Low-grade inflammation plays a pivotal role in gastrointestinal dysfunction in irritable bowel syndrome

The pathogenesis of irritable bowel syndrome (IBS) is considered to be multifactorial and includes psychosocial factors, visceral hypersensitivity, infection, microbiota and immune activation. It is becoming increasingly clear that low-grade inflammation is present in IBS patients and a number of biomarkers have emerged. This review describes the evidence for low-grade inflammation in IBS and explores its mechanism with particular focus on gastrointestinal motor dysfunction. Understanding of the immunological basis of the altered gastrointestinal motor function in IBS may lead to new therapeutic strategies for IBS.     

A Strain-Specific Antigen in Japanese Helicobacter pylori Recognized in Sera of Japanese Children

An enzyme immuno assay (EIA) test based on Japanese strain-derived high-molecular-weight cell-associated proteins (JHM-CAP) was evaluated by comparing with a previously developed EIA test based on a U.S. strain-derived high-molecular-weight cell-associated proteins (HM-CAP). Serum samples of 131 Japanese asymptomatic children (mean age, 5.5 years; range, 0 to 21 years) were tested that include 43 positive and 88 negative children as judged by Helicobacter pylori stool antigen test (HpSA test). Both tests showed comparable and reliable specificities, but the sensitivity of JHM-CAP EIA, at 93.0%, was much higher than that of HM-CAP EIA, at 67.4%. More false-negative results of HM-CAP were obtained in children under 10 years of age. Immunoblot analysis revealed that the JHM-CAP but not the HM-CAP preparation had a 100-kDa antigen recognized by JHM-CAP positive sera. It was concluded that JHM-CAP EIA is highly accurate for the serodiagnosis of H. pylori infection in Japanese young children and that the high sensitivity of JHM-CAP EIA in contrast to HM-CAP EIA is due to the presence of a 100-kDa antigen in Japanese strains that may be recognized by the host immune system at an early stage of infection.     

A case of Cowden disease with a germline mutation in exon5 of PTEN gene diagnosed based on typical esophageal multiple polypoid lesions observed on a medical checkup

A man in his fifties had a medical checkup. Mucosal papillomatosis in his oral cavity and palmoplantar keratosis were observed. Esophagogastroduodenoscopy revealed multiple polypoid lesions both in the esophagus and stomach. In addition, colonoscopy showed schwannoma in the rectum. He underwent an operation for adenomatous goiter. At first his typical esophageal multiple polypoid lesion was a diagnostic cue to Cowden disease (CD). Other clinical findings convinced us that he was suffering from CD. He was, then, diagnosed as CD according to the criteria of International Cowden Consortium although he had no family medical history suspicious of CD. Interestingly, genetic testing revealed that the patient had a germline mutation in exon5 of PTEN on chromosome 10. It was a point mutation of C to T transition at codon130, resulting in nonsense mutation (CGA→TGA). A close follow-up, especially cancer surveillance, is necessary for him since CD is associated with a high risk of developing malignant disease. It is noted that the typical esophageal features can be a diagnostic cue to CD, as shown in the present case.     

Overexpression of phosphorylated histone H3 is an indicator of poor prognosis in gastric adenocarcinoma patients.

Ki-67 immunostaining is commonly used for assessing cell proliferation, but studies of its use as a prognostic indicator have revealed discordant results in gastric cancer patients. Recently, antibodies for phosphorylated histone H3 have been used to identify dividing cells because of its precise overexpression in mitosis. The authors tested the hypothesis that phosphorylated histone H3 overexpression might be a good prognostic indicator for gastric cancer patients by conducting an immunohistochemical comparison with Ki-67 in gastric cancer samples. One hundred twenty-two surgically resected primary cases were selected and histologically categorized in accordance with Lauren's classification. No correlation was found between phosphorylated histone H3 and Ki-67 regarding overexpression. However, correlations between phosphorylated histone H3 overexpression and clinicopathologic variables were noted for histologic type (intestinal type predominant in high labeling indices [LIs], defined as over the value of the 75th percentile; P<0.01), vessel invasion (positive in high LIs; P=0.05), and lymph node metastasis (positive in high LIs; P=0.04). With regard to Ki-67 overexpression, no correlation was evident with the clinicopathologic variables except histologic type (intestinal type predominant; P=0.05). By the Kaplan-Meier method with the log-rank test, cases overexpressing phosphorylated histone H3 showed a poorer prognosis than cases with low expression (P<0.01). In contrast, Ki-67 expression did not influence prognosis. Multivariate analyses indicated phosphorylated histone H3 overexpression to be an independent prognostic factor, together with lymphatic invasion and venous invasion (P<0.01). In conclusion, it seems likely that phosphorylated histone H3 plays an important role in the prognosis of gastric cancer, and its immunohistochemical investigation is useful for the prediction of prognosis in gastric cancer.     

