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Biomedical subjects

Taiji Akamatsu

Publications and source records attributed to Taiji Akamatsu.

At least 19 recordsLinked to original sources
PubMed2006

Quantitative determination of gland mucous cells-type mucin using a monoclonal antibody, HIK1083: its pathophysiological changes in human gastric juice.

BACKGROUND: Pathological alteration in gastric mucosa is caused by Helicobacter pylori infection and is detectable by histological analysis. In particular, the alteration of gland mucous cells (GMCs)-type mucin, which plays a protective role against H. pylori infection, is critical in the pathogenesis of H. pylori-related gastritis. We established an assay for GMCs-type mucin and quantitatively assessed the pathophysiological changes in its content in human gastric juice samples. METHODS: The assay method for GMCs-type mucin was based on ELISA using a monoclonal antibody (HIK1083), and was used it to measure GMCs-type mucin in gastric juice obtained from patients with or without H. pylori infection. RESULTS: All the basic characteristics of the current method were satisfactory to quantify the GMCs-type mucin content in gastric juice. The GMCs-type mucin content, but not total mucin content, was significantly higher in patients with H. pylori infection (n=17; 437+/-476 U, mean+/-SD) than in those without H. pylori infection (n=55; 168+/-322 U, p<0.05). CONCLUSIONS: The current method is suitable for the quantitative analysis of GMCs-type mucin in gastric juice. The change in GMCs-type mucin content in gastric juice may be possibly implicated in the pathophysiology of the gastric mucosa and in the patient's gastric mucosal lesions.

Animals↗
PubMed2006

Ultrastructure of Helicobacter pylori in human gastric mucosa and H. pylori-infected human gastric mucosa using transmission electron microscopy and the high-pressure freezing-freeze substitution technique.

BACKGROUND: Conventional ultrastructural analyses of Helicobacter pylori and H. pylori-infected gastric mucosa by transmission electron microscopy (TEM) have limitations because of structural artifacts introduced during fixation. METHODS: We used high-pressure freezing (HPF) followed by freeze substitution for TEM to investigate the ultrastructure of H. pylori and H. pylori-infected gastric mucosa. For HPF-freeze substitution, human gastric biopsy specimens were placed in the HPF instrument at a pressure of approximately 2,000 atm at the temperature of liquid nitrogen. Specimens were then transferred to an instrument for freeze substitution. Specimens were first placed in acetone containing 2% OsO4 at -85 degrees C. The temperature was increased to -3 degrees C, followed by embedding in Quetol 812. Ultrathin sections were double-stained by uranium acetate/lead nitrate. HPF and conventionally prepared samples were examined by TEM. RESULTS: The H. pylori envelope was clearly seen to consist of an outer membrane, periplasmic space, and plasma membrane. The periplasmic space was filled with electron-dense materials. A peptidoglycan layer was only occasionally visible. A thick, very fine filamentous or reticular fringe corresponding to the bacterial glycocalyx was seen surrounding the H. pylori cells. At the adhesion loci of H. pylori to gastric epithelial cells, H. pylori was connected to the epithelial cells by very fine, thickly arranged filaments or more closely, with a contact zone. The epithelial cells showed indentations or pedestals. CONCLUSIONS: The well-developed, thick bacterial glycocalyx of H. pylori appears to strongly interact with external cellular components and may play an important role in the adhesion of H. pylori to epithelial cells.

Adult↗
PubMed2006

Comparison of localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma with and without Helicobacter pylori infection.

