Biomedical subjects

K Sumikawa

Publications and source records attributed to K Sumikawa.

At least 37 records · Page 2Linked to original sources

PubMed1999

Acute and chronic nicotine exposure differentially facilitate the induction of LTP.

We report here that acute and chronic nicotine exposure facilitated the induction of long-term potentiation (LTP), a leading candidate for a cellular mechanism underlying learning and memory, in the hippocampus. Furthermore, acute application of nicotine in chronic nicotine-treated hippocampus further facilitated the induction of LTP, suggesting that acute and chronic nicotine effects on LTP induction are mediated by different mechanisms. These findings not only provide evidence for chronic nicotine-induced synaptic changes in the hippocampus, but also an explanation of the cellular basis of nicotine-induced cognitive enhancement.

Action Potentials↗

PubMed1999

Positive- and negative-regulation of Ca2+ entry through ACh receptor channels by phosphorylation.

During development of mammalian neuromuscular junctions, the expression of ACh receptors (AChRs) switches from an embryonic form to an adult form, which provides a higher Ca2+ permeable channel. The lack of this switch can prevent normal development of neuromuscular junctions. In non-mammalian species, however, the switch appears not to occur. The results of the present study show that Ca2+ entry through non-mammalian AChR channels was controlled by differential phosphorylation rather than a subunit switch. This finding provides support for the hypothesis that localized Ca2+ influx through AChR channels has a critical role in the formation and maintenance of neuromuscular junctions.

Animals↗

PubMed1999

Arachidonic acid induces a long-lasting facilitation of hippocampal synaptic transmission by modulating PKC activity and nicotinic ACh receptors.

The present study was conducted to understand the effect of arachidonic acid on nicotinic acetylcholine (ACh) receptor-mediated synaptic plasticity. Arachidonic acid persistently (>/=1 h) potentiated currents through neuronal nicotinic ACh receptors (alpha7 and alpha4beta2) expressed in Xenopus oocytes, and the effect was blocked by the selective protein kinase C (PKC) inhibitors, such as GF109203X, PKCI, and co-expressed active PKC inhibitor peptide. This free fatty acid markedly increased nicotine-sensitive glutamate release from hippocampal slices and enhanced the rate of nicotine-sensitive miniature excitatory postsynaptic currents without affecting the amplitude in cultured hippocampal CA1 neurons under the influence of PKC. Furthermore, arachidonic acid induced a long-lasting (>/=3 h) facilitation of hippocampal CA1 synaptic transmission in slices, and the effect was blocked by nicotinic ACh receptor antagonists, alpha-bungarotoxin and mecamylamine. The facilitation, whereas independent of N-methyl-D-aspartate (NMDA) receptors, shares a common mechanism with long-term potentiation (LTP) induced by tetanic stimulation. The results of the present study thus suggest that arachidonic acid sustains enhanced activity of nicotinic ACh receptors by interacting with a PKC pathway, thereby increasing glutamate release from presynaptic terminals, and then leading to an 'LTP-like' facilitation of hippocampal synaptic transmission.

Animals↗

PubMed1999

Arachidonic acid potentiates currents through Ca2+-permeable AMPA receptors by interacting with a CaMKII pathway.

The present study investigated the effect of arachidonic acid on the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, presumably heteromeric receptors formed of GluR1, GluR2, and GluR3, expressed in Xenopus oocytes. Arachidonic acid (10 microM) potentiated currents through receptors expressing GluR1 and 3 (GluR1,3) to 170% of basal level during initial 20 min following application, being still evident at 60-min washing-out of the drug, while it never or little enhanced currents through receptors expressing GluR1 and 2 (GluR1,2) or GluR1, 2, and 3 (GluR1,2,3) (110% 30 min after treatment). The effect of arachidonic acid on GluR1,3 currents was not observed in Ca2+-free extracellular solution, and the potentiation was blocked by either KN-93, a selective Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitor, or NP217, an active CaMKII inhibitor peptide, when co-expressed with the receptors. In contrast, the protein synthesis inhibitor, cycloheximide, the selective inhibitor of cAMP-dependent protein kinase (PKA), H-89, the selective inhibitors of protein kinase C (PKC), PKCI and GF109203X, the mitogen-activated protein (MAP) kinase kinase inhibitor, PD98059, or the inactive CaMKII inhibitors, KN-92 and NP218, had no effect on the currents. In the assay of intracellular calcium mobilizations, Ca2+ influx in response to receptor activation was greatest with receptors formed in oocytes expressing GluR1,3. The results of the present study indicate that arachidonic acid induces a long-lasting potentiation of GluR1,3 currents, possibly as a result of the interaction with a CaMKII pathway.

