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Akihiko Oka,
Yuji Amano,
Yasushi Uchida,
Kouji Kagawa,
Yasumasa Tada,
Ryusaku Kusunoki,
Nobuhiko Fukuba,
Ichiro Moriyama,
Takafumi Yuki,
Shunji Ishihara,
Yoshikazu Kinoshita
Pancreas 01/2013; 42(1):182-184. · 2.39 Impact Factor
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Ryusaku Kusunoki,
Yuji Amano,
Takafumi Yuki, Akihiko Oka,
Mayumi Okada,
Yasumasa Tada,
Goichi Uno,
Ichiro Moriyama,
Norihisa Ishimura,
Shunji Ishihara,
Yoshikazu Kinoshita
[show abstract]
[hide abstract]
ABSTRACT: BackgroundThe use of carbon dioxide (CO2) insufflation during endoscopic procedures is effective in reducing patient discomfort caused by bloating. However, transcutaneous
arterial CO2 (PtCO2) monitoring usually is required for safety during long endoscopic procedures. To evaluate a new capnometer for monitoring
end-tidal carbon dioxide (EtCO2) concentrations and to compare PtCO2 with EtCO2 measured in the same patient, a prospective comparative study of EtCO2 and PtCO2 values measured simultaneously was designed.
MethodsThe study enrolled 20 consecutive patients (18 men and two women; mean age, 70.1years) with upper gastrointestinal neoplasms
scheduled for endoscopic submucosal dissection (ESD) using conscious sedation with CO2 insufflation, and EtCO2 and PtCO2 were simultaneously measured by each capnometer. Patient status was evaluated before ESD by the American Society of Anesthesiologists
(ASA) physical status classification system, and eight patients were judged as class 1, nine patients as class 2, and three
patients as class 3. The exclusion criteria ruled out patients with chronic obstructive pulmonary disease or ASA class 4 or
5 physical status. The correlation between EtCO2 and PtCO2 values and the availability of EtCO2 capnography were investigated.
ResultsThe mean EtCO2 value during ESD was 34.7±4.5mmHg, and the mean PtCO2 value was 51.6±2.4mmHg. There was a statistically significant correlation between EtCO2 and PtCO2 (r=0.331; P=0.002). Hypoxic events (<90% oxygen saturation [SpO2]) caused by decreased respiratory rate occurred for 12 patients. In 10 (83%) of 12 events, a significant reduction in EtCO2 was seen before the decrease in SpO2.
ConclusionsThe EtCO2 values correlated with the PtCO2 values, and the respiratory monitoring methods allowed earlier detection of hypoxia during ESD with conscious sedation than
transcutaneous monitoring. The EtCO2 capnometer was considered to be available for the ESD procedure with the patient under conscious sedation using CO2 insufflation.
KeywordsCapnography–ESD–EtCO2
–PtCO2
Surgical Endoscopy 04/2012; 26(2):501-506. · 4.01 Impact Factor
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Yoshiyuki Mishima,
Yuji Amano,
Takafumi Yuki,
Ryusaku Kusunoki, Akihiko Oka,
Goichi Uno,
Norihisa Ishimura,
Mamiko Hamaoka,
Noriyoshi Ishikawa,
Shunji Ishihara,
Yoshikazu Kinoshita
[show abstract]
[hide abstract]
ABSTRACT: We present a rare case of Barrett’s cancer with a particular histology composed of various differentiated adenocarcinoma (AC)
and squamous cell carcinoma (SCC) cells. A 52-year-old man with a long-standing complaint of heartburn visited a medical center
for an annual check-up by esophagogastroduodenoscopy (EGD). Although high-grade reflux esophagitis with Barrett’s esophagus
was identified 3years earlier, he had not visited a hospital for medication. In 2008, he underwent EGD and a 0–IIa+IIc
type of superficial cancerous lesion was found in the long segment of Barrett’s esophagus. The histology of this lesion was
confirmed as adenosquamous carcinoma by biopsy specimens. Based on the results of computed tomography, endoscopic ultrasonography,
and a barium study, the cancer was found to invade the submucosal layer, and the patient underwent surgery. A histological
study after the surgery demonstrated various subtypes of AC, such as mucinous, signet-ring cell and tubular AC, with a focal
SCC component. Barrett’s AC containing SCC is very rare, and its carcinogenesis is of interest.
KeywordsBarrett’s cancer–Barrett’s esophagus–Adenosquamous carcinoma
Clinical Journal of Gastroenterology 04/2012; 4(1):5-9.
