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Biomedical subjects

Hironori Yamamoto

Publications and source records attributed to Hironori Yamamoto.

At least 19 recordsLinked to original sources
PubMed2007

Effects of a palatinose-based liquid diet (Inslow) on glycemic control and the second-meal effect in healthy men.

Postprandial hyperglycemia induces prolonged hyperinsulinemia, which is a risk factor for type 2 diabetes mellitus. Foods with a low glycemic index blunt the rapid rise in postprandial plasma glucose and insulin levels. We herein investigated the effects of a novel, palatinose-based liquid diet (Inslow, Meiji Dairy Products, Tokyo, Japan) on postprandial plasma glucose and insulin levels and on the rate of substrate oxidation in 7 healthy men. Furthermore, to examine the effects of Inslow on the second-meal effect, we quantified our subjects' postprandial plasma glucose, insulin, and free fatty acid levels for up to 7 hours after they ingested a breakfast containing Inslow or control formula, followed by a standard lunch 5 hours later. Our results showed that peak plasma glucose and insulin levels 30 minutes after Inslow loading were lower than after control formula loading. Postprandial fat oxidation rates in the Inslow group were higher than in the control formula group (P < .05). In the second-meal effect study, plasma glucose and insulin levels after lunch in the Inslow group were lower than in the control formula group (P < .01), although the peak levels in these groups were not different. The free fatty acid concentration in the Inslow group immediately before lunch was significantly lower than in the control formula group (P < .05). In conclusion, consumption of Inslow at breakfast appears to improve patient glycemic control by reducing their postprandial plasma glucose and insulin levels after lunch (second-meal effect).

Adult↗
PubMed2006

Differential gene expression between flat adenoma and normal mucosa in the colon in a microarray analysis.

BACKGROUND: Flat adenomas in the colon are associated with a relatively higher potential for malignancy. Distinct genes may be involved in the development of flat adenoma. The aim of this study was to profile gene expression changes in flat adenomas in the colon. METHODS: A genomewide expression analysis was carried out by using flat adenoma and adjacent normal mucosa in the colon to detect differences in gene expression. Because the right and left colon have different embryonic origins, each sample was classified according to its location, and the gene expression levels between flat adenoma and adjacent normal mucosa were also compared among samples derived from the right or left colon. RESULTS: A total of 180 genes were differentially expressed between flat adenoma and normal mucosa in the colon, including matrix metalloproteinase 7 (MMP7), cadherin 3 (CDH3), S100P, and dual oxidase 2 (DUOX2). In addition, a total of 89 and 49 genes were differentially expressed between flat adenoma and normal mucosa among the samples from the right and left colon, respectively. Subsequent quantitative real-time reverse transcriptase-polymerase chain reaction supported the reliability of the expression analysis. Immunohistochemical analysis confirmed differential CDH3 and MMP7 protein expression. CONCLUSIONS: This is the first report characterizing the genes differentially expressed in flat adenomas using a microarray analysis. Considerable differences in the gene expression profiles of flat adenomas also exist between the right and left colon. These data should lead to new insights into the pathogenesis of flat adenomas in the colon as well as to new therapeutic strategies.

Adenoma↗
PubMed2006

Endoscopic submucosal dissection of early gastric cancer.

The purpose of this review was to examine a remarkable technical advance regarding the indications for and the technique of endoscopic resection of early gastric cancer. Endoscopic mucosal resection (EMR) of early gastric cancer with no risk of lymph node metastasis has been a standard technique in Japan, probably owing to the high incidence of gastric cancer in Japan and the fact that more than half of Japanese gastric cancer cases are diagnosed at an early stage. Very recently, several EMR techniques have become increasingly accepted and regularly used in Western countries. Although these minimally invasive techniques are safe, convenient, and efficacious, they are unsuitable for large lesions in particular. Difficulty in correctly assessing the depth of tumor invasion and an increase in local recurrence when standard EMR procedures are used have been reported in cases of large lesions, because such lesions are often resected piecemeal owing to the technical limitations of standard EMR. A new development in therapeutic endoscopy, called endoscopic submucosal dissection (ESD), allows the direct dissection of the submucosa, and large lesions can be resected en bloc. ESD is not limited by resection size and is expected to replace surgical resection. However, it is still associated with a higher incidence of complications than standard EMR procedures and requires a high level of endoscopic skill. The endoscopic indications, techniques, and management of complications of ESD for early gastric cancer for properly carrying out established therapeutic endoscopy are described.

