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R Y Osamura

Publications and source records attributed to R Y Osamura.

At least 73 records · Page 4Linked to original sources
PubMed1998

Serous borderline ovarian tumor with functioning stroma in a postmenopausal woman: immunohistochemical analysis of steroidogenic pathway.

An epithelial ovarian tumor with estrogenic manifestations (vaginal bleeding, vaginal softening) was encountered in a 70-year-old woman. The preoperative serum levels of estrone, estradiol, and testosterone were elevated. A right ovarian serous papillary tumor of borderline malignancy was removed and found to have a cellular, focally luteinized stroma. Steroidogenic enzymes, including 3beta-hydroxysteroid dehydrogenase and P450 cytochromes specific for cholesterol side-chain cleavage (P450scc), 17alpha-hydroxylation (P45017alpha), and aromatization (P450arom), were immunohistochemically demonstrated in the stromal cells. Immunohistochemical evaluation of these enzymes suggest significant functional differences among the enzymatically-activated stromal cells. That only rare stromal cells were immunoreactive for P450arom suggests that most of the testosterone synthesized in the tumor is extragonadally converted to estrogen, resulting in tumor-associated estrinism.

3-Hydroxysteroid Dehydrogenases↗
PubMed1998

Expression of Pit-1 mRNA and activin/inhibin subunits in clinically nonfunctioning pituitary adenomas. In situ hybridization and immunohistochemical analysis.

The pituitary-specific transcriptional factor Pit-1 is known to play a role in the development and differentiation of pituitary cells. Recent investigations have suggested a role for this transcriptional factor in pituitary adenomas, especially growth hormone (GH)- and prolactin (PRL)-secreting pituitary adenomas. In this study we analyzed the expression of Pit-1 mRNA and its protein in 24 clinically nonfunctioning pituitary adenomas in comparison with normal pituitary glands using in situ hybridization (ISH) and immunohistochemistry (IHC). The interaction between inhibin/activin, a member of the transforming growth factor-beta family, and Pit-1 was also studied. Immunohistochemically, Pit-1 protein was detected in 9 of 24 adenomas (37.5 %), and 8 of these 9 were also positive for the alpha subunit of glycoprotein (alphaSU). The expression of Pit-1 mRNA was detected in 14 of 24 (58.3%) clinically nonfunctioning adenomas, and it was found in all cases which expressed the Pit-1 protein. By the combined ISH and IHC method, Pit-1 mRNA was frequently observed in alphaSU-immunopositive cells in adenomas. The inhibin/activin alpha subunit was detected in all 24 adenomas and the betaA subunit was detected in 13 of 24 adenomas. The inhibin/activin betaA subunit was detected frequently with Pit-1 mRNA. From our observations, the inhibin/activin betaA subunit in nonfunctioning adenomas may have related the expression of Pit- mRNA in these adenomas.

Activins↗
PubMed1998

Localization of prohormone convertases 1/3 and 2 in the human pituitary gland and pituitary adenomas: analysis by immunohistochemistry, immunoelectron microscopy, and laser scanning microscopy.

Prohormone convertase (PC) 1/3 and PC2 are involved in post-translational processing of endocrine tissues, including the pancreatic islets and pituitary glands. Our immunohistochemical studies disclosed the presence of PC1/3 and PC2 in non-neoplastic pituitary glands, especially in corticotrophs, gonadotrophs, and thyrotrophs. Among 58 pituitary adenomas obtained by trans-sphenoidal surgery, adrenocorticotropin (ACTH)-secreting adenomas showed a high incidence of the presence of PC1/3 and PC2, i.e., nine of nine cases were positive for ACTH. Five of nine cases showed consistency between PC2 localization and alpha-melanocyte stimulating hormone immunoreactivity, which suggests the functional correlation between PC2 and the processing of ACTH. In four cases, we observed inconsistency in immunolocalization, which suggested the possibility of inactive PC2 and abnormal processing of alpha-melanocyte stimulating hormone. The high incidence of PC1/3 and PC2 in nonfunctioning adenomas might be related to the processing of chromogranin A.

Adenoma↗
PubMed1997

Application of confocal laser scanning microscopy (CLSM) to visualize prolactin (PRL) and PRL mRNA in the normal and estrogen-treated rat pituitary glands using non-fluorescent probes.

