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A Taketomi

Publications and source records attributed to A Taketomi.

At least 19 recordsLinked to original sources

Domain analysis of the actin-binding and actin-remodeling activities of drebrin.

Drebrin is an actin-binding protein which is expressed at highly levels in neurons. When introduced into fibroblasts, it has been known to bind to F-actin and to cause remodeling of F-actin. Here, we performed a domain analysis of the actin-binding and actin-remodeling activities of drebrin. Various fragments of drebrin cDNA were fused with green fluorescent protein cDNA and introduced into Chinese hamster ovary cells. Association of the fusion protein with F-actin and remodeling of the F-actin were examined. We found that the central 85-amino-acid sequence (residues 233-317) was sufficient for the binding to and remodeling of F-actin. The binding activity of this fragment was relatively low compared with that of full-length drebrin, but all the types of abnormalities of F-actin that are observed with full-length drebrin were also observed with this fragment. When this sequence was further fragmented, the actin-binding activity was greatly reduced and the actin-remodeling activity disappeared. The actin-binding activity of the central region of drebrin was confirmed by a cosedimentation assay of chymotryptic fragments of drebrin with purified actin. These data indicate that the actin-binding domain and actin-remodeling domain are identical and that this domain is located at the central region of drebrin.

Actins↗

Multi-forms of human MTH1 polypeptides produced by alternative translation initiation and single nucleotide polymorphism.

The human MTH1 gene for 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase, produces seven types (types 1, 2A, 2B, 3A, 3B, 4A and 4B) of mRNAs. The B-type mRNAs with exon 2b-2c segments have three additional in-frame AUGs in their 5' regions. We report here that these transcripts produce three forms of MTH1 polypeptides (p22, p21 and p18) in in vitro translation reactions. Three polypeptides were also detected in extracts of human cells, using western blotting. B-type mRNAs with a polymorphic alteration (GU-->GC) at the beginning of exon 2c that converts an in-frame UGA to CGA yielding another in-frame AUG further upstream, produced an additional polypeptide (p26) in vitro. Substitution of each AUG abolished the production of each corresponding polypeptide. Cell lines from individuals with the GC allele contain more B-type mRNAs than do those of GT homozygotes, and the former produce all of four polypeptides but the latter lack p26. Amounts of each polypeptide reflected copy number of the GC allele in each cell line. There is an apparent linkage dis-equilibrium between the two polymorphic sites, GT/GC at exon 2c and Val83/Met83 at codon 83 for p18.

Base Sequence↗

Multifocal occurrence of gastric carcinoma in patients with a family history of gastric carcinoma.

BACKGROUND: Smoking and alcoholic beverage drinking habits as well as a family history of cancer are well known risk factors for the multifocal occurrence of squamous cell carcinoma of the esophagus and the head and neck region. However, the role of these risk factors in multiple gastric carcinoma remains to be clarified. The purpose of this study was to examine the risk factors for multiple gastric carcinoma. METHODS: The smoking and drinking habits as well as the family history of 157 patients with synchronous multiple gastric carcinoma and 157 patients with solitary gastric carcinoma who were similar with regard to gender, age, stage of the tumor, and year of admission were investigated. The risk of a multiple occurrence of gastric carcinoma also was elevated using the odds ratio (OR). RESULTS: The ORs of a multifocal occurrence of gastric carcinoma in patients who currently smoked and drank alcoholic beverages were 1.1 and 0.8, respectively, although the ORs were not related to the quantity of smoking or drinking. In patients with a close relative with gastric carcinoma the OR was 2.1 (95% confidence interval [CI], 1.3-3.7). In those patients with > or =2 close relatives with gastric carcinoma, the OR increased to 5.1 (95% CI, 1.2-21.1). Conversely, no significant elevation in the ORs was recognized regarding a family history of other cancers. CONCLUSIONS: In this study, a family history of gastric carcinoma was found to be clearly associated with the multifocal occurrence of gastric carcinoma; however, no significant correlation between the multifocal occurrence of gastric carcinoma in these patients and their smoking and drinking habits was recognized.

Alcohol Drinking↗

Natural killer cell activity in patients with hepatocellular carcinoma: a new prognostic indicator after hepatectomy.

