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Y Shirai

Publications and source records attributed to Y Shirai.

At least 127 records · Page 7Linked to original sources
PubMed1998

Mutations of p53 in gallbladder carcinomas in high-incidence areas of Japan and Chile.

Gallbladder adenocarcinomas from patients in two high-prevalence areas, Niigata (Japan) and Santiago (Chile), were analyzed for acquired mutations in exons 5-8 of the p53 tumor suppressor gene, and the characteristics of p53 alterations in the two groups were compared. Of 42 tumors, 22 (52.4%) harbored 25 alterations identified by PCR amplification and direct sequencing (13 of 22 tumors from Niigata and 12 of 20 tumors from Santiago). All alterations were single base pair substitutions, 20 (80%) leading to an amino acid substitution or a chain-termination signal, and 5 (20%) were silent. Immunohistochemically, 55 of 84 cases (65.5%) showed overexpression of p53 protein, with no significant difference in frequency between the two areas. Missense mutations correlated highly with overexpression of the p53 protein (93.4%). Mutations of p53 occurred in all four exons examined, most commonly in exon 5, but in no particular "hot spot." In base-change spectra, all 12 mutations from Santiago showed transitions, with 4 arising at the CpG dinucleotide (33.3%). In contrast, no such transition was found at CpG sites in Niigata, and 4 of 13 mutations (30.8%) were transversions. The data indicated that p53 mutations are highly important in carcinogenesis in the gallbladder. In addition, the difference in p53 mutational spectra in Niigata and Santiago indicate a likely regional difference in mutagenesis.

Adult↗
PubMed1998

[Genetic alterations in gallbladder carcinoma: a review].

Earlier evidence suggests that gallbladder carcinoma (GBC) has three carcinogenic pathways; de novo development; adenoma-carcinoma sequence; and hyperplasia-carcinoma sequence associated with an anomalous arrangement of the pancreaticobiliary duct (AAPBD). We review gene abnormalities in GBC reported to date. p53 mutation and its protein overexpression are frequently observed in de novo carcinoma and GBC with AAPBD, but never found in carcinoma with adenoma. The incidence of K-ras codon 12 mutation in GBCs with AAPBD is significantly higher than that in the other types. Mutation of K-ras is never detected in carcinoma with adenoma. These findings suggest that diverse genetic pathways may exist in gallbladder carcinogenesis and reflect morphologic variations.

Adenoma↗
PubMed1997

Direct visualization of the translocation of the gamma-subspecies of protein kinase C in living cells using fusion proteins with green fluorescent protein.

We expressed the gamma-subspecies of protein kinase C (gamma-PKC) fused with green fluorescent protein (GFP) in various cell lines and observed the movement of this fusion protein in living cells under a confocal laser scanning fluorescent microscope. gamma-PKC-GFP fusion protein had enzymological properties very similar to that of native gamma-PKC. The fluorescence of gamma-PKC- GFP was observed throughout the cytoplasm in transiently transfected COS-7 cells. Stimulation by an active phorbol ester (12-O-tetradecanoylphorbol 13-acetate [TPA]) but not by an inactive phorbol ester (4alpha-phorbol 12, 13-didecanoate) induced a significant translocation of gamma-PKC-GFP from cytoplasm to the plasma membrane. A23187, a Ca2+ ionophore, induced a more rapid translocation of gamma-PKC-GFP than TPA. The A23187-induced translocation was abolished by elimination of extracellular and intracellular Ca2+. TPA- induced translocation of gamma-PKC-GFP was unidirected, while Ca2+ ionophore-induced translocation was reversible; that is, gamma-PKC-GFP translocated to the membrane returned to the cytosol and finally accumulated as patchy dots on the plasma membrane. To investigate the significance of C1 and C2 domains of gamma-PKC in translocation, we expressed mutant gamma-PKC-GFP fusion protein in which the two cysteine rich regions in the C1 region were disrupted (designated as BS 238) or the C2 region was deleted (BS 239). BS 238 mutant was translocated by Ca2+ ionophore but not by TPA. In contrast, BS 239 mutant was translocated by TPA but not by Ca2+ ionophore. To examine the translocation of gamma-PKC-GFP under physiological conditions, we expressed it in NG-108 cells, N-methyl-D-aspartate (NMDA) receptor-transfected COS-7 cells, or CHO cells expressing metabotropic glutamate receptor 1 (CHO/mGluR1 cells). In NG-108 cells , K+ depolarization induced rapid translocation of gamma-PKC-GFP. In NMDA receptor-transfected COS-7 cells, application of NMDA plus glycine also translocated gamma-PKC-GFP. Furthermore, rapid translocation and sequential retranslocation of gamma-PKC-GFP were observed in CHO/ mGluR1 cells on stimulation with the receptor. Neither cytochalasin D nor colchicine affected the translocation of gamma-PKC-GFP, indicating that translocation of gamma-PKC was independent of actin and microtubule. gamma-PKC-GFP fusion protein is a useful tool for investigating the molecular mechanism of gamma-PKC translocation and the role of gamma-PKC in the central nervous system.

