Biomedical subjects

A Furukawa

Publications and source records attributed to A Furukawa.

At least 19 recordsLinked to original sources

PubMed2006

High maneuverability guidewire with functionally graded properties using new superelastic alloys.

Nitinol shape memory alloys (SMAs) are attracting considerable attention as core materials for medical guidewires because of their excellent flexibility and shape retention. However, since Nitinol guidewires possess low rigidity, the pushability and torquability of the guidewires are insufficient. On the other hand, although guidewires made of stainless steel have high pushability, plastic deformation occurs easily. We have developed a new class of superelastic guidewires with functionally graded properties from the tip to the end by using new SMA core materials such as Cu-Al-Mn-based or Ni-free Ti-Mo-Sn SMAs. The tip portion of the guidewire shows excellent superelasticity (SE), while the body portion possesses high rigidity. These functionally graded characteristics can be realized by microstructural control. These guidewires with functionally graded properties show excellent pushability and torquability and are considerably easier to handle than conventional guidewires with Nitinol or stainless steel cores. Moreover, a metallic catheter using a Ni-free Ti-based SMA with high biocompatibility is introduced.

Alloys↗

PubMed2005

Hippocampal synthesis of estrogens and androgens which are paracrine modulators of synaptic plasticity: synaptocrinology.

Hippocampal pyramidal neurons and granule neurons of adult male rats are equipped with a complete machinery for the synthesis of pregnenolone, dehydroepiandrosterone, testosterone, dihydrotestosterone and 17beta-estradiol. Both estrogens and androgens are synthesized in male hippocampus. These brain steroids are synthesized by cytochrome P450s (P450scc, P45017alpha and P450arom), hydroxysteroid dehydrogenases and reductases from endogenous cholesterol. The expression levels of enzymes are as low as 1/300-1/1000 of those in endocrine organs. Synthesis is dependent on the acute Ca(2+) influx upon neuron-neuron communication via NMDA receptors. Estradiol is particularly important because estradiol rapidly modulates neuronal synaptic transmission such as long-term potentiation via synaptic estrogen receptors. Xenoestrogens may also act via estrogen-driven signaling pathways.

Androgens↗

PubMed2005

Numerical simulation studies of the convective instability onset in a supercritical fluid.

Numerical simulation studies in 2D with the addition of noise are reported for the convection of a supercritical fluid, 3He , in a Rayleigh-Bénard cell. The noise addition is to accelerate the instability growth after starting the heat flow across the fluid, so as to bring simulations into better agreement with published experimental observations. Homogeneous temperature noise and spatial longitudinal periodic temperature variations in either top or bottom plates were programmed into the simulations. The second method was the most effective in speeding up the instability onset. For a small amplitude of the longitudinal perturbations, a semiquantitative agreement with the observations was obtained. The results are discussed in relation to predictions by El Khouri and Carlès.

Journal Article↗

PubMed2005

Arsenic contamination of groundwater in Nawabganj, Bangladesh, focusing on the relationship with other metals and ions.

Serious arsenic contamination of groundwater in Bangladesh has been frequently reported and is of great concern. In this research, repeated water sampling from the same 10 tubewells in Nawabganj municipality, Bangladesh, was conducted and analysed, focusing on the seasonal variation of water quality and the relationship among arsenic and other metals and ions. For the seasonal variation of water quality, arsenic and iron concentrations were higher in the rainy season in general although the tendency was not consistent and it depended on the tubewell and the time. Correlation between arsenic and iron could not be observed in this study (r = -0.01) when using all cases. This was because no correlation was observed in the higher arsenic concentration range. Arsenic removal by co-precipitation with coexisting iron is known as one of the locally applicable techniques in Bangladesh, but the result from this study suggests that some additional treatments such as the extra injection of iron should be performed in some cases, especially where the arsenic concentration is high. The correlation between arsenic and other substances was also analysed. As a result, manganese (r = 0.37), molybdenum (r = 0.33) and sulfate ion (r = -0.33) significantly correlated with arsenic (p < 0.05). The negative correlation between arsenic and sulfate ion implies the dissolution of arsenic into groundwater under reductive conditions although there are some exceptional cases.

