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T Takeda

Publications and source records attributed to T Takeda.

At least 91 records · Page 5Linked to original sources
PubMed2001

Activation of c-Src gene product in hepatocellular carcinoma is highly correlated with the indices of early stage phenotype.

BACKGROUND/AIMS: The aim of this study was to investigate whether c-Src is involved in carcinogenesis and progression of human hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. METHODS: We designed an immunohistochemical study using Clone 28, an antibody that specifically recognizes the activated form of c-Src. RESULTS: Hepatocytes in normal liver, chronic hepatitis with or without cirrhosis, atypical adenomatous hyperplasia, as well as bile ductular cells, and infiltrating mononuclear cells were all negative for immunohistochemical staining for the activated c-Src. Among 87 cases of HCC tested, 40 (46%) were positively stained for the activated c-Src, and this positive staining was inversely correlated with the Ki-67 labeling index (LI) (P = 0.0031), intrahepatic metastasis (P = 0.0099), TNM stage (P = 0.0062), alpha-fetoprotein (P = 0.0103) and epidermal growth factor-receptor expression (P = 0.0153). Positive staining for the activated c-Src was more frequently observed in well- or moderately-differentiated carcinoma (P = 0.0256). In multivariate analysis, the activated c-Src expression was independently related to the Ki-67 LI (P = 0.0197). In contrast to positive staining in HCC, cholangiocarcinoma were classified as negative in all 19 cases examined. CONCLUSIONS: These results strongly suggest the involvement of activated c-Src in early stages of HCC, and suggest that cholangiocarcinoma might employ different signaling mechanisms.

Carcinoma, Hepatocellular↗
PubMed2001

Cerebrospinal fluid otorrhea in a patient with congenital inner ear dysplasia.

A case of a 10-month-old boy with a cerebrospinal fluid (CSF) fistula in his right ear is reported. In the same ear, the patient also showed congenital inner ear dysplasia. The CSF fistula was obstructed surgically. Surgical exploration showed a fistula superior to the oval window and a normally shaped stapes. The stapes was removed and the fistula was closed by obliteration of the vestibulum with the temporal fascia and fat tissue. The location of the fistula was very rare; to our knowledge, this is the first reported case of CSF fistula superior to the oval window. The relationship between perilymphatic fistula and the microfissure revealed by temporal bone study is discussed.

Cerebrospinal Fluid Otorrhea↗
PubMed2001

Inhibition effects of gangliosides G(M1), G(D1a) and G(T1b) on base-catalyzed isomerization of prostaglandin A(2).

Micellar inhibition effect of gangliosides on a degradation of drug was investigated, where ganglioside G(M1) (GM1), G(D1a) (GD1a) and G(T1b) (GTlb) whose sialic acid residue is one, two and three, respectively, were used. The base-catalyzed isomerization of prostaglandin A(2) (PGA(2)) to prostaglandin B(2) (PGB(2)) was chosen as a model experiment. The rate for the isomerization of PGA(2) was determined by measuring the concentration of PGA(2) (and PGB(2)) with a high-performance liquid chromatography. Gangliosides micelles inhibited the isomerization of PGA(2). The inhibition effect of GT1b micelles was larger than that of GD1a micelles. This result would be due to the larger absolute value of surface potential of GT1b micelles, which brings about a larger electrostatic repulsion between micellar surface and OH(-). The terminal sialic acid residue of ganglioside was effective to inhibit the isomerization of PGA(2). GM1 micelles without terminal sialic acid residue but with large aggregation number exhibited a superior steric shielding effect rather than an electrostatically repulsive effect. The inhibition effect of GM1 micelles was enhanced by the mixed micellization with the other ganglioside with a terminal sialic acid residue. GM1-GD1a or GM1-GT1b mixed micelles remarkably inhibited the isomerization of PGA(2). The physiological activity of PGs in the biological membranes containing gangliosides was also discussed.

Journal Article↗
PubMed2001

Fas ligand expression in BRCA1-associated hereditary breast carcinoma clearly differs from that in sporadic breast carcinoma.

