Details of a Researcher - NAKASE Hiroshi

Papers - NAKASE Hiroshi

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S状結腸原発内分泌細胞癌の一剖検例

吉田幸成, 石井良文, 佐々木泰史, 菊地剛史, 秋野公臣, 檜森亮吾, 青木敬則, 見田裕章, 安達靖代, 中村正弘, 足立靖, 加藤康夫, 川上賢太郎, 仲瀬裕志, 遠藤高夫

日本大腸肛門病学会雑誌 ( (一社)日本大腸肛門病学会 ) 70 ( 2 ) 89 - 89 2017.02

Maternal and fetal outcomes in pregnant Japanese women with inflammatory bowel disease: our experience with a series of 23 cases.

Naoki Minami, Minoru Matsuura, Yorimitsu Koshikawa, Satoshi Yamada, Yusuke Honzawa, Shuji Yamamoto, Hiroshi Nakase

Intestinal research 15 ( 1 ) 90 - 96 2017.01 [Refereed] [International journal]

BACKGROUND/AIMS: Our physicians work to expand the possibilities to treat female patients with inflammatory bowel disease (IBD) who wish to become pregnant. Although many drugs, including 5-aminosalicylate (5-ASA), corticosteroids, immunomodulators, and biologics, are used safely during pregnancy, few reports have described the therapeutic regimen throughout pregnancy and the management of patients who relapse during pregnancy precisely. The aim of this study was to assess the management of patients with IBD during pregnancy. METHODS: We identified 19 patients (five with Crohn's disease and 14 with ulcerative colitis [UC]) who became pregnant with a total of 23 pregnancies between May 2005 and May 2015 by reviewing the medical records of Kyoto University Hospital. The following data were collected: the maternal variables, the IBD treatment type, the disease activity, the pregnancy outcome, and the mode of delivery. RESULTS: Among the 19 patients, 18 had become pregnant after being diagnosed with IBD, while one had developed UC newly after pregnancy. Throughout the gestation, all patients were treated with probiotics, 5-ASA, prednisolone, cytapheresis, or infliximab. The relapse rate during pregnancy was 21.7% (5/23 cases). The five patients who experienced a relapse were able to pursue their pregnancy after intensification of their treatments. There were no adverse fetal or neonatal problems, except in one case that required an emergency Caesarean section because of placental dysfunction and in which a very low-birth-weight infant was born preterm. CONCLUSIONS: Our present data confirmed that even if the disease flares up during pregnancy, good pregnancy outcomes can be achieved with an optimal intensification of the patient's treatment.

DOI PubMed

High prevalence of vitamin B-12 insufficiency in patients with Crohn's disease

Misora Ao, Hidemi Tsuji, Kenichiro Shide, Yuki Kosaka, Akari Noda, Nobuya Inagaki, Hiroshi Nakase, Kiyoshi Tanaka

ASIA PACIFIC JOURNAL OF CLINICAL NUTRITION ( H E C PRESS, HEALTHY EATING CLUB PTY LTD ) 26 ( 6 ) 1076 - 1081 2017 [Refereed]

Background and Objectives: In Crohn's disease (CD), belonging to inflammatory bowel disease, the small intestine is involved in most cases. Most frequently affected is the distal ileum, where vitamin B-12 is specifically absorbed. Therefore, malabsorption of vitamin B-12 is quite likely to occur in patients with CD. In this study, we have studied the vitamin B-12 status in CD patients. Methods and Study Design: Forty eight patients with CD were evaluated for their food intake, and circulating concentrations of vitamin B-12, folic acid, and homocysteine (Hcy) as a sensitive marker for the insufficiency of these vitamins and a risk factor of atherosclerosis. Results: Plasma Hcy concentration was significantly correlated with serum vitamin B-12 concentration alone, and 60.4 % of the subjects had hyperhomocysteinemia. Receiver Operating Characteristics (ROC) analysis showed that serum concentration of vitamin B-12, but not folic acid, predicted hyperhomocysteinemia. Their intake of vitamin B-12 was much higher than the Japanese RDA, but not correlated with blood concentrations of vitamin B-12 or Hcy, probably due to malabsorption. Conclusions: Vitamin B-12 insufficiency and hyperhomocysteinemia were highly prevalent in CD patients. Recently, the significance of extra-intestinal complications of CD has been increasingly recognized, and our finding is likely to be of clinical importance.

