Toshie Nata

Heat-killed body of lactobacillus brevis SBC8803 ameliorates intestinal injury in a murine model of colitis by enhancing the intestinal barrier function

Background: Probiotics have been clinically administered to improve intestinal damage in some intestinal inflammations. However, probiotic treatments are not always effective for these intestinal disorders because live bacteria must colonize and maintain their activity under unfavorable conditions in the intestinal lumen when displaying their functions. This study investigated the physiological functions of a heat‐killed body of a novel probiotic, Lactobacillus brevis SBC8803, on the protection of intestinal tissues, the regulation of cytokine production, the improvement of intestinal injury, and the survival rate of mice with dextran sodium sulfate (DSS)‐induced colitis. Methods: Heat shock protein (Hsp) induction and mitogen‐activated protein kinase (MAPK) phosphorylation in intestinal epithelia by heat‐killed L. brevis SBC8803 were examined by Western blotting. The barrier function of intestinal epithelia was measured with [3H]‐mannitol flux in the small intestine under oxidant stress. The effects of the bacteria on improving epithelial injury and cumulative survival rate were investigated with a DSS colitis model. Results: Heat‐killed L. brevis SBC8803 induced Hsps, phosphorylated p38 MAPK, regulated the expression of tumor necrosis factor alpha (TNF‐&agr;), interleukin (IL)‐1&bgr; and IL‐12, and improved the barrier function of intestinal epithelia under oxidant stress. The induction of Hsp and the protective effect were negated by p38 MAPK inhibitor. These functions relieve intestinal impairments and improve the survival rate in mice with lethal colitis. Conclusions: The administration of heat‐killed L. brevis SBC8803 helps to successfully maintain intestinal homeostasis, while also curing intestinal inflammation. A therapeutic strategy using heat‐killed bacteria is expected to be beneficial for human health even in conditions unsuitable for live probiotics because the heat‐killed body is able to exhibit its effects without the requirement of colonization. (Inflamm Bowel Dis 2011;)

The diagnostic accuracy of high-resolution endoscopy, autofluorescence imaging and narrow-band imaging for differentially diagnosing colon adenoma.

BACKGROUND AND STUDY AIMS Conventional colonoscopy can result in unnecessary biopsy or endoscopic resection due to its inability to distinguish adenomas from hyperplastic polyps. This study therefore evaluated the efficacy of high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow-band imaging (NBI) in discriminating colon adenoma from hyperplastic polyps. PATIENTS AND METHODS This was a prospective multicenter study in patients undergoing AFI and NBI examinations. HRE, AFI, and NBI images were classified into two groups based on morphological characteristics, the predominant color intensities, and the visibility of meshed capillary vessels, respectively. Each of the endoscopic photographs were independently evaluated by a single endoscopist. The images were then assessed by three specialists and three residents, the latter having performed < 500 colonoscopies and < 30 NBI and AFI examinations. Diagnostic test statistics were calculated to compare the accuracy in differentiating colon adenoma from hyperplastic polyps for each method. RESULTS A total of 183 patients were enrolled in the study and 339 adenomas and 85 hyperplastic polyps were identified. AFI and NBI could distinguish adenoma from hyperplastic polyps with an accuracy of 84.9 % and 88.4 %, respectively, whereas HRE exhibited an accuracy of 75.9 %. In the 358 lesions in which the AFI diagnosis was consistent with that of NBI, the accuracy, sensitivity, and specificity were high, at 91.9 %, 92.7 %, and 92.9 %, respectively. During the study comparing specialists and residents, AFI and NBI dramatically improved the diagnostic accuracy of residents from 69.1 % to 86.1 % and 84.7 %, respectively. CONCLUSIONS Both AFI and NBI are considered to be feasible tools that can discriminate colon adenoma from hyperplastic polyps, and their use may be particularly beneficial for less-experienced endoscopists.

MicroRNA‐146b improves intestinal injury in mouse colitis by activating nuclear factor‐κB and improving epithelial barrier function

The precise role of microRNAs in inflammatory disease is not clear. The present study investigated the effect of microRNA (miR‐146b) with respect to improving intestinal inflammation.

