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Biomedical subjects

Y Takada

Publications and source records attributed to Y Takada.

At least 37 records · Page 2Linked to original sources

Living related liver transplantation.

The introduction of cyclosporine was a major advance in liver transplantation, leading to increased numbers of liver transplant cases and, at the same time, a relative shortage of available donor organs. As one of the modalities to decrease the mortality rate on the waiting list, living related liver transplantation (LRLT) was initiated. In the LRLT program of Kyoto University, which started in June 1990, the number of cases has increased yearly as its application expanded from pediatric to adult patients. A landmark in LRLT was the introduction of right lobe grafts, which have become a standard procedure in adult-to-adult living donor liver transplantation. The basic immunosuppressive regimen consisted of tacrolimus and low-dose steroids from the beginning of our LRLT program. However, since documentation of significant improvements in clinical efficacy with Neoral compared to Sandimmun-based immunosuppression, the role of cyclosporine in LRLT is now being reevaluated.

Adult↗

[Squamous cell carcinoma caused by dysplasia on the bullous wall].

We experienced a squamous cell lung carcinoma caused by dysplasia around the bullous wall after right upper lobectomy by tuberculosis. A case is 70 years old male who was resected right upper lobe caused by tuberculosis 50 years ago. He was pointed out an abnormal shadow on the chest X-ray in March 2002. There were bullous change in right lung field on the chest computed tomography (CT). There was appeared a tumor contiguous to the bullous wall. A part of bullous wall surrounding the tumor was thickened bronchio-alveolar lavage gave proof of squamous cell carcinoma. Right basal segmentectomy and subcarinal lymph node dissection was done, because of severe adhesion a right middle lobe. Radiation therapy at the mediastinum is performed, because of positive subcarinal lymph nodes. It is rare case of squamous cell carcinoma caused by dysplasia, we reported.

Aged↗

The S haplotypes lacking SLG in the genome of Brassica rapa.

Self-incompatibility (SI) discriminating self- and non-self pollen is regulated by S-locus genes in Brassica. In most of the S haplotypes, a highly polymorphic S-locus glycoprotein ( SLG) gene is tightly linked to genes for the SI determinants, S-receptor kinase ( SRK) and SP11, although the precise function of SLG in SI has not been clarified. In the present study, we performed DNA gel blot analysis for S(32), S(33), and S(36) haplotypes of Brassica rapa showing normal SI phenotypes and concluded that there might be no SLG in their genome. RNA gel blot analysis of the SLG-less S haplotypes indicated the possible existence of eSRK transcripts in the stigma. These three S haplotypes are useful resources to discern the molecular mechanism of the SI reaction without SLG.

Brassica↗

Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer.

To determine a standard combination chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC), we conducted a phase III trial of irinotecan (CPT-11) to test the hypotheses that CPT-11+cisplatin is superior to cisplatin+vindesine and that CPT-11 monotherapy is not inferior to cisplatin+vindesine. A total of 398 patients with previously untreated NSCLC were randomised to receive cisplatin+CPT-11 (CPT-P), cisplatin+vindesine (VDS-P) or CPT-11 alone (CPT). In the CPT-P arm, CPT-11 60 mg m(-2) was administered on days 1, 8 and 15, and cisplatin 80 mg m(-2) was administered on day 1. In the VDS-P arm, cisplatin 80 mg m(-2) was administered on day 1, and vindesine 3 mg m(-2) was administered on days 1, 8 and 15. In the CPT arm, CPT-11 100 mg m(-2) was administered on days 1, 8 and 15. The median survival time was 50.0 weeks for patients on CPT-P, 45.6 weeks for those on VDS-P and 46.0 weeks for those on CPT (P=0.115, CPT-P vs VDS-P; P=0.089, CPT vs VDS-P), and the hazard ratio was 0.85 (95% confidence interval (CI): 0.65-1.11) for CPT-P vs VDS-P and 0.83 (0.64-1.09) for CPT vs VDS-P. The response rate was 43.7% for patients on CPT-P, 31.7% for those on VDS-P and 20.5% for those on CPT. Major adverse reactions were grade 4 neutropenia observed in 37, 54 and 8% of the patients on CPT-P, VDS-P and CPT, respectively; and grades 3 and 4 diarrhoea observed in 12, 3 and 15% of the patients, respectively. CPT-P therapy produces comparable survival to VDS-P in patients with advanced NSCLC. CPT-11 monotherapy is not inferior to VDS-P in terms of survival. The CPT-11-containing regimen is one of the most efficacious and well tolerated in the treatment of advanced NSCLC.

