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Biomedical subjects

K Kakudo

Publications and source records attributed to K Kakudo.

At least 55 records · Page 3Linked to original sources
PubMed1999

Overexpression and genetic abnormality of p53 in parathyroid adenomas.

To study the significance of p53 abnormality in parathyroid tumors, 32 parathyroid adenomas and 22 hyperplastic glands from 14 cases of secondary hyperparathyroidism were analysed using immunohistochemistry, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), single-strand conformation polymorphism (SSCP) and DNA sequencing. Immunohistochemical study revealed p53 overexpression in four parathyroid adenomas, of which two showed diffuse and one showed focal nuclear pleomorphism. Genetic analysis disclosed allelic loss in one, and a point mutation (R290H) and a polymorphism (L257 L) in another of the two other adenomas with diffuse nuclear pleomorphism. No abnormalities were discovered in the other two adenomas, although one had a R72P polymorphism in exon 4. There was no evidence of malignancy of the four tumors in either clinical or pathological terms. None of the 22 hyperplastic glands showed p53 overexpression. These results demonstrate that p53 abnormality can occur in benign parathyroid adenomas and is more prevalent in those with nuclear pleomorphism than in those without.

Adenoma↗
PubMed1999

Genetic variants of calcitonin receptor and breast cancer in Japanese.

Calcitonin (CT) inhibits the growth of human breast cancer cell lines and calcitonin receptor (CTR) is expressed in breast cancer lines and breast cancer tissue. In this study, the allele frequencies of the CTR gene were compared in the peripheral blood and tumour from 46 breast cancer patients with 50 peripheral blood samples from Japanese women. The allele frequencies of CTR gene did not differ between them. There was no significant association of CTR allele frequencies in invasive breast carcinomas. These results indicate that allelic variation of the CTR gene is not a significant risk factor for the development of breast carcinoma in Japanese women. Further studies are needed to clarify the role of CT and CTR in human breast tissue.

Journal Article↗
PubMed1999

Clonal emergence in uremic parathyroid hyperplasia is not related to MEN1 gene abnormality.

It is difficult to differentiate between parathyroid neoplasia and hyperplasia. In an attempt to elucidate the clonality of uremic parathyroid hyperplasia and the molecular genetic abnormalities accounting for clonal emergence, we analyzed 20 cases of uremic parathyroid hyperplasia. Clonalities were determined using the X-chromosome-linked human androgen receptor (HUMARA) gene and the phosphoglycerate kinase (PGK) gene, and multiple endocrine neoplasia type 1 (MEN1) gene abnormality was analyzed by studying loss of heterozygosity (LOH) in 11q13 and somatic mutations in the MEN1 gene. As a positive control, a case of MEN1 with Zollinger-Ellison syndrome was analyzed simultaneously. Our analysis revealed that a majority (75%) of the uremic parathyroid hyperplasia tissues, including an autograft with recurrent hyperparathyroidism, was of monoclonal origin. Clonality did not correlate with serum carboxyl-terminal parathyroid hormone (C-PTH) level, calcium level, hemodialytic duration, gland weight or pathological features. Neither LOH in 11q13 nor somatic mutation in the MEN1 gene was detected. For the MEN1 case, a germline mutation (W198X) was detected in exon 3. We concluded that a majority of the uremic parathyroid hyperplasia cases was in fact monoclonal neoplasia. MEN1 gene abnormality played a minor role, if any, in the clonal emergence in uremic parathyroid hyperplasia.

Clone Cells↗
PubMed1999

A case of ectopic thyroid in lateral neck associated with Graves' disease.

Thyroid follicles in the lateral position of the neck are usually thought to represent the metastasis of thyroid carcinoma. Here we present a case of a 28-year-old woman with accessory ectopic thyroid associated with Graves' disease. Despite a history of Graves' disease poorly controlled with large dose propylthiouracil she was found to be pregnant and artificial abortion was planned. Thyroid scintigraphy was carried out, which indicated an uptake into the region above the left lobe as well as into both lobes of the thyroid gland. In order to control hyperthyroidism and to exclude the possibility of metastasis, total thyroidectomy with tumor resection was performed before the artificial abortion. Pathological examinations of the thyroid gland indicated findings compatible with Graves' disease. The lateral neck mass was revealed to be composed of nonneoplastic thyroid tissue, showing similar histological findings to those of the goiter, which were consistent with Graves' disease. Taken together with several previous reports, it appears that there are some cases with lateral ectopic thyroid tissue, whose pathogenetic mechanism remains to be elucidated.

Abortion, Induced↗
PubMed1999

[Consent to enrollment in randomized clinical trials].

