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ABSTRACT: Although commonly practiced in Japan, the effectiveness of regular screening with upper gastrointestinal (UGI) endoscopy against gastric cancer has not been well evidenced. The aim of the study was to investigate if gastric cancer-related mortality can be reduced by regular endoscopy.
The medical records of 833 patients with gastric ulcer (GU) and 2547 without ulcer (NU) were analyzed; these patients received long-term, repeated endoscopic examinations between 1969 and 2004. Gastric cancer incidence, death by gastric cancer, and overall survival were compared with those in a Japanese general population by calculating the standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs).
The interval between UGI endoscopic examinations was 1.4 +/- 1.4 years in the GU group and 1.8 +/- 1.5 years in the NU group. During follow-up, 32 patients with GU and 61 in the NU group developed gastric cancer, showing annual incidence rates of 0.40% (95% CI: 0.24-0.56%) and 0.38% (0.28-0.48%), and SIRs of 2.21 (1.44-2.98) and 1.72 (1.29-2.15), respectively. The 5-year survival rate exceeded 80% among patients who developed gastric cancer. SMRs for gastric cancer and overall deaths were 0.50 (0.01-0.99) and 1.05 (0.87-1.23) in GU patients, and 0.45 (0.15-0.74) and 0.78 (0.69-0.88) in NU patients. There were no significant differences between the two groups in gastric cancer incidence, mortality from gastric cancer, and overall survival.
Mortality from gastric cancer could be reduced by regular UGI endoscopy in a population with a high incidence of gastric cancer.
Scandinavian journal of gastroenterology 02/2008; 43(5):574-80. · 2.08 Impact Factor
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ABSTRACT: Long-term lamivudine treatment induces the emergence of lamivudine-resistant hepatitis B virus (HBV). The objective of this study was to develop a fluorescent biprobe hybridization (FBH) assay for the detection and quantification of HBV mutants in the clinical course of lamivudine-treated patients and to evaluate its clinical usefulness.
We developed an FBH assay to detect mutations in the HBV DNA polymerase gene. The assay's detection sensitivity was determined using a dilution series of wild-type/mutant plasmid DNA. Blood samples obtained from 27 lamivudine-treated patients were analyzed.
Mutant DNA levels as low as 10% of total HBV DNA were detected (sensitivity = 100%, specificity = 80%). HBV mutants were detected in five of the 27 patients during an average follow-up of 20 months after lamivudine administration. In one of the five patients, the YIDD mutant was detected at the initiation of lamivudine treatment, while the remaining four patients were identified as having YIDD mutants within 3 months after beginning lamivudine administration. Of the five patients with an HBV mutant, four developed breakthrough hepatitis more than 10 months after the detection of HBV mutants, following the reappearance or a re-increase of HBV DNA, characterized by a predominance of the mutant. The YIDD mutant was detected in one patient, even when the titer of the serum HBV DNA was below the detection limit of commercially available quantitative polymerase chain reaction.
The FBH assay is an efficient method for detecting and quantifying HBV mutants, as early as 3 months after lamivudine administration.
Journal of Gastroenterology 08/2006; 41(7):693-701. · 4.16 Impact Factor
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Hirotsugu Watabe,
Yutaka Yamaji,
Makoto Okamoto,
Shintaro Kondo,
Miki Ohta,
Tsuneo Ikenoue,
Jun Kato,
Goichi Togo, Masayuki Matsumura,
Haruhiko Yoshida,
Takao Kawabe,
Masao Omata
[show abstract]
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ABSTRACT: Hemorrhage is among the most serious complications of colorectal polypectomy and may occur after a longer postprocedure interval.
We aimed to elucidate the risk factors for delayed postpolypectomy hemorrhage, including both polyp characteristics and the general condition of the patients.
Retrospective cohort study.
A total of 6617 cases of colorectal polypectomy was performed in 3138 consecutive patients in Japan.
The risk factors for delayed postpolypectomy hemorrhage were assessed among polyp characteristics (form, size, histologic features) and the method of resection by unconditional logistic regression. Patient conditions (smoking, alcohol, hypertension, diabetes mellitus, hyperlipidemia) were compared between case-control pairs matched on polyp-related characteristics by conditional logistic regression.
