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Biomedical subjects

K Kuma

Publications and source records attributed to K Kuma.

At least 19 recordsLinked to original sources

Analysis of thyroid carcinoma based on material registered in Japan during 1977-1986 with special reference to predominance of papillary type.

BACKGROUND: As geographic differences have been observed in the characteristics of thyroid carcinoma, an analysis was made on thyroid carcinoma in the iodine rich country of Japan. METHODS: A total of 10,973 patients with histologically confirmed thyroid carcinoma registered in Japan from 1977-1986 were analyzed. Cases detected incidentally at autopsy and cases of nonepithelial tumor were excluded. This series included approximately 27% of all thyroid carcinoma cases in Japan. RESULTS AND CONCLUSIONS: Histologic distribution showed that papillary carcinoma accounted for 78.4% of cases, follicular carcinoma accounted for 17.2%, medullary carcinoma for 1.4%, squamous cell carcinoma for 0.3%, and anaplastic carcinoma for 2.7%. There is a tendency in Japan to diagnose papillary carcinoma as follicular carcinoma and to diagnose malignant lymphoma as anaplastic carcinoma. It was considered that the percentage of papillary carcinoma was higher and the percentage of follicular carcinoma and anaplastic carcinoma was lower than foregoing values. The characteristics of thyroid carcinoma in Japan were described, and the low incidence of nonpapillary carcinoma compared with papillary carcinoma was discussed in relation to iodine excess as an etiologic factor.

Adolescent

New approach for detection of amplification in cancer DNA using restriction landmark genomic scanning.

We developed a new approach for detecting the gene amplification of cancer DNAs with restriction landmark genomic scanning (RLGS). In cancer research, much effort has been made to find the amplified loci of cancer DNAs, because many lines of evidence indicate association between oncogene amplification and carcinogenesis. Conventionally, such gene amplification has been detected by using Southern hybridization with DNA probes. However, only the information of one locus can be obtained by one hybridization procedure, and analysis of many loci throughout the genome is too laborious and time consuming, even if only several candidate genes are investigated. On the other hand, the "in-gel renaturation method" was reported as another alternative for detection of amplified regions. However, even though this method is much improved, it is difficult to detect less than 7-fold amplification, which is often higher than the amplification of many cancer cases. To overcome these limitations and, in addition, to locate the amplified DNA two dimensionally, we applied RLGS for analysis of DNA amplification in cancer tissues, such as breast cancer (infiltrative tubuloadenocarcinoma), neuroblastoma, meningioma (endotheliomatous meningioma), and thyroid cancer (papillary adenocarcinoma). In some cases of breast cancer, several amplified spots located on the same amplicon were detected. In thyroid cancer, in which no amplification has yet been reported, low-grade amplification was also detected. In this report, we demonstrated that RLGS allows us to screen 2000-3000 restriction landmarks distributed on the genome simultaneously, and even low-grade amplification could be detected effectively. Thus, RLGS has proven to be a very useful method in detecting DNA amplification.

Breast Neoplasms

Diagnostic usefulness of dipeptidyl aminopeptidase IV monoclonal antibody in paraffin-embedded thyroid follicular tumours.

Monoclonal antibodies to dipeptidyl aminopeptidase IV (DAP IV, EC 3.4.14.5) were raised and selectively applied to paraffin-embedded sections of thyroid carcinoma. Five monoclonal antibodies were found to stain paraffin sections of thyroid carcinomas. Using one of these antibodies (44-4), we studied retrospectively aberrant expression of DAP IV in thyroid carcinoma to determine whether immunohistochemical staining with DAP IV antibody is useful in pathological diagnosis. In almost all cases of thyroid follicular and papillary carcinoma, tumour cells were positive (99.0 per cent) with DAP IV, whereas the cases of follicular adenoma showed a low incidence (27.1 per cent) of positive staining. Follicular adenoma with incomplete capsular invasion had a higher positive incidence (50 per cent) than follicular adenoma without incomplete capsular invasion (9.6 per cent). In positive staining cases previously diagnosed as benign tumours, 11 benign cases reacting positively with DAP IV were rediagnosed as carcinoma after re-examination of more thyroid paraffin block sections or serial sections. These findings suggest that DAP IV monoclonal antibody is very useful in distinguishing thyroid follicular carcinoma from follicular adenoma.

