Papular and reticular elastolytic giant cell granuloma: rapid spontaneous regression.
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Biomedical subjects
Publications and source records attributed to Kenji Ishii.
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Singing in unison is usually easier than singing alone, but the neural mechanism underlying these two contrasting modes of singing remains unknown. We investigated neural correlates of singing by a functional magnetic resonance imaging study focusing on the capacities of spontaneity and synchronization and compared them with those of speaking. The left inferior frontal gyrus appears important for self-generation of text in singing and speaking without auditory input, whereas the left posterior planum temporale plays a key role in synchronizing both text and melody, in combination with the bilateral inferior parietal lobule for singing along, and with the left angular gyrus for speaking in chorus. These findings indicate that text and melody are not processed symmetrically or parallel in singing a well-learned song.
PURPOSE: [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX) is a positron-emitting adenosine A(2A) receptor (A2AR) antagonist for visualisation of A2AR distribution by positron emission tomography (PET). The aims of this paper were to use a kinetic model to analyse the behaviour of [(11)C]TMSX in the brain and to examine the applicability of the Logan plot. We also studied the applicability of a simplified Logan plot by omitting metabolite correction and arterial blood sampling. METHODS: The centrum semiovale was used as a reference region on the basis of a post-mortem study showing that it has a negligibly low density of A2ARs. Compartmental analysis was performed in five normal subjects. Parametric images of A2AR binding potential (BP) were also generated using a Logan plot with or without metabolite correction and with or without arterial blood sampling. To omit arterial blood sampling, we applied a method to extract the plasma-related information using independent component analysis (EPICA). RESULTS: The estimated K (1)/k (2) was confirmed to be common in the centrum semiovale and main cortices. The three-compartment model was well fitted to the other regions using the fixed value of K (1)/k (2) estimated from the centrum semiovale. The estimated BPs using the Logan plot matched those derived from compartment analysis. Without the metabolite correction, the estimate of BP underestimated the true value by 5%. The estimated BPs agreed regardless of arterial blood sampling. CONCLUSION: A three-compartment model with a reference region, the centrum semiovale, describes the kinetic behaviour of [(11)C]TMSX PET images. A2ARs in the human brain can be visualised as a BP image using [(11)C]TMSX PET without arterial blood sampling.
The majority of patients with type I Gaucher's disease never develop neurological signs or symptoms. However, several case reports of Parkinson's disease associated with type I Gaucher's disease have been published, suggesting a genetic link between the two diseases. Hence, detailed clinical investigations are required when the two diseases occur simultaneously, in order to determine whether this is coincidental or whether a true association is present. We present a Japanese man in whom parkinsonism was associated with type I Gaucher's disease. Findings of brain positron tomography (PET) and metaiodobenzylguanidine (MIBG) cardiac scintigraphy are presented.
We investigated feasibility of positron emission tomography (PET) with [11C]SA4503 for evaluating the sigma1 receptor occupancy rate by neuroleptics. Haloperidol, which is well known to bind dopamine D2-like receptor (D2R) as well as to be a representative non-selective antagonist for sigma1 receptor (sigma1R), was selected as a model drug. Three healthy male subjects underwent 60-min [11C]raclopride-PET and 90-min [11C]SA4503-PET scans successively at a 120-min interval twice in a day for baseline measurement and on another day for haloperidol-loading measurement 16 hours after peroral administration of 3 mg of haloperidol. Binding potential (BP) of [11C]raclopride and [11C]SA4503 was quantitatively evaluated and the sigma1R and D2R occupancy rates were determined. D2R occupancy rates by haloperidol were 64% and 62% in the caudate and putamen, respectively, 16 h after the administration, while sigma1R occupancy rates were approximately 80% in all seven regions investigated including the caudate, putamen and cerebellum 18 h after the administration, suggesting that the sigma1R receptor occupancy rate by haloperidol was slightly larger than the D2R receptor occupancy rate. We concluded that [11C]SA4503-PET can be used for evaluating the sigma1R occupancy rates by neuroleptics or other drugs.