Hemorrhage occurred in 38 lesions (0.57%) of 37 patients (1.2%): 22 required endoscopic hemostasis and 1 required blood transfusion. Although polyp size was associated with the occurrence of delayed hemorrhage (10.0 +/- 6.9 mm in hemorrhage cases vs 5.6 +/- 3.8 mm in others, P < .0001), other polyp-related factors were not significant. Hypertension was a complication in 25 of 37 (68%) cases and in 21 of 74 (28%) matched controls, showing an adjusted odds ratio of 5.6 (95% CI 1.8-17.2, P = .001). Other patient characteristics were not significant. The interval between polypectomy and hemorrhage was significantly longer in patients with hypertension (median 6 days, range 2-14 days) than in those without hypertension (2.5 days, 1-9 days; P = .019).
This study does not provide information regarding prevention of hemorrhage.
Hypertension is a significant risk factor for delayed colorectal postpolypectomy hemorrhage. The interval between polypectomy and hemorrhage can be as long as 14 days in the presence of hypertension.
Gastrointestinal Endoscopy 08/2006; 64(1):73-8. · 4.88 Impact Factor
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Makoto Okamoto,
Takao Kawabe,
Ken Ohata,
Gouichi Togo,
Tetsuya Hada,
Tetsurou Katamoto,
Masataka Tanno, Masayuki Matsumura,
Yutaka Yamaji,
Hirotsugu Watabe,
Tsuneo Ikenoue,
Haruhiko Yoshida,
Masao Omata
[show abstract]
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ABSTRACT: Amebiasis is a common parasitic infectious disease in developing countries. In developed countries, it is occasionally encountered in travelers to the tropics and in homosexual males. During the past eight years, we detected four cases of amebic colitis among 5,193 subjects who underwent colonoscopy because of positive fecal occult blood test results in a mass screening. All four cases did not have any abdominal symptoms. Ulcerative lesions were observed only in the cecum and ascending colon; another portion of the colon and rectum appeared normal. We may encounter amebic colitis during colonoscopic examination even in subjects who are asymptomatic.
The American journal of tropical medicine and hygiene 12/2005; 73(5):934-5. · 2.59 Impact Factor
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Tsuneo Ikenoue,
Fumihiko Kanai,
Yohko Hikiba,
Toshiyuki Obata,
Yasuo Tanaka,
Jun Imamura,
Miki Ohta,
Amarsanaa Jazag,
Bayasi Guleng,
Keisuke Tateishi,
Yoshinari Asaoka, Masayuki Matsumura,
Takao Kawabe,
Masao Omata
[show abstract]
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ABSTRACT: Mutations in the PIK3CA gene, which encodes the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), have been reported in human cancers, including colorectal cancer. Most of the mutations cluster at hotspots within the helical and kinase domains. Whereas H1047R, one of the hotspot mutants, is reported to have elevated lipid kinase activity, the functional consequences of other mutations have not been examined. In this study, we examined the effects of colon cancer-associated PIK3CA mutations on the lipid kinase activity in vitro, activation of the downstream targets Akt and p70S6K in vivo and NIH 3T3-transforming ability. Of eight mutations examined, all showed increased lipid kinase activity compared with wild-type p110alpha. All the mutants strongly activated Akt and p70S6K compared with wild-type p110alpha as determined by immunoblotting using phospho-specific antibodies. These mutants also induced morphologic changes, loss of contact inhibition, and anchorage-independent growth of NIH 3T3 cells. The hotspot mutations examined in this study, E542K, E545K, and H1047R, all had high enzymatic and transforming activities. These results show that almost all the colon cancer-associated PIK3CA mutations are functionally active so that they are likely to be involved in carcinogenesis.