In the present study, we performed concomitant visualization of immunohistochemistry (IHC) and in situ hybridization (ISH) on the materials processed for conventional light microscopic specimens using non-fluorescent Confocal Laser. Scanning Microscopy (CLSM). CLSM was used in the reflection confocal mode using horseradish peroxidase (HRP)-3-3'diaminobenzidine (DAB)-osmium (osmium black) and nitroblue tetrazolium (NBT) as non-fluorescent detection methods (probes). To obtain clearer images of the organelles, images that were built up as electronic signals in CLSM were processed in an image analysis system (IAS). By using the combination of CLSM and IAS, in IHC, immunohistochemical localization of prolactin (PRL) was in well-developed lamellar or whorling rough endoplasmic reticula (RER), Golgi apparatus, and secretory granules. With ISH, the expression and distribution of PRL messenger ribonucleic acid (mRNA) was observed in a fashion suggesting polysome-like structures on RER. These observations were confirmed by immunoelectron microscopy and electron microscopic ISH. The herein-described method is expected to be useful to perform the concomitant observation of IHC and ISH at subcellular levels using the conventional light microscopic specimens.

Animals↗
PubMed1997

Transcription factors in normal and neoplastic pituitary tissues.

Transcription factors are proteins that bind to regulatory elements in DNA and have critical roles in gene regulation during development, in cellular growth and differentiation. The four major groups of transcription factors have been classified according to the motif in the DNA-binding domains and include: (1) the helix-turn-helix group, which includes the Pit-1/GHF-1 (Pit-1) transcription factor; (2) the zing finger group, which includes estrogen and other steroid hormone receptors; (3) the leucine zipper group, which includes c-fos protooncogene, and (4) the helix-loop-helix group, which includes the c-myc oncogene. Members of all four groups have been described in normal and neoplastic anterior pituitary gland tissues. Pit-1 has been shown to regulate prolactin (PRL), growth hormone (GH), and thyroid-stimulating hormone (TSH) cells during development and differentiation. Genetic defects in this transcription factor have led to specific diseases in rodents and humans such as dwarfism and cretinism. Estrogen receptor (ER) protein plays a critical role in the regulation of gene expression in some anterior pituitary cells. There is a differential distribution of ER in anterior pituitary cells and tumors; PRL, gonadotroph, and null cell tumors are the principal adenomas expressing ER. The protooncogene c-fos is regulated by estrogen in various tissues, linking the regulation of one transcription factor by another transcription factor with a different motif. The c-myc oncogene has been detected in the pituitary gland and in some pituitary tumors, although the exact role of this oncogene in pituitary tumor development is uncertain. Because of the critical role that transcription factors play in pituitary cell development and differentiation, we can anticipate many more studies to elucidate their many functions in normal and neoplastic pituitary tissues.

Animals↗
PubMed1997

Excessive formation of basement membrane substance in clear-cell carcinoma of the ovary: diagnostic value of the "raspberry body" in ascites cytology.

Formation of basement membrane-like substance or so-called collagen core was characteristic of clear-cell carcinoma of the ovary in ascites cytology. The hyaline extracellular material was stained light green in Papanicolaou smears and pinkish to purplish red in Giemsa preparations and was frequently observed within the cancer cell clusters in all ten samples of clear-cell carcinoma. Such a structure termed "raspberry body" was focally seen in one of 30 specimens of serous cystadenocarcinoma and one of 30 samples containing reactive mesothelial cells. The "raspberry body" was not found in ascitic fluid from ten patients with mucinous cystadenocarcinoma and two with endometrioid carcinoma. Overproduction of the acidic-charged basement membrane substance was confirmed by 1) cytochemical positivity for periodic acid-Schiff, alcian blue (pH 2.5 or pH 1.0), colloidal iron, and periodic acid-methenamine silver, 2) immunocytochemical demonstration of laminin and type 4 collagen, and 3) ultrastructural identification of excessive formation of the basal lamina. Recognition of the "raspberry body" helps cytopathologists make a cytologic diagnosis of this chemotherapy-resistant malignancy disseminated in ascitic fluid.

Adenocarcinoma, Clear Cell↗
PubMed1997

Malignant carcinoid tumor of the anterior mediastinum metastasis to a prolactin-secreting pituitary adenoma: a case report.

BACKGROUND: Although the pituitary gland is known to harbor metastatic deposits, metastasis from a carcinoid tumor is extremely rare. Metastasis to a pituitary adenoma also is an infrequent occurrence. CASE REPORT: A case of malignant carcinoid tumor of the anterior mediastinum with metastasis to a prolactin-secreting pituitary adenoma is presented in this 46-year-old woman. This metastatic pituitary tumor demonstrated a high proliferative potential. CONCLUSION: To our knowledge, this case represents the first documentation of metastasis from a malignant carcinoid tumor to a pituitary adenoma.

