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T Kanamaru

Publications and source records attributed to T Kanamaru.

At least 19 recordsLinked to original sources
PubMed2001

Theoretical analysis of array-enhanced stochastic resonance in the diffusively coupled FitzHugh-Nagumo equation.

The array-enhanced stochastic resonance (AESR) in the diffusively coupled FitzHugh-Nagumo equation is investigated. The two properties of AESR, namely, the scaling of the optimal noise intensity and the enhancement of the maximum value of the correlation coefficient as a function of the coupling strength, are analyzed theoretically. By transforming the dynamics of N elements into that of the mean and the deviation from it, it is found that AESR is caused by the correlation between them. A low-dimensional model that reproduces the above properties is constructed.

Animals↗
PubMed2001

Fluctuation-induced memory retrieval in a pulsed neural network storing sparse patterns with hierarchical correlations.

An associative memory in a pulsed neural network composed of the FitzHugh-Nagumo models storing sparse patterns with hierarchical correlations is investigated. The memory patterns composed of 0/1 digits are represented by the synchronous periodic firings of the neurons. It is found that the target pattern and the OR pattern are retrieved individually by controlling the intensity of fluctuations in the system.

Animals↗
PubMed2001

A novel hydrophobic diheme c-type cytochrome. Purification from Corynebacterium glutamicum and analysis of the QcrCBA operon encoding three subunit proteins of a putative cytochrome reductase complex.

Electrophoresis of a Corynebacterium glutamicum membrane preparation in the presence of sodium dodecyl sulfate, followed by staining for peroxidase activity (heme staining), showed only one band at about 28 kDa. This 28 kDa protein was purified from C. glutamicum membranes by chromatography in the presence of decylglucoside using DEAE-Toyopearl and hydroxylapatite columns, as the sole c-type cytochrome in the bacterium. The cytochrome showed an alpha band at 551 nm, and its E(m, 7) was about 210 mV. A QcrCAB operon encoding the subunits of a putative quinol cytochrome c reductase was found 3'-downstream of ctaE encoding subunit III of cytochrome aa(3) in the C. glutamicum genome. The deduced amino acid sequence of qcrC, composed of 283 amino acid residues, contained two heme C-binding motifs and was in agreement with partial peptide sequences obtained from the 28 kDa protein after V8 protease digestion. We propose to name this protein cytochrome cc. The presence of cytochrome cc is a common feature of high G+C content Gram-positive bacteria, since we could confirm this protein by electrophoresis; homologous QcrCAB operons are also known in Mycobacterium and Streptomyces. QcrA and qcrB of C. glutamicum encode the Rieske Fe-S protein and cytochrome b, respectively, although these proteins were not co-purified with cytochrome cc. The phylogenetic tree of cytochromes b and b(6) show that C. glutamicum cytochrome b, along with those of other bacteria in the high G+C group, is rather different from the Bacillus counterparts, but highly similar to the Deinococci and Thermus cytochromes. This indicates that there is a fourth group of bacteria in addition to the three clades: proteobacterial cytochrome b, cyanobacterial b(6) and green sulfur-low G+C Gram-positive bacteria.

Amino Acid Sequence↗
PubMed2001

In vitro and in vivo antibacterial activities of TAK-083, an agent for treatment of Helicobacter pylori infection.

The antibacterial activity of TAK-083 was tested against 54 clinical isolates of Helicobacter pylori and was compared with those of amoxicillin, clarithromycin, and metronidazole. The growth-inhibitory activity of TAK-083 was more potent than that of amoxicillin, clarithromycin, or metronidazole (the MICs at which 90% of the strains are inhibited were 0.031, 0.125, 64, and 8 microg/ml, respectively). The antibacterial activity of TAK-083 was highly selective against H. pylori; there was a >30-fold difference between the concentration of TAK-083 required to inhibit the growth of H. pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure of H. pylori strains to TAK-083 at the MIC or at a greater concentration resulted in an extensive loss of viability. When four H. pylori strains were successively subcultured in the medium containing subinhibitory concentrations of TAK-083, no significant change in the MICs of this compound was observed. TAK-083 strongly inhibited the formation of tryptophanyl-tRNA in H. pylori while exhibiting little effect on the same system in eukaryotes. TAK-083 was efficacious in the treatment of gastric infection caused by H. pylori in Mongolian gerbils. The results presented here indicate that TAK-083 is a promising candidate for the treatment of H. pylori infection.