BRCA1-associated hereditary breast carcinomas (HBCs) are diagnosed at a younger age and are known to show biological aggressiveness such as a high histological grade, frequent aneuploidy, compared to sporadic breast carcinomas. However, results of studies on their prognosis have been controversial. We hypothesized that some factors such as a high incidence of cell death could offset the aggressiveness of BRCA1-associated HBCs, and therefore investigated Fas and Fas ligand (Fas L) expression in 19 BRCA1-associated HBCs and 56 age-adjusted control cases. Glandepithelial and myoepithelial cells in the mammary glands expressed Fas in high incidence, but all were negative for Fas L. Fas was expressed in 89.5% of BRCA1-associated HBCs and 94.4% of the controls and no significant differences could be established between the two groups. However, in 73.7% of BRCA1-associated HBCs, Fas L was clearly expressed in the infiltrating mononuclear cells, whereas this was observed in only 14.3% of the control cases and statistical significance was established between the two groups (p < 0.0001). These results strongly suggest that carcinoma cells in BRCA1-associated HBCs are more likely to be attacked by mononuclear cells via Fas L, and this may explain, at least in part, the discrepancy with respect to the prognosis. On the other hand, carcinoma cells also expressed Fas L significantly more often (p < 0.0001) in BRCA1-associated HBCs (52.6%) than in sporadic cases (3.6%). This can be considered a kind of counterattack against the mononuclear cells or, alternatively, may enhance the Fas-Fas L pathway in an autocrine/paracrine fashion. The clinical significance of Fas L expressing carcinoma cells remains to be elucidated.

Adult↗
PubMed2001

Expression of heparin-binding epidermal growth factor-like growth factor in breast carcinoma.

The expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) was investigated for 76 cases of breast carcinoma. HB-EGF was expressed in 71.8% of the carcinoma cases but only slightly in normal mammary glands. Interestingly, its expression was inversely related to biological aggressiveness of the breast carcinoma. These results suggest that HB-EGF may play a crucial role in the early stage of this carcinoma.

Adult↗
PubMed2001

Chicken microsatellite primers are not efficient markers for Japanese quail.

Domestic fowl or chicken (Gallus gallus) and Japanese quail (Coturnix japonica) belong to the family Phasianidae. The exchange of marker information between chicken and quail is an important step towards the construction of a high-resolution comparative genetic map in Phasianidae, which includes several poultry species of agricultural importance. We tested chicken microsatellite markers to see if they would be suitable as genetic linkage markers in Japanese quail. Twenty-six per cent (31/120) of chicken primers amplified individual loci in Japanese quail and 65% (20/31) of the amplified loci were found to be polymorphic. Eleven of the polymorphic loci were excluded as uninformative because of the lack of amplification in some individuals or high frequency of nonspecific amplification. The sequence information of the remaining nine loci revealed six of them to contain microsatellites that were nearly identical with those of the orthologous regions in chicken. For these six loci, allele frequencies were estimated in 50 unrelated quails. Although the very few chicken markers that do work well in quail could be used as anchor points for a comparative mapping, most chicken markers are not useful for studies in quail. Therefore, more effort should be committed to developing quail-specific markers rather than attempting to adapt chicken markers for work in quail.

Animals↗
PubMed2001

Identification of Tetrahymena hsp60 as a 14-nm filament protein/citrate synthase-binding protein and its possible involvement in the oral apparatus formation.

BACKGROUND: Tetrahymena 14-nm filament protein (14FP) is bifunctional, with roles as a citrate synthase in mitochondria and as a cytoskeletal protein in nuclear events during fertilization and in oral morphogenesis. In this study, to further our understanding of the bifunctional property of 14FP, we attempted to screen 14FP-binding proteins using affinity column chromatography. RESULTS: Through the screening of 14FP-binding proteins using 14FP-affinity chromatography, we detected 65 kDa and 70 kDa proteins that bound to 14FP in an ATP dependent manner. From the N-terminal amino acid sequence, these proteins were identified as the Tetrahymena mitochondrial chaperones, hsp60 and mthsp70, respectively. Tetrahymena hsp60 was recognized with a monoclonal antibody raised against human hsp60. Immunofluorescence and immunoelectron microscopy using the monoclonal antibody showed that Tetrahymena hsp60 was localized to mitochondria. Moreover, Tetrahymena hsp60 was also present at extramitochondrial sites including basal bodies of cilia and oral apparatus, and particularly at the developing oral apparatus during cell division. CONCLUSION: These results suggest that Tetrahymena hsp60 is localized in basal bodies and is involved in cortical patterning such as the formation of the oral apparatus as well as having a role in the folding of mitochondrial proteins in mitochondria.

