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Biomedical subjects

S Nakamura

Publications and source records attributed to S Nakamura.

At least 145 records · Page 8Linked to original sources

Ventral striatal vs. accumbal (shell) mechanisms and non-cyclase-coupled dopamine D(1)-like receptors in jaw movements.

This study compared the effects of intracerebral injections of the dopamine D(1)-like receptor agents 3-methyl-6-chloro-7,8-dihydroxy-1-[3-methylphenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine (SK&F 83959) and [R]-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390) into the ventrolateral striatum or the shell of the nucleus accumbens on the synergistic induction of jaw movements by intravenous (i.v.) co-administration of [R]-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SK&F 38393) or SK&F 83959 with the dopamine D(2)-like receptor agonist, quinpirole. In the ventrolateral striatum, SCH 23390 and SK&F 83959 each blocked jaw movements induced by i.v. SK&F 38393 with quinpirole, while only SCH 23390 blocked i.v. SK&F 83959 with quinpirole. SCH 23390 was less effective in the accumbens shell than in the ventrolateral striatum, and SK&F 83959 was ineffective to block i.v. SK&F 38393 with quinpirole, while neither SCH 23390 nor SK&F 83959 blocked i.v. SK&F 83959 with quinpirole. As SK&F 83959 inhibits the stimulation of adenylyl cyclase via dopamine D(1A) receptors but acts as an agonist at a putative dopamine D(1)-like receptor site not linked to cyclase, an important role is indicated for non-cyclase-coupled dopamine D(1)-like receptor sites as well as dopamine D(1A) receptors in the regulation of jaw movements via dopamine D(1)-like/D(2)-like receptor synergism, particularly in the ventrolateral striatum.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Determination of estrogens in river water by gas chromatography-negative-ion chemical-ionization mass spectrometry.

A method for the determination of estrogens (17alpha-estradiol, 17beta-estradiol, estrone, ethynyl estradiol, and estriol) as pentafluorobenzyl-trimethylsilyl (PFB-TMS) derivatives by gas chromatography-mass spectrometry (GC-MS) with negative-ion chemical-ionization (NICI) is described. The NICI of all the derivatives produced an intense [M-PFB]- ion as the base peak. The reagent gas (methane) flow-rate and the ion source temperature were determined to be 2.0 ml/min and 240 degrees C, respectively, for the optimized NICI-selected ion monitoring (SIM) conditions. The sensitivities of the PFB-TMS derivatives in the NICI mode were 8.0-130 times higher than those of the PFB-TMS derivatives in electron ionization (EI) mode, and 12-25 times higher than those of all the TMS derivatives in the EI mode. This method was applied to the analysis of estrogens in river water using a solid-phase extraction as the sample preparation. The recoveries of the target chemicals from a river-water sample spiked with standards at 2 ng/l level were 85.8-126.5% (RSD, 6.2-13.0%). The methodical detection limits ranged from 0.10 to 0.28 ng/l.

Estrogens↗

Association between polymorphisms of folate- and methionine-metabolizing enzymes and susceptibility to malignant lymphoma.

Genetic alteration is considered a probable cause of malignant lymphoma. Folate and methionine metabolism play essential roles in DNA synthesis and DNA methylation, and their metabolic pathways might thus affect disease susceptibility. In the present study, 2 polymorphisms were evaluated for a folate metabolic enzyme, methylenetetrahydrofolate reductase (MTHFR), and one was evaluated for methionine synthase (MS). The 2 polymorphisms, MTHFR677 C-->T and MTHFR1298 A-->C, are reported to reduce the enzyme activity, which causes intracellular accumulation of 5,10-methylenetetrahydrofolate and results in a reduced incidence of DNA double-strand breakage. The MS2756 A-->G polymorphism also reduces the enzyme activity and results in the hypomethylation of DNA. To evaluate the association between malignant lymphoma susceptibility and these polymorphisms, hospital-based case-control study was conducted in Aichi Cancer Center. Ninety-eight patients with histologically confirmed lymphoma and 243 control subjects without cancer were evaluated. Unconditional logistic regression analyses revealed a higher susceptibility with the MTHFR677 CC and the MTHFR1298 AA genotypes (odds ratio, 2.26; 95% confidence interval, 1.26-4.02) when those harboring at least one variant allele in either polymorphism of MTHFR were defined as the reference. For the MS polymorphism, the MS2756 GG genotype also showed a higher susceptibility (odds ratio, 3.83; 95% CI, 1.21-12.1) than those with MS2756 AA or AG types. The significance was not altered when these 3 polymorphisms were evaluated in combination, and the results suggest that folate and methionine metabolism play important roles in the occurrence of malignant lymphomas. Further studies to confirm the association and detailed biologic mechanisms are now required.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Effect of AF64A, a cholinergic neurotoxin, on footshock stimulation-induced locus coeruleus excitation in rats.

