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Biomedical subjects

R Y Osamura

Publications and source records attributed to R Y Osamura.

At least 55 records · Page 3Linked to original sources
PubMed2000

Pituitary stone--case report.

A 50-year-old male with acromegalic features presented with a pituitary stone in a growth hormone-secreting adenoma. Endocrinological examination showed "low growth hormone acromegaly." The serum growth hormone level responded to the thyrotropin-releasing hormone test and was not suppressed by oral glucose loading. Neuroimaging revealed an adenoma including a large calcification (pituitary stone) located in the right lateral wing. The adenoma with stone was totally removed by transsphenoidal surgery. The patient regained almost normal response of serum growth hormone. Histological examination showed the stone was composed of thick calcification surrounded by necrotic adenoma tissue and chronic hemorrhage. Large intratumoral pituitary stone is very rare, although calcification is sometimes observed in the adenoma capsule. The long history of this disease and previous apoplexy within the tumor may have caused the pituitary stone in this patient.

Acromegaly↗
PubMed2000

Long-term surgical outcome in 16 patients with thyrotropin pituitary adenoma.

OBJECT: Thyrotropin-secreting pituitary adenomas are rare lesions of the endocrinological system. Although introduction of a hypersensitive radioimmunoassay for thyrotropin enables the recognition of inappropriate secretion of this hormone, the aforementioned lesions remain uncommon and unfamiliar to most neurosurgeons. It has been reported previously that surgical cure of thyrotropin-secreting adenomas is more difficult than in other functional adenomas because of the large size and invasive features of the former. However, the long-term outcome after surgery has not been well documented. The authors report on a surgical series of 16 patients with thyrotropin adenoma and the results of long-term follow up. METHODS: Sixteen patients ages 23 to 62 years (12 women and four men) underwent transsphenoidal removal of thyrotropin adenomas between 1983 and 1999. These patients had the syndrome of inappropriate thyrotropin secretion (SITS) with pituitary mass lesions. Four of the patients had undergone previous subtotal thyroidectomy and/or radioiodine thyroid ablation, and 11 had been treated with antithyroid medication. Radiological investigations demonstrated macroadenomas in 14 patients, and 10 of those had cavernous sinus invasion. Surgical findings showed unusually fibrous and firm tumors in 13 (81.2%) of 16 patients. Preoperative octreotide administration was revealed to be effective for serum thyrotropin reduction as well as tumor shrinkage. Transsphenoidal surgery was performed with no morbidity resulting. Surgical remission was achieved in 10 (62.5%) of 16 patients, and total remission was achieved in 14 patients (87.5%) with a combination of additional radiation or medical therapy. In the other two patients, SITS persisted because of tumor rests in the cavernous sinus. Therefore, radiation and/or antithyroid therapy was administered. In the mean follow-up period of 7.5 years (range 11 months-15.8 years), no recurrence of tumor was observed on magnetic resonance images, whereas recurrence of SITS was found in two patients with no tumor regrowth. In addition, coexistent primary hyperthyroidism was found in two other patients despite remission of SITS after surgery. CONCLUSIONS: Transsphenoidal surgery can achieve a good long-term outcome in patients with thyrotropin-secreting pituitary adenomas if surgery is performed before these become larger, invasive tumors. In the authors' experience, thyrotropin-secreting adenomas are fibrous and firm, which makes it difficult to achieve surgical remission. In addition, even satisfactory resection of the tumor sometimes results in recurrence of SITS or hyperthyroid symptoms due to coexistent primary hyperthyroidism. It is emphasized that a careful follow-up review is necessary after surgery, especially in patients with a long preoperative history of hyperthyroidism.

Adenoma↗
PubMed2000

Three-dimensional imaging of tumor angiogenesis.

