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T Katsuyama

Publications and source records attributed to T Katsuyama.

At least 19 recordsLinked to original sources

Co-localization of TFF2 with gland mucous cell mucin in gastric mucous cells and in extracellular mucous gel adherent to normal and damaged gastric mucosa.

Trefoil factor 2 (TFF2) is mucin associated peptide that has a mucosal barrier function in addition to participating in repair and healing. We examined the localization of TFF2 and gastric mucins in gastric mucous cells, the surface mucous gel layer (SMGL) adherent to normal gastric mucosa, and in the mucoid cap covering gastric erosions. Carnoy's solution, or formalin/picric acid-fixed paraffin embedded materials from resected stomachs and formalin-fixed paraffin embedded gastric biopsy materials were used. Sections were immunostained for the TFF2 and histochemically stained for gastric mucins. In addition, thick sectioned gastric mucosa fixed in Carnoy's solution were stained with FITC-labeled GSA-II lectin specific for gland mucous cell mucin and examined for three-dimensional images of the SMGL using a confocal laser scanning microscope. The TFF2 and gland mucous cell mucin were found intermixed together in the gastric gland mucous cells, in the SMGL in laminated layers, and in the mucoid cap. A laminated arrangement of continuous sheets of gland mucous cell mucin in the SMGL was demonstrated in the three-dimensional images. Co-localization of the TFF2 with gland mucous cell mucin suggests a physical interaction between the TFF2 and gland mucous cell mucin. The TFF2 trapped in the adherent mucins may be responsible for mucosal defense, healing, and repair.

Biopsy↗

Effect of Helicobacter pylori eradication on ongoing mutation of immunoglobulin genes in gastric MALT lymphoma.

Gastric low-grade mucosa-associated lymphoid tissue (low-grade MALT) lymphomas has been associated with Helicobacter pylori (H. pylori) infection. Although infiltrating T cells with specificity for H. pylori are known to stimulate the development of MALT lymphomas, the effect of H. pylori eradication on rearranged immunoglobulin heavy chain (IgH) genes of low-grade gastric MALT lymphomas is unclear. Gastric biopsies from five cases were investigated by cloning and sequence analysis of rearranged IgH genes before and after the treatment for H. pylori. In all cases, IgH genes were mutated from their germline counterpart. The frequency of intraclonal sequence heterogeneity before the eradication of H. pylori varied from 0.25 to 0.49%. Clones obtained from the tumours before the eradication of H. pylori in cases 1 and 2 showed a tendency to display a mutation pattern by positive antigen selection and their monoclonarity disappeared after the eradication. The frequency of intraclonal sequence heterogeneity of the clones obtained from cases 3, 4 and 5 (0.12% in case 3, 0.10% in 4 and 0.18% in 5) after the eradication of H. pylori was lower than that in tumours before the eradication (0.30% in case 3, 0.49% in 4 and not determined in 5). These findings suggest that low-grade gastric MALT lymphomas expand due to the persistent presence of H. pylori in vivo. The characteristic feature of tumour clones obtained from the tumours after the eradication of H. pylori is a very low intraclonal heterogeneity, which may potentially be independent of H. pylori.

Aged↗

Fibrinogens Kosai and Ogasa: Bbeta15Gly-->Cys (GGT-->TGT) substitution associated with impairment of fibrinopeptide B release and lateral aggregation.

We found two heterozygous dysfibrinogenemias, designated fibrinogen Kosai and fibrinogen Ogasa. Kosai was associated with arteriosclerosis obliterans but Ogasa showed no bleeding or thrombotic tendencies. The plasma fibrinogen concentrations from the two propositi (Ogasa and Kosai) were much lower when determined by the thrombin-time method (0.94 and 1.06 g L(-1), respectively) than when determined by the immunological method (2.87 and 2.72 g L(-1), respectively). We performed DNA sequencing and functional analyses to clarify the relationship between the structural and functional abnormalities. Genetic analysis of PCR-amplified DNA from the propositi identified the heterozygous substitution Bbeta15Gly-->Cys (GGT-->TGT). Western blotting analysis of purified fibrinogen revealed the existence of albumin-fibrinogen complexes. Functional analyses indicated that compared with the normal control, the propositi's fibrinogen released only half the normal amount of fibrinopeptide B and showed markedly impaired polymerization. In addition, the observation of thinner fibers in fibrin clots (by scanning electron microscopy) indicated markedly defective lateral aggregation in the variant fibrinogens. The impaired functions may be due to the substitution of Cys for Bbetao15Gly plus the existence of some additional disulfide-bonded forms.

