Biomedical subjects

Kenji Ishii

Publications and source records attributed to Kenji Ishii.

At least 37 records · Page 2Linked to original sources

PubMed2005

Magnetoencephalography and positron emission tomography studies of a patient with auditory agnosia caused by bilateral lesions confined to the auditory radiations.

The aim of this study was to investigate auditory cortex function in the context of auditory stimuli in a patient with auditory agnosia due to bilateral lesions confined to the auditory radiations. A male patient experienced mild left temporal hemiplegia because of right putaminal hemorrhage at the age of 43 years. Thereafter he recovered completely but hypertension persisted. When he was 53 years old, he suffered left putaminal hemorrhage and went into a coma. After recovering from the coma and right hemiplegia he could hear but could not discriminate speech sounds. Brain CT and MRI demonstrated small bilateral lesions confined to the auditory radiations. Magnetoencephalography demonstrated the disappearance of middle latency responses and auditory-evoked potential studies showed a very small Pa peak. In contrast, a positron emission tomography study demonstrated a marked increase in blood flow in the bilateral auditory cortex in response to both click and monosyllable stimuli. It is speculated that the auditory cortex receives functional projections from the cochlea via non-specific pathways in the cerebral hemispheres.

Agnosia↗

PubMed2005

Extraction of a plasma time-activity curve from dynamic brain PET images based on independent component analysis.

A compartment model has been used for kinetic analysis of dynamic positron emission tomography (PET) data [e.g., 2-deoxy-2-18F-fluoro-D-glucose (FDG)]. The input function of the model [the plasma time-activity curve (pTAC)] was obtained by serial arterial blood sampling. It is of clinical interest to develop a method for PET studies that estimates the pTAC without needing serial arterial blood sampling. For this purpose, we propose a new method to extract the pTAC from the dynamic brain PET images using a modified independent component analysis [extraction of the pTAC using independent component analysis (EPICA). Source codes of EPICA are freely available at http://www5f.biglobe.ne.jp/ũkimura/Software/top.html]. EPICA performs the appropriate preprocessing and independent component analysis (ICA) using an objective function that takes the various properties of the pTAC into account. After validation of EPICA by computer simulation, EPICA was applied to human brain FDG-PET studies. The results imply that the EPICA-estimated pTAC was similar to the actual measured pTAC, and that the estimated blood volume image was highly correlated with the blood volume image measured using 15O-CO inhalation. These results demonstrated that EPICA is useful for extracting the pTAC from dynamic PET images without the necessity of serial arterial blood sampling.

Algorithms↗

PubMed2005

[Establishment of brain bank for aging research].

We have established a brain bank for the prevention and treatment of aging-related movement and cognitive disturbances, as a joint project between a rural care hospital and a research institute. The resources of the bank are to be used for collaborative studies approved by the bank's committee. The collaborative investigators should also be qualified by the institute to conduct the research jointly. The collaborative studies require authorization by the institutional review board (IRB) of the institute, the hospital and each facility involved in collaborative studies. The bank continues to have the responsibility for the resources, after the transfer of the resources to the facilities of collaborative investigators, pursuant to Article 18 of the Cadaver Autopsy and Preservation Act Thus, the status of resource utilization and outcomes from their use in studies will be monitored periodically (every 6 months). We shared the philosophy with the brain banks in the United States that the resources of the bank, donated on the basis of a charitable spirit, belong to the public domain and are regarded as public resources to be used to contribute to promoting public welfare.

Aging↗

PubMed2005

Imaging of somatotopic representation of sensory cortex with intrinsic optical signals as guides for brain tumor surgery.

