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Cyclophosphamide-associated enteritis presenting with severe protein-losing enteropathy in granulomatosis with polyangiitis:A case report

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World Journal of Gastroenterology 2021年第20期27卷 2657-2663页

作者： hiroko sato Tsuyoshi Shirai Hiroshi Fujii Tomonori Ishii Hideo Harigae Department of Hematology and Rheumatology Tohoku University Graduate School of MedicineSendai 9808574Japan

BACKGROUND Although cyclophosphamide(CPA)is the key drug for the treatment of autoimmune diseases including vasculitides,it has some well-known adverse effects,such as myelosuppression,hemorrhagic cystitis,infertility,and ***,CPA-associated severe enteritis is a rare adverse effect,and only one case with a lethal clinical course has been ***,the appropriate management of patients with CPA-associated severe enteritis is *** SUMMARY We present the case of a 61-year-old woman diagnosed with granulomatosis with polyangiitis based on the presence of symptoms in ear,lung,and,kidney with positive myeloperoxidase-antineutrophil cytoplasmic *** received pulsed methylprednisolone followed by prednisolone 55 mg/d and intravenous CPA at a dose of 500 mg/*** days after the second course of intravenous CPA,she developed nausea,vomiting,and diarrhea,and was admitted to the *** testing revealed hypoalbuminemia,suggesting proteinlosing *** tomography revealed wall thickening of the stomach,small intestine,and colon with contrast enhancement on the lumen *** and immunosuppressive therapy were not effective,and the patient’s enteritis did not improve for>4 *** her condition became seriously exhausted,corticosteroids were tapered and supportive therapies including intravenous hyperalimentation,replenishment of albumin and gamma globulin,plasma exchange,and infection control were *** supportive therapies improved her condition,and her enteritis gradually *** was finally discharged 7 mo *** Immediate discontinuation of CPA and intensive supportive therapy are crucial for the survival of patients with CPA-associated severe enteritis.

关键词： Antineutrophil cytoplasmic antibody Cyclophosphamide Enteritis Granulomatosis with polyangiitis Plasma exchange Vasculitis Case report

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抗百日咳毒素单克隆抗体与毒素活性的关系

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微生物学免疫学进展 1988年第4期 47-51页

作者： hiroko sato ,杨晓明

用骨髓瘤SP 2/0与主要亚单位S234复合物免疫的BALB/C 小鼠脾细胞杂交的杂交株产生了两种不同的单克隆抗体,抗百日咳毒素S2亚单位抗体命名为 9G8,抗S2和S3亚单位抗体命名为11E6。 11E 6对S2和S3都能结合,可能表示在S2和S3之间存在着共同... 详细信息

用骨髓瘤SP 2/0与主要亚单位S234复合物免疫的BALB/C 小鼠脾细胞杂交的杂交株产生了两种不同的单克隆抗体,抗百日咳毒素S2亚单位抗体命名为 9G8,抗S2和S3亚单位抗体命名为11E6。 11E 6对S2和S3都能结合,可能表示在S2和S3之间存在着共同抗原性。1B7和3F10能中和百日咳毒素的 ADP-核糖转化活性或S1,而9 G 8和11E 6不能中和。 1B7表现出对百日咳毒素的白细胞促进活性、胰岛激活性、渗透性活性及CHO细胞凝集性有很有效的中和作用,而 3 F10不能中和,虽然两种抗体抗ADP-核糖转移活性的活性相同。 11E6有中和白细胞促进活性、胰岛素活性、CHO凝集活性和血凝活性的活性,而无中和渗透性活性的作用。9G8有轻微的中和白细胞促进活性和CHO细胞凝集活性的作用。

关键词：单克隆抗体 PT LP 单抗百日咳毒素

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Pathological classification of intrahepatic cholangiocarcinoma based on a new concept

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World Journal of Hepatology 2010年第12期2卷 419-427页

作者： Yasuni Nakanuma Yasunori sato Kenichi Harada Mokoto Sasaski hiroko Ikeda Department of Human Pathology Kanazawa University Graduate School of Medicine Pathology Diagnosis Section Kanazawa University Hospital

Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic dif-f-e-re-ntiation. To date-,ICC was large-ly classifie-d into adenocarcinoma and rare variants. Herein,we propose to subclassify the former,based on recent progress in the-study of-ICC including the-gross classification and hepatic progenitor/stem cells and on the pathological similarities between biliary and pancreatic neoplasms. That is,ICC is classifiable into the conventional (bile duct) type,the bile ductular type,the intraductal neoplasm type and rare variants. The conventional type is further divided into the small duct type (peripheral type) and large bile duct type (perihilar type). The former is a tubular or micropapillary adenocarcinoma while the latter involves the intrahepatic large bile duct. Bile ductular type resembles proliferated bile ductules and shows a replacing growth of the hepatic *** progenitor cell or stem cell phenotypes such as neural cell adhesion molecule expression are frequently expressed in the bile ductular type. Intraductal type includes papillary and tubular neoplasms of the bile duct (IPNBs and ITNBs) and a superficial spreading type. IPNB and ITNB show a spectrum from a preneoplastic borderline lesion to carcinoma and may have pancreatic counterparts. At invasive sites,IPNB is associated with the conventional bile duct ICC and mucinous carcinoma. Biliary mucinous cystic neoplasm with ovarian-like stroma in its wall is different from IPNB,particularly IPNB showing cystic dilatation of the affected ducts. Rare variants of ICC include squamous/adenosquamous cell carcinoma,mucinous/signet ring cell carcinoma,clear cell type,undifferentiated type,neuroendocrine carcinoma and so on. This classification of-ICC may ope-n up a ne-w fie-ld of-re-se-arch of-ICC and contribute-to the-clini cal approach to ICC.

关键词： Intrahepatic cholangiocarcinoma Adenocarcinoma Bile duct Bile ductule Intraductal neoplasm

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Biliary drainage strategy of unresectable malignant hilar strictures by computed tomography volumetry

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World Journal of Gastroenterology 2015年第16期21卷 4946-4953页

作者： Ei Takahashi Mitsuharu Fukasawa Tadashi sato Shinichi Takano Makoto Kadokura hiroko Shindo Yudai Yokota Nobuyuki Enomoto First Department of Internal Medicine Faculty of MedicineUniversity of Yamanashi

AIM:To identify criteria for predicting successful drainage of unresectable malignant hilar biliary strictures(UMHBS) because no ideal strategy currently ***:We examined 78 patients with UMHBS who underwent biliary *** was considered effective when the serum bilirubin level decreased by ≥ 50% from the value before stent placement within 2 wk after drainage, without additional *** that occurred within 7 d after stent placement were considered as early *** drainage, the liver volume of each section(lateral and medial sections of the left liver and anterior and posterior sections of the right liver) was measured using computed tomography(CT) *** liver volume was calculated based on the volume of each liver section and the type of bile duct stricture(according to the Bismuth classification).Tumor volume, which was calculated by using CT volumetry, was excluded from the volume of each *** operating characteristic(ROC) analysis was performed to identify the optimal cutoff values for drained liver *** addition, factors associated with the effectiveness of drainage and early complications were ***:Multivariate analysis showed that drained liver volume [odds ratio(OR) = 2.92, 95%CI:1.648-5.197; P < 0.001] and impaired liver function(with decompensated liver cirrhosis)(OR = 0.06, 95%CI:0.009-0.426; P = 0.005) were independent factors contributing to the effectiveness of *** analysis for effective drainage showed cutoff values of 33% of liver volume for patients with preserved liver function(with normal liver or compensated livercirrhosis)and 50%for patients with impaired liver function(with decompensated liver cirrhosis).The sensitivity and specificity of these cutoff values were82%and 80%for preserved liver function,and 100%and 67%for impaired liver function,*** patients who met these criteria,the rate of effective drainage among those with

关键词： Biliary drainage Computed tomographyvolumetry Hilar biliary stricture Cholangiocarcinoma Liver function Cholangitis

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A case of primary biliary cirrhosis complicated by Behcet's disease and palmoplantar pustulosis

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World Journal of Gastroenterology 2006年第13期12卷 2136-2138页

作者： Haruyo Iwadate Hiromasa Ohira Hironobu Saito Atsushi Takahashi Tsuyoshi Rai Junko Takiguchi Tomomi Sasajima hiroko Kobayashi Hiroshi Watanabe Yukio sato Department of Internal Medicine Ⅱ Fukushima Medical University School of Medicine Fukushima Japan

