93 results on '"Yoshinori Okabayashi"'
Search Results
2. Requirement of autophosphorylated tyrosine 992 of EGF receptor and its docking protein phospholipase Cγ1 for membrane ruffle formation
- Author
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Yoshiaki Kido, Yasunori Kanaho, Masakazu Yamazaki, Masahiro Nogami, Masato Kasuga, Yoshinori Okabayashi, Hiroshi Watanabe, Tomohiko Maehama, and Takehiko Sasaki
- Subjects
rac1 GTP-Binding Protein ,Biophysics ,Small G Protein ,CHO Cells ,Phospholipase ,Biochemistry ,Phospholipase Cγ1 ,Tyrosine phosphorylation ,chemistry.chemical_compound ,Structural Biology ,Cricetinae ,Genetics ,Animals ,Epidermal growth factor receptor ,Phosphorylation ,Tyrosine ,Molecular Biology ,CHO cell ,Epidermal Growth Factor ,Phospholipase C ,biology ,Phospholipase C gamma ,Cell Membrane ,Autophosphorylation ,Cell Biology ,Cell biology ,ErbB Receptors ,chemistry ,Membrane ruffle ,Type C Phospholipases ,biology.protein ,Cell Surface Extensions ,Mitogen-Activated Protein Kinases ,Signal transduction ,Rac1 ,Signal Transduction - Abstract
Stimulation of the epidermal growth factor receptor (EGFR) produces membrane ruffles through the small G protein Rac1; however, the signaling pathway from EGFR to Rac1 has not yet been clarified. Here, we show that autophosphorylation of EGFR at tyrosine 992 is required for EGF-induced membrane ruffle formation in CHO cells. Signaling from the autophosphorylated tyrosine 992 appears to be mediated by phospholipase C (PLC) gamma 1. Furthermore, activation of Rac1 by EGF is inhibited by a PLC inhibitor. These results, taken together, suggest that autophosphorylation of EGFR at tyrosine 992 and the subsequent PLC gamma 1 activation transduce the signal to Rac1 to induce membrane ruffle formation.
- Published
- 2003
3. Stimulatory effects of bilirubin on amylase release from isolated rat pancreatic acini
- Author
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Toshiharu Akiyama, Mitsuo Tashiro, Yoshinori Okabayashi, Issei Imoto, Yoshihide Hirohata, Makoto Otsuki, Masatoshi Fujii, and Yoshikuni Nagashio
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Male ,medicine.medical_specialty ,Physiology ,Bilirubin ,8-Bromo Cyclic Adenosine Monophosphate ,In Vitro Techniques ,Phospholipases A ,chemistry.chemical_compound ,Phospholipase A2 ,Acinus ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Amylase ,Enzyme Inhibitors ,Rats, Wistar ,Pancreas ,Calcimycin ,Protein Kinase C ,chemistry.chemical_classification ,Ionophores ,Hepatology ,biology ,Gastroenterology ,Protein-Tyrosine Kinases ,medicine.disease ,Rats ,Endocrinology ,Enzyme ,medicine.anatomical_structure ,chemistry ,Type C Phospholipases ,Amylases ,Pancreatic juice ,biology.protein ,Acute pancreatitis ,Calcium ,Intracellular ,Signal Transduction ,Vasoactive Intestinal Peptide - Abstract
Considered to be an etiologic factor of acute pancreatitis, hypersecretion of pancreatic juice and digestive enzymes is often associated with hyperbilirubinemia. We explored the intracellular mechanisms through which bilirubin affects pancreatic exocrine secretory function by examining the effect of bilirubin on isolated rat pancreatic acini. Bilirubin stimulated amylase release in a concentration- and time-dependent manner, significantly increasing amylase release at concentrations >5 mg/100 ml and after 15 min of incubation. Coincubation of bilirubin with vasoactive intestinal polypeptide, 8-bromo-cAMP, or A-23187 had a synergistic effect on amylase release, whereas coincubation with CCK-8, carbamylcholine, or 12- O-tetradecanoylphorbol 13-acetate had an additive effect. Bilirubin did not affect acinar cAMP content or Ca2+efflux. Intracellular Ca2+pool depletion had no influence on bilirubin-evoked amylase release. The protein kinase C (PKC) inhibitors staurosporine and calphostin C partially but significantly inhibited bilirubin-stimulated amylase release, whereas the PKA inhibitor H-89 did not. The tyrosine kinase (TK) inhibitor genistein, phospholipase A2(PLA2) inhibitor indoxam, and PLC inhibitor U-73122 also inhibited amylase release. Bilirubin significantly translocated PKC activity from the cytosol to the membrane fraction and activated TK in cytosol and membrane fractions. These results indicate that bilirubin stimulates amylase release by activating PKC and TK in rat pancreatic acini and that PLC and PLA2partly mediate this process.
- Published
- 2002
4. Differential Control of Cellular Gene Expression by Diffusible and Non-Diffusible EGF
- Author
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Yukio Imanishi, Eisuke Nishida, Yoshihiro Ito, Takaya Morooka, Masato Kasuga, Guoping Chen, and Yoshinori Okabayashi
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MAPK/ERK pathway ,medicine.medical_treatment ,Cellular differentiation ,Gene Expression ,Stimulation ,PC12 Cells ,p38 Mitogen-Activated Protein Kinases ,Biochemistry ,Diffusion ,Immobilization ,Epidermal growth factor ,Nerve Growth Factor ,medicine ,Animals ,Molecular Biology ,Epidermal Growth Factor ,biology ,Chemistry ,Growth factor ,Cell Differentiation ,General Medicine ,Rats ,Cell biology ,Nerve growth factor ,Cell culture ,Mitogen-activated protein kinase ,biology.protein ,Mitogen-Activated Protein Kinases ,Cell Division - Abstract
Cell gene expression is affected by both the kind and mode of growth factor stimulation (diffusive vs. non-diffusive). Epidermal growth factor (EGF) was pattern-immobilized on a polystyrene plate. Although the growth of the rat phaeochromocytoma cell line PC12 is stimulated by diffusible EGF, and differentiation is stimulated by diffusible nerve growth factor (NGF), immobilized (non-diffusible) EGF stimulated PC12 differentiation. The immobilized EGF caused a long-lasting stimulation of the intracellular signal protein mitogen-associated protein MAP kinase (MAPK, also known as ERK) and p38 (a subfamily of the MAPK superfamily) in cells, as did diffusible NGF. The switching between growth stimulation and differentiation is considered to be due to the duration of the stimulus. The function of the biosignal conjugate was regulated using conjugation methodology.
- Published
- 2001
5. [Untitled]
- Author
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Yoshinori Okabayashi, Koichi Inushima, Masato Kasuga, Yoko Inoue, Yoko Matsumura, Sachiko Kimura, and Kazuhiko Sakaguchi
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medicine.medical_specialty ,biology ,Physiology ,Kinase ,Gastroenterology ,Endocrinology ,Gastrointestinal hormone ,Mitogen-activated protein kinase ,Internal medicine ,Acinar cell ,biology.protein ,medicine ,Kinase activity ,Tyrosine kinase ,Proto-oncogene tyrosine-protein kinase Src ,Cholecystokinin - Abstract
Cholecystokinin (CCK), a known mitogen for the exocrine pancreas, is shown to activate 70-kDa S6 kinase in isolated pancreatic acini. In this study, we examined the kinetics and cellular mechanisms of CCK-induced p70 S6 kinase activation in vivo and in vitro. Fasted mice were intraperitoneally injected with 0.01–10 μg/kg CCK analoge cerulein. Cerulein caused a concentration-dependent activation of p70 S6 kinase, with the maximal effect at 1–10 μg/kg. After 1 μg/kg cerulein administration, the kinase activity was increased at 5 min, peaked at 10 min, and subsequently decreased. Cerulein also caused a rapid and transient activation of Src. Prior administration of the tyrosine kinase inhibitor herbimycin A compeletely inhibited cerulein-induced Src activation, while the inhibition of p70 S6 kinase activity was partial. Similar results were obtained with pancreatic acinar cell line AR42J cells. These results suggest that tyrosine kinases, including Src as a possible candidate, are partly implicated in the signaling pathway of CCK-induced p70 S6 kinase activation in the exocrine pancreas.
- Published
- 2001
6. [Untitled]
- Author
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Yoshinori Okabayashi, Masato Kasuga, Yoshihiro Yutsudo, Sachiko Kimura, and Koichi Inushima
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medicine.medical_specialty ,Pancreatic disease ,biology ,Physiology ,Gastroenterology ,medicine.disease ,Cystic fibrosis ,Cystic fibrosis transmembrane conductance regulator ,Endocrinology ,Internal medicine ,Genotype ,medicine ,biology.protein ,Pancreatitis ,Allele ,ΔF508 ,Allele frequency - Abstract
Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and the 5T genotype of the polythymidine tract at the exon 9 splice branch/acceptor site are shown to be associated with chronic pancreatitis in Caucasian patients. In contrast to Western countries, cystic fibrosis is extremely rare in Japan. In this study, we investigated the association of mutations or polymorphisms of the CFTR gene with chronic pancreatitis in Japanese patients. Forty-seven patients with chronic pancreatitis (alcohol-related in 31, idiopathic in 14, and familial in 2) were examined for the ΔF508 and R117H mutations and polymorphisms of intron 8. DNA was extracted from leukocytes. Mutations and polymorphisms were examined by the allele-specific polymerase chain reactions and confirmed by direct sequencing. None of the patients had ΔF508 or R117H mutations in the CFTR gene. All of 47 healthy Japanese showed the homozygous 7T/7T genotype, whereas the frequencies of 5T, 7T, and 9T alleles were 0.043, 0.894, and 0.064 in the patients, respectively. The difference in allele frequency is statistically significant. Therefore, the present study indicates the association of polymorphism of the polythymidine tract in intron 8 of the CFTR gene with chronic pancreatitis in Japanese patients.
- Published
- 2000
7. [Untitled]
- Author
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Yoshinori Okabayashi, Takako Kochi, Yoshihiro Yutsudo, Koichi Inushima, Masato Kasuga, and Sachiko Kimura
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Genetics ,medicine.medical_specialty ,Pancreatic disease ,biology ,Physiology ,Gastroenterology ,Aldehyde dehydrogenase ,Locus (genetics) ,medicine.disease ,Internal medicine ,Genotype ,medicine ,biology.protein ,Pancreatitis ,Allele ,ALDH2 ,Alcohol dehydrogenase - Abstract
In order to clarify the genetic factors in alcohol-related chronic pancreatitis among Japanese, we determined the genotype of two major alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). The restriction fragment-length polymorphisms of the ADH2 and the ALDH2 genes were analyzed in 47 normal subjects and 31 patients with alcoholic pancreatitis. No significant difference between the patient and control groups was found in the ADH2 genotypes. A significant genetic difference between the two groups was found in the ALDH2 locus. The frequency of the ALDH2*1 allele was found to be 0.681 and that of the ALDH2*2 allele was 0.319 in the controls, while these values were 0.935 and 0.065 in the patients, respectively. Most of the patients (27 of 31) were ALDH2*1/2*1, only four were ALDH2*1/2*2, and none of the patients were ALDH2*2/2*2. These results indicate that genetic polymorphism of the ALDH2 gene influences the risk of developing alcoholic pancreatitis in Japanese.
