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H Saji

Publications and source records attributed to H Saji.

At least 19 recordsLinked to original sources
PubMed1992

Cloning and sequencing of a cDNA encoding ascorbate peroxidase from Arabidopsis thaliana.

A cDNA clone encoding ascorbate peroxidase (AP, EC 1.11.1.11) was isolated from a phage lambda gt11 library of cDNA from Arabidopsis thaliana by immunoscreening with monoclonal antibodies against the enzyme, and then sequenced. The cDNA insert hybridized to a 1.1 kb poly(A)+ RNA from leaves of A. thaliana. Genomic hybridization suggests that the cDNA obtained here corresponds to a single-copy gene. The N-terminal amino acid sequence of Arabidopsis AP was determined by protein sequencing of the immunochemically purified enzyme, and proved to be homologous to the N-terminal amino acid sequence of the chloroplastic AP of spinach. The predicted amino acid sequence of the mature AP of A. thaliana, deduced from the nucleotide sequence, consists of 249 amino acid residues, which is 34% homologous with cytochrome c peroxidase of yeast, but less homologous with other plant peroxidases. Amino acid residues at the active site of yeast cytochrome c peroxidase are conserved in the amino acid sequence of Arabidopsis AP. The poly(dG-dT) sequence, which is a potential Z-DNA-forming sequence, was found in the 3' untranslated region of the cDNA.

Amino Acid Sequence↗
PubMed1992

Preparation and biodistribution in mice of [11C]carfentanil: a radiopharmaceutical for studying brain mu-opioid receptors by positron emission tomography.

A potent mu-opioid agonist, [11C]carfentanil, was prepared by the methylation of carfentanil carboxylic acid with [11C]methyl iodide in order to study brain mu-opioid receptors by positron emission tomography. Synthesis (including purification) was completed within 25 min and the radiochemical yield was approximately 40%. The radiochemical purity of the product was more than 99% and its specific activity was 3.7-7.4 GBq/mumol. Biodistribution studies performed in mice after intravenous injection showed a high brain uptake and rapid blood clearance, so a high brain/blood ratio of 1.5-1.8 was found from 5 to 30 min. Regional cerebral distribution studies in the mouse showed a significantly higher uptake of [11C]carfentanil by the thalamus and striatum than by the cerebellum, with the radioactivity in the striatum disappearing more rapidly than that in the thalamus. Treatment with naloxone significantly reduced the uptake of [11C]carfentanil by the thalamus and striatum. These results indicate that [11C]carfentanil binds specifically to brain mu-opioid receptors.

Animals↗
PubMed1992

An artificial amino acid radiopharmaceutical for single photon emission computed tomographic study of pancreatic amino acid transports 123I-3-iodo-alpha-methyl-L-tyrosine.

123I-3-iodo-alpha-methyl-L-tyrosine (123I-L-AMT) was selected and its characteristics on pancreas accumulation, metabolic selectivity and metabolic stability of 125I-L-AMT were studied. The studies on rat tissue slice as well as mouse biodistribution proved very high accumulation of 125I-labeled L-AMT in the pancreas, which was remarkably inhibited by the active transport inhibitor, ouabain. 125I-L-AMT does not enter into protein synthesis and general amino acid catabolism. Moreover, 125I-L-AMT was very stable against enzymatic deiodination. Thus, the above studies indicated that the 123I-labeled L-AMT was an "artificial amino acid" radiopharmaceutical to be used for the selective measurement of the membrane amino acid transport rate in the pancreas.

Amino Acids↗
PubMed1992

HLAs and genes in Japanese patients with multiple sclerosis: evidence for increased frequencies of HLA-Cw3, HLA-DR2, and HLA-DQB1*0602.