A 46-year-old woman was diagnosed with palmoplantar pustulosis （PPP） at the Department of Dermatology, Fukushima Medical University Hospital in 2000, and was treated with ointment. However, because liver dysfunction developed in 2003, she was referred to our department, where primary biliary cirrhosis （PBC） was also diagnosed on the basis of clinical findings. One year later, at the age of 49, she developed manifestations of Behcet＇s disease （BD）, including erythema nodosum in the lower extremities. Because she had a history of uveitis, recurrent oral ulceration was present, and the HLA typing was positive for B51, BD was additionally diagnosed. Liver function normalized within three months of the start of treatment with ursodesoxycholic acid （UDCA）. This is the first case of PBC associated with BD and PPP.

关键词： Primary biliary cirrhosis Behcet's disease Palmoplantar pustulosis

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Clinical significance of hypoechoic submandibular gland lesions in type 1 autoimmune pancreatitis

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World Journal of Gastroenterology 2017年第18期23卷 3295-3300页

作者： Shinichi Takano Mitsuharu Fukasawa Makoto Kadokura hiroko Shindo Ei Takahashi Sumio Hirose Yoshimitsu Fukasawa satoshi Kawakami Tadashi sato Nobuyuki Enomoto First Department of Internal Medicine Faculty of Medicine University of Yamanashi

To assess the role of ultrasonography of submandibular glands (SGs) in the diagnosis of type 1 autoimmune pancreatitis (AIP).METHODSThirty-seven patients who were definitively diagnosed with type 1 AIP according to the international consensus diagnostic criteria (ICDC) for AIP at our institution between December 1990 and April 2016 were retrospectively reviewed. Findings by physical examination, ultrasonography, and scintigraphy of SGs were analyzed to reach a diagnosis based on the ICDC for AIP. The efficacy of corticosteroid treatment in the resolution of hypoechoic lesions in SGs was also evaluated by assessment with ultrasonography before and after treatment in 18 *** sensitivity of multiple hypoechoic lesions in SGs by ultrasonography for the diagnosis of sialadenitis in type 1 AIP (84%) was higher than that of physical examination (46%), scintigraphy (28%), and SGs thickness (49%). Ultrasonographic evidence of hypoechoic lesions in SGs improved the definitive diagnosis of sialadenitis and type 1 AIP by the ICDC criteria in 11 (30%) and 2 (5.4%) cases, respectively. Multiple hypoechoic lesions in SGs were resolved or disappear by corticosteroid administration in 14 of 16 cases with hypoechoic lesions in SGs, whereas the ultrasonographic findings in the remaining 2 cases with hypoechoic lesions in SGs and the 2 cases with homogenous SG parenchyma remained unchanged after corticosteroid *** ultrasonography to detect multiple hypoechoic lesions might be useful for type 1 AIP diagnosis by improving diagnostic accuracy together with the ICDC sialadenitis criteria.

关键词： Autoimmune pancreatitis Ultrasonography Submandibular glands International consensus diagnostic criteria Sialadenitis

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Clinicopathological study of primary biliary cirrhosis with interface hepatitis compared to autoimmune hepatitis

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World Journal of Gastroenterology 2014年第13期20卷 3597-3608页

作者： Mio Kobayashi Yuko Kakuda Kenichi Harada Yasunori sato Motoko Sasaki hiroko Ikeda Mitsuhiro Terada Munenori Mukai Shuichi Kaneko Yasuni Nakanuma Department of Human Pathology Kanazawa University Graduate School of MedicineKanazawa 920-8640Japan Division of Pathology Kanazawa University HospitalKanazawa 920-8641Japan Department of Gastroenterology Kouseiren Takaoka HospitalTakaoka 933-8555Japan Department of Pathology Kouseiren Takaoka HospitalTakaoka 933-8555Japan Department of Gastroenterology Kanazawa University Graduate School of MedicineKanazawa 920-8640 Japan