Amoxicillin↗
PubMed2001

[Species differences in the in vitro metabolism of 2,4,5,2',3',4'-hexachlorobiphenyl].

In vitro Metabolism of 2,4,5,2',3',4'-hexachlorobiphenyl (CB138) was studied using liver microsomes from rats, hamsters and guinea pigs. Guinea pig liver microsomes formed four metabolites named as M-1, M-2, M-3 and M-4 and these metabolites were all increased to about 4-5 fold of untreated microsomes by pretreatment of phenobarbital. Liver microsomes of rats and hamsters showed much less activity to metabolize CB138 than those of guinea pigs. Only phenobarbital-treated microsomes produced very small amounts of M-3 in rats and M-1, M-2 and M-3 in hamsters, but untreated and MC-treated microsomes did not. When mass spectra of the methylated derivatives of M-1, M-2, M-3 and M-4 were measured in GC/MS, the former two possess the molecular ion of 354 and the latter two had the molecular ion of 388. In addition, the mass fragmentation pattern indicated that M-1, M-2, M-3 and M-4 are 2-OH-4,5,2',3',4'-pentachlorobiphenyl, 5-OH-2,4,2',3',4'-pentachlorobiphenyl, 3-OH-CB138 and 2-OH-3,4,5,2',3',4'-hexachlorobiphenyl, respectively. Of four metabolites, the chemical structures of M-3 and M-4 were supported by the synthesized authentic compounds. From these results, it is suggested that the metabolism of CB138 in guinea pig liver proceeds mainly via 2,3-epoxide as an intermediate and a PB-inducible P450, CYP2B18, is the most important isozyme in CB138 metabolism.

Animals↗
PubMed2000

Clinical significance of urokinase-type plasminogen activator activity in hepatocellular carcinoma.

BACKGROUND AND METHODS: The plasminogen activation system plays a crucial role in the process of cancer invasion and metastasis. To evaluate the most effective factor in the invasion, metastasis and prognosis of hepatocellular carcinoma (HCC), we examined urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor (PAI)-1, PAI-2 and uPA activity by enzyme-linked immunosorbent assays (ELISA) in HCC tissues obtained from 46 patients. The results were compared with the patients' clinicopathological features and prognoses. RESULTS: Of the clinicopathological features, only histological portal involvement or intrahepatic metastasis, or both (INV), was significantly correlated to the disease-free survival rates (DFS; P < 0.05). The levels of uPA, PAI-1 and PAI-2 antigens were significantly associated with INV and histological grade. The DFS was not different, however, between cases with uPA, PAI-1 and PAI-2 values above and below the median. The high levels of uPA activity were closely related to INV (P < 0.001), and the activity gradually raised histological grades (P < 0.0001). The DFS was significantly different between patients with uPA activity below and above the median (0.70 ng/mL; P = 0.0092); it was also significantly different between such patients without INV (P < 0.05). CONCLUSIONS: Urokinase-type plasminogen activator activity may be the most sensitive factor affecting HCC invasion in the plasminogen activation system and a strong predictor for the recurrence of HCC. We suggest that cases with uPA activity of more than 0.70 ng/mL should be carefully followed up for possible HCC recurrence.

Adolescent↗
PubMed2000

Associative memory retrieval induced by fluctuations in a pulsed neural network.

An associative memory retrieval in a pulsed neural network composed of the FitzHugh-Nagumo neurons is investigated. The memory is represented in the spatio-temporal firing pattern of the neurons, and the memory retrieval is accomplished using the fluctuations in the system. The storage capacity of the network is investigated numerically. It is demonstrated that this pulsed neural network is capable of an alternate retrieval of two patterns.

