Serum dioxin and immunologic response in veterans of Operation Ranch Hand.
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The authors studied immune response and exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin) among veterans of Operation Ranch Hand, the US Air Force unit responsible for the aerial spraying of herbicides in Vietnam from 1962 to 1971. A comparison group of Air Force veterans who served in Southeast Asia but were not involved in spraying herbicides was included. The authors studied delayed-type hypersensitivity skin test responses to Candida albicans, mumps, Trichophyton, and a bacterial antigen made from lysed Staphylococcus aureus. Lymphocyte measurements included total lymphocyte counts; T-cell (CD3, CD4, CD5, and CD8), B-cell (CD20), and NK-cell (CD16 and CD56) subsets; and expression of the activation antigen CD25 on CD3 T cells. The authors quantitated the serum concentrations of immunoglobulin (Ig)A, IgG, and IgM; examined sera for the presence of monoclonal immunoglobulins (M proteins); and looked for a broad range of autoantibodies (rheumatoid factor, antinuclear antibody, smooth muscle autoantibody, mitochondrial autoantibody, parietal cell autoantibody, and thyroid microsomal autoantibodies). They measured the level of dioxin in 1987 or 1992, extrapolated the result to the time of service in Vietnam, and assigned each veteran to one of four exposure categories: Comparison and three Ranch Hand groups (Background, Low, or High). Overall, the authors found no evidence of a consistent relation between dioxin exposure category and immune system alteration. (+info)
Subunit structure of 27 S thyroid iodoprotein.
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The dissociation of thyroid 27 S iodoprotein by sodium dodecyl sulfate (SDS) and by succinic anhydride was investigated by means of ultracentrifugation and polyacrylamide gel electrophoresis. The iodoprotein obtained from either a human or hog was dissociated into three kinds of subunits (S-19, S-17 and S-12) by SDS treatment. At increased concentrations of SDS, the S-12 subunit was predominant among the dissociation products. The succinylation of 27 S iodoprotein showed essentially the same dissociation pattern as in the case of SDS treatment. This dissociation products of the protein preparations of different animals were qualitatively the same as those of thyroglobulin of the respective animals, confirming the hypothesis that 27 S iodoprotein was composed of two molecules of thyroglobulin. However, the extent of dissociation of 27 S iodoprotein measured by S-12 formation showed higher resistancy of the protein to the dissociating agents than that of thyroglobulin. The contents of sialic acid and hexose as well as iodoamino acids of 27 S iodoprotein were found to be the same as, or not far from, those of thyroglobulin; The dissociability and chemical composition of 27 S iodoprotein was discussed with reference to the subunit structure of the protein. (+info)
Shape of large bound polysomes in cultured fibroblasts and thyroid epithelial cells.
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Large bound polysomes were observed by conventional electron microscopy in surface or en face views of the rough endoplasmic reticulum (RER) in two cultured cell types. Cultured thyroid follicular epithelial cells and dermal fibroblasts, both from rats, were prepared for electron microscopy. Ultrathin sections were cut in the plane of the flattened cells to maximize the incidence of RER surface views. Some observations were also made on tissue sections of rat thyroid. Most of the large, RER-bound polysomes in both cell types appeared as two parallel rows of ribosome, thus resembling the shape of long hairpins, although probably closed at both ends. The two parallel rows of ribosomes were about 14 nm apart, and the center-to-center distance between ribosomes in the strands averaged 25 nm. Most of the large bound polysomes in thyroid epithelial cells were presumably making thyroglobulin subunits (330 kDa), while a majority of those in the fibroblasts were probably making prepro-alpha chains of collagen I (150 kDa). It was not possible in this material to see complete large polysomes, because their size usually caused them to extend out of the plane of section. In addition to the hairpin polysomes, there were smaller numbers of other forms. A characteristic large spiral polysome was seen occasionally in both cell types and contained as many as 31 ribosomes. One or two dense particles were sometimes seen in the center of spiral or circular polysomes. The consistent hairpin shape of most large bound polysomes observed in this study suggests that their shape is quite stable. (+info)
Non-autocrine, constitutive activation of Met in human anaplastic thyroid carcinoma cells in culture.