- Published
- 2000
8. Supramaximal CCK and CCh concentrations abolish VIP potentiation by inhibiting adenylyl cyclase activity
- Author
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Yoshinori Okabayashi, Makoto Otsuki, Toshiharu Akiyama, Issei Imoto, and Yoshihide Hirohata
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Male ,endocrine system ,medicine.medical_specialty ,Carbachol ,Physiology ,Vasoactive intestinal peptide ,8-Bromo Cyclic Adenosine Monophosphate ,Neuropeptide ,Stimulation ,In Vitro Techniques ,Sincalide ,Adenylyl cyclase ,chemistry.chemical_compound ,Acinus ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Pancreas ,Cholecystokinin ,Dose-Response Relationship, Drug ,Hepatology ,Cell Membrane ,Colforsin ,Pilocarpine ,Gastroenterology ,Drug Synergism ,Long-term potentiation ,Rats ,Kinetics ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Adenylyl Cyclase Inhibitors ,Amylases ,Tetradecanoylphorbol Acetate ,Bombesin ,hormones, hormone substitutes, and hormone antagonists ,Vasoactive Intestinal Peptide ,medicine.drug - Abstract
Exocrine pancreatic secretion stimulated by vasoactive intestinal polypeptide (VIP), which acts through the adenylyl cyclase-cAMP pathway, is potentiated by stimulation with other secretagogues such as CCK and carbachol (CCh). However, the potentiating effect is abolished by the same secretagogues at supramaximal concentrations. In the present study, we examined the mechanisms by which supramaximal concentrations of CCK octapeptide (CCK-8) or CCh reduce the VIP-induced potentiation of amylase secretion from isolated rat pancreatic acini. VIP-stimulated amylase secretion was potentiated by submaximal stimulatory concentrations of CCK-8 and CCh but was reduced by the same reagents at higher concentrations. Supramaximal concentrations of CCK-8 or CCh also reduced forskolin-induced potentiation of amylase release but did not reduce that induced by 8-bromo-cAMP. Moreover, supramaximal concentrations of CCK-8 or CCh inhibited VIP-stimulated intracellular cAMP production as well as adenylyl cyclase activity. 12- O-tetradecanoylphorbol 13-acetate (TPA) also reduced the magnitude of the potentiation of amylase release caused by VIP plus CCK-8 or CCh, although TPA itself decreased neither VIP-stimulated adenylyl cyclase activity nor intracellular cAMP accumulation. These results indicate that supramaximal concentrations of CCK-8 and CCh reduce the potentiating effect of VIP and forskolin on amylase secretion by inhibiting the adenylyl cyclase activity. In addition, protein kinase C is suggested to be partly implicated in this inhibitory mechanism. The mechanisms that lead to such inhibition may be interlinked but distinct from each other.
- Published
- 1998
9. Tryptophan modulates exocrine secretory function in rat pancreatic acini
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Yoshinori Okabayashi, Hiroshi Hasegawa, Makoto Koide, Toshio Okutani, Kenji Matsushita, Makoto Otsuki, Yoshiaki Kido, Masato Kasuga, and Masatoshi Fujii
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Male ,medicine.medical_specialty ,Carbachol ,In Vitro Techniques ,digestive system ,Sincalide ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Drug Interactions ,Secretion ,Amylase ,Rats, Wistar ,Pancreas ,Cholecystokinin ,Dose-Response Relationship, Drug ,biology ,Activator (genetics) ,Tryptophan ,Gastroenterology ,Bombesin ,Rats ,Endocrinology ,Parasympathomimetics ,chemistry ,Amylases ,biology.protein ,Calcium ,Intracellular ,medicine.drug - Abstract
We investigated the effect of tryptophan (Trp) on exocrine secretory function, using isolated rat pancreatic acini. Trp inhibited cholecystokinin-octapeptide (CCK-8)-stimulated amylase secretion, causing a downward shift in the dose-response curve. The inhibitory effect of Trp was dose-dependent and was observed only on the sustained secretion, there being no effect on the initial phase of amylase secretion. Trp (10 mM) also inhibited amylase secretion in response to carbachol and bombesin, as well as fluoride, a potent activator of guanine-nucleotide binding proteins. Since Ca2+ influx is necessary for sustained secretion, we examined the effect of Trp on Ca2+ influx and efflux. Trp increased the CCK-8-stimulated Ca2+ influx rate without affecting Ca2+ efflux, suggesting that Trp elevates intracellular Ca2+ levels. Increasing intracellular Ca2+ levels with A23187 resulted in the inhibition of CCK-8-stimulated amylase secretion. These results indicate that Trp inhibits CCK-stimulated sustained amylase secretion, in part by increasing Ca2+ influx into acinar cells.
- Published
- 1996
10. EGF-Induced Activation of 70-kDa S6 Kinase in CHO Cells Expressing Human EGF Receptors
- Author
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Yoshinori Okabayashi, Yoshiaki Kido, Masato Kasuga, Toshio Okutani, Yutaka Sugimoto, and Kazuhiko Sakaguchi
- Subjects
Biophysics ,CHO Cells ,Protein Serine-Threonine Kinases ,Mitogen-activated protein kinase kinase ,Biochemistry ,MAP2K7 ,Wortmannin ,Mice ,Phosphatidylinositol 3-Kinases ,chemistry.chemical_compound ,Cricetulus ,Cricetinae ,Animals ,Humans ,Insulin ,ASK1 ,c-Raf ,Cloning, Molecular ,Molecular Biology ,Epidermal Growth Factor ,MAP kinase kinase kinase ,Akt/PKB signaling pathway ,Ribosomal Protein S6 Kinases ,Cell Biology ,Molecular biology ,Cell biology ,Androstadienes ,Enzyme Activation ,ErbB Receptors ,Kinetics ,Phosphotransferases (Alcohol Group Acceptor) ,chemistry ,Cyclin-dependent kinase 9 ,hormones, hormone substitutes, and hormone antagonists - Abstract
We investigated epidermal growth factor (EGF)-induced activation of 85-kDa/110-kDa phosphatidylinositol (PI)-3-kinase and 70-kDa S6 kinase in Chinese hamster ovary cells expressing the human EGF receptor. EGF-induced activation of p70 S6 kinase was comparable to that induced by insulin, whereas that of PI-3-kinase in anti-phosphotyrosine immunoprecipitates was very small compared with insulin. Wortmannin, a p85/p110 PI-3-kinase inhibitor, inhibited EGF-induced activation of p70 S6 kinase in a dose-dependent manner. Given that several proteins homologous to catalytic subunit of p85/p110 PI-3-kinase have been identified and that wortmannin inhibits distinct form of PI-3-kinase, the present results suggest that wortmannin-sensitive kinases that resemble catalytic subunit of p85/p110 PI-3-kinase may participate in the signaling pathway from EGF receptors to p70 S6 kinase.
- Published
- 1995
11. A case of ischemic colitis during pregnancy
- Author
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Kiyoshi Oshiro, Fukashi Ochi, Sakan Maeda, Toshiyuki Sakai, Yoshinori Okabayashi, Shinpei Tateiwa, Masahiko Sugano, Masatoshi Fujii, and Yasuo Okamoto
- Subjects
Pregnancy ,medicine.medical_specialty ,business.industry ,General surgery ,Gastroenterology ,Hepatology ,medicine.disease ,Ischemic colitis ,Colorectal surgery ,Text mining ,Surgical oncology ,Internal medicine ,medicine ,business ,Abdominal surgery - Published
- 2003
12. Grb2/Ash binds directly to tyrosines 1068 and 1086 and indirectly to tyrosine 1148 of activated human epidermal growth factor receptors in intact cells
- Author
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Yoshinori Okabayashi, Yutaka Sugimoto, Kazuhiko Sakaguchi, Masato Kasuga, Toshio Okutani, Tadaomi Takenawa, Yoshiaki Kido, and K Matuoka
- Subjects
Proto-Oncogene Proteins pp60(c-src) ,CHO Cells ,Biochemistry ,Receptor tyrosine kinase ,Mice ,Epidermal growth factor ,Cricetinae ,Animals ,Humans ,Tyrosine ,Receptor ,Molecular Biology ,Cells, Cultured ,Adaptor Proteins, Signal Transducing ,GRB2 Adaptor Protein ,biology ,Autophosphorylation ,Proteins ,Cell Biology ,Molecular biology ,ErbB Receptors ,biology.protein ,Phosphorylation ,GRB2 ,Protein Binding ,Proto-oncogene tyrosine-protein kinase Src - Abstract
The activation of receptor tyrosine kinases generates tyrosine-phosphorylated recognition motifs for the binding of signaling proteins containing Src homology 2 domains. We determined the binding sites of Grb2/Ash, an Src homology 2 domain-containing adaptor protein, within epidermal growth factor (EGF) receptors, using Chinese hamster ovary cells overexpressing human EGF receptor mutants in which one of the autophosphorylation sites was retained. In intact cells, the amount of Grb2/Ash coimmunoprecipitated with mutant receptors retaining tyrosines 992, 1068, 1086, 1148, or 1173 was approximately 10, 85, 55, 50, or 20% of wild-type levels, respectively. The association of Grb2/Ash with in vitro autophosphorylated EGF receptor mutants was detectable in those retaining either tyrosines 1068 or 1086 but not in other mutants including those retaining tyrosine 1148. In peptide inhibition assay, phosphorylated peptides representing tyrosines 1068 and 1086 inhibited the binding of Grb2/Ash to in vitro autophosphorylated wild-type EGF receptors, whereas the other peptides representing tyrosines 992, 1148, and 1173 failed to inhibit the binding. Given that tyrosine 1148 of the activated EGF receptor is a major binding site of Shc (Okabayashi, Y., Kido, Y., Okutani, T., Sugimoto, Y., Sakaguchi, K., and Kasuga, M. (1994) J. Biol. Chem. 269, 18674-18678), these results indicate that tyrosines 1068 and 1086 of activated human EGF receptors are direct high affinity binding sites of Grb2/Ash and that tyrosine 1148 is an indirect binding site through Shc in intact cells.
- Published
- 1994
13. Tyrosines 1148 and 1173 of activated human epidermal growth factor receptors are binding sites of Shc in intact cells
- Author
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Kazuhiko Sakaguchi, Yoshinori Okabayashi, Yoshiaki Kido, Yutaka Sugimoto, Toshio Okutani, and Masato Kasuga
- Subjects
Phenylalanine ,Recombinant Fusion Proteins ,Molecular Sequence Data ,CHO Cells ,Transfection ,SH2 domain ,environment and public health ,Biochemistry ,Receptor tyrosine kinase ,Structure-Activity Relationship ,Cell surface receptor ,Epidermal growth factor ,Cricetinae ,Animals ,Humans ,Amino Acid Sequence ,Phosphorylation ,Tyrosine ,Molecular Biology ,Glutathione Transferase ,Binding Sites ,Base Sequence ,Sequence Homology, Amino Acid ,biology ,Autophosphorylation ,Cell Biology ,Molecular biology ,ErbB Receptors ,Kinetics ,Oligodeoxyribonucleotides ,Mutagenesis, Site-Directed ,biology.protein ,Oligopeptides ,hormones, hormone substitutes, and hormone antagonists ,Proto-oncogene tyrosine-protein kinase Src - Abstract
Autophosphorylation of receptor tyrosine kinases provides binding sites for signaling proteins containing Src homology 2 (SH2) domains. We determined the binding sites of Shc, SH2-containing adaptor protein, within epidermal growth factor (EGF) receptors, using Chinese hamster ovary cells overexpressing EGF receptor mutants in which autophosphorylation sites, either alone or in combination, were replaced by phenylalanine. Binding of Shc to EGF receptor mutants lacking single tyrosine residues at 1148 or 1173 decreased by approximately 60 or approximately 15%, respectively, whereas other single point mutants bound the wild-type level of Shc. Binding of Shc markedly decreased in mutants lacking both tyrosine residues at 1148 and 1173. In peptide inhibition assay, phosphorylated nonameric peptide representing tyrosine 1148, DNPDpYQQDF, but not pentameric peptide, pYQQDF, inhibited the binding of glutathione S-transferase-Shc SH2 domain fusion protein to in vitro autophosphorylated EGF receptors, suggesting that N-terminal sequences adjacent to phosphotyrosine are necessary for the association of Shc. Based on results of peptide inhibition assays in which phosphorylated peptides representing tyrosines 992, 1148, and 1173 inhibited Shc binding to the receptor, we constructed another EGF receptor mutant in which one of these tyrosine residues was retained. The amount of Shc bound to mutant receptors retaining tyrosines 1148, 1173, or 992 was approximately 80, approximately 40, or approximately 10% of wild-type level, respectively. These results indicate that tyrosine 1148 of activated human EGF receptors is a major binding site of Shc and tyrosine 1173 is a secondary binding site in intact cells.