Cancer Research 07/2005; 65(11):4562-7. · 7.86 Impact Factor
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Tsuneo Ikenoue,
Fumihiko Kanai,
Yohko Hikiba,
Yasuo Tanaka,
Jun Imamura,
Miki Ohta,
Amarsanaa Jazag,
Bayasi Guleng,
Yoshinari Asaoka,
Keisuke Tateishi,
Takayuki Kawakami, Masayuki Matsumura,
Takao Kawabe,
Masao Omata
[show abstract]
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ABSTRACT: Mutations in the B-raf gene have been reported in a number of human cancers, including melanoma and lung cancer. More than 80% of the reported B-raf mutations were V599E; however, non-V599E mutations have been frequently found in non-small cell lung cancers as compared with melanoma. Some non-V599E mutations have been found surrounding Thr439, which is thought likely to be one of the three Akt phosphorylation sites in the B-raf protein. However, as a previous report indicated that Thr439 was not phosphorylated by Akt, the functional consequences of these mutations have been unclear. Here, we examined the effects of cancer-related B-raf mutations surrounding Thr439 on the activation of the mitogen-activated protein/ extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (Erk) pathway and the transformation of NIH 3T3 fibroblasts. Among the three reported mutations (K438Q, K438T, and T439P) found in non-small cell lung carcinoma and melanoma, none elevated the activity of the MEK/Erk cascade as determined by in vitro kinase assays, immunoblots using antibody specific for phosphorylated Erk, or Elk1-dependent reporter assays. The inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling by LY294002 increased the Erk activation induced by the mutant B-raf proteins, as well as by wild-type B-raf. Furthermore, the B-raf mutants did not have increased NIH 3T3-transforming activities, as determined by colony-formation assays. These results suggest that the B-raf mutations surrounding Thr439 found in human cancers are unlikely to contribute to increased oncogenic properties of B-raf.
Molecular Carcinogenesis 06/2005; 43(1):59-63. · 3.16 Impact Factor
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Takeshi Tsujino,
Yutaka Komatsu,
Hiroyuki Isayama,
Kenji Hirano,
Naoki Sasahira,
Natsuyo Yamamoto,
Nobuo Toda,
Yukiko Ito,
Yousuke Nakai,
Minoru Tada, Masayuki Matsumura,
Haruhiko Yoshida,
Takao Kawabe,
Yasushi Shiratori,
Masao Omata
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ABSTRACT: Pancreatitis remains the major complication of endoscopic retrograde cholangiopancreatography (ERCP), and hyperenzymemia after ERCP is common. Because ulinastatin, a protease inhibitor, has proved effective in the treatment of acute pancreatitis, the aim of this study was to assess the efficacy of ulinastatin for the prevention of post-ERCP pancreatitis and hyperenzymemia.
In a multicenter, randomized, double-blind, placebo-controlled trial, patients undergoing a first ERCP were randomized to receive ulinastatin (150,000 U) or placebo by intravenous infusion for 10 minutes starting immediately before ERCP. All patients were hospitalized at least 24 hours after ERCP for evaluation of clinical symptoms. Serum pancreatic enzyme levels were measured before and at 4 and 18 hours after ERCP. The primary end point was the incidence of post-ERCP pancreatitis and the secondary objective was the occurrence of hyperenzymemia.
A total of 406 patients were enrolled (204 in the ulinastatin group and 202 in the placebo group). There were no differences between the 2 groups regarding baseline characteristics, details of fluoroscopic findings, or endoscopic procedure. The incidence of hyperenzymemia was significantly lower in the ulinastatin group than in the placebo group (amylase, P = .011; lipase, P = .008). Six patients in the ulinastatin group and 15 patients in the placebo group developed pancreatitis (2.9% vs. 7.4%, P = .041). There was no case of severe pancreatitis in either group. Patients who received ulinastatin did not present any side effects related to the medication.
Prophylactic short-term administration of ulinastatin decreases the incidence of pancreatitis and hyperenzymemia after ERCP.
Clinical Gastroenterology and Hepatology 04/2005; 3(4):376-83. · 5.63 Impact Factor
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Masayuki Matsumura
Nippon rinsho. Japanese journal of clinical medicine 09/2004; 62 Suppl 8:175-9.