Action Potentials↗
PubMed1999

Inhibitory role of plasminogen activator inhibitor-1 in invasion and proliferation of HLE hepatocellular carcinoma cells.

Plasminogen activator inhibitor (PAI)-1, a serine protease inhibitor, inactivates urokinase-type plasminogen activator (uPA) and regulates degradation of the extracellular matrix; whether it functions for or against tumor progression, however, has been the subject of controversy. To assess the role of PAI-1 in invasion and proliferation of hepatocellular carcinoma (HCC) cells, HLE cells were transfected with a vector capable of expressing an antisense PAI-1 transcript. Analysis of seven stably transfected clones (PAI-1-) showed reductions of 81% in PAI-1 mRNA by northern blot analysis and 63% in the cellular PAI-1 antigen level by enzyme-linked immunosorbent assay (ELISA). There was no change in the levels of secreted PAI-1 or PAI-2. The activity of cellular uPA increased by 54%, without change in the protein level or the secreted uPA activity evaluated by ELISA. Morphologically, PAI-1 antisense induced a spindle shape with narrower cytoplasmic processes in HLE cells. The forced inhibition of PAI-1 increased the invasion and the growth of PAI-1- cells by 75% and 82%, respectively. These results suggest that PAI-1 plays a role in inhibiting invasion and proliferation, and the balance between uPA and PAI-1 expression is important to assess the invasiveness of HCC cells.

Carcinoma, Hepatocellular↗
PubMed1999

Levels of telomerase catalytic subunit mRNA as a predictor of potential malignancy.

This study investigated the relationship between the levels of human telomerase reverse transcriptase (hTERT) mRNA and that of telomerase activity in hepatocellular carcinoma (HCC). A significant correlation between hTERT mRNA expression and telomerase activity by transfecting the gene encoding hTERT into telomerase-negative human fibroblast cells has clearly been demonstrated. However, the relationship between levels of telomerase activity and that of hTERT mRNA has yet to be elucidated. In this study, the levels of hTERT mRNA were analyzed in 24 HCC patients by real-time PCR. And the intensity of telomerase activity was analyzed by fluorescence-based TRAP method. The difference of hTERT mRNA level was highly significant between tumor tissues and non-cancerous liver tissues. And there were significant correlations between the levels of hTERT mRNA and that of telomerase activity (r=0.751) in tumor tissues. We observed a strong correlation between levels of hTERT mRNA and that of telomerase activity in HCC. Our results suggest that the levels of hTERT mRNA would be useful in genetic diagnostic tests, instead of telomerase activity, to screen at-risk patients of HCC in human liver tissues.

Adult↗
PubMed1999

[Comparative study on metabolism of three tetrachlorobiphenyls with animal liver microsomes].

In vitro metabolism of 3,5,3',4'-, 3,5,3',5'- and 2,4,3',4'-tetrachlorobiphenyls (TCBs) was studied using liver microsomes from rats, guinea pigs and hamsters. 3,5,3',4'-TCB was metabolized to 4-hydroxy-3,5,3',4'-TCB with liver microsomes of 3-methyl-cholanthrene (MC)- and 3,4,5,3',4'-pentachlorobiphenyl (PenCB)-treated rats but not of phenobarbital (PB)-treated ones. This result suggests that a MC-inducible cytochrome P450 isoform, probably CYP1A1, is more important in the in vitro metabolism of 3,5,3',4'-TCB in rat liver and that the isoform attacks the 3,5-dichloro-substituted phenyl ring more predominantly than 3,4-dichloro-substituted one. In 3,5,3',5'-TCB metabolism, liver microsomes from MC- and 3,4,5,3',4'-PenCB-treated hamsters formed 4-hydroxy-3,5,3',5'-TCB to a similar extent to rats reported previously. Guinea pig liver microsomes formed no metabolite. In 2,4,3',4'-TCB metabolism, PB accelerated 3-, 5- and 4-hydroxylations in guinea pigs and also 3- and 5-hydroxylations in hamsters, suggesting the involvement of a PB-inducible P450 isoform, presumably P450GP-1 and P450HPB-1, respectively. On the other hands, MC- and 3,4,5,3',4'-PenCB-treatment resulted in the marked increase of 4-hydroxylation in hamsters, but in the suppression of 4-hydroxylation in guinea pigs. From these results, it is suggested that the hydroxylation of coplanar TCBs such as 3,5,3',4'- and 3,5,3',5'-TCB is catalyzed by a MC-inducible P450 in rats and hamsters, whereas non-coplanar TCBs such as 2,4,3',4'-TCB which possesses both PB- and MC-like inducing ability of liver enzymes are metabolized by one or more kinds of P450 isoform induced by PB and MC.