DOI

Evaluation of a novel fluorescent nanobeacon for targeted imaging of Thomsen-Friedenreich associated colorectal cancer.

Hiroshi Nakase, Shinji Sakuma, Takumi Fukuchi, Takuya Yoshino, Kohta Mohri, Kohei Miyata, Hironori Kumagai, Ken-Ichiro Hiwatari, Kazufumi Tsubaki, Tetsuya Ikejima, Etsuo Tobita, Meiying Zhu, Kevin J Wilson, Kay Washington, John C Gore, Wellington Pham

International journal of nanomedicine ( DOVE MEDICAL PRESS LTD ) 12 1747 - 1755 2017 [Refereed] [International journal]

The Thomsen-Friedenreich (TF) antigen represents a prognostic biomarker of colorectal carcinoma. Here, using a nanobeacon, the surface of which was fabricated with peanut agglutinin as TF-binding molecules, we demonstrate that the nanobeacon is able to detect TF antigen in frozen and freshly biopsied polyps using fluorescence microscopy. Our results provide important clues about how to detect aberrant colonic tissues in the most timely fashion. Given the versatile application method for this topical nanobeacon, the protocol used in this work is amenable to clinical colonoscopy. Moreover, the prospects of clinical translation of this technology are evident.

DOI PubMed

DNA and Histone Methylation in Colon Cancer: Its Biological Impact and Clinical Implications

Hiromu Suzuki, Eiichiro Yamamoto, Hiroshi Nakase, Tamotsu Sugai

Cancer Drug Discovery and Development ( Humana Press Inc. ) ( 9783319597843 ) 461 - 487 2017

Colorectal cancers (CRCs) are thought to arise through accumulation of genetic and epigenetic alterations. CRC genomes exhibit dual-faceted DNA methylation abnormality, global hypomethylation with CpG island hypermethylation, and CRCs are classified into two groups based on whether their genomes exhibit microsatellite instability (MSI) or chromosomal instability (CIN). In addition, a subset of CRCs is characterized by concurrent hypermethylation of multiple CpG islands, known as the CpG island methylator phenotype (CIMP). Genomic instability and epigenetic alterations are tightly linked, and CRCs with MSI largely overlap CIMP-positive tumors, while CIN is associated with global DNA hypomethylation. Dysregulation of histone methylation and altered expression of histone modifying enzymes are also commonly observed in CRC, indicating their critical roles in CRC development. Evidence now suggests that DNA and histone methylation could potentially serve as biomarkers useful for CRC diagnosis, risk assessment and prediction of therapeutic effects and prognosis. Although many studies examining clinical applications are still at an early phase, it is anticipated that further investigation will lead to improved prevention and management of CRC.

DOI

Heparin bridge therapy and post-polypectomy bleeding.

Toshiyuki Kubo, Kentaro Yamashita, Kei Onodera, Tomoya Iida, Yoshiaki Arimura, Masanori Nojima, Hiroshi Nakase

World journal of gastroenterology ( BAISHIDENG PUBLISHING GROUP INC ) 22 ( 45 ) 10009 - 10014 2016.12 [Refereed] [International journal]

AIM: To identify risk factors for post-polypectomy bleeding (PPB), focusing on antithrombotic agents. METHODS: This was a case-control study based on medical records at a single center. PPB was defined as bleeding that occurred 6 h to 10 d after colonoscopic polypectomy and required endoscopic hemostasis. As risk factors for PPB, patient-related factors including anticoagulants, antiplatelets and heparin bridge therapy as well as polyp- and procedure-related factors were evaluated. All colonoscopic hot polypectomies, endoscopic mucosal resections and endoscopic submucosal dissections performed between January 2011 and December 2014 were reviewed. RESULTS: PPB occurred in 29 (3.7%) of 788 polypectomies performed during the study period. Antiplatelet or anticoagulant agents were prescribed for 210 (26.6%) patients and were ceased before polypectomy except for aspirin and cilostazol in 19 cases. Bridging therapy using intravenous unfractionated heparin was adopted for 73 patients. The univariate analysis revealed that anticoagulants, heparin bridge, and anticoagulants plus heparin bridge were significantly associated with PPB (P < 0.0001) whereas antiplatelets and antiplatelets plus heparin were not. None of the other factors including age, gender, location, size, shape, number of resected polyps, prophylactic clipping and resection method were correlated with PPB. The multivariate analysis demonstrated that anticoagulants and anticoagulants plus heparin bridge therapy were significant risk factors for PPB (P < 0.0001). Of the 29 PPB cases, 4 required transfusions and none required surgery. A thromboembolic event occurred in a patient who took anticoagulant. CONCLUSION: Patients taking anticoagulants have an increased risk of PPB, even if the anticoagulants are interrupted before polypectomy. Heparin-bridge therapy might be responsible for the increased PPB in patients taking anticoagulants.