We examined whether the degree of hemodynamic stress in patients with chronic occlusive cerebral vascular disease can be quantitatively evaluated with the use of perfusion-weighted magnetic resonance imaging (PWI). Thirty-six patients with moyamoya disease (mean age, 26.8 years; range, 18 to 59) underwent PWI and positron emission tomography (PET) within a month's interval. The PWI data were calculated by three different analytic methods. The cerebral blood flow (CBF) ratio, cerebral blood volume (CBV) ratio, and mean transit time (MTT) of the anterior circulation were calculated using the cerebellum as a control region and compared with PET data on the same three parameters and oxygen extraction fraction (OEF). Parametric maps of PWI attained a higher resolution than the PET maps and revealed focal perfusion failure on a gyrus-by-gyrus level. The relative CBV and MTT obtained with PWI showed significant linear correlations with the corresponding PET values (CBV, R2 = 0.47 to 0.58; MTT, R2 = 0.32 to 0.68). We also found that we could detect regions with abnormally elevated OEF and CBV based on the delay of PWI-measured MTT relative to the control region by defining a 2.0-sec delay as a threshold. The sensitivity and specificity were 92.3% and 100% in detecting regions with abnormally elevated OEF, and 20.0% and 100% in detecting regions with abnormally elevated CBV, respectively. Among the parameters obtained with PWI, our results suggested that the relative CBV value and delay of MTT might be quantitatively manipulated to assist in clinical decision-making for patients with moyamoya disease.
AIMS: The strength of sedation due to antihistamines can be evaluated by using positron emission tomography (PET). The purpose of the present study is to measure histamine H(1) receptor (H(1)R) occupancy due to olopatadine, a new second-generation antihistamine and to compare it with that of ketotifen. METHODS: Eight healthy males (mean age 23.5 years-old) were studied following single oral administration of olopatadine 5 mg or ketotifen 1 mg using PET with (11)C-doxepin in a placebo-controlled crossover study design. Binding potential ratio and H(1)R occupancy were calculated and were compared between olopatadine and ketotifen in the medial prefrontal (MPFC), dorsolateral prefrontal (DLPFC), anterior cingulate (ACC), insular (IC), temporal (TC), parietal (PC), occipital cortices (OC). Plasma drug concentration was measured, and correlation of AUC to H(1)R occupancy was examined. RESULTS: H(1)R occupancy after olopatadine treatment was significantly lower than that after ketotifen treatment in the all cortical regions (P < 0.001). Mean H(1)R occupancies for olopatadine and ketotifen were, respectively: MPFC, 16.7 vs. 77.7; DLPFC, 14.1 vs. 85.9; ACC, 14.7 vs. 76.1; IC, 12.8 vs. 69.7; TC, 12.5 vs. 66.5; PC, 13.9 vs. 65.8; and OC, 19.5 vs. 60.6. Overall cortical mean H(1)R occupancy of olopatadine and ketotifen were 15% and 72%, respectively. H(1)R occupancy of both drugs correlated well with their respective drug plasma concentrations (P < 0.001). CONCLUSION: It is suggested that 5 mg oral olopatadine, with its low H(1)R occupancy and thus minimal sedation, could safely be used an antiallergic treatment for various allergic disorders. Abbreviations histamine H(1) receptor (H(1)R), histamine H(1) receptor occupancy (H(1)RO), dopamine D(2) receptor (D(2)R), positron emission tomography (PET), blood-brain barrier (BBB), binding potential ratio (BPR), distribution volume (DV).
AIM: To assess the effectiveness of ability grouping in a fall prevention structured exercise program for elderly people. METHODS: We enrolled 124 subjects from among 2,582 elderly people aged 70 to 84 years living in the Tsurugaya district in Sendai City. Exclusion criteria were 1) motor fitness scale (MFS) score 9 points or more, 2) severe sensory, cognitive, or 3) physical disorders, and 4) nursing care grade 2 or more. Those ranked in the lower fourth and in the upper 3 fourths of the timed up and go test (TUGT) were each randomly assigned to 3 groups. Subjects in groups A and B had an exercise program for lower and higher fitness subjects separately, whereas all subjects in group C underwent a single exercise program. The exercise program, once a week for 12 weeks, consisted of strength and stability training. TUGT, lateral reach (LR), leg power per body weight and MFS were measured after the intervention and compared with the baseline values. RESULTS: There were no difference in the baseline characteristics among the groups. For group A, no significant changes in physical fitness measures, for group B a small but significant deterioration in LR, and for group C a small but significant deterioration in LR and TUGT were observed. MFS score improved significantly in all groups. CONCLUSION: Ability grouping appeared to be effective for a short-term exercise program in maintaining the physical ability, but the effectiveness did not reach statistical significance in the randomized controlled design.