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Tsuneo Ikenoue,
Yohko Hikiba,
Fumihiko Kanai,
Jun Aragaki,
Yasuo Tanaka,
Jun Imamura,
Takaaki Imamura,
Miki Ohta,
Hideaki Ijichi,
Keisuke Tateishi,
Takayuki Kawakami, Masayuki Matsumura,
Takao Kawabe,
Masao Omata
[show abstract]
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ABSTRACT: Recently, mutations in the B-Raf gene have been identified in a variety of human cancers, such as melanoma and colorectal carcinoma, and more than 80% of the B-Raf mutations have been V599E. Although other mutations have been reported, their functional consequences are poorly understood. In our earlier study, we demonstrated that colon tumor-associated B-Raf mutations within the kinase activation segment are not necessarily associated with an increase in mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase (MEK/Erk) or nuclear factor kappaB (NFkappaB) signaling activity or in NIH3T3-transforming ability. In this study, we examined the effect of colon tumor-associated mutations within the B-Raf glycine-rich loop (G loop) on MEK/Erk and NFkappaB signaling and on the transformation of NIH3T3 fibroblasts or IEC-6 intestinal epithelial cells. Of the six G loop mutations examined, only the B-Raf G468A significantly increased MEK/Erk and NFkappaB signaling and NIH3T3 transformation. Only this mutation induced transformed phenotypes of IEC-6 cells. In contrast, the B-Raf G468E mutation significantly decreased MEK/Erk signaling and NIH3T3 transformation and had no effect on NFkappaB signaling. The B-Raf F467C mutation moderately elevated MEK/Erk signaling and NIH3T3 transformation. The other three B-Raf mutations, R461I, I462S, and G463E, did not increase MEK/Erk or NFkappaB signaling or NIH3T3 transformation. Except for F467C, none of the tumors with B-Raf mutations examined in this study had K-Ras mutations. These results suggest that some of the B-Raf G loop mutations reported in colorectal tumors do not increase kinase or transforming activities but might contribute to carcinogenesis via other mechanisms or be irrelevant to carcinogenesis.
Cancer Research 06/2004; 64(10):3428-35. · 7.86 Impact Factor
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Tsuneo Ikenoue,
Yohko Hikiba,
Fumihiko Kanai,
Hideaki Ijichi,
Goichi Togo,
Miki Ohta,
Hirotsugu Watabe,
Yutaka Yamaji,
Makoto Okamoto,
Jun Aragaki, Masayuki Matsumura,
Takao Kawabe,
Masao Omata
[show abstract]
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ABSTRACT: The BRAF gene is mutated in 66% of melanomas and less frequently in various human cancers. More than 80% of these mutations are T to A transversions at nucleotide 1796 (T1796A), leading to a substitution of glutamic acid for valine at amino acid 599 (V599E). We established a new method for rapidly detecting V599E mutations using real-time polymerase chain reaction and melting curve analysis. Furthermore, we examined mutations in gastrointestinal cancer cell lines using this method. We found a mutation in 1 of 12 (8%) colorectal cancer cell lines, but no mutation was detected in 9 gastric cancer cell lines. These results suggest that the BRAF mutation is unlikely to be involved in gastric carcinogenesis.
Cancer Genetics and Cytogenetics 03/2004; 149(1):68-71. · 1.39 Impact Factor
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Tsuneo Ikenoue,
Yohko Hikiba,
Fumihiko Kanai,
Yasuo Tanaka,
Jun Imamura,
Takaaki Imamura,
Miki Ohta,
Hideaki Ijichi,
Keisuke Tateishi,
Takayuki Kawakami,
Jun Aragaki, Masayuki Matsumura,
Takao Kawabe,
Masao Omata
[show abstract]
[hide abstract]
ABSTRACT: Mutations in the B-Raf gene have been reported in a number of human cancers, including colorectal carcinoma. More than 80% of the B-Raf mutations were V599E. Although other mutations have been reported, their functional consequences were unclear. Here, we examined the effect of colon tumor-associated B-Raf mutations within the kinase activation segment, including V599E, on extracellular signal-regulated kinase (Erk) and nuclear factor kappaB (NFkappaB) signaling, and on the transformation of NIH3T3 fibroblasts. Among the six mutations examined, only the B-Raf V599E and K600E mutations greatly increased Erk and NFkappaB signaling, and the transformation of NIH3T3 cells. The B-Raf F594L mutation moderately elevated Erk signaling and NIH3T3 transformation, but did not significantly increase NFkappaB signaling. Although the basal kinase activity of the B-Raf T598I mutant was comparable with that of wild-type, its oncogenic Ras-induced kinase activity was decreased to 60% of wild-type activity. The B-Raf D593V and G595R mutants showed severely reduced kinase activity and affected neither NFkappaB signaling nor NIH3T3 transforming activity. These results suggest that the B-Raf activation segment mutations other than V599E reported in colorectal tumors do not necessarily contribute to carcinogenesis by increasing kinase and transforming activities.