AIM:To investigate histological and immunohistochemical differences in hepatitis between autoimmune hepatitis(AIH)and primary biliary cirrhosis(PBC)with AIH ***:Liver needle biopsies of 41 PBC with AIH features and 43 AIH patients were *** activity of periportal and lobular inflammation was scored0(none or minimal activity)to 4(severe),and the degree of hepatitic rosette formation and emperipolesis was semiquantatively scored *** infiltration of mononuclear cells positive for CD20,CD38,CD3,CD4,and CD8 and positive for immunoglobulins(IgG,IgM,and IgA)at the periportal areas(interface hepatitis)and in the hepatic lobules(lobular hepatitis)were semiquantitatively scored in immunostained liver sections(score 0-6).Serum aspartate aminotransferase(AST),immunoglobulins,and autoantibodies at the time of liver biopsy were correlated with the histological and immunohistochemical scores of individual ***:Lobular hepatitis,hepatitic rosette formation,and emperipolesis were more extensive and frequent in AIH than in ***3+,CD4+,and CD8+cell infiltration scores were higher in the hepatic lobules and at the interface in AIH but were also found in *** degree of mononuclear cell infiltration correlated well with the degree of interface and lobular hepatitis in PBC,but to a lesser degree in ***20+cells were mainly found in the portal tracts and,occasionally,at the interface in both *** AST correlated well with the hepatocyte necroinflammation and mononuclear cell infiltration,specifically CD38+cells in *** correlation existed between autoantibodies and inflammatory cell infiltration in PBC or *** most AIH cases were IgG-predominant at the interface,PBC cases were divided into IgM-predominant,IgM/IgGequal,and IgG-predominant types,with the latter sharing several features with ***:These results suggest that the hepatocellular injuries associated with interface and lobular hepatitis in AIH and PBC with inte

关键词： Primary biliary cirrhosis Autoimmune hepa-titis Interface hepatitis Lobular hepatitis Plasma cell subclass

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Risk factors for perforation during endoscopic retrograde cholangiopancreatography in post-reconstruction intestinal tract

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World Journal of Clinical Cases 2019年第1期7卷 10-18页

作者： Shinichi Takano Mitsuharu Fukasawa hiroko Shindo Ei Takahashi Sumio Hirose Yoshimitsu Fukasawa satoshi Kawakami Hiroshi Hayakawa Hiroshi Yokomichi Makoto Kadokura Tadashi sato Nobuyuki Enomoto First Department of Internal Medicine Faculty of Medicine University of Yamanashi Yamanashi 409-3898 Japan Department of Health Sciences Interdisciplinary Graduate School and Engineering University of Yamanashi Yamanashi 409-3898 Japan

BACKGROUND Endoscopic retrograde cholangiopancreatography(ERCP) in patients with surgically altered anatomy has been a major challenge to gastrointestinal endoscopists with low success rates for reaching the target site as well as high complication rates. The knowledge of ERCP-related risk factors is important for reducing unexpected *** To identify ERCP-related risk factors for perforation in patients with surgically altered *** The medical records of 187 patients with surgically altered anatomy who underwent ERCP at our institution between April 2009 and December 2017 were retrospectively reviewed. An analysis of patient data, including age, sex, type of reconstruction, cause of surgery, aim of ERCP, success rate of reaching target site,success rate of procedure, adverse events, type of scope, time to reach the target site, and duration of procedure, was performed. In patients with Billroth-Ⅱ reconstruction, additional potential risk factors were the shape of the inserted scope and whether the anastomosis was antecolic or *** All patients(n = 187) had surgical anatomy, such as Billroth-Ⅰ(n = 22), Billroth-Ⅱ(n = 33), Roux-en-Y(n = 54), Child, or Whipple reconstruction(n = 75). ERCP was performed for biliary drainage in 43 cases(23%), stone removal in 29 cases(16%),and stricture dilation of anastomosis in 59 cases(32%). The scope was unable to reach the target site in 17 cases(9%), and an aimed procedure could not be accomplished in 54 cases(29%). Adverse events were pancreatitis(3%),hyperamylasemia(10%), cholangitis(6%), cholestasis(4%), excessive sedation(1%), perforation(2%), and others(3%). Perforation occurred in three cases, all of which were in patients with Billroth-Ⅱ reconstruction; in these patients, further analysis revealed loop-shaped insertion of the scope to be a significant risk for perforation(P = 0.01).CONCLUSION Risk factors for perforation during ERCP in patients with surgically altered anatomy were Billro

关键词： Surgically altered anatomy Billroth-Ⅱ Endoscopic retrograde cholangiopancreatography Perforation

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Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C

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World Journal of Gastroenterology 2016年第27期22卷 6224-6234页

