Hiroyoshi Ota

A novel gene, MALT1 at 18q21, is involved in t(11;18) (q21;q21) found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue.

The t(11;18) (q21;q21) translocation is a characteristic chromosomal aberration in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. We previously identified a YAC clone y789F3, which includes the breakpoint at 18q21 in a MALT lymphoma patient. BAC and PAC contigs were constructed on the YAC, and BAC 193f9 was found to encompass the breakpoint region. In the present study, we further narrowed down the breakpoint region at 18q21 in five MALT lymphoma patients by means of FISH and Southern blot analyses using the plasmid contig constructed from BAC 193f9. The breakpoints at 18q21 in three of the five MALT lymphoma patients were found to be clustered approximately within the 20 kb region. By using exon amplification and cDNA library screening, we identified a novel cDNA spanning the breakpoint region that exhibited aberrant mRNA signals in four of the five MALT lymphoma patients. The nucleotide sequence predicted an 813 amino acid protein that shows significant sequence similarity to the CD22β and laminin 5 α3b subunit. We refer to the gene encoding this transcript as MALT1 (Mucosa-Associated Lymphoid Tissue lymphoma translocation gene 1). The alteration of MALT1 by translocation strongly suggests that this gene plays an important role in the pathogenesis of MALT lymphoma.

Guidelines for the Management of Helicobacter pylori Infection in Japan: 2009 Revised Edition

Background:  Over the past few years, the profile of Helicobacter pylori infection has changed in Japan. In particular, the relationship between H. pylori and gastric cancer has been demonstrated more clearly. Accordingly, the committee of the Japanese Society for Helicobacter Research has revised the guidelines for diagnosis and treatment of H. pylori infection in Japan.

Mice deficient in protein tyrosine phosphatase receptor type Z are resistant to gastric ulcer induction by VacA of Helicobacter pylori

The vacuolating cytotoxin VacA produced by Helicobacter pylori causes massive cellular vacuolation in vitro and gastric tissue damage in vivo, leading to gastric ulcers, when administered intragastrically. Here we report that mice deficient in protein tyrosine phosphatase receptor type Z (Ptprz, also called PTP-ζ or RPTP-β, encoded by Ptprz) do not show mucosal damage by VacA, although VacA is incorporated into the gastric epithelial cells to the same extent as in wild-type mice. Primary cultures of gastric epithelial cells from Ptprz+/+ and Ptprz−/− mice also showed similar incorporation of VacA, cellular vacuolation and reduction in cellular proliferation, but only Ptprz+/+ cells showed marked detachment from a reconstituted basement membrane 24 h after treatment with VacA. VacA bound to Ptprz, and the levels of tyrosine phosphorylation of the G protein–coupled receptor kinase–interactor 1 (Git1), a Ptprz substrate, were higher after treatment with VacA, indicating that VacA behaves as a ligand for Ptprz. Furthermore, pleiotrophin (PTN), an endogenous ligand of Ptprz, also induced gastritis specifically in Ptprz+/+ mice when administered orally. Taken together, these data indicate that erroneous Ptprz signaling induces gastric ulcers.

Histochemistry of the surface mucous gel layer of the human colon

BACKGROUND AND AIMS: Histochemical analysis of the surface mucous gel layer of the human colon is difficult, as it dissolves in fixatives. This study was undertaken to explore the surface mucous gel layer on the normal mucosa and neoplastic tissues of the large intestine. In addition, the distribution of different mucins secreted from goblet cells was studied with a series of histochemical stains for mucins. METHODS: Twenty four surgically resected specimens were fixed in Carnoys solution and embedded in paraffin. In four cases, the surface mucous gel layer was also studied in frozen sections. Serial sections were stained by a battery of histochemical techniques characterising mucins. RESULTS AND CONCLUSION: The surface mucous gel layer consisted of the inner and outer layers. The first covered the luminal surface of the mucosa, consisted of mucins, and showed a vertical striped pattern. The second overlaid the first, showed a lateral striped pattern, and was contaminated with bacteria and other substances. Their thickness in paraffin sections varied considerably among the sites in the large intestine, but was the thickest in the rectum and measured 12.7 (SEM 6.0) microns and 88.8 (SEM 80.1) microns respectively. Mucins forming the inner layer were obviously derived from goblet cells underlying it.

Helicobacter pylori-Induced Chronic Active Gastritis, Intestinal Metaplasia, and Gastric Ulcer in Mongolian Gerbils

The establishment of persisting Helicobacter pylori infection in laboratory animals has been difficult, but in 1996 Hirayama reported the development of a successful Mongolian gerbil model. The present study was undertaken with two aims: to better characterize the normal histological structure and histochemical properties of the gastric mucosa of the Mongolian gerbil; and to evaluate the progression of the histopathological features of H. pylori-induced gastritis in this animal model for one year after the experimental infection. Seventy-five Mongolian gerbils were used. Mongolian gerbils were sacrificed at 2, 4, 8, 12, 26, 38, and 52 weeks after H. pylori inoculation. Sections prepared from stomachs immediately fixed in Carnoys solution were stained with hematoxylin and eosin and Alcian blue at pH 2.5/periodic acid-Schiff, a dual staining consisting of the galactose oxidase-cold thionin Schiff reaction and paradoxical Concanavalin A staining, and with immunostaining for H. pylori and BrdU. H. pylori infection induced in the Mongolian gerbil a chronic active gastritis, in which a marked mucosal infiltration of neutrophils on a background of chronic inflammation became detectable 4 weeks after inoculation and continued up to 52 weeks. Intestinal metaplasia and gastric ulcers appeared after 26 weeks in some of the animals, whereas others developed multiple hyperplastic polyps. The Mongolian gerbil represents a novel and useful model for the study of H. pylori-induced chronic active gastritis and may lend itself to the investigation of the epithelial alterations that lead to intestinal metaplasia and gastric neoplasia.