OBJECTIVE: We have launched a new intervention study, called "Research of Productivity by Intergenerational Sympathy (REPRINTS)" in which senior volunteers engage in reading picture books to children. The "REPRINTS" program consistently involves social roles and intellectual activity, two higher-level functional capacities. This study reported findings and problems experienced through "REPRINTS" during the first year, ascertained potential effectiveness of social activity, and proposed methods for continued activity. METHODS: Basic concepts of "REPRINTS"program include "contribution to society", "life-long learning", and "group activity." Sixty seven volunteers and 74 controls, all aged 60 years and over living in three areas, ie., Chuo-ku, central Tokyo, Kawasaki city, suburb of Tokyo and Nagahama city, a local city, participated in a baseline health check-up in June, 2004. After completion of 3-month training seminars (once a week, 2 hr per session), volunteers visited public elementary schools and kindergartens in groups of 6-10 persons for 6 months. They were assessed again by follow-up health check-up in March, 2005. RESULTS: At baseline, the proportion of those who had no grand children (41.8% vs. 20.3%, P= 0.006), average school years (13.4 +/- 2.5 vs. 12.3 +/- 2.5 years, P= 0.008), having any experience of volunteer activities (79.1% vs. 52.7%, P=0.001), and an usual walking speed (86.7 +/- 12.3 vs. 81.3 +/- 12.9 m/min, P=0.012) were significantly higher in volunteers than in controls. There was no significant difference in other baseline characteristics between the two groups. At follow-up, social network scores for 56 volunteers were significantly improved: frequency of contact with grandchildren and others around neighborhood and size of circles of friends and acquaintances were increased, as compared to controls. Social support scores for the volunteers significantly decreased in the receiving aspect, while increased in the giving aspect. In addition, consciousness of loving community and self-rated health were significantly enhanced and hand-grip strength showed significantly less decline in volunteers than in controls. CONCLUSIONS: Through engaging in the intergenerational and intellectual volunteer programs for 9 months, subjective health, social support and network, consciousness of loving community and some aspects of physical performance were significantly promoted in senior volunteers. Coordination of existing administrative services enabled us to establish this "REPRINTS" health promotion program for community-dwelling older adults.
Clinical recovery after stroke can be significant and has been attributed to plastic reorganization and recruitment of novel areas previously not engaged in a given task. As equivocal results have been reported in studies using single imaging or electrophysiological methods, here we applied an integrative multimodal approach to a group of well-recovered chronic stroke patients (n = 11; aged 50-81 years) with left capsular lesions. Focal activation during recovered hand movements was assessed with EEG spectral analysis and H2(15)O-PET with EMG monitoring, cortico-cortical connectivity with EEG coherence analysis (cortico-cortical coherence) and corticospinal connectivity with transcranial magnetic stimulation (TMS). As seen from comparisons with age-matched controls, our patients showed enhanced recruitment of the lateral premotor cortex of the lesioned hemisphere [Brodmann area (BA) 6], lateral premotor and to a lesser extent primary sensorimotor and parietal cortex of the contralesional hemisphere (CON-H; BA 4 and superior parietal lobule) and left cerebellum (patients versus controls, Z > 3.09). EEG coherence analysis showed that after stroke cortico-cortical connections were reduced in the stroke hemisphere but relatively increased in the CON-H (ANOVA, contrast analysis, P < 0.05), suggesting a shift of functional connectivity towards the CON-H. Nevertheless, fast conducting corticospinal transmission originated exclusively from the lesioned hemisphere. No direct ipsilateral motor evoked potentials (MEPs) could be elicited with TMS over the contralesional primary motor cortex (iM1) in stroke patients. We conclude that (i) effective recovery is based on enhanced utilization of ipsi- and contralesional resources, (ii) basic corticospinal commands arise from the lesioned hemisphere without recruitment of ('latent') uncrossed corticospinal tract fibres and (iii) increased contralesional activity probably facilitates control of recovered motor function by operating at a higher-order processing level, similar to but not identical with the extended network concerned with complex movements in healthy subjects.