作者： Takafumi Saito Masahiro Sugimoto Kazuo Okumoto Hiroaki Haga Tomohiro Katsumi Kei Mizuno Taketo Nishina Sonoko sato Kaori Igarashi hiroko Maki Masaru Tomita Yoshiyuki Ueno Tomoyoshi Soga Department of Gastroenterology Yamagata University School of Medicine Institute for Advanced Biosciences Keio University

AIM: To clarify the characteristics of metabolite profiles in virus-related hepatocellular carcinoma (HCC) patients using serum metabolome ***: The serum levels of low-molecular-weight metabolites in 68 patients with HCC were quantified using capillary electrophoresis chromatography and mass spectrometry. Thirty and 38 of the patients suffered from hepatitis B virus-related HCC (HCC-B) and hepatitis C virus-related HCC (HCC-C), ***: The main metabolites characteristic of HCC were those associated with glutathione metabolism, notably 13 γ-glutamyl peptides, which are by-products of glutathione induction. Two major profiles, i.e., concentration patterns, of metabolites were identified in HCC patients, and these were classified into two groups: an HCC-B group and an HCC-C group including some of the HCC-B cases. The receiver operating characteristic curve for the multiple logistic regression model discriminating HCC-B from HCC-C incorporating the concentrations of glutamic acid, methionine and γ-glutamyl-glycine-glycine showed a highly significant area under the curve value of 0.94 (95%CI: 0.89-1.0, P < 0.0001).CONCLUSION: The serum levels of γ-glutamyl peptides, as well as their concentration patterns, contribute to the development of potential biomarkers for virus-related HCC. The difference in metabolite profiles between HCC-B and HCC-C may reflect the respective metabolic reactions that underlie the different pathogeneses of these two types of HCC.

关键词： Metabolome Hepatocellular carcinoma γ -glutamyl peptides Glutathione Oxidative stress

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Intragingival injection of Porphyromonas gingivalis-derived lipopolysaccharide induces a transient increase in gingival tumour necrosis factor-a, but not interleukin-6,in anaesthetised rats

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International Journal of Oral Science 2015年第3期7卷 155-160页

作者： hiroko Taguchi Yuri Aono Takayuki Kawato Masatake Asano Noriyoshi Shimizu Tadashi Saigusa Department of Orthodontics Nihon University School of Dentistry Department of Pharmacology Nihon University School of Dentistry at Matsudo Department of Pharmacology Nihon University School of Dentistry Department of Oral Health Sciences Nihon University School of Dentistry Department of Pathology Nihon University School of Dentistry

This study used in vivo microdialysis to examine the effects of intragingival application of lipopolysaccharide（LPS） derived from Porphyromonas gingivalis（Pg-LPS） on gingival tumour necrosis factor（TNF）-a and interleukin（IL）-6 levels in rats. A microdialysis probe with an injection needle attached to the surface of the dialysis membrane was implanted into the gingiva of the upper incisor. For comparison, the effects of LPS derived from Escherichia coli（Ec-LPS） on IL-6 and TNF-a levels were also analysed. Pg-LPS（1 mg/1 m L） or Ec-LPS（1 or 6 mg/1 m L） was applied by microsyringe, with gingival dialysates collected every hour. Enzyme-linked immunosorbent assay（ELISA） revealed that gingival dialysates contained approximately 389 pg？m L21 of IL-6 basally; basal TNF-a levels were lower than the detection limit of the ELISA. Pg-LPS failed to alter IL-6 levels but markedly increased TNF-a levels, which remained elevated for 2 h after treatment. Neither IL-6 nor TNF-a were affected by Ec-LPS. Reverse transcriptase-polymerase chain reaction（RT-PCR） analysis revealed that the gingiva expresses Toll-like receptor（TLR） 2 and TLR4 m RNA. Immunohistochemical examination showed that TLR2 and TLR4 are expressed by gingival epithelial cells. The present study provides in vivo evidence that locally applied Pg-LPS, but not Ec-LPS, into the gingiva transiently increases gingival TNF-a without affecting IL-6. The present results suggest that TLR2 but not TLR4 expressed on gingival epithelial cells may mediate the Pg-LPS-induced increase in gingival TNF-a in rats.

关键词： Porphyromonas gingivalis lipopolysaccharide gingiva tumour necrosis factor-a microdialysis

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