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Biomedical subjects

K Kuma

Publications and source records attributed to K Kuma.

At least 19 recordsLinked to original sources
PubMed2002

Expression of cdc25A and cdc25B proteins in thyroid neoplasms.

Cdc25B and cdc25A phosphates are prominent stimulators of cell cycle progression and recent studies have also suggested their oncogenic roles. To elucidate the role of these proteins in thyroid neoplasms, we immunohistochemically investigated their expression, and neither protein was expressed in normal follicular cells. Cdc25B was frequently overexpressed in follicular adenoma and minimally invasive follicular carcinoma, but the incidence was significantly lower in widely invasive follicular carcinoma. Furthermore, the cdc25B expression level significantly decreased with the dedifferentiation of thyroid carcinoma. Cdc25A overexpression was observed in high incidences in all types of thyroid neoplasms. These results suggest that cdc25B and cdc25A play oncogenic roles in thyroid follicules and that cdc25B works predominantly in the early phase of the progression of thyroid carcinoma, whereas cdc25A plays a fundamental role in the development of thyroid neoplasms.

Adenoma↗
PubMed2002

Caveolin-1 overexpression is an early event in the progression of papillary carcinoma of the thyroid.

Caveolin-1 is a major structural component of caveolae, which are plasma membrane microdomains implicated in the regulation of intracellular signalling pathways. Previous in vitro and in vivo studies on the function of caveolin-1 in carcinoma showed controversial results, indicating that the physiological role of caveolin-1 varies according to the origin of carcinoma. In this study, we investigated caveolin-1 expression in thyroid neoplasms by means of immunohistochemistry using a rabbit polyclonal antibody against caveolin-1. Normal follicular cells did not express caveolin-1. In papillary carcinoma, caveolin-1 expression was observed in high incidence, and especially in microcancer (less than 1.0 cm in diameter), caveolin-1 was positive in all cases except one. In undifferentiated (anaplastic) carcinoma, its incidence was significantly reduced. On the other hand, all cases of follicular carcinoma and adenoma were classified as negative for caveolin-1. These results suggest that caveolin-1 may play a role predominantly in the early phase of papillary carcinoma, whereas it has little influence on follicular tumours.

Adenoma↗
PubMed2001

Extremely reduced evolutionary rate of TATA-box binding protein in higher vertebrates and its evolutionary implications.

Previously we showed that the evolutionary rates of the Pax proteins are markedly reduced in higher vertebrates, as compared with those in the ancestral lineage of vertebrates, and we suggested that the reduced Pax protein evolution might be explained by increased functional constraints due to gene recruitment for other purposes or repeated expression in different developmental stages. To clarify the problem of whether the evolutionary rate variation found in the Pax proteins is an evolutionary feature generally recognized in most transcription factors, we have cloned and sequenced cDNAs encoding the TATA-box binding protein (TBP), a general transcription factor of eukaryotes, from Oryzias latipes, a Japanese medaka, Lampetra reissneri, a lamprey, and Ephydatia fluviatilis, a freshwater sponge. An evolutionary rate analysis of TBP has revealed that the evolutionary rate of TBP is extremely low in higher vertebrates, but not in the ancestral lineage of vertebrates, as found in the Pax proteins. In contrast, no marked reduction of the evolutionary rate in higher vertebrates is observed in the aldolase C, a house keeping enzyme. It is therefore likely that the increased functional constraint on TBP is responsible for the extremely low evolutionary rate in higher vertebrates. The temporal pattern of the evolutionary rate variation during vertebrate evolution was discussed.

Animals↗
PubMed2001

Overexpression of kalpha1 tubulin mRNA in thyroid anaplastic carcinoma.

The expression levels of (k)alpha1 tubulin in 84 benign and malignant thyroid tissues were measured by means of real-time quantitative reverse transcription-polymerase chain reaction. An increased expression of (k)alpha1 tubulin mRNA was observed in all of five anaplastic carcinomas and some of the papillary carcinomas. Expression levels of (k)alpha1 tubulin relative to thyroglobulin mRNA were slightly increased in papillary carcinomas and greatly increased in anaplastic carcinomas. Chemotherapeutic agents which are targeted to microtubules may be considered as an alternative choice for the treatment of anaplastic carcinomas and some differentiated carcinomas in which increased expression of (k)alpha1 mRNA is observed.

