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Biomedical subjects

Tooru Shimosegawa

Publications and source records attributed to Tooru Shimosegawa.

At least 91 records · Page 5Linked to original sources
PubMed2004

Rupture of rectal varices treated with endoscopic variceal ligation.

We report here 3 cases of rectal varices treated with endoscopic variceal ligation and discuss the pathogenesis, treatment, and prognosis of rectal varices with referring to previous reports. Of the 3 patients, 2 had been diagnosed as liver cirrhosis and 1 as extrahepatic portal hypertension. All of the 3 patients had previously undergone treatment of esophagogastric varices. The rupture of rectal varices appeared to have some relationship with the treatment of esophageal varices. In previous reports, 73% of patients with ruptured rectal varices treated with endoscopic injection sclerotherapy or endoscopic variceal ligation had undergone treatments of esophageal varices. The endoscopic treatments resulted in a favorable prognosis in 2 patients. Although no fatality from endoscopic injection sclerotherapy or endoscopic variceal ligation has been reported, 1 of the present 3 cases died of liver failure.

Aged↗
PubMed2004

Ribavirin upregulates interleukin-12 receptor and induces T cell differentiation towards type 1 in chronic hepatitis C.

BACKGROUND AND AIM: The mechanisms of ribavirin as an immune modulator have not been fully revealed, contrary to its clinical benefit in chronic hepatitis C. Recently, host immune defense, especially cytotoxic T lymphocytes and T helper cells, have been considered to be closely related to the pathophysiology of chronic viral hepatitis. The aim of the present study was to evaluate the function of ribavirin in cellular immunity. METHODS: Peripheral blood mononuclear cells and total RNA were prepared from chronic hepatitis C patients. To evaluate the polarization of T helper cells, we performed intracellular cytokine assay and quantified the production of key cytokines. mRNA levels of interleukin-12 receptor (IL-12R), interferon (IFN)-gamma and interleukin-4 (IL-4) were measured by real time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The population of T helper 1 cells increased significantly both in mitogen and hepatitis C virus (HCV) core protein stimulated cells with 0.1 microg/mL of ribavirin. However, the population of T helper 2 cells did not seem to be affected by ribavirin. The level of IL-12R beta2 chain mRNA was also upregulated to 130% after 24 h incubation with 0.1 microg/mL ribavirin (P = 0.037), whereas the beta1 chain did not change significantly under these conditions. In addition, 0.1 microg/mL ribavirin could upregulate the levels of IFN-gamma or IL-4 mRNA in some cases. CONCLUSION: Ribavirin, perhaps by acting directly on CD4+ T cells, induces T cell differentiation towards type 1, depending on the upregulated signal of the IL-12/IL-12R pathway.

Antiviral Agents↗
PubMed2004

Expression of Mg2+-dependent, HCO3- -stimulated adenine triphosphatase in the human duodenum.

BACKGROUND AND AIM: Mg2+-dependent, HCO3- -stimulated adenine triphosphatase (Mg2+-HCO3- -ATPase) is an enzyme that catabolizes ATP in the presence of HCO3- and Mg2+. The activity of this ATPase is known to be present in the duodenum, but its physiological role remains unclear. In the present study, the aim was to study the distribution and biochemical profiles of Mg2+-HCO3- -ATPase in the human duodenum. METHODS: The histochemistry of Mg2+-HCO3- -ATPase, its localization using electron microscopy (EMS), and the measurement of enzyme activity were carried out by using mucosal samples of the bulb, and the second and third portions of the duodenum, obtained from six volunteers by endoscopic biopsy. RESULTS: The Mg2+-HCO3- -ATPase was detected in the brush border along the luminal surface of human duodenal epithelial cells. The EMS confirmed its localization to the surface of microvilli. The activity of Mg2+-HCO3- -ATPase was higher in the distal portions of the human duodenum than in the bulb. Its maximal activity was obtained under a pH of 8.5, and in the presence of 1.0 mmol/L MgCl2 and 50 mmol/L NaHCO3, but the activity was undetectable in pH <7.4 or >9.5. CONCLUSION: The results of the present study suggested that Mg2+-HCO3- -ATPase may work for luminal alkalization in the distal portions of the human duodenum and may contribute to maintaining the activity of pancreatic digestive enzymes.

