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Biomedical subjects

H Takeda

Publications and source records attributed to H Takeda.

At least 109 records · Page 6Linked to original sources
PubMed2001

Circulating transforming growth factor beta 1 as a predictor of liver metastasis after resection in colorectal cancer.

Plasma transforming growth factor beta1 (TGF-beta1) has been reported to be correlated with the extent of disease in colorectal cancer, but it is not known whether measuring this cytokine can help predict liver metastasis after curative resection. We prospectively studied whether plasma TGF-beta1 levels could predict liver metastasis in 117 patients with colorectal cancer before and after curative resection. Blood samples were drawn before and 2 weeks after surgery to determine the cytokine levels. Abdominal ultrasonography or computed tomography was done every 3 months after surgery. The primary end point for follow-up was recurrence. Seventy-seven of 117 cases (66%) had preoperative levels of the cytokine higher than the borderline limit of 7.5 ng/ml. Postoperative levels were >7.5 ng/ml in 29 of 117 patients (25%). The median follow-up period was 42 months (range, 5--66 months), with follow-up of all 117 patients. No recurrence was observed in 13 patients with Dukes' stage A lesions. Liver metastasis occurred in 18 of 104 patients (17%) with Dukes' stage B or C disease. Fourteen of 18 patients (78%) who developed liver metastasis had shown a postoperative plasma TGF-beta1 level of >7.5 ng/ml. Cox proportional hazards regression analysis showed that the postoperative level was a significant predictive factor for liver metastasis (P < 0.001). A single point measurement of plasma TGF-beta1 levels at 2 weeks after curative resection seems to be able to predict liver metastasis in colorectal cancer. This finding suggests the value of a prospective trial of liver-targeted adjuvant therapy for patients with elevated postoperative plasma TGF-beta1 levels.

Aged↗
PubMed2001

[Analysis of chimerism in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation].

Serial monitoring of chimerism after allogeneic hematopoietic stem cell transplantation (HSCT) can be performed easily and rapidly using PCR-based assays analyzing informative tandem repeat genetic markers. Sequential analysis of individual chimerism status was performed in 34 patients who underwent myeloablative allo-HSCT using a commercial multiplex short tandem repeat (STR) kit. Mixed chimerism (MC) was found in 14 of the patients for more than one month. The incidence of MC seemed to be dependent on the type of disease or pretransplantation regimen. There was no significant difference in relapse rates between MC and complete donor chimerism (CC) in all patients. However, the relapse rate was significantly higher in MC than in CC among patients with acute leukemia. The severity of acute graft-versus-host disease (aGVHD) was significantly reduced in the patients with MC. Most of the MC patients with hematologic malignancies had transient mixed T-lymphoid chimerism, and CC was achieved within 6 months after HSCT in such cases. Patients with MC beyond 6 months after HSCT and patients with reappearance of autologous signals (MC after CC) may have an enhanced risk of relapse.

Adolescent↗
PubMed2001

Dynamic viewer of medical events in electronic medical record.

Medical record should enable doctors to comprehend the patient's history and select suitable medical treatment. In paper based medical records, medical events (examination, treatment etc.) are recorded successively, and problem oriented recording is difficult to be applied to patients with much information and a long history. Consequently it is not easy to understand the patient's history from paper based medical records. In order to solve this problem, we developed the flow sheet system in our electronic medical record (EMR). To make a flow sheet, we analyzed the structure of the medical event data. In this paper we introduced the medical event information model for our EMR. Furthermore, we clarified the specification of the data presentation on the flow sheet. We developed the flow sheet on the basis of these analyses. Because there are 3 layers in the vertical axis of the flow sheet, many items of the medical event can be displayed on the screen. When user clicks the cell, the corresponding detail data including images are shown. This system functions to link medical event items with a problem, and shows the bundled items on the flow sheet when the user selects the problem. We implemented this system in Osaka University Hospital. The number of the types of medical events and those of detail events in inpatients are 5.0+1.7 (mean+SD) and 60+47, respectively. The medical doctors in Osaka University Hospital evaluated this system, and concludes that the flow sheet data presentation makes comprehension of the patient's history easier than paper based records. As to the function of bundling the items relevant to the problem, they feel it is especially useful for patients with chronic disease. Thus the flow sheet data presentation in EMR is useful for medical practice.

