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Hiroto Kita

Publications and source records attributed to Hiroto Kita.

At least 19 recordsLinked to original sources
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

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

A case of hepatic pseudolymphoma observed without surgical intervention.

We report a case of liver pseudolymphoma that has been followed up without surgical resection after the diagnosis. A 63-year-old woman with a hepatic hypo-echoic lesion, 16mm in diameter was referred to our hospital. Laboratory data on admission were within normal limits. Serum HbsAg and HCVAb were negative. Abdominal computed tomography revealed an enhanced round lesion at the same location of the liver. Histopathological examination of the biopsy specimen demonstrated aggregation of the small round cells, lacking cytologic atypia or mitotic figures. These cells were B lymphocytes with staining of kappa and lambda light chains at equal frequency. Furthermore, monoclonal band was not detected by the polymerase chain reaction (PCR) method for the position of the third complementarity-determing region (CDR3) in the immunoglobulin heavy chain (IgH). These results suggested that the cells infiltrated in the lesion were polyclonal and benign nature. This case was observed carefully without surgical operation. During the course, Helicobacter pylori were successfully eradicated. Follow-up study after 18 months showed that the diameter of the tumor had decreased from 16mm to 8mm, suggesting no evidence of the malignant transformation.

Journal Article↗
PubMed2006

Sonic hedgehog stimulates the proliferation of rat gastric mucosal cells through ERK activation by elevating intracellular calcium concentration.

Sonic Hedgehog (Shh), a member of hedgehog peptides family, is expressed in gastric gland epithelium. To elucidate Shh function to gastric mucosal cells, we examined the effect of Shh on the proliferation of a rat normal gastric mucosal cell line, RGM-1. RGM-1 cells express essential components of Shh receptor system, patched-1, and smoothened. Shh enhanced DNA synthesis in RGM-1 cells and elevated intracellular calcium concentration ([Ca2+]i). In addition, Shh as well as calcium ionophore A32187 rapidly activated ERK. However, Shh failed to activate ERK under calcium-free culture condition. Pretreatment of cells with PD98059 attenuated the DNA synthesis promoted by Shh. Moreover, when cells were pretreated with cyclopamine, Shh could not elevate [Ca2+]i, activate ERK or promote DNA synthesis. On the other hand, although Shh induced Gli-1 nuclear accumulation in RGM-1 cells, Shh activated ERK even in cells pretreated with actinomycin D. These results indicate that Shh promotes the proliferation of RGM-1 cells through an intracellular calcium- and ERK-dependent but transcription-independent pathway via Patched/Smoothened receptor system.

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↗
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

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↗
PubMed2005

Enteroscopy.

Wireless capsule endoscopy and double-balloon endoscopy are new methods of enteroscopy that have been introduced in recent years. Wireless capsule endoscopy is an epoch-making examination method that makes possible an endoscopic imaging examination of the entire small intestine without discomfort and without confining patients to a medical facility. Although it is expected to be useful as an initial examination for finding diseases of the small intestine, it cannot be used for biopsy or treatment. One risk associated with the capsule endoscopy technique is entrapment by strictures. Double-balloon endoscopy is based on a new insertion technique in which two balloons, one at the distal end of the endoscope and the other at the distal end of an overtube, are operated in combination, and the endoscope is inserted while simultaneously shortening the intestine. It can be inserted through either the mouth or the anus, allowing the observation of the entire gastrointestinal tract. It features excellent maneuverability even in the distal small intestine, and enables back-and-forth observation, biopsy, and endoscopic treatment at any given site. These two new enteroscopy techniques are expected to lead to innovations in how diseases of the small intestine are approached.

Endoscopes, Gastrointestinal↗
PubMed2005

Endoscopic therapy of early gastric cancer.

Endoscopic therapy of early gastric cancer is applicable for differentiated-type mucosal carcinomas that have an extremely low potency of lymph-node metastasis. Among various kinds of endoscopic therapy, endoscopic mucosal resection is the most recommended procedure, because pathological evaluation of affected tissues is available using this method. Recently, endoscopic submucosal dissection, a novel method of endoscopic mucosal resection, has gained interest as a more reliable therapeutic procedure. In the present chapter several issues will be presented on endoscopic therapy for early gastric cancer, including endoscopic diagnosis of early gastric cancer, currently accepted indications of endoscopic therapy, and the possibility of extending the indication and techniques used for mucosal resection.

Dissection↗
PubMed2005

Technical modification of the double-balloon endoscopy to access to the proximal side of the stenosis in the distal colon.

BACKGROUND: The inability to pass endoscopes beyond strictures is a considerable problem in patients with a colonic stricture. METHODS: In patients with bowel obstruction, we have modified the insertion method for double-balloon endoscopy with a long, transnasal decompression tube. OBSERVATIONS: We have succeeded in reaching the proximal side of the stricture from the oral approach across the entire small bowel in a patient. CONCLUSIONS: This modified double-balloon enteroscopy is useful for patients with bowel obstruction in whom a long decompression tube is already placed.

Colonic Diseases↗