• Title/Summary/Keyword: Anti-thyroid antibodies

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Radioimmunotherapy (I): Development of Radioimmunoconjugates (방사면역치료(I): 방사면역접합체 개발)

  • Choi, Tae-Hyun;Lim, Sang-Moo
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.2
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    • pp.66-73
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    • 2006
  • Monoclonal antibodies are designed to bind specifically to certain antigen, give therapeutic effect to the target and to be produced in large scale with homogeneity. The monoclonal antibodies conjugated with radionuclide can deliver therapeutic irradiation to the target, and showed successful results in certain malignancies, which is known as radioimmunotherapy. The target-to-background ratio depends on the antigen expression in the target and normal tissues, which is related to the therapeutic efficacy and toxicity in radioimmunotherapy. For the solid tumor beta-ray energy should be high, but lower beta energy is better for the hematological malignancies. I-l31 is widely used in thyroid cancer with low cost and high availability. Labeling monoclonal antibody with I-131 is relatively simple and reproducible. Some preclinical data for the I-131 labeled monoclonal antibodies including acute toxicity and efficacy are available from already published literatures in KIRAMS, physician sponsored clinical trial protocols using Rituximab, KFDA approved anti-CD20 chimeric monoclonal antibody and I-131 were approved by KFDA and currently are ongoing.

Zebrafish (Danio rerio) Thyroid Hormone Receptor $\alpha$1 Counteracts Retinoic Acid-induced Transcription

  • Rhee, Myubg-Chull;Lee, Woonghee;Chang, Mi-Sook;Lee, Sang-Kyou
    • Animal cells and systems
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    • v.2 no.1
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    • pp.133-137
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    • 1998
  • The present study aims to characterize a cDNA encoding zebrafish thyroid hormone receptor $\alpha{1}$ $(zTR\alpha{1)}$ in order to investigate its possible role in the early stage of embryonic development. A mobility shift assay showed that $zTR\alpha{1}$ overexpressed in COS7 cells specifically bound to thyroid hormone response element (TRE). In addition, the specific interaction of anti-rat $TR\alpha{1}$ antibodies with $zTR\alpha1$/TRE complexes demonstrated that the cDNA clone encoded zebrafish thyroid hormone receptor $\alpha{1}$. Transient cotransfection assays showed that $zTR\alpha{1}$ repressed the transcription which was induced by retinoic acid (RA), a well-characterized embryonic morphogen. These results suggest that zTRal may be involved in regulating the RA-induced gene transcription during early embryonic development.

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Clinical Prognostic Score for Predicting Disease Remission with Differentiated Thyroid Cancers

  • Somboonporn, Charoonsak;Mangklabruks, Ampica;Thakkinstian, Ammarin;Vatanasapt, Patravoot;Nakaphun, Suwannee
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.6
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    • pp.2805-2810
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    • 2016
  • Background: Differentiated thyroid cancer is the most common endocrine malignancy with a generally good prognosis. Knowing long-term outcomes of each patient helps management planning. The study was conducted to develop and validate a clinical prognostic score for predicting disease remission in patients with differentiated thyroid cancer based on patient, tumor and treatment factors. Materials and Methods: A retrospective cohort study of 1,217 differentiated thyroid cancer patients from two tertiary-care hospitals in the Northeast of Thailand was performed. Associations between potential clinical prognostic factors and remission were tested by Cox proportional-hazards analysis in 852 patients (development cohort). The prediction score was created by summation of score points weighted from regression coefficients of independent prognostic factors. Risks of disease remission were estimated and the derived score was then validated in the remaining 365 patients (validation cohort). Results: During the median follow-up time of 58 months, 648 (76.1%) patients in the development cohort had disease remission. Five independent prognostic factors were identified with corresponding score points: duration from thyroid surgery to $^{131}I$ treatment (0.721), distant metastasis at initial diagnosis (0.801), postoperative serum thyroglobulin level (0.535), anti-thyroglobulin antibodies positivity (0.546), and adequacy of serum TSH suppression (0.293). The total risk score for each patient was calculated and three categories of remission probability were proposed: ${\leq}1.628$ points (low risk, 83% remission), 1.629-1.816 points (intermediate risk, 87% remission), and ${\geq}1.817$ points (high risk, 93% remission). The concordance (C-index) was 0.761 (95% CI 0.754-0.767). Conclusions: The clinical prognostic scoring model developed to quantify the probability of disease remission can serve as a useful tool in personalized decision making regarding treatment in differentiated thyroid cancer patients.

