Biomedical subjects

Kanji Sato

Publications and source records attributed to Kanji Sato.

21 records · Page 2Linked to original sources

PubMed2003

Genes regulated by thyrotropin and iodide in cultured human thyroid follicles: analysis by cDNA microarray.

Thyrotropin (TSH) regulates a number of genes in thyrocytes, leading to iodide uptake, de novo synthesis and release of thyroid hormones, and cell proliferation, accompanied by increased blood flow. At higher doses of iodide, however, the TSH-induced increases in thyroid hormone release and blood flow are downregulated, and high iodide intake occasionally worsens autoimmune thyroiditis. To elucidate the genes involved in such effects, we cultured human thyrocytes and examined genes modulated by TSH and iodide, using a cDNA microarray study, which can analyze 2400 genes in each run. When thyroid follicles were cultured with TSH for 2 days, more than 100 genes were upregulated. These genes included those for enzymes involved in carbohydrate and lipid metabolism, adenylate and guanylate cyclases, and enzyme involved in cell proliferation. When thyroid follicles were cultured with high iodide concentrations (10(-5) M) for 24 hours, more than 100 genes were upregulated. Interesting genes were interleukin-8, IFP53, 90-kd heat shock protein, osteopontin, and intercellular adhesion molecule-1. These results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot hybridization. In summary, TSH upregulated a number of genes regulating thyroid functions. It is intriguing that thyroid follicles cultured with a high iodide concentration (10(-5) M) increased the expression levels of genes capable of modulating lymphocyte functions, even though immunocompetent cells were extensively removed by the present experimental culture conditions. Although we have analyzed only approximately 6%-8% of all human genes, the cDNA microarray study is a powerful tool to elucidate the effects of TSH and iodide on thyroid function.

Blotting, Southern↗

PubMed2002

A novel missense mutation of AIRE gene in a patient with autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED), accompanied with progressive muscular atrophy: case report and review of the literature in Japan.

Autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy (APECED) also known as autoimmune polyglandular syndrome type I, is a rare autosomal recessive disorder that results in several autoimmune diseases due to mutations in the AIRE (autoimmune regulator) gene. A 39-year-old female patient developed chronic mucocutaneous candidiasis at 3 yrs, idiopathic hypoparathyroidism at 11 yrs, chronic hepatitis at 23 yrs, Addison's disease and diabetes mellitus type I at 27 yrs. In addition, the patient developed progressive muscular atrophy of unknown etiology at the beginning of the third decade, and is bedridden at the present time. Her grandparents, parents, brother and daughter did not develop any features of APECED, but her father died of hepatoma. Direct sequencing of the AIRE gene revealed a novel missense mutation at exon 1 (R15C), which was identified to be of maternal origin. The other mutation was not found despite repeated sequencing of the whole coding regions. The R15C mutation was not detected in patients with idiopathic hypoparathyroidism (N= 10), idiopathic Addison's disease (N = 3), and normal subjects (N = 55). Although we could not analyze the father's gene, these results suggest that the patient is probably a compound heterozygote of the AIRE gene, in which the other abnormal allele could not be identified by the present analytical method. These data are compatible with the recent review that only one defective allele was detectable in some patients with clinically evident APECED. We found only six Japanese patients compatible with diagnosis of APECED, indicating that this autoimmune disease is extremely rare in our country.

Adult↗

PubMed2002

Propylthiouracil-induced lupus-like syndrome developing in a Graves' patient with a sibling with systemic lupus erythematosus.

A 13-year-old girl with Graves' disease, whose younger sister had systemic lupus erythematosus, developed polyarthralgia, fever, neutropenia, hypergammaglobulinemia, and microscopic hematuria after treatment with propylthiouracil (PTU) for 2 years. Myeloperoxidase-anti-neutrophil cytoplasmic antibodies were strongly positive. Anti-single- and anti-double-stranded DNA antibodies were positive, whereas LE cells and anti-Sm antibodies were negative. PTU was discontinued and all symptoms subsided gradually. Two years later, the microscopic hematuria had disappeared completely. Both patients had the identical HLA-DR alleles (HLA-DR9). These present two cases in siblings suggest that both sisters had lupus diathesis, and that the elder sister developed a PTU-induced lupus-like syndrome.

Adolescent↗