Quadruple extra-mammary Paget's disease.
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Aged↗
Biomedical subjects
Hiroshi Yasuda
Publications and source records attributed to Hiroshi Yasuda.
Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor receptor and mitogen-activated protein kinases in gastric carcinoma cells.
Bile acids, which have been implicated in gastrointestinal-tract cell carcinogenesis, share properties with tumor promoters in that both affect signal transduction pathways responsible for cell proliferation and apoptosis. In the present study, we demonstrate that EGFR-ERK1/2 is activated following treatment of AGS human gastric carcinoma cells with bile acids. EGFR phosphoactivation is ligand-dependent, since treatment of cells with HB-EGF antisera or CM197 (a selective inhibitor of HB-EGF) markedly inhibits deoxycholate (DC)-promoted activation. Membrane-type bile acid receptor (M-BAR)/TGR5 is a recently identified G-protein-coupled receptor (GPCR). In AGS cells, siRNAs that target M-BAR suppress DC-induced phosphorylation of EGFR. Furthermore, introduction of siRNAs targeting ADAM17 transcripts resulted in suppression of DC-induced activation of EGFR and ERK1/2. These results suggest that in AGS cells, DC transactivates EGFR through M-BAR- and ADAM/HB-EGF-dependent mechanisms.
Adenocarcinoma↗
Biochemical safety evaluation of transgenic rice seeds expressing T cell epitopes of Japanese cedar pollen allergens.
UNLABELLED: Transgenic rice seeds, which express a hybrid peptide comprising seven predominant human T cell epitopes (7Crp) derived from Japanese cedar pollen allergens, have been shown to function as an effective edible vaccine for the control of pollen allergen-induced responses. In this study, we characterized biochemical properties of transgenic seeds expressing the 7Crp peptide. The levels of chemical compositions, such as carbohydrate, protein, lipid, amino acid, fatty acid, mineral, and vitamin, were substantially equivalent between transgenic 7Crp and its nontransgenic counterpart seeds. The contents of three major allergenic proteins in transgenic seeds were not enhanced by expression of the 7Crp peptide when compared with those of nontransgenic seeds. The 7Crp peptide expressed in seeds was susceptible to simulated gastric/intestinal fluids. N-Glycosylation was not observed in the 7Crp peptide sequence. These results indicate that transgenic 7Crp seeds are substantially equivalent to nontransgenic parental seeds except for the presence of the 7Crp peptide. KEYWORDS: Food safety assessment; transgenic rice seed; edible vaccine; peptide-based immunotherapy; Japanese cedar pollinosis.
Allergens↗
Space radiation dosimetry by combination of integrating dosemeters.
Generally, individual monitoring is performed with a small personal dosemeter which responds to radiation by giving a necessary operational quantity such as personal dose equivalent. In space, however, such a personal dosemeter has not yet been available and a dose equivalent is estimated through elaborate work using etched track detectors. It would be advantageous if we could simply measure the personal dose of an astronaut using conventional integrating dosemeters only. This possibility is discussed based on the concept of efficiency combination.
Cosmic Radiation↗
A preliminary analysis of trace elements in the scalp hair of patients with severe motor disabilities receiving enteral nutrition.
The concentrations of essential trace elements (copper, zinc, selenium, manganese, chromium, molybdenum, cobalt, and iodine) in the scalp hair of 21 patients with severe motor disabilities receiving enteral nutrition were measured using inductively coupled plasma-mass spectrometry. Preliminary results show that copper, selenium, and molybdenum concentrations in the patients' hair were significantly lower than those in an age-matched control group (p<0.01). This suggests that intake of these elements may be reduced in patients receiving restricted enteral nutrition, although the clinical significance of these results should be discussed.
Adolescent↗
The correlation between expression and localization of a foreign gene product in rice endosperm.
