bluuebunny/crossref_metadata_2025_split huggingface dataset:
Helicobacter pylori‐induced atrophic gastritis progressing to gastric cancer exhibits sonic hedgehog loss and aberrant CDX2 expression
Authors: SHIOTANI A. , IISHI H. , UEDO N. , ISHIHARA R. , ISHIGURO S. , TATSUTA M. , NAKAE Y. , KUMAMOTO M. , HINOI T. , MERCHANT J. L. 
Published: June 2006

SummaryBackgroundThe loss of sonic hedgehog is an early change that occurs in the mucosa prior to neoplastic transformation and correlates with the type of intestinal metaplasia. Aberrant expression of CDX has also been shown to correlate with the development of intestinal metaplasia.AimTo examine CDX2 expression in the non‐cancerous mucosa of patients with gastric cancer and compared it to CDX2 expression in controls with intestinal metaplasia.MethodsSixty patients who had undergone endoscopic mucosal resection for early gastric cancer and 60 gender‐ and age‐matched controls were studied. Two specimens each were obtained from the greater and lesser curves of the corpus and from the greater curve of the antrum. Expression of CDX2 and sonic hedgehog were evaluated by immunostaining.ResultsGastric cancer was associated with a higher frequency of incomplete intestinal metaplasia (OR = 8.3; 95%CI, 3.7–18.9, P < 0.001). CDX2 negatively correlated with sonic hedgehog expression, however, multivariate analysis revealed that CDX2 correlated with the intestinal metaplasia scores. Sonic hedgehog indices were lower and CDX2 staining in the corpus lesser curve was higher in the cancer group than in the controls. Sonic hedgehog indices in the corpus decreased and CDX2 indices in both areas increased in patients in the ascending order of those without intestinal metaplasia, those with complete intestinal metaplasia and those with incomplete intestinal metaplasia (P < 0.001).ConclusionsLoss of sonic hedgehog expression and aberrant expression of CDX2 correlates with the type of intestinal metaplasia and may play a role in carcinogenesis.
Colonic mucosal lesions associated with long‐term administration of non‐steroidal anti‐inflammatory drugs
Authors: OHKUSA T. , TERAI T. , ABE S. , KOBAYASHI O. , BEPPU K. , SAKAMOTO N. , KUROSAWA A. , OSADA T. , HOJO M. , NAGAHARA A. , OGIHARA T. , SATO N. 
Published: June 2006

SummaryBackgroundEffects of long‐term administration of non‐steroidal anti‐inflammatory drugs (NSAIDs) on the colon have not been well characterized.AimTo investigate colonoscopic findings and prevalence of adverse events following long‐term use of NSAIDs.MethodsThe study included 425 patients (mean 66.4 years) treated for over one year with NSAIDs, and 2125 age‐ and sex‐matched patients without NSAIDs as controls. Eligible candidates were selected by medical record review for underlying diseases, pre‐endoscopic symptoms, category of NSAIDs used, and duration of use. We used endoscopy to study lesion characteristics.ResultsThe occurrence rate of colonic lesions or bleeding in the NSAIDs user (13/425, 3.1%) was higher than that in controls (28/2125, 1.3%) (p = 0.017). Colitis was found in 10 of the 13 patients. The sigmoid colon, descending colon or both (70.0%) was commonly involved, and showed segmental ischemic colitis features in 8 of the 13 patients (61.5%). Among these, duration of use ranged from 1‐30 years (mean 7.8). Nine of 13 patients (69.2%) took low‐dose aspirin.ConclusionThe prevalence of colonic lesions in long‐term NSAIDs users is much lower than that of upper gastrointestinal side effects, but higher than that of colonic lesions in non‐NSAIDs users. The most common features of NSAIDs‐associated colitis were segmental ischeznia.
Enhanced plasma ghrelin levels in patients with functional dyspepsia
Authors: NISHIZAWA T. , SUZUKI H. , NOMOTO Y. , MASAOKA T. , HOSODA H. , MORI M. , OHARA T. , MORISHITA T. , KANGAWA K. , HIBI T. 
Published: June 2006