A Case of Cytomegalovirus-Induced Gastric Lesions

Abstract: A 26-year-old woman was admitted to our hospital with epigastric pain, a husky voice, high-grade fever, hepatosplenomegaly and enlargement of the kidneys. An upper gastrointestinal endoscopy revealed scattered non-circular erythematous erosions, up to 5mm in diameter, in the gastric body and fornix. A histological examination of the biopsied specimens stained with hematoxylin and eosin showed the presence of intranuclear inclusion bodies in the glandular epithelial cells. Cytomegalovirus (CMV) antigen was found in the inclusion bodies using the enzyme-labeled antibody method. Subsequently, a needle biopsy taken from the kidney revealed a non-Hodgkin's lymphoma. Our review of the literature indicates that CMV-induced gastric lesions are endoscopically characteristic and can be diagnosed from their multiple, erythematous, non-circular depressed lesions.     

Evaluation of a urine antibody test for Helicobacter pylori in Japanese children

OBJECTIVE: To evaluate the accuracy of a urine-based enzyme-linked immunosorbent assay (ELISA) kit for anti-Helicobacter pylori immunoglobulin G antibody (urine-HpELISA) in children, we compared its sensitivity and specificity in reference to (13)C-urea-breath test (UBT) and H pylori stool antigen test (HpSA). STUDY DESIGN: Japanese children without significant upper abdominal symptoms were included (n=100; mean age, 7.0 years; range, 2 to 15). UBT, HpSA, and urine-HpELISA were performed. RESULTS: Of 100 children, 36 and 64 were judged H pylori-positive and H pylori-negative, respectively, by UBT and HpSA. Thirty-four of 36 positive children were positive by urine-HpELISA, and 62 out of 64 negative children were negative by urine-HpELISA. Thus, the urine-HpELISA had 94.4% sensitivity and 96.9% specificity, with accuracy of 96.0%. CONCLUSIONS: The urine-HpELISA is a rapid, inexpensive, reliable, and easy-to-perform method for the diagnosis of H pylori infection in children. It may be useful not only for diagnosis but also for mass screening for epidemiological studies in pediatric population.     

Effect of tranilast on matrix metalloproteinase-1 secretion from human gingival fibroblasts in vitro

BACKGROUND: Some drugs such as phenytoin, calcium blockers, or cyclosporins are known to cause gingival fibrous hyperplasia, an unwanted side effect. Decreased collagen catabolism in overgrown gingival tissue has been proposed as one of the reasons causing the disease. The effect of tranilast, which suppresses collagen synthesis and cell proliferation, on matrix metalloproteinase (MMP-1) secretion from human gingival fibroblast, was studied in vitro. METHODS: Human gingival fibroblasts were cultured from specimens taken from healthy, periodontal, and overgrown gingival tissues. The effects of tranilast on cell proliferation and MMP-1 secretion from gingival fibroblast were assessed. Inhibitory effect of transforming growth factor (TGF)-beta secretion from gingival fibroblast by tranilast was also evaluated. RESULTS: Tranilast did not interfere with cell proliferation at the low concentrations. MMP-1 concentration significantly increased at the lower doses of tranilast up to about 2-fold compared to controls (P < 0.05). In contrast, higher doses of tranilast significantly decreased activity to 30% and 20%, respectively. MMP-1 secretion was inhibited significantly by phenytoin, nifedipine, and cyclosporin A and the depressed MMP-1 recovered to the control level with tranilast. The amount of secretion from normal and periodontitis gingival fibroblast specimens did not differ, but that from the overgrown gingiva was significantly less than the other types. Moreover, TGF-beta secretion was significantly inhibited by 300 microM of tranilast. CONCLUSIONS: Tranilast upregulates the expression of type 1 collagenase suppressed by gingival overgrowth-inducing drugs, and inhibits TGF-beta secretion from gingival fibroblasts. Therefore, tranilast could be considered as an agent for controlling gingival over-growth.     

A case of advanced primary biliary cirrhosis treated with granulocyte and monocyte apheresis

Generally, the most effective treatment for advanced primary biliary cirrhosis (PBC) is liver transplantation, but adjunct therapies are needed. We report here a first case of advanced PBC treated with a new immunotherapy, granulocyte and monocyte apheresis (GCAP). A column (Adacolumn, Japan Immunoresearch Laboratory Takasaki, Japan) was filled with cellulose acetate beads to selectively adsorb granulocytes and monocytes/macrophages. A 49-year-old woman was diagnosed with PBC in 1987. In June 2001, steroid pulse therapy and adjuvant fresh frozen plasma was given for moderate jaundice but without success. In July, as total bilirubin rapidly increased, treatment with GCAP was started and succeeded in suppressing the rapid deterioration of total bilirubin (value changes after each of four applications: 15.4-->14.0, 27.2-->25.1, 25.8-->24.0, 25.7-->23.7 mg/dL) and improving prothrombin time (16.4-->14.5 s). Although GCAP therapy did not prevent a fatal outcome, it suppressed rapid deterioration of jaundice and increased quality of life for a month.