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Hiroshi Toyama

Publications and source records attributed to Hiroshi Toyama.

16 recordsLinked to original sources
PubMed2006

Persistent dopamine functions of neurons derived from embryonic stem cells in a rodent model of Parkinson disease.

The derivation of dopamine neurons is one of the best examples of the clinical potential of embryonic stem (ES) cells, but the long-term function of the grafted neurons has not been established. Here, we show that, after transplantation into an animal model, neurons derived from mouse ES cells survived for over 32 weeks, maintained midbrain markers, and had sustained behavioral effects. Microdialysis in grafted animals showed that dopamine (DA) release was induced by depolarization and pharmacological stimulants. Positron emission tomography measured the expression of presynaptic dopamine transporters in the graft and also showed that the number of postsynaptic DA D(2) receptors was normalized in the host striatum. These data suggest that ES cell-derived neurons show DA release and reuptake and stimulate appropriate postsynaptic responses for long periods after implantation. This work supports continued interest in ES cells as a source of functional DA neurons.

Animals↗
PubMed2005

Postural muscle activity patterns during standing at rest and on an oscillating floor.

Postural muscle activity pattern was examined in the eyes-closed state after adequate adaptation to floor anteroposterior oscillation. Twenty-three subjects were grouped almost evenly according to dominance of anterior or posterior postural muscles in the trunk and thigh during quiet stance. In the posterior-dominant group, this dominance was maintained at every frequency in most subjects. In the anterior-dominant group, this dominance was maintained in most subjects at 0.1 and 0.5 Hz but changed to posterior dominance at 1.0 and 1.5 Hz in about half the subjects. Periodicity of muscle activity was evaluated by EMG amplitude spectrum at the floor oscillation frequency. Periodicity of posterior-dominant muscles in the trunk and thigh increased with increasing oscillatory frequency. In the trunk, the periodicity did not differ significantly between posterior-dominant and anterior-dominant groups. However, in the thigh, periodicity was significantly lower in the anterior-dominant muscles. This was considered to be caused by nonperiodic alternating action of the anterior and posterior muscles. In the lower leg, posterior dominance was observed in quiet stance and at all oscillation frequencies. Periodicity of soleus and gastrocnemius increased at higher frequencies and was higher in gastrocnemius than in soleus. The periodicity difference between both muscles decreased with increasing oscillation frequency.

Adolescent↗
PubMed2005

PET imaging of brain with the beta-amyloid probe, [11C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer's disease.

PURPOSE: The purpose of this study was to evaluate the capacity of [11C]6-OH-BTA-1 and positron emission tomography (PET) to quantify beta-amyloid (Abeta) plaques in the Tg2576 mouse model of Alzheimer's disease (AD). METHODS: PET imaging was performed with the NIH ATLAS small animal scanner in six elderly transgenic mice (Tg2576; age 22.0+/-1.8 months; 23.6+/-2.6 g) overexpressing a mutated form of human beta-amyloid precursor protein (APP) known to result in the production of Abeta plaques, and in six elderly wild-type litter mates (age 21.8+/-1.6 months; 29.5+/-4.7 g). Dynamic PET scans were performed for 30 min in each mouse under 1% isoflurane inhalation anesthesia after a bolus injection of 13-46 MBq of [11C]6-OH-BTA-1. PET data were reconstructed with 3D OSEM. On the coronal PET image, irregular regions of interest (ROIs) were placed on frontal cortex (FR), parietal cortex (PA), striatum (ST), thalamus (TH), pons (PO), and cerebellum (CE), guided by a mouse stereotaxic atlas. Time-activity curves (TACs) (expressed as percent injected dose per gram normalized to body weight: % ID-kg/g) were obtained for FR, PA, ST, TH, PO, and CE. ROI-to-CE radioactivity ratios were also calculated. Following PET scans, sections of mouse brain prepared from anesthetized and fixative-perfused mice were stained with thioflavin-S. RESULTS: TACs for [11C]6-OH-BTA-1 in all ROIs peaked early (at 30-55 s), with radioactivity washing out quickly thereafter in both transgenic and wild-type mice. Peak uptake in all regions was significantly lower in transgenic mice than in wild-type mice. During the later part of the washout phase (12-30 min), the mean FR/CE and PA/CE ratios were higher in transgenic than in wild-type mice (1.06+/-0.04 vs 0.98+/-0.07, p=0.04; 1.06+/-0.09 vs 0.93+/-0.08 p=0.02) while ST/CE, TH/CE, and PO/CE ratios were not. Ex vivo staining revealed widespread Abeta plaques in cortex, but not in cerebellum of transgenic mice or in any brain regions of wild-type mice. CONCLUSION: Marked reductions in brain uptake of this radioligand in transgenic mice may be due to reduced cerebral blood flow relative to that in wild-type mice. Specific [11C]6-OH-BTA-1 binding to Abeta plaques, if any, is probably very low, as reflected in the small FR/CE and PA/CE ratio differences. FR/CE and PA/CE ratios are considerably higher in AD patients while Abeta plaque densities in 22-month-old transgenic mice may be expected to show essentially the same density as is observed in the AD brain. This implies that the absence of tracer retention in 22-month-old transgenic mice may be due to the smaller number of Abeta plaque binding sites and/or to lower affinity of the binding sites for [11C]6-OH-BTA-1 as compared with AD patients. [11C]6-OH-BTA-1 shows excellent brain uptake in mice.

