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Biomedical subjects

Takuya Hayashi

Publications and source records attributed to Takuya Hayashi.

At least 19 recordsLinked to original sources
PubMed2006

Quantitative mapping of basal and vasareactive cerebral blood flow using split-dose 123I-iodoamphetamine and single photon emission computed tomography.

A new method has been developed for diffusible tracers, to quantify CBF at rest and after pharmacological stress from a single session of dynamic scans with dual bolus administration of a radiotracer. The calculation process consisted of three steps, including the procedures of incorporating background radioactivity contaminated from the previous scan. Feasibility of this approach was tested on clinical SPECT studies on 16 subjects. Two sequential SPECT scans, 30 min apart, were carried out on each subject, after each of two split-dose administrations of 111 MBq IMP. Of these, 11 subjects received acetazolamide at 10 min before the second IMP injection. Additional PET scans were also carried out on 6 subjects on a separate day, at rest and after acetazolamide administration. The other 5 subjects were scanned only at rest during the whole study period. Quantitative CBF obtained by this method was in a good agreement with those determined with PET (y(ml/100 g/min)=1.07x(ml/100 g/min)-1.14, r=0.94). Vasareactivity was approximately 40% over the whole cerebral area on healthy controls, which was consistent with a literature value. Reproducibility of CBF determined in the rest-rest study was 1.5+/-5.7%. Noise enhancement of CBF images, particularly the second CBF, was reduced, providing reasonable image quality. Repeat assessment of quantitative CBF from a single session of scans with split-dose IMP is accurate, and may be applied to clinical research for assessing vascular reactivity in patients with chronic cerebral vascular disease.

Aged↗
PubMed2006

Sodium chloride-catalyzed oxidation of multiwalled carbon nanotubes for environmental benefit.

A sodium chloride (NaCl) catalyst (0.1 w/w %) lowers the oxidation temperature of graphitized multiwalled carbon nanotubes: MWCNT-20 (diameter: 20-70 nm) and MWCNT-80 (diameter: 80-150 nm). The analysis of the reaction kinetics indicates that the oxidation of MWCNT-20 and MWCNT-80 mixed with no NaCl exhibits single reaction processes with activation energies of E(a) = 159 and 152 kJ mol(-1), respectively. The oxidation reaction in the presence of NaCl is shown to consist of two different reaction processes, that is, a first reaction and a second reaction process. The first reaction process is dominant at a low temperature of around 600 degrees C, while the second reaction process becomes more dominant than the first one in a higher temperature region. The activation energies of the first reaction processes (MWCNT-20: E(a1) = 35.7 kJ mol(-1); MWCNT-80: E(a1) = 43.5 kJ mol(-1)) are much smaller than those of the second reaction processes (MWCNT-20: E(a2) = 170 kJ mol(-1); MWCNT-80: E(a2) = 171 kJ mol(-1)). The comparison of the kinetic parameters and the results of the spectroscopic and microscopic analyses imply that the lowering of the oxidation temperature in the presence of NaCl results from the introduction of disorder into the graphitized MWCNTs (during the first reaction process), thus increasing the facility of the oxidation reaction of the disorder-induced nanotubes (in the second reaction process). It is found that the larger nanopits and cracks on the outer graphitic layers are caused by the catalytic effect of NaCl. Therefore, the NaCl-mixed samples showed more rapid and stronger oxidation compared with that of the nonmixed samples at the same residual quantity.

Journal Article↗
PubMed2006

Gene transfer of hepatocyte growth factor gene improves learning and memory in the chronic stage of cerebral infarction.