SummaryBackgroundGhrelin, growth‐hormone‐releasing peptide, has been reported to accelerate food intake and gastrointestinal motility.AimThe present study was designed to investigate the plasma ghrelin levels in patients with functional dyspepsia (FD).Patients and MethodsNinety‐seven patients, who showed no evidence of peptic ulcer disease or gastrointestinal cancer on upper gastrointestinal endoscopy, were recruited. Seventeen patients who had no gastrointestinal symptoms were recruited as controls. Forty‐seven patients were diagnosed to be suffering from FD, based on the Rome II criteria. The FD patients were further subdivided into those with ulcer‐like FD, dysmotility‐like FD and non‐specific‐type FD, based on their Gastrointestinal Symptom Rating Scale (GSRS) scores. Fourteen patients were categorized as having gastro‐oesophageal reflux disease, and 19 patients were excluded as having the irritable bowel syndrome, based on the GSRS. The plasma ghrelin levels were measured by radioimmunoassay.ResultsThe plasma ghrelin levels were significantly higher in FD patients, especially in those with dysmotility‐like FD, as compared with those in controls. The plasma ghrelin levels were also correlated well with the indigestion scores.ConclusionPlasma ghrelin levels are significantly higher in patients with dysmotility‐like FD, suggesting that this parameter could become useful as a novel supportive marker for the diagnosis of FD.
Evaluation of the role of Helicobacter pylori as a promoter of gastric cancer from the viewpoint of structural chromosomal aberration
Authors: OHARA T. , KASANUKI J. , MORISHITA T. , YAMAMOTO N. , SHIBAHARA T. , SUZUKI H. , MASAOKA T. , NISHIZAWA T. , HIBI T. 
Published: June 2006

SummaryAimTo examine whether Helicobacter pylori induces structural chromosomal aberrations, such as loss of heterozygosity (LOH) and microsatellite instability (MSI) in the infected gastric mucosa.MethodsSubjects were 13 patients with H. pylori‐positive and 9 with H. pylori‐negative gastric cancer and 20 patients with H. pylori‐positive and 4 patients with H. pylori‐negative chronic gastritis. Gastric mucosal tissues were endoscopically sampled from each subject. Each sample was checked for structural chromosomal aberrations (LOH and MSI) by PCR and microsatellite analysis, using a total of 31 primers corresponding to the regions containing the major genes of chromosomes 1q, 5q, 7q, 17p, 17q, 18q and 21q.ResultsAll tissue samples obtained from cancer‐affected regions of the stomach had structural chromosomal aberrations (LOH or MSI), irrespective of H. pylori infection. The degree of structural chromosomal aberration was greater in poorly differentiated than well‐differentiated adenocarcinoma. In addition, structural chromosomal aberrations were also found in a few samples obtained from the chronic atrophic gastritis group, irrespective of H. pylori infection.ConclusionsIt seems unlikely that H. pylori serves as a direct promoter of gastric cancer, and H. pylori‐positive chronic gastritis may not always be a precancerous state.
Interaction between Helicobacter pylori and immune response to CagA: CagA antibody may down‐regulate bacterial colonization and tyrosine phosphorylation
Authors: DEGUCHI R. , WATANABE K. , KOGA Y. , KIJIMA H. , TAKAGI A. 
Published: June 2006

