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Biomedical subjects

T Ichihara

Publications and source records attributed to T Ichihara.

At least 37 records · Page 2Linked to original sources
PubMed2001

Glut1 expression in T1 and T2 stage colorectal carcinomas: its relationship to clinicopathological features.

Glucose uptake is mediated by glucose transporter (Glut) proteins, which exhibit altered expression in a variety of malignant neoplasms. Glut1 expression is thought to be a potential marker for malignant transformation. The aim of the present study was to investigate the expression of Glut1 protein in colorectal adenomas, T1 and T2 stage carcinomas. Immunohistochemical detection of Glut1 protein was examined in 141 formalin-fixed and paraffin-embedded colorectal tumour specimens (57 adenomas, 84 carcinomas). The degree of Glut1 immunostaining of a specimen was graded according to the proportion of Glut1-positive cells in it; absent (positive cells are 0%), weakly positive (less than 10%), moderately positive (10-50%), and strongly positive (more than 50%). Glut1 expression was present in 18% of the adenomas with low-grade dysplasia, and in 63% of the adenomas with high-grade dysplasia. The positivity in such lesions was usually weak, but was moderate in 8% of the adenomas with high grade dysplasia. For the carcinomas, there were significant correlations between Glut1-positivity and depth of invasion (T1 45% versus T2 74%, P<0.01), histological differentiation (well 49% versus moderately to poorly 74%, P< 0.05) and morphological type (polypoid 42% versus depressed 73%, P< 0.05), if the cut-off value was set at 10% of cells. In conclusion, we clarified the relationship between Glut1 expression and clinicopathological features in T1 and T2 stage colorectal carcinomas, and our results suggested a high malignant potential of the depressed-type carcinoma.

Adenocarcinoma↗
PubMed2001

Resistance to fulminant hepatitis and carcinogenesis conferred by overexpression of retinoblastoma protein in mouse liver.

Previously, retinoblastoma (Rb) transgenic mice were produced under the control of the Rb gene promoter and showed dwarf characteristics. Here, we created transgenic mice, in which the human Rb gene was controlled by the hepatocyte nuclear factor-1 gene promoter/enhancer and was expressed primarily in the liver. The liver of these novel transgenic mice was normally developed. Intriguingly, these mice showed resistance to fulminant hepatitis induced by anti-Fas antibody as well as resistance to chemical carcinogenesis in the liver. These results show that the Rb protein acts as an anti-apoptotic and anti-oncogenic agent in vivo. Our novel construct may be useful as a gene cassette in gene therapy for prevention of fulminant hepatitis and hepatoma.

Animals↗
PubMed2001

Detection of DNA hybridization by use of a lanthanide fluorescent intercalator that specifically binds to double stranded DNA.

Toward development of a DNA microarray system in which neither labeling nor amplification of the nucleic acids from living cell is required, we have developed a new method for the detection and quantification of target DNA hybridized with probe DNA fixed on a solid surface. This method utilizes a fluorescent intercalator: naphthalene diimide derivative carrying two fluorescent tetradentate beta-diketone-Eu3+ chelates. This compound selectively binds to double stranded DNA (dsDNA) fixed on a plastic assay plate. The amount of the compound bound to single stranded DNA (ssDNA) is negligible. The fluorescent intensity of Eu3+ was in proportion to the amount of the fixed DNA, showing that the compound quantitatively binds to dsDNA. Therefore, this method can be used not only to detect dsDNA, but also to measure the amount of DNA on a solid surface.

DNA↗
PubMed2001

[Detection of TDH-producing Vibrio parahaemolyticus O3:K6 from naturally contaminated shellfish using an immunomagnetic separation method and chromogenic agar medium].

We attempted to isolate TDH-producing Vibrio parahaemolyticus O3:K6 from shellfish. Asari samples were incubated with TSB supplemented with 2% (w/v) NaCl for 6 h, and then the 6-h cultures were incubated with salt polymyxin broth for 18 h. After the two-step enrichment, a 1 ml portion of the culture was treated with magnetic beads coated with K6 antibody for immunoconcentration of V. parahaemolyticus O3:K6. The immunoconcentrated and untreated cultures were plated onto a chromogenic agar and TCBS agar media for isolation of V. parahaemolyticus. TDH-producing V. parahaemolyticus O3:K6 was isolated from 3 out of 66 lots (4.5%) of naturally contaminated Asari. Six of 4,265 colonies suspected as V. parahaemolyticus (0.14%) were TDH-producing V. parahaemolyticus O3:K6.