BACKGROUND: Natural cytotoxicity mediated by natural killer (NK) cells is believed to play an important role in host anticancer defense mechanisms. The aim of this study was to examine the prognostic significance of NK cell activity after hepatectomy in patients with hepatocellular carcinoma. METHODS: The NK cell activity in 210 patients with hepatocellular carcinoma was measured and evaluated in relation to clinicopathologic variables using univariate and multivariate analyses. RESULTS: The NK cell activity was decreased significantly in hepatocellular carcinoma patients compared with the control groups (P < 0.001). No correlation was observed between NK cell activity and the clinicopathologic variables. Multivariate analyses indicated that NK cell activity as well as intrahepatic metastases, platelet count, and serum albumin level were independent prognostic factors. CONCLUSIONS: This study suggests that the preoperative NK cell activity will help predict recurrence and prognosis after hepatectomy in patients with hepatocellular carcinoma.

Adult↗

Family aggregation of carcinoma of the hypopharynx and cervical esophagus: special reference to multiplicity of cancer in upper aerodigestive tract.

The role of family history in the multiple occurrence of cancer in the upper aerodigestive tract (UADT) remains unclear. The family histories of close relatives were examined in 167 patients with either hypopharyngeal or cervical esophageal cancer (PhCe cancer) and in 167 control subjects with benign diseases. The odds ratio for PhCe cancer was 2.6 in relation to family history of UADT cancers. Based on the family histories of close relatives, 167 cases with PhCe cancer were divided into 3 groups (Group I, 18 cases with a family history of UADT cancer; Group II, 37 cases with a family history of other cancers; Group III, 112 cases with no family history of any cancers). The mean age of the cases in group I was 59.4, which was younger than in group III (64.2). Second primary squamous-cell carcinomas in the UADT were more frequently recognized in group I (39%) than in group III (11%). However, no differences were observed in the smoking and drinking habits of male patients between each group. These results thus suggest that a family history of UADT cancers appears to be associated with the multiple occurrence of UADT cancers as well as the development of PhCe cancer.

Aged↗

Submucosal gastric cancer with lymph node metastasis.

BACKGROUND AND OBJECTIVES: The intraoperative assessment of lymph node metastasis of gastric cancer remains difficult and the characteristics of recurrence after gastrectomy are not well known regarding submucosal cancer. METHODS: We examined 452 patients with submucosal gastric cancer and compared the clinicopathologic features as well as recurrence patterns between the 71 cases with lymph node metastasis (group I) and the 381 without it (group II). RESULTS: The mean tumor sizes were 44.8 and 33.5 mm, respectively (P < 0.01). The incidences of lymphatic invasion and vascular invasion were 91.5% (65/71) and 45.1% (32/71) in group I, which were significantly higher than those in group II (36.7 and 14.2%, 140/381 and 54/381, respectively, P < 0.01). A total of 21 patients (4.6%, 21/452) experienced recurrence after undergoing a gastrectomy and hematogenic recurrence was the most frequent type of recurrence (2.0%, 9/452). However, in group I, lymphatic recurrence was most frequently observed (7.0%, 5/71), and it was more frequent than in group II (0.3%, 1/381, P < 0.01). The median intervals between gastrectomy and recurrence were 34.5 and 64.0 months in groups I and II, respectively (P < 0.05). CONCLUSIONS: The submucosal cancer with larger size, lymphatic invasion, and vascular invasion has high risks for lymph node metastasis. Furthermore, a strict follow-up for lymphatic as well as hematogenic recurrence is important for the patients with node positive submucosal cancer, especially within 5 years after operation.

Female↗

Perioperative change in albumin messenger RNA levels in patients with hepatocellular carcinoma.

A quantitative assay of albumin messenger RNA (mRNA) in blood samples was designed using the competitive reverse-transcription polymerase chain reaction, and the significance of measuring albumin mRNA levels in the blood of patients with hepatocellular carcinoma (HCC) in hepatic resection was evaluated. Albumin mRNA levels were measured in the following: (1) peripheral blood in 11 patients with HCC and 20 control subjects without liver disease, (2) blood in the portal and hepatic veins in five patients with HCC immediately after laparotomy, and (3) a perioperative series of peripheral blood in eight patients with HCC. Two patients with HCC whose albumin mRNA level in peripheral blood was markedly high were both at stage IVa. On the other hand, 20 control subjects showed negative or <5 x 10(3) transcripts/microgram RNA of albumin mRNA expression. Immediately after laparotomy, the albumin mRNA levels in the tumor-draining hepatic vein were greater than in the portal and non-tumor-draining hepatic veins in four of five patients with HCC. Albumin mRNA levels in peripheral blood showed a marked increase after mobilization and/or resection of the liver and, thereafter, gradually decreased at postoperative day 7 in all eight patients with HCC. A new method to measure the albumin mRNA levels in blood samples was developed, and high albumin mRNA levels in the peripheral blood of patients with advanced-stage HCC suggest the presence of HCC cells in the circulation. Increased levels in the tumor-draining hepatic vein could indicate the spontaneous release of tumor cells or nontumorous hepatocytes or an increased albumin transcription in activated blood mononuclear cells. An increase in the levels in peripheral blood during an operation is intermittent. Therefore, an increased albumin mRNA level in the tumor-draining vein suggests, but does not prove, that the increased albumin mRNA level reflects tumor cells entering the systemic circulation. This alone does not prove that the prognosis is worsened.