Carcinoma↗
PubMed2001

Quantitative measurement of thyroglobulin mRNA in peripheral blood of patients after total thyroidectomy.

Previous studies have reported the clinical usefulness of reverse transcription-polymerase chain reaction (RT-PCR) detection of thyroglobulin (TG) mRNA in the peripheral blood of patients with differentiated thyroid carcinoma. To evaluate this usefulness, we measured TG mRNA in the peripheral blood of patients diagnosed with thyroid carcinoma after total thyroidectomy by real-time quantitative RT-PCR using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA as an internal control. Surprisingly, we detected TG mRNA in all samples obtained after total thyroidectomy, including those from 4 medullary carcinomas. Further, there was no statistical difference in expression levels of TG mRNA in the patients with or without metastasis, and no significant correlation was found between serum TG concentrations and the expression levels of TG mRNA. These results give rise to a question regarding the clinical applications of not only RT-PCR detection but also quantitative measurement of TG mRNA in peripheral blood.

Adolescent↗
PubMed2001

Identification of susceptibility loci for autoimmune thyroid disease to 5q31-q33 and Hashimoto's thyroiditis to 8q23-q24 by multipoint affected sib-pair linkage analysis in Japanese.

Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is caused by multiple genetic and environmental factors. The clinical and immunological features of GD and HT are distinct; however, there are multiplex families with both GD and HT, and cases in which GD evolves into HT. Thus, there may be specific susceptibility loci for GD or HT, and common loci controlling the susceptibility to both GD and HT may exist. A genome-wide analysis of data on 123 Japanese sib-pairs affected with AITD was made in which GD- or HT-affected sib-pairs (ASPs) were studied to detect GD- or HT-specific susceptibility loci, and all AITD-ASPs were used to detect AITD-common susceptibility loci. Our study revealed 19 regions on 14 chromosomes (1, 2, 3, 5, 6, 8, 9, 10, 11, 12, 13, 15, 18 and 22) where the multipoint maximum LOD score (MLS) was >1. Especially, chromosome 5q31-q33 yielded suggestive evidence for linkage to AITD as a whole, with an MLS of 3.14 at D5S436, and chromosome 8q23-q24 yielded suggestive evidence for linkage to HT, with an MLS of 3.77 at D8S272. These observations suggest the presence of an AITD susceptibility locus at 5q31-q33 and a HT susceptibility locus at 8q23-q24.

Abatacept↗
PubMed2001

Large-scale analysis of mutations in RET exon 16 in sporadic medullary thyroid carcinomas in Japan.

Germline mutations in the RET proto-oncogene are the cause of multiple endocrine neoplasia type 2 (MEN 2A and 2B) and familial medullary thyroid carcinoma (FMTC). Some cases of sporadic medullary thyroid carcinoma (MTC) have also been reported to have mutations in the RET gene. However, two previous reports have given discrepant results on the frequency of the mutations in RET in sporadic MTCs in Japan. To clarify this problem, we analyzed mutations in RET exon 16 in 72 sporadic MTCs by means of the two methods used in the previous studies, direct sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Mutations in exon 16 were detected in only 2 of 72 cases of sporadic MTC. These results suggest that when a MTC has a mutation in RET exon 16, it is more likely to be a hereditary MTC than a sporadic one in Japan.

Adult↗
PubMed2001

Serum concentration of androstenediol and androstenediol sulfate in patients with hyperthyroidism and hypothyroidism.

