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Takeshi Azuma

Publications and source records attributed to Takeshi Azuma.

At least 37 records · Page 2Linked to original sources
PubMed2004

Association between diversity in the Src homology 2 domain--containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer.

We investigated the relationship between the diversity of Helicobacter pylori CagA protein and clinical outcome. The cagA gene was sequenced in 115 clinical isolates. The binding affinity of CagA to Src homology 2 domain-containing tyrosine phosphatase (SHP-2) was examined by in vitro infection. Two major CagA subtypes were observed--the East Asian and the Western type. The grades of inflammation, activity of gastritis, and atrophy were significantly higher in patients with gastritis infected with the East Asian CagA-positive strain than in patients with gastritis infected with cagA-negative or Western CagA-positive strains. All strains isolated from patients with gastric cancer were East Asian CagA positive. East Asian CagA exhibited stronger SHP-2-binding activity than did Western CagA. These findings suggest that infection with East Asian CagA-positive H. pylori is associated with atrophic gastritis and gastric cancer and that persistent active inflammation induced by the East Asian CagA-positive strain may play a role in the pathogenesis of disease.

Amino Acid Sequence↗
PubMed2004

The diversity of vacA and cagA genes of Helicobacter pylori in East Asia.

It has been reported that Helicobacter pylori infection with the type I strain, which expresses the VacA and CagA antigens, is associated with duodenal ulcer. We examined the diversity of vacA and cagA genes in 143 isolates obtained from patients with duodenal ulcer or chronic gastritis in East Asia (two different areas of Japan, Fukui and Okinawa, and also in Hangzhou, China) by polymerase chain reaction (PCR) and sequence analysis. Diversities of cagA and vacA genes were detected in East Asia. The prevalence of cagA-positive H. pylori was significantly different between Fukui and Okinawa (P=0.0032). The prevalence of Western type CagA was significantly higher in Okinawa than in Fukui (P<0.0001). However, there was no significant association between the genotype of cagA and clinical outcome. In Japan, the predominant vacA genotype was s1c/m1b. In contrast, in Hangzhou, the predominant vacA genotype was s1c/m2, and they were all East Asian CagA-positive. These findings suggest that a distinct distribution of the vacA and cagA genotypes is present in East Asia, regardless of clinical outcome.

Adult↗
PubMed2004

Helicobacter pylori CagA protein variation associated with gastric cancer in Asia.

Recent molecular analysis has provided the pathological actions of CagA on gastric epithelial cells. CagA is injected into epithelial cells via the type IV secretion system and undergoes tyrosine phosphorylation in the cells. In addition, translocated CagA forms a physical complex with SHP-2. There are two major CagA subtypes; the East Asian and the Western type. The East Asian CagA protein possesses stronger SHP-2 binding activity than the Western CagA. The grades of inflammation, activity of gastritis, and atrophy are significantly higher in gastritis patients infected with the East Asian CagA-positive strain than in gastritis patients infected with the cagA-negative or Western CagA-positive strains. The prevalence of the East Asian CagA-positive strain is associated with the mortality rate of gastric cancer in Asia. Endemic circulation of H. pylori populations carrying biologically more active CagA proteins in East Asian countries, where the mortality rate of gastric cancer is among the highest in the world, may be involved in increasing the risk of gastric cancer in these populations.

Amino Acid Sequence↗
PubMed2004

Recurrent peptic ulcers in patients following successful Helicobacter pylori eradication: a multicenter study of 4940 patients.

OBJECTIVE: Although curative treatment of Helicobacter pylori infection markedly reduces the relapse of peptic ulcers, the details of the ulcers that do recur is not well characterized. The aim of this study is to describe the recurrence rate and specific features of peptic ulcers after cure of H. pylori infection. METHODS: This was a multicenter study involving 4940 peptic ulcer patients who were H. pylori negative after successful eradication treatment and were followed for up to 48 months. The annual incidence of ulcer relapse in H. pylori-cured patients, background of patients with relapsed ulcers, time to relapse, ulcer size, and site of relapsed ulcers were investigated. RESULTS: Crude peptic ulcer recurrence rate was 3.02% (149/4940). The annual recurrence rates of gastric, duodenal and gastroduodenal ulcer were 2.3%, 1.6%, and 1.6%, respectively. Exclusion of patients who took NSAIDs led annual recurrence rates to 1.9%, 1.5% and 1.3%, respectively. The recurrence rate was significantly higher in gastric ulcer. Recurrence rates of patients who smoked, consumed alcohol, and used NSAIDs were significantly higher in those with gastric ulcer recurrence compared to duodenal ulcer recurrence (e.g. 125 of 149 [83.9%] relapsed ulcers recurred at the same or adjacent sites as the previous ulcers). CONCLUSIONS: Curative treatment of H. pylori infection is useful in preventing ulcer recurrence. Gastric ulcer is more likely to relapse than duodenal ulcer. Recurrent ulcer tended to recur at the site of the original ulcers.

