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The eye has an environment that is specific unto itself in terms of pharmacokinetics: the inner and outer blood-retinal barriers separate the retina and the vitreous from the systemic circulation and vitreous body, which physiolog...
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The eye has an environment that is specific unto itself in terms of pharmacokinetics: the inner and outer blood-retinal barriers separate the retina and the vitreous from the systemic circulation and vitreous body, which physiologically has no cellular components, occupies the vitreous cavity, an inner space of the eye, and reduces practical convection of molecules. Considering this, development of a drug delivery system (DDS) is becoming increasingly important in the treatment of vitreoretinal diseases not only to facilitate drug efficacy but also to attenuate adverse effects. The DDS has three major goals: enhances drug permeation (e.g., iontophoresis and transscleral DDS), controls release of drugs (e.g., microspheres, liposomes, and intraocular implants), and targets drugs (e.g., prodrugs with high molecular weight and immunoconjugates). Comprehensive knowledge of these should lead to development of innovative treatment modalities.
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The Meteorological Research Institute of the Japan Meteorological Agency has developed a cloud-resolving nonhydrostatic 4-dimensional variational assimilation system (NHM-4DVAR), based on the Japan Meteorological Agency Nonhydrost...
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The Meteorological Research Institute of the Japan Meteorological Agency has developed a cloud-resolving nonhydrostatic 4-dimensional variational assimilation system (NHM-4DVAR), based on the Japan Meteorological Agency Nonhydrostatic Model (JMA-NHM), in order to investigate the mechanism of heavy rainfall events induced by mesoscale convective systems (MCSs). A horizontal resolution of the NHM-4DVAR is set to 2 km to resolve MCSs, and the length of the assimilation window is 1-hour. The control variables of the NHM-4DVAR are horizontal wind, vertical wind, nonhydrostatic pressure, potential temperature, surface pressure and pseudo relative humidity. Perturbations to the dynamical processes, and the advection of water vapor are considered, but these to the other physical processes are not taken into account. The NHM-4DVAR is applied to the heavy rainfall event observed at Nerima, central part of Tokyo metropolitan area, on 21 July 1999. Doppler radar's radial wind data, Global Positioning System's precipitable water vapor data, and surface temperature and wind data are assimilated as high temporal and spatial resolution data. The Nerima heavy rainfall is well reproduced in the assimilation and subsequent forecast, with respect to time sequence of 10-minute rainfall amount. The formation mechanism of the Nerima heavy rainfall is clarified from this study. A surface convergence line of horizontal winds was made of a southerly sea breeze and north-easterly winds over the Kanto plain around Nerima. Since the rise of temperature over the northern part of the Kanto plain was suppressed, due to a shield of clouds against sunshine, the difference of temperature between the convergence line and its northern side became large. Consequently, the wind convergence was enhanced around Nerima. An air with high equivalent potential temperature was lifted over this enhanced convergence line to generate cumulonimbi that caused the Nerima heavy rainfall.
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The organization of the laminar and topographical projections from the presubiculum to the entorhinal area was studied in the rat by anterograde labeling with Phaseolus vulgaris leucoagglutinin and retrograde labeling with horsera...
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The organization of the laminar and topographical projections from the presubiculum to the entorhinal area was studied in the rat by anterograde labeling with Phaseolus vulgaris leucoagglutinin and retrograde labeling with horseradish peroxidase conjugated to wheat germ agglutinin. We found that the pattern of presubiculo-entorhinal projections differs between the superficial and deep layers of the presubiculum. The superficial layers (layers II and III) of the presubiculum gave rise to bilateral projections to layers I-VI of the medial entorhinal area (MEA). Many terminals were distributed in layer III, fewer in layer II and the deep portion of layer I, and many fewer terminals in the deep layers (layers V and VI) of MEA. In contrast, the deep layers (layers V and VI) of the presubiculum gave rise to ipsilateral projections to the entorhinal area. Many axon terminals were distributed in layers V and VI of MEA and the most superficial portion of layer I of MEA, but very few in layers II and III. In addition, the ramifications in layer I extended to the lateral entorhinal area (LEA). Using two-dimensional unfolded maps of parahippocampal cortices, we elucidated the distinct topographical relationship in the presubiculo-entorhinal projection: 1) The septotemporal or longitudinal axis of the presubiculum corresponded to the axis on the MEA/LEA boundary, where the septal presubiculum projected toward the rhinal fissure and the temporal presubiculum projected away from the fissure. 2) The proximodistal axis of the presubiculum corresponded to the axis from the MEA/LEA boundary to the MEA/parasubiculum boundary that was virtually perpendicular to the MEA/LEA boundary, where the proximal portion of the presubiculum (close to the subiculum) projected to the region near the MEA/LEA boundary. J. Comp. Neurol. 473:463-484, 2004.
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The presubiculum is one of the important regions of the parahippocampal area known to be responsible for processing and integrating spatial representation information. To understand better the functional roles played by the presub...
