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Biomedical subjects

Y Ikeuchi

Publications and source records attributed to Y Ikeuchi.

At least 19 recordsLinked to original sources
PubMed2001

Promotion of radiation-induced formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by nitro 5-deazaflavin derivatives.

6-Nitro- and 8-nitro-5-deazaflavin derivatives have been found to enhance prominently the radiation-induced formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) at the expense of formation of 2,6-diamino-4-hydroxy-5-formamidopyrimidine nucleosides (FapydGuo) both in deaerated and in N(2)O saturated aqueous 2'-deoxyguanosine solutions. The radiosensitizing capacity of a 9-nitro-5-deazflavin derivative was observed only in the N(2)O saturated aqueous solutions.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2001

S-myotrophin promotes the hypertrophy of myotube as insulin-like growth factor-I does.

We have reported previously that a novel muscle cell growth factor, having a structure of a peptide with sugar chains, was successfully purified from porcine skeletal muscle. It was named s-myotrophin. To determine the role of s-myotrophin in skeletal muscle growth, the effect of s-myotrophin on primary cultured chick skeletal muscle cells (composed almost totally of multinucleated myotubes) was investigated by comparing s-myotrophin with Insulin-like growth factor-I (IGF-I). Both s-myotrophin and IGF-I significantly increased creatine kinase activity of the cultures; both substances gave similar responses. Intracellar protein content was also increased by the addition of these factors. The content of myosin and actin in s-myotrophin treated culture in the differentiation medium was significantly higher than that of the control (unstimulated). The content of those proteins in IGF-I treated culture was also higher than that of control, but the differences were not statistically significant. Immunoblot analysis confirmed that the amounts of myosin and actin in the myocytes were greatly increased by s-myotrophin stimulation and also by IGF-I stimulation. Morphological observations using an anti-desmin antibody staining procedure demonstrated that the size of both s-myotrophin and IGF-I treated myotubes was appreciably larger than that of control myotubes. These results suggest that s-myotrophin is a potent mediator of skeletal muscle cell hypertrophy thorough the accumulations of muscle structural proteins.

Actins↗
PubMed2001

Pressure-induced denaturation of monomer beta-lactoglobulin is partially irreversible: comparison of monomer form (highly acidic pH) with dimer form (neutral pH).

This study was conducted to assess the effect of high hydrostatic pressure on monomer beta-lactoglobulin (BLg) at acid pH by fluorescence spectroscopy under pressure and by circular dichroism (CD) and (1)H NMR spectroscopies after release of pressure. The intrinsic (tryptophan) fluorescence measurement and the study of 8-anilinonaphthalene-1-sulfonate (ANS) binding to BLg indicated that at pH 2.0 the recovery of center of spectral mass or ANS fluorescence was almost complete upon pressure release. No difference in (1)H NMR spectra was observed between pressurized and unpressurized BLg. In addition, NMR detection of the H/D exchange of aromatic protein indicated that the conformation of the vicinity of tryptophan residues could be refolded almost completely after release of pressure. These results seemingly confirm that the pressure-induced denaturation of BLg at pH 2.0 is reversible. However, cis-parinaric acid binding ability of pressurized BLg was largely lost, although its retinol binding ability was the same as its unpressurized one. Furthermore, CD spectra of the far-UV region and 2D NMR spectra evidently revealed the difference in the conformation of the molecule between unpressurized and pressurized BLg. These results are interpreted as an existence of partially fragile structure in the BLg molecule by high pressure.

Circular Dichroism↗
PubMed2000

A cortical motor region that represents the cutaneous back muscles in the macaque monkey.

A cortical motor region that represented the cutaneous muscles on the back was identified on the medial wall of the frontal lobe in the macaque monkey. In this region, neurons responded to somatosensory stimuli such as light touch or squeezing of the back skin, and intracortical microstimulation elicited contraction of the back skin. Such a region was located primarily on the dorsal bank of the cingulate sulcus, corresponding to the dorsal cingulate motor area.

Animals↗
PubMed2000

Quantification of the degradation products of sevoflurane using four brands of CO2 absorbent in a standard anesthetic circuit.