Glucagon-like peptide 1 (GLP-1) is a 30 amino acid peptide hormone involved in insulin stimulation that is dependent upon blood glucose levels. We have previously reported that when this short peptide gene was directly expressed under the control of a glutelin promoter and its signal peptide, it was not accumulated in transgenic rice seed due to gene silencing. However, when the modified GLP-1 (mGLP-1) gene was enlarged to 5xmGLP-1 (mGLPx5) by tandem repeat, no silencing was observed. The mGLPx5 peptide could be accumulated in rice seed and its localization was mainly limited to the endoplasmic reticulum (ER). We also investigated alternative cellular localization sites that would increase accumulation. The relationship between the expression level and localization was examined by attaching the chitinase signal peptide to mGLPx5 to direct it into the intercellular space (apoplast), or by expression as a fusion protein with glutelin by insertion into a variable region of the acidic subunit, thus directing the peptide to protein body II (PB II). Attachment of the KDEL ER retention signal to the 6xmGLP-1 (mGLPx6) or its fusion to the C-terminus of the 13 kDa prolamin directed the peptide to the ER or PB I, respectively. Unexpectedly, these results indicated that mGLPx5 without any signal except for the glutelin signal peptide was accumulated to the greatest extent in rice endosperm. It can thus be concluded that the ER is a suitable intracellular organelle for accumulation of mGLPx5 peptide.
Chitinases↗
Acute necrotizing esophagitis: role of nonsteroidal anti-inflammatory drugs.
BACKGROUND: Acute necrotizing esophagitis (ANE) is a rarely described entity that is thought to be a cause of upper gastrointestinal (UGI) bleeding, The present study examined the incidence of ANE among patients with UGI bleeding, as well as the clinical features of ANE, and the coexisting illnesses and medication histories of ANE patients. METHODS: A retrospective analysis of clinical and endoscopic findings and the clinical course in 16 patients with ANE was carried out over a 3-year period. RESULTS: We observed 16 patients (6%) of ANE in 239 patients with UGI bleeding during the 3-year period. The average age of the patients was 62.5 years. The lesions predominantly affected the lower third of the esophagus, and hiatal hernia was the most common (63%) coexisting endoscopic finding. All patients had coexisting disease. Fifty percent of patients with ANE (eight patients) had taken nonsteroidal anti-inflammatory drugs (NSAIDs). ANE also occurred in four patients with diabetic ketoacidosis. Supportive therapy, including parenteral nutrition and administration of a proton pump inhibitor, was effective. CONCLUSIONS: ANE is more common than has been previously reported, and it should be included in the differential diagnosis of UGI bleeding. ANE could be characterized as an "acute esophageal mucosal lesion," particularly in aged patients with hiatal hernia and among those who consume NSAIDs.
Acute Disease↗
Tinea profunda cysticum caused by Trichophyton rubrum.
A 57-year-old Japanese woman developed multiple subcutaneous cysts located on the pubic region, thighs, back, and buttocks. She had been treated with systemic prednisolone and azathioprine for 3 years because of autoimmune hepatitis. Histologic examination revealed that the lesions were pseudocysts with numerous spores and hyphae. Trichophyton rubrum was identified in culture from the content of several examined cysts. The serum beta-D-glucan level was high (313 pg/mL), and a computed tomographic scan of the chest cavity showed infective embolism in the lung. To our best knowledge, this is the first reported case of multiple-cystic tinea profunda, presumably with systemic dermatophyte infection. Systemic T-cell immunosuppression, as represented by a relatively low percentage of memory T cells and negative delayed-type hypersensitivity tests, is considered to cause this rare manifestation of dermatophytosis.
Cysts↗
Changes in optical transmission caused by gamma ray induced coloring in photoluminescence dosimeter.
Transmission of visible light and ultraviolet radiation was examined for a phosphate-glass photoluminescence dosimeter irradiated with Co source gamma rays in the dose range of 1-60 Gy (H2O). The transmission for the wavelengths (lambda) less than 600 nm decreased with increasing irradiation dose beginning at 6 Gy. An approximate 20% reduction of transmission was observed for a 60 Gy exposure at the wavelength of ultraviolet radiation used for excitation (lambda = 337 nm). However, no change of transmission was seen in longer wavelength region (lambda > 600 nm), which includes the range of photoluminescence (lambda = 610-710 nm). Relative efficiencies of measured photoluminescence agreed well with estimations that were calculated from the transmission reduction of ultraviolet radiation. This fact indicates that reduction of photoluminescence efficiency induced by high-dose gamma rays is attributable mostly to attenuation of the ultraviolet radiation from an excitation source, rather than saturation of trapping or recombination centers.