Detection of Human Taurine Transporter and Production of Monoclonal Antibody

  • An, Hye-Suk;Han, Hee-Chang;Lee, Sun-Min;Park, Taesun;Park, Kun-Koo;Kim, Ha-Won
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2001.11a
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    • pp.102-102
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    • 2001
  • Taurine (2-ethaneaminosulfonic acid) is one of the major intracellular ${\beta}$ -amino acids in mammals and is required for a number of biological processes including membrane stabilization, osmoregulation, antioxidation, detoxification, modulation of calcium flux and neurornodulation. The taurine transporter (TAUT) which contains 12 hydrophobic membrane-spanning domains has been cloned from dog kidney, rat brain, mouse brain, human thyroid, placenta and retina. In this study, The TAUT cDNA from the human intestinal epithelial cell, HT-29 was cloned and sequenced. Reverse-transcription polymerase chain reaction (RT-PCR) was performed to amplify partial cDNA encoding human intestinal TAUT. The coding region of the PCR product was 732 bp long. The primers were designed to encode highly conserved amino acid sequences near the transmembrane domains III (IPYFIFLF) and Ⅵ (KYKYNSYR) both in human and mouse. The TAUT cDNA amplified was ligated into the pGEX 4T-1 expression vector. The resulting sequence of human intestinal TAUT cDNA (Accession number of NCBI Genebank is AF346763) was identical to the sequences of the TAUTs previously determined in the human placenta and retina except 3 base pairs from that of the reported human thyroid. TAUT specific antibodies were generated to use them as biological tools in the studies of the biological role of TAUT. Peptides of 149-162 amino acid residue (14 amino acids) of the TAUT were synthesized. The synthetic peptide used in this study was LFQSFQKELPWAHC. This region was chosen not only to avoid putative glycosylation sites but also to exclude regions of known homology with GABA transporters in the extracellular hydrophilic domains. The synthetic peptide, TAUT-1 was conjugated with carrier protein, kehole lympet hemocyanin (KLH) to use as an antigen. When used for immunization on a rabbit to produce polyclonal antiserum, the conjugates elicited high -titered specific anti-TAUT-1 antibodies, which reacted well with the ovalbumin (OVA) conjugated peptides in ELISA. The KLH-conjugated peptide was also used as immunizing antigen in BALB/c mice to produce TAUT specific monoclonal antibodies. From the culture supernatant of the hybridoma, the specificity of anti-TAUT-1 monoclonal antibodies was confirmed by ELISA. Further applications of more tools in TAUT expression analysis will be performed such as western blotting and flow cytometry.

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Association with Autoimmune Disease in Patients with Premature Ovarian Failure (조기 난소기능 부전증 환자에서 자가면역 질환과의 상관관계)

  • Park, Joon-Cheol;Kim, Jong-In;Rhee, Jeong-Ho
    • Clinical and Experimental Reproductive Medicine
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    • v.31 no.3
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    • pp.149-154
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    • 2004
  • Objective: To assess the association with autoimmune endocrine diseases and detection rate of autoimmune antibodies and its clinical significance in patients with premature ovarian failure. Methods: Twenty eight patients with primary or secondary amenorrhea manifesting hormonal and clinical features of premature ovarian failure (primary POF: 7, secondary POF: 21) were investigated. We tested them TFT, 75 g OGTT, ACTH and S-cortisol for thyroiditis, IDDM, Addison's disease, and antithyoglobulin antibody, antimicrosomal antibody, antinuclear antibody, rheumatic factor, anti-smooth muscle antibody, anti-acetylcholine receptor antibody for non-organ specific autoimmune disorders. Results: Only one patient was diagnosed as IDDM and no patients had abnormal TFT or adrenal function test. More than one kind of autoantibody was detected in 11 patients of all (39.2%): 5 patients (71.4%) of primary POF group and 6 patients (21.4%) of secondary POF group. Eleven patients (39.3%) had antithyroglobulin antibody, 4 (14.3%) had antimicrosomal antibody, 2 (7.1%) had antinuclear antibody, 2 (7.1%) had rheumatic factor, 1 (3.6%) had anti-smooth muscle antibody, 1 (3.6%) had anti-acetylcholine receptor antibody. Conclusions: Premature ovarian failure may occur as a component of an autoimmune polyglandular syndrome, so patients should be measured with free thyroxine, thyroid-stimulating hormone, fasting glucose and electrolytes. Measurement of thyroid autoantibodies in POF patients may be important in identifying patients at risk of developing overt hypothyoidism, but other autoantibodies may not be suitable for screening test.