Chronic Disease↗
PubMed2001

PACS linked to EPR.

We developed a new PACS linked to Electronic Patient Record system (EPR). It was a hospital-wide PACS storing all the radiological examinations. The images and reports were linked on EPR. The concept of navigation servers and segment servers was introduced for prefetchig and quick displaying. After the start of operation, increasing retrieval indicated its effectiveness on practical work in spite of remaining delivery of radiographs.

Computer Communication Networks↗
PubMed2001

[Comparison between real-time pollen monitor KH-3000 and Burkard sampler].

Special apparatus capable of instantly measuring airborne Cryptomeria japonica pollen grains were recently appeared on the market. We examined one of them called real-time pollen monitor KH-3000 (Yamato Manufacturing Co. Ltd.). To confirm the accuracy of the monitor, comparison was made with conventional Burkard Seven-Day Recording Volumetric Spore Trap operating simultaneously at the same place. Most peaks from KH-3000 were coincided with Cry j 1 from Burkard sampler, and the greater part of the counts from KH-3000 had a strong resemblance to the counts from Cry j 1. Therefore, it is confirmed that KH-3000 counts the numbers of airborne C. japonica pollen grains. KH-3000 sometimes counts particles which do not belong to pollen grains, however. It is also confirmed that some pollens other than C. japonica, such as walnut (Juglans spp.) pollen, a part of grass pollen were counted.

Air Pollutants↗
PubMed2000

Pretreatment with diazepam suppresses the reduction in defensive freezing behavior induced by fluvoxamine in the conditioned fear stress paradigm in mice.

The effects of the selective serotonin (5-hydroxytryptamine (5-HT)) reuptake inhibitor fluvoxamine, given alone or in combination with the benzodiazepine anxiolytic diazepam on the defensive freezing behavior of mice in the conditioned fear stress paradigm were examined. Fluvoxamine (5-20 mg/kg, i.p.) induced a dose-dependent reduction in freezing behavior. In contrast, while low doses of diazepam (0.125 and 0.25 mg/kg, i.p.) reduced the freezing behavior, such effects were not observed with high doses of diazepam (0.5 and 1 mg/kg, i.p.). In the combination study, fluvoxamine (20 mg/kg, i.p. ) did not reduce the freezing behavior in mice that had been pretreated with diazepam (0.125-1 mg/kg, i.p.). None of the doses of fluvoxamine and diazepam used in the present study had any effects on motor activity under non-stressed conditions. These results suggest that benzodiazepines may negatively influence the clinical efficacy of selective 5-HT reuptake inhibitors in the treatment of anxiety disorders.

Animals↗
PubMed2000

Calcineurin inhibitor attenuates left ventricular hypertrophy, leading to prevention of heart failure in hypertensive rats.

BACKGROUND: There is controversy regarding the contribution of calcineurin activation to the development of pressure-overload left ventricular (LV) hypertrophy and heart failure. The aim of this study was to explore whether the inhibition of calcineurin may prevent the transition to heart failure in hypertensive rats and, if so, to clarify in which developmental stage of LV hypertrophy calcineurin plays a key role. METHODS AND RESULTS: Dahl salt-sensitive rats placed on an 8% NaCl diet from the age of 7 weeks (hypertensive rats) were randomized to no treatment (n=6) or treatment with the calcineurin inhibitor FK506 (1 mg x kg(-1) x d(-1)) from 8 weeks (FKE, n=7) or from 17 weeks (FKL, n=7). Rats placed on a 0.3% NaCl diet were defined as control rats (n=6). The administration of FK506 from 8 weeks attenuated, although it did not block, LV hypertrophy observed in the untreated rats and prevented the transition to heart failure. The development of LV fibrosis, however, was not attenuated by the administration of FK506 from 8 weeks. The administration of FK506 from 17 weeks brought no benefit for cardiac remodeling or LV function and failed to prevent heart failure. CONCLUSIONS: Calcineurin inhibition, if started from the initial stage of pressure overload, attenuated the development of LV hypertrophy without any effect on LV fibrosis and prevented the transition to heart failure. The activation of calcineurin is involved in the development of LV hypertrophy but not of LV fibrosis, and this involvement may be crucial at the initial stage.

