Details of a Researcher - NAKASE Hiroshi

Papers - NAKASE Hiroshi

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Rectal leiomyoma with fibromuscular obliteration mimicking adematous lesion

H. Nakase, M. Ide, S. Yazumi, N. Watanabe, T. Itoh, M. Matsuura, C. Kawanami, K. Okazaki, T. Chiba

Endoscopy 34 ( 3 ) 241 2002 [Refereed]

Immunological and molecular analysis of B lymphocytes in low-grade MALT lymphoma of the stomach. Are there any useful markers for predicting outcome after Helicobacter pylori eradication?

Yumi Matsushima, Yoshikazu Kinoshita, Hirokazu Fukui, Toru Maekawa, Shujiro Yazumi, Akihiko Okada, Hiroshi Nakase, Chiharu Kawanami, Masahiro Iwano, Kimio Hashimoto, Zenju Takeda, Kazuichi Okazaki, Tsutomu Chiba

Journal of gastroenterology ( SPRINGER-VERLAG TOKYO ) 37 ( 6 ) 428 - 33 2002 [Refereed] [Domestic journal]

BACKGROUND: Although Helicobacter pylori eradication is effective in treating low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma, the condition in some patients deteriorates even after the eradication. Therefore, it is important to predict the disease outcome before starting H. pylori eradication. We investigated the usefulness of flow cytometry, quantifying CD19- and CD20-positive B lymphocytes in MALT lymphoma tissue, for predicting the disease outcome after H. pylori eradication. METHODS: Tissue specimens from 14 patients with H. pylori-positive low-grade gastric MALT lymphoma were examined by histology, Southern blotting, and flow cytometry before therapy. Serum levels of soluble interleukin (IL)-2 receptor were also measured. The relationship between the data and the prognosis after H. pylori eradication was analyzed. RESULTS: Remission occurred in 10 of the 14 patients. The condition in the 4 remaining patients deteriorated even after H. pylori eradication. The percentages of CD19- and CD20-positive cells in MALT lymphoma tissue from the patients in remission were both significantly lower than those in the tissue from patients not in remission. Indeed, 4 of the 5 patients in whom both CD19- and CD20-positive cells accounted for more than 50% of the total number of lymphocytes had gastrectomy, whereas all patients in whom both CD19- and CD20-positive cells accounted for less than 50% of the total number of lymphocytes achieved remission. Although immunoglobulin gene rearrangement was present in all patients operated on, there were also 6 patients whose MALT lymphoma was ameliorated in spite of the presence of gene rearrangement. The serum level of soluble IL-2 receptor was in the normal range in all patients tested. CONCLUSIONS: Analysis of mature B-cell markers in MALT lymphoma tissue is more useful than the examination of immunoglobulin gene rearrangement or serum levels of soluble IL-2 receptor in predicting the outcome of low-grade gastric MALT lymphoma after H. pylori eradication.

DOI PubMed CiNii J-GLOBAL

新しいdrug delivery systemによる大腸炎治療－マイクロスフェアーを用いた治療方法の開発－．

仲瀬裕志, 松浦稔, 玉置敬之, 河南智晴, 千葉勉, 田畑泰彦

炎症と免疫 10 71 - 76 2002

Rectal immunization with antigen-containing microspheres induces stronger Th2 responses than oral immunization: a new method for vaccination

H Nakase, K Okazaki, Y Tabata, K Uchida, S Uose, M Ohana, T Nishi, T Watanabe, M Matsuura, H Hisatsune, K Matsumura, T Itoh, C Kawanami, T Chiba

VACCINE ( ELSEVIER SCI LTD ) 20 ( 3-4 ) 377 - 384 2001.11 [Refereed]

The rectum as an effective site for induction of systemic and local immunity has received little attention. Rectal immunization with microspheres-containing ovalbumin (MS-OVA) was tested for its ability to elicit systemic and mucosal immune responses. Rectal immunization with MS-OVA enhanced both Th2 dominant OVA-specific IgG levels in the serum and OVA-specific IgA levels in fecal extracts more prominently than did oral immunization. Cytokine analysis of CD4(+) T cells indicated a predominant induction of Th2-type responses compared to Th1-type responses following rectal immunization compared to oral immunization. These results demonstrate that rectal immunization with microspheres could be an effective new vaccination method. (C) 2001 Elsevier Science Ltd. All rights reserved.

