Infection of sabA-positive H. pylori does not induce anti-Lewis X antibody in host

BACKGROUND/AIMS: H. pylori uses the sialic acid-binding adhesin (SabA) to recognize Lewis X (LeX) antigen of gastric epithelial cells. SabA is associated with nonopsonic activation of human neutrophils. The aims of this study were to examine the association of bacterial sabA status to the presence of anti-LeX antibody in host and the grade of gastritis. METHODOLOGY: 44 H. pylori strains cultured from gastric biopsies were examined by PCR for presence of 23SrRNA, cagA, and sabA. Serum samples were obtained from all the patients to measure the level of anti-LeX antibody. Histological grade of gastritis was graded according to the updated Sydney System. RESULTS: 23SrRNA gene and the cagA gene were seen in all the samples while 21 strains were sabA positive. The mean titer of anti-LeX antibody was 0.09 and 0.18 in patients infected with sabA-positive and -negative strain, respectively (NS). The grade of inflammatory infiltration was not significantly different between groups in both the corpus and the antral mucosa. CONCLUSIONS: Possession of the sabA gene by infected H. pylori strain might not associate with the presence of anti-LeX antibody in the host. Possession of sabA gene by infected H. pylori might not associate with severity of gastric mucosal inflammation.     

Development of a Questionnaire Method to Discriminate Between Typical and Atypical Genotypes of Low Km Aldehyde Dehydrogenase in a Japanese Population

Nearly half of all Orientals exhibit aversive symptoms, such as "Oriental flushing" or palpitation, during alcohol consumption. This high alcohol sensitivity among Orientals has been attributed to a highly prevalent polymorphism in low K_m aldehyde dehydrogenase (ALDH2). In the present study, we attempted to develop a reliable questionnaire method to probe the frequency of alcohol drinking-related symptoms to estimate the ALDH2 genotype. Four-hundred twenty-four male and 100 female workers provided blood samples for polymerase chain reaction analysis and completed the questionnaire. We performed a stepwise logistic regression analysis to discriminate between the typical homozygote ( ALDH2*1/*1 ) and the atypical heterozygote ( ALDH2*1/*2 ) in male subjects. Because of the limitation in the sample size for ALDH2*2/*2 , this genotype was not included in the analysis. Results revealed that only three symptoms (facial flushing, flushing elsewhere, and palpitation) were enough to correctly predict the ALDH2 genotypes in ∼89% of all subjects. The present questionnaire method ( AL cohol Sensitivity screening Test; ALST) takes a little time and effort for the genotype determination, and may be especially useful in epidemiological studies with a large sample size or with subjects from whom DNA samples are not available.     

Noninvasive detection of coronary artery bypass graft patency by intravenous electron beam computed tomographic angiography

This study evaluates the usefullness of intravenous electron beam computed tomographic angiography (EBA) for the detection of coronary artery bypass graft patency in 43 patients (33 men and 10 women, mean age, 65 years) who had coronary artery bypass graft surgery. EBA was performed a few days before selective bypass graft angiography (SGA). Forty axial cross-sections of angiographic images of the heart were acquired consecutively by an electrocardiographic trigger signal at 40% of the RR interval, which corresponds to the end-systolic phase. EBA data were reconstructed as a three-dimensional shaded surface display of the heart and bypass grafts. Detectability of the patency of bypass gratis was evaluated, taking selective angiographic images of the bypass grafts as a gold standard. One hundred and nine grafts (96%) out of 114 grafts were subjected to evaluation: 37 grafts were left internal mammary artery grafts (LIMA), 7 were right internal mammary artery grafts (RIMA), 6 were gastroepiploic artery grafts (GEA), 7 were free gastroepiploic artery grafts with venous drainage (free-GEA), 7 were radial artery grafts (RAG), and 45 were saphenous vein gratis (SVG). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBA were 98%, 100%, 100%, 91%, and 98%, respectively. EBA sampled at the end-systolic period was determined to be useful for the detection of coronary artery bypass graft patency and occlusion.     

