AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treat...AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.展开更多
AIM: To investigate the role that the hedgehog (Hh) signaling pathway, which includes sonic hedgehog (Shh), Patched (Ptc), Smoothened (Smo) and Gli-1, plays in hu- man gastrointestinal stromal tumors (GISTs). METHODS:...AIM: To investigate the role that the hedgehog (Hh) signaling pathway, which includes sonic hedgehog (Shh), Patched (Ptc), Smoothened (Smo) and Gli-1, plays in hu- man gastrointestinal stromal tumors (GISTs). METHODS: Surgically resected specimens from pa- tients with GISTs, leiomyomas and schwannomas were examined by immunohistochemical staining for aberrant expression of hedgehog signaling components, Shh, Ptc, Smo and Gli-1, respectively. RESULTS: In GISTs, 58.1% (18 of 31), 77.4% (24 of 31), 80.6% (25 of 31) and 58.1% (18 of 31) of the specimens stained positive for Shh, Ptc, Smo and Gli-1, respectively. In leiomyomas, 92.3% (12 of 13), 92.3% (12 of 13), 69.2% (9 of 13) and 92.3% (12 of 13) stained positive for Shh, Ptc, Smo and Gli-1, respectively. In schwannomas, 83.3% (5 of 6), 83.3% (5 of 6), 83.3% (5 of 6) and 100% (6 of 6) stained positive for Shh, Ptc, Smo and Gli-1, respectively. Immunohistochemistry revealed that the expressions of Shh and Gli-1 were sig- nificantly higher in leiomyomas than in GISTs (P < 0.05, respectively). Shh expression strongly correlated with the grade of tumor risk category and with tumor size (P < 0.05, respectively). However, the expressions of Ptc and Smo did not correlate with histopathological differentiation. CONCLUSION: These results suggest that the Hh sig- naling pathway may play an important role in myogenic differentiation and the malignant potential of human in-testinal stromal tumors.展开更多
MIA： Human β-defensin （HBD）-1 and HBD-2 are endogenous antimicrobial peptides. Unlike HBD-1, the HBD-2 expression is augmented by Helicobacter pylori （H pylon）. We sought to determine HBD-1 and HBD-2 concentrati...MIA： Human β-defensin （HBD）-1 and HBD-2 are endogenous antimicrobial peptides. Unlike HBD-1, the HBD-2 expression is augmented by Helicobacter pylori （H pylon）. We sought to determine HBD-1 and HBD-2 concentrations in gastric juice during Hpylori infection. METHODS： HBD-1 and HBD-2 concentrations were measured by radioimmunoassay in plasma and gastric juice of 49 Hpylori-infected and 33 uninfected subjects and before and after anti-H pyloritreatment in,13 patients with Hpylori-associated gastritis. Interleukin （IL）-1β and IL-8 concentrations in gastric juice were measured by enzyme-linked immunosorbent assay （ELISA）. Histological grades of gastritis were determined using two biopsy specimens taken from the antrum and corpus. Reverse phase high performance liquid chromatography （RP-HPLC） was used to identify HBD-2. RESULTS： HBD-2 concentrations in gastric juice, but not in plasma, were significantly higher in Hpylori-positive than -negative subjects, albeit the post-treatment levels were unchanged. Immunoreactivity for HBD-2 was exclusively identified in Hpylori-infected mucosa by RPHPLC. HBD-2 concentrations in gastric juice correlated with histological degree of neutrophil and mononuclear cell infiltration in the corpus. IL-1β levels correlated with those of IL-8, but not HBD-2. Plasma and gastric juice HBD-1 concentrations were similar in H pylori-infected and uninfected subjects. CONCLUSION： Our results place the β-defensins, especiallyHBD-2, in the front line of innate immune defence. Moreover, HBD-2 may be involved in the pathogenesis of Hpylori-associated gastritis, possibly through its function as immune and inflammatory mediator.展开更多
AIM: The beta-catenin has been recognized as a critical member of the Wnt signaling pathway and plays an important role in the generation/differentiation of many tissues. Inappropriate activation of this pathway has b...AIM: The beta-catenin has been recognized as a critical member of the Wnt signaling pathway and plays an important role in the generation/differentiation of many tissues. Inappropriate activation of this pathway has been implicated in carcinogenesis. The mechanism underlying the development as well as its prognosis of hepatocellular carcinoma (HCC) has remained unclear. The purpose of this study is to analyze the expression of beta-catenin in HCC in