[Painless thyroiditis].
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Autoantibodies↗
Biomedical subjects
N Amino
Publications and source records attributed to N Amino.
[Primary hypothyroidism].
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Autoimmune Diseases↗
Preoperative diagnosis of thyroid papillary and anaplastic carcinomas by real-time quantitative reverse transcription-polymerase chain reaction of oncofetal fibronectin messenger RNA.
The restricted expression of oncofetal fibronectin (onfFN) mRNA in thyroid papillary and anaplastic carcinomas was recently reported. In this study, we measured the copy number of onfFN mRNA in RNAs extracted from fine needle aspiration biopsies by real-time quantitative reverse transcription-PCR using thyroglobulin mRNA as an internal control. By measuring the onfFN:thyroglobulin mRNA ratio, preoperative aspirates from 31 papillary carcinomas and an anaplastic carcinoma can be distinguished from those from 5 adenomatous goiters, 5 follicular adenomas, and 4 follicular carcinomas. Thus, quantification of onfFN by real-time quantitative reverse transcription-PCR may be useful for the preoperative diagnosis of papillary and anaplastic carcinomas.
Base Sequence↗
Rapid screening of specific changes in mRNA in thyroid carcinomas by sequence specific-differential display: decreased expression of acid ceramidase mRNA in malignant and benign thyroid tumors.
Sequence specific-differential display (SS-DD) is a powerful method for screening significant changes in gene expression between normal and malignant tissues. Using this method, we detected 3 genes for which the expression is much decreased in thyroid tumors. After sub-cloning and sequencing analysis, one of the genes was revealed to be acid ceramidase (AC). The expression of AC in normal thyroids and thyroid tumors was examined by semi-quantitative reverse-transcription-polymerase-chain-reaction (RT-PCR). Obvious decreases in the expression of AC mRNA were observed in 5/6 follicular adenomas, 2/2 adenomatous goiters, 3/6 papillary carcinomas and 1/2 follicular carcinomas. To confirm this result, real-time quantitative PCR analysis (TaqMan PCR) was carried out. The relative expression level of AC mRNA compared with that of GAPDH mRNA was reduced in follicular adenomas, follicular carcinomas, and papillary carcinomas. Further, the expression of AC mRNA was extremely reduced in 2 anaplastic carcinomas. These results suggest a possible relationship between thyroid tumorigenesis and the expression of AC mRNA. Moreover, the increased expression of AC mRNA in normal thyroid tissues suggests some fundamental roles of AC in thyroid function.
Acid Ceramidase↗
Analysis of splice variants of the fibronectin gene in thyroid carcinomas by reverse transcription-polymerase chain reaction: increased expression of oncofetal fibronectin mRNA in papillary carcinomas is not caused by the alternation in splicing.
The expression levels of each splice variant of the fibronectin gene in the normal thyroid and in thyroid tumors were examined by reverse transcription-polymerase chain reaction (RT-PCR). In thyroid papillary carcinomas, insertion of a variant exon in the ED-A and ED-B domains, and three of five types of splice variants in the IIICS domain were observed. In spite of the marked increase in the expression of oncofetal fibronectin mRNA with the IIICS sequence in papillary and anaplastic carcinomas in the previous reports, the relative expression levels of each splice variant with or without the IIICS sequence showed no difference among all the tumor types. Therefore, the much increased expression of oncofetal fibronectin mRNA in these carcinomas is not caused by the alternation in splicing, but may be caused by an increase in promoter activity or stability of mRNA of the fibronectin gene.
Adenocarcinoma, Follicular↗
PIT1 abnormality.
The PIT1 gene product, Pit-1/GHF-1, binds to and transactivates the promoter sequences of the growth hormone, prolactin, and thyroid-stimulating hormone beta (also called thyrotropin) subunit genes. Abnormalities of the PIT1 gene, which encodes a pituitary-specific POU-domain DNA binding factor, cause a combined deficiency of growth hormone, prolactin, and thyrotropin (PIT1 abnormality). PIT1 abnormality is a typical 'transcription factor disease (abnormality)', as DNA-binding studies and transactivation studies with mutant Pit-1/GHF-1 protein and its target sequences made clear how the mutated protein causes the abnormality. PIT1 abnormality occurs both recessively and dominantly, according to the function of the mutated protein. Furthermore, observation of patients of different ages with the same mutation showed progressive phenotype as the patients grow old.