There is no specific treatment to improve the functional recovery in the chronic stage of ischemic stroke. To provide the new therapeutic options, we examined the effect of overexpression of hepatocyte growth factor (HGF) in the chronic stage of cerebral infarction by transferring the HGF gene into the brain using hemagglutinating virus of Japan envelope vector. Sixty rats were exposed to permanent middle cerebral artery occlusion (day 1). Based on the sensorimotor deficits at day 7, the rats were divided equally into control vector or HGF-treated rats. At day 56, rats transfected with the HGF gene showed a significant recovery of learning and memory in Morris water maze tests (control vector 50+/-4 s; HGF 33+/-5 s; P<0.05) and passive avoidance task (control vector 132.4+/-37.5 s; HGF 214.8+/-26.5 s; P<0.05). Although the total volume of cerebral infarction was not related to the outcome, immunohistochemical analysis for Cdc42 and synaptophysin in the peri-infarct region revealed that HGF enhanced the neurite extension and increased synapses. Immunohistochemistry for glial fibriary acidic protein revealed that the formation of glial scar was also prevented by HGF gene treatment. Additionally, the number of the arteries was increased in the HGF group at day 56. These data demonstrated that HGF has a pivotal role for the functional recovery after cerebral infarction through neuritogenesis, improved microcirculation, and the prevention of gliosis. Our results also provide evidence for the feasibility of gene therapy in the chronic stage of cerebral infarction.

Animals↗
PubMed2006

Medical application of carbon-nanotube-filled nanocomposites: the microcatheter.

Carbon nanotubes hold great promise for use in biomedical fields. Among numerous potential applications, including DNA and protein sensors, bioseparators, biocatalysts, and tissue scaffolds, this article emphasizes the use of carbon-nanotube-filled polymer composites as medical devices, namely, microcatheters. The currently hot topic of the biocompatibility (e.g., toxic properties) of carbon nanotubes is discussed. In addition, critical issues that must be clarified for the full utilization of current carbon-nanotube science and technology in biomedical fields are discussed.

Animals↗
PubMed2006

In situ Raman study on single- and double-walled carbon nanotubes as a function of lithium insertion.

We investigated the electrochemical lithium ion (Li(+)) insertion/desertion behavior on highly pure and bundled single- and double-walled carbon nanotubes (SWNTs and DWNTs) using an in situ Raman technique. In general, two storage sites could host Li(+) in SWNT and DWNT bundles when varying an external potential: a) the outer surface sites, and b) the interstitial spaces within the bundles. The most sensitive changes in the tangential mode (TM) of the Raman spectra upon doping with Li(+) can be divided into two regions. The first region was found from 2.8 to 1.0 V (the coverage of Li(+) on the outer surface of a bundled nanotube) and was characterized by the loss of resonant conditions via partial charge transfer, where the G(+) line of the SWNT and the TM of the outer tube of DWNTs experienced a highly depressed intensity, but remained almost constant in frequency. The appearance of a Breit-Wigner-Fano (BWF) profile provided strong evidence of metallic inner tubes within DWNTs. The second region was observed when the applied potentials ranged from 0.9 to 0 V and was characterized by Li(+) diffusion into the interstitial sites of the bundled nanotube material. This phenomenon invoked a large downshift of the G(-) band in SWNTs, and a small downshift of the TM of the inner tube of DWNTs caused by expansion of the C--C bonds due to the charge transferred to the nanotubes, and the disappearance of the BWF profile through the screening effect of the interstitial Li(+) layers.

Electrochemistry↗
PubMed2006

Use of a compact pixellated gamma camera for small animal pinhole SPECT imaging.

OBJECTIVES: Pinhole SPECT which permits in vivo high resolution 3D imaging of physiological functions in small animals facilitates objective assessment of pharmaceutical development and regenerative therapy in pre-clinical trials. For handiness and mobility, the miniature size of the SPECT system is useful. We developed a small animal SPECT system based on a compact high-resolution gamma camera fitted to a pinhole collimator and an object-rotating unit. This study was aimed at evaluating the basic performance of the detection system and the feasibility of small animal SPECT imaging. METHODS: The gamma camera consists of a 22 x 22 pixellated scintillator array of 1.8 mm x 1.8 mm x 5 mm NaI(Tl crystals with 0.2-mm gap between the crystals coupled to a 2" flat panel position-sensitive photomultiplier tube (Hamamatsu H8500) with 64 channels. The active imaging region of the camera was 43.8 mm x 43.8 mm. Data acquisition is controlled by a personal computer (Microsoft Windows) through the camera controller. Projection data over 360 degrees for SPECT images are obtained by synchronizing with the rotating unit. The knife-edge pinhole collimators made of tungsten are attached on the camera and have 0.5-mm and 1.0-mm apertures. The basic performance of the detection system was evaluated with 99mTc and 201Tl solutions. Energy resolution, system spatial resolution and linearity of count rate were measured. Rat myocardial perfusion SPECT scans were sequentially performed following intravenous injection of 201TlCl. Projection data were reconstructed using a previously validated pinhole 3D-OSEM method. RESULTS: The energy resolution at 140 keV was 14.8% using a point source. The system spatial resolutions were 2.8-mm FWHM and 2.5-mm FWHM for 99mTc and 201Tl line sources, respectively, at 30-mm source distance (magnification factor of 1.3) using a 1.0-mm pinhole. The linearity between the activity and count rate was good up to 10 kcps. In a rat study, the left ventricular walls were clearly visible in all scans. CONCLUSIONS: We developed a compact SPECT system using compact gamma camera for small animals and evaluated basic physical performances. The present system may be of use for quantitation of biological functions such as myocardial blood flow in small animals.

