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Biomedical subjects

J Nakamura

Publications and source records attributed to J Nakamura.

At least 91 records · Page 5Linked to original sources
PubMed2000

Adenosine A(2A) receptor antagonists KF17837 and KW-6002 potentiate rotation induced by dopaminergic drugs in hemi-Parkinsonian rats.

The effects of novel adenosine A(2A) receptor antagonists KF17837 ((E)-1,3-dipropyl-8-(3,4-dimethoxystyryl)-7-methyl-3, 7-dihydro-1H-purine-2,6-dione) and KW-6002 ((E)-1,3-diethyl-8-(3, 4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione), on rotational behavior induced by apomorphine or L-DOPA (L-3, 4-dihydroxyphenylalanine) were investigated in rats with unilateral 6-hydroxydopamine lesions. Both KF17837 and KW-6002 slightly induced rotational behavior per se. However, KF17837 and KW-6002 significantly increased the total counts of turning induced by apomorphine at doses of 3 mg/kg, p.o. and 10 mg/kg, p.o., and at doses of 1 mg/kg, p.o. and higher, respectively. KF17837 and KW-6002 also potentiated the rotational behavior induced by L-DOPA at a dose of 3 mg/kg, p.o. Furthermore, i.c.v. injection (10 microg/20 microl) of a selective adenosine A(2) receptor agonist CGS 21680 [2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoaden osine] partially prevented the rotational behavior induced by apomorphine and this inhibition was reversed by KW-6002 (1 mg/kg, p.o.). The increase in total counts of apomorphine-induced turning by the adenosine A(2A) receptor antagonists seems to be mainly attributable to prolongation of turning duration rather than enhancement of intensity. These results suggest that these adenosine A(2A) receptor antagonists may be useful to ameliorate shortening in the duration of dopaminergic drug response in patients with advanced Parkinson's disease.

Animals↗
PubMed2000

Relationship between serum cholesterol levels and meta-chlorophenylpiperazine-induced cortisol responses in healthy men and women.

We investigated the effect of cholesterol on serotonergic receptor function in 20 healthy male and 10 healthy female subjects using cortisol responses to meta-chlorophenylpiperazine (m-CPP) neuroendocrine challenge tests. M-CPP, a metabolite of the antidepressant trazodone, has been widely used in psychopharmacology research as a probe of serotonin function. In the human brain, m-CPP binds both to various serotonergic receptors, mainly 5-HT(2C), and to alpha(2)-adrenoceptors. After an overnight fast, the subjects received m-CPP (0.5 mg/kg) or identical placebo capsules orally in a randomized, double blind, crossover design. Blood was obtained for measurement of cholesterol and cortisol. In some analyses, especially in males, there were significant positive correlations between serum cholesterol levels and cortisol responses. These findings suggest the possibility that serum cholesterol levels may be positively associated with serotonergic receptor function. The existence of such an association may provide an explanation for reported increases in depression, suicide and violence in individuals with low or lowered cholesterol.

Adult↗
PubMed2000

Strain relaxation in InAs/GaAs(111)A heteroepitaxy

We have studied strain-relaxation processes in InAs heteroepitaxy on GaAs(111)A using rocking-curve analysis of reflection high-energy electron diffraction. Strain relaxation in the direction parallel to the surface occurs at approximately 1.5 bilayers (BL) thickness. On the other hand, the lattice constant in the direction normal to the surface remains almost unchanged below approximately 3 BL thickness and is estimated to be approximately 3.3 A. This value, slightly larger than that of bulk GaAs (3.26 A), does not quite reach the value predicted by classical elastic theory, 3.64 A. The present result has been supported by the first-principles total-energy calculations.

Journal Article↗
PubMed2000

5'-nicked apurinic/apyrimidinic sites are resistant to beta-elimination by beta-polymerase and are persistent in human cultured cells after oxidative stress.