Ca(2+) Mg(2+)-ATPase↗
PubMed2004

The prevalence of Helicobacter pylori infection and the status of gastric acid secretion in patients with Barrett's esophagus in Japan.

OBJECTIVES: The acidity of the refluxate into the esophagus is a key factor for the pathogenesis of gastroesophageal reflux disease. Helicobacter pylori (H. pylori) infection can influence gastric acid secretion. We have reported that H. pylori infection prevents reflux esophagitis by decreasing gastric acid secretion in Japanese patients, but the role of this organism in Barrett's esophagus is unclear. The aim of this study was to investigate the prevalence of H. pylori infection and gastric acid secretion in Japanese patients with reflux esophagitis with or without Barrett's esophagus. METHODS: We enrolled 112 reflux esophagitis patients who were examined for the status of H. pylori and acid secretion in this study. They were divided into three groups, according to the presence or absence of Barrett's esophagus as follows: reflux esophagitis group without Barrett's esophagus (reflux esophagitis alone) (80 patients); short-segment Barrett's esophagus group (16 patients); and long-segment Barrett's esophagus group (LSBE) (16 patients). Age- and sex-matched control subjects were also assigned to the 80 patients with reflux esophagitis alone. The prevalence of H. pylori infection was determined by histology, rapid urease tests, and serum IgG antibodies. Gastric acid secretion was evaluated by the endoscopic gastrin test (EGT). RESULTS: The overall prevalence of H. pylori infection in the reflux esophagitis patient group (24.1%) was significantly lower than the control group (71.2%) (odds ratio 0.13, 95% confidence interval 0.07-0.24; p < 0.0001). The prevalence of H. pylori infection in the patients with Barrett's esophagus tended to be lower than that in the patients with reflux esophagitis alone (reflux esophagitis alone; 30.0%, SSBE; 18.7%, LSBE; 0%), especially in the patients with LSBE compared with the reflux esophagitis alone group (p < 0.01). The EGT value of the respective reflux esophagitis patient group was significantly higher than the control group. The EGT value in the patients with Barrett's esophagus tended to be higher than that in the patients with reflux esophagitis alone, but the difference was not statistically significant. When examined in H. pylori-negative subjects, no difference was found in the EGT value between the control subjects and the patients with reflux esophagitis alone, but it was significantly higher in patients with Barrett's esophagus than the control subjects (p < 0.05). On the other hand, when examined in the H. pylori-positive subjects, the EGT value was significantly higher in the patients with reflux esophagitis alone than in the control subjects (p < 0.01). CONCLUSIONS: H. pylori infection may play a protective role in the development of Barrett's esophagus, especially in the development of LSBE in Japan. Gastric acid hypersecretion may be concerned with the development of Barrett's esophagus in addition to the absence of H. pylori infection.

Adolescent↗
PubMed2004

Panniculitis of the descending colon caused by enterocolic phlebitis: a case report.

A 73-year-old male was referred to our hospital for abdominal pain, diarrhea and general fatigue lasting for 3 weeks. Physical examination of the abdomen revealed a firm mass in the left abdominal region. Computed tomography revealed a mass around the descending colon. Colonoscopy and barium enema revealed poor extensibility of the lumen with edematous mucosa, and narrowing of the descending colon with rugged mucosal surface. Because of the clinical symptoms and findings, the patient was diagnosed clinically as suffering from panniculitis of the descending colon. He underwent the left hemi-colectomy with side-to-side colo-colostomy after making of a loop ileostomy. Histological analysis of the resected colon showed an infiltration of inflammatory cells, predominantly lymphocytes, into veins and venules of the submucosa, muscularis propria and fat tissue of the colonic mesentery, with an involvement of all layers of the vessel wall. Arteries were escaped from inflammatory changes. The histopathological diagnosis of enterocolic phlebitis and venulitis was made because of these findings.