Adolescent↗

Expression level of integrin alpha 5 on tumour cells affects the rate of metastasis to the kidney.

Tumour metastasis is known clinically to have organ specificity. We hypothesised that integrins might be involved in determining the organ specificity of tumour metastasis. Here, we report the results of spontaneous metastasis tested in nude mice that were inoculated with Chinese hamster ovary (CHO) cells expressing integrin alpha 5 beta 1 at various levels. The growth of the primary tumour inversely correlated with the alpha 5 expression level on CHO cells, which is consistent with a previous report (Schreiner et al, 1991). The rates of pulmonary, lymph node, and adrenal metastases that developed in nude mice were not related to changes of the alpha 5 expression level on CHO cells. Kidney metastasis developed in 40% of nude mice inoculated with alpha 5B2 cells (CHO cells overexpressing alpha 5) and in 20% of mice with CHO-K1 cells (CHO cells expressing native alpha 5), whereas inoculation with CHO-B2 cells (alpha 5-defective mutants) and alpha 5CHO cells with the highest expression of alpha 5 did not lead to development of kidney metastasis. Furthermore, alpha 5CHO, which shows the slowest growth of these cell types, did not lead to primary tumours in nude mice. These findings suggest that there is an appropriate level of alpha 5 expression on tumour cells that leads to metastasis. Microscopic observations revealed that micrometastasis in the kidney was formed in glomeruli. An adhesion assay using frozen sections of the kidney demonstrated that alpha 5B2 cells, but not CHO-B2 cells, effectively adhered to glomeruli. Kidney metastasis in vivo and the adhesion of alpha 5B2 to glomeruli shown ex vivo were significantly suppressed by the administration of GRGDS peptide. Finally, we conclude that the interaction of alpha 5 beta 1 on tumour cells with fibronectin in kidney glomeruli is involved in kidney metastasis and that the tumour has appropriate levels of integrins crucial for metastasis.

Adrenal Gland Neoplasms↗

Neonatal craniopharyngioma and inference of tumor inception time: case report and review of the literature.

BACKGROUND: Craniopharyngioma is a rare neonatal tumor, although it is the most common tumor of the parasellar region in childhood. Only a few cases have been antenatally diagnosed. We report a case of neonatal craniopharyngioma surgically treated after birth and its inferred tumor inception time. CASE DESCRIPTION: A routine ultrasound at 33 weeks of gestation revealed a high echoic mass at the center of the head in this fetus. The baby was delivered normally at 40 weeks with no abnormal appearance of its body surface. Hypotonicity of her lower limbs was observed. The tumor was totally removed uneventfully by an interhemispheric trans-lamina-terminalis approach at 8 months after birth. CONCLUSION: A kinetic study of the tumor showed that tumor inception time was on the 45.6th day of gestation. The present case is the fourth successful resection of neonatal craniopharyngioma. The literature is reviewed.

Craniopharyngioma↗

Casting behavior of titanium alloys in a centrifugal casting machine.