Animals↗

PubMed1999

Protective role of glutathione synthesis in response to oxidized low density lipoprotein in human vascular endothelial cells.

Impairment of endothelial cells by oxidized low density lipoprotein (OxLDL) is believed to be the first step in atherogenesis. It is also believed that oxidative stress/antioxidant imbalance is involved in the cell damage by OxLDL. However, little is known about the interaction between OxLDL and antioxidants. In this study, we show that treatment of human vascular endothelial cells with OxLDL caused a gradual increase of glutathione (gamma-glutamylcysteinyl glycine, GSH) levels in 24 h. OxLDL increased the intracellular levels of reactive oxygen species (ROS) and stimulated the expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme for the GSH synthesis, the mitogen-activated protein kinase (MAPK) activity, and the AP-1-DNA binding activity. The luciferase activity of gamma-GCS promoter containing AP-1 site was activated by OxLDL. Collectively, OxLDL induces gamma-GCS expression mediated by AP-1 resulting in an increase of GSH levels. The MAPK activity stimulated by ROS may be involved in the activation of AP-1. The increase in GSH by OxLDL may afford cellular protection against OxLDL-induced oxidative stress.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1999

Effects of controlled hypotension with sevoflurane anaesthesia on hepatic function of surgical patients.

The effects of controlled hypotension induced with trimethaphan (TMP), nitroglycerin (TNG) or prostaglandin E1 (PGE1) during sevoflurane anaesthesia on hepatic function were studied in 28 patients undergoing spinal fusion surgery. Patients were randomly divided into three groups to receive TMP (group A, n = 10), TNG (group B, n = 10) or PGE1 (group C, n = 8). Anaesthesia was maintained with N2O and sevoflurane. The mean arterial blood pressure was maintained at 60 mmHg for 90 min. Measurements included arterial ketone body ratio (AKBR-acetoacetate/3-hydroxybutyrate), SGOT, SGPT, LDH, blood glucose and blood gases were made. Measurements were taken before hypotension, 60 min and 90 min after starting hypotension, 60 min after recovery from hypotension and on the post-operative day. AKBR showed no significant change. SGOT, SGPT and LDH were within normal limits. Controlled hypotension induced with TMP, TNG or PGE1 under sevoflurane anaesthesia in surgical patients did not cause hepatocellular damage.

Adult↗

PubMed1999

Splanchnic perfusion during controlled hypotension with haemodilution under isoflurane anaesthesia in elderly patients.

We investigated the effects of controlled hypotension with haemodilution under isoflurane anaesthesia on splanchnic perfusion in elderly patients. We determined the intramucosal pH using gastric tonometry in 28 patients scheduled for hip surgery. Patients without cardiac disease were assigned to two groups according to age. Group A (adult patients, n = 14) included patients aged less than 60 years (range 29-58 years, 47 +/- 11 years, mean +/- SD) and group B (elderly patients, n = 14) more than 65 years (68-78 years, 72 +/- 5 years). Anaesthesia was maintained with N2O-O2-isoflurane. After induction of anaesthesia, haemodilution was produced by drawing 800-1000 mL of blood and replacing it with the same amount of hydroxyethyl starch. Final haematocrit values were 23-24% in all groups. Controlled hypotension was induced with prostaglandin E1 (PGE1) and mean blood pressure was maintained at approximately 60 mmHg for approximately 80 min. Measurements, including gastric intramucosal pH (pHi), arterial blood pH (pHa) and serum lactate were measured before haemodilution (T0), after haemodilution (T1), 80 min after starting hypotension (T2), 60 min after recovery from hypotension (T3) and on the 1st post-operative day (T4). The values of pHa and lactate showed no change in the groups throughout the time course. The gastric pHi values showed significant decreases from 7.418 +/- 0.035 to 7.334 +/- 0.024 (P < 0.05) in group A and from 7.428 +/- 0.029 to 7.320 +/- 0.039 (P < 0.05) in group B after haemodilution, while no further decreases were found at 80 min after starting the hypotension (7.329 +/- 0.038 in group A and 7.322 +/- 0.031 in group B) and 60 min after recovery from hypotension (7.331 +/- 0.029 in group A and 7.328 +/- 0.034 in group B). It can be concluded that moderate haemodilution under isoflurane anaesthesia might impair splanchnic perfusion in adult and elderly patients. The addition of controlled hypotension with PGE1 or an increase in age did not further impair splanchnic perfusion nor the splanchnic oxygen supply.

