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Biomedical subjects

H Saji

Publications and source records attributed to H Saji.

At least 91 records · Page 5Linked to original sources
PubMed1995

Evaluation of radioiodinated iodoclorgyline as a SPECT radiopharmaceutical for MAO-A in the brain.

An in vivo estimation of the newly synthesized MAO-A specific inhibitor, [125I]-labeled N-[3(2,4-dichloro-6-iodophenoxy)propyl]-N-methyl-2- propynylamine ([125I]-iodoclorgyline), was performed. Retention of the radioactivity of this radioligand was observed in the brain from 1 h post-injection. Pretreatments with clorgyline and l-deprenyl showed selective binding of [125I]-iodoclorgyline to MAO-A in the brain at 24 h post-injection. Moreover, a good correlation (r = 0.907) between the uptake of [125I]-iodoclorgyline and MAO-A enzyme activity in the cortex was observed in the pretreatment study with several doses of clorgyline. Although improvement to increase the brain/blood ratio is desirable because of slow blood clearance of the radioactivity, radioiodinated iodoclorgyline may serve as a useful SPECT radiopharmaceutical for quantitative analysis of MAO-A in the brain.

Animals↗
PubMed1995

[125I]iomazenil binding in the brains of spontaneously epileptic rats: an ex vivo quantitative autoradiographic study.

Central benzodiazepine receptor binding was studied in spontaneously epileptic rats (SER) and in their parent strain. Kyoto-Wistar (KW) rats, by ex vivo quantitative autoradiography with [125I]iomazenil. Thirteen-week-old SER developed tonic and absence-like seizures following mild stimulation by tapping at 5 min before injection of the radioligand. When compared with age-matched KW rats, a significant 76% elevation of radioactivity was observed in the SER hippocampus, while there was no difference in hippocampal blood flow obtained using [125I]N-isopropyl-p-iodoamphetamine. Since benzodiazepine receptors act to enhance inhibitory GABA transmission, this finding suggests a possible mechanism for seizure-induced enhancement of inhibition.

Animals↗
PubMed1995

Application of [125I] (S)-5-iodonicotine, a new radioiodinated ligand, in the assay of nicotinic acetylcholine receptor binding in the brain.

[125I](S)-5-Iodonicotine was prepared and its application in the assay of nicotinic acetylcholine receptor binding in the brain was studied. [125I](S)-5-Iodonicotine bound to the rat cortical membrane with high affinity (Kd, 15.0 nm). Various nicotinic cholinergic compounds showed competition with [125I](S)-5-iodonicotine for the binding sites in the rats cortical membrane, and the specificity of its binding was correlated well with that of [H3] cytisine (r = 0.98). These findings suggest that [125I](S)-5-iodonicotine binds to the same sites as [H3] cytisine and indicate that [125I](S)-5-iodonicotine can be applied as a brain nicotine receptor binding assay.

Alkaloids↗
PubMed1995

Noninvasive measurement of cerebral blood flow and glucose metabolic rate in the rat with high-resolution animal positron emission tomography (PET): a novel in vivo approach for assessing drug action in the brains of small animals.

The cerebral metabolic rate of glucose (CMRglc) and cerebral blood flow (CBF) in rats were estimated noninvasively with a high-resolution animal positron emission tomography (PET) system that we recently developed. Qualifications of CMRglc and CBF were attempted with radiotracers, 18F-2-fluoro-2-deoxyglucose and 15O-water, respectively. From the data obtained with PET, the CMRglc and CBF values under pretreatment conditions were respectively calculated as 51 +/- 14 mumol/min/100 g and 61 +/- 7 ml/min/100 g under pentobarbital-anesthesia. These values were in close agreement with published data obtained with the autoradiographic technique. Moreover, an increase of 69% (mean) in CBF was detected after i.v. acetazolamide administration. The results indicate that this high-resolution animal PET scanner holds great potential for the assessment of drug-related metabolic and circulatory effects in intact and experimental animals.

Acetazolamide↗
PubMed1995

SPECT imaging of dopamine D2 receptors with 2'-iodospiperone.

