Biomedical subjects

Yuzuru Ikehara

Publications and source records attributed to Yuzuru Ikehara.

At least 19 recordsLinked to original sources

PubMed2026

Regnase-1-mediated regulation of neutrophils modulates SARS-CoV-2 pneumonia.

The innate immune response to viral infection needs to be tightly regulated to ensure effective pathogen clearance while avoiding excessive immune activation. During SARS-CoV-2 infection, however, the immune system often fails to elicit appropriate responses, resulting in cytokine-release syndrome in patients with COVID-19. In this study, we show that reduced expression of Regnase-1, an RNase that negatively regulates immune cell activation, confers resistance to infection with the mouse-adapted SARS-CoV-2 MA10 strain. In Regnase-1+/- mice, altered neutrophil function contributed to the amelioration of MA10-induced pneumonia. Single-cell RNA sequencing of lung tissue during MA10 infection revealed four distinct neutrophil subsets, and among these, a subset characterized by an interferon-stimulated gene (ISG) signature was decreased in Regnase-1+/- mice. Furthermore, Regnase-1+/- neutrophils exhibited reduced ISG expression without corresponding changes in proinflammatory gene expression. Regnase-1 was found to repress the expression of Tsc22d3, a gene involved in the negative regulation of interferon responses, through its 3' untranslated region. Collectively, these findings suggest that Regnase-1 attenuates resistance to SARS-CoV-2 MA10 infection by promoting excessive interferon responses in neutrophils.

Animals↗

PubMed2007

Babesia bovis: subcellular localization of host erythrocyte membrane components during their asexual growth.

In the present study, the subcellular localization of the host red blood cell (RBC) membrane components, the alpha2-3-linked sialic acid (SA) residues and the lipid bilayer, was observed during the asexual growth of Babesia bovis using two erythrocyte probes, the SA-specific lectin (MALII) and the lipophilic fluorescent (PKH2) probes, respectively. In confocal laser scanning microscopy with MALII, the SA residues on the surface of parasitized RBCs appeared to accumulate into the intracellular parasites as the parasites matured as well as to remain on the surface of extracellular parasites. Furthermore, when PKH2-labeled RBCs were infected with B. bovis, PKH2 signals were also observed around both the intracellular and the extracellular parasites, similarly to the results of MALII. These results indicated that the components derived from the host erythrocyte membrane are incorporated into the intracellular parasites during their asexual growth within the parasitized RBC, suggesting the possible formation of a parasitophorous vacuole-based network or a parasite surface coat.

Animals↗

PubMed2006

A polymorphism of C-to-T substitution at -31 IL1B is associated with the risk of advanced gastric adenocarcinoma in a Japanese population.

Proinflammatory cytokine gene polymorphisms have been demonstrated to associate with gastric cancer risk, of which IL1B-31T/C and -511C/T changes have been well investigated due to the possibility that they may alter the IL1B transcription. The signal transduction target upon interleukin 1 beta (IL1beta) stimulation, the nuclear factor of kappa B (NFkappaB) activation, supports cancer development, signal transduction in which is mediated by FS-7 cell-associated cell surface antigen (FAS) signaling. Based on recent papers describing the prognostic roles of the polymorphisms and the NFkappaB functions on cancer development, we sought to determine if Japanese gastric cancer patients were affected by the IL1B -31/-511 and FAS-670 polymorphisms. A case-control study was conducted on incident gastric adenocarcinoma patients (n=271) and age-gender frequency-matched control subjects (n=271). We observed strong linkage disequilibrium between the T allele at -511 and the C allele at -31 and between the C allele at -511 and the T allele at -31 in IL1B in both the cases and controls (R (2)=0.94). Neither IL1B-31, -511 nor FAS-670 polymorphisms showed significantly different risks of gastric adenocarcinoma. Though FAS-670 polymorphisms did not show any significant difference, the proportion of subjects with IL1B-31TT (or IL1B-511CC) increased according to stage (trend P=0.019). In particular, subjects with stage IV had a two times higher probability of having either IL1B-31TT (or IL1B-511CC) genotype compared with stage I subjects. These observations suggest that IL1B-31TT and IL1B-511CC are associated with disease progression.