SummaryBackgroundCagA+Helicobacter pylori strains are associated with the development of gastroduodenal diseases. H. pylori possess a type IV secretion system that is responsible for the translocation of CagA into host cells.AimTo investigate the correlation between the CagA status and the severity of histological gastritis and to analyse the tyrosine phosphorylation of CagA.MethodsA total of 149 H. pylori status was determined via urine antibody to H. pylori, histological examination and serum antibody against CagA. Histological gastritis was evaluated using the updated Sydney system and scored from 0 to 3. Tyrosine phosphorylation was analysed using immunoprecipitation and immunoblotting.ResultsAnti‐CagA titres were correlated with the severity of mononuclear cell infiltration. In contrast, mean anti‐CagA in patients with grade 2 bacterial density was significantly higher than those with grade 0 (P < 0.01). Mean anti‐titre in patients with grade 3 tended to be lower than that seen with grade 2. CagA tyrosine phosphorylation was significantly more common in bacteria isolated from CagA‐antibody‐negative patients (93%;13/14) than from CagA‐antibody‐positive patients (29%; 4/14, P = 0.0007).ConclusionsHost–bacteria interaction is regarded as one of the important factors in the development of gastroduodenal diseases.
Evaluation of gastro‐oesophageal flap valve is useful for diagnosing gastro‐oesophageal reflux disease
Authors: IWAMOTO M. , KATO K. , MIZUNO S. , MIYAMOTO S. , TAKEUCHI R. , IWASAKI A. , ARAKAWA Y. 
Published: June 2006

SummaryBackgroundGastro‐oesophageal flap valve (GEFV) grade correlated with endoscopic reflux oesophagitis (RE) prevalence.AimTo investigate relationships among gastro‐oesophageal reflux disease (GERD) symptoms, RE and/or non‐erosive reflux disease (NERD) and GEFV grades in subjects undergoing endoscopy.MethodsWe enrolled 1305 subjects from whom endoscopic results and the results of a self‐administered questionnaire (QUEST) were available. Subjects were evaluated for GERD symptoms (QUEST score), GEFV grade, RE and gastric mucosal atrophy.ResultsTotal GERD prevalence, including symptomatic GERD (QUEST score ≥ 4) and/or RE, was 27%. RE grade and prevalence increased with GEFV grade. QUEST scores and GEFV grades showed a positive correlation. NERD prevalence was 14% and increased with GEFV grade, but the relationship was weaker than that between RE and GEFV. Comparing RE‐negative subjects by GEFV grade, GERD symptoms were noted in 10%, 19%, 36% and 52% with GEFV grades I, II, III and IV, respectively. Neither type of gastric mucosal atrophy correlated with GEFV grade.ConclusionsTotal GERD, NERD and RE prevalences increased with GEFV grade. Subjects with high GEFV grades often complain of GERD symptoms, even without RE. Our findings suggest that endoscopic GEFV evaluation provides a useful clinical index for diagnosing GERD.
Review article: duodenal bicarbonate – mucosal protection, luminal chemosensing and acid–base balance
Authors: KAUNITZ J. D. , AKIBA Y. 
Published: June 2006

SummaryThe duodenum serves as a buffer zone between the stomach and the jejunum. Over a length of only 25 cm, large volumes of strong acid secreted by the stomach must be converted to the neutral–alkaline chyme of the hindgut lumen, generating large volumes of CO2.The duodenal mucosa consists of epithelial cells connected by low‐resistance tight junctions, forming a leaky epithelial barrier. Despite this permeability, the epithelial cells, under intense stress from luminal mineral acid and highly elevated Pco2, maintain normal functioning.Bicarbonate ion uniquely protects the duodenal epithelial cells from acid‐related injury. The specific protective mechanisms likely involve luminal bicarbonate secretion, intracellular pH buffering and interstitial buffering. Furthermore, the duodenum plays an active role in foregut acid–base homeostasis, absorbing large amounts of H+ and CO2.We have studied mucosal protection and acid–base balance using live‐animal fluorescence ratio microimaging and by performing H+ and CO2 balance studies on duodenal perfusates. On the basis of these data, we have formulated novel hypotheses with regard to mucosal protection.
Evaluation of alcohol metabolism in humans using the non‐invasive [13C]‐ethanol breath test – influence of gender, Helicobacter pylori infection and polymorphism of alcohol‐oxidizing enzymes
Authors: SUZUKI M. , TANAKA S. , KOMATSU H. , NAKANE T. , SASAKI N. , MARUYAMA K. , SUZUKI H. , ISHII H. , SUEMATSU M. , HIBI T. 
Published: June 2006