3T3 Cells↗
PubMed1997

Combined pancreaticoduodenectomy and hepatectomy for patients with locally advanced gallbladder carcinoma: long term results.

BACKGROUND: The objective of this study was to evaluate the efficacy of combined pancreaticoduodenectomy and hepatectomy for the treatment of patients with locally advanced gallbladder carcinoma. METHODS: Long term results over 5 years of follow-up were analyzed retrospectively in 17 consecutive patients with gallbladder carcinoma who underwent combined pancreaticoduodenectomy and hepatectomy with radical lymphadenectomy. The indications for pancreaticoduodenectomy were direct invasion of the adjacent organs (stomach, duodenum, or pancreas) and/or the presence of peripancreatic (head only) lymph node metastases. The hepatectomy performed was a nonanatomic resection of the gallbladder bed in 15 patients and an extended right hepatectomy in 2 patients. There was 1 in-hospital death (6%). RESULTS: Overall, 5 patients (29%) survived 5 years after surgery. Of these patients, four had Stage IVB disease with positive peripancreatic lymph nodes. Eight of the 10 patients who underwent a potentially curative resection survived longer than 3 years, whereas none of the 7 patients with residual tumor survived beyond 15 months. The 5-year survival of 50% (median survival: 58.5 months) in those undergoing a potentially curative resection was significantly better than the 5-year survival of 0% (median survival: 8 months) observed in those patients with residual tumor (P = 0.00086). CONCLUSIONS: Combined pancreaticoduodenectomy and hepatectomy is an efficacious treatment for patients with locally advanced gallbladder carcinoma, but only if a potentially curative resection is feasible. The presence of peripancreatic (head only) lymph node disease is not a contraindication for this procedure.

Adenocarcinoma↗
PubMed1997

Lymph node spread from carcinoma of the gallbladder.

BACKGROUND: Lymph node spread is the most common pattern of progression in gallbladder carcinoma (GBC) and is a prognostic factor. The purpose of this study was to determine the prevalence of lymph node metastases in patients with resected advanced GBC, and to evaluate the curative effects of radical surgery for patients with lymph node metastasis. METHODS: One hundred and eleven consecutive patients who had undergone radical surgery for GBC were included in this study. The pattern of lymph node metastases was examined histopathologically, using the TNM staging of the American Joint Committee on Cancer. RESULTS: There was no neurovascular invasion or lymph node involvement in 15 patients with pT1 tumors. Sixty of 96 patients with pT2-4 tumors had lymph node metastases. The pericholedochal lymph node was the most common metastatic lymph node, followed by the cystic lymph node. The frequency of metastases in retroportal, posterosuperior pancreaticoduodenal, and interaorticocaval lymph nodes was >15% in all cases. pT3-4 tumors had significantly more lymph node involvement (79%) and significantly higher N2:N1 ratios (2.5) than pT2 tumors (46% and 0.6, respectively). There was no difference in 5-year survival between N0 and N1 groups in pT2-4 tumors (66% in N0 and 53% in N1). Patients with N2 disease had a significantly worse prognosis, but 4 patients survived >5 years. CONCLUSIONS: The cystic and pericholedochal lymph nodes are the initial site of spread from GBC. The frequency of lymph node involvement is strongly influenced by the depth of invasion of the primary tumor. GBC limited to such lymph node metastases can be cured by surgery in >50% of such cases.

Adenocarcinoma↗
PubMed1997

Prothoracicotropic hormone-producing neurosecretory cells in the silkworm, Bombyx mori, express a muscarinic acetylcholine receptor.