Alzheimer Disease↗
PubMed2005

Perception of large change in distribution of heel pressure during backward leaning.

We investigated the perception of the large change in distribution of heel pressure during backward leaning. Subjects were 12 healthy adults who reported perceiving a large change in distribution of heel pressure by a handheld switch while leaning voluntarily backward on a sole pressure analyzer and on a heel force plate. The large change was indicated at the center of heel pressure. Morphological features of the foot were measured on an X-ray film. The position of heel pressure center and the morphological locations were represented as relative distance (%) from the hindmost point of the heel, where foot length represented 100%. Center of heel pressure changed largely during backward leaning, and the position at which large change occurred was the same as that of the peak of the distribution. Large change in distribution of heel pressure was perceived at a position 1.3% posterior from that at which the large change actually occurred. The correlation between perceived and actual positions was significant (r = .91). Significant correlations were found between position of a large change of center and locations of heel pressure of both the lateral process of the calcaneal tuberosity and the top of the talar trochlea (r = .86; r = .71, respectively). The results indicate that subjects accurately perceive large changes in distribution of heel pressure and that the morphological features of the foot contribute to these changes.

Adult↗
PubMed2004

Synthesis and evaluation of two 18F-labeled 6-iodo-2-(4'-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine derivatives as prospective radioligands for beta-amyloid in Alzheimer's disease.

This study evaluated (18)F-labeled IMPY [6-iodo-2-(4'-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine] derivatives as agents for imaging beta-amyloid plaque with positron emission tomography (PET). The precursor for radiolabeling and reference compounds was synthesized in up to five steps from commercially accessible starting materials. One of the two N-methyl groups of IMPY was substituted with either a 3-fluoropropyl (FPM-IMPY) or a 2-fluoroethyl (FEM-IMPY) group. FPM-IMPY and FEM-IMPY were found to have moderate affinity for Abeta-aggregates with K(i) = 27 +/- 8 and 40 +/- 5 nM, respectively. A "one-pot" method for (18)F-2-fluoroethylation and (18)F-3-fluoropropylation of the precursor was developed. The overall decay-corrected radiochemical yields were 26-51%. In PET experiments with normal mouse, high uptake of activity was obtained in the brain after iv injection of each probe: 6.4% ID/g for [(18)F]FEM-IMPY at 1.2 min, and 5.7% ID/g for [(18)F]FPM-IMPY at 0.8 min. These values were similar to those of [(123)I/(125)I]IMPY (7.2% ID/g at 2 min). Polar and nonpolar radioactive metabolites were observed in both plasma and brain homogenates after injection of [(18)F]FEM or [(18)F]FPM-IMPY. In contrast to the single-exponential washout of [(123)I/(125)I]IMPY, the washouts of brain activity for the two fluorinated analogues were biphasic, with an initial rapid phase over 20 min and a subsequent much slower phase. Residual brain activity at 2 h, which may represent polar metabolites trapped in the brain, was 4.5% ID/g for [(18)F]FEM-IMPY and 2.1% ID/g for [(18)F]FPM-IMPY. Substantial skull uptake of [(18)F]fluoride was also clearly observed. With a view to slow the metabolism of [(18)F]FEM-IMPY, an analogue was prepared with deuteriums substituted for the four ethyl hydrogens. However, D(4)-[(18)F]FEM-IMPY showed the same brain uptake and clearance as the protio analogue. Metabolism of the [(18)F]FEM-IMPY was appreciably slower in rhesus monkey than in mouse. Autoradiography of postmortem brain sections of human Alzheimer's disease patients with [(18)F]FEM-IMPY showed high displaceable uptake in gray matter and low nonspecific binding in the white matter. This study demonstrates that the IMPY derivatives have favorable in vivo brain pharmacokinetics and a moderate affinity for imaging beta-amyloid plaques; however, further improvements are needed to reduce radioactive metabolites, increase binding affinity, and reduce lipophilicity.