OBJECT: Intrinsic optical signals in response to somatosensory stimuli were intraoperatively recorded during brain tumor surgery. In the present study, the authors report on the use of this technique as an intraoperative guide for the safe resection of tumors adjacent to or within the sensorimotor cortex. METHODS: In 14 patients with tumors adjacent to or within the sensorimotor cortex, intrinsic optical signals in response to somatosensory stimuli were recorded by illuminating the brain surface with Xe white light and imaging the reflected light passing through a bandpass filter (605 nm). Results were compared with intraoperative recordings of sensory evoked potentials in all 14 patients and with noninvasive mapping modalities such as magnetoencephalography and positron emission tomography in selected patients. In all but two patients, the somatosensory optical signals were recorded on the primary sensory cortex. Optical signals elicited by stimulation of the first and fifth digits and the three branches of the trigeminal nerve were recorded at different locations on the sensory strip. This somatotopic information was useful in determining the resection border in patients with glioma located in the sensorimotor cortex. CONCLUSIONS: Optical imaging of intrinsic signals is a useful technique with superior spatial resolution for delineating the somatotopic representation of human primary sensory cortex. Furthermore, it can be used as an intraoperative monitoring tool to improve the safety and accuracy of resections of brain tumors adjacent to or within the sensorimotor cortex.

Adult↗

PubMed2005

Usefulness of L-[methyl-11C] methionine-positron emission tomography as a biological monitoring tool in the treatment of glioma.

OBJECT: The authors retrospectively analyzed the data obtained in patients who had undergone L-[methyl-11C] methionine (MET)-positron emission tomography (PET) studies to clarify the relationship between MET uptake and tumor biological features and to discuss the clinical usefulness of MET-PET studies. METHODS: One hundred ninety-four patients with cerebral glioma or suspected glioma underwent PET scanning 20 minutes after injection of MET, whose uptake into the tumor was expressed as a ratio to contralateral healthy brain tissue (T/N ratio). Analyses were performed to determine how MET uptake correlated with tumor pathological features and prognosis. The T/N ratios before and after various treatments were also examined. There were significant differences in the T/N ratio among the nonneoplastic lesions, low-grade gliomas, and malignant gliomas. Furthermore, there were significant correlations between patient survival and pretreatment T/N ratios. Among patients with malignant gliomas, a significant difference in survival was observed between cases with and without postoperative tumor remnant based on elevated MET uptake. The MET uptake was heterogeneous even among the homogeneous tumor areas demonstrated on MR imaging. Malignant pathological features were detected in the areas with the highest MET uptake. The effectiveness of radiotherapy or chemotherapy was expressed as a significantly decreased T/N ratio in some of the tumor types. CONCLUSIONS: The ability of MET-PET to reflect the biological nature of gliomas makes it an excellent method for monitoring active tumor tissue, and treatments based on its findings should provide a powerful clinical protocol in the course of glioma therapy.

Brain Neoplasms↗

PubMed2005

Adenosine A1 receptor mapping of the human brain by PET with 8-dicyclopropylmethyl-1-11C-methyl-3-propylxanthine.

UNLABELLED: Adenosine is an endogenous modulator of synaptic functions in the central nervous system. To investigate the physiologic and pathologic roles of the adenosine receptors in the human brain, PET is a powerful in vivo technique. In this study, we quantitatively evaluated the distribution of a major subtype A(1) adenosine receptor in the human brain by PET with a newly developed radioligand, 8-dicyclopropylmethyl-1-(11)C-methyl-3-propylxanthine ((11)C-MPDX). METHODS: In 5 healthy volunteers, after PET measurement of the regional cerebral blood flow (rCBF) with (15)O-H(2)O, a 60-min PET scan with (11)C-MPDX was performed. The distribution volume (DV) of (11)C-MPDX was quantitatively evaluated by Logan's graphical analysis. RESULTS: (11)C-MPDX was taken up at a high level, reaching a peak at 2-2.5 min, followed by a rapid decrease. The unchanged form of (11)C-MPDX in plasma was 75% at 60 min after injection. The DV of (11)C-MPDX was large in the striatum and thalamus, moderate in the cerebral cortices and pons, and small in the cerebellum. The distribution pattern of (11)C-MPDX in the brain was coincident with that of adenosine A(1) receptors in vitro, reported previously, but discretely different from that of rCBF. CONCLUSION: (11)C-MPDX PET has the potential for mapping adenosine A(1) receptors in the human brain.

