Endoscopic and Histological Features of the Large Intestine in Patients with Atopic Dermatitis

Although atopic dermatitis is known to be closely associated with food antigens, the actual changes in the gastrointestinal tract have not been clarified. The aim of this study was to investigate the macroscopic and histological features of the large intestine in patients with atopic dermatitis. We studied 15 outpatients who had generalized atopic dermatitis. Eight non-dermatitis subjects of a similar age without inflammatory bowel disease were also enrolled as controls. Total colonoscopy, pathological evaluation of biopsy specimens, and detection of Candida albicans were performed in all subjects. Four patients were re-examined after 6 months of treatment with an antifungal drug. Among the 15 patients with atopic dermatitis, 4 patients had melanosis coli. On pathological examinations, prominent infiltration of eosinophils and fragmentation of granulocyte nuclei were observed. There were no changes after an antifungal therapy. In the patients with melanosis coli, lipofuscin deposits were observed in the lamina propria. Candida albicans was not detected in any of the subjects. In conclusion, patients with atopic dermatitis may have a predisposition to develop chronic inflammation of the large intestine

Analysis of Beta-Tubulin Gene Exon 4 Mutations in Advanced Stage III or IV Gastric Cancer

The mechanisms that cause chemoresistance of gastric cancer have yet to be elucidated. Taxanes and promising agents that were recently approved for treatment of advanced or recurrent gastric cancer. Mutations of beta-tubulin, which is a target of taxianes, have been shown to confer chemoresistance against these agents. The aim of the present study is to investigate the presence of mutations of the beta-tubulin in gastric cancer tissues. Sixty-six patients with advanced stage III or IV gastric cancer patients enrolled in this study. Paired samples of gastric cancer tissue and normal mucosa were obtained by endoscopy. The guanosine 5'-triphosphate (GTP)-binding site in exon 4 of the beta-tubulin gene was examined by polymerase chain reaction single-strand conformational polymorphism (PCR-SSCP) analysis, followed by sequencing of the products with abnormally shifted bands. SSCP analysis showed abnormal bands upstream of the GTP-binding site in 7 of the 66 patients, but sequence analysis found no nucleotide substitutions in these patients. Three variant bands were also detected down stream of the the GTP-binding site, but the sequences of the 3 products corresponded to those of two independent pseudogenes. Thus, none of the tumor samples showed mutation of the beta-tubulin exon 4 GTP-binding site. In conclusion, these findings suggest that mutations of the beta-tubulin gene are rare and are unlikely to be an important cause of taxane resistance to taxians

The Role of RANTES Promoter Polymorphism in Functional Dyspepsia

Altered inflammatory immune responses have been shown to be associated with functional gastro intestinal disorder. We aimed to clarify the effect of functional promoter polymorphism of RANTES, which is a potent chemoattractant peptide for memory T lymphocytes and eosinophils, on the risk of functional dyspepsia in a Japanese population. RANTES promoter C-28G polymorphism was genotyped in 246 subjects including 134 FD patients according to Roma III criteria and 112 non-symptomatic healthy controls. Although frequency of RANTES promoter polymorphisms in overall dyspeptic patients and non-symptomatic healthy controls did not show any significant differences, a significant association was found between G carrier and reduced risk of PDS according to Roma III criteria (age, sex, H. pylori infection adjusted OR  = 0.23, 95% CI = 0.06–0.80). We also found that the same genotype held a lower risk of PDS in H. pylori positive PDS subjects (age, sex adjusted OR = 0.11, 95% CI = 0.01–0.94). Our data suggest that RANTES promoter -28G carriers is associate with a reduced risk of PDS especially in H. pylori positive subjects

Absence of Common Polymorphisms of Toll Like Receptor 4 (TLR4): Asp299Gly, Thr399Ile in Patients with Gastroduodenal Diseases in Japan

Host genetic factors may play a key role in determining the long-term outcome of the Helicobacter pylori (H. pylori) infection. Toll-like receptor 4 (TLR4) mediated recognition of lipo-polysaccharide (LPS) is required for efficient recognition of gram-negative bacterial infections. The aim of this study is to investigate the effects of common polymorphisms of TLR4 Asp299Gly, Thr399Ile in patients with gastroduodenal diseases in Japanese population. The study was performed in 149 gastric cancer (GC) cases (mean age 64.0 ± 12.4, M:F = 109:40) and 94 patients without evidence of GC (mean age 64.1 ± 12.3, M:F = 65:25) as the control group. TLR4 Asp299Gly, Thr399Ile were determined by Polymerase chain reaction-length of polymorphisms (PCR-RFLP) in all the patients. Asp299Gly, Thr399Ile were not detected in all 243 patients enrolled in this study. In conclusion, our data suggest that TLR4 Asp299Gly, Thr399Ile are very rare in Japanese population and thus they may not be a important factor in determining the outcome of H. pylori infected individuals in Japan