Arsenic↗

PubMed2003

Convection in a very compressible fluid: comparison of simulations with experiments.

The time profile DeltaT(t) of the temperature difference, measured across a very compressible fluid layer of supercritical 3He after the start of a heat flow, shows a damped oscillatory behavior before steady-state convection is reached. The results for DeltaT(t) obtained from numerical simulations and from laboratory experiments are compared over a temperature range where the compressibility varies by a factor of approximately 40. First the steady-state convective heat current j(conv) as a function of the Rayleigh number Ra is presented, and the agreement is found to be good. Second, the shape of the time profile and two characteristic times in the transient part of DeltaT(t) from simulations and experiments are compared, namely (1) t(osc), the oscillatory period, and (2) t(p), the time of the first peak after starting the heat flow. These times, scaled by the diffusive time tau(D) versus Ra, are presented. The agreement is good for t(osc)/tau(D), where the results collapse on a single curve showing a power-law behavior. The simulation hence confirms the universal scaling behavior found experimentally. However for t(p)/tau(D), where the experimental data also collapse on a single curve, the simulation results show systematic departures from such a behavior. A possible reason for some of the disagreements, both in the time profile and in t(p), is discussed.

Journal Article↗

PubMed2002

Identification of a novel variant of the human NR2B gene promoter region and its possible association with schizophrenia.

N-methyl-D-aspartate (NMDA) receptor dysfunction is involved in the pathogenesis of schizophrenia. We determined the nucleotide sequence of the 5'-upstream region of the human NMDA receptor 2B (NR2B) subunit gene and identified a novel T-200G variant located in one of the Sp1 binding sites. To investigate the effect of this variant on the transcriptional activity of the hNR2B gene, we performed gene reporter assays using PC12 pheochromocytoma cells transiently transfected with luciferase reporter plasmids. In the absence of nerve growth factor (NGF), luciferase activities did not significantly differ between the two alleles and the control plasmid. However, luciferase reporter activity of the T allele was significantly up-regulated compared to that of the G allele in the presence of NGF (P = 0.0013), indicating that this polymorphic site is a critical region for NR2B gene regulation through NGF-induced Sp1-binding. A case control study showed that the frequency of the G allele (P = 0.0164) was significantly higher in 100 schizophrenics than in 100 controls. These findings suggest that the T-200G variant causes dysfunction of NMDA receptors consisting of the NR2B subunit and may be involved in the development of schizophrenia. Replication studies of independent samples and family-based association studies are necessary to further evaluate the significance of our findings.

5' Untranslated Regions↗

PubMed2002

Molecular dynamics simulation of a DNA containing a single strand break.

Molecular dynamics simulations were performed for a dodecamer DNA containing a single strand break (SSB), which has been represented by a 3'-OH deoxyribose and 5'-OH phosphate in the middle of the strand. Molecular force field parameters of the 5'-OH phosphate region were determined from an ab initio calculation at the HF/6-31G level using the program package GAMESS. The DNA was placed in a periodic boundary box with water molecules and Na+ counter-ions to produce a neutralised system. After minimisation, the system was heated to 300 K, equilibrated and a production run at constant NTP was executed for 1 ns using AMBER 4.1. Snapshots of the SSB-containing DNA and a detailed analysis of the equilibrated average structure revealed surprisingly small conformational changes compared to normal DNA. However, dynamic properties calculated using the essential dynamics method showed some features that may be important for the recognition of this damage by repair enzymes.

Base Pairing↗

PubMed2001

Remarkable effect of aluminum reagents on rearrangements of epoxy acylates via stable cation intermediates and its application to the synthesis of (S)-(+)-sporochnol A.