Relevance of Both Daily Hassles and the ALDH2 Genotype to Problem Drinking among Japanese Male Workers

The effects of genetic polymorphisms in the ALDH2 and ADH2 genes and stress levels, as assessed by the daily hassles scale on the prevalence of problem drinkers, were investigated in males in a Japanese occupational population. The frequency of problem drinkers was estimated by the Kurihama Alcoholism Screening Test (KAST). The prevalence of those with a high KAST score (≥0.0) was significantly higher in ALDH2*1/*1 (18.4%) than in ALDH2*1/*2 (4.8%). Multiple logistic regression analysis revealed significant contributions by levels of alcohol consumption, the ALDH2 genotype, and daily hassles to the prevalence of those with a high KAST score. When we analyzed the data for each ALDH2 genotype, heavier alcohol consumption (≥28.8 ml/day), older age (≥40 years old), and very high daily hassles levels (≥20) significantly increased the prevalence of problem drinkers in ALDH2*1/*1. On the contrary, no variables other than heavier alcohol consumption influenced the prevalence in ALDH2*1/*2. In summary, the present study revealed significant contributions of both daily hassles and the ALDH2 genotype to the increase of problem drinkers in an occupational population. Health promotion activities to prevent from alcohol dependence should focus on ALDH2*1/*1 , especially those of middle age, and should include stress management as a part of their activities.     

Role of tissue trace elements in liver cancers and non-cancerous liver parenchyma

BACKGROUND/AIMS: The role of trace elements in liver fibrosis, carcinogenesis and progression of hepatocellular carcinoma (HCC) has not yet been clarified. The aim of this study is to analyze the characteristics of trace elements in liver cancers and non-cancerous liver and to discuss their role in hepatic fibrosis, hepatocarcinogenesis and progression of HCC. METHODOLOGY: The amount of zinc (Zn), iron (Fe), and copper (Cu) in 20 HCCs, 2 cholangiocellular carcinomas (CCC), 7 metastatic liver cancers (Meta) and their non-tumorous liver parenchyma were measured using an atomic absorption spectrophotometer. RESULTS: The amounts of Zn and Fe in non-tumorous liver parenchyma were reduced by liver fibrosis, and the amounts were lower in HCC tissue compared to non-tumorous liver parenchyma. The amounts of Zn and Cu were higher in HCC than the amounts found in CCC and Meta. The amount of Zn in HCC tissue decreased, but the amount of Fe increased in tumors more than 4cm in diameter. CONCLUSIONS: These results suggest that the decrease in the amount of Zn and Fe found in non-tumorous liver parenchyma correlates with liver fibrosis leading to cirrhosis and hepatocarcinogenesis. Also that decreases in Zn and increases of Fe in HCC tissue correlates with HCC tumor progression.     

Malignant Transformation of the Mouse Anorectal Epithelium Induced by an Inoculated Human Cancer Cell Line

Four kinds of human cancer cell lines and one mouse cancer cell line were inoculated into the subepithelial area of the anorectum of female nude mice. Among the cell lines, two cell lines (KATO III and Lu 135) showed the potential enforcement of atypical changes in the adjacent mouse anorectal epithelium. Moreover, the submucosal invasion of the malignant transformed cells of the mouse epithelium was demonstrated in specimens obtained from three KATO III-inoculated mice. This exciting and novel phenomenon clearly demonstrates the need to change the present general concept of a single-cell origin of cancer tissue. This valuable and novel discovery may change the basis of oncology research while also providing new ideas for projects to investigate the mechanisms of carcinogenesis from several aspects such as molecular biology, cell biology, and pathology. Moreover, the novel experimental design itself is also extremely useful as a simple model for investigating the mechanisms of oncogenesis.     

Granulocytapheresis (GCAP) for severe alcoholic hepatitis-A preliminary report.

AIM: To evaluate the efficacy of granulocytapheresis therapy in alcoholic hepatitis. METHODS: We attempted to trap leukocytes in the peripheral circulation using the granulocytapheresis (GCAP) technique in patients with severe alcoholic hepatitis who showed a marked elevation of peripheral leukocytes. Corticosteroids were co-administered. RESULTS: The Maddrey's indices for these patients varied between 42 and 117 and MELD scores for alcoholic hepatitis (Mayo) ranged from 20 to 44. Survival rate was 50% (3/6), which is better than the results reported recently for similar patients in a national survey (29%). The effect of GCAP was reflected in decreases in interleukin-6 and interleukin-8 levels as well as in serum concentrations of soluble intercellular adhesion molecule. White blood cell counts were not affected. In the surviving patients, the Maddrey's indices and MELD scores for alcoholic hepatitis varied between 49 and 67, and 20 and 22, respectively, showing that GCAP is effective in patients with disease of moderate severity. Hemolytic anemia occurred in one patient after GCAP therapy. Other events such as pancreatitis, pneumonia, and cerebral hemorrhage were considered to be related to the alcoholic hepatitis itself. CONCLUSION: GCAP therapy deserves further evaluation as a new therapeutic modality for a moderately severe alcoholic hepatitis.     

