Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two patients (G2, G3) with iodine organification defect were studied. The first patient (G2), a 25-year-old women with no clinical hypothyroidism, had had her goiter for 10 years; 62% of the thyroidal iodine was released by perchlorate indicating iodine organification defect. The thyroid tissue obtained at thyroidectomy contained a normal concentration of thyroid peroxidase (I2 formation from I-) when tested after solubilization of the enzyme by trypsin and digitonin treatment of the particulate material. 1. The enzymatic activity (G2-TPO) behaved on DEAE cellulose chromatography very differently from those of hog (P-TPO) or another human goiter peroxidase (G1-TPO) (Pommier, et al., J Clin Endocrinol Metab 39: 69, 1974): the molarity of elution was 2M NaCl instead of 0.15 mM. 2. Both P-TPO and G2-TPO catalyzed iodide peroxidation (I- leads to I2) but the Km (iodide) value for G2-TPO was much lower (2.3 x 10(-2) M) when compared with that of P-TPO (3.7 x 10(-3) M) or G1-TPO (3.5 x 10(-3) M). In addition, the optimum pH for this reaction differed markedly (pH 6.1 instead of 7.9). 3. G2-TPO was poorly efficient in catalyzing the oxidation of gaiacol to tetragaiacol. 4. G2-TPO was unable to perform the iodination of non-iodinated goiter thyroglobulin whatever the pH and the iodide concentration. 5. Thyroglobulin from this goiter (G2) was almost not iodinated (0.0014%), i.e., 0.07 atoms iodine/mole thyroglobulin), and its total content in the gland was very low (0.3-4 g/1000 g wet tissue instead of 25 g). A clear discrepancy was thus shown between the euthyroid state of this patient and the total lack of iodinating activity of the isolated peroxidase. The second patient (G3), a 17-year-old man with clinical hypothyroidism, had had his goiter for 5 years. 100% of the thyroidal iodine was released by perchlorate indicating a complete iodine organification defect. The thyroid tissue obtained at thyroidectomy contained no peroxidase activity when tested before and after treatment of the particulate material by trypsin and digitonin and even in the presence of hematin. Thyroglobulin from this goiter, which was almost non-iodinated (0.0014%), was present in normal amounts in the gland (congruent to 25 g/1000 g).
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PMID:Thyroid iodine organification defects: a case with lack of thyroglobulin iodination and a case without any peroxidase activity. 126 32

Evidence has accumulated in the last few years that the expression of the microsomal/peroxidase antigen (M/TPO-Ag) in thyroid cells is induced by TSH, through pathways which involve intracellular cAMP accumulation and protein synthesis. These data have been found true in any thyroid system studied so far, both in terms of immunologic and enzymatic activity of TPO. TSH and cAMP also increase the levels of the specific mRNA for TPO in thyroid cells from different species. Whether this phenomenon is due to a direct transcriptional regulation of the TPO gene, as shown in dog thyroid cells, or to posttranscriptional effects, as it would appear in FRTL-5 cells, remains to be clarified by future experiments. Thyroid stimulating antibody (TSAb) of Graves' disease also stimulates the expression of M/TPO-Ag. This finding gives further support to the relevance of TSAb in the pathogenesis of hyperthyroidism and explains the well known observation that the "microsomal" antigen is particularly abundant in glands of Graves' patients. The modulation of M/TPO-Ag surface expression by TSH can explain the decrease of circulating anti-MAb observed during L-thyroxine therapy in hypothyroid patients with Hashimoto's thyroiditis. Other agents, such as methimazole and sodium iodide, which influence thyroid cell function, do not directly interfere with the expression of M/TPO-Ag. Cytokines, such as gamma-interferon, interleukin-1, and interleukin-6 have been shown to inhibit the TSH-induced increase of TPO mRNA, but further investigations are required to elucidate the exact role of cytokines in the regulation of M/TPO-Ag expression.
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PMID:The microsomal/peroxidase antigen: modulation of its expression in thyroid cells. 166 95

To evaluate possible immunological mechanisms involved in the development of postpartum thyroiditis with transient hyperthyroidism followed by transient hypothyroidism (PPT), antithyroid peroxidase antibodies (anti-TPO), antimicrosomal antibody (AMA) related immunoglobin G subclass and antibody-dependent cell-mediated cytotoxicity (ADCC) were studied in 43 post-partum (PP) women who were euthyroid at delivery and completed a subsequent 1 year follow up. Among the 25 mothers who developed PPT, 14 had positive AMA (PPT:AMA+) and 11 negative AMA (PPT:AMA-) at delivery. Among the 18 mothers who remained euthyroid (E) up to one year post-partum and were used as controls, 8 were AMA positive (E:AMA+) and 10 AMA negative (E:AMA-) at delivery. AMA measured by a hemagglutination method correlated well with anti-TPO antibodies measured by RIA in the PP mothers studied. When AMA-related IgG subclass activity was analysed comparing PPT women with appropriate euthyroid controls at the different time intervals studied, it was seen that PPT:AMA+ when compared to E:AMA+ women have significantly increased activity of AMA related IgG1 at all PP time intervals studied (p less than 0.001), but IgG4 was only increased at 5-7 months PP (p less than 0.05). PPT:AMA-when compared to E:AMA- have significantly increased IgG4 at 2-4 (p less than 0.001), 5-7 and 10-12 (p less than 0.05) months PP, but IgG1 is only increased at 5-7 months PP (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increase in antimicrosomal antibody-related IgG1 and IgG4, and titers of antithyroid peroxidase antibodies, but not antibody dependent cell-mediated cytotoxicity in post-partum thyroiditis with transient hyperthyroidism. 209 Jun 68

