Biomedical subjects

A Furuya

Publications and source records attributed to A Furuya.

At least 19 recordsLinked to original sources

PubMed2006

Isoflurane and sevoflurane during reperfusion prevent recovery from ischaemia in mitochondrial KATP channel blocker pretreated hearts.

BACKGROUND AND OBJECTIVE: Inhalation anaesthetics given only during post-ischaemic reperfusion have some protective effect against reperfusion injury in the heart. Adenosine triphosphate-regulated mitochondrial potassium channels have been shown to be an important mediator of cardioprotection. Thus, we investigated whether 5-hydroxydecanoate, a putative mitochondrial potassium channel blocker, prevents the cardioprotective effect of volatile anaesthetics. METHODS: Forty rats were randomly allocated to four groups of equal size: control group, 5-hydroxydecanoate group, 5-hydroxydecanoate + sevoflurane group and 5-hydroxydecanoate + isoflurane group. Seven minutes after the start of perfusion, normal saline (control group) or 5-hydroxydecanoate (the other groups) was administered. Ten minutes after the start of perfusion, the heart was rendered globally ischaemic for 10 min. One minute before the end of the ischaemic period, 2.7% sevoflurane or 1.4% isoflurane were administered in the 5-hydroxydecanoate + sevoflurane or 5-hydroxydecanoate + isoflurane groups respectively. The heart was reperfused for 10 min. RESULTS: Adenosine triphosphate content at the end of reperfusion in the 5-hydroxydecanoate + sevoflurane group was significantly lower (P < 0.05) than those in the control and the 5-hydroxydecanoate + isoflurane groups (19.9 +/- 8.7, 28.1 +/- 3.4 and 30.4 +/- 2.3 micromol g(-1), respectively). In addition, the combination of inhalation anaesthetics and 5-hydroxydecanoate decreased the ratios of recovered hearts from ischaemia (5-hydroxydecanoate + sevoflurane group: 40%, 5-hydroxydecanoate + isoflurane group 50%). CONCLUSION: 5-hydroxydecanoate alone caused no significant changes in haemodynamics and myocardial metabolism. However, the combination of 5-hydroxydecanoate and volatile anaesthetics impaired the recovery from ischaemia. Although animal data cannot be extrapolated to human beings, we suggest that more attention be paid to patients on sulphonylurea drugs, which inhibit potassium channels, when they are anaesthetized with volatile anaesthetics.

Anesthetics, Inhalation↗

PubMed2003

Serum stem cell growth factor for monitoring hematopoietic recovery following stem cell transplantation.

Stem cell growth factor (SCGF) is a novel cytokine for primitive hematopoietic progenitor cells. Although it has burst-promoting activity and granulocyte/macrophage colony-promoting activity in vitro, its significance in hematopoiesis in vivo has not been elucidated. In this study, we have established enzyme-linked immunosorbent assay (ELISA) to quantify human SCGF and measured serum cytokines in normal volunteers and 27 patients undergoing stem cell transplantation (SCT), including six autologous and 21 allogeneic transplants. SCGF levels gradually increased after SCT regardless of graft-versus-host disease or type of transplant. The maximum level of SCGF was observed during the rapid granulocyte recovery phase in patients subjected to an autologous transplantation, and during the granulocyte stabilization phase in allogeneic patients. SCGF levels in PBSCT patients began to rise earlier than in BMT patients. Two patients with no increment of SCGF after SCT showed delayed engraftment. The source of SCGF was further analyzed by RT-PCR and we found that SCGF was highly expressed in bone marrow (BM) CD34(+) and CD34(-)CD33(+) cells, but not in BM CD34(-)CD33(-) cells, BM stromal cells and peripheral blood cells. The cell population expressing SCGF in BM possess the colony-forming cell activity. Therefore, serum SCGF can be an indicator of hematopoietic recovery following SCT.

Adolescent↗

PubMed2002

Effects of nicorandil on myocardial function and metabolism in the post-ischaemic reperfused heart with or without inhalation anaesthetics.

