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Biomedical subjects

K Ishiwata

Publications and source records attributed to K Ishiwata.

At least 19 recordsLinked to original sources
PubMed2006

Nematode infection in Alymphoplasia (aly) mice: worm species-dependent differential effect of defects of the gut-associated lymphatic tissue system.

Mice homologous for the alymphoplasia mutation (aly) show the systemic absence of secondary lymphoid tissues, with disorganized splenic architecture, including the absence of the germinal centre and follicular dendritic cells. In this study, we examined the influence of defects of gut-associated lymphoid tissue (GALT), such as Peyer's patches and the mesenteric lymph nodes, on the host response to helminth infection in aly/aly mice. The present study showed that most of the worms were expelled by day 7 after Nippostrongylus brasiliensis infection in both control aly/+ and aly/aly mice. In aly/aly mice, the number of peripheral blood eosinophils, intestinal goblet cells and mucosal mast cells were increased by N. brasiliensis infection in aly/aly mice to the same level as in the controls. Conversely, aly/aly mice developed more severe Heligmosomoides polygyrus infections than control aly/+ mice, as demonstrated by increased faecal egg counts, with reduced immune responses such as the numbers of intestinal goblet cells and mucosal mast cells. These results suggested that the dependency of GALT in activation of Th2 responses against gastrointestinal nematodes was different depending on the species of nematode.

Animals↗
PubMed2005

Function of sigma1 receptors in Parkinson's disease.

OBJECTIVE: The objective of this study was to investigate the mapping of sigma1 receptors in Parkinson's disease (PD) using [11C]SA4503 and positron emission tomography (PET), and to assess whether sigma1 receptors are involved in the damaged dopaminergic system in PD patients. MATERIALS AND METHODS: We studied seven normal volunteers and six PD patients. The low density of dopamine transporters and the normal or high density of dopamine receptors were confirmed in the putamen of all patients using [11C]CFT and [11C]RAC PET. A dynamic series of PET data acquisition was performed with arterial blood sampling. We computed the binding potential (BP) of [11C]SA4503. RESULTS: In PD patients, the BP was significantly lower on the more affected than the less affected side of the anterior putamen, although there was no significant difference with respect to the BP between patients and controls. CONCLUSIONS: Release of dopamine is reduced asymmetrically in the putamen of early PD. [11C]SA4503 PET is an indicator of presynaptic dopaminergic damage in PD.

Adult↗
PubMed2004

Evaluation of [18F]fluorinated sigma receptor ligands in the conscious monkey brain.

PET-imaging of the sigma receptors is very helpful to understand processes, e.g., several central nervous system (CNS)-diseases in which the sigma receptors are involved. The [(18)F]fluoroethylated analogs of SA4503 and SA5845 ([(18)F]FE-SA4503 and [(18)F]FE-SA5845) were evaluated in conscious monkeys to estimate its suitability for human application for PET. Conscious monkeys (Macaca Mulatta) were either scanned with [(18)F]FE-SA4503 or [(18)F]FE-SA5845 (n = 3 for both groups, 220-802 MBq). After a dynamic study of 120 min, radioactivity was displaced by intravenous (i.v.) injection of haloperidol (1 mg/kg). One month later the same set of three monkeys were scanned with [(18)F]FE-SA4503 for 120 min and "cold" SA4503 (1 mg/kg) was infused to displace the radioactivity, and the other three monkeys were pretreated with haloperidol (1 mg/kg) before the 120-min PET-scan with [(18)F]FE-SA5845. Cortical areas (cingulate, frontal, occipital, parietal, temporal), striatum, and thalamus showed high radioactivity uptake. Infusion of haloperidol displaced the radioactivity levels of the two radioligands. The same effect was found for [(18)F]FE-SA4503 after SA4503 displacement. Pretreatment with haloperidol blocked the [(18)F]FE-SA5845 binding to give PET-images with low and uniform uptake in the brain. The findings demonstrated the reversible binding of the two radioligands. Metabolite analysis showed that 14% and 23% parent compound of [(18)F]FE-SA5845 and [(18)F]FE-SA4503, respectively, at 120 min postinjection was present in plasma. Kinetic analysis showed that the binding potential of [(18)F]FE-SA5845 was higher in all brain regions than that of [(18)F]FE-SA4503 (4.75-8.79 vs. 1.65-4.04). The highest binding potential was found in the hippocampus, followed by the cortical regions, thalamus, cerebellar hemisphere, striatum and vermis. Both [(18)F]FE-SA compounds bound specifically to cerebral sigma receptors of the monkey and have potential for mapping sigma receptors in the human brain.