Multi-facility joint randomized clinical trials for cancer treatment are the most common method of current clinical study. However, the difference in the rate of participation in multi-facility randomized clinical trials may damage the resulting general validity. Therefore, we studied whether the rate of participation in randomized clinical trials is different between university hospitals and other general hospitals using a questionnaire (with anonymity preserved). There were 744 subjects from university hospitals and 339 from general hospitals participating in the study. The results showed that 10.9 percent of those from university hospitals were willing to participate, against 28.1 percent who were not. Of those from general hospitals (public hospitals in this study) 10.6 percent answered that they would participate and 27.4 percent that they would not. Little difference was found in the rate of participation in randomized clinical trials between university hospitals and other general hospitals. The focus is thus on doctors to solve the possible differences between the facilities in further multi-facility joint studies.

Adolescent↗
PubMed1999

Accumulated basement membrane material in hyalinizing trabecular tumors of the thyroid.

We report here four additional cases of hyalinizing trabecular adenoma of the thyroid and describe the findings of the accumulated basement membrane (BM) material. Focal lumpy depositions of BM material were noted in the stroma of all four tumors and were particularly prominent in two. Antibodies against type IV collagen and laminin strongly immunoreacted with this material, which also showed diastase-resistant periodic acid-Schiff positivity. The ultrastructural findings of accumulated basement membrane was examined in detail. The most striking ultrastructural findings were seen at the periphery of the cell clusters, where the basal aspect of the tumor cells rested on a highly accumulated BM materials displaying mesh-like, fir-branching, or frame-like appearances. Intracytoplasmic BM islands were frequently observed in neoplastic cells. These BM islands were membrane-bounded and focally continuous with the cell surface membrane, suggesting pseudointracytoplasmic depositions of BM material due to marked cytoplasmic infoldings. From the findings, electron microscopic features of accumulated BM material are very characteristic in hyalinizing trabecular adenomas and can be discernible from other histologic types of BM-producing tumors.

Adenoma↗
PubMed1999

Quantitative and qualitative analysis of stain color using RGB computer color specification.

OBJECTIVE: To establish standardized Papanicolaou stain for cytology using RGB color specification. This new method was formerly used in DTP software application for computer color specification. STUDY DESIGN: RGB color specification was taken from a color film, optical constituents of which were made into computer software. Cell samples used in this study were from 100 sputum specimens stained with Papanicolaou stain. We analyzed the color tone of the cytoplasm of squamous cells in the smear. RESULTS: The R and B value of eosinophilic cells were demonstrated statistically by different values between normal, borderline atypical and malignant squamous cells. G and B values of light green-philic cells demonstrated a statistical difference between normal, borderline atypical and malignant squamous cells. No significant differences were found in RGB value between normal, borderline atypical and malignant squamous orangeophilic cells. CONCLUSION: Using our own method of analyzing Papanicolaou-stained sputum, a new quantitative and qualitative analysis of stain color for standardized Papanicolaou stain was introduced.

Carcinoma, Squamous Cell↗
PubMed1999

Functional properties of nociceptive neurons in the nucleus centralis lateralis of the cat thalamus.

We studied functional properties of nociceptive neurons in the thalamic intralaminar nuclei, especially the nucleus centralis lateralis (CL) in urethane-chloralose anesthetized cats. Nociceptive neurons were found in the intralaminar nuclei, i.e. CL, nucleus centralis medialis (CeM) and nucleus parafascicularis (Pf). One third of these nociceptive neurons had their receptive fields throughout the body, including the orofacial area. Namely, they received convergent nociceptive input from the trigeminal and spinal nerve territories. These neurons with widely complex receptive fields were similar to those we found in the middle third of the caudal bulbar reticular formation (RF). Electrical stimulation of the CL antidromically activated about half of the caudal bulbar RF neurons tested. Furthermore, electrical stimulation of the cingulate gyrus antidromically activated some of CL neurons. These findings suggest that most of the CL neurons receiving nociceptive input from throughout the body receive information directly or indirectly via the caudal bulbar RF, and that certain of this information is then conveyed to the cingulate gyrus.

Afferent Pathways↗
PubMed1999

Correlation of E-cadherin and alpha-catenin expression with differentiation of oral squamous cell carcinoma.

The precise mechanism of disruption of cell-cell adhesion in oral squamous cell carcinomas has yet to be established. We therefore sought to clearly this mechanism by investigating expression of both E-cadherin (E-CD) and alpha-catenin (alpha-CAT), which is an intracellular CD-binding molecule, in squamous cell carcinomas of the tongue, gingiva and floor of the mouth using immunohistochemical and immunoblotting techniques. We found that reduced expression of both E-CD and alpha-CAT occurred more frequently in moderately- and poorly-differentiated carcinomas than in well-differentiated specimens (p < 0.001), and this reduced expression showed no regional specificity. Relatively frequent loss of alpha-CAT expression in poorly-differentiated carcinomas was detected by both immunohistochemical and immunoblotting analyses. These findings suggest that E-CD and alpha-CAT are both important regulators of intercellular adhesion, and that the reduction of these molecules is also linked to the process of tumor dedifferentiation.