BACKGROUND: Nicorandil, which is an ATP-sensitive K channel opener, has been reported to protect the ischaemic myocardium. However, its interaction with inhalation anaesthetics on the ischaemic myocardium has not been well elucidated. So, we have investigated whether isoflurane or sevoflurane modify the effects of nicorandil on cardiac function and metabolism in the rat heart-lung preparation. METHODS: Animals were allocated to 4 groups as follows: Control group, no drug; Nic group, nicorandil; Nic+Iso group, nicorandil and isoflurane; Nic+Sev group, nicorandil and sevoflurane. Seven minutes after the start of perfusion, nicorandil was administered and 10 min after the start of perfusion, the heart was rendered globally ischaemic for 10 min, and then the heart was reperfused for 10 min. RESULTS: LVdP/dt max in the Nic group was higher than those in the other groups. Right atrial pressure in the Nic+Iso and Nic+Sev groups was significantly higher than in the Control and Nic groups. Myocardial ATP in the Nic group was higher than in the other groups. DHBA levels in the perfusate in the Nic and Nic+Iso groups were lower than those in the Control and Nic+Sev groups, but those in the Nic+Sev group were higher than those in the other groups. CONCLUSIONS: Nicorandil improved post-ischaemic cardiac function and preserved high-energy phosphates. However, these beneficial effects of nicorandil were abolished by the combination with isoflurane or sevoflurane. In addition, sevoflurane increased hydroxyl radical formation in the post-ischaemic reperfused heart.

Adenosine Triphosphate↗

PubMed2002

Pharmacokinetic and pharmacodynamic analysis of TS-943, a selective non-peptide platelet glycoprotein-IIb/IIIa (GPIIb/IIIa) receptor antagonist, using a nonlinear mixed effect model in dogs.

A simultaneous analysis of the pharmacokinetics and pharmacodynamics of TS-943, a selective nonpeptide platelet glycoprotein-IIb/IIIa (GPIIb/IIIa) receptor antagonist, was made in dogs using a nonlinear mixed effect model. Plasma concentrations of TS-943 were determined after bolus intravenous injection, constant infusion and bolus plus constant infusion. Pharmacokinetic/pharmacodynamic data were fitted using NONMEM software. The pharmacokinetics of TS-943 fitted a two-compartment open model with first-order elimination. The pharmacodynamic model that best fitted platelet aggregation was an inhibitory sigmoid Emax model. The final estimates for E0 (baseline effect), Emax (maximum effect), IC50 (50% inhibitory concentration) and gamma (Hill coefficient) were 66.3%, 64.3%, 104 ng mL(-1) and 1.37, respectively. Correlations between TS-943 plasma concentration and extension of template bleeding time were examined by fitting with an exponential model. The TS-943 plasma concentration necessary to double bleeding time (C2-BTE) was approximately 209 ng mL(-1). The model estimated that the C2-BTE/IC50 (inhibition of platelet aggregation) ratio was approximately 2.0-fold in dogs. Our results suggest that the ratio values for dogs and man are comparable. A nonlinear mixed effect model was a useful tool for exploring the concentration-effect relationship for both efficacy and safety of TS-943 in dogs and man. In this study, the dog was found to be a useful model for screening of efficacy and safety of TS-943 in man.

Amidines↗

PubMed2001

Stimulation of RNA polymerase II elongation by hepatitis delta antigen.

Transcription elongation by RNA polymerase II (RNAPII) is negatively regulated by the human factors DRB-sensitivity inducing factor (DSIF) and negative elongation factor (NELF). A 66-kilodalton subunit of NELF (NELF-A) shows limited sequence similarity to hepatitis delta antigen (HDAg), the viral protein required for replication of hepatitis delta virus (HDV). The host RNAPII has been implicated in HDV replication, but the detailed mechanism and the role of HDAg in this process are not understood. We show that HDAg binds RNAPII directly and stimulates transcription by displacing NELF and promoting RNAPII elongation. These results suggest that HDAg may regulate RNAPII elongation during both cellular messenger RNA synthesis and HDV RNA replication.

Amino Acid Sequence↗

PubMed2001

Intravenous ketamine attenuates arterial pressure changes during the induction of anaesthesia with propofol.

