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Biomedical subjects

F Clark

Publications and source records attributed to F Clark.

At least 37 records · Page 2Linked to original sources
PubMed1986

A technique for the isolation and mitogenic activation of thyroglobulin-specific human B lymphocytes.

In previous studies we demonstrated that Hashimoto peripheral blood lymphocytes enriched for thyroglobulin (Tg) binding activity could be activated to secrete increased amounts of Tg antibody by Epstein - Barr virus (EBV) but not by pokeweed mitogen (PWM). We now report an investigation into the requirements for the isolation of Tg receptor positive (TgR+) B cells capable of being stimulated by PWM. The interaction between Hashimoto lymphocytes and Tg coated erythrocytes followed by red cell lysis interfered with the ability of the population to synthesize Tg antibody. However, this could be overcome if the rosettes formed between Tg coated erythrocytes and the Tg receptors on B cells were dissociated by digestion followed by red cell lysis and overnight incubation before the addition of PWM. Using this approach, Hashimoto TgR+ B cells could be stimulated by the mitogen to secrete immunoglobulin with a higher Tg antibody specific activity than unfractionated lymphocytes. Consequently, enriched populations of antigen specific human B cells capable of responding to mitogenic signals can be prepared by a positive selection technique.

Antibody Formation↗
PubMed1986

TSH receptor antibody synthesis by thyroid lymphocytes.

Several indirect observations have indicated that lymphocyte in the thyroid may be an important site of TSH receptor antibody synthesis in Graves' disease and we now describe an investigation of this possibility using improved lymphocyte isolation and TSH receptor antibody assay procedures. Our studies demonstrate that thyroid lymphocytes spontaneously produce TSH receptor antibody in culture. Furthermore, experiments with mitogen tend to suggest that these cells, in contrast to lymphocytes from lymph nodes draining the thyroid, are part of an active immune response to the TSH receptor.

Adult↗
PubMed1986

Association between thyroid microsomal antibodies of subclass IgG-1 and hypothyroidism in autoimmune postpartum thyroiditis.

The potential role of thyroid microsomal (Mic) antibodies in the development of postpartum hypothyroidism was investigated in 34 euthyroid women, whose sera were found to contain Mic antibodies in pregnancy. Additional serum samples were obtained 2. 5 and 10-12 months after delivery and analysed for IgG class and IgG subclass levels of Mic antibodies by ELISA techniques. Characteristically, Mic antibodies decreased from early pregnancy to 2 months postpartum, increased two-fold 5 months postpartum and had returned 10-12 months postpartum to the early pregnancy level. Mic antibodies were predominantly subclass IgG-1 or IgG-4 with only minor contributions from IgG-2 and IgG-3. In each individual the percentage contribution made by each IgG subclass to Mic antibody was essentially similar in early pregnancy and the postpartum period despite changes in total IgG class Mic antibody. During the year following delivery, thyrotoxicosis alone (Graves' disease) developed in 5 women. In the remaining 29 patients the absolute levels of Mic antibodies of IgG-4 subclass were similar 5 months postpartum in women with maximal serum thyrotropin (TSH) greater than 20 mU/1 (mean optical density in ELISA +/- s.d.; 0.84 +/- 0.538; n = 13) and in women with maximal TSH less than 10 mU/l (0.69 +/- 0.457; n = 16). In contrast, significantly higher values were observed for Mic antibody of IgG-1 subclass in patients with TSH greater than 20 mU/l (1.14 +/- 0.440) compared with women with maximal TSH less than 10 mU/l (0.65 +/- 0.289) (P less than 0.001 by t-test for groups). These results imply that the magnitude of Mic antibody levels of subclass IgG-1 but not IgG-4 is associated with the development of postpartum hypothyroidism and possibly with tissue destruction in autoimmune thyroid disease in general.

Adult↗
PubMed1986

Subpopulations of thyroid autoantibody secreting lymphocytes in Graves' and Hashimoto thyroid glands.

Lymphocytes isolated from Graves' and Hashimoto thyroid tissue by enzymatic (dispase) digestion or mechanical disaggregation were markedly different in terms of their ability to synthesize thyroid autoantibodies in culture. Dispase digestion, followed by removal of thyroid follicular cells, gave a lymphocyte population with a high T:B cell ratio (6:1). However, the ability of these cell suspensions to synthesize microsomal (Mic) and thyroglobulin (Tg) antibodies spontaneously was significantly increased compared with lymphoid suspensions isolated by mechanical means. Spontaneous synthesis of thyroid autoantibodies was not markedly enhanced in cell suspensions prepared from patients' lymph node tissue by digestion compared with mechanical disaggregation. Further, Mic and Tg antibody production by thyroid lymphocytes prepared using dispase was inhibited by pokeweed mitogen (PWM) whereas in most cases suspensions prepared from the same tissues by mechanical dispersion synthesized low or undetectable levels of autoantibodies whether PWM was present or absent. Digestion of tissue debris remaining after mechanical removal of lymphocytes gave suspensions which had an increased proportion of suppressor/cytotoxic T cells compared with suspensions produced mechanically or by digestion alone; however, in terms of spontaneous autoantibody synthesis and PWM induced inhibition, these suspensions were similar to these obtained by digestion alone. It would therefore seem that enzymatic digestion of thyroid tissue resulted in the isolation of a lymphoid population which was different from that extracted by mechanical disaggregation. The digestion process appears to permit the recovery of lymphocytes closely associated with thyroid follicular cells and our studies suggest that it is this population which makes the major contribution to autoantibody synthesis.