Animals↗
PubMed1999

[Analysis of the long-term prognosis for conjunctival malignant melanomas in Japan].

PURPOSE: To investigate the long-term prognosis for primary conjunctival malignant melanomas in Japan. MATERIALS & METHODS: We conducted a survey of 61 cases which had been reported in a 38-year period (1959 to 1996). We gathered information regarding the survival of patients, the post-operative follow-up period, the causes of death, and recurrences. Answers were obtained segarding 51 cases (84%). Detailed progress was identified in 23 of these cases. The survival rates were calculated using the Kaplan-Meier method. RESULTS: The survival rates were 95.1% after 1 year, 72.9% after 3 years, and 53.4% after 5 years. These values are relatively low compared with those reported in Europe and the United States.

Adolescent↗
PubMed1999

Clinical implications of telomerase activity in resected hepatocellular carcinoma.

This study investigated the relationship of telomerase activity to its clinical implications in hepatocellular carcinoma (HCC). Telomerase activity was quantatively examined by a non-radioisotope quantitative system based on a TRAP-eze (ONCOR) in 42 HCC nodules and 40 non-cancerous liver tissue adjacent to the HCC nodules, obtained by surgical resection. Telomerase activity was confirmed in 37 HCC nodules (88.1%), being more statistically intense in de-differentiated tumors (p<0.01). Telomerase activity was positive in 9 cases (22.5%) of non-cancerous liver tissue and its activation was closely associated with the biologically malignant potential of the tumor itself such as the histological grade, portal vascular invasion, and intrahepatic metastasis (p<0. 05). The disease-free survival rate with its activity was also statistically lower than that without its activity of the non-cancerous tissue (p<0.01). These results indicate that telomerase may be a useful marker of biological characteristics in HCC and may lead to more effective surgical procedures.

Alanine Transaminase↗
PubMed1998

Surgical significance of telomerase activity in noncancerous liver tissue from patients with hepatocellular carcinoma.

Telomerase activity has been detected in tissue from noncancerous liver of patients with chronic liver disease, but its functional significance remains to be elucidated. We therefore evaluated the telomerase activity in surgically obtained noncancerous liver tissue from 20 hepatocellular carcinoma (HCC) patients. Two samples of noncancerous liver tissue were obtained from each patient: one from the parenchyma adjacent to the HCC nodules of the resected specimen; the other from the parenchyma distant from the HCC nodules of the remnant liver. Telomerase activity was assayed by a non-radioisotope quantitative system based on "TRAP-eze." Five samples from the noncancerous liver tissue adjacent to the HCC nodules (25.0%) were telomerase-positive; all such cases showed high-grade malignant potential, such as intrahepatic metastasis and/or portal vascular invasion and infiltration of the fibrous capsule in the corresponding HCC nodules, and telomerase positivity showed neither a relationship with the histological activity index scores nor a correlation with liver function. Interestingly, no telomerase activity was detected in any of the 20 samples obtained from the parenchyma of the remnant liver. These results indicate that telomerase in noncancerous liver tissue is associated not with the hepatic condition accompanying HCC, but with the biological characteristics of the tumor itself, and may derive from infiltrating cancer cells. Determination of telomerase status may aid in designing more effective surgical procedures.

Aged↗
PubMed1998

Biological effects and cellular uptake of c-myc antisense oligonucleotides and their cationic liposome complexes.