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The presubiculum is one of the important regions of the parahippocampal area known to be responsible for processing and integrating spatial representation information. To understand better the functional roles played by the presubiculum, it is essential to elucidate how output signals from the presubiculum distribute to its target regions. In the present study, the axonal branching patterns of single pyramidal neurons in layer V of the rat presubiculum were investigated by using in vivo injection of a viral vector expressing membrane-targeted palmitoylation site-attached green fluorescent protein. We found that individual layer V neurons provide axonal branches to one or two cortical areas with one or more recurrent collaterals to the presubiculum. These neurons were classified into six types, based on their axonal collateralization pattern: neurons with axon branches to 1) both the retrosplenial granular cortex and the parasubiculum, 2) both the retrosplenial granular cortex and the subiculum, and 3) both the medial entorhinal area and the subiculum, and neurons with axonal branches terminating only in 4) the retrosplenial granular cortex, 5) the subiculum, and 6) the presubiculum. Types 1-5 also provide recurrent axons to the presubiculum. Our data demonstrate that layer V of the presubiculum consists of at least six types of cortical projection neurons with various patterns of axonal collateralization. These findings suggest that single presubicular layer V neurons may distribute information to one or two cortical areas participating in the neural circuitry of spatial representation and also send such information back to the presubiculum itself.
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Structures within the piriform cortex (PC) including the endopiriform nucleus (DEN) and pre-endopiriform nucleus (pEn) have been implicated to be involved in seizure genesis in models of temporal lobe epilepsy. We used stereologic...
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Structures within the piriform cortex (PC) including the endopiriform nucleus (DEN) and pre-endopiriform nucleus (pEn) have been implicated to be involved in seizure genesis in models of temporal lobe epilepsy. We used stereological methods to examine the specificity and extent of neuron loss in the PC of pilocarpine-treated rats. Both 7 days and 2 months post-status epilepticus rats showed significant neuron loss in the pEn and DEN, layer III of the intermediate PC, and layers II and III of the caudal PC. Total losses in the PC were 40 and 46% in 7 days and 2 months post-status epilepticus rats, respectively (p<0.01). The numbers of parvalbumin (PV)- and cholecystokinin (CCK)-immunopositive neuron profiles significantly decreased, and somatostatin (SS)-immunopositive neuron profiles tended to decrease. A large decrease in the number of PV-immunopositive neuron profiles occurred in the pEn, adjoining parts of the DEN and deep layer III of the PC, portions of the DEN bordering the claustrum and agranular insular cortex, and layer III of the caudal PC. The regions with decreased numbers of PV-, CCK-, and SS-immunopositive neuron profiles overlapped with those where many Nissl-stained neurons were lost and many degenerating cell bodies were detected. These results suggest that the decreases in the numbers of PV/SS/CCK-immunopositive neurons are related to neuron loss rather than to a low rate of synthesis of their peptides or proteins.
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In order to improve the biological characteristics of DA-3934 (5), a novel gastrin/cholecystokinin (CCK)-B receptor antagonist, phenoxyacetic acid derivatives replacing the N-methyl-N-phenylcarbamoylmethyl moiety of 5 with various...
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In order to improve the biological characteristics of DA-3934 (5), a novel gastrin/cholecystokinin (CCK)-B receptor antagonist, phenoxyacetic acid derivatives replacing the N-methyl-N-phenylcarbamoylmethyl moiety of 5 with various alkyl chains have been synthesized and their biological activity evaluated. The relationship between the structure of these compounds and their human gastrin receptor binding affinity showed that there should be the optimal size among the various N-alkyl chains. Also a significant increase in the receptor binding affinity was achieved by several compounds. Among those compounds, 2-[3-[3- [N-cyclohexylmethyl-N-[2-(N-methyl- N-phenylcarbamoylmethoxy)phenyl]carbamoylmethyl]ureido]pheny l]acetic acid (22c) and (+/-)-2-[3-[3-[N-[2-(N-methyl-N- phenylcarbamoylmethoxy)phenyl]-N-(3-methylpentyl)carbamoy lmethyl]ureido] phenyl]acetic acid (22h) exhibited high affinity for human gastrin receptors and were also more potent inhibitors in a pentagastrin-induced gastric acid secretion model than the parent compound, 5. The ED50 values of these compounds when administered intraduodenally to rats were 0.12 and 0.63 mg/kg, respectively.
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To investigate developmental changes in the neural responses to a biological motion stimulus, we measured event-related potentials (ERPs) in 50 children aged from 7 to 14 years, and 10 adults. Two kinds of visual stimuli were pres...
