Search PubMed⌕ Search

Biomedical subjects

H Takeda

Publications and source records attributed to H Takeda.

At least 181 records · Page 10Linked to original sources

Pharmacological characterization of dopamine transport in cultured rat astrocytes.

The effects of GBR-12909 (selective DA uptake inhibitor), zimelidine (selective 5-HT uptake inhibitor) and nisoxetine (selective NE uptake inhibitor) on the uptake of 30 nM [3H]DA into cultured rat astrocytes were examined. [3H]DA uptake was inhibited by approximately 50% by GBR-12909 or zimelidine in a concentration-dependent manner (100 nM to approximately 10 microM). Furthermore, the inhibition curves of GBR-12909 were biphasic, and uptake was completely inhibited by a high concentration of GBR-12909 (100 microM). [3H]DA uptake was also inhibited by approximately 50% by nisoxetine in a concentration-dependent manner (0.1 to approximately 100 nM), and nisoxetine was more potent than GBR-12909 or zimelidine. The inhibitory potencies were in the order nisoxetine > GBR-12909 > zimelidine. The uptake of [3H]DA under Na+-free conditions was approximately 50% of that under normal conditions. Thus, DA was taken up by both Na+-dependent and Na+-independent mechanisms. Nisoxetine (100 nM), zimelidine (100 microM) and GBR-12909 (10 microM) inhibited [3H]DA uptake into astrocytes only in the presence of Na+. On the other hand, this uptake was completely inhibited by a high concentration of GBR-12909 (100 microM) in the absence of Na+. The present data suggest that the Na+-dependent uptake of [3H]DA in cultured rat astrocytes may occur in the NE uptake system. Furthermore, astrocytes express the extraneuronal monoamine transporter (uptake2), which is an Na+-independent system, and this transporter is involved in the inactivation of centrally released DA.

Animals↗

Region-dependent G-protein activation by mu-, delta 1- and delta 2-opioid receptor agonists in the brain: comparison between the midbrain and forebrain.

The ability of selective mu- ([D-Ala2, NHPhe4, Gly-ol]enkephalin: DAMGO), delta1- ([D-Pen2, Pen5]enkephalin: DPDPE) and delta2- ([D-Ala2]deltorphin II: DELT II) opioid receptor agonists to activate G-proteins in the midbrain and forebrain of mice and rats was examined by monitoring the binding of guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS). The levels of [35S]GTPgammaS binding stimulated by DAMGO in the mouse and rat midbrain were significantly greater than those by DPDPE or DELT II. However, relatively lower levels of stimulation of [35S]GTPgammaS binding by all of the agonists than would have been predicted from the receptor densities were observed in either the limbic forebrain or striatum of mice and rats. The effects of DAMGO, DPDPE and DELT II in all three regions were completely reversed by selective mu-, delta1- and delta2-antagonists, respectively. The results indicate that the levels of mu-, delta1- and delta2-opioid receptor agonist-induced G-protein activation in the midbrain are in good agreement with the previously determined distribution densities of each receptor type. Furthermore, the discrepancies observed in the forebrain might reflect differential catalytic efficiencies of receptor-G-protein coupling.

Analgesics, Opioid↗

Role of endothelin receptor subtypes in the behavioral effects of the intracerebroventricular administration of endothelin-1 in conscious rats.

The role of endothelin receptor subtypes, i.e., ET(A) and ET(B) receptors, in the behavioral effects of the intracerebroventricular (ICV) administration of endothelin-1 were examined in conscious rats. ICV administration of endothelin-1 (1-9 pmol/rat) dose dependently produced barrel rolling and other convulsive behaviors including bodily twitching, rigidity, back crawling, fore/hindlimb dystonia, fore/hindlimb clonus, tail extension, and facial clonus. Moreover, a marked increase in spontaneous locomotor activity was observed in animals that were treated with a low dose of endothelin-1 (1 pmol/rat, ICV). Endothelin-1 (9 pmol/rat, ICV)-induced barrel rolling and other convulsive behaviors were completely suppressed by the coadministration of BQ-123 (15 nmol, ICV), a specific endothelin ET(A) receptor antagonist, but not of BQ-788 (15 nmol/rat, ICV), a specific endothelin ET(B) receptor antagonist. In contrast, increased locomotor activity produced by treatment with a low dose of endothelin-1 (1 pmol/rat, ICV) was antagonized by coadministration of BQ-788, but not of BQ123. These results indicate that endothelin-1, which has affinity for both endothelin ET(A) and ET(B) receptors, most likely acts on central ET(A) receptors to evoke barrel rolling and other convulsive behaviors. In addition, activation of central ET(B) receptors may be involved in the increase in spontaneous locomotor activity. These results suggest that brain endothelin receptor subtypes may be involved in the regulation of various physiological functions.