Adenoma

Interchromosomal gene conversion as a possible mechanism for explaining divergence patterns of ZFY-related genes.

The divergence pattern of mammalian ZFY-related genes from human (ZFY and ZFX) and mouse (Zfy-1 and Zfx) was reexamined on the basis of nucleotide substitutions at the synonymous codon-alternating positions. It is possible to explain the unusual divergence pattern of the mammalian Y-linked ZF genes by interchromosomal gene conversion by X-linked ZF genes. Furthermore, the rates of evolution of mammalian X- and Y-linked ZF genes were shown to agree well with those expected from our model.

Animals

Increase of serum somatomedin C in hyperthyroid patients with pregnancy.

In thyrotoxic women with pregnancy, serum somatomedin C (SmC) concentration was markedly elevated (mean +/- SD 13.57 +/- 4.66 U/ml) compared to thyrotoxic women without pregnancy (1.24 +/- 1.09 U/ml), non-pregnant euthyroid women previously treated for hyperthyroidism (0.87 +/- 0.30 U/ml), normal subjects with pregnancy (6.08 +/- 3.36 U/ml) and pregnant euthyroid women previously treated for hyperthyroidism (5.98 +/- 1.52 U/ml). Since SmC/growth hormone ratio was significantly more in thyrotoxic pregnant women than in normal pregnant women and euthyroid pregnant women previously treated for hyperthyroidism, and since human placental lactogen (HPL), human chorionic gonadotropin (HCG) and prolactin (PRL) do not crossreact with SmC antibody, it is suggested that excess thyroid hormone during pregnancy results in excessive hepatic somatomedin C production.

Adult

Peroxidase and coupling activities of thyroid peroxidase in benign and malignant thyroid tumor tissues.

The coupling activity of thyroid peroxidase (TPO) in thyroid glands from patients with benign adenoma, papillary carcinoma, and diffuse goiter (Graves' disease) was measured for the first time, in addition to the peroxidase activity of these tissues. The peroxidase activity of TPO in the mitochondria-microsomes fraction was measured with guaiacol or iodide as the second substrate. In the case of papillary carcinoma, the mean protein-based specific activity obtained by the guaiacol assay was about 1/7 of that of diffuse goiter. The iodide oxidation activity of carcinoma was very low, about 1/25 [corrected] of that in diffuse goiter and 1/70 of that in adenoma. The peroxidase activity in adenoma was almost similar in the guaiacol oxidation assay and approximately one half in the iodide oxidation assay as compared with that in diffuse goiter. There was a close correlation between the guaiacol and iodide oxidation assays in individual patients with adenoma and diffuse goiter, but not in patients with papillary carcinoma. The coupling activity of TPO was measured with thyroglobulin purified from pooled toxic diffuse goiters and chemically iodinated to contain little additional T3 and T4. The specific coupling activity of TPO in mitochondria-microsomes from carcinoma was significantly lower (about 1/5) than that of diffuse goiter, and the activity in adenoma was not significantly different (about 1/2) from that of diffuse goiter. The data of coupling activities has a close correlation with that of peroxidase activities in individual patients with adenoma but not in patients with carcinoma. Based on these findings, the qualitative abnormality of TPO and its relation to the cold 123I scintigram in thyroid tumors are discussed.

Adenoma

Thyroid-stimulating antibodies and thyroid stimulation-blocking antibodies during the pregnancy and postpartum period: a case report.

This report describes a unique pattern of changes in thyroid function and thyroid antibodies in a woman during the course of two pregnancies and two postpartum periods. A 25-year-old woman developed hypothyroidism in the postpartum period after the delivery of her first child. She was found to have potent thyroid stimulation-blocking antibodies (TSBAb) in the serum. One year later, she became pregnant again, and during the pregnancy, TSBAb had decreased to an undetectable level. She gave birth to the second healthy child and developed postpartum thyrotoxicosis, probably due to destruction of the thyroid gland, which gradually resolved. In this postpartum period, serum TSBAb levels increased. Eight months postpartum, she developed what appeared to be Graves' disease with an elevated 123I-thyroid uptake. Serum thyroid-stimulating antibodies (TSAb) were found at that time, and the TSBAb had disappeared from her serum.