BACKGROUND: The clinical features and clinical course of Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma are unclear and a treatment strategy has not yet been established. AIM: To clarify the clinical differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma, we compared these two types of gastric MALT lymphoma. MATERIALS AND METHODS: Fifty-seven patients with localized gastric MALT lymphoma were studied. H. pylori infection was present in 41 and absent in 16. Treatment consisted of antibiotic therapy and/or 30 Gy radiation therapy. Response assessment was performed every 3-6 months by esophagogastroduodenoscopy including gathering biopsy samples, endoscopic ultrasonography, clinical examination, and various imaging procedures. The median follow-up period was 37 months. RESULTS: There were no significant differences between H. pylori-positive and H. pylori-negative gastric MALT lymphoma patients in terms of sex, age, stage, gross phenotype, affected area of the stomach, or the presence of monoclonality. Complete regression was achieved with antibiotic therapy against H. pylori-negative gastric MALT lymphoma in one of nine patients (11.1%), compared to 28 of 38 patients (73.7%) with H. pylori-positive gastric MALT lymphoma (p < .001). Radiation therapy showed high effectiveness for the local control of H. pylori-negative or antibiotic-resistant gastric MALT lymphoma (92.9%), although distant recurrence was recognized in three of 14 patients (21.4%). Two of 16 patients (12.5%) with H. pylori-negative gastric MALT lymphoma died because of the transformation of the disease into diffuse large B-cell lymphoma. There was a significant difference in both the overall and cause-specific survival rate between the two groups (p = .038). CONCLUSION: Radiation therapy is the effective treatment for H. pylori-negative or antibiotic-resistant localized gastric MALT lymphoma. However, careful systemic follow-up for distant involvement should be required. Transformation into diffuse large B-cell lymphoma is thought to be the important cause of death in patients with gastric MALT lymphoma.

Adult↗
PubMed2006

Intestinal diffuse large B-cell lymphoma associated with celiac disease: a Japanese case.

Intestinal non-Hodgkin's lymphoma (NHL), especially the T-cell type, is well known to be associated with celiac disease (CD), an enteropathic disorder with a propensity for certain racial and genetic backgrounds. CD is typically characterized by gastrointestinal (GI) symptoms, anti-transglutaminase antibodies in the sera, and microscopical findings of the intestinal mucosa, which resolve with a gluten-free diet (GFD). In Asian populations, including the Japanese, CD and the associated NHL have been supposed to be quite rare, and studies concerning the frequency of CD or its relationship with NHL are scarce. We describe a Japanese middle-aged man with intestinal diffuse large B-cell lymphoma associated with CD. Following multi-combined chemotherapy, the patient's lymphoma has been in a state of complete response, and his GI symptoms have improved with a GFD. This case suggests that the possibility of CD and its association with intestinal NHL should be kept in mind, even in Asian populations.

Aged↗
PubMed2005

Helicobacter heilmannii infection: clinical, endoscopic and histopathological features in Japanese patients.

Gastric biopsy materials of 4074 consecutive Japanese patients undergoing esophagogastroduodenoscopy were reviewed, along with those of 15 patients with Helicobacter heilmannii infection (11, chronic gastritis; four, mucosa-associated lymphoid tissue (MALT) lymphoma). In four patients with H. heilmannii infection, the materials were examined by transmission electronmicroscopy. Urea breath test (three patients) and antibody test (five patients) were performed in patients with H. heilmannii infection. In two patients with MALT lymphoma, H. heilmannii was eradicated. The prevalence of H. heilmannii was 0.1% in the consecutive series. In chronic gastritis, the gastric mucosa was endoscopically normal (13.3%), had erythema (33.3%), or had erosions (53.3%); histologically, it showed no epithelial change, mild mononuclear cell infiltration, and slight and focal neutrophil infiltration; Helicobacter heilmannii was positive with anti-H. pylori antibody, and was detected in the mucous gel layer and in foveolae. In MALT lymphoma, the gastric mucosa was coarsely granular with enlarged mucosal folds without ulcers (two cases), with small ulcers (one case), or with multiple erosions (one case). Urea breath test and antibody test were both negative. Eradication of H. heilmannii resulted in remission of MALT lymphoma. Helicobacter heilmannii infection is therefore uncommon in Japanese adults, but is associated with chronic gastritis and gastric MALT lymphoma.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2004

Histochemical, ultrastructural, and three-dimensional observation of smooth muscle cells in human gastric mucosa.