SummaryBackgroundThe [13C]‐ethanol breath test (EBT) has been proposed as a novel non‐invasive laboratory test to detect the degradation of ethanol into CO2. However, this method has not yet been evaluated clinically.AimTo investigate the factors that influence [13C]‐EBT.MethodsTwenty‐six healthy volunteers were instructed to drink 100 mL of beer (4 g ethanol) containing 100 μL of [13C]‐ethanol. Breath samples were collected every 15 min before and after the intake of ethanol solution and 13CO2‐enrichment was measured using mass spectrometry. CO2 excretion was then calculated, and the results were evaluated using kinetic parameters (Tmax, Cmax, AUC).Results T
max (min) was significantly shorter in men than in women but not Cmax and AUC. Infection with H. pylori had no impact on all kinetic parameters. Genetic alcohol dehydrogenase (ADH) polymorphisms did not affect 13CO2 excretion, but Cmax (11.1 ± 3.4% dose/h, n = 16) and AUC (10.5 ± 3.4% dose) were slightly increased in aldehyde dehydrogenase (ALDH)‐deficient individuals (heterozygote of ALDH2*2) (13.2 ± 3.2 and 12.9 ± 4.5, respectively; n = 10).Conclusions[13C]‐EBT is capable of assessing the metabolic processing of 100 mL beer in a non‐invasive way. Kinetic parameters are partially influenced by ALDH polymorphism but not by gender, H. pylori infection or ADH polymorphism.
Hypoxia‐inducible factor‐1 alpha and vascular endothelial growth factor expression in ischaemic colitis and ulcerative colitis
Authors: OKUDA T. , AZUMA T. , OHTANI M. , MATSUNAGA S. , MASAKI R. , SATOMI S. , INAGAKI T. , MURAMATSU A. , LEE S. , SUTO H. , ITO Y. , YAMAZAKI Y. , ITO S. , KURIYAMA M. 
Published: June 2006

SummaryBackgroundHypoxia‐inducible factor‐1 alpha (HIF‐1 alpha) is a transcriptional factor induced by ischaemic crisis in many tissues. Vascular endothelial growth factor (VEGF) is an important growth factor that plays a major role in angiogenesis.AimWe examined the aetiology and pathophysiology of human ischaemic colitis and ulcerative colitis from the viewpoint of the expression of these two ischaemic factors.MethodsThirty‐two patients with ischaemic colitis, 16 with ulcerative colitis and 25 normal controls underwent colonoscopy. Biopsy samples were taken from a colitis lesion and a normal region in the same patient. In the normal controls, four biopsy samples were obtained from each subject. Biopsy samples were subjected to real‐time polymerase chain reaction.ResultsHypoxia‐inducible factor and VEGF were overexpressed in ischaemic colitis lesions and quickly decreased to normal levels in the healing phase. In contrast, HIF but not VEGF was overexpressed in active ulcerative colitis lesions. In the remission phase of ulcerative colitis, VEGF decreased to low levels, although HIF was continuously overexpressed.ConclusionsOverexpression of HIF and VEGF contribute to the tolerance of ischaemia in patients with active ischaemic colitis. The inconsistency in their expression might be associated with the chronic intestinal damage characteristic of ulcerative colitis.
Effect of eradication of Helicobacter pylori on genetic instabilities in gastric intestinal metaplasia
Authors: TANAKA A. , WATARI J. , TANABE H. , MAEMOTO A. , FUJIYA M. , ASHIDA T. , DAS K. M. , KOHGO Y. 
Published: June 2006