We studied the effect of ethylcholine mustard aziridinium ion (AF64A), a cholinergic neurotoxin, on the footshock stimulation (FS)-induced excitation of the locus coeruleus (LC) neurons in rats. The FS-evoked LC excitation was significantly reduced in AF64A-treated rats, in comparison with normal rats. In particular, the early component of LC excitation was less pronounced. The number of choline acetyltransferase immunoreactive neurons in the septal complex was significantly lower than those in normal rats, except for in the ventral subgroup. These findings suggest that the cholinergic neuron system is involved in the early component of LC excitation in rats.

Action Potentials↗

Analysis of waterborne paints by gas chromatography-mass spectrometry with a temperature-programmable pyrolyzer.

Gas chromatography-mass spectrometry (GC-MS) with a temperature-programmable pyrolyzer was used for the analysis of waterborne paints. Evolved gas analysis (EGA) profiles of the waterborne paints were obtained by this temperature-programmed pyrolysis directly coupled with MS via a deactivated metal capillary tube. The EGA profile suggested the optimal thermal desorption conditions for solvents and additives and the subsequent optimal pyrolysis temperature for the remaining polymeric material. Polymers were identified from pyrograms with the assistance of a new polymer library. The solvents were identified from the electron ionization mass spectra with the corresponding chemical ionization mass spectra. The additive was identified as zinc pyrithione by comparison with authentic standard. Zinc pyrithione cannot be analyzed by GC-MS as it is. However, the thermal decomposition products of zinc pyrithione could be detected. The information on the decomposition temperature and products was useful for the identification of the original compound.

Gas Chromatography-Mass Spectrometry↗

Plasma thrombin-antithrombin III complex is associated with the severity of experimental autoimmune encephalomyelitis.

Previous studies have shown that activation of blood coagulation and fibrin depositions around CNS vessels are observed in animals with experimental autoimmune encephalomyelitis (EAE), which provides an animal model for human autoimmune demyelinating disorders. We examined the values of peripheral blood fibrinogen, thrombin-antithrombin III complex (TAT), fibrinolytic activity, and fibrin degradation products in Lewis rats with EAE to elucidate the role of the blood coagulation-fibrinolysis system in EAE. Plasma TAT values increased immediately prior to development of symptoms, and decreased according to the improvement of symptoms. There was significant correlation between TAT values and clinical scores of EAE; other markers were not correlated with the symptoms of EAE. These results suggest that plasma TAT levels are sensitive markers of the severity of EAE, and may be useful clinical indicators for the severity of human autoimmune demyelinating disorders.

Animals↗

Influence of age on the results of brachytherapy for early tongue cancer.

PURPOSE: To determine the influence of elder age on the results of brachytherapy for early (T1-2 N0 M0) oral tongue cancer and examine the compatibility of low-dose rate (LDR) with high-dose rate (HDR) brachytherapy. METHODS AND MATERIALS: We analyzed 591 patients treated at Osaka University Hospital between 1967 and 1999. We compared the results of radiotherapy for 156 elderly patients (137 LDR and 19 HDR) 65 years of age or older and 435 patients (383 LDR and 52 HDR) less than 65 years of age. RESULTS: HDR brachytherapy showed the same local control rate as LDR brachytherapy (81% at 3 years). Elderly patients showed a poorer local control rate (75% at 3 years) than the younger group (83% at 3 years)(p = 0.002). Multivariate analysis identified age as the only prognostic factor for local control (p = 0.002). CONCLUSIONS: HDR brachytherapy achieved the same result as LDR brachytherapy. However, the elderly patient showed a higher rate of local recurrence after brachytherapy.