DOI PubMed

Adalimumab Monotherapy and a Combination with Azathioprine for Crohn's Disease: A Prospective, Randomized Trial.

Takayuki Matsumoto, Satoshi Motoya, Kenji Watanabe, Tadakazu Hisamatsu, Hiroshi Nakase, Naoki Yoshimura, Tetsuya Ishida, Shingo Kato, Tomoo Nakagawa, Motohiro Esaki, Masakazu Nagahori, Toshiyuki Matsui, Yuji Naito, Takanori Kanai, Yasuo Suzuki, Masanori Nojima, Mamoru Watanabe, Toshifumi Hibi

Journal of Crohn's & colitis 10 ( 11 ) 1259 - 1266 2016.11 [Refereed] [International journal]

BACKGROUND AND AIMS: The efficacy of azathioprine for Crohn's disease under adalimumab treatment remains obscure. METHODS: In an open-labelled prospective study, we evaluated the efficacy of adalimumab with and without azathioprine in patients with active Crohn's disease, who were naïve to biologics and thiopurines. The patients were randomly assigned to subcutaneous administration of adalimumab [monotherapy group] or to exactly the same schedule of adalimumab with azathioprine [25-100mg daily] [combination group] for 52 Weeks. The primary endpoint was clinical remission at WWeek 26. We also evaluated the score for simple endoscopic severity of Crohn's disease before the therapy and at WWeeks 26 and 52. RESULTS: A total of 176 patients were randomized to either the monotherapy group [n = 85] or to the combination group [n = 91]. Eighteen patients [21.2%] from the monotherapy group and 7 patients [7.7%] from the combination group withdrew owing to active disease, and 15 patients [16.5%] from the combination group and 1 patient [1.2%] from the monotherapy group withdrew due to side effects of the medications. Non-responder imputation analysis revealed that the remission rate at WWeek 26 did not differ between the monotherapy group and the combination group [71.8% vs 68.1%; OR 0.84, p = 0.63]. The rate of endoscopic improvement at WWeek 26 was significantly higher in the combination group [84.2%, n = 57] than in the monotherapy group [63.8%, n = 58] [p = 0.019]. CONCLUSION: The clinical efficacy of a combination of adalimumab and azathioprine at WWeek 26 did not differ from that of adalimumab monotherapy in patients with Crohn's disease naïve to both medications.

DOI PubMed

CD68 on rat macrophages binds tightly to S100A8 and S100A9 and helps to regulate the cells' immune functions.

Kohki Okada, Satoshi Arai, Hiroshi Itoh, Souichi Adachi, Masahiko Hayashida, Hiroshi Nakase, Masaki Ikemoto

Journal of leukocyte biology ( FEDERATION AMER SOC EXP BIOL ) 100 ( 5 ) 1093 - 1104 2016.11 [Refereed] [International journal]