Adult↗

A case of primary low grade mucosa associated lymphoid tissue (MALT) lymphoma of the oesophagus.

We report a very rare case of primary low grade mucosa associated lymphoid tissue (MALT) lymphoma of the oesophagus. An 83 year old woman was referred to our hospital in June 1999 for further examination and treatment of oesophageal tumour. Although a physical examination and laboratory data showed no significant abnormalities, endoscopic observation revealed two slightly elevated submucosal tumour-like lesions of the oesophagus. Tissue specimens were obtained by endoscopic mucosal resection of the oesophagus using a cap fitted panendoscope. The lesions were composed of diffuse small atypical lymphoid cells--that is, centrocyte-like cells--which were stained with CD20, L26, BCL-2, and kappa, but not with CD3, CD5, CD10, or cyclin D1. Monoclonality was detected by polymerase chain reaction analysis using the primer for CDR-3 of immunoglobulin H and diagnosed as low grade MALT lymphoma of the oesophagus. The tumours were considered to be completely resected and therefore additional treatment was not administered. The patient is alive and well 22 months after treatment and diagnosis.

Aged↗

Evaluation of urinary rapid test for Helicobacter pylori in general practice.

There is increasing interest in noninvasive tests for the diagnosis of Helicobacter pylori (H. pylori) infection. One such test, a urine-based rapid test kit (RAPIRUN H. pylori Antibody, Otsuka Pharmaceutical Co., Ltd.) for detection of antibody to H. pylori, has been developed and is considered ideal. In addition to its noninvasiveness and safe handling-due to use of urine as a sample-the assay procedure used for the urinary rapid test is very simple. Only 10-20 minutes are required to complete an assay, and no instruments are needed. The aim of this study was to examine the clinical usefulness of this urine-based rapid test. A total of 189 patients, including 76 patients with gastroduodenal disease, were recruited. A pair of random single-void urine and serum samples was collected from each of the 189 patients, and antibody to H. pylori in the urine and serum samples was measured using the urine-based rapid test kit and three commercially available serum-based ELISA kits. For the patients with gastroduodenal disease, invasive diagnostic methods using endoscopic biopsy specimens such as culture, histology, and rapid urease test were also performed. The sensitivity, specificity, and accuracy of the urinary rapid test were evaluated on the basis of the three serum ELISA results or the invasive diagnostic results. In addition, various urinalyses were performed, and the effects of substances existing in urine on the urinary rapid test results were examined. Of the 189 patients, the urinary rapid test was positive for 110 (58.2%), negative for 78 (41.3%), and invalid for only one patient (0.5%). Based on the three serum-based ELISA results, the sensitivity, specificity, and accuracy of the urinary rapid test were 93.7, 88.9, and 92.2%, respectively. On the basis of the biopsy-based test results, the sensitivity of the urinary rapid test was 100% and its accuracy (95.2%) was equivalent or superior to that of each serum-based ELISA. In addition, no significant differences were observed between groups positive and negative on urinary rapid testing in any urinalysis parameter examined. The novel urinary rapid test kit evaluated in this study enables simple, rapid, and accurate diagnosis of H. pylori infection, and is an ideal test method for point-of-care testing.

Adult↗

Tobacco use and occupational exposure to carcinogens, but not N-acetyltransferase 2 genotypes are major risk factors for bladder cancer in the Japanese.

Our study investigated the risks of genotypes of N-acetyltransferase 2 (NAT2), tobacco use and/or occupational exposure to carcinogens in patients with bladder cancer and in age- and sex-matched controls in Japanese. NAT2 genotypes were categorized into two groups, homozygous mutant (slow acetylator genotype) and homozygous and heterozygous wild type (fast acetylator genotype). The percentage of NAT2 slow acetylator types was 6.7% in the bladder cancer patients, close to the value for controls (6.1%). There was no association between NAT2 slow acetylator genotype and the risk of bladder cancer. This association was also insignificant when subjects were restricted to those who used tobacco or those occupationally exposed to carcinogens. In contrast, tobacco use in combination with exposure to carcinogens was a significant risk factor, as based on the odds ratio and chi-square test. The combination of both factors should be an additive risk factor for bladder cancer. In this study, we demonstrated that the environmental factors of smoking habit and occupational exposure for carcinogenicity are much more important than genetic factors in bladder cancer.