Antibodies, Monoclonal↗
PubMed1998

Gene rearrangement of immunoglobulin as a marker of thyroid lymphoma.

Thyroid lymphoma occurs most commonly in the thyroid gland in association with Hashimoto's thyroiditis. Histologic findings occasionally cannot distinguish lymphoma from Hashimoto's thyroiditis, which creates a serious problem of whether treatment should be initiated. For this study, we examined 33 lymphoma tissues and 10 thyroid tissues from patients with Hashimoto's thyroiditis for the presence of gene rearrangement of immunoglobulin, which represents clonality of B-cell-derived tumors. Genomic DNA from thyroid tissues was digested with Bam H1 and Hind III restriction enzymes followed by electrophoresis. A Southern blot was performed with an IgH-JH probe or IgL-J kappa probe to detect gene rearrangement. Of the 33 lymphoma tissues, 27 (85%) showed gene rearrangement of immunoglobulin, whereas none of Hashimoto's thyroiditis tissue showed gene rearrangement. Five patients with a positive histologic diagnosis of lymphoma showed a negative gene rearrangement and were treated as having lymphoma. We encountered one case of lymphoma (plasmacytoma) in which gene rearrangement (not histologic findings) was diagnostic. Gene rearrangement of immunoglobulin can be used to detect thyroid lymphoma, particularly when the histologic diagnosis is inconclusive. The sensitivity of detecting thyroid lymphoma by the Southern blot method was about 85% in the present series.

Aged↗
PubMed1998

Clonal analysis helps to differentiate aberrant thyroid tissue from thyroid carcinoma.

A rare case of multiple aberrant of thyroid tissues in the tongue and lymph nodes of the bilateral neck was studied by immunohistochemistry and molecular clonal analysis to determine whether these tissues represent aberrant ectopic thyroid or metastases of a thyroid carcinoma. The thyroid tissues in the tongue and lymph nodes were all of polyclonal origins, consistent with ectopic thyroid in the tongue and bilateral cervical lymph nodes, rather than malignant thyroid tissues. This case shows that molecular clonal analysis can be used to distinguish aberrant thyroid from metastases of thyroid carcinoma.

Adult↗
PubMed1998

Solitary fibrous tumour: significance of p53 and CD34 immunoreactivity in its malignant transformation.

AIMS: To clarify the association of p53 and CD34 expression with development of malignant solitary fibrous tumour we have studied 10 cases of solitary fibrous tumour arising in the pleura, retroperitoneum and pelvic cavity with clinicopathological features of malignancy. METHODS AND RESULTS: Tumours were localized solid masses with or without necrosis in eight and they nearly totally occupied the pleural cavity in two. Basic histology of the tumours was the proliferation of spindle cells arranged in 'patternless' pattern or in interlacing bundles with nuclear atypia and mitotic activities of various degree. In two, high-grade foci were present within low or intermediate-grade tumours. Recurrent tumours also showed more atypical features than primary tumours in two. Immunohistochemical studies showed CD34 positivity in seven, but three of them showed marked diminution or complete loss of CD34 expression in high-grade foci or a recurrent tumour. Three high-grade cases showed totally negative staining for CD34. p53 was strongly expressed in cases with fatal outcome, clinical recurrence, nuclear atypia, high mitotic activity or local invasion, whereas almost negative in benign tumours. CONCLUSIONS: Malignant solitary fibrous tumours may occur de novo or by transformation within benign or low-grade tumours and may be associated with p53 mutation. Although CD34 is a useful marker in the diagnosis of solitary fibrous tumour, one should bear in mind that its expression can be lost in high-grade tumours.

Adult↗
PubMed1998

Somatic mutations in the RET protooncogene in Japanese and Chinese sporadic medullary thyroid carcinomas.