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[show abstract]
[hide abstract]
ABSTRACT: Milk fat globule-epidermal growth factor 8 (MFG-E8), a glycoprotein secreted from various cells, enhances engulfment of apoptotic cells by forming a link between phosphatidylserine on apoptotic cells and α(v)β(3)-integrin on phagocytes. This process is essential for maintaining the host immune system under physiological conditions. Apart from this scavenging function, MFG-E8 also directly regulates a variety of cellular functions, such as attenuating inflammation and healing of injured tissues. Furthermore, recent studies have revealed that MFG-E8 has anti-inflammatory and regenerating roles during intestinal inflammation. This review highlights novel findings regarding the roles of MFG-E8 in intestinal pathophysiology as well as its therapeutic potential for gut inflammatory disorders.
Digestion 01/2012; 85(2):103-7. · 2.05 Impact Factor
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Kousaku Kawashima,
Shunji Ishihara,
Koji Doi,
Yusuke Uemura,
Yasuhiko Ohno,
Kosuke Fukuda,
Koji Onishi,
Yasumasa Tada, Akihiko Oka,
Ryusaku Kusunoki,
Nobuhiko Fukuba,
Takafumi Yuki,
Yoshikazu Kinoshita
[show abstract]
[hide abstract]
ABSTRACT: We herein describe a rare case of ulcerative colitis associated with unilateral hypoglossal nerve palsy. A 64-year-old woman developed severe active ulcerative colitis and was treated with prednisolone. The dose of oral prednisolone was reduced to 7.5 mg/day, following which the patient noticed slight dysphagia and a speech disturbance. She was diagnosed with unilateral hypoglossal nerve palsy, which was thought to be caused by mononeuritis. She was treated with intravenous methylprednisolone at a dose of 500 mg/day, which improved the neuropathy. When the neuropathy occurred, the patient was in a mildly active stage of ulcerative colitis. We concluded that the mononeuritis observed in the present case was likely an extraintestinal manifestation of ulcerative colitis.
Internal Medicine 01/2012; 51(22):3135-7. · 0.94 Impact Factor
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Ryusaku Kusunoki,
Yuji Amano,
Takafumi Yuki, Akihiko Oka,
Mayumi Okada,
Yasumasa Tada,
Goichi Uno,
Ichiro Moriyama,
Norihisa Ishimura,
Shunji Ishihara,
Yoshikazu Kinoshita
Surgical Endoscopy 12/2011; · 4.01 Impact Factor
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Ryusaku Kusunoki,
Yuji Amano,
Takafumi Yuki, Akihiko Oka,
Mayumi Okada,
Yasumasa Tada,
Goichi Uno,
Ichiro Moriyama,
Norihisa Ishimura,
Shunji Ishihara,
Yoshikazu Kinoshita
[show abstract]
[hide abstract]
ABSTRACT: The use of carbon dioxide (CO(2)) insufflation during endoscopic procedures is effective in reducing patient discomfort caused by bloating. However, transcutaneous arterial CO(2) (PtCO(2)) monitoring usually is required for safety during long endoscopic procedures. To evaluate a new capnometer for monitoring end-tidal carbon dioxide (EtCO(2)) concentrations and to compare PtCO(2) with EtCO(2) measured in the same patient, a prospective comparative study of EtCO(2) and PtCO(2) values measured simultaneously was designed.
The study enrolled 20 consecutive patients (18 men and two women; mean age, 70.1 years) with upper gastrointestinal neoplasms scheduled for endoscopic submucosal dissection (ESD) using conscious sedation with CO(2) insufflation, and EtCO(2) and PtCO(2) were simultaneously measured by each capnometer. Patient status was evaluated before ESD by the American Society of Anesthesiologists (ASA) physical status classification system, and eight patients were judged as class 1, nine patients as class 2, and three patients as class 3. The exclusion criteria ruled out patients with chronic obstructive pulmonary disease or ASA class 4 or 5 physical status. The correlation between EtCO(2) and PtCO(2) values and the availability of EtCO(2) capnography were investigated.
The mean EtCO(2) value during ESD was 34.7 ± 4.5 mmHg, and the mean PtCO(2) value was 51.6 ± 2.4 mmHg. There was a statistically significant correlation between EtCO(2) and PtCO(2) (r = 0.331; P = 0.002). Hypoxic events (<90% oxygen saturation [SpO(2)]) caused by decreased respiratory rate occurred for 12 patients. In 10 (83%) of 12 events, a significant reduction in EtCO(2) was seen before the decrease in SpO(2).