Animals↗

Localization of B2 bradykinin receptor mRNA in the rat retina and sclerocornea.

The expression of the B2 bradykinin receptor (BKR) mRNA in the adult rat eye was investigated by RNA blot and in situ hybridization analyses. Blot hybridization analysis of poly(A)+ RNA from the whole eye identified RNA species of 6000 and 4000 nucleotides, consistent with those observed in brain, lung, kidney and uterus. In situ hybridization analysis using digoxigenin-labeled riboprobes revealed intense labeling in the retinal ganglion cell layer and in a population of cells adjacent to the sclerocorneal junction. These data suggest that the B2 BKR is involved in biological processes in both retina and sclerocornea.

Animals↗

Regulation of dopamine uptake by basic fibroblast growth factor and epidermal growth factor in cultured rat astrocytes.

We examined the characteristics of dopamine (DA) uptake and its regulation by neurotrophic factors such as basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in cultured rat astrocytes. In the presence of inhibitors of monoamine oxidase (MAO) and catechol-O-methyl-transferase (COMT), astrocytes took up DA by Na(+)-dependent and Na(+)-independent mechanisms that were sensitive to a reduction in temperature. The Na(+)-dependent and Na(+)-independent components increased linearly with increasing [3H]DA concentration (1-1000 microM), and showed no saturation. Na(+)-dependent DA uptake was significantly inhibited by ouabain, a Na(+)-K+ ATPase inhibitor. In bFGF-treated astrocytes, [3H]DA uptake increased in a time-dependent manner until 48 h, and declined after 72 h in both the presence and absence of Na+. In EGF-treated astrocytes, [3H]DA uptake increased in a time-dependent manner until 72 h in both the presence and absence of Na +. This enhancement of DA uptake induced by EGF or bFGF was significantly inhibited when the cells were cultured with actinomycin D, cycloheximide, or brefeldin A. Actinomycin D and brefeldin A also significantly inhibited the basal uptake of [3H]DA into astrocytes. These results suggest the existence of Na(+)-dependent and Na(+)-independent DA uptake in cultured rat astrocytes, and that EGF or bFGF might stimulate the expression and translocation of the extraneuronal DA transporter.

Animals↗

Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction.

OBJECTIVES: We tested to find out whether pravastatin restores the infarct size (IS)-limiting effect of ischemic preconditioning (IP) and if it has any effect on the IP-induced activation of adenosine producing enzyme ecto-5'-nucleotidase which plays a key role in the IP-induced cardioprotection. BACKGROUND: The IS-limiting effect of IP is blunted by hypercholesterolemia. Recently, HMG-CoA reductase inhibitors are shown to have direct cytoprotective effects. METHODS: Rabbits were fed with a normal or cholesterol (1%) added diet with or without pravastatin (5 mg/kg/day) treatment. Infarct size was measured after 30 min occlusion and 3 h reperfusion of circumflex coronary artery with or without the IP procedure (5 min occlusion and 10 min reperfusion). Additionally, ecto-5'-nucleotidase activities of ischemic and nonischemic myocardium were measured immediately after IP procedure. RESULTS: This dose of pravastatin did not normalize the increased level of serum cholesterol. The IS-limiting effect of preceding IP (IS reduced from 36.7% to 9.6%, p < 0.001) was abolished by hypercholesterolemia (from 46.1% to 31.3%, p = NS) and restored by pravastatin treatment (from 35.2% to 9.4%, p < 0.001). Pravastatin treatment did not affect IS or the effect of IP under normocholesterolemia. The activation of ecto-5'-nucleotidase presented as the activity ratio of ischemic to nonischemic myocardium (3.1-fold in normocholesterolemia) was blunted by hypercholesterolemia (1.8-fold, p < 0.05) and restored by pravastatin treatment (2.9-fold). CONCLUSIONS: Pravastatin, at the dose serum cholesterol was not normalized, restored the IS-limiting effect of IP and IP-induced ecto-5'-nucleotidase activation, which were both blunted by hypercholesterolemia. The activation of ecto-5'-nucleotidase may be worth further investigation as a possible mechanism for the hypercholesterolemia-induced retardation and pravastatin-mediated restoration of the cardioprotective effect of IP.