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Activation of Met by its ligand HGF has been shown to elicit both mitogenic and motogenic responses in thyrocytes in vitro. In the present study we have investigated the expression of Met in human anaplastic thyroid carcinoma cells in culture. There was a variation in expression level and size of Met in the different cell lines; high Met expression was found in four cell lines, compared to non-neoplastic human thyrocytes. Treatment with glucoproteinase F showed that the size differences observed were due to variances in the degree of glycosylation. Interestingly, in cell lines with high expression of Met, the receptor proteins were found to be constitutively tyrosine phosphorylated. None of these cell lines expressed HGF mRNA, and addition of suramin did not affect the level of tyrosine phosphorylation of Met in unstimulated cells, suggesting the absence of autocrine stimulatory pathways. Furthermore, we did not observe MET gene amplification, activating mutations or phosphatase defects. The tyrosine phosphorylated receptors appeared functionally active since the receptors associated with the adaptor molecule Shc. In summary, we have found ligand-independent constitutively activated Met in four out of six anaplastic thyroid carcinoma cell lines. (+info)
Thyroid nodular disease after radiotherapy to the neck for childhood Hodgkin's disease.
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Patients who receive radiotherapy to the neck are at risk of developing thyroid dysfunction. This prospective study of patients whose treatment for Hodgkin's disease in childhood included radiotherapy to the neck aimed to investigate the incidence and natural history of thyroid dysfunction and the morphological changes of the gland demonstrated on ultrasound. Forty-seven patients were investigated by clinical examination, thyroid function tests and thyroid ultrasound. Only six patients had a clinically detectable abnormality, but 64% had abnormal thyroid function tests. All patients had an abnormal thyroid ultrasound scan and 42% had at least one focal abnormality. A significant association was found between the presence of a focal lesion on ultrasound and young age at radiotherapy, longer follow-up and the length of time that the thyroid-stimulating hormone (TSH) level had been elevated. During follow-up, 65% of patients not on thyroxine developed new focal abnormalities. The longest time interval between radiotherapy and an increase in TSH level was 94 months, and from radiotherapy to the appearance of a focal abnormality on thyroid ultrasound was over 18 years. Three patients were found to have a thyroid carcinoma. These findings indicate the importance of long-term follow-up for patients treated by neck irradiation for Hodgkin's disease in childhood. (+info)
Local versus WHO/International Council for Control of Iodine Deficiency Disorders-recommended thyroid volume reference in the assessment of iodine deficiency disorders.
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OBJECTIVE: Iodine deficiency endemia is defined by the goitre prevalence and the median urinary iodine concentration in a population. Lack of local thyroid volume reference data may bring many health workers to use the European-based WHO/International Council for Control of Iodine Deficiency Disorders (ICCIDD)-recommended reference for the assessment of goitre prevalence in children in different developing countries. The present study was conducted in non-iodine-deficient areas in Malaysia to obtain local children's normative thyroid volume reference data, and to compare their usefulness with those of the WHO/ICCIDD-recommended reference for the assessment of iodine-deficiency disorders (IDD) in Malaysia. DESIGN AND METHODS: Cross-sectional thyroid ultrasonographic data of 7410 school children (4004 boys, 3406 girls), aged 7-10 years, from non-iodine-deficient areas (urban and rural) in Peninsular Malaysia were collected. Age/sex- and body surface area/sex-specific upper limits (97th percentile) of normal thyroid volume were derived. Thyroid ultrasonographic data of similar-age children from schools located in a mildly iodine-deficient area, a severely iodine-deficient area, and a non-iodine-deficient area were also collected; spot urines were obtained from these children for iodine determination. RESULTS: The goitre prevalences obtained using the local reference were consistent with the median urinary iodine concentrations in indicating the severity of IDD in the areas studied. In contrast, the results obtained using the WHO/ICCIDD-recommended reference showed lack of congruency with the median urinary iodine concentrations, and grossly underestimated the problem. The local sex-specific reference values at different ages and body surface areas are not a constant proportion of the WHO/ICCIDD-recommended reference. A further limitation of the WHO/ICCIDD-recommended reference is the lack of normative values for children with small body surface areas (<0.8m2) commonly found in the developing countries. CONCLUSION: The observations favour the use of a local reference in the screening of children for thyroid enlargement. (+info)
Thyroid volumes in US and Bangladeshi schoolchildren: comparison with European schoolchildren.
