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Biomedical subjects

M Senda

Publications and source records attributed to M Senda.

At least 19 recordsLinked to original sources

Development of a GSO positron/single-photon imaging detector.

We have developed and tested a GSO (gadolinium oxyorthosilicate) position-sensitive gamma detector which can be used with positron and single-photon radionuclides for imaging breast cancer or sentinel lymph node detection. Because GSO has a relatively good energy resolution for annihilation gammas as well as low energy gamma photons, and does not contain any natural radioisotopes, it can be used for positron imaging and lower energy single-photon imaging. The imaging detector consists of a GSO block, 2 inch square multi-channel position-sensitive photo-multiplier tube (PSPMT), and associated electronics. The size of a single GSO element was 2.9 mm x 2.9 mm x 20 mm and these elements were arranged into 15 x 15 matrixes to form a block that was optically coupled to the PSPMT. It was possible to separate all GSO crystals into a two-dimensional position histogram for annihilation gammas (511 keV) and low energy gamma photons (122 keV). The typical energy resolution was 24% FWHM and 37% FWHM for 511 keV and 122 keV gamma photons, respectively. For the positron imaging, coincidence between the imaging detector and a single gamma probe is measured. For the single-photon imaging, a tungsten collimator is mounted in front of the imaging detector. With this configuration, it was possible to image both positron radionuclides and low energy single-photon radionuclides. We measured spatial resolution and sensitivity as well as image quality of the developed imaging detector. Results indicated that the developed imaging detector has the potential to be a new and useful instrument for nuclear medicine.

Breast Neoplasms↗

Efficacy of an inactivated feline panleucopenia virus vaccine against a canine parvovirus isolated from a domestic cat.

Canine parvovirus type 2a (CPV-2a) and type 2b (CPV-2b) have recently been isolated from cats throughout the world, and CPV-2b strain FP84 has been reported to be virulent in domestic cats. Although live feline panleucopenia virus (FPLV) vaccines protect domestic cats from CPV infection, the efficacy of inactivated FPLV vaccines has not been established. In this study, two domestic cats were vaccinated with a commercial inactivated FPLV vaccine and challenged with CPV-2b strain FP84 isolated from a domestic cat. The cats were protected against CPV-2b strain FP84 infection and their clinical signs were suppressed, although the two unvaccinated cats showed the typical clinical signs of parvovirus infection.

Animals↗

Molecular linkage mapping and phylogeny of the chalcone synthase multigene family in soybean.

Chalcone synthase (CHS), the key enzyme in the flavonoid biosynthesis pathway, is encoded by a multigene family, CHS1-CHS8 and dCHS1 in soybean. A tandem repeat of CHS1, CHS3 and CHS4, and dCHS1 that is believed to be located in the vicinity comprises the I locus that suppresses coloration of the seed coat. This study was conducted to determine the location of all CHS members by using PCR-based DNA markers. Primers were constructed based on varietal differences in either the nucleotide sequence of the 5'-upstream region or the first intron of two cultivars, Misuzudaizu, with a yellow seed coat (II), and Moshidou Gong 503, with a brown seed coat (ii). One hundred and fifty recombinant inbred lines that originated from a cross between these two cultivars were used for linkage mapping together with 360 markers. Linkage mapping confirmed that CHS1, CHS3, CHS4, dCHS1, and the I locus are located at the same position in molecular linkage group (MLG) A2. CHS5 was mapped at a distance of 0.3 cM from the gene cluster. CHS2 and CHS6 were located in the middle region of MLGs A1 and K, respectively, while CHS7 and CHS8 were found at the distal end of MLGs D1a and B1, respectively. Phylogenetic analysis indicated that CHS1, CHS3, CHS4, and CHS5 are closely related, suggesting that gene duplication may have occurred repeatedly to form the I locus. In addition, CHS7 and CHS8 located at the distal end and CHS2, CHS6, and CHS members around the I locus located around the middle of the MLG are also related. Ancient tetraploidization and repeated duplication may be responsible for the evolution of the complex genetic loci of the CHS multigene family in soybean.