Carcinoid Tumor↗
PubMed1997

Immunohistochemical detection of human natural killer cell like immunoreactivity in human pituitary adenomas, using monoclonal antibody NK-1.

Natural killer (NK) cells are specialized lymphocytes which are characterized as non-T and non-B cells, as they lack classic T and B cell surface markers. Recently, NK like immunoreactivity has been identified in endocrine and neuronal tissues as well as in the tumors derived from the neuroectoderm and neuroendocrine system. We examined the expression of NK-1 like immunoreactivity in 6 normal pituitary glands and in 55 cases of neoplastic pituitaries (16 growth hormone (GH) producing adenomas, 14 prolactin (PRL) producing adenomas, 4 thyrotropin (TSH) producing adenomas, 5 adrenocortocitropin (ACTH) producing adenomas and 16 non-functioning adenomas) immunohistochemically. The expression of the S-100 protein, which is a marker for folliclo-stellate (FS) cells, which have been reported to secrete cytokines as immuno-endocrine modulators, were also examined. In normal pituitary glands, NK-1 was detected in all 6 tissues in the cytoplasm of about 5-10% of the anterior pituitary cells. By serial sectioning and double immunostaining, NK-1 immunopositivity was frequently found to be localized in ACTH cells. The colocalization with other anterior pituitary hormones such as GH. PRL, the beta-subunit of luteinizing hormone (LH beta), follicle stimulating hormone (FSH beta). TSH beta and alpha-subunit of glycoprotein (alpha SU) was not observed. The S-100 immunopositive FS cells, which were scattered among hormone producing cells, were closely associated with NK-1 immunoreactive cells in the normal pituitaries. Among the 55 cases of pituitary adenomas, NK-1 was present in all the types of pituitary tumors, and a total of 33 (60.0%) contained NK-1 positive tumor cells. The frequency of NK-1 immunoreactivity in the individual adenoma types was; 14 of 16 GH producing adenomas (87.5%), 7 of 14 PRL producing adenomas (50%). 3 of 4 TSH producing adenomas (75%), 3 of 5 ACTH producing adenomas (60%), and 5 of 16 nonfunctioning adenomas (31.3%). By double immunostaining, NK-1 was found to be frequently colocalized with ACTH in ACTH producing adenomas, and was colocalized with PRL in PRL producing adenomas, or with GH, PRL or the alpha-subunit in GH producing adenoma cells. NK-1 immunoreactive cells were observed in close association with S-100 immunopositive FS cells in the adenomas. Our results may indicate that NK-1 positive cells may have functions as a paracrine modulators of their neighboring cells, which includes S-100 positive FS cells.

Adenoma↗
PubMed1997

Growth hormone-releasing hormone (GRH)-producing pancreatic tumor with no evidence of multiple endocrine neoplasia type 1.

The characteristic features of a 48-year-old male presenting with isolated acromegaly caused by a GRH-producing pancreatic endocrine tumor bearing no relation to MEN1 was reported. The clinical features, laboratory findings, and sellar enlargement were improved after removal of the pancreatic tumor. The resected pancreatic tumor showed positive GRH immunoreactivity and contained abundant GRH mRNA. This tumor is extremely rare and to date only 10 cases have been reported. In the management of acromegaly, the measurement of GRH is recommended and the search for an ectopic source will prevent unnecessary and potentially ineffective pituitary surgery.

Acromegaly↗
PubMed1997

A case of angiosarcoma of the breast.

This is a case report of a 20-year-old woman who had primary angiosarcoma of the left breast, with metastases to the spleen and ovary. Eight months after detecting a mass in her breast, she underwent mastectomy with biopsy of the ipsilateral axillary lymph nodes, splenectomy and bilateral oophorectomy. Five months after the operation, the patient succumbed to lung metastases. Angiosarcoma of the breast is a rare condition with a poor prognosis, and there are no established chemotherapeutic regimens as yet. Immunohistochemical staining for endoglin, known to be expressed mainly on the surface of endothelial cells, was positive. This suggests the possibility of treating angiosarcoma with anti-endoglin monoclonal antibodies.

Adult↗
PubMed1997

A case of multiple endocrine neoplasia type 2B.

A sporadic case of multiple endocrine neoplasia type 2B in a twenty-six year old man who manifested medullary thyroid carcinoma, multiple mucosal neuromas of the tongue and a marfanoid habitus is reported. At the time of diagnosis, he also had multiple liver and lung metastases. Genetic analysis of his lymphocytes revealed a point mutation in exon 16 of the RET proto-oncogene. Since multiple endocrine neoplasia type 2B has a relatively poor prognosis because of the occasional aggressive behavior of medullary thyroid carcinoma, the necessity of the genetic diagnosis of multiple endocrine neoplasia in the early stage is suggested.