Alzheimer Disease↗
PubMed2004

Evaluation of anesthesia effects on [18F]FDG uptake in mouse brain and heart using small animal PET.

This study evaluates effects of anesthesia on (18)F-FDG (FDG) uptake in mouse brain and heart to establish the basic conditions of small animal PET imaging. Prior to FDG injection, 12 mice were anesthetized with isoflurane gas; 11 mice were anesthetized with an intraperitoneal injection of a ketamine/xylazine mixture; and 11 mice were awake. In isoflurane and ketamine/xylazine conditions, FDG brain uptake (%ID/g) was significantly lower than in controls. Conversely, in the isoflurane condition, %ID/g in heart was significantly higher than in controls, whereas heart uptake in ketamine/xylazine mice was significantly lower. Results suggest that anesthesia impedes FDG uptake in mouse brain and affects FDG uptake in heart; however, the effects in the brain and heart differ depending on the type of anesthesia used.

Anesthesia↗
PubMed2004

Absolute quantification of regional cerebral glucose utilization in mice by 18F-FDG small animal PET scanning and 2-14C-DG autoradiography.

UNLABELLED: The purpose of this study was to evaluate the feasibility of absolute quantification of regional cerebral glucose utilization (rCMR(glc)) in mice by use of (18)F-FDG and a small animal PET scanner. rCMR(glc) determined with (18)F-FDG PET was compared with values determined simultaneously by the autoradiographic 2-(14)C-DG method. In addition, we compared the rCMR(glc) values under isoflurane, ketamine and xylazine anesthesia, and awake states. METHODS: Immediately after injection of (18)F-FDG and 2-(14)C-DG into mice, timed arterial samples were drawn over 45 min to determine the time courses of (18)F-FDG and 2-(14)C-DG. Animals were euthanized at 45 min and their brain was imaged with the PET scanner. The brains were then processed for 2-(14)C-DG autoradiography. Regions of interest were manually placed over cortical regions on corresponding coronal (18)F-FDG PET and 2-(14)C-DG autoradiographic images. rCMR(glc) values were calculated for both tracers by the autoradiographic 2-(14)C-DG method with modifications for the different rate and lumped constants for the 2 tracers. RESULTS: Average rCMR(glc) values in cerebral cortex with (18)F-FDG PET under normoglycemic conditions (isoflurane and awake) were generally lower (by 8.3%) but strongly correlated with those of 2-(14)C-DG (r(2) = 0.95). On the other hand, under hyperglycemic conditions (ketamine/xylazine) average cortical rCMR(glc) values with (18)F-FDG PET were higher (by 17.3%) than those with 2-(14)C-DG. Values for rCMR(glc) and uptake (percentage injected dose per gram [%ID/g]) with (18)F-FDG PET were significantly lower under both isoflurane and ketamine/xylazine anesthesia than in the awake mice. However, the reductions of rCMR(glc) were markedly greater under isoflurane (by 57%) than under ketamine and xylazine (by 19%), whereas more marked reductions of %ID/g were observed with ketamine/xylazine (by 54%) than with isoflurane (by 37%). These reverse differences between isoflurane and ketamine/xylazine may be due to competitive effect of (18)F-FDG and glucose uptake to the brain under hyperglycemia. CONCLUSION: We were able to obtain accurate absolute quantification of rCMR(glc) with mouse (18)F-FDG PET imaging as confirmed by concurrent use of the autoradiographic 2-(14)C-DG method. Underestimation of rCMR(glc) by (18)F-FDG in normoglycemic conditions may be due to partial-volume effects. Computation of rCMR(glc) from (18)F-FDG data in hyperglycemic animals may require, however, alternative rate and lumped constants for (18)F-FDG.

Anesthetics↗
PubMed2003

Anticipatory activation of postural muscles associated with bilateral arm flexion in subjects with different quiet standing positions.

