Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to investigate quantitatively the interference of thyroglobulin autoantibodies in the RIA of human thyroglobulin (hTG). Anti-hTG autoantibodies were combined with purified hTG to produce samples with known antibody titers and hTG concentrations. These samples were analyzed in the RIA. By using anti-human globulin serum it was first shown that immune complexes formed between labeled hTG and human anti-hTG. It was then shown that the most important factor in determining the direction of the interference was the specificity of the precipitating (second) antiserum with respect to these immune complexes. When the precipitating antiserum was specific, i.e. did not recognize human antibodies, the immune complexes remained in the supernatant and the measured hTG concentration was falsely elevated. When the precipitating antiserum cross-reacted with human antibodies, the direction of the interference depended on the sample volume. At small volumes there was false depression while at large volumes there was false elevation of apparent hTG levels, depending on the capacity of the precipitating antiserum to combine with human antibodies. Anti-hTG titers far below those detected by the tanned-red cell hemagglutination test had very large effects, to the point where measurements of hTG could not be made, when a cross-reactive precipitating antiserum was used. Therefore, the procedure which investigators have used until now, to exclude samples with anti-hTG hemagglutination titers above an arbitrary limit, is not adequate. It is necessary, until methods are developed which avoid the problem of autoantibody interference, to characterize each assay to determine the limits of anti-hTG that can be tolerated. The factors which influence anti-hTG interference in the hTG RIA are 1) the specificity of the precipitating antiserum, 2) the sample volume, 3) the maximum tracer binding, and 4) the anti-hTG titer.
 ...
PMID:Radioimmunoassay of human thyroglobulin: effect of antithyroglobulin autoantibodies. 26 87

Recent advances in protein metabolism and in glycoprotein synthesis bring further insight into endemic goiter epidemiology. Retinol circulates in the blood stream in close parallelism with retinol-binding protein and prealbumin (RBP-PA), a protein complex whose liver secretory rate is dependent upon hormonal and nutritional status. On the other hand, normal glycosylation reaction occurs through the formation of a retinol-linked sugar complex. It is suggested that the relative drop of serum retinol levels, as a result of modified hormonal climate and/or declining protein status, might constitute a critical factor capable of inducing a defective incorporation of mannose into native thyroglobulin, leading to an early depression of the full glycoprotein production. This concept affords a comprehensive explanation of the following unresolved data recorded in goitrous areas: (1) clinical and biochemical discrepancies between subjects living in the same morbid territory, (2) persistence of endemicity in spite of appropriate iodine supplementation, (3) similar prevalence of goiter hypertrophy in male and female prepubertal children, (4) increased frequency of goiter enlargement in the four most vulnerable groups, namely preschool children of both sexes, adolescent girls, pregnant women, and elderly persons, (5) decreased impact of thyroid swelling accompanying improved socio-economic status, even without iodine addition, and (6) resurgence of goitrous hyperplasia as an effect of seasonal or sporadic deterioration of nutritional habits, even when iodine supply remains unchanged.
 ...
PMID:Hormonal and nutritional status: critical conditions for endemic goiter epidemiology? 56 53

Cell-mediated immune responses were studied in autoimmune diseases of thyrogastric type, Hashimoto's thyroiditis and autoimmune pernicious anaemia-type gastritis. Specific cell-mediated immunity was investigated by the leucocyte migration inhibition procedure, and general cell-mediated immunity (T-cell performance) was studied by standard in vivo and in vitro tests. In thyrogastric autoimmune diseases inhibition of migration of leucocytes was induced by thyroglobulin and gastric parietal cell microsomes; under conditions of presumably low cellular sensitization, stimulation of migration was observed. There was no depression of general cell-mediated immunity, in contrast to what occurs in systemic lupus erythematosus and related autoimmune diseases. A weak association of autoimmune gastritis with HL-A3 and HL-A7 (P LESS THAN 0.05) lost significance when an appropriate correction was applied; this weakness with HL-A clearly does not explain the strong genetic component in thyroid and gastric autoimmunity.
 ...
PMID:Thyrogastric autoimmune disease. Studies on the cell-mediated immune system and histocompatibility antigens. 108 89

We have reported earlier that administration of 3-nitro-L-tyrosine (MNT), 8 mM in drinking water, to rats receiving a low iodine diet (LID) results in greater TSH secretion, larger goiters, and more rapid uptake and release of radioiodine than LID alone, and ultimately may produce hypothyroidism. These findings have been confirmed, and hypothyroidism documented by demonstrating depressed levels of hepatic mitochondrial alpha-glycerophosphate dehydrogenase. Also, prolonged treatment with MNT + LID produced a depression in labeled iodothyronine (ITh) synthesis, as judged by chromatographic analysis of thyroid digests from rats killed 4 or 24 hours after ip injection of radioiodine, or two weeks after adding radioiodine to drinking fluid. Low thyroidal ITh levels were accompanied by low levels of ITh in serum, despite the presence of various other labeled organic iodine compounds. Cessation of MNT treatment, or ip injection of small amounts (0.5-1.0 mug) of Na 127I together with radioiodine 4 h before sacrifice reversed the defect, and large amounts of ITh were found in both thyroid and serum. Labeled thyroprotein from MNT-treated rats showed increased susceptibility to disaggregation during freezing at pH 8.5; this abnormality was also reversed by stable iodine treatment. In glands labeled with radioiodine 24 h before sacrifice, stable iodine injection 20 h later was followed by increased thyroidal ITh. It is concluded that profound iodine deficiency, induced by MNT + LID, can lead to diminished ITh synthesis, or a "coupling defect". The results provide an explanation for the finding of low thyroidal ITh in patients with hereditary deficiency of tyrosine dehalogenase. The findings confirm an important role for iodine supply in ITh synthesis and thyroglobulin stability, and suggest that rats treated with MNT + LID provide a model for study of the effects of extreme iodine deficiency.
 ...
PMID:Induction of a coupling defect in rats during inhibition of tyrosine dehalogenase. 124 38