We propose a novel algorithm for voxel-by-voxel compartment model analysis based on a maximum a posteriori (MAP) algorithm. Voxel-by-voxel compartment model analysis can derive functional images of living tissues, but it suffers from high noise statistics in voxel-based PET data and extended calculation times. We initially set up a feature space of the target radiopharmaceutical composed of a measured plasma time activity curve and a set of compartment model parameters, and measured the noise distribution of the PET data. The dynamic PET data were projected onto the feature space, and then clustered using the Mahalanobis distance. Our method was validated using simulation studies, and compared with ROI-based ordinary kinetic analysis for FDG. The parametric images exhibited an acceptable linear relation with the simulations and the ROI-based results, and the calculation time took about 10 min. We therefore concluded that our proposed MAP-based algorithm is practical.
Ferroelectric materials are widely used in modern electric devices such as memory elements, filtering devices and high-performance insulators. Ferroelectric crystals have a spontaneous electric polarization arising from the coherent arrangement of electric dipoles (specifically, a polar displacement of anions and cations). First-principles calculations and electron density analysis of ferroelectric materials have revealed that the covalent bond between the anions and cations, or the orbital hybridization of electrons on both ions, plays a key role in establishing the dipolar arrangement. However, an alternative model-electronic ferroelectricity-has been proposed in which the electric dipole depends on electron correlations, rather than the covalency. This would offer the attractive possibility of ferroelectric materials that could be controlled by the charge, spin and orbital degrees of freedom of the electron. Here we report experimental evidence for ferroelectricity arising from electron correlations in the triangular mixed valence oxide, LuFe(2)O(4). Using resonant X-ray scattering measurements, we determine the ordering of the Fe(2+) and Fe(3+) ions. They form a superstructure that supports an electric polarization consisting of distributed electrons of polar symmetry. The polar ordering arises from the repulsive property of electrons-electron correlations-acting on a frustrated geometry.
We have previously proposed a statistical method for extracting a plasma time-activity curve (pTAC) from dynamic PET images, named EPICA, for kinetic analysis of cerebral glucose metabolism. We assumed that the dynamic PET images consist of a blood-related component and a tissue-related component which are spatially independent in a statistical sense. The aim of this study is to investigate the utility of EPICA in imaging total distribution volume (DVt) and binding potential (BP) with Logan plots in a neuroreceptor mapping study. We applied EPICA to dynamic [(11)C]MPDX PET images in 25 subjects, including healthy subjects and patients with brain diseases, and validated the estimated pTACs. [11C]MPDX is a newly developed radiopharmaceutical for mapping cerebral adenosine A1 receptors. EPICA successfully extracted pTAC for all 25 subjects. Parametric images of DVts were estimated by applying Logan plots with the EPICA-estimated pTAC and then used to define a reference region. The BPs estimated using EPICA were evaluated in 18 subjects by ROI-based comparison with those obtained using the nonlinear least squares method (NLSM). The calculated BPs were identical to the estimates using NLSM in each subject. We conclude that EPICA is a promising technique that generates parametric images of DVt and BP in neuroreceptor mapping without requiring arterial blood sampling.
PURPOSE: Positron emission tomography (PET), the blood flow response in the primary visual cortex (V1) to two visual stimuli, low temporal frequency (6 Hz) to activate the parvocellular system, and high temporal frequency (25 Hz) to activate the magnocellular system were used to investigate pathophysiologic mechanism of amblyopia. METHODS: Five women and one man who were aged between 26 and 60 years, who were ophthalmologically normal except for amblyopia, and who had corrected visual acuity in the amblyopic eye of 0.6 or worse were examined. An intravenous injection of the H(2)(15)O was given, and the regional cerebral blood flow was measured by PET during full-field stimulation with either 6 Hz or 25 Hz flicker to the amblyopic or the sound eye. RESULT: The activation of blood flow in the contra-lateral area V1 by the 6-Hz stimulation of the sound eye was greater than that during the stimulation of the amblyopic eye (P<0.05, small volume correction, n=6). With 25-Hz stimulation of the sound and amblyopic eyes, the blood flow in the contra-lateral and ipsi-lateral areas V1 was not significantly different. CONCLUSION: The decreased activation of blood flow in the contra-lateral V1 by low temporal frequency stimuli supports the hypothesis that the parvocellular pathway in amblyopic eyes is depressed.