- Published
- 1994
14. Signal transduction pathways from insulin receptors to Ras. Analysis by mutant insulin receptors
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R Yamamoto-Honda, Masato Nakafuku, Takashi Kadowaki, Kazuyoshi Yonezawa, Yoshinori Okabayashi, Y Kaziro, Y Kaburagi, A Ando, Tadahiro Kitamura, and Kiyotaka Y. Hara
- Subjects
medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,CHO Cells ,Biology ,Transfection ,environment and public health ,Biochemistry ,Proto-Oncogene Proteins p21(ras) ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cricetinae ,Internal medicine ,Insulin receptor substrate ,medicine ,Animals ,Humans ,Insulin ,Phosphorylation ,Tyrosine ,Phosphotyrosine ,Molecular Biology ,Tyrosine phosphorylation ,Cell Biology ,Receptor, Insulin ,IRS2 ,Cell biology ,Enzyme Activation ,Insulin receptor ,Endocrinology ,chemistry ,Mutagenesis, Site-Directed ,biology.protein ,Signal transduction ,Signal Transduction - Abstract
We have examined the involvement of insulin receptor (IR) substrate-1 (IRS-1) and/or Shc in the upstream of Ras activation in insulin signaling using Chinese hamster ovary (CHO) cell lines overexpressing wild-type (CHO-IR) cells) or mutant insulin receptors. In CHO-IR cells, insulin rapidly phosphorylated IRS-1 and Shc at tyrosine residues and stimulated the formation of the active GTP-bound Ras (Ras.GTP). In contrast, a CHO cell line overexpressing the kinase-negative mutant insulin receptor substituting Arg1018 for Lys1018 was unable to tyrosine-phosphorylate IRS-1 and Shc and failed to activate Ras in response to insulin. A CHO cell line overexpressing the mutant insulin receptor, substituting Ala960 for Tyr960 and which was known to exhibit impaired tyrosine phosphorylation of IRS-1 and biological effects evoked by insulin, showed severely impaired insulin-dependent tyrosine phosphorylation of Shc and moderately impaired activation of Ras. Another cell line overexpressing the mutant insulin receptor, lacking 82 amino acids of the C terminus of beta-subunit and which was recently reported to retain normal insulin-dependent tyrosine phosphorylation of IRS-1, showed slightly impaired Ras activation at 10(-7) M insulin with severely reduced tyrosine phosphorylation of Shc protein. Furthermore, insulin did not induce the association of tyrosine-phosphorylated IRS-1 and Shc in CHO-IR cells. These results suggest that Shc and IRS-1 lie in the separate signaling pathways and that the tyrosine phosphorylation of IRS-1 with or without some low level of Shc phosphorylation may be enough to stimulate the submaximal accumulation of Ras.GTP complex and may need synergistically the higher level of tyrosine phosphorylation of Shc to induce the full activation of Ras in insulin signaling.
- Published
- 1994
15. Potentiating effect of insulin on exocrine secretory function in isolated rat pancreatic acini
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Yoshinori Okabayashi, Kenji Matsushita, Makoto Otsuki, Hiroshi Hasegawa, Makoto Koide, and Masato Kasuga
- Subjects
Male ,medicine.medical_specialty ,medicine.medical_treatment ,In Vitro Techniques ,Biology ,digestive system ,Sincalide ,Ouabain ,Secretin ,Acinus ,Internal medicine ,medicine ,Animals ,Insulin ,Phosphorylation ,Rats, Wistar ,Pancreas ,Pancreatic hormone ,Cholecystokinin ,Hepatology ,Gastroenterology ,Rats ,Kinetics ,medicine.anatomical_structure ,Endocrinology ,Gastrointestinal hormone ,Amylases ,Sodium-Potassium-Exchanging ATPase ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Background/Aims: Insulin is shown to exert various regulatory effects on the exocrine pancreatic function. We investigated the direct effect of insulin on exocrine pancreatic secretion. Methods: The effects of insulin on amylase release, 125I-secretin binding and Na+- and K+-activated adenosine triphosphate phosphohydrolase (Na+,K+-ATPase) activity were measured using the isolated rat pancreatic acini. Results: Insulin potentiated the amylase release elicited by secretin plus cholecystokinin (CCK), but not by either secretin or CCK alone. The potentiating effect of insulin was dependent on the concentration and preincubation time. Insulin had no effect on 125I-secretin binding. Ouabain, a specific Na+,K+-ATPase inhibitor, caused a concentration-dependent inhibition of the potentiated secretion by insulin without affecting the secretory response to secretin plus CCK. In membranes prepared from acini treated with insulin, Na+,K+-ATPase activity was significantly increased. Similar results were obtained when acini were treated with insulin in combination with secretin plus CCK. Conclusions: Insulin exerts a direct effect on pancreatic acinar cells and potentiates exocrine secretion elicited by secretin in combination with CCK, in part, by increasing Na+,K+-ATPase activity.
- Published
- 1994
16. Abstracts of selected papers presented at the 32nd Annual Meeting of the Japanese Society of Gastroenterology
- Author
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Naohiro Sata, Yutaka Atomi, Gakuji Ohshio, Tadao Manabe, Shin-ichiro Watanabe, Tadashi Takeuchi, Kyoko Miyasaka, Akihiro Funakoshi, Tetsuo Hayakawa, Kenji Nagai, Atsuo Murata, Michio Ogawa, Kazunori Takeda, Seiki Matsuno, Tomoaki Tomiya, Kenji Fujiwara, Toshio Nakamura, Toshio Nakanishi, Iwao Sasaki, Keiichi Yoshino, Hiroyasu Makuuchi, Yuji Sawaguchi, Junichi Uchino, Hajime Yokoi, Yoshifumi Kawarada, Hirokazu Komatsu, Masaya Oda, Toshiyuki Komada, Noriyuki Kitami, Nobuhiro Sato, Masami Inada, Sumio Kawata, Michiaki Koga, Michitami Yano, Susumu Takano, Masao Omata, Mitsuru Yasunaga, Hiroyuki Shirasawa, Kiyoaki Ouchi, Hitoshi ASakura, Nobuo Okabe, Tsuneyoshi Yao, Tadao Bamba, Yoshihide Fujiyama, Kiyotaka Okawa, Shigeyoshi Harihara, Toshifumi Ohkusa, Masataka Sasabe, Yasutsugu Shoji, Joji Utsunomiya, S. Hayashi, T. Furukawa, Nobuyuki Matsuhashi, Kentaro Sugano, Hideo Yamazaki, Nobuo Hiwatashi, Tomofumi Ashida, Tokiyoshi Ayabe, Masakazu Takazoe, Noboru Inoue, A. Kitano, K. Kobayashi, Yoshihiro Fukuda, Kazutami Tamura, Hiroshi Koyama, Hirohumi Niwa, Shuji Takahashi, Toshikazu Yoshikawa, Shiuichi Mizuno, Ei Sasaki, Atsushi Toyonaga, Yoshinori Okabayashi, Makoto Otsuki, Keiko Shiratori, Susumu Ozawa, Shigeki Tanaka, Hideyuki Wakasugi, Yusaku Tazawa, Hajime Takikawa, Hironaka Kawasaki, Naomi Tanaka, Goro Kajiyama, Takashi Shimoyama, and Kyotaro Kanazawa
- Subjects
Gastroenterology - Published
- 1992
17. Abstracts of Selected Papers Presented at the 76th General Meeting of the Japanese Society of Gastroenterology
- Author
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Yasuyuki Watanabe, Toshi Nakanishi, Yoshio Mori, Masao Oto, Morikazu Onji, Yasuyuki Ohta, Tetsuo Kuroki, Sukeo Yamamoto, Yoshiaki Iwasaki, Takao Tsuji, Yusei Ikeda, Gotaro Toda, T. Saitoh, H. Asakura, Saburo Onishi, Shinji Iwasaki, M. Oda, T. Azuma, Takaaki Ikeda, Yasushi Hasumura, K. Usui, H. Ishii, Hitoshi Nakano, Kyuichi Tanikawa, Kyoichi Inoue, Kiyohiro Higuchi, Satoshi Hasumura, Scishi Nagamori, Takeshi Okanoue, Michio Morimoto, Norio Koide, Norio Hayashi, Nobuhiro Sato, Shigeki Ono, Fuminori Moriyasu, Kohji Miyazaki, Takeharu Hisatsugu, Yasuhito Kawamura, Yasuni Nakanuma, Kazuo Tarao, Akio Shimizu, Jiro Nishida, Masaya Oda, Yoshinori Okabayashi, Makoto Otsuki, Ryo Hosotani, Takayoshi Tobe, null Sumii, Toshinari Kimura, Hiroyuki Mutoh, Akira Terano, H. Terashima, T. Yabana, Koji Yakabe, Takashi Nakamura, Tadataka Yamada, T. Chiba, T. Fujita, Yoshitake Ikeda, Masaki Kitajima, Shinobu Nakajo, Kiyoharu Minemori, Takashi Nakanishi, and Masaru Okuno
- Subjects
medicine.medical_specialty ,business.industry ,Surgical oncology ,Internal medicine ,General surgery ,Gastroenterology ,Medicine ,Hepatology ,business ,Colorectal surgery ,Abdominal surgery - Published
- 1992
18. Effect of Ethanol on Pancreatic Exocrine Secretion in Rats
- Author
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Yoshinori Okabayashi, Takashi X. Fujisawa, Satoshi Tani, Takahiko Nakamura, Makoto Otsuki, and Masatoshi Fujii
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Scopolamine ,Vasoactive intestinal peptide ,Stimulation ,digestive system ,Sincalide ,Secretin ,chemistry.chemical_compound ,Endocrinology ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Secretion ,Pancreas ,Ethanol ,Dose-Response Relationship, Drug ,Hepatology ,Pancreatic Exocrine Secretion ,Rats, Inbred Strains ,Rats ,medicine.anatomical_structure ,chemistry ,Amylases ,Calcium ,Carbachol ,hormones, hormone substitutes, and hormone antagonists ,Intracellular ,Vasoactive Intestinal Peptide - Abstract
The effect of ethanol on pancreatic exocrine secretion was studied in isolated rat pancreatic acini. Ethanol caused a dose-dependent stimulation of amylase release, and a twofold increase of amylase release was observed with 600 mM ethanol. Ethanol inhibited cholecystokinin octapeptide (CCK-8)- and carbamylcholine-stimulated amylase release and similarly inhibited binding of [125I]CCK-8 and [N-methyl-3H]scopolamine to isolated rat pancreatic acini in a dose-dependent manner. The inhibitory effect of ethanol was fully reversible with respect to CCK-8-induced amylase release. On the other hand, ethanol potentiated secretin- and vasoactive intestinal peptide (VIP)-stimulated amylase release. Ethanol induced a small but significant increase in Ca2+ efflux, whereas CCK-8 induced an immediate and large increase, but ethanol significantly inhibited CCK-8-stimulated Ca2+ efflux. The present study clearly demonstrates the dual effects of ethanol on pancreatic exocrine function: stimulation and inhibition. We suggest that mobilization of intracellular Ca2+ may be involved in the mechanism of ethanol's action on isolated rat pancreatic acini.
- Published
- 1991
19. Action of a New Cholinergic Agonist, Aclatonium Napadisilate, on Isolated Rat Pancreatic Acini
- Author
-
Makoto Otsuki, Yoshinori Okabayashi, Takahiko Nakamura, Masatoshi Fujii, Satoshi Tani, and Takashi X. Fujisawa
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Scopolamine Derivatives ,Muscarinic agonist ,Endocrinology ,Internal medicine ,Muscarinic acetylcholine receptor ,Internal Medicine ,medicine ,Animals ,Receptor ,Pancreas ,Hepatology ,Pancreatic Exocrine Secretion ,biology ,Chemistry ,Calcium Radioisotopes ,Rats, Inbred Strains ,N-Methylscopolamine ,Receptors, Muscarinic ,Acetylcholine ,Rats ,medicine.anatomical_structure ,Parasympathomimetics ,Amylases ,Digestive enzyme ,biology.protein ,Cholinergic ,Calcium ,Carbachol ,Endocrine gland - Abstract
The effect of aclatonium napadisilate, a newly synthesized choline ester, on pancreatic exocrine function was compared with that of the muscarinic agonist carbamylcholine in isolated rat pancreatic acini. Both compounds increased amylase release and 45Ca2+ efflux in a dose-dependent fashion, and similarly decreased the binding of [N-methyl-3H]scopolamine to isolated rat pancreatic acini. While aclatonium napadisilate was 20-30 times less potent than carbamylcholine in stimulations of amylase release and 45Ca2+ efflux, the potency of aclatonium napadisilate in inhibiting [N-methyl-3H]scopolamine binding was nearly the same as that of carbamylcholine. These results indicate that aclatonium napadisilate stimulates pancreatic exocrine secretion via muscarinic receptors and Ca2+ mobilization, and its intrinsic activity is less than carbamylcholine in the isolated rat pancreatic acini. Since aclatonium napadisilate is known to increase motility and peristalsis of the gastrointestinal tract, stimulatory effects of aclatonium napadisilate, shown in the present study, on digestive enzyme secretion from the pancreas may provide additional benefit of aclatonium napadisilate in the treatment of various gastrointestinal disorders.
