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Background/Aims: Ultrasonography should be used for screening of hepatocellular carcinoma, but there are few reports on the relationship between liver ultrasonographic findings and the development of hepatocellular carcinoma (HCC). Using prospective follow-up studies, we examined the role of liver with a hypoechoic nodular pattern as a high-risk factor in HCC. Methods: The study was performed by follow-up on 593 patients with chronic liver disease recorded at our hospital. The ultrasonographic pattern of the liver parenchyma was classified either as a small or large hypoechoic nodular pattern or as a nonnodular pattern. Patients were followed up from the time of initial ultrasonographic examination (1985–1987) until January 1, 1991. Results: During the follow-up period (average, 4.2 years, range, 0.3–6.0 years), 62 patients were found to have HCC (12%). Patients whose livers showed small or large hypoechoic nodular pattern had a significantly higher risk of HCC than did patients whose livers showed a nonnodular pattern (rate ratios were 14.0 and 20.0, respectively, adjusted for age, sex, hepatitis virus markers, ICG R15, α-fetoprotein concentration, and ultrasonographic pattern of the liver). Conclusions: Liver showing a hypoechoic nodular pattern is a major risk factor in HCC.

Angiogenesis-Related Factors At the Residual Inflammation in Patients With Ulcerative Colitis in Clinical Remission Stage Miwako Kagawa, Toshiya Okahisa, Yoshifumi Takaoka, Yasuteru Fujino, Jinsei Miyoshi, Toshi Takaoka, Tetsu Tomonari, Shinji Kitamura, Yasuyuki Okada, Kaizo Kagemoto, Masanori Takehara, Kumiko Tanaka, Sayo Matsumoto, Tomofumi Teramae, Hiroshi Miyamoto, Naoki Muguruma, Tetsuji Takayama

Background & Aims: Epidermal growth factor (EGF)-like growth factors are induced after acute gastric injury and may play an important role in mucosal repair. However, the mechanisms that trigger these growth factors are poorly understood. We determined the role of EGF receptor (EGFR) in stress-induced expression of heparinbinding EGF-like growth factor (HB-EGF) in a rat gastric epithelial cell line (RGM1 cells). Methods: RGM1 cells were transfected with a plasmid containing complementary DNA encoding a dominant-negative human EGFR (HERCD533). Cells were treated with hydrogen peroxide (0-400 μmol/L) or sorbitol (600 mmol/L). Tyrosine phosphorylation of EGFR was determined by immunoprecipitation and Western blotting with an antiphosphotyrosine antibody. HB-EGF messenger RNA and protein were determined with Northern and Western blotting, respectively. Cell growth was evaluated by cell number and [ 3 H]thymidine incorporation. Results: Oxidative stress and osmotic stress induced tyrosine phosphorylation of EGFR within 2 minutes, followed by a marked increase in HB-EGF and amphiregulin transcripts in RGM1 cells. Introduction of HERCD533 into the cells inhibited not only tyrosine phosphorylation of EGFR but also growth response to EGF. Furthermore, oxidative stress-induced HB-EGF messenger RNA expression was impaired in HERCD533-expressing cells. Conclusions: EGFR plays a crucial role in the stress-induced expression of EGF-like growth factors in gastrointestinal epithelial cells. GASTROENTEROLOGY 2001;120:108-116

protein were collected. Cytokine levels in cell supernatants were determined using the Bioplex 3D suspension array system (Bio-Rad). Preadipocyte supernatants were also applied on cultures of human colonic NCM-460 cells for 24hs and RNA and protein were collected. Inflammatory molecule mRNA expression and activation of intracellular kinases were evaluated with Luminex inflammatory panels (FlexScript LDA), and phospho-protein multiplex panels, respectively. Results: Preadipocytes isolated from IBD patients demonstrated differential mediator secretion patterns compared to preadipocytes from control and obese patients. Of the 42 proinflammatory cytokines and growth factors tested, IL-7/IL-8/Gro/MCP3/VEGF/ PDGF-AA showed statistically significant differences between control, obese and IBD preadipocytes (p ,0.05). Notably, there were significant differences in mediator secretion between preadipocytes isolated from UC and CD patients, in particular VEGF and PDGF (p , 0.01 for both). NCM-460 cells had distinct GSK-3, AKT kinase activation (p , 0.05 for both) and cytokine mRNA expression patterns of TNF, IL-2, IL-3, IL-17, VEGF, MIP-1 β, MIP-3, RANTES (p,0.05) following exposure to preadipocyte supernatants from all three pathological conditions compared to controls. Conclusions: Our data suggest the existence of preadipocyte-disease-dependent mediators contributing to the generation of differential colonocyte responses. Together with reports indicating altered levels of several adipokines during IBD, our results provide the first direct evidence for the importance of adipose tissue homeostasis during obesity in determining the outcome of IBD. Supported by NIH P50 DK064539 (CP & IK), DK047343, DK060729 (CP), The Broad Foundation (BMRP) (IK, RA), and the Blinder Research Foundation for Crohn's Disease (AS).

Purpose: Mobility disorders of the alimentary tract including irritable bowel syndrome (IBS) is now increasing worldwide. Measurement of intracolonic pressure has been conventionally employed for assessment of colonic motility. However, it is very laborious and burdensome for a routine examination. Therefore, in this study, we performed electrocolonography (ECoG), an easy and simple methodology, and investigated its usefulness for evaluation of colonic motility in comparison with the conventional methodology. Method: Twenty-five well-informed healthy volunteers were enrolled. ECoG was performed using a portable electrogastrograph (NIPRO EGG, A&D, Tokyo, Japan). After detecting a sigmoid colon using external ultrasonography, 4 electrodes of ECoG were attached to the abdomen. The ECoG was recorded by a bipolar lead between the central electrode and 3 surface probe electrodes (Ch1-3) at 1-second interval with frequencies of 1.5-6.0 cpm. Mosapride (10mg) or butylscopolamine (10mg) was orally administered during the examinations. For the analysis of ECoG data, the dominant frequencies and peak powers in 3 channels were calculated using a Fast Fourier Transform. In the 3 subjects, intracolonic pressure was measured using mobility visualization system (ManoScan 360, Sierra Scientific Instruments, CA) concurrently with ECoG. A catheter with 36 pressure sensors was introduced through the anus to the sigmoid colon, and the change of the pressure at each point was recorded. Results: Colonic peristalsis at about 2 cpm (1.95 0.41 cpm) was observed by mobility measuring system. The pressure was significantly increased by administration of mosapride, and was decreased by butylscopolamine, consistent with the previous reports. While, a dominant frequency at 2 cpm, which represented action potential of colonic peristalsis, was observed in all channels of ECoG. The peak power of the dominant frequency was significantly increased by mosapride (pre 15.0 ± 7.38uV, after 52.0 ± 50.3uV) and was significantly decreased by butylscopolamine (pre 15.2 ± 6.27uV, after 0.35 ± 0.24uV), corresponding to the change of intracolonic pressure. The dominant frequency did not change after administration of mosapride or butylscopolamine in ECoG. Conclusion:We could detect action potential of colonic peristalsis by ECoG, an easy and simple methodology, and showed the usefulness of ECoG for assessing colonic motility.