Alcohol Drinking↗
PubMed2004

Evolutionary dynamics of insertion sequences in Helicobacter pylori.

Prokaryotic insertion sequence (IS) elements behave like parasites in terms of their ability to invade and proliferate in microbial gene pools and like symbionts when they coevolve with their bacterial hosts. Here we investigated the evolutionary history of IS605 and IS607 of Helicobacter pylori, a genetically diverse gastric pathogen. These elements contain unrelated transposase genes (orfA) and also a homolog of the Salmonella virulence gene gipA (orfB). A total of 488 East Asian, Indian, Peruvian, and Spanish isolates were screened, and 18 and 14% of them harbored IS605 and IS607, respectively. IS605 nucleotide sequence analysis (n = 42) revealed geographic subdivisions similar to those of H. pylori; the geographic subdivision was blurred, however, due in part to homologous recombination, as indicated by split decomposition and homoplasy tests (homoplasy ratio, 0.56). In contrast, the IS607 populations (n = 44) showed strong geographic subdivisions with less homologous recombination (homoplasy ratio, 0.2). Diversifying selection (ratio of nonsynonymous change to synonymous change, >>1) was evident in approximately 15% of the IS605 orfA codons analyzed but not in the IS607 orfA codons. Diversifying selection was also evident in approximately 2% of the IS605 orfB and approximately 10% of the IS607 orfB codons analyzed. We suggest that the evolution of these elements reflects selection for optimal transposition activity in the case of IS605 orfA and for interactions between the OrfB proteins and other cellular constituents that potentially contribute to bacterial fitness. Taken together, similarities in IS elements and H. pylori population genetic structures and evidence of adaptive evolution in IS elements suggest that there is coevolution between these elements and their bacterial hosts.

DNA Transposable Elements↗
PubMed2004

Distinct diversity of the cag pathogenicity island among Helicobacter pylori strains in Japan.

The severity of Helicobacter pylori-related disease is correlated with the presence of a cag pathogenicity island (PAI). Genetic diversity within the cag PAI may have a modifying effect on the pathogenic potential of the infecting strain. We analyzed the complete cag PAI sequences of 11 representative Japanese strains according to their vacA genotypes and clinical effects and examined the relationship between the diversity of the cag PAI and clinical features. The cag PAI genes were divided into two major groups, a Western and a Japanese group, by phylogenetic analysis based on the entire cag PAI sequences. The predominant Japanese strains formed a Japanese cluster which was different from the cluster formed by Western strains. The diversity of the cag PAI was associated with the vacA and cagA genotypes. All strains with the s1c vacA genotype were in the Japanese cluster. In addition, all strains with the East Asian-type cagA genotype were also in the Japanese cluster. Patients infected with the Japanese-cluster strain had high-grade gastric mucosal atrophy. These results suggest that a distinct diversity of the cag PAI of H. pylori is present among Japanese strains and that this diversity may be involved in the development of atrophic gastritis and may increase the risk for gastric cancer.

Antigens, Bacterial↗
PubMed2004

Gastric dysmotility associated with accumulation of mitochondrial A3243G mutation in the stomach.