- Published
- 1990
20. Effect of a New Cholecystokinin Receptor Antagonist Loxiglumide on Acute Pancreatitis in Two Experimental Animal Models
- Author
-
Makoto Otsuki, Hiroshi Itoh, Satoshi Tani, Takahiko Nakamura, Yoshinori Okabayashi, and Masatoshi Fujii
- Subjects
Male ,Taurocholic Acid ,medicine.medical_specialty ,Proglumide ,medicine.drug_class ,Glutamine ,Endocrinology, Diabetes and Metabolism ,Cholecystokinin receptor ,Subcutaneous injection ,Endocrinology ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Ceruletide ,Cholecystokinin ,Hepatology ,business.industry ,Rats, Inbred Strains ,medicine.disease ,Receptor antagonist ,Rats ,Disease Models, Animal ,Pancreatitis ,Acute Disease ,Acute pancreatitis ,Receptors, Cholecystokinin ,business ,medicine.drug - Abstract
We evaluated the effects of a new cholecystokinin (CCK) receptor antagonist, loxiglumide, in a model of mild pancreatitis induced by repeated injections of cerulein and in a severe necrotizing form of pancreatitis induced by retrograde ductal injection of sodium taurocholate (NaTc) in rats. A single subcutaneous injection or oral administration of 50 mg/kg of body weight of loxiglumide almost completely reduced the increases of serum amylase activity and pancreatic wet weight, and caused histologic improvements of the cerulein-induced acute pancreatitis when given 30 min before the first cerulein injection. Loxiglumide was also effective in reducing the elevated serum amylase activity, pancreatic wet weight, and histologic alterations even when administered after the induction of acute pancreatitis. However, loxiglumide offered no apparent beneficial effects when given 30 min before and 3 h after the induction of acute pancreatitis by NaTc as determined by changes in serum amylase activity, pancreatic wet weight, and histology. These results do not necessarily suggest that CCK is not important in the pathogenesis of pancreatitis, but do suggest that the sole blockade of peripheral CCK receptors is ineffective against NaTc-induced severe necrotizing pancreatitis.
- Published
- 1990
21. Enzyme immunoassay for human pancreatic amylase
- Author
-
Yoshinori Okabayashi, Takahiko Nakamura, Makoto Otsuki, Satoshi Tani, Takashi Fujisawa, and Masatoshi Fujii
- Subjects
medicine.medical_specialty ,medicine.drug_class ,Guinea Pigs ,Clinical Biochemistry ,Serum amylase ,Cross Reactions ,Monoclonal antibody ,Immunoenzyme Techniques ,Mice ,Species Specificity ,Reference Values ,Internal medicine ,medicine ,Animals ,Humans ,Amylase ,Pancreas ,chemistry.chemical_classification ,medicine.diagnostic_test ,biology ,Chemistry ,Antibodies, Monoclonal ,General Medicine ,Amylase isoenzymes ,Molecular biology ,Rats ,Isoenzymes ,Enzyme ,Endocrinology ,Immunoassay ,Amylases ,biology.protein ,Clinical value ,Antibody - Abstract
An enzyme immunoassay (EIA) for human pancreatic amylase has been developed for the detection of human serum amylase content. Our monoclonal antibody is highly specific for human pancreatic amylase; it cross reacted negligibly with the salivary isoenzyme. We developed a solid phase enzyme immunoassay for determination of pancreatic amylase in human serum with this antibody. The assay required 20 microL of serum and the standard curve was linear to at least 1000 ng/mL of pancreatic amylase. Inter- and intra-assay CVs were less than 10%. The results obtained by the EIA correlated well with those determined by the conventional electrophoretic method. In normal subjects, the mean concentration of serum pancreatic amylase determined by the EIA was found to be 92.3 +/- 26.1 ng/mL (mean +/- SD). The EIA we describe is useful for directly determining pancreatic amylase in human serum. Specifically distinguishing pancreatic from salivary amylase may have considerable clinical value.
- Published
- 1990
22. Regulatory effect of cholecystokinin on subsequent insulin binding to pancreatic acini
- Author
-
Yoshiaki Kido, Hiroshi Hasegawa, Makoto Otsuki, Yoshinori Okabayashi, Toshio Okutani, Makoto Koide, and Takahiko Nakamura
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,media_common.quotation_subject ,Biology ,Binding, Competitive ,digestive system ,Cholecystokinin receptor ,Sincalide ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Insulin ,Binding site ,Receptor ,Internalization ,Pancreas ,Calcimycin ,Cholecystokinin ,media_common ,Cell Membrane ,digestive, oral, and skin physiology ,Rats, Inbred Strains ,Receptor, Insulin ,Rats ,Kinetics ,medicine.anatomical_structure ,Endocrinology ,Gastrointestinal hormone ,Tetradecanoylphorbol Acetate ,Carbachol ,hormones, hormone substitutes, and hormone antagonists - Abstract
We investigated the regulatory effect of cholecystokinin (CCK) on subsequent insulin binding to pancreatic acinar cells. Rat isolated acini were preincubated with various concentrations of CCK octapeptide (CCK-8) at 37 degrees C. Acini were then washed, resuspended in the binding buffer, and incubated with 8.3 pM 125I-labeled insulin for 60 min at 37 degrees C. Pretreatment with CCK-8 caused inhibition of subsequent 125I-insulin binding that was time and concentration dependent. Significant inhibition was observed with 3 pM CCK-8. Computer analysis of the competition-inhibition study with a nonlinear least-squares curve-fitting program revealed that CCK-8 pretreatment of acini reduced the receptor affinity of the high-affinity binding site. This inhibitory action of CCK-8 was not due to the alteration in degradation or internalization of the tracer. When acini were pretreated with 100 pM CCK-8 for 120 min at 4 degrees C, a reduction in the receptor affinity of the high-affinity binding site was also observed. In pancreatic membrane prepared from acini preincubated with 100 pM CCK-8 for 120 min at 37 degrees C, displacement of 125I-insulin (83 pM) by unlabeled insulin (24 degrees C, 1 h) revealed that CCK-8 inhibited 125I-insulin binding by altering the receptor affinity of the high-affinity binding site. In acinar preparations the inhibitory effect of CCK-8 on 125I-insulin binding was abolished when acini were preincubated with CCK-8 and CCK receptor antagonist L 374718 at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1990
23. Beneficial effects of the synthetic trypsin inhibitor camostate in cerulein-induced acute pancreatitis in rats
- Author
-
Masatoshi Fuji, Yoshinori Okabayashi, Hiroshi Itoh, Satoshi Tani, Takahiko Nakamura, Makoto Otsuki, and Takashi Fujisawa
- Subjects
Male ,Camostat ,medicine.medical_specialty ,Pancreatic disease ,Gabexate ,Physiology ,Trypsin inhibitor ,Guanidines ,Secretin ,chemistry.chemical_compound ,Internal medicine ,medicine ,Acinar cell ,Animals ,Pancreas ,business.industry ,Gastroenterology ,Esters ,Rats, Inbred Strains ,Organ Size ,medicine.disease ,Rats ,Proglumide ,Endocrinology ,Pancreatitis ,chemistry ,Acute Disease ,Amylases ,Pancreatic juice ,Acute pancreatitis ,Trypsin Inhibitors ,business ,Ceruletide - Abstract
The therapeutic effect and the mechanism of action of the synthetic trypsin inhibitor camostate were studied in a rat model of acute interstitial pancreatitis induced by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Rats with acute pancreatitis were given either 100 mg/kg body weight camostate or volume- and pH-adjusted water via an orogastric tube 30 min after the last cerulein injection. The elevation of serum amylase activity was significantly reduced by camostate treatment and the peak value was seen 1 hr earlier than that observed in the rats that did not receive camostate. Camostate also inhibited the reduction in pancreatic content of lipase and amylase seen during experimental pancreatitis. These effects were accompanied by alleviation of the histologic signs of acute pancreatitis such as cellular infiltration and acinar cell vacuolization. After oral administration, camostate and its metabolite were absorbed from the intestine and were detectable in plasma for more than 6 hr in concentrations high enough to have antiprotease activity. In addition, camostate in the duodenum was able to increase pancreatic juice flow and protein output and to stimulate endogenous secretin release. These results suggest that oral administration of camostate reduces the severity of cerulein-induced acute pancreatitis by releasing endogenous secretin and by its antiprotease activity.
- Published
- 1990
24. Protein kinase Calpha is implicated in cholecystokinin-induced activation of 70-kd S6 kinase in AR42J cells
- Author
-
Yoshihiro, Yutsudo, Yoshiaki, Kido, Yoshinori, Okabayashi, Michihiro, Matsumoto, Wataru, Ogawa, Motoi, Ohba, Toshio, Kuroki, and Masato, Kasuga
- Subjects
Enzyme Activation ,Pancreatic Neoplasms ,Protein Kinase C-alpha ,Mutagenesis ,Tumor Cells, Cultured ,Animals ,Gene Expression ,Ribosomal Protein S6 Kinases, 70-kDa ,Cholecystokinin ,Pancreas, Exocrine ,Adenoviridae ,Rats - Abstract
We showed previously that cholecystokinin (CCK)-induced 70-kd S6 kinase activation is partly mediated by protein kinase C (PKC) in pancreatic acinar AR42J cells. Here, we examined which isoform of PKC is involved in this process.AR42J cells were infected with adenovirus vectors carrying the kinase-deficient alpha, delta, and epsilon isoforms of PKC, the dominant-negative form of the 85-kd regulatory subunit of phosphatidylinositol (PI) 3-kinase, and the dominant-negative form of Sos. CCK-induced p70 S6 kinase activation was determined in AR42J cells infected with these adenovirus vectors.CCK-induced p70 S6 kinase activity was significantly reduced in cells overexpressing the dominant-negative p85 subunit of PI 3-kinase but not in cells overexpressing dominant-negative Sos or beta-galactosidase. CCK-induced p70 S6 kinase activity was inhibited in parallel with the expression levels of kinase-deficient PKCalpha, whereas it was unaffected by the expression of kinase-deficient PKCdelta or PKCepsilon.PKCalpha is implicated in CCK-induced activation of p70 S6 kinase in AR42J cells.
- Published
- 2005
25. A case of acute pancreatitis associated with cationic trypsinogen N29T mutation
- Author
-
Masahiko Sugano, Kiyoshi Oshiro, Yoshinori Okabayashi, Yoshiaki Kido, Fukashi Ochi, Toshiyuki Sakai, Masaki Mita, and Masatoshi Fujii
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,Pancreatic disease ,Trypsinogen ,Endocrinology, Diabetes and Metabolism ,DNA Mutational Analysis ,Mutation, Missense ,Biology ,Bioinformatics ,chemistry.chemical_compound ,Endocrinology ,Internal Medicine ,medicine ,Humans ,Trypsin ,Hepatology ,Base Sequence ,DNA ,medicine.disease ,chemistry ,Pancreatitis ,Mutation (genetic algorithm) ,Acute Disease ,Acute pancreatitis ,Female - Published
- 2003
26. Pedunculated early carcinoma of supra-ampullary duodenum presenting as acute pancreatitis
- Author
-
Masahiko Sugano, Shinpei Tateiwa, Yoshinori Okabayashi, Kiyoshi Oshiro, Toshiyuki Sakai, Fukashi Ochi, Masatoshi Fujii, and Yasuo Okamoto
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pancreatic disease ,medicine.medical_treatment ,Gastroenterology ,Diagnosis, Differential ,Endocrinology ,Duodenal Neoplasms ,Internal medicine ,medicine ,Carcinoma ,Humans ,Duodenal Neoplasm ,business.industry ,medicine.disease ,Polypectomy ,Major duodenal papilla ,medicine.anatomical_structure ,Oncology ,Pancreatitis ,Acute Disease ,Duodenum ,Acute pancreatitis ,Radiology ,business - Abstract
Background. A 43-yr-old man was admitted to our hospital after sudden onset of epigastric pain. He was diagnosed with acute pancreatitis by clinical, laboratory, and radiographic signs. Examinations for the etiology of acute pancreatitis revealed a duodenal tumor arising at the proximal portion of the descending limb, extending by a long stalk, and coming into contact with Vater's papilla. The tumor was snare-resected endoscopically. Histological examination showed an early carcinoma. Extra-ampullary carcinoma of the duodenum should be considered an unusual cause of acute pancreatitis secondary to obstruction of the major duodenal papilla. Endoscopic polypectomy is effective because of the difficulty in making a precise diagnosis by endoscopic biopsy.