5'-Nucleotidase↗

Removal of vegetal yolk causes dorsal deficencies and impairs dorsal-inducing ability of the yolk cell in zebrafish.

To examine the nature of cytoplasm determinants for dorsal specification in zebrafish, we have developed a method in which we remove the vegetal yolk hemisphere of early fertilized eggs (vegetal removed embryos). When the vegetal yolk mass was removed at the 1-cell stage, the embryos frequently exhibited typical ventralized phenotypes: no axial structures developed. The frequency of dorsal defects decreased when the operation was performed at later stages. Furthermore, the yolk cell obtained from the vegetal-removed embryos lost the ability to induce goosecoid in normal blastomeres while the normal yolk cell frequently did so in normal and vegetal-removed embryos. These results suggested that the vegetal yolk cell mass contains the dorsal determinants, and that the dorsal-inducing ability of the yolk cell is dependent on the determinants.

Animals↗

High quality image oriented telemedicine with multimedia technology.

Researchers at Osaka and Kyoto University hospital performed three experiments, beginning in 1995, which looked at high quality-oriented telemedicine. This paper describes the system design for the three projects. Experiment 1 applied high-definition TV images and B-ISDN for distance learning and medical information exchange. Experiment 2 developed a super high-definition medical image filing system and the images were transmitted via B-ISDN for teleconferences and experiment 3 utilized digital, high-definition, TV images and communication satellites for teleconferences. Multimedia and communication technologies were considered to be fundamental components of telemedicine. The three projects were evaluated initially for quality of images, operability and utility. The experimental design and its implementation showed that it was possible to provide high quality image-oriented telemedicine in the health care environment. Obstacles to establishing practical telemedicine are also discussed.

Computer Communication Networks↗

Fecal clearance of alpha1-antitrypsin with lansoprazole can detect protein-losing gastropathy.

Detecting plasma protein loss from the stomach is quite difficult by measuring fecal alpha1-AT clearance because alpha1-AT is rapidly destroyed in the gastric juice at values below pH 3. We examined protein loss from the stomach using fecal alpha1-AT clearance with lansoprazole, a proton pump inhibitor. A 38-year-old Japanese male presented with hypoproteinemia (total serum protein: 4.4 g/dl). Abdominal scintigraphy using technetium-99m-labeled albumin revealed distinct radioactivity accumulation in the small intestine. It strongly suggested excessive protein loss to the gastrointestinal tract. Although, regular fecal alpha1-AT clearance was within the normal range (<13 ml/day), the fecal alpha1-AT clearance with the administration of lansoprazole was 80.5 ml/day. The results indicated that this method using lansoprazole is simple and useful for detecting protein-losing gastropathy.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Functional and molecular biological evidence for a possible beta3-adrenoceptor in the human detrusor muscle.

The possible existence of a beta3-adrenergic receptor (beta3-AR) in the human detrusor muscle was investigated by in vitro functional studies and analysis of mRNA expression. Isoprenaline, noradrenaline and adrenaline each produced a concentration-dependent relaxation of the human detrusor. The rank order for their relaxing potencies was isoprenaline (pD2 6.37+/-0.07) > or = noradrenaline (pD2 6.07+/-0.12) > or = adrenaline (pD2 5.88< or =0.11). Neither dobutamine (beta1- and beta2-AR agonist) nor procaterol (beta2-AR agonist) produced any significant relaxation at concentrations up to 10(-5) M. BRL37344A, CL316243 and CGP-12177A (beta3-AR agonists), relaxed the preparations significantly at concentrations higher than 10(-6) M. The pD2 values for BRL37344A, CL316243 and CGP-12177A were 6.42+/-0.25, 5.53+/-0.09 and 5.74+/-0.14, respectively. CGP-20712A (10(-7) - 10(-5) M), a beta1-AR antagonist, did not affect the isoprenaline-induced relaxation. On the other hand, ICI-118,551, a beta2-AR antagonist, produced a rightward parallel shift of the concentration-relaxation curve for isoprenaline only at the highest concentration used (10(-5) > M) and its pKB value was 5.71+/-0.19. Moreover, SR58894A (10(-7) - 10(-5) M), a beta3-AR antagonist, caused a rightward shift of the concentration-relaxation curve for isoprenaline in a concentration-dependent manner. The pA2 value and slope obtained from Schild plots were 6.24+/-0.20 and 0.68+/-0.31. The beta1-, beta2- and beta3-AR mRNAs were all positively expressed in detrusor smooth muscle preparations in a reverse transcription polymerase chain reaction assay. In conclusion, the present results provide the first evidence for the existence of the beta3-AR subtype in the human detrusor. They also suggest that the relaxation induced by adrenergic stimulation of the human detrusor is mediated mainly through beta3-AR activation.