OBJECTIVE: We analyzed the accumulation of a mitochondrial A-to-G mutation at nucleotide position 3243 (A3243G) in the stomach and gastric motility in patients with gastric symptoms, post-prandial nausea/vomiting and epigastralgia. METHODS: Detection and quantification of A3243G mutation in mtDNA in the gastric mucosa, oral mucosa, leukocyte, and skeletal muscle were performed. Gastric motility was evaluated by gastric myoelectrical activity on electrogastrography (EGG), and gastric emptying was evaluated by measurement of plasma paracetamol concentration before and after meals. PATIENTS OR MATERIALS: Four patients with A3243G mutation in the leukocyte mtDNA and gastric symptoms were examined. RESULTS: The A3243G mutation was detected at higher percentages in the gastric body (69-94% for mutation; mean, 83%) than in the angle portion (37-82%; mean, 52%), the antrum (40-84%; mean, 57%) or leukocytes (28-52%; mean, 39%), and at slightly higher percentages than in the skeletal muscles (45-87%; mean, 70%) or oral mucosae (52-86%; mean, 69%) in the four patients examined. Abnormal EGGs were observed in the three patients examined. The pre-prandial myoelectrical activities were low in these patients (49% in patient 1, 54% in patient 2, 63% in patient 3; normal >70%). The plasma concentrations of paracetamol were low (3.6 microg/ml in patient 1, 2.4 microg/ml in patient 2, <2.0 microg/ml in patient 3; normal, 7-12 microg/ml). CONCLUSION: Accumulation of mitochondrial A3243G mutation in the stomach is a contributory factor in gastric dysmotility and gastric symptoms in patients with the mutation in their leukocytes.

Adult↗
PubMed2004

Fulminant varicella infection complicated with acute respiratory distress syndrome, and disseminated intravascular coagulation in an immunocompetent young adult.

Primary varicella infection in immunocompetent adults is very rare, but it has a high mortality rate because of serious complications. We describe a case of varicella infection in a previously healthy young adult complicated with acute respiratory distress syndrome (ARDS), rhabdomyolysis, acute hepatitis and disseminated intravascular coagulation (DIC). Acyclovir was administered for varicella infection and the ARDS was successfully treated with steroidpulse therapy, hemofiltration and a mechanical respiratory support with a positive end-expiratory pressure. Early administration of antiviral agents and extensive management were thought to be necessary for such patients with severe complications.

Adult↗
PubMed2003

Human CD4+ CD25+ regulatory T cells suppress NKT cell functions.

CD4+CD25+ regulatory T cells play an important role in peripheral tolerance. These cells have been reported to be capable of suppressing the response of CD4+CD25- T cells in vitro. The depletion of these cells evokes effective immune responses to tumor cells in vivo. In this study, we demonstrate that CD4+CD25+ T cells also suppress all subsets of Valpha24+NKT cells (Valpha24+CD4-CD8- double negative, Valpha24+CD4+, and Valpha24+CD8+) in both proliferation and cytokine production [IFN-gamma, interleukin-4 (IL-4), IL-13, and IL-10]. This suppression is mediated by cell-to-cell contact but not by a humoral factor or the inhibition of antigen-presenting cells. Moreover, the cytotoxic activity of Valpha24+NKT cells against some tumor cell lines is suppressed by CD4+CD25+ T cells. This finding is important in developing an effective immunotherapy for cancer.

CD4-Positive T-Lymphocytes↗
PubMed2003

Effects of percutaneous endoscopic gastrostomy tube placement on gastric antral motility and gastric emptying.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is the preferred method for providing enteral nutritional support in patients with dysphagia. We examined gastric antral myoelectrical activity and gastric emptying before and after PEG tube placement to evaluate the effects of PEG on gastric motility. METHODS: PEG was performed in 41 patients; 21 fed by total parenteral nutrition (TPN) and 20 who received nasogastric tube feeding (NGF). Antral myoelectrical activity and gastric emptying were examined before and 4 weeks after PEG tube placement. RESULTS: The percentage of normal-range electrogastrograms (EGGs) was significantly lower in the TPN group than in the NGF group in both the pre- and postprandial periods before PEG tube placement. Enteral feeding after PEG tube placement improved gastric motility in the patients with TPN. The percentage of normal-range EGGs increased significantly after PEG tube placement in both the pre- and postprandial periods, and plasma concentrations of paracetamol increased significantly after PEG tube placement in patients with TPN. A total of 7.3% of the patients developed the complication of gastroesophageal reflux (GER) after PEG tube placement. Gastric myoelectrical activity and gastric emptying were improved in these patients with GER after PEG tube placement. In contrast, the prevalence of esophageal hiatus hernia was significantly higher in patients with GER after PEG tube placement than in patients without GER after PEG tube placement. CONCLUSIONS: Prolonged TPN with bowel rest induces physiological dysfunction of gastric motility. Enteral nutrition is the preferable physiological nutritional route. GER after PEG tube placement is not related to gastric motility. Esophageal hiatus hernia seems to be a major risk factor for GER complications after PEG tube placement. Percutaneous endoscopic gastrostomy (PEG) is the preferred method for providing enteral nutritional support in patients with dysphagia. We examined gastric antral myoelectrical activity and gastric emptying before and after PEG tube placement to evaluate the effects of PEG on gastric motility.

