Gamma-aminobutyric acid (GABA) and cell proliferation: focus on cancer cells.

In addition to its role in the adult mammalian nervous system as an inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) is involved in the proliferation, differentiation, and migration of several kinds of cells including cancer cells. GABA is synthesized predominantly from glutamate by glutamate decarboxylase and exerts its effects via ionotropic GABA(A) receptors and/or metabotropic GABA(B) receptors. In this review, the current state of knowledge regarding the role of the GABAergic system in peripheral nonneuronal cell proliferation is described, and recent advances in elucidation of the mechanisms leading to cell proliferation are discussed.

Overexpression of a DEAD box/RNA helicase protein, rck/p54, in human hepatocytes from patients with hepatitis C virus-related chronic hepatitis and its implication in hepatocellular carcinogenesis.

Hepatitis C virus (HCV) infection is the most common cause of chronic hepatitis, which frequently progresses to hepatocellular carcinoma. The pathogenesis of its persistent infection and tumour progression has not been fully characterized yet. The RCK gene was previously cloned at the breakpoint of the t(11;14)(q23;q32) chromosome translocation observed in human B-cell lymphoma cell line RC-K8. The RCK protein, rck/p54, which is a 54-kDa cytoplasmic protein belonging to the DEAD box/RNA helicase family, is considered to facilitate the translation of mRNA(s) of genes for cell proliferation and malignant transformation not only in B-cell lymphomas having the t(11;14) translocation but also in other solid tumours. The aim of this work was to examine the involvement of rck/p54 in carcinogenesis of hepatocellular carcinoma from HCV-related chronic hepatitis. We examined the expression of rck/p54 in 29 cases of HCV-related chronic hepatitis and eight cases of hepatocellular carcinoma by immunohistochemistry and Western blot analysis. Twenty-six of 29 cases with HCV-related chronic hepatitis and all cases with hepatocellular carcinoma tested overexpressed rck/p54 protein. The expression of rck/p54 was lowered by treatment with IFN-alpha in two cases who showed the decrease in HCV RNA levels. These findings suggest that rck/p54 protein is possibly involved in the replication of HCV genomes in hepatocytes and in tumourigenesis of hepatocellular carcinomas.

Expression of the EP4 prostaglandin E2 receptor subtype with rat dextran sodium sulphate colitis: colitis suppression by a selective agonist, ONO-AE1-329.

Expression of the EP4 receptor, a prostaglandin (PG)E2 receptor subtype, as well as disease suppression by the administration of a selective EP4 agonist (ONO-AE1-329) was investigated in the colorectal mucosa of rats with dextran sodium sulphate (DSS)-induced colitis. Rats were given drinking water containing 3% DSS for 2 weeks. Expression of EP4 receptor mRNA was barely detectable under normal conditions according to reverse transcription-polymerase chain reaction (RT-PCR). By 1 week after the initial administration of DSS, the receptor mRNA was strongly expressed. After ONO-AE1-329 was administered intracolonically to rats with DSS colitis for 7 consecutive days, erosion and ulceration decreased. Peripheral white blood cell (WBC) counts became less elevated. Interleukin (IL)-1beta and growth-regulated gene product/cytokine-induced neutrophil chemoattractant (GRO/CINC-1) concentrations in colorectal mucosa were lower than in colitis control group (IL-1beta: 12.8 +/- 4.6 and 30.8 +/- 6.2 microg/mg protein, P < 0.05; GRO/CINC-1: 15.5 +/- 3.0 and 39.2 +/- 5.4 microg/mg protein, P < 0.05), and the expression of the corresponding cytokine mRNA was strongly suppressed. IL-10 concentration was higher than in control group (14.5 +/- 1.7 and 7.9 +/- 1.2 microg/mg, P < 0.05), and the mRNA was more strongly expressed. These results suggest that the EP4 receptor is important in colonic inflammation, and that PGE2 suppresses DSS colitis at least partly via the EP4 receptor and the above cytokine changes. Intracolonic administration of selective EP4 agonist might have therapeutic applicability in inflammatory bowel disease such as ulcerative colitis.

Co-overexpression of DEAD box protein rck/p54 and c-myc protein in human colorectal adenomas and the relevance of their expression in cultured cell lines.