BACKGROUND AND OBJECTIVE: To investigate whether the administration of ketamine before induction with propofol produces a smaller decrease in arterial pressure. METHODS: Twenty-two patients were assigned to one of two groups to receive either propofol with ketamine (n = 11) or propofol alone (n = 11, control). Anaesthesia was induced with 2 mg kg-1 propofol and 0.5 mg kg-1 ketamine or 2 mg kg-1 propofol alone. Ketamine was administered 1 min prior to induction with propofol. Immediately after induction with propofol, vecuronium (0.15 mg kg-1) was administered. Four minutes after administration of vecuronium, tracheal intubation was performed. Anaesthesia was maintained using sevoflurane (0.5%) in 66% nitrous oxide until 3 min after intubation. Systolic, diastolic and mean arterial pressure and heart rate were recorded on arrival, directly before induction with propofol, prior to tracheal intubation, immediately after intubation and at 3 min after intubation. RESULTS AND CONCLUSIONS: Administration of ketamine before induction with propofol preserved haemodynamic stability compared with induction with propofol alone.

Anesthesia↗

PubMed2001

Effects of cibenzoline on cardiac function and metabolism in the rat heart--lung preparation.

BACKGROUND AND OBJECTIVE: Although there is concern that cibenzoline, an antidysrhythmic drug for the treatment of ventricular and supraventricular dysrhythmias, may be associated with dose-dependent inhibition of myocardial contractility there are few reports about the relationship between myocardial metabolism and cardiac function when it is used. The present study was designed to investigate the effects of cibenzoline on cardiac function and metabolism. The effects of cibenzoline on cardiac function and myocardial metabolism were assessed in the isolated rat heart-lung preparation. METHODS: Thirty-two male Wistar-ST rats were divided into four groups: control, and those to receive cibenzoline, either 300, 900 or 3000 ng mL(-1). The cibenzoline was administered into the perfusate 5 min after the start of perfusion. Heart rates in the 3000 ng mL(-1) group were significantly lower than those in the control group. Cardiac output in the 3000 ng mL(-1) group at 15 and 30 min was significantly lower than in the control group. In all groups, values for %LV dP/dt max (the ratio of values at each time to those at 5 min) at 20, 25, 30 min were significantly higher than at 5 min. Myocardial adenosine triphosphate concentration in the 3000 ng mL(-1) group was significantly lower than in controls. There was no difference between groups in the lactate/pyruvate ratio. CONCLUSION: The therapeutic range of cibenzoline has few effects on cardiac function and metabolism, although concentrations 10 times greater may cause a deterioration in myocardial metabolism.

Adenosine Diphosphate↗

PubMed2001

Effects of glibenclamide on hydroxyl radical formation in the postischaemic reperfused heart with or without inhalation anaesthetics.

BACKGROUND AND OBJECTIVE: We investigated whether glibenclamide (glyburide) affects myocardial metabolism and hydroxyl radical formation in the rat heart-lung preparation with or without inhalation anaesthetics. METHODS: Thirty-seven male Wistar rats were allocated to four groups: (a) control group (C), received vehicle only; (b) group G, received glibenclamide 10 microM L-1; (c) group I, received glibenclamide 10 microM L-1 and 1.4% isoflurane during perfusion; (d) group S, received glibenclamide 10 microM L-1 and 2.7% sevoflurane during perfusion. Glibenclamide was administered 7 min after the start of perfusion. Ten minutes later, the heart was rendered globally ischaemic for 10 min by reducing the preload and afterload to zero, and then the heart was reperfused for 10 min. The formation of hydroxyl radicals in perfusate blood and heart was measured with high performance liquid chromatography using salicylic acid. Hydroxyl radicals react with salicylic acid, yielding dihydroxybenzoic acids. RESULTS: The recovery time from ischaemia in group G was significantly longer than the other groups. However, there were no differences in myocardial metabolites and dihydroxybenzoic acids concentrations in the perfusate and heart among the four groups. CONCLUSIONS: Glibenclamide prolonged recovery time from ischaemia, but did not affect hydroxyl radical formation in the postischaemic reperfused heart. In addition, isoflurane and sevoflurane shortened this time. These facts suggest that mechanisms other than effects of volatile anaesthetics on hydroxyl radical formation are responsible for their protective effects in this model.