S100A8 and S100A9 (S100 proteins) are regulators of immune cells of myeloid origin. Whereas S100 proteins are found at high concentrations in such cells, their immunologic roles remain unclear. We focused on cluster of differentiation 68 (CD68). The aim of this study is to investigate whether CD68 binds to extracellular S100A8 and/or S100A9 and subsequently participates in the regulation of the cells' immune functions. ELISA and affinity chromatography showed that both recombinant rat S100A8 (r-S100A8) and r-S100A9 bound to r-CD68, but not to r-CD14. Flow cytometry clearly showed evidences supporting above the 2 results. As analyzed by flow cytometry, a less amount of r-S100A8 or r-S100A9 bound to the macrophages treated with some deglycosylation enzymes. In an in vitro assay, the expression levels of S100A8 and S100A9 were significantly suppressed after the macrophages had been treated with an anti-CD68 antibody (ED1). As stimulated macrophages with r-S100A9, the expression of IL-1β mRNA in macrophages, which were treated with anti-TLR4 or -RAGE antibodies, was significantly suppressed. r-S100A8 up-regulated IL-6 and IL-10 mRNAs, while r-S100A9 did TNF-α and IL-6 mRNAs, although these regulations were not statistically significant. Small interfering CD68 also significantly suppressed activation of macrophages through an autocrine pathway by r-S100A8 or r-S100A9. In macrophages stimulated with LPS, fluorescent immunologic staining showed that most CD68 colocalized with S100A8 or S100A9 and that the levels of all 3 molecules were markedly increased. In conclusion, CD68 on macrophages binds to S100A8 and S100A9 and thereby, plays a role in the regulation of the cells' immune functions.

DOI PubMed

Lipocalin 2 prevents intestinal inflammation by enhancing phagocytic bacterial clearance in macrophages.

Takahiko Toyonaga, Minoru Matsuura, Kiyoshi Mori, Yusuke Honzawa, Naoki Minami, Satoshi Yamada, Taku Kobayashi, Toshifumi Hibi, Hiroshi Nakase

Scientific reports 6 35014 - 35014 2016.10 [Refereed] [International journal]

Lipocalin 2 (Lcn2), also called neutrophil gelatinase B-associated lipocalin (NGAL), is an anti-microbial peptide originally identified in neutrophil granules. Although Lcn2/NGAL expression is increased in the inflamed intestinal tissues of patients with inflammatory bowel disease, the role of Lcn2/NGAL in the development of intestinal inflammation remains unclear. Here we investigated the role of Lcn2/NGAL in intestinal inflammation using a spontaneous mouse colitis model, interleukin-10 knock out (IL-10 KO) mice. Lcn2 expression in the colonic tissues of IL-10 KO mice increased with the development of colitis. Lcn2/IL-10 double-KO mice showed a more rapid onset and development of colitis compared to IL-10 KO mice. Lcn2 enhanced phagocytic bacterial clearance in macrophages in vitro after infection with Escherichia coli. Transfer of Lcn2-repleted macrophages prevented the development of colitis in Lcn2/IL-10 double-KO mice in vivo. Our findings revealed that Lcn2 prevents the development of intestinal inflammation. One crucial factor seems to be the enhancement of phagocytic bacterial clearance in macrophages by Lcn2.

DOI PubMed

Targeting cytomegalovirus during ulcerative colitis flare-ups.

Hiroshi Nakase, Kei Onodera

Expert review of gastroenterology & hepatology 10 ( 10 ) 1119 - 1125 2016.10 [Refereed] [International journal]

INTRODUCTION: Human cytomegalovirus (CMV) is a common cause of opportunistic infection leading to severe and fatal disease in immune-compromised individuals. In inflammatory bowel disease patients, particularly those with ulcerative colitis (UC), CMV is often reactivated because these patients are frequently treated with immunosuppressive agents. Many reports have described the relationship between CMV reactivation and UC exacerbation, however, a therapeutic strategy for CMV infection in UC patients has not been established. Area covered: This review highlights therapeutic strategies for UC patients with CMV infection. Recent findings have suggested a benefit from antiviral therapy in patients with histologically proven CMV colitis and/or a high colonic CMV load as determined by quantitative PCR. Expert commentary: To decide who requires antiviral therapies and when we start antiviral therapies, prospective studies of large numbers of UC patients with CMV infection are needed. However, we should know that the bottom-line therapy for UC patients with CMV infection is to optimally control mucosal inflammation.

DOI PubMed

Erratum: Treatment of inflammatory bowel disease in Asia: the results of a multinational web-based survey in the 2nd Asian Organization for Crohn's and Colitis (AOCC) meeting in Seoul.