A remarkable effect of (C(6)F(5)O)(3)Al for promoting the rearrangement of epoxy acylates via stable cation intermediates was found, and new methods for constructing chiral benzylic, vinylic, and acetylenic quaternary carbon centers were developed. During the study, the importance of the ionic nature of the O-metal bond in the intermediates of such epoxides was addressed. This method was applied to the asymmetric total synthesis of (S)-(+)-sporochnol A.

Alkenes↗

PubMed2001

Metabolic activation of mitomycin C by NADPH-ferredoxin reductase in vitro.

Mammalian NADPH-ferredoxin reductase (EC 1.18.1.2) functions in the mitochondrial electron transport chain for cytochrome P-450-dependent steroid hydroxylation. Significant homology of three-dimensional structure exists in the surroundings of FAD between NADPH-ferredoxin reductase and NADH-cytochrome b5 reductase. The latter is involved in the bioreduction of mitomycin C (MC), a prototype antitumor agent. In this study, we assessed the capacity of NADPH-ferredoxin reductase to activate MC. Mitomycin C increased the NADPH oxidase activity of NADPH-ferredoxin reductase. In the absence of ferredoxin, the Km value of NADPH-ferredoxin reductase for MC was 73.5 +/- 2.3 microM. While in the presence of 500 nM ferredoxin, a Lineweaver-Burk plot exhibited a biphasic curve. NADPH-ferredoxin reductase-mediated reduction of MC resulted in the formation of an alkylated complex of 4-(p-nitrobenzyl) pyridine and an increase in plasmide DNA single-strand breaks under hypoxic conditions. With the addition of 500 nM ferredoxin, the amount of the alkylated complex of 4-(p-nitrobenzyl) pyridine and the plasmide DNA single-strand breaks increased by 40% and 37%, respectively. However, neither alkylated complex of 4-(p-nitrobenzyl) pyridine nor DNA strand breaks was observed in the presence of SOD and catalase under aerobic conditions. These findings demonstrate that NADPH-ferredoxin reductase is capable of catalyzing the bioactivation of mitomycin C under hypoxic conditions in vitro.

Alkylation↗

PubMed2001

Phase transitions of binary alloys with elastic inhomogeneity.

In elastically inhomogeneous alloys, in which the shear modulus depends on the composition, coarsening in phase separation can be pinned even without quenched disorder. Here networks in the soft phase enclose the domains in the hard phase. Highly asymmetric strains in the two regions create large free energy barriers that prevent further coarsening. Thus a phase transition occurs between the one-phase and the glassy two-phase states. We numerically obtain the phase diagram and show that this transition is discontinuous at any composition. Therefore there is no critical point.

Journal Article↗

PubMed2001

Endoscopic transanal decompression with a drainage tube for acute colonic obstruction: clinical aspects of preoperative treatment.

PURPOSE: The study was undertaken to evaluate the clinical usefulness of endoscopic transanal decompression with a newly developed drainage tube for the treatment of acute colonic obstruction. METHODS: Thirty-six patients ranging in age from 46 to 87 years (average age = 69 years) with acute colorectal obstruction secondary to carcinoma were treated by means of intubation with a flexible drainage tube using combined endoscopic and fluoroscopic guidance. After tube placement, the obstructed colon was aspirated, decompressed, and cleaned with a 50 ml syringe and saline solution. The drainage tube was kept inserted and the colon was irrigated two or three times per day using 500 to 1,000 ml of saline until there were no contents in the colon. The colon was almost empty at the time of operation. The success rate, benefits, and complications of this technique were evaluated. RESULTS: Placement of the drainage tube was successful in 34 (94.4 percent) of 36 patients. Immediately after aspiration and decompression, symptoms related to obstruction were relieved in 21 patients (61.8 percent), within one hour in 9 patients (26.5 percent) and within four hours in 4 patients (11.8 percent). All 34 patients had elective single-stage surgery without severe complications at the anastomotic site such as anastomotic leakage and postanastomotic stenosis that needed treatment a few days after placement of the drainage tube. In the two cases of unsuccessful placement of the drainage tube, emergent colostomy was performed. CONCLUSION: Decompression with a transanal drainage tube is an easy and safe technique to relieve colonic obstruction effectively without any excess burden to patients. Because the procedure permits single-stage surgery in most cases, it is also cost effective.