Acetaminophen↗
PubMed2003

Primary hepatic neuroendocrine carcinoma coexisting with hepatocellular carcinoma in hepatitis C liver cirrhosis: report of a case.

Primary hepatic neuroendocrine carcinoma is an extremely rare tumor of the liver. We herein describe a case of primary hepatic neuroendocrine carcinoma with lymph node metastases, coexisting with hepatocellular carcinoma, on a background of hepatitis C cirrrhosis, in a 72-year-old man. Abdominal ultrasonography and computed tomography (CT) showed a tumor (3 cm in diameter) in Couinaud's hepatic segment 8 (S8) with regional lymph node metastases. Whole-body CT, magnetic resonance imaging (MRI), and endoscopy did not reveal primary lesions outside the liver. Feridex MRI and [(18)F]fluorodeoxyglucose positron emission tomography were strongly suspicious of malignancy. A limited hepatectomy with regional lymph node dissection was performed. Histopathology, immunohistochemistry, and electron microscopy confirmed a diagnosis of primary neuroendocrine carcinoma on a background of liver cirrhosis. A tumor (1.5 cm in diameter) found in hepatic S5 at operation was also simultaneously resected, and histologically diagnosed to be hepatocellular carcinoma. We also review previous reports of hepatic neuroendocrine carcinoma and discuss hypotheses for the histogenesis of these tumors as well as prognostic implications. Given the background cirrhosis and coexisting hepatocellular carcinoma, we speculate that one of the hepatocellular carcinomas underwent neuroendocrine differentiation.

Aged↗
PubMed2003

Dendritic cell vaccination for patients with chronic myelogenous leukemia.

In this pilot study, we investigated the ability of autologous dendritic cells (DCs) pulsed ex vivo with leukemia-specific peptide to stimulate host antitumor immunity when administrated as a vaccine. Three patients with chronic myelogenous leukemia (CML) received three series of four administration of bcr-abl peptide-pulsed (1) blood DCs injected intravenously, (2) immature monocyte-derived DCs injected intradermally or (3) mature monocyte-derived DCs injected intradermally. Vaccination was well tolerated. No major toxicity occurred in any of the patients. In method (1), one patient developed peptide-specific cellular immune response with no clinical response. In method (2), one patient developed peptide-specific cellular immune response with no clinical response. In method (3), all patients developed peptide-specific cellular immune response with no clinical response. The clinical benefits of bcr-abl peptide-specific vaccination in CML remain to be determined. Further vaccine development is necessary to increase the clinical effect.

Cancer Vaccines↗
PubMed2003

Turnover of acinar and islet cells in the pancreas of monosodium glutamate-treated obese mice.

OBJECTIVE: Subcutaneous administrations of monosodium glutamate (MSG) to neonatal animals result in obesity and induce the toxicity on the central nervous system, and furthermore, have an effect on entero-pancreatic hormone. The effect of MSG on the cell turnover of organs, especially the pancreas, has received little attention until now. This study was designed to examine the effect of MSG on pancreatic cell turnover by immunohistochemistry and [(3)H]thymidine autoradiography. RESEARCH METHODS AND PROCEDURES: Male JcI-ICR strain mice were SC injected with MSG (2 mg/g body weight daily) for 5 days after birth, received 112 repeated injections of [(3)H]thymidine at 6-hour intervals for 28 days after birth, and then were killed immediately thereafter, or 30, 60, or 120 days after the last injection. Autoradiography was performed on sections immunostained for glucagon, insulin, and somatostatin. RESULTS: After continuous labeling, most pancreatic cells were labeled, and thereafter, labeling of cells decreased in control and MSG-treated mice. The mean grain counts of acinar cells in MSG-treated mice decreased more slowly than those in control mice. On the other hand, those of islet cells, including glucagon, insulin, and somatostatin cells, decreased more rapidly in MSG-treated mice than those in control mice. DISCUSSION: Cell turnover of acinar cells was decelerated and that of islet cells including glucagon, insulin, and somatostatin cells was accelerated in MSG-treated mice pancreas. MSG-induced hypothalamic lesions exert the contrary influences on the cell turnover of acinar and islet cells.

