The need for a national information infrastructure.
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Biomedical subjects
Publications and source records attributed to F Clark.
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An Insect Activity Monitor was created to measure the behavioural responses of fleas (Siphonaptera). The apparatus allows for a range of visual, chemo- and mechanoreceptor cues to be presented. The jumping response is detected by counting amplified pulses produced as the fleas land on a stretched membrane held over a microphone. Horizontal movements are detected using a system of infra-red beams and phototransistors which, when broken, are counted as a measure of activity. The apparatus was tested using Ceratophyllus hirundinis (Curtis), Ceratophyllus farreni (Rothschild) and Ceratophyllus rusticus (Wagner), co-inhabiting species from the nests of the house martin (Delichon u.urbica L.). No unaided emigration or immigration has been demonstrated in these species (Clark, 1988) and much of their time is spent confined to the darkness of the nest. In addition to species contrasts, females were more active than males and fleas were more active at 25 degrees C than at 18 degrees C. The more active bird flea Ceratophyllus garei (Rothschild) from the nest of pheasant (Phasianus colchicus L), was tested for responses to light of varying intensity. Activity was stimulated by white light, but not proportional to light intensity.
This paper discusses three major issues in the provision of occupational therapy services to persons with learning disabilities and/or mild to moderate perceptual and motor deficits. The issues are (a) the historical influence of federal legislation on the scope and content of occupational therapy services to persons with these disabilities; (b) the provision of occupational therapy services for this population from infancy to adulthood; and (c) the context of service provision and efficacy of occupational therapy models.
In autoimmune thyroid disease lymphoid cells infiltrating the thyroid gland occur in conspicuous aggregates or as a diffusely distributed population invading the thyroid follicles. Consequently cytokines secreted by activated T cells or macrophages could influence neighbouring thyroid cells as well as other lymphocytes. We have investigated this possibility using recombinant cytokines. Thyroid cell survival was assessed in terms of mitochondrial dehydrogenase activity in monolayers exposed to tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-1 (IL-1 alpha and beta) and interleukin-2 (IL-2) in the presence or absence of thyroid-stimulating hormone (TSH). Neither TNF-alpha nor IL-2 affected thyroid cell survival, IFN-gamma was usually inhibitory and IL-1 alpha slightly enhanced cell survival in some experiments. However, the effects were small and variable and were not enhanced by potentially synergistic combinations of cytokines, longer periods of exposure, or different culture conditions. In contrast, IFN-gamma, IL-2 and TNF-alpha inhibited the ability of thyroid lymphocytes from patients with Graves' disease and Hashimoto's thyroiditis to synthesize autoantibodies to thyroid peroxidase (TPO) and thyroglobulin (Tg). Comparison of lymphoid populations isolated by digestion and/or mechanical disaggregation indicated that a population of activated B cells, plasma cells and T cells, intimately associated with thyroid cells since they could only be extracted by digestion, was influenced by cytokines. Our studies suggest that in addition to its well-recognized ability to induce MHC class II antigens on thyroid cells, IFN-gamma may inhibit thyroid cell proliferation and TNF-alpha, IFN-gamma and IL-2 may down-regulate thyroid autoantibody synthesis.
Animal models of autoimmune thyroid disease are associated with thyroglobulin (Tg) as autoantigen whereas in man the autoimmune response to microsomal antigen/thyroid peroxidase (TPO) appears to play a major role in thyroiditis. Consequently, we have compared the ability of TPO and Tg to induce thyroid autoantibodies and thyroid damage in mice known to be susceptible (CBA/J) or resistant (BALB/c) to thyroiditis induced using murine Tg. Groups of three to five mice were immunized twice using Freund's complete adjuvant with 80-100 micrograms highly purified porcine (p) TPO, pTg, rat (r) Tg, human Tg, bovine serum albumin (BSA) or BSA + 0.2 micrograms pTg (the level of Tg contamination of TPO). Four weeks after immunization with TPO, plasma from CBA/J (but not BALB/c) mice contained IgG class antibodies which bound to TPO-coated tubes in the presence or absence of excess Tg (and could therefore be clearly distinguished from Tg antibodies) but there was no evidence of thyroiditis in either strain of mice. In contrast, in CBA/J mice immunized with rTg and, to a lesser extent in mice that had received pTg, thyroid tissue was infiltrated with lymphoid cells and/or neutrophils and antibodies to pTg (but not pTPO) were present. Our observations demonstrate that induction of TPO antibody alone is insufficient to lead to thyroiditis in CBA/J mice. Further, these studies emphasize the complex interactions between MHC and different thyroid antigens in the processes leading to thyroid destruction.