PURPOSE: CO(2) absorbents convert sevoflurane to fluoromethyl-2,2-difluoro-1-(trifluoromethyl) vinyl ether (compound A), whose toxicity in rats raises concern regarding the safety of sevoflurane in a low-flow system. The type of CO(2) absorbent is one of factors that affect compound A concentration in the anesthetic circuit. The aim of the present study was to investigate the concentration of compound A in an anesthetic model circuit following the use of different brands of soda lime and Baralyme. METHODS: We measured the concentrations of compound A in four different brands of CO(2) absorbent using a low-flow (1 l.min(-1) fresh gas) model circuit in which 2% sevoflurane was circulated. Sodasorb II, Baralyme, Sofnolime and Wakolime-A were used as CO(2) absorbents. The concentration of compound A was measured hourly, and the temperature of the CO(2) absorbent was monitored. RESULTS: The maximum concentration of compound A in the circuit was highest for Baralyme (25.5 +/- 0.6 ppm) (mean +/- SD), followed by Sodasorb II (18.9 +/- 1.6 ppm), Wakolime-A (16.1 +/- 0.7 ppm), and Sofnolime (15.8 +/- 1.4 ppm). The maximum temperature was 50.8 +/- 1.3 degrees C for Baralyme, 48.8 +/- 1.3 degrees C for Wakolime-A, 47.0 +/- 1.4 degrees C for Sodasorb II, and 43.5 +/- 3.9 degrees C for Sofnolime. CONCLUSION: The relative concentrations of compound A in the low-flow circuit were Baralyme > Sodasorb II > Wakolime-A = Sofnolime.

Journal Article↗
PubMed2000

Synthesis and antitumor activities of novel 5-deazaflavin-sialic acid conjugate molecules.

6-Nitro-5-deazaflavin derivatives bearing O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha- and beta-D-galacto-non-2-ulopyranosylonate)alkyl group (sialosylalkyl group) at N(3) or N(10) and 8-amino-5-deazaflavin substituted with the sialosylalkyl group at the amino group were synthesized and their physicochemical properties as well as antitumor effects on KB and L1210 cells have been investigated. The configurations of the glycosides were determined by 1H NMR and rate of hydrolysis of the glycosidic bond. It has been found that these conjugate molecules show significant antitumor activities. Combination of an 8-amino-5-deazaflavin with the sialosylalkyl group have been found to give rise to significant increase in antitumor activities of the compound. Antitumor effects of 6-nitro-5-deazaflavin-sialic acid conjugate molecules were similar or rather weak in comparison with those of the 6-nitro-5-deazaflavin derivatives without sialosylalkyl group.

Animals↗
PubMed2000

The effects of prolonged low-flow sevoflurane anesthesia on renal and hepatic function.

UNLABELLED: We assessed the effects of prolonged low-flow sevoflurane anesthesia on renal and hepatic functions by comparing high-flow sevoflurane with low-flow isoflurane anesthesia. Thirty patients scheduled for surgery of > or =10 h in duration randomly received either low-flow (1 L/min) sevoflurane anesthesia (n = 10), high-flow (6-10 L/min) sevoflurane anesthesia (n = 10), or low-flow (1 L/min) isoflurane anesthesia (n = 10). We measured the circuit concentrations of Compound A and serum fluoride. Renal function was assessed by blood urea nitrogen, serum creatinine, creatinine clearance, and urinary excretion of glucose, albumin, protein, and N:-acetyl-beta-D-glucosaminidase. The hepatic function was assessed by serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase, and total bilirubin. Compound A exposure was 277 +/- 120 (135-478) ppm-h (mean +/- SD [range]) in the low-flow sevoflurane anesthesia. The maximum concentration of serum fluoride was 53.6 +/- 5.3 (43.4-59.3) micromol/L for the low-flow sevoflurane anesthesia, 47.1 +/- 21.2 (21.4-82.3) micromol/L for the high-flow sevoflurane anesthesia, and 7.4 +/- 3.2 (3.2-14.0) micromol/L for the low-flow isoflurane anesthesia. Blood urea nitrogen and serum creatinine were within the normal range, and creatinine clearance did not decrease throughout the study period in any group. Urinary excretion of glucose, albumin, protein, and N:-acetyl-beta-D-glucosaminidase increased after anesthesia in all groups, but no significant differences were seen among the three groups at any time point after anesthesia. Lactate dehydrogenase and alkaline phosphatase on postanesthesia Day 1 were higher in the high-flow sevoflurane group than in the low-flow sevoflurane group. However, there were no significant differences in any other hepatic function tests among the groups. We conclude that prolonged low-flow sevoflurane anesthesia has the same effect on renal and hepatic functions as high-flow sevoflurane and low-flow isoflurane anesthesia. IMPLICATIONS: During low-flow sevoflurane anesthesia, intake of Compound A reached 277 +/- 120 ppm-h, but the effect on the kidney and the liver was the same in high-flow sevoflurane and low-flow isoflurane anesthesia.