We studied the distribution of binding sites for anti-peroxidase monoclonal antibody and anti-microsomal antibodies on isolated human thyroid follicles and a human thyroid cell line. Both open follicles and cells were incubated first with antibodies at +4 degrees C, then with colloidal gold labelled protein A. The topography of the binding sites for monoclonal anti-peroxidase antibody corresponded closely to the expected cell surface distribution of endogenous thyroid peroxidase since labelling was observed at the apical cell surface of the follicles. Furthermore, labelling was restricted to the microvilli level; while smooth membrane territories were devoid of binding sites. In some cases, incubations at 4 degrees C were followed by warming the follicles and cells up to 37 degrees C for 20 minutes in order to study internalization of ligands. Ligands were then observed in intracellular organelles: endosomes and lysosomes. Essentially the same results were observed when human antibodies to the microsomal antigen were used. Controls with microsomal antibodies depleted in anti-peroxidase were negative. In conclusion these findings show that: 1) thyroid peroxidase is present in limited areas on the apical cell surface, 2) labelling of follicles and cells by the anti-microsomal antibodies had the same pattern of distribution as the monoclonal anti-peroxidase antibody, thus suggesting that they recognize the same apical antigens, and 3) TPO/MIC antigen traffics from the cell surface towards lysosomes when the cells are incubated at 37 degrees C.
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PMID:Immunocytochemical study of localization and traffic of thyroid peroxidase/microsomal antigen. 249 23

Cortical projections to subdivisions of the cingulate cortex in the rhesus monkey were analyzed with horseradish peroxidase and tritiated amino acid tracers. These projections were evaluated in terms of an expanded cytoarchitectural scheme in which areas 24 and 23 were divided into three ventrodorsal parts, i.e., areas 24a-c and 23a-c. Most cortical input to area 25 originated in the frontal lobe in lateral areas 46 and 9 and orbitofrontal areas 11 and 14. Area 25 also received afferents from cingulate areas 24b, 24c, and 23b, from rostral auditory association areas TS2 and TS3, from the subiculum and CA1 sector of the hippocampus, and from the lateral and accessory basal nuclei of the amygdala (LB and AB, respectively). Areas 24a and 24b received afferents from areas 25 and 23b of cingulate cortex, but most were from frontal and temporal cortices. These included the following areas: frontal areas 9, 11, 12, 13, and 46; temporal polar area TG as well as LB and AB; superior temporal sulcus area TPO; agranular insular cortex; posterior parahippocampal cortex including areas TF, TL, and TH and the subiculum. Autoradiographic cases indicated that area 24c received input from the insula, parietal areas PG and PGm, area TG of the temporal pole, and frontal areas 12 and 46. Additionally, caudal area 24 was the recipient of area PG input but not amygdalar afferents. It was also the primary site of areas TF, TL, and TH projections. The following projections were observed both to and within posterior cingulate cortex. Area 29a-c received inputs from area 46 of the frontal lobe and the subiculum and in turn it projected to area 30. Area 30 had afferents from the posterior parietal cortex (area Opt) and temporal area TF. Areas 23a and 23b received inputs mainly from frontal areas 46, 9, 11, and 14, parietal areas Opt and PGm, area TPO of superior temporal cortex, and areas TH, TL, and TF. Anterior cingulate areas 24a and 24b and posterior areas 29d and 30 projected to area 23. Finally, a rostromedial part of visual association area 19 also projected to area 23. The origin and termination of these connections were expressed in a number of different laminar patterns. Most corticocortical connections arose in layer III and to a lesser extent layer V, while others, e.g., those from the cortex of the superior temporal sulcus, had an equal density of cells in both layers III and V.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cingulate cortex of the rhesus monkey: II. Cortical afferents. 362 55