Endoscopy, Gastrointestinal↗
PubMed2006

Existence of autocrine loop between interleukin-6 and transforming growth factor-beta1 in activated rat pancreatic stellate cells.

Interleukin (IL)-6 is a proinflammatory cytokine assumed to participate in pancreatic fibrosis by activating pancreatic stellate cells (PSCs). Autocrine TGF-beta1 is to central in PSC functional regulation. In this study, we examined IL-6 secretion from culture-activated rat PSCs and its regulatory mechanism. Activated PSCs express and secrete IL-6. When anti-TGF-beta1 neutralizing antibody was added in the culture medium, IL-6 secretion from activated PSCs was inhibited, whereas exogenous TGF-beta1 added in the culture medium enhanced IL-6 expression and secretion by PSCs in a dose dependent manner. Infection of PSCs with an adenovirus expressing dominant-negative Smad2/3 attenuated basal and TGF-beta1-stimulated IL-6 expression and secretion of PSCs. We also demonstrated the reciprocal effect of PSCs-secreted IL-6 on autocrine TGF-beta1. Anti-IL-6 neutralizing antibody inhibited TGF-beta1 secretion from PSCs. Preincubation of cells with 10 nM PD98059, an extracellular signal-regulated kinase (ERK)-dependent pathway inhibitor, attenuated IL-6-enhanced TGF-beta1 expression and secretion of PSCs. In addition, IL-6 activated ERK in PSCs. These data indicate the existence of autocrine loop between IL-6 and TGF-beta1 through ERK- and Smad2/3-dependent pathways in activated PSCs.

Animals↗
PubMed2006

Restraint stress alters the duodenal expression of genes important for lipid metabolism in rat.

Stress, such as trauma and injury, is known to cause transcriptional changes in various tissues; however, there is little information on tissue-specific gene expression in response to stress. Here, we have examined duodenal gene expression in rats subjected to whole-body immobilization in order to elucidate the mechanism underlying the stress response in the duodenum--one of the tissues that is most sensitive to external stress. DNA microarray analysis revealed that the immobilization for 2 weeks caused great changes in gene expression in the rat duodenum: 165 genes exhibited more than a two-fold change in expression level (103 up-regulated; 62 down-regulated). In addition, functional classification of these genes showed that immobilization preferentially stimulated the expression of genes related to lipid metabolism, including genes encoding mitochondrial HMG-CoA synthase, a key enzyme in ketogenesis; solute carrier 27A2, a fatty acid transporter; and dienoyl CoA reductase, a key enzyme in beta-oxidation. To elucidate the factors mediating these immobilization-induced changes, we treated rats and small intestinal IEC-6 cells with dexamethasone and hydrogen peroxide. In both rats and IEC-6 cells, treatment with dexamethasone induced changes in gene expression that mimicked the immobilization-mediated increase in expression of the mitochondrial HMG-CoA synthase and dienoyl CoA reductase transcripts, suggesting that stress-induced synthesis of glucocorticoid hormones mediates, at least in part, the stress response in the duodenum. These results suggest that immobilization may alter lipid metabolism in the small intestine by modifying the expression of specific genes through which the small intestine may seek to protect itself from stress-induced damage.

Animals↗
PubMed2006

Cyclooxygenase-2 is required for activated pancreatic stellate cells to respond to proinflammatory cytokines.

Cyclooxygenase-2 (COX-2) mediates various inflammatory responses and is expressed in pancreatic tissue from patients with chronic pancreatitis. To examine the role of COX-2 in chronic pancreatitis, we investigated its participation in regulating functions of pancreatic stellate cells (PSCs), using isolated rat PSCs. COX-2 was expressed in culture-activated PSCs but not in freshly isolated quiescent PSCs. TGF-beta1, IL-1beta, and IL-6 enhanced COX-2 expression in activated PSCs, concomitantly increasing the expression of alpha-smooth muscle actin (alpha-SMA), a parameter of PSC activation. The COX-2 inhibitor NS-398 blocked culture activation of freshly isolated quiescent PSCs. NS-398 also inhibited the enhancement of alpha-SMA expression by TGF-beta1, IL-1beta, and IL-6 in activated PSCs. These data indicate that COX-2 is required for the initiation and promotion of PSC activation. We further investigated the mechanism by which cytokines enhance COX-2 expression in PSCs. Adenovirus-mediated expression of dominant negative Smad2/3 inhibited the increase in expression of COX-2, alpha-SMA, and collagen-1 mediated by TGF-beta1 in activated PSCs. Moreover, dominant negative Smad2/3 expression attenuated the expression of COX-2 and alpha-SMA enhanced by IL-1beta and IL-6. Anti-TGF-beta neutralizing antibody also attenuated the increase in COX-2 and alpha-SMA expression caused by IL-1beta and IL-6. IL-6 as well as IL-1beta enhanced TGF-beta1 secretion from PSCs. These data indicate that Smad2/3-dependent pathway plays a central role in COX-2 induction by TGF-beta1, IL-1beta, and IL-6. Furthermore, IL-1beta and IL-6 promote PSC activation by enhancing COX-2 expression indirectly through Smad2/3-dependent pathway by increasing TGF-beta1 secretion from PSCs.

