Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.11.1.8 (thyroid peroxidase)
3,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The helper effects of thyroid antigen-specific T-cell clones (TCC) on antibody production by peripheral B-cells were studied and compared with similar effects of self major histocompatibility complex II (MHC-II)-reactive TCC as well as uncloned CD4+ cells. Ten TCC were derived from thyroid tissue or peripheral blood mononuclear cells (PBMC) in patients with Graves' disease. Uncloned CD4+ cells were also obtained from PBMC in patients with autoimmune thyroid disease. All TCC were CD3+/CD4+. B-Cells from patients with mainly high serum levels of microsomal antibodies (McAb) were cultured alone and with either TCC or uncloned CD4+ cells in the presence or absence of thyroid antigens [microsomal antigen/thyroid peroxidase (McAg/TPO) and thyroglobulin (Tg)] or pokeweed mitogen (PWM). Total immunoglobulin G (IgG) and specific thyroid antibodies were measured by enzyme-linked immunosorbent assay. Self MHC-II-reactive TCC induced B-cell production of total IgG and even McAb independent of antigens or PWM. Specific TCC required thyroid antigens to induce antibodies. The optimal McAg/TPO or Tg concentration was 10 ng/mL for total IgG production and 1 ng/mL McAg/TPO for McAb synthesis. The addition of PWM did not affect McAb production, but enhanced total IgG synthesis by B-cells under the influence of some specific TCC. Uncloned CD4+ cells induced both total IgG and McAb synthesis in the presence of PWM. With thyroid antigens, uncloned CD4+ cells induced total IgG synthesis at levels comparable to those of specific TCC, but induced smaller quantities of McAb in the presence of McAg/TPO. Our antigen-specific TCC could, therefore, stimulate specific B-cells to produce thyroid antibodies in vitro. Self MHC-II-reactive TCC could also induce specific antibodies by B-cells. Both self MHC-II-reactive CD4+ cells and antigen-specific CD4 cells may play an important role in the pathogenesis and/or perpetuation of autoimmune thyroid disease.
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PMID:The regulatory role of human helper T-cell clones on antithyroid antibody production by peripheral B-cells. 169 23

Parallel measurements of circulating thyroglobulin (Tg), microsomal [TPO(mic)] and TSH-receptor antibodies [TSH-R(rr)] were performed in 30 cases of Graves' hyperthyroid patients who received antithyroid drug (ATD) therapy for 2.8 +/- 1.7 years (range: 0.5-5.0 years). Before ATD therapy, positive Tg, TPO(mic) and TSH-R(rr) antibodies were found in 33.3%, 83.3% and 86.7% of our patients with Graves' disease, respectively. The titers of Tg and TPO(mic) antibodies remained unchanged in most patients after ATD treatment. However, the TSH-R(rr) antibody titers decreased in 46.7%, elevated in 26.7% and unchanged in 26.7% after ATD therapy. Six cases got long-term remission. Measurements of Tg and TPO antibodies have no value in forecasting the outcome of the disease. The change of circulating TSH-R(rr) antibody from positive to negative is more predictive of remission after ATD therapy than the decrease of thyrotropin-binding inhibiting immunoglobulin index only. However, the former change indicating a persistent remission is not certain.
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PMID:Change of circulating thyroid autoantibody titers in Graves' hyperthyroidism after antithyroid drugs therapy. 170 60

The present investigation was designed to determine the origins in the temporal lobe, and terminations in the pons, of the temporopontine pathway. Injections of tritiated amino acids were placed in multimodal regions in the upper bank of the superior temporal sulcus (STS), and in unimodal visual, somatosensory, and auditory areas in different sectors of the lower bank of the STS, the superior temporal gyrus (STG), and the supratemporal plane (STP). The distribution of terminal label in the nuclei of the basis pontis was studied using the autoradiographic technique. Following injections of isotope into the multimodal areas (TPO and PGa) in the upper bank of the STS, intense aggregations of label were observed in the extreme dorsolateral, dorsolateral, and lateral nuclei of the pons, and modest amounts of label were seen in the peripeduncular nucleus. The caudalmost area TPO projected in addition to the ventral and intrapeduncular pontine nuclei. The second auditory area, AII, and the adjacent auditory association areas of the STG and STP contributed modest projections to the dorsolateral, lateral, and peripedunuclar nuclei, but generally spared the extreme dorsolateral nucleus. The lower bank of the STS, which subserves central vision, the somatosensory associated region at the fundus of the rostral STS, and the primary auditory area did not project to the pons. The higher order, multimodal STS contribution to the corticopontocerebellar circuit may provide a partial anatomical substrate for the hypothesis that the cerebellum contributes to the modulation of nonmotor functions.
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PMID:Projections to the basis pontis from the superior temporal sulcus and superior temporal region in the rhesus monkey. 171 69