Cobalt Radioisotopes↗
Reduced exposure to mercury in patients receiving enteral nutrition.
The exposure to mercury (Hg) of various groups of people with different dietary backgrounds has been assessed because of its hazardous effects, but little is known about that in patients receiving enteral nutrition. Therefore, we studied the Hg exposure in 25 patients with severe motor disabilities, who received liquid enteral feedings for more than one year, by determining total mercury (T-Hg) in their hair samples with inductively coupled plasma-mass spectrometry. The geometric mean of the T-Hg level in hair from the patients was 88 ng/g hair (+/- 1 geometric standard deviation [GSD], 34 - 228 ng/g), whereas that for the control group on a normal diet was 1,900 ng/g (+/- 1 GSD, 1,022 - 3,531 ng/g). The T-Hg levels in the patients' hair were far lower than those in the controls (p < 0.001). The T-Hg levels in the enteral feedings used were below the detection limit of cold-vapor atomic absorption spectrophotometry (< 10 ng/g). The present study has shown that Hg exposure is low in patients receiving enteral nutrition, indicating that food is a primary source of Hg exposure.
Adolescent↗
Simultaneous superficial temporal artery to middle cerebral or anterior cerebral artery bypass with pan-synangiosis for Moyamoya disease covering both anterior and middle cerebral artery territories.
Some patients with moyamoya disease treated by conventional surgical procedures may develop postoperative refractory ischemia and perioperative cerebral infarction in the anterior cerebral artery (ACA) territory. We present a novel operative procedure for moyamoya disease to avoid the risk of ischemia in the ACA territory, which consists of simultaneous superficial temporal artery (STA) to middle cerebral artery (MCA) or ACA bypass with pan-synangiosis, encephalo-duro-arterio-myo-synangiosis for the lateral frontal and temporal areas, and encephalo-galeo-arterio-synangiosis for the medial frontal area. This procedure can establish direct bypass to the ACA territory at the first intervention. Simultaneous STA-MCA and STA-ACA bypasses with pan-synangiosis is suitable for patients with moyamoya disease associated with severely impaired perfusion of the ACA territory requiring direct bypass surgery.
Adolescent↗
Autocrine loop between TGF-beta1 and IL-1beta through Smad3- and ERK-dependent pathways in rat pancreatic stellate cells.
Pancreatic stellate cells (PSCs) are activated during pancreatitis and promote pancreatic fibrosis by producing and secreting ECMs such as collagen and fibronectin. IL-1beta has been assumed to participate in pancreatic fibrosis by activating PSCs. Activated PSCs secrete various cytokines that regulate PSC function. In this study, we have examined IL-1beta secretion from culture-activated PSCs as well as its regulatory mechanism. RT-PCR and ELISA have demonstrated that PSCs express IL-1beta mRNA and secrete IL-1beta peptide. Inhibition of TGF-beta(1) activity secreted from PSCs by TGF-beta(1)-neutralizing antibody attenuated IL-1beta secretion from PSCs. Exogenous TGF-beta(1) increased IL-1beta expression and secretion by PSCs in a dose-dependent manner. Adenovirus-mediated expression of dominant-negative (dn)Smad2/3 expression reduced both basal and TGF-beta(1)-stimulated IL-1beta expression and secretion by PSCs. Coexpression of Smad3 with dnSmad2/3 restored IL-1beta expression and secretion by PSCs, which were attenuated by dnSmad2/3 expression. In contrast, coexpression of Smad2 with dnSmad2/3 did not alter them. Furthermore, inhibition of IL-1beta activity secreted from PSCs by IL-1beta-neutralizing antibody attenuated TGF-beta(1) secretion from PSCs. Exogenous IL-1beta enhanced TGF-beta(1) expression and secretion by PSCs. IL-1beta activated ERK, and PD-98059, a MEK1 inhibitor, blocked IL-1beta enhancement of TGF-beta(1) expression and secretion by PSCs. We propose that an autocrine loop exists between TGF-beta(1) and IL-1beta in activated PSCs through Smad3- and ERK-dependent pathways.