Adult↗

PubMed1999

Comparative analysis of systemic and coronary hemodynamics during sevoflurane- and isoflurane-induced hypotension in dogs.

We studied the effects of sevoflurane on myocardial contractility and systemic and coronary hemodynamics, as compared with the effects of isoflurane in dogs under the same cardiac work conditions. Sixteen mongrel dogs were anesthetized with alpha-chloralose. Heart was paced at 100 beats/min after producing a complete atrioventricular (A-V) block. Controlled hypotension to a mean arterial pressure (MAP) of 60 mm Hg was induced and maintained by inhalation of either anesthetic, lasting for 60 min. Measurements were made at baseline, 15 min (T1), and 60 min (T2) after starting hypotension, and 30 min after discontinuing equihypotension (T3). Although left ventricular systolic segment shortening (%SS) decreased approximately 20% in both groups, cardiac output (CO) decreased only in sevoflurane during equihypotension (-27.6% at T2). Sevoflurane decreased the coronary blood flow (CBF; -34.8% at T2) with no significant change of coronary vascular resistance (CVR), whereas isoflurane produced a significant decrease in CVR resulting in no change of CBF despite of decreased coronary perfusion pressure (-37.4% at T2). These systemic and coronary vascular effects were continued even at T3. In conclusion, myocardial depressant effects were comparable between sevoflurane and isoflurane. Both systemic and coronary vasodilatory effects of isoflurane are greater than those of sevoflurane.

Anesthetics, Inhalation↗

PubMed1999

Effects of clonidine on human middle cerebral artery flow velocity and cerebrovascular CO2 response during sevoflurane anesthesia.

The present study was designed to evaluate the effects of clonidine on human middle cerebral artery flow velocity and the cerebrovascular CO2 response during sevoflurane anesthesia using transcranial Doppler ultrasonography. The subjects were nine awake volunteers (group A) and 18 patients receiving oral preanesthetic medication of clonidine, 3-4 mcg/kg, (group C), or placebo (group S). In groups C and S, anesthesia was induced with inhalation of sevoflurane-nitrous oxide. After tracheal intubation, anesthesia was maintained with 2% end-tidal sevoflurane alone. In group A, each volunteer wore a nose clip and breathed through a mouthpiece using a Mapleson D breathing system. The time-mean middle cerebral artery flow velocity (Vmca) was measured during hypocapnia, normocapnia, and hypercapnia. In groups S and C, the Vmca values were significantly lower than those of group A at each PaCO2 level. The Vmca value of group C was significantly lower than that of group S in hypercapnia, but not in hypocapnia or normocapnia. The CO2 response slope of group C was significantly lower than those of groups A and S. The results indicate that clonidine, administered as an oral preanesthetic medication, reduces Vmca in hypercapnia but not in hypocapnia or normocapnia, and reduces the cerebrovascular CO2 response during sevoflurane anesthesia.

Adrenergic alpha-Agonists↗

PubMed1999

Propofol inhibits muscarinic acetylcholine receptor-mediated signal transduction in Xenopus Oocytes expressing the rat M1 receptor.

The effects of propofol, 2,6-diisopropylphenol, an intravenous general anesthetic, on signal transduction mediated by the rat M1 muscarinic acetylcholine (ACh) receptor (M1 receptor) were examined in electrophysiological studies by analyzing receptor-stimulated, Ca2+-activated Cl--current responses in the Xenopus oocyte expression system. In oocytes expressing the M1 receptor, ACh induced the Ca2+-activated C1- current, in a dose-dependent manner (EC50= 114 nM). Propofol (5-50 microM) reversibly and dose-dependently inhibited induction of the Ca2+-activated Cl- current by ACh (100 nM) (IC50=5.6 microM). To determine a possible site affected by propofol in this signal transduction, we tested the effects of this anesthetic (10 microM) on the activation of current by injection of CaCl2 and aluminum fluoride (AlF4-). Propofol did not affect activation of the current by the intracellular injected Ca2+, or activation of the current by the intracellular injected AlF4-. These results indicate that propofol does not affect G protein, the inositol phosphate turnover, release of Ca2+ from Ca2+ store or the Ca2+-activated Cl- channel. Propofol apparently inhibits the M1 receptor-mediated signal transduction at the receptor site and/or the site of interaction between the receptor and associated G protein.