The EtCO(2) values correlated with the PtCO(2) values, and the respiratory monitoring methods allowed earlier detection of hypoxia during ESD with conscious sedation than transcutaneous monitoring. The EtCO(2) capnometer was considered to be available for the ESD procedure with the patient under conscious sedation using CO(2) insufflation.
Surgical Endoscopy 09/2011; 26(2):501-6. · 4.01 Impact Factor
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Digestive Endoscopy 04/2011; 23(2):195-6. · 1.19 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Autophagy is an evolutionarily conserved process that maintains cellular homeostasis via synthesis, degradation, and subsequent recycling of cellular products under various physiological conditions. However, the link between autophagy and the innate immune system remains unknown. In the present study, we evaluated Toll-like receptor (TLR)-mediated autophagy induction in intestinal epithelial cells (IECs) and its relationship to interleukin (IL)-8 production. IEC-6, HCT-15, RAW264.7, and THP-1 cells were cultured with or without various TLR ligands, followed by evaluation of the expressions of pro-inflammatory cytokines [IL-8, cytokine-induced neutrophil chemoattractants (CINC)-2β, macrophage inflammatory protein (MIP)-2] by real-time PCR and ELISA. To reveal the status of autophagy in IECs and macrophages, light chain 3 (LC3)-II expression was examined using Western blotting and immunofluorescence with confocal microscopy. Also, to evaluate the influence of TLR ligands on autophagy-mediated innate-immune responses, autophagy-related gene (Atg)7 specific siRNA was transfected into intestinal epithelial cells and IL-8 expression was determined following exposure to various TLR ligands. Cells treated with the TLR ligands produced considerable amounts of pro-inflammatory cytokines (IL-8, CINC-2β, MIP-2). Furthermore, the basal levels of LC3-II were markedly higher in IECs as compared to those in macrophages. Our findings indicated that autophagy induction following TLR ligand stimulation was not significantly evident in IECs as compared to macrophages. In addition, Atg7 gene expression silencingled to down-regulation of TLR-mediated IL-8 expression in IECs, which indicates a potential role of autophagy in generating innate-immune responses. In conclusion, autophagy may be an important intracellular machinery for inducing the innate immune system in IECs.
International Journal of Molecular Medicine 03/2011; 27(3):337-44. · 1.98 Impact Factor
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Ryusaku Kusunoki,
Shunji Ishihara,
Mariko Sato,
Yoshiko Sumita,
Yoshiyuki Mishima,
Mayumi Okada,
Yasumasa Tada, Akihiko Oka,
Nobuhiko Fukuba,
Naoki Oshima,
Ichiro Moriyama,
Takafumi Yuki,
Shuichi Sato,
Yuji Amano,
Yohko Murakawa,
Yoshikazu Kinoshita
[show abstract]
[hide abstract]
ABSTRACT: Takayasu's arteritis (TA) and Crohn's disease (CD) are chronic inflammatory diseases of uncertain etiology. Although co-existence of these rare diseases is estimated to occur in 1 in 10 billion individuals, a theoretically unexpected association has been reported in several patients and it is suggested that those associations may have been more than an unusual coincidence. Herein, we report a case of TA associated with clinically inactive CD. A Japanese woman was diagnosed with colonic CD at the age of 15, developed aortic valve regurgitation at 19, and then presented with general fatigue, low grade fever, and painful sensations in her left arm at 25. She was diagnosed with TA based on computed tomography scanning and magnetic resonance angiography findings, and treatments with prednisolone and cyclosporine were started. Thereafter, valve replacement and right coronary artery bypass graft surgery were performed. The possible pathophysiological mechanism responsible for concurrent existence of TA and CD may be associated with immune disorders. Early diagnosis of vascular lesions for patients with inflammatory bowel disease is highly encouraged.
Internal Medicine 01/2011; 50(15):1581-5. · 0.94 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Kyphosis is a risk factor for the presence of hiatal hernia, which is a strong predictor of Barrett's esophagus. However, the association between kyphosis and Barrett's esophagus has not yet been clarified. To investigate this relationship, the Cobb angle, a marker of kyphosis, was measured in patients with and without Barrett's esophagus.
From January 2006 to December 2010, 26 patients with long-segment Barrett's esophagus (LSBE) were retrospectively enrolled. As the comparative groups, 100 consecutive patients with short-segment Barrett's esophagus (SSBE) and 100 consecutive control patients without Barrett's esophagus were also enrolled in this study. Cobb angles were measured on lateral chest radiographs, and kyphosis was defined as a Cobb angle of greater than 50°. Kyphosis, along with other patient characteristics, were evaluated as possible predictors for SSBE and LSBE.