Acyltransferases↗

Severe haemodynamic stress in selected subtypes of patients with moyamoya disease: a positron emission tomography study.

BACKGROUND: The optimum management of patients with moyamoya disease remains controversial. OBJECTIVES: To examine retrospectively the correlation between the degree of haemodynamic stress and the clinical presentation by measuring cerebral haemodynamics and metabolism using positron emission tomography (PET). METHODS: 57 patients with moyamoya disease (mean age 32 years, range 12 to 64), classified into five groups according to clinical manifestations, underwent PET measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate for oxygen (CMR(O2)), and oxygen extraction fraction (OEF) using (15)O labelled gases. The regional values in patient groups were compared with a normal group. RESULTS: CBF in non-symptomatic patients, patients presenting with transient ischaemic attacks (TIA), and patients with haemorrhagic onset (H) was not significantly lower than in normal controls in any region. CBV in the TIA group and in patients with infarction associated with TIA (I/TIA) was significantly higher than in the controls in most regions. OEF in the frontal, parietal, and temporal cortex was significantly higher in the I/TIA group than in the controls. Patients in the H group and those with a permanent deficit with infarction (PD group) had decreased metabolism with normal OEF. Multivariate analysis to test the distribution of the three dimensional vector (CBF, CBV, OEF) showed significant differences between every possible pair among the six groups except NS v H and H v PD in the frontal cortex. CONCLUSIONS: The haemodynamic status of moyamoya disease is not uniform, and severe haemodynamic stress occurs in selected subgroups of patients.

Adolescent↗

Midbrain hypometabolism as early diagnostic sign for progressive supranuclear palsy.

OBJECTIVE: Progressive supranuclear palsy (PSP) is often misdiagnosed in early phase. The purpose of this study is to investigate the feature of [(18)F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography images for the early diagnosis of PSP. METHODS: We studied 15 patients with PSP and 16 normal subjects. Using SPM99 and analysis of covariance to eliminate the effect of aging, the differences between PSP and normals were displayed as a statistical map. In the PSP, we also investigated the correlation with duration and with the subscores of Unified Parkinson's Disease Rating Scale. RESULTS: The glucose metabolism of midbrain was significantly lower in PSP than in normals. However, correlation was not found between the metabolism of midbrain and clinical deterioration. CONCLUSIONS: The statistical map clearly demonstrated the hypometabolism of midbrain in PSP, which is independent of the clinical deterioration. The hypometabolism of midbrain is one of the most promising sign for early diagnosis of PSP.

Adult↗

PET neuroreceptor imaging as predictor of severe cerebral ischemic insult.

Measurement of the adenosine A1 receptor (A1-R) with positron emission tomography (PET) using a newly developed positron ligand, [1-methyl-11C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX). were performed in a cat middle cerebral artery (MCA) occlusion and reperfusion. Eighteen adult cats underwent PET measurement of; 1) cerebral blood flow (CBF). 2) A1-R, 3) central benzodiazepine receptor (BDZ-R) and 4) glucose metabolism with 15O labeled water, MPDX, 11C-flumazenil (FMZ) and 18F-fluorodeoxyglucose (FDG), respectively. The CBF, A1-R, BDZ-R and FDG uptake were serially measured after 60 min occlusion of MCA in this order. MPDX binding and FMZ binding, but not CBF and FDG uptake, were significantly reduced in the groups with severer ischemic insult than in the groups with no or milder insults. Of the two receptor ligands, the reduction rate of the MPDX binding to A1-Rs was larger in a group that caused fatal ischemic insult. The newly developed PET in vivo imaging technique using MPDX was suitable in evaluating the function of adenosine and A1-Rs in relation to cerebral ischemia.