The RCK gene was cloned through a study of the breakpoint of the t(11;14)(q23;q32) chromosomal translocation observed in a human B-cell lymphoma and overexpression of the protein (rck/p54) due to the translocation was shown to be associated with malignant transformation. The rck/p54 protein belongs to the DEAD box protein/RNA helicase family, which has a variety of functions such as translation initiation, pre-mRNA splicing and ribosome assembly. It is considered that rck/p54 protein may have significant effects on the mRNA structure of genes associated with cell proliferation, facilitating protein synthesis. Expression of rck/p54 in colorectal adenomas, which are a premalignant lesion of colorectal cancer, was examined by Western blot analysis and immunohistochemistry. The rck/p54 protein was found to be overexpressed in tumor tissues resected from 17 of 26 cases (65.4%) of colorectal adenomas and 13 of 14 c-myc-positive cases (92.8%) also co-overexpressed rck/p54 protein. Thus, a significant correlation between rck/p54 and c-myc co-overexpression was found (Spearman's rank correlation, P = 0.0018). We demonstrate that overexpression of rck/p54 in two different cell lines, COS 7 and human colorectal cancer cell line SW480, caused an increase in c-myc protein levels by enhancement of its translation efficiency and/or stabilization of its mRNA. These results suggest that rck/p54 of the DEAD box protein/RNA helicase family may contribute to cell proliferation and carcinogenesis in the development of human colorectal tumors at the translational level by increasing synthesis of c-myc protein.

Novel Rana keratin genes and their expression during larval to adult epidermal conversion in bullfrog tadpoles.

The conversion of the larval to adult epidermis during metamorphosis of tadpoles of bullfrog, Rana catesbeiana, was investigated utilizing newly cloned Rana keratin cDNAs as probes. Rana larval keratin (RLK) cDNA (rlk) was cloned using highly specific antisera against Xenopus larval keratin (XLK). Tail skin proteins of bullfrog tadpoles were separated by 2-dimensional gel electrophoresis and subjected to Western blot analysis with anti-XLK antisera. The Rana antigen detected by this method was sequenced and identified as a type II keratin. We cloned rlk from tadpole skin by PCR utilizing primers designed from these peptide sequences of RLK. RLK predicted by nucleotide sequences of rlk was a 549 amino acid -long type II keratin. Subtractive cloning between the body and the tail skin of bullfrog tadpole yielded a cDNA (rak) of Rana adult keratin (RAK). RAK was a 433 amino acid-long type I keratin. We also cloned a Rana keratin 8 (RK8) cDNA (rk8) from bullfrog tadpole epidermis. RK8 was 502 amino acid-long and homologous to cytokeratin 8. Northern blot analyses and in situ hybridization experiments showed that rlk was actively expressed through prometamorphosis in larva-specific epidermal cells called skein cells and became completely inactive at the climax stage of metamorphosis and in the adult skin. RAK mRNA was expressed in basal cells of the tadpole epidermis and germinative cells in the adult epidermis. The expression of rlk and rak was down- and up-regulated by thyroid hormone (TH), respectively. In contrast, there was no change in the expression of RK8 during spontaneous and TH-induced metamorphosis. RK8 mRNA was exclusively expressed in apical cells of the larval epidermis. These patterns of keratin gene expression indicated that the expression of keratin genes is differently regulated by TH depending on the type of larval epidermal cells. The present study demonstrated the usefulness of these genes for the study of molecular mechanism of postembryonic epidermal development and differentiation.

Long-term histological prognosis and serum fibrosis markers in chronic hepatitis C patients treated with interferon.

BACKGROUND: Interferon (IFN) therapy is effective in 20-40% of patients with chronic hepatitis C, but the relationship between histological changes and the response to interferon is still unclear. We investigated the long-term histological prognosis and the changes of serum fibrosis markers after interferon therapy relation to the response. METHODS AND RESULTS: One hundred and eighteen patients with chronic hepatitis C who received interferon therapy were divided into four groups based on the detection of viremia and the serum alanine aminotransferase (ALT) level after treatment. A histological examination was performed by using the histological activity index and the criteria of the METAVIR score. Serum fibrosis markers were used to measure the levels of hyaluronic acid and type IV collagen 7s. Responders, whose serum ALT levels became normal after treatment, demonstrated histological improvement. Histological improvement was more rapid in sustained virological responders with hepatitis C virus (HCV) RNA seronegativity than in biochemical responders with HCV-RNA seropositivity. Only sustained virological responders exhibited histological cure. In partial responders, whose serum ALT levels decreased to less than twice the upper of normal, and non-responders whose serum ALT levels were not reduced, liver fibrosis was unchanged or showed progression. Serum fibrosis markers increased with progression of the histological stage and varied depending on the response to interferon. CONCLUSION: Normalization of serum ALT levels after interferon therapy led to a histological improvement, and that with viral clearance achieved histological cure. Serum fibrosis markers were useful indicators for long-term according to the response of IFN therapy.