Sixty-two metastases or recurrences of differentiated thyroid carcinomas were investigated using conventional histology and immunocytochemistry for thyroglobulin (TG), thyroxine (T4) and triiodothyronine (T3). In each patient, 131I total body scans had been performed 4-10 weeks before surgery. Twenty-seven of the 62 tumours exhibited a predominance of follicles (A1), while 35 either exclusively or predominantly consisted of papillae or, in the case of follicular carcinomas, were predominantly trabecular or solid in structure (A2). TG and T4 immunoreactivity was observed in 60 cases, only 4 of these also expressing T3. Positive radioiodine uptake (RIU) was noted in 27 of 62 (44%) cases (A1:18/27 = 67%; A2:9/35 = 26%), 25 of which showed intraluminal TG and T4 positivity. Two follicular carcinomas showing RIU lacked follicular lumina, but exhibited strong diffuse cytoplasmic positivity for both TG and T4. In another 95 differentiated thyroid carcinomas, the structure of primary and secondary lesions was assessed. Of these, 27 (28%) showed a discordant pattern (A1/A2 or A2/A1) when comparing the structure of primary and secondary lesions. Our data suggest that differentiated thyroid carcinomas show a dissociation of TG/T4 expression and RIU, defects of iodine uptake and storage being found more frequently than a depression of TG and T4 synthesis. Intact synthesis of TG and T4, but not of T3 may be regarded as a prerequisite for RIU. Positive RIU is based on the presence of mature neoplastic follicles containing TG and T4 immunoreactive colloid and among follicular carcinomas, positive RIU may be encountered in neoplasms lacking follicular lumina but exhibiting strong cytoplasmic TG and T4 staining. Finally, the RIU of recurrent and metastatic PC and FC is not predictable from histological features of the primaries.
 ...
PMID:Histology and immunocytochemistry of differentiated thyroid carcinomas do not predict radioiodine uptake: a clinicomorphological study of 62 recurrent or metastatic tumours. 146 56

This study has considered the effects of primary affective disorders and lithium therapy on a number of factors thought to be important in the development of autoimmune thyroid disease. These factors were examined in (a) controls with no history of any such disorders; (b) patients with primary affective disorders treated with drugs other than lithium and (c) patients with primary affective disorders treated with lithium alone. Eight of 40 patients who were receiving lithium therapy were found to be positive for thyroid microsomal and/or thyroglobulin antibodies, compared to only 3/40 patients who were receiving some other form of treatment for their depression. Peripheral blood mononuclear cells from patients receiving lithium were found to have significantly reduced numbers of suppressor/cytotoxic T cells (P less than 0.05). In addition, suppressor T cells from these patients showed a significantly reduced response to stimulation with concanavalin A (P less than 0.01). These effects were greatest in patients found to be antibody positive. Increased B cell activity, as measured by increased IgG and IgM release following mitogen stimulation, was seen in patients receiving lithium and in those patients receiving other forms of treatment for their depression. This would suggest that the increase is a feature of primary affective disorders and is not due specifically to lithium treatment. It would appear from this study that lithium therapy induces antibody formation in susceptible individuals and this may ultimately lead to the development of thyroid disease.
 ...
PMID:The effect of lithium therapy on parameters thought to be involved in the development of autoimmune thyroid disease. 206 Jan 44