Animals↗
PubMed2004

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↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2003

Evaluation of the antigenic similarities of adult-worm extracts from three Gnathostoma species, using sera from Mexican and Japanese patients with Gnathostoma infections.

The antigenic similarities of adult-worm extracts of Gnathostoma spinigerum, G. hispidum and G. doloresi, all of which are important food-borne parasites causing larva migrans in humans, were evaluated. The 40 sera used came from gnathostomiasis cases in Mexico, where G. binucleatum is endemic, or in Japan, where G. doloresi predominates. When used as the fixed antigens in microplate-ELISA, the adult-worm extracts from the three different species of Gnathostoma were found to have equal binding capacity to the Gnathostoma-specific IgG antibodies in the sera of the Mexican and Japanese patients. The correlation coefficients for the optical densities seen in the ELISA, between any two of the three Gnathostoma extracts, were all >0.900. The dose-response curves produced when four sera were tested, in the microplate-ELISA, against the three different Gnathostoma extracts were nearly identical, indicating that the antigens in each of the extracts had similar avidity. Furthermore, the results of competitive-inhibition ELISA indicated that the antigenic specificities of the three extracts were almost identical. An antigen of 40 kDa, which SDS-PAGE and immunoblot analysis revealed to be present in all three extracts, was recognized by the sera from the gnathostomiasis cases. When the sera were investigated by dot-blot ELISA, they also gave similar results whichever extract was used as the antigen source. It appears that, in the serodiagnosis of gnathostomiasis by microplate- or dot-ELISA, each of the three adult-worm extracts would be equally useful, regardless of the causative species of Gnathostoma.

Animals↗
PubMed2002

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↗
PubMed2001

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↗
PubMed2001

Effects of single and repeated administration of 1,2,3,4-tetrahydroisoquinoline analogs on the binding of [11C]raclopride to dopamine D2 receptors in the mouse brain.

We investigated the effects of intraperitoneal injection of 1,2,3,4-tetrahydroisoquinoline (TIQ) analogs and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the binding of [11C]raclopride to striatal dopamine D2 receptors in mice. The binding of [11C]raclopride, but not of [11C]N-methylspiperone or [11C]nemonapride with higher affinity, to the receptors was significantly decreased immediately after TIQ injection. Neither a dopamine transporter blocker induced such effect nor TIQ affected the dopamine transporter-radioligand binding. Among the compounds investigated, including parkinsonism-inducing TIQ and (R/S)-1-benzyl-TIQ, parkinsonism-preventing (R)- and (S)-1-methyl-TIQ, and probable N-methylated metabolites of TIQ and 1-methyl-TIQ, TIQ and (S)-1-methyl-TIQ had the strongest effect on the binding of [11C]raclopride, and N-methylated derivatives showed less of an effect than the respective parent compounds. The decrease in the binding of [11C]raclopride continued for 7 hours and was followed by an increase until 10 days after the single and subchronic administration of TIQ. These findings suggest that TIQ analogs profoundly stimulated dopamine release which resulted in the competitive inhibition of the binding of [11C]raclopride to dopamine D2 receptors, but did not induce degeneration of the receptors.

Animals↗
PubMed2001

Apolipoprotein-E phenotype and basal activity of low-density lipoprotein receptor are independent of changes in plasma lipoprotein subfractions after cholesterol ingestion in Japanese subjects.

