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Biomedical subjects

Y Osamura

Publications and source records attributed to Y Osamura.

At least 19 recordsLinked to original sources

Selective insufficiency of IFN-gamma secretion in patients with hyper-IgE syndrome.

BACKGROUND: Hyper-immunoglobulin E (IgE) syndrome is a complex immune deficiency characterized by chronic eczematous dermatitis, recurrent staphylococcal infections, pneumatoceles, reduced neutrophil chemotaxis, and variably impaired T cell function. Although decreased interferon-gamma (IFN-gamma) production in patients with hyper-IgE syndrome is pointed out and known as a cause of reduced neutrophil chemotaxis, precise mechanism of their inadequate production of IFN-gamma remains unknown. To elucidate the pathogenesis of the defective production of IFN-gamma in patients with hyper-IgE syndrome, we assessed the in vitro production and secretion of IFN-gamma by peripheral blood mononuclear cells (PBMCs) from patients with hyper-IgE syndrome. METHODS: Chemotaxis of neutrophils, mRNA levels of several cytokines, intracellular production and extracellular secretion of IFN-gamma, interleukin-2 (IL-2), and IL-4 by PBMCs from three patients with hyper-IgE syndrome were determined. RESULTS: The transcription of IFN-gamma mRNA and the production of its protein molecules progressed normally. However, selective insufficiency in the secretion of IFN-gamma molecules was found in patients with hyper-IgE syndrome. Confocal laser scanning microscopy clearly demonstrated the accumulation of IFN-gamma in patients with hyper-IgE syndrome. CONCLUSION: We demonstrated that there was a selective insufficiency in the secretion of IFN-gamma in patients with hyper-IgE syndrome. We hope that this fact would offer a new paradigm for understanding this disease.

Adult↗

Expression of cadherins and their undercoat proteins (alpha-, beta-, and gamma-catenins and p120) and accumulation of beta-catenin with no gene mutations in synovial sarcoma.

E-cadherin, the major intercellular adhesion molecule of epithelial cells, is important in determining the architecture of sarcomas, especially those showing epithelioid features. In addition to its role in cell adhesion, beta-catenin, a cadherin undercoat protein, has been shown to function as a downstream transcriptional activator of the Wnt/Wingless signaling pathway. In order to evaluate the significance of the cadherin cell adhesion system and the Wnt/Wingless signaling pathway in the morphogenesis and/or tumorigenesis of synovial sarcoma (a major type of sarcoma with epithelioid features), immunoreactivity for pan-cadherin, E-cadherin, and their undercoat proteins (alpha-, beta-,and gamma-catenins and p120) was evaluated in 15 synovial sarcomas. Immunoreactivity for pan-cadherin, E-cadherin, alpha-catenin, beta-catenin, and p120 was observed in all 15 specimens. Immunoreactivity for pan-cadherin was stronger than that for E-cadherin. Expression of gamma-catenin was detected in ten specimens. Although beta-catenin was observed only at the cell-cell boundaries in four specimens, it was present in the nucleus and cytoplasm and at the cell-cell boundaries in the other 11, suggesting constitutional activation of the Wnt/Wingless signaling pathway in synovial sarcoma. Direct sequencing for exon 3 of the beta-catenin gene, however, revealed no mutations in any of the 15 specimens. In conclusion, other types of cadherin besides E-cadherin, together with cadherin undercoat proteins, may play a role in cell adhesion in synovial sarcoma. Furthermore, mechanisms other than mutation of exon 3 of the beta-catenin gene may activate the Wnt/Wingless signaling pathway in this type of tumor.

Adolescent↗

Gene expression of angiogenesis related factors in glioma.

Angiogenesis plays an important role in growth and proliferation of cancer. Various angiogenic and angiostatic factors regulate angiogenesis. In this study, we examined gene expression of the angiopoietin family including angiopoietin 1 (Ang1) and angiopoietin 2 (Ang2) in 39 gliomas and 5 glioma-xenografts by RT-PCR. Ang1 and Ang2 genes were expressed in 54%, and 77% of gliomas, respectively. The expression of Ang1 was significantly correlated with the expression of Ang2. Both Ang1 and Ang2 were shown to be expressed in the glioma cells. Ang2 gene expression was correlated with VEGF gene expression. Angiopoietin molecules may synergistically cooperate in growth and vascularization in glioma.

Angiopoietin-1↗

Interleukin 10 expression is correlated with thrombospondin expression and decreased vascular involvement in colon cancer.

Interleukin 10 (IL-10) is an immuno-suppressive cytokine produced by T-lymphocytes, and a regulatory molecule for angiogenesis in various cancers. We examined IL-10 gene expression in 53 colon cancer patients who underwent surgical resection. IL-10 gene expression was correlated with TSP1 and TSP2 gene expression (P=0.0049, P=0.0285). Colon cancer with IL-10 gene expression (19/53) showed significantly decreased venous involvement (P=0.0433). The mean vessel counts in the colon cancers with IL-10 gene expression were significantly lower than those without IL-10 gene expression (P<0.001). These results suggested that IL-10 stimulates angiostatic factor gene expression, and results in suppression of venous involvement.