- Published
- 2003
27. Role of Akt in growth and survival of PANC-1 pancreatic cancer cells
- Author
-
Masato Kasuga, Zan Yao, Tadahiro Kitamura, Yoshinori Okabayashi, Yoshihiro Yutsudo, and Wataru Ogawa
- Subjects
Pancreatic disease ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Cellular differentiation ,Genetic Vectors ,Apoptosis ,Biology ,Protein Serine-Threonine Kinases ,Phosphatidylinositol 3-Kinases ,Endocrinology ,Pancreatic cancer ,Proto-Oncogene Proteins ,Internal Medicine ,medicine ,Tumor Cells, Cultured ,Humans ,Insulin-Like Growth Factor I ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Phosphoinositide-3 Kinase Inhibitors ,Hepatology ,Cell growth ,Growth factor ,medicine.disease ,Enzyme Activation ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Mutation ,Cancer research ,Pancreas ,Proto-Oncogene Proteins c-akt ,Cell Division ,Protein Binding - Abstract
Akt is involved in different cellular processes such as cell growth, cell differentiation, and anti-apoptosis.To investigate the role of Akt in cell growth and survival in PANC-1 pancreatic cancer cells.Insulin-like growth factor (IGF)-I induced Akt activation in a dose-dependent manner and stimulated anchorage-dependent and anchorage-independent cell growth of PANC-1 cells. In PANC-1 cells infected with adenovirus vectors carrying kinase-deficient Akt, anchorage-dependent and anchorage-independent cell growth was significantly reduced in the presence or absence of IGF-I compared with cells infected with adenovirus vectors carrying wild-type Akt, although IGF-I significantly stimulated cell growth in both transfected cell lines. Conversely, in PANC-1 cells infected with adenovirus vectors carrying kinase-deficient Akt, typical DNA laddering was undetectable in DNA fragmentation assay, and DNA 3;-OH reactivity was not detected in TUNEL assay. We then examined the role of phosphatidylinositol 3-kinase (PI3-K), an upstream mediator of Akt, on cell survival. In PANC-1 cells infected with adenovirus vector carrying a deletion mutant of the 85-kDa regulatory subunit of PI3-K and in cells treated with PI3-K inhibitor wortmannin, typical DNA laddering was evident in DNA fragmentation assay. In TUNEL assay, nuclear condensation and DNA 3;-OH reactivity was observed in approximately 30% of these cells.The present results indicate that Akt is implicated in cell growth, but not in survival in PANC-1 cells. These results suggest that there may be an alternative survival signal cascade from PI3-K in PANC-1 cells.
- Published
- 2001
28. Shc and CEACAM1 interact to regulate the mitogenic action of insulin
- Author
-
Yoshinori Okabayashi, Matthew N. Poy, Mats A. Fernström, Sonia M. Najjar, and Randall J. Ruch
- Subjects
Male ,Src Homology 2 Domain-Containing, Transforming Protein 1 ,MAP Kinase Signaling System ,Recombinant Fusion Proteins ,Down-Regulation ,Biology ,Protein Serine-Threonine Kinases ,SH2 domain ,environment and public health ,Biochemistry ,Culture Media, Serum-Free ,Mice ,Phosphatidylinositol 3-Kinases ,Antigens, CD ,Insulin receptor substrate ,Proto-Oncogene Proteins ,Animals ,Humans ,Insulin ,Phosphorylation ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Cells, Cultured ,Adaptor Proteins, Signal Transducing ,Proteins ,Cell Biology ,3T3 Cells ,Antigens, Differentiation ,Precipitin Tests ,IRS2 ,Receptor, Insulin ,Cell biology ,Carcinoembryonic Antigen ,Insulin receptor ,Adaptor Proteins, Vesicular Transport ,Shc Signaling Adaptor Proteins ,Mitogen-activated protein kinase ,Receptors, Mitogen ,biology.protein ,Hepatocytes ,GRB2 ,biological phenomena, cell phenomena, and immunity ,Mitogens ,Cell Adhesion Molecules ,Proto-Oncogene Proteins c-akt ,Cell Division ,Protein Binding - Abstract
CEACAM1, a tumor suppressor (previously known as pp120), is a plasma membrane protein that undergoes phosphorylation on Tyr(488) in its cytoplasmic tail by the insulin receptor tyrosine kinase. Co-expression of CEACAM1 with insulin receptors decreased cell growth in response to insulin. Co-immunoprecipitation experiments in intact NIH 3T3 cells and glutathione S-transferase pull-down assays revealed that phosphorylated Tyr(488) in CEACAM1 binds to the SH2 domain of Shc, another substrate of the insulin receptor. Overexpressing Shc SH2 domain relieved endogenous Shc from binding to CEACAM1 and restored MAP kinase activity, growth of cells in response to insulin, and their colonization in soft agar. Thus, by binding to Shc, CEACAM1 sequesters this major coupler of Grb2 to the insulin receptor and down-regulates the Ras/MAP kinase mitogenesis pathway. Additionally, CEACAM1 binding to Shc enhances its ability to compete with IRS-1 for phosphorylation by the insulin receptor. This leads to a decrease in IRS-1 binding to phosphoinositide 3'-kinase and to the down-regulation of the phosphoinositide 3'-kinase/Akt pathway that mediates cell proliferation and survival. Thus, binding to Shc appears to constitute a major mechanism for the down-regulatory effect of CEACAM1 on cell proliferation.
- Published
- 2001
29. Shc mediates ligand-induced internalization of epidermal growth factor receptors
- Author
-
Yoshinori Okabayashi, Masato Kasuga, and Kazuhiko Sakaguchi
- Subjects
Src Homology 2 Domain-Containing, Transforming Protein 1 ,Macromolecular Substances ,media_common.quotation_subject ,Amino Acid Motifs ,Biophysics ,Adaptor Protein Complex 2 ,Fluorescent Antibody Technique ,Peptide ,Peptide binding ,Biology ,Endocytosis ,Ligands ,environment and public health ,Biochemistry ,Cell Line ,Iodine Radioisotopes ,Adaptor Protein Complex alpha Subunits ,Epidermal growth factor ,Animals ,Humans ,Internalization ,Receptor ,Molecular Biology ,media_common ,Adaptor Proteins, Signal Transducing ,chemistry.chemical_classification ,Epidermal Growth Factor ,Membrane Proteins ,Proteins ,Cell Biology ,Ligand (biochemistry) ,Immunohistochemistry ,In vitro ,Peptide Fragments ,Cell biology ,ErbB Receptors ,Adaptor Proteins, Vesicular Transport ,chemistry ,Shc Signaling Adaptor Proteins ,COS Cells ,Mutagenesis, Site-Directed ,biological phenomena, cell phenomena, and immunity ,hormones, hormone substitutes, and hormone antagonists ,Protein Binding - Abstract
In order to clarify the physiological relevance of the interaction between Shc and adaptins, components of plasma membrane-coated pit adaptor complex AP2, we investigated the role of Shc in ligand-induced endocytosis of epidermal growth factor (EGF) receptors. In vitro peptide binding assay showed that α-adaptin bound to the wild-type peptide corresponding to amino acids 346–355 of Shc, RDLFDMKPFE, but not to the mutant peptide in which both phenylalanines at 349 and 354 were substituted for alanines (FA). Using adenovirus vectors carrying a herpes simplex virus epitope-tagged 52-kDa wild-type Shc and Shc FA, we examined the interaction between Shc, AP2, and EGF receptors in intact cells. Alpha-adaptin bound to wild-type Shc in an EGF-dependent manner, whereas EGF-dependent association of α-adaptin with Shc FA was markedly reduced. In addition, EGF increased the amount of α-adaptin coprecipitated with EGF receptors in cells expressing wild-type Shc but not Shc FA. These results suggest that EGF stimulates Shc-AP2 complex formation and association of Shc-AP2 complexes with EGF receptors. Internalization assay showed that 125 I-EGF internalization was reduced in cells overexpressing Shc FA. Immunofluorescence study showed that punctate staining along the plasma membrane border as well as punctate pattern characteristic of cytoplasmic vesicles near the plasma membrane was enhanced in cells expressing wild-type Shc. These results suggest, therefore, the implication of Shc in ligand-induced endocytosis of EGF receptors in intact cells.
- Published
- 2001
30. A case of acute pancreatitis complicating Salmonella enteritis
- Author
-
Seitetsu Yoon, Ryoji Yoneda, Hirotoshi Hamaguchi, Hirohisa Ueno, Yoshinori Okabayashi, Masato Kasuga, and Motoyoshi Sakaue
- Subjects
Adult ,medicine.medical_specialty ,Pancreatic disease ,Salmonella enteritidis ,Salmonella enteritis ,Gastroenterology ,Enteritis ,Bacterial enteritis ,Endocrinology ,Internal medicine ,Medicine ,Humans ,business.industry ,Lipase ,medicine.disease ,Oncology ,Pancreatitis ,Acute Disease ,Amylases ,Salmonella Infections ,Acute pancreatitis ,Female ,business ,Complication ,Tomography, X-Ray Computed - Abstract
We report a case of acute pancreatitis complicating Salmonella enteritis. A 43-yr-old woman who was admitted to our department because of Salmonella enteritis developed clinical acute pancreatitis with laboratory and radiographic signs on the fourth hospital day. She was free from symptoms on the eighth hospital day, but her elevated serum amylase and lipase levels persisted for more than 2 m.o. In this case, clinical acute pancreatitis was a complication of bacterial enteritis caused by Salmonella enteritidis, and it was characterized by onset a few days after the onset of enteritis and by sustained elevation of serum pancreatic enzyme levels.
- Published
- 2000
31. Shc phosphotyrosine-binding domain dominantly interacts with epidermal growth factor receptors and mediates Ras activation in intact cells
- Author
-
Yoko Matsumura, Yoshinori Okabayashi, Yoshiaki Kido, Sachiko Kimura, Masato Kasuga, Kazuhiko Sakaguchi, and Koichi Inushima
- Subjects
Phosphotyrosine binding ,Src Homology 2 Domain-Containing, Transforming Protein 1 ,CHO Cells ,Biology ,SH2 domain ,Arginine ,environment and public health ,src Homology Domains ,chemistry.chemical_compound ,Endocrinology ,Cricetinae ,Animals ,Humans ,Phosphotyrosine ,Molecular Biology ,Adaptor Proteins, Signal Transducing ,Lysine ,Autophosphorylation ,Cell Membrane ,Proteins ,Tyrosine phosphorylation ,Biological Transport ,General Medicine ,Cell biology ,Protein Structure, Tertiary ,ErbB Receptors ,Molecular Weight ,Adaptor Proteins, Vesicular Transport ,chemistry ,Biochemistry ,Amino Acid Substitution ,Shc Signaling Adaptor Proteins ,biology.protein ,Mutagenesis, Site-Directed ,ras Proteins ,GRB2 ,biological phenomena, cell phenomena, and immunity ,Phosphotyrosine-binding domain ,hormones, hormone substitutes, and hormone antagonists ,Proto-oncogene tyrosine-protein kinase Src - Abstract
The adaptor protein Shc contains a phosphotyrosine binding (PTB) domain and a Src homology 2 (SH2) domain, both of which are known to interact with phosphorylated tyrosines. We have shown previously that tyrosine 1148 of the activated epidermal growth factor (EGF) receptor is a major binding site for Shc while tyrosine 1173 is a secondary binding site in intact cells. In the present study, we investigated the interaction between the PTB and SH2 domains of Shc and the activated human EGF receptor. Mutant 52-kDa Shc with an arginine-to-lysine substitution at residue 175 in the PTB domain (Shc R175K) or 397 in the SH2 domain (Shc R397K) was coexpressed in Chinese hamster ovary cells overexpressing the wild-type or mutant EGF receptors that retained only one of the autophosphorylation sites at tyrosine 1148 (QM1148) or 1173 (QM1173). Shc R397K was coprecipitated with the QM1148 and QM1173 receptors, was tyrosine-phosphorylated, and associated with Grb2 and Sos. In contrast, coprecipitation of Shc R175K with the mutant receptors was barely detectable. In cells expressing the QM1173 receptor, Shc R175K was tyrosine-phosphorylated and associated with Grb2, while association of Sos was barely detectable. In cells expressing the QM1148 receptor, tyrosine phosphorylation of Shc R175K was markedly reduced. When both Shc R175K and 46-kDa Shc R397K were coexpressed with the mutant receptors, p46 Shc R397K was dominantly tyrosine-phosphorylated. In cells expressing the wild-type receptor, Shc R397K, but not Shc R175K, translocated to the membrane in an EGF-dependent manner. In addition, Ras activity stimulated by the immunoprecipitates of Shc R397K was significantly higher than that by the immunoprecipitates of Shc R175K. The present results indicate that tyrosine 1148 of the activated EGF receptor mainly interacts with the Shc PTB domain in intact cells. Tyrosine 1173 interacts with both the PTB and SH2 domains, although the interaction with the PTB domain is dominant. In addition, Shc bound to the activated EGF receptor via the PTB domain dominantly interacts with Grb2-Sos complex and plays a major role in the Ras-signaling pathway.