SummaryBackgroundThere is little evidence of changes in genetic variations in gastric intestinal metaplasia (GIM) after the eradication of Helicobacter pylori (H. pylori).AimTo investigate the effects of H. pylori eradication on genetic GIM variability in patients with and without gastric cancer in a one‐year prospective study.MethodsWe analysed microsatellite instability (MSI) and loss of heterozygosity (LOH) in GIM. Subjects included Gr. A (n = 39): chronic gastritis, and Gr. B (n = 53): intestinal‐type early gastric cancer patients who underwent endoscopic mucosal resection (n = 25) and surgical resection (n = 28).ResultsThe frequency of incidence of MSI in GIM was 10.3% and 28.3% for Gr. A and Gr. B, respectively. Gr. B showed a significantly (p = 0.03) higher incidence rate than Gr. A for MSI, but not for LOH. The frequency of MSI declined in both groups post‐eradication, and patients that were positive for MSI before treatment were negative after H. pylori eradication. Unfortunately, however, GIM scores did not decline significantly post‐treatment for either group.ConclusionsMSI in GIM may be associated with gastric carcinogenesis. H. pylori eradication reduced MSI during the one‐year post‐treatment period, although no histological improvement in GIM was observed. These changes in MSI may explain the decrease in gastric cancer incidence after the eradication of H. pylori.
Coinfection of Helicobacter pylori and Neisseria subflava is closely associated with lymph follicle formation in human stomach
Authors: NAKAMURA M. , MATSUI H. , SERIZAWA H. , MURAYAMA S. Y. , YAMAGUCHI T. , TAKAHASHI T. , MATSUMOTO T. , YAMADA H. , HIBI T. , TSUCHIMOTO K. 
Published: June 2006

SummaryBackgroundMany reports have described coinfection of Helicobacter pylori and other bacteria in the gastric mucosa in humans. However, relatively few have reported the relation of coinfection with pathological characteristics.AimTo culture and identify bacteria other than H. pylori from the gastric mucosa of 64 patients undergoing scheduled gastric biopsy for various gastric conditions. The relation of coinfection with the pathological changes was also investigated.MethodsFrom colonies showing characteristics different to those of H. pylori, bacteria were identified by the 16S rRNA gene sequence using FASTA. Cluster analysis was performed using GENETYX‐MAC and a phylogenetic tree was constructed using the UPGMA method. The correlation of pathological observation and the existence of identified bacteria and H. pylori were also analysed.ResultsForty‐eight per cent of patients were positive to H. pylori, and 27% were positive to Neisseria species. Coinfection of the two bacterial existences was significantly linked. DNA sequencing studies revealed these Neisseria strains to coincide mostly with Neisseria subflava. With regard to the interaction of pathological characteristics, Neisseria and H. pylori coinfection was closely related to lymph follicle formation.ConclusionsCoinfection of H. pylori and N. subflava was found to be closely related to lymph follicle formation.
Molecular mechanisms involved in interleukin‐8 production by normal human oesophageal epithelial cells
Authors: YOSHIDA N. , IMAMOTO E. , UCHIYAMA K. , KURODA M. , NAITO Y. , MUKAIDA N. , KAWABE A. , SHIMADA Y. , YOSHIKAWA T. , OKANOUE T. 
Published: June 2006