Adult↗

PubMed2005

Aortic wall inflammation due to Takayasu arteritis imaged with 18F-FDG PET coregistered with enhanced CT.

UNLABELLED: The purpose of this study was to evaluate the ability of (18)F-FDG PET to identify aortitis and to localize and follow disease activity in patients with Takayasu arteritis. The value of using (18)F-FDG PET coregistered with enhanced CT in determining vascular lesion sites and inflammatory activity was assessed. METHODS: Takayasu arteritis was diagnosed according to the predefined criteria. Eleven patients with Takayasu arteritis in the active stage, 3 patients with Takayasu arteritis in the inactive stage, and 6 healthy subjects underwent (18)F-FDG PET coregistered with enhanced CT and the inflammatory vascular lesion was evaluated by using the standardized uptake value (SUV) of (18)F-FDG accumulation as an index. Two patients with active disease were analyzed by sequential (18)F-FDG PET scans during treatment. RESULTS: The (18)F-FDG PET revealed intense (18)F-FDG accumulation (SUV > or = 2.7) in the vasculature of 2 of the 11 cases in the active stage of Takayasu arteritis. The other 9 patients in the active stage revealed weak (18)F-FDG accumulation (2.3 > or = SUV > or = 1.2). No significant (18)F-FDG accumulation was observed in the patients with inactive disease (SUV < or = 1.2) and 6 control healthy subjects (SUV < 1.3). Given the cutoff SUV is 1.3, the sensitivity of (18)F-FDG PET analysis of Takayasu arteritis is 90.9% and the specificity is 88.8%. (18)F-FDG PET coregistered with enhanced CT localized (18)F-FDG accumulation in the aortic wall in the patients with Takayasu arteritis who had weak (18)F-FDG accumulation that could not otherwise be identified anatomically. Finally, (18)F-FDG accumulation resolved with therapy in 2 active cases. The disappearance of (18)F-FDG accumulation did not coincide with the level of general inflammatory markers. CONCLUSION: The (18)F-FDG PET images coregistered with enhanced CT images showed the distribution and inflammatory activity in the aorta, its branches, and the pulmonary artery in patients with active Takayasu arteritis, even those who had weak (18)F-FDG accumulation. The intensity of accumulation decreased in response to therapy.

Adolescent↗

PubMed2004

Cortisol-induced CXCR4 augmentation mobilizes T lymphocytes after acute physical stress.

The aim of this study was to elucidate the mechanism responsible for lymphopenia after exercise. Seven young healthy men volunteered for this study. Peripheral blood mononuclear cells (PBMC) were cultured with cortisol and analyzed for C-X-C motif chemokine receptor 4 (CXCR4) expression by flow cytometry. To determine the effects of exercise, subjects performed exhaustive cycling exercise. PBMC were cultured with plasma obtained before and after the cycling exercise. Alternatively, PBMC obtained before and after exercise were cultured without plasma or glucocorticoid to examine whether PBMC were primed in vivo for CXCR4 expression. We analyzed cortisol- or plasma-treated PBMC to determine their ability to migrate through membrane filters in response to stromal cell-derived factor 1alpha/CXCL12. Cortisol dose- and time-dependently augmented CXCR4 expression on T lymphocytes, with <6 h of treatment sufficient to augment CXCR4 on T lymphocytes. Postexercise plasma also augmented CXCR4 expression. Cortisol or postexercise plasma treatment markedly enhanced migration of T lymphocytes toward CXCL12. Augmentation of CXCR4 on T lymphocytes by cortisol or plasma was effectively blocked by the glucocorticoid receptor antagonist RU-486. Thus exercise-elicited endogenous cortisol effectively augments CXCR4 expression on T lymphocytes, which may account for lymphopenia after exercise.