Adult

Decreases in alpha beta T cell receptor negative T cells and CD8 cells, and an increase in CD4+ CD8+ cells in active Hashimoto's disease and subacute thyroiditis.

We examined peripheral lymphocyte subsets in patients with autoimmune thyroid disease, or subacute thyroiditis, in the active stage when possible. During destructive thyrotoxicosis arising from alpha beta T cell receptor (TCR) negative T (WT31-CD3+) cells and CD8 (CD4-CD8+) cells decreased and those of CD4+CD8+ cells increased slightly, resulting in proportional increases in CD4 (CD4+CD8-) cells, non-T, non-B (CD5-CD19-) cells, and the CD4/CD8 cell ratio. Changes were similar in active subacute thyroiditis. During stimulative thyrotoxicosis in active Graves' disease, the numbers of such T lymphocyte subsets were not changed, but only the number of CD5+ B (CD5+CD19+) cells increased markedly, resulting in proportional decreases in total T (CD3+) cells, alpha beta+ TCR T (WT31+CD3+) cells, CD8 cells, and non-T, non-B cells. A serial study of some of the patients showed opposite changes in alpha beta TCR- T cells, the CD4/CD8 cell ratio, and CD5+ B cells between the active stages of Graves' and Hashimoto's diseases. alpha beta TCR- T cells were mostly gamma delta TCR+ T (IIF2+ CD3+) cells in these patients. These data suggest that alpha beta TCR-T (gamma delta TCR+ T), CD8, and CD4+ CD8+ cells are important in thyroid destruction in Hashimoto's disease and subacute thyroiditis, and that CD5+ B cells are important in thyroid stimulation in Graves' disease.

Adult

The role of thyroid stimulating antibody (TSAb) in the thyroid function of patients with post-partum hypothyroidism.

OBJECTIVE: We investigated the association between thyroid function and the biological activities of thyroid stimulating antibodies (TSAb) and thyroid stimulation blocking antibodies (TSBAb) in patients with post-partum hypothyroidism. DESIGN: A prospective study. PATIENTS: We studied 25 patients with post-partum hypothyroidism who visited our thyroid clinic during the period from 1985 to 1990. MEASUREMENTS: We measured TSH binding inhibitory immunoglobulin (TBII) and TSAb activity at the initial presentation of each of the 25 patients. Women found to have elevated TSAb activity were followed up. Upon finding negative TSAb activity along with positive TBII activity in the serum at the initial presentation, we measured TSBAb activity. Women found to have elevated levels of TSBAb at the initial presentation were also followed up. RESULTS: Elevated TBII activity was found in six of the 25 patients, as was high TSAb activity (205-2651%, normal 55.0-145.0%) in five of these six and in one other patient at the initial presentation. Markedly elevated TSBAb activity (89%) was found in one TBII positive patient. We were able to follow up serially five TSAb positive patients and the TSBAb positive patient over periods ranging from 11.5 to 26.5 months post-partum. The maximal value of TSAb activity was observed at the initial presentation in all TSAb positive patients, following which the activities gradually decreased. One of these patients developed Graves' hyperthyroidism associated with high TSAb activity (1223%) at 10.5 months post-partum. One of the other patients was restored to euthyroid with elevated TSAb activity (279%), but thereafter developed hypothyroidism in conjunction with the disappearance of TSAb activity at 26.5 months post-partum. In the other two patients, normalization of thyroid function was observed with elevated TSAb activity. Thereafter, thyroid function remained within the normal range even with the disappearance of TSAb activity. In the other patient, normalization of thyroid function was observed at 11.5 months post-partum, 3 months after the disappearance of TSAb activity. In the TSBAb positive patient, TSBAb activity decreased to 21% by 17.5 months post-partum associated with normalization of thyroid function. CONCLUSION: The present study demonstrates the presence of elevated levels of TSAb activity in some patients with post-partum hypothyroidism. In these patients, Graves' hyperthyroidism may be induced by TSAb activity, and hypothyroidism may reoccur with the disappearance of the TSAb activity. Furthermore, post-partum hypothyroidism may be due to increased TSBAb activity in some patients.