- Published
- 1998
32. Multiple gastric ulcers caused by a rice cake as an intragastric foreign body
- Author
-
Kunihiko Wakamura, Daisuke Obata, Masanori Sakashita, Takahiro Horimatsu, Yoshinori Okabayashi, Masatoshi Fujii, Kazuya Iwamoto, and Shinwa Tanaka
- Subjects
Male ,Multiple gastric ulcers ,medicine.medical_specialty ,Gastric Outlet Obstruction ,business.industry ,Foreign-Body Reaction ,General surgery ,Gastroenterology ,Oryza ,Hepatology ,medicine.disease ,Endoscopy, Gastrointestinal ,Colorectal surgery ,Surgical oncology ,Internal medicine ,Pyloric Antrum ,Humans ,Medicine ,Stomach Ulcer ,Foreign body ,Tomography, X-Ray Computed ,business ,Aged ,Abdominal surgery - Published
- 2006
33. Epidermal growth factor stimulates the tyrosine phosphorylation of SHPS-1 and association of SHPS-1 with SHP-2, a SH2 domain-containing protein tyrosine phosphatase
- Author
-
Yoshinori Okabayashi, Takashi Matozaki, Tetsuya Noguchi, Yohsuke Fujioka, Fukashi Ochi, Hitoshi Takeda, Masahiro Tsuda, Masato Kasuga, Takuji Yamao, Kaoru Fukunaga, and Toshiyuki Takada
- Subjects
SH2 Domain-Containing Protein Tyrosine Phosphatases ,Immunoblotting ,Biophysics ,Neural Cell Adhesion Molecule L1 ,Protein Tyrosine Phosphatase, Non-Receptor Type 11 ,Protein tyrosine phosphatase ,CHO Cells ,SH2 domain ,Biochemistry ,Receptor tyrosine kinase ,src Homology Domains ,chemistry.chemical_compound ,Cricetinae ,Animals ,Humans ,Phosphorylation ,Receptors, Immunologic ,Molecular Biology ,Membrane Glycoproteins ,biology ,Epidermal Growth Factor ,Chemistry ,Protein Tyrosine Phosphatase, Non-Receptor Type 6 ,Intracellular Signaling Peptides and Proteins ,Tyrosine phosphorylation ,Cell Biology ,Molecular biology ,Antigens, Differentiation ,Precipitin Tests ,Rats ,ErbB Receptors ,biology.protein ,Tyrosine ,GRB2 ,Protein Tyrosine Phosphatases ,Platelet-derived growth factor receptor ,Proto-oncogene tyrosine-protein kinase Src - Abstract
SHPS-1 is a 120 kDa glycosylated receptor-like protein that contains immunoglobulin-like domains in its extracellular region and four potential tyrosine phosphorylation for SH2 domain binding sites in its cytoplasmic region. Epidermal growth factor (EGF) stimulated the rapid tyrosine phosphorylation of SHPS-1 and subsequent association of SHPS-1 with SHP-2, a protein tyrosine phosphatase containing SH2 domains, in Chinese hamster ovary cells overexpressing human EGF receptors. In the cells overexpressing SHPS-1, the tyrosine phosphorylation of SHPS-1 was more evident than that observed in parent cells. However, overexpression of SHPS-1 alone did not affect the activation of MAP kinase in response to EGF. These results suggest that SHPS-1 may be involved in the recruitment of SHP-2 from the cytosol to the plasma membrane in response to EGF.
- Published
- 1997
34. Enhancement of the mitogenic effect by artificial juxtacrine stimulation using immobilized EGF
- Author
-
Yoshinori Okabayashi, Yukio Imanishi, Jing-Song Li, Yoshiaki Kido, Masato Kasuga, Takashi Takahashi, and Yoshihiro Ito
- Subjects
medicine.medical_treatment ,Acrylic Resins ,Stimulation ,macromolecular substances ,CHO Cells ,Biochemistry ,Mice ,Epidermal growth factor ,Cricetinae ,medicine ,Animals ,Methylmethacrylates ,Phosphorylation ,Protein kinase A ,Molecular Biology ,DNA synthesis ,Epidermal Growth Factor ,Chemistry ,Chinese hamster ovary cell ,Growth factor ,Autophosphorylation ,technology, industry, and agriculture ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,equipment and supplies ,Juxtacrine signalling ,Molecular biology ,Enzyme Activation ,ErbB Receptors ,Calcium-Calmodulin-Dependent Protein Kinases ,hormones, hormone substitutes, and hormone antagonists - Abstract
Mouse epidermal growth factor (EGF) was covalently conjugated with the water-soluble polymer, poly(acrylic acid) (EGF-PAA), or with the water-insoluble polymer, surface-hydrolyzed poly(methyl methacrylate) (EGF-PMMA). Immobilized EGF (EGF-PMMA) stimulated DNA synthesis in Chinese hamster ovary cells overexpressing EGF receptors in amounts that were 5 to 10% of those of free EGF required for comparable effects. In addition, the maximal mitogenic effect of EGF-PMMA was greater than that of unconjugated EGF or EGF-PAA. EGF, EGF-PAA, and EGF-PMMA induced the autophosphorylation of EGF receptors and the stimulation of mitogen-activated protein kinase. However, whereas the onset of these effects was delayed with EGF-PMMA, they persisted for much longer than those of EGF and EGF-PAA. Unlike EGF and EGF-PAA, EGF-PMMA was not associated with cells after their removal from culture and did not induce receptor internalization. Culturing cells with PMMA-immobilized EGF thus represents a model system for studying "juxtacrine" stimulation of cells by membrane-bound growth factors.
- Published
- 1997
35. Ethanol inhibits CCK-induced enzyme secretion by affecting calcium-pump activity in isolated rat pancreatic acini
- Author
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Yoshinori Okabayashi, Issei Tachibana, Kenji Matsushita, Makoto Otsuki, Toshiharu Akiyama, and Makoto Koide
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,chemistry.chemical_element ,Calcium-Transporting ATPases ,Calcium ,Sincalide ,chemistry.chemical_compound ,Endocrinology ,GTP-Binding Proteins ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Secretion ,Rats, Wistar ,Cyclic GMP ,Pancreas ,Cholecystokinin ,Ethanol ,Hepatology ,Pancreatic Exocrine Secretion ,Chemistry ,Activator (genetics) ,Rats ,Intracellular signal transduction ,Cytosol ,Kinetics ,Amylases ,Sodium Fluoride - Abstract
The aim of this study was to clarify the effect of ethanol on stimulus-secretion coupling in pancreatic exocrine secretion. We investigated the effects of 600 mM ethanol on cholecystokinin octapeptide (CCK-8)-stimulated amylase release, cytosolic free Ca 2+ concentration ([Ca 2+ ] i ) and Ca 2+ fluxes using in vitro isolated rat pancreatic acini. Ethanol, given alone, stimulated both the initial and the sustained phases of amylase release. On the other hand, ethanol inhibited only the sustained phase of amylase release stimulated by CCK-8. Ethanol also inhibited amylase release in response to fluoride, a direct activator of guanine nucleotide-binding protein, suggesting that ethanol affects intracellular signal transduction molecules. Ethanol had no influences on the initial rise but increased the sustained rise in [Ca 2+ ] i stimulated by CCK-8 and inhibited CCK-8-stimulated Ca 2+ outflux without affecting Ca 2+ influx. 8-Bromoguanosine 3' :5'-cyclic monophosphate, a membrane-permeable analogue of cGMP regulating membrane Ca 2+ -pump activity in various cells, completely reversed the ethanol-induced inhibition of amylase release and Ca 2+ outflux in response to CCK-8 as well as fluoride. Given that Ca 2+ plays a critical role in stimulus-secretion coupling in pancreatic exocrine secretion, our results indicate that 600 mM ethanol inhibits CCK-8-stimulated amylase release by inhibiting Ca 2+ -pump activity on the plasma membrane.
- Published
- 1996
36. Role of endogenous bile on basal and postprandial CCK release in humans
- Author
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Yoshinori Okabayashi, Makoto Koide, and Makoto Otsuki
- Subjects
Adult ,Male ,medicine.medical_specialty ,Ampulla of Vater ,Time Factors ,Physiology ,Common Bile Duct Neoplasms ,Peptide hormone ,Biology ,digestive system ,Basal (phylogenetics) ,Eating ,Adenoma, Bile Duct ,Internal medicine ,Blood plasma ,medicine ,Bile ,Humans ,Cholecystokinin ,Aged ,Cholestasis ,digestive, oral, and skin physiology ,Gastroenterology ,Liter ,Middle Aged ,Pancreatic Neoplasms ,medicine.anatomical_structure ,Postprandial ,Endocrinology ,Gastrointestinal hormone ,Bile Duct Neoplasms ,Duodenum ,Drainage ,Female - Abstract
The role of intraduodenal bile in regulation of plasma cholecystokinin (CCK) levels were investigated in patients with obstructive jaundice under external bile diversion and under physiological bile flow into the duodenum by internal bile drainage. Basal plasma CCK levels determined by a specific and sensitive bioassay in patients under external bile drainage (2.2 +/- 0.2 pmol/liter; mean +/- SE) were significantly higher than those in control subjects (1.0 +/- 0.3 pmol/liter). In control subjects, the peak CCK response (6.2 +/- 0.7 pmol/liter) to a test meal was seen at 45 min, whereas that in patients under external bile drainage, it was seen at 20 min after a test meal (17.6 +/- 3.2 pmol/liter; P0.01 vs controls). After peak response, plasma CCK levels in controls gradually decreased, but remained significantly elevated during a 3-hr observation period. In patients under bile diversion, the test meal caused a prompt plasma CCK peak, with a transient fall followed by a continuous rise until 180 min postprandially. In six patients, external bile diversion was changed to internal biliary drainage with a stent tube within two weeks to maintain physiological bile flow into the duodenum. Internal bile drainage normalized basal (0.9 +/- 0.2 pmol/liter) as well as meal-stimulated CCK release (peak value: 5.0 +/- 0.8 pmol/liter). These results demonstrate that endogenous bile exerts tonic inhibition on basal and postprandial plasma CCK levels in humans.
- Published
- 1993
37. Effect of islet hormones on secretin-stimulated exocrine secretion in isolated perfused rat pancreas
- Author
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Yoshinori Okabayashi, Hiroshi Hasegawa, Makoto Koide, Toshio Okutani, Makoto Otsuki, Yoshiaki Kido, Kenji Matsushita, and Masato Kasuga
- Subjects
Male ,endocrine system ,medicine.medical_specialty ,Physiology ,Biology ,In Vitro Techniques ,Octreotide ,digestive system ,Secretin ,Pancreatic Juice ,Internal medicine ,medicine ,Animals ,Drug Interactions ,Rats, Wistar ,Ouabain ,Pancreas ,Pancreatic hormone ,Pancreatic juice secretion ,geography ,geography.geographical_feature_category ,Dose-Response Relationship, Drug ,Gastroenterology ,Pancreatic Ducts ,Islet ,Pancreatic Hormones ,Stimulation, Chemical ,Rats ,Somatostatin ,Endocrinology ,medicine.anatomical_structure ,Gastrointestinal hormone ,Pancreatic juice ,hormones, hormone substitutes, and hormone antagonists - Abstract
To clarify the effect of islet hormones on pancreatic ductular cell function, we measured the exocrine secretion elicited by 10 pM secretin in the presence or absence of islet hormones using an isolated perfused rat pancreas model. Insulin significantly increased secretin-stimulated pancreatic juice secretion, but not protein secretion. The potentiating effect of insulin on pancreatic juice secretion was concentration-dependent, and the maximal effect was observed with 1 microM insulin. Ouabain, a specific Na+,K(+)-ATPase inhibitor, caused concentration-dependent inhibition of the potentiating effect of insulin without affecting secretin action. Glucagon (100 nM) significantly inhibited secretin-stimulated pancreatic juice secretion and also tended to inhibit protein secretion. A somatostatin analog, SMS 201-995 (10 nM) significantly inhibited both the pancreatic juice and protein secretion stimulated by secretin. The inhibitory effect of SMS 201-995 was concentration-dependent and was maximal at 1-10 nM. These results demonstrate that insulin potentiates the secretory response to secretin, at least partly by increasing Na+,K(+)-ATPase activity, whereas glucagon and somatostatin inhibit this response. Thus, pancreatic islet hormones regulate the secretory function of pancreatic ductular and centroacinar cells.