We investigated changes in activation timing and magnitude of the postural muscles according to initial standing positions. The subjects were divided into three groups depending on the position of the center of foot pressure (CFP) during quiet standing, namely backward, middle, and forward. Subjects maintained standing postures at various CFP positions in the anteroposterior direction, and then started bilateral arm movement at their own pace. The activation magnitude of the biceps femoris (BF) and erector spinae (ES) did not differ among any of the initial CFP positions. In only the BF, the preceding action to the anterior deltoid (AD) was clearly observed at more forward CFP positions in the order of the forward, middle and backward groups. Between initial CFP positions adjacent to quiet standing posture, the smallest change was observed in the preceding activation time of the BF. Significant correlation was observed between the background activity and activation time in both the BF and ES.

Adult↗
PubMed2003

Influences of illusionary position perception on anticipatory postural control associated with arm flexion.

We examined the effect of illusionary perception on anticipatory postural control associated with arm flexion with subjects in a standing position, using vibration stimulation of the Achilles' tendon. Arm flexion was performed five times under each of the following conditions: (1) quiet standing, (2) vibration of the Achilles' tendon at 100 Hz frequency and 1.5 mm amplitude with the trunk fixed by a stopper during quiet standing, and (3) a perceived standing position during vibration. The reproduced positions were located forward by about 20% of the foot length compared with the quiet standing position; these positions showed no significant differences among the five trials. In the first trial of arm flexion during vibration, the biceps femoris began activating approximately 40 ms before the anterior deltoid. The same time difference between activation of the two muscles was observed in the reproduced condition. As the vibration trials were repeated, this activation timing approached the value in the quiet standing condition. In both the biceps femoris and erector spinae, the mean amplitude of electromyogram for the first 50 ms after the start of activation did not differ significantly among the three conditions.

Achilles Tendon↗
PubMed2003

Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain.

SUMMARY: The authors developed and applied two new linearized reference tissue models for parametric images of binding potential (BP) and relative delivery (R1) for [11C]DASB positron emission tomography imaging of serotonin transporters in human brain. The original multilinear reference tissue model (MRTM(O)) was modified (MRTM) and used to estimate a clearance rate (k'2) from the cerebellum (reference). Then, the number of parameters was reduced from three (MRTM) to two (MRTM2) by fixing k'2. The resulting BP and R1 estimates were compared with the corresponding nonlinear reference tissue models, SRTM and SRTM2, and one-tissue kinetic analysis (1TKA), for simulated and actual [11C]DASB data. MRTM gave k'2 estimates with little bias (<1%) and small variability (<6%). MRTM2 was effectively identical to SRTM2 and 1TKA, reducing BP bias markedly over MRTM(O) from 12-70% to 1-4% at the expense of somewhat increased variability. MRTM2 substantially reduced BP variability by a factor of two or three over MRTM or SRTM. MRTM2, SRTM2, and 1TKA had R1 bias <0.3% and variability at least a factor of two lower than MRTM or SRTM. MRTM2 allowed rapid generation of parametric images with the noise reductions consistent with the simulations. Rapid parametric imaging by MRTM2 should be a useful method for human [11C]DASB positron emission tomography studies.

Aniline Compounds↗
PubMed2003

Latency of saccadic eye movement during contraction of bilateral and unilateral shoulder girdle elevators.

We compared the timed latencies of saccadic eye movement during isometric contraction of the bilateral and unilateral shoulder girdle elevators in a sitting posture. Muscle contraction force was increased in 10% increments from 0% to 60% of the maximal voluntary contraction (MVC) of each side. Saccadic latency was measured as the latency to the beginning of eye movement toward the lateral target that was moved at random intervals in 20 degree amplitude jumps. Eye movement was measured using the electro-oculogram technique. During bilateral contraction, saccadic latency decreased until 30% MVC and then began to increase at 40% MVC. During unilateral contraction, saccadic latency decreased until 30% MVC in a similar pattern as in bilateral condition, was constant from 30% MVC to 50% MVC, followed by a slight increase at 60% MVC. The saccadic latencies at 10% and 40-60% MVC were significantly shorter during unilateral contraction than bilateral contraction. Thus, the relative force for producing a marked shortening of saccadic latency is observed within a wider range during unilateral contraction than bilateral contraction.

