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Minoru Tada

Publications and source records attributed to Minoru Tada.

26 records · Page 2Linked to original sources

Di-Ras, a distinct subgroup of ras family GTPases with unique biochemical properties.

The small GTPase Ras family regulates a variety of cell functions including proliferation and differentiation. Here we have identified novel Ras members, human Di-Ras1 and Di-Ras2, belonging to a distinct branch of the GTPase family. Di-Ras1 and Di-Ras2 specifically expressed in heart and brain share 30-40% overall identity with other members of Ras family, however, they have the following characteristic substitutions at highly conserved regions among the Ras family. 1) Thr-63 and Ser-65 in Di-Ras are substituted for Ala-59 and Gln-61 positions in Ha-Ras, respectively, that are known to be critical for GTP hydrolysis. 2) Within the effector domains, Di-Ras has Ile at a position corresponding to Asp-33 in Ha-Ras, which is important for its interaction with the downstream effector Raf. As predicted by these substitutions, Di-Ras has only a quite low level of GTPase activity and exists predominantly as a GTP-bound form upon its expression in living cells. Moreover, Di-Ras fails to interact with the Ras-binding domain of Raf, resulting in no stimulation of mitogen-activated protein kinase. Interestingly, introduction of Di-Ras into HEK293T cells induces large cellular vacuolation. These findings raise the possibility that Di-Ras might regulate cell morphogenesis in a manner distinct from other members of Ras family.

Amino Acid Sequence↗

Quantity of mutant K-ras gene in pancreatic secretions for diagnosis of pancreatic carcinoma with different assays: analysis of 100 patients.

BACKGROUND: Two types of quantitative assay kits for K-ras mutations, PCR-preferential homoduplex formation assay (PHFA) and enriched PCR and enzyme-linked mini-sequence assay (ELMA), were recently developed. The K-ras mutations were analyzed using these assays. MATERIALS AND METHODS: DNA was extracted from the pancreatic juice which was obtained by endoscopy from 38 patients with pancreatic neoplasms (23 adenocarcinomas and 15 intraductal papillary neoplasms) and from 62 without it. RESULTS: The results of the two methods were mutually correlative. K-ras mutation was detected at high levels (mutant ras genes occupied >2% of all K-ras genes) in 25 of the 38 cases (66%) with pancreatic neoplasm. It was also detected at high levels in 9 of the 14 cases (64%) with pancreatic cyst. In contrast, the mutant gene was detected at a lower level (<2%) in other cases. CONCLUSIONS: Quantitative analysis of the mutant ras gene provided a useful tool for diagnosing the pancreatic carcinoma when the percentage of the mutant is high, especially when the types of mutation were either GAT or GTT.

Adenocarcinoma↗

Polyurethane-covered metal stent for management of distal malignant biliary obstruction.

BACKGROUND: The efficacy of polyurethane-covered metal expandable stents for treatment of neoplastic distal biliary obstruction was analyzed. METHODS: Twenty-one patients with unresectable malignant tumors involving the mid to distal bile duct who were seen with obstructive jaundice were consecutively enrolled. Eighteen patients underwent endoscopic implantation of a polyurethane-covered metal stent and 3 patients underwent transhepatic insertion because of duodenal obstruction. The stent patency, complications, and patient survival were analyzed. RESULTS: Effective biliary decompression was achieved in all patients. Adverse events were minor: mild pancreatitis (1) and cholecystitis (2) occurred within 7 days of stent insertion. Mean survival and stent patency were 233 days and 206 days, respectively. Stent occlusion occurred in 3 patients (14%) after a mean of 188 days. Tumor ingrowth through the stent mesh was not observed. However, 2 stents were occluded by tumor overgrowth and 1 by compacted alimentary debris. CONCLUSIONS: A polyurethane membrane may prevent tumor ingrowth and reduce the occlusion rate for expandable metal stents implanted in patients with malignant obstruction of the distal bile duct.

Adult↗

Quantitative analysis of K-ras gene mutation in pancreatic tissue obtained by endoscopic ultrasonography-guided fine needle aspiration: clinical utility for diagnosis of pancreatic tumor.

