Biomedical subjects

Satoshi Fukumoto

Publications and source records attributed to Satoshi Fukumoto.

At least 19 recordsLinked to original sources

PubMed2026

Characterization of stem cells from exfoliated deciduous teeth from a patient with Alagille syndrome carrying a JAG1 mutation.

PURPOSE: Alagille syndrome (ALGS) is an autosomal dominantly inherited disorder primarily caused by mutations in the Jagged Canonical Notch Ligand 1 (JAG1) gene. Although many pluripotent stem cells are well established, no patient-derived stem cells from exfoliated deciduous teeth (SHED) have been developed. In this study, we aimed to establish SHED from an ALGS patient carrying a heterozygous JAG1mut mutation. METHODS: We isolated SHED from a deciduous tooth of an ALGS patient with a heterozygous JAG1 mutation (ALGS-SHED) by the colony-forming unit-fibroblast (CFU-F) method. We then compared the characteristics of ALGS-SHED and healthy donor-derived control SHED (CONT-SHED). RESULTS: ALGS-SHED displayed mesenchymal stem cell features as indicated by CFU-F formation, immunophenotype, and mesenchymal multipotency into adipocytes, chondrocytes, and osteoblasts. ALGS-SHED showed reduced population doubling capacity and exhibited induced chondrogenic potency and diminished osteogenic potency, but similar hepatic potency. ALGS-SHED damaged in situ potency to form bile duct-like tubular structures in the livers of chronically CCl4-injured mice. CONCLUSIONS: We successfully established ALGS-SHED from an ALGS patient carrying a heterozygous JAG1 mutation. Our established ALGS-SHED may represent a potential model for studying ALGS involving a JAG1 mutation.

Alagille Syndrome↗

PubMed2006

Amelogenin is a negative regulator of osteoclastogenesis via downregulation of RANKL, M-CSF and fibronectin expression in osteoblasts.

Amelogenin is a novel enamel matrix protein. Knockout mice showed enhanced osteoclast formation and resorption of tooth cementum. This study investigated the effects of amelogenin on osteoclastogenesis. In co-cultures with calvaria osteoblasts and purified bone marrow cells, amelogenin inhibited osteoclastogenesis dramatically. Furthermore, amelogenin inhibited the expression of receptor activator of nuclear factor kappaB ligand (RANKL), macrophage-colony stimulating factor (M-CSF) and fibronectin in osteoblasts, while RANKL expression was induced by fibronectin and inhibited by treatment with fibronectin small interfering RNA. These results suggest that the inhibitory effects of amelogenin on osteoclastogenesis lead to downregulation of RANKL, M-CSF and fibronectin production in osteoblasts.

Amelogenin↗

PubMed2006

Current topics in pharmacological research on bone metabolism: osteoclast differentiation regulated by glycosphingolipids.

Glycosphingolipids are thought to play important roles in the development and function of several tissues, although the function of glycolipids in osteoclastogenesis has not been clearly demonstrated. In the present study, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), a glucosylceramide synthase inhibitor, completely inhibited osteoclastogenesis induced by macrophage-colony stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL). Following treatment with D-PDMP, nearly all glycosphingolipid expression was dramatically reduced on the surface of bone marrow cells, which suggests that glycosphingolipids are necessary for osteoclastogenesis. To determine which kinds of glycolipids are important for osteoclastogenesis, we added several types of purified glycolipids to D-PDMP treated bone marrow cells, as the precursor of osteoclasts is known to express glucosylceramide (GlcCer) and lactosylceramide (LacCer). Following treatment with RANKL, ganglioside GM3 and GM1 were increased in the treated bone marrow cells, whereas other types were not detected using thin layer chromatography analysis. In cells cultured with those glycolipids, exogenously added LacCer rescued osteoclastogenesis blocking by D-PDMP. Furthermore, receptor activator of nuclear factor kappaB (RANK) induced the recruitment of tumor necrosis factor (TNF)-associated factors 2 and 6 (TRAF2 and 6, respectively) to the cytoplasmic tail of RANKL with activated IkappaB kinase and IkappaB phosphorylation, while D-PDMP treatment inhibited RANKL and induced IkappaB phosphorylation, and that inhibition was recovered by LacCer. In addition, RANK, TRAF2, TRAF6, and LacCer were found localized in lipid rafts on the cell surfaces. These results suggest that glycosphingolipids, especially LacCer, are important for the initial step of RANKL-induced osteoclastogenesis via lipid rafts.