Animals↗
PubMed2006

[Adult bacterial meningitis complicated by cerebral infarction: report of three cases].

Fatality rates and the number of patients suffering from the after sequelae of bacterial meningitis have still remained high despite the development of new antibiotics. Cerebrovascular complications have been reported less frequently in adult cases than in child cases. We experienced 3 consecutive cases of bacterial meningitis in adults complicated by brain infarction. Primary causative organism were the Group B Streptococci in one case and the Streptococcus pneumoniae in other two cases. MRI, especially with FLAIR method and of coronal view, disclosed abnormal intensity areas near the brain surface. Conventional angiography and MR-angiography in the two cases showed tapering and stenosis of arteries. These cases suggest that routine use of MRI/ MRA in bacterial meningitis reveal neuro-vascular complications more frequently and easily. The benefits of adjunctive steroid therapy in the treatment of bacterial meningitis might be beneficial to suppression of these neurovascular complication cased by inflammatory vasculitis.

Aged↗
PubMed2005

Controlled release of paclitaxel from photocrosslinked chitosan hydrogels and its subsequent effect on subcutaneous tumor growth in mice.

A photocrosslinkable chitosan (Az-CH-LA) aqueous solution containing paclitaxel resulted in an insoluble hydrogel within 30 s of ultrtaviolet light (UV)-irradiation. About 35-40% of the paclitaxel was released from the paclitaxel-incorporated chitosan hydrogel into phosphate buffered saline (PBS) within 1 day, after which gradual release occurred during 3 days under in vitro non-degradation conditions of the hydrogel. The paclitaxel remaining in the chitosan hydrogel retained its biological activity in vitro for at least 21 days, and was released from the chitosan hydrogel in vivo upon degradation of the hydrogel. The paclitaxel-incorporated Az-CH-LA hydrogel inhibited the growth of subcutaneously induced tumors with Lewis lung cancer (3LL) cells more effectively than those treated with only Az-CH-LA, only paclitaxel, and a non-treated group (control) for at least 11 days. Furthermore, paclitaxel-incorporated chitosan hydrogel markedly reduced the number of CD34-positive vessels in subcutaneous 3LL tumors, indicating a strong inhibition of angiogenesis. These results suggested that application of paclitaxel-incorporated Az-CH-LA hydrogel has an inhibitory activity on angiogenesis and tumor growth.

Animals↗
PubMed2005

Understanding of cerebral energy metabolism by dynamic living brain slice imaging system with [18F]FDG.

Recently, lactate has been receiving great attention as an energy substrate in the brain. In this study, the role of lactate was evaluated by "bioradiography" system with 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG), which is a positron emitting radiotracer for glucose uptake quantification. "Bioradiography" is the dynamic living tissue slice imaging system for positron-emitter labeled compounds. We investigated the brain energy metabolism under resting state and neural activated conditions induced by KCl addition. The monocarboxylate transporter inhibitor, alpha-cyano-4-hydroxycinnamate (4-CIN), had no effect on [(18)F]FDG uptake rate in rat brain slices before KCl addition. On the other hand, addition of 4-CIN induced larger [(18)F]FDG uptake rates under the activated condition in comparison with the control condition. Because neurons cannot utilize lactate under the 4-CIN loaded conditions, this indicates that activated neurons consume lactate as an energy substrate. The lactate concentration in the incubation medium was increased with KCl treatment in both groups and the extent was slightly greater in 4-CIN group. These results suggested that: (1) the brain mainly uses glucose, not lactate, as an energy substrate in resting state; (2) when neuron is stimulated, excess amounts of lactate might be produced in astrocytes and the lactate is mobilized as an energy substrate.

