients with "silent" thyroiditis tested. The majority of the Fc receptor-bearing cells in SAT patients was shown to be phagocytic. There was no evidence for increased killer cell or suppressor cell activity, functions which reside in Fc receptor-bearing mononuclear cell populations, in SAT patients. There was no close correlation between the % EA-RFC and parameters of thyroid damage (erythrocyte sedimentation rate and serum T4 levels) or thyroid antibody titers. While an increase in the % EA-RFC in SAT patients may represent a nonspecific response to a viral inflammation of the thyroid gland, the abnormalities may be markers of a more specific immunological response to thyroid antigen release. Abnormalities of blood mononuclear cell numbers in Graves' hyperthyroidism and SAT are reviewed.

Adolescent↗
PubMed1980

Peripheral blood lymphocyte transformation in response to human thyroid fractions in patients with Graves' hyperthyroidism and ophthalmopathy.

Peripheral blood lymphocyte (PBL) transformation in response to human thyroid fractions was carried out in patients with Graves' hyperthyroidism and ophthalmopathy. The fractions used were, an extract, a soluble (cytosol) fraction, and membranes prepared by differential centrifugation at (i) 6500 x g (mitochondria), (ii) 10 000 x g (plasma membranes as used in the radioreceptor assay for thyroid stimulating antibody (TSAb) and (iii) 40 000 x g (microsomes). Results were expressed as stimulation indices (SI). Mean SI for patients were significantly increased compared with those for normals for cytosol and mitochondria but not the other fractions. Taking the upper limit of normal as mean +2 SD for normal subjects for each fraction, positive tests were found in 12 of 35 patients tested. This was in response to extract in 3 of 32 patients, to the soluble fraction in 10 of 31 patients, to mitochondria in 2 of 13 patients, to plasma membranes in 1 of 33 patients, and to microsomes in 1 of 27 patients. Positive tests were associated with hyperthyroidism but not ophthalmopathy.

Adult↗
PubMed1979

Thyroid binding antibodies and other immunological abnormalities in patients with Graves' ophthalmopathy: effect of treatment with cyclophosphamide.

Patients with Graves' ophthalmopathy were studied for a possible role of thyroid binding antibodies (TBAb) as measured by a radioreceptor assay, and for in vitro evidence of immunoreactivity to orbital antigens. The effect of cyclophosphamide (CY) treatment on the immunological parameters and the clinical course of the eye disease was also studied. The mean TBAb index for all patients with eye disease was significantly less than that for the normal and for patients with Graves hyperthyroidism who lacked eye disease. The mean TBAb index for patients with ophthalmopathy and past or present hyperthyroidism was significantly less than for those patients with eye disease but no associated hyperthyroidism ('euthyroid Graves' disease'). TBAb levels did not correlate with the severity of duration of the eye disease and did not change during treatment with CY. Significant titres of serum antibodies against human eye muscle extract or subcellular fractions, or macrophage inhibitory factor (MIF) production in response to human orbital tissue extract were not detected in patients with eye disease. The congestive changes improved in all patients treated with CY, although the degree of proptosis and eye muscle involvement improved in only 3 of 24 and 11 of 20 patients respectively with these abnormalities. TBAb are unlikely to play a role in the pathogenesis of Graves' ophthalmopathy and the hyperthyroidism and eye disease should be considered separate autoimmune disorders. The apparently anomalous finding of a higher mean TBAb index in patients with eye disease and hyperthyroidism than in those with hyperthyroidiam alone may reflect a more severe defect of suppressor T cell function in the former group. Because evidence for specific immunoreactivity against orbital antigens was not found in this study other approaches to defining the underlying immunological mechanisms will have to be sought.

Adult↗
PubMed1978

Studies of immunoreactivity to human lacrimal gland fractions in patients with ophthalmic Graves' disease.

In vitro evidence for immunoreactivity against human lacrimal gland fractions was sought in patients with ophthalmic Graves' disease. There was no significant increase in interstitial lymphoid tissue on lacrimal gland biopsy. Serum antibodies against lacrimal fractions were not detected using the indirect immunofluorescent technique. Using the tanned cell hemagglutination test with lacrimal antigen, antibodies were detected in 2 of 15 patients with eye disease, 2 of 15 hyperthyroid patients without eye disease, and 2 of 20 normal subjects. Macrophage inhibitory factor (MIF) production in response to human lacrimal extract was not demonstrated in any of 11 patients with eye disease tested. On the other hand, MIF was demonstrated in 2 of 10 patients with Graves' disease selected for absence of eye disease. Significant peripheral blood lymphocyte transformation in response to human lacrimal extract, or a soluble or membrane fraction, was demonstrated in 9 of 22 patients tested; in 6 of 21 patients to extract, in 3 of 21 patients to a soluble fraction and in 7 of 10 patients to a membrane fraction. The possible significance of lacrimal gland inflammation and role(s) in the pathogenesis of ophthalmic Graves' disease are discussed.