Acetylglucosaminidase↗
PubMed2000

Excitatory cortical inputs to pallidal neurons via the subthalamic nucleus in the monkey.

How the motor-related cortical areas modulate the activity of the output nuclei of the basal ganglia is an important issue for understanding the mechanisms of motor control by the basal ganglia. In the present study, by using awake monkeys, the polysynaptic effects of electrical stimulation in the forelimb regions of the primary motor and primary somatosensory cortices on the activity of globus pallidus (GP) neurons, especially mediated by the subthalamic nucleus (STN), have been characterized. Cortical stimulation induced an early, short-latency excitation followed by an inhibition and a late excitation in neurons of both the external and internal segments of the GP. It also induced an early, short-latency excitation followed by a late excitation and an inhibition in STN neurons. The early excitation in STN neurons preceded that in GP neurons. Blockade of STN neuronal activity by muscimol (GABA(A) receptor agonist) injection resulted in abolishment of both the early and late excitations evoked in GP neurons by cortical stimulation. At the same time, the spontaneous discharge rate of GP neurons decreased, pauses between the groups of spikes of GP neurons became prominent, and the firing pattern became regular. Injection of (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) [N-methyl-D-aspartate (NMDA) receptor antagonist], but not 1,2,3, 4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium [NBQX (non-NMDA receptor antagonist)], into the STN attenuated the early and late excitations in GP neurons, suggesting that cortico-subthalamic transmission is mediated mainly by NMDA receptors. Interference with the pallido-subthalamic transmission by bicuculline (GABA(A) receptor antagonist) injection into the STN made the inhibition distinct without affecting the early excitation. The present results indicate that the cortico-subthalamo-pallidal pathway conveys powerful excitatory effects from the motor-related cortical areas to the GP with shorter conduction time than the effects conveyed through the striatum.

Animals↗
PubMed1999

Anthropogenic radionuclides in seawater of the Far Eastern Seas.

Large quantities of radioactive wastes have been dumped in the Far Eastern Seas by the former Soviet Union and the Russian Federation, and small amounts of radioactive wastes have been dumped by Japan and the Republic of Korea. In order to investigate the concentrations of anthropogenic radionuclides in the nine dumping areas, a second expedition was conducted in 1995 by Japan, the Republic of Korea, the Russian Federation and IAEA, following the first expedition in 1994. The results show that 137Cs, 90Sr and 239 + 240Pu concentrations in surface and bottom waters at dumping areas do not significantly differ from the values observed in background areas, and from historical values. There is no clear effect of possible contamination due to radioactive waste dumping. The concentrations and water column inventories of 137Cs, 90Sr and 239 + 240Pu in the Far Eastern seas are controlled by physical oceanic processes such as horizontal transport and biogeochemical processes such as scavenging.

Cesium Radioisotopes↗
PubMed1999

Marine radioactivity assessment of Mururoa and Fangataufa atolls.

The International Atomic Energy Agency (IAEA) carried out an international project. 'The Study of the Radiological Situation at the Atolls of Mururoa and Fangataufa' with the aim of assessing the present and future radiological situation at the atolls and making recommendations for either monitoring or remedial actions if they are deemed necessary. The paper concentrates on marine radioactivity aspects and gives an estimation of present radionuclide concentrations in water, sediment and biota of the Mururoa and Fangataufa lagoons and the surrounding ocean. The dominant radionuclide in both lagoons is Pu in sediments (the total inventory is approximately 30 TBq). A decline in radionuclide concentrations has been observed in recent years in lagoon water, with the exception of 3H and 90Sr, for which a contribution from underground sources is to be expected. Radionuclide concentrations in biota from the lagoons and the surrounding ocean are low and consistent with previous measurements. The observed radionuclide concentrations in both lagoons imply that no radiological risk exists for hypothetical inhabitants of Mururoa and Fangataufa Atolls.

Animals↗
PubMed1999

Radionuclide concentrations in underground waters of Mururoa and Fangataufa Atolls.