Since dental casting requires replication of complex shapes with great accuracy, this study examined how well some commercial titanium alloys and experimental titanium-copper alloys filled a mold cavity. The metals examined were three types of commercial dental titanium [commercially pure titanium (hereinafter noted as CP-Ti), Ti-6Al-4V (T64) and Ti-6Al-7Nb (T67)], and experimental titanium-copper alloys [3%, 5% and 10% Cu (mass %)]. The volume percentage filling the cavity was evaluated in castings prepared in a very thin perforated sheet pattern and cast in a centrifugal casting machine. The flow behavior of the molten metal was also examined using a so-called "tracer element technique." The amounts of CP-Ti and all the Ti-Cu alloys filling the cavity were similar; less T64 and T67 filled the cavity. However, the Ti-Cu alloys failed to reach the end of the cavities due to a lower fluidity compared to the other metals. A mold prepared with specially designed perforated sheets was effective at differentiating the flow behavior of the metals tested. The present technique also revealed that the more viscous Ti-Cu alloys with a wide freezing range failed to sequentially flow to the end of the cavity.

Alloys↗

Mold filling of titanium alloys in two different wedge-shaped molds.

Pure titanium and titanium alloys are potential materials for the fabrication of cast dental appliances. One important factor in producing sound castings is the capacity of the metal to fill the mold. This study used a wedge-shaped mold to compare the mold filling of titanium with that of conventional dental casting alloys. The metals used were CP Ti, Ti-6Al-7Nb, Ti-6Al-4V, Ti with 1 and 4wt% Cu and ADA Type III gold alloy and an Ni-Cr alloy. The castings were cut into four pieces parallel to the triangular surface. Mold filling was evaluated as the distance between the tip of the cast wedge and theoretical tip of the triangle. The mold filling of the gold alloy was superior compared to all the metals tested, while the mold filling of the Ni-Cr alloy was the worst. There were no statistical differences at the 30 degrees marginal angle for all the cast titanium metals. At the sharper 15 degrees angle, CP Ti and Ti-6Al-7Nb was superior to both the Ti-Cu alloys. Although the mold filling of titanium was inferior compared to the gold alloy, the data justify the use of titanium for the production of dental appliances.

Dental Alloys↗

Rapid, specific and active site-catalyzed effect of tissue-plasminogen activator on hippocampus-dependent learning in mice.

In the present study we trained tissue-plasminogen activator (tPA)-knockout (tPA -/-) and wild-type (tPA +/+) male mice in step-down inhibitory avoidance learning, a hippocampus-dependent task. tPA -/- displayed significantly shorter latencies to step down at 90 min, one, two and seven days after training indicating the learning deficit in these animals (P < 0.05 vs tPA +/+). The locomotor activity, the level of anxiety in an elevated-plus maze, as well as the pain threshold did not differ between the two strains of mice. The learning disability of tPA -/- was overcome by more intense training. The learning deficit was also partially restored by limited intrahippocampal delivery of tPA (infused for 2 h before training; P < 0.05 vs control), but not by the delivery of urokinase plasminogen activator, indicating the acute need for tPA in learning. The beneficial effect of tPA was abolished by co-infusion of its inhibitor tPA-STOP, indicating that the facilitatory effect of tPA on learning requires a proteolytic step. However, tPA activity in the hippocampus was not indispensable for effective memory retrieval in tPA-infused tPA -/- mice. Thus, rapid, specific and proteolytic action of tPA facilitates hippocampus-dependent learning, but not retrieval of previously acquired information.

Animals↗

Ventricular activation and recovery measured in electrocardiographic limb leads correlate with measurements from specific areas in body surface mapping.

AIMS: Dispersion of ventricular depolarization-repolarization in 12-lead electrocardiograms (ECGs) has been reported to provide noninvasive information on arrhythmogenicity. However, there are two methods to calculate the dispersion from ECGs including and excluding limb leads. The aim of this study was to examine whether temporal parameters from limb leads represent activation and repolarization of a particular part of the body surface. METHODS AND RESULTS: We compared the temporal parameters of activation time (AT), activation-recovery interval (ARI), and recovery time (RT) from limb leads of ECGs with those from an 87-lead body surface maps. The study population consisted of 50 normal subjects (25 men and 25 women, 19.4 +/- 1.6 years). The temporal parameters in leads I, II, and III were highly (r > 0.9) correlated with those in unipolar leads over the left lateral, left lower, and right lower chest, respectively. The temporal parameters in leads aVR, aVL, and aVF showed a significant correlation (r > 0.8) with those in unipolar leads over the right upper, left upper, and lower anterior chest, respectively. The mean AT, ARI, and RT from each limb lead of ECG were almost the same as those of unipolar leads over the corresponding areas of the body surface. CONCLUSIONS: These findings suggest that ATs, ARIs, and RTs from limb leads may represent those from unipolar leads of particular areas over the body surface in normal subjects. The temporal parameters from limb leads of ECGs may provide information on activation and repolarization as well as the precordial leads of ECGs.