Aging↗
Postpartum onset of acute heart failure possibly due to postpartum autoimmune myocarditis. A report of three cases.
Autoimmune diseases, especially autoimmune thyroid disease, frequently develop after delivery due to the immune rebound mechanism. Most cases have transient dysfunction of affected organs. Cardiac dysfunction developed after delivery is called postpartum or peripartum cardiomyopathy. However, the aetiology of the disease is not clarified yet. Here we report three cases that developed acute heart failure in the postpartum period. One was complicated with an atrioventricular block and postpartum autoimmune thyroiditis. All patients recovered to normal cardiac function or pre-attack condition after 1 month of therapy with conventional drugs and bed rest. All three had positive antiheart antibody detected by indirect immunofluorescence assay, and one had antibody to heart myosin detected by enzyme-linked immunosorbent assay. Moreover, one of two patients examined revealed lymphocytic infiltration by endomyocardial biopsy. Antibodies to 26 viruses were not elevated significantly during the first 2 weeks after admission in any case. It is strongly suggested that heart failure is induced by postpartum autoimmune myocarditis, and thus clinicians should be aware of this disease.
Acute Disease↗
Increased serum concentration of interleukin-12 in patients with silent thyroiditis and Graves' disease.
We previously reported that interleukin-5 (IL-5), secreted from Th2 cells, was increased in patients with Graves' disease, but not in patients with silent thyroiditis. In this study, we investigated serum levels of interleukin-12 (IL-12) in order to examine the role of Th1-type immune response in the pathogenesis of autoimmune thyroid diseases. Serum levels of IL-12 were determined by a highly sensitive sandwich enzyme-linked immunosorbent assay in 68 patients with Hashimoto's thyroiditis (26 of whom had silent thyroiditis), 74 patients with Graves' disease, 8 patients with subacute thyroiditis, and 27 normal controls. Serum levels of IL-12 in thyrotoxic patients with silent thyroiditis (385.2 +/- 164.5 pg/mL, mean +/- SD), and in thyrotoxic patients with Graves' disease (343.6 +/- 163.8 pg/mL) were significantly increased compared with serum levels in normal subjects (163.9 +/- 66.8 pg/mL, p < 0.0001, p < 0.0001, respectively) or in thyrotoxic patients with subacute thyroiditis (241.9 +/- 46.5 pg/mL, p < 0.01, < 0.05, respectively). The ratio of IL-12 to IL-5 in thyrotoxic patients with silent thyroiditis (64.2 +/- 39.7) was significantly higher than that in normal controls (33.7 +/- 13.3, p < 0.01) or in thyrotoxic patients with Graves' disease (40.6 +/- 36.0, p < 0.05). These data suggest that Th1-type immune response is predominant in silent thyroiditis, and that not only Th2-type immune response but also Th1-type immune response is important in the pathogenesis of Graves' disease.
Adult↗
Measurement of the expression of oncofetal fibronectin mRNA in thyroid carcinomas by competitive reverse transcription-polymerase chain reaction.
Abundant expression of oncofetal fibronectin mRNA has been observed in thyroid papillary and anaplastic carcinomas. In this study, we measured relative expression levels of oncofetal fibronectin mRNA in thyroid cancer tissues by competitive reverse transcription polymerase chain reaction (RT-PCR) using thyroglobulin mRNA as an internal control. By this method, all papillary and anaplastic carcinomas and 3 of 6 follicular carcinomas were distinguished from benign tissues, such as normal thyroid tissues, follicular adenomas, and adenomatous goiters. Furthermore, 2 anaplastic carcinomas were clearly distinguished from differentiated carcinomas. These results suggest the possibility of establishing a more accurate preoperative or postoperative diagnosis of papillary and anaplastic carcinomas by measuring the relative expression level of oncofetal fibronectin to thyroglobulin in thyroid tumors.