Acute Disease↗

PubMed2004

Regulated shedding of PAR1 N-terminal exodomain from endothelial cells.

G protein-coupled receptors can trigger metalloproteinase-dependent shedding of proteins from the cell surface. We now report that G protein-coupled receptors can themselves undergo regulated metalloproteinase-dependent shedding. The N-terminal exodomain of protease-activated receptor-1 (PAR1), a G protein-coupled receptor for thrombin, displayed regulated shedding in endothelial cells, which normally express this receptor. Cleavage occurred at a site predicted to render the receptor unresponsive to thrombin. A chimeric protein in which the N-terminal exodomain of PAR1 was fused to an unrelated transmembrane segment was shed as efficiently as PAR1, shedding of both proteins was stimulated by phorbol ester and by a PAR1 agonist. TNFalpha protease inhibitor-2 (TAPI-2), phenanthroline, and tissue inhibitor of metalloproteinase-3 (TIMP-3) but not TIMP-1 or -2 inhibited such shedding. These and other data suggest that the information that specifies PAR1 shedding resides within its N-terminal exodomain rather than its heptahelical segment, that activation of protein kinase C or of PAR1 itself can stimulate PAR1 shedding in trans, and that ADAM17/TACE or a metalloproteinase with similar properties mediates PAR1 shedding. Regulated shedding reduced the amount of cell surface PAR1 available for productive cleavage by thrombin by half or more, but thus far we have been unable to demonstrate an effect of PAR1 shedding on cellular responsiveness to thrombin. Nonetheless, regulated shedding of G protein-coupled receptors represents a new mechanism by which signaling by this important class of receptors might be modulated.

Alkaline Phosphatase↗

PubMed2004

Database of normal human cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen measured by positron emission tomography with 15O-labelled carbon dioxide or water, carbon monoxide and oxygen: a multicentre study in Japan.

Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO(2)) by positron emission tomography (PET) with oxygen-15 labelled carbon dioxide (C(15)O(2)) or (15)O-labelled water (H(2)(15)O), (15)O-labelled carbon monoxide (C(15)O) and (15)O-labelled oxygen ((15)O(2)) is useful for diagnosis and treatment planning in cases of cerebrovascular disease. The measured values theoretically depend on various factors, which may differ between PET centres. This study explored the applicability of a database of (15)O-PET by examining between-centre and within-centre variation in values. Eleven PET centres participated in this multicentre study; seven used the steady-state inhalation method, one used build-up inhalation and three used bolus administration of C(15)O(2) (or H(2)(15)O) and (15)O(2). All used C(15)O for measurement of CBV. Subjects comprised 70 healthy volunteers (43 men and 27 women; mean age 51.8+/-15.1 years). Overall mean+/-SD values for cerebral cortical regions were: CBF=44.4+/-6.5 ml 100 ml(-1) min(-1); CBV=3.8+/-0.7 ml 100 ml(-1); OEF=0.44+/-0.06; CMRO(2)=3.3+/-0.5 ml 100 ml(-1) min(-1). Significant between-centre variation was observed in CBV, OEF and CMRO(2) by one-way analysis of variance. However, the overall inter-individual variation in CBF, CBV, OEF and CMRO(2) was acceptably small. Building a database of normal cerebral haemodynamics obtained by the(15)O-PET methods may be practicable.

Blood Volume↗

PubMed2004

Quantitative measurement of histamine H(1) receptors in human brains by PET and [11C]doxepin.

The aim of this study is to establish a method for quantitative measurement of histamine H(1) receptor (H1R) in human brain by PET and [(11)C]doxepin ([(11)C]DOX). The estimated parameters with a two-compartment model were stable for the initial values for parameter estimation but those with a three-compartment model were not. This finding suggests that the H1R measured by the [(11)C]DOX and PET can be evaluated with a two-compartment model.

Adult↗

PubMed2004

Evaluation of in vivo selective binding of [11C]doxepin to histamine H1 receptors in five animal species.