Animals↗

PubMed2005

Laminin alpha5 is required for dental epithelium growth and polarity and the development of tooth bud and shape.

In tooth development, the oral ectoderm and mesenchyme coordinately and reciprocally interact through the basement membrane for their growth and differentiation to form the proper shape and size of the tooth. Laminin alpha5 subunit-containing laminin-10/11 (LM-511/521) is the major laminin in the tooth germ basement membrane. Here, we have examined the role of laminin alpha5 (Lama5) in tooth development using laminin alpha5-null mouse primary dental epithelium and tooth germ organ cultures. Lama5-null mice develop a small tooth germ with defective cusp formation and have reduced proliferation of dental epithelium. Also, cell polarity and formation of the monolayer of the inner dental epithelium are disturbed. The enamel knot, a signaling center for tooth germ development, is defective, and there is a significant reduction of Shh and Fgf4 expression in the dental epithelium. In the absence of laminin alpha5, the basement membrane in the inner dental epithelium becomes discontinuous. In normal mice, integrin alpha6beta4, a receptor for laminin alpha5, is strongly localized at the basal layer of the epithelium, whereas in mutant mice, integrin alpha6beta4 is expressed around the cell surface. In primary dental epithelium culture, laminin-10/11 promotes cell growth, spreading, and filopodia-like microspike formation. This promotion is inhibited by anti-integrin alpha6 and beta4 antibodies and by phosphatidylinositol 3-kinase inhibitors and dominant negative Rho-GTPase family proteins Cdc42 and Rac. In organ culture, anti-integrin alpha6 antibody and wortmannin reduce tooth germ size and shape. Our studies demonstrate that laminin alpha5 is required for the proliferation and polarity of basal epithelial cells and suggest that the interaction between laminin-10/11-integrin alpha6beta4 and the phosphatidylinositol 3-kinase-Cdc42/Rac pathways play an important role in determining the size and shape of tooth germ.

Animals↗

PubMed2005

Transforming growth factor-beta3 promotes mesenchymal cell proliferation and angiogenesis mediated by the enhancement of cyclin D1, Flk-1, and CD31 gene expression during CL/Fr mouse lip fusion.

BACKGROUND: Cleft lip with or without cleft palate is the most common congenital anomaly in the craniofacial region. Knowledge of the molecular mechanisms behind normal lip fusion can contribute to better intervention and improved functional clinical outcome. Transforming growth factor-beta3 (TGF-beta3) has been implicated in lip morphogenesis. Therefore, we hypothesized that TGF-beta3 functions during lip fusion through regulation of angiogenesis and mesenchymal cell cycle progression during early developmental stages. METHODS: To test this hypothesis we used the CL/Fraser mouse model, which has a high incidence of cleft lip. Lips isolated from embryonic day (ED) 11.5 mouse embryos were allowed to develop in serum-free organ cultures in the presence or absence of TGF-beta3. The lips that developed in these cultures fused in 2 days. RESULTS: During normal development, we detected positive immunoreactions for TGF-beta3 at the site of fusion. We also detected mesenchymal cells that were immunopositive for Flk-1 and CD31, which are markers for endothelial cell precursors. Exogenous TGF-beta3 accelerated lip fusion in culture. This enhancement was associated with an increase in the number of capillary blood vessels in the lips cultured in the presence of TGF-beta3, in comparison with controls. In tandem, TGF-beta3 increased the level of expression of both Flk-1 and CD31. Our data suggest that an elevated level of TGF-beta3 may promote angiogenesis in developing lips that is mediated by increased Flk-1 and CD31 expression. We also detected increased cyclin D1 expression (a marker for cell proliferation) in the presence of TGF-beta3, which suggests that TGF-beta3 promoted cell proliferation. CONCLUSIONS: TGF-beta3 promoted cell proliferation and angiogenesis in lip mesenchymal tissues. These events led to enhanced lip fusion in the presence of TGF-beta3.

Animals↗

PubMed2005

Review: extracellular matrix regulates tooth morphogenesis.