DOI PubMed

Therapeutic effects on intestinal Behcet's disease of an intravenous drug delivery system using dexamethasone incorporated in lipid emulsion

H Nakase, K Okazaki, C Kawanami, K Uchida, M Ohana, S Uose, T Nishi, T Itoh, A Okano, A Nishio, H Takakuwa, T Chiba

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY ( BLACKWELL PUBLISHING ASIA ) 16 ( 11 ) 1306 - 1308 2001.11 [Refereed]

Recurrent intestinal ulcer is a frequent problem in the management of Behcet's disease. However, no standard therapy for intestinal Behect's disease has been established. We report two patients with intestinal Behcet disease and recurrent ileal ulcers who were treated successfuly with a lipid emulsion of dexamethasone. In one patient, the cecal ulcer did not relapse after the intravenous administration initiation of a lipid emulsion of dexamethasone once a week, despite the discontinuation of prednisolone. In the other patient, the cecal ulcer showed a healing tendency, and oral administration of prednisolone was reduced from 40 to 15 mg/day after intravenous administration of a lipid emulsion of dexamethasone. Both patients experienced no complications associated with the administration of the emulsion. These results suggest that an intravenous drug delivery system using a lipid emulsion of dexamethasone is useful for treatment of intestinal Behcet's disease. (C) 2001 Blackwell Science Asia Pry Ltd.

DOI PubMed

Successful treatment with steroids of upper gastrointestinal acute graft vs. host disease after hematopoietic stem cell transplantation

T Nishi, K Okazaki, S Fujii, K Uchida, S Uose, H Nakase, M Ohana, T Nishihara, T Chiba

ENDOSCOPY ( GEORG THIEME VERLAG KG ) 33 ( 11 ) 985 - 987 2001.11 [Refereed]

A 39-year-old man with acute myeloid leukemia underwent completely matched related hematopoietic stem cell transplantation. On post-transplantation day 83 he was diagnosed as having upper gastrointestinal graft-versus-host disease (GVHD) by endoscopic examination and pathological examination of endoscopic biopsy specimens, and daily administration of 60 mg of water-soluble prednisolone and 50 mg of cyclosporine was started. After steroid therapy, the symptoms of upper gastrointestinal GVHD disappeared completely and endoscopic findings dramatically improved.

DOI PubMed

Analysis of cytokines in the early development of gastric secondary lymphoid follicles in Helicobacter pylori-infected BALB/c mice with neonatal thymectomy

K Uchida, K Okazaki, A Debrecceni, T Nishi, H Iwano, M Inai, S Uose, H Nakase, M Ohana, C Oshima, Y Matsushima, C Kawanami, H Hiai, T Masuda, T Chiba

INFECTION AND IMMUNITY ( AMER SOC MICROBIOLOGY ) 69 ( 11 ) 6749 - 6754 2001.11 [Refereed]

Immunological interaction between the host and Helicobacter pylori seems to play a critical role in follicular formation in gastric mucosa. We reported H. pylori-induced follicular gastritis model using neonatally thymectomized mice. In this study, we investigated the involvement of various cytokines in this model. BALB/c mice were thymectomized on the third day after birth (nTx). At 6 weeks old, these mice were orally infected with H. pylori. Histological studies showed that follicular formation occurred from 8 weeks after the infection and that most of the infiltrating lymphocytes were CD4(+) and B cells. Neutrophils increased transiently at I week after the infection. Gamma interferon, interleukin-7 (IL-7), and IL-7 receptor were expressed in the stomach of the nTx mice irrespective of the infection. In contrast, expressions of the tumor necrosis factor alpha, IL-4 and lymphotoxin-a. genes were remarkably upregulated by the infection. Our findings suggest that follicular formation may require cooperative involvement of a Th2-type immune response, tumor necrosis factor alpha and lymphotoxin-a in addition to the Th1-type immune response in H. pylori-induced gastritis in nTx mice.