Relationship between the Thyroid Hormone and Viral Infections in Pregnancy (임신 중 바이러스성 감염요인과 갑상선 호르몬의 상관성)

  • Lim, Dong-Kyu;Park, Chang-Eun
    • Korean Journal of Clinical Laboratory Science
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    • v.54 no.1
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    • pp.28-37
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    • 2022
  • Pregnancy requires an important interpretation of thyroid function tests. The presence of anti-thyroid antibodies and viral infectious agents affect the health of both the fetus and the mother. Hence, a selective evaluation of thyroid function in pregnancy is required. This study is a retrospective cross-sectional survey to examine the correlation between thyroid hormones and viral infections during pregnancy. The results showed that the triiodothyronine (T3) decreased with increasing age, especially in the hepatitis C virus (HCV)-positive group (P<0.01). In addition, although negative for the human immunodeficiency virus (HIV), thyroxine (FT4) showed a significant increase in near-threshold or twin pregnant women (P<0.05). The thyroid stimulating hormone (TSH) was highly distributed at the age of 30, and there was no statistically significant correlation with other viral infection factors. In addition, as a result of dividing and analyzing the result of TSH by the quantiles, FT4 and T3 showed a positive correlation but showed a negative correlation with TSH (P<0.05). Therefore, the evaluation of prenatal thyroid screening during pregnancy and viral infection factors should reflect the time of pregnancy, exposure to infection, and the quantitative values. Adequate thyroid hormone and viral infections availability is important for an uncomplicated pregnancy and optimal fetal development.

Nonconvulsive Status Epilepticus Associated with Hashimoto's Encephalopathy (하시모토뇌병증과 연관된 비경련뇌전증지속상태)

  • Lee, Jung-Ju;Kang, Kyusik;Park, Jong-Moo;Shin, Hyeeun;Kwon, Ohyun;Kim, Byung Kun
    • Annals of Clinical Neurophysiology
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    • v.16 no.2
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    • pp.70-73
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    • 2014
  • Nonconvulsive status epilepticus usually presents with altered mentation without distinct manifestations of seizures. It may be related with various medical disorders. Hashimoto's encephalopathy is characterized by various neurological manifestations accompanied by high titers of anti-thyroid antibodies. Here, we report a patient with nonconvulsive status epilepticus caused by Hashimoto's encephalopathy who showed a dramatic response to steroids.

Baseline Stimulated Thyroglobulin Level as a Good Predictor of Successful Ablation after Adjuvant Radioiodine Treatment for Differentiated Thyroid Cancers

  • Fatima, Nosheen;uz Zaman, Maseeh;Ikram, Mubashir;Akhtar, Jaweed;Islam, Najmul;Masood, Qamar;Zaman, Unaiza;Zaman, Areeba
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.15
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    • pp.6443-6447
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    • 2014
  • Background: To determine the predictive value of the baseline stimulated thyroglobulin (STg) level for ablation outcome in patients undergoing adjuvant remnant radioiodine ablation (RRA) for differentiated thyroid carcinoma (DTC). Materials and Methods: This retrospective study accrued 64 patients (23 male and 41 female; mean age of $40{\pm}14$ years) who had total thyroidectomy followed by RRA for DTC from January 2012 till April 2014. Patients with positive anti-Tg antibodies and distant metastasis on post-ablative whole body iodine scans (TWBIS) were excluded. Baseline STg was used to predict successful ablation (follow-up STg <2 ng/ml, negative diagnostic WBIS and negative ultrasound neck) at 7-12 months follow-up. Results: Overall, successful ablation was noted in 37 (58%) patients while ablation failed in 27 (42%). Using the ROC curve, a cut-off level of baseline STg level of ${\leq}14.5ng/ml$ was found to be most sensitive and specific for predicting successful ablation. Successful ablation was thus noted in 25/28 (89%) of patients with baseline STg ${\leq}14.5ng/ml$ and 12/36 (33%) patients with baseline STg >14.5 ng/ml ((p value <0.05). Age >40 years, female gender, PTS >2 cm, papillary histopathology, positive cervical nodes and positive TWBIS were significant predictors of ablation failure. Conclusions: We conclude that in patients with total thyroidectomy followed by I-131 ablation for DTC, the baseline STg level is a good predictor of successful ablation based on a stringent triple negative criteria (i.e. follow-up STg < 2 ng/ml, a negative DWBIS and a negative US neck).