Adenosine Triphosphate↗

PubMed2001

[Anesthetic management of a child with congenital sensory neuropathy with anhydrosis].

Congenital sensory neuropathy with anhydrosis is a rare disorder characterized by insensitivity to pain with normal tactile perception, self-mutilation, anhydrosis, recurrent unexplained fever, mental retardation and variable autonomic abnormality. We managed a 14-year-old boy with this syndrome who underwent repair of right femur fracture. Anesthesia was induced with propofol and ketamine. Adequate depth of anesthesia was carefully controlled by processed electroencephalogram, and core body temperature was maintained at 37.0 degrees C during the surgery. The patient was well sedated, and nausea and vomiting were not noted postoperatively. Use of droperidol and propofol may be beneficial for anesthetic management of this syndrome, because droperidol exerts residual hypnotic effect postoperatively, and both drugs have antiemetic property.

Adolescent↗

PubMed2000

Establishment of the anti-Klotho monoclonal antibodies and detection of Klotho protein in kidneys.

A novel gene, klotho (kl), which is involved in the development of a syndrome resembling human aging in mice, was recently identified. The kl gene encodes a single-pass membrane protein whose extracellular domain carries homology to beta-glucosidases. There also exists a splice variant of kl mRNA which encodes a putative secreted protein in both human and mouse. In this study, to characterize the physiological roles of Klotho protein, we established three monoclonal antibodies (mAbs) against the recombinant human Klotho protein. The mAbs are named KM2076 (rat IgG(2)a), KM2119 (rat IgG(2)b), and KM2365 (mouse IgG(1)). In Western blots, KM2076 and KM2119 specifically recognized a 130 kDa Klotho protein in the mouse and human kidney membrane fractions. To detect the human Klotho protein, the sandwich-type ELISA system with KM2076 and KM2365 was established. Using the ELISA system, we detected the human Klotho protein as low as 20 ng/ml in the supernatant of Chinese hamster ovary cells (CHO cells), introduced the human klotho gene. KM2076 and KM2119 specifically gave a positive staining by immunohistochemical staining in paraffin or frozen sections of the kidneys from wild-type mice but not in those from kl mice. Strong staining was observed especially in cortical renal tubules of the mouse kidney, where expression of klotho transcripts overlaps. KM2076 also showed a similar reaction pattern in the paraffin sections of rat and human kidneys. The mAbs established in this paper will serve as useful analytical, pathological, and diagnostic tools to disclose the role of Klotho protein in the suppression of a syndrome resembling human aging.

Aging↗

PubMed2000

Gastric pH profiles of beagle dogs and their use as an alternative to human testing.

Gastric pH levels were measured in samples of gastric aspirates from eight fasted beagle dogs. The gastric pH in fasting dogs fluctuated from 2.7 to 8.3, with a mean of 6.8+/-0.2 (SE). Each dog received the following four treatments in randomly-assigned order: (A) distilled water; (B) a placebo capsule; (C) pentagastrin, and (D) ranitidine. The gastric pH remained relatively constant after distilled water administration. In contrast, the treatments with pentagastrin and placebo capsule each lowered gastric pH. Pretreatment with pentagastrin was more successful in lowering gastric pH than that with placebo capsule. On the other hand, the pH rose above 7.0 in all dogs by the first hour after treatment with ranitidine. This animal model may be helpful in evaluating the biopharmaceutics of drugs exhibiting pH-dependent dissolution or decomposition.

Animals↗

PubMed2000

T-cell-specific expression of kinase-defective Eph-family receptor protein, EphB6 in normal as well as transformed hematopoietic cells.