Aged↗
PubMed2004

[Helicobacter pylori-related cytokines influence gastric acid secretion and gastric mucosal inflammation in gastroduodenal ulcers].

Helicobacter pylori(H. pylori) is an important pathogenic factor for gastroduodenal ulcers and gastric cancer. The level of gastric acid output may influence the outcome of those diseases. With low acid output, H. pylori can spread to the corpus of the stomach, resulting in progression to atrophic gastritis. It may cause an increased risk of gastric cancer and ulcer. In contrast, with high output, H. pylori is confined in the gastric antrum, which develops antrum-predominant gastritis. This may contribute to an increased risk of duodenal ulcer. It is well known that inflammatory cytokines including interleukin (IL)-1 beta, IL-8 and tumor necrosis factor alpha modulate gastric acid secretion. Therefore, the host immune response by the cytokines may cause these disparate pathways in gastric acid secretion.

Gastric Acid↗
PubMed2004

[Reflux esophagitis after H. pylori eradication].

We have reported that prevalence of H. pylori infection and grade of atrophic gastritis were significantly lower, while acid secretion was significantly greater in the patients with reflux esophagitis than those without it. We have also reported that increased gastric acid secretion after H. pylori eradication may explain a reason for developing reflux esophagitis. Therefore, H. pylori is considered to be a protective factor for the development of reflux esophagitis via the induction of gastric hyposecretion. Conversely, according to recent large population-based studies, no evidence was obtained that supports the increased frequency of heartburn symptoms or reflux oesophagitis after the eradication of H. pylori. One reason for the discrepancy may be the difference in the evaluation of gastro-esophageal reflux, another reason may be the difference in acid secretion before the clearance of H. pylori in individual subjects, because the effects of H. pylori on acid secretion vary from patient to patient.

Esophagitis, Peptic↗
PubMed2004

[Anti-cytokine therapy for severe acute pancreatitis].

The systemic manifestations of acute pancreatitis (AP) are responsible for the majority of pancreatitis-associated morbidity and mortality. Recent studies have established that severe AP is a disease with systemic inflammatory response syndrome as well as compensatory anti-inflammatory response syndrome. Based on their roles in the pathogenesis of AP, new therapies have been sought and tested, including those preventing the biological activity of two pro-inflammatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin-1 (IL-1). Biological activity of TNF might be blunted by anti-TNF-alpha antibody or soluble TNF receptor, and IL-1 receptor antagonist might blunt that of IL-1. Although anti-cytokine therapies against IL-1, TNF-alpha or macrophage migration inhibitory factor showed promising results in experimental models of AP, the question remains as to whether similar antagonism during clinical pancreatitis would benefit patients with severe AP. Major considerations include the suitability of AP to cytokine antagonism in clinical settings, the possibility that such a therapy may lead to the development of immunosuppression and consequent infection, and whether a therapeutic window for such antagonism

Acute Disease↗
PubMed2004

[Influence of urease activity of the oral cavity and oropharynx on 13C-urea breath test].

We examined whether 13C-urea breath test with powdered 13C-Urea is affected with urease activity in the oral cavity and oropharynx in H. pylori negative cases. We also examined whether the degree of gargling affects the results of 13C-UBT. The results demonstrated that the urease activity not only in the oral cavity, but in the oropharynx may influence the UBT value. Therefore, it is possible that the UBT value may be affected with relic urease activity in the oropharynx if only the oral cavity is gargled. In conclusion, Gargling of the oropharynx in addition to the oral cavity is important to obtain true negative diagnosis with 13C-UBT in patients without Helicobacter pylori infection.