Adult↗

Identification of proacrosin binding protein sp32 precursor as a human cancer/testis antigen.

Serological expression cloning of antigens eliciting a humoral immune response to a syngeneic mouse sarcoma identified pem (mouse placenta and embryonic expression gene) as a new member of the cancer/testis family. To identify the human homologue of pem, mouse pem sequences and pem-related expressed sequence tags from human testis were used as PCR primers for amplification using human testis cDNA. However, rather than pem, another gene, designated OY-TES-1, was isolated and found to be the human homologue of proacrosin binding protein sp32 precursor originally identified in mouse, guinea pig, and pig. OY-TES-1 maps to chromosome 12p12-p13 and contains 10 exons. Southern blot analysis suggests the presence of two OY-TES-1-related genes in the human genome. In normal tissues, OY-TES-1 mRNA was expressed only in testis, whereas in malignant tissues, a variable proportion of a wide array of cancers, including bladder, breast, lung, liver, and colon cancers, expressed OY-TES-1. Serological survey of 362 cancer patients with a range of different cancers showed antibody to OY-TES-1 in 25 patients. No OY-TES-1 sera reactivity was found in 20 normal individuals. These findings indicate that OY-TES-1 is an additional member of the cancer/testis family of antigens and that OY-TES-1 is immunogenic in humans.

Amino Acid Sequence↗

Genetic studies in Parkinson's disease with an alpha-synuclein/NACP gene polymorphism in Japan.

Dinucleotide repeat polymorphism has been observed in the promoter of the alpha-synuclein (alpha-SYN)/NAC precursor protein (NACP) gene. Alpha-SYN/NACP allele 3 (described by Xia et al. (Ann. Neurol., 40 (1996) 207), equivalent to allele 1 described by Krüger et al. (Ann. Neurol. 45 (1999) 611) is reported to be significantly more frequent among patients with sporadic Parkinson's disease (sPD) than controls. In this study, we genotyped the same alpha-SYN/NACP polymorphism in Japanese sPD patients and healthy controls, but found that any aliele showed no significant difference between the two groups.

Aged↗

Ultrasound activates the auditory cortex of profoundly deaf subjects.

Using three-dimensional PET, the cortical areas activated by bone-conducted ultrasound were measured from five profoundly deaf subjects and compared with the cortical areas of normal-hearing subjects activated by stimuli through bone-conducted ultrasonic, air-conducted, bone-conducted, and vibro-tactile hearing aids. All of the hearing aids, including the ultrasonic hearing aid, consistently activated the medial portion of the primary auditory cortex of the normal volunteers. The same cortical area was also significantly activated in the profoundly deaf subjects although the percentage increase in regional cerebral blood flow (rCBF) was smaller than in normal subjects. These results suggest that extra-cochlear routes convey information to the primary auditory cortex and can therefore produce detectable sound sensation even in the profoundly deaf subjects, who reported a sensation themselves.

Adult↗

XAS and MCD studies in Eu0.6Sr0.4MnO3.

Eu(1-x)Sr(x)MnO3 system is one of the perovskite manganites that exhibit the giant magneto resistance effect and the transition from the insulator phase to the metal. Eu(0.6)Sr(0.4)MnO3 behaves as a ferromagnetic semiconductor and has an Insulator-Metal (IM) transition induced by external magnetic field, which could be found only in this system among the perovskite manganites group. The mechanism of the transition was investigated by X-ray Magnetic Circular Dichroism (XMCD) at the Mn L2,3-edges of and the Eu M4,5-edges in Eu(0.6)Sr(0.4)MnO3.