Hiroshi Nakase, Bora Keum, Byong Duk Ye, Soo Jung Park, Hoon Sup Koo, Chang Soo Eun

Intestinal research 14 ( 4 ) 381 - 381 2016.10 [Refereed] [International journal]

PubMed

多発性骨髄腫に有効なヒストンメチル化阻害薬の探索

石黒一也, 北嶋洋志, 新沼猛, 丸山玲緒, 甲斐正広, 西山廣陽, 進藤哲哉, 池田博, 石田禎夫, 佐々木泰史, 時野隆至, 仲瀬裕志, 鈴木拓

日本癌学会総会記事 ( (一社)日本癌学会 ) 75回 P - 2096 2016.10

自己免疫性膵炎におけるEUS-FNAの役割穿刺針の検討

本谷雅代, 榮浪洋介, 若杉英樹, 志谷真啓, 阿久津典之, 佐々木茂, 仲瀬裕志

Gastroenterological Endoscopy ( (一社)日本消化器内視鏡学会 ) 58 ( Suppl.2 ) 1972 - 1972 2016.10

ラット大腸3次元培養における間葉系幹細胞のニッチ作用

川上賢太郎, 一色裕之, 有村佳昭, 小野寺馨, 永石歓和, 山下健太郎, 藤宮峯子, 仲瀬裕志

日本消化器病学会雑誌 ( (一財)日本消化器病学会 ) 113 ( 臨増大会 ) A758 - A758 2016.09

Diagnostic accuracy of endoscopic features of pediatric acute gastrointestinal graft-versus-host disease.

Eitaro Hiejima, Hiroshi Nakase, Minoru Matsuura, Yusuke Honzawa, Hirokazu Higuchi, Satoshi Saida, Katsutsugu Umeda, Hidefumi Hiramatsu, Souichi Adachi, Kazushi Izawa, Tomoki Kawai, Takahiro Yasumi, Ryuta Nishikomori, Toshio Heike

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 28 ( 5 ) 548 - 55 2016.07 [Refereed] [International journal]

BACKGROUND AND AIM: Acute gastrointestinal graft-versus-host disease (GI-GVHD) is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). There are very few studies on specific endoscopic findings in pediatric acute GI-GVHD. The aim of this retrospective case-control study was to elucidate the characteristic endoscopic findings in pediatric acute GI-GVHD that improve the diagnostic accuracy of endoscopy. METHODS: All consecutive patients under 18 years of age who underwent allogeneic HSCT in Kyoto University Hospital from May 2003 to October 2014 were identified retrospectively. Patients who underwent GI endoscopy as a result of sustained GI symptoms were identified. Intestinal villous patterns were evaluated by magnification endoscopy with the water-immersion technique. The patients were diagnosed with acute GI-GVHD and non-GVHD on the basis of biopsy histology. Endoscopic findings of the two groups were compared. RESULTS: Of the 171 patients who underwent HSCT, 30 underwent GI endoscopy. Of these, 17 and nine were diagnosed with acute GI-GVHD and non-GVHD, respectively. Compared with non-GVHD, acute GI-GVHD was associated significantly more often with short blunt villi in the duodenum (P = 0.013), variable defect villi and short blunt villi in the ileum (P = 0.009 and 0.035, respectively), and edema, erosion, and tortoiseshell-like mucosae in the colon (P = 0.017, 0.023, and 0.017, respectively). CONCLUSION: Pediatric acute GI-GVHD was associated with several characteristic features on magnifying endoscopy with the water-immersion technique. These features will be useful for endoscopic diagnosis of pediatric acute GI-GVHD.

DOI PubMed

Treatment of inflammatory bowel disease in Asia: the results of a multinational web-based survey in the 2(nd) Asian Organization of Crohn's and Colitis (AOCC) meeting in Seoul.