relation to histological grades and viral hepatitis backgrounds. METHODS: Thirty-two sections were selected at random from autopsy and surgical cases of HCC. Immuohistologically, the location and positivity of beta-catenin expression in HCC was examined. RESULTS: Normal hepatocytes did not express beta-catenin. In 78% of HCC beta-catenin was expressed at the membrane of the cells, with or without cytoplasmic and/or nuclear expression. The tumor cells with well-and moderately-differentiated grades expressed frequently at the membrane and cytoplasm compared with poorly-differentiated type. Nuclear expression of beta-catenin was prone to occur in the tumor cells of poorly-differentiated grade. There were 15% of hepatitis C virus (HCV) backgrounds with nuclear expression. In contrast, there was 38% with nuclear expression in hepatitis B virus (HBV) backgrounds. In nonB-nonC hepatitis, no case expressed nuclear beta-catenin. CONCLUSION: The beta-catenin expression in HCC cells was heterogenous among types of hepatitis viral infection. Wnt signaling pathway might be deeply involved in less-differentiated HCC and HBV background. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.展开更多
AIM: To investigate the role of angiopoietin (Ang) -1, -2 and -4 and its receptors, Tie-1 and -2, in the growth and differentiation of gastrointestinal stromal tumors (GISTs).METHODS: Thirty GISTs, seventeen leiomyoma...AIM: To investigate the role of angiopoietin (Ang) -1, -2 and -4 and its receptors, Tie-1 and -2, in the growth and differentiation of gastrointestinal stromal tumors (GISTs).METHODS: Thirty GISTs, seventeen leiomyomas and six schwannomas were examined by immunohistochemistry in this study.RESULTS: Ang-1, -2 and -4 proteins were expressed in the cytoplasm of tumor cells, and Tie-1 and -2 were expressed both in the cytoplasm and on the membrane of all tumors. Immunohistochemical staining revealed that 66.7% of GISTs (20 of 30), 76.5% of leiomyomas (13 of 17) and 83.3% of schwannomas (5 of 6) were positive for Ang-1. 83.3% of GISTs (25 of 30), 82.4% of leiomyomas (14 of 17) and 100% of schwannomas (6 of 6) were positive for Ang-2. 36.7% of GISTs (11 of 30), 58.8% of leiomyomas (10 of 17) and 83.3% of schwannomas (5 of 6) were positive for Ang-4. 60.0% of GISTs (18 of 30), 82.4% of leiomyomas and 100% of schwannomas (6 of 6) were positive for Tie-1. 10.0% of GISTs (3 of 30), 94.1% of leiomyomas (16 of 17) and 33.3% of schwannomas (2 of 6) were positive for Tie-2. Tie-2 expression was statistically different between GISTs and leiomyomas (P < 0.001). However, there was no correlation between expression of angiopoietin pathway components and clinical risk categories.CONCLUSION: Our results suggest that the angiopoietin pathway plays an important role in the differentiation of GISTs, leiomyomas and schwannomas.展开更多
AIM： To examine an association between the cytotoxic Tlymphocyte antigen 4 （CTLA4） gene that plays a role in downregulation of T-cell activation and inflammatory bowel disease consisting of ulcerative colitis （UC...AIM： To examine an association between the cytotoxic Tlymphocyte antigen 4 （CTLA4） gene that plays a role in downregulation of T-cell activation and inflammatory bowel disease consisting of ulcerative colitis （UC） and Crohn＇s disease （CD） in the Japanese.METHODS： We studied 108 patients with UC, 79 patients with CD, and 200 sex-matched healthy controls, with respect to three single nucleotide polymorphisms （SNPs） in CTLA4, such as C-318T in the promoter region, A＋49 Gin exon 1 and G＋6230A in the 3＇ untranslated region （3＇-UTR） by a PCR-restriction fragment length polymorphism method, and to an （AT）, repeat polymorphism in 3＇-UTR by fragment analysis with fluorescence-labeling on denaturing sequence gels. Frequency of alleles and genotypes and their distribution were compared statistically between patients and controls and among subgroups of patients, using X^2 and Fisher exact tests.RESULTS： The frequency of ＂A/A＂ genotype at the G＋6230A SNP site was statistically lower in UC patients than in controls （3.7% vs 11.0%, P = 0.047, odds ratio （OR） = 0.311）. Moreover, the frequency of ＂G/G＂ genotype at the A＋49G SNP site was significantly higher in CD patients with fistula （48.6%） than those without it （26.2%）（P = 0.0388, OR=2.67）.CONCLUSION： The results suggest that CTLA4 located at 2q33 is a determinant of UC and responsible for fistula formation in CD in the Japanese.展开更多