- Published
- 1993
38. In vitro inhibitory effect of somatostatin on secretin action in exocrine pancreas of rats
- Author
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Yoshinori Okabayashi, Yoshiaki Kido, Kenji Matsushita, Yutaka Sugimoto, Makoto Koide, Hiroshi Hasegawa, Masato Kasuga, and Toshio Okutani
- Subjects
Male ,medicine.medical_specialty ,Vasoactive intestinal peptide ,8-Bromo Cyclic Adenosine Monophosphate ,Biology ,In Vitro Techniques ,Octreotide ,digestive system ,Sincalide ,Secretin ,Receptors, G-Protein-Coupled ,Receptors, Gastrointestinal Hormone ,Internal medicine ,medicine ,Cyclic AMP ,Somatostatin receptor 2 ,Animals ,Rats, Wistar ,Pancreas ,Pancreatic hormone ,Cholecystokinin ,Delta cell ,Hepatology ,Dose-Response Relationship, Drug ,Somatostatin receptor ,Gastroenterology ,Rats ,Kinetics ,Somatostatin ,Endocrinology ,Amylases ,Receptors, Vasoactive Intestinal Peptide ,hormones, hormone substitutes, and hormone antagonists ,Vasoactive Intestinal Peptide - Abstract
Background: Exocrine pancreatic function is influenced by pancreatic islet hormones. Although the existence of somatostatin receptors has been shown on pancreatic acinar cells, the in vitro effect of somatostatin on exocrine secretory function has not been established. Methods: Using isolated rat pancreatic acini, the effect of somatostatin analog SMS 201-995 (SMS) and somatostatin 14 (S-14) on amylase release, cyclic adenosine monophosphate (cAMP) production, and hormone binding were determined. Results: SMS inhibited the potentiating effect of secretin on amylase response to cholecystokinin octapeptide (CCK-8) in a concentration-dependent manner. The inhibitory effects of SMS and S-14 were similar on a molar basis and were observed when vasoactive intestinal polypeptide (VIP) but not 8bromoadenosine 3′:5′ cyclic monophosphate was used instead of secretin and when carbachol, bombesin, A23187, and 12-O-tetradecanoylphorbol 13-acetate were used instead of CCK-8. SMS inhibited secretin-induced cAMP production, and the dose-inhibition curve for cAMP was similar to that for amylase release. SMS had no influence on 125 I-secretin and 125 I-VIP binding. Conclusions: Somatostatin acts directly on acinar cells and inhibits secretin potentiation of secretory response in part by inhibiting secretin-induced cAMP production.
- Published
- 1993
39. Involvement of endogenous cholecystokinin in the development of acute pancreatitis induced by closed duodenal loop
- Author
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Makoto Otsuki, Hiroshi Itoh, Satoshi Tani, Makoto Koide, and Yoshinori Okabayashi
- Subjects
Male ,medicine.medical_specialty ,Pancreatic disease ,Proglumide ,Duodenum ,Endocrinology, Diabetes and Metabolism ,Cholecystokinin receptor ,Subcutaneous injection ,Endocrinology ,Internal medicine ,Internal Medicine ,Medicine ,Animals ,Rats, Wistar ,Pancreas ,Cholecystokinin ,Hepatology ,business.industry ,Lipase ,medicine.disease ,Rats ,Disease Models, Animal ,medicine.anatomical_structure ,Pancreatitis ,Acute Disease ,Amylases ,Acute pancreatitis ,business ,medicine.drug - Abstract
Involvement of endogenous cholecystokinin (CCK) in the development of acute pancreatitis induced in rats by closed duodenal loop (CDL) was examined, and the effects of the potent and specific CCK receptor antagonist loxiglumide on this model of acute pancreatitis were evaluated. Plasma CCK bioactivity was markedly elevated 3 and 6 h after onset of acute pancreatitis. A single subcutaneous injection of 50 mg/kg body wt of loxiglumide 30 min before the induction of acute pancreatitis completely eliminated the hypercholecystokinemia. Loxiglumide given 3 h after the induction of acute pancreatitis suppressed plasma CCK bioactivity, which had risen up to 30-fold over basal value (0 h) at 3 h, to nearly the basal level. Loxiglumide pretreatment, in addition, significantly prevented the rise in serum amylase and lipase activity, as well as the increase in ascitic volume. It also ameliorated histological alterations of hemorrhagic and necrotizing pancreatitis. Reduction of plasma CCK bioactivity by loxiglumide after the onset of pancreatitis slowed the rate of progression of pancreatitis. However, pancreatic wet weight and cellular infiltration were not significantly influenced by loxiglumide treatment. These observations suggest that endogenous CCK is not involved in the initiation of acute hemorrhagic and necrotizing pancreatitis induced by CDL, but is involved in the development of pancreatitis in this model.
- Published
- 1993
40. Fasting prevents acute pancreatitis induced by cerulein in rats
- Author
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Yoshinori Okabayashi, Makoto Otsuki, Takahiko Nakamura, Takashi Fujisawa, Masatoshi Fujii, Makoto Koide, Hiroshi Itoh, and Satoshi Tani
- Subjects
Male ,medicine.medical_specialty ,Pancreatic disease ,Physiology ,Peptide hormone ,Secretin ,Internal medicine ,medicine ,Animals ,Amylase ,Pancreas ,Cholecystokinin ,biology ,business.industry ,Gastroenterology ,Rats, Inbred Strains ,Fasting ,medicine.disease ,Rats ,Endocrinology ,Proglumide ,Gastrointestinal hormone ,Pancreatitis ,Acute Disease ,biology.protein ,Acute pancreatitis ,business ,Ceruletide - Abstract
We examined the effect of fasting on the course of experimental acute pancreatitis induced in rats by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Rats were either fasted from 24 hr before to 9 hr after the first cerulein injection or fed ad libitum throughout the experiment. Twenty-four hours of fasting reduced cerulein-induced increases in serum levels of amylase and anionic trypsin(ogen) to 50 and 70% of those in fed rats, respectively. Increases in pancreatic wet weight after cerulein injections were also less in fasted rats than in fed rats. Pancreatic content of trypsin was significantly decreased after a 24-hr fast, and no further changes were induced by cerulein injections. The histological signs of acute pancreatitis were greatly alleviated by fasting. However, 24 hr of fasting did not alter the sensitivity and responsiveness of the exocrine pancreas to cerulein in both in vivo and in vitro. Plasma CCK bioactivity and immunoreactive secretin concentration in 24-hr-fasted rats were significantly lower than those in fed rats. Administration of CCK receptor antagonist, loxiglumide, 12 hr prior to the induction of acute pancreatitis reduced the increase in serum amylase activity in fed rats to nearly the same levels as that in fasted rats and alleviated histological signs of pancreatitis to some extent. These present observations suggest that fasting lessens the severity of cerulein-induced acute pancreatitis by reducing endogenous CCK release.
- Published
- 1990
41. Proglumide analogues CR 1409 and CR 1392 inhibit cholecystokinin-stimulated insulin release more potently than exocrine secretion from the isolated perfused rat pancreas
- Author
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Yoshinori Okabayashi, Makoto Otsuki, Shigeaki Baba, Takashi X. Fujisawa, Masatoshi Fujii, Takahiko Nakamura, Hiroshi Hasegawa, Satoshi Tani, and Makoto Koide
- Subjects
Male ,medicine.medical_specialty ,Proglumide ,Endocrinology, Diabetes and Metabolism ,Glutamine ,Radioimmunoassay ,Neuropeptide ,Stimulation ,Biology ,In Vitro Techniques ,digestive system ,Cholecystokinin receptor ,Islets of Langerhans ,Endocrinology ,Internal medicine ,Insulin Secretion ,Internal Medicine ,medicine ,Animals ,Insulin ,Receptor ,Pancreas ,Cholecystokinin ,Hepatology ,digestive, oral, and skin physiology ,Rats, Inbred Strains ,Rats ,Secretory protein ,Pancreatic juice ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
The effects of proglumide-related cholecystokinin (CCK) receptor antagonists CR 1409 and CR 1392 on CCK-octapeptide (CCK-8)-stimulated immunoreactive insulin (IRI) release and exocrine secretion were examined simultaneously in the isolated perfused rat pancreas. The CR 1409, at concentrations of 10-100 nM, significantly inhibited CCK-8 (100 pM) stimulation on IRI release but failed to inhibit the stimulatory effect of CCK-8 on both pancreatic juice flow and protein secretion. Increasing concentrations of CR 1409 inhibited both CCK-8-stimulated IRI release and exocrine secretion. Half-maximal inhibition was observed with approximately 2 nM for IRI release and 1 microM for protein secretion. When a higher dose (1 nM) of CCK-8 was used, the inhibitory effect of 10 nM CR 1409 on CCK-8-stimulated IRI release was abolished, whereas 10 microM CR 1409 retained significant inhibitory effect. Furthermore, 1 microM carbachol-induced IRI release was not altered by the addition of 10 microM CR 1409. The CR 1392 also had an inhibitory effect on both CCK-8-stimulated IRI release and exocrine secretion. The concentration of CR 1392 that caused half-maximal inhibition of CCK-8-stimulated IRI release was 300 times lower than that of exocrine secretion. In addition, 1 microM carbachol-stimulated IRI release was not altered by 100 microM CR 1392. Thus, the inhibitory effects of CR 1409 and CR 1392 on IRI release were mediated through the interaction at the CCK receptor and were more potent than those on juice and protein secretion. This study suggests, therefore, that CCK receptors on B cells might be different from those on acinar cells in terms of their relative affinities for antagonists.
- Published
- 1990
42. Effect of Gymnema sylvestre, R.Br. on glucose homeostasis in rats
- Author
-
Hiroshi Hasegawa, Yoshinori Okabayashi, Makoto Koide, Satoshi Tani, Makoto Otsuki, Masatoshi Fujii, Takashi Fujisawa, and Takahiko Nakamura
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Trypsinogen ,Endocrinology, Diabetes and Metabolism ,Diabetes Mellitus, Experimental ,chemistry.chemical_compound ,Endocrinology ,Oral administration ,Reference Values ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Glucose homeostasis ,Animals ,Homeostasis ,Insulin ,Amylase ,Pancreas ,Plants, Medicinal ,biology ,business.industry ,Body Weight ,Rats, Inbred Strains ,General Medicine ,Organ Size ,biology.organism_classification ,medicine.disease ,Rats ,Streptozocin ,Kinetics ,medicine.anatomical_structure ,chemistry ,Amylases ,biology.protein ,Gymnema sylvestre ,business - Abstract
Effect of Gymnema sylvestre , R.Br. ( G. sylvestre ; GS 4 ) on glucose homeostasis was studied in rats. In the first set of experiments, the acute effect of GS 4 was examined in both non-diabetic and streptozocin (30 mg/kg)-induced mildly diabetic rats. Administration of 1 g/kg body weight of GS 4 to 18-h fasted non-diabetic rats significantly attenuated the serum glucose response to oral administration of 1 g/kg glucose. The immunoreactive insulin (IRI) response in GS 4 -administered rats was lower, but not significantly, than that in control rats. In mildly diabetic rats, a 60 min increment in serum glucose concentrations was significantly reduced by GS 4 administration. No IRI response was observed in these diabetic rats irrespective of GS 4 administration. In the second set of experiments, the chronic effect of GS 4 was examined in mildly diabetic rats. Two weeks after the induction of diabetes, the rats were divided into two groups that had similar impairment of glucose tolerance assessed by an oral glucose loading test. The rats were fed for 32–35 days with either a control diet or a diet supplemented with GS 4 . After 4 weeks, GS 4 showed a tendency to reduce the serum glucose concentrations in the fed state and to improve the glucose tolerance. Gain in body weight, food intake, pancreas weight and the pancreatic contents of IRI, protein, amylase and trypsinogen were unaltered in the GS 4 -treated group compared with the control. These results suggest the usefulness of G. sylvestre in the treatment of certain classes of non-insulin-dependent diabetes mellitus.