Mineralized tissues are unique in that they use proteins to attract and organize calcium and phosphate ions into a structured mineral phase, thus precise knowledge of the expression and extracellular distribution of matrix proteins is very important to understand their function. Tooth development is regulated by sequential and reciprocal interactions between neural crest-derived mesenchymal cells and the oral environment. However, the precise molecular mechanisms that mediate interactions between epithelium and mesenchymal cells are not clear, although basement membrane (BM) components have been shown to play important roles in these regulatory events. In addition, the extracellular matrix layer, whose main components are laminin, collagen IV, nidogen, and sulfated proteoglycan, and the BM layer are both considered to be involved with cell proliferation and differentiation. During tooth morphogenesis, extracellular matrices are dramatically changed. Further, the BM components, laminin and collagen IV support dental epithelium; however, in the late stage, they begin the processes of enamel matrix secretion and calcification, after which the BM structure between the dental epithelium and mesenchyme disappears. In addition, tooth abnormalities associated with several kinds of human diseases that cause mutations in the extracellular matrix, as well as the molecular mechanisms of the basement membrane and enamel matrix during tooth morphogenesis, are not clearly understood. In our review, we discuss the role of the extracellular matrix, with focus on the BM and enamel matrix during tooth morphogenesis.

Ameloblasts↗

PubMed2005

TGF-beta3 induces ectopic mineralization in fetal mouse dental pulp during tooth germ development.

Several members of the transforming growth factor (TGF)-beta superfamily are expressed in developing teeth from the initiation stage through adulthood. Of those, TGF-beta1 regulates odontoblast differentiation and dentin extracellular matrix synthesis. However, the molecular mechanism of TGF-beta3 in dental pulp cells is not clearly understood. In the present study, beads soaked with human recombinant TGF-beta3 induced ectopic mineralization in dental pulp from fetal mouse tooth germ samples, which increased in a dose-dependent manner. Further, TGF-beta3 promoted mRNA expression, and increased protein levels of osteocalcin (OCN) and type I collagen (COL I) in dental pulp cells. We also observed that the expression of dentin sialophosphoprotein and dentin matrix protein 1 was induced by TGF-beta3 in primary cultured dental pulp cells, however, not in calvaria osteoblasts, whereas OCN, osteopontin and osteonectin expression was increased after treatment with TGF-beta3 in both dental pulp cells and calvaria osteoblasts. Dentin sialoprotein was also partially detected in the vicinity of TGF-beta3 soaked beads in vivo. These results indicate for the first time that TGF-beta3 induces ectopic mineralization through upregulation of OCN and COL I expression in dental pulp cells, and may regulate the differentiation of dental pulp stem cells to odontoblasts.

Animals↗

PubMed2005

Essential roles of ameloblastin in maintaining ameloblast differentiation and enamel formation.

During tooth development, dental epithelial cells interact with extracellular matrix components, such as the basement membrane and enamel matrix. Ameloblastin, an enamel matrix protein, plays a crucial role in maintaining the ameloblast differentiation state and is essential for enamel formation. Ameloblastin-null mice developed severe enamel hypoplasia. In mutant mice, dental epithelial cells started to differentiate into ameloblasts, but ameloblasts soon lost cell polarity, proliferated, and formed multiple cell layers, indicative of some aspects of preameloblast phenotypes. In addition, the expression of amelogenin, another component of the enamel matrix, was specifically reduced in mutant ameloblasts. More than 20% of amelobastin-null mice developed odontogenic tumors. We also found that recombinant ameloblastin specifically bound to ameloblasts and inhibited proliferation of dental epithelial cells. These results suggest that ameloblastin is an important regulator to maintain the differentiation state of ameloblasts.

Ameloblasts↗

PubMed2005

Differential enhancing effects of alpha2,8-sialyltransferase on the cell proliferation and mobility.

alpha2,8-Sialyltransferase (alpha2,8S-T, GD3 synthase) has been reported to be involved in the enhanced cell proliferation of malignant tumors. Using a cloned cDNA of alpha2,8S-T, transfectant cells were established and the effects of the gene expression on the cell phenotypes were analyzed. In contrast with PC12 cells, in which we reported marked growth enhancement based on the transfection of alpha2,8S-T, Swiss3T3 cells showed no enhancement in either cell proliferation or phosphorylation of MAP kinases after the transfection of alpha2,8S-T when treated with platelet-derived growth factor. Correspondingly, the receptor for platelet-derived growth factor also showed no increased phosphorylation upon the factor stimulation. However, in the wound-healing scratching assay, the Swiss3T3 transfectant cells demonstrated increased mobility as the PC12 transfectant cells. These results suggest that the enhancing effects of alpha2,8S-T on the proliferation and mobility are differential depending on the cell types, and ganglioside-associating molecules in the individual cell types need to be investigated.

