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Shinji Naito

Publications and source records attributed to Shinji Naito.

13 recordsLinked to original sources
PubMed2006

Expression of Ets-1 proto-oncoprotein in gastrointestinal stromal tumors, leiomyomas and schwannomas.

AIM: Gastrointestinal stromal tumors (GISTs) are rare. GISTs differ from other mesenchymal tumors of the gastrointestinal tract (e.g. leiomyomas and schwannomas). The purpose of this study was to investigate the role of Ets-1 in the growth and differentiation of GISTs. METHODS: Twenty-eight GISTs, nine leiomyomas and six schwannomas were examined by immunohistochemical staining method for Ets-1 in this study. Specimens were selected from surgical pathology archival tissues at Nagasaki University Hospital. RESULTS: Ets-1 protein was expressed in the cytoplasm of cells in all of these tumors. Immunohistochemical staining revealed that 27 GISTs (96.4%), six leiomyomas (66.7%), and five schwannomas (83.3%) were positive for Ets-1. Ets-1 expression was statistically different between GISTs and leiomyomas (P<0.005). However, there was no correlation between Ets-1 expression and clinical risk categories. CONCLUSION: Ets-1 plays an important role in the growth and differentiation of GISTs, leiomyomas and schwannomas.

Biomarkers, Tumor↗
PubMed2005

Rice Annotation Database (RAD): a contig-oriented database for map-based rice genomics.

A contig-oriented database for annotation of the rice genome has been constructed to facilitate map-based rice genomics. The Rice Annotation Database has the following functional features: (i) extensive effort of manual annotations of P1-derived artificial chromosome/bacterial artificial chromosome clones can be merged at chromosome and contig-level; (ii) concise visualization of the annotation information such as the predicted genes, results of various prediction programs (RiceHMM, Genscan, Genscan+, Fgenesh, GeneMark, etc.), homology to expressed sequence tag, full-length cDNA and protein; (iii) user-friendly clone / gene query system; (iv) download functions for nucleotide, amino acid and coding sequences; (v) analysis of various features of the genome (GC-content, average value, etc.); and (vi) genome-wide homology search (BLAST) of contig- and chromosome-level genome sequence to allow comparative analysis with the genome sequence of other organisms. As of October 2004, the database contains a total of 215 Mb sequence with relevant annotation results including 30 000 manually curated genes. The database can provide the latest information on manual annotation as well as a comprehensive structural analysis of various features of the rice genome. The database can be accessed at http://rad.dna.affrc.go.jp/.

Chromosomes, Plant↗
PubMed2005

Sympathetic hyperfunction causes increased sensitivity of the autonomic nervous system to whole-body X irradiation.

Although the etiology of radiation sickness is still unknown, disturbance of the autonomic nervous system is suggested to be a factor. This study was designed to compare the radiosensitivity of spontaneously hypertensive rats possessing sympathetic hyperfunction and control Wistar-Kyoto rats, and to analyze the effects of radiation on the autonomic nervous system in both strains. After a 7.5-Gy dose of whole-body X irradiation, the blood pressure decreased significantly at 8 h and 2 days in the spontaneously hypertensive rats, but not in the Wistar-Kyoto rats. Epinephrine levels in the adrenal gland of spontaneously hypertensive rats decreased at 4, 8 and 24 h, unlike the Wistar-Kyoto rats. Radiation evoked a stronger increase in norepinephrine in the jejunum and colon of spontaneously hypertensive rats than in Wistar-Kyoto rats. Acetylcholine levels in the jejunum of spontaneously hypertensive rats decreased, in contrast to the increase in Wistar-Kyoto rats within 24 h after irradiation. The survival rate of spontaneously hypertensive rats was lower than that of Wistar-Kyoto rats and weight loss, appetite loss and morphological changes in the jejunum were greater in spontaneously hypertensive rats than in Wistar-Kyoto rats after irradiation. These results indicated that X irradiation caused greater activities in autonomic nervous function and severe radiation injury in spontaneously hypertensive rats. Sympathetic hyperfunction may be associated with a higher sensitivity to radiation, including radiation injury and radiation sickness.