Adult↗
PubMed2003

PTH/PTH-related protein receptor interacts directly with Tctex-1 through its COOH terminus.

COOH-terminal cytoplasmic domains of G protein-coupled receptors (GPCRs) have been shown to carry determinants that control their cell surface localization, internalization, and recycling. In attempts to seek cellular proteins that mediate these processes of PTH/PTH-related protein receptor (PTHR), one of the class B GPCRs, we have found that Tctex-1, a 14kDa light chain of cytoplasmic dynein motor complex, interacts with the COOH-terminal tail of the receptor. A 34-amino-acid stretch of the receptor responsible for binding to Tctex-1 has a bipartite structure consisting of a motif previously implicated in binding of some proteins to Tctex-1 and a putative new consensus sequence. Site-directed mutations or a 20-amino-acid deletion in the bipartite consensus binding sequence abolished the association of the PTHR COOH terminus with Tctex-1 in vitro. A GFP-fused mutant PTHR impaired in binding to Tctex-1 expressed in MDCK cells showed a decreased rate of internalization in response to PTH compared to that of the wild type.

Amino Acid Motifs↗
PubMed2003

Tochu (Eucommia ulmoides) leaf extract prevents ammonia and vitamin C deficiency induced gastric mucosal injury.

The ingestion of dietary antioxidants, including vitamin C (VC), is suggested to play an important role in the prevention of gastric cancer associated with Helicobacter pylori (HP) infection. Recently, water extracts of Tochu (Du-zhong, Eucommia ulmoidea OLIVER) leaves (WETL) have been reported to have potent antioxidant and antimutagenic effects. The present study investigated the effect(s) of VC and WETL on gastric mucosal injury induced by ammonia and a VC deficient diet. Guinea pigs fed the water containing ammonia and/or a VC-deficient diet were simultaneously treated with WETL or VC. Intramucosal levels of thiobarubiturate reactive substances (TBARS), an index of lipid peroxidation, increased significantly in animals fed ammoniated water and VC-deficient diets. This was accompanied by accelerated cell proliferation and increases in immunohistochemical staining indices for oxidative stress-induced DNA adducts and strand breaks (e.g., BrdU-uptake, 8-OhdG, ssDNA and the TUNEL reaction). The administration of either WETL or VC to the ammoniated water and VC-deficient diets ameliorated the increases in intramucosal TBARS levels and labeling indices of BrdU, 8-OHdG, ssDNA and TUNEL, i.e., the levels were similar to those measured in the normal-fed control animals. These data suggest that insufficient VC ingestion may be an important risk factor for gastric cancer development in patients with HP infections. Furthermore, our results suggest that WETL or some constituent may contribute to the prevention of oxidative gastric injury that precedes carcinogenesis.

Ammonia↗
PubMed2003

Rho kinase inhibitors block activation of pancreatic stellate cells.

1. In response to pancreatic injury and in cell culture, pancreatic stellate cells (PSCs) are transformed ('activated') into highly proliferative myofibroblast-like cells, which express alpha-smooth muscle actin (alpha-SMA), and produce type I collagen and other extracellular matrix components. There is accumulating evidence that activated PSCs play important roles in pancreatic fibrosis and inflammation. 2. The small GTP-binding protein Rho has emerged as an important regulator of the actin cytoskeleton and cell morphology through the downstream effector Rho kinase (ROCK). But, the roles of Rho-ROCK pathway in PSCs are unknown. Here, we examined the effects of (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide (Y-27632) and HA-1077 (fasudil), specific inhibitors of ROCK, on the activation of PSCs. 3. PSCs were isolated from the pancreas of male Wistar rats after perfusion with collagenase P. The actin cytoskeleton was analyzed by phalloidin staining. Expression of RhoA and ROCK was examined by immunostaining and Western blotting. Effects of Y-27632 and HA-1077 on alpha-SMA expression, platelet-derived growth factor-induced proliferation and chemotaxis, and collagen production were assessed. 4. Culture-activated PSCs developed a well-spread cell shape, with extended stress fiber formation. PSCs expressed RhoA, ROCK-1, and ROCK-2. 5. Y-27632 caused disassembly of stress fibers. Y-27632 and HA-1077 inhibited alpha-SMA expression, proliferation, chemotaxis, and type I collagen production in culture-activated PSCs. 6. In addition, Y-27632 and HA-1077 inhibited spontaneous activation of freshly isolated PSCs in culture on plastic. 7. These findings suggest a role of Rho-ROCK pathway in the activation process of PSCs by regulating the actin cytoskeleton, and a potential application of Rho-ROCK pathway inhibitors for the treatment of pancreatic inflammation and fibrosis.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2003