Adrenergic alpha-Agonists↗

Mosaic analysis with oep mutant reveals a repressive interaction between floor-plate and non-floor-plate mutant cells in the zebrafish neural tube.

The floor plate is located at the ventral midline of the neural tube in vertebrates. Floor-plate development is severely impaired in zebrafish one-eyed pinhead (oep) mutants. oep encodes a membrane-bound protein with an epiblast growth factor (EGF) motif and functions autonomously in floor-plate precursors. To understand the cell behavior and cell-cell interaction during floor-plate development, the distribution and gene expression of wild-type and oep mutant cells in genetic mosaics were examined. When mutant shield cells were transplanted into a wild-type host, an ectopic neural tube with a floor plate was induced. However, the floor plate of the secondary axis was consistently devoid of mutant cells while its notochord was composed entirely of mutant cells. This indicates that oep shield cells adopt only a notochord fate in a wild-type environment. In reciprocal transplants (wild to oep), however, grafted shield cells frequently contributed to part of the floor-plate region of the secondary neural tube and expressed floor-plate markers. Careful examination of serial sections revealed that a mutant neural cell, when located next to the wild-type cells at the ventral midline, inhibited floor-plate differentiation of the adjacent wild-type cells. This inhibition was effective over an area only one- or two-cells wide along the anteroposterior axis. As the cells located at the ventral midline of the oep neural tube are thought to possess a neural character, similar to those located on either side of the floor plate in a wild-type embryo, this inhibition may play an important role during normal development in restricting the floor-plate region into the ventral-most midline by antagonizing homeogenetic signals from the floor-plate cells.

Animals↗

Intraoperative radiotherapy for the abdominal lymphatic system in patients with esophageal carcinoma.

We applied intraoperative radiotherapy (IORT) to the esophageal carcinoma in an attempt to prevent abdominal lymph node recurrence, and retrospectively studied patterns of failure and controllability of abdominal lymph nodes in patients treated with or without IORT. Between July 1986 and October 1997, 81 patients with radically resected esophageal carcinoma, aged 42-76 years (mean 61), were divided into two groups, the IORT group (39 patients) and the non-IORT group (42 patients). All patients except two, who received transhiatal esophagectomy for superficial carcinoma, underwent subtotal esophagectomy with thoracic and abdominal with/without cervical lymphadenectomy. Fourteen patients underwent only surgical resection, and the remaining 67 patients received radiotherapy to the mediastinum post-operatively (40-50 Gy/20-25 Fr/4-5 W) in 37 and preoperatively (44 Gy/40 Fr/4 W) in 30 patients. Preoperative irradiation was performed as a neoadjuvant chemoradiotherapy consisting of two courses of cisplatin (each patient received 80-100 mg, mean 60 mg m(-2), day 1, bolus injection) and 5-fluorouracil (each patient received 500-1000 mg day(-1), mean 400 mg m(-2), days 1-4, continuous infusion). The target volume of IORT encompassed the upper abdominal lymph node area including lymph node groups of right/left cardia, left gastric artery, celiac artery and abdominal para-aorta. A single dose of high-energy electrons (9-12 MeV) of 20-23 Gy, prescribed to the 90% isodose curve, was delivered. Treatment for the abdominal lymphatic system was classified into four categories: surgery alone in 30 patients, surgery with chemotherapy in 12, surgery with IORT in 15, surgery with chemotherapy and IORT in 24. There were no complications related to IORT. Forty patients (49%) had recurring carcinoma: in the lymph nodes (36%), in distant organs (27%) and locally (6%). The incidence of lymph node metastasis was 29% in the neck, 32% in the mediastinum, and 27% in the abdomen. Abdominal lymph node recurrence in the IORT group was less frequent than in the non-IORT group (p=0.048). In particular, 24 patients treated with a combination of surgery, chemotherapy and IORT had no recurrence in the abdominal lymphatic system. The overall median survival was 46 months, the survival at 1, 3, and 5 years being 85%, 52%, and 44% respectively. However, there was no difference in survival between the IORT group and the non-IORT group. The IORT for the abdominal lymphatic system was feasible for reduction of the rate of abdominal lymphatic recurrence without survival benefit in this study. This retrospective finding should be confirmed by a prospective randomized study.