DOI PubMed

Substrate recognition mechanism of carboxypeptidase Y

H Nakase, S Murata, H Ueno, R Hayashi

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY ( TAYLOR & FRANCIS LTD ) 65 ( 11 ) 2465 - 2471 2001.11 [Refereed]

To clarify the substrate-recognition mechanism of carboxypeptidase Y, Fmoc-(Glu)(n)Ala-OH (n=1 to 6), Fmoc-(Glu)(n)Ala-NH2 (1 to 5), and Fmoc-Lys(GIU)(3)Ala-NH2 were synthesized, and kinetic parameters for these substrates were measured. K-m for Fmoc-peptides significantly decreased as peptide length increased from n =1 to n=5 with only slight changes in k(cat). K-m for Fmoc-(Glu)(5,6)Ala-OH were almost the same as one for protein substrates described previously (Nakase et al., Bull. Chem. Soc. Jpn., 73, 2587-2590). These results show that the enzyme has six subsites (S-1' and S-1-S-5)Each subsite affinity calculated from the K-m revealed subsite properties, and from the differences of subsite affinity between pH 6.5 and 5.0, the residues in each subsite were predicted. For Fmoc-peptide amide substrates, the priorities of amidase and carboxamide peptidase activities were dependent on the substrate. It is likely that the interactions between side chains of peptide and subsites compensate for the lack of P-1'-S-1' interaction, so the amidase activity prevailed for Fmoc-(Glu)(3,5)Ala-NH2. These results suggest that these subsites contribute extensively to substrate recognition rather than a hydrogen bond network.

DOI PubMed CiNii

Recent concept and diagnostic evaluation of graft-versus-host disease

OKAZAKI K., NISHI T., WATANABE N., MATSUURA M., NAKASE H., KAWANAMI C., CHIBA T.

The Japanese journal of proctology ( The Japan Society of Coloproctology ) 54 ( 10 ) 965 - 969 2001.10

Organ transplantation, especially allogeneic bone marrow transplantation, has been established and is increasing. Graft-versus-host disease (GVHD), which often involves the skin, liver, and GI tract, is one of the most common complications of transplantation. Clinical symptoms and skin biopsy usually make the diagnosis of GI GVHD. However, GI symptoms of GVHD are nonspecific, such as nausea, vomiting, diarrhea, GI bleeding, and abdominal pain. Although it is difficult because of few endoscopic and histological findings, specific endoscopic findings, such as sloughing of the mucosa and apoptosis, are very useful to make a diagnosis of GVHD. In this review, we discuss the current concept and diagnostic evaluation for GI GVHD.

DOI CiNii

Successful treatment of severe acute pancreatitis by the combination therapy of continuous arterial infusion of a protease inhibitor and continuous hemofiltration

H Nakase, T Itani, J Mimura, T Kawasaki, H Komori, K Okazaki, T Chiba

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY ( BLACKWELL PUBLISHING ASIA ) 16 ( 8 ) 944 - 945 2001.08 [Refereed]

DOI

A critical role for IL-713 signaling in the development of Helicobacter felis-induced gastritis in mice

M Ohana, K Okazaki, C Oshima, D Andra's, T Nishi, K Uchida, S Uose, H Nakase, Y Matsushima, T Chiba

GASTROENTEROLOGY ( W B SAUNDERS CO ) 121 ( 2 ) 329 - 336 2001.08 [Refereed]