Acute Disease↗

PubMed2001

Analyzing the eye movement of dentists during their reading of CT images.

In order to evaluate the eye movements of dentists when they were interpreting radiographs, ten normal computed tomography (CT) images and ten images with pathologic lesions were shown to eight dentists, and the pattern of their eye movement was qualitatively analyzed. Six fixation point parameters were calculated, including the time required to discriminate between normal and pathologic images (X(1)), the total fixation point count (X(2)), the total travel distance between fixation points (X(3)), the average time spent on each fixation point (X(4)), the total gaze fixation time (X(5)), and the maximum gaze fixation time spent on each image (X(6)). When the subjects were interpreting pathologic images, X(2) and X(4) were shorter; however, when they were viewing normal images, time was spent on observing multiple fixation points before the completion of the interpretive process. While pathologic images were recognized through top-down processing, there was a tendency for normal images to be recognized through bottom-up processing. The results of discriminant analysis, using a linear discriminant function, indicated that the independent variables X(2) and X(4) and the dependent variable X(5) were the only variables that contributed significantly to differentiating between normal and pathologic images. The linear discriminant function was Z = 9.0 x 10(-2) x X(2) + 3.0 x X(4) - 2.1 (discriminant score: Z < 0, pathologic image; Z > or = 0, normal image). When the mean value of each individual's gaze fixation data was substituted into the discriminant formula, the hit rate for normal and pathologic images was discriminated at 94% (15 of 16).

Journal Article↗

PubMed2001

The optical interconversion of the P-450 and P-420 forms of neuronal nitric oxide synthase: effects of sodium cholate, mercury chloride and urea.

We investigated whether or not neuronal nitric oxide synthase (nNOS) (EC 1.14.13.39) was converted to the P-420 form on exposure to sodium cholate, mercury chloride or urea, and the reconversion of the P-420 to the P-450 form. Sodium cholate and mercury chloride induced the conversion of nNOS from the P-450 to the P-420 form in concentration- and incubation time-dependent manners, and the nNOS activity decreased. In the presence of glycerol, L-arginine and/or tetrahydrobiopterin, the sodium cholate-treated P-420 form could be reconverted to the P-450 form under constant experimental conditions, and the nNOS activity could also be restored. The mercury chloride-treated P-420 form of nNOS could be reconverted to the P-450 form on incubation with reduced glutathione (GSH) or L-cysteine, and the nNOS activity was recovered. However, no reconversion of the mercury chloride-treated P-420 form to the P-450 form was observed in the presence of glycerol, L-arginine, or tetrahydrobiopterin. Urea (4.0 M) dissociated nNOS into its subunits, but nNOS remained in the P-450 form. The nNOS monomer was more susceptible to sodium cholate. After removing the urea by dialysis, and supplementation of the nNOS solution with glycerol, L-arginine or BH(4), the P-420 was reconverted to the P-450 form, and the reassociation of nNOS monomers was also observed. These results suggested that nNOS was more stable as to exposure to sodium cholate, mercury chloride or urea in comparison to microsomal cytochrome P-450, which may be due to the different heme environment and protein structure.

Animals↗

PubMed2001

Low synthesis of retinoic acid due to impaired cytochrome P450 1a1 expression in mouse xeroderma pigmentosum fibroblasts.

New tumor formation was suppressed by retinoic acid (RA) administration in xeroderma pigmentosum (XP) patients who have a defect in nuclear excision repair. However, the inhibition is not due to enhanced removal of UV-damaged DNA. These results prompted us to investigate whether or not RA metabolism is abnormal in XP fibroblasts and what the underlying mechanism is. Compared with wild type fibroblasts, low activities of RA synthesis were determined on HPLC in mouse fibroblasts lacking XP group A (XPA) gene and UV-induced XPA deficient cancer cells. Moreover, we observed an impaired expression of cytochrome P450 1a1 in XPA deficient fibroblasts by RT-PCR and a decreased expression of retinoic acid receptor gamma in XPA deficient cancer cells by Western blotting. Finally, pre-treatment of RA isoforms significantly protected the XPA deficient fibroblasts from UV-induced death. These results suggest that decreased structure activity of RA synthesis, resulting from impaired mRNA expression of cytochrome P450 1a1 may, at least together with UV irradiation, involve in skin carcinogenesis in XP patients.