Animals↗

Meningio-angiomatosis in a patient with focal epilepsy: value of PET in diagnoses and preoperative planning of surgery.

A 17-year-old boy with epileptic seizures due to meningio-angiomatosis without neurofibromatosis type 2 is presented. Low grade astrocytoma in the left temporal lobe was resected when he was 11 years old. A recurrence was suspected on following-up MRI and a positive PET scan with 11C-methionine PET 6 years later around the resected area. The language area was mapped using H2(15)O PET activation technique. The lesion was completely resected while preserving the verbal area assisted by three-dimensional imaging protocol of MR-registered PET. The patient was well and seizure-free for 8 years thereafter without antiepileptic drugs. Histologically, there was an increase of dilated arterioles and meningothelial cell-like spindle cells around them, which are characteristic pathological features of meningio-angiomatosis. It is most likely that angiomatous tissue developed perivascular meningiomatous components and formed the meningio-angiomatosis in our presented case. In addition, we presented our protocol of functional neuro-imaging which was useful in terms of the functional neurosurgery.

Adolescent↗

Longitudinal follow-up study of adenoviral vector-mediated gene transfer of dopamine D2 receptors in the striatum in young, middle-aged, and aged rats: a positron emission tomography study.

Overexpression of dopamine D(2) receptors by adenoviral vector-mediated gene transfer in the rat striatum was evaluated by positron emission tomography in vivo and by ex vivo autoradiography in 5-, 13-, and 24-month-old Fischer 344 rats. Each rat had hemilateral gene transfer of D(2) receptors mediated by adenoviral vectors (AdCMV.DopD(2)R) in the striatum with contralateral striatal injection of control vectors (AdCMV.LacZ). At day 2 or 3 after vector injection positron emission tomography or ex vivo autoradiography was performed. The binding potential of a radiolabeled D(2) receptors ligand, [11C]raclopride, was significantly higher in the D(2) receptors gene-transferred striatum than the control side in each age group at a similar degree. The binding potential in the AdCMV.DopD(2)R-injected striatum of 24-month-old rats was similar to that in the AdCMV.LacZ-injected striatum of 5-month-old rats (0.99+/-0.14 versus 0.91+/-0.08). A significant age-associated decrease of the binding potential of [11C]raclopride was found in the control vector-injected side, and a significant increase of the binding potential in the adenoviral vector-injected side in all three age groups, suggesting no aging effect on the overexpression of D(2) receptors. A group of rats underwent follow-up assessment by positron emission tomography. The overexpression of D(2) receptors decreased with time in all three groups; however, the decrease rate of the D(2) receptors expression was significantly smaller in the 24-month-old group than in the 5-month-old group. We confirmed that the adenoviral vector-mediated gene transfer of D(2) receptors compensated the decreased density of striatal D(2) receptors in the 24-month-old rats up to the level in the control striatum of 5-month-old rats, and the decrease rate of the overexpression was significantly smaller in aged rats.

Adenoviridae↗

Synthesis and evaluation of [18F]fluoroethyl SA4503 as a PET ligand for the sigma receptor.

The sigma receptor might be involved in several diseases in the central nervous system. It occurs in the endocrine, immune, and other peripheral organ systems and is expressed in a variety of human tumors. The [18F]fluoroethyl analog of the sigma1-selective ligand SA4503 ([18F]FE-SA4503) was prepared and evaluated in animals to investigate its suitability for in vivo measurement of sigma receptors with positron emission tomography (PET). [18F]FE-SA4503 was synthesized by [18F]fluoroethylation of the corresponding O-demethyl precursor in an overall radiochemical yield of 4-7% (EOB) with a specific activity of >100 TBq/mmol. The radioligand had higher in vitro affinity for the sigma receptor than SA4503 (IC(50) sigma1 6.48 nM, IC50 sigma2 2.11 nM). [18F]FE-SA4503 was injected into mice. Uptake could be blocked by co-injection of the sigma receptor ligands haloperidol, pentazocine, and cold SA4503, but not with other receptor ligands. Ex vivo autoradiography studies in rats showed regional distribution in the brain similar to [11C]SA4503. Hippocampus, thalamus, and cortical areas were clearly delineated by [18F]FE-SA4503. The uptake was blocked by SA4503 treatment. In the rat brain, only a small portion of metabolites (6.6% of brain radioactivity) was detected at 30 min postinjection, whereas in plasma the fraction of metabolites amounted to 51.3% of plasma radioactivity. The kinetics of [18F]FE-SA4503 was measured with PET in the conscious monkey brain. High uptake values were found in the cortex, thalamus, cerebellum, and striatum, reaching a plateau value at 30 min postinjection. It is concluded that [18F]FE-SA4503 showed specific binding to sigma receptors in three animal species.