Background & Aims: Interleukin (IL)-7 is a critical cytokine in the development of T and B cells and is involved in gastrointestinal pathophysiology. The aim of this study was to investigate the involvement of IL-7 receptor (IL-7R) signaling in Helicobacter-induced gastritis. Methods: C57BL/6 mice (n = 40) were inoculated with H. felis. Twenty mice were injected intraperitoneally with neutralizing IL-7R antibody (A7R34) every seventh day for 3 months. Histology, serum anti-H. felis antibody, and gene expression of IL-7, IL-7R, and proinflammatory cytokines in the gastric mucosa were evaluated. Results: Seventeen of 20 (85%) infected mice without A7R34 developed severe atrophic gastritis, whereas there was no gastritis in A7R34-treated infected mice. There was no difference in the serum levels of anti-H. felis antibody between the 2 groups. IL-7, IL-7R, IL-1 alpha, tumor necrosis factor alpha, and interferon gamma messenger RNA expressions were up-regulated in control infected mice, whereas only IL-7 messenger RNA was up-regulated in A7R34-treated infected mice. Immunohistochemistry indicated positive cytoplasmic staining of IL-7 in the gastric epithelial cells. Conclusions: These data suggest a critical role for IL-7 receptor signaling in the development of Helicobacter-induced gastritis in mice.

DOI PubMed

Isolated metastatic gastric cancer to the colon: A unique endoscopic appearance

H Nakase, S Yazumi, C Kawanami, K Okazaki, T Chiba, S Yoshizaki, S Mise

GASTROINTESTINAL ENDOSCOPY ( MOSBY, INC ) 54 ( 1 ) 76 - 76 2001.07 [Refereed]

An oral drug delivery system targeting immune-regulating cells ameliorates mucosal injury in trinitrobenzene sulfonic acid-induced colitis

H Nakase, K Okazaki, Y Tabata, S Uose, M Ohana, K Uchida, T Nishi, A Debreceni, T Itoh, C Kawanami, M Iwano, Y Ikada, T Chiba

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS ( AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS ) 297 ( 3 ) 1122 - 1128 2001.06 [Refereed]

Control of immune-regulating cells in the colonic mucosa is important in the treatment of patients with inflammatory bowel disease (IBD). The aim of study was to examine the therapeutic effect of dexamethasone (DX) microspheres on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, a model for human Crohn's disease. DX microspheres and DX alone were administered orally to rats with TNBS-induced colitis. The macroscopic score. histological score, myeloperoxidase (MPO) activity, nitric oxide (NO) production, and gene expressions of proinflammatory cytokines, cyclooxygenase (COX)-1, and COX-2 in the colonic tissue were determined. Proliferating cell nuclear antigen (PCNA) staining and expression of nuclear transcription factor (NF)-kappaB in colonic tissues were also investigated. Macroscopic score, histological score, MPO activity, and NO production in rats treated with DX microspheres were significantly lower than in those treated with DX alone. The gene expression of proinflammatory cytokines and COX-2 in rats treated with DX microspheres was down-regulated, compared with that in rats treated with DX alone. The number of PCNA-positive cells in the DX microsphere group was larger than in the group treated with DX alone. DX microspheres suppressed NF-kappaB activation in TNBS-induced colitis more strongly than DX alone. Oral administration of DX microspheres appears to ameliorate mucosal injury in TNBS-induced colitis, This drug delivery system could be an ideal therapy for human IBD.

PubMed J-GLOBAL

Budd-Chiari syndrome and extrahepatic portal obstruction associated with congenital antithrombin III deficiency

H Nakase, T Kawasaki, T Itani, J Mimura, H Komori, K Okazaki, T Chiba

JOURNAL OF GASTROENTEROLOGY ( SPRINGER-VERLAG ) 36 ( 5 ) 341 - 345 2001.05 [Refereed]

We report a patient with Budd-Chiari syndrome (BCS) and extrahepatic portal obstruction (EHO) associated with congenital antithrombin (AT) III deficiency. A 35-year-old man was admitted to Nishi Kobe Medical Center for evaluation of abnormal intrahepatic veins. By various imaging modalities, BCS and EHO were diagnosed. Laboratory data revealed parallel decreases in activity and antigen concentration of AT III despite normal liver function. Taken together, the etiology of both BCS and EHO was considered to be thrombosis, associated with congenital AT III deficiency. Two years after beginning warfarin therapy, the patient has no symptoms and his liver function remains normal. Anticoagulant therapy is considered useful for preventing progression of the disease.