We have studied a member (JBM) of a family MO previously described, with congenital goiter, hypothyroidism, and presence of hyposialylated Tg in the follicular lumen. Other congenital goiters (MA and JNA) with virtual absence of Tg were studied similarly. The presence of apparently normal-sized Tg in JBM tissue was confirmed in the present study by radioimmunoassay, Sephacryl S300 column chromatography, immunoelectrophoresis, and SDS agarose gel electrophoresis. Dot blot hybridization analysis with Tg and TPO probes indicated that mRNA hybridization levels of JBM tissue were similar to control thyroid tissues. Congenital goiter tissues showed relatively lower TSH receptor mRNA content in comparison with normal thyroid tissues. DNA was digested with five restriction endonucleases (Taq I, Eco Rv, Pvu II, Pst I, and Eco RI), and the results revealed polymorphisms previously described with the Tg gene. No significant differences in the TPO Pst I pattern were observed in comparison with control samples. We conclude that no major alterations of the Tg and TPO gene expression are detectable and that no significant deletions of these genes are present. The biochemical abnormality in the JBM Tg molecule may be a posttranslational error during the assembly of the protein.
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PMID:Normal thyroglobulin and thyroperoxidase gene expression in thyroid congenital defective thyroglobulin synthesis. 172 86

The efferent connections of different cytoarchitectonic areas of the superior temporal sulcus (STS) in the rhesus monkey with parieto-temporo-occipital cortex were investigated using autoradiographic methods. Four rostral-to-caudal subdivisions of cortex (area TPO) in the upper bank of the STS have distinct projection patterns. Rostral sectors (areas TPO-1 and -2) project to the rostral superior temporal gyrus (areas Ts1, Ts2, and Ts3), insula of the Sylvian fissure, and parahippocampal gyrus (perirhinal and prorhinal cortexes, areas TF, TH, and TL); caudal sectors (TPO-3 and -4) project to the caudal superior temporal gyrus (areas paAlt and Tpt), supratemporal plane (area paAc), circular sulcus of the Sylvian fissure (area reIt), as well as medial paralimbic (areas 23, 24, and retrosplenial cortex) and extrastriate (areas 18 and 19) cortexes. Area TPO-1 does not project to the parietal lobe; area TPO-2 projects to the inferior parietal lobule; area TPO-3 to the lower bank of the intraparietal sulcus (IPS) (area POa); and area TPO-4 to medial parietal cortex (area PGm). Vision-related cortex (area TEa) in the rostral lower bank of the STS sends fibers to the rostral inferotemporal region (areas TE1, -2, and -3) and parahippocampal gyrus (perirhinal cortex, areas TF and TL). Visual zones in the caudal lower bank and depth of the sulcus (area OAa, or MT and FST) project to the caudal inferotemporal region (areas TE3 and TEO), lateral preoccipital region (area V4), and lower bank of the IPS (area POa). A zone in the rostral depth of the STS (area IPa) projects to the rostral inferotemporal region, parahippocampal gyrus, insula of the Sylvian fissure, parietal operculum, and lower rim of the IPS (area PG). STS projections to parieto-temporo-occipital cortex have "feedforward," "feedbackward," and "side-to-side" laminar patterns of termination similar to those of other cortical sensory systems. The differential connectivity supports the cytoarchitectonic parcellation of the STS and suggests functional heterogeneity.
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PMID:Post-rolandic cortical projections of the superior temporal sulcus in the rhesus monkey. 176 45

A new commercial method for measurement of anti-thyroid peroxidase (anti-TPO DYNOtest, Henning, Berlin) was evaluated in normal subjects and in patients with autoimmune thyroid and non-thyroid diseases, and compared to an immune fluorescence method for measurement of anti-microsomal antibodies (MicAb), and a radioimmunological method for quantifying thyroglobulin antibodies (TgAb). The majority of normal subjects had anti-TPO levels below 52 U/ml and patients with Hashimoto's thyroiditis had levels above 200 U/ml, with a good correlation to MicAb. In other autoimmune thyroid diseases the correlation was less pronounced. In non-thyroid autoimmune diseases MicAb showed falsely positive reactions in the presence of other autoantibodies, e.g. mitochondrial antibodies. The present study indicates that the anti-TPO method should probably replace measurements of MicAb for routine clinical use, thus providing a sensitive, precise, antigen specific method with the ability to reveal quantitative fluctuations. The study also indicates that TgAb could be abolished in routine diagnosis of autoimmune thyroid diseases and be reserved for special clinical situations, research purposes as well as measurement in sera before evaluation of serum thyroglobulin levels.
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PMID:Anti-thyroid peroxidase antibodies in thyroid disorders and non-thyroid autoimmune diseases. 177 57

Different monospecific antisera against thiol-protein disulfide oxidoreductase (TPO, EC 1.8.4.2, protein-disulfide isomerase, EC 5.3.4.1) were raised in rabbits by immunization with purified human TPO and characterized by means of Laurell and immunoblot techniques. A competitive anti-TPO-EIA with insolubilized TPO has been used to determine this enzyme in cells and tissue homogenates. The assay shows a sensitivity of 1.2 ng/ml and a specificity of about 99%. The TPO content in relation to the total protein was found to be: in pancreas 0.65%, liver 0.45%, spleen 0.12%, placenta 0.16%, tonsils 0.06% and lymph nodes 0.03%.
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PMID:[Immunochemical determination of human thiol protein disulfide oxidoreductase in cell and tissue homogenates by competitive EIA]. 180 96