Animals↗
PubMed2005

Thrombogenicity and blood coagulation of a microcatheter prepared from carbon nanotube-nylon-based composite.

Here we describe the fabrication of nanocomposite-based microcatheter through-melt extrusion utilizing high-purity carbon nanotubes as filler and nylon as matrix. Homogeneous dispersion of carbon nanotubes in nylon can provide novel microcatheters with enhanced mechanical properties (easier to handle) and extremely reduced thrombogenicity or antithrombotic property. The present microcatheter with high performance is highly promising for medical applications.

Animals↗
PubMed2005

Atomic nanotube welders: boron interstitials triggering connections in double-walled carbon nanotubes.

Here we demonstrate that the incorporation of boron (B) atoms between double-walled carbon nanotubes (DWNTs) during thermal annealing (1400-1600 degrees C) results in covalent nanotube "Y" junctions, DWNT coalescence, and the formation of flattened multiwalled carbon nanotubes (MWNTs). These processes occur via the merging of adjacent tubes, which is triggered by B interstitial atoms. We observe that B atom interstitials between DWNTs are responsible for the rapid establishment of covalent connections between neighboring tubes (polymerization), thereby resulting in the fast annealing of the carbon cylinders with B atoms embedded in the newly created carbon nanotube network. Once B is in the lattice, tube faceting (polygonization) starts to occur, and the electronic properties are expected to change dramatically. Therefore, B atoms indeed act as atomic nanotube fusers (or welders), and this process could now be used in assembling novel electronic nanotube devices, nanotube networks, carbon nanofoams and heterojunctions exhibiting p-type electronic properties.

Boron↗
PubMed2005

Rapid quantitative measurement of CMRO(2) and CBF by dual administration of (15)O-labeled oxygen and water during a single PET scan-a validation study and error analysis in anesthetized monkeys.

Cerebral blood flow (CBF) and rate of oxygen metabolism (CMRO(2)) may be quantified using positron emission tomography (PET) with (15)O-tracers, but the conventional three-step technique requires a relatively long study period, attributed to the need for separate acquisition for each of (15)O(2), H(2)(15)O, and C(15)O tracers, which makes the multiple measurements at different physiologic conditions difficult. In this study, we present a novel, faster technique that provides a pixel-by-pixel calculation of CBF and CMRO(2) from a single PET acquisition with a sequential administration of (15)O(2) and H(2)(15)O. Experiments were performed on six anesthetized monkeys to validate this technique. The global CBF, oxygen extraction fraction (OEF), and CMRO(2) obtained by the present technique at rest were not significantly different from those obtained with three-step method. The global OEF (gOEF) also agreed with that determined by simultaneous arterio-sinus blood sampling (gOEF(A-V)) for a physiologically wide range when changing the arterial PaCO(2) (gOEF=1.03gOEF(A-V)+0.01, P<0.001). The regional values, as well as the image quality were identical between the present technique and three-step method for CBF, OEF, and CMRO(2). In addition, a simulation study showed that error sensitivity of the present technique to delay or dispersion of the input function, and the error in the partition coefficient was equivalent to that observed for three-step method. Error sensitivity to cerebral blood volume (CBV) was also identical to that in the three-step and reasonably small, suggesting that a single CBV assessment is sufficient for repeated measures of CBF/CMRO(2). These results show that this fast technique has an ability for accurate assessment of CBF/CMRO(2) and also allows multiple assessment at different physiologic conditions.

Algorithms↗
PubMed2005

Expression of hypoxia-inducible factor-1alpha in esophageal squamous cell carcinoma.