In 1997 an expedition to Mururoa and Fangataufa Atolls was carried out to sample underground waters from cavity-chimneys and carbonate monitoring wells. The aim of this study was to determine the prevailing concentration and distribution status of radionuclides. Elemental analysis of interstitial waters was carried out in the water fraction as well as in particles collected at 11 underground monitoring wells. 238Pu, 239,240Pu, 241Am, 137Cs, 90Sr, 3H, 125Sb, 155Eu and 60Co were analyzed in both fractions by alpha-, beta- and gamma-spectrometry. Measurements showed that at 60% of the sites, pH and Eh seemed to be related to tidal cycles; in contrast HTO was constant during the sampling time. Interstitial waters from carbonates and transition zones shared similar chemical composition that were not different from that of the surrounding seawater. Waters collected from basalt cavities left after nuclear tests, (Aristee and Ceto) have a different chemical signature characterized by a deficiency in Mg, K and SO4 as well as enrichment in Sr, Si, Al and Cl compared to the rest of the stations. Radionuclide concentrations present in both, water and particulate fractions, were significantly higher at Ceto and Aristee than at any other monitoring wells, except for Fuseau and Mitre monitoring wells (Fangataufa) where values similar to Ceto were found (e.g. 239,240Pu: > 20 mBq g-1). Considering that Pu isotopes showed high Kd values compared to non-sorbing radionuclides such as 3H, 90Sr and 137Cs it is very unlikely that migration from cavities to monitoring wells accounts for the concentration of Pu isotopes and Am at Fuseau 30 and Mitre 27. Perhaps the contact of lagoon waters with the well before sealing could be a possible source of the transuranics found at these sites. The 238Pu/239,240Pu ratios measured in the particles were similar to that of the lagoon (0.38), thus supporting this hypothesis. The fact that transuranics were found only in the particle fraction, in the water (colloids included) these radionuclides were below detection limits, may be accounted for the conspicuous quantity of iron oxy-hydroxides present in the particulate fraction that under the appropriate redox conditions may be interacting selectively with elements in solution (scavenging) resulting in the enhanced transuranic signal. While transuranics have been found in places of their origin, radionuclides with low Kd values (3H, 90Sr, 137Cs) have already been transported to monitoring wells, as well as to the atolls' lagoons and the open ocean.

Nuclear Warfare↗
PubMed1999

Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine under anaerobic conditions by reductively activated nitro 5-deazaflavin derivatives.

Electrolytically reduced 6- and 8-nitro-5-deazaflavin derivatives have been found to interact to react specifically with guanine base by means of cyclic voltammetry. Electrolytic reductions of 6- and 8-nitro-5-deazaflavin derivatives in the presence of the 2'-deoxyguanosine under anaerobic conditions resulted in prominent formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1998

The enhancing of a cysteine proteinase activity at acidic pH by protein engineering, the role of glutamic 50 in the enzyme mechanism of caricain.

Carica papaya produces four cysteine proteinases. Calculations show that the Cys25, His159 essential ion pair is fully ionised at pH 2.99, where activity cannot be detected, but apparently an additional ionisation with a pKa of 4 is essential for activity (an electrostatic switch). Caricain (EC 3.4.22.30) wt and D158E genetic backgrounds were used to study the contribution of E50A to activity. E50 or E135 are candidates for the switch, E50A would be expected to reduce activity. However, activity increased at pH 5.0 in both backgrounds and at the pH optimum in D158E E50A but decreased slightly in the wt background. This challenges the hypothesis of an electrostatic switch.

Binding Sites↗
PubMed1998

A modified microsyringe for extracellular recording of neuronal activity.

We describe a modified Hamilton microsyringe that allows extracellular recording of neuronal activity and subsequent injections. It is assembled with a Hamilton removable needle and a syringe for injection, a Teflon-coated tungsten wire for recording, and polyimide tubing as a sheath. The device is inexpensive and easy to handle in anatomical and physiological experiments in awake monkeys.

Animals↗
PubMed1998

Synthesis and evaluation of nitro 5-deazaflavin-pyrrolecarboxamide(s) hybrid molecules as novel DNA targeted bioreductive antitumor agents.