Adult↗

Spontaneous and repetitive cardiac slowdown in the freely moving spiny lobster, Panulirus japonicus.

The fluctuation of heartbeat interval was investigated to assess cardio-regulatory nervous function in freely moving spiny lobsters. This was performed by time series analysis of the heartbeat interval recorded from restrained animals, freely moving animals, and isolated hearts. The heart rate of freely moving animals exhibited on/off switching: i.e., an elevated and maintained rate was repetitively interrupted by periods of decreased rate. Each period was initiated by a sudden decrease in rate and was terminated by an exponential return to normal activity. In order to explain this characteristic change in heart rate, we have constructed a neurotransmitter release-reuptake model for such bi-stable activity of cardio-regulatory nerves. The model was successful in reproducing the characteristic observed fluctuation. In freely moving animals, the brain seems to regulate the heart through the inhibitory nerve in an "on/off" manner. In the hearts of restrained animals and isolated hearts, the heart rate exhibited white-noise like fluctuation. This implies that stress impairs the normal bi-stable regulatory mode.

Animals↗

Immunohistochemical localization of heparan sulfate proteoglycan in human gastrointestinal tract.

Heparan sulfate proteoglycans (HS-PGs) are associated with important cell functions, for example, cell motility, cell adhesion, and oncogenesis. We examined the localization of HS-PGs in normal and carcinoma tissues of the gastrointestinal tract to help elucidate their roles in these organs. Fresh surgical materials from 134 patients with carcinoma of the stomach or large intestine and 26 patients with various diseases of the small intestine were immunostained after fixation with 10E4 (an antibody against the HS of HS-PG) as a primary antibody. Immunoelectron microscopy (immunogold method) was also performed. The basolateral surfaces of normal tissues of the large and small intestines were strongly stained with antibody confirmed by electron microscopy. In the stomach, lesions with intestinal metaplasia showed the same staining as the intestines, although normal gastric tissue showed staining only in some parts of the basal layer of fundic and pyloric glands. Carcinoma tissues in all cases examined showed staining with antibody. Better results were obtained after fixation in acetic alcohol or zinc-containing solutions than in ordinary formalin. These characteristic localizations of HS-PG in intestines and stomachs suggest that this kind of HS-PG staining could be a hallmark characteristic of the intestine.

Adult↗

Paradoxical role of Helicobacter pylori infection: protective effect against ethanol-induced gastric mucosal injury in Mongolian gerbils.

We investigated the effect of ethanol (a representative necrotizing agent) on gastritis induced by Helicobacter pylori infection in Mongolian gerbils. Seventy-eight gerbils were used. Four and 12 weeks after H. pylori inoculation, 30% ethanol was administered into the stomach. The stomachs were removed after 30 min, the intramucosal prostaglandin (PG) E2 concentration was measured, and histopathology was recorded. H. pylori infection caused chronic active gastritis, gastric erosion, hypersecretion of mucin from gland mucus cells, and a rise in the activity of intramucosal PGE2. After ethanol administration, gastric erosion was significantly less in animals infected with H. pylori than in uninfected animals. In conclusion, in the early stage of H. pylori infection, accentuation of intramucosal PGE2 and hypersecretion of mucin from gland mucus cells have a protective effect against gastric mucosal injury induced by necrotizing agents.

Animals↗

Familial gastrointestinal stromal tumor with hyperpigmentation: association with a germline mutation of the c-kit gene.