Adult↗
PubMed1997

Subcellular organelle analysis applying confocal laser scanning microscopy to the steroid-producing epithelial ovarian tumor: a technical note.

An epithelial ovarian tumor with steroid production was examined in a 70-year-old postmenopausal female. The stromal cells of this tumor were rather dense and occasionally characterized by luteinization or hyperthecosis, which has been associated with steroidogenesis. Subcellular visualization using confocal laser scanning microscopy (CLSM) successfully led to the identification of 3 beta-hydroxysteroid dehydrogenase (HSD) in both mitochondria-like small particles and endoplasmic reticulum-like linear profiles, and P450-aromatase also in endoplasmic reticulum-like linear profiles, on the three-dimensional images.

Aged↗
PubMed1997

Double squamous cell carcinomas, verrucous type and poorly differentiated type, of the urinary bladder unassociated with bilharzial infection.

A case of a 66-year-old Japanese woman with two synchronous urinary bladder tumors, namely verrucous carcinoma and poorly differentiated squamous cell carcinoma, is described. Both tumors were accompanied by widespread squamous metaplasia in the background and unassociated with bilharzial infection. The poorly differentiated squamous cell carcinoma, having a satellite tumor in its proximity, was large and in an advanced stage. The verrucous carcinoma was small with minimal invasion to the muscularis propria. The boundary between both tumors was well defined, suggesting colliding growth appearance. Immunoexpression of cytokeratins of verrucous carcinoma was similar to that of squamous metaplasia, and significant differences between verrucous carcinoma and poorly differentiated squamous cell carcinoma were demonstrated in their immunoexpression of cytokeratins.

Aged↗
PubMed1997

Immunohistochemical expression of retinoid X receptor isoforms in human pituitaries and pituitary adenomas.

Retinoid X receptors (RXRs) are transcriptional factors that belong to the steroid/thyroid hormone receptor superfamily. There are 3 RXR isoforms-alpha, beta, gamma-known to bind 9-cis-retinoic acid as their ligand. The expression of RXRs in human pituitary glands and pituitary adenomas has not been extensively investigated. To determine whether specific RXR isoforms may play roles in the state of differentiation of pituitary adenomas, we have investigated the immunohistochemical expression of RXR alpha and RXR gamma in 6 nontumorous pituitaries and in 60 different pituitary adenomas using isoform-specific antibodies. In the nontumorous pituitaries. RXR alpha was expressed in the nuclei of almost all cells, while RXR gamma was only expressed in thyrotropin (TSH) cells and in some cells positive for growth hormone (GH) and glycoprotein alpha-subunit (alpha SU) but not in luteinizing hormone (LH) beta-subunit, follicle-stimulating hormone (FSH) beta-subunit, prolactin (PRL) or adrenocorticotropin (ACTH) cells by double immunostaining. All 60 adenomas were RXR alpha positive, and 39 of 60 adenomas (65%) were positive for RXR gamma. The incidence of RXR gamma immunoreactivity in the different adenoma types was: 13 of 16 GH-producing adenomas (81.3%), 9 of 14 PRL-secreting adenomas (64.3%), 6 of 6 TSH-secreting adenomas (100%), 2 of 5 ACTH-secreting adenomas (40%) and 9 of 19 nonfunctioning adenomas (47.4%) including immunohistochemically gonadotropin-subunit-positive adenomas. The colocalization of RXR gamma with the TSH beta subunit, GH and alpha SU in the same adenoma cells was frequently observed, and sometimes RXR gamma was colocalized with PRL, ACTH, FSH beta or LH beta as shown by double immunostaining. We conclude that RXR alpha is expressed in both human pituitaries and pituitary adenomas. In contrast, RXR gamma is expressed more broadly in pituitary adenomas than in normal pituitaries and thus may play a role in the differentiation-specific cell types in the human pituitary both under physiological and pathological conditions.

Adenoma↗
PubMed1997

Cellular proliferation and secretion in secondary hyperparathyroidism during renal failure.