The biological effects and cellular uptake of human c-myc antisense oligonucleotides and their liposome complexes were investigated in vitro using human promonocytic leukemia U937 cells. Antisense phosphorothioate oligonucleotides (S-Oligo) significantly inhibited the growth of U937 cells in a dose-dependent manner. However, no significant effect on cell proliferation was observed with unmodified phosphodiester (P-Oligo) and partially phosphorothioated (PS3-Oligo) oligonucleotides with an antisense sequence and S-Oligo with sense and G-quartet control sequences. In cellular uptake experiments, radiolabeled S-Oligo was taken up by U937 cells more than P-Oligo and PS3-Oligo. Similar results were obtained in mouse peritoneal macrophages used for comparison. Confocal microscopic studies demonstrated a significant distribution of FITC-labeled oligonucleotides on the cell surface and in the cytoplasm in a punctate pattern, but not in the nucleus. When complexed with cationic liposomes, cellular uptake of FITC-labeled P-Oligo or S-Oligo was significantly increased and the fluorescence was located mainly in the nucleus, indicating that the uptake and intracellular pharmacokinetics of both oligonucleotides can be modified by complexation. An inhibitory effect of the complexes was observed at a dose which is ineffective in the case of the oligonucleotides alone. However, this effect was also associated with cytotoxicity of the cationic liposomes, suggesting that optimization of this formulation will be necessary to achieve a more efficient delivery of the oligonucleotides to U937 cells.

Animals↗
PubMed1997

Expression of urokinase-type plasminogen activator receptor in hepatocellular carcinoma.

It is well known that a urokinase-type plasminogen activator receptor (uPAR) is a key protein in the plasminogen activation system, which plays a proteolytically important role in the invasion and metastasis of various cancer cells. To assess the expression of uPAR in hepatocellular carcinoma (HCC), we analyzed the expression of uPAR messenger RNA (mRNA) and the protein in 31 pair-samples of solitary HCC and nontumorous liver tissues from the same patients. Fifteen samples exhibited no histological potential of recurrence, such as portal involvement or intrahepatic metastasis (group A), and 16 samples exhibited such histological features (group B). Seventy-one percent of the cases showed uPAR signals, and these signals were mainly localized at the cytoplasm of the tumor cells and tended to be at the front of invasive foci. 87.5% of the cases in group B showed uPAR signals against 53.3% of the cases in group A (P < .05). The rate of recurrence in the uPAR positive/negative cases in group A was 75.0% and 14.3%, respectively (P < .05). In non-neoplastic cases, e.g., chronic active hepatitis and cirrhosis, weak uPAR mRNA and protein signals were detected in hepatocytes neighboring the portal tracts, suggesting that this protein plays some role in such cases. The present study indicates that uPAR plays an important role at least in its initial stage in invasion and metastasis of HCC, and that uPAR expression can be a candidate predictor of these factors.

Antigens, Neoplasm↗
PubMed1997

Telomerase activity in hepatocellular carcinoma as a predictor of postoperative recurrence.

Telomerase is a ribonucleoprotein that stabilizes telomeres and allows unlimited cell division. It has been reported that most cancer cells evince reactivated telomerase. We examined telomerase activity in 29 patients with hepatocellular carcinoma (HCC) by a polymerase chain reaction-based semiquantitative assay. Of 24 HCCs, telomerase activity was positive in 23 (95.8%), of which 16 showed strong activity. In 11 well differentiated HCCs, telomerase activity was strong in 5, weak in 5, and undetected in 1 and in 13 moderately differentiated HCCs, it was strong in 11 and weak in 2. Five of 6 HCCs less than 2 cm in diameter expressed strong telomerase activity, while weak telomerase activity was detected in 7 of 19 (36.8%) resected noncancerous liver tissues from the HCC patients. Five of these 7 patients (71%) manifested recurrence within 6 months after surgery. The recurrence rate in these patients whose noncancerous liver tissue was positive for telomerase activity was significantly higher than that in patients in whom it was negative (P = 0.017). These results suggest that the presence of telomerase activity may be a useful diagnostic marker of HCC, regardless of tumor size, and that its detection in resected noncancerous liver tissues may serve as a useful predictor of postoperative recurrence.

Adult↗