Amino Acid Sequence↗
PubMed2001

Comparison of real-time quantitative polymerase chain reaction with three other assays for quantitation of hepatitis C virus.

BACKGROUND AND AIMS: Evaluation of serum levels of hepatitis C virus (HCV) is important for predicting the response to interferon treatment and monitoring its therapeutic efficacy. The aim of this study was to evaluate real-time quantitative polymerase chain reaction (PCR) as a method for the measurement of HCV-RNA. METHODS: The subjects were 50 patients with chronic hepatitis C: 36 with genotype 1b, eight with genotype 2a, and six with genotype 2b. Samples were tested for HCV-RNA by using real-time quantitative PCR with the ABI Prism 7700 sequence detection system, a branched DNA signal amplification assay, and an Amplicor monitor test; and for HCV core protein by using a fluorescent enzyme immunoassay. RESULTS: The detection range of the real-time quantitative PCR was between 10(1)-10(8) copies/mL of HCV-RNA. Hepatitis C virus RNA was detectable in all 50 samples by the use of real-time quantitative PCR, but was undetectable in 14 samples by the use of a branched DNA assay and in two samples by using the Amplicor monitor test; HCV core protein was undetectable in three samples. A significant correlation was found between the results of real-time quantitative PCR and those of the three other assays: branched DNA assay (r = 0.837, P < 0.0001), Amplicor monitor test (r = 0.853, P < 0.0001), and HCV core protein concentrations (r = 0.549, P < 0.0001). CONCLUSIONS: Our results showed that the real-time quantitative PCR was a highly sensitive assay for the measurement of HCV-RNA.

Adult↗
PubMed2001

Method to detect substitutions in the interferon-sensitivity-determining region of hepatitis C virus 1b for prediction of response to interferon therapy.

Substitutions deduced by direct sequencing in the interferon-sensitivity-determining region (ISDR) of hepatitis C virus (HCV) are related to patients' responses to interferon (IFN), but sequencing is time consuming and results are only for the dominant virus. We developed a rapid method to detect such changes. With serum from 50 patients with chronic hepatitis C (genotype 1b) given IFN-alpha, a way to detect changes in ISDR by hybridization with oligonucleotide probes that had a prototype nucleotide sequence of HCV-J was established. Hybridization intensity was expressed as optical density (OD(NS5A)). The method was checked with serum from 100 more patients. In the study of 50 patients, all 21 with the prototype sequences had a high OD(NS5A) (> or = 0.4), and all 8 patients with a mutant-type sequence had low values (< or = 0.2). Twelve (95% confidence interval, 36-81%) of 20 patients with OD(NS5A) of <0.4 and 2 (1%-22%) of 30 patients with OD(NS5A) > or = 0.4 had complete responses (CR). All nine (66%-100%) patients with OD(NS5A) <0.4 and little HCV RNA (<100 kIU/mL) had CR, but none (0%-14%) of the 24 patients with high values from both predictors had CR. In the study of 100 patients, OD(NS5A) and the HCV RNA level were independent predictors of the effects of IFN. By multivariate analysis, the odds ratio for a CR in patients with OD(NS5A) of > or = 0.4 was 0.015 (0. 001-0.190) compared with the other patients (P =.001). In conclusion, our method should be useful in identification of prototype strains, which generally resist IFN therapy.

Amino Acid Substitution↗
PubMed2001

Expression and clinical significance of the erbB family in intrahepatic cholangiocellular carcinoma.