Genomic DNA is continuously exposed to oxidative stress. Whereas reactive oxygen species (ROS) preferentially react with bases in DNA, free radicals also abstract hydrogen atoms from deoxyribose, resulting in the formation of apurinic/apyrimidinic (AP) sites and strand breaks. We recently reported high steady-state levels of AP sites in rat tissues and human liver DNA (Nakamura, J., and Swenberg, J. A. (1999) Cancer Res. 59, 2522-2526). These AP sites were predominantly cleaved 5' to the lesion. We hypothesized that these endogenous AP sites were derived from oxidative stress. In this investigation, AP sites induced by ROS were quantitated and characterized. A combination of H(2)O(2) and FeSO(4) induced significant numbers of AP sites in calf thymus DNA, which were predominantly cleaved 5' to the AP sites (75% of total aldehydic AP sites). An increase in the number of 5'-AP sites was also detected in human cultured cells exposed to H(2)O(2), and these 5'-AP sites were persistent during the post-exposure period. beta-Elimination by DNA beta-polymerase efficiently excised 5'-regular AP sites, but not 5'-AP sites, in DNA from cells exposed to H(2)O(2). These results suggest that 5'-oxidized AP sites induced by ROS are not efficiently repaired by the mammalian short patch base excision repair pathway.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Polymorphisms of the sigma(1) receptor gene in schizophrenia: An association study.

Possible involvement of sigma receptors in the pathogenesis of schizophrenia has been suggested. In this study we searched systematically for polymorphisms in the 5'-franking region of the sigma(1) receptor. Genetic variation in this region could reduce the expression of the gene, and this suggestion is compatible with findings of reduced sigma binding sites in several cortical regions of schizophrenia. We confirmed G-241T and G-240T polymorphisms; these two consecutive polymorphisms were resolved to be in complete linkage disequilibrium with each other by single-strand conformation polymorphism (SSCP) analysis. We also identified the A61C (Gln2Pro) polymorphism, which was in almost complete linkage disequilibrium with G-241T/G-240T. There was no significant difference in the distribution of alleles or overall genotypes of the polymorphisms between schizophrenic patients (n = 129) and controls (n = 140). We found slight increased homozygosity for T-241/T-240 and C61 in patients compared with controls using multiple comparison (p = 0. 045). However, the significance did not remain when a Bonferroni correction was made (p = 0.135). These results do not support that the sigma(1) receptor gene plays a major role in the pathogenesis of schizophrenia. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:118-122, 2000.

Adult↗
PubMed2000

Synapsin III gene polymorphisms and schizophrenia.

Synapsins are synaptic vesicle-associated phosphoproteins and are thought to play crucial roles in synaptogenesis and neurotransmitter release. Synaptic abnormalities have been reported in the pathophysiology of schizophrenia. In addition, the synapsin III gene, a member of the synapsin gene family, has been located at 22q12-13, which has been suggested as a potential susceptibility locus for schizophrenia. We investigated a genetic association between schizophrenia and the synapsin III gene polymorphisms (-631C/G and -196G/A) in 160 schizophrenic patients and 153 controls. No significant positive association between either polymorphism and schizophrenia was observed. Furthermore, no significant association was observed between either polymorphism and the diagnostic subtypes. Our results suggested that the synapsin III gene polymorphisms do not confer increased susceptibility to schizophrenia.

Base Sequence↗
PubMed2000

Nd:YAG laser irradiation of the human dental pulp: implications as a predictor of pulp hemodynamics.

BACKGROUND AND OBJECTIVE: The aim of study this was to evaluate in vivo the pulpal blood flow rate, pulpal responsiveness, systemic blood pressure, and pulse rate during Nd:YAG laser irradiation of an isolated tooth. STUDY DESIGN/MATERIALS AND METHODS: Thirteen volunteers from the Tsurumi Dental University faculty participated in this study after giving their consent to the Nd:YAG laser irradiation test protocol. Gingivobuccal areas adjacent to mandibular canines were used for clinical evaluation. Each area was coated with India ink and treated with a Nd:YAG laser for 30 sec at 120-mJ pulses at 10 pulses/sec. Pulpal blood flow was measured by a laser Doppler flowmeter during Nd:YAG laser irradiation of the tooth. All pulp responses were measured by an electric pulp tester before and after Nd:YAG laser irradiation. In addition, the systemic blood pressure and pulse rate were monitored throughout the laser irradiation procedure. RESULTS: For all subjects involved in this study, the pulpal blood flow rate increased during laser irradiation. Threshold values of the electric pulp tests increased in six cases and decreased in six cases. One case showed no change. After 1 month, the threshold values for each subject had returned to previously recorded values. Neither systemic blood pressure nor pulse rate was affected during Nd:YAG laser irradiation. Pulpal blood flow was strongly influenced immediately after Nd:YAG laser irradiation, seen as an increase in the flow rate. CONCLUSION: The results of this study suggest that effects of the Nd:YAG laser irradiation are similar to those of low power laser for the improvement of local blood flow.

Adult↗
PubMed2000

Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes.