DOI CiNii J-GLOBAL

mRNA expression of cytokines and chemokines in the normal gastric surface mucous epithelial cell line GSM06 during bacterial infection with Helicobacter felis

A Debreceni, K Okazaki, Y Matsushima, M Ohana, H Nakase, K Uchida, S Uose, T Chiba

JOURNAL OF PHYSIOLOGY-PARIS ( EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER ) 95 ( 1-6 ) 461 - 467 2001.01 [Refereed]

Background and aim: A group of the proinflammatory and chemotactic cytokines (chemokines) has been considered as an important factor in the pathomechanism of different bacterial diseases, among them the common Helicobacter pylori infection. Experimental results obtained with gastric biopsy samples of H. pylori positive patients, and with H. pylori infected tumor originated gastric cell lines indicated that these cytokines have essential roles in the development and maintenance of the immune response and inflammation of the gastric mucosa during H. pylori infection. Although the mRNA expression was shown in these biopsy samples and cell lines, it is not yet proved that the normal gastric mucosal epithelial cells themselves express these cytokines. The establishment of a gastric surface mucous cell line with non-tumor origin (GSM06), and the usage of Helicobacter felis as a model of the classic H. pylori infection gave us the possibility to check this question. Materials and methods: in this study GSM06 cells were infected with different numbers (10(5), 10(6), 10(7), 10(8), 10(9) bacterium/ml medium) of H.felis for two different time periods (2, 4 h). Cells treated with medium only were used as control. Then the mRNA expression of the following cytokines was measured by RT-PCR method in the GSM06 cells: proinflammatory cytokine IL1-beta, and chemokine RANTES, eotaxin, MCP-1, MIP1-alpha and MIP1-beta. Results: we found that neither mRNA of the investigated cytokines was expressed constitutively, however the GSM06 cells expressed the mRNA of each cytokine during H. felis infection. Conclusion: our results prove that normal gastric surface mucous epithelial cells express immunologically active peptides during H.felis infection. We may suppose that the epithelial cells of the gastric mucosa contribute to the immune response and inflammation by expressing proinflammatory (IL1-beta) and chemotactic (RANTES, eotaxin, MCP-1, MIP1-alpha and beta) cytokines during H. pylori infection in human. (C) 2001 Elsevier Science Ltd. All rights reserved.

DOI PubMed

粘膜免疫の分子機構とその破綻－Drug Delivery Systemを応用した炎症性腸疾患治療法の開発．

仲瀬裕志, 千葉勉, 田畑泰彦

医学のあゆみ 199 119 - 123 2001

Effects of Helicobacter pylori infection on Zollinger-Ellison syndrome

T Watanabe, Y Matsushima, H Nakase, M Iwano, R Hosotani, M Imamura, Y Kinoshita, T Chiba

JOURNAL OF GASTROENTEROLOGY ( SPRINGER-VERLAG ) 35 ( 10 ) 735 - 741 2000.10 [Refereed]

Both Zollinger-Ellison syndrome (ZES) and Helicobacterpylori infection are major etiologic factors for peptic ulcer. The aim of this study was to investigate the effect of H. pylori infection on ZES with special reference to acid secretion. Sixteen patients with ZES were selected (median age, 59 years; range, 39-66 years; M/F, 9/7), and H. pylori status, ulcer location, gastric acid secretion, serum pepsinogen (PG) I and II concentrations, and PG I/II ratio were determined. The seroprevalence of H. pylori infection was 50%, whereas active H. pylori infection was seen in only 25% of the patients. Thirteen patients had duodenal ulcer (DU), 1 had gastric ulcer (GU), and 2 had both GU and DU. DU was seen in both H. pylori-positive and H. pylori-negative patients, whereas GU was found only in H. pylori-positive patients. Both basal and maximal acid outputs were significantly lower in H. pylori-positive patients than in H. pylori-negative patients (P < 0.05). Moreover, both serum PG I and the PG I/II ratio were significantly lower in H, pylori-positive patients than in H. pylori-negative patients. These results indicate that ZES is an independent risk factor for DU, but H. pylori infection may play some role in the development of GU in ZES. In patients with ZES, N. pylori infection may reduce both hypersecretion from parietal cells and PG I secretion from chief cells, and hyperacidity of the stomach in ZES may have eradicated H. pylori in some patients.