Although most kinase-defective growth factor receptor proteins are associated with pathogenic conditions, a kinase-defective Eph-family receptor protein, EphB6, is expressed in normal human tissues. We generated monoclonal antibodies specific for human EphB6 to characterize its expression on human hematopoietic cells. A very small population of normal human peripheral white blood cells (0.57 +/- 0.07%, n = 12) expressed EphB6. The EphB6-positive cells were CD2+, CD7+, CD3+ and CD4+ or CD8+ lymphocytes, but they did not express CD19 or CD11b. In human bone marrow, only 1.5 +/- 0.19% of lymphocytes expressed EphB6. Compared with the expression in peripheral lymphocytes, prominent expression of EphB6 protein was demonstrated in CD4+CD8+ double-positive mouse thymocytes. The T-cell lineage-specific expression was strictly conserved in human leukemia/lymphoma cells. Among T-cell-derived leukemia cells, the expression level of EphB6 seemed to decrease with maturation of the cells. These results suggest that EphB6 expression is regulated in T-cell development.

Animals↗

PubMed2000

ELISA for urinary trehalase with monoclonal antibodies: a technique for assessment of renal tubular damage.

BACKGROUND: alpha,alpha-Trehalase, located on renal proximal tubules, is a glycoprotein that hydrolyses alpha,alpha-trehalose to two glucose molecules. Urinary trehalase reflects damage to renal proximal tubules, but its activity has not been measured routinely because measurement of catalytic activity is rather complicated and because conventional assays for enzyme activity might not reflect all of the trehalase protein because of enzyme inactivation in urinary samples. METHODS: We established novel monoclonal antibodies for human trehalase and a sandwich ELISA for quantification of urinary trehalase. We determined the urinary trehalase protein concentration with this ELISA and trehalase catalytic activity, and the results of these two methods were compared. RESULTS: The ELISA system was more sensitive than the detection of enzyme activity and could detect a subtle difference in the amount of trehalase present in renal diseases. The within- and between-assay CVs in the ELISA were 6.7-7.6% and 6.2-8.2%, respectively. Highly significant increases in both the quantity and activity were seen in patients with nephrotic syndrome (acute phase), Lowe syndrome, and Dent disease. The quantities were 70- to 200-fold greater, whereas enzyme activities were, at most, 10-fold higher than those of control subjects. In the detection of small amounts of trehalase in patients with chronic glomerulonephritis and renal anomalies, quantities were better than enzyme activities. CONCLUSIONS: We have established an ELISA system for quantification of urinary trehalase that uses novel monoclonal antibodies. Our ELISA system is simpler and more sensitive than a conventional activity assay and reflects trehalase protein. This ELISA can be a useful as a common tool for clinical assessment of renal proximal tubular damage.

Acetylglucosaminidase↗

PubMed2000

Population pharmacokinetics and pharmacodynamics of TS-943 for selective nonpeptide platelet glycoprotein IIb/IIIa receptor antagonist in normal healthy subjects.

The pharmacokinetics and pharmacodynamics of TS-943 were evaluated with use of NONMEM in 36 healthy male subjects after constant infusion of five different single-dose regimens. Population analysis showed the plasma concentration-time profiles of TS-943 to be best-fit characterized by a two-compartment open model with constant infusion and first-order elimination. The pharmacodynamic model that best fitted the platelet aggregation was a sigmoid Emax model. The final estimates for baseline effect, 50% inhibitory concentration (IC50), and the Hill coefficient were 79.4%, 23.4 ng/mL and 1.63, respectively. The maximum effect (Emax) was fixed at 80% (submaximal aggregation response). In addition, correlations between TS-943 plasma concentration and extension of template bleeding time were examined by fitting with an exponential model. The model estimates that the TS-943 plasma concentration necessary to double template bleeding time is approximately 63 ng/mL (ie, 2.7-fold greater than the IC50). The population approaches for pharmacokinetic-pharmacodynamic investigation can be useful for the analysis of concentration-effect relationships and concentration-adverse event relationships for a platelet glycoprotein IIb/IIIa receptor antagonist.

Adult↗

PubMed1999

NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation.