Animals↗
PubMed2000

Characterization of beta-adrenoceptor subtypes in the ferret urinary bladder in vitro and in vivo.

In the present study, the beta-adrenoceptor subtypes distributed in the detrusor of the ferret were investigated in functional experiments in vitro and in vivo using a variety of beta-adrenoceptor agonists and antagonists. All the beta-adrenoceptor agonists tested relaxed the isolated detrusor strip, the rank order of potency being (+/-)-(R*, R*)-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]phenoxy]- acetic acid sodium (BRL 37344A)>(+/-)-4-(3-t-butylamino-2-hydroxypropoxy) benzimidazol-2-one (CGP-12177A), isoprenaline and (R, R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethylamino]propyl]-1, 3-benzodioxole-2,2-dicarboxylate (CL 316,243)>dobutamine and procaterol. In antagonist experiment, 3-(2-allylphenoxy)-1-[(1S)-1,2, 3,4-tetrahydro-naphth-1-ylamino]-(2S)-2-propanol hydrochloride (SR 58894A), but neither 2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4-trifluoromethyl)1H-imidaz ole-2-yl)-phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulphonate (CGP-20712A) nor erythro-(+/-)-1-(7-methylindan-4-yloxy)-3-isopropylaminob utan-2-ol hydrochloride (ICI-118,551), caused a rightward shift of the concentration-relaxation curve for isoprenaline. In in vivo experiments, isoprenaline and CL 316,243 each reduced bladder pressure in a dose-dependent manner. CL 316,243 was the only drug that did not produce any significant influences on blood pressure and heart rate at doses that reduced bladder pressure. The present functional study provides the first evidence that relaxation of the ferret detrusor by beta-adrenoceptor activation is mediated mainly via the beta(3)-adrenoceptor, as in the human detrusor.

Adrenergic beta-Agonists↗
PubMed2000

The novel kappa-opioid receptor agonist TRK-820 has no affect on the development of antinociceptive tolerance to morphine in mice.

The effects of the novel kappa-opioid receptor agonist 17-cyclopropylmethyl-3,14beta-dihydroxy-4, 5alpha-epoxy-6beta-[N-methyl-trans-3-(3-furyl)acrylamido+ ++]morphinan hydrochloride (TRK-820) on the development of antinociceptive tolerance to morphine were investigated in mice and compared with those of trans-3,4-dichloro-N-(2-(1-pyrrolidinyl)-cyclohexyl) benzenacetamide methane sulfonate hydrochloride (U-50,488H), a well-defined exogenous kappa-opioid receptor agonist. Morphine (1. 25-20 mg/kg, s.c.) produced a dose-related antinociceptive effect in the 51 degrees C warm-plate test. Daily treatment with morphine (10 mg/kg, s.c.) resulted in the development of antinociceptive tolerance. The development of antinociceptive tolerance to morphine was dose-dependently suppressed by the co-administration of U-50, 488H (1-10 mg/kg, s.c.) with morphine, but not TRK-820 (0.003-0.03 mg/kg, s.c.). These results suggest that TRK-820-sensitive kappa-opioid receptor subtypes may not be involved in modulating the development of antinociceptive tolerance to morphine.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2000

Requirement for protein-tyrosine phosphatase SHP-2 in insulin-induced activation of c-Jun NH(2)-terminal kinase.