Actins↗
PubMed2006

Immobilization decreases duodenal calcium absorption through a 1,25-dihydroxyvitamin D-dependent pathway.

Immobilization induces significant and progressive bone loss, with an increase in urinary excretion and a decrease in intestinal absorption of calcium. These actions lead to negative calcium balance and the development of disuse osteoporosis. The aims of this study were to evaluate the molecular mechanisms of decreased intestinal calcium absorption and to determine the effect of dietary 1,25-dihydroxyvitamin D [1,25(OH)2D] and a high-calcium diet on bone loss due to immobilization. The immobilized rat model was developed in the Bollman cage III to induce systemic disuse osteoporosis in the animals. There was a significant decrease in lumbar bone mineral density (BMD) and intestinal calcium absorption in the immobilized group compared with the controls. Serum 25-hydroxyvitamin D concentration did not change, but 1,25(OH)2D concentration decreased significantly. The mRNA levels of renal 25-hydoxyvitamin D 24-hydroxylase (24OHase) increased, whereas those of renal 25-hydroxyvitamin D 1-alpha hydroxylase (1alpha-hydroxylase), duodenal transient receptor potential cation channel, subfamily V, member 6 (TRPV6), TRPV5, and calbindin-D9k were all decreased. A high-calcium diet did not prevent the reduction in lumbar BMD or affect the mRNA expression of proteins related to calcium transport. Dietary administration of 1,25(OH)2D increased the intestinal calcium absorption that had been downregulated by immobilization. TRPV6, TRPV5, and calbindin-D9k mRNA levels were also upregulated, resulting in prevention of the reduction in lumbar BMD. Therefore, it is concluded that dietary 1,25(OH)2D prevented decreases in intestinal calcium absorption and simultaneously prevented bone loss in immobilized rats. However, it remains unclear that calcium absorption and expression of calcium transport proteins are essential for the regulation of lumbar BMD.

Animals↗
PubMed2006

Double-balloon endoscopy: from concept to reality.

The history of the double-balloon endoscope from conception to development and practical application has been described. The theory itself is quite simple, and there were opinions doubting its practicality at the early stage of development.Double-balloon endoscopes, however, are commercially available now. They have been used widely, and their usefulness has been recognized. When development of the double-balloon endoscope was progressing, development of capsule endoscopes also was progressing. The authors often heard opinions that, since capsule endoscopes were expected to become commercially available in the near future, it was out-of-date to devise a method to insert an enteroscope into the small intestine. The authors, however, believed that if the use of capsule endoscopes spread, the necessity of an enteroscope that can reach the entire area in the small intestine would not disappear, but become even bigger. If any abnormal finding is detected by a capsule endoscope, the necessity of enteroscopy for a detailed examination increases. This is being proven at present.

Catheterization↗
PubMed2006

Ubiquitin ligase Cbl-b downregulates bone formation through suppression of IGF-I signaling in osteoblasts during denervation.