Adenoma↗
CD30 expression and interleukin-4 and interferon-gamma production of intrathyroidal lymphocytes in Graves' disease.
We reported that serum levels of interleukin-5 (IL-5) and soluble CD30, mainly secreted from T helper 2 (Th2) cells, were increased in Graves' disease. To clarify the immune balance of Th1/Th2 within the Graves' thyroid gland, we have compared the expression of CD30, a preferential marker for T cells producing type 2 cytokines, and the production of interferon-gamma (IFN-gamma) and IL-4 between intrathyroidal lymphocytes (ITL) and peripheral blood lymphocytes (PBL). In PBL, none of these parameters were different between patients and normal subjects. The proportion of CD30+ cells in ITL was markedly higher (5.1%+/-2.8%, p < 0.0001) than that in patients' PBL (0.4%+/-0.3%). Likewise, both the proportions of IFN-gamma+ (14.8%+/-5.5%) and IL-4+ cells (2.4%+/-0.5%) in ITL were higher than those in PBL (9.6%+/-2.5%; p < 0.01, 1.5%+/-0.4%; p < 0.0001, respectively). The proportion of type 0 (both IFN-gamma and IL-4 positive, 1.0%+/-0.4% p < 0.001), type 1 (IFN-gamma positive, 14.0%+/-5.6%, p < 0.01) or type 2 cells (IL-4 positive, 1.4%+/-0.5%, p < 0.05) in ITL was significantly higher as compared with those in PBL (0.4%+/-0.1%, 9.0%+/-2.4%, 1.1%+/-0.3%, respectively). The ratios of ITL/PBL in CD30+ (23.3+/-30.6) and type 0 cells (2.5+/-1.2) were higher than the ratios in other subsets. The proportion of CD30+ cells correlated with the proportion of type 0 cells (r = 0.686, p < 0.01), but not with type 1 or type 2 cells. These findings suggest that there is no obvious deviation of Th2/Th1 profile in the Graves' thyroid gland, although intrathyroidal CD30+ T cells and Th0 cells may play some role in the development of autoimmune abnormalities in Graves' disease.
Adolescent↗
Postpartum autoimmune thyroid syndrome: a model of aggravation of autoimmune disease.
Postpartum thyroid dysfunction is rather a common problem during the postpartum period being found in approximately 5% of mothers in the general population. It occurs from subclinical autoimmune thyroiditis that is aggravated after parturition and causes various types of thyroid dysfunction. Immune activity is physiologically suppressed during pregnancy so that the fetus is not rejected, and rebounds above the normal level after parturition. Graves' disease and Hashimoto's thyroiditis also spontaneously ameliorate during pregnancy, and are often aggravated after parturition. The high-risk mothers for postpartum thyroid dysfunction are well screened by antithyroid microsomal antibody (MCAb) and 60% to 70% of MCAb-positive mothers develop postpartum thyroid dysfunction, which is transient in most cases. New onset of Graves' disease may be screened by thyroid-stimulating antibody (TSAb) and 70% of TSAb-positive mothers develop either transient or persistent postpartum Graves' disease that usually occurs 3 to 6 months postpartum. Immune rebound after parturition may cause not only autoimmune thyroid diseases but other autoimmune diseases, which may be investigated with similar strategies to those in postpartum autoimmune thyroid disease. Thus, we found that postpartum onset of rheumatoid arthritis was found in 0.08% of women in the general population and could be partially predicted by measuring rheumatoid factors in early pregnancy. There are several case reports of other autoimmune diseases that develop after delivery; postpartum renal failure or postdelivery hemolytic-uremic syndrome, postpartum idiopathic polymyositis, postpartum syndrome with antiphospholipid antibodies, postpartum autoimmune myocarditis. Many other possible postpartum autoimmune diseases are still unexplored. Puerperal diseases should be carefully examined in relation to autoimmune abnormalities in the affected organs.