The mean Cobb angles in the non-BE, SSBE, and LSBE groups were 31.6° (95% CIs, 29.3°-33.9°), 34.8° (32.1°-37.4°) and 49.4° (44.9°-53.9°), respectively. Statistically significant differences were found between the LSBE and the other 2 groups (p<0.001). The mean Cobb angles were 33.3°±12.4° and 37.0°±14.1°, respectively in patients without and with hiatal hernia (p=0.039). Predictors for Barrett's esophagus of any length were erosive esophagitis and hiatal hernia. Kyphosis had the highest odds ratio for the presence of LSBE (OR, 1.50; 95% CI, 1.05-1.94; p=0.033). Other predictors were hiatal hernia and the absence of Helicobacter pylori infection.
Kyphosis is a risk factor for the presence of LSBE in Japanese patients.
Internal Medicine 01/2011; 50(22):2725-30. · 0.94 Impact Factor
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Yoshiyuki Mishima,
Shunji Ishihara,
Md Monowar Aziz, Akihiko Oka,
Ryusaku Kusunoki,
Aya Otani,
Yasumasa Tada,
Yong-Yu Li,
Ichiro Moriyama,
Naoki Oshima,
Takafumi Yuki,
Yuji Amano,
Satoshi Matsumoto,
Yoshikazu Kinoshita
[show abstract]
[hide abstract]
ABSTRACT: A unique subset of B cells expressing interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) plays an essential role in preventing inflammation and autoimmunity. We investigated the presence of this cell subset in intestines and its role in the pathogenesis of ileitis using SAMP1/Yit and age-matched control AKR/J mice. Mononuclear cells were isolated from mesenteric lymph nodes (MLNs) and the expressions of B220, CD1d, CD5, Toll-like receptor 4 (TLR4) and TLR9 in isolated cells were analysed. Purified B cells were stimulated with lipopolysaccharide (LPS) or CpG-DNA, then IL-10 and TGF-β(1) expressions were examined by enzyme immunoassay and flow cytometry. Production of IL-1β by TLR-mediated macrophages co-cultured with or without purified MLN B cells from SAMP1/Yit and AKR/J mice was evaluated. In addition, interferon-γ (IFN-γ) production in intestinal T cells co-cultured with MLN B cells were also assessed in SAMP1/Yit and AKR/J strains. The production levels of IL-10 and TGF-β(1) stimulated by LPS and CpG-DNA were significantly lower in B cells separated from MLNs from the SAMP1/Yit strain. B cells expressing IL-10 and TGF-β(1) were mainly located in a population characterized by the cell surface marker CD1d(+) . Interleukin-1β production by TLR-activated macrophages co-cultured with MLN B cells from SAMP1/Yit mice was significantly higher than that of those from AKR/J mice. Interestingly, IFN-γ production by T cells was noted only when they were co-cultured with SAMP1/Yit but not the AKR/J B cells. These results are the first to show that disorders of regulatory B-cell function under innate immune activation may cause disease pathogenesis in a murine model of Crohn's disease.
Immunology 12/2010; 131(4):473-87. · 3.32 Impact Factor
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Farzana Binte Rahman,
Shunji Ishihara,
Md Monowar Aziz,
Yoshiyuki Mishima,
Naoki Oshima,
Yong-Yu Li,
Alvaro A Sanchez-Siles,
Aya Otani, Akihiko Oka,
Ryusaku Kusunoki,
Yasumasa Tada,
Ichiro Moriyama,
Norihisa Ishimura,
Takafumi Yuki,
Hideaki Kazumori,
Yuji Amano,
Shuichi Sato,
Mesban Uddin Ansary,
Yoshikazu Kinoshita
[show abstract]
[hide abstract]
ABSTRACT: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been shown to stimulate the growth and migration of human keratinocytes in an autocrine or paracrine manner. Bearing in mind the preceding narratives, present study was designed to explore the role of HB-EGF on esophageal epithelial cell growth, migration and anti-apoptosis.
HET-1A and TTn cells were treated with recombinant HB-EGF, and cell proliferation and migration were assessed by MTT and Boyden chamber assays, respectively. Anti-apoptotic effects of HB-EGF was studied by Bcl-2/Bcl-xL gene expression and utilizing a TNF-related death apoptosis inducing ligand (TRAIL).