Adult↗

Changes in urinary output during laparoscopic adrenalectomy.

OBJECTIVE: To better understand the physiological effects of pneumoperitoneum, by examining changes in urinary output during gaseous and gasless laparoscopic adrenalectomy. PATIENTS AND METHODS: Laparoscopic adrenalectomy was performed with gas in six patients and without in three. Urinary output was measured during insufflation and after desufflation. RESULTS: In all patients who received gas, the urinary output was significantly decreased during insufflation and significantly increased after desufflation. However, there were no changes in urinary output in patients who did not receive gas. CONCLUSION: For the safety of laparoscopic surgery it is important to recognise that oliguria occurs during pneumoperitoneum, although the changes in urinary output caused no complications in renal function.

Adrenalectomy↗

Chaotic dynamics in circulation with Tohoku University vibrating flow pump.

For the development of a totally implantable ventricular assist system (VAS), we have been developing the vibrating flow pump (VFP), which can generate oscillated blood flow with a relative high frequency (10-50 Hz) for a totally implantable system. In this study, the effects of left ventricular assistance with this unique oscillated blood flow were analyzed by the use of nonlinear mathematics for evaluation as the whole circulatory regulatory system, not as the decomposed parts of the system. Left heart bypasses using the VFP from the left atrium to the descending aorta were performed in chronic animal experiments using healthy adult goats. The ECG, arterial blood pressure, VFP pump flow, and the flow of the descending aorta were recorded in the data recorder during awake conditions and analyzed in a personal computer system through an A-D convertor. By the use of nonlinear mathematics, time series data were embedded into the phase space, the Lyapunov numerical method, fractal dimension analysis, and power spectrum analysis were performed to evaluate nonlinear dynamics. During left ventricular assistance with the VFP, Mayer wave fluctuations were decreased in the power spectrum, the fractal dimension of the hemodynamics was significantly decreased, and peripheral vascular resistance was significantly decreased. These results suggest that nonlinear dynamics, which mediate the cardiovascular dynamics, may be affected during left ventricular (LV) bypass with oscillated flow. The decreased power of the Mayer wave in the spectrum caused the limit cycle attractor of the hemodynamics and decreased peripheral resistance. Decreased sympathetic discharges may be the origin of the decreased Mayer wave and fractal dimension. These nonlinear dynamic analyses may be useful to design optimal VAS control.

Analog-Digital Conversion↗

A future prediction type artificial heart system.

The demand of the biological system needs to be predicted to consider the quality of life (QOL) of a patient with an artificial heart system. The purpose of this study was the prediction of the imminent cardiac output and the predictive control for an artificial heart. For that purpose, autonomic nerve information was applied in this study. Nervous sympathicus action potentials were measured, and a prediction function of cardiac output was made using the sympathetic tone and preload and after-load measurement with multiple regression analysis. The predicted value showed significant correlation with the measured value after 2.9 s. Currently, however, long-term instrumentation of the nervous sympathicus potential is difficult. Thus, hemodynamic fluctuations, which recently have attracted attention, were used in this study. A prediction function using the Mayer wave, which represented nervous sympathicus, was determined. As a result, mid-term prediction became possible. Furthermore, a measurement of the vagal nerve was used as a possible long-term prediction parameter. For long-term prediction, Hurst exponent analysis was used in this study. Vagal nerve discharges in the changing position showed alteration of long-term determination. In conclusion, the future prediction control of an artificial heart takes shape using these prediction functions.

Action Potentials↗

Vagal nerve activity recording in the awake condition for the control of an artificial heart system.

To detect useful information for an artificial heart control system, we paid attention to the autonomic nervous system. For stable recording, we used vagal nerve activity in chronic animal experiments using healthy adult goats in an awake condition because this nerve was sufficiently bold and large enough. Vagal nerve discharges were successfully recorded from awake goats. They were synchronized with respiration and responded to the hemodynamic changes induced by drug administration, suggesting that they may provide useful information for an artificial heart control algorithm. For automatic control, some time delay plays a vitally important role. Thus, predictive control for an artificial heart system may be desirable. It may be embodied by the use of autonomic nerve information.

Action Potentials↗