Identification and characterization of novel rat and human gonad-specific organic anion transporters.

We have isolated three novel organic anion transporter cDNAs designated rat GST-1 (gonad-specific transporter), rat GST-2, and human GST, expressed at high levels in the testis. Rat GST-1, GST-2, and human GST consist of 748, 702, and 719 amino acids, respectively, and all molecules possess the 12 predicted transmembrane domains, which is a common structure of organic anion transporters. Northern blot analyses and in situ hybridization revealed that both of the rat molecules are highly expressed in the testis, especially in Sertoli cells, spermatogonia, and Leydig cells. Weak signals are also detected in the epididymis and ovary in adult rat. The exclusive expression of human GST mRNA in the testis was confirmed by RT-PCR. The pharmacological experiments of Xenopus laevis oocytes injected with the respective rat GST-1- and GST-2-cRNAs revealed that both rat GST-1 and GST-2 transport taurocholic acid, dehydroepiandrosterone sulfate, and T4 with Michaelis-Menten kinetics (taurocholic acid, Km = 8.9 and 2.5 microm, dehydroepiandrosterone sulfate, Km = 25.5 and 21.microm, and T4, Km = 6.4 and 5.8 for rat GST-1 and GST-2, respectively). T3 was also transported by rat GST-1 and GST-2. These data suggest that rat GST-1 and GST-2 might be one of the molecular entities responsible for transporting dehydroepiandrosterone sulfate and thyroid hormones involved in the regulation of sex steroid transportation and spermatogenesis in the gonad.

Amino Acid Sequence↗
PubMed2003

Microsatellite instability and loss of heterozygosity in the nondysplastic colonic epithelium of ulcerative colitis.

Background. A major longterm risk for patients with ulcerative colitis (UC) is the development of colorectal dysplasia and cancer. Microsatellite instability (MI) has now been reported not only in colitic cancers but also in dysplasias, and even in nondysplastic inflamed mucosa. With the conventional microdissection technique, however, contamination by nonepithelial cells cannot be prevented and this could produce less reliable results than other methods. Therefore, we examined the condition of MI and loss of heterozygosity (LOH) of UC epithelium using a crypt isolation technique. Methods. One hundred and twenty-nine biopsy samples from 21 patients with UC were investigated for histology and microsatellite status, using nine microsatellite markers. A total of 1031 polymenase chain reaction (PCR) products were evaluated. Results. We found that no microsatellite markers displayed instability, but LOH at the 3p locus was detected in the nondysplastic epithelium of one patient with longstanding UC. Conclusions. Our study strongly suggests that MI does not contribute to the progression of the colitis-dysplasia sequence.

Adolescent↗
PubMed2003

Clinical course and longterm prognosis of Japanese patients with Crohn's disease: predictive factors, rates of operation, and mortality.