Agar↗
PubMed2001

Comparison of the relation between timing and force control during finger-tapping sequences by pianists and non pianists.

To examine the relation between timing and force control during finger taping sequences by both pianists and nonpianists, participants tapped a force plate connected to strain gauges. A series of finger tapping tasks consisted of 16 combinations of pace (intertap interval: 180, 200, 400, or 800 ms) and peak force (50, 100, 200, or 400 g). Analysis showed that, although movement timing was independent of force control under low or medium pace conditions, there were strong interactions between the 2 parameters under high pace conditions. The results indicate that participants adapted the movement by switching from separately controlling these parameters in the slow and moderate movement to coupling them in the fast movement. While variations in the intertap interval affected force production by nonpianists, they had little effect for pianists. The ratios of time-to-peak force to press duration increased linearly in pianists but varied irregularly in nonpianists, as the required force decreased. Thus, pianists regulate peak force by timing control of peak force to press duration, suggesting that training affects the relationship between the 2 parameters.

Adult↗
PubMed2001

Independence of timing and force control during finger-tapping sequences by pianists.

To examine the relation between timing and forcc control during finger-tapping sequences by both the 10 pianists and the 13 nonpianists, participants tapped a force plate connected to strain gauges. A series of finger-tapping tasks consisted of 16 combinations of pace and peak force. Analysis showed that pianists had smaller correlation between intertap interval and peak force than nonpianists. Thus, force control was more independent of timing for pianists than for nonpianists.

Adult↗
PubMed2000

Mechanism of action of aragusterol a (YTA0040), a potent anti-tumor marine steroid targeting the G(1) phase of the cell cycle.

Aragusterol A (YTA0040), isolated from the Okinawan marine sponge of the genus Xestospongia, is a potent anti-tumor marine steroid that possesses a unique structural component. This compound showed broad-spectrum anti-proliferative activity against a panel of 14 human cancer cell lines (IC(50) = 0.01-1.6 microM). P-glycoprotein-mediated, multidrug-resistant cells showed cross-resistance to YTA0040 cells, whereas cisplatin-resistant non-small-cell lung-cancer (NSCLC) sublines showed a collateral sensitivity to YTA0040. In transplantable murine tumor models, YTA0040 displayed a broad spectrum and high degree of anti-tumor activity when administered i.p. or p.o. (life span T/C = 135-234%). In P388 murine leukemia cells, YTA0040 caused dose- and time-dependent suppression of nucleic acid and protein synthesis, with protein synthesis being more potently and rapidly inhibited than nucleic acid synthesis. Flow-cytometric analysis revealed that YTA0040 blocked the entry of human NSCLC-derived A549 cells into S phase, leading to arrest in the G(1) phase of the cell cycle. Western blot analysis demonstrated that YTA0040 caused a dose-dependent decrease in the levels of expression of hyperphosphorylated pRb and cyclin A in A549 cells. The level of p53 protein expression was decreased by YTA0040 treatment. A higher concentration of YTA0040 down-regulated the levels of expression of CDK2, CDK4, cyclin D1 and cyclin E. These findings indicated that YTA0040 arrested human NSCLC cells in late G(1) phase of the cell cycle through inhibition of pRb phosphorylation. Inhibition of pRb phosphorylation by YTA0040 resulted from down-regulation of levels of expression of the CDKs and cyclins involved in the G(1)/S transition and not from induction of p53 and/or the CDK inhibitor p21.

Animals↗
PubMed2000

Flat-elevated and depressed, subtypes of flat early colorectal cancers, should be distinguished by their pathological features.