Hiroshi Nakase, Bora Keum, Byoung Duk Ye, Soo Jung Park, Hoon Sup Koo, Chang Soo Eun

Intestinal research 14 ( 3 ) 231 - 9 2016.07 [Refereed] [International journal]

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) management guidelines have been released from Western countries, but no adequate data on the application of these guidelines in Asian countries and no surveys on the treatment of IBD in real practice exist. Since there is a growing need for a customized consensus for IBD treatment in Asian countries, Asian Organization of Crohn's and Colitis performed a multinational survey of medical doctors who treat IBD patients in Asian countries. METHODS: A questionnaire was developed between August 2013 and November 2013. It was composed of 4 domains: personal information, IBD diagnosis, IBD treatment, and quality of IBD care. Upon completion of the questionnaire, a web-based survey was conducted between 17 March 2014 and 12 May 2014. RESULTS: In total, 353 medical doctors treating IBD from ten Asian countries responded to the survey. This survey data suggested a difference in available medical treatments (budesonide, tacrolimus) among Asian countries. Therapeutic strategies regarding refractory IBD (acute severe ulcerative colitis [UC] refractory to intravenous steroids and refractory Crohn's disease [CD]) and active UC were coincident, however, induction therapies for mild to moderate inflammatory small bowel CD are different among Asian countries. CONCLUSIONS: This survey demonstrated that current therapeutic approaches and clinical management of IBD vary among Asian countries. Based on these results and discussions, we hope that optimal management guidelines for Asian IBD patients will be developed.

DOI PubMed

Retrospective Analysis of Growth Speed of 54 Lesions of Colitis-associated Colorectal Neoplasia.

Kazutomo Yamasaki, Toshiyuki Matsui, Takashi Hisabe, Yutaka Yano, Fumihito Hirai, Tsuyoshi Morokuma, Yasushi Iwao, Takayuki Matsumoto, Hidehisa Ohi, Akira Andoh, Motohiro Esaki, Kunihiko Aoyagi, Akira Sugita, Hiroshi Nakase, Mikihiro Fujiya, Daijiro Higashi, Kitaro Futami

Anticancer research ( INT INST ANTICANCER RESEARCH ) 36 ( 7 ) 3731 - 40 2016.07 [Refereed] [International journal]

AIM: This study used a multicenter questionnaire survey to evaluate the morphology and progression of the initial lesion in cases of colitis-associated colorectal neoplasia (CRN). PATIENTS AND METHODS: Endoscopic images of lesions that had been definitively diagnosed as CRN by pathological examination were retrospectively reviewed. RESULTS: This resulted in the identification of 54 initial lesions in 49 patients. The 54 initial lesions fell into the following categories: 22 endoscopically visible localized lesions consisting of 18 elevated lesions and 4 depressed lesions, as well as 32 lesions that were not endoscopically visible as localized and consisted of 20 active-phase mucosal lesions and 12 remission-phase mucosal lesions. Nineteen of the lesions eventually became advanced cancers, while 35 lesions eventually became early-stage cancers. The final lesions were 40 elevated lesions, 5 flat or depressed lesions and 9 stenotic lesions. The form of growth of the advanced cancers was progressive stenosis or increased elevation. For approximately 69% of the early-stage cancers, the growth form was increasing elevation or development of elevation. For 73.6% of the advanced cancers, the initial lesion underwent rapid growth and became advanced cancer within 3 years; they accounted for 25.9% of the total cancers. Approximately 40% of the initial lesions of CRN were endoscopically visible as localized lesions, while approximately 60% were judged to be inflammatory mucosal lesions. CONCLUSION: It will be necessary to proactively take biopsy inflammatory mucosal lesions in order to discover tumors early and periodic surveillance should be performed with the knowledge that tumors may grow very quickly.

PubMed

Effects of Granulocyte and Monocyte Adsorptive Apheresis in Renal Transplantation Recipients with Concomitant Cytomegalovirus Infection

T. Naganuma, Y. Takemoto, T. Iwai, N. Kuwabara, J. Uchida, T. Nakatani, K. Kitamura, A. Masuda, K. Ohmori, M. Matsuura, H. Nakase

Transplantation Proceedings ( Elsevier USA ) 48 ( 3 ) 929 - 932 2016.04 [Refereed]