Association of Ob-R gene polymorphism and insulin resistance in Japanese men

Leptin and its receptors are known to play a role in glucose metabolism. We succeeded in cloning human Ob-R cDNA and revealed 7 single nucleotide polymorphisms (SNPs) (Lys109Arg, Arg223Gln, Ser343Ser, Ser492Thr, Lys656Asn, Ala976Asp, and Pro1019Pro) in the coding region of Ob-Rb. Although these 7 SNPs were not associated with an obese phenotype, several studies have reported that some of them were associated with impaired glucose metabolism. To clarify whether the Arg223Gln and A3057G (Pro1019Pro) polymorphisms influence glucose metabolism in Japanese, 696 Japanese men were genotyped. Individually, the Arg223Gln and the A3057G polymorphisms were not associated with the glucose metabolic parameters. No associations were found between haplotype and clinical parameters. However, in 327 subjects with normal glucose tolerance (NGT), the subjects with Arg/Gln or Gln/Gln + A/A haplotype showed significantly higher serum insulin levels and homeostasis model assessment (HOMA) index than those with Arg/Arg + A/A haplotype and Arg/Gln or Gln/Gln + A/G or G/G haplotype. The subjects with Arg/Gln or Gln/Gln + A/A haplotype showed a significantly lower fasting glucose to insulin (GI) ratio than those with Arg/Arg + A/A haplotype. These results suggest that the Ob-R gene may serve as a modifier gene for insulin resistance in Japanese men.     

Protocol digest of randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer: Japan clinical oncology group study (JCOG1407)

Gemcitabine is one of the standard treatments for locally advanced pancreatic cancer. Recent studies on metastatic pancreatic cancer have shown that combination chemotherapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP) prolonged the overall survival compared with gemcitabine alone. To select the most promising chemotherapy, a randomized phase II selection design trial was started in July 2016 to compare between modified FOLFIRINOX and GnP for patients with locally advanced pancreatic cancer. A total of 124 patients will be enrolled from 36 Japanese institutions within 2.5 years. The primary endpoint is the proportion of 1-year overall survival, and secondary endpoints are progression-free survival, distant metastasis-free survival, response rate in patients with target lesions, CA19-9 response, adverse events, treatment-related death, early death, grade 4 non-hematological toxicity, and dose intensity. This trial has been registered with the UMIN Clinical Trials Registry [http://www.umin.ac.jp/ctr/index.htm], and the registration number is UMIN000023143.     

A single nucleotide polymorphism in Prostate Stem Cell Antigen is associated with endoscopic grading in Kyoto classification of gastritis

The risk allele of a single nucleotide polymorphism (SNP) rs2294008 in the Prostate stem cell antigen (PSCA) gene is strongly associated with gastric cancer. Although the Kyoto classification score is believed to be an indicator of gastric cancer risk, it lacks supporting genetic evidence. We investigated the effect of this risk allele of PSCA SNP on the Kyoto score. Participants without a history of gastric cancer or Helicobacter pylori (H. pylori) eradication underwent esophagogastroduodenoscopy, H. pylori evaluation, and SNP genotyping. The Kyoto score is the sum of scores obtained from endoscopy-based atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness. The Kyoto score is novel in the light of scoring for gastritis. A total of 323 patients were enrolled (number of individuals with genotype CC: 52; CT: 140; TT: 131, average age: 50.1 years, male: 50.8%). The patient baseline characteristics including age, sex, body mass index, smoking, drinking, family history of gastric cancer, and H. pylori status had no association with PSCA SNP. The Kyoto score was higher in T (CT or TT genotype; risk allele) carriers than in CC carriers. Atrophy, enlarged folds, and diffuse redness scores were higher in T allele carriers (risk allele) than in CC genotype individuals. In multivariate analysis, the Kyoto score was independently associated with PSCA SNP (OR: 1.30, p = 0.012). Thus, the Kyoto score was associated with a genetic predisposition.