The present study was undertaken to clarify the histochemical and ultrastructural properties and the three-dimensional distribution of the smooth muscle cells (SMCs) located in the lamina propria (LP) of the human gastric mucosa. Standard paraffin sections obtained from stomachs surgically resected for gastric cancer were immunostained for alpha-smooth muscle actin (alpha-SMA), vimentin, desmin, laminin, and type IV collagen. In addition, 100-microm-thick sections were fluorostained for alpha-SMA and CD34, while three-dimensional images were prepared by confocal laser scanning microscope. Ultrastructural studies were carried out using normal gastric biopsy specimens. The results indicated that SMCs in the LP differed between the upper and lower regions, SMCs in the lower LP being fairly typical SMCs, whereas those in the upper LP had apparently lost reactivity for desmin but gained that for vimentin. The basal lamina became sparser, but a fibronexus was occasionally seen in SMCs in the upper LP. Three-dimensional images revealed bundles of SMCs in the upper LP encircling several foveolae to form acinus-like structures and, in the upper LP, SMCs branching into fine fibrils with a brush-like (corpus) or besom-like (i.e., a twiggy "witch's broom") appearance (antrum).

Actins↗
PubMed2004

Autoimmune pancreatitis is closely associated with gastric ulcer presenting with abundant IgG4-bearing plasma cell infiltration.

BACKGROUND: Autoimmune pancreatitis is characterized by high serum IgG4 concentrations and lymphoplasmacytic infiltration. Because of the diversity of extrapancreatic involvement in this disease, the present study sought to identify other associated GI-tract lesions. METHODS: EGD findings were compared between a group of 23 patients with autoimmune pancreatitis undergoing ERCP for obstructive jaundice and 230 age- and gender-matched control patients. To clarify the histopathologic differences found between these two groups, the histopathologic findings (Updated Sydney System) and the immunohistochemistry of each IgG subclass were compared between 8 patients with autoimmune pancreatitis and gastric ulcer, and 23 control patients with gastric ulcer from which biopsy specimens had been obtained. RESULTS: Gastric ulcer was found significantly more frequently in patients with autoimmune pancreatitis compared with control patients (34.8% vs. 13.5%; p=0.007). There was no significant difference between the groups with respect to the frequency of other GI lesions. Four of 8 gastric ulcers in patients with autoimmune pancreatitis were linear, with the long axis perpendicular to the incisura on the lesser curvature of the stomach. The activity score for the gastric lesions was significantly lower in patients with autoimmune pancreatitis compared with control patients (mean score 0.38 vs. 1.08; p=0.012). There were no significant differences in histopathologic findings with respect to inflammation, atrophy, metaplasia, or Helicobacter pylori scores between the two groups. IgG4-bearing plasma cells were significantly more abundant in gastric lesions in patients with autoimmune pancreatitis compared with those in control patients (mean score 1.75 vs. 0.39; p=0.0008). CONCLUSIONS: Autoimmune pancreatitis is closely associated with gastric ulcer with abundant IgG4-bearing plasma cell infiltration.

Aged↗
PubMed2004

Gastric MALT lymphomas are divided into three groups based on responsiveness to Helicobacter Pylori eradication and detection of API2-MALT1 fusion.

Gastric MALT lymphoma shows unique features including regression by Helicobacter pylori eradication and API2-MALT1 fusion. We performed a molecular and clinicopathologic study for 115 cases. All eradication-responsive cases were devoid of API2-MALT1 fusion. All tumors positive for the fusion and all negative for H. pylori infection were nonresponsive to the eradication. Consequently, gastric MALT lymphomas were divided into three groups: Eradication-responsive and fusion-negative (group A, n = 72), eradication-nonresponsive and fusion-negative (group B, n = 22), and eradication-nonresponsive and fusion-positive (group C, n = 21). Group A tumors were characterized by low clinical stage and superficial gastric wall involvement, and group C tumors by low H. pylori infection rate, advanced clinical stage, and nuclear BCL10 expression. All group C tumors showed exclusively low-grade histology. Group B tumors, which have not been well recognized, frequently showed nodal involvement, deep gastric wall involvement, and advanced clinical stage, and sometimes an increased large cell component. A multivariate discriminant analysis revealed that responsiveness to the eradication could be predicted accurately by negative API2-MALT1 fusion, positive H. pylori infection, low clinical stage, and superficial gastric wall invasion, the former being the most important factor for the prediction. This 3-group categorization may be helpful for a comprehensive understanding of gastric MALT lymphoma.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Possible relationship between Helicobacter pylori infection and cap polyposis of the colon.