DOI PubMed CiNii

A patient with improvement of ulcerative colitis after appendectomy

K Okazaki, H Onodera, N Watanabe, H Nakase, S Uose, M Matsushita, C Kawanami, M Imamura, T Chiba

GASTROENTEROLOGY ( W B SAUNDERS CO ) 119 ( 2 ) 502 - 506 2000.08 [Refereed]

Recently, several retrospective studies have shown an inverse association between appendectomy and development of ulcerative colitis. We describe a 21-year-old man with distal ulcerative colitis and appendiceal involvement. The patient passed bloody stools continually during the 3 years before admission. Macroscopic and microscopic findings showed chronic moderate inflammation of the appendix and rectum. The ratio of CD4 to CD8 lymphocytes isolated from rectal and appendiceal mucosa was increased (4.3 and 3.8, respectively) compared with controls (n = 11; 1.0 in the rectum and 1.4 in the appendix). Clinical symptoms and colonoscopic and microscopic findings improved significantly after appendectomy. In addition, the amount of interferon gamma secreted from rectal lymphocytes was reduced to 83 pg/mL after surgery (before appendectomy, 254 pg/mL). However, interleukin 4 production was below detectable levels both before and after appendectomy. These findings suggest that appendectomy resulted in altered T-helper (Th)1/Th2 balance in this patient. In the 3 years since surgery, the patient has been in good condition without recurrence of symptoms. This is the first report demonstrating therapeutic benefit of appendectomy in a patient with ulcerative colitis and potential mechanistic relationship.

DOI PubMed

Autoimmune-related pancreatitis is associated with autoantibodies and a Th1/Th2-type cellular immune response

K Okazaki, K Uchida, M Ohana, H Nakase, S Uose, M Inai, Y Matsushima, K Katamura, K Ohmori, T Chiba

GASTROENTEROLOGY ( W B SAUNDERS CO ) 118 ( 3 ) 573 - 581 2000.03 [Refereed]

Background & Aims: Although autoimmunity may be involved in some cases of pancreatitis, the mechanism is still unknown. To clarify this, we studied serum autoantibodies, subsets of lymphocytes, and the Th1/ Th2 balance of cellular immune responses in patients with autoimmune-related pancreatitis (AIP), Methods: Seventeen patients with AIP (8 men and 9 women; age, 53.2 +/- 13.0 years) were studied. Autoantibodies including antilactoferrin (ALF) or carbonic anhydrase II antibody (ACA-II) were examined using the enzyme-linked immunosorbent assay (ELISA) or the indirect fluorescein antibody method. Intracellular cytokines (interferon gamma and interleukin 4) and subtypes of peripheral blood lymphocytes were examined by flow cytometry and ELISA, Results: More than one autoantibody was observed in all 17 patients. Serum antinuclear antibody was detected in 13 of 17 patients, ALF antibody in 13, ACA-II antibody in 10, rheumatoid factor in 5; and anti-smooth muscle antibody in 3, but antimitochondrial antibody in none. The serum levels of ACA-II and LF antibody were not correlated. HLA-DR(+)CD8(+) and HL4-DR(+)CD4(+) cells were significantly increased in peripheral blood (P < 0.05). CD4(+) cells producing interferon gamma and the secreted levels were significantly increased compared with those in controls (P < 0.05), but interleukin 4 was not increased. Conclusions: An autoimmune mechanism against CA-II or LF, and Th1-type immune response, may be involved in AIP.

DOI PubMed

Endoscopic resection of small inflammatory fibroid polyp of the colon

H Nakase, J Mimura, T Kawasaki, T Itani, H Komori, K Hashimoto, K Okazaki, T Chiba

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE ) 39 ( 1 ) 25 - 27 2000.01 [Refereed]

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Papers - NAKASE Hiroshi