Acetylcholine↗

PubMed1999

Malignant pheochromocytoma with multiple hepatic metastases treated by chemotherapy and transcatheter arterial embolization.

A 62-year-old Japanese male developed multiple hepatic metastases two years after resection of pheochromocytoma of the right adrenal gland. Transcatheter arterial embolization (TAE) was performed for the purpose of the treatment of hepatic metastases resistant to 27 cycles of combined chemotherapy consisting of cyclophosphamide, vincristine, and dacarbazine. After TAE, the hepatic metastatic lesions decreased in size and hypertension passed its crisis. The present case suggests the utility of TAE for multiple hepatic metastases under careful blood pressure monitoring.

Adrenal Gland Neoplasms↗

PubMed1999

[Endoscopic resection of the thoracic sympathetic trunk for the treatment of frequent syncopal attack of idiopathic long QT syndrome].

A 22 year old man was diagnosed as having Jervell and Lange-Nielsen syndrome (JLNS), which includes a prolonged QTc, congenital neural deafness, and syncopal attacks or sudden death. In spite of medication with beta blocker, syncopal attack increased in frequency since his sister suddenly had died of JLNS. Because left stellate ganglion block improved the QTc dispersion, left cardiac sympathectomy was scheduled under the video-assisted thoracic surgery. After the premedication with midazolam, anesthesia was induced with thiamylal, and maintained with nitrous oxide, sevoflurane, and fentanyl. Serious arrhythmias were not observed throughout the perioperative period. Sympathetic trunk was successfully resected from the top of 1st ganglion to the bottom of 4th ganglion of left thoracic sympathetic trunk. Horner's sign did not appear after the surgery. Although the shortening of QTc was not significant, QTc dispersion during exercise was improved, and syncopal attack was not observed until 6 months after the surgery.

Adult↗

PubMed1999

[Epidural abscess associated with epidural block in a patient with immunosuppressive disease].

A patient with myeloproliferative disorders and diabetes mellitus received epidural block twice for treatment of the low back and leg pain. The drugs used were 1% mepivacaine 4 ml for the first and 1% mepivacaine 6 ml and dexamethazone 4 mg for the second on the next day. Epidural abscess was noticed 2 days later when pus was aspirated through a block needle. MRI revealed the abscess localized at L5/S1. Intensive treatment including epidural drainage and antibiotics succeeded in healing the abscess. Use of epidural block for immunocompromized patients should be decided carefully.

Abscess↗

PubMed1999

[Monitored anesthesia care for a patient with malignant pheochromocytoma].

Monitored anesthesia care (MAC) is being increasingly used in the 1990s for a wide variety of diagnostic and therapeutic procedures. The primary objective in providing MAC is to ensure patients' comfort and safety, whether in the operating room or in other places. We experienced MAC for a patient with pheochromocytoma. A 63-year-old man with hepatic metastasis of malignant pheochromocytoma, received transcatheter arterial embolization (TAE) in the angiographic room. Hypertension and ventricular arrhythmia occurred during the hepatic arterial embolization. However, we successfully controlled the hemodynamic changes using phentolamine and propranolol under the close monitoring. He showed an uneventful recovery during postoperative period except for mild hypotension on the third day which needed temporary norepinephrine infusion.

Adrenal Gland Neoplasms↗

PubMed1999

Systemic and coronary hemodynamic effects of JTV-506, a novel potassium channel opener, in conscious dogs: comparison with cromakalim and nicorandil.