SummaryBackgroundIncrease in interleukin‐8 in the oesophageal mucosa has been associated with the pathogenesis of reflux oesophagitis.AimTo assess the effect of bile acids on the interleukin‐8 expression in normal human oesophageal epithelial cells and to determine its molecular mechanisms.MethodsHuman oesophageal epithelial cells were stimulated with unconjugated bile acids, conjugated bile acids and inflammatory cytokines. Protein and mRNA of interleukin‐8 were measured by enzyme‐linked immunosorbent assay and quantitative real‐time polymerase chain reaction, respectively. In addition, we examined protein kinases and transcription factors involved in interleukin‐8 synthetic pathways using protein kinase inhibitors and luciferase expression vectors, respectively.ResultsUnconjugated bile acids induced interleukin‐8 production from human oesophageal epithelial cells stronger than conjugated bile acids. However, conjugated bile acids in acidic media resulted in remarkable increase of interleukin‐8 production compared with those in neutral‐pH media. Mutation of the binding site of NF‐kB, AP‐1 and NF‐IL6 abrogated the induction of luciferase activities by 100%, 70% and 30%, respectively. Inhibitor of protein kinase A, protein kinase C or p38 mitogen‐activated protein kinase attenuated the production of interleukin‐8 by cholic acid.ConclusionsThese results indicate that bile acids induce interleukin‐8 expression from oesophageal epithelial cells mainly via the activation of NF‐kB as well as AP‐1.
Review article: anti‐tryptase therapy in inflammatory bowel disease
Authors: YOSHIDA N. , ISOZAKI Y. , TAKAGI T. , TAKENAKA S. , UCHIKAWA R. , ARIZONO N. , YOSHIKAWA T. , OKANOUE T. 
Published: June 2006

SummaryA number of studies have shown that activated mast cells are involved in the pathogenesis of inflammatory and allergic diseases.Tryptase is one of the serine proteases that stored almost exclusively in the secretory granules of mast cells. It acts to induce microvascular leakage, the chemotaxis of inflammatory cells, and stimulates the release of inflammatory cytokines through the mitogen‐activated protein kinase /activator protein‐1 pathway and protease‐activated receptor (PAR) nuclear factor‐κB pathway.Recent studies have strongly indicated that tryptase and PAR are implicated in the pathogenesis of inflammatory bowel disease and experimental colitis.The effect of anti‐tryptase therapy on human inflammatory bowel disease and experimental colitis has been demonstrated. The result of a pilot study has revealed that systemic administration of a specific tryptase inhibitor is safe and there is evidence of activity in the treatment of ulcerative colitis. Recently, we found that nafamostat mesilate, which selectively inhibits tryptase activity at low concentration, could reduce intestinal inflammation in rats. In addition, nafamostat mesilate enema improved clinical and endoscopic findings in ulcerative colitis patients, resistant to conventional therapy such as corticosteroids and sulfasalazine/5‐aminosalicylic acid.These studies suggest that anti‐tryptase therapy may represent a new therapeutic strategy for human inflammatory bowel disease.
Gene expression clusters of a lipopolysaccharide‐stimulated pathway in peripheral blood monocytes of Japanese patients with Crohn's disease
Authors: NAITO Y. , TAKAGI T. , MIZUSHIMA K. , UETA M. , KINOSHITA S. , HANDA O. , KOKURA S. , ICHIKAWA H. , YOSHIDA N. , YOSHIKAWA T. 
Published: June 2006

SummaryBackgroundRecent reports support the notion that patients with Crohn's disease have a dysregulated innate immune response to endogenous flora.AimTo reveal the distinct gene expression clusters of a lipopolysaccharide‐stimulated pathway in the peripheral blood monocytes of Japanese patients with Crohn's disease.Materials and methodsTotal RNA was extracted from peripheral blood monocytes of four patients in the remission stage of Crohn's disease as well as four controls, and gene expression profiles before and after lipopolysaccharide stimulation were investigated using a high‐density oligonucleotide probe array. To focus on innate immunity, the expression of genes to be studied was narrowed down to 118 probe sets which were selected using the following keywords: lipopolysaccharide, toll, myd and tir along with a software of NetAffx Analysis Center.ResultsUsing hierarchical clustering analysis, we picked up to 44 and 36 probe sets for which expression had decreased before and after lipopolysaccharide stimulation, respectively, in patients with Crohn's disease compared with healthy volunteers. The expression of TLR5, 7, MyD88, SIGIRR, and Tollip was decreased both before and after lipopolysaccharide stimulation in patients with Crohn's disease.ConclusionWe found several interesting clusters in monocytes before and after stimulation with lipopolysaccharide. These genes may have been responsible for the immunological differences between the Crohn's disease and control patients.