The inheritance of autoantibodies to thyroglobulin and thyroid peroxidase (thyroid microsomal antigen) has been reevaluated with newly developed ultrasensitive assays that depend on the direct interaction between antibody and radiolabeled antigen. In a study of 16 families with autoimmune thyroid disease, autoantibodies to thyroid peroxidase (TPO) were found to be inherited as a dominant Mendelian trait in females with reduced penetrance in males. Similar results were obtained with thyroglobulin (Tg) autoantibodies. Genetic linkage analysis of the loci for TPO and Tg autoantibodies with 28 polymorphic serological markers (including HLA and Gm allotypes) was carried out in 9 families. LOD scores for some serological markers (such as Gm) were uninformative, but linkage with other markers, notably the HLA antigens -A, B, -DR, -DQ, and BF on chromosome 6, could be excluded. Further studies using a comprehensive panel of gene probes to analyze DNA from families with autoimmune thyroid disease should permit the localization of the gene cluster responsible for regulating the ability to produce autoantibodies to TPO and Tg in man.
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The synthesis of two new series of dicarboxylic acid dipeptides and two sulfhydryl-containing inhibitors are described. The in vitro enkephalinase inhibition data and some in vivo analgesic data are presented for these compounds. For the dibenzylglutaric acid series structure-activity relationships and in vivo analgesic activity are discussed. The reverse amides, i.e., 4-amino-2,4-dibenzylbutyric acid derivatives, are also discussed. Two sulfhydryl-containing inhibitors showed good in vivo potency in the mouse jump-latency hot-plate test after peripheral administration at moderate low doses.
This quasi-experimental pilot study examined the association of a maternal preparation program with womens' competence in maternal care behaviors, self-perceived adaptation to the maternal role, and satisfaction with the maternal preparation received in conjunction with obstetric and delivery care. Sixteen subjects participated in the program. A cost-benefit questionnaire was completed by the program participants to examine whether the availability of such a maternal preparation program would influence future selections of a hospital for delivery. Our Occupational Therapy Maternal Role Preparation Program was provided to the subjects in four sessions. The program included material on physiological changes in the new mother, orchestration of activities of daily living, infant development and individual differences, and the mother-infant relationship. Results were statistically significant only for the factor of the mothers' satisfaction with their obstetric care and preparation for the maternal role, in favor of the treatment group. In addition, all 8 members of the treatment group reported that they thought the program was helpful and would recommend it to other mothers.
"When you're in big trouble is when opportunities appear. That's when you really begin to search the landscape for ways to change. It often takes dire straits or major stresses to effect change," says Frank Clark, Ph.D., chancellor for Information Services at the University of Tennessee, Memphis. In an interview with Computers in Healthcare, Dr. Clark says the university has begun building an ambitious information network, one that has attracted such partners as DEC, Apple, Siemens, U.S. Sprint and South Central Bell. With its underlying emphasis on information, resource sharing and preventive medicine, the Memphis Metropolitan Campus Network fits one cost-containment model that Clark believes we'll see more of in the future.
The functional affinity and heterogeneity of autoantibodies to thyroglobulin (Tg) were measured by an IgG subclass-specific solid-phase competition ELISA in patients with autoimmune thyroid disease. High-affinity IgG1 and IgG4 antibodies formed the major anti-Tg response. Both titre and affinity of IgG3 and IgG2 anti-Tg were generally low but in some Hashimoto's disease patients high-affinity IgG2 anti-Tg were found and IgG2 anti-Tg, unlike those of other subclasses, showed very restricted heterogeneity. The affinity of IgG4 anti-Tg was similar in patients with thyroid disease and their clinically euthyroid (normal) relatives. In contrast, a progressive increase in IgG1 anti-Tg affinity was seen in clinically euthyroid individuals compared with their relatives with thyroid disease and high titred Hashimoto's disease patients, suggesting that either rising titres of high affinity IgG1 anti-Tg or affinity maturation of IgG1 anti-Tg may be indicative of impending hypothyroidism.
The purpose of this study was to construct and conduct preliminary reliability and validity studies on a questionnaire designed to measure a mother's ability to provide an adequate sensory environment for her newborn child. The questionnaire was conceptualized as an extension and application of sensory integrative theory into the domain of maternal role preparation. The instrument assessed (a) a mother's knowledge of the sensory capacity of the newborn and (b) a mother's perception of her ability to influence the development of her child. The subjects were 55 primiparas of newborn infants who responded to the questionnaire within 3 days postpartum. The findings demonstrated that the questionnaire measured the two traits reliably. Additionally they indicated that knowledge of the sensory capacity of the newborn correlated positively with perceived influence on development. Maternal age did not correlate with the mothers' knowledge of the sensory capacity of the child, but did correlate with perceived influence of mothers on development. Educational level of the respondent correlated with scores on both subscales. With further research, it is foreseen that this questionnaire may be used by occupational therapists as a part of a screening interview for identifying mothers who may be at risk for failure to provide adequate sensory experiences for their children.