OBJECTIVE: To three-dimensionally visualize the microvessel environment of tumor angiogenesis by confocal laser scanning microscopy (CLSM). STUDY DESIGN: To reveal underlying mechanisms of tumor angiogenesis, a 7, 12-dimethylbenz(a) anthracene-induced rat cancer model was used. For demonstrating tumor vasculature, fluorescence injection method (FITC-conjugated gelatin solution) was employed. FITC gelatin was injected into the left ventricle of the rat heart. After complete perfusion, the mammary glands were resected, fixed under ice cold conditions and subjected to immunohistochemistry (IHC) for tumor cells. The LSM-410 (Carl Zeiss, Jena, Germany) was employed on thick sections (300-2,000 microns) to elucidate detailed microvessel networks (MVN) and tumor cells. RESULTS: Tumor vasculature on thick sections was clearly detected by CLSM at the maximum focus depth of 2,000 microns. Three-dimensional (3-D), reconstructed images of normal mammary glands showed regular and linear MVN. In DMBA-induced mammary cancer, vascular density of MVN was markedly increased and showed an anastomosing, irregular MVN pattern. Furthermore, focal segmentation and tortuous, branching patterns of microvessels were also seen. CONCLUSION: Application of the fluorescence injection method and IHC using CLSM was very useful for studying the 3-D relationship between tumor angiogenesis and neoplastic epithelial changes. These results suggest that application of this technique is ideal for studying 3-D imaging of tumor angiogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

Expression of Ptx1 in the adult rat pituitary glands and pituitary cell lines: hormone-secreting cells and folliculo-stellate cells.

The pituitary homeobox1 gene (Ptx1) was initially identified as encoding a pituitary-restricted transcription factor for the proopiomelanocortin (POMC) gene. In order to elucidate the expression pattern of the Ptx1 protein, we investigated the localization of the protein in adult rat pituitary gland and in various pituitary cell lines. We produced an antibody specific for Ptxl protein, and confirmed its specificity by Western blot analysis. Immunohistochemically, many nuclei in the anterior pituitary cells as well as in the intermediate cells were positive for Ptxl staining with this specific antibody. Immunohistochemical double staining revealed the presence of Ptx1 not only in all types of hormone-secreting cells but also in some folliculo-stellate (FS) cells. Furthermore, the expression of Ptx1 mRNA was confirmed in various pituitary cell lines and in the FS cell line by using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Our studies indicated that Ptxl may not only play a role as a basic transcriptional factor for production of various hormones, but may also play some important role(s) in FS cells. Possible synergistic actions with other factors remain to be investigated. The novel finding of Ptx1 in FS cells is of particular interest, and may suggest that FS cells and hormone-secreting cells are derived from a common cellular ancestor.

Animals↗
PubMed1999

Distribution of adrenomedullin (AM), proadrenomedullin N-terminal 20 peptide, and AM mRNA in the rat gastric mucosa by immunocytochemistry and in situ hybridization.

Adrenomedullin (AM) is a novel vasorelaxant peptide isolated from pheochromocytoma. Proadrenomedullin N-terminal 20 peptide (PAMP) is a hypotensive peptide generated by posttranslational enzymatic processing of a 185-amino acid pro-AM molecule, the same precursor as AM. In this study, we investigated localizations of these peptides by immunocytochemistry and AM mRNA by non-radioisotopic in situ hybridization followed by the streptavidin and biotin complex (ABC) method and catalyzed signal amplification (CSA) in the rat adrenal medulla and gastric mucosa. In the gastric mucosa, both AM- and PAMP-like immunoreactivities were found in the neuroendocrine cells, but PAMP-positive cells were more abundant than AM-positive ones. By immunoelectron microscopy, AM and PAMP were localized exclusively in the secretory granules. The distribution pattern of AM mRNA-positive cells, only a limited portion of which had AM and/or PAMP, was also similar to that of the two peptides. But AM mRNA was detected also in a few epithelial cells as well as neuroendocrine cells. The two peptides might play an important role in the control of local circulation in the rat stomach.

Adrenomedullin↗
PubMed1999

Pit-1 positive alpha-subunit positive nonfunctioning human pituitary adenomas: a dedifferentiated GH cell lineage?

Pit-1 is a transcription factor which has been reported to regulate differentiation toward GH, PRL and TSH in the anterior pituitary glands. In the human pituitary adenomas, Pit-1 is highly expressed in GH secreting and TSH secreting adenomas as it can well be anticipated. Interestingly, human non-functioning pituitary adenomas also express Pit-1, especially it was expressed in all alpha SU positive nonfunctioning adenomas. The human anterior pituitary cells are special in comparison with rodents in a finding that alpha SU is frequently colocalized with GH. As alpha SU is the first hormone appearing during fetal development in the rodent pituitary glands, it may be postulated that alpha SU Pit-1 positive cells undergo differentiation in the GH cell lineage. From this background, this paper proposes that "alpha SU positive Pit-1 Positive" cells are the ones in the GH cell lineage, more specifically a dedifferentiated cell lineage toward alpha SU/GH/Pit-1.