Adenocarcinoma↗

PubMed2006

Mice lacking alpha1,3-fucosyltransferase IX demonstrate disappearance of Lewis x structure in brain and increased anxiety-like behaviors.

The 3-fucosyl-N-acetyllactosamine [Lewis x (Le(x)), CD15, SSEA-1] carbohydrate structure is expressed on several glycolipids, glycoproteins, and proteoglycans of the nervous system and has been implicated in cell-cell recognition, neurite outgrowth, and neuronal migration during development. To characterize the functional role of Le(x) carbohydrate structure in vivo, we have generated mutant mice that lack alpha1,3-fucosyltransferase IX (Fut9(-/-)). Fut9(-/-) mice were unable to synthesize the Le(x) structure carried on glycoproteins and glycolipids in embryonic and adult brain. However, no obvious pathological differences between wild-type and Fut9(-/-) mice were found in brain. In behavioral tests, Fut9(-/-) mice exhibited increased anxiety-like responses in dark-light preference and in elevated plus maze tests. Immunohistochemical analysis showed that the number of calbindin-positive neurons was decreased in the basolateral amygdala in Fut9(-/-) mice. These observations indicated that the carbohydrates synthesized by Fut9 play critical roles in functional regulations of interneurons in the amygdalar subdivisions and suggested a role for the Le(x) structure in some aspects of emotional behavior in mice.

Amygdala↗

PubMed2006

A carbohydrate recognition-based drug delivery and controlled release system using intraperitoneal macrophages as a cellular vehicle.

The lymphoid tissue in the omentum, at the so-called milky spots, is known as an initial place for disseminated cancer cells to develop into solid tumors. In the present study, i.p. macrophages significantly took up oligomannose-coated liposomes (OMLs) that were injected into the peritoneal cavity, and then gradually accumulated in the omentum and the other lymphoid tissues within 24 hours of i.p. injection of OMLs. When 5-fluorouracil (5-FU) was encapsulated in the OMLs, >60% of administered 5-FU accumulated in the omentum. Treatment of macrophages at 39 degrees C for 30 minutes led to the release of 5-FU from the macrophages, suggesting that controlled release from macrophages could be achieved by mild hyperthermia. We encased magnetic nanoparticles, which are known to convert electromagnetic energy to heat in the OMLs to achieve in vivo hyperthermia at the site. Using this system in a mouse i.p. metastasis model, we successfully controlled tumor development by coadministration of OML-encased 5-FU and OML-encased magnetic nanoparticles, followed by treatment with an alternating magnetic field. No apparent reduction was seen in tumor growth with the administration of OML-encased magnetic nanoparticles or OML-encased 5-FU alone. Thus, we have established the use of i.p. macrophages as a novel drug delivery system for the control of cancer metastatic to milky spots.

Animals↗

PubMed2006

Apical Golgi localization of N,N'-diacetyllactosediamine synthase, beta4GalNAc-T3, is responsible for LacdiNAc expression on gastric mucosa.

beta1,4-N-acetylgalactosaminyltransferase III (beta4GalNAc-T3), which was recently cloned and identified, exhibits GalNAc transferase activity toward a GlcNAcbeta residue with beta1,4-linkage, forming the N,N'-diacetyllactosediamine, GalNAcbeta1,4GlcNAc (LacdiNAc or LDN). Though LacdiNAc has not been found in the gastric mucosa, a large amount of transcript was detected in our previous study. To increase our knowledge of beta4GalNAc-T3 expression and its product LacdiNAc, we examined the exact localization of beta4GalNAc-T3 in human gastric mucosa using a newly developed antibody, monoclonal antibody (mAb) K1356. This antibody specifically detected the enzyme that transfected the beta4GalNAc-T3 gene into MKN45 cells, and the terminal betaGalNAc epitope yielded on the cell surface was recognized by a lectin, Wisteria floribunda agglutinin (WFA). beta4GalNAc-T3 was localized in the supra-nuclear region of surface mucous cells in gastric mucosa, and WFA positively stained the mucins secreted by the cells. In contrast, in the cells of the glandular compartment in the fundic glands and a few cells in the pyloric glands, beta4GalNAc-T3 was observed in the basolateral position of the nucleus, where no WFA reactivity was detected. The anti-Tn (GalNAcalpha-O-Ser/Thr) antibody staining did not overlap with the WFA staining. By measuring the binding activity of WFA using automated frontal affinity chromatography (FAC), we found WFA to bind most strongly LacdiNAc among the sugar chains examined. Neither beta4GalNAc-T3 nor WFA-positive staining was detected in intestinal metaplastic cells. These results suggest that the supra-nuclear expression of beta4GalNAc-T3 is essential for the formation of LacdiNAc on the surface mucous cells and that LacdiNAc and beta4GalNAc-T3 are novel differentiation markers of surface mucous cells in the gastric mucosa.