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OBJECTIVE: The World Health Organization (WHO) recently adopted thyroid volume ultrasonography results from European schoolchildren as the international reference for assessing iodine deficiency disorders. Our objective was to describe thyroid volumes measured by ultrasonography in US and Bangladeshi schoolchildren and compare these with European schoolchildren. METHODS: Cross-sectional studies were performed in schoolchildren in the US (n=302) and Bangladesh (n=398). Data were collected on the following: thyroid size by palpation and ultrasonography; urinary iodine; age; sex; weight; and height. RESULTS: Applying the new WHO thyroid volume references to the Bangladeshi children resulted in prevalence estimates of enlarged thyroid of 26% based on body surface area (BSA) and 7% based on age. In contrast, in the US children, the prevalence estimates were less than 1% for each reference. In the US children, the best single predictor of thyroid volume was BSA (R2=0.32), followed by weight (R2=0.31). Using linear regression, upper normal limits (97th percentile) of thyroid volume from US children were calculated for BSA, weight and age, and were found to be lower than the corresponding references based on BSA and age from European schoolchildren. CONCLUSIONS: In areas with malnutrition, such as Bangladesh, the BSA reference should be preferred to the reference based on age. Results from the US children indicated that a thyroid volume reference based on weight alone would perform as well as the one based on BSA. European schoolchildren had larger thyroids than US children, perhaps due to a residual effect of iodine deficiency in the recent past in some areas in Europe. (+info)
The predominant form of non-toxic goiter in Greece is now autoimmune thyroiditis.
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Endemic non-toxic goiter (NTG) in Greece has been attributed primarily to iodine deficiency. Thirty years ago about 60% of the prepubertal boys and girls examined in endemic goiter regions presented with NTG and among them thyroid autoimmunity was rarely detected. Although iodine supplementation has corrected this deficiency during the past 30 years, new cases of NTG still appear. To evaluate the prevalence and type of NTG and the effect of iodine supplementation on them in Greece at present, we performed two cross-sectional clinical studies and a retrospective pathology one: (i) thyroid gland volume and urinary iodine excretion (UIE) were assessed in a representative sample of 1213 schoolchildren from previously endemic and non-endemic regions; (ii) serum thyroxine, tri-iodothyronine, TSH, thyroid autoantibodies (AAB) (anti-thyroid peroxidase and anti-thyroglobulin antibodies) and UIE (in 60 patients) were measured in 300 consecutive patients with NTG from Athens and Heraklion; and (iii) we compared the prevalence of autoimmunity among fine needle aspiration smears of benign thyroid pathologies performed by the same pathologist between 1985 and 1986 (975 cases) and between 1994 and 1995 (2702 cases). We found that 12. 5% of the schoolchildren examined in regions with a previous history of endemic goiter had NTG, whereas this percentage was only 1.7% in areas without such a history. In Athens (61.6%) and Heraklion (58. 5%) a substantial number of NTG patients were AAB positive and biochemically hypothyroid. UIE in Athens did not differ between patients with autoimmune goiter (ATG) and simple goiter. The prevalence of autoimmune stigmata in pathology smears has increased from 5.94% (years 1985-1986) to 13.91% (years 1994-1995) (P<0.05). We conclude that: (i) the persistence of endemic goiter in regional foci despite iodine deficiency correction suggests a possible role for a naturally occurring goitrogen; (ii) ATG is the predominant form of NTG in Greece nowadays; and (iii) the five-fold decrease in the prevalence of NTG during the past 30 years followed by the increase of ATG may support the relative character of the latter. (+info)