Androstenediol (5-androsten-3beta, 17beta-diol, ADIOL) and androstenediol 3-sulfate (ADIOLS) are active metabolites of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS), respectively, and have estrogenic activity and immunoregulatory function. We examined serum concentrations of ADIOL, ADIOLS, DHEA, DHEAS and pregnenolone sulfate (5-pregnen-3beta-ol-20-one sulfate, PREGS) in patients with Graves' thyrotoxicosis (male/female 9/14), hypothyroidism (11/20) and in normal controls (14/29). In hypothyroidism serum levels of all these steroids were significantly decreased in both genders. In hyperthyroidism, in contrast, serum levels of ADIOLS (male 1.49 +/- 0.69, female 0.64 +/- 0.31 micromol/l), DHEAS (male 7.43 +/- 3.91, female 5.13 +/- 2.03 micromol/l), and PREGS (male 1.13 +/- 0.58, female 1.07 +/- 0.85 micromol/l) were markedly increased, but serum concentrations of ADIOL and DEHA were not significantly different from controls (ADIOLS male 0.36 +/- 0.33, female 0.14 +/- 0.09 micromol/l; DHEAS male 2.88 +/- 1.70, female 1.86 +/- l1.03pmol/l; PREGS male 0.18 +/- 0.12, female 0.11 +/- 0.08 micromol/l; ADIOL male 3.76 +/- 1.35, female 1.91 +/- 1.17 nmol/l; DHEA male 9.23 +/- 3.49, female 13.5 +/- 10.8nmol/l). Serum concentrations of all these steroids correlated with the serum concentration of the thyroid hormones in these patients. Serum albumin and sex hormone-binding globulin concentrations were not related to these changes in the concentrations of steroids. These findings indicate that serum concentrations of ADIOLS, ADIOL, DHEAS, DHEA and PREGS were decreased in hypothyroidism, whereas serum ADIOLS, DHEAS and PREGS concentrations were increased but ADIOL and DHEA were normal in hyperthyroidism. Thyroid hormone may stimulate the synthesis of these steroids and sulfotransferase is speculated to be increased in hyperthyroidism. Increased ADIOLS might contribute to menstrual disturbances and gynecomastia in hyperthyroidism.

Adult↗
PubMed2001

Blocking type anti-tSH receptor antibodies detected by radioreceptor assay in Graves' disease.

We previously developed a radioreceptor assay which is presumably specific for detection of blocking-type anti-TSH receptor (TSHR) antibodies using unsolubilized porcine TSHR. Employing this assay, we measured blocking TSH-binding inhibitory immunoglobulin (TBII) in the sera from 30 untreated Graves' patients and compared the results with those of a bioassay measuring thyroid stimulation blocking antibodies (TSBAb). Blocking TBII was positive in 9 of 30 sera (30%) and the blocking TBII activity was correlated with the total TBII value, which was measured by the radioreceptor assay using solubilized porcine TSHR. On the other hand, TSBAb determined with the conventional bioassay was positive in only 2 sera (6.7%), and no correlation was observed with the TSAb activity. In some cases in which the TSAb activity was rather high, TSBAb could not be detected by bioassay, whereas blocking TBII was positive. There was no correlation of blocking TBII activity with goiter size, thyroid hormone level, or proptosis. However, there was a tendency for anti-thyroid therapy to require a shorter time for FT4 normalization in blocking TBII subjects, suggesting that blocking-type anti-TSHR antibody plays some role in the pathophysiology of Graves' disease. In conclusion, blocking type anti-TSHR antibodies are often found in the sera of Graves' patients when the blocking-specific radioreceptor assay is applied.

Adolescent↗
PubMed2001

[Extremely high level of serum thyroglobulin after surgery in a patient with follicular thyroid carcinoma. Recurrence, distant metastasis, or other etiology?].

A 67-year-old female patient with a tumor of the thyroid underwent right lobectomy of the thyroid. The tumor was histologically diagnosed as a follicular carcinoma of the thyroid. Serum studies revealed very high (> 8,000 ng/ml) levels of thyroglobulin after surgery. We suspected distant metastases from follicular carcinoma or recurrence in the left lobe of the thyroid. She therefore underwent left lobectomy of the thyroid. No recurrence of follicular carcinoma was recognized in the resected thyroid tissue, but severe autoimmune thyroiditis was diagnosed histologically. Total-body 131I scintigraphy did not show abnormal distant uptake. Serum studies revealed very low levels of thyroglobulin (< 2.0 ng/ml) after the second surgery. We speculate that silent thyroiditis might have occurred after the first surgery, resulting in the high levels of serum thyroglobulin. Silent thyroiditis should be considered as a possible cause of high serum thyroglobulin levels.

Adenocarcinoma, Follicular↗
PubMed2000

Unilateral surgery supported by germline RET oncogene mutation analysis in patients with sporadic medullary thyroid carcinoma.