Adolescent↗

Characterization of expressed genes in the SLL2 region of self-compatible Arabidopsis thaliana.

Self-incompatibility in Brassica species is regulated by a set of S-locus genes: SLG, SRK, and SP11/SCR. In the vicinity of the S-locus genes, several expressed genes, SLL2 and SP2/ClpP, etc., were identified in B. campestris. Arabidopsis thaliana is a self-compatible Brassica relative, and its complete genome has been sequenced. From comparison of the genomic sequences between B. campestris and A. thaliana, microsynteny between gene clusters of Arabidopsis and Brassica SLL2 regions was observed, though the S-locus genes, SLG, SRK, and SP11/SCR were not found in the region of Arabidopsis. Almost all genes predicted in this region of Arabidopsis were expressed in both vegetative and reproductive organs, suggesting that the genes in the SLL2 region might not be related to self-incompatibility. Considering the recent speculation that the S-locus genes were translocated as a single unit between Arabidopsis and Brassica, the translocation might have occurred in the region between the SLL2 and SP7 genes.

Arabidopsis↗

Crystallization and preliminary X-ray diffraction studies of monomeric isocitrate dehydrogenase by the MAD method using Mn atoms.

NADP(+)-dependent isocitrate dehydrogenase (E.C. 1.1.1.42; IDH) is an enzyme of the Krebs cycle and catalyzes the oxidative decarboxylation reaction from DL-isocitrate to alpha-ketoglutarate, with a concomitant reduction of the coenzyme NADP(+) to NADPH. Single crystals of monomeric IDH from Azotobacter vinelandii in complex with DL-isocitrate and Mn(2+) were obtained by the hanging-drop vapour-diffusion method at room temperature. One crystal diffracted to a resolution of 2.9 A and was found to belong to the orthorhombic system; the space group was determined to be P2(1)2(1)2(1), with unit-cell parameters a = 108.4, b = 121.7, c = 129.7 A. The asymmetric unit contains two molecules of monomeric IDH, corresponding to a V(M) value of 2.66 A(3) Da(-1). The crystals were frozen in a capillary by a flash-cooling technique and MAD data were collected using Mn atoms as anomalous scatterers on beamline BL41XU at SPring-8, Japan. The positions of two Mn atoms binding to two independent IDH molecules were located from Bijvoet difference Patterson maps.

Azotobacter vinelandii↗

Dosimetric predictors of radiation esophagitis in patients treated for non-small-cell lung cancer with carboplatin/paclitaxel/radiotherapy.

PURPOSE: To establish dosimetric predictors of radiation esophagitis (RE) in patients treated with a combination of carboplatin, paclitaxel, and radiotherapy. METHODS AND MATERIALS: Three-dimensional radiotherapy plans of 26 patients with non-small-cell lung cancer who received 50-60 Gy of radiotherapy concurrently with weekly administration of carboplatin (AUC 2) and paclitaxel (40-45 mg/m(2)) were reviewed in conjunction with RE. The factors analyzed included the following: percentages of organ volumes receiving >40 Gy (V40), >45 Gy (V45), >50 Gy (V50), and >55 Gy (V55); the length of esophagus (total circumference) treated with >40 Gy (LETT40), >45 Gy (LETT45), >50 Gy (LETT50), and >55 Gy (LETT55); the maximum dose in the esophagus (Dmax); and the mean dose in the esophagus (Dmean). Data were obtained on the basis of superposition algorithm. RESULTS: All factors except Dmax showed statistical correlation with RE. Good correlations were shown between RE and LETT45 (rho = 0.714) and V45 (rho = 0.686). CONCLUSIONS: LETT45 and V45 appear to be useful dosimetric predictors of RE. It is also suggested that Dmax does not predict RE.