Animals↗
PubMed2002

The CagA protein of Helicobacter pylori is translocated into epithelial cells and binds to SHP-2 in human gastric mucosa.

Recent experiments have indicated that CagA of Helicobacter pylori is injected into epithelial cells via the type IV secretion system and undergoes tyrosine phosphorylation in cells and that translocated CagA binds the SRC homology 2 domain-containing tyrosine phosphatase (SHP-2). We investigated these phenomena in in vivo human gastric mucosa. Tyrosine-phosphorylated CagA and CagA-coimmunoprecipitated SHP-2 were detected in gastric mucosa from H. pylori-positive patients with atrophic gastritis and in noncancerous tissues from H. pylori-positive patients with early gastric cancer. In contrast, CagA was not detected in gastric mucosa with either intestinal metaplasia or cancer. Our results provide the first evidence that CagA is translocated into the gastric epithelial cells, receives tyrosine phosphorylation, and binds SHP-2 in in vivo human gastric mucosa. Deregulation of SHP-2 by CagA may play a role in the acquisition of a cellular-transformed phenotype at a relatively early stage of multistep gastric carcinogenesis.

Antigens, Bacterial↗
PubMed2002

Correlation between variation of the 3' region of the cagA gene in Helicobacter pylori and disease outcome in Japan.

Genetic diversity within the cag pathogenicity island (PAI) of Helicobacter pylori may have a modifying effect on the pathogenic potential of the infecting strain. The genetic structure of the cag PAI was examined in Japanese isolates. The composition and nucleotide sequences of the cag PAI were quite similar among strains; however, diversity between 2 cag genes (virB10 and cagA) was observed. The variety in the number of repetition of the 5-amino acid sequence R1 (EPIYA) in the 3' region of the cagA gene was identified. The frequencies of the genotypes that contained >4 R1 sequences were significantly higher in atrophic gastritis-causing strains than in duodenal ulcer-causing strains. One-third of strains with >4 R1 sequences were gastric cancer-causing strains. Although the cag PAI is conserved in H. pylori isolates in Japan, H. pylori infection with the cagA genotype with >4 R1 sequences may correlate with the pathogenesis of atrophic gastritis and gastric cancer.

Amino Acid Sequence↗
PubMed2002

Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites.

Helicobacter pylori is a causative agent of gastritis and peptic ulcer. cagA(+) H. pylori strains are more virulent than cagA(-) strains and are associated with gastric carcinoma. The cagA gene product, CagA, is injected by the bacterium into gastric epithelial cells and subsequently undergoes tyrosine phosphorylation. The phosphorylated CagA specifically binds SHP-2 phosphatase, activates the phosphatase activity, and thereby induces morphological transformation of cells. CagA proteins of most Western H. pylori isolates have a 34-amino acid sequence that variably repeats among different strains. Here, we show that the repeat sequence contains a tyrosine phosphorylation site. CagA proteins having more repeats were found to undergo greater tyrosine phosphorylation, to exhibit increased SHP-2 binding, and to induce greater morphological changes. In contrast, predominant CagA proteins specified by H. pylori strains isolated in East Asia, where gastric carcinoma is prevalent, had a distinct tyrosine phosphorylation sequence at the region corresponding to the repeat sequence of Western CagA. This East Asian-specific sequence conferred stronger SHP-2 binding and morphologically transforming activities to Western CagA. Finally, a critical amino acid residue that determines SHP-2 binding activity among different CagA proteins was identified. Our results indicate that the potential of individual CagA to perturb host-cell functions is determined by the degree of SHP-2 binding activity, which depends in turn on the number and sequences of tyrosine phosphorylation sites. The presence of distinctly structured CagA proteins in Western and East Asian H. pylori isolates may underlie the strikingly different incidences of gastric carcinoma in these two geographic areas.

Amino Acid Sequence↗