- Published
- 1990
43. Effects of L-364,718 on pancreatic exocrine and endocrine secretion in the rat
- Author
-
Makoto Koide, Makoto Otsuki, Takahiko Nakamura, Takashi X. Fujisawa, Satoshi Tani, Yoshinori Okabayashi, and Masatoshi Fujii
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Radioimmunoassay ,Scopolamine Derivatives ,Devazepide ,Biology ,In Vitro Techniques ,digestive system ,Sincalide ,Islets of Langerhans ,Endocrinology ,Acinus ,Internal medicine ,Insulin Secretion ,Internal Medicine ,medicine ,Animals ,Insulin ,Secretion ,Amylase ,Pancreas ,Cholecystokinin ,Gastrin ,Benzodiazepinones ,Hepatology ,Pancreatic Exocrine Secretion ,digestive, oral, and skin physiology ,Rats, Inbred Strains ,N-Methylscopolamine ,Receptors, Muscarinic ,Rats ,medicine.anatomical_structure ,Amylases ,biology.protein ,hormones, hormone substitutes, and hormone antagonists - Abstract
We examined the inhibitory effect of L-364,718, a nonpeptide cholecystokinin (CCK) antagonist, on CCK stimulation of pancreatic exocrine and endocrine secretion in both the isolated pancreatic acini and the isolated perfused pancreata of rats. In the isolated acini, L-364,718 inhibited CCK octapeptide (CCK-8)-stimulated amylase release and binding of 125I-CCK-8 in a dose-dependent manner without appreciable effects on the basal amylase secretion. L-364,718 also inhibited amylase release in response to caerulein and gastrin I, but had no effect on amylase release stimulated by other secretagogues or by agents bypassing receptors. Similarly, binding of N-methylscopolamine to pancreatic acini was not inhibited by L-364,718. In the isolated perfused pancreata, L-364,718 inhibited CCK-8-stimulated pancreatic exocrine secretion and insulin release. The inhibitory effects of L-364,718 were more potent for insulin release than for exocrine secretion and persisted even after the removal of L-364,718 infusion. These results clearly demonstrate that L-364,718 is a specific, potent, and prolonged antagonist of CCK's stimulatory actions on pancreatic acinar and B cells.
- Published
- 1990
44. Regulating insulin-receptor-gene expression by differentiation and hormones
- Author
-
Ira D. Goldfine, Craig D. Logsdon, Antonio Brunetti, Alexander R McDonald, Betty A. Maddux, K. Y. Wong, Yoshinori Okabayashi, and P. W. Mamula
- Subjects
medicine.medical_specialty ,Macromolecular Substances ,Protein Conformation ,Endocrinology, Diabetes and Metabolism ,Cellular differentiation ,medicine.medical_treatment ,Downregulation and upregulation ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Humans ,Receptor ,Advanced and Specialized Nursing ,Messenger RNA ,biology ,business.industry ,Insulin ,Cell Differentiation ,Transfection ,Hormones ,Receptor, Insulin ,Cell biology ,Models, Structural ,Insulin receptor ,Endocrinology ,Gene Expression Regulation ,Cell culture ,biology.protein ,business - Abstract
Insulin regulates cell function by first binding to the insulin receptor (IR) localized on the cell surface. With the cloning of IR cDNA and the IR-gene promoter, the regulation of the IR gene during differentiation and by various hormones can be studied. Muscle is a major target tissue for insulin action. BC3H1 cells, a mouse muscle cell line in culture, are a model cell type for studying insulin action. Differentiation in these cells results in a 5- to 10-fold increase in IR binding and a 5- to 10-fold increase in IR content. Studies of IR mRNA by Northern and slot-blot analyses reveal a 10-fold increase in IR mRNA after differentiation. These studies indicate that there is a selective increase in IR-gene expression during muscle differentiation. A similar increase in IRgene expression is observed for the IR during pancreatic acinar cell differentiation. Glucocorticoids increase IR content in several target tissues. Studies in cultured IM-9 lymphocytes indicate that glucocorticoids induce a 5-fold increase in IR mRNA levels. Studies of IR mRNA half-life indicate that glucocorticoids do not alter IR mRNA stability. When the transcription of the IR is measured by elongation assays, glucocorticoids directly stimulate IR transcription 5- to 10-fold. The effect is detectable within 30 min of glucocorticoid treatment and is maximal within 2 h. Therefore, these studies demonstrate that the IR gene is under the direct regulation of glucocorticoids. Insulin downregulates the IR in various target tissues. Prior studies indicate that this downregulation was partly because of accelerated IR degradation. Studying AR42J pancreatic acinar cells, we also found that insulin accelerates IR degradation. Moreover, in these cells, insulin decreases IR biosynthesis by ∼50%. Studies of IR mRNA indicate there is a concomitant decrease in IR mRNA levels after insulin treatment. Thus, insulin decreases IR-gene expression. The genomic structure of the IR promoter has been elucidated. Primer extension and nuclease S, analysis indicate that IR mRNA has multiple start sites. The promoter fragment was ligated to a promoterless “reporter” plasmid containing the bacterial gene chloramphenicol acetyltransferase (CAT). When this plasmid is transfected into cultured cells, CAT activity is detected, indicating promoter activity. Various portions of a genomic fragment were ligated to a promoter to study glucocorticoid regulation of the IR promoter. These studies indicate that IR-gene expression is regulated by differentiation and hormonal agents. Differentiation in muscle and acinar pancreas is associated with an increase in IRmRNA. When differentiated cells are studied, glucocorticoids upregulate IR-gene expression, whereas insulin downregulates this function.
- Published
- 1990
45. New model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats
- Author
-
Takahiko Nakamura, Hiroshi Itoh, Satoshi Tani, Masatoshi Fujii, Makoto Koide, Makoto Otsuki, Takashi Fujisawa, and Yoshinori Okabayashi
- Subjects
Male ,medicine.medical_specialty ,Necrosis ,Time Factors ,Arginine ,Physiology ,medicine.medical_treatment ,Intraperitoneal injection ,Necrotic Change ,Internal medicine ,medicine ,Acinar cell ,Animals ,Amylase ,Pancreas ,chemistry.chemical_classification ,biology ,Gastroenterology ,Rats, Inbred Strains ,Trypsin ,Rats ,Enzyme ,Endocrinology ,chemistry ,Pancreatitis ,Acute Disease ,biology.protein ,medicine.symptom ,medicine.drug - Abstract
We examined the biological and histologic characteristics of a new experimental model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats. Rats were given a single intraperitoneal injection of 500 mg/100 g body weight of L-arginine. At 12-24 hr after the arginine injection, serum levels of amylase, lipase, and anionic trypsin(ogen) reached respective peak values 2, 5, and 20 times those of control rats without arginine and returned to control levels after 24-48 hr. The contents of pancreatic protein, DNA, and digestive enzymes were markedly reduced after the arginine injection and reached their nadirs at 72 hr. After 14 days these levels were almost normal. Histologic examination revealed a number of small vesicles within acinar cells at 6 hr, which were identified as markedly swollen mitochondria by the electron microscope. Other intracellular organelles and nuclei also showed degenerative changes. At 12 hr interstitial edema appeared, and acinar cell necrosis was seen after 24 hr. The extent and severity of necrotic changes of pancreatic exocrine tissue with inflammatory cell infiltration were maximal at 72 hr. At seven days, pancreatic acinar cells began to regenerate, and pancreatic architecture appeared almost normal after 14 days. The present study has demonstrated that the administration of excessive doses of arginine induces a new, noninvasive experimental model of acute necrotizing pancreatitis.
- Published
- 1990
46. Depressed type of inflammatory fibroid polyp of the colon
- Author
-
Yoshinori Okabayashi, Takuya Takahashi, Kazuya Iwamoto, Daisuke Obata, Masatoshi Fujii, Masanori Sakashita, and Shinwa Tanaka
- Subjects
Pathology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Colorectal cancer ,Gastroenterology ,Transverse colon ,Colonoscopy ,medicine.disease ,Chromoendoscopy ,Lesion ,medicine.anatomical_structure ,Submucosa ,Biopsy ,Medicine ,medicine.symptom ,business ,Inflammatory fibroid polyp - Abstract
Dear Editor: A 45-year-old man, who has been suffering from recurrent diarrhea and constipation, was referred to our hospital. Colonoscopy showed a reddened depressed lesion with marginal elevation in the transverse colon, near the hepatic flexure. After the mucosal surface was sprayed with indigo carmine or crystal violet dye, magnifying endoscopy revealed a type VI pit pattern of the Kudo’s classif ication in the central depression and a type I pit pattern in the surrounding area. Endoscopic ultrasonography showed that the lesion was inf iltrating into the submucosal layer. Therefore, we considered that the lesion might be a submucosal invasive colon cancer presenting like a submucosal tumor, although the biopsy specimen taken from the lesion did not contain distinct malignant components. Since we could not deny that the lesion was a malignant tumor, laparoscopy-assisted right hemicolectomy was performed. The resected specimen measured 18×18 mm in size. Zoom stereomicroscopy of the resected specimen demonstrated a type VN pit pattern in the part of the central depression, a type VI pit pattern in the rest area of the central depression, and a type I pattern in the surrounded area. Histological examination showed an enormous proliferation in the connective tissues and infiltration of eosinophils mainly in the submucosa. There were thickwalled vessels surrounded by the proliferative f ibromuscular f ibers, resulting in onion skin appearances. These f indings were compatible with inflammatory f ibroid polyp. The term “inflammatory f ibroid polyp” was introduced by Helwig and Rainer in 1953. Its etiology, suggested to be the involvement of inflammatory mechanisms or reactive responses, remains unclear. It usually forms a pedunculated or subpedunculated submucosal tumor, with erosion or ulceration overlying the mucosa. The lesions are solitary and occur predominantly in the stomach, small intestine, and rarely in the colon. Because it is usually located in the base mucosa and submucosa, diff iculty in obtaining a histological diagnosis before treatment was reported. Magnifying colonoscopy with chromoendoscopy was reported to be useful in differentiating almost all lesions detected at colonoscopy before histological evaluation. Kudo proposed the classification of the pit patterns: types I, II, IIIL, IIIs, IV, and V. Type V is divided into two types: VI and VN. In this classification, type I corresponds to normal gland, whereas type V corresponds to cancerous gland with type VN pointing towards submucosal infiltration. In the present study, magnifying endoscopy showed a type VI pit pattern in the central depression and a type I pattern in the surrounding area. These f indings, as well as depressed type macroscopic appearance, suggested that the lesion might be a depressed colon cancer, which is thought to posses high malignant potential. Zoom stereomicroscopic f indings corresponded to the endoscopic f indings, except for a demonstration of type VN pit pattern in the part of the central depression. In this case, the area showing type VN or VI pit pattern is thought to correspond to the lesion where the surface epithelium was abraded by benign erosive inflammation. With this result, it is suggested that endoscopists should be aware, when performing endoscopic examinations, that a colonic depressed lesion presenting a type V pit pattern can be an inflammatory f ibroid polyp. Int J Colorectal Dis (2007) 22:1409 DOI 10.1007/s00384-006-0180-z
- Published
- 2007
47. Vanishing gastric tumor
- Author
-
Masahiko Sugano, Toshiyuki Sakai, Masatoshi Fujii, Fukashi Ochi, Kiyoshi Oshiro, Yasuo Okamoto, Yoshinori Okabayashi, and Sinpei Tateiwa
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Stomach ,Gastroenterology ,MEDLINE ,Middle Aged ,Anisakiasis ,Neoplasm regression ,Endoscopy ,medicine.anatomical_structure ,Neoplasm Regression, Spontaneous ,Stomach Neoplasms ,Internal medicine ,Gastroscopy ,medicine ,Humans ,Female ,Radiology, Nuclear Medicine and imaging ,Gastric tumor ,business - Published
- 2002
48. Role of cholecystokinin in acute pancreatitis
- Author
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Makoto Koide, Issei Tachibana, Hisashi Shirohara, Shigekazu Nakano, Nobuaki Watanabe, Makoto Otsuki, Yoshinori Okabayashi, László Czakó, and Satoshi Tani
- Subjects
medicine.medical_specialty ,business.industry ,Physiology (medical) ,Internal medicine ,medicine ,Acute pancreatitis ,medicine.disease ,business ,Gastroenterology ,Pathology and Forensic Medicine ,Cholecystokinin - Published
- 1994
49. Hydrocortisone treatment increases the sensitivity and responsiveness to cholecystokinin in rat pancreas.
- Author
-
MAKOTO OTSUKI, YOSHINORI OKABAYASHI, TAKAHIKO NAKAMURA, MASATOSHI FUJII, SATOSHI TANI, ATSUSHI OHKI, and SHIGEAKI BABA
- Published
- 1989
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50. Effect of Bt2cGMP on action of cholecystokinin in isolated perfused rat pancreas.
- Author
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MAKOTO OTSUKI, YOSHINORI OKABAYASHI, ATSUSHI OHKI, TAKAHIKO NAKAMURA, SATOSHI TANI, MASATOSHI FUJII, TORU OKA, SANKARAN, HARIHARAN, and SHIGEAKI BABA
- Published
- 1986
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