Mitogen-activated protein kinases, including extracellular signal-regulated kinases and c-Jun NH(2)-terminal kinases (JNKs), are activated by insulin. Although the mechanism by which the insulin receptor activates extracellular signal-regulated kinases is relatively well defined, the pathway that leads to JNK activation is poorly understood. Overexpression of a catalytically inactive mutant (SHP-2C/S) of the protein-tyrosine phosphatase SHP-2 in Rat-1 fibroblasts that also express human insulin receptors has now revealed that activation of JNKs by insulin and epidermal growth factor, but not that by anisomycin or sorbitol, requires SHP-2. A dominant negative mutant (RasN17) of Ha-Ras blocked insulin-induced JNK activation, whereas a dominant negative mutant (RacN17) of Rac1 or a specific inhibitor (LY294002) of phosphoinositide 3-kinase did not, indicating a role for Ras, but not for Rac or phosphoinositide 3-kinase, in this effect. SHP-2C/S markedly inhibited Ras activation in response to insulin without affecting insulin-induced tyrosine phosphorylation of cellular substrates or the dissociation of the Crk-p130(Cas) complex. In contrast, SHP-2C/S did not inhibit activation of JNKs induced by a constitutively active mutant (RasV12) of Ha-Ras. Furthermore, expression of myristoylated SOS, which functions as a potent activator of Ras, induced JNK activation even when SHP-2 was inactivated. These results suggest that SHP-2 contributes to JNK activation in response to insulin by positively regulating the Ras signaling pathway at the same level as, or upstream from, SOS.

Animals↗
PubMed2000

cDNA and deduced amino acid sequences of apolipophorin-IIIs from Bombyx mori and Bombyx mandarina.

The cDNA sequence for apolipophorin-III from two strains of Bombyx mori (N4 and P50) and the Japanese and Chinese strains of Bombyx mandarina were determined. Both the cDNA and deduced amino acid sequences of the four apolipophorin-IIIs were highly similar (95-98%). The four Bombyx sequences also showed significant similarity to the sequence of apolipophorin-III from another lepidopteran, Manduca sexta (83-84%), particularly in the five amphipathic alpha-helices that are proposed to play a critical role in the binding of apolipophorin-III to lipophorin. In the coding region, the nucleotide sequences for the Chinese strain of B. mandarina and the P50 strain of B. mori were identical, supporting the suggestion that P50 is the current strain most closely related to the original domesticated strain. The N4 strain of B. mori is more closely related to these two strains than is the Japanese strain of B. mandarina, suggesting that Japanese strain of B. mandarina separated from the Chinese strain of B. mandarina before domestication of B. mori. Arch.

Amino Acid Sequence↗
PubMed2000

Effects of San'o-shashin-to on the antioxidative mechanism in spontaneous familial hypercholesterolaemic rabbits.

We investigated the effects of the Kampo medicine San'o-shashin-to which showed strong antioxidative effects in vitro on antioxidative mechanism in Kurosawa and Kusanagi- hypercholesterolaemic (KHC) rabbits, which are a good model of spontaneous familial hypercholesterolaemia. A 1-g kg(-1)dose of San'o-shashin-to was administered orally for 24 weeks and changes in plasma lipids, low-density lipoprotein (LDL) oxidation and redox dynamics of alpha-tocopherol in plasma and erythrocyte membrane were measured in a control group and San'o-shashin-to-treated group. A significant prolongation of the lag time was found in the 12th and 24th week of the experiment in San'o-shashin-to-treated group, indicating antioxidative effects on LDL. At the end of the administration period, the alpha-tocopherolquinone/alpha-tocopherol ratio in erythrocyte membrane, which reflects the utilization rate of alpha-tocopherol was significantly higher in San'o-shashin-to-treated group. There were no significant differences in the two groups with regards to plasma lipids. These results indicate that San'o-shashin-to had antioxidative effects on LDL in vivo and beneficial effects on redox dynamics of alpha-tocopherol, which is the strongest endogenous antioxidant.