Animals↗

Fast formation of statistically reliable FDG parametric images based on clustering and principal components.

Formation of parametric images requires voxel-by-voxel estimation of rate constants, a process sensitive to noise and computationally demanding. A model-based clustering method for a two-parameter model (CAKS) was extended to the FDG three-parameter model. The concept was to average voxels with similar kinetic signatures to reduce noise. Voxel kinetics were categorized by the first two principal components of the tissue time-activity curves for all voxels. k2 and k3 were estimated cluster-by-cluster, and K1 was estimated voxel-by-voxel within clusters. When CAKS was applied to simulated images with noise levels similar to brain FDG scans, estimation bias was well suppressed, and estimation errors were substantially smaller--1.3 times for Ki and 1.5 times for k3-than those of conventional voxel-based estimation. The statistical reliability of voxel-level estimation by CAKS was comparable with ROI analysis including 100 voxels. CAKS was applied to clinical cases with Alzheimer's disease (ALZ) and cortico basal degeneration (CBD). In ALZ, the affected regions had low Ki (K1k3/(k2 +k3)) and k3. In CBD, Ki was low, but k3 was preserved. These results were consistent with ROI-based kinetic analysis. Because CAKS decreased the number of invoked estimations, the calculation time was reduced substantially. In conclusion, CAKS has been extended to allow parametric imaging of a three-compartment model. The method is computationally efficient. with low bias and excellent noise properties.

Algorithms↗

Asymmetric activation of chiral alkoxyzinc catalysts by chiral nitrogen activators for dialkylzinc addition to aldehydes: super high-throughput screening of combinatorial libraries of chiral ligands and activators by HPLC-CD/UV and HPLC-OR/RIU systems.

Asymmetric catalysts, prepared by chiral ligand exchange or chiral modification, can evolve further into highly activated catalysts through engineering with chiral activators. Two new methodologies for "super high-throughput screening" (SHTS) of chiral ligands and activators have been developed as a combination of HPLC-CD/UV (CD/ UV = circular dichroism/ultraviolet spectroscopy) or -OR/RIU (OR/RIU = optical rotation/refractive index unit) with a combinatorial chemistry (CC) factory. With these techniques, the % ee of the product is determined within minutes without separation of the enantiomeric products by using a nonchiral stationary phase. Therefore, those SHTS techniques combined with our 'asymmetric activation' concept can provide a powerful strategy for finding the best activated chiral catalyst.

Journal Article↗

Effect of in vitro ischemic or hypoxic treatment on mitochondrial electron transfer activity in rat brain slices assessed by gas-tissue autoradiography using.