Despite advances in the understanding of the genotype-phenotype correlation in multiple endocrine neoplasia type 2A and 2B (multiple endocrine neoplasia (MEN) 2A, MEN 2B), and familial medullary thyroid carcinoma (FMTC), the frequency and prognostic relevance of RET protooncogene mutations in sporadic medullary thyroid carcinomas (MTCs) remain controversial. To study somatic mutations in the RET protooncogene in Japanese and Chinese sporadic MTCs and to analyze comparatively the correlation between RET mutation and tumor differentiation, we investigated somatic mutations in the RET protooncogene in 20 Japanese and 20 Chinese sporadic MTCs by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Of the 40 sporadic MTCs, 13 had a point mutation in codon 918 of exon 16, a frequency of 32.5%. There was no significant difference in the frequency between Japanese and Chinese sporadic MTCs, as 30% of the Japanese and 35% of the Chinese sporadic MTCs contained this mutation. We did not observe any correlation between the presence or absence of codon 918 mutation and tumor differentiation in either Japanese or Chinese sporadic MTCs. Our findings indicate that the frequency of RET somatic mutations is similar in Japanese and Chinese sporadic MTCs, and the presence or absence of RET mutation does not correlate with the differentiation of sporadic MTCs.

Carcinoma, Medullary↗
PubMed1998

Overexpression of p53 protein correlates with a high risk of malignant transformation of adenomas in patients with multiple colorectal adenomas.

To assess the correlation of p53 oncoprotein expression with the high risk of developing carcinomas in patients with multiple colorectal adenomas, 25 cases with histologic carcinoma in adenoma (CIA) were examined by immunohistochemistry using a monoclonal antibody specific to human p53 protein (wild and mutant). The 25 cases were classified into multiple and single groups. The former contained 13 cases with synchronous multiple colorectal adenomas (one to six adenomas) and adenocarcinoma. The latter included 12 cases with single CIA only. This study revealed an overall incidence of 57.14% of p53 overexpression in carcinomatous lesions and 31.9% in adenomatous lesions, which was statistically significant (P < 0.05). The carcinomatous lesions showed a diffuse staining pattern, whereas the adenomatous lesions showed a focal pattern. A significant finding was that the incidence of p53 overexpression was significantly higher in multiple groups (81.25%) than in single groups (31.43%) in the carcinomatous (P < 0.01) rather than in the adenomatous (P < 0.05) lesions. There were no correlations between p53 overexpression and proliferation activity or carcinoembryonic antigen expression. The results indicate that p53 abnormality may be an important genetic factor responsible for the high risk of developing carcinomas in patients with multiple adenomas.

Adenoma↗
PubMed1998

Extensive intraductal component (EIC) and estrogen receptor (ER) status in breast cancer.

The extensive intraductal component (EIC) of primary breast carcinoma is a special spread pattern observed in the breast. Extensive intraductal component may extend diffusely over the entire breast. Therefore, EIC is considered to be an important risk factor for local recurrence in breast-conserving therapy. However, the pathogenesis of EIC remains uncertain. Whether or not the estrogen receptor (ER) has an influence on its biologic behavior has not been fully studied. A consecutive series of 142 breast carcinomas submitted to the pathology department were examined on step gross sections of 5.0 mm thick. Extensive intraductal component was determined and divided into three types. Estrogen receptor was examined using both immunohistochemistry (ER-IHC) and enzyme immunoassay (ER-EIA). Extensive intraductal component was found in 78 of 138 (56.52%) invasive carcinomas including invasive ductal carcinoma with a predominant intraductal component. Estrogen receptor-IHC positivity was 42.96% (61/142) in the invasive breast carcinoma. Estrogen receptor positivity showed no significant difference between EIC-positive and -negative cases, as well as between EIC and invasive main tumor in the EIC-positive cases. But within the EIC-positive group, ER positivity was found to be higher in the peripheral type of EIC-II and EIC-III than in the central type of EIC-I (P < 0.05). Although ER may not play an essential role in the pathogenesis of EIC, it has shown some significance in the development of peripheral type EIC because of its higher presence in the peripheral type of EIC-II and EIC-III than in the central type of EIC-I.

Antibodies, Monoclonal↗
PubMed1998

Genetic alterations in primary and secondary hyperparathyroidism.

Hyperparathyroidism refers to a term representing a wide spectrum of parathyroid disorders that are characterized by the increased production of parathyroid hormone. Hyperparathyroidism was once thought to be rare but is now more commonly recognized, affecting 1 in 500 women over 40 years of age. Yet the interpretation of parathyroid pathology is still controversial and confusing. Over the past 10 years, genetic changes (ret and menin genes) involved in the pathogenesis of MEN 2 and MEN 1 have been discovered in succession. Different mutations of the calcium-sensing receptor gene have been identified in neonatal severe hyperparathyroidism and familial hypocalciuric hypercalcemia, respectively. The HRPT 2 gene responsible for the development of hereditary hyperparathyroidism and jaw tumors has been localized on the 1q21-31 locus. Several genetic alterations have also been characterized in primary and secondary hyperparathyroidism. Different genetic alterations appear to involve the development of different types of hyperparathyroidism. These novel advances give us new insights into the pathogenesis of hyperparathyroidism and allow better differentiation between the different types of parathyroid disorders.

Adult↗