The specific binding of [(11)C]doxepin, which has been used as a radioligand for mapping histamine H(1) receptors in human brain by positron emission tomography, was evaluated in five animal species. In mice the [(11)C]doxepin uptake was reduced by treatment with cold doxepin and two H(1) receptor antagonists, but not with H(2)/H(3) antagonists. The specific binding evaluated with treatment with (+)-chlorpheniramine (H(1) antagonist) was in the range of 10-30% in mouse, rat, rabbit, and monkey, but was not detected in guinea pig.

Animals↗

PubMed2004

Potential of [11C]TMSX for the evaluation of adenosine A2A receptors in the skeletal muscle by positron emission tomography.

We examined the potential of [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX) for the assessment of adenosine A2A receptors in muscle. In rodents, specific binding of [11C]TMSX was observed in muscle and heart by blockade with A2A-selective CSC and non-selective theophylline, but not with A1-selective DPCPX. Swimming exercise fluctuated radioligand-receptor binding in these tissues. In a PET study of two subjects, theophylline-infusion slightly deceased the distribution volume of [11C]TMSX in the heart (20% reduction) and muscle (10% reduction), which suggested the specific binding.

Adult↗

PubMed2004

Quantitative analysis of adenosine A1 receptors in human brain using positron emission tomography and [1-methyl-11C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine.

Fully quantitative analysis of the adenosine A(1) receptor (A1R) in the brain with (11)C-MPDX and positron emission tomography is reported. The kinetics is described using a two-tissue three-compartment model, and estimated binding potentials correspond well with the estimates made by Logan plot. The image of the binding potential of the MPDX is physiologically reasonable. We conclude that MPDX is applicable to the visualization of the A1Rs in the brain with Logan plot.

Adult↗

PubMed2004

Simplified PET measurement for evaluating histamine H1 receptors in human brains using [11C]doxepin.

The aim of this study was to develop simplified positron emission tomography measurement using [(11)C]doxepin ([(11)C]DOX) to evaluate histamine H(1) receptors (H1Rs) in human brains. We evaluated the correlation between the distribution volume (DV) of [(11)C]DOX, estimated quantitatively with a two-compartment model, and the [(11)C]DOX uptake obtained at various time intervals and normalized using the metabolite-corrected plasma radioactivity. We found that the static 70- to 90-min images normalized using the plasma radioactivity at 10 min postinjection reflected the DV of [(11)C]DOX-H1R binding.

Adult↗

PubMed2004

Usefulness of [11C]methionine PET in the diagnosis of dysembryoplastic neuroepithelial tumor with temporal lobe epilepsy.

PURPOSE: We assessed the diagnostic value of [11C]methionine (MET) positron emission tomography (PET) in the differential diagnosis of dysembryoplastic neuroepithelial tumors (DNETs) among benign tumors associated with temporal lobe epilepsy (TLE). METHODS: This series consisted of seven TLE patients with benign tumors in the temporal lobe. After MET-PET study, all seven patients underwent tumor resection along with focus excision. The uptake of tracers was evaluated by the lesion-to-contralateral ratio (L/C ratio) and the standardized uptake value (SUV). We also assessed the relation between MET uptake and proliferation capacity observed in the surgical specimens. RESULTS: Whereas four patients with DNETs did not show high MET uptake visually, the ganglioglioma and gliomas of the remaining three patients were identified as high-MET-uptake lesions. In the DNETs, the SUV ranged from 1.03 to 1.41, and the L/C ratio ranged from 0.99 to 1.14. MET uptake was significantly lower in the patients with DNETs than in the patients with ganglioglioma and brain gliomas (SUV, p = 0.045; L/C ratio, p = 0.0079). The Ki-67 labeling index was 4% in one patient with DNET and 5% in one patient with pleomorphic xanthoastrocytoma (higher labeling index). The higher labeling index was not related to high MET uptake based on the SUV (p = 0.91) and L/C ratio (p = 0.38). CONCLUSIONS: Negative MET uptake in benign temporal lobe tumors with TLE is consistent with a preoperative diagnosis of DNET.