EP1 and EP4 receptors mediate exocytosis evoked by prostaglandin E(2) in guinea-pig antral mucous cells.

Effects of prostaglandin E(2) (PGE(2)) on exocytosis of mucin were studied in mucous cells isolated from guinea-pig antrum using video-microscopy. Stimulation with PGE(2) elicited a sustained increase in the frequency of exocytotic events in a dose-dependent manner, which was under regulation by both Ca(2+) and cAMP. Stimulation with a selective prostanoid EP4 receptor agonist (ONO-AEI-329, 10 microM), which activates cAMP signals, elicited a sustained increase in the frequency of exocytotic events (30 % of that evoked by 1 microM PGE(2)). Stimulation with an EP1 agonist (17-P-T-PGE(2), 1 microM), which activates Ca(2+) signals, increased the frequency of exocytotic events to a lesser extent (5 % of that evoked by 1 microM PGE(2)), while addition of an EP1 antagonist (ONO-8713, 10 microM) decreased the frequency of exocytotic events (approximately 40 % of that evoked by 1 microM PGE(2)). However, addition of the EP1 agonist potentiated the frequency of exocytotic events evoked by the EP4 agonist or forskolin (which elevates cAMP levels) and increased the sensitivity of the exocytotic events to forskolin. These results suggest that the Ca(2+) signal activated via the EP1 receptor potentiates the cAMP-regulated exocytotic events activated via the EP4 receptor during PGE(2) stimulation, by increasing the sensitivity of the exocytotic response to cAMP. In conclusion, exocytotic events in PGE(2)-stimulated antral mucous cells were regulated by interactions between EP1 and EP4 receptors. Experimental Physiology (2001) 86.4, 451-460.

Medium-chain fatty acids stimulate interleukin-8 production in Caco-2 cells with different mechanisms from long-chain fatty acids.

BACKGROUND AND AIM: It has been suggested that dietary fat exacerbates intestinal inflammation. We investigated the effect of fatty acids on interleukin (IL)-8 production in a human intestinal epithelial cell line (Caco-2). METHODS: The cells were cultured as monolayers on microporous membranes in culture inserts. Oleic acid (OA), capric acid (CA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were applied to the apical compartment of Caco-2 cell monolayers. The concentration of IL-8 in the basolateral medium was measured by using enzyme-linked immunosorbent assay, and the expression of IL-8 mRNA was measured by using competitive reverse transcription--polymerase chain reaction. Protein kinase C inhibitors (GF109203X and calphostin C) and H-7 (a protein kinase inhibitor) were used to study the mechanisms by which IL-8 production is stimulated. RESULTS: Both OA and CA enhanced IL-8 production (approximately fivefold), whereas DHA and EPA did not. Both OA and CA also enhanced IL-1-induced IL-8 production. The onset of OA-induced IL-8 production was delayed compared with that of CA-induced IL-8 production. Both OA and CA enhanced IL-8 mRNA expression (approximately fivefold) after 6 and 3 h, respectively. The protein kinase inhibitor (H-7) reduced both OA- and CA-induced IL-8 production by 88.0 and 85.9%, respectively. The protein kinase C inhibitors (GF109203X and calphostin C) reduced OA-induced IL-8 production by 29.3 and 54.5%, respectively, but showed no effect on CA-induced IL-8 production. CONCLUSIONS: These findings suggest that not only OA but also CA stimulates IL-8 production in intestinal epithelial cells, and the mechanisms of action differ between OA and CA.

Estimation of mucosal inflammatory mediators in rat DSS-induced colitis. Possible role of PGE(2) in protection against mucosal damage.