Using an anti-muscarinic acetylcholine receptor (mAChR) antibody and an anti-prothoracicotropic hormone (PTTH) antibody, double immunofluorescence staining was performed on brain sections of the silkworm, Bombyx mori. Four pairs of dorsolateral neurosecretory cells, along with some intercerebral neurosecretory cells, were immunoreactive to anti-mAChR antibody. Among these immunoreactive cells, two pairs of dorsolateral neurosecretory cells were identified to be PTTH-producing neurosecretory cells. Nerve fibers in the median and paramedian protocerebral areas, and nerve terminals in the corpus allatum also showed immunoreactivity to the anti-mAChR antibody. Some of these nerve terminals expressing mAChRs were overlapped by immunostaining with the anti-PTTH antibody. These results indicated that PTTH-producing neurosecretory cells of Bombyx mori expressed an mAChR, and that muscarinic, cholinergic transmission might directly regulate PTTH release from neurosecretory cells.

Animals↗
PubMed1997

Patterns of lymphatic spread of carcinoma of the ampulla of Vater.

BACKGROUND: The pattern of lymphatic spread of ampullary cancer is poorly documented. This pattern was clarified in order to define the rational extent of radical lymphadenectomy. METHOD: Thirty-nine consecutive patients who underwent pancreaticoduodenectomy with radical lymphadenectomy were included in the study. A total of 1447 lymph nodes dissected from the resected specimens was examined to detect the presence of metastatic foci. RESULTS: Twenty-one of the 39 patients had a total of 97 positive nodes. The sites of nodal involvement were the posterior pancreaticoduodenal (20 of 21 patients), inferior pancreaticoduodenal artery (IPDA; 12 of 21), anterior pancreaticoduodenal (three of 21), trunk of the superior mesenteric artery (three of 20), pericholedochal (three of 21), retroportal (two of 21), and para-aortic (three of five) regions. No metastases were found in the hepatic artery, cystic duct, perigastric, right coeliac, middle colic artery or right caval node groups. CONCLUSION: Ampullary cancer mainly spreads to the posterior pancreaticoduodenal node group, then to the IPDA node group, and finally to the para-aortic area. The rational extent of radical lymphadenectomy should include the pancreaticoduodenal, superior mesenteric, pericholedochal, retroportal and para-aortic nodes.

Ampulla of Vater↗
PubMed1997

Ischemic stricture of the rectosigmoid colon caused by division of the superior rectal artery below Sudeck's point during sigmoidectomy: report of a case.

Despite Sudeck's cautionary report regarding the risk of colon necrosis following a pull-through procedure, published in 1907, most colorectal surgeons do not pay close attention to Sudeck's critical point when operating in the rectosigmoid region. We report herein the case of a patient who developed an ischemic stricture, 6 cm in length, in the rectosigmoid colon distal to the anastomosis following a radical sigmoidectomy with division of the superior rectal artery immediately distal to Sudeck's point. This is the first documentation of a patient developing an ischemic stricture attributable to sigmoidectomy. Division of the artery distal to Sudeck's point most probably impaired the blood supply to the rectosigmoid colon, which subsequently resulted in occlusive ischemic colitis. Thus, there is a risk that division of the superior rectal artery distal to Sudeck's point may lead to colonic ischemia in the remaining rectosigmoid region following sigmoidectomy.

Aged↗
PubMed1997

Early gastric cancer manifested as brain metastasis: report of a case.

A case of early gastric cancer, limited to submucosal layer, which was manifested as cerebral metastasis is presented herein. A 47-year-old man was admitted to Nagaoka Chuo General Hospital with convulsions and a disturbance in consciousness, where a computed tomography (CT) scan revealed a cerebral tumor in the left temporal lobe. The resected tumor was identified as a metastatic adenocarcinoma. Further investigation revealed gastric cancer involving the posterior wall of the cardia. At laparotomy, multiple and small metastases of the liver and a jejunal metastasis were found and a palliative total gastrectomy was performed. The surgical specimen revealed a protruding, poorly differentiated medullary adenocarcinoma, with invasion of the submucosal layer. The patient died 4 months after undergoing the laparotomy. This case report is presented to make clinicians aware of the possibility that early gastric cancers may present as brain metastasis.

Brain Neoplasms↗
PubMed1997

Ischemic colitis arising in watershed areas of the colonic blood supply: a report of two cases.

There are several weak points in the colonic blood supply, known as watershed areas, which result from incomplete anastomoses of the marginal arteries. These watershed areas are more vulnerable to ischemic injury than other parts of the colon. We report herein the cases of two patients who developed ischemic colitis well localized in the cecum, and in the rectosigmoid region at Sudeck's point, respectively. This report and our review of the literature suggest that watershed areas, including the splenic flexure, or Griffith's point, Sudeck's point, and the ileocecal region, are high-risk regions for the development of ischemic colitis.