Animals↗

PubMed2004

GD3 synthase gene found expressed in dental epithelium and shown to regulate cell proliferation.

GD3 synthase is one of the key enzymes involved with ganglioside synthesis, and its activity regulates the main profile of ganglioside expression. We analyzed the expression of the GD3 synthase gene in laser-dissected teeth germs using RT-PCR. The GD3 synthase gene was found expressed in brain, thymus, and tooth germ tissues, however, not in liver or skin specimens. Further, it was highly expressed during the early stage of tooth germ development (embryonic day 14.5), especially in dental epithelia, which gradually reduced in the molar site until postnatal day 7, whereas it was not in dental mesenchyme tissues. In addition, dental epithelial cells transiently transfected with the GD3 synthase gene showed enhanced proliferation. These results indicate that the GD3 synthase gene may be involved in early tooth development, particularly in the proliferation of dental epithelium.

Animals↗

PubMed2004

Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts.

Tooth morphogenesis results from reciprocal interactions between oral epithelium and ectomesenchyme culminating in the formation of mineralized tissues, enamel, and dentin. During this process, epithelial cells differentiate into enamel-secreting ameloblasts. Ameloblastin, an enamel matrix protein, is expressed by differentiating ameloblasts. Here, we report the creation of ameloblastin-null mice, which developed severe enamel hypoplasia. In mutant tooth, the dental epithelium differentiated into enamel-secreting ameloblasts, but the cells were detached from the matrix and subsequently lost cell polarity, resumed proliferation, and formed multicell layers. Expression of Msx2, p27, and p75 were deregulated in mutant ameloblasts, the phenotypes of which were reversed to undifferentiated epithelium. We found that recombinant ameloblastin adhered specifically to ameloblasts and inhibited cell proliferation. The mutant mice developed an odontogenic tumor of dental epithelium origin. Thus, ameloblastin is a cell adhesion molecule essential for amelogenesis, and it plays a role in maintaining the differentiation state of secretory stage ameloblasts by binding to ameloblasts and inhibiting proliferation.

Ameloblasts↗

PubMed2004

Overexpressed GM1 suppresses nerve growth factor (NGF) signals by modulating the intracellular localization of NGF receptors and membrane fluidity in PC12 cells.

Ganglioside GM1 has been considered to have a neurotrophic factor-like activity. To analyze the effects of endogenously generated GM1, the rat pheochromocytoma cell line PC12 was transfected with the GM1/GD1b/GA1 synthase gene and showed increased expression levels of GM1. To our surprise, GM1+-transfectant cells (GM1+ cells) showed no neurite formation after stimulation with nerve growth factor (NGF). Autophosphorylation of NGF receptor TrkA and activation of ERK1/2 after NGF treatment were scarcely detected in GM1+ cells. Binding of 125I-NGF to PC12 cells was almost equivalent between GM1+ cells and controls. However, dimer formation of TrkA upon NGF treatment was markedly suppressed in GM1+ cells in both cross-linking analysis with Bis(sulfosuccinimidyl)suberate 3 and 125I-NGF binding assay. The sucrose density gradient fractionation of the cell lysate revealed that TrkA primarily located in the lipid raft fraction moved to the non-raft fraction in GM1+ cells. p75NTR and Ras also moved from the raft to non-raft fraction in GM1+ cells, whereas flotillin and GM1 persistently resided in the lipid raft. TrkA kinase activity was differentially regulated when GM1 was added to the kinase assay system in vitro, suggesting suppressive/enhancing effects of GM1 on NGF signals based on the concentration. Measurement of fluorescence recovery after photobleaching revealed that the membrane fluidity was reduced in GM1+ cells. These results suggested that overexpressed GM1 suppresses the differentiation signals mediated by NGF/TrkA by modulating the properties of the lipid raft and the intracellular localization of NGF receptors and relevant signaling molecules.

Animals↗

PubMed2004

Infection-induced up-regulation of the costimulatory molecule 4-1BB in osteoblastic cells and its inhibitory effect on M-CSF/RANKL-induced in vitro osteoclastogenesis.