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To investigate developmental changes in the neural responses to a biological motion stimulus, we measured event-related potentials (ERPs) in 50 children aged from 7 to 14 years, and 10 adults. Two kinds of visual stimuli were presented: a point-light walker (PLW) stimulus and a scrambled point-light walker (sPLW) stimulus as a control. The sPLW stimulus had the same number of point-lights and the same velocity vector of point-lights as the PLW stimulus, but the initial starting positions were randomized. Consistent with previous ERP studies, one positive peak (P1) and two negative peaks (N1 and N2) were observed at around 130, 200 and 330 ms, respectively, in bilateral occipitotemporal regions, in all age groups. The latency of the P1 component was significantly shorter for the PLW than sPLW stimulus in all age groups, whereas the amplitude was significantly larger for the PLW than sPLW stimulus only for the 7-year-old group. The P1 amplitude and N1 latency were linearly decreased with age. The negative amplitudes of both N1 and N2 components of the PLW stimulus were significantly larger than those of the sPLW stimulus in all age groups. P1-N1 amplitude was changed by development, but not N2 amplitude. These results suggest that the intensity (P1) and timing (N1) of early visual processing for the PLW stimulus changed linearly throughout childhood and P1-N1 amplitude at occipitotemporal electrodes and N1 latency in 10-year-olds, but not 11-year-olds, was significantly larger than that in adults. For the amplitudes of the N2 component in response to PLW and sPLW stimuli in 7-8-year-old subjects were not statistically different from those in adults at occipitotemporal electrodes. These results suggest that the neural response to the PLW stimulus has developed by 10 years of age at the occipitotemporal electrode.
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In the present study, we investigate the top-down centrifugal modulation of neural responses to a task-relevant noxious stimulation triggering voluntary movement by recording magnetoencephalography (MEG) and electroencephalography...
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In the present study, we investigate the top-down centrifugal modulation of neural responses to a task-relevant noxious stimulation triggering voluntary movement by recording magnetoencephalography (MEG) and electroencephalography (EEG) simultaneously. An auditory warning signal was followed 2-3 s later by a noxious YAG laser stimulation as an imperative signal delivered to the left hand dorsum. Ten normal subjects performed three different conditions, Control, Movement, and Count. In Control, the subjects were asked to relax and rest quietly with no task. In Movement, the subjects extended the left index finger after imperative stimuli. In Count, the subjects counted the number of imperative stimuli silently. The amplitude of the N2 component recorded by EEG, which peaked about 220 ms after noxious stimulation, was significantly attenuated in Movement, but not in Count, compared to Control. The root-mean-square (RMS) from both hemispheres, and areal mean signal (AMS) amplitudes and the equivalent current dipole (ECD) strengths from SI/PPC and bilateral SII recorded at around 170 ms by MEG were not significantly different among the three conditions. In contrast, ECD strengths and AMS amplitudes from the anterior cingulate cortex (ACC), which showed a similar peak to the N2 component, were smaller in Movement than Control and Count. We therefore suspect that neural activities related to generator mechanisms of N2, especially including ACC, are inhibited by movement-related neural activities during the preparatory period. The present findings indicate a characteristic of pain-motor integration in a movement preparatory period.
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In 197.1, Bom et al developed one of the first catheter-based real-time imaging techniques for use in the cardiac system. In placing a set of phased-array ultrasound transducers within the cardiac chambers, Bom and colleagues show...
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In 197.1, Bom et al developed one of the first catheter-based real-time imaging techniques for use in the cardiac system. In placing a set of phased-array ultrasound transducers within the cardiac chambers, Bom and colleagues showed that higher frequencies than those used in transthoracic ultrasound imaging could be used to produce high-resolution images of cardiac structures. By the late 1980s, Yock et al had successfully miniaturized a single-transducer system to enable transducer placement within coronary arteries. Since then, intravascular ultrasound (IVUS) -has become a pivotal catheter-based imaging technology, having provided practical guidance for percutaneous interventions and scientific insights into vascular biology in clinical settings. Technical developments currently being explored consist of further device improvements, a variety of advanced image analyses, and the extension of this ultrasound-based approach to diverse intravascular imaging techniques with other energy sources.
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Previous studies have suggested that the biodegradability of octacalcium phosphate-collagen (OCP/Col) composite by osteoclasts is accelerated in association with mechanical stress suffered by the host tissue around the implant. Th...
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Previous studies have suggested that the biodegradability of octacalcium phosphate-collagen (OCP/Col) composite by osteoclasts is accelerated in association with mechanical stress suffered by the host tissue around the implant. The present study was designed to investigate whether alleviation of mechanical stress restores the bone regenerative properties of OCP/Col, as previously shown in nonload-bearing sites. OCP/Col discs supported with a polytetrafluoroethylene (PTFE) ring, which has a higher modulus than OCP/Col, were implanted in a rat subperiosteal pocket for up to 12 weeks. The structural features of the implant and biological responses were analyzed by X-ray diffraction, Fourier transform infrared spectroscopy, histomorphometry, histochemistry, and tissue mRNA expression around the implants. The effect of compression was analyzed using mouse stromal ST-2 cells by deforming the cell-seeded OCP/Col discs in vitro with or without a PTFE ring. The results clearly indicated the restoration of bone formation by the alleviation of mechanical stress and the upregulation of osteoblast-related genes, such as osterix on the other hand, the implantation of OCP/Col on calvaria or in an in vitro test without PTFE support resulted in the upregulation of osteoclast-related genes, such as tartrate-resistant acid phosphatase (TRAP) and cathepsin K, in the tissues or receptor activator of the nuclear factor-kappaB ligand (RANKL) in ST-2 cells. The results confirmed that calvaria augmentation is enhanced by implanting OCP/Col if suitable conditions regarding mechanical stress are provided.
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