UNLABELLED: Unloading can prevent bone formation by osteoblasts. To study this mechanism, we focused on a ubiquitin ligase, Cbl-b, which was highly expressed in osteoblastic cells during denervation. Our results suggest that Cbl-b may mediate denervation-induced osteopenia by inhibiting IGF-I signaling in osteoblasts. INTRODUCTION: Unloading, such as denervation (sciatic neurectomy) and spaceflight, suppresses bone formation by osteoblasts, leading to osteopenia. The resistance of osteoblasts to growth factors contributes to such unloading-mediated osteopenia. However, a detailed mechanism of this resistance is unknown. We first found that a RING-type ubiquitin ligase, Cbl-b, was highly expressed in osteoblastic cells after sciatic neurectomy in mice. In this study, we reasoned that Cbl-b played an important role in the resistance of osteoblasts to IGF-I. MATERIALS AND METHODS: Cbl-b-deficient (Cbl-b(-/-)) or wildtype (Cbl-b(+/+)) mice were subjected to sciatic neurectomy. Bone formation in these mice was assessed by calcein labeling and histomorphometric analyses. We examined IGF-I signaling molecules in femora of these mice by Western blot and immunohistochemical analyses. We also examined the mitogenic response of Cbl-b-overexpressing or -deficient osteoblastic cells to various growth factors. RESULTS: In Cbl-b(+/+) mice, denervation decreased femur mass and bone formation, whereas it increased the expression of Cbl-b protein in osteoprogenitor cells and in osteocalcin-positive cells (osteoblastic cells) in hindlimb bone. In contrast, in Cbl-b(-/-) mice, bone mass and bone formation were sustained during denervation. Denervation inhibited the mitogenic response of osteoprogenitor cells most significantly to IGF-I. Therefore, we focused on Cbl-b-mediated modification of IGF-I signaling. Denervation decreased the amounts of insulin receptor substrate-1 (IRS-1), phosphatidly inositol 3-phosphate kinase (PI3K), and Akt-1 proteins in femora of Cbl-b(+/+) mice, whereas the amounts of these IGF-I signaling molecules in femora of Cbl-b(-/-) mice were constant after denervation. On a cellular level, primary osteoblastic cells from Cbl-b(-/-) mice were more stimulated to proliferate by IGF-I treatment compared with those from Cbl-b(+/+) mice. Furthermore, overexpression of Cbl-b increased ubiquitination and degradation of IRS-1 in primary Cbl-b(-/-) osteoblastic cells, leading to their impaired mitogenic response to IGF-I. CONCLUSIONS: These results suggest that Cbl-b induces resistance of osteoblasts to IGF-I during denervation by increasing IRS-1 degradation and that Cbl-b-mediated modification of IGF-I signaling may contribute to decreased bone formation during denervation.

Animals↗
PubMed2006

[Vitamin D and phosphate metabolism; relationship with aging-regulating gene].

It has been known that phosphate homeostasis is mainly regulated by parathyroid hormone and vitamin D. Fibroblast growth factor 23 (FGF23) has been identified as a novel factor that regulates vitamin D and phosphate metabolism. Genetic defect of FGF23 in mice revealed not only abnormal vitamin D and phosphate metabolism, but also premature aging-like phenotype that is quite similar to Klotho mice. Regulation of vitamin D and phosphate metabolism is closely related to aging processes as well as bone and mineral metabolism.

Aging↗
PubMed2005

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↗
PubMed2005

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↗
PubMed2005

Alternative promoters and renal cell-specific regulation of the mouse type IIa sodium-dependent phosphate cotransporter gene.

The type IIa sodium-dependent phosphate cotransporter (NPT2a) expressed in renal proximal tubules represents an important determinant in maintaining inorganic phosphate (Pi) homeostasis. In the present study, we identified two variant transcripts of the mouse NPT2a gene, Npt2a-v1 and Npt2a-v2, characterized by the presence of alternative first exons (either exon 1A or exon 1B). The chromosomal structure analysis revealed that the Npt2a gene comprises of two promoters (promoters 1 and 2) and 14 exons, and spans approximately 17 kb. Quantitative PCR analysis showed that renal mRNA levels of both the variants markedly decreased in X-linked vitamin D-resistant hypophosphatemic rickets (Hyp) mice compared to normal littermates. Interestingly, transcriptional activity of a reporter gene, containing Npt2a promoters 1 and 2, was renal cell-specifically increased by 1alpha, 25(OH)2D3 and its analogs. The deletion analysis revealed that the CAAT box in the Npt2a promoter 2 is important for the 1alpha, 25(OH)2D3-dependent renal cell-specific activation of the reporter gene. These data suggested that two alternative promoters control the renal expression of Npt2a gene and both Npt2a variant transcripts are down regulated in Hyp mice.

5' Flanking Region↗
PubMed2005

Interferon-gamma activates transcription of NADPH oxidase 1 gene and upregulates production of superoxide anion by human large intestinal epithelial cells.