Bacterial infection sometimes impairs bone metabolism. In this study, we infected the osteoblastic cell line MC3T3-E1 with Mycobacterium bovis bacillus Calmette-Guérin (BCG) and identified genes that were up-regulated in the BCG-infected cells by the suppression subtractive hybridization method. A gene encoding 4-1BB (CD137), a member of the tumor necrosis factor-alpha receptor family, was found to be one of the up-regulated genes. Up-regulation of 4-1BB was also observed by infection with Escherichia coli, Salmonella typhimurium, and Staphylococcus aureus, and by treatment with lipopolysaccharides and heat-killed BCG. Bone marrow cells and the macrophage-like cell lines J774 and RAW264.7 were found to express 4-1BB ligand (4-1BBL). Recombinant 4-1BB (r4-1BB) that was immobilized on culture plates strongly inhibited macrophage colony stimulating factor (M-CSF)/receptor activator of nuclear factor-kappaB ligand (RANKL)-induced in vitro osteoclast formation from bone marrow cells. Anti-4-1BBL antibody also inhibited osteoclast formation to a lesser extent, indicating involvement of reverse signaling through 4-1BBL during inhibition of osteoclast formation. A casein kinase I (CKI) inhibitor markedly suppressed the inhibitory effect of r4-1BB on M-CSF/RANKL-induced osteoclast formation, suggesting that CKI might be involved in 4-1BB/4-1BBL reverse signaling. r4-1BB showed no effects on M-CSF- or RANKL-induced phosphorylation of I-kappaB, ERK1/2, p38, or JNK, whereas RANKL-induced phosphorylation of Akt, a downstream target of phosphatidylinositol 3-kinase (PI3K), was completely abolished by r4-1BB, suggesting that 4-1BB/4-1BBL reverse signaling may interfere with PI3K/Akt pathway. r4-1BB also abolished RANKL-mediated induction of nuclear factor of activated T cells-2. This study may elucidate a novel role of 4-1BB in cell metabolism, especially osteoclastogenesis.

4-1BB Ligand↗

PubMed2004

A novel technique of finger-assisted laparoscopic surgery.

BACKGROUND: Although advanced and complex laparoscopic procedures are now being performed, tactile sensation is limited with available laparoscopic instrumentation. For immediate hemostasis, it sometimes is necessary to convert laparoscopic into open surgery. METHODS: We improved the procedure with the aid of an abdominal wall sealing device, a Lap protector, and a surgical grove. With this simple apparatus, we can easily switch from laparoscopic to open surgery and vice versa. RESULTS: Only 4 cm of skin incision was made. The operator can use his or her finger and most of the usual surgical instruments during the laparoscopic surgery. CONCLUSIONS: Finger-assisted laparoscopic surgery is affordable to perform the advanced laparoscopic procedure. This new technique made laparoscopic abdominal surgery easier and safer for beginners in laparoscopic surgery and skilled surgeons in open surgery. For the experts, this technique set up the safety door for the emergency in laparoscopic surgery.

Aged↗

PubMed2003

Laminin alpha2 is essential for odontoblast differentiation regulating dentin sialoprotein expression.

Laminin alpha2 is subunit of laminin-2 (alpha2beta1gamma1), which is a major component of the muscle basement membrane. Although the laminin alpha2 chain is expressed in the early stage of dental mesenchyme development and localized in the tooth germ basement membrane, its expression pattern in the late stage of tooth germ development and molecular roles are not clearly understood. We analyzed the role of laminin alpha2 in tooth development by using targeted mice with a disrupted lama2 gene. Laminin alpha2 is expressed in dental mesenchymal cells, especially in odontoblasts and during the maturation stage of ameloblasts, but not in the pre-secretory or secretory stages of ameloblasts. Lama2 mutant mice have thin dentin and a widely opened dentinal tube, as compared with wild-type and heterozygote mice, which is similar to the phenotype of dentinogenesis imperfecta. During dentin formation, the expression of dentin sialoprotein, a marker of odontoblast differentiation, was found to be decreased in odontoblasts from mutant mice. Furthermore, in primary cultures of dental mesenchymal cells, dentin matrix protein, and dentin sialophosphoprotein, mRNA expression was increased in laminin-2 coated dishes but not in those coated with other matrices, fibronectin, or type I collagen. Our results suggest that laminin alpha2 is essential for odontoblast differentiation and regulates the expression of dentin matrix proteins.

Animals↗

PubMed2003

The Krüppel-like factor epiprofin is expressed by epithelium of developing teeth, hair follicles, and limb buds and promotes cell proliferation.