A series of 6-nitro-5-deazaflavins bearing at N(3) or N(10) position the pyrrolecarboxamide(s) group as DNA minor groove binder has been synthesized. These hybrid molecules show similar redox properties to those of 6-nitro-5-deazaflavins with no pyrrolecarboxamide(s) group, suggesting that they generate stable one- and two-electron reduction product(s). Electrolytic reductions of the hybrid molecules were carried out at a controlled potential under anaerobic conditions in the presence of plasmid pBR322 DNA. Significant conversions of the supercoiled circular pBR322 DNA (form I) to the open circular DNA (form II) have been found by treatment with the reductively activated 6-nitro-5-deazaflavin derivatives. Their DNA damaging effects have been found to be enhanced as the number of pyrrolecarboxamide group as the DNA binder increases. Antitumor activities of the hybrid molecules towards KB and L1210 cells were evaluated in vitro. It has been found that the antitumor effects of the compounds on KB cells slightly change and those on L1210 cells decrease as the number of the pyrrolecarboxamide group increases. These results reveal that the combination of 6-nitro-5-deazaflavin molecule with the pyrrolecarboxamide(s) group increase the DNA binding properties of the compounds, giving rise to promoted DNA damaging effects, and also suggest that the combination would affect the capacity of the compounds to act as the substrate for intracellular reductases and/or the cellular uptake of the compounds.

Animals↗
PubMed1998

Effects of the water content of soda lime on compound A concentration in the anesthesia circuit in sevoflurane anesthesia.

BACKGROUND: Sevoflurane anesthesia is usually performed with fresh gas flow rates greater than 2 l/min due to the toxicity of compound A in rats and limited clinical experience with sevoflurane in low-flow systems. However, to reduce costs, it would be useful to identify ways to reduce compound A concentrations in low-flow sevoflurane anesthesia. This goal of this study was to determine if compound A concentrations can be reduced by using soda lime with water added. METHODS: Low-flow sevoflurane anesthesia (fresh gas flow of 1 l/min) was performed in 37 patients using soda lime with water added (perhydrated soda lime) or standard soda lime as the carbon dioxide (CO2) absorbent. The soda lime was not changed between patients, but rather was used until CO2 rebreathing occurred. The perhydrated soda lime was prepared by spraying 100 ml distilled water onto 1 kg fresh soda lime, and water was added only when a new bag of soda lime was placed into the canister. Compound A concentrations in the circle system, soda lime temperatures, inspired and end-tidal CO2 and end-tidal sevoflurane concentrations, and CO2 elimination by the patient were measured during anesthesia. RESULTS: Compound A concentrations were significantly lower for the perhydrated soda lime (1.9 +/- 1.8 ppm; means +/- SD) than for the standard soda lime (13.9 +/- 8.2 ppm). No differences were seen between the two types of soda lime with regard to the temperature of the soda lime, end-tidal sevoflurane concentrations, or CO2 elimination. Compound A concentration decreased with the total time of soda lime use for both types of soda lime. The CO2 absorption capacity was significantly less for perhydrated soda lime than for standard soda lime. CONCLUSIONS: Compound A concentrations in the circuit can be reduced by using soda lime with water added. The CO2 absorption capacity of the soda lime is reduced by adding water to it, but this should not be clinically significant.

Anesthesia, Closed-Circuit↗
PubMed1998

Rough surfaced smooth endoplasmic reticulum in rat and mouse cerebellar Purkinje cells visualized by quick-freezing techniques.

The in vivo structure of the smooth endoplasmic reticulum (ER) was visualized in rat and mouse cerebellar Purkinje cells by using quick-freezing techniques followed by freeze-substitution for ultrathin-sectioning or freeze-fracturing and deep-etching for replicas. High magnification electron microscopy of the ultrathin sections revealed a surprising finding that all the smooth ER are apparently rough surfaced, and heavily studded with a large number of small dense projections. In the soma the smooth ER appears to be similar to its rough counterpart, except that the projections are slightly smaller, less electron dense and less protrusive on the ER membranes than the ribosomes. The projections were short rectangles, 20 x 20 x 6 nm3 in size, covering the cytoplasmic surface of the smooth ER in a checker-board manner where closely packed. After freeze-etching and replication, they appeared to be composed of four subparticles, surrounding a central channel. Thus the projections are very similar to the foot structure (ryanodine receptor) of the sarcoplasmic reticulum. Furthermore, they were distributed exclusively in the ER compartment and were highly concentrated especially in the smooth ER. This localization of the projections coindides with the intracellular distribution of the inositol 1,4,5-trisphosphate (IP3) receptor determined by quantitative immunogold electron microscopy. These findings would suggest that the projections are tetramers of IP3 receptor molecules and could be used as a morphological marker for the smooth ER in Purkinje cells, which spreads from the soma to the axon and dendrite, up to the tips including the spines. In Purkinje cells tubular smooth ER runs freely in a serpentine fashion or are intertwined to make large membraneous tangles without forming cisternal stacks. It is highly probable that the ER cisternal stacks do not exist naturally in Purkinje cells but are formed artificially during the various procedures for chemical fixation.

Animals↗