UNLABELLED: SPECT imaging of dopamine D2 receptors was performed using 123I-labeled 2'-iodospiperone (2'-ISP). METHODS: Iodine-123-2'-ISP was administered to 12 normal subjects. Serial SPECT scans were obtained in six normal subjects for kinetic studies and static SPECT images were obtained in four normal subjects. Two additional normal subjects had serial whole-body imaging to calculate radiation dosimetry. RESULTS: Serial SPECT scans demonstrated rapid initial brain uptake followed by gradual washout from the cerebral cortex and cerebellum, while the activity in the basal ganglia was stable for 2 hr and gradually decreased thereafter. There was fast clearance of blood activity with rapid conversion of 2'-ISP to the hydrophilic metabolites. The basal ganglia-to-frontal cortex ratio increased with time and plateaued between 2 and 4 hr postinjection. The basal ganglia-to-frontal cortex ratio obtained during this period demonstrated an age-dependent decrease similar to other D2 ligands. CONCLUSION: 2'-ISP can be used for mapping dopamine D2 receptors in human brain with SPECT. The relatively high background activity, however, suggests that further modification of the compound may be needed prior to widespread clinical use.

Adult↗
PubMed1995

Paraquat tolerance of transgenic Nicotiana tabacum with enhanced activities of glutathione reductase and superoxide dismutase.

Transgenic tobacco with enhanced cytosolic activities of glutathione reductase and superoxide dismutase were generated by cross-fertilization. Leaves of the hybrids exhibited further increased tolerance to a O2-.-generating herbicide paraquat than those of their parents. This result indicates the efficiency of manipulating more than one gene in improving resistance of plants to photooxidative stress.

Drug Resistance↗
PubMed1994

11C-labeled 2'-iododiazepam for PET studies of benzodiazepine receptors: synthesis and comparison of biodistribution with its radioiodinated compound.

For PET studies of benzodiazepine receptors, N-11C-methyl-2'-iododiazepam (2'-IDZ) was synthesized by N-methylation of its desmethyl derivative with 11C-methyl iodide, and was subsequently purified by HPLC. The labeling and purification procedures were completed within 45 min after 11C-methyl iodide trapping, and the radiochemical yield (corrected for decay) was approximately 40% based on the initial trapped radioactivity of 11C-methyl iodide. Biodistribution studies in mice demonstrated that 11C-2'-IDZ was rapidly and noticeably accumulated in the brain, and subsequently decreased with time. Accumulation was greater in the cortex than in other brain regions. When compared with 125I-2'-IDZ, the distribution was almost the same until 5 min after injection, but levels were low after 20 min. Metabolic studies indicated that the difference between these two compounds in the time course of brain radioactivity distribution may be due to N-demethylation in vivo.

Animals↗
PubMed1994

Radioiodinated nordiazepam analog for in vivo assessment of benzodiazepine receptors by single photon emission tomography.

2'-Iodo-nordiazepam (2'-IND), a nordiazepam analog iodinated at the 2'-position of the C-5 phenyl ring, was synthesized and evaluated as a potential radiopharmaceutical for investigating brain benzodiazepine receptors by SPECT. [125I]2'-IND was synthesized by the halogen exchange reaction and purified by HPLC. In an in vitro competitive binding study using [3H]diazepam and rat cortical synaptosomol membranes, 2'-IND showed an almost equal affinity for benzodiazepine receptors as diazepam. In a saturation binding study using rat cortical synaptosomal membranes, 2'-IND displayed a Kd of 1.10 nM and a Bmax of 1.87 pmol/mg protein. Biodistribution and metabolism studies in mice showed that [125I]2'-IND exhibited rapid and high accumulation in the brain, and that the cerebral uptake and distribution of this compound occurred in the intact form. Furthermore, the administration of diazepam and flumazenil reduced cortical uptake by approx. 20%, suggesting that the uptake of 2'-IND occurred at least partly in association with benzodiazepine receptors.

Animals↗
PubMed1994

A new simplified method of gene typing.

SSP-PCR (sequence-specific primer) DNA typing was performed in Terasaki trays using 1.5 microliters of DNA, and the ethidium-stained PCR product was measured by direct fluorometric reading. Elimination of the gel electrophoresis step greatly simplified the SSP method. 17 serological DR specificities were discriminated for 239 DNA samples utilizing the new method, standard SSP, sequence-specific oligonucleotide probe (SSOP), and restriction fragment length polymorphism (PCR-RFLP). Results showed 98% concordance between the SSP-PCR assay and conventional methods. DRB1 alleles were determined by PCR-RFLP in 59 samples, by SSP in 110 samples, and by consensus (all methods) in the remaining samples.