Adenocarcinoma↗

Is it permissible to omit mediastinal dissection for peripheral non-small-cell lung cancers with tumor diameters less than 1.5 cm?

BACKGROUND: Recently the pros and cons of limited surgery for small-sized peripheral non-small-cell lung cancers (PNSCLCs), such as omission of mediastinal dissection, etc., have been vigorously debated. We analyzed whether hilar/mediastinal lymph node metastases were present in 30 small-sized PNSCLCs. MATERIAL AND METHODS: In the nine years from 1990 to 1998, 294 lung cancer patients underwent lobectomy or pneumonectomy combined with hilar/mediastinal dissection in the Tokai University Hospital. Thirty of these patients diagnosed as having cT1N0M0 PNSCLC with tumor diameters of 1.5 cm or less by computed tomography, are evaluated in this article. RESULTS: The 30 PNSCLC patients consisted of 14 males and 16 females with a mean age of 61 +/- 9 years. Twenty six patients (87%) had no hilar nor mediastinal lymph node metastases (pN0), one patient (3%) had a hilar lymph node metastasis (pN1), and three patients (10%) had mediastinal lymph node metastases (pN2). CONCLUSIONS: Mediastinal lymph node metastases were histologically observed in 3 (10%) of 30 PNSCLC patients with tumor diameters of 1.5 cm or less. Our results show that mediastinal dissection is still necessary even for small-sized lung cancers.

Carcinoma, Non-Small-Cell Lung↗

Parvovirus B19 infection induces apoptosis of erythroid cells in vitro and in vivo.

OBJECTIVE: intrauterine parvovirus B19 infection is related to non-immune hydrops fetalis, the pathogenesis of which is based on the strict tropism of B19 for erythroid precursor cells and the massive destruction of the infected erythroid cells, although the mechanism of beta19-induced cytotoxicity has not been studied in detail. The purpose of this study is to provide empirical evidence that beta19 induces apoptosis of erythroid cells both in vitro and ill vivo. METHODS: we analysed culture cells infected in vitro by B19 and tissues of nine cases of hydrops fetalis caused by B19 intrauterine infection by histological and biological methods. RESULTS: cells infected iil vitro by B19 showed nuclear changes characteristic of apoptosis by light microscopic examination and DNA extracted from the infected cells was fragmented. Electron microscopic examination showed the nuclei of infected cells contained crescent-shaped clumps of heterochromatin with increased density and double staining with anti-B1 9 antibody and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling (TUNEL) confirmed apoptosis of individual cells. Tissues of cases of hydrops fetalis caused by B19 contained erythroid cells with nuclear inclusions and characteristic nuclear changes of apoptosis by light microscopy. The double-staining confirmed apoptosis of erythroid cells in the tissues. Immunohistochemical analysis with antibodies against cellular factors involved in apoptosis showed that caspase3, p53 and p21 were positive in infected cells.

Apoptosis↗

Small mucosal carcinoma of the stomach with para-aortic lymph node metastasis: a case report and review of the literature.

A 38-year-old woman presented with a mucosal gastric carcinoma measuring 0.7 x 0.5 cm and para-aortic lymph node metastasis. Radiographic and endoscopic studies showed a small depressed lesion on the anterior border of the gastric angle, which was classified as a type II c + III lesion. Histological examination of the biopsy specimen revealed a signet-ring cell carcinoma. Distal gastrectomy with wide lymph node excision was performed. Detailed study of the resected specimen revealed that the tumour was limited to the mucosa, but metastasized to both the perigastric and para-aortic lymph nodes. The patient received adjuvant immunochemotherapy postoperatively. However, multiple bone metastases developed at 3 years and she died 4 years after the operation.

Adult↗

The role of histamine in ethanol-induced gastric mucosal injury in the rat.

It has been suggested that changes in the micro circulatory system are related to the early production of acute gastric mucosal injury and inflammatory factors such as prostaglandins, histamine, etc., have been considered as contributing to the development of the injury. We assessed the permeability of the gastric mucosa in rats with ethanol-induced acute mucosal injury by measuring the leakage rate of 51chronium-ethylene-diamine-tetraacetic acid (51Cr-EDTA) into the gastric juice. Histamine concentrations in the gastric mucosa was measured by high performance liquid chromatography. The enterochromaffin-like (ECL) cell counts in the gastric mucosa was performed following histamine staining with an enzyme-labeled antibody, and the histamine released due to degranulation was observed. We also investigated the kinetics of endogenous histamine in the gastric mucosa. Five minutes after the administration of ethanol, an increase in permeability, an increase in histamine concentration, and a decrease in ECL cell count were found in the gastric mucosa. These results suggest that endogenous histamine in the gastric mucosa is closely related to the early development of acute gastric mucosal injury.