A 62-year-old man presented with upper abdominal discomfort underwent upper gastrointestinal endoscopy. Gastroscopy and endoscopic ultrasonography revealed a submucosal tumor (SMT) with homogenous echogenicity origina...A 62-year-old man presented with upper abdominal discomfort underwent upper gastrointestinal endoscopy. Gastroscopy and endoscopic ultrasonography revealed a submucosal tumor (SMT) with homogenous echogenicity originated from extragastric organs. An abdominal contrast-enhanced computed tomography (CT) showed that the well-marginated ovoid mass, approximately 6 cm in diameter, enhanced homogenously to a similar degree as splenic parenchyma. 99mTechnetium sulfur colloid scintigraphy revealed the splenic nature of the mass. A diagnosis of accessory spleen mimicking gastric SMT was made. Subsequent follow-up was uneventful without performing splenectomy.展开更多
AIM： To investigate the frequency and distribution of /V-acetyltransferase 2 （NAT2） and uridine 5＇-diphosphate （UDP）-glucuronosyltransferase 1A7 （UGT1A7） genes in patients with ulcerative colitis （UC） and Cr...AIM： To investigate the frequency and distribution of /V-acetyltransferase 2 （NAT2） and uridine 5＇-diphosphate （UDP）-glucuronosyltransferase 1A7 （UGT1A7） genes in patients with ulcerative colitis （UC） and Crohn＇s disease （CD）. METHODS： Frequencies and distributions of IVAT2 and UGT1A7SNPs as well as their haplotypes were investigated in 95 patients with UC, 60 patients with CD, and 200 gender-matched, unrelated, healthy, control volunteers by PCR-restriction fragment length polymorphism （RFLP）, PCR-denaturing high-performance liquid chromatography （DHPLC）, and direct DNA sequencing. RESULTS： Multiple logistic regression analysis revealed that the frequency of haplotype, NAT2＊7B, significantly increased in CD patients, compared to that in controls （P= 0.0130, OR = 2.802, 95%CI = 1.243-6.316）. However, there was no association between NAT2 haplotypes and UC, or between any UGT1A7haplotypes and inflammatory bowel disease （IBD）. CONCLUSION： It is likely that the NAT2 gene is one ofthe determinants for CD in Japanese. Alternatively, a new CD determinant may exist in the 8p22 region, where NAT2 is located.展开更多
AIM： To produce an antibody against rat eosinophil cationic protein （ECP） and to examine the effects of the antibody in rats with dextran sulfate sodium （DSS）-induced colitis. METHODS： An antibody was raised aga...AIM： To produce an antibody against rat eosinophil cationic protein （ECP） and to examine the effects of the antibody in rats with dextran sulfate sodium （DSS）-induced colitis. METHODS： An antibody was raised against rat ECP. Rats were treated with 3% DSS in drinking water for 7 d and received the antibody or normal serum. The colons were examined histologically and correlated with clinical symptoms. Immunohistochemistry and Western blot analysis were estimated as a grade of inflammation. RESULTS： The ECP antibody stained the activated eosinophils around the injured crypts in the colonic mucosa. Antibody treatment reduced the severity of colonic ulceration and acute clinical symptoms （diarrhea and/or bloodstained stool）. Body weight gain was significantly greater and the colon length was significantly longer in anti-ECPtreated rats than in normal serum-treated rats. Expression of ECP in activated eosinophils was associated with the presence of erosions and inflammation. The number of Ki-67-positive cells in the regenerated surface epithelium increased in anti-ECP-treated rats compared with normal serum-treated rats. Western blot analysis revealed reduced expression of macrophage migration inhibitory factor （MIF） in anti-ECP-treated rats. CONCLUSION： Our results indicate that treatment with ECP antibody, improved DSS-induced colitis in rats, possibly by increasing the regenerative activity of the colonic epithelium and downregulation of the immune response, and suggest that anti-ECP may promote intestinal wound healing in patients with ulcerative colitis （UC）.展开更多
基金by Grant-in-Aid for Scientif ic Research (Category B, No. 18390168) for K Tsukamoto by the Ministry of Education, Culture, Sports, Science and Technology of Japan