In order to investigate the mucosal injury mechanism in UC, we made dextran sulfate sodium (DSS)-induced colitis in rat and examined pathological findings, MPO activity, PGE(2) level, and local mRNA expression and secretion of IL-1 beta, TNF-alpha, GRO/CINC-1 and IL-10 in DSS colitis mucosa. Moreover, we estimated the correlation between the severity of mucosal damage and changes of these local inflammatory mediators' values. Neutrophil infiltration was marked and MPO activity was locally increased in proportion to the severity of mucosal damage. The mRNA expression and secretion of IL-1 beta, GRO/CINC-1 and IL-10 were increased. Especially, the secretions of IL-1 beta and GRO/CINC-1 were increased in proportion to the severity of mucosal damage. However, those of TNF-alpha were not increased in the colitis mucosa. An abnormal macrophage function and the presence of macrophage subtypes producing different cytokines would be predicted from our TNF-alpha data. The lesion was less severe in the colonic mucosa with higher levels of endogenous PGE(2), while it was more severe in the colonic mucosa with lower levels of endogenous PGE(2), implicating this compound as an inhibitory factor against the development of inflammation in the affected mucosa. Our results suggest that PGE(2) might have therapeutic applicability to UC.

Enprostil, a prostaglandin-E(2) analogue, inhibits interleukin-8 production of human colonic epithelial cell lines.

We previously reported that intracolonic administration of enprostil, a prostaglandin-E(2) (PGE(2)) analogue, had therapeutic effects on acute colitis induced in rodents by dextran sulfate sodium (DSS). In addition, production of growth-regulated gene product/cytokine-induced neutrophil chemoattractant-1 [GRO/CINC-1; an interleukin(IL)-8 like cytokine] was suppressed in the inflamed tissues. In the present study we used a human colon cancer cell line (HT-29) to investigate enprostil effects on the IL-8 production of intestinal epithelial cells stimulated by various stimulants. In a MTT assay, concentrations of enprostil >10(-5)M had cytotoxitic effects on HT-29 cells. Furthermore, 10(-6) M enprostil suppressed IL-8 production in HT-29 cells, SW620 and CaCo2 stimulated with interleukin-1 beta (IL-1 beta) or lipopolysaccharide (LPS), but did not suppress this response when cells were stimulated with tumour necrosis factor (TNF)-alpha. These results suggest that enprostil affects a point in the pathway between the IL-1 receptor or LPS receptor and nuclear factor-kappa B(NF-kappa B), without affecting the pathway between the TNF receptor and NF-kappa B, with the latter factor being required for the IL-8 gene transcription. The therapeutic effect of exogenous enprostil on DSS colitis may involve the inhibition of IL-8 production in colonic epithelial cells stimulated by IL-1 beta or LPS.

Frequent altered expression of fragile histidine triad protein in human colorectal adenomas.

Fragile histidine triad (FHIT) gene is involved in deletions on the short arm of chromosome 3 in various human cancers. We found that 47% of colorectal adenomas, which is a higher frequency than that of K-ras, showed altered expression of the Fhit protein by Western blot analysis. The amount of Fhit protein was inversely correlated with the degree of dysplasia. Importantly, 27% of low-grade dysplastic adenomas showed altered expression of Fhit protein. Additionally, expression of human Fhit protein in human colon carcinoma cell line SW480 exhibited a marked inhibition of growth and rendered SW480 cells highly susceptible to undergo apoptosis compared with control cells. These findings suggest that altered expression of the FHIT gene is a quite early aberration in the development of colorectal tumors and that Fhit protein may act as a tumor suppressor.

Comparison of tests for fecal lactoferrin and fecal occult blood for colorectal diseases: a prospective pilot study.

OBJECTIVE: This prospective pilot study was conducted to compare the usefulness of measuring fecal lactoferrin (Lf) to that of fecal occult blood (FOB) test for detection of colorectal diseases. PATIENTS AND METHODS: The subjects were 351 patients who underwent colonoscopy. A fecal sample was obtained on the day before colonoscopy. Fecal Lf was measured by enzyme-linked immunosorbent assay. The FOB test was performed by combined assay (latex agglutination) of hemoglobin and transferrin. RESULTS: The specificities of the fecal Lf and FOB tests were the same (88.7%). For patients with colorectal cancer (13), colorectal polyp (69), ulcerative colitis (18), Crohn's disease (13), non-specific colitis (8), internal hemorrhoids (60), colon diverticulum (27), and miscellaneous diseases of the colon (10), the rates of positivity for fecal Lf were 7/13, 14/69, 12/18, 7/13, 4/8, 22/60, 8/27, and 6/10, respectively. The corresponding rates for FOB were 8/13, 12/69, 11/18, 4/13, 4/8, 9/60, 2/27, and 1/10. For patients with internal hemorrhoids, the rate of positivity for fecal Lf was significantly higher than that for FOB. In other disease groups, there was no significant difference in the rate of positivity between fecal Lf and FOB. CONCLUSION: These findings suggest that measurement of fecal Lf is as useful as FOB in detecting colorectal diseases.

