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Takeshi Azuma

Publications and source records attributed to Takeshi Azuma.

48 records · Page 3Linked to original sources

Cutting edge: analysis of human V alpha 24+CD8+ NK T cells activated by alpha-galactosylceramide-pulsed monocyte-derived dendritic cells.

Human Valpha24(+) NKT cells constitute a counterpart of mouse Valpha14(+) NKT cells, both of which use an invariant TCR-alpha chain. The human Valpha24(+) NKT cells as well as mouse Valpha14(+) NKT cells are activated by glycolipids in a CD1d-restricted manner and produce many immunomodulatory cytokines, possibly affecting the immune balance. In mice, it has been considered from extensive investigations that Valpha14(+)CD8(+) NKT cells that express invariant TCR do not exist. Here we introduce human Valpha24(+)CD8(+) NKT cells. These cells share important features of Valpha24(+) NKT cells in common, but in contrast to CD4(-)CD8(-) (double-negative) or CD4(+) Valpha24(+) NKT cells, they do not produce IL-4. Our discovery may extend and deepen the research field of Valpha24(+) NKT cells as well as help to understand the mechanism of the immune balance-related diseases.

Antigens, CD1↗

Intraductal mucinous tumors occurring simultaneously in the liver and pancreas.

A case of simultaneous intraductal mucinous tumors of the liver and pancreas in a 67-year-old man is described. Abdominal ultrasonography and computed tomography (CT) revealed the presence of cystic lesions with intraluminal septae both in the caudate lobe of the liver and in the uncinate process of the pancreas; these cystic lesions communicated with the hepatic duct and pancreatic duct, respectively. Mucin retention was observed in the cysts, and cholestasis was induced by mucin secretion into the common bile duct. The lesions were resected by left hepatic lobectomy with caudate lobectomy, and segmental pancreatectomy. Both lesions were multilocular cystic tumors with no papillary projections or focal mass effect in their walls. Histologically, both cystic lesions were a mixture of hyperplasia and adenoma lined by low papillary columnar epithelium. There were no cellular or histological features to suggest malignant change. The fibrous intratumor interstitium lacked any mesenchymal or ovarian-like stroma. The hepatic lesion was considered to be of a similar nature to intraductal papillary mucinous tumor (IPMT) of the pancreas. However, the two lesions occurred simultaneously in the liver and pancreas. This case is of interest in regard to the diagnosis and management of mucinous hepatopancreatobiliary lesions.

Aged↗

Clinical relevance of cagE gene from Helicobacter pylori strains in Japan.

It has been reported that H. pylori-containing cagE was associated with duodenal ulcer. The aims of the present study were to clarify the association between the cagE gene and clinical outcome and to analyze the relationship between the cagE gene and two other virulence factors--cagA and vacA--in two areas in Japan (Fukui and Okinawa) where the prevalence of duodenal ulcer and gastric cancer risk are quite different. Eighty of 81 isolates possessed the cagE gene, and all isolates possessed the cagA gene. The vacA genotype s1c/ml was a major genotype in both areas in Japan. There was no significant association between cagE, cagA status, or vacA genotype and clinical outcome. Phylogenetic analysis of the cagE gene indicated that most Japanese isolates formed a different cluster from strains isolated in the West with an association with the vacA genotype. In conclusion, the strains with cagE, cagA, and the s1c/ml genotype of vacA are predominant in Japan regardless of clinical outcome and construct a different phylogenetic cluster from those in the West.

Adult↗

Cell proliferation and renewal of normal hepatocytes and bile duct cells in adult mouse liver.

BACKGROUND/AIMS: The source of new cells in the normal adult liver has been controversial. Some investigators have hypothesized the streaming liver model. On the other hand, others reject this hypothesis. We examined hepatic cell kinetics by a special labeling method with [3H]thymidine. METHODS: ICR mice received 112 repeated injections of [3H]thymidine at 6 h intervals for 28 days after birth and were killed immediately thereafter, or 100, 200 or 300 days after the last injection. Immediately after killing the animals, samples of the liver were taken and autoradiography was performed. RESULTS: After continuous labeling, more than 90% of the cells in the liver were labeled. Mean grain counts of hepatocytes decreased to half over approximately 100 days. Those of bile duct cells decreased at a slower rate (50%) than hepatocytes. Mean grain counts of hepatocytes decreased over the regions, although those in perivenular region decreased more rapidly in comparison to those in periportal region. CONCLUSIONS: The present study indicated that most cells in the liver arise postnatally. The changes in labeling of cells show that there is no special zone for proliferation of hepatocytes and they renew in all regions of the hepatic lobule, suggesting (i) that hepatocytes are supplied by postnatal replication and (ii) streaming of hepatocytes from periportal to pericentral regions does not occur in the adult mouse liver. The bile duct cells renewed more rapidly than hepatocytes.