Antibodies

Piriform sinus fistula and the ultimobranchial body.

Piriform sinus fistulae are an underlying abnormality common in patients with acute suppurative thyroiditis. The fistulae arise from the hypopharynx, and end in or adjacent to the thyroid lobe. These congenital fistulae seem to be remnants of one of the pharyngeal pouches in embryonic development, but their exact origin is still controversial. Resected specimens of the thyroid glands and fistulae from 15 patients were examined immunohistochemically with rabbit antisera to human calcitonin and thyroglobulin. The fistulae were lined by squamous, columnar or ciliated epithelium, and sometimes formed branches in the thyroid lobe. Near the branches solid cell nests existed. Mucous glands, follicular structures and thymic tissue were found in the fistula. The follicular structures stained for thyroglobulin. Immunostaining for calcitonin revealed aggregates of many C cells in the thyroid near the fistula. A few calcitonin-positive cells were also found in the fistula. These findings, along with the anatomical relation of the fistulae to major structures of the neck, strongly suggest that the fistulae are remnants related to the ultimobranchial body, and that the fistulae trace the migration route of the ultimobranchial body to the thyroid gland.

Adolescent

Function of DR-positive thyrocytes from patients with Graves' disease: quantitative analysis of thyroid peroxidase content by fluorescent photometry.

A considerable number of thyrocytes in patients with autoimmune thyroiditis ectopically express HLA-DR antigen. Furthermore, it has been reported that interferon-gamma-induced DR-positive thyrocytes in vitro secrete less thyroid hormone in response to TSH stimulation compared with DR-negative ones. However, the function of the intrinsically DR-positive thyrocytes is unknown. To evaluate their function, we stained by immunofluorescence for both DR antigen and thyroid peroxidase (TPO) in thyroid epithelial cells from patients with Graves' disease. We also measured the quantity of DR antigen and TPO using fluorescent photometry. The content of TPO was not significantly reduced in DR-positive thyrocytes compared with that in DR-negative thyrocytes. The TPO content is one measure of thyrocyte function. There was no significant difference between DR-positive and DR-negative thyrocytes. In conclusion, the function of DR-positive thyrocytes in vivo was not suppressed compared with that of DR-negative thyrocytes.

Adult

Thyrotoxicosis after needle aspiration of thyroid cyst.

We report a new type of thyrotoxicosis (postaspiration thyrotoxicosis) that occurred after needle aspiration of thyroid cysts. In a retrospective study five patients with thyroid cysts developed transient thyrotoxicosis without significant symptoms of hyperthyroidism after needle aspiration. These patients had elevated serum thyroid hormone levels with suppressed serum TSH and thyroid radioiodine uptake. The thyroid hormone content in the cystic fluid was greater in patients who developed thyrotoxicosis than in patients who did not. In a prospective study we examined thyroid function tests after needle aspiration in 52 consecutive patients with thyroid cysts and 63 patients with solid thyroid nodules and confirmed an occurrence of postaspiration thyrotoxicosis in a patient with thyroid cyst. Our observation indicates that postaspiration thyrotoxicosis occurs only in patients with thyroid cyst and that the incidence of this disorder is probably less than 1% of patients who undergo thyroid needle aspiration. Although the exact mechanism of elevated serum hormone levels is unknown, an inflammatory process after needle aspiration might have triggered the release of thyroid hormone.

Adult

Epithelial hyperplasia and decreased colloid content of the thyroid gland in triiodothyronine-predominant Graves' disease.

Patients with T3-predominant Graves' disease have an increased serum T3 level despite a normal or even lower level of serum T4 caused by antithyroid drug treatment. This study investigated the morphological characteristics of the thyroid gland in this type of hyperthyroidism. Ultrasound showed a similar thyroid echogenicity in both T3-predominant and ordinary Graves' disease, but thyroid weight was significantly greater in T3-predominant Graves' disease than in the controls [91 +/- 37 g vs. 48 +/- 17 g (mean +/- SD); P < 0.01]. The height of thyroid follicular epithelial cells were significantly greater in T3-predominant Graves' disease than in the controls (9.6 +/- 1.0 vs. 6.4 +/- 1.1 microns), but the epithelial height did not correlate significantly with the serum TSH receptor antibody titers. Epithelial cells occupied 26.4 +/- 10.9% of the total thyroid tissue in T3-predominant Graves' disease, while they occupied only 14.5 +/- 6.8% in the controls. Intracolloidal vacuoles also occupied a significantly greater area in the T3-predominant group (6.6 +/- 3.9% vs. 1.9 +/- 1.0% for controls). These findings suggest that the thyroid gland is more active in T3-predominant Graves' disease and has a more rapid turnover of intrathyroidal iodine than in the ordinary type of Graves' disease.