Flat-type colorectal tumors have are being detected with increasing frequency. It has become clear that these flat lesions contain two subtypes; flat-elevated and depressed lesions. However, their clinicopathological features and roles in colorectal carcinogenesis remain obscure. We classified colorectal adenomas and submucosal invasive cancers into three types: polypoid, flat-elevated, and depressed types. A clinicopathological study of 2505 colorectal tumors (2407 adenomas, 98 submucosal invasive cancers) was then performed. Furthermore, 64 tumors (25 adenomas with high-grade dysplasia, 39 submucosal invasive cancers) from which DNA was extracted were examined for K-ras gene mutation. The percentages of each configuration in the resected materials were 62.0%, 36.4%, and 1.6% of the polypoid, flat-elevated, and depressed types, respectively. The rate of submucosal invasive cancer in the depressed type was always high regardless of size. In the polypoid and flat-elevated types, lesions of larger size showed higher rates of invasion. Analysis of submucosal invasive cancers revealed no adenomatous components in any of the depressed-type lesions; in the polypoid and flat-elevated types the frequencies of cancer with adenomatous components were 83.6% and 77.8%, respectively. The flat-elevated type was more frequently located (77.8%) in the proximal colon than the other types (polypoid type 16.4%, depressed type 25.0%). The incidence of K-ras gene mutation was 47.2%, 18.2%, and 0% in the polypoid, flat-elevated, and depressed types, respectively. These findings suggest that the flat-elevated and depressed types are similar in that they are both morphologically flat and have infrequent incidences of K-ras gene mutation, but these two lesions differ in their pathological features. Especially, depressed type lesions have a tendency to invade the submucosal layer even when they are small. Therefore one should always be aware of this type of lesion during colonoscopic examination.

Adenoma↗
PubMed2000

Laparoscopic lower anterior resection is equivalent to laparotomy for lower rectal cancer at the distal line of resection.

BACKGROUND: Procedures that involve resection of the distal rectum challenge the current limitations of laparoscopic technology, because of lack of compact articulating stapling instruments. METHOD: We improve the procedure with the aid of a Lap disk, an abdominal wall sealing device that was developed for hand-assisted manipulation. A linear stapler capable of changing its stop angle is inserted through the disk, and the rectum is transected by the disk during a second pneumoperitoneum. RESULTS: The transection line becomes equivalent to that obtained with laparotomy. CONCLUSION: This new technique made laparoscopic lower anterior resection possible to transect the lower rectum in the same way as is done with laparotomy.

Abdominal Muscles↗
PubMed2000

Quantitative planar imaging method for measurement of renal activity by using a conjugate-emission image and transmission data.

We are proposing a method to accurately measure renal activity in renography using Tc-99m labeled tracers. This method uses a conjugate-view image and transmission data for attenuation correction, the triple energy window (TEW) method for scatter correction, and background correction techniques that consider the source volume for accurate background activity correction. To examine this method in planar imaging, we performed two renal phantom studies with various uniform background activity concentrations. One study used two ideal box-shaped kidney phantoms with a thickness of 2 or 4 cm in a water tank and the other study employed two real kidney-shaped phantoms in a fillable abdominal cavity. For these studies the kidney phantom-to-background activity concentration ratio (S) was changed from 5 to infinity. The transmission data were obtained with an external Tc-99m line array source. The anterior- and posterior-view emission images were acquired with a dual-headed gamma camera simultaneously and the TEW method was used to correct scatter for the emission and transmission images. The results showed that this method with both the accurate background correction and scatter correction could give depth-independent count rates and could estimate the true count rate with errors of less than 5% for all S values. However, if either accurate background correction or scatter correction was performed alone, the absolute error increased to about 50% for the smaller S values. Our proposed method allows one to accurately and simply measure the renal radioactivity by planar imaging using the conjugate-emission image and transmission data.

Kidney↗
PubMed2000

Studies on the mechanism of action of the gastric H+,K(+)-ATPase inhibitor SPI-447.

3-Amino-5-methyl-2(2-methyl-3-thienyl)- imidazo[1,2-a]thieno[3,2-c]pyridine, SPI-447, is a potent gastric H+,K(+)-ATPase inhibitor, but a detailed mechanism of the inhibition is unknown. This study was designed to investigate the mechanism by which SPI-447 inhibits gastric H+,K(+)-ATPase. For this purpose, the inhibitory action of SPI-447 on gastric H+,K(+)-ATPase from porcine gastric mucosa was compared with that of omeprazole (an irreversible inhibitor) and SCH28080 (a reversible inhibitor). All compounds produced dose-dependent inhibition of gastric H+,K(+)-ATPase, and the inhibitory intensities were increased under acidic conditions. The anti-H+,K(+)-ATPase actions of SPI-447 and SCH28080 were attenuated by dilution, but not influenced by glutathione pretreatment. In contrast, that of omeprazole was not influenced by dilution, but was suppressed by glutathione pretreatment. KCl addition reversed the inhibition of H+,K(+)-ATPase-mediated H(+)-transport by SPI-447 and SCH28080, but had no effect on that by omeprazole. The anti-gastric H+,K(+)-ATPase action of SPI-447 was additive with that of SCH28080. SPI-447 and SCH28080 had no effect on Na+,K(+)-ATPase activity. These findings indicated that the inhibitory mechanism of SPI-447 on gastric H+,K(+)-ATPase was similar to that of SCH28080, but different from that of omeprazole; i.e., 1) reversible, 2) SH-group independent, 3) K(+)-competitive, and 4) highly specific against gastric H+,K(+)-ATPase.