The role of T lymphocytes in the pathogenesis of experimental autoimmune thyroiditis in mice is well established while the role of B lymphocytes is unclear. Mice with thyroid lesions have thyroglobulin antibodies whereas these antibodies can occur in mice immunized with Tg that do not develop thyroid lesions. To determine whether thyroglobulin antibodies are necessary for the development of the thyroid infiltrates with mononuclear cells, which are characteristic for experimental autoimmune thyroiditis, AKR mice chronically treated from birth with goat anti-mouse IgM antibodies were immunized with mouse thyroglobulin in Freund's complete adjuvant when they were 7 weeks old. Control mice, similarly immunized, were chronically injected from birth with normal goat gamma-globulin. Three weeks after immunization, all mice were sacrificed, thyroglobulin antibodies in the serum were measured by hemagglutination assay and enzyme-linked immunosorbent assay, and thyroid pathology was assessed. The serum concentration of IgG and IgM, the percentage of B and T lymphocytes in the spleen (flow cytometry), and the in vitro proliferative response of spleen lymphocytes to stimulation by PHA, LPS, and Tg were also measured. All mice treated with anti-IgM antibodies did not have detectable thyroglobulin antibodies but 63% of these mice and 88% of control mice (all of which had thyroglobulin antibodies) had thyroid lesions. Mice treated with anti-IgM antibodies that did not have thyroid lesions had a more pronounced depression of B lymphocytes than similarly treated mice that had thyroid lesions. These experiments suggest that thyroglobulin antibodies are not necessary for the development of thyroid infiltrates with mononuclear cells. B lymphocytes could still participate in the production of experimental autoimmune thyroiditis by presenting thyroglobulin to helper T lymphocytes.
 ...
PMID:Experimental autoimmune thyroiditis in mice chronically treated from birth with anti-IgM antibodies. 278 67

Serum concentrations of total triiodothyronine (T3) and thyroxine (T4) as well as serum thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) were measured in 24 patients with epilepsy taking anticonvulsants (either phenytoin, carbamazepine, or valproic acid as single treatment) and in a control group of 28 patients with scoliosis but without thyroid disease. The T4 as well as the TSH concentrations were depressed in patients on phenytoin or carbamazepine treatment. The T3 concentration was increased in the patients on carbamazepine or valproic acid treatment, whereas the Tg levels were unaffected by all three drugs. Thus, a slight depression of the TSH concentration within the normal range does not influence the Tg release. The lack of change in the Tg concentration also speaks against a direct effect of the antiepileptic drugs on the thyroid gland.
 ...
PMID:Thyroglobulin and thyroid hormones in patients on long-term treatment with phenytoin, carbamazepine, and valproic acid. 393 23

Thyroid function and presence of thyroid autoantibodies were assessed in a group of 75 consecutive female patients with mood disturbances and in a group of 38 healthy women of similar age recruited as controls. Nine patients suffered from major (endogenous) depression and 66 from minor (neurotic) depression. The individual patients had normal values of circulating thyroid hormones. Nevertheless, endogenously depressed patients had total serum triiodothyronine (M +/- SE = 1.49 +/- 0.09 nmol/l) and both total (83.9 +/- 4.3 nmol/l) and free serum thyroxine (13.9 +/- 1.1 pmol/l) lower than in the group of minor depressed and in the group of controls (p < 0.01, in both comparison). The median value of serum thyrotropin was 5.22 mU/l in the major depressed patients versus 1.72 mU/l in the minor depressed and 1.69 mU/l in the controls. Thyroid function test results in the minor depressed group did not significantly differ from those in the controls. Five of the 9 endogenously depressed patients were subclinically hypothyroid, while none of the 66 patients with minor depressive disorder showed thyroid dysfunction. Antibodies against thyroglobulin and/or thyroid peroxidase were positive in all the 5 endogenously depressed women with subclinical hypothyroidism, revealing a symptomless autoimmune thyroiditis, which was also confirmed by ultrasonography in all cases and histopathologically demonstrated in one case. None of the endogenously depressed women without thyroid dysfunction and none of the 66 minor depressives were seropositive for thyroid autoantibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Subclinical hypothyroidism resulting from autoimmune thyroiditis in female patients with endogenous depression. 786 3

Decreased turnover of thyroid indices and blunting of TSH release after TRH administration has been associated with depressive disorder. A further decrease in plasma thyroid hormone; during antidepressant treatment has been reported. However, the putative association between the plasma thyroid indices' concentration and response has not been addressed. In the present study 21 depressed inpatients underwent a four-week double blind antidepressant with amitriptyline and mianserin; their plasma thyroid hormone indices (total thyroxine [TT4], free thyroxine [FT4], total triiodothyronine [TT3], free triiodothyronine [FT3], thyrotropin [TSH], and thyroglobulin [TBG]) were quantified to elucidate their involvement in depression and during antidepressant drug treatment. Depressed patients' plasma TSH, when corrected for age, was significantly lower than that of healthy subjects. During antidepressant treatment the entire patient cohort showed a significant decrease in plasma TT4 and FT4 concentrations. Responders showed a significant drop in TT4 FT4, FT3, and T4/TBG, but nonresponders only a decrease in FT4. During mianserin treatment, a decrease was observed in TT4, FT4, FT3, and T4/TBG. FT4 and FT3 baseline levels correlated positively with the improvement in the Hamilton Depression Rating Score (HDRS). These findings show that depressed inpatients' serum TSH levels are within the reference range, but significantly lower than those of healthy subjects, and those patients who turn out to be nonresponders have potentially lower availability of thyroid hormones than responders. Therefore, we hypothesize that in order to assure clinical improvement in depression, an adequate capacity of the thyroid hormone pool is necessary to compensate for the additional antidepressant-provoked decrease in serum thyroid hormone availability.
 ...
PMID:Low plasma thyroid indices of depressed patients are attenuated by antidepressant drugs and influence treatment outcome. 889 43


1 2 3 Next >>