Alitretinoin↗

PubMed2001

Effect of isosorbide dinitrate on nitric oxide synthase under hypoxia.

Nitric oxide synthase (NOS) catalyzes nitric oxide (NO) formation from L-arginine in the presence of molecular oxygen and NADPH. NO is involved in the regulation of microvasculature. Isosorbide dinitrate (ISDN) and glyceryl trinitrate (GTN) have been widely used as vasodilators to treat acute myocardial ischemia, their biological effects being due to the release of NO. In this investigation, the effects of ISDN and GTN on NOS activity in the presence or absence of oxyhemoglobin under hypoxia and normoxia were studied. The apparent K(m) values for molecular oxygen were 21.6 +/- 1.5 and 9.4 +/- 1.3 micromol/l for nNOS and eNOS, respectively. ISDN liberated NO in a concentration- and pH-dependent manner, but no differences between hypoxia and normoxia were observed. The NO release from ISDN was also measured directly by an electron spin resonance spectral method with N-(dithiocarboxy)sarcosine-Fe complex as a NO-trapping agent. ISDN increased nNOS and eNOS activities in the presence of 30 micromol/l oxyhemoglobin under hypoxia, while it did not affect nNOS and eNOS activities under normoxia. In the absence of oxyhemoglobin, ISDN inhibited nNOS and eNOS activities under both hypoxic and normoxic experimental conditions. The rate of oxygen release from oxyhemoglobin under hypoxia was increased 3 times in the presence of 1 mmol/l ISDN. In contrast to ISDN, GTN could not release NO spontaneously, and it also did not affect nNOS and eNOS activities in the absence or presence of 30 micromol/l oxyhemoglobin under both hypoxic and normoxic conditions. These results indicated that the NO release from ISDN is different from that of GTN, and the increase of NOS activity by ISDN in the presence of oxyhemoglobin under hypoxia is ascribed to the increase in molecular oxygen concentration.

Animals↗

PubMed2000

Reductive activation of mitomycin C by neuronal nitric oxide synthase.

Mitomycin C (MC) requires bioreduction prior to the generation of alkylating moieties. NADPH-cytochrome P450 reductase is predominant in metabolic activation of MC in hypoxic cancer cells. In this study, neuronal nitric oxide synthase (nNOS), whose reductase domain is structurally similar to that of NADPH-cytochrome P450 reductase, was assessed for its ability to activate MC. nNOS under anaerobic conditions catalyzed the reduction of MC, which was measured as the decrease in absorbance at 375 nm. Neither the heme blocker potassium cyanide (1 mM) nor the nNOS competitive inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mM) affected the bioreduction of MC, whereas 0.1 mM diphenyleneiodonium chloride, which binds to the reductase domain of nNOS, inhibited MC reduction completely. The reduction of MC by nNOS was influenced by Ca(2+)/calmodulin. In the absence of Ca(2+)/calmodulin, the rate of MC reduction decreased by 28% at pH 6.6. The formation of an alkylated complex of 4-(p-nitrobenzyl)pyridine occurred in a manner analogous to that observed in MC metabolic experiments. The rate of MC reduction and the formation of the alkylated complex of 4-(p-nitrobenzyl)pyridine at pH 6.6 were increased by 43 and 54%, respectively, as compared with that at pH 7.6. nNOS-activated MC resulted in the consumption of oxygen in air. The rate of oxygen consumption decreased by 50% in the presence of 2000 U/mL of catalase. MC inhibited nNOS activity in a noncompetitive manner. These findings demonstrate that nNOS is capable of catalyzing the bioreduction of MC.