Recombinant HB-EGF promotes human esophageal epithelial cell proliferation in a dose dependent manner, where 1 and 10 ng/ml doses were found to be most effective. HB-EGF induced cell migration was noted in TTn, but not in HET-1A cells. Recombinant HB-EGF induced the Bcl-2, Bcl-xL mRNA/protein expression in HET-1A and TTn cells. TRAIL induced the apoptosis in TTn, whereas it was significantly inhibited in HB-EGF treated conditions. Finally, we also revealed HB-EGF induced phosphorylation of EGFR and p38 MAPK in those cell lines, while all cellular functions were repressed by EGFR inhibitor AG1478.
HB-EGF promotes esophageal epithelial cell proliferation, migration and induces anti-apoptotic gene expression via EGFR/p38 MAPK phosphorylation.
Scandinavian journal of gastroenterology 11/2010; 45(11):1350-9. · 2.08 Impact Factor
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Md Monowar Aziz,
Shunji Ishihara,
Mohammad Azharul Karim Rumi,
Yoshiyuki Mishima,
Naoki Oshima,
Chikara Kadota,
Ichiro Moriyama,
Yong-Yu Li,
Farzana Binte Rahman,
Aya Otani, Akihiko Oka,
Norihisa Ishimura,
Yasunori Kadowaki,
Yuji Amano,
Yoshikazu Kinoshita
[show abstract]
[hide abstract]
ABSTRACT: The lactogenic hormone prolactin (PRL) regulates milk protein gene expression in mammary glands. To maintain homeostatic balance in the body, milk fat globule epidermal growth factor 8 (MFG-E8) is vital for phagocytic clearance of apoptotic cells. We investigated the effects of PRL on MFG-E8 expression in macrophages by evaluating its promoter function. Macrophages were stimulated with PRL, and the expression of MFG-E8 was determined using real-time PCR and Western blotting. The role of MFG-E8 on phagocytosis of apoptotic cells in PRL-treated macrophages was assessed using microscopy, while the response of PRL to MFG-E8 expression was evaluated using luciferase assay. Following treatment with PRL, significant up-regulations of the PRL receptor and MFG-E8 were observed in macrophages, though PRL-treated macrophages more efficiently engulfed apoptotic cells. The results of MFG-E8 promoter analysis showed considerable up-regulation of promoter activity in macrophages following PRL treatment and results from mutation analysis of the MFG-E8 promoter suggested that the C/EBPbeta binding site was responsible for PRL-induced activation of the MFG-E8 promoter. C/EBPbeta activity was found to be up-regulated in PRL-treated cells as revealed by an electrophoretic mobility shift assay (EMSA). In conclusion, PRL is a potent inducer of MFG-E8 expression in macrophages, while its effect is mediated by the presence of a responsive element in the MFG-E8 promoter.
Apoptosis 06/2008; 13(5):609-20. · 4.07 Impact Factor
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Md. Monowar Aziz,
Shunji Ishihara,
Mohammad Azharul Karim Rumi,
Yoshiyuki Mishima,
Naoki Oshima,
Chikara Kadota,
Ichiro Moriyama,
Yong-Yu Li,
Farzana Binte Rahman,
Aya Otani, Akihiko Oka,
Norihisa Ishimura,
Yasunori Kadowaki,
Yuji Amano,
Yoshikazu Kinoshita
[show abstract]
[hide abstract]
ABSTRACT: The lactogenic hormone prolactin (PRL) regulates milk protein gene expression in mammary glands. To maintain homeostatic balance
in the body, milk fat globule epidermal growth factor 8 (MFG-E8) is vital for phagocytic clearance of apoptotic cells. We
investigated the effects of PRL on MFG-E8 expression in macrophages by evaluating its promoter function. Macrophages were
stimulated with PRL, and the expression of MFG-E8 was determined using real-time PCR and Western blotting. The role of MFG-E8
on phagocytosis of apoptotic cells in PRL-treated macrophages was assessed using microscopy, while the response of PRL to
MFG-E8 expression was evaluated using luciferase assay. Following treatment with PRL, significant up-regulations of the PRL
receptor and MFG-E8 were observed in macrophages, though PRL-treated macrophages more efficiently engulfed apoptotic cells.
The results of MFG-E8 promoter analysis showed considerable up-regulation of promoter activity in macrophages following PRL
treatment and results from mutation analysis of the MFG-E8 promoter suggested that the C/EBPβ binding site was responsible
for PRL-induced activation of the MFG-E8 promoter. C/EBPβ activity was found to be up-regulated in PRL-treated cells as revealed
by an electrophoretic mobility shift assay (EMSA). In conclusion, PRL is a potent inducer of MFG-E8 expression in macrophages,
while its effect is mediated by the presence of a responsive element in the MFG-E8 promoter.
APOPTOSIS 04/2008; 13(5):609-620. · 4.79 Impact Factor