Animals↗
PubMed2004

Stimulation of in vitro angiogenesis by nitric oxide through the induction of transcription factor ETS-1.

The aim of this study was to examine whether transcription factor ETS-1, which is responsible for the expression of metalloproteinases and integrin beta(3), is implicated in the induction of nitric oxide (NO)-induced angiogenesis. Bovine aortic endothelial cells were cultured on type I collagen gel to measure the length of the formed tube-like structure, which is a marker for in vitro angiogenesis. The addition of S-nitroso-N-acetylpenicillamine (SNAP), an NO-donor, to confluent endothelial cells stimulated the formation of the tube-like structure, with disappearance of covered endothelial cell monolayers. Another NO-donor 2,2'-(hydroxynitrosohydrazono)bis-ethanamine (NOC 18) also induced the formation of the tube-like structure. In contrast to the induction of the formation of the tube-like structure by SNAP, it reduced cell proliferation. SNAP and NOC 18 also increased the expression of the ets-1 mRNA level in a concentration-dependent manner. The maximum expression was observed at 2h after their addition. Moreover, the SNAP-induced in vitro angiogenesis, ets-1 mRNA expression and ETS-1 protein expression were strongly reduced by the treatment with ets-1 antisense oligonucleotide. These results strongly suggest that NO stimulates in vitro angiogenesis through the induction of ETS-1 expression. NO appears to stimulate endothelial cell differentiation to the angiogenic phenotype via the induction of ETS-1 transcription factor.

Animals↗
PubMed2004

Immunohistochemical examination of mucinous cystadenoma of the testis.

A case of mucinous cystadenoma of the testis in a 55-year-old man is reported. The tumor was confined to the testis and was clearly separated from the epididymis. There was no connection between the tumor cyst and the rete testis. The lumen of the cyst was lined with a single-layer of columnar cells interspersed with goblet cells. There was neither stromal invasion nor metastasis to other organs and there were no ovarian or germ cell neoplastic elements in the tumor. Immunohistochemical analysis revealed that MUC2, MUC5AC, carcinoembryonic antigen, CA19-9, CK7 and CK20 proteins were expressed on the tumor epithelial cells, whereas expression of MUC6, alpha-fetoprotein, CA125, human chorionic gonadotrophin, estrogen receptor, progesterone receptor, calretinin, chromogranin A, p53, cyclin D1 and bcl-2 proteins was absent. Ki-67 protein was weakly and sparsely expressed in the nuclei of epithelial cells. The mucinous cystadenoma in the present case, which was devoid of a connection to testicular appendices and had the immunohistochemical characteristics of gastrointestinal mucosa, might have originated from one-sided differentiation of teratoma cells.

Biomarkers, Tumor↗
PubMed2003

Expression of parathyroid hormone (PTH)-related peptide (PthrP) and PTH/PTHrP receptor in osteoclast-like giant cells.

Osteoclast-like giant cells (OCGC), which resemble osteoclasts at both the morphologic and immunohistochemical levels, develop in neoplastic tissue. In bone marrow, parathyroid hormone (PTH)-related peptide (PTHrP) can induce osteoclast differentiation by stimulating osteoclast progenitors through the PTH/PTHrP receptor (PPR). To evaluate the possible involvement of PTHrP in OCGC formation in tumors, we analyzed both PTHrP and PPR expression by immunohistochemistry in giant cell tumor of bone (GCTB) and anaplastic thyroid cancer (ATC) containing OCGC. In all cases of either GCTB (n = 5) or ATC (n = 4), intense stainingfor PTHrP was found in OCGC, but only faintly in mononuclear cells. PPR expression in OCGC was also demonstrated in 3 cases of GCTB and 2 cases of ATC. Double staining for PPR and proliferating cell nuclear antigen (PCNA) revealed that PPR was mainly expressed by PCNA-negative mononuclear cells and OCGC in these tumors. This suggests that OCGC might be derived from non-proliferating mononuclear cells by PTHrP stimulation via PPR. Furthermore, the profiles of PTHrP and PPR expression in OCGC were compared with those in the neoplastic GC found in malignancy (n = 6), osteoclasts in bone with osteoarthritis (n = 5), reactive GC, including Langhans-type and foreign body-type in pulmonary tuberculosis (n = 8), and ruptured epidermal cyst (n = 14) in order to clarify whether their distribution pattern was unique to OCGC. In all cases of malignancy, expression of both PTHrP and PPR was observed ubiquitously in neoplastic GC and mononuclear cells regardless of PCNA immunoreactivity. In contrast, in osteoclasts and reactive GC, PTHrP immunoreactivity was seen in all cases and in 7 of 22 cases, respectively, but no PPR expression was observed in either. In situ hybridization confirmed PTHrP expression at the transcriptional level in OCGC and neoplastic GC, but not in osteoclasts. Thus, although PTHrP expression was commonly observed in various types of multinucleated giant cells, their immunohistochemical profiles for PPR were distinct. We conclude that PPR might play a role during OCGC formation in GCTB and ATC.