Cancer Research 01/2004; 63(23):8132-7. · 7.86 Impact Factor
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ABSTRACT: Hepatitis delta virus (HDV) is a naturally occurring satellite of hepatitis B virus (HBV). There are few studies of the effects of the combination of HBV and HDV proteins (HDV antigens [HDAgs]) on intracellular signaling pathways. To understand the influence of HBV and HDV coinfection on hepatocytes, we investigated the effect of HBV proteins and HDAgs on the serum response element (SRE)-dependent pathway. Reporter assays revealed that only HBV X protein (HBx), alone or with the large isoform of HDAg (LHDAg), synergistically activated the SRE-dependent pathway. The effect of HBx and LHDAg on Elk1 or serum response factor (SRF) was examined, because both proteins bind to the SRE. HBx activated the transcriptional ability of Elk1, whereas LHDAg activated the transcriptional ability of SRF. Thus, HBx and LHDAg synergistically activated the SRE-dependent pathway. These results may help us understand clinical phenomena in patients coinfected with HBV and HDV.
The Journal of Infectious Diseases 04/2003; 187(5):820-8. · 6.41 Impact Factor
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Tsuneo Ikenoue,
Hideaki Ijichi,
Naoya Kato,
Fumihiko Kanai,
Tsutomu Masaki,
William Rengifo,
Makoto Okamoto, Masayuki Matsumura,
Takao Kawabe,
Yasushi Shiratori,
Masao Omata
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ABSTRACT: We investigated the frequency and mechanism of beta-catenin/T cell factor (Tcf) signaling activation in a panel of 36 human gastrointestinal and liver cancer cell lines. Reporter assay and electrophoretic mobility shift assay revealed that the beta-catenin/Tcf signaling was upregulated in 12 of 12 (100%) colorectal, 5 of 8 (68%) gastric, 2 of 7 (29%) hepatic, and none of 9 pancreatic cancer cell lines. The activation of the pathway was mainly due to the mutation of adenomatous polyposis coli (APC) or beta-catenin, and Tcf-4 was highly expressed in these cell lines with upregulated signaling. Nuclear beta-catenin was observed not only in the signaling-activated cell lines, but also in 14 of 25 (56%) primary gastric cancers, 15 of 20 (75%) colon cancers, 5 of 19 (26%) hepatocellular carcinomas, and none of 13 pancreatic cancers. The presence of signaling-upregulated gastric cancer cell lines with intact APC and beta-catenin suggests the involvement of other mechanisms than mutations of APC or beta-catenin.
Japanese journal of cancer research: Gann 12/2002; 93(11):1213-20.
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ABSTRACT: alpha-fetoprotein (AFP) messenger RNA (mRNA) has been proposed as a marker of hepatocellular carcinoma (HCC) cells disseminated into the circulation, but its clinical significance remains controversial. We prospectively assessed the prognostic value of AFP mRNA in patients undergoing curative hepatic resection for HCC. Peripheral blood samples were taken from 87 patients before and after surgery to determine the presence of AFP mRNA by use of a reverse-transcription polymerase chain reaction. A primary endpoint was recurrence-free interval. AFP mRNA was detectable preoperatively in 31 patients (36%) and postoperatively in 30 patients (34%). With a median follow-up period of 28 months (range, 3-41 months), HCC recurred in 46 patients (53%). Among 4 groups separated according to preoperative and postoperative AFP mRNA status, patients with consistent positivity of AFP mRNA showed the highest recurrence rate (85%) and trend to distant or multiple recurrence. The recurrence-free interval was significantly shorter in patients with postoperative positivity of AFP mRNA than in those without (53% [95% CI, 36-71] vs. 88% [95% CI, 79-96] at 1 year, 37% [95% CI, 17-57] vs. 60% [95% CI, 46-75] at 2 years; P =.014), whereas the preoperative positivity of AFP mRNA provided no significance (P =.100). Cox's proportional-hazards model identified the postoperative positivity of AFP mRNA as an independent prognostic factor for HCC recurrence (relative risk, 2.33; 95% CI, 1.26-4.34; P =.007). In conclusion, postsurgical recurrence of HCC can be predicted by detecting AFP mRNA-expressing cells in peripheral blood.