BACKGROUND: Cap polyposis is a rarely encountered disease characterized by multiple distinctive inflammatory colonic polyps located from the rectum to the distal colon. The etiology of this disease is still unknown, and no specific treatment has been established. AIM: We report three cases of cap polyposis that were cured following eradication therapy for Helicobacter pylori infection. METHODS AND RESULTS: Three women were referred to Shinshu University Hospital because of mucoid and/or bloody diarrhea. Laboratory data showed hypoproteinemia in all cases; markers of inflammation such as C-reactive protein were negative. Colonoscopy revealed multiple sessile polyps with mucus adherent on the apices of the mucosal folds in the rectum and/or the sigmoid colon. The intervening mucosa was normal. Microscopic examinations of biopsy specimens taken from sessile polyps revealed inflamed mucosa with elongated tortuous crypts attenuated towards the mucosal surface. A granulation tissue 'cap' was observed on the surface of the mucosa. Various treatments were unsuccessful, including administration of metronidazole or prednisolone, avoidance of straining at defecation, and surgical or endoscopic resection. All were diagnosed with H. pylori infection in the stomach. Helicobacter pylori was not detected in the biopsy specimens from the colonic inflammatory polyps by immunohistochemical study using polyclonal anti-H. pylori antibody. After successful eradication therapy the clinical symptoms improved. Disappearance of cap polyposis was confirmed by colonoscopy in all three cases. CONCLUSION: We speculate that H. pylori infection might play a role in the pathogenesis of cap polyposis.

Adult↗
PubMed2003

Helicobacter pylori infection up-regulates gland mucous cell-type mucins in gastric pyloric mucosa.

BACKGROUND: Two types of mucous cell are present in gastric mucosa: surface mucous cells (SMCs) and gland mucous cells (GMCs), which consist of cardiac gland cells, mucous neck cells, and pyloric gland cells. We have previously reported that the patterns of glycosylation of SMC mucins are reversibly altered by Helicobacter pylori infection. In this study, we evaluated the effects of H. pylori infection on the expression of GMC mucins in pyloric gland cells. METHODS: Gastric biopsy specimens from the antrums of 30 H. pylori-infected patients before and after eradication of H. pylori and 10 normal uninfected volunteers were examined by immunostaining for MUC6 (a core protein of GMC mucins), alpha1,4-N-acetyl-glucosaminyl transferase (alpha4GnT) (the glycosyltransferase which forms GlcNAcalpha1-4Galbeta-R), and GlcNAcalpha1-4Galbeta-R (a GMC mucin-specific glycan). RESULTS: MUC6, alpha4GnT, and HIK1083-reactive glycan were expressed in the cytoplasm, supranuclear region, and secretory granules in pyloric gland cells, respectively. The immunoreactivity of MUC6 and alpha4GnT, but not of GlcNAcalpha1-4Galbeta-R, in the pyloric gland increased in H. pylori-associated gastritis, and after the eradication of H. pylori, the increased expression of MUC6 and alpha4GnT in the gastric mucosa of H. pylori-infected patients decreased to almost normal levels. This up-regulation was correlated with the degree of inflammation. CONCLUSIONS: In addition to the synthesis of GMC mucins increasing reversibly, their metabolism or release may also increase reversibly in H. pylori-associated gastritis. The up-regulation of the expression of gastric GMC mucins may be involved in defense against H. pylori infection in the gastric surface mucous gel layer and on the gastric mucosa.

Adult↗
PubMed2003

Helicobacter pylori and hetertopic gastric mucosa in the upper esophagus (the inlet patch).