Animals↗
PubMed2000

[Right thoracotomy for reoperative mitral valve replacement].

We report a case of 67-year-old male who underwent reoperative mitral valve replacement through the right thoracotomy. He had undergone primary double valve replacement with mechanical valve for aortic valve and tissue valve for mitral valve respectively, and tricuspid annular plasty 11 years ago. The second operation was performed through the right thoracotomy under moderately hypothermic cardiopulmonary bypass. The mechanical valve was replaced via right side of left atrium approach under ventricular fibrilation at 25 centigrade of bladder temperature. He recovered well without any major complications.

Aged↗
PubMed1999

Inhibition of liver glutathione S-transferase placental form-positive foci development in the rat hepatocarcinogenesis by Porphyra tenera (Asakusa-nori).

The effects of Asakusa-nori, Porphyra tenera (PT), a popular edible seaweed in Japan, on the development of putative preneoplastic lesions, glutathione S-transferase placental form (GST-P)-positive foci, in the male F344 rat liver were examined using a medium-term bioassay system. PT significantly decreased both the number and area of GST-P-positive foci in rat livers initiated with diethylnitrosamine (DEN). To investigate possible mechanisms of inhibition, effects of PT on 5-bromo-2'-deoxyuridine (BrdU) labeling in GST-P-positive foci and the surrounding area of hepatocytes were studied. The ratio of the GST-P-positive foci to surrounding tissue labeling indices was decreased in the PT-treated group as compared with the DEN alone group. Ornithine decarboxylase activity in the liver was slightly increased and spermidine/spermine N'-acetyltransferase activity was slightly decreased in the PT-treated animals. These results suggest that PT possesses chemopreventive effects against DEN-induced hepatocarcinogenesis.

Acetyltransferases↗
PubMed1999

Membrane-type matrix metalloproteinase-1 expression and activation of gelatinase A as prognostic markers in advanced pediatric neuroblastoma.

BACKGROUND: Recently a novel membrane-type matrix metalloproteinase-1 (MT-MMP-1) was discovered to be a specific activator of progelatinase A, and was correlated with tumor invasion. To the authors' knowledge, no information regarding the expression of MT-MMP-1 has been reported in childhood malignancies. In this study, the authors attempted to elucidate the specific mechanisms that underlay the invasive behavior of neuroblastoma (NB) cells with respect to the expression of MT-MMP-1 and its determined prognostic value, especially in pediatric patients with advanced Evans' Stage IV NB. METHODS: Thirty specimens from surgically excised NB (mainly Stage IV) were collected retrospectively. The total levels of progelatinase A (68 kilodaltons [kD]) and its activated form (62 kD) in the tumor lysates were quantified by gelatin zymography. The expression of MT-MMP-1 was estimated by immunostaining with a monoclonal antibody (113-5B7). RESULTS: Progelatinase A and the activated form were detected in each of the 30 specimens. The gelatinase A activation ratio, 62 kD/(62 kD + 68 kD), strongly correlated with the high levels of MT-MMP-1 expression found in specimens of advanced tumor stage. In the patients with advanced Stage IV NB, the activation ratio was strongly associated with unfavorable clinical outcome; the 5-year survival was 88.9% in the patients with a low activation ratio (< or = 26%) versus only 21.2% in the patients with a high activation ratio (>26%). CONCLUSIONS: Gelatinase A activation correlates with high expression of MT-MMP-1 on NB cells and is associated strongly with advanced stage and poor clinical outcome. These results are consistent with the notion that MT-MMP-1 expression is an important prognostic determinant of the biologic behavior of NB.

Adolescent↗
PubMed1999

Role of platelet activating factor on severity of ischemic colitis.

