Life Style Factors Influencing Serum Pepsinogen Levels in Healthy Japanese: a Prospective Study

Background: Gastric cancer mass screening using serum pepsinogen has been recognized and several advantages of this methods over photofluorography have been shown by previous study. Aims: To determine the factors influence the serum pepsinogen levels in healthy subjects. Subjects & Methods: One thousand and one hundred fourteen subjects who were screened for gastric cancer as part of a periodic health check. Blood samples were taken after fasting and stored below –20 ° C, until pepsinogen levels were assayed. Results: The subjects consist of 338 males (mean age 52.6+14.0) and 776 females (mean age 49.0+11.9). Age ranges from 19 to 81 years. The overall prevalence of chronic atrophic gastritis using a criterion PG I £ 70 hg/ml and PG I/II ratio £ 3.0 was 21.99 % in 1996 and 23.97 % in 2000. Bivariate analysis revealed a significant association between age, more salt consumption, fish favorable over meat and less than three time meal intake covariates with the lowering of PG I/II ratio. Smoking, drinking, BMI, weight and gender did not affect the changes of PG I/II ratio. Conclusion: Age and more salt consumption covariates have a strongest association with the decreased of PG I/II by multivariate analysis

Differential gene expression in the murine gastric fundus lacking interstitial cells of Cajal.

BACKGROUND: The muscle layers of murine gastric fundus have no interstitial cells of Cajal at the level of the myenteric plexus and only possess intramuscular interstitial cells and this tissue does not generate electric slow waves. The absence of intramuscular interstitial cells in W/WV mutants provides a unique opportunity to study the molecular changes that are associated with the loss of these intercalating cells. METHOD: The gene expression profile of the gastric fundus of wild type and W/WV mice was assayed by murine microarray analysis displaying a total of 8734 elements. Queried genes from the microarray analysis were confirmed by semi-quantitative reverse transcription-polymerase chain reaction. RESULTS: Twenty-one genes were differentially expressed in wild type and W/WV mice. Eleven transcripts had 2.0-2.5 fold higher mRNA expression in W/WV gastric fundus when compared to wild type tissues. Ten transcripts had 2.1-3.9 fold lower expression in W/WV mutants in comparison with wild type animals. None of these genes have ever been implicated in any bowel motility function. CONCLUSIONS: These data provides evidence that several important genes have significantly changed in the murine fundus of W/WV mutants that lack intramuscular interstitial cells of Cajal and have reduced enteric motor neurotransmission

Differential gene expression profile in the small intestines of mice lacking pacemaker interstitial cells of Cajal.

BACKGROUND: We previously identified eight known and novel genes differentially expressed in the small intestines of wild type and W/WV mice, which have greatly reduced populations of the interstitial cells of Cajal, that are responsible for the generation of electrical slow waves, by using a differential gene display method. METHODS: By using the same method we isolated additional candidate genes that were specifically down- or up-regulated in W/WV mice. Novel transcripts were designated as DDWMEST. RESULTS: We isolated seven candidates that were specifically down- or up-regulated in W/WV mice. Two novel transcripts, DDWMEST 1 and -91 were increased in both fed and fasted W/WV mice. Expression of another five genes was suppressed in W/WV mice: ARG2 (Arginase II), ONZIN (encoding leukemia inhibitory factor regulated protein), and three novel transcripts: DDWMEST62, -84, and -100. Together with the previous report, we identified fifteen differentially expressed genes in total in the small intestines of W/WV mice. Eight of these genes were reduced in the jejunums of W/WV mice compared to age matched wild type mice, whereas the other seven genes showed an increase in expression. Differential expression was the same in fasted and fed animals, suggesting that the differences were independent of the dietetic state of the animal. CONCLUSIONS: Several known and novel genes are differentially expressed in the small intestines of W/WV mice. Differential gene comparison might contribute to our understanding of motility disorders associated with the loss of the interstitial cells of Cajal.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Expression of Cyclooxygenase Enhances Tumor Invasion and Metastasis in Human Gastric Carcinoma