文摘AIM: To investigate an association between N -acetyltransferase 2 (NAT2 )-haplotypes/diplotypes and adverse effects in Japanese pulmonary tuberculosis patients. METHODS: We studied 100 patients with pulmonary TB treated with anti-TB drugs including INH. The frequencies and distributions of single nucleotide polymorphisms, haplotypes, and diplotypes of NAT2 were determined by the PCR-restriction fragment length polymorphism method, and the results were compared between TB patients with and without adverse effect, using multivariate logistic regression analysis.RESULTS: Statistical analysis revealed that the frequency of a variant haplotype, NAT2*6A , was signifi cantly increased in TB patients with hepatotoxicity, compared with those without hepatotoxicity [P = 0.001, odds ratio (OR) = 3.535]. By contrast, the frequency of a wild-type (major) haplotype, "NAT2*4", was signif icantly lower in TB patients with hepatotoxicity than those without hepatotoxicity (P < 0.001, OR = 0.265). There was no association between NAT2-haplotypes and skin rash or eosinophilia. CONCLUSION: The present study shows that NAT2 is one of the determinants of anti-TB drug-induced hepatotoxicity. Moreover, the haplotypes, NAT2*4 and NAT2*6A, are useful new biomarkers for predicting anti- TB drug-induced hepatotoxicity.
文摘AIM: To investigate the role that the hedgehog (Hh) signaling pathway, which includes sonic hedgehog (Shh), Patched (Ptc), Smoothened (Smo) and Gli-1, plays in hu- man gastrointestinal stromal tumors (GISTs). METHODS: Surgically resected specimens from pa- tients with GISTs, leiomyomas and schwannomas were examined by immunohistochemical staining for aberrant expression of hedgehog signaling components, Shh, Ptc, Smo and Gli-1, respectively. RESULTS: In GISTs, 58.1% (18 of 31), 77.4% (24 of 31), 80.6% (25 of 31) and 58.1% (18 of 31) of the specimens stained positive for Shh, Ptc, Smo and Gli-1, respectively. In leiomyomas, 92.3% (12 of 13), 92.3% (12 of 13), 69.2% (9 of 13) and 92.3% (12 of 13) stained positive for Shh, Ptc, Smo and Gli-1, respectively. In schwannomas, 83.3% (5 of 6), 83.3% (5 of 6), 83.3% (5 of 6) and 100% (6 of 6) stained positive for Shh, Ptc, Smo and Gli-1, respectively. Immunohistochemistry revealed that the expressions of Shh and Gli-1 were sig- nificantly higher in leiomyomas than in GISTs (P < 0.05, respectively). Shh expression strongly correlated with the grade of tumor risk category and with tumor size (P < 0.05, respectively). However, the expressions of Ptc and Smo did not correlate with histopathological differentiation. CONCLUSION: These results suggest that the Hh sig- naling pathway may play an important role in myogenic differentiation and the malignant potential of human in-testinal stromal tumors.
文摘MIA： Human β-defensin （HBD）-1 and HBD-2 are endogenous antimicrobial peptides. Unlike HBD-1, the HBD-2 expression is augmented by Helicobacter pylori （H pylon）. We sought to determine HBD-1 and HBD-2 concentrations in gastric juice during Hpylori infection. METHODS： HBD-1 and HBD-2 concentrations were measured by radioimmunoassay in plasma and gastric juice of 49 Hpylori-infected and 33 uninfected subjects and before and after anti-H pyloritreatment in,13 patients with Hpylori-associated gastritis. Interleukin （IL）-1β and IL-8 concentrations in gastric juice were measured by enzyme-linked immunosorbent assay （ELISA）. Histological grades of gastritis were determined using two biopsy specimens taken from the antrum and corpus. Reverse phase high performance liquid chromatography （RP-HPLC） was used to identify HBD-2. RESULTS： HBD-2 concentrations in gastric juice, but not in plasma, were significantly higher in Hpylori-positive than -negative subjects, albeit the post-treatment levels were unchanged. Immunoreactivity for HBD-2 was exclusively identified in Hpylori-infected mucosa by RPHPLC. HBD-2 concentrations in gastric juice correlated with histological degree of neutrophil and mononuclear cell infiltration in the corpus. IL-1β levels correlated with those of IL-8, but not HBD-2. Plasma and gastric juice HBD-1 concentrations were similar in H pylori-infected and uninfected subjects. CONCLUSION： Our results place the β-defensins, especiallyHBD-2, in the front line of innate immune defence. Moreover, HBD-2 may be involved in the pathogenesis of Hpylori-associated gastritis, possibly through its function as immune and inflammatory mediator.