Animals↗

Myofibroblastoma of the breast: report of a case.

We report herein the case of a 36-year-old woman in whom a breast mass was diagnosed histologically and immunohistochemically as myofibroblastoma (MFB). The patient initially presented with a breast mass measuring 1.0 x 1.5 cm which was demonstrated by mammography as a well-circumscribed, round tumor with two coarse calcifications. On ultrasonography, the tumor showed slight shadowy internal echoes. Histological examination of an excisional biopsy specimen demonstrated a tumor consisting of spindle-shaped cells and broad bands of hyalinized collagen with cartilaginous and osseous components, but no epithelial components were observed. Immunohistochemically, the tumor cells were diffusely positive for alpha smooth muscle actin, and a diagnosis of MFB was made. A wide excision of the breast was performed as a secondary procedure, and the patient is well and free from recurrence 1 year after her operation. We present this case to stress the need for breast surgeons to be aware of the existence of MFB when considering the differential diagnosis of stromal lesions of the breast to avoid performing unnecessarily extensive procedures.

Adult↗

A case of pituitary somatotroph adenoma with concomitant secretion of growth hormone, prolactin, and adrenocorticotropic hormone--an adenoma derived from primordial stem cell, studied by immunohistochemistry, in situ hybridization, and cell culture.

Somatotroph adenomas often secrete prolactin (PRL) besides growth hormone (GH) and are sometimes immunostained for other anterior pituitary hormones or their subunits, such as thyroid-stimulating hormone (TSH) beta-subunit and glycoprotein hormone alpha-subunit (alpha SU). However, somatotroph adenomas showing hypersecretion of adrenocorticotropic hormone (ACTH) are extremely rare. There have been, to our knowledge, only five published reports on somatotroph adenomas accompanied by excessive ACTH secretion. Here we report a case of intracavernously invading somatotroph macro-adenoma with high serum GH, PRL, and ACTH levels. We examined the case using immunohistochemistry (IHC), in situ hybridization (ISH), and cell culture, and confirmed GH, PRL, and ACTH, as well as alpha SU, production, and the expression of Pit-1 protein by the adenoma, which is known as a transcriptional factor for GH, PRL, and TSH, not for ACTH. Therefore, the presence of unknown transcriptional factor other than Pit-1, common to GH, PRL, and ACTH, may be speculated to be expressed in this adenoma. In our previous study, we had found plurihormonal mRNA expression, especially for ACTH, the beta-subunit of follicle-stimulating hormone and luteinizing hormone in some somatotroph adenomas, using non-radio-isotopic ISH, and suggested that these adenomas might be derived from plurihormonal primordial stem cells. Our present case is significant from the viewpoint of histogenesis of pituitary adenomas, because it further supports the cell origin of somatotroph adenomas from plurihormonal primordial stem cells, and moreover it suggests the presence of unknown transcriptional factor other than Pit-1, common to GH, PRL, and ACTH.

Adenoma↗

Cyclic Cushing's disease in long-term remission with a daily low dose of bromocriptine.

A 56-year-old male patient with cyclic Cushing's disease remained in a state of remission for more than one year with a relatively low dose of bromocriptine (2.5-3.75 mg/day). It has been reported that bromocriptine treatment for cyclic Cushing's disease induces only a transient remission; in the most effective cases, a relatively high dose (40 mg/day) was necessary. In the hypercortisolemic state, plasma adrenocorticotropic hormone (ACTH) and serum cortisol were not suppressed by dexamethasone and did not respond to corticotropin-releasing factor (CRF). An antehypophysectomy was not effective, even though the resected tissue contained ACTH-positive microadenomas. The present observations thus indicate the effectiveness of bromocriptine for some patients with this rare disorder.

Adenoma↗

[Intermediate filaments].

The antibodies for intermediate filaments, including keratin, vimentin, desmin, GFAP and neurofilaments, have been much useful in routinely-processed immunohistochemical study for identifying characteristics of tumor cells or making the definite diagnosis. In general, when neoplastic transformation has taken place, the affected cells would reveal to some extent alterated immunolocalization of intermediate filaments in the cytoplasm. Whether the tumor cells are of epithelial or non-epithelial origin is significant from diagnostic points of view when utilizing those intermediate filaments as tumor markers. But there are many "exceptional" cases of epithelial tumors with expression of vimentin, or those of non-epithelial tumors with expression of keratin, indicating some "variants". Immunohistochemical application of the intermediate filaments is indispensable not only as "a diagnostic tool for surgical pathologists", but also a method for analyzing relationship between morphological changes and functional aspects of the tumor cells.

Humans↗