Alkylation↗

PubMed2000

Blood-brain barrier transport of 125I-labeled basic fibroblast growth factor.

PURPOSE: This study was carried out to examine the blood-brain barrier (BBB) transport of human basic fibroblast growth factor (bFGF) and investigate its mechanism. METHODS: The BBB transport of 125I-bFGF was measured by several in vivo methods including intravenous administration, in situ internal carotid artery perfusion, and intracerebral microinjection. The in vitro binding of 125I-bFGF was characterized using freshly prepared bovine brain capillaries. RESULTS: The distribution volume of 125I-bFGF in the postvascular supernatant increased with the perfusion time, and exceeded the space occupied by the brain microvasculature and its trichloroacetic acid (TCA) precipitability was more than 90%. 125I-bFGF avidly bound to isolated bovine brain capillaries with a Bmax of 206 +/- 48 pmol/mg protein, and a Kd of 36.5 +/- 15.7 nM. This binding was significantly inhibited by unlabeled bFGF and heparin in a concentration-dependent manner. The cationic peptides, protamine and poly-L-lysine (each 300 microM), produced over 85% inhibition of 125I-bFGF binding to brain capillaries. Furthermore, glycosaminoglycans with a sulfate residue, chondroitin sulfate B and C (each 10 microg/mL) also inhibited the binding of 125I-bFGF The in vivo transcytosis of 125I-bFGF from the luminal side to the brain was also inhibited by the presence of heparin (10 microg/mL) and poly-L-lysine (300 microM), whereas neither hyaruronic acid (10 microg/mL) nor insulin (10 microM) had any effect. In addition to these results, the brain efflux index method was used to confirm that the transcytosis of 125I-bFGF from brain to blood across the BBB was negligible. CONCLUSIONS: These results suggest that 125I-bFGF is transported across the BBB, possibly by an adsorptive-mediated transcytosis mechanism that is triggered by binding to negatively charged species on the luminal membrane surface of the brain microvasculature, such as heparan sulfate proteoglycans.

Animals↗

PubMed1999

Molecular cloning of retinal oxidase/aldehyde oxidase cDNAs from rabbit and mouse livers and functional expression of recombinant mouse retinal oxidase cDNA in Escherichia coli.

Retinal oxidase (EC 1.2.3.11) is a molybdenum-containing flavoenzyme with high enzymatic activity as to retinoic acid synthesis. In this study, we provide direct evidence that retinal oxidase is identical to aldehyde oxidase (EC 1.2.3.1) by cDNA cloning. Retinal oxidase and aldehyde oxidase, purified from rabbit liver cytosol using the original methods, showed completely identical HPLC patterns and amino acid sequences for three corresponding polypeptides (103 amino residues). The primary structural information obtained from the cleaved polypeptides permitted molecular cloning of the full-length cDNA of rabbit liver retinal oxidase (aldehyde oxidase). We also cloned and sequenced the full-length cDNA of mouse retinal oxidase. The cDNAs of rabbit and mouse retinal oxidase have a common sequence approximately 4.6 kb long, comprising 4-kb coding regions. The open reading frames of the cDNAs predict single polypeptides of 1334 and 1333 amino acids; the calculated minimum molecular mass of each is approximately 147,000. Northern blot analysis showed that the rabbit retinal oxidase mRNA was widely expressed in tissues. Finally, we successfully constructed a prokaryotic expression system for mouse retinal oxidase. The purified recombinant retinal oxidase from Escherichia coli showed a typical spectrum of aldehyde oxidases and a lower Km (3.8 microM) for retinal and a higher Vmax (807 nmol/min/mg protein) for retinoic acid synthesis than those of rabbit retinal oxidase (8 microM and 496 nmol/min/mg protein). This represents the first eukaryotic molybdenum-containing flavoprotein to be expressed in an active form in a prokaryotic system.

Aldehyde Oxidoreductases↗