DRB is a classic inhibitor of transcription elongation by RNA polymerase II (pol II). Since DRB generally affects class II genes, factors involved in this process must play fundamental roles in pol II elongation. Recently, two elongation factors essential for DRB action were identified, namely DSIF and P-TEFb. Here we describe the identification and purification from HeLa nuclear extract of a third protein factor required for DRB-sensitive transcription. This factor, termed negative elongation factor (NELF), cooperates with DSIF and strongly represses pol II elongation. This repression is reversed by P-TEFb-dependent phosphorylation of the pol II C-terminal domain. NELF is composed of five polypeptides, the smallest of which is identical to RD, a putative RNA-binding protein of unknown function. This study reveals a molecular mechanism for DRB action and a regulatory network of positive and negative elongation factors.

Amino Acid Sequence↗

PubMed1999

A novel human nucleoside diphosphate (NDP) kinase, Nm23-H6, localizes in mitochondria and affects cytokinesis.

Nucleoside diphosphate kinases (NDP kinases) are enzymes known to be conserved throughout evolution and have been shown to be involved in various biological events, in addition to the "housekeeping" phosphotransferase activity. We present the molecular cloning of a novel human NDP kinase gene, termed Nm23-H6. Nm23-H6 gene has been mapped at chromosome 3p21.3 and is highly expressed in heart, placenta, skeletal muscle, and some of the cancer cell lines. Recombinant Nm23-H6 protein has been identified to exhibit functional NDP kinase activity. Immunolocalization studies showed that both endogenous and inducibly expressed Nm23-H6 proteins were present as short, filament-like, perinuclear radical arrays and that they colocalized with mitochondria. Cell fractionation study also demonstrated the presence of Nm23-H6 protein in a mitochondria-rich fraction. Moreover, induction of overexpression of Nm23-H6 in SAOS2 cells, using the Cre-loxP gene activation system, resulted in growth suppression and generation of multinucleated cells. Flow cytometric analysis also demonstrated that the proportion of cells with more than 4N DNA content increased to 28.1% after induction of Nm23-H6, coinciding with the appearance of multinucleated cells. These observations suggest that Nm23-H6, a new member of the NDP kinase family, resides in mitochondria and plays a role in regulation of cell growth and cell cycle progression.

Amino Acid Sequence↗

PubMed1999

Immunohistological distributions of fibronectin, tenascin, type I, III and IV collagens, and laminin during tooth development and degeneration in fetuses of minke whale, Balaenoptera acutorostrata.

The immunohistological distributions of fibronectin, tenascin, type I, III and IV collagens, and laminin were observed in the tooth buds of fetuses of minke whale, Balaenoptera acutorostrata. Distributions of extracellular matrices (ECMs) examined in this study except for tenascin were generally similar to those of terrestrial mammalian species during development of the tooth bud. Tenascin in the fetuses of minke whale showed characteristic distributions in the dental lamina and the enamel organ in the early tooth developmental stage. In the physiological degeneration stage of tooth bud development, immunoreactivity of the ECMs were very weakly and limitedly detected in the dental papilla and the surrounding mesenchyme. Immunoreactivity of tenascin and type I and III collagens were positively detected in the developing baleen plate germ which was associated with the degenerating tooth bud. These findings suggested that expressions of the ECMs were related to the formation of the tooth bud and baleen plate germ, and that the lack of the ECMs was related to the degeneration of the tooth bud in the fetal minke whale.

Animals↗

PubMed1999

[Anesthetic management of cesarean section for conjoined twins].

A 31-year-old female patient underwent cesarean section for conjoined twins under general anesthesia. In the 33rd week of pregnancy, MRI showed the twins to be a thoracopagus, whose hearts and livers are combined. The patient was not informed that her fetus combined. General anesthesia was induced with thiamylal 200 mg and vecuronium 8 mg in the presence of two pediatricians. Anesthesia was maintained with 66% nitrous oxide in oxygen until the delivery. Just after the delivery, methylergometrine maleate 0.2 mg, midazolam 5 mg, and fentanyl 100 micrograms were administered intravenously. PGF2 alpha was administered in the uterus because of inadequate contraction of the uterus. Apgar score was 0 point at both 1 minute and 5 minutes. Autopsy showed their hearts and livers combined. Conjoined twins tend to die early after birth because of abnormality in their hearts. We selected general anesthesia for this case considering mother's feeling, and we successfully held intraoperative bleeding down with methylergometrine maleate and extra PGF2 alpha.

Adult↗