Aged↗

[Pyrimidine nucleoside phosphorylase activity, 5-fluorouracil concentration and thymidylate synthase inhibition rate in colorectal cancer after oral administration of 5'-doxifluridine].

To assess the mechanism of the anticancer effect of doxifluridine (5'-DFUR), a clinicopharmacological study was performed. So far, no comparative study has been reported between the thymidylate synthase (TS) inhibition rate and the 5-FU concentration in colorectal cancer after oral administration of 5'-DFUR. In 37 patients with colorectal cancer, 5'-DFUR was administered orally/preoperatively (800 mg/day x more than 4 days before operation and 300 mg on the day of operation). The mean total dosage was 6.9 g. Specimens of tumor and normal intestinal tissue were obtained 4.4 hours on average after final administration. The TS inhibition rate as well as the 5-FU concentration and the activity of pyrimidine nucleoside phosphorylase (PyNPase) were analyzed in both tissues. The PyNPase activity was significantly higher in the tumor tissue than in the normal tissue (137.9 +/- 10.8 vs. 31.0 +/- 4.7 micrograms FU/mg protein/hr, p < 0.0001). The 5-FU concentration was also significantly higher in the tumor tissue than in the normal tissue (101.3 +/- 30.6 vs. 23.2 +/- 5.5 ng/g, p = 0.024). The TS inhibition rate correlated with the 5-FU concentration in the tumor tissue (r = 0.527, p = 0.047). These findings suggest that the TS inhibition rate may be an index of the anticancer effect of 5'-DFUR in colorectal cancer.

Adenocarcinoma↗

Requirement for two conserved cysteine residues in the Ada protein of Escherichia coli for transactivation of the ada promoter.

Cysteine residue 69 of the Escherichia coli Ada transcription factor, which accepts a methyl group from methylphosphotriester in methylated DNA, was substituted by each of 19 other amino acids. Only the mutant Ada (C69H), carrying a histidine substitution of Cys69, exhibited a limited degree of transactivating potential for the ada promoter in E. coli cells although the mutant protein was completely devoid of methylphosphotriester-DNA methyltransferase activity. Using a multicopy plasmid system for the expression of Ada protein, we have shown that Ada C69H has a transactivating capacity equivalent to that of wild-type Ada protein in the absence of an alkylating agent. This indicates that the zinc-binding capacity of histidine at residue 69 is likely to be sufficient for Ada to recognize and bind to the ada promoter. Furthermore, transactivation of the ada promoter by Ada C69H was enhanced up to 6-fold by treatment with methylating agents. An additional substitution was made with alanine in Ada C69H, replacing Cys321, the site for acceptance of a methyl group from O6-methylguanine and O4-methylthymine residues in DNA, with alanine. This renders the protein completely inactive as a methyltransferase but this derivative is constitutively active as a transactivator for the ada promoter. Therefore, acquisition of a methyl group at Cys321 apparently enhances the transactivating capacity of Ada protein on the ada promoter. We propose that the transcription-regulating function of Ada protein is under dual control by methylation of cysteine residues at positions 69 and 321; the former enhances DNA binding, while the latter enhances the transactivating capacity of the protein.

Amino Acid Sequence↗

Postoperative hepatitis status as a significant risk factor for recurrence in cirrhotic patients with small hepatocellular carcinoma.

BACKGROUND: Recurrence of small hepatocellular carcinoma (HCC) is common. Recent studies have suggested that the status of the underlying liver parenchyma is a significant risk factor for recurrence of HCC. METHODS: The postoperative values of transaminase were examined every 6 months after surgery in 57 patients with a surgically resected solitary small HCC measuring up to 3 cm in greatest dimension. Based on the patterns of the transaminase values, the patients were divided into two groups. Group 1 (n = 20) had a high transaminase level; the values of postoperative transaminase were always more than 100 IU/L. Group II (n = 37) had a low transaminase level; the values of postoperative transaminase were sometimes lower than 100 IU/L. RESULTS: The cumulative carcinoma-free survival rates in Groups I and II were 91% and 80%, respectively, at 1 year, 64.5% and 5.5%, respectively, at 3 years, and 48.2% and 0%, respectively, at 5 years after surgery. The disease free survival rates in Group I were significantly lower than those in Group II (P = 0.0007), although no significant differences in histologic risk factors for recurrence or in clinical backgrounds were observed. With regard to the recurrence pattern, solitary recurrence was more frequently observed in Group I (P = 0.02), compared with the patients in Group II. A histologic comparison between the primary and recurrent tumor in patients who underwent re-resection for solitary recurrence demonstrated the possible multicentric occurrence of HCC in 2 of 8 patients (25%) in Group I. CONCLUSIONS: This study suggests that the hepatitis status of the remnant liver plays an important role in the recurrence rates and patterns of small HCC after hepatectomy.