Back-to-Back Comparison of Auto-Fluorescence Imaging (AFI) Versus High Resolution White Light Colonoscopy for Adenoma Detection

BackgroundSome patients under close colonoscopic surveillance still develop colorectal cancer, thus suggesting the overlook of colorectal adenoma by endoscopists. AFI detects colorectal adenoma as a clear magenta, therefore the efficacy of AFI is expected to improve the detection ability of colorectal adenoma. The aim of this study is to determine the efficacy of AFI in detecting colorectal adenoma.MethodsThis study enrolled 88 patients who underwent colonoscopy at Asahikawa Medical University and Kushiro Medical Association Hospital. A randomly selected colonoscopist first observed the sigmoid colon and rectum with conventional high resolution endosopy (HRE). Then the colonoscopist changed the mode to AFI and handed to the scope to another colonoscopist who knew no information about the HRE. Then the second colonoscopist observed the sigmoid colon and rectum. Each colonoscopist separately recorded the findings. The detection rate, miss rate and procedural time were assessed in prospective manner.ResultsThe detection rate of flat and depressed adenoma, but not elevated adenoma, by AFI is significantly higher than that by HRE. In less-experienced endoscopists, AFI dramatically increased the detection rate (30.3%) and reduced miss rate (0%) of colorectal adenoma in comparison to those of HRE (7.7%, 50.0%), but not for experienced endoscopists. The procedural time of HRE was significantly shorter than that of AFI.ConclusionsAFI increased the detection rate and reduced the miss rate of flat and depressed adenomas. These advantages of AFI were limited to less-experienced endoscopists because experienced endoscopists exhibited a substantially high detection rate for colorectal adenoma with HRE.

Autofluorescence imaging and the quantitative intensity of fluorescence for evaluating the dysplastic grade of colonic neoplasms

Background and aimsAutofluorescence imaging (AFI) is a novel technology which can capture fluorescence emitted from intestinal tissues. While AFI is useful for detecting colorectal neoplasms, it is unclear whether AFI can facilitate the diagnosis by differentiating the extent of dysplasia of colorectal neoplasms. This study investigated the efficacy of AFI in discriminating high-grade from low-grade adenoma.Materials and methodsSixty-seven patients who underwent colonoscopy with AFI were enrolled in this study. The AFI images obtained from 158 lesions in these patients were visually classified into four categories, namely, green (G), green with magenta spots (GM), magenta with green spots (MG), and magenta (M), according to their color intensities, immediately after the examination. The AFI images of the lesions were quantified using an image-analytical software program (F index). Either the F index or the visual assessment was prospectively compared with the dysplastic grade.ResultsThe F index of the high-grade adenomas was significantly lower than that of the low-grade adenomas, hyperplasia, and normal mucosa (p < 0.05). The incidence of the lesions classified into the M classification for high-grade adenomas (55.6%) was significantly higher than that of either low-grade adenomas (20.8%) or hyperplasia (0%). No correlation was observed between the F index or the visual classification and the tumor shape. The F index was not influenced by the size of the lesion, while the size was significantly associated with the visual classification of AFI.ConclusionsAFI, particularly the F index, is considered to be a useful procedure for estimating the dysplastic grade of colonic adenomas.

Endosopic autofluorescence imaging is useful for the differential diagnosis of intestinal lymphomas resembling lymphoid hyperplasia.

Background A method for the differential diagnosis of intestinal lymphomas resembling lymphoid hyperplasia (LH) by endoscopy remains to be clearly established. Objective To evaluate the usefulness of autofluorescence imaging (AFI) in diagnosing intestinal lymphoma. Setting Single-center study. Design Prospective study. Patients One hundred forty-three samples obtained from the intestinal tissues of 21 patients with malignant lymphoma were included in the study. Interventions The terminal ileum and entire colon were observed using conventional endoscopy equipped with AFI. The AFI images were taken by 3 endoscopists and then were evaluated by 3 predominant color intensities; green, magenta, and blended. To quantify the strength of fluorescence captured by AFI, the area of the obtained biopsy specimens on images was manually traced, the signal density of either magenta or green was measured, and then the ratio of the reverse gamma value of green divided by that of magenta was defined as the Fluorescence index (F index). Main Outcome Measurements The ability to use AFI to distinguish intestinal lymphoma from normal or LH. Results The cell density is inversely proportional to the F index. The F index of lymphoma was significantly lower than that of normal mucosa or LH. The visual classification of AFI showed the overall accuracy in diagnosing lymphoma was 91.5%, and was well correlated with the F index. Limitations Single-center study. Conclusions AFI-embossed lymphoma lesions seemed as magenta and could be discriminated from LH or normal mucosa with a high overall accuracy through perception of the cell density of the lesion. Therefore, AFI is considered to be an effective procedure for determining the accurate stage and appropriate therapy in intestinal lymphoma.