The distribution of HLA-A, B, C, DR and DRB1, DQB1, DPB1 alleles was studied in 60 Japanese patients with clinically definite multiple sclerosis (MS) using serologic and genomic analysis. We found significant associations with HLA-Cw3 (p = 0.002, pc = 0.012, RR = 3.2), DR2 (p = 0.007, RR = 2.6), and DQB1*0602 (p = 0.04, RR = 4.0) in Japanese patients for the first time. The combined presence of Cw3 and DR2 gave a higher risk than each antigen alone. The reported increase in the frequency of DPw4 in Japanese MS patients [12] could not be confirmed by our genomic study. The frequencies of all of the residues in each variable region of the amino acid sequences of DQ beta and DP beta chains were not different between the MS patients and the controls. These results suggest that MS susceptibility may result from polygenic influences and from the presence of environmental factors.

Alleles↗
PubMed1992

Preparation of 123I-labeled 2'-iodospiperone and imaging of D2 dopamine receptors in the human brain using SPECT.

[123I]2'-ISP was readily prepared using a radioiodine exchange reaction with a radiochemical yield of approx. 50% after HPLC purification. The radiochemical purity of the product was more than 98% and the specific activity was 5.55-11.1 GBq/mumol. Biodistribution studies performed in mice indicated that injection of [123I]2'-ISP with albumin produced a higher gastric uptake and a lower brain uptake than injection of the radioligand in a weakly acidic solution. In addition, toxicity tests performed in mice demonstrated that acute toxic effects would be very unlikely to be encountered if 2'-ISP was used for diagnostic purposes. A preliminary imaging study with [123I]2'-ISP in a healthy human volunteer showed its specific uptake by the basal ganglia, a region of the brain known to have a high density of D2 dopamine receptors.

Animals↗
PubMed1992

Accumulation of radioactivity in the pancreas after intravenous administration of [13N]ammonia.

A biodistribution study of [13N]ammonia in rats showed a high accumulation of radioactivity in the pancreas soon after the intravenous injection of this tracer. In humans, the pancreas was also clearly visualized by dynamic positron emission tomography soon after the intravenous injection of [13N]ammonia. To investigate the mechanism of the pancreatic accumulation of [13N]ammonia, in vitro studies with pancreatic slices and in vivo biodistribution and metabolism studies were carried out in rats. The results indicated that [13N]ammonia enters the pancreas from the blood by diffusion at a rate dependent on local blood flow, and then is rapidly incorporated into the amino acid fraction (mainly the glutamine fraction), followed by its incorporation into protein. These findings suggest that [13N]ammonia could be useful for diagnostic imaging of the pancreas.

Ammonia↗
PubMed1992

Synthesis and biological evaluation of a 13N-labeled opioid peptide.

The 13N-labeled opioid tetrapeptide, Tyr-D-Met(O)-Phe-Gly-[13N]NH2 (SD-62), was synthesized by amidation of its activated p-nitrophenol ester with [13N]ammonia (total synthesis time: 25 min, radiochemical yield: 48%). When injected intravenously into mice, [13N]SD-62 was taken up by the brain and this uptake was blocked by naloxone. In addition, the time course of changes in brain radioactivity paralleled that of the analgesic activity of this compound, suggesting that SD-62 underwent binding to brain opioid receptors. Thus, [13N]SD-62 appears to hold some promise for use as a radiopharmaceutical for in vivo studies of opioid peptide behavior, using positron emission tomography.

Amino Acid Sequence↗
PubMed1992

Investigation of radiopharmaceuticals for pancreatic imaging: accumulation of amines in the pancreas.

To develop radiopharmaceuticals for pancreatic imaging, radioiodinated ethyl benzene derivatives containing various functional groups (amino, carboxyl, and methyl groups) were synthesized and the effects of these functional groups were compared in vitro and in vivo. At 2 min after intravenous injection, the amino derivative, 2-(4-iodophenyl)-N,N-dimethyl ethylamine, displayed about twice the pancreatic uptake and a more than 8-fold higher pancreas/liver ratio than the carboxyl and methyl derivatives. This high and selective in vivo accumulation on the amino derivative in the pancreas was well supported by in vitro studies on the uptake by pancreatic tissue slices. The mechanism promoting pancreatic accumulation of radiopharmaceuticals with an amino group is also discussed.