The IgG subclass distribution of autoantibodies to thyroglobulin and thyroid microsomal antigen was studied in 21 patients with Graves' disease during fluctuations in total IgG class autoantibody levels induced by various forms of therapy. In addition, changes in autoantibody subclass distributions were investigated during the natural course of Hashimoto's disease in seven patients taking thyroxine. The autoantibodies were principally of subclasses IgG1 and/or IgG4 in Graves' patients although IgG2 contributed significantly to thyroglobulin antibodies in 5/7 Hashimoto sera. In Graves' disease the distribution of microsomal and thyroglobulin antibodies among the IgG subclasses remained essentially unchanged over periods of 6 months-2 years whether autoantibody levels decreased during carbimazole therapy or increased transiently following 131Iodine treatment or subtotal thyroidectomy. Similar observations were made for thyroglobulin antibodies in Hashimoto patients studied over 2 1/2-4 years; furthermore, the IgG subclass distribution of microsomal antibodies was usually different from that of thyroglobulin antibodies in the same patient. These observations suggest that the microsomal and/or thyroglobulin antibody subclass distribution is characteristic for a particular individual and may be regarded as the 'fingerprint' of an individual's response to these thyroid autoantigens.
Thyroid lymphocytes synthesize thyroid autoantibodies in close proximity to thyroid cells and consequently soluble mediators such as TSH and interleukins (IL) 1 and 2 may have unforeseen effects on lymphocytes and thyrocytes, respectively. Investigations of thyroid autoantibody synthesis by thyroid lymphocytes in vitro showed that TSH did not affect microsomal (Mic) antibody production, but thyroglobulin (Tg) antibody synthesis was decreased, probably as a result of complexing between Tg antibody and Tg secreted by small numbers of thyrocytes in the cell suspension. IL-1 and IL-2 partially mimicked the inhibitory effects on spontaneous autoantibody synthesis induced by Pokeweed mitogen (PWM) in cultures of thyroid lymphocytes. This inhibition may require a number of soluble mediators released by T cells in response to the mitogen; however, depletion studies indicated that the cell type responsible for PWM inhibition is unlikely to be a suppressor T cell and may be an NK cell. IL-1 and IL-2 had little effect on the viability of thyrocyte monolayers in an 18 h assay, but antibody dependent cells cytotoxicity (ADCC) using blood lymphocytes and thyroid autoantibody positive sera was demonstrated; further, the cytotoxicity appeared to be due to Mic antibodies. It is possible that IL-1 and/or IL-2 (as well as other cytokines) may affect thyroid cells after longer periods of exposure, either by altering them functionally or by direct damage. However, assuming that NK cells are present in sufficient numbers in the gland, ADCC could play a major role in the development of hypothyroidism in Hashimoto's disease.
Microsomal and thyroglobulin (Tg) antibodies in patients with autoimmune thyroid disease are usually predominantly of subclasses IgG1 and/or IgG4 and the distribution pattern is characteristic for the serum of an individual. We have studied the role of T cells in synthesis of total IgG and Tg antibody IgG subclasses (measured by ELISA) in cultures of peripheral blood lymphocytes (PBL) from Hashimoto patients. Unfractionated PBL incubated with the T dependent activator pokeweed mitogen (PWM) synthesized IgG of all four IgG subclasses in the proportions 69% IgG1, 20% IgG2, 8% IgG3 and 3% IgG4; these values are similar to the proportions of the subclasses in serum. In contrast, the IgG subclass of Tg antibody was predominantly IgG1 in one patient, approximately equal proportions of IgG1 and IgG4 in four patients, and almost completely restricted to IgG4 in one patient; these patterns were similar to the subclass distribution of the autoantibodies in the individual patients' serum. B cells incubated alone secreted little Tg antibody but the response could be restored to the original levels and proportions of IgG1 and/or IgG4 Tg antibody by the addition of T cells either from the same individual or from another donor. Further, removal of suppressor T cells had little effect on the proportions of IgG1 and IgG4 Tg antibody although the total amounts of Tg antibody of both subclasses were sometimes increased. Our studies indicate that T cells are required in this in vitro system to elicit Tg antibody synthesis and to control the magnitude of the antibody response. However, the characteristic IgG subclass distribution of Tg antibody in an individual is determined at the level of the B cell.
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.
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.
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