The type I family of growth factor receptors is known to play a role in the development of several carcinomas, but its role in hepatic malignancies is not clearly understood. In this study we investigated the expression of this family of EGF-R, c-erbB-2, c-erbB-3 and c-erbB-4 in 38 intrahepatic cholangiocellular carcinomas (CCC) by means of immunohistochemistry. EGF-R expression was related to lymph node metastasis, aberrant p53 expression, proliferating activity, and carcinoma differentiation. c-erbB-2 expression was observed in more than 50% of the cases, but was not related to any clinicopathological features, c-erbB-3 expression was linked to lymph node metastasis, and c-erbB-4 expression was directly related to proliferating activity and lymph node metastasis. These results indicate that: 1) EGF-R contributes greatly to CCC progression, and c-erbB-3 and c-erbB-4 have roles similar to but less than that of EGFR, and 2) c-erbB-2 is expressed in CCC in high incidence, but its clinical role in CCC remains unclear.

Bile Duct Neoplasms↗
PubMed2001

Regulation of initiation of S phase, replication checkpoint signaling, and maintenance of mitotic chromosome structures during S phase by Hsk1 kinase in the fission yeast.

Hsk1, Saccharomyces cerevisiae Cdc7-related kinase in Shizosaccharomyces pombe, is required for G1/S transition and its kinase activity is controlled by the regulatory subunit Dfp1/Him1. Analyses of a newly isolated temperature-sensitive mutant, hsk1-89, reveal that Hsk1 plays crucial roles in DNA replication checkpoint signaling and maintenance of proper chromatin structures during mitotic S phase through regulating the functions of Rad3 (ATM)-Cds1 and Rad21 (cohesin), respectively, in addition to expected essential roles for initiation of mitotic DNA replication through phosphorylating Cdc19 (Mcm2). Checkpoint defect in hsk1-89 is indicated by accumulation of cut cells at 30 degrees C. hsk1-89 displays synthetic lethality in combination with rad3 deletion, indicating that survival of hsk1-89 depends on Rad3-dependent checkpoint pathway. Cds1 kinase activation, which normally occurs in response to early S phase arrest by nucleotide deprivation, is largely impaired in hsk1-89. Furthermore, Cds1-dependent hyperphosphorylation of Dfp1 in response to hydroxyurea arrest is eliminated in hsk1-89, suggesting that sufficient activation of Hsk1-Dfp1 kinase is required for S phase entry and replication checkpoint signaling. hsk1-89 displays apparent defect in mitosis at 37 degrees C leading to accumulation of cells with near 2C DNA content and with aberrant nuclear structures. These phenotypes are similar to those of rad21-K1 and are significantly enhanced in a hsk1-89 rad21-K1 double mutant. Consistent with essential roles of Rad21 as a component for the cohesin complex, sister chromatid cohesion is partially impaired in hsk1-89, suggesting a possibility that infrequent origin firing of the mutant may affect the cohesin functions during S phase.

Cell Cycle Proteins↗
PubMed2001

Characterization of ascorbate peroxidases from unicellular red alga Galdieria partita.

Galdieria partita, a unicellular red alga isolated from acidic hot springs and tolerant to sulfur dioxide, has at least two ascorbate peroxidase (APX) isozymes. This was the first report to demonstrate that two isozymes of APX are found in algal cells. Two isozymes were separated from each other at the hydrophobic chromatography step of purification and named APX-A and APX-B after the elution order in the chromatography. APX-B accounted for 85% of the total activity. Both isozymes were purified. APXs from Galdieria were monomers whose molecular weights were about 28,000, similar to stromal APX of higher plants. APX-A cross-reacted with monoclonal antibody raised against APX of Euglena gracilis in immunoblotting, but APX-B did not, although the antibody can recognize all other APXs tested. The amino-terminal sequences of APX-A and -B from Galdieria had some homology with each other but little homology with those from other sources. Their Km values for ascorbate and hydrogen peroxide were comparable with those of APX from higher plants. Unlike the green algal enzymes, the donor specificities of Galdieria APXs were as high as those of plant chloroplastic APX. On the contrary, these APXs reduced tertiary-butyl hydroperoxide as an electron acceptor as APXs from Euglena and freshwater Chlamydomonas do. The inhibition of APX-A and -B by cyanide and azide, and characteristics of their light absorbance spectra indicated that they were heme peroxidases.