Thromboxane A2 (TXA2) and its precursor prostaglandin H2 (PGH2) induce platelet aggregation and vascular contraction through shared cell surface receptors commonly referred to as TXA2 or TXA2/PGH2 receptors. Whether different subclasses of TXA2/PGH2 receptors exist in platelets and vascular smooth muscle cells is controversial. In this study, TXA2 receptors on washed rat and human platelets and cultured rat aortic smooth muscle cells (RASMC) were characterized using radioligand competition binding assays with the 125I-labeled TXA2/PGH2 receptor agonist [1S-(1 alpha,2 beta(5Z),3 alpha(1E,3R*),4 alpha)] -7- [3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl) -7- oxabicyclo-[2.2.1]- heptan-2-yl] -5- heptenoic acid (I-BOP) and various agonists and antagonists. Scatchard analyses of equilibrium binding data revealed Kd values of 205 +/- 68 pM (N = 6), 2.2 +/- 0.3 nM (N = 9) and 310 +/- 60 pM (N = 7) and Bmax values of 1.3 +/- 0.45 fmol/10(6) platelets, 2.8 +/- 0.2 fmol/10(6) platelets and 20.9 +/- 2.2 fmol/10(6) cells for rat and human platelets and RASMC, respectively. Concentration-dependent increases in intracellular free Ca2+ concentrations induced by I-BOP were observed in RASMC loaded with the calcium sensitive dye fura-2. The IC50 values for various TXA2/PGH2 analogues in competition binding assays with 125I-BOP were determined. Based on their IC50 values, the rank orders were I-BOP less than L657925 less than ONO11113 less than or equal to SQ29548 less than PTA-TPO less than PTA-NO less than or equal to L657926 less than or equal to I-PTA-OH less than PTA-OH[2] = meta-I-PTA-PO less than or equal to ONO11120[2] = ONO11120[1] less than PTA-OH[1] in rat platelets. I-BOP less than SQ29548 less than PTA-TPO = L657925 less than or equal to ONO11113 less than I-PTA-OH less than PTA-NO less than or equal to meta-I-PTA-PO less than or equal to PTA-OH[2] less than ONO11120[2] less than or equal to ONO11120[1] less than L657926 less than or equal to PTA-OH[1] in human platelets, and I-BOP less than L657925 less than ONO11113 less than or equal to SQ29548 less than ONO11120[2] less than or equal to L657926 less than or equal to PTA-OH[2] less than PTA-TPO less than ONO11120[1] less than I-PTA-OH less than meta-I-PTA-PO less than PTA-NO less than PTA-OH[1] in RASMC.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Platelet and vascular thromboxane A2/prostaglandin H2 receptors. Evidence for different subclasses in the rat. 183 Apr 82

A human Fab fragment (SP2) which binds specifically to human thyroid peroxidase has been generated by expressing random combinations of heavy and light chain immunoglobulin genes (derived from Graves' thyroid cDNA) in a bacteriophage lambda library. In common with many serum TPO autoantibodies, the cloned Fab fragment is IgG1 kappa and has a high affinity for TPO (approximately 10(-9) M). On the basis of their nucleotide sequences, the heavy and light chain genes coding for SP2 belong to families VHI, (D), JH3 and VKI, JK2, respectively. These data provide the first characterization at a molecular level of a human thyroid peroxidase antibody associated with autoimmune thyroid disease.
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PMID:A human Fab fragment specific for thyroid peroxidase generated by cloning thyroid lymphocyte-derived immunoglobulin genes in a bacteriophage lambda library. 183 77

Anti-microsomal (anti-Mic Ab) and anti-thyroperoxidase antibody activities (anti-TPO Ab) were compared by using commercially available radioassay kits. Sera were collected from 52 patients with Graves disease before and after administration of carbimazole (1-methyl-2-thio-3-carbethoxyimidazole). The two antibody concentrations were significantly correlated, both before treatment (r = 0.835, P less than 0.001, n = 52) and at the end of treatment (r = 0.584, P less than 0.001, n = 52). Twenty-nine (Group I) of the 52 patients were in remission for two years after drug withdrawal, whereas 23 (Group II) relapsed. Within each group, the anti-Mic and anti-TPO Ab concentrations were significantly correlated (Group I: r = 0.781, P less than 0.0001; Group II: r = 0.866, P less than 0.0001). Relapse vs nonrelapse was linked to the antibody positivities measured before treatment: 91% vs 65% (chi 2 = 4.75, P less than 0.02) for anti-Mic Ab and 87% vs 62% (chi 2 = 4.05, P less than 0.02) for anti-TPO Ab. We conclude that assays of anti-Mic and anti-TPO Ab are equally reliable analytically and equally informative clinically. Because of its rapid implementation, the anti-TPO assay may advantageously replace anti-Mic Ab assay, especially for forming a prognosis of Graves disease.
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PMID:Comparison of thyroperoxidase and microsomal antibody assays in sera from patients with Graves disease. 191 84


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