First Korean case of a STAT1 gene mutation: chronic mucocutaneous candidiasis, hypothyroidism, chronic hepatitis and systemic lupus erythematosus

  • Kim, Kang-in;Lee, Hanbyul;Jung, So Yoon;Lee, Dong Hwan;Lee, Jeongho
    • Journal of Genetic Medicine
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    • v.15 no.2
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    • pp.92-96
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    • 2018
  • Chronic mucocutaneous candidiasis (CMC) is characterized by increased susceptibility to chronic and recurrent infections of the skin, mucous membranes, and nails by Candida species. It is a primary immunodeficiency disorder that is difficult to diagnose because of its heterogeneous clinical manifestations and genetic background. A 20-month-old boy who did not grow in height for 3 months was diagnosed as having hypothyroidism and he had hepatitis which was found at 5 years old. He presented with persistent oral thrush and vesicles on the body, the cause of which could not be identified from laboratory findings. No microorganism was detected in the throat culture; however, the oral thrush persisted. Immunological tests showed that immunoglobulin (Ig) subclass IgG and cluster of differentiation (CD)3, CD4, and CD8 levels were within normal limits. We prescribed oral levothyroxine and fluconazole mouth rinse. The patient was examined using diagnostic exome sequencing at the age of 6 years, and a c.1162A>G (p.K388E) STAT1 gene mutation was identified. A diagnosis of CMC based on the STAT1 gene mutation was, thus, made. At the age of 8 years, the boy developed a malar-like rash on his face. We conducted tests for detection of antinuclear antibodies and anti-dsDNA antibodies, which showed positive results; therefore, systemic lupus erythematosus (SLE) was also suspected. Whole exome sequencing is important to diagnose rare diseases in children. A STAT1 gene mutation should be suspected in patients with chronic fungal infections with a thyroid disease and/or SLE.

Correlation of Serum Thyroglobulin and Thyroglobulin in the Wash out of the Needle in Thyroid Cancer (갑상선암에서의 혈중 Thyroglobulin 농도와 침생검 검체 Washout Solution의 Thyroglobulin 농도와의 상관관계)

  • An, Jae-Seok;Kim, Ji-Na;Won, Woo-Jae
    • The Korean Journal of Nuclear Medicine Technology
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    • v.13 no.3
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    • pp.152-155
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    • 2009
  • Purpose: The most widely accepted tool for follow up management of thyroid cancer patients is serum thyroglobulin (Tg) measurement, but its value is limited by the interference of anti-thyroglobulin antibodies (anti-Tg Ab). Recently thyroglobulin measurement in the wash out of fine-needle aspiration biopsy specimens (Tg-FNAB) is frequently used for differential diagnosis of recurrences/metastases. The aim of this study was the investigation of the diagnostic utility of Tg-FNAB compared with serum Tg. Materials and Methods: We enrolled 41 consecutive patients with thyroid cancer who were evaluated for Tg-FNAB between January 2007 and February 2008 retrospectively. We ruled out 6 patients who anti-Tg Ab positive (${\geq}$100 U/mL) in the RIA (BRAHMS anti-Tgn RIA 100Det; BRAHMS Aktiengesell schaft, Berlin, Germany). Serum Tg and Tg-FNAB were measured by immunoradiometric assay (BRAHMS Tg pluS RIA 100 Det; BRAHMS Aktienge sellschaft, Berlin, Germany). We evaluated for Tg-FNAB compared with serum Tg and corresponding cytological smear. To compare the values of the two the t-test was used. Results: Tg-FNAB values were significantly higher (median 1,060 ng/mL, range 0.2~434,000 ng/mL) than serum Tg (median 2.5 ng/mL, range 0.9~131 ng/mL) (p=0.0394). The rate of correspondence with Tg-FNAB between cytological result was 87.9% and 65.9% in the case of serum Tg. Tg-FNAB was positive in 28 (24 with positive and 4 with suspicious cytology). Of the remaining 13 patients with negative Tg-FNAB, 1 had suspicious and 12 had unsuspicious cytology. serum Tg was positive in 26 (17 with positive and 3 with suspicious and 6 with unsuspicious cytology), Of the remaining 15 patients with negative serum Tg, 8 was positive in cytological result and 1 had suspicious and 6 had unsuspicious cytology. Conclusions: Tg-FNAB measurement is more accurate with high sensitivity (87.9%) than serum Tg (65.9%). The Tg-FNAB was a useful predictor for detecting recurrences/metastases with serum Tg.

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