Antibody Formation↗
Preoperative diagnosis of medullary thyroid carcinoma by RT-PCR using RNA extracted from leftover cells within a needle used for fine needle aspiration biopsy.
Fine needle aspiration Biopsy (FNAB) is commonly used to diagnose thyroid tumors. In some clinical situations, however, accurate diagnosis requires a more objective method than cytological examination alone. Medullary thyroid carcinomas (MTC) derive from C cells in the thyroid and express some specific messenger RNAs (mRNA), such as those transcribed from the RET proto-oncogene, the calcitonin gene, and the gene for carcinoembryonic antigen (CEA), which usually do not exist in normal thyroid follicular cells or thyroid tumors of follicular epithelial descent. Recently, we established a new method for the molecular diagnosis of thyroid tumors without additional invasion to the patient by extracting RNA for RT-PCR from the leftover cells inside the needles used for fine needle aspiration biopsy (Aspiration Biopsy-Reverse Transcription-Polymerase Chain Reaction, ABRP). By applying the ABRP method to the detection of RET, calcitonin, and CEA mRNAs, an accurate molecular-based diagnosis for MTC maybe established as an adjunct to cytological diagnosis. In this study, 35 aspirates were obtained at the time of surgery from thyroid tumors, including 11 MTCs. The expression of these mRNAs in the leftover cells inside the needles used for the aspiration was then examined. Transcripts from all three genes were detected in the samples from all 11 MTCs, but none of these mRNAs were detected in the other tumors or normal thyroid tissues. Furthermore, MTC was preoperatively diagnosed in three patients by ABRP detection of these mRNAs, and these diagnoses were confirmed by subsequent cytological and histopathological analyses. Thus RT-PCR detection of RET, calcitonin, and CEA mRNAs in FNABs may be an efficient molecular adjunct for diagnosing MTC.
Adult↗
Therapeutic controversy: Screening for postpartum thyroiditis.
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Adult↗
Screening of specific changes in mRNAs in thyroid tumors by sequence specific differential display: decreased expression of c-fos mRNA in papillary carcinoma.
To examine the specific changes in gene expression in thyroid carcinomas, we performed sequence specific-differential display (SS-DD) analysis by using a specific degenerate primer for the superfamily of the small G protein. After subcloning and sequencing analysis, one of the genes that showed decreased expression in thyroid papillary carcinomas was revealed to be the proto-oncogene c-fos. Expression of c-fos mRNA in benign and malignant tissues was examined by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blotting. The expression of c-fos was detected in all twelve normal thyroid tissues, whereas it decreased in thirteen of fifteen papillary carcinomas. These results indicate that the increased expression of c-fos mRNA is not necessarily to be an oncogenic feature of thyroid tumors. Further, its constant expression in normal thyroid tissues may play a role in the maintenance of thyroid function.
Adenoma↗
A novel mutation of the KAL1 gene in Kallmann syndrome.
Kallmann syndrome is defined by the association of hypogonadotropic hypogonadism and anosmia, for which three modes of transmission have been described: X-linked, autosomal recessive and autosomal dominant. The KAL1 gene, responsible for the X-linked form of the disease, has been isolated and its intron-exon organization determined. We report sequence analysis using PCR-direct sequencing method of the entire coding region and splice site junctions of the KAL1 gene in three males with Kallmann syndrome. We found a novel mutation in one case and no mutation in the other two cases. The mutation consisted of a C to T substitution in exon 1 converting codon 66 (CAG) encoding glutamine into a termination codon (TAG)/(Q66X). As a consequence of this mutation, the function of the KAL1 protein consisting of 680 amino acids was severely truncated so as to be consistent with Kallmann syndrome. As only this patient had unilateral renal hypoplasia among the three cases, this would suggest the existence of KAL1 gene mutation in this abnormality.
Adolescent↗
Polyethylene glycol increases the detection of anti-thyrotropin receptor antibodies by a radioreceptor assay.
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Autoantibodies↗