OBJECTIVES: Helicobacter pylori (H. pylori) may colonize gastric mucosa wherever it is found in the GI tract. Heterotopic gastric mucosa in the upper esophagus (inlet patch) is a potential site for H. pylori infection and may provide a reservoir for oral-oral transmission or a niche where antibiotics might have difficulty reaching. The aim of this study was to analyze the intensity and distribution of H. pylori in the inlet patch. METHODS: Whenever a cervical inlet patch was observed, mucosal biopsy samples were taken to confirm the endoscopic diagnosis and to search for H. pylori and active inflammation. In addition, mucosal biopsy samples were also taken from the gastric mucosa. Formalin-fixed biopsy specimens were cut and stained with a new dual stain developed in our laboratory. The stain is a combination of periodic acid-Schiff and a silver stain that allows simultaneous visualization of H. pylori and gastric type epithelium. The density of H. pylori was scored using a visual analog scale of 0 to 5. The type of mucosa in the inlet patch was also recorded. RESULTS: The study included 48 patients; 37 had H. pylori gastritis and 27 of these (73%) had H. pylori identified on their heterotopic gastric mucosa. A higher density of H. pylori in the stomach was associated with a higher prevalence in the inlets. Active inflammation correlated with active infection in the inlet patch and the presence of antral type mucosa. CONCLUSION: H. pylori colonization of heterotopic gastric mucosa in the upper esophagus is common and is closely related to the H. pylori density in the stomach. The fact that H. pylori was not found in all cases suggests that another event such as reflux may be required for H. pylori to colonize heterotopic mucosa.

Adolescent↗
PubMed2002

Patterns of gastric atrophy in intestinal type gastric carcinoma.

BACKGROUND: 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. METHODS: Resected stomachs from patients with intestinal type gastric carcinoma were routinely processed, sectioned (an average of 108 sections/stomach), and stained with a triple stain. Sections were scored on a visual analog scale for Helicobacter pylori and intestinal metaplasia. The type of epithelium (antral, oxyntic, transitional) was recorded. Atrophy was defined as the loss of normal glandular components and included intestinal metaplasia and/or pseudo-pyloric metaplasia of the corpus. Pseudo-pyloric metaplasia was identified by the presence of pepsinogen I in mucosa that was topographically corpus but phenotypically antrum. RESULTS: Sixteen stomachs with intestinal type gastric carcinoma were examined. In none of the specimens examined was MAG (independent foci of atrophy) identified. In the majority (88%), atrophy was present as a continuous sheet. Islands of intestinal metaplasia (multifocal intestinal metaplasia) were present within a sheet of pseudo-pyloric metaplasia. A few specimens (12%) had a non-atrophic corpus with almost total replacement of antral epithelium with intestinal metaplasia. Multifocal dysplasia distant from the original tumor was found both in areas with and without intestinal metaplasia. CONCLUSIONS: Contrary to popular belief, atrophy in intestinal type gastric carcinoma is not present as independent foci, but rather as a continuous sheet. Previous studies failed to identify pseudo-pylori metaplasia as a marker for atrophy.

Aged↗
PubMed2002

Detection of genetic alterations in the p53 suppressor gene and the K-ras oncogene among different grades of dysplasia in patients with colorectal adenomas.