BACKGROUND: The purpose of this study was to clarify the long-term course of Crohn's disease (CD) and predictors of its prognosis in Japan. METHODS: This was a historical cohort study of 276 patients with CD who had been diagnosed between 1965 and 1998. The clinical course was evaluated by the course of the CD score (CCDS) according to the required treatments. The predictive factors were examined by stepwise regression test. The cumulative rates of operation and survival were calculated by the Kaplan-Meier method. RESULTS: Patients with colitis-type CD had significantly lower annual and cumulative operation rates than those with other types, and showed significantly better progress, estimated by the CCDS, than patients with ileocolitis type. Reliable predictors for the 2- to 5-year clinical course after starting treatment were the CCDS, the presence of laparotomy during the initial year, and onset at age 30 years or more. The predictors for the 6- to 10-year clinical course were the duration of symptoms at diagnosis and onset at age 16 years or less. The predictors for the 11- to 15-year clinical course were the CCDS, the maximum International Organization of the Study of Inflammatory Bowel Disease (IOIBD) assessment score during the first year after starting treatment, and the effectiveness of the initial treatment. Relative survival rates at 5, 10, 15, and 20 years after the onset were 98.9%, 98.1%, 97.7%, and 94.9%, respectively. CONCLUSIONS: CD patients with colitis type showed a better clinical course and had significantly different clinical features compared with the patients with ileitis and ileocolitis type. Prediction of the longterm course of CD is possible by using clinical factors during the first year after starting treatment. The relative survival rates in Japanese patients with CD are not different from those seen in Western countries. The purpose of this study was to clarify the long-term course of Crohn's disease (CD) and predictors of its prognosis in Japan.

Adolescent↗
PubMed2003

Strong telomerase activity of B lymphocyte from mesenteric lymph nodes of patients with inflammatory bowel disease.

Telomerase acitivity can be induced in human B lymphocytes by in vitro stimulation of their antigen receptors. To determine whether telomerase activity is induced in vivo, we analyzed telomerase activity in B lymphocytes from the mesenteric lymph nodes of patients with inflammatory bowel disease (IBD), whose lymph nodes are well known to be strongly stimulated, and from those of noninflamed controls. Seven IBD patients and 4 noninflamed controls were enrolled. Telomerase activity was assayed by telomeric repeat amplification protocol with minor modifications. The mesenteric lymph nodes from patients with IBD had stronger telomerase activity than those from controls or peripheral mononuclear cells. Isolation of CD19+ B lymphocytes from these lymph nodes showed that this strong activity resides in this lymphocytes subpopulation. This study provides the evidence that telomerase activity is induced in human B lymphocytes in human inflammatory disease.

Adult↗
PubMed2003

Cloning and characterization of a novel variant (mM-rdgBbeta1) of mouse M-rdgBs, mammalian homologs of Drosophila retinal degeneration B gene proteins, and its mRNA localization in mouse brain in comparison with other M-rdgBs.

We report the cloning, characterization and localization in the brain of a novel isoform termed mM-rdgBbeta1 (mouse type of mammalian retinal degeneration Bbeta1 protein) in comparison with the localization of three known mammalian homologs (M-rdgBbeta, M-rdgB1, M-rdgB2). mM-rdgBbeta1 cDNA contains a sequence of 119 bp as a form of insertion in the open reading frame of the known mM-rdgBbeta, and encodes a protein of 269 amino acids with a calculated molecular mass of 31.7 kDa, different from the molecular mass of 38.3 kDa of mM-rdgBbeta. It also contains a phosphatidylinositol transfer protein (PITP)-like domain similar to the known three homologs, as well as D-rdgB. The recombinant mM-rdgBbeta1 protein shows the specific binding activity to phosphatidylinositol but not to other phospholipids. This novel molecule is localized not only in the cytoplasm but also in the nucleus, different from the cytoplasmic localization of mM-rdgBbeta. In in situ hybridization analysis, the gene expression for mM-rdgBbeta1 in the brain, though weak, is rather confined to the embryonic stage, different from wider expression of mM-rdgBbeta in the gray matters of pre- and post-natal brains. Taken together, mM-rdgBbeta1 is suggested to play a role in the phosphoinositide-mediated signaling in the neural development.

Amino Acid Sequence↗