Genetic Polymorphisms of Molecules Associated with Innate Immune Responses, TRL2 and MBL2 Genes in Japanese Subjects with Functional Dyspepsia

Inflammatory changes in the gastric mucosa are commonly observed in Japanese patients with functional dyspepsia (FD). However, detailed data regarding the possible association between the genetic factors of inflammation related molecules and FD are not available. Toll like receptor 2 (TLR2) and mannan-binding lectin (MBL) protein play important roles in the innate immune activation. We aimed to clarify the association between common polymorphisms of TLR2 and MBL2 genes with FD in Japanese subjects. TLR2 −196 to −174 del and MBL2 codon54 G/A polymorphisms were genotyped in 111 FD patients according to Rome III criteria and 106 asymptomatic controls. Non-significant correlation was found between TLR2 and MBL2 polymorphisms with FD. However, in Helicobacter pylori (H. pylori) positives, we found significant inverse association between TLR2 −196 to −174 del carrier and FD among H. pylori positive subjects (Adjusted odds ratio (OR) = 0.48, 95% confidence interval (CI) = 0.23–0.996, p = 0.0488). We also found significant inverse association between the same genotype with postprandial distress syndrome (PDS) among H. pylori positive subjects (Adjusted OR = 0.22, 95% CI = 0.07–0.69, p = 0.0099). Our data suggest that TLR2 −196 to −174 del carriers’s status but not MBL2 codon54 G/A is inversely related to the risk with FD in H. pylori-infected subjects

Survival rates of early-stage HCV-related liver cirrhosis patients without hepatocellular carcinoma are decreased by alcohol

Although alcohol abuse is the most common cause of liver cirrhosis in the United States, the enhancing effects of alcohol on the long-term prognosis of hepatitis C virus (HCV) related liver cirrhosis has not been clarified. To investigate how alcohol abuse influences the prognosis of hepatitis virus related liver cirrhosis, we studied 716 Japanese patients. Cumulative survival and hepatocellular carcinoma (HCC) development rates were analyzed in alcohol abusive, cirrhotic patients with or without hepatitis virus infection. Patients who abused alcohol were younger (p<0.0001) than HCV infected, non-abusive patients. The overall survival rate among patients with alcoholic cirrhosis (Al group), HCV related cirrhosis (HCV group), and HCV infected + alcoholic cirrhosis (HCV + Al group), showed no significant differences, although the 10-year cumulative survival rate of Al group was the highest of the three groups. The HCC development rate of Al group was the lowest. In addition, alcohol abuse decreased the survival rates of HCV group in the early stage with no HCC (p = 0.0028). In conclusion, alcohol abuse might affect the progression of liver damage in HCV infected patients with liver cirrhosis in the early stage, although the influence of alcohol abuse on the long term prognosis seems to be rather small

The Role of Mannan-Binding Lectin (MBL) Gene Polymorphism in Ulcerative Colitis

Series studies suggest that enteropathogenic microorganisms play a substantial role in the clinical initiation and relapses of ulcerative colitis (UC). Mannan-binding lectin (MBL) is an important constituent of the innate immune system, and deficiency of MBL has been reported to increase the overall susceptibility of an individual to infectious disease. This study was aimed to investigate the associations between polymorphisms of the MBL gene and UC. Recruited in this study were 108 Japanese patients with UC and 144 healthy control subjects. Polymorphism at codon 54 of exon 1 of the MBL gene was investigated by polymerase chain reaction based restriction fragment length polymorphism. In general, no significant difference in MBL polymorphism was found between UC patients and health controls. However, the frequency of A carriers was significantly higher in the relapsing cases than controls (Odds ration = 2.19, 95%CI, 1.10–4.34; p = 0.023), and similar tendency was also found in A/A genotype. In conclusion, the polymorphism at codon 54 of exon 1 of the MBL gene associated with the susceptibility to the relapsing phenotype of ulcerative colitis. It suggests that codon 54 A variants of MBL gene may have an increased risk for the flare-ups of UC

Chronic Ingestion of Ethanol Induces Hepatocellular Carcinoma in Mice Without Additional Hepatic Insult