Adenoma↗
PubMed1999

Pituitary somatotroph adenoma producing growth hormone (GH)-releasing hormone (GHRH) with an elevated plasma GHRH concentration: a model case for autocrine and paracrine regulation of GH secretion by GHRH.

An acromegalic patient with a pituitary somatotroph adenoma associated with an extremely elevated plasma GHRH concentration is presented. The preoperatively high concentration of plasma GHRH returned to the normal level after successful removal of the adenoma. GHRH production and GHRH gene expression were confirmed in the adenoma by studies including immunohistochemistry and in situ hybridization. Expression of GHRH receptor messenger ribonucleic acid was verified by in situ hybridization. Immunohistochemical double staining for GH and GHRH revealed their colocalization in single adenoma cells. These findings confirmed the autocrine or paracrine regulation of GH production by endogenous GHRH from the adenoma cells. GHRH synthesis in the pituitary gland has recently been demonstrated, however, there have been no previous reports of a GHRH-producing pituitary somatotroph adenoma associated with an elevated plasma GHRH concentration. The existence of this GHRH-producing adenoma suggests a possible role of locally generated GHRH in the progression of somatotroph adenomas, i.e. the monoclonally established somatotroph adenomas develop further under the influence of locally produced GHRH. The demonstration of GHRH production by this somatotroph adenoma is of importance in clarifying the autocrine or paracrine regulation of GH production and the progression of human somatotroph adenomas.

Acromegaly↗
PubMed1999

Expression of Rab3, a Ras-related GTP-binding protein, in human nontumorous pituitaries and pituitary adenomas.

Rab proteins are low molecular weight GTP-binding proteins. Among these proteins, the Rab3 isoforms are considered to be involved in the exocytosis of synaptic vesicles and secretory granules in the central nervous system and anterior pituitary gland. In recent reports, the expression of Rab3 isoforms in anterior pituitary glands of mammalian species was extensively investigated. In the present study, we investigated the localization of Rab3 protein in 5 human nontumorous pituitaries and 114 human pituitary adenomas using immunohistochemical methods. In five human nontumorous pituitaries, Rab3 protein was expressed in the cytoplasm of anterior pituitary cells. Double staining for anterior pituitary hormones revealed the expression of Rab3 in growth hormone-secreting cells, but rare expression was observed in the other anterior pituitary hormone-secreting cells. Among the pituitary adenomas, 71 (62.3%) of 114 pituitary adenomas were positive for Rab3. Among the different pituitary adenoma types, the incidence of Rab3 immunopositivity was highest in growth hormone-secreting adenomas (100%), followed by adrenocorticotropic hormone-secreting adenomas (71.4%), thyroid-stimulating hormone-secreting adenomas (57.1%), nonfunctioning adenomas (56.0%), and prolactin-secreting adenomas (33.3%). After an embedding immunoelectron microscopic study, Rab3 was localized along the limiting membrane of secretory granules in the Rab3-positive pituitary adenomas. Western blotting showed the molecular weight of Rab3 to be 25 kDa in the pituitary adenomas, which were immunohistochemically positive for Rab3 protein. These results suggested that Rab3 might be involved in regulating the exocytosis of secretory granules of the anterior pituitary cells, especially growth hormone-secreting ones, which are particularly characterized by densely granulated cytologic features.

Adenoma↗
PubMed1999

Renal expression of insulin-like growth factor-l in acute renal failure: a preliminary report.

Renal expression of insulin-like growth factor-I (IGF-I) was examined in the specimens obtained at renal biopsy from five patients with acute renal failure (ARF) at the recovering phase. IGF-I peptide and mRNA were demonstrated in the cytoplasm of the epithelial cells of focal proximal tubules in four patients in whom renal function had been ameliorating. The stainings of IGF-I peptide and mRNA were intense in patients with favorable prognosis. Either IGF-I immunoreactivity or mRNA was not detected in the renal tissues in five cases with chronic renal insufficiency and four patients with renal carcinoma. Our preliminary findings suggest that IGF-I is locally produced in the kidney during the recovery period of ARF and might play roles in the repair processes, and extend the experimental observations in animal models into human pathophysiology.

Acute Kidney Injury↗
PubMed1999

Immunohistochemical expressions of prohormone convertase (PC)1/3 and PC2 in carcinoids of various organs.