Secondary hyperparathyroidism is one of the severe complications of chronic renal failure. In this study, we investigated the cellular components of parathyroid tissue, with measurements of various serum parathyroid hormone (PTH) types in the circulation, and evaluated their clinical significance in hemodialysis patients. Thirty-eight patients who underwent both subtotal parathyroidectomy and autotransplantation in Tokai University Hospital from 1979 to 1994 were divided into two groups. Group 1 (G-1) was not administered active-type vitamin D3 (VD; 19 patients; 15 males and 4 females), and group 2 (G-2) was administered VD (19 patients; 10 males and 9 females). The parathyroid tissues which were obtained from G-1 and G-2 patients were classified into three classes based on the size of the oxyphilic cell area (class I < 25%, class II 25-50% and class III > 50%). Our results showed that the proliferation index of parathyroid tissues in the oxyphilic cell area was higher in G-2 than that in G-1. Immunohistochemically, MIB-1 staining was more intense than that in the chief cell area in G-2 patients. Moreover, the proliferative index in the same specimen was also higher in the oxyphilic cell area than in the chief cell area. It was suggested that the oxyphilic cells proliferated independently. Furthermore, synthesis of PTH in the oxyphilic cell area was revealed immunohistochemically by the presence of PTH and was confirmed by positive staining of PTH mRNA in the oxyphilic cell area with in situ hybridization. HS(M-terminal)- and C-PTH levels in the serum were significantly higher in class III than in class I (p < 0.01). No significant difference of HS- and C-PTH levels between class II and class III was noted. Moreover, no significant difference of intact-PTH levels was found in all three classes. From the above findings, it was suggested that proliferation of the parathyroid tissues or secretory state of PTH in hemodialysis-maintained patients with secondary hyperparathyroidism, which was closely related to the proliferation of oxyphilic cells, can be more accurately reflected by HS- and C-PTH levels than by the intact-PTH level. Therefore, it was suggested that HS- and C-PTH levels in the serum are important indices for accurate evaluation of the pathology and suitable therapy of secondary hyperparathyroidism, as well as observation of the clinical course.

Adult↗
PubMed1997

Modulation of protein kinases and microtubule-associated proteins and changes in ultrastructure in female rat pituitary cells: effects of estrogen and bromocriptine.

This study focused on the intracellular signal transduction system and microtubule-associated proteins (MAPs), such as MAP-2 and Tau protein. The modulation of these proteins and their correlation with ultrastructural changes were investigated in rat pituitary prolactin (PRL) cells. Adult female Wistar rats were treated with estrogen and bromocriptine and their pituitary glands were removed for analysis of the expression of tubulin, MAP-2, Tau protein, protein kinase C (PKC), and calcium calmodulin (CaM) kinase. Western blot analysis showed that estrogen increased and bromocriptine decreased the expression of PKC alpha, beta 1, beta 2, CaM kinase alpha, beta, MAP-2, and Tau protein. MAP-2 and Tau protein, which are cytosolic proteins, being translated on free ribosomes, were associated with the membrane of whirling rough endoplasmic reticulum (RER) in estrogen-treated cells and dissociated with vesiculated RER induced by bromocriptine. These results suggested that the modulation of MAP-2 and Tau protein may reflect changes of PKC and CaM kinase, and that the quantitative changes and intracellular modulation of MAPs induced by estrogen and bromocriptine, i.e., estrogen-induced association and bromocriptine-induced dissociation of MAP-2 and Tau protein with membrane of RER, may reflect the dynamics of microtubules and are associated with structural changes in the RER and changes in the synthesis and intracellular transport of PRL.

Animals↗
PubMed1997

Retinoid X receptors in the kidney: their protein expression and functional significance.

Retinoid X receptors (RXRs) heterodimerize with 1,25-dihydroxyvitamin D3 (VD) receptor (VDR), and play important roles in VD-regulated transactivation. VD acts on many tissues including kidney for the regulation of calcium homeostasis. In the kidney, the expression of VDR in the tubular cells has been well studied. In contrast, little is known about the localization and the functional significance of RXRs there. In order to elucidate these questions, we first performed immunohistochemical analyses of rat kidney using isoform-specific antimouse RXR antibodies we have previously reported. Interestingly, all RXR isoforms, predominantly RXR alpha, mainly localized to the proximal and the distal tubules, but not to the glomeruli. The serial section staining using anti-VDR antibody showed the colocalization of RXR alpha and VDR in those tubular cells. In order to elucidate the functional significance of endogenous receptors in the tubular cells, we next performed transient transfection studies using the tubular-cell derived Madin-Darby bovine kidney cells, which express both endogenous VDR and RXR. We transfected a reporter plasmid containing direct repeat 3 (DR3) sequence, to which only RXR/VDR heterodimer can bind, and found that VD and 9-cis retinoic acid, as well as VD and RXR selective agonist LG100153, had an additive effect for the DR3 transactivation. Taken together, we speculate that endogenous RXRs co-localize with VDR, and coregulate VD-dependent genes in the tubular cells of the kidney as RXR/VDR heterodimer.

Animals↗