Adolescent

Comparison of the incidence of association of periodic paralysis and hyperthyroidism in Japan in 1957 and 1991.

Periodic paralysis has been known to be associated with thyrotoxicosis in Japan. The incidence was 8.6% among male and 0.4% among female thyrotoxic patients according to a survey performed in the three major thyroid clinics in Japan in 1957. To determine the changes in the incidence during the intervening 34 years, the same type of survey was carried out again in 1991 at the same three major thyroid clinics previously involved. The incidence of paralysis in 1991 was 4.3% among male and 0.04% among female thyrotoxic patients, indicating more than a 40% decrease in the incidence. The possible cause of the decrease is related to the changes in food consumption, namely, to the fact that less carbohydrate and more potassium were taken in 1991 than in 1957.

Diet

Development of Graves' disease after subacute thyroiditis: two unusual cases.

This report describes two unusual cases of subacute thyroiditis from which Graves' disease with hyperthyroidism developed seven to eight years after complete recovery. The first case is a 45-year-old woman who developed hyperthyroidism seven years after recovering from subacute thyroiditis. This patient had a genetic predisposition to both subacute thyroiditis HLA-BW35 and Graves' disease (HLA-BW46). The second case is a 60-year-old woman who developed hyperthyroidism eight years after the episode of subacute thyroiditis; her HLA showed neither BW 35 nor BW 46. It has been reported that if hyperthyroidism is to develop following subacute thyroiditis it occurs within one year. Our observation indicates that it may occur seven or eight years later.

Female

Expression of dipeptidyl aminopeptidase IV activity in thyroid carcinoma.

Dipeptidyl aminopeptidase IV activity staining was performed in various thyroid tissues to evaluate this enzyme activity as a thyroid tumor marker. A total of 195 thyroid tissues were tested for their enzyme activity expression. All papillary and follicular carcinomas, 40 cases and 3 cases, respectively, showed enzyme activity, although two other carcinomas, one medullary and one anaplastic, were not stained. Follicular adenoma expressed enzyme activity in 4 of 26 cases. Fifty-two cases with adenomatous goiter, 54 with Graves' disease and 13 with chronic thyroiditis were judged to be negative. Five normal thyroids expressed no activity except for occasional positive staining of capillary endothelia. These data suggest that dipeptidyl aminopeptidase IV activity staining is very useful for pathological diagnosis of thyroid tumors.

Dipeptidyl Peptidase 4

Monocytoid B-cell lymphoma arising in extranodal organs.

Six cases of monocytoid B-cell lymphoma (MBCL) developing in extranodal sites (thyroid, three; stomach, two; rectum, one) are described. Patients were all women aged 46 to 65 years (median, 53 years). Three patients with thyroid lymphoma presented with an increasing goiter, two with positive serum antithyroid antibodies, and one patient had chronic lymphocytic thyroiditis (CLTH). The histologic type of surgically resected specimens was a diffuse proliferation of atypical lymphoid cells with monocytoid appearance, i.e., abundant pale cytoplasm with distinct cell border and small reniform nucleus. These cells were CD20+, 22+, 24-, 9- showing their B-cell origin. The monoclonal nature of the proliferating cells was confirmed by restricted expression of immunoglobulin (Ig) light chain and/or gene rearrangement study in three cases. Two cases of thyroid lymphoma in which the monoclonality could not be confirmed had histologic appearances characteristic of malignant lymphoma. All three patients with gastric or rectal lymphoma had reactive lymphoid hyperplasia (RLH) near the tumors. These findings showed presence of MBCL in the extranodal sites with invariable coexistence with lymphoid follicles formed by CLTH in thyroid or RLH in stomach and rectum.

Aged