The pathogenesis of pericyte loss, an initial deficit in the early stage of diabetic retinopathy, remains unclear. Polyol pathway hyperactivity has been implicated in the pathogenesis of diabetic retinopathy, and recent studies have suggested that apoptosis may be involved in pericyte loss. The present study was conducted to investigate whether high glucose induces apoptosis in cultured bovine retinal pericytes. The effect of an aldose reductase inhibitor, SNK-860, was also examined. After a 5 day incubation with various concentrations of glucose (5.5-40 m M) in the presence or absence of SNK-860, the cell viability and the percentages of dead cells were measured, and staining with the TUNEL method and Hoechst 33342, and DNA electrophoresis were performed. High glucose reduced the viability and increased the percentages of dead cells. TUNEL-positive cells were observed in pericytes under high glucose, but not in those under 5.5 m M glucose. In the staining of nuclei with Hoechst 33342, the percentage of apoptotic cells in total cells counted under high glucose was higher than that under 5.5 m M glucose. DNA electrophoresis of pericytes cultured with high glucose demonstrated a 'ladder pattern'. Hyperosmolarity also induced apoptosis in pericytes, but less than that by high glucose. SNK-860 inhibited the glucose-induced apoptosis in pericytes. These observations suggest that the pericyte loss in diabetic retinopathy involves an apoptotic process, and that the polyol pathway hyperactivity plays an important role in inducing apoptosis in pericytes by high glucose.

Aldehyde Reductase↗
PubMed2000

Combined use of the adenosine A(2A) antagonist KW-6002 with L-DOPA or with selective D1 or D2 dopamine agonists increases antiparkinsonian activity but not dyskinesia in MPTP-treated monkeys.

The novel selective adenosine A(2A) receptor antagonist KW-6002 improves motor disability in MPTP-treated parkinsonian marmosets without provoking dyskinesia. In this study we have investigated whether KW-6002 in combination with l-DOPA or selective D1 or D2 dopamine receptor agonists enhances antiparkinsonian activity in MPTP-treated common marmosets. Combination of KW-6002 with the selective dopamine D2 receptor agonist quinpirole or the D1 receptor agonist SKF80723 produced an additive improvement in motor disability. Coadministration of KW-6002 with a low dose of L-DOPA also produced an additive improvement in motor disability, and increased locomotor activity. The ability of KW-6002 to enhance antiparkinsonian activity was more marked with L-DOPA and quinpirole than with the D1 agonist. However, despite producing an enhanced antiparkinsonian response KW-6002 did not exacerbate L-DOPA-induced dyskinesia in MPTP-treated common marmosets previously primed to exhibit dyskinesia by prior exposure to L-DOPA. Selective adenosine A(2A) receptor antagonists, such as KW-6002, may be one means of reducing the dosage of L-DOPA used in treating Parkinson's disease and are potentially a novel approach to treating the illness both as monotherapy and in combination with dopaminergic drugs.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2000

Loss of standard type of CD44 expression in invaded area as a good indicator of lymph-node metastasis in colorectal carcinoma.

PURPOSE: Recent advances have made possible the treatment of small invasive colorectal cancer by means of polypectomy or endoscopic mucosal resection. CD44 expression in cancer cells was identified as an indicator of lymph-node metastasis, which could be evaluated in specimens removed by colonoscopy. METHODS: The correlation between lymph-node metastasis and the expression of standard-type CD44 in cancer cells was examined immunohistologically using the invaded cancer cells of 61 tissue samples of superficially invasive colorectal cancer. We defined the above as invasive cancer restricted within the colorectal wall. Of the 61 samples, 31 had submucosal invasion and 30 had muscular invasion. RESULTS: Standard-type CD44 expression in the area of invasion in cases with lymph-node metastasis was remarkably down-regulated. In 43 cases with no lymph-node metastasis, 36 (83.7 percent) of patients had CD44 expression in invaded cells, whereas only two of 18 cases (11.1 percent) with lymph-node metastasis had expression of standard-type CD44 in the same area (P < 0.0001). A total of 69.6 percent (16/23) of patients with loss of standard-type CD44 expression in invaded sites were found to have positive metastasis in the lymph nodes. These results suggest that standard-type CD44 in invasive colon cancer cells could suppress metastasis to the regional lymph nodes. CONCLUSION: In cases of invasive colorectal cancer, the loss of standard-type CD44 expression in the invaded area is a sensitive marker for metastasis to the lymph nodes. Further investigation with larger patient groups is required to clarify the reliability of loss of standard-type CD44 expression as an indicator for additional surgery after endoscopic resection of submucosal invasive colorectal carcinoma.