Hepatology 05/2002; 35(4):853-60. · 11.66 Impact Factor
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ABSTRACT: Microsatellite instability (MSI) induces carcinoma through the alteration of target genes; TGF- RII, BAX, IGFIIR, hMSH3, and hMSH6. The grade of MSI is classified into two categories according to the number of positive microsatellite markers; MSI-H and MSI-L. To elucidate the relationship between the propriety of grading MSI, target genes and clinical features of sporadic colorectal cancers, MSI and frameshift mutation of target genes were examined in 132 colorectal cancer patients. Fourteen and 12 cases showed MSI-H and MSI-L, respectively. Of the 14 MSI-H cases, 13 cases showed alteration of target genes. However, of the 12 MSI-L cases, only one case showed alteration of one target gene. Furthermore, all 14 MSI-H patients had cancers of the right colon and were typically older in age than the MSI-negative patients. These results imply a strong relationship between MSI-H and carcinogenesis by the frameshift mutation of target genes.
Digestive Diseases and Sciences 07/2001; 46(8):1615-1622. · 2.12 Impact Factor
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Tsuneo Ikenoue,
Goichi Togo,
Keiichi Nagai,
Hideaki Ijichi,
Jun Kato,
Yutaka Yamaji,
Makoto Okamoto,
Naoya Kato,
Takao Kawabe,
Atsushi Tanaka, Masayuki Matsumura,
Yasushi Shiratori,
Masao Omata
[show abstract]
[hide abstract]
ABSTRACT: To identify additional genes targeted for microsatellite instability (MSI), we search for human genes which contain mononucleotide repeats in their coding region, selected 7 genes (RAD50, DNA-PKcs, FLASH, Apaf-1, XPG, CtIP, and MLSN1), and analyzed frameshift mutations in them. Here we report that 60% (3 out of 5) of human colorectal cancer cell lines exhibiting a high frequency of MSI (MSI-H) and 46% (6 out of 13) of MSI-H primary colorectal tumors had mutations in the (A)9 repeat of RAD50 recombinational repair gene. In contrast, no frameshift mutations were found in any of the 5 MSI-negative colorectal cancer cell lines, 8 colorectal tumors exhibiting a low frequency of MSI (MSI-L), or 28 MSI-negative colorectal tumors. No mutations were found in the mononucleotide repeats of 6 other genes, even in MSI-H cancers. These results suggest that RAD50 frameshift mutations may play a role in the tumorigenesis of MSI-H colorectal cancers.