文摘AIM: The beta-catenin has been recognized as a critical member of the Wnt signaling pathway and plays an important role in the generation/differentiation of many tissues. Inappropriate activation of this pathway has been implicated in carcinogenesis. The mechanism underlying the development as well as its prognosis of hepatocellular carcinoma (HCC) has remained unclear. The purpose of this study is to analyze the expression of beta-catenin in HCC in relation to histological grades and viral hepatitis backgrounds. METHODS: Thirty-two sections were selected at random from autopsy and surgical cases of HCC. Immuohistologically, the location and positivity of beta-catenin expression in HCC was examined. RESULTS: Normal hepatocytes did not express beta-catenin. In 78% of HCC beta-catenin was expressed at the membrane of the cells, with or without cytoplasmic and/or nuclear expression. The tumor cells with well-and moderately-differentiated grades expressed frequently at the membrane and cytoplasm compared with poorly-differentiated type. Nuclear expression of beta-catenin was prone to occur in the tumor cells of poorly-differentiated grade. There were 15% of hepatitis C virus (HCV) backgrounds with nuclear expression. In contrast, there was 38% with nuclear expression in hepatitis B virus (HBV) backgrounds. In nonB-nonC hepatitis, no case expressed nuclear beta-catenin. CONCLUSION: The beta-catenin expression in HCC cells was heterogenous among types of hepatitis viral infection. Wnt signaling pathway might be deeply involved in less-differentiated HCC and HBV background. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved.
文摘AIM: To investigate the role of angiopoietin (Ang) -1, -2 and -4 and its receptors, Tie-1 and -2, in the growth and differentiation of gastrointestinal stromal tumors (GISTs).METHODS: Thirty GISTs, seventeen leiomyomas and six schwannomas were examined by immunohistochemistry in this study.RESULTS: Ang-1, -2 and -4 proteins were expressed in the cytoplasm of tumor cells, and Tie-1 and -2 were expressed both in the cytoplasm and on the membrane of all tumors. Immunohistochemical staining revealed that 66.7% of GISTs (20 of 30), 76.5% of leiomyomas (13 of 17) and 83.3% of schwannomas (5 of 6) were positive for Ang-1. 83.3% of GISTs (25 of 30), 82.4% of leiomyomas (14 of 17) and 100% of schwannomas (6 of 6) were positive for Ang-2. 36.7% of GISTs (11 of 30), 58.8% of leiomyomas (10 of 17) and 83.3% of schwannomas (5 of 6) were positive for Ang-4. 60.0% of GISTs (18 of 30), 82.4% of leiomyomas and 100% of schwannomas (6 of 6) were positive for Tie-1. 10.0% of GISTs (3 of 30), 94.1% of leiomyomas (16 of 17) and 33.3% of schwannomas (2 of 6) were positive for Tie-2. Tie-2 expression was statistically different between GISTs and leiomyomas (P < 0.001). However, there was no correlation between expression of angiopoietin pathway components and clinical risk categories.CONCLUSION: Our results suggest that the angiopoietin pathway plays an important role in the differentiation of GISTs, leiomyomas and schwannomas.