Animals↗

Cell kinetics of slow renewing cell populations in mice stomach.

BACKGROUND: The renewal rates of parietal and chief cells in the gastric mucosa and smooth muscle cells of muscularis propria have not been examined as precisely as superficial epithelial cells. To examine cell renewal of these cells, continuous labeling with tritiated ([3H])-thymidine was performed. METHODS: Mice received 112 repeated injections of [3H]-thymidine at 6-hour intervals for 28 days after birth and were killed immediately thereafter, or 60, 120, 200 or 300 days after the last injection. RESULTS: After continuous labeling, most cells in the stomach were labeled. At 60 days, unlabeled parietal cells in the neck area of the gland and unlabeled chief cells in the middle part of the gland appeared. Thereafter, the area of unlabeled cells expanded downwards to the bottom of the gland. Times required for labeling of total cell populations of parietal and chief cells to half were less than 60 days and more than 200 days, respectively. At 300 days, most parietal cells and about half of the chief cells remained labeled in the bottom of the gland. The labeling index of smooth muscle cells was about 100% for 300 days. CONCLUSIONS: The time required for the newly formed parietal and chief cells to reach the lower end of the gland was more than 300 days. As a total cell population, the renewal rate of parietal cells was more rapid than that of chief cells. However, in terms of the downward migrating cell population, the renewal rate of parietal cells was a little slower than that of chief cells. Smooth muscle cells showed almost no renewal.

Animals↗

Dendritic cell immunotherapy for patients with metastatic renal cell carcinoma: University of Tokyo experience.

BACKGROUND: Dendritic cells (DC) are the most potent antigen-presenting cells and induce host antitumor immunity through the T-cell response. A clinical study of immunotherapy using cultured DC loaded with tumor antigen, for patients with metastatic renal cell carcinoma (RCC) was performed. METHODS: Dendritic cells were generated by culturing monocytes from peripheral blood for 7 days in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. On day 6 the DC were pulsed with lysate from autologous tumor as the antigen and with keyhole limpet hemocyanin (KLH) as immunomodulator. The patients were given four doses of lysate-pulsed DC by intradermal injection with a 2-week interval between doses. Clinical effect and immune response were, respectively, evaluated by radiological examination and delayed-type hypersensitivity (DTH) test. RESULTS: Three patients were enrolled and the immunotherapy was well tolerated without significant toxicity. The vaccination induced a positive DTH reaction to tumor lysate in two patients and to KLH in all patients. Clinical responses consisted of one case of no change and two cases of progression of disease. However, we did not see a significant reduction of tumor volume in any case. CONCLUSION: Dendritic cell vaccination can safely induce an immunological response against RCC. Further trials are needed to fully evaluate its efficacy.

Adult↗

Heterogeneous cell renewal of pancreas in mice: [(3)H]-thymidine autoradiographic investigation.

INTRODUCTION: Although cell kinetics of the gastrointestinal mucosa has been extensively examined, that of the pancreas has not been fully analyzed. AIM: To determine the renewal rate of pancreatic cells directly. METHODOLOGY: Postnatal proliferative activity and cellular renewal of the parenchymal cells in ICR mouse pancreas were studied by immunohistochemistry and [(3)H]-thymidine autoradiography. RESULTS: In the single labeling experiments, the proliferative activity of the parenchymal cells in pancreas showed peaks at a few days after birth, decreased thereafter, and reached a low level at 2 months after birth. Continuous labeling experiments revealed that, in the adult pancreas, the half lives of acinar cells, islet cells, and duct epithelial cells were approximately 70 days, 47 days, and 40 days, respectively. Moreover, in the exocrine pancreas, acinar cells of the peri-insular region proliferated more actively than those of the tele-insular region. The renewal rate of glucagon cells was more rapid than that of insulin cells or somatostatin cells. Large ducts showed a high rate of cell renewal in comparison with small ducts. CONCLUSION: The results of this study indicate that cell renewal rates of the pancreas are not homogeneous, but heterogeneous.

Analysis of Variance↗

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2-Pyridinylmethylsulfinylbenzimidazoles↗

SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein.

Helicobacter pylori CagA protein is associated with severe gastritis and gastric carcinoma. CagA is injected from the attached Helicobacter pylori into host cells and undergoes tyrosine phosphorylation. Wild-type but not phosphorylation-resistant CagA induced a growth factor-like response in gastric epithelial cells. Furthermore, CagA formed a physical complex with the SRC homology 2 domain (SH2)-containing tyrosine phosphatase SHP-2 in a phosphorylation-dependent manner and stimulated the phosphatase activity. Disruption of the CagA-SHP-2 complex abolished the CagA-dependent cellular response. Conversely, the CagA effect on cells was reproduced by constitutively active SHP-2. Thus, upon translocation, CagA perturbs cellular functions by deregulating SHP-2.

Amino Acid Substitution↗