Animals↗
Angiotensin II promotes the proliferation of activated pancreatic stellate cells by Smad7 induction through a protein kinase C pathway.
Activated pancreatic stellate cells (PSCs) play major roles in promoting pancreatic fibrosis. We previously reported that angiotensin II (Ang II) enhances activated PSC proliferation through EGF receptor transactivation. In the present study, we elucidated a novel intracellular mechanism by which Ang II stimulates cellular proliferation. TGF-beta1 inhibits activated PSC proliferation via a Smad3 and Smad4-dependent pathway in an autocrine manner. We demonstrated that Ang II inhibited TGF-beta1-induced nuclear accumulation of Smad3 and Smad4. Furthermore, Ang II rapidly induced inhibitory Smad7 mRNA expression. Adenovirus-mediated Smad7 overexpression inhibited TGF-beta1-induced nuclear accumulation of Smad3 and Smad4, and potentiated activated PSC proliferation. PKC inhibitor Go6983 blocked the induction of Smad7 mRNA expression by Ang II. In addition, 12-O-tetradecanoyl-phorbol 13-acetate, a PKC activator, increased Smad7 mRNA expression. These results suggest that Ang II enhances activated PSC proliferation by blocking autocrine TGF-beta1-mediated growth inhibition by inducing Smad7 expression via a PKC-dependent pathway.
Adenoviridae↗
Regions in the G protein gamma subunit important for interaction with receptors and effectors.
G betagamma dimers containing the gamma11 or gamma1 subunits are often less potent and effective in their ability to regulate effectors compared with dimers containing the gamma2 subunit. To explore the regions of the gamma subunit that affect the activity of the betagamma dimer, we constructed eight chimeric gamma subunits from the gamma1 and gamma2 subunits. Two chimeras were made in which the N-terminal regions of gamma1 and gamma2 were exchanged and two in which the C-terminal regions were transposed. Another set of chimeras was made in which the CAAX motifs of the chimeras were altered to direct modification with different prenyl groups. All eight gamma chimeras were expressed in Sf9 cells with the beta1 subunit, G betagamma dimers were purified, and then they were assayed in vitro for their ability to bind to the G alpha(i1) subunit, to couple G alpha(i1) to the A1 adenosine receptor, to stimulate phospholipase C-beta, and to regulate type I or type II adenyl cyclases. Dimers containing the C-terminal sequence of the gamma2 subunit modified with the geranylgeranyl lipid had the highest affinity for G(i1)alpha (range, 0.5-1.2 nM) and were most effective at coupling the G(i1)alpha subunit to receptor. These dimers were most effective at stimulating the phosphatidylinositol-specific phospholipase C-beta isoform and inhibiting type I adenyl cyclase. In contrast, betagamma dimers containing the N-terminal sequence of the gamma2 subunit and a geranylgeranyl group are most effective at activating type II adenyl cyclase. The results indicate that both the N- and C-terminal regions of the gamma subunit impart specificity to receptor and effector interactions.
Adenylyl Cyclases↗
Roles of CTPL/Sfxn3 and Sfxn family members in pancreatic islet.
Pancreatic AR42J cells have the feature of pluripotency of the precursor cells of the gut endoderm. Betacellulin (BTC) and activin A (Act) convert them into insulin-secreting cells. Using mRNA differential display techniques, we have identified a novel mitochondrial transporter, which is highly expressed during the course of differentiation, and have designated it citrate transporter protein-like protein (CTPL). Recently sideroflexin 1 (Sfxn1) was shown to be a susceptible gene of flexed-tail (f/f) mice, and CTPL has turned out to be a rat orthologous protein of Sfxn3, a member of sideroflexin family. CTPL/Sfxn3 was targeted to mitochondrial membrane like Sfxn1. The expression levels of CTPL/Sfxn3, Sfxn2, and Sfxn5 were upregulated in the early phase of differentiation into insulin-secreting cells but the expression levels of Sfxn1 and Sfxn3 did not change. All Sfxn family members were expressed in rat pancreatic islet. The expression levels of CTPL/Sfxn3, Sfxn2, and Sfxn5 were also upregulated in islets of streptozotocin-induced diabetic rats compared to normal rats. The downregulation of CTPL/Sfxn3 in a rat insulinoma cell line, INS-1, with the antisense oligonucleotide did not affect the insulin secretion. Taken together, CTPL/Sfxn3 and some other family members might be important in the differentiation of pancreatic beta-cells as a channel or a carrier molecule and be related to the regeneration of pancreatic endocrine cells.