Colectomy↗
PubMed1997

Acute acalculous cholecystitis after cardiovascular surgery.

The development of acute acalculous cholecystitis (AAC) after cardiovascular surgery is an infrequent but devastating complication, the etiology and management of which remains controversial. To evaluate the etiology, treatment, and outcome of patients with AAC, the cases of six patients encountered within an 8-year period who developed AAC after cardiovascular surgery requiring cardiopulmonary bypass (CPB) were reviewed. Atherosclerotic risk factors including diabetes, hyperlipidemia, and smoking were evident in five patients, three of whom had a history of stroke or arteriosclerosis obliterans, while low cardiac output was recognized in three. Percutaneous transhepatic cholecystostomy was performed in five patients, and another required cholecystectomy for peritonitis due to gangrene of the gallbladder. Two patients died of respiratory failure and sepsis after 15 and 82 days of percutaneous drainage, respectively; however, the four survivors had an excellent outcome without any biliary tract disease during a mean follow-up period of 5.3 years. In conclusion, AAC after cardiovascular surgery may result from hypoperfusion of the gallbladder due to various factors including CPB, visceral atherosclerosis, and low cardiac output. We advocate early percutaneous cholecystostomy for patients without peritonitis, while early cholecystectomy is indicated for those with peritonitis.

Acute Disease↗
PubMed1997

Lymph node recurrence of gallbladder carcinoma successfully managed by systemic chemotherapy with 5-fluorouracil and mitomycin C: report of a 5-year survivor.

Although gallbladder cancer (GBC) is believed to be chemoresistant, the effectiveness of chemotherapy against lymph node metastasis has been reported. We report a 70-year-old woman with advanced GBC in whom isolated, widespread lymph nodal recurrence after a radical resection responded completely to systemic chemotherapy with mitomycin C and 5-fluorouracil. This patient remains symptom-free with no evidence of disease at 6 years after surgery (5 years after the initiation of chemotherapy). Both our case and a literature review suggest that nodal disease appears more chemosensitive than the primary lesion in GBC. Chemotherapy may provide long-term palliation for selected patients with isolated nodal recurrence.

Aged↗
PubMed1997

Intraoperative ultrasonography versus cholangiography during laparoscopic cholecystectomy: a prospective comparative study.

BACKGROUND: The purpose of this study was to compare the functional utility of intraoperative ultrasonography (IOUS) and cholangiography (IOC) during a laparoscopic cholecystectomy for the treatment of gallstone disease. STUDY DESIGN: A prospective study comparing IOUS and IOC was carried out in 65 patients. Intraoperative ultrasonography was conducted first using a 7.5-MHz linear array probe. After IOUS, IOC was then conducted in all patients. The respective usefulness of IOUS and IOC in the identification of gallstones, detection of hepatobiliary structures, and demonstration of congenital anomalies was then compared. RESULTS: Intraoperative ultrasonography was successful in all 65 patients, and IOC was successful only in 54. The time required for IOUS was significantly shorter (p < 0.0001) than for IOC. Intraoperative ultrasonography imaged the hepatic ducts and their confluence, the common hepatic duct, the common bile duct, and the ampulla of Vater in 97, 100, 97, and 51% of cases, respectively. Intraoperative cholangiography, on the other hand, depicted these structures in 85, 89, 100, and 94% of cases, respectively. Intraoperative ultrasonography demonstrated the cystic duct and its confluence in 94% of cases. Biliary anomalies were identified by IOUS in 12 patients and by IOC in 13. Intraoperative ultrasonography could detect the hilar vascular structures in most patients and visualized anomalies of the hepatic arteries in 5 patients. In this series, 5 patients had choledocholithiasis. The sensitivities, specificities, positive and negative predictive values, and accuracies in identifying these bile duct stones were 80, 98, 80, 98, and 97% by IOUS, and 80, 97, 67, 98, and 95% by IOC, respectively. CONCLUSIONS: Intraoperative ultrasonography is superior to cholangiography with respect to its safety, shorter examination period, and ease of administration in all patients. In addition, IOUS is also better for identifying subtle anatomic detail. Intraoperative ultrasonography compares favorably with IOC in terms of utility in exploring bile ducts for stones. Intraoperative ultrasonography is an effective procedure for biliary exploration during a laparoscopic cholecystectomy.

Cholangiography↗