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that plays an important role in tumor growth and metastasis by regulating energy metabolism and inducing angiogenesis. Elevated levels of HIF-1alpha, a subunit of HIF-1, are noted in various malignant tumors, but it is unclear whether this is so in esophageal carcinoma. The purpose of this study was to evaluate the implications of HIF-1alpha expression in esophageal squamous cell carcinoma. In 215 patients with esophageal carcinoma, we examined immunoreactivity for HIF-1alpha protein, vascular endothelial growth factor (VEGF) protein and p53 protein. In 38 patients, we examined the expression of HIF-1alpha messenger ribonucleic acid (mRNA) (using the semiquantitative reverse transcriptase-polymerase chain reaction [RT-PCR]). A positive HIF-1alpha protein expression was recognized in 95% of the patients, and was strongly apparent within both the nuclei and/or cytoplasm of tumor cells. The proportion of patients in the 'high score' group for HIF-1alpha protein expression increased significantly with increasing VEGF protein expression. Immunoreactivity for HIF-1alpha protein was found to have a significant effect on disease-free survival rate in our univariate analysis, but no effect on overall survival rate. In RT-PCR, HIF-1alpha mRNA scores correlated significantly with scores for HIF-1alpha protein expression, but not with any clinicopathologic factor or either of the survival rates. The detection of HIF-1alpha protein and mRNA would appear to offer limited information as to progression and prognosis in esophageal carcinoma.

Adult↗
PubMed2005

Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model.

Parkinson disease (PD) is a neurodegenerative disorder characterized by loss of midbrain dopaminergic (DA) neurons. ES cells are currently the most promising donor cell source for cell-replacement therapy in PD. We previously described a strong neuralizing activity present on the surface of stromal cells, named stromal cell-derived inducing activity (SDIA). In this study, we generated neurospheres composed of neural progenitors from monkey ES cells, which are capable of producing large numbers of DA neurons. We demonstrated that FGF20, preferentially expressed in the substantia nigra, acts synergistically with FGF2 to increase the number of DA neurons in ES cell-derived neurospheres. We also analyzed the effect of transplantation of DA neurons generated from monkey ES cells into 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated (MPTP-treated) monkeys, a primate model for PD. Behavioral studies and functional imaging revealed that the transplanted cells functioned as DA neurons and attenuated MPTP-induced neurological symptoms.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2005

Parametric imaging of myocardial blood flow with 15O-water and PET using the basis function method.

UNLABELLED: Regional myocardial blood flow (MBF) can be measured with 15O-water and PET using the 1-tissue-compartment model with perfusable tissue fraction, which provides an MBF value that is free from the partial-volume effect. Studies with 15O-water have several advantages, such as the ability to repeat a scan. However, because of the short scanning time and the small distribution volume of 15O-water in the myocardium, the image quality of 15O-water is limited, impeding the computation of MBF and perfusable tissue fraction at the voxel level. We implemented the basis function method for generating parametric images of MBF, perfusable tissue fraction, and arterial blood volume (Va) with 15O-water and PET. The basis function method linearizes the solution of the 1-tissue-compartment model, which results in a computationally much faster method than the conventional nonlinear least-squares fitting method in estimating the parameters. METHODS: To validate the basis function method, we performed a series of PET studies on miniature pigs (n = 7). After acquisition of the transmission scan for attenuation correction and the 15O-CO scan for obtaining the blood-pool image, repeated PET scans with 15O-water were obtained with varying doses of adenosine or CGS-21680 (selective adenosine A(2a) receptor agonist). MBF, perfusable tissue fraction, and Va values of the myocardial region for each scan were computed using the basis function method and the nonlinear least-squares method, and the parameters estimated by the 2 methods were compared. RESULTS: MBF images generated by the basis function method demonstrated an increase in blood flow after administration of adenosine or CGS-21680. The MBF values estimated by the basis function method and by the nonlinear least-squares method correlated strongly. CONCLUSION: The basis function method produces parametric images of MBF, perfusable tissue fraction, and Va with 15O-water and PET. These images will be useful in detecting regional myocardial perfusion abnormalities.

Algorithms↗