Adult↗

Amino acid residues in the alpha IIb subunit that are critical for ligand binding to integrin alpha IIbbeta 3 are clustered in the beta-propeller model.

Several distinct regions of the integrin alpha(IIb) subunit have been implicated in ligand binding. To localize the ligand binding sites in alpha(IIb), we swapped all 27 predicted loops with the corresponding sequences of alpha(4) or alpha(5). 19 of the 27 swapping mutations had no effect on binding to both fibrinogen and ligand-mimetic antibodies (e.g. LJ-CP3), suggesting that these regions do not contain major ligand binding sites. In contrast, swapping the remaining 8 predicted loops completely blocked ligand binding. Ala scanning mutagenesis of these critical predicted loops identified more than 30 discontinuous residues in repeats 2-4 and at the boundary between repeats 4 and 5 as critical for ligand binding. Interestingly, these residues are clustered in the predicted beta-propeller model, consistent with this model. Most of the critical residues are located at the edge of the upper face of the propeller, and several critical residues are located on the side of the propeller domain. None of the predicted loops in repeats 1, 6, and 7, and none of the four putative Ca(2+)-binding predicted loops on the lower surface of the beta-propeller were important for ligand binding. The results map an important ligand binding interface at the edge of the top and on the side of the beta-propeller toroid, centering on repeat 3.

Amino Acid Sequence↗

Specific interaction of angiostatin with integrin alpha(v)beta(3) in endothelial cells.

Angiostatin, the N-terminal four kringles (K1-4) of plasminogen, blocks tumor-mediated angiogenesis and has great therapeutic potential. However, angiostatin's mechanism of anti-angiogenic action is unclear. We found that bovine arterial endothelial (BAE) cells adhere to angiostatin in an integrin-dependent manner and that integrins alpha(v)beta(3), alpha(9)beta(1), and to a lesser extent alpha(4)beta(1), specifically bind to angiostatin. alpha(v)beta(3) is a predominant receptor for angiostatin on BAE cells, since a function-blocking antibody to alpha(v)beta(3) effectively blocks adhesion of BAE cells to angiostatin, but an antibody to alpha(9)beta(1) does not. epsilon-Aminocaproic acid, a Lys analogue, effectively blocks angiostatin binding to BAE cells, indicating that an unoccupied Lys-binding site of the kringles may be required for integrin binding. It is known that other plasminogen fragments containing three or five kringles (K1-3 or K1-5) have an anti-angiogenic effect, but plasminogen itself does not. We found that K1-3 and K1-5 bind to alpha(v)beta(3), but plasminogen does not. These results suggest that the anti-angiogenic action of angiostatin may be mediated via interaction with alpha(v)beta(3). Angiostatin binding to alpha(v)beta(3) does not strongly induce stress-fiber formation, suggesting that angiostatin may prevent angiogenesis by perturbing the alpha(v)beta(3)-mediated signal transduction that may be necessary for angiogenesis.

Angiogenesis Inhibitors↗

Effect of bile acids on biliary excretion of cyclosporin A in the rat.

Cyclosporin A, a substrate of P-glycoprotein (P-gp), is known to cause cholestasis in humans and in rat experimental models. Tauroursodeoxycholate is reported to be effective in CyA-induced cholestasis in rats. In the present study, to investigate the mechanism of the inhibition of CyA induced cholestasis, effect of bile acids on biliary cyclosporin A excretion was studied in rats. Infusion of both taurocholate and tauroursodeoxycholate at the rate of 0.8 mmol/min per 100 g bodyweight increased bile flow and biliary cyclosporin A excretion, and the extent was more prominent with tauroursodeoxycholate. It was suggested that these findings were caused by the enhanced vesicular targeting of P-gp to the canalicular membrane by bile acids, thus increasing the numbers of P-gp in the canalicular membrane.

Journal Article↗