Patterns of Gastric Atrophy in Intestinal Type Gastric Carcinoma

Multifocal atrophic gastritis (MAG) is currently considered a precancerous lesion leading to intestinal type gastric carcinoma. The current study aimed to describe the topography of atrophy in stomachs with early gastric carcinoma.

Alternating laminated array of two types of mucin in the human gastric surface mucous layer

SummaryAttempts have been made to develop a procedure for preserving and analysing the surface mucous layer of the human stomach in paraffin sections. Histologically normal gastric mucosae were obtained from 20 surgically removed stomachs. Of the different fixatives tested, Carnoys solution gave rise to the most satisfactory results. In Haematoxylin-Eosin stained sections, the surface mucous layer appeared as a thick eosinophilic layer coating the gastric mucosal surface and measured 55.4±2.5 μm in the fundus and 21.8±1.0 μm in the pylorus respectively. A dual staining method consisting of galactose oxidase-cold thionine Schiff and paradoxical concanavalin A staining was applied to the surface mucous layer in order to reveal the distribution pattern of mucins secreted by two types of mucous cell in the gastric mucosa: surface mucous cells and gland mucous cells. As a result of this staining, an alternating laminated layer was visualized which consisted of the particular two types of mucin. In five cases, the surface mucous layer was examined in unfixed frozen sections. This layer was only partially preserved but revealed the same laminated structure. These results indicated that gland mucous cell mucins contribute to form the surface mucous layer.

Acquisition versus Loss of Helicobacter pylori Infection in Japan: Results from an 8-Year Birth Cohort Study

Studies of the pattern of change in the epidemiology of Helicobacter pylori infection are scarce. A longitudinal cohort study consisted of 644 children and adults, and two independent cross-sectional surveys were conducted in rural Japan between 1986 and 1994. The anti-H. pylori IgG seroconversion rates were 1.1% and 1% per year for children and adults, respectively. The seroreversion rate per year was 1.8% for children and 1.5% for adults. The cohort study was confirmed by the two cross-sectional studies. H. pylori prevalence fell in all age groups in both children (odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.2-1.0, P = .05) and adults (OR = 0.4, 95% CI = 0.3-0.6, P = .001). The rate of loss of H. pylori infection was greater than the acquisition. Data regarding acquisition and loss of H. pylori infection are critical to understanding the epidemiology of the infection and to developing treatment and vaccination strategies.

A dual staining method for identifying mucins of different gastric epithelial mucous cells

SummaryA dual staining method has been developed to identify two types of mucous secreting cells in the gastric mucosa of human and rat in one and the same tissue section. Sections were stained first using the galactose oxidase-cold thionin Schiff (GOCTS) procedure and then with paradoxical Concanavalin A staining (PCS). Surface mucous cell mucin stained blue with GOCTS, whereas gland mucous cell mucin stained brown with PCS. This method enabled us to differentiate these two types of mucins not only in gastric epithelial cell cytoplasm but also in the extracellular space. Sugar residues detected by GOCTS were explored by employing four species of lectins, which were peanut andAllomyrina dichotoma agglutinins for β-galactose andVicia villosa andWistaria floribunda agglutinins for β-N-acetylgalactosamine. The effect of oxidation with galactose oxidase was also examined on the affinities of reactive sites for these lectins. The results indicated that, in the human stomach, the sugar residues responsible for this reactivity were most likely β-N-acetylgalactosamine and β-galactose in specimens lacking secretion of blood group determinants and β-N-acetylgalactosamine in those showing the secretion. In the rat stomach, on the other hand, sugar residues responsible for GOCTS were not elucidated by these lectins.

Local bone formation by injection of recombinant human bone morphogenetic protein-2 contained in polymer carriers

The regenerating potential of human bone is limited. The repair of large bone defects often associated with bone tumor resections is not observed, and nonunion or delayed union of bone is a serious problem for fracture treatment. In these cases, autogeneic or allogeneic bone grafting has been routinely indicated, but these approaches require invasive surgical procedures. An alternative approach described in this paper involves the injection of bone morphogenetic proteins (BMPs) in a polymeric delivery system. We demonstrate that synthetic biodegradable polymers, poly-D,L-lactic acid-polyethylene glycol (PLA-PEG) block copolymers, which exhibit an exquisite temperature-dependent liquid-semisolid transition, work well as an injectable delivery system for recombinant human (rh) BMP-2. The thermosensitive property of the PLA-PEG/rhBMP-2 composite is permissive to percutaneous injection when heated. The fluidity of this composite decreases as it cools down to body temperature and the resultant semisolid form provides a scaffold for bone formation through the gradual local release of the rhBMP-2. This new type of injectable osteoinductive material will enable a less invasive approach to surgeries involving the restoration or repair of bone tissues.