We have investigated the effect of in vitro ischemic or hypoxic treatment on mitochondrial electron transport function in brain slices using gas-tissue autoradiography technique with [15O]O2. Brain slices were preincubated in Krebs-Ringer phosphate medium bubbled with 100% O2 for 30 min at 37 degrees C. (1) Control culture was incubated in the same medium bubbled with 100% O2 for 5-40 min at 37 degrees C, then for another 30 min under the same conditions. (2) In vitro ischemia was induced by placing the culture in the medium deprived of glucose and bubbled with 100% N2 for 5-40 min, then returning it to control conditions and culturing for another 30 min. (3) In vitro hypoxia was induced by placing the culture in the medium with glucose and bubbled with 100% N2 for 5-40 min, then returning it to the control conditions for 30 min. After the three different treatments, the [15O]O2 fixation by brain slices reflect to mitochondrial electron transport function was determined using gas-tissue autoradiography technique with [15O]O2. The fixation of [15O]O2 by striatum, cerebral cortex and hippocampus was reduced dependent upon the period of in vitro ischemic treatment. In contrast, the [15O]O2 fixation by those brain regions was only slightly reduced by hypoxia treatment. The reduction in [15O]O2 fixation induced by ischemic treatment was prevented by an antioxidant: glutathione, glutathione monoethyl ester or acetylsalicylic acid. The preventive effect of antioxidants on the mitochondrial damage induced by ischemia was more remarkable in the striatum than in the cerebral cortex and hippocampus. In the comparison of [15O]O2 fixation between ischemia-treated young and senescent brain slices, reduction of 15O fixation by every brain region examined was more prominent in senescence than in the young. These results suggest that gas-tissue autoradiography using [15O]O2 is useful to assess mitochondrial electron transport dysfunction induced by ischemia treatment in brain slices and that the oxidative stress participates in the mechanism of ischemia-induced dysfunction in mitochondria.

Age Factors↗

Auditory triggered mental imagery of shape involves visual association areas in early blind humans.

Previous neuroimaging studies identified a large network of cortical areas involved in visual imagery in the human brain, which includes occipitotemporal and visual associative areas. Here we test whether the same processes can be elicited by tactile and auditory experiences in subjects who became blind early in life. Using positron emission tomography, regional cerebral blood flow was assessed in six right-handed early blind and six age-matched control volunteers during three conditions: resting state, passive listening to noise sounds, and mental imagery task (imagery of object shape) triggered by the sound of familiar objects. Activation foci were found in occipitotemporal and visual association areas, particularly in the left fusiform gyrus (Brodmann areas 19-37), during mental imagery of shape by both groups. Since shape imagery by early blind subjects does involve similar visual structures as controls at an adult age, it indicates their developmental crossmodal reorganization to allow perceptual representation in the absence of vision.

Adult↗

Comparison of parametric FBP and OS-EM reconstruction algorithm images for PET dynamic study.

An ordered subsets expectation maximization (OS-EM) algorithm is used for image reconstruction to suppress image noise and to make non-negative value images. We have applied OS-EM to a digital brain phantom and to human brain 18F-FDG PET kinetic studies to generate parametric images. A 45 min dynamic scan was performed starting injection of FDG with a 2D PET scanner. The images were reconstructed with OS-EM (6 iterations, 16 subsets) and with filtered backprojection (FBP), and K1, k2 and k3 images were created by the Marquardt non-linear least squares method based on the 3-parameter kinetic model. Although the OS-EM activity images correlated fairly well with those obtained by FBP, the pixel correlations were poor for the k2 and k3 parametric images, but the plots were scattered along the line of identity and the mean values for K1, k2 and k3 obtained by OS-EM were almost equal to those by FBP. The kinetic fitting error for OS-EM was no smaller than that for FBP. The results suggest that OS-EM is not necessarily superior to FBP for creating parametric images.

Algorithms↗

Tuberous sclerosis: epileptogenicity and multimodal presurgical evaluations.

We report on a patient with tuberous sclerosis-related epilepsy who benefited from surgical treatment. Various presurgical evaluations, including positron emission tomography (PET), made it possible for us to localize the epileptic focus accurately. In this paper, we stress the importance of performing multimodal evaluations to determine which tubers really possess epileptogenicity. In addition, the implications of PET in tuberous sclerosis-related epilepsy are described.

Cerebral Cortex↗