Adult↗
PubMed1978

Multi-system immunologically mediated disease: T lymphocyte deficiency and thyroid immunologic disease--a report of four cases.

Four cases are described of multi-system immunologically-mediated disease (systemic lupus erythematosus (two cases), polymyositis, and sarcoidosis) in association with thyroid autoimmunity. In all patients there was evidence of T lymphocyte deficiency, namely poor response of peripheral blood lymphocytes (PBL) to T cell mitogens (four cases) and failure or decreased ability to become sensitized to dinitrochlorobenzene (three cases), although two patients were ill and two were being treated with steroids. There was also evidence of B lymphocyte deficiency since PBL of no patient responded normally to pokeweed mitogen, a B and T lymphocyte mitogen. In two patients there was evidence of cell-mediated immunity to human thyroid antigens. Although thyroid stimulating antibody was not detected in the one patient with Graves' disease tested, significant titres of thyroid antibodies were detected in all cases. Possible relationships between T lymphocyte deficiency, organ-specific autoimmune disease and immunologically-mediated multi-system disorders are discussed.

Adult↗
PubMed1978

Thyroid stimulating antibodies in patients with subacute thyroiditis.

A radioreceptor assay was used to measure thyroid stimulating antibodies (TSAb) during the acute and recovery phases in 7 patients with subacute thyroiditis. High levels of TSAb were detected in 4 patients during the acute phase. In two other patients, tests were borderline positive. In the latter two patients tests were negative by two weeks, whilst in the 4 patients with strongly positive tests initially, levels persisted for several weeks, falling to within the normal range by 3 months in the two patients in whom repeated tests were carried out. TSAb probably do not play a role in the transient hyperthyroidism commonly seen in this disorder, since the detection of TSAb did not correlate with clinical or biochemical evidence of hyperthyroidism. Thus, in this disorder, TSAb are apparently able to bind to thyroid membranes in vitro, but not stimulate the gland in vivo. On the other hand TSAb could possibly play a role in the recovery phase. The possible role of suppressor cells in the development of the transient immune abnormalities which are associated with temporary thyroid damage is discussed.

Adult↗
PubMed1978

Thyroid-stimulating antibodies in patients with autoimmune disorders.

A radioreceptor assay was used to measure thyroid-stimulating antibody (TSAb) in 1) patients with Graves' disease with untreated hyperthyroidism, selected for absence of clinically significant eye disease; 2) patients with Graves' ophthalmopathy, with and without previously treated hyperthyroidism; 3) patients with other thyroid disorders; 4) patients with other autoimmune disorders; and 5) normal subjects. TSAb was detected in 14 of 15 (93%) patients with Graves' hyperthyroidism and in 10 of 16 (63%) patients with Graves' ophthalmopathy. Of the patients with Graves' ophthalmopathy, TSAb was detected in 9 of 10 patients who had once been hyperthyroid and in only 1 of 6 patients who had never been hyperthyroid (euthyroid Graves' disease). TSAb was detected in 1 patient with idiopathic Addison's disease (autoimmune adrenalitis) and in 1 patient with juvenile diabetes mellitus (both of whom were euthyroid), and borderline levels were found in 1 patient with Sjögren's syndrome and 1 patient with methyldopa-induced antired blood cell antibodies. TSAb was not detected in normal subjects or patients with other thyroid disorders. The conclusions are: 1) the test is very useful in the diagnosis of Graves' disease; 2) Graves' eye disease may be a frequently associated but separate disorder; and 3) because TSAb may be present in some euthyroid patients with other autoimmune disorders, TSAb production may occur primarily because of a disorder in the immune system.

Adolescent↗
PubMed1977

Total and "activated" peripheral blood T lymphocytes in patients with thyroid disorders.

The percentage of total and "activated" peripheral blood T lymphocytes was measured in patients with (i) hyperthyroid Graves' disease selected for absence of ophthalmopathy, (ii) treated Graves' disease, with ophthalmopathy, and (iii) other thyroid disorders including subacute thyroiditis, using sheep red blood cell rosette tests. No patient had significantly increased levels of either total or "activated" T lymphocytes. On the other hand, the percentage of total T cells was below normal in 8 of 18 patients with hyperthyroid Graves' disease and in 6 of 18 patients with ophthalmopathy compared with only one of 12 patients with nodular goitres. Similarly, low levels of "activated" T cells were demonstrated in 5 of 18 patients with hyperthyroid Graves' disease and in 10 of 18 patients with ophthalmopathy compared with only one of 12 patients with nodular goitres. Three of four patients with subacute thyroiditis tested had depressed levels of total T lymphocytes whilst only one had low levels of "activated" T lymphocytes. Levels returned to normal during the recovery phase in the two patients with positive tests who were retested. Depressed levels of T lymphocyte populations in patients with Graves' disease and subacute thyroiditis may be due to feedback suppression and/or "exhaustion" in association with the thyroidal and orbital immunological reactions.

Adult↗