Journal Article↗

Activated Fyn phosphorylates alpha-synuclein at tyrosine residue 125.

alpha-Synuclein is a presynaptic protein of unknown function that has been implicated in the pathogenesis of several neurodegenerative diseases, including Parkinson's and Alzheimer's diseases. To gain insight into the functions of alpha-synuclein, we sought protein kinases that phosphorylate alpha-synuclein in the central nervous system. In contrast to Lyn, PYK2, FAK, MAPK/ERK1, SAPK/JNK, and Cdk5, only Fyn could phosphorylate alpha-synuclein. In addition, A30P and A53T mutations did not affect the phosphorylation of alpha-synuclein by Fyn. Mutation analysis revealed that activated Fyn phosphorylates specifically tyrosine residue 125 of alpha-synuclein. The distribution of alpha-synuclein and Fyn expression was similar in various parts of the brain and was colocalized in subcellular structures. Since Fyn regulates various signal transduction pathways in the central nervous system and plays an essential role in the neuronal cell differentiation, survival, and plasticity, results of this paper indicate that phosphorylation of alpha-synuclein might be involved in one of the Fyn-mediated signaling pathways in neuronal cells.

Animals↗

Identification of a novel autoantigen UACA in patients with panuveitis.

To identify the target autoantigens in Vogt-Koyanagi-Harada disease, we made use of an immunoscreening of a bovine uveal cDNA expression library with serum samples obtained from patients with Vogt-Koyanagi-Harada disease. We identified a novel bovine antigen and homologous human autoantigen and designated it as UACA (uveal autoantigen with coiled coil domains and ankyrin repeats). mRNA of human UACA is expressed most abundantly in skeletal muscles and in various human tissues, including choroid, retina, and epidermal melanocytes. IgG autoantibodies were quantitated in an ELISA, using recombinant C-terminal 18.0% fragment of human UACA. The prevalence of IgG anti-UACA autoantibodies in patients with panuveitis (Vogt-Koyanagi-Harada disease, Behçet's disease, sarcoidosis) was significantly higher than that in healthy controls (19.6-28.1% vs 0%, P < 0.05) indicating that autoimmunity directed against UACA is a common phenomenon in these diseases.

Adolescent↗

Molecular dynamics study on hydrophobic effects in aqueous urea solutions.

Hydrophobic effects in aqueous urea were analyzed by molecular dynamics simulations. The contribution of solvents to the potential of mean force between two methane molecules was calculated by using molecular dynamics simulations and was compared with the solubility data of hydrocarbons in aqueous urea. Both the simulation results and the solubility data indicated that urea stabilizes methane-methane association. The stabilization was due to increasing the solvation free energies of small hydrocarbons such as methane by addition of urea. The solvation free energies of larger hydrocarbons, on the other hand, are decreased by addition of urea. This effect of the solute size on hydrophobic free energies in aqueous urea was also analyzed by using molecular dynamics simulations by means of division of the solvation process into two parts: the cavity formation and the introduction of the solute-solvent attractive interactions. In the cavity formation, urea increased hydrophobic free energies, and in the introduction of the solute-solvent attractive interactions, urea decreased hydrophobic free energies. The influence of urea on hydrophobic free energies was determined by the balance of effects of the two parts of the solvation process.

Computer Simulation↗

Fractal analysis of senile plaque observed in various animal species.

In the present study, the fractal dimension (FD), a concept to determine morphological complexity, was applied to morphological estimation of animal and human senile plaque using a computer-aided method. The FDs of mature plaque in a 17-year-old dog were significantly higher than those of diffuse plaque in 11- to 16-year-old dogs. In both types of plaque, the FD tended to increase as the size expanded and there was a significant difference between the slope values of the approximate line for diffuse and mature plaque. In humans, there was also a significant difference in FD value between diffuse and mature plaque. No significant differences were observed between the two types of plaque in a bear or a cynomolgus monkey. The FD of feline diffuse plaque was significantly lower than that of a camel, bear and monkey. These results indicated that the diffuse and mature plaque of the dog might form in a different manner, and similar events may occur in human senile plaque formation. In addition, specific shapes and different FD values of the diffuse plaque among animals suggested that the original conditions for plaque formation would be different.

Aging↗