Carcinoma, Hepatocellular↗

Simplified inflow control using stapling devices for major hepatic resection.

We describe the efficacy of a new technique for hepatic inflow division using stapling devices in major hepatic resections. We studied 28 consecutive patients who underwent major hepatic resection at a tertiary referral center by en masse inflow control of Glisson's pedicle in 1993 and 1994, of whom 10 underwent inflow control with stapling devices. Although stapling devices were used for larger tumors (mean +/- SD, 12.2 +/- 8.6 vs 5.7 +/- 5.0 cm; P = .02), the operation time (261 +/- 57 vs 301 +/- 143 minutes), operative blood loss (2071 +/- 1318 vs 4792 +/- 6586 mL), postoperative intra-abdominal bleeding (0% [0/10] vs 17% [3/18]), and hospital stay (16.0 +/- 2.6 vs 20.6 +/- 7.4 days) were favorable for resections with staplers vs resections without staplers; the overall incidences of postoperative complications (40% [4/10] vs 39% [7/18]) and hospital death (10% [1/10] vs 6% [1/18]) were comparable in the two groups. We conclude that stapling devices allow simple, quick, and safe en masse inflow control in major hepatic resections.

Aged↗

[Continuous hepatic arterial infusion chemotherapy with low-dose CDDP plus 5-FU for liver metastases from colorectal carcinoma].

Seven patients with unresectable liver metastases from colorectal carcinoma were treated with low-dose CDDP plus 5-FU continuous hepatic arterial infusion chemotherapy. A hepatic artery catheter was placed into the gastroduodenal artery at laparotomy or percutaneously placed into the proper hepatic artery via left subclavian artery. Through an injection port placed beneath the skin, 5-FU (300 mg/m2/day) was continuously infused for 5 days; CDDP (6 mg/m2/day) was infused for 5 successive days a week. One cycle consisted of 4 weeks. The response rate was 71% (1 CR, 4 PR, 2 NC). The CEA level decreased in all cases. The median survival was 17 months. Major toxicities were abdominal pain and appetite loss due to extrahepatic perfusion of the drugs. Failure in maintaining the catheter was a problem in most cases. The pharmacokinetic study demonstrated high hepatic extraction of CDDP and 5-FU (40% and 90%, respectively). These results suggest that continuous hepatic arterial infusion chemotherapy with low-dose CDDP plus 5-FU is effective for patients with unresectable liver metastases from colorectal carcinoma.

Adult↗

Generation and elimination of 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate, a mutagenic substrate for DNA synthesis, in human cells.

8-Oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-oxo-dGTP) is a potent mutagenic substrate for DNA synthesis. The present study deals with generation and degradation of 8-oxo-dGTP in the nucleotide pool of human cells. (1) 8-Oxo-dGTP can be generated not only by direct oxidation of dGTP but also by phosphorylation of 8-oxo-dGDP by nucleoside diphosphate kinase. (2) 8-Oxo-dGTP is rapidly degraded to 8-oxo-dGMP by cellular 8-oxo-dGTPase activity. 8-Oxo-dGMP thus produced cannot be rephosphorylated; guanylate kinase, which phosphorylates both GMP and dGMP to the corresponding nucleoside diphosphates, is totally inactive for 8-oxo-dGMP. (3) 8-Oxo-dGMP is further degraded to 8-oxo-deoxyguanosine by a nucleotidase. The enzyme was partially purified from an extract of human Jurkat cells, and the mode of action was elucidated. 8-Oxo-dGMP is the most preferred substrate of the enzyme, and other nucleoside monophosphates are cleaved at significantly lower rates: Km for 8-oxo-dGMP is 10 times lower than that for dGMP, the second best substrate for the enzyme. The enzyme appears to convert 8-oxo-dGMP, which accumulates in the cellular nucleotide pool, to a form readily excretable to the cell exterior.