Base Sequence↗
PubMed1993

Local cerebral glucose utilization in the interictal state of the spontaneously epileptic rat (SER).

Local cerebral glucose utilization (LCGU) in spontaneously epileptic rats (SER) and in their parent strains, zitter (ZI) and Kyoto-Wistar (KW) rats was studied by autoradiography with [14C]2-deoxyglucose. Compared to the LCGU in age-matched KW rats, LCGU in 8-week-old SERs, which had not yet exhibited epileptic seizures, was low in all brain regions examined, and there were no significant differences among the regions. Moreover, there were no differences in LCGU among all regions examined in both SERs and in ZI rats. By contrast, the interictal LCGU in 13-week-old SERs, which did exhibit epileptic seizures, was generally lower than in the other two strains, particularly in the hippocampus and amygdala. These findings suggest that the epileptogenic focus in SERs may lie in the hippocampus and amygdala.

Animals↗
PubMed1993

Genomic DNA structure of a gene encoding cytosolic ascorbate peroxidase from Arabidopsis thaliana.

A genomic DNA clone encoding cytosolic ascorbate peroxidase was isolated from a genomic library of Arabidopsis thaliana, using a cDNA for the enzyme as a probe. Nucleotide sequence and primer extension analyses of this gene (APX1) revealed nine exons split by eight introns, one of which is inserted in the 5'-untranslated region. The exon/intron organization of the APX1 gene differs from that of the guaiacol peroxidase genes.

Amino Acid Sequence↗
PubMed1993

Myocardial accumulation of a dopamine D2 receptor-binding radioligand, 2'-iodospiperone.

125I-2'-iodospiperone (2'-ISP), which has a high and selective affinity for dopamine D2 receptors, produced a high myocardial accumulation of radioactivity in the early phase after intravenous injection into mice. A human scintigraphic study also showed that the myocardium was clearly visualized soon after intravenous injection of the tracer. Analysis of the myocardial homogenate obtained from mice showed that 125I-2'-ISP was metabolically stable and was taken up the myocardium in its intact form. Administration of spiperone significantly reduced the myocardial uptake of 125I-2'-ISP in mice. Treatment with haloperidol and (+) butaclamol, which have a high affinity for dopamine D2 receptors, also tended to reduce the myocardial uptake of radioactivity, while (-)-butaclamol, which has no affinity for dopamine D2 receptors, caused no change in uptake. These findings suggest that the myocardial accumulation of 2'-ISP occurred in association with dopamine D2 (DA2) receptors.

Animals↗
PubMed1993

High reactivity of [11C]CH3I with thiol group in the synthesis of C-11 labeled radiopharmaceuticals.

High reactivity of [11C]-methyl iodide ([11C]CH3I) with the thiol group was demonstrated with cysteamine and other compounds containing a thiol and another functional groups in each structure. The methylation of the thiol group in cysteamine with [11C]CH3I was very rapid at 0 degree C with no catalyst, and gave a high radiochemical yield and purity without any detectable by-product. Moreover, this reaction was not disturbed by the other functional groups, such as -NH2, -OH and -COOH in the same structure. This S-methylation reaction is very useful for producing a new radiopharmaceutical labeled with the short lived positron emitting nuclide C-11.

Carbon Radioisotopes↗
PubMed1993

An approach for assaying benzodiazepine receptor binding with radioiodinated ligand: 125I-labeled diazepam derivative.

[125I]2'-Iododiazepam (IDZ) was prepared and its application in a benzodiazepine receptor binding assay was studied. [125I]2'-IDZ binds to the rat cortical membrane with a high affinity (Kd, 0.66 nM). Various benzodiazepines showed competition with [125I]2'-IDZ for the binding sites in the rat cortical membrane, and the specificity of its binding correlated well with that of [3H]diazepam (r = 0.992, p < 0.001). These findings suggested that [125I]2'-IDZ binds to the same sites as [3H]diazepam and indicated that [125I]2'-IDZ can be used in a benzodiazepine receptor assay.

Animals↗