Immunoprecipitation of nucleosomal DNA is a novel procedure to improve the sensitivity of serum screening for the p16 hypermethylation associated with colon cancer

BACKGROUND We developed a novel method of methylation-specific PCR (MSP) using immunoprecipitation with anti-histone antibody (IP-MSP) to efficiently detect serum methylated DNA tightly bound to de-acetylated histones. MATERIALS AND METHODS The detection limit of IP-MSP for p16 methylation was determined with a standard made by cell line (SKCO-1) lysate. p16 methylation of tumor and/or serum of 51 colorectal cancers and 10 adenoma patients, and 10 healthy volunteers was detected with conventional MSP or IP-MSP. RESULTS IP-MSP detected p16 methylation from 0.5pg/mul of the cell lysate. The sensitivity of IP-MSP for detecting serum p16 methylation in 27 patients with tumors characterized by p16 methylation was significantly higher than that with conventional method (81% versus 59%), particularly in Stage II patients (91% versus 45%). IP-MSP detected no p16 hypermethylation in sera of adenoma patients and volunteers. CONCLUSIONS IP-MSP is thus considered to be a promising procedure to detect serum methylated DNA in colorectal cancer patients.

Collagenous colitis appeared after 6-year administration of lansoprazole

Collagenous colitis (CC) is one of the causes of undefined watery diarrhea, which is histologically accompanied by thickening of the subepithelial collagen layer. CC associated with lansoprazole normally occurs within several weeks after initial administration, but no case presenting after long-term administration of lansoprazole has yet been reported. A 77-year-old male with 6-year history of administration of lansoprazole complained of watery diarrhea and weight loss. Colonoscopy revealed disappearance of vascular networks and red spots in the sigmoid colon. Biopsy specimen showed erosion and collagen bands thickened, so the patient was diagnosed as CC. After lansoprazole discontinuation, the watery diarrhea disappeared and histological abnormalities improved.

Ex vivo activation of angiogenic property in human peripheral blood-derived monocytes by thrombopoietin

Human peripheral blood mononuclear cells (PB-MNCs) have angiogenic properties, which make them promising cells for use in angiogenic therapy approaches in regenerative medicine. To explore an efficient method for expanding pro-angiogenic cells from PB-MNCs, we developed a novel serum-free culture system composed of X-VIVO15 medium supplemented with vascular endothelial growth factor, basic fibroblast growth factor, and thrombopoietin (TPO). Using this ex vivo culture, we obtained floating spheres composed mainly of CD11b+ monocytes expressing c-Mpl (TPO receptor) and which exhibited acetylated low-density lipoprotein uptake and phagocytosis. Expression of IL-8, CXCR4, and vasohibin-2 mRNA was upregulated in these cells. In the presence of TPO, the number and size of the spheres were increased. In a nude mouse hind-limb ischemia model, the intramuscular injection of spheroid cells treated with TPO rescued blood perfusion more effectively than that without TPO. These results indicate that the ex vivo addition of TPO augments the pro-angiogenic activity of peripheral CD11b+ monocytes, suggesting that this method shows promise for uses in human cell therapy aimed at the induction of vascular regeneration by activating the angiogenic properties of human peripheral blood-derived monocytes.

Capsule endoscopy is a feasible procedure for identifying a Diphyllobothrium nihonkaiense infection and determining the indications for vermifuge treatment.

Diphyllobothrium is a member of Cestoda family, which is the largest parasite of humans. The diagnosis of diphyllobothriasis is based on the detection of eggs in the stool. Because the remainder of the scolex causes a relapse in diphyllobothriasis, the scolex must be completely discharged to cure the parasite infection. However, the scolex or forefront of the Diphyllobothrium is difficult to detect with gastroduodenoscopy and colonoscopy, because most Diphyllobothrium attach to the jejunal wall. In the present case, capsule endoscopy detected proglottids as well as forefront of the parasite at jejunum. Based on the results of capsule endoscopy, the patient underwent additional vermifuge (anthelminthic) treatment to cure the diphyllobothriasis and discharged a worm measuring 3 m in length with a scolex. Capsule endoscopy is a practical option to determine whether additional vermifuge treatment is required through the detection of the proglottids as well as a scolex or forefront of the parasite.