Amines↗
PubMed1992

Evaluation of N-alkyl derivatives of radioiodinated spiperone as radioligands for in vivo dopamine D2 receptor studies: effects of lipophilicity and receptor affinity on the in vivo biodistribution.

A series of radioiodinated spiperone (2'-ISP) derivatives bearing amide N-alkyl substituents (N-methyl-2'-ISP, N-ethyl-2'-ISP, and N-propyl-2'-ISP) were synthesized and evaluated as potential singlet photon emission computed tomographic radiopharmaceuticals for visualizing dopaminergic receptors. The lipophilicity of these ligands (i.e., the partition coefficient for octanol-phosphate buffer) increased as the chain length increased. Investigation of blood-brain barrier permeability in rats showed a parabolic relationship between the brain uptake index and the partition coefficient. In vitro competitive binding studies showed that the relative affinity for the dopamine D2 receptor was in the order of N-propyl-2'-ISP greater than 2'-ISP greater than N-methyl-2'-ISP approximately N-ethyl-2'-ISP. In vivo biodistribution studies showed that the initial brain uptake correlated fairly well with the brain uptake index and that the kinetics of the radioactivity specifically bound to the striatum were strongly influenced by the dopamine receptor binding affinity of the compounds. Thus, the in vivo behavior of these N-alkylated 2'-ISP derivatives involved a complex interplay between receptor affinity, lipophilicity, and blood-brain barrier permeability.

Animals↗
PubMed1992

Synthesis of (S)-N-[methyl-11C]nicotine and its regional distribution in the mouse brain: a potential tracer for visualization of brain nicotinic receptors by positron emission tomography.

A nicotine agonist, 11C-labeled (S)-nicotine, was synthesized by N-methylation of (S)-nornicotine with [11C]-methyl iodide in dimethylformamide-dimethylsulfoxide in order to study nicotinic receptors in the human brain by positron emission tomography. The radiochemical yield of this N-methylation reaction was more than 90% within 5 min. After purification by high performance liquid chromatography the radiochemical purity of the product was more than 99% and the specific radioactivity was 7.4-11.1 GBq/mumol. The regional distribution of (S)-[11C]nicotine in the mouse brain after intravenous injection was compared with that of (R)-[11C]nicotine. After injection of (S)-[11C]nicotine, the regional uptake of radioactivity was in the following order: cortex greater than thalamu approximately hippocampus greater than striatum greater than hypothalamus greater than cerebellum. Moreover, (S)-[11C]nicotine was displaced from the brain by unlabeled (S)-nicotine, but unlabeled (R)-nicotine caused no change in uptake. In contrast, (R)-[11C]nicotine showed a lower brain uptake and lesser regional differences in radioactivity.

Animals↗
PubMed1991

Human platelet-specific antigen, Siba, is associated with the molecular weight polymorphism of glycoprotein Ib alpha.

Platelet-specific antigen Sib(a) has been highly implicated in the pathogenesis of refractoriness to human leukocyte antigen (HLA)-matched platelet transfusions in Japan. We provide evidence that the Sib(a) antigen is located on the glycoprotein (GP) Ib alpha and has a close association with the molecular weight (mol wt) polymorphism of GPIb. In modified antigen-capture ELISA (MACE), anti-Sib(a) antibody reacted only with GPIb/IX held by a murine anti-GPIb/IX monoclonal antibody (MoAb). The reactivity of anti-Sib(a) antibody to Sib(a)-positive (Sib(a+)) platelets was abolished after they were treated with Serratia marcescens protease. Platelets from 50 healthy volunteers were semiquantitatively phenotyped for Sib(a) antigen by MACE and divided into three distinct groups: strongly positive, positive, and negative. They were also analyzed by sodium dodeyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and periodic acid-silver staining for mol wt polymorphism of GPIb, phenotyped as A, B, C, or D. Without exception, Sib(a+) platelets showed larger phenotypes (A or B). Removal of sialic acid from Sib(a+) platelets did not reduce the binding of anti-Sib(a). Finally, anti-Sib(a) antibody specifically immunoprecipitated A and B phenotypes of GPIb from Sib(a+) platelets. Thus, Sib(a) antigen evidently is located in the region of glycocalicin that is present only on the A and B phenotypes of GPIb.