Background: Expression of COX-2 in vitro has been shown to have a number of cellular effects including increasing proliferation, reducing apoptosis promoting angiogenesis, decreasing E-cadherin expression and increasing invasive/metastatic potential. Aims: To determine the role of COX-2 in the development and metastasis potential of gastric carcinoma in human subjects. Methods: Tissue samples were obtained from surgically removed specimens of 48 patients with primary gastric adenocarcinoma who underwent gastrectomy from January 1998 to December 1999. The specimens were stained for HE while COX-2 expressions in cancer fold and antrum site were evaluated immunohistochemically. Expression of COX-2 was defined as positive when either one of cancer lesion or antrum site showed immunoreactivity. Results: Preliminary result from 12 out of 48 cases, COX-2 immunoreactivity was detected in 50% (6 of 12 specimens). Expression of COX-2 were more frequent in tumor with serosal invasion (5 of 6 specimens), lymph node metastases (3 of 3 specimens), tumor size more than 4 cm and were significant, statistically (p<0.05). The expression of COX-2 in well differential carcinoma type was similar with in poorly differentiated carcinoma type. Conclusion: COX-2 expression in gastric carcinoma tissue is correlated closely with tumor size, serosal invasion and lymph node metastases, indicating that COX-2 is involved in the growth and metastases of gastric carcinoma

An RNA-dependent RNA polymerase gene in bat genomes derived from an ancient negative-strand RNA virus

Endogenous bornavirus-like L (EBLL) elements are inheritable sequences derived from ancient bornavirus L genes that encode a viral RNA-dependent RNA polymerase (RdRp) in many eukaryotic genomes. Here, we demonstrate that bats of the genus Eptesicus have preserved for more than 11.8 million years an EBLL element named eEBLL-1, which has an intact open reading frame of 1,718 codons. The eEBLL-1 coding sequence revealed that functional motifs essential for mononegaviral RdRp activity are well conserved in the EBLL-1 genes. Genetic analyses showed that natural selection operated on eEBLL-1 during the evolution of Eptesicus. Notably, we detected efficient transcription of eEBLL-1 in tissues from Eptesicus bats. To the best of our knowledge, this study is the first report showing that the eukaryotic genome has gained a riboviral polymerase gene from an ancient virus that has the potential to encode a functional RdRp

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases

Aims The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. Methods and Results We performed WES of 23 probands diagnosed with early-onset (<65 years) CCSD and analyzed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency < 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as “pathogenic” by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that 2 variants in KCNH2 and SCN5A, 4 variants in SCN10A, and 1 variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from “Uncertain significance” to “Likely pathogenic” in 6 probands. Conclusions Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD. Translational Perspective Whole-exome sequencing (WES) may be helpful in determining the causes of cardiac conduction system disease (CCSD), however, the identification of pathogenic variants remains a challenge. We performed WES of 23 probands diagnosed with early-onset CCSD, and identified 12 pathogenic or likely pathogenic variants in 11 of these probands (48%) according to the 2015 ACMG standards and guidelines. In this context, functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants, and SCN10A may be one of the major development factors in CCSD

Differential gene expression profile in the small intestines of mice lacking pacemaker interstitial cells of Cajal

BACKGROUND: We previously identified eight known and novel genes differentially expressed in the small intestines of wild type and W/W(V )mice, which have greatly reduced populations of the interstitial cells of Cajal, that are responsible for the generation of electrical slow waves, by using a differential gene display method. METHODS: By using the same method we isolated additional candidate genes that were specifically down- or up-regulated in W/W(V )mice. Novel transcripts were designated as DDWMEST. RESULTS: We isolated seven candidates that were specifically down- or up-regulated in W/W(V )mice. Two novel transcripts, DDWMEST 1 and -91 were increased in both fed and fasted W/W(V )mice. Expression of another five genes was suppressed in W/W(V )mice: ARG2 (Arginase II), ONZIN (encoding leukemia inhibitory factor regulated protein), and three novel transcripts: DDWMEST62, -84, and -100. Together with the previous report, we identified fifteen differentially expressed genes in total in the small intestines of W/W(V )mice. Eight of these genes were reduced in the jejunums of W/W(V )mice compared to age matched wild type mice, whereas the other seven genes showed an increase in expression. Differential expression was the same in fasted and fed animals, suggesting that the differences were independent of the dietetic state of the animal. CONCLUSIONS: Several known and novel genes are differentially expressed in the small intestines of W/W(V )mice. Differential gene comparison might contribute to our understanding of motility disorders associated with the loss of the interstitial cells of Cajal