Carcinoma↗
PubMed2003

The induction of heme oxygenase-1 by exogenous nitric oxide in ex vivo normal human skin.

Gaseous carbon monoxide (CO) has received attention as a neurotransmitter and as a material involved in persistent dilatation of vessels. CO is released by heme oxygenase (HO) during the process from heme to bilirubin or biliverdin. Many reports have revealed that exogenous nitric oxide (NO) can induce HO-1 in vitro, which is the induced isoform of HO. In the present study, we attempted an ex vivo system as an explant culture. A quantitative analysis was performed in combination with a reverse transcription-competitive polymerase chain reaction method, which proved to be very accurate, as well as a qualitative analysis with an immunohistochemistry. With this system we confirmed the induction of HO-1 mRNA and protein by exogenous NO in normal human skin. Our results concluded that this ex vivo system was very useful, because skin samples could be handled easily under conditions close to the in vivo situation.

Adult↗
PubMed2002

Ets-1 upregulates matrix metalloproteinase-1 expression through extracellular matrix adhesion in vascular endothelial cells.

Ets-1 is a transcription factor regulating the expression of matrix-degrading proteinases and is believed to play a critical role in cell migration and tumor invasion. The aim of this study is to investigate the direct induction of ets-1 with consequential upregulation of collagenase-1 (MMP-1) by cell adhesion to extracellular matrix and to identify intracellular signal transduction pathways involved in ets-1 induction in cultured endothelial cells. The expressions of ets-1 mRNA and protein as well as MMP-1 protein were induced by cell adhesion to type I collagen and antisense ets-1 oligonucleotides impaired that MMP-1 expression. In addition, protein tyrosine kinase (PTK) and protein kinase C (PKC) inhibitors abrogated their induction, showing the suppression of focal adhesion kinase phosphorylation. These results suggest that ets-1 induced by cell adhesion to extracellular matrix directly upregulates MMP-1 expression via PTK and PKC activation in cultured endothelial cells.

Animals↗
PubMed2002

Altered expression of beta-catenin during radiation-induced colonic carcinogenesis.

Radiotherapy for malignant pelvic disease is commonly accompanied by treatment-induced proctitis, and rarely by colorectal cancer. Translocation of the beta-catenin protein, which is a key downstream effector of the Wnt signal transduction pathway, is frequently found in colorectal cancer. Nuclear beta-catenin enhances transcriptional activity of the cyclin D1 gene in cancer cells. Here, we evaluate the involvement of the Wnt pathway in radiation-induced colon carcinogenesis with rats (n = 36). Beta-catenin, APC, and cyclin D1 expression profiles were analyzed by immunohistochemistry in radiation-induced chronic colon injury including cancers and ulcerative lesions in rats (n = 12 in treated group, n = 12 in control group). In total, 3 cases of invasive adenocarcinomas were developed in the irradiated portion 50 weeks after a single dose of 36 Gy irradiation. Nuclear translocation of beta-catenin was observed in all radiation-induced colon cancers, whereas this protein was also found in the cytoplasm and/or nucleus of 9 cases of non-neoplastic irradiated colonocytes. Nuclear translocation of beta-catenin correlated with loss of APC and gain of cyclin D1 expression, suggesting activation of the Wnt pathway during radiation-induced colorectal carcinogenesis. A single dose of 10 Gy was also given for acute injury (n = 12: 3 each in days 0, 3, 5, and 7, respectively). Beta-catenin expression was distributed in the cytoplasm of degenerating glands at day 3 and 5, and was observed in the cell membrane of those glands with histological normalization at day 7 after irradiation. Because translocation of beta-catenin was found in irradiated-colonic mucosa as well as colon cancer, disruption of beta-catenin expression might be one of the early events in radiation-induced colonic carcinogenesis.