Compared to hereditary medullary thyroid carcinoma (MTC), sporadic MTC tends to be unicentric and confined to one lobe. Patients with sporadic MTC usually undergo total thyroidectomy because of a possible hereditary or bilateral process. We evaluated the usefulness of germline RET oncogene mutation analysis in surgery for apparently sporadic MTC and performed unilateral surgery on patients without detectable mutation. In 36 patients with a preoperative diagnosis of apparently sporadic MTC, we performed germline RET oncogene mutation analyses: before surgery in 8 recent patients and after surgery in 28 who had been treated before 1996. Of the latter, 5 had bilateral MTC. DNA samples were extracted from their peripheral blood, and the polymerase chain reaction products of the RET proto-oncogene were analyzed using single-strand conformation polymorphism analysis and the direct sequencing methods. Before 1996 we often performed total thyroidectomy but changed to hemithyroidectomy thereafter, except in one patient with associated Graves' ophthalmopathy. Our minimal standard practice included systematic central and ipsilateral neck dissection. The outcome was assessed in terms of gastrin- and calcium-stimulated plasma calcitonin levels. Germline RET mutations were found in six patients. Five of these patients had bilateral MTC, whereas all 30 patients without mutation had unilateral disease. Hemithyroidectomy in seven of our recent patients resulted in normalization of plasma calcitonin levels in all, although four were found to have microscopic lymph node involvement. In conclusion, hemithyroidectomy with systematic central and ipsilateral neck dissection is an appropriate procedure for patients with sporadic MTC without detectable germline RET mutations.

Adult↗
PubMed2000

Gene expression profiles in thyroid carcinomas.

The gene expression profiles of human thyroid carcinomas were analysed by serial analysis of gene expression (SAGE) which allows quantitative and simultaneous analysis of a large number of transcripts. More than 29,000 transcripts derived from a normal thyroid tissue and four thyroid tumours were analysed. While extensive similarity was noted between the expression profiles of the normal thyroid tissue and three differentiated thyroid tumours, many transcripts, such as osteonectin, a-tubulin, glyceraldehyde-3-phosphate dehydrogenase, glutathione peroxidase, and thyroglobulin, were expressed at extremely different levels in differentiated and undifferentiated carcinomas. These data provide new information that might be used to identify genes useful for the diagnosis and treatment of thyroid carcinomas.

Adenoma↗
PubMed2000

Class switch recombination of the chicken IgH chain genes: implications for the primordial switch region repeats.

In mammals and the amphibian, Xenopus, isotypes of antibodies have been shown to be changed through class switch recombination within the IgH chain gene locus. Here, we identified switch (S) repetitive sequences in the 5' introns of the Ig C(mu) and C(gamma) genes of the chicken. The S(mu) region is composed of two homologous regions, S(mu)1 and S(mu)2. The S(mu)1 region is an upstream 3.7 kb sequence composed of 37 repeats of a consensus sequence containing tandem repeats of the decamer ACCAGTATGG. The S(mu)2 region is a downstream 1.4 kb sequence consisting of simple tandem repeats of a decamer CCCAGTACAG. The S(gamma) region contains repeats of the decamer TATGGGGCAG. Analysis of chicken IgG-producing hybridomas revealed that the C(mu) gene was deleted from the chromosome by the recombination occurring between the S(mu) and S(gamma) regions. Recombination breakpoints at the C(mu) gene of splenocytes from an immunized chicken were scattered around the S(mu) region and two such breakpoints, the precise position of which were determined, were located within possible hairpin loop structures at the palindromic sequence of S(mu)1. A primordial palindromic sequence from which the prevalent switch repeat motifs of mammals, chickens and amphibians may have diverged is presented.

Animals↗
PubMed2000

Expression of oncofetal fibronectin messenger ribonucleic acid in fibroblasts in the thyroid: a possible cause of false positive results in molecular-based diagnosis of thyroid carcinomas.