We describe 2 siblings with multiple gastrointestinal stromal tumors (GISTs) and cutaneous hyperpigmentation. Both had a point mutation of the c-kit gene. The patients were sisters who had exhibited cutaneous hyperpigmentation since their late teens, but the diagnosis of multiple gastrointestinal submucosal tumors was not made until they were 41 and 45 years old. Histologic examination showed that these tumors were GISTs expressing CD34 and Kit protein. Both patients died of GISTs. Single-strand conformation polymorphism analysis showed a mutation of c-kit in tumor DNA extracted from paraffin-embedded specimens. Direct sequencing analysis showed that the point mutation occurred at codon 559 of exon 11 (Val-->Ala). The same single-point mutation was detected in DNA extracted from peripheral leukocytes obtained from the younger sister and her 2 children (who had similar general hyperpigmentation) as well as in DNA from a skin biopsy specimen taken from the older sister. The germline mutation at codon 559 of the c-kit gene found in the present familial GISTs differed from that in a previously reported case of familial GISTs. We propose that GISTs caused by a germline mutation of the c-kit gene should be referred to as GIST-cutaneous hyperpigmentation disease.

Adult↗

Role of N-methyl-N-nitrosourea in the induction of intestinal metaplasia and gastric adenocarcinoma in Mongolian gerbils infected with Helicobacter pylori.

BACKGROUND: Progression from intestinal metaplasia to neoplasia has not been demonstrated experimentally. The hypothesis that gastric adenocarcinoma arises from intestinal metaplasia was tested in a Mongolian gerbil model of Helicobacter pylori (H. pylori) infection. METHODS: One hundred and fourteen specific pathogen-free gerbils were divided in five groups. A and D: infected with H. pylori and administered the carcinogen N-methyl-N-nitrosourea (MNU); C and E: received MNU; B: H. pylori, but no MNU. Animals were killed at 41 weeks, stomachs were mapped, and the relationship between metaplasia and cancer was assessed. RESULTS: Intestinal metaplasia occurred more frequently in the H. pylori-infected, MNU-treated gerbils than in those receiving H. pylori inoculation only (P < 0.01). Carcinomas arose only in H. pylori-infected animals receiving MNU (8 well differentiated, 2 poorly differentiated, and 10 signet ring). Intestinal metaplasia occurred more frequently in association with intestinal-type carcinoma. CONCLUSIONS: Intestinal metaplasia and adenocarcinoma arise in stomachs subjected to the same injuries (in this study, H. pylori and MNU). Only two intestinal-type carcinomas were contiguous to intestinal metaplasia; all other tumors developed most commonly at non-metaplastic sites. This suggests that in this animal model H. pylori and MNU induce several phenotypes of gastric cancer, but intestinal metaplasia may be a direct precursor only in a subset of the intestinal-type tumors.

Adenocarcinoma↗

Serum immunoglobulin G immune response to Helicobacter pylori antigens in Mongolian gerbils.

The Mongolian gerbil model for Helicobacter pylori infection is an animal model that mimics human disease. We examined the serum immune response to H. pylori infection in gerbils by enzyme-linked immunosorbent assay (ELISA) and Western blotting, both with whole-cell (H. pylori) extracts. A total of 66 7-week-old specific-pathogen-free male gerbils were inoculated orogastrically with H. pylori strain ATCC 43504. Sera were collected 1, 2, 4, 8, 12, 26, 38, and 52 weeks after H. pylori inoculation. Sixty-nine noninfected gerbils and their sera were used as controls. The specificity of the ELISA was 95.7%. The frequency of seropositivity increased over time: 2 of 10 (20%), 7 of 10 (70%), and 7 of 7 (100%) samples of sera from inoculated gerbils were positive for H. pylori at 2, 4, and 8 weeks postinoculation, respectively. Western blot assays showed that the primary immunoglobulin G (IgG) response against low-molecular-mass (25-, 30-, and 20-kDa) proteins appeared after a lag period of 2 to 8 weeks after inoculation. Antibodies against 160-, 150-, 110-, 120-, 80-, 66-, and 63-kDa proteins were observed 12 weeks after inoculation. The early reactive 30-kDa protein was identified as a urease alpha subunit by N-terminal amino acid sequencing. After 26 weeks, two groups of animals could be distinguished: one group developed ulcers (n = 5), and the other developed hyperplastic polyps without ulcers (n = 19). Gerbils in the gastric ulcer group showed significantly higher serum anti-H. pylori IgG levels than did gerbils in the hyperplastic group (P = 0.001) as measured by ELISA. Furthermore, a higher proportion of animals developed antibodies to H. pylori proteins of 26, 25, and 20 kDa in the ulcer group than those animals with hyperplastic polyps (75 to 100% versus 17 to 50%) in Western blot assays. These results highlight the importance of the immune response of the host in the development of H. pylori-related gastric lesions.