NADPH oxidase 1 (Nox1), a homolog of gp91(phox), is dominantly expressed in large intestinal epithelium, and reactive oxygen species derived from Nox1 are suggested to serve a role in host defense. We report that interferon (IFN)-gamma, a crucial transactivator of the gp91(phox) gene, also stimulates expression of Nox1 mRNA and protein in large intestinal epithelium (T84 cells), leading to fourfold upregulation of superoxide anion (O(2)(-)) generation. Introduction of small interfering Nox1 RNA completely blocked this priming. We cloned the region from -4,831 to +195 bp of the human Nox1 gene. To reveal IFN-gamma-responsive cis elements, we performed transient expression assays using a reporter gene driven by serially truncated Nox1 promoters in T84 cells. IFN-gamma-responsive elements were located between -4.3 and -2.6 kb, and one gamma-activated sequence (GAS) element present at -3,818 to -3,810 bp exhibited this IFN-gamma-dependent promoter activity. IFN-gamma caused tyrosine phosphorylation of signal transducer and activator of transcription 1 (STAT1) and produced a protein-GAS complex that was recognized by anti-STAT1 antibody. The introduction of three-point mutation of GAS, which did not interact with STAT1, completely canceled the IFN-gamma-dependent promoter activity of the region from -4,831 to +195 bp. A Janus protein tyrosine kinase 2 inhibitor (AG490) blocked the IFN-gamma-stimulated tyrosine phosphorylation of STAT1, promoter activity of the -4,831 to +195 bp region, Nox1 mRNA expression, and O(2)(-) production, also suggesting a crucial role of STAT1 and GAS in the IFN-gamma-stimulated transcription of the Nox1 gene. Our results support a potential contribution of Nox1 to mucosal host defense and inflammation in the colon.

Amino Acid Sequence↗
PubMed2005

Non-steroidal anti-inflammatory drug-induced small bowel injuries identified by double-balloon endoscopy.

AIM: To clarify clinical features of the NSAID-induced small bowel lesions using a new method of endoscopy. METHODS: This is a retrospective study and we analyzed seven patients with small bowel lesions while taking NSAIDs among 61 patients who had undergone double-balloon endoscopy because of gastro-intestinal bleeding or anemia between September 2000 and March 2004, at Jichi Medical School Hospital in Japan. Neither conventional EGD nor colonoscopy revealed any lesions of potential bleeding sources including ulcerations. Double-balloon endoscopy was carried out from oral approach in three patients, from anal approach in three patients, and from both approaches in one patient. RESULTS: Ulcers or erosions were observed in the ileum in six patients and in the jejunum in one patient, respectively. The ulcers were multiple in all the patients with different features from tiny punched out ulcers to deep ulcerations with oozing hemorrhage or scar. All the patients recovered uneventfully and had full resolution of symptoms after suspension of the drug. CONCLUSION: NSAIDs can induce injuries in the small bowel even in patients without any lesions in both the stomach and colon.

Administration, Oral↗
PubMed2005

A case of esophageal stricture due to metastatic breast cancer diagnosed by endoscopic mucosal resection.

Metastasis of breast cancer to the esophagus has been reported but is rare. It is often difficult to diagnose metastases of breast cancer to the esophagus because they are often located in the submucosa and covered with normal mucosa. Although several methods have been reported in order to obtain specimens for pathological diagnosis, the adverse effects including bleeding and perforation were considerable problems. We report a case of a patient with esophageal stricture due to metastatic breast cancer to the esophagus. Pathological diagnosis was successfully obtained using endoscopic mucosal resection of the esophagus.

Adenocarcinoma↗
PubMed2005

Clinical outcomes of enteroscopy using the double-balloon method for strictures of the small intestine.

AIM: To evaluate the clinical outcome of enteroscopy, using the double-balloon method, focusing on the involvement of neoplasms in strictures of the small intestine. METHODS: Enteroscopy, using the double-balloon method, was performed between December 1999 and December 2002 at Jichi Medical School Hospital, Japan and strictures of the small intestine were found in 17 out of 62 patients. These 17 consecutive patients were subjected to analysis. RESULTS: The double-balloon enteroscopy contributed to the diagnosis of small intestinal neoplasms found in 3 out of 17 patients by direct observation of the strictures as well as biopsy sampling. Surgical procedures were chosen for these three patients, while balloon dilation was chosen for the strictures in four patients diagnosed with inflammation without involvement of neoplasm. CONCLUSION: Double-balloon enteroscopy is a useful method for the diagnosis and treatment of strictures in the small bowel.

Adult↗