Accuracy of detection of colorectal neoplasia using an immunochemical occult blood test in symptomatic referred patients: comparison of retrospective and prospective studies.

OBJECTIVE: In this study the sensitivity and specificity of immunochemical tests for colorectal neoplasia were evaluated in retrospective and prospective studies. METHODS: Four types of fecal blood tests--a chemical test (Hemoccult II) and three different immunochemical tests including a test which detects hemoglobin and transferrin- were performed in the retrospective study. In the prospective study the test for hemoglobin and transferrin was used for all patients that underwent total colonoscopy. PATIENTS: One hundred seven patients with colorectal neoplasia, 57 with gastroduodenal bleeding, and 62 with normal digestive tracts were examined retrospectively. One thousand two hundred and ninety-eight nonspecifically symptomatic patients whose endoscopic examination was negative for hemorrhagic lesions in the upper digestive tract were examined prospectively. RESULTS: In the retrospective study, sensitivities for the detection of colorectal cancers and adenomas with diameters > or =10 mm using the tests which detect hemoglobin and transferrin were 98% and 89%, respectively. These were the highest sensitivity among the four tests. The specificity of this test was 97%, which was higher than that of the Hemoccult II test. In the prospective study, the sensitivities of the tests for hemoglobin and transferrin for the detection of colorectal cancers and adenomas with diameters > or =10 mm were 79% and 33%, respectively. The specificity was 95%. CONCLUSIONS: The test for hemoglobin and transferrin showed the highest sensitivity and specificity for colorectal neoplasia in the retrospective study. The sensitivity and specificity of this test were not so high in the prospective study, but they may be clinically applicable in the evaluation of patients with various nonspecific symptoms.

Immunohistochemical expression of vascular endothelial growth factor can predict response to 5-fluorouracil and cisplatin in patients with gastric adenocarcinoma.

The combination of 5-fluorouracil (5-FU) and cisplatin is used most commonly for gastric carcinoma. Recent studies have indicated that vascular endothelial growth factor (VEGF) is related to drug delivery through angiogenesis and vascular permeability. In this study, we evaluated the efficacy and toxicity of continuous infusion of 5-FU and low dose cisplatin infusion as first-line treatment in patients with unresectable gastric adenocarcinoma. We also examined the relationship between chemotherapy response and immunohistochemical expression of VEGF in the biopsy samples of gastric primary. All 30 patients enrolled in this study were assessable for response, adverse reactions, and VEGF expression. The regimen consisted of 5-FU (350 mg/m2/day every day by continuous venous infusion) and low dose cisplatin (7 mg/m2/day by drip infusion over 1 h on days 1-5 every week). This treatment was repeated weekly for 3 consecutive weeks. Four weeks after the second cycle, mesurable lesions were estimated for response. An overall response rate was 46.7% (14/30). Patients with intestinal histologic type (10/12) and good performance status ([PS], 13/18) showed good response rate (83.3%, and 72.2%, respectively) compared to patients with diffuse histologic type (4/18) and poor PS [(1/12) 22.2%, and 8. 3%, respectively]. The response rate of VEGF-positive cases and VEGF-negative cases was 75% (12/16), and 16.7% (2/14), respectively. Multivarite analysis revealed that VEGF-positive and good PS had a significant impact on chemotherapy response in this treatment. The most common garde 3 or higher toxicities were myelosuppression (30%) and diarrhea (13.3%). Continuous infusion of 5-FU and low dose cisplatin infusion is an effective treatment for patients with unresectable gastric carcinoma, and VEGF expression may be a useful predictor of chemotherapy response in this regimen.

Breath and blood ammonia in liver cirrhosis.