Background Granulocyte and monocyte adsorptive apheresis (GMAA) is widely used as a treatment for active ulcerative colitis (UC) in Japan. Much attention has been paid to the possibility of GMAA for the treatment and control of cytomegalovirus (CMV) reactivation in patients with refractory UC and concomitant CMV infection. In this study, the effects of the combination of GMAA and antiviral therapy were examined in renal transplant recipients with concomitant CMV infection. Methods Combination therapy of GMAA and antiviral drugs was performed 9 times in 7 renal transplant recipients with concomitant CMV infection. Four of the cases were positive for CMV-IgG, and 3 were negative. The clinical presentation of CMV infection was viremia in 6 cases and disease (CMV retinitis) in 1 case. CMV infection was diagnosed by using an antigenemia assay (C7-HRP). GMAA session was performed once, and the duration of the session was 120 min. Immediately after the GMAA session, ganciclovir was administered at 5 mg/kg/body weight. CMV infection was monitored based on C7-HRP and CMV-DNA in the peripheral blood samples. Results All cases became negative for C7-HRP and CMV-DNA within 21 days (median, 14 days range, 3-21 days) and 17 days (median, 6 days range, 3-17 days), respectively, after starting the combination therapy. No side effects of GMAA were observed. Conclusions This case series found that GMAA in combination with antiviral drugs may shorten the duration of treatment against CMV infection in renal transplant recipients. Further studies in a larger number of patients are required to confirm these results.

DOI PubMed

Cytomegalovirus Colitis, Cytomegalovirus Hepatitis and Systemic Cytomegalovirus Infection: Common Features and Differences.

Hiroshi Nakase, Hans Herfarth

Inflammatory intestinal diseases 1 ( 1 ) 15 - 23 2016.04 [Refereed] [International journal]

Cytomegalovirus (CMV) is a ubiquitous human herpes virus, which, after often asymptomatic primary infection, establishes a lifelong latent infection that can periodically be reactivated in both immunocompetent and immunosuppressed carriers. Whereas the diagnostic approach in case of a suspicion of CMV reactivation is well defined, the indication for antiviral therapy can often only be made in the context of an extent of organ involvement, the immune status, and comorbidities of the patient. This article reviews the epidemiology, diagnosis, and therapy of CMV reactivation with a focus on inflammatory bowel diseases and potentially different diagnostic and therapeutic approaches in Asia and the Western world.

PubMed

Exon skipping causes atypical phenotypes associated with a loss-of-function mutation in FLNA by restoring its protein function.

Hirotsugu Oda, Tatsuhiro Sato, Shinji Kunishima, Kenji Nakagawa, Kazushi Izawa, Eitaro Hiejima, Tomoki Kawai, Takahiro Yasumi, Hiraku Doi, Kenji Katamura, Hironao Numabe, Shinya Okamoto, Hiroshi Nakase, Atsushi Hijikata, Osamu Ohara, Hidenori Suzuki, Hiroko Morisaki, Takayuki Morisaki, Hiroyuki Nunoi, Seisuke Hattori, Ryuta Nishikomori, Toshio Heike

European journal of human genetics : EJHG ( NATURE PUBLISHING GROUP ) 24 ( 3 ) 408 - 14 2016.03 [Refereed] [International journal]

Loss-of-function mutations in filamin A (FLNA) cause an X-linked dominant disorder with multiple organ involvement. Affected females present with periventricular nodular heterotopia (PVNH), cardiovascular complications, thrombocytopenia and Ehlers-Danlos syndrome. These mutations are typically lethal to males, and rare male survivors suffer from failure to thrive, PVNH, and severe cardiovascular and gastrointestinal complications. Here we report two surviving male siblings with a loss-of-function mutation in FLNA. They presented with multiple complications, including valvulopathy, intestinal malrotation and chronic intestinal pseudo-obstruction (CIPO). However, these siblings had atypical clinical courses, such as a lack of PVNH and a spontaneous improvement of CIPO. Trio-based whole-exome sequencing revealed a 4-bp deletion in exon 40 that was predicted to cause a lethal premature protein truncation. However, molecular investigations revealed that the mutation induced in-frame skipping of the mutated exon, which led to the translation of a mutant FLNA missing an internal region of 41 amino acids. Functional analyses of the mutant protein suggested that its binding affinity to integrin, as well as its capacity to induce focal adhesions, were comparable to those of the wild-type protein. These results suggested that exon skipping of FLNA partially restored its protein function, which could contribute to amelioration of the siblings' clinical courses. This study expands the diversity of the phenotypes associated with loss-of-function mutations in FLNA.

DOI PubMed

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Papers - NAKASE Hiroshi