In order to clarify the expression of prohormone convertase (PC) 1/3 and PC2 in various carcinoids and non-carcinoid endocrine tumors, we performed indirect immunoperoxidase staining on total of 19 cases of carcinoids (9 cases of bronchial carcinoids, 4 cases of rectal carcinoids, 4 cases of gastric carcinoids and 2 cases of bile duct carcinoids). Our study also included 7 non-carcinoid endocrine tumors. Seventy-nine% and 26% of carcinoids highly or strongly expressed positive staining for PC1/3 and PC2, respectively. High and strong expressions (3+ or 4+) of both PC1/3 and PC2 were noted in only bronchial carcinoids. Strong expressions for only PC1/3 were noted in rectal carcinoids. Bile duct carcinoids also demonstrated higher expressions of PC1/3 than those of PC2. These results suggested that high expressions of both PC1/3 and PC2 in bronchial carcinoids might reflect their diverse and frequent peptide production. The expressions of PC1/3 mRNA and PC2 mRNA detected by in situ hybridization in the bronchial carcinoids and rectal carcinoids were correlated with immunoexpressions of both of the antigens. The granular immunoexpression pattern of PC1/3 and PC2 visualized by confocal laser scanning microscopy would suggest the site of post-translational processing in the secretory granules. Non-carcinoid endocrine tumors showed low expressions (+ or 2+) of PC1/3 and PC2, except for thyroid medullary carcinoma showing high immunoexpression of PC1/3. Other non-carcinoid endocrine tumors (parathyroid adenomas and adrenal pheochromocytomas) revealed low immunoexpressions for both PC1/3 and PC2.

Adolescent↗
PubMed1998

Assessment of the proliferative activity of superficial esophageal carcinoma using MIB-1 immunostaining for the Ki-67 antigen.

BACKGROUND AND OBJECTIVES: Lymph node metastasis or vascular invasion may occur in superficial esophageal squamous cell carcinoma when it invades to or into the muscularis mucosae. Therefore, the correlation between histopathological characteristics and the proliferative activity of superficial esophageal carcinoma was investigated. METHODS: Thirty-eight cases of esophageal squamous cell carcinoma, including 14 cases of mucosal carcinoma and 24 cases of submucosal carcinoma, who underwent surgical resection without preoperative treatment, were studied using monoclonal antibody MIB-1 for the Ki-67 antigen immunohistochemically. The labeling index (LI) was calculated with a computed image analyzer. RESULTS: The LI of MIB-1 at the invasive tip of m3 carcinoma was significantly higher than that of m1 or m2 carcinoma (P < 0.01). The LI at the invasive tip was significantly higher than that at the core of sm2 (P < 0.05) and submucosal carcinoma overall (P < 0.01). The LI values at both the invasive tip and core of poorly differentiated carcinoma in submucosal carcinoma were higher than that of well or moderately differentiated carcinoma with a significant difference (P < 0.05). The LI at the invasive tip of submucosal carcinoma with lymph node metastasis or lymphatic invasion was significantly higher than that without them (P < 0.05). CONCLUSION: Proliferative activities of cancer cells in superficial esophageal squamous cell carcinoma, immunostaining with the MIB-1, were related to the depth of invasion, differentiation, lymph node metastasis, and lymphatic invasion with a significant difference.

Antibodies, Monoclonal↗
PubMed1998

An improved ultrastructural double-staining method for rat growth hormone and its mRNA using LR White resin: a technical note.

An improved new method for the simultaneous visualization of mRNA and encoded protein in LR White resin-embedded specimens is described. This pre-embedding electron microscopical in situ hybridization (procedure) localized rat growth hormone mRNA specifically as high electron-density products on the polysomes of the rough endoplasmic reticulum. A subsequent post-embedding immunoreaction, using protein A colloidal gold particles, identified growth hormone as gold particles both in the cisternae of the rough endoplasmic reticulum and on the secretory granules. In our previous report, we used Epon resin for tissue embedment, which required an etching process using hydrogen peroxide or sodium periodate for immunoreactivity retrieval. In general, osmification and embedment in Epon resin are reported to decrease the immunoreactivity of the targeted protein, and the etching process using hydrogen peroxide or sodium periodate results in deosmification and shades off the signals of mRNA. To resolve these problems, we have recently used LR White resin for tissue embedment. In LR White resin-embedded tissues, retrieval of immunoreactivity using hydrogen peroxide or sodium periodate is not required, and, therefore, the gradation of the signals of mRNA can be avoided.

Acrylic Resins↗