Adenocarcinoma↗
PubMed2002

Differential roles of ICAM-1 and E-selectin in polymorphonuclear leukocyte-induced angiogenesis.

Ets-1, which stimulates metalloproteinase gene transcription, has a key role in angiogenesis. We first examined whether activated polymorphonuclear leukocytes (PMNs) enhanced angiogenesis through the induction of Ets-1. Addition of activated PMNs to endothelial cells stimulated both in vitro angiogenesis in collagen gel and Ets-1 expression. Both angiogenesis and Ets-1 expression induced by PMNs were reduced by ets-1 antisense oligonucleotide, suggesting that Ets-1 is an important factor in PMN-induced angiogenesis. Although intercellular adhesion molecule (ICAM)-1 and E-selectin are involved in PMN-induced angiogenesis, the mechanisms underlying their roles in angiogenesis have yet to be elucidated. PMN-induced Ets-1 expression was reduced by a monoclonal antibody against ICAM-1 but not E-selectin despite the inhibition of PMN-induced angiogenesis by both antibodies. Moreover, the stimulation of angiogenesis by H(2)O(2) without PMNs was inhibited by a monoclonal antibody to E-selectin but not ICAM-1. These findings suggested that ICAM-1 in endothelial cells may act as a signaling receptor to induce Ets-1 expression, whereas E-selectin seems to function in the formation of tubelike structures in vascular endothelial cell cultures.

Animals↗
PubMed2002

Autocrine/paracrine involvement of parathyroid hormone-related peptide in vascular leiomyoma.

Vascular leiomyomas are believed to arise from the smooth muscle of blood vessels and are characterized by the proliferation of vascular smooth muscle cells (VSMC) and numerous slit-like vascular lumens. Parathyroid hormone (PTH)-related peptide (PTHrP) plays an important role in local autocrine and/or paracrine regulation of cellular growth and function in VSMC. To investigate the interaction between VSMC and endothelial cells, we evaluated the distribution of PTHrP and PTH/PTHrP-receptor in 10 vascular leiomyomas of the skin by immunohistochemistry and in situ hybridization (ISH) of paraffin-embedded specimens. Both immunohistochemistry and ISH revealed that PTH/PTHrP-receptors are expressed in endothelial cells lining areas with slit-like vascular lumens and very weakly expressed in proliferating VSMC in all vascular leiomyomas. On the other hand, PTHrP itself was localized mainly in proliferating VSMC. These results support the hypothesis that PTHrP acts through the PTH/PTHrP-receptor via an autocrine and/or paracrine mechanism from VSMC to endothelial cells in the formation of characteristic microenvironments of vascular leiomyoma cell composition.

Adult↗
PubMed2002

[A case of cerebral syphilitic gumma].

A 38-year-old man experienced an intermittent low-grade fever with generalized eruption, followed by rapidly progressive right hemiplegia. Neuroimaging revealed a ring-like enhanced mass in the left premotor cortex surrounded by marked perifocal edema. The syphilitic titer was high both in the serum and in the cerebrospinal fluid. Open biopsy of the lesion revealed the tumor consisted of inflammatory cells associated with plasmacyte infiltration to the perivascular region as well as to the dura, which is consistent with the definition of syphilitic gumma. The abnormalities in neurology and in neuroimaging improved dramatically after antisyphilitic treatment. Difficulties in differentiating a cerebral gumma from other diseases are discussed.

Adult↗