PURPOSE: Ischemic colitis develops after a sudden decrease in colonic blood supply and has a variety of clinical manifestations. The aim of this study was to assess the role of platelet activating factor in the pathogenesis of ischemic colitis with use of the platelet activating factor antagonist TCV-309. METHODS: Rats were randomly divided into four groups. Rats in Group RV underwent ring attachment around the rectum to induce partial obstruction and ligation of the marginal vessels of the left colon. As control, rats in Group R underwent the ring attachment and rats in Group V underwent the vascular ligation. Rat in Group C underwent sham operation. The effects of TCV-309 on lesion formation in the colon were evaluated. Thiobarbituric acid reactant level was determined in colonic mucosa, and the incidence and severity of ischemic lesions were also determined. RESULTS: Lesions of colitis were frequently observed in Group RV. TCV-309 did not prevent lesion formation, nor did it suppress the increase in thiobarbituric acid reactant level in Group RV. However, TCV-309 mitigated the severity of the lesion. CONCLUSIONS: Partial obstruction of the colon tends to induce ischemic colitis, and additional ischemia completes lesion formation. Platelet activating factor may play a role in the progression of ischemic lesions.

Animals↗
PubMed1999

Selectively induced high MRP gene expression in multidrug-resistant human HL60 leukemia cells.

A subclone HL60/DOX was selected from a human leukemic HL60 cell line for resistance to doxorubicin (DOX) by exposure to stepwise increasing concentrations of the drug and coexposure to a potential P-glycoprotein (P-gp) inhibitor, cepharanthine (a biscoclaurine alkaloid). Compared with the parent HL60 cells, the HL60/DOX cells were 13.0-fold more resistant to DOX and showed multidrug-resistant (MDR) phenotype characterized by 4.6-fold, 2.3-fold, and 5.7-fold cross-resistance to vincristine, pirarubicin, and etoposide, respectively, but no cross-resistance to alkylating agent, cisplatin. Immunocytochemical analyses using the specific monoclonal antibody, MRPr1, and quantitative analyses using a competitive reverse transcription-polymerase chain reaction (CRT-PCR) confirmed overexpression of MRP gene products (about 8-fold determined by CRT-PCR) in this resistant clone. The P-gp expression was not detectable by the monoclonal antibody, C219, in the HL60/DOX cells, and that was consistent with extremely low levels of mdr1 mRNA expression determined by CRT-PCR in this clone. Drug accumulation and efflux studies demonstrated the significantly increased efflux rate of DOX compared to the parent HL60 cells. This enhancement of DOX efflux was reversed by the addition of 10 microM verapamil. To investigate the additional underlying mechanisms contributing to MDR phenotype in the HL60/DOX cells, the levels of DNA topoisomerases (Topo) including Topo I, Topo IIalpha, and Topo IIbeta, and gamma-glutamylcystein synthetase (y-GCS) expression were determined using CRT-PCR techniques. Normal expression of each enzyme at the transcriptional level was demonstrated in this resistant clone. Southern blot analysis of the gene organization in the HL60/DOX cells revealed the amplification of MRP gene. These results indicate that alteration of the drug accumulation from enhanced efflux appears to be a major mechanism(s) of MDR phenotype and attributable to high levels of MRP expression in the HL60/DOX cells. Overexpression of MRP in this clone is regulated by the genomic amplification of DNA and increased levels of the MRP mRNA, independently with the normal expression of Topo I, Topo IIalpha, Topo IIbeta, or gamma-GCS.

ATP-Binding Cassette Transporters↗
PubMed1999

Microsatellite analysis of childhood leukemia: correlation of 9p and 12p chromosome abnormalities with expression of related genes.

BACKGROUND: Loss of heterozygosity (LOH) and DNA replication error (RER) have been thought to be involved in carcinogenesis, but have not been investigated in childhood leukemia and lymphoma. METHODS: Eighty samples from 65 patients with childhood leukemia and lymphoma were examined using seven different microsatellite markers for RER analysis. Additionally, LOH in two chromosome regions (9p and 12p) was investigated. Furthermore, expression of the TEL, TEL/AML1 and p27(KIP1) genes on 12p and the p16 gene on 9p were detected by reverse transcriptase polymerase chain reaction. RESULTS: Replication errors were detected in 5/65 patients (7.7%). Most (4/5 patients) RER were preferentially located in the 9p and 12p regions. There were two patients who had DNA abnormalities in both 9p and 12p, one with common acute lymphoblastic leukemia (ALL) showed 9p LOH and the TEL/AML1 fusion gene on 12p and the other with common ALL and 12p RER had diminished expression of both the p27(KIP1) gene on 12p and the p16 gene on 9p. CONCLUSIONS: Combined DNA alterations on 9p and 12p, involving LOH, RER and/or gene mutation and chromosomal translocation, were found in childhood acute leukemia, especially in common ALL.

Child↗