Abstract Background Chronic intake of alcohol increases the risk of gastrointestinal and hepatic carcinogenesis. The present study was focused to investigate the incidence and mechanism of pathogenesis of hepatocellular carcinoma (HCC) during chronic ingestion of alcohol without any additional hepatic injury. Methods Ethanol was administered to Institute for Cancer Research male mice through drinking water for 70 weeks at concentrations of 5 % (first week), 10 % (next 8 weeks), and 15 % thereafter. The animals were killed at 60 and 70 weeks, the livers were examined for hepatic tumors, and evaluated for foci of cellular alteration (FCA). Immunohistochemical staining was performed in the liver sections for cytochrome P4502E1 (CYP2E1), 4-hydroxy-nonenal (4-HNE), and proto-oncogene, c-Myc. Results At the 60th week, 40 % of the mice in the ethanol group had visible white nodules (5-10 mm) in the liver, but not in the control mice. At the 70th week, several larger nodules (5-22 mm) were present in the livers of 50 % mice in the ethanol group. In the control group, one mouse developed a single nodule. All nodules were histologically trabecular HCC composed of eosinophilic and vacuolated cells. In the livers of both control and ethanol group, several foci with cellular alteration were present, which were significantly higher in ethanol group. Staining for CYP2E1, 4-HNE and c-Myc depicted marked upregulation of all these molecules in the FCA. Conclusions Our data demonstrated that upregulation of CYP2E1 and subsequent production of reactive oxygen species along with the persistent expression of c-Myc play a significant role in the pathogenesis of HCC during chronic ingestion of ethanol

Gastrointestinal Stromal Tumor of the Stomach with Narrow Stalk-Like Based, Uneven Protruding Appearance Presenting with Severe Acute Anemia despite Small Size

We report the case of a 56-year-old woman who had a gastrointestinal stromal tumor (GIST) of the stomach. She was admitted to our hospital for epigastric pain, nausea, and severe acute anemia (hemoglobin level 4.3 g/dl). Esophagogastroduodenoscopy revealed a narrow stalk-like based, hemorrhagic and uneven protruding lesion in the lesser curvature of the gastric upper corpus. Although the tumor was less than 2 cm in diameter and was probably a benign GIST according to histology, laparoscopy-assisted local resection was needed because the patient had continuous severe anemia and epigastric pain. Histological assessment showed that the elongated spindle-like tumor cells originated from the intrinsic muscle layer, and was shown with growth to the mucosal side, cropping out to the surface in most areas of the protruding lesion. Only a small part of the tumor was within nontumoral gastric mucosa. Most of the tumor cells demonstrated immunoreactivity for KIT and CD34 in the cytoplasm but not for αSMA, S100, and desmin. Mitotic activity (0/50 high power field) and the labeling index for MIB-1 (about 1%) were low. The GIST of the stomach described in this report was a rare case with a narrow stalk-like based, uneven protruding mass presenting with severe acute anemia despite small size

A Genetic Variant of the CD14 C-159T in Patients with Functional Dyspepsia (FD) in Japanese Subjects

Inflammatory changes in the gastric mucosa are commonly observed in Japanese patients with functional dyspepsia (FD). However, detailed data regarding the relationship between the genetic regulatory factors of inflammation and FD are not available. CD14 is an important mediator of the inflammatory response in the first line of host defense by recognition of Lipopolysaccharide (LPS). We aimed to investigate the association between CD14 promoter C-159T polymorphism and FD in a Japanese population. 108 patients with FD and 99 non-dyspeptic subjects enrolled in this study. Dyspeptic symptoms were divided according to Rome III criteria. CD14 gene C-159T polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism. In the non-dyspeptics, the CD14 genotype distribution was 28CC (28.3%), 51CT (51.5%), 21TT (21.2%). Meanwhile, the CD14 genotype distribution in FD was 31CC (28.4%), 56CT (51.4%), 22TT (20.2%). The genotype distribution was not significantly different. There was no significant difference between two groups in the genotype distribution. We did not found any association between CD14 genotypes and dyspeptic patients in different gender and Helicobacter pylori infection status. No significant association was also found between CD14 polymorphism and any of different subtypes of FD according to Rome III while there was a weak correlation between TT genotype and PDS in male subjects (TT vs others, OR = 3.18, 95% CI = 0.98−10.26, p = 0.06). In conclusion, our results suggest that CD14 polymorphism is unlikely to associate with susceptibility of dyspeptic symptoms. The role of inflammation related-gene polymorphisms to the development of dyspepsia needs to further evaluation