Oncofetal fibronectin (onfFN) messenger ribonucleic acid (mRNA) is abundantly expressed in thyroid papillary and anaplastic carcinomas. These carcinomas can be preoperatively diagnosed by the detection of onfFN mRNA in fine needle aspiration biopsies (FNABs). However, previous reports have noted that the expression of onfFN mRNA was observed in 3.7% of the FNABs that were diagnosed as negative cytology. To clarify this discrepancy, we examined the expression of onfFN mRNA in fibroblasts in the thyroid. By RT-PCR and real-time quantitative RT-PCR analyses, we detected a high copy number of onfFN mRNA in cultured fibroblasts obtained from the normal thyroid tissues dissected surgically. Thus, we conclude that the contaminated fibroblasts in FNABs due to tumor necrosis or acute or chronic inflammation may be a cause of false positive results in molecular-based diagnosis of thyroid carcinomas.

Carcinoma↗
PubMed2000

Diagnosis of thyroid malignant lymphoma by reverse transcription-polymerase chain reaction detecting the monoclonality of immunoglobulin heavy chain messenger ribonucleic acid.

Distinguishing between thyroid malignant lymphoma and lymphocytic thyroiditis (Hashimoto's thyroiditis) is quite difficult and problematic. Molecular techniques to detect clonal lymphoid proliferation based on Ig heavy chain (IgH) gene rearrangement may be used to facilitate more accurate diagnosis of malignant lymphoma. We recently established a method for diagnosing thyroid tumors by analyzing ribonucleic acids (RNAs) extracted from the needles used for fine needle aspiration biopsy (aspiration biopsy-RT-PCR). By applying the aspiration biopsy-RT-PCR method to detection of the monoclonality of IgH messenger RNA (mRNA), an accurate molecular-based diagnosis of malignant lymphoma can be established as an adjunct to cytological diagnosis. We first studied RNAs from fresh tissues samples of 8 cases of Hashimoto's thyroiditis and 18 malignant lymphomas to detect the monoclonality of IgH mRNA by seminested RT-PCR. Monoclonality was detected in 8 of 18 (44.4%) malignant lymphomas, but in none of the 8 cases of Hashimoto's thyroiditis. We then studied aspirates from 10 cases of thyroid malignant lymphoma, 4 cases of Hashimoto's thyroiditis, and 1 case each of adenomatous goiter and papillary carcinoma. Monoclonality was detected in the aspirates from 4 of 10 malignant lymphomas (40%), but not from other tissues. Thus, RT-PCR detection of monoclonality of IgH mRNA in addition to cytological examination may be useful in diagnosing thyroid malignant lymphoma.

Adenoma↗
PubMed2000

Serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, and pregnenolone sulfate concentrations in patients with hyperthyroidism and hypothyroidism.

BACKGROUND: Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have been suggested to have protective effects against cardiovascular disease, cancer, immune-modulated diseases, and aging. We examined serum concentrations of DHEA, DHEA-S, and pregnenolone sulfate (PREG-S) in patients with thyroid dysfunction. METHODS: Steroids extracted with methanol from serum sample were separated into an unconjugated fraction (DHEA) and a monosulfate fraction (DHEA-S and PREG-S), using a solid-phase extraction and an ion-exchange column. After separation of unconjugated steroids by HPLC, the DHEA concentration was measured by enzyme immunoassay. The monosulfate fraction was treated with arylsulfatase, and the freed steroids were separated by HPLC. The DHEA and PREG fractions were determined by gas chromatography-mass spectrometry, and the concentrations were converted into those of DHEA-S and PREG-S. RESULTS: Serum concentrations of DHEA, DHEA-S, and PREG-S were all significantly lower in patients with hypothyroidism (n = 24) than in age- and sex-matched healthy controls (n = 43). By contrast, in patients with hyperthyroidism (n = 22), serum DHEA-S and PREG-S concentrations were significantly higher, but the serum DHEA concentration was within the reference interval. Serum concentrations of these three steroids correlated with serum concentrations of thyroid hormones in these patients. Serum albumin and sex hormone-binding globulin concentrations were not related to these changes in the concentration of steroids. CONCLUSIONS: Serum concentrations of DHEA, DHEA-S, and PREG-S were decreased in hypothyroidism, whereas serum DHEA-S and PREG-S concentrations were increased but DHEA was normal in hyperthyroidism. Thyroid hormone may stimulate the synthesis of these steroids, and DHEA sulfotransferase might be increased in hyperthyroidism.

Adult↗
PubMed1999

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↗