Adult↗
PubMed1985

The effect of carbimazole on thyroid autoantibody synthesis by thyroid lymphocytes.

Thyroid autoantibody synthesis was investigated in cultures of lymphocytes isolated from several sources, including thyroid and lymph nodes from patients with hyperthyroid Graves' disease treated preoperatively with carbimazole or propranolol. The ability of thyroid lymphocytes to secrete immunoglobulins, including thyroid microsomal or thyroglobulin autoantibodies, was markedly reduced in lymphocyte suspensions obtained from patients treated with carbimazole compared with suspensions from patients treated with propranolol. This effect (which was greater in individuals treated with carbimazole for longer periods) was attributable to a significant reduction in the number of viable lymphocytes present after the 14-day culture interval. In contrast, the type of preoperative therapy had little effect on cultures of lymphocytes obtained from lymph nodes draining the thyroid. Although it is not yet clear whether carbimazole exerts its effects in vivo by direct immunosuppression or indirectly by altering the thyroid microenvironment, our observations indicate that the fall in serum levels of thyroid autoantibodies that occurs during carbimazole therapy is related to an effect of the drug on lymphocytes within the thyroid.

Antibody Formation↗
PubMed1985

Insulin secretion, adipocyte insulin binding and insulin sensitivity in thyrotoxicosis.

The pattern of insulin secretion following an oral glucose load and the insulin receptor status and insulin sensitivity of adipocytes have been studied in patients with thyrotoxicosis and in matched controls. Thyrotoxic subjects showed normal basal and peak levels of serum immunoreactive insulin (peak, 69.0 +/- 6.8 vs 54.3 +/- 8.8 mU/l) and serum C-peptide (peak, 1.95 +/- 0.13 vs 1.71 +/- 0.12 nmol/l for thyrotoxic and control subjects, respectively). Peak serum proinsulin was higher in the thyrotoxic group (64.8 +/- 7.3 vs 39.0 +/- 3.7 pmol/l; P less than 0.01). Maximum specific insulin binding to adipocytes was decreased in the thyrotoxic group (1.80 +/- 0.18 vs 2.62 +/- 0.27%; P less than 0.025) and half-maximum displacement of tracer insulin was similar in the two groups, suggesting that reduced receptor number rather than reduced affinity accounted for the difference. However, adipocyte insulin sensitivity was normal as judged by half-maximal stimulation values of 13.9 +/- 3.6 vs 11.4 +/- 2.1 pmol/l, respectively for lipogenesis and 24.3 +/- 2.2 vs 24.6 +/- 3.6 pmol/l, respectively for glucose transport. Hence, thyroid hormone excess appears to affect adipocyte insulin receptor number directly, but change in receptor number is not associated with change in adipocyte insulin sensitivity in hyperthyroidism. The normal insulin secretion together with the failure to demonstrate abnormal insulin sensitivity of one of the major peripheral tissues suggests that disturbed hepatic rather than peripheral insulin responsiveness may be responsible for the glucose intolerance of hyperthyroidism.

Adipose Tissue↗
PubMed1985

A comparison of impact of undergraduate and graduate occupational therapy education on professional productivity.

This article presents an account of the evolutionary changes in occupational therapy graduate education at the University of Southern California (USC) in response to the increasing professional demands and the expanding knowledge base of the field. The contention that undergraduate and graduate education represented by these changes would result in different student products was tested. A questionnaire survey was used to assess the responses of 189 former undergraduate and graduate occupational therapy students of USC on issues relating to professionalism, leadership, attitudes, and scholarly contributions. Results of this study support the theory that graduate education of a specific kind and quality enhances the professionalization of occupational therapy more so than does undergraduate education.

Adult↗
PubMed1985

Functional analysis of T and B cells from blood and thyroid tissue in Hashimoto's disease.

B lymphocytes from Hashimoto blood and thyroid tissue have been cultured with autologous T cells from thyroid/blood to assess their ability to synthesise IgG and thyroid autoantibody. Thyroid B cells were able to synthesize microsomal antibody spontaneously in the absence of T cells or pokeweed mitogen (PWM) and this synthesis was increased in the presence of thyroid T cells without PWM or with blood T cells with PWM. In contrast, blood B cells did not secrete thyroid autoantibody spontaneously but could be induced to do so by thyroid T cells spontaneously or by blood T cells with PWM. Despite these differences, lymphocytes from blood and thyroid tissue secreted microsomal or thyroglobulin antibodies in culture which were similar in terms of the IgG subclass distribution. It would appear, therefore, that although the state of activation of B and T cells is different in blood and thyroid tissue, the precursors of thyroid autoantibody secreting cells are the same.