文摘AIM： To examine an association between the cytotoxic Tlymphocyte antigen 4 （CTLA4） gene that plays a role in downregulation of T-cell activation and inflammatory bowel disease consisting of ulcerative colitis （UC） and Crohn＇s disease （CD） in the Japanese.METHODS： We studied 108 patients with UC, 79 patients with CD, and 200 sex-matched healthy controls, with respect to three single nucleotide polymorphisms （SNPs） in CTLA4, such as C-318T in the promoter region, A＋49 Gin exon 1 and G＋6230A in the 3＇ untranslated region （3＇-UTR） by a PCR-restriction fragment length polymorphism method, and to an （AT）, repeat polymorphism in 3＇-UTR by fragment analysis with fluorescence-labeling on denaturing sequence gels. Frequency of alleles and genotypes and their distribution were compared statistically between patients and controls and among subgroups of patients, using X^2 and Fisher exact tests.RESULTS： The frequency of ＂A/A＂ genotype at the G＋6230A SNP site was statistically lower in UC patients than in controls （3.7% vs 11.0%, P = 0.047, odds ratio （OR） = 0.311）. Moreover, the frequency of ＂G/G＂ genotype at the A＋49G SNP site was significantly higher in CD patients with fistula （48.6%） than those without it （26.2%）（P = 0.0388, OR=2.67）.CONCLUSION： The results suggest that CTLA4 located at 2q33 is a determinant of UC and responsible for fistula formation in CD in the Japanese.
文摘A 62-year-old man presented with upper abdominal discomfort underwent upper gastrointestinal endoscopy. Gastroscopy and endoscopic ultrasonography revealed a submucosal tumor (SMT) with homogenous echogenicity originated from extragastric organs. An abdominal contrast-enhanced computed tomography (CT) showed that the well-marginated ovoid mass, approximately 6 cm in diameter, enhanced homogenously to a similar degree as splenic parenchyma. 99mTechnetium sulfur colloid scintigraphy revealed the splenic nature of the mass. A diagnosis of accessory spleen mimicking gastric SMT was made. Subsequent follow-up was uneventful without performing splenectomy.
文摘AIM： To investigate the frequency and distribution of /V-acetyltransferase 2 （NAT2） and uridine 5＇-diphosphate （UDP）-glucuronosyltransferase 1A7 （UGT1A7） genes in patients with ulcerative colitis （UC） and Crohn＇s disease （CD）. METHODS： Frequencies and distributions of IVAT2 and UGT1A7SNPs as well as their haplotypes were investigated in 95 patients with UC, 60 patients with CD, and 200 gender-matched, unrelated, healthy, control volunteers by PCR-restriction fragment length polymorphism （RFLP）, PCR-denaturing high-performance liquid chromatography （DHPLC）, and direct DNA sequencing. RESULTS： Multiple logistic regression analysis revealed that the frequency of haplotype, NAT2＊7B, significantly increased in CD patients, compared to that in controls （P= 0.0130, OR = 2.802, 95%CI = 1.243-6.316）. However, there was no association between NAT2 haplotypes and UC, or between any UGT1A7haplotypes and inflammatory bowel disease （IBD）. CONCLUSION： It is likely that the NAT2 gene is one ofthe determinants for CD in Japanese. Alternatively, a new CD determinant may exist in the 8p22 region, where NAT2 is located.
基金Supported by a grant-in-aid from the Ministry of Science, Education, Sports and Culture of Japan, No. 14570193
文摘AIM： To produce an antibody against rat eosinophil cationic protein （ECP） and to examine the effects of the antibody in rats with dextran sulfate sodium （DSS）-induced colitis. METHODS： An antibody was raised against rat ECP. Rats were treated with 3% DSS in drinking water for 7 d and received the antibody or normal serum. The colons were examined histologically and correlated with clinical symptoms. Immunohistochemistry and Western blot analysis were estimated as a grade of inflammation. RESULTS： The ECP antibody stained the activated eosinophils around the injured crypts in the colonic mucosa. Antibody treatment reduced the severity of colonic ulceration and acute clinical symptoms （diarrhea and/or bloodstained stool）. Body weight gain was significantly greater and the colon length was significantly longer in anti-ECPtreated rats than in normal serum-treated rats. Expression of ECP in activated eosinophils was associated with the presence of erosions and inflammation. The number of Ki-67-positive cells in the regenerated surface epithelium increased in anti-ECP-treated rats compared with normal serum-treated rats. Western blot analysis revealed reduced expression of macrophage migration inhibitory factor （MIF） in anti-ECP-treated rats. CONCLUSION： Our results indicate that treatment with ECP antibody, improved DSS-induced colitis in rats, possibly by increasing the regenerative activity of the colonic epithelium and downregulation of the immune response, and suggest that anti-ECP may promote intestinal wound healing in patients with ulcerative colitis （UC）.