Antigens, Differentiation↗

PubMed2006

Biological significance of isolated tumor cells and micrometastasis in lymph nodes evaluated using a green fluorescent protein-tagged human gastric cancer cell line.

PURPOSE: The biological significance of isolated tumor cells and micrometastasis in lymph node defined by the International Union against Cancer remains essentially unknown because of the lack of appropriate animal models. In the present study, we developed a lymph node micrometastasis model featuring a human gastric cancer cell line tagged with green fluorescent protein gene (GCIY-EGFP), which allows visualization of even isolated tumor cells in the development of metastasis without histologic procedure. Using this model, we investigated the effect of surgery and chemotherapy on the growth of early-phase metastasis formation in the lymph nodes. EXPERIMENTAL DESIGN: The time course of spontaneous inguinal lymph node metastasis after s.c. inoculation of GCIY-EGFP cells into nude mice was examined with fluorescence dissecting microscopy. Then, the effects of surgical removal of the primary tumor with or without anti-asialo GM1 treatment or postoperative chemotherapy on the growth of isolated tumor cells and micrometastasis in the lymph nodes were examined. RESULTS: GCIY-EGFP cells were found to metastasize spontaneously to the inguinal lymph nodes to form isolated tumor cells, micrometastasis, and, finally, develop macroscopic metastasis at 1 to 2, 3 to 5, and 5 weeks postinjection, respectively. When the primary tumors were removed within 2 weeks of inoculation, isolated tumor cells, but not micrometastasis, in the lymph nodes regressed by 4 weeks after surgery in all the mice examined (five of five). This spontaneous regression of isolated tumor cells was completely reversed by anti-asialo GM1 treatment, which could deplete natural killer cells effectively in nude mice. Chemotherapy following resection of the primary tumor at an early stage partially eliminated the remaining micrometastasis in the lymph nodes. CONCLUSIONS: These results suggest that isolated tumor cells in the regional lymph nodes regressed by removal of the primary tumor mainly via natural killer cell-mediated antitumor activity and that micrometastasis in the lymph nodes could be effectively eliminated by the postoperative chemotherapy.

Animals↗

PubMed2005

Establishment and characterization of three novel human gastric cancer cell lines with differentiated intestinal phenotype derived from liver metastasis.

Gastric cancers with liver metastasis are fatal diseases with rapid progression and poor patient outcome. To date, however, the molecular basis of their growth and metastasis remains essentially unknown, largely because of the presence of few available gastric cancer cell lines established from liver metastasis. In the present study, we developed two novel cultured cell lines (designated GLM-1 and GLM-2) and one transplantable line in nude mice (designated GLM-3) derived from liver metastasis of gastric cancer patients. These GLM cell lines share unique biological features such as differentiation, growth and metastasis. They form moderately differentiated tumors with CD10 positive and MUC2 negative intestinal absorptive phenotype when injected into nude mice. Their growth is stimulated by EGF and TGF-alpha in vitro like other gastric cancer cell lines. However, GLM cells differ from conventional gastric cancer cell lines in their high apoptotic rate, even in the absence of apoptosis inducing stimuli as revealed by Caspase3/7 assay and the TUNEL method. This apoptosis is further enhanced by phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), but not by MEK1/2 inhibitor (U0126), indicating the strong dependency of their survival on PI3K/Akt pathway rather than MAPK pathway, the major downstream signaling pathways of EGFR. GLM-1 cells can metastasize to the liver after intrasplenic injection, and GLM-3 cells have spontaneous lung metastatic potential after subcutaneous transplantation, respectively. These results indicate that the GLM series are the first cell lines reflecting the intestinal-type differentiated adenocarcinoma, a major subtype of gastric cancer with liver metastasis. Therefore, they would be excellent models for understanding the mechanism of metastatic growth and the development of a new molecular targeting therapy for gastric cancer with liver metastasis.