Cell-Free System↗

A new approach for liver surgery. Transdiaphragmatic hepatectomy for cirrhotic patients with hepatocellular carcinoma.

OBJECTIVE: To clarify the efficacy of transdiaphragmatic hepatectomy. DESIGN: Transdiaphragmatic hepatectomy and transabdominal hepatectomy were retrospectively compared. SETTING: This technique is used in cirrhotic patients with hepatocellular carcinoma located near the diaphragm. PATIENTS: Thirty-six cirrhotic patients with hepatocellular carcinoma who underwent transdiaphragmatic (group 1 [n = 8]) or transabdominal (group 2 [n = 28]) hepatectomies between April 1985 and March 1993 were investigated. All patients underwent a partial hepatectomy for hepatocellular carcinoma less than 3 cm in diameter located in segment VII or VIII or near the confluence of the hepatic veins. MAIN OUTCOME MEASURE: Intraoperative and postoperative clinical parameters, including operative time, blood loss, and length of hospital stay. RESULTS: The mean +/- SD operative time was significantly shorter in group 1 (184 +/- 25 minutes) than in group 2 (270 +/- 79 minutes). The intraoperative blood loss was significantly smaller in group 1 (857 +/- 622 mL) than in group 2 (1318 +/- 926 mL). The rate of postoperative complications was lower in group 1 (13% [n = 1]) than in group 2 (43% [n = 12]). The postoperative hospital stay was significantly shorter in group 1 (16 +/- 5 days) than in group 2 (23 +/- 16 days). CONCLUSIONS: Transdiaphragmatic hepatectomy is a useful technique for cirrhotic patients with hepatocellular carcinoma located near the diaphragm.

Abdomen↗

Occurrence of intraperitoneal septic complications after hepatic resections between 1985 and 1990.

In this study, the risk factors related to intraperitoneal septic complications occurring after hepatectomy (IPSCH) as well as the effect of various perioperative variables on the outcome of IPSCH between 1985 and 1990 were analyzed. Twenty-one of 211 patients (10.0%) developed IPSCH. The findings in the patients with IPSCH were compared with those in 190 patients without IPSCH. The significant variables associated with the development of IPSCH included a high incidence of accompanying chronic renal failure (14.3% vs 2.1%), a larger blood loss during surgery (2,130 vs 1,340 ml) as well as a greater amount of intraoperative blood replacement (1,130 vs 570 ml), and a greater weight of the resected liver (367 vs 233 g). IPSCH occurred in 10 of 12 patients who had postoperative bile leakage. Eighteen patients (85.7%) with IPSCH were discharged from the hospital after non-operative management; however, the hospital death rate (14.3% vs 1.1%) was significantly higher in patients with IPSCH. This review suggests that the incidence of IPSCH has not decreased recently. Thus, to prevent IPSCH, at least following bile leakage, it is necessary to perform a careful division of the liver parenchyma followed by a bile leakage test, and when this complication occurs unexpectedly in patients who have a good functional reserve of the remnant liver, IPSCH can be effectively drained percutaneously under ultrasound guidance.

Abdominal Abscess↗

Des-gamma-carboxy prothrombin and proliferative activity of hepatocellular carcinoma.

BACKGROUND: Des-gamma-carboxy prothrombin (DCP) is a useful marker for the prognosis of hepatocellular carcinoma (HCC). In this report we investigated the relationship between the positivity of DCP and proliferative activity of HCC and discuss the cause of poor prognosis of DCP-positive HCC. METHODS: Immunohistochemical and clinicopathologic study was done in 114 patients with resected HCC measuring less than 6 cm in diameter by using monoclonal antibody for proliferating cell nuclear antigen (PCNA). RESULTS: PCNA labeling index (PCNA-LI) was significantly higher in the patients with DCP-positive HCC than in those with DCP-negative HCC; also a positive correlation was noted between the PCNA-LI and the DCP level. We divided patients into two groups according to the PCNA-LI. In the high PCNA-LI group the patients with DCP-positive HCC exhibited a higher PCNA-LI than did the patients with DCP-negative HCC. As for pathologic prognostic factors, the DCP-positive high PCNA-LI group showed the highest incidence of tumor thrombus of the portal vein and intrahepatic metastasis while also exhibiting the lowest recurrence-freedom rate. From multivariate analysis we find that DCP, as well as PCNA-LI, is one of the risk factors for recurrence of HCC after hepatectomy. CONCLUSIONS: Our results thus suggest that DCP-positive HCC showed high PCNA-LI, and this might be the main cause for early intrahepatic spread and poor prognosis of DCP-positive HCC.

Adult↗