Adolescent↗

PubMed2004

Comparative effects of candesartan and amlodipine in a monkey atherosclerotic model.

Angiotensin II receptor blockers could prevent the development of atherosclerosis beyond reducing blood pressure in monkeys fed a high-cholesterol diet. However, it has been unclear whether hypotensive effects improve atherosclerosis in primates. We investigated whether antihypertensive agents, an angiotensin II receptor antagonist, candesartan, and a calcium channel blocker, amlodipine, prevent areas of atherosclerotic lesions in the aorta of monkeys fed a high-cholesterol diet. Seventeen male monkeys fed a high-cholesterol diet for 6 months were grouped as follows: a high-cholesterol diet group (n=5), a candesartan-treated group (1 mg/kg per day, n=6) and an amlodipine-treated group (5 mg/kg per day, n=6). Candesartan and amlodipine showed a similar hypotensive effect by decreasing the systolic blood pressure approximately 20 mmHg, while these agents did not affect serum cholesterol levels. The ratio of atherosclerotic area to total area in thoracic aorta was significantly decreased by treatment with candesartan, but the ratio tended to be decreased by treatment with amlodipine. Although the angiotensin-converting enzyme activity in plasma was not changed by treatment with candesartan or amlodipine, the angiotensin-converting enzyme activity in the thoracic aorta was obviously reduced by treatment with candesartan, but not with amlodipine. Therefore, a blockade of angiotensin II action rather than a hypotensive effect may play an important role in preventing the development of atherosclerosis in primates.

Amlodipine↗

PubMed2004

Tumor imaging with 2 sigma-receptor ligands, 18F-FE-SA5845 and 11C-SA4503: a feasibility study.

UNLABELLED: Our objective was to study 2 radioligands for visualization of sigma-receptors with PET. METHODS: Two radioligands-sigma(1)-selective (11)C-1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine ((11)C-SA4503) and nonsubtype-selective 1-(4-2'-(18)F-fluoroethoxy-3-methoxyphenethyl)-4-(3-(4-fluorophenyl)propyl)piperazine ((18)F-FE-SA5845)-were evaluated for tumor imaging. RESULTS: Binding studies to rat glioma cells (C6) and human nonsmall cell lung cancer cells (N417) indicated interaction of (18)F-FE-SA5845 with 2 sites and interaction of (11)C-SA4503 with a single site. Specific binding of (18)F-FE-SA5845 was 93% +/- 2% and that of (11)C-SA4503 was 78% +/- 6% of the total cellular uptake of radioactivity. Uptake of the (18)F-labeled ligand, but not that of the (11)C-labeled ligand, appeared to be related to the growth phase of the cells. Biodistribution experiments in C6 tumor-bearing nude rats (Ham HSD RNU rnu) indicated tumor-to-plasma ratios of 13.3 for (11)C-SA4503 and 8.0 for (18)F-FE-SA5845 and tumor-to-muscle ratios of 5.0 for (11)C-SA4503 and 4.9 for (18)F-FE-SA5845, 60 min after injection, which were reduced to values ranging from 1.4 to 2.0 after pretreatment of animals with haloperidol (2 micromol/kg). Tumor uptake of (18)F-FE-SA5845 showed a negative correlation with tumor size (P < 0.0001), in contrast to that of (11)C-SA4503, suggesting that tissue binding of the former ligand is related to cellular proliferation. A study with (11)C-SA4503 in a human volunteer indicated high uptake in liver, kidney, and heart but relatively low background in thorax and lower abdomen. CONCLUSION: Both (18)F-FE-SA5845 and (11)C-SA4503 demonstrate specific binding to sigma-receptors in vivo and may be useful for the detection of pulmonary and abdominal tumors. However, the (18)F-labeled compound may be better for tumor staging than the (11)C-labeled drug.

Aged↗