Animals↗
Localization of actin filaments on mitotic apparatus in tobacco BY-2 cells.
Actin filaments are among the major components of the cytoskeleton, and participate in various cellular dynamic processes. However, conflicting results had been obtained on the localization of actin filaments on the mitotic apparatus and their participation in the process of chromosome segregation. We demonstrated by using rhodamine-phalloidin staining, the localization of actin filaments on the mitotic spindles of tobacco BY-2 cells when the cells were treated with cytochalasin D. At prophase, several clear spots were observed at or near the kinetochores of the chromosomes. At anaphase, the actin filaments that appeared to be pulling chromosomes toward the division poles were demonstrated. However, as there was a slight possibility that these results might have been the artifacts of cytochalasin D treatment or the phalloidin staining, we analyzed the localization of actin filaments at the mitotic apparatus immunologically. We cloned a novel BY-2 alpha-type actin cDNA and prepared a BY-2 actin antibody. The fluorescence of the anti-BY-2 actin antibody was clearly observed at the mitotic apparatus in both non-treated and cytochalasin D-treated BY-2 cells during mitosis. The facts that similar results were obtained in both actin staining with rhodamine-phalloidin and immunostaining with actin antibody strongly indicate the participation of actin in the organization of the spindle body or in the process of chromosome segregation. Furthermore, both filamentous actin and spindle bodies disappeared in the cells treated with propyzamide, which depolymerizes microtubules, supporting the notion that actin filaments are associated with microtubules organizing the spindle body.
Actin Cytoskeleton↗
The critical role of disulfide bond formation in protein sorting in the endosperm of rice.
Many seed storage proteins, including monomeric 2S albumin and polymeric prolamin, contain conserved sequences in three separate regions, termed A, B, and C, which contain the consensus motifs LxxC, CCxQL, and PxxC, respectively. Protein-sorting mechanisms in rice (Oryza sativa) endosperm were studied with a green fluorescent protein (GFP) fused to different segments of rice alpha-globulin, a monomeric, ABC-containing storage protein. The whole ABC region together with GFP was efficiently transported to protein storage vacuoles (type II protein bodies [PB-II]) in the endosperm cells and sequestered in the matrix that surrounds the crystalloids. Peptide Gln-23 to Ser-43 in the A region was sufficient to guide GFP to PB-II. However, GFP fused with the AB or B region accumulated in prolamin protein bodies. Substitution mutations in the CCxQL motif in the B region significantly altered protein localization in the endosperm cells. Furthermore, protein extracts containing these substituted proteins had increased amounts of the endoplasmic reticulum (ER) chaperons BiP (for binding protein), protein disulfide isomerase, and calnexin as a part of protein complexes that were insoluble in a detergent buffer. These results suggest that the ER chaperons and disulfide bonds formed at the dicysteine residues in CCxQL play critical roles in sorting fused proteins in the endosperm cells.
Alpha-Globulins↗
Genetically modified rice seeds accumulating GLP-1 analogue stimulate insulin secretion from a mouse pancreatic beta-cell line.
Glucagon-like peptide-1 (7-36) amide (GLP-1) is the most potent physiological insulinotropic hormone in humans. We produced large amounts of a GLP-1 analogue, [Ser8, Gln26, Asp34]-GLP-1, which is resistant to trypsin-digestion, as part of a chimeric rice seed storage protein, a 26 kDa globulin, in genetically modified rice seeds. Junction sites between GLP-1 analogue and globulin were replaced by tryptic cleavage sites. The highest level of GLP-1 analogue accumulation was approximately 20-50 microg per seed. We found that GLP-1 analogue derived from trypsin-digested genetically modified rice seeds stimulated insulin secretion from a mouse pancreatic beta-cell line, MIN6.
Animals↗