OBJECTIVES: Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) has become established in the diagnosis of pancreatic cancer. The combination of pathological diagnosis and analysis for mutant K-ras gene was investigated to improve the accuracy of diagnosis. METHODS: EUS-FNA was performed in 34 patients with pancreatic masses (26 adenocarcinomas and eight chronic pancreatitis). Mutant ras gene was analyzed semiquantitatively in the specimens obtained by EUS-FNA as well as in pancreatic juice obtained by ERCP. RESULTS: Mutant gene was detected at high amounts (more than 2% of total ras genes) in 20 of 26 (77%) specimens of EUS-FNA and in 12 of 19 (63%) of pancreatic juice in cases with pancreatic carcinoma. Cytological diagnosis of malignancy by EUS-FNA was found in 16 of 26 (62%) patients with pancreatic cancer. Accurate diagnosis of the carcinoma was 21 of 26 (81%) by combined cytology and molecular method of EUS-FNA, and increased to 23 of 26 (88%) by adding molecular analysis of pancreatic juice. In contrast, mutant gene was absent or low level despite suspicious cytology in patients with benign pancreatic lesion. CONCLUSION: Quantitative analysis of mutant ras gene supplemented conventional cytology of EUS-FNA and ERCP. Detection of mutation at high amounts may represent pancreatic cancer, whereas its absence increased the possibility of benign lesion.

Adenocarcinoma↗

Histological analysis of the papilla after endoscopic papillary balloon dilation.

BACKGROUND/AIMS: Endoscopic papillary balloon dilation is an effective procedure in the management of bile duct stones and is believed to preserve the papillary function. The papillary architecture is also considered to be preserved. However, little is known about the effects of balloon dilation on papillary structure. The present study was conducted to elucidate these effects. METHODOLOGY: Since May 1994, endoscopic papillary balloon dilation was performed in 467 patients (407 patients for removal of bile duct stone, 57 for insertion of stent and 3 for baby cholangioscope). Of those, histological examinations were undertaken in 10 patients. The indications of endoscopic papillary balloon dilation were bile duct stone removal in 2 patients, stent insertion in 8. The specimens were obtained 2 to 63 weeks after endoscopic papillary balloon dilation during surgical operation in 6 patients and autopsy in 4 patients. Serial sections through the papilla were stained by hematoxylin and eosin and Masson's trichrome. The specimens were also obtained from 4 patients without biliary disease as control. RESULTS: No smooth muscle disruption nor architectural distortion was observed except for one patient who had mild disruption of smooth muscle caused by a biliary drainage tube. However, mild to moderate inflammation and fibrosis were seen in 9 patients and in 8, respectively. CONCLUSIONS: The papillary architecture is not affected by endoscopic papillary balloon dilation. This may imply that endoscopic papillary balloon dilation preserves papillary function.

Aged↗

"Duodenal intussusception" due to adenoma of the papilla of Vater.

The case of a 55-year-old woman with a pedunculate adenoma of the papilla of Vater is presented. Diagnostic imaging modalities including ultrasonography, CT scan, magnetic resonance of cholangiopancreatography, simultaneous duodenography and cholangiography, and angiography showed a giant tumor protruding intraluminally and moving forward in the duodenum by peristalsis. It had a duodenal intussusception-like appearance, with remarkable left-lower deviation of the common bile duct and major pancreatic duct in the papilla of Vater as far as the left side of the aorta. Episodes of jaundice or ileus were absent, probably because the tumor was mobile in the duodenum. As biopsy specimens showed no malignancy and intraductal ultrasonography in the common bile duct revealed no intraductal invasion of the tumor in the papilla of Vater, the patient underwent transduodenal papillectomy with papilloplasty with pancreatic ductoplasty. Pathological diagnosis of consecutive specimens was a papillary adenoma with moderate atypia and occasional tubular structure. There seems to be an exceptional subtype of the tumor in the papilla of Vater, like this case, demonstrating the duodenal intussusception-like appearance without prominent clinical symptoms.

Adenoma↗

Early removal of bile duct stones in patients with acute biliary pancreatitis by endoscopic papillary balloon dilatation.

BACKGROUND/AIMS: Endoscopic papillary balloon dilatation has been accepted as a novel alternative to endoscopic sphincterotomy for the management of bile duct stones. Hence, little or no attempt was made to retrieve stones in cases with acute biliary pancreatitis by endoscopic papillary balloon dilatation. METHODOLOGY: The present study was conducted in ten patients with acute biliary pancreatitis associated with cholestasis or biliary infection. Two patients came with disseminated intravascular coagulopathy, one Child C liver cirrhosis, and another with prolonged prothrombin time of unknown etiology. After the papilla was dilated with a balloon-tipped catheter, the stones were removed with either a retrieval basket catheter, a retrieval balloon, or both. RESULTS: Clearance of the common bile duct was achieved in all ten patients without any serious complications such as pancreatitis aggravation or hemorrhage. Clinical signs and laboratory findings were strikingly improved in all patients. CONCLUSIONS: The results suggest that bile duct stones can be effectively and safely removed by means of endoscopic papillary balloon dilatation even in patients with acute pancreatitis.

Aged↗