Adenocarcinoma↗

PubMed2005

Babesia caballi and Babesia equi: implications of host sialic acids in erythrocyte infection.

The present study investigated the involvement of host sialic acids in the erythrocyte infection by two equine Babesia parasites, Babesia equi and Babesia caballi. We observed that the in vitro growth of both parasites is influenced by the removal of sialic acids from the surface of equine erythrocytes (RBC). When the parasites were cultured with neuraminidase (Nm, EC 3.2.1.18)-treated RBC, in which alpha2-3-linked sialic acid residues were removed from four membrane proteins of the RBC, B. caballi showed a significant inhibition of the erythrocyte invasion, while the intracellular development of B. equi seemed to be significantly affected. The possible involvement of host sialic acid in the erythrocyte invasion by B. caballi was also supported by a significant reduction in the parasite growth accompanied by an increased number of extracellular merozoites after the addition of exogenous 3'-sialyllactose (Neu5Acalpha(2-3)Galbeta(1-4)Glc) into the culture. These results suggest that the alpha2-3-linked sialic acid residues on host RBC play important roles in the erythrocyte infections by B. caballi and B. equi.

Animals↗

PubMed2005

Helicobacter pylori-dependent NF-kappa B activation in newly established Mongolian gerbil gastric cancer cell lines.

Mongolian gerbils are an ideal animal model to explore the role of H. pylori on cancer development. However, there have been no established adenocarcinoma cell lines from this model animal. In the present study, we have established cancer cell lines from a primary gastric cancer tissue of a Mongolian gerbil. The derived cells could be stably attached with H. pylori, revealed under a scanning electron microscope, and easily transplanted to the nude mice. Rapid phosphorylation of IkappaB, Erk1/2, and AKT of these cells was observed by Interleukin-1 beta stimulation, and luciferase reporter gene assay on transcriptional activation of Nuclear Factor kappa B after challenging with either H. pylori NCTC11637 or its isogenic cagE-knockout mutant, H. pylori revealed the cagE-dependent NF-kappaB transcriptional activation. The newly established cancer cell lines from the in vivo gastric carcinogenesis model animal, the Mongolian gerbil, can be used to develop effective therapeutic strategies against gastric cancer, especially in exploring the effect of H. pylori, and thus might greatly contribute to gastric cancer prevention and treatment in humans.

Animals↗

PubMed2005

Establishment and characterization of a human colonic mucinous carcinoma cell line with predominant goblet-cell differentiation from liver metastasis.

Many human colorectal adenocarcinoma cell lines have been developed. However, differentiated type colorectal cancer cell lines, particularly, the goblet-cell differentiated type, are scarce. In the present study a novel colorectal adenocarcinoma cell line (designated as COLM-6) with predominant goblet-cell differentiation was established from the rectal mucinous adenocarcinoma of a Japanese woman. COLM-6 cells grow in a typical epithelial monolayer in culture. They expressed epidermal growth factor (EGF) receptor and HER2 on their surface and accordingly, their growth was significantly stimulated by EGF, transforming growth factor (TGF)-alpha and heregulin. COLM-6 cells form tumor with typical mucinous adenocarcinomatous appearance in nude mice. Immunohistochemical analysis of these subcutaneous tumors demonstrated that COLM-6 cells strongly express MUC2 as a goblet-cell marker and Cdx2 in the nucleus. Some weakly express villin and carbonic anhydrase 1 as a columnar absorptive-cell marker as well. They were also positive for adenomatous polyposis coli (APC) cytoplasmically and expressed beta-catenin in their cytoplasm and cell membrane without nuclear accumulation. These results indicate that COLM-6 cell line has unique characteristics and may provide a useful tool to study the mechanism of growth and differentiation of colonic epithelium as well as the biological behavior of colorectal mucinous adenocarcinoma.