We compared the coronary and systemic hemodynamic effects of JTV-506, a novel potassium channel opener, with those of cromakalim and nicorandil in chronically instrumented conscious dogs. Experiments were performed in 7 dogs which had undergone the implantation of flow probes on the ascending aorta and left circumflex coronary artery, and of catheters into the descending thoracic aorta and left ventricular cavity, respectively. On different days at least 10 days after the implantation, dogs were randomly assigned to the doses of JTV-506 (2, 5 or 10 microg/kg), cromakalim (10 microg/kg), nicorandil (0.2 mg/kg) or glibenclamide (5 mg/kg) plus JTV-506 (5 microg/kg). Each dose of the three drugs produced dose-related increases in heart rate, coronary blood flow, cardiac output, dP/dt(max) and %SS, and produced decreases in arterial blood pressure, left ventricular systolic pressure, and coronary and systemic vascular resistance. JTV-506 at doses of 2 and 5 microg/kg reduced arterial blood pressure only slightly as compared to its significant coronary vasodilating effect. An increase in myocardial oxygen consumption (as estimated by pressure-work index) was also observed in response to each dose of three drugs. At doses that reduced coronary vascular resistance by 75%, JTV-506 produced a greater increase in coronary blood flow, as compared with cromakalim and nicorandil. JTV-506 has the longest duration of action as compared with cromakalim and nicorandil. Glibenclamide pretreatment completely abolished the effects of JTV-506 on coronary and systemic hemodynamics. These results suggest that JTV-506 is relatively more potent in the coronary bed with minimal systemic influence, and exerts a longer time course of action.

Animals↗

PubMed1998

Glutathione downregulates the phosphorylation of I kappa B: autoloop regulation of the NF-kappa B-mediated expression of NF-kappa B subunits by TNF-alpha in mouse vascular endothelial cells.

Nuclear factor-kappa B (NF-kappa B) regulates gene expression upon immune and inflammatory responses. It has been demonstrated that redox regulation by thiols is involved in the signal-transduction cascade. In this study, we examined the effect of glutathione (GSH) on the NF-kappa B activity and the expression of NF-kappa B subunits induced by tumor necrosis factor-alpha (TNF-alpha) using mouse vascular endothelial cells. GSH inhibited the serine phosphorylation of I kappa B-alpha by TNF-alpha, leading to the downregulation of NF-kappa B-DNA binding activity followed by decreased expression of p65/p50 and I kappa B mRNAs. The regulation of the autoregulatory loop for the NF-kappa B activation and the expression of NF-kappa B subunits may be important in endothelial cells in response to cytokines.

Animals↗

PubMed1998

Effects of PKC and PKA phosphorylation on desensitization of nicotinic acetylcholine receptors.

The present study was designed to assess the effect of protein kinase C (PKC) and cAMP-dependent protein kinase (PKA) on desensitization of Torpedo acetylcholine (ACh) receptors by analyzing summated macroscopic currents in an outside-out patch-clamp configuration. Normal ACh receptors desensitized with a fast (6 ms) and slow time constant (104 ms). There was no significant difference in the current decay time between normal ACh receptors and mutant ACh receptors that possibly mimics PKC phosphorylation of the receptors. The selective PKC inhibitor, PKCl, prolonged the rate of desensitization of normal ACh receptors, and the similar effect was obtained with mutant ACh receptors lacking PKC phosphorylation sites. Phosphorylation of normal ACh receptors by the catalytic subunit of PKA or mutant ACh receptors that possibly mimic PKA phosphorylation of the receptors increased the rate of desensitization, but, in contrast, the receptors lacking PKA phosphorylation sites prolonged the current decay time. The results of the present study demonstrate that PKC or PKA phosphorylation of ACh receptors accelerates the rate of desensitization.

Animals↗

PubMed1998

Nicotinic receptors are regulated by protein kinase C activated via a nicotinic receptors-mediated signaling pathway.

The present study was conducted to examine the effect of protein kinase C (PKC) on nicotinic acetylcholine (ACh) receptors expressed in Xenopus oocytes by monitoring single-channel currents. In an outside-out patch-clamp configuration, ACh (1 microM) elicited single channel currents with a slope conductance of 31 pS (control) in normal Torpedo ACh receptors. Activation of PKC via an endogenous phosphatidylinositol signaling pathway elevated the slope conductance to 41 pS, which effect was blocked by the selective PKC inhibitor, staurosporine. Mutant ACh receptor channels, which mimic PKC phosphorylation of the receptors, exhibited a slope conductance of 41 pS. Notably, pretreatment with a higher concentration of ACh (100 microM) caused an increase in the slope conductance of the channels for 1 microM ACh (43 pS), which was the same level as obtained with either PKC activation or mutant ACh receptors, and this effect was also inhibited by staurosporine. In addition, the control slope conductance was reduced by PKC inhibitor peptide (24 pS), which corresponded to that obtained with another mutant ACh receptors lacking PKC phosphorylation sites (18 pS). Mouse muscle ACh receptors were also regulated by the same mechanism. The results of the present study suggest that ACh activates PKC via nicotinic ACh receptors, which alternatively, modulates the properties of the receptor channels.

Animals↗