We investigated whether the apolipoprotein-E (apoE) phenotype and the basal activity of low-density lipoprotein (LDL) receptor, which were reported to be the major determinants for increase in plasma LDL levels by cholesterol ingestion, have the same role in Japanese subjects whose diet is low in fat and cholesterol. Cholesterol (750 mg/d) was added to the ordinary diet as a dried egg-yolk supplement for 4 wk to 110 subjects. Plasma levels of lipids, apolipoproteins, and cholesterol in lipoprotein subfractions were measured at the beginning and end of the test period. Phenotyping of apoE was determined by an isoelectric focusing-immunoblotting method, and LDL receptor activity in lymphocytes was determined by flow cytometry. Plasma levels of cholesterol in less-dense LDL (LDL(1)) and less-dense high-density lipoprotein (HDL(2)) were slightly but significantly increased, 3.4% and 4.1%, respectively, by cholesterol ingestion, but the increases were not statistically significant in any of E2, E3, and E4 groups. The distribution of the apoE phenotype was equivalent in all three LDL-cholesterol groups (no change, increase, and decrease by cholesterol ingestion). Plasma levels of LDL, LDL(1), and LDL(2) cholesterol were not significantly increased in the three groups of subjects with lymphocyte LDL-receptor activities (low, medium, and high). As with apoE phenotype, LDL-receptor activities were the same in all three LDL-cholesterol groups. In addition, there were no significant correlations between LDL-receptor activity and changes in plasma levels of lipids, apolipoproteins, and cholesterol in lipoprotein subfractions. Therefore, we concluded that cholesterol ingestion significantly increases plasma levels of less-dense LDL and HDL, but neither apoE phenotype nor basal LDL-receptor activity explain the variability in changes in plasma lipoprotein subfractions by cholesterol ingestion in Japanese subjects.

Apolipoproteins E↗
PubMed2001

Synthesis and preliminary evaluation of a carbon-11-labeled adenosine transporter blocker [(11)C]KF21562 .

We prepared an (11)C-labeled adenosine transporter blocker, [1-methyl-(11)C]-3-[1-(6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]-1,6-dimethyl-2,4(1H, 3H)-quinazolinedione ([(11)C]KF21652) and examined its potential as a positron emission tomography (PET) ligand for mapping adenosine transporters in the brain and peripheral organs. The log P(7.4) value of KF21652 was 3.14, and the K(i) value was 13 nM for adenosine transporters using [(3)H]nitrobenzylthioinosine as a radioligand. In mice, the highest initial uptake was found in the liver, followed by the kidney and small intestine. The brain uptake was very low. The radioactivity level slightly increased with time in the liver and small intestine, but decreased in the other organs. Coinjection of carrier KF21652 slightly decreased the uptake of [(11)C]KF21562 only in the liver, but not in any other organs. Ex vivo autoradiography of the rat brain showed that [(11)C]KF21652 was scarcely incorporated into the brain. On the other hand, in vitro autoradiography showed the binding of [(11)C]KF21562 to adenosine transporters with high nonspecific binding. These results show that the compound is not a suitable PET ligand for mapping adenosine transporters.

Adenosine↗
PubMed2001

[11C]Raclopride binding was reduced in vivo by sigma(1) receptor ligand SA4503 in the mouse brain, while [11C]SA4503 binding was not by raclopride.