Adenocarcinoma, Mucinous↗

PubMed2005

Mixed gastric- and intestinal-type metaplasia is formed by cells with dual intestinal and gastric differentiation.

We have proposed to divide intestinal metaplasia (IM) into two categories, i.e., a mixed gastric and intestinal (GI) type, and a solely intestinal (I) type, based on the residual gastric phenotype cells. The GI-mixed-type IM can be identified by the presence of both cells with either gastric or intestinal phenotypes in a single gland. This study is conducted to elucidate whether cells in the GI-mixed-type IM glands can simultaneously present both gastric and intestinal phenotypes. MUC5AC, MUC2, CD10 and villin expressions were investigated in 20 samples from five gastric cancer cases, directly using either AlexaFluor 488- or 568-labeled specific monoclonal antibodies and observed by fluorescent microscopy and confocal laser-scanning microscopy. GI-mixed IM glands comprise a population expressing MUC5AC and MUC2, MUC5AC and villin, and MUC5AC and CD10. MUC2 and villin expressions were reciprocally increased with decreasing MUC5AC expression, while CD10 expression was limited to cells with only a residual MUC5AC expression or no expression. These results suggest that a heterogeneous cell population with both gastric and intestinal phenotypes would develop into a single intestinal phenotype, as reflected in the progression of intestinal metaplasia from GI-mixed-type- to I-type IM-type glands.

Animals↗

PubMed2004

Negative regulation of T cell receptor signaling by Siglec-7 (p70/AIRM) and Siglec-9.

Siglec-7 (p70/AIRM) and Siglec-9 are "CD33"-related siglecs expressed on natural killer (NK) cells and subsets of peripheral T cells. Like other inhibitory NK cell receptors, they contain immunoglobulin receptor family tyrosine-based inhibitory motifs in their cytoplasmic domains, and Siglec-7 has been demonstrated to negatively regulate NK cell activation. Based on reports of the presence of these siglecs on T cells, we sought to determine if they are capable of modulating T cell receptor (TCR) signaling using Jurkat T cells stably and transiently transfected with Siglec-7 or Siglec-9. Following either pervanadate stimulation or TCR engagement, both Siglecs exhibited increased tyrosine phosphorylation and recruitment of SHP-1. Effects of Siglec-7 and -9 were also evident in downstream events in the signaling pathway. Both siglecs reduced phosphorylation of Tyr319 on ZAP-70, known to play a pivotal role in up-regulation of gene transcription following TCR stimulation. There was also a corresponding decreased transcriptional activity of nuclear factor of activated T cells (NFAT) as determined using a luciferase reporter gene. Like all siglecs, Siglec-7 and -9 recognize sialic acid-containing glycans of glycoproteins and glycolipids as ligands. Mutation of the conserved Arg in the ligand binding site of Siglec-7 (Arg124) or Siglec-9 (Arg120) resulted in reduced inhibitory function in the NFAT/luciferase transcription assay, suggesting that ligand binding is required for optimal inhibition of TCR signaling. The combined results demonstrate that both Siglec-7 and Siglec-9 are capable of negative regulation of TCR signaling and that ligand binding is required for optimal activity.

Amino Acid Motifs↗

PubMed2004

Growth-inhibitory effect of heparin on Babesia parasites.

We examined the inhibitory effects of three heparins on the growth of Babesia parasites. The multiplication of Babesia bovis, B. bigemina, B. equi, and B. caballi in in vitro cultures and that of B. microti in vivo were significantly inhibited in the presence of heparins, as determined by light microscopy. Treatment with various concentrations of heparin showed complete clearance of the intracellular parasites. Interestingly, a higher percentage of abnormally multidividing B. bovis parasites was observed in the presence of low concentrations of heparin. Furthermore, fluorescein isothiocyanate-labeled heparin was preferably found on the surfaces of extracellular merozoites, as detected by confocal laser scanning microscopy. These findings indicate that the heparin covers the surfaces of babesial merozoites and inhibits their subsequent invasion of erythrocytes.