Crude thyroid peroxidase extracted from human thyroid microsomes was covalently bound onto polyacrylic and polyfunctional copolymerized microparticles. We observed agglutination of the thyroid peroxidase-microparticle conjugate with 13 monoclonal antibodies (mAbs) specific for epitopes on four different antigenic domains of human thyroid peroxidase (TPO; EC 1.11.1.7), after addition of anti-mouse immunoglobulins. We quantified agglutination by measuring with a specially designed nephelometer the light scattered by the conjugates. This allowed us to develop a microparticle-enhanced nephelometric immunoassay for human anti-TPO autoantibodies (aAbs) with defined epitopic specificity, based on the ability of aAbs to inhibit mAb-induced agglutination. Applied to patients with autoimmune thyroid diseases, this assay confirmed the polyclonality of anti-TPO aAbs and their preferential reactivity toward epitopes located on the A and B antigenic domains of the TPO molecule. The same specificities seem to be present in patients with Hashimoto thyroiditis or Graves disease.
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PMID:Microparticle-enhanced nephelometric immunoassay of anti-thyroid peroxidase autoantibodies in thyroid disorders. 751 May 93

We evaluated the prevalence of antithyroid peroxidase antibodies (anti-TP0 Ab) in 402 patients with thyroid disease and 30 healthy controls by a commercial radioimmunoassay (RIA) and compared the results with the passive hemagglutination (HA) method. The patients in the study had autoimmune thyroid disorders (AITD) such as Graves' disease and Hashimoto's disease or had nonautoimmune thyroid diseases (NAITD) such as thyroid cancer, congenital goiter, endemic goiter, and nodular goiter. Subjects were recruited from a population with a mild iodine deficiency (Sao Paulo, Brazil). The effect of specific therapy (for either thyrotoxicosis or chronic thyroiditis) on the circulating anti-TPO levels was also investigated. Positive anti-TPO Ab was detected in 89.9% of the patients with AITD as compared with a prevalence of positive tests of only 4.8% in patients with NAITD. Positive microsomal antibody (M Ab) was found in 68.4% of the patients with AITD and in 6.4% of the patients with NAITD. A positive and significant correlation was obtained between M Ab and anti-TPO Ab. A positive anti-TPO test with negative anti-M was found in 14.1% of the patients with AITD but in only 4.3% of the patients with NAITD and normal controls. These results suggest that anti-TPO Ab by RIA is more sensitive and specific than M Ab by HA. In patients with AITD, anti-TPO Ab levels usually decreased after treatment, suggesting that this parameter could be used in the follow-up of these thyroid disorders.
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PMID:Prevalence of anti-thyroid peroxidase antibodies in autoimmune and nonautoimmune thyroid disorders in a relatively low-iodine environment. 774 31

Thyroid peroxidase antibody levels were measured in 409 patients who came to the thyroid pathology consultation of our Institution between September, 1990, and November, 1991, and were compared with a reference population. In the first 231 patients, we compared the results obtained with two commercial kits. The correlation coefficient between both populations of results was assessed to be 0.919. Only one of the kits was selected later ("Immutest anti-TPOR", Henning, Germany) because normal and pathological values overlapped to a lesser extent. In a population of controls (reference population). 4 cases out of 82 (4.8%) had values exceeding 100 U/ml (arbitrary units), this value being regarded as the boundary of normal conditions. Out of the 409 assays made in patients examined during the thyroid pathology consultation, 137 (33.5%) had pathological values ranging from 100 to 5000 U/ml and even more. Peroxidase antibodies are mainly found in patients with primary hypothyroidism (positive in 82% of cases) and graves' hyperthyroidism (positive in 81%). We have also observed the highest levels in these two conditions. In addition, we have demonstrated a group of patients with normal thyroid conditions who were positive for peroxidase antibodies, sometimes in a family with a history of thyroid pathology. These may be at higher risks to develop hypothyroidism in the future than the general population. A TRH test in some subjects and the clinical evolution of these patients lead us to advocating TPO antibody assay for screening on the first consultation. Endocrine surveillance is advisable in case of positive results.
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PMID:[Determination of thyroid peroxidase antibodies in common thyroid pathology. Methodological and clinical approach]. 802 44

TPO is the key enzyme involved in the thyroid hormone synthesis. The human TPO (hTPO) gene locates on chromosome 2 and consists of 17 exons and 16 introns. Compared with other peroxidases, hTPO is 42% homologous with granulocyte myeloperoxidase. Thyroid cells contain multiple TPO mRNA transcripts of various size. However, the reason is unknown. TTF-1 and TTF-2 are known to regulate TPO gene expression. Moreover, the other factors are becoming clear to regulate it. Congenital TPO defects result in hypothyroidism and goiter. Recent studies clarify a human mutation causing TPO deficiency.
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PMID:[Thyroid peroxidase (TPO) gene and pathogenic TPO mutation]. 819 71

Antibodies against thyroid microsomal antigen (thyroid peroxidase, TMA/TPO) and myeloperoxidase (MPO) were measured from 115 patients with vasculitic disorders and 144 patients with suspected thyroid disorders. Nineteen patients, three with vasculitis and 16 with thyroid disorders, were shown to have both TPO and MPO antibodies, suggesting cross-reactivity of these antibodies. Their cross-reactivity was further strengthened by studying the capacity of antibodies to tolerate dilution in enzyme immunoassay and reactivity with synthetic TPO/MPO peptides.
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PMID:Cross-reactivity between antibodies to thyroid microsomal antigens and myeloperoxidase. 829 80


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