[11C]Raclopride is widely used as a representative dopamine D(2)-like receptor ligand in positron emission tomography (PET) studies, and [11C]1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride ([11C]SA4503) is a recently developed selective ligand for mapping sigma(1) receptors in the brain. The striatal uptake of [11C]raclopride in mice was reduced by co-injection of an excess amount of SA4503, in spite of the fact that raclopride had no effect on the brain uptake of [11C]SA4503 as shown in a previous study. The blocking effect of SA4503 on the striatal uptake of [11C]raclopride was dose-dependent, but disappeared by 1 h or 6 h after intraperitoneal injection of SA4503. The brain uptake of [11C]SA4503 was not affected by a dopamine transporter inhibitor GBR 12909, nor was [11C]beta-CIT-FP inhibited by SA4503. The IC(50) values of raclopride for sigma(1) and sigma(2) receptor subtypes measured in vitro were 11800 nM and 4950 nM, respectively, suggesting that the affinity was too low for [11C]raclopride to bind in vivo to sigma receptors. On the other hand, the IC(50) value of SA4503 for dopamine D(2) receptors was 470 nM, that is approximate 1/25 of the affinity of raclopride for the dopamine D(2) receptors. Therefore, possible explanations for the partial blocking effects of SA4503 on the striatal uptake of [11C]raclopride are: (1) an excess amount of SA4503 may reduce the [11C]raclopride uptake due to its low affinity for dopamine D(2) receptors, or (2) SA4503 may enhance endogenous dopamine release, which results in the competitive inhibition of the [11C]raclopride uptake. These findings support that both [11C]raclopride and [11C]SA4503 are selective in vivo ligands for dopamine D(2)-like receptors and sigma(1) receptors, respectively, in spite of the partial blocking effect of SA4503 on the striatal uptake of [11C]raclopride.

Animals↗
PubMed2001

Natural resistance of 129/SvJ mice to Strongyloides venezuelensis infection.

The susceptibility of 129/SvJ mice to infection with Strongyloides venezuelensis was compared with that of C57BL/6 mice. After a primary infection, daily egg output in faeces (EPG) from 129/SvJ mice was lower and terminated earlier than that from C57BL/6 mice. Adult worm recovery from the small intestine of 129/SvJ mice on day 7 was also lower than that of C57BL/6 mice. When the numbers of larvae recovered from the lungs were examined on days 2, 3 and 4 after a primary infection, they were comparable between the two strains. On the other hand, when an equal number of larvae recovered from the lungs of each strain on day 3 were implanted orally into homologous strain mice, the magnitude of EPG and the number of adult worms in the small intestine on day 5 after implantation were significantly lower in 129/SvJ than in C57BL/6 mice. The number of mucosal mast cells in the jejunum was not significantly different between 129/SvJ and C57BL/6 naive mice. Total chondroitin sulphate concentration in the gut washings obtained from naive mice was significantly higher in 129/SvJ (11.34 +/- 9.48) than in C57BL/6 mice (1.09 +/- 0.77, P < 0.05). These results indicate that the natural resistance of 129SvJ mice to S. venezuelensis infection is expressed at the intestine, probably due to higher concentration of chondroitin sulphate, which prevents establishment of S. venezuelensis.

Animals↗
PubMed2001

Evaluation of neurotoxicity of TIQ and MPTP and of parkinsonism-preventing effect of 1-MeTIQ by in vivo measurement of pre-synaptic dopamine transporters and post-synaptic dopamine D(2) receptors in the mouse striatum.

Parkinsonism-inducing neurotoxicity of 1,2,3,4-tetrahydroisoquinoline (TIQ), as contrasted to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and parkinsonism-preventing effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTIQ) have been investigated in mice by measuring their effects on the in vivo binding of radioligand to pre-synaptic dopamine transporters (DATs) or to dopamine D(2) receptors (D2R) in the striatum. A significant reduction of the ligand-DATs binding was found in the mice treated with MPTP, but not with TIQ, under the dosage inducing behavioral abnormality and loss of tyrosine hydroxylase-positive cells in the substantia nigra. A slight decrease in the ligand-DATs binding was observed in the mice given a larger dose of TIQ. Compensatory up-regulation in the post-synaptic D2Rs was found in the MPTP-treated mice. Pre-treatment with (S)-enantiomer, but not (R)-enantiomer, of 1-MeTIQ prevented the degeneration of DATs to some extent. We concluded that the TIQ-induced parkinsonism model is different from the MPTP-induced model as evaluated by the radioligand-DATs binding and that (S)-1-MeTIQ has a preventing effect for the degeneration of the DATs to a certain extent.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