Antigens, Human Platelet↗
PubMed1991

Accumulation and metabolism of [125I]HIPDM in the rat pancreas.

Our previous studies have shown a high accumulation of [125I]N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3- propanediamine (HIPDM) in the human pancreas. In this study, the pancreatic accumulation and metabolism of [125I]HIPDM were studied in rats to determine the factors influencing its uptake by this organ. In biodistribution studies, [125I]HIPDM showed a high uptake by the pancreas similar to that by the brain and lungs, both organs with a low tissue pH. TLC analysis of pancreatic homogenate after the injection of [125I]HIPDM showed that it was metabolically stable in this organ. Moreover, in the pancreatic homogenate, the bulk of the radioactivity was recovered from the microsomal fraction, and the radioactivity bound to microsomal particles showed release that was dependent on the Ca2+ or Mg2+ concentration in the incubation medium. These results suggest that the initial pancreatic uptake of [125I]HIPDM may be a function of blood flow and governed by the pH gradient hypothesis, while subsequent retention may occur secondary to ionic binding within the pancreas.

Animals↗
PubMed1991

Postoperative erythroderma with change of HLA phenotypes from heterozygotes to homozygotes: a report of two cases.

Fatal "postoperative erythroderma" (POE) developed in 2 patients treated with liver lobectomy and the transfusion of fresh blood. Their clinical features and skin-histological findings were indicative of acute graft-versus-host disease (GVHD). The HLA phenotypes of circulating lymphocytes of the 2 patients were heterozygous but became homozygous late in the clinical course and were identical with those of the blood donors. One of the patient's haplotypes was identical with the donor's homozygous haplotype. These findings suggest the mechanism of development of POE in apparently immunocompetent patients. The donor's T lymphocytes are histocompatible with the patient's tissues, are not rejected, and become engrafted. The patient's tissues are not histocompatible with the donor's, so that GVHD develops.

Blood Donors↗
PubMed1991

A synthetic method suitable for the rapid preparation of 13N-labeled dermorphin analogue, H-Tyr-D-Met(O)-Phe-Gly-NH2 (SD-62).

A synthetic method suitable for the preparation of 13N-labeled dermorphin analogue, H-Tyr-D-Met(O)-Phe-Gly-NH2 (SD-62), was established; i.e., SD-62 was synthesized by a 5 min treatment of the active ester precursor with ammonia. When the 13N-labeled SD-62, prepared by this method with [13N]ammonia, was administered into mice, the time profile of the radioactivity accumulation in the brain paralleled well that of the analgesic activity.

Analgesics, Opioid↗
PubMed1991

Heterogeneity of non-insulin-dependent diabetes mellitus in HLA types and clinical features: comparison with insulin-dependent diabetes mellitus.

We determined HLA types in 110 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) and studied the relationship between the HLA phenotypes and clinical features. Sixty-nine patients with insulin-dependent diabetes mellitus (IDDM) and 100 healthy blood donors served as controls. Concerning HLA DR and DQ loci, frequencies of DR4, DRw9 and DQw3.2 were higher, and those of DR2, DRw8, DRw11, DRw12 and DQw1 were lower in patients with IDDM compared than in healthy controls. There were no differences between NIDDM and normal controls in the frequency of a particular HLA DR antigen except for a decreased frequency in DRw11 in the former. The frequency of DQw3.2 antigen in NIDDM was intermediate between IDDM and normal controls. There were some differences between DQw3.2-positive and -negative NIDDM patients in clinical features. Those who showed low C-peptide responses during oral glucose tolerance test were more frequently found among DQw3.2-positive NIDDM patients. These results suggest that Type 1 diabetes mellitus may have a mild clinical course and is found among the Japanese NIDDM population.

Age Factors↗
PubMed1991

[Opioid receptor].

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Brain Chemistry↗