Amino Acid Sequence↗
PubMed2001

The efficacy of esophageal detector devices in verifying tracheal tube placement: a randomized cross-over study of out-of-hospital cardiac arrest patients.

We performed this prospective study to evaluate the efficacy of esophageal detector devices (EDDs), both the bulb and the syringe-type, to indicate positioning of endotracheal tubes (ETTs) in out-of-hospital cardiac arrest patients. Forty-eight adult patients with out-of-hospital cardiac arrest were enrolled. Immediately after tracheal intubation and ETT cuff inflation in the emergency department, the patients were allocated randomly to two cross-over groups. In Group 1 (n = 24), patients underwent a bulb test and a syringe test in sequence. In Group 2 (n = 24), patients underwent a syringe test and a bulb test in sequence. End-tidal carbon dioxide (ETCO(2)) was also monitored. In 56 attempts at tracheal intubation, the bulb, the syringe, and ETCO(2) indicated all eight esophageal intubations. In 48 tracheal intubations, the bulb test correctly indicated 34 tracheal intubations (sensitivity, 70.8%). The syringe test identified 35 tracheal intubations (sensitivity, 72.9%). The results of both tests agreed in 33 tracheal intubations. ETCO(2) was detected in 31 tracheal intubations (sensitivity, 64.6%). No statistical difference was found among the tests. EDDs were less sensitive in detecting tracheal intubation for out-of-hospital cardiac arrest patients. Therefore, proper clinical judgment in conjunction with these devices should be used to confirm ETT placement in these difficult situations.

Adult↗
PubMed2001

Appraisal of transarterial immunoembolization for hepatocellular carcinoma: a clinicopathologic study.

Recurrence of hepatocellular carcinoma (HCC) is frequent, even after apparently curative resection. Preoperative transcatheter arterial chemoembolization (TAE) does not improve disease-free survival after hepatic resection. We previously reported the potential usefulness of transarterial immunoembolization (TIE), a newly developed arterial embolization technique using OK-432 and fibrinogen, as preoperative treatment. In this study, we further investigated the effect of TIE by histologic examination of the resected specimens and compared it with conventional TAE in a prospective nonrandomized manner. Thirty-nine patients underwent TIE (n = 17) or TAE (n = 22) before curative hepatectomy for HCC. Transarterial immunoembolization was performed according to the standard protocol using OK-432, fibrinogen, and thrombin. Histologic changes in cancerous and noncancerous liver tissues were examined at different stages after TIE. Histologic grading of cancer cell injury according to the modified Shimosato criteria (Grades 0-IV, in increasing order of severity of cell injury) and postoperative disease-free survival were compared between the two groups. Based on the results of histopathology, TAE was more effective than TIE against the main tumor. In contrast, TIE was significantly more effective than TAE against extracapsular invasion and intrahepatic metastasis. Disease-free survival after hepatectomy tended to be better in patients pretreated with TIE than TAE. Postoperative tumor recurrences in the TIE group (n = 4) occurred in the nontreatment regions, whereas tumor recurrences in TAE group developed mostly (8 of 11 patients) in treated liver regions. Based on results of histologic examination, TIE seems to be more effective than conventional TAE against extracapsular invasion and intrahepatic metastasis. Data for disease-free survival and recurrence site suggest TIE may be a useful preoperative treatment.

Antineoplastic Agents↗
PubMed2001

Expression of p57/Kip2 protein in pancreatic adenocarcinoma.