Animals↗

PubMed2003

Lewis type 1 antigen synthase (beta3Gal-T5) is transcriptionally regulated by homeoproteins.

The type 1 carbohydrate chain, Galbeta1-3GlcNAc, is synthesized by UDP-galactose:beta-N-acetylglucosamine beta1,3-galactosyltransferase (beta3Gal-T). Among six beta3Gal-Ts cloned to date, beta3Gal-T5 is an essential enzyme for the synthesis of type 1 chain in epithelium of digestive tracts or pancreatic tissue. It forms the type 1 structure on glycoproteins produced from such tissues. In the present study, we found that the transcriptional regulation of the beta3Gal-T5 gene is controlled by homeoproteins, i.e. members of caudal-related homeobox protein (Cdx) and hepatocyte nuclear factor (HNF) families. We found an important region (-151 to -121 from the transcription initiation site), named the beta3Gal-T5 control element (GCE), for the promoter activity. GCE contained the consensus sequences for members of the Cdx and HNF families. Mutations introduced into this sequence abolished the transcriptional activity. Four factors, Cdx1, Cdx2, HNF1alpha, and HNF1beta, could bind to GCE and transcriptionally activate the beta3Gal-T5 gene. Transcriptional regulation of the beta3Gal-T5 gene was consistent with that of members of the Cdx and HNF1 families in two in vivo systems. 1) During in vitro differentiation of Caco-2 cells, transcriptional up-regulation of beta3Gal-T5 was observed in correlation with the increase in transcripts for Cdx2 and HNF1alpha. 2) Both transcript and protein levels of beta3Gal-T5 were determined to be significantly reduced in colon cancer. This down-regulation was correlated with the decrease of Cdx1 and HNF1beta expression in cancer tissue. This is the first finding that a glycosyltransferase gene is transcriptionally regulated under the control of homeoproteins in a tissue-specific manner. beta3Gal-T5, controlled by the intestinal homeoproteins, may play an important role in the specific function of intestinal cells by modifying the carbohydrate structure of glycoproteins.

Amino Acid Motifs↗

PubMed2003

Alpha1,3-fucosyltransferase IX (Fut9) determines Lewis X expression in brain.

The expression of the Lewis X (Lex) carbohydrate structure in brain is developmentally regulated and is thought to play a role in cell-cell interaction during neuronal development. Mice possess three functional alpha1,3-fucosyltransferase genes: Fut4, Fut7, and Fut9. Fut7 is known to have no activity to synthesize Lex. In the present study, the relative activities of Fut4 and Fut9 for Lex synthesis were determined using recombinant enzymes. Fut9 exhibited very strong activity for oligosaccharide acceptors and glycolipid acceptors, that is, more than 10- and 100-fold, respectively, than that of Fut4. Furthermore, both cerebrum and cerebellum at various stages of development (E17, P0, P7, P30, P100) expressed 15-100 times more Fut9 transcript than Fut4 transcript. Neurons and astrocytes in primary culture also expressed 10-15 times more Fut9 than Fut4 transcript. Moreover, alpha1,3-Fut activity toward a polylactosamine chain in homogenates of brain tissues and primary cultured cells showed a pattern typical of Fut9, not Fut4. The developmental profile of activity for the synthesis of Lex was well correlated with that of Fut9 transcript. Immunohistochemistry with anti-Fut9 monoclonal antibody revealed the distribution of the Lex structure. These results showed that Fut9 is the most responsible enzyme for the synthesis of Lex in brain.

Aging↗

PubMed2003

ABO blood type, Lewis and Secretor genotypes, and chronic atrophic gastritis: a cross-sectional study in Japan.