We identified a cDNA clone for epiprofin, which is preferentially expressed in teeth, by differential hybridization using DNA microarrays from an embryonic day 19.5 mouse molar cDNA library. Sequence analysis revealed that this cDNA encodes a member of the Krüppel-like factor family containing three characteristic C2H2-type zinc finger motifs. The full-length cDNA was obtained by the 5' Cap capture method. Except for its 5'-terminal sequence, the epiprofin mRNA sequence is almost identical to the predicted sequence of Krüppel-like factor 14/Sp6 (specificity protein 6), which was previously identified in expressed sequence tag data bases and GenBank by an Sp1 zinc finger DNA-binding domain search (Scohy, S., Gabant, P., Van Reeth, T., Hertveldt, V., Dreze, P. L., Van Vooren, P., Riviere, M., Szpirer, J., and Szpirer, C. (2000) Genomics 70, 93-101). This sequence difference is due to differences in the assignment of the location of exon 1. In situ hybridization revealed that epiprofin mRNA is expressed by proliferating dental epithelium, differentiated odontoblast, and also hair follicle matrix epithelium. In addition, whole mount in situ hybridization showed transient expression of epiprofin mRNA in cells of the apical ectodermal ridge in developing limbs and the posterior neuropore. Transfection of an epiprofin expression vector revealed that this molecule is localized in the nucleus and promotes cell proliferation. Thus, epiprofin is a highly cell- and tissue-specific nuclear protein expressed primarily by proliferating epithelial cells of teeth, hair follicles, and limbs that may function in the development of these tissues by regulating cell growth.

Amino Acid Sequence↗

PubMed2003

Suppression of lung metastasis of mouse Lewis lung cancer P29 with transfection of the ganglioside GM2/GD2 synthase gene.

Ganglioside functions in tumor metastasis were analyzed by carbohydrate remodeling of a mouse Lewis lung cancer (subline P29) by introducing beta1,4GalNAc-T cDNA. Although P29 was originally a low-metastatic subline in the s.c. injection system, it showed high potential in lung metastasis when i.v.-injected via the tail vein. Two lines of GM(2)(+) transfectants showed markedly reduced metastatic potential to the lung compared to 2 control lines. However, cell proliferation rates and expression levels of various cell adhesion molecules, e.g., integrin family members, SLe(x) and CD44, were essentially unchanged after transfection of the cDNA. Then, cell adhesion to fibronectin-coated dishes was examined, showing that GM(2) (+) transfectants attached to the plates much more slowly than controls, suggesting functional modulation of integrins with newly expressed GM(2). Phosphorylation of the FAK located at downstream of integrin molecules was markedly reduced in GM(2)(+) transfectants, suggesting that GM(2) suppressed cell adhesion signals via fibronectin-integrin interaction.

Animals↗

PubMed2003

Expression of cyclooxygenases in Helicobacter pylori gastritis and residual gastritis after distal gastrectomy.

It has long been thought that duodenal reflux induces residual gastritis after distal gastrectomy. H. pylori infection appears to be another factor in residual gastritis; and H. pylori induced gastritis may exist preoperatively or may have been introduced postoperatively. Up until now, the surgical effect itself and H. pylori infection have not been well differentiated as causes of residual gastritis. Our aim in this study was to clarify the relationship between the surgical effect and H. pylori infection in residual gastritis. A residual gastritis model using the Mongolian gerbil has been established with microsurgical technique. Residual gastritis with and without H. pylori infection has been studied by histopathological examination and quantitated by Rauws' score. The expression of cyclooxygenase (both COX-1 and COX-2) has also been examined immunohistologically. Elevation of pH in gastric juice after surgery was confirmed. H. pylori infection led to deterioration after surgery. The postoperative Rauws' score with infection is higher than without infection. Levels of COX-1 were higher after surgery in both animals. COX-2 was not expressed in the animals without infection and only a little was expressed in the animals with infection. COX-2 was strongly expressed in the operated animals with infection, but the surgical effect was minute in the animals without infection. Residual gastritis consisted of both surgical gastritis and H. pylori gastritis. H. pylori gastritis is curable with eradication of the organism, but surgical gastritis is not. The COX inhibitor can be a good candidate in preventing residual gastritis after eradication of the H. pylori organism. The clinical implications of COX expression for patients with residual gastritis might deserve further study in the point of treatment of surgical and H. pylori gastritis.

Animals↗