[11C]TMSX is a new positron emission tomography (PET) radioligand that provides visualization of adenosine A(2A) receptors (A(2A)Rs) in the brain, heart and skeletal muscle. Here we report on the first visualization of the A(2A)Rs in the human brain by PET and [11C]TMSX in a male healthy volunteer, compared with the adenosine A1 receptors (A1Rs) and dopamine D2 receptors (D2Rs) which were measured by PET with [11C]MPDX and [11C]raclopride, respectively. The distribution volume (DV) of [11C]TMSX in the baseline was relatively high in the head of caudate nucleus, putamen, and thalamus and relatively low in the cortical regions. Infusion of theophylline, a nonselective A(2A)R antagonist (Ki for A(2A)Rs = 16000 nM for theophylline vs 5.9 nM for TMSX), slightly reduced the DVs in the head of caudate nucleus (8.0% reduction) and putamen (4.5% reduction), but not in the other regions having much lower levels of A(2A)Rs, demonstrating the A(2A)R-specific binding of [11C]TMSX. On the other hand, the A1Rs were widely distributed in the whole brain except for the cerebellum, while the binding potential of [11C]raclopride was predominantly high in the striatum. We concluded that [11C]TMSX is an applicable PET ligand for mapping the A(2A)Rs in the caudate nucleus and putamen in clinical studies because of no availability of other radioligands until now. The [11C]TMSX PET is of great interest for studying the pathophysiology of neurological and psychiatric disorders together with the [11C]raclopride PET for D2Rs evaluation and/or the [11C]MPDX PET for A1Rs evaluation.
The aim of the present study is to evaluate the validity of the simplified reference tissue model (SRTM) and of Logan graphical analysis with reference tissue (LGAR) for quantification of histamine H1 receptors (H1Rs) by using positron emission tomography (PET) with [11C]doxepin. These model-based analytic methods (SRTM and LGAR) are compared to Logan graphical analysis (LGA) and to the one-tissue model (1TM), using complete datasets obtained from 5 healthy volunteers. Since HIR concentration in the cerebellum can be regarded as negligibly small, the cerebellum was selected as the reference tissue in the present study. The comparison of binding potential (BP) values estimated by LGAR and 1TM showed good agreement; on the other hand, SRTM turned out to be unstable concerning parameter estimation in several regions of the brain. By including the results of noise analysis, LGAR became a reliable method for parameter estimation of [11C]doxepin data in the cortical regions.
We performed preclinical and clinical studies of O-[11C]methyl-L-tyrosine, a potential tracer for imaging amino acid transport of tumors by positron emission tomography (PET). Examinations of the radiation-absorbed dose by O-[11C]methyl-L-tyrosine and the acute toxicity and mutagenicity of O-methyl-L-tyrosine showed suitability of the tracer for clinical use. The whole-body imaging of monkeys and healthy humans by PET showed low uptake of O-[11C]methyl-L-tyrosine in all normal organs except for the urinary track and bladder, suggesting that the O-[11C]methyl-L-tyrosine PET has the potential for tumor imaging in the whole-body. Finally, the brain tumor imaging was preliminarily demonstrated.
We examined the densities of adenosine A(2A) receptors in cardiac and skeletal muscles between untrained and endurance-trained subjects using positron emission tomography (PET) and [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX), a newly developed radioligand for mapping adenosine A(2A) receptors. Five untrained and five endurance-trained subjects participated in this study. The density of adenosine A(2A) receptors was evaluated as the distribution volume of [11C]TMSX in cardiac and triceps brachii muscles in the resting state using PET. The distribution volume of [11C]TMSX in the myocardium was significantly greater than in the triceps brachii muscle in both groups. Further, distribution volumes [11C]TMSX in the trained subjects were significantly grater than those in untrained subjects (myocardium, 3.6+/-0.3 vs. 3.1+/-0.4 ml g(-1); triceps brachii muscle, 1.7+/-0.3 vs. 1.2+/-0.2 ml g(-1), respectively). These results indicate that the densities of adenosine A(2A) receptors in the cardiac and skeletal muscles are greater in the endurance-trained men than in the untrained men.