BACKGROUND: Although it is believed that p53 suppressor gene mutations, compared with mutations in the K-ras oncogene, occur at a later stage of colorectal tumorigenesis, the distribution of these genetic alterations at an early stage remains poorly characterized. METHODS: The authors analyzed the immunoreactivity for p53 protein (p53 protein expression), which reflects the functionally altered p53 gene, and K-ras mutations at codons 12 in 68 colorectal adenomas with both low-grade and high-grade dysplasia obtained from 62 patients. RESULTS: The prevalence of p53 positive immunostaining was significantly greater compared with the prevalence of K-ras mutations both in low-grade dysplasia and in high-grade dysplasia. Twenty-two adenomas (32.3%) showed positive immunostaining for p53 protein in high-grade dysplasia and also were positive for p53 in surrounding low-grade dysplastic tissues; 20 adenomas (29.4%) showed positive immunostaining for p53 protein in high-grade dysplasia and were negative for p53 in surrounding low-grade dysplastic tissues; 8 adenomas (11.7%) showed negative immunostaining for p53 protein in high-grade dysplasia and were positive for p53 in surrounding low-grade dysplastic tissues; and 18 adenomas (26.4%) showed negative immunostaining for p53 protein in both high-grade dysplasia and in surrounding low-grade dysplastic tissues. On the whole, a significant difference (P < 0.05) was seen in the frequency of p53 positive immunostaining between low-grade dysplasia and high-grade dysplasia (44.1% and 61.8%, respectively) but not in that of K-ras mutations (20.3% and 23.4%, respectively). CONCLUSIONS: The results of this study suggest that mutation of the p53 suppressor gene occurs earlier in the adenoma-carcinoma sequence than K-ras mutation, providing a clue for further understanding of the role of the p53 gene in the early stage of colorectal tumorigenesis.

Adenoma↗
PubMed2002

Local gastric and serum concentrations of rebamipide following oral ingestion in healthy volunteers.

The purpose of this study was to investigate whether sufficient concentrations of rebamipide (COR) are actually present in the stomach after its oral ingestion at an ordinary clinical dose. Twenty healthy volunteers (total 42 man-days) participated in the study. After ingestion of 100, 200, or 300 mg of rebamipide, endoscopy was performed at 1, 2, 4, and 6 hr, and gastric mucosa or gastric mucus was taken from the antrum. Venous blood samples were taken simultaneously. Samples were analyzed by high-performance liquid chromatography. The COR in the gastric mucosa and gastric mucus did not depend on the original amount ingested. After ingestion of rebamipide, each COR was higher than 10(-4) M (37 microg/g tissue) at 1 or 2 hr. On the other hand, the COR in serum did depend on the amount ingested and was lower than 10(-6) M (0.37 microg/ml) at every time tested. These results suggest that the COR in the stomach exceeds the levels that are needed for various antiulcer actions and that the rebamipide levels present in the gastric mucosa and gastric mucus result from local penetration.

Administration, Oral↗
PubMed2002

Additive effect of pronase on the efficacy of eradication therapy against Helicobacter pylori.

BACKGROUND: Helicobacter pylori (H. pylori) colonizes not only the surface of the surface mucous cells but also the surface mucous gel layer (SMGL). Thus, we examined the possible value of pronase, a mucolytic agent, as a potential eradication therapy. MATERIALS AND METHODS: One hundred and thirty-five patients were randomly assigned to two treatment groups. Sixty-eight patients received 30 mg of lansoprazole once daily, 500 mg of amoxicillin and 250 mg of metronidazole thrice daily for 2 weeks (LAM group), while the other 67 patients received the same dosage of those agents plus 18,000 tyrosine units of pronase thrice daily for 2 weeks (LAMP group). Eradication was assessed 4-6 weeks after treatment by immunohistochemical tests and cultures. We also determined the in vitro activity of pronase against H. pylori, and evaluated the synergistic effects between pronase and the other three drugs. To investigate the effect of pronase on the structure of the SMGL, surgically removed stomachs obtained from patients who had taken pronase were examined histopathologically. RESULTS: The cure rates for H. pylori infection in the LAMP group were significantly higher than those in the LAM group (intention to treat analysis: 94.0 vs. 76.5%, p =.0041). Pronase exhibited no antibacterial activity against H. pylori., and no in vitro synergistic effects were observed. In the patients who took pronase before surgery, the SMGL was thinner than in the patients who did not take pronase, and the structure of the SMGL was markedly disrupted. CONCLUSIONS: Pronase has an additive effect in curing H. pylori infection. Pronase has no apparent in vitro activity against H. pylori, but may improve the local delivery of antibiotics by virtue of its removal and disruption of the SMGL.

2-Pyridinylmethylsulfinylbenzimidazoles↗