Cancer Science 05/2001; 92(6):587 - 591. · 3.33 Impact Factor
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Yasushi Shiratori,
Tateo Kawase,
Ryo Nakata,
Mitsugu Tanaka,
Yohko Hikiba,
Ken 'Ichi Okano, Masayuki Matsumura,
Yasuro Niwa,
Yutaka Komatsu,
Shuichiro Shiina,
Masao Omato
[show abstract]
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ABSTRACT: We have previously demonstrated that administration of killed streptococcal preparation (OK432), a biological response modifier, increased the number of asialo GM1-positive cells in the liver, enhanced NK activity of hepatic mononuclear cells, and reduced the number of hepatic metastases of colon 38 adenocarcinoma that were inoculated into the superior mesenteric vein of C57BL/6 strain mice. In the present study, to clarify the role of the spleen in immune surveillance of the liver, the effect of splenectomy on hepatic metastasis of colon carcinoma and on hepatic NK activity has been examined. The number of hepatic metastasis increased in the splenectomized mice, compared with that in sham-operated mice. Administration of OK432 increased the number of asialo GM1-positive cells in the liver and enhanced NK activity of hepatic mononuclear cells in both groups, but NK activity of hepatic mononuclear cells in the splenectomized mice was less than that of the sham-operated mice. An enhanced NK activity of these cells was abolished by treatment with anti-asialo-GM1 antibody plus complementin vitro. Interleukin-2 mRNA expression was increased in the spleen 2 hr after OK432 administration and persisted until 8 hr, but was scarcely noted in the liver. On the other hand, NK activity of hepatic mononuclear cells in the asialo GM1-positive cell-depleted (previous administration of antiserum against asialo GM1) mice was enhanced after OK432 administration in the sham operated and splenectomized mice, but an enhanced NK activity in these mice was only partially or not at all abolished by treatment with anti-asialo GM1 antibody plus complementin vitro, respectively. These results suggest that the spleen could play an important role in an immune surveillance of the liver. In addition, OK432 first enhanced NK activity of hepatic mononuclear cells, which are sensitive to the antibody against asialo GM1. However, when asialo GM1-positive cells were depleted, OK432 enhanced NK activity of hepatic mononuclear cells, which are resistant to anti-asialo GM1 serum.
Digestive Diseases and Sciences 10/1995; 40(11):2398-2406. · 2.12 Impact Factor
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Yasushi Shiratori,
Hiroshi Takada,
Kenji Hai,
Hiroki Kiriyama,
Emmanuel Mawet,
Yutaka Komatsu,
Yasuro Niwa, Masayuki Matsumura,
Shuichiro Shiina,
Tateo Kawase,
Kazunori Matsumoto,
Kazuo Kamii,
Masao Omata,
Mitsugu Tanaka
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ABSTRACT: In an attempt to clarify a mechanism of neutrophil infiltration in the liver of alcoholics and possible therapeutic effect of antiallergic agents on accumulation of these cells in the liver, we investigated chemotaxis of neutrophils by stimulation of a chemotactic factor released from rat hepatocytes exposed to ethanol. When hepatocytes were incubated with more than 30 mM ethanol for 24 hr, chemotactic activity for both rat and human neutrophils was demonstrated in the conditioned medium. An enhanced chemotactic activity of the conditioned medium was reduced in the presence of antibody against KC/gro protein, one of the interleukin-8-related cytokines in rodents. Antiallergic agents such as azelastine or ketotifen at a concentration of >0.01 M markedly reduced chemotaxis of neutrophils. Prednisolone at a concentration of >10 M also reduced chemotaxis of neutrophils. These results suggest that neutrophil accumulation in the liver of human alcoholics could be induced by a chemotactic factor produced by the ethanol-treated hepatocytes and that antiallergic agents could be effective against the extent of alcoholic hepatitis by reducing chemotaxis of neutrophils.
Digestive Diseases and Sciences 06/1994; 39(7):1569-1575. · 2.12 Impact Factor
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Yasuo Imai,
Takao Kawabe,
Morio Takahashi, Masayuki Matsumura,
Yutaka Komatsu,
Eiji Hamada,
Yasuo Niwa,
Masahiro Kurita,
Shuichiro Shiina,
Tadahito Shimada,
Shinichi Ota,
Yasushi Shiratori,
Akira Terano,
Masao Omata
[show abstract]
[hide abstract]
ABSTRACT: A 63-year old woman who had experienced melena for 2 weeks was admitted to Tokyo University Hospital. Gastric adenocarcinoma
was diagnosed endoscopically and histologically, and a total gastrectomy was performed soon thereafter. Pathological examination
of the resected stomach revealed choriocarcinoma of the stomach. Although chemotherapy was administered after surgery, she
died 3 months after admission. Autopsy confirmed the diagnosis of primary gastric choriocarcinoma, a rare, but highly malignant
tumor. It is characteristic; macroscopically it forms a necrotic mass with bleeding, and microscopically it often consists
of adenocarcinoma and choriocarcinoma. Since its prognosis is extremely poor, we must take into account the possibility of
primary gastric choriocarcinoma when a hemorrhagic gastric tumor with necrosis is found.
Journal of Gastroenterology 01/1994; 29(5):642-646. · 4.16 Impact Factor