BACKGROUND: the H type I structure, synthesized by the secretor (Se) enzyme in gastric foveolar cells, and its metabolite, Lewis b (le(b)) antigen, mediate the adhesion of Helicobacter pylori ( H. Pylori) to the gastric epithelium, whereas H. Pylori does not bind to modified forms of Le(b) specific for blood types A and B. Such host factors as Le and Se genotypes and ABO blood type may affect the establishment of H. Pylori infection and, once infected, the risk of chronic atrophic gastritis. METHODS: we investigated the cross-sectional relation of abo blood type and Le and Le genotypes to gastric atrophy, assessed by serum pepsinogen levels, in japanese residents from two sources. RESULTS: among the 151 h. Pylori-positive participants of the h. Pylori eradication program, odds ratios (ors) for gastric atrophy, adjusted for age, sex, and smoking, were elevated for blood types a (or = 5.35; 95% confidence interval (ci), 2.11-13.58) and b (or = 4.79; 95% ci, 1.77-12.93) relative to type o. Ors for blood types a and b were also elevated in h. Pylori-negative subjects. These associations were not observed among 250 h. Pylori-positive health check-up examinees. The le genotype was not associated with gastric atrophy in either study population. The se/ se genotype was associated with statistically nonsignificant elevation of gastric atrophy risk in both populations. CONCLUSIONS: the present data showed a strong association of blood types a and b with gastric atrophy in one, but not the other, study population. Discrepant results between the two populations warrant further investigation. Background: the h type i structure, synthesized by the secretor (se) enzyme in gastric foveolar cells, and its metabolite, lewis b (le(b)) antigen, mediate the adhesion of helicobacter pylori ( h. Pylori) to the gastric epithelium, whereas h. Pylori does not bind to modified forms of le(b) specific for blood types a and b. Such host factors as le and se genotypes and abo blood type may affect the establishment of h. Pylori infection and, once infected, the risk of chronic atrophic gastritis. Methods: we investigated the cross-sectional relation of abo blood type and le and se genotypes to gastric atrophy, assessed by serum pepsinogen levels, in japanese residents from two sources. Results: among the 151 h. Pylori-positive participants of the h. Pylori eradication program, odds ratios (ors) for gastric atrophy, adjusted for age, sex, and smoking, were elevated for blood types a (or = 5.35; 95% confidence interval (ci), 2.11-13.58) and b (or = 4.79; 95% ci, 1.77-12.93) relative to type o. Ors for blood types a and b were also elevated in h. Pylori-negative subjects. These associations were not observed among 250 h. Pylori-positive health check-up examinees. The le genotype was not associated with gastric atrophy in either study population. The se/ se genotype was associated with statistically nonsignificant elevation of gastric atrophy risk in both populations. Conclusions: the present data showed a strong association of blood types a and b with gastric atrophy in one, but not the other, study population. Discrepant results between the two populations warrant further investigation.

Adult↗

PubMed2003

Effect of early eradication on Helicobacter pylori-related gastric carcinogenesis in Mongolian gerbils.

Helicobacter pylori (Hp) infection and gastric carcinogenesis are known to have a close relationship, but the effect of eradication of Hp on Hp-related gastric carcinogenesis has not been fully studied experimentally. To evaluate the effect of eradication in gastric carcinogenesis, an experimental model with eradication in the early, middle or late period was studied using Hp-infected and N-methyl-N-nitrosourea (MNU)-treated Mongolian gerbils. The animals were divided into seven groups: group A (MNU + Hp + eradication at 15 w), group B (MNU + Hp + eradication at 35 w), group C (MNU + Hp + eradication at 55 w), group D (MNU + Hp), group E (MNU), group F (Hp) and group G (control). The tumor incidences at week 75 in the early (group A), middle (group B) and late (group C) eradicated groups were 6.7%, 27.3% and 38.2%, respectively. The incidence of 56.3% in the non-eradicated group was the highest (group D). Incidences in group E, group F and group G were 6.3%, 0.0% and 0.0%, respectively. The tumor incidences were related to the period of inflammatory status induced by Hp infection. Hp infection strongly enhanced gastric carcinogenesis initiated with a chemical carcinogen, and following eradication at an early period this enhancing effect was effectively reduced. Eradication at an early stage of inflammation might be effective in preventing Hp-related gastric carcinogenesis.

Animals↗