Animals↗
PubMed2000

Different effects of 5-HT1A receptor agonists and benzodiazepine anxiolytics on the emotional state of naive and stressed mice: a study using the hole-board test.

OBJECTIVES: The effects of 5-HT(1A) receptor agonists on the emotional behavior of naive or stressed mice were examined and compared with those of benzodiazepine anxiolytics. METHODS: Changes in the emotional state of mice were evaluated in terms of changes in exploratory activity, i.e. total locomotor activity, numbers and duration of rearing and head-dipping and latency to the first head-dipping, using an automatic holeboard apparatus. RESULTS: The 5-HT(1A) receptor full agonists flesinoxan (0.03-1 mg/kg, IP) and 8-OH-DPAT (0.03-1 mg/kg, IP), and the partial agonist buspirone (0.3-10 mg/kg, IP) dose-dependently decreased all of the exploratory behaviors. Significant decreases in both the number and duration of head-dips, and an increase in the latency to head-dipping were observed at 30 min after exposure to acute restraint stress (60 min). These emotional changes were scarcely improved by post-stress treatment with 5-HT(1A) receptor agonists, at doses that alone did not produce a significant behavioral effect. In contrast, pretreatment with flesinoxan (0.1-1 mg/kg, IP) or 8-OH-DPAT (0.1-1 mg/kg, IP) 24 h prior to exposure to stress dose-dependently suppressed the decrease in various exploratory behaviors that was observed immediately after the exposure to acute restraint stress. Moreover, pretreatment with buspirone (1-10 mg/kg, IP) 24 h prior to exposure to stress also significantly suppressed the decrease in rearing behavior and the increase in head-dip latency. However, changes in the emotional response to stress stimuli were not observed in mice that had been pretreated with the benzodiazepine anxiolytics diazepam (0.1-1 mg/kg, IP) and chlordiazepoxide (2-8 mg/kg, IP). CONCLUSIONS: The present study clearly demonstrates that the behavioral effects of 5-HT(1A) receptor agonists in both naive and stressed mice were quite different from those of benzodiazepine anxiolytics, as previously reported by us. Notably, 5-HT(1A) receptor agonists but not benzodiazepine anxiolytics protect against various emotional changes produced by stress stimuli, and the results suggest that activation of 5-HT(1A) receptors may facilitate some mechanism(s) involved in the recognition of and/or ability to cope with stressful situation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Identification of 187 single nucleotide polymorphisms (SNPs) among 41 candidate genes for ischemic heart disease in the Japanese population.

To investigate whether common variants in the human genetic background are associated with pathogenesis of ischemic heart diseases, we systematically surveyed 41 possible candidate genes for single-nucleotide polymorphisms (SNPs) by directly sequencing 96 independent alleles at each locus, derived from 48 unrelated Japanese patients with myocardial infarction, including 25.8 kb 5' flanking regions, 56.8 kb exonic and 35.4 kb intronic sequences, and 1.8 kb 3' flanking regions. In this genomic DNA of nearly 120 kb, we identified 187 SNPs: 55 in 5' flanking regions, seven in 5' untranslated regions (UTRs), 52 in coding elements, 64 in introns, eight in 3' UTRs, and one in a 3' flanking region. Among the 52 coding SNPs, 26 were non-synonymous changes. Allelic frequencies of some of the polymorphisms were significantly different from those reported in European populations. For example, the Q506R substitution in the coagulation factor V gene, the so-called "Leiden mutation", has a reported frequency of 2.3% in Europeans, but we detected the Leiden mutation in none of the Japanese genomes that we investigated. The allelic frequencies of the -33A>G SNP in the thrombomodulin gene were also very different; this allele occurred at a 12% frequency in the Japanese patients that we examined, although it had been detected in none of 82 Caucasians reported previously. These data support the hypothesis that some SNPs are specific to particular ethnic groups.

3' Untranslated Regions↗