Adolescent↗
PubMed2003

Perceived standing position after reduction of foot-pressure sensation by cooling the sole.

We investigated the influence of the reduction of foot-pressure sensation by cooling the sole of the foot, at 1 degree C for 30 or 40 minutes, on the perception of standing position varied in the anteroposterior direction. The subjects were 16 healthy undergraduates. Firstly, for 4 of the subjects, cooling the sole of the foot decreased sensory information from the mechanoreceptors in the sole, by testing for an increase in the threshold for two-point discrepancy discrimination on the sole of the foot and for the disappearance of postural change with vibration to the sole. Next, the perception of standing position was measured by reproduction of a given standing reference position involving forward or backward leaning under both normal and cooled conditions of the feet. Standing position was varied in relation to the location of the center of foot pressure, defined as distance from the heel in percentage of the length of the foot. The reference positions, representing various locations of the center of foot pressure, were set at 10% increments from 20% to 80% of the length of the foot. With eyes closed, the subject first experienced the reference position and then attempted to reproduce it. The mean location of the center of foot pressure in the quiet standing posture was 45.7%. At the 40%, 50%, and 60% reference positions, those closest to quiet standing, absolute errors of reproduction were significantly larger than at other reference positions in both the normal and the cooled conditions. They were significantly larger in the cooled than in the normal condition. The 50% and 60% reference positions were reproduced significantly further forward in the cooled than in the normal condition. These results may be explained as due to an absence of marked changes in sensory information from both muscular activity and foot pressure when moving to reference positions close to the quiet standing posture.

Adult↗
PubMed2003

Evaluation of 2 scatter correction methods using a striatal phantom for quantitative brain SPECT.

OBJECTIVE: Scatter correction is an important factor in quantitative SPECT. In this study, we evaluated 2 methods of scatter correction for brain SPECT. The first is based on thresholding the energy spectrum (ES), and the second is based on a modification of the transmission-dependent convolution subtraction (TDCS) method. METHODS: SPECT imaging of a skull striatal phantom was performed using a triple-head camera with and without scatter correction. The striatal compartments were filled with (123)I, and the brain shell cavity (background) was filled with varying concentrations of (123)I to obtain striatal-to-background ratios of 2, 5, 10, 15, 20, and 25 to 1, respectively, which were considered to be the expected ratios. SPECT-measured ratios of striatal-to-background counts were determined with scatter correction (both ES and TDCS methods) and without scatter correction and were then compared with the expected ratios. RESULTS: Without scatter correction, measured striatal-to-background ratios were underestimated by an average of 41.7%, compared with the expected ratios. The ES method of scatter correction underestimated the striatal-to-background ratios by an average of 27.4%, a significant improvement (P < 0.04) over those without scatter correction. With the TDCS method of scatter correction, the ratios were underestimated by only 3.3% (P < 0.03). TDCS ratios were significantly (P < 0.04) higher than ES ratios and were nearly identical to the expected ratios. CONCLUSION: These results suggest that scatter correction significantly improves the striatal-to-background ratios. The TDCS method appears to correct scatter more effectively than does the ES method for the striatal phantom, thus providing more accurate quantification.

Algorithms↗
PubMed2002

Strategies to improve neuroreceptor parameter estimation by linear regression analysis.

In an attempt to improve neuroreceptor distribution volume (V) estimates, the authors evaluated three alternative linear methods to Logan graphical analysis (GA): GA using total least squares (TLS), and two multilinear analyses, MA1 and MA2, based on mathematical rearrangement of GA equation and two-tissue compartments, respectively, using simulated and actual PET data of two receptor tracers, [(18)F]FCWAY and [(11)C]MDL 100,907. For simulations, all three methods decreased the noise-induced GA bias (up to 30%) at the expense of increased variability. The bias reduction was most pronounced for MA1, moderate to large for MA2, and modest to moderate for TLS. In addition, GA, TLS, and MA1, methods that used only a portion of the data (T > t*, chosen by an automatic process), showed a small underestimation for [(11)C]MDL 100,907 with its slow kinetics, due to selection of t* before the true point of linearity. These noniterative methods are computationally simple, allowing efficient pixelwise parameter estimation. For tracers with kinetics that permit t* to be accurately identified within the study duration, MA1 appears to be the best. For tracers with slow kinetics and low to moderate noise, however, MA2 may provide the lowest bias while maintaining computational ease for pixelwise parameter estimation.

Basal Ganglia↗