INTRODUCTION: Evaluation of the biologic character of carcinomas requires understanding of cell cycle regulators. AIMS: To investigate p57 expression in human pancreatic adenocarcinoma and cyst adenoma. METHODOLOGY: We examined the expression of p57(Kip2), a member of the Cip/Kip family, in 45 pancreatic adenocarcinomas, 7 cystadenomas, and 7 chronic pancreatitis cases. RESULTS: The p57 labeling index (LI) in duct epithelia in chronic pancreatitis averaged 32.8+/-8.3 and was significantly higher than in normal duct epithelia (18.8+/-6.6; p = 0.0011). For the carcinoma, the LI averaged 46.0+/-20.9, which was significantly higher than that for normal duct epithelia (p < 0.0001) and cystadenoma (16.0 11.2; p = 0.0007). However, it was significantly reduced in cases with stage IV disease (p = 0.0351), lymph node metastasis (p = 0.0003), larger size (p = 0.0094), capsular invasion (p = 0.0462), lymphatic invasion (p = 0.0351), and cell proliferating activity (p = 0.0002). In multivariate analysis, p57 LI in pancreatic adenocarcinoma was independently linked to high proliferating activity (p = 0.0230). CONCLUSION: These results suggest that p57 plays a role in the hyperplastic change of the ducts in chronic pancreatitis and that pS7 overexpression contributes to the downregulation of cell proliferation, and its decreased expression contributes to the progression of pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed2001

Usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose for predicting outcome in patients with hepatocellular carcinoma.

OBJECTIVES: The present study was designed to assess the usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) for predicting outcome in patients with hepatocellular carcinoma. METHODS: FDG-PET was performed in 48 patients with hepatocellular carcinoma. For quantitative evaluation, a region of interest (ROI) was placed over the area of maximum activity within the lesion. A background ROI was then placed over the nontumor region of the liver. The average activity within each ROI was subsequently corrected for radioactive decay, and the standardized uptake value (SUV) was calculated by dividing the tissue activity by the injected dose of radioactivity per unit body weight. SUV ratio was expressed as the tumor-to-nontumor ratio of the SUV. RESULTS: The tumor-volume doubling time, as index of the growth rate of hepatocellular carcinoma, correlated significantly with SUV ratio but did not correlate with SUV. On the basis of the SUV ratio, the patients were divided into two groups of similar size: group A, SUV ratio of < or = 1.5; and group B, SUV ratio > 1.5. The cumulative survival rate was significantly lower in group B than in group A. On the basis of the SUV, the patients were divided into two groups of roughly equal size: group C, < or = SUV 2.6; and group D, > SUV 2.6. The cumulative survival rate was similar in these groups. On regression analysis with the Cox proportional hazards model, the SUV ratio and tumor number were significantly related to survival. CONCLUSIONS: These results suggest that FDG-PET is useful not only for the evaluation of the malignancy of hepatocellular carcinoma but also for the prediction of outcome in patients with hepatocellular carcinoma.

Adult↗
PubMed2001

Comparison of in-phantom dose distributions for coronary angiography using an x-ray machine and synchrotron radiation.

Coronary cineangiography using synchrotron radiation is anticipated, owing to the high intensity and availability of monoenergy. To investigate allowable dose levels in clinical application, absorbed dose distribution in a tissue substitute phantom for a conventional x-ray machine was measured with thermoluminescent dosimeters at the University of Tsukuba under the practical conditions used for digital angiography. The dose rate at a 0.5-cm depth was 0.145 Gy/s, and the dose per frame was 0.725 mGy for the irradiation period of 5 ms per frame. For synchrotron radiation, the dose distribution measurement was made at a 5-GeV AR (Accumulation Ring) of the High Energy Accelerator Research Organization, in which a polymethylmethacrylate (PMMA) phantom was irradiated with the strongest beam available at the facility, which was 33.32 keV, 5.2 x 6.2 cm2 beam. Using this beam, a 1-mm-diameter coronary artery has been visualized at 1% iodine concentration at the AR. Nonhomogeneous strength distribution in the beam was observed in the vertical direction. The maximum dose rate was 0.556 Gy/s, and it attenuated to 1/3000 at a 30-cm depth in the beam center. At the deep positions, the doses were influenced by the high harmonics, which was confirmed with an EGS4 Monte Carlo calculation. Outside the beam, beam contamination on both sides of the main beam affected the doses. For comparison to the x-ray machine, the measured dose was analytically converted to that needed for a 5.2 x 16 cm2 beam that is used for clinical application. The dose rate at 0.5-cm depth was found to be 0.215 Gy/s, which is 1.48 times larger than that for x-rays. Moreover, the attenuation rate in the phantom was significantly greater than that of the x-ray machine, because of the difference of the energy spectra between the x-rays and synchrotron radiation used.

Biophysical Phenomena↗