Animals↗

Helicobacter pylori and two ultrastructurally distinct layers of gastric mucous cell mucins in the surface mucous gel layer.

BACKGROUND AND AIMS: Helicobacter pylori locate not only on the apical surface of surface mucous cells but also in the mucous gel layer covering the gastric mucosa. The present study was undertaken to observe the mucous gel layer itself and any H pylori in this layer at the electron microscopic level, and to determine whether H pylori proliferate in this layer. METHODS: We examined resected human stomachs (five cases, fixed in Carnoy's solution, paraffin embedded) under the light microscope, and gastric biopsy specimens (10 cases, fixed in glutaraldehyde with or without osmium, epoxy embedded) under the electron microscope. We performed histochemical staining for gastric mucins and immunostaining for H pylori, gastric gland mucous type mucins, and intestinal mucins. RESULTS: Under the electron microscope, surface mucous cell type mucins and gland mucous cell type mucins in the mucous gel layer covering gastric mucosa without intestinal metaplasia showed reticular and band like structures, respectively. H pylori were frequently found as small aggregates within the mucous gel layer of surface mucous cell type mucins, and H pylori within these aggregates were seen dividing. H pylori were frequently found in the mucous gel layer of the surface mucous cell type mucins along the border with the layer of gland mucous cell mucins. Occasionally, H pylori were trapped by frayed thin threads of the gland mucous cell type mucins. CONCLUSIONS: The two types of gastric mucins in the mucous gel layer differ in ultrastructure. H pylori preferentially colonise and form microcolonies within the mucous gel layer of surface mucous cell type mucins. Mucins from gland mucous cells may disturb the movement of H pylori within the mucous gel layer.

Adult↗

Expression of apoptosis-associated speck-like protein containing a caspase recruitment domain, a pyrin N-terminal homology domain-containing protein, in normal human tissues.

Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is a pyrin N-terminal homology domain (PYD)- and caspase recruitment domain (CARD)-containing a proapoptotic molecule. This molecule has also been identified as a target of methylation-induced silencing (TMS)-1. We cloned the ASC cDNA by immunoscreening using an anti-ASC monoclonal antibody. In this study, we determined the binding site of the anti-ASC monoclonal antibody on ASC and analyzed the expression of ASC in normal human tissues. ASC expression was observed in anterior horn cells of the spinal cord, trophoblasts of the placental villi, tubule epithelium of the kidney, seminiferous tubules and Leydig cells of the testis, hepatocytes and interlobular bile ducts of the liver, squamous epithelial cells of the tonsil and skin, hair follicle, sebaceous and eccrine glands of the skin, and peripheral blood leukocytes. In the colon, ASC was detected in mature epithelial cells facing the luminal side rather than immature cells located deeper in the crypts. These observations indicate that high levels of ASC are abundantly expressed in epithelial cells and leukocytes, which are involved in host defense against external pathogens and in well-differentiated cells, the proliferation of which is regulated.

Animals↗

Cell lineage specificity of newly raised monoclonal antibodies against gastric mucins in normal, metaplastic, and neoplastic human tissues and their application to pathology diagnosis.

The specificity of monoclonal antibodies against gastric mucins (designated as HIK1083, PGM 36, and PGM 37) was studied immunohistochemically in normal, metaplastic, and neoplastic human tissues. These antibodies labeled class III mucin-producing cells identified by paradoxical concanavalin A staining in normal stomach, duodenum (Brunner gland), biliary tract, and main pancreatic duct; in mucinous metaplasia of pancreas and gallbladder; and in adenocarcinomas of stomach (90%), bile duct (80%), gallbladder (100%), pancreas (80%), lung (100% of goblet cell type adenocarcinomas), ovary (67% of mucinous carcinomas), and uterine cervix (100% of adenoma malignum tumors). Normal and neoplastic cells of esophagus, colon, salivary gland, kidney, endometrium, breast, prostate, and liver, as well as normal small intestine, lung, and uterine cervix, were all negative. The antibodies used should be valuable for the detection of class III mucin and class III mucin-producing cells in normal, metaplastic, and neoplastic tissues.

Antibodies, Monoclonal↗