Autoantibodies↗
PubMed1984

The relationship between human adipocyte and monocyte insulin binding.

The assumption that insulin binding to monocytes reflects that of insulin binding to adipocytes has been examined. In normal, diabetic, thyrotoxic and cirrhotic subjects no correlation was observed between monocyte and adipocyte insulin binding. Extrapolation is not justified from monocyte binding data to conclusions about insulin-sensitive tissues.

Adipose Tissue↗
PubMed1984

Polycystic ovarian syndrome in identical twins.

Two 21-year-old female twins are described. They presented simultaneously with hirsutism and oligomenorrhoea. Investigation showed they had polycystic ovaries, they were identical and were not cases of post-pubertal adrenogenital syndrome.

Adult↗
PubMed1984

Dichotic listening performance in normal children and adults.

The purpose of this study was to investigate normative expectations on the dichotic listening test in order to determine the influence of sex and development on dichotic listening performance. Thirty 5-to-6 year olds, thirty 11-to-12 year olds, and 30 adults, 15 males and 15 females in each group, were tested by using consonant-vowel dichotic stimuli. There were no significant differences between males and females except for the 11- to 12-year-old females who were significantly more accurate than the males. Degree of ear asymmetry did not differ among the three age groups; however, the adults and 11-to-12 year olds were significantly more accurate than the 5-to-6 year olds. Guidelines are suggested for the interpretation of dichotic listening test data.

Adult↗
PubMed1984

Defective regulation of the immune response to tetanus toxoid in Hashimoto's disease.

The humoral immune response to tetanus toxoid has been studied in patients with Hashimoto's disease. Although the magnitude of the response was similar to that observed in normal subjects, the Hashimoto patients demonstrated an inability to regulate their levels of tetanus toxoid antibody. This apparent defect in the control of antibody synthesis may be an important factor in both the initiation and perpetuation of autoimmune thyroid disease.

Adolescent↗
PubMed1983

Fenclofenac-secondary effects upon the pituitary thyroid axis.

To elucidate the mechanism of suppression of TSH responsiveness to TRH induced by the initiation of fenclofenac therapy, the early period of drug administration was examined in detail and the effect of the drug during a thyrotrophin releasing hormone infusion was assessed. In addition, the effect of fenclofenac upon the response of ACTH, cortisol, growth hormone and prolactin to insulin-induced hypoglycaemia was examined. The effect of fenclofenac upon an equilibrium dialysis method for estimating free thyroid hormones was evaluated and was found to be insignificant within the therapeutic concentration range of the drug. A sharp, short-lived rise in free thyroxine (21.7 +/- 2.0 to 26.8 +/- 1.9 pmol/l; P less than 0.03) was observed 60 min after the first dose of fenclofenac. Repeated peaks of free thyroxine during chronic fenclofenac treatment, superimposed upon the previously described steady decline of free and total serum thyroxine, are postulated to cause the observed suppression of TSH release which is present only until free and total serum thyroxine levels reach their nadir. The time course of the changes seen during thyrotrophin releasing hormone infusion suggested that the pituitary suppression was secondary to a rise in free thyroxine. The responses to hypoglycaemia of those pituitary hormones examined were not affected by fenclofenac.

Adult↗
PubMed1983

Insulin sensitivity in hyperthyroidism: measurement by the glucose clamp technique.

Sensitivity to porcine insulin has been compared in overnight fasted hyperthyroid and control subjects using a euglycaemic clamp technique. Basal values for blood glucose, lactate, pyruvate, alanine, serum insulin and C-peptide were similar in the two groups, whilst blood glycerol (hyperthyroid 0.11 +/- 0.02 (mean +/- S.E.) vs. control 0.06 +/- 0.01 mmol/l, P less than 0.01) and blood 3-hydroxybutyrate (0.28 [0.03-0.79, range ]vs 0.09 [0.01-0.29 ]mmol/l, P less than 0.05) were increased in hyperthyroidism. During the 2 hour insulin infusion (0.05 U/kg/h), serum insulin plateaued at the same level (44 +/- 4 vs 44 +/- 1 mU/l) and insulin metabolic clearance rates were similar (1.21 +/- 0.10 vs 1.25 +/- 0.03 l/min). Serum C-peptide levels also decreased by similar amounts (40 +/- 8 vs 47 +/- 6%). The amount of glucose infused to maintain euglycaemia was identical during the second hour of insulin infusion (290 +/- 50 vs 330 +/- 30 mg/kg) as were the increments in lactate and pyruvate concentrations. Blood glycerol values decreased in both groups although values in hyperthyroid patients remained significantly higher than in controls. 3-Hydroxybutyrate concentrations fell to similar values in the two groups. These findings suggest that insulin-stimulated glucose metabolism and inhibition of ketogenesis are normal in hyperthyroidism.

3-Hydroxybutyric Acid↗