BACKGROUND/AIMS: Hyperammonemia causes dysfunction of multiple organs in patients with cirrhosis, including hepatic encephalopathy. Blood ammonia concentrations are monitored with respect to disease progression and efficacy of treatment. Fetor hepaticus, the characteristic breath odor in hepatic encephalopathy has called little quantitative attention to breath ammonia. We studied the dynamics of ammonia metabolism in cirrhosis in terms of the relationship between breath and blood ammonia. METHODOLOGY: Breath and blood ammonia levels were measured simultaneously in 20 cirrhotic patients and in 10 healthy volunteers. Breath ammonia was measured using ammonia electrodes in collected expired air. Helicobacter pylori serum antibody titers were also measured, since the organism produces ammonia. RESULTS: Blood ammonia correlated positively with breath ammonia in patients with cirrhosis. Breath ammonia levels were significantly higher in cirrhotic patients (0.745 ppm) than in controls (0.278 ppm), and higher in cirrhotic patients with hyperammonemia (0.997 ppm) than in those without (0.558 ppm). Breath and blood ammonia decreased together with treatment of hyperammonemia. H. pylori seropositivity was 20% in controls, 27.3% in cirrhotic patients with normal blood ammonia, and 66.7% in those with hyperammonemia. CONCLUSIONS: Breath ammonia measurement may be useful in diagnosis, treatment assessment, and follow-up in hepatic encephalopathy.

Alteration of colonic mucin after ureterosigmoidostomy.

PURPOSE: Patients undergoing urinary diversion by ureterosigmoidostomy after complete cystectomy for malignant bladder tumors show a high incidence of neoplasia at and near the site of anastomosis. We examined a risk factor for tumor occurrence in the area of anastomosis, alterations of mucus glycoproteins in the surrounding colonic mucosa. METHODS: Colonoscopy was performed in 37 patients who had undergone ureterosigmoidostomy. Biopsy specimens were obtained near the ureteral anastomosis and were stained with hematoxylin and eosin, high iron-diamine alcian blue (pH 2.5), and a fluorescent lectin conjugate (peanut agglutinin). RESULTS: At the anastomotic site colonoscopy showed protruding lesions in 26 of 37 patients (71 percent), all histologically representing inflammatory granulomas. The mucosa around the anastomosis was normal in endoscopic appearance; however, histologically, slight inflammatory cell infiltration, edema, and increased numbers of Paneth cells were observed. Alcian blue staining revealed an increase in mucosal sialomucin postoperatively compared with preoperatively. The proportion of peanut agglutinin-binding mucin, not observed in normal mucosa but seen in malignant or premalignant tissue, was increased. CONCLUSION: As postoperative interval increases, changes in properties of the "background" mucosa become greater, which suggests an association with colonic carcinogenesis.

Therapeutic effect of intracolonically administered nuclear factor kappa B (p65) antisense oligonucleotide on mouse dextran sulphate sodium (DSS)-induced colitis.

Cytokines such as IL-1, tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-8 are increased in inflamed colonic mucosa after administration of mouse DSS. Nuclear factor kappaB (NF-kappaB) is a transcription factor which regulates the expression of these cytokine genes. The effect of intracolonically administered NF-kappaB (p65) antisense phosphorothioate oligonucleotide was examined in mouse DSS-induced colitis using drinking water containing 5% DSS. When antisense oligonucleotide was given on day 0, the disease activity index (DAI) representing clinical symptoms improved and the histological score decreased; furthermore, IL-1, IL-6, and TNF-alpha concentrations in rectal mucosa were lower compared with the control group. Clinical and histological improvement was also observed when antisense oligonucleotide was begun on day 2 but not on day 7. In addition, the distribution of antisense oligonucleotides was investigated by confocal laser microscopy. In colonic mucosa, oligonucleotides were predominantly localized to cells in the lamina propria, but also in the epithelium. Western blot analysis using homogenized rectal mucosa showed the decreased expression of NF-kappaB p65 in the antisense oligonucleotide-treated group, although it was increased in the colitis group. These results suggest that intracolonic administration of NF-kappaB antisense oligonucleotide may be effective in ulcerative colitis.

Acquired ileal diverticulum: an unusual bleeding source.

Acquired ileal diverticulum is an uncommon condition and diagnosis is often difficult when bleeding occurs from this source. Here we describe two cases of ileal diverticulum with massive bleeding. Both patients presented with anal bleeding, but upper and lower gastrointestinal endoscopy did not reveal the source. Selective visceral angiography finally detected bleeding lesions in the terminal ileum. Surgical resection was performed in both patients, confirming that the bleeding arose from diverticula less than 1 cm in size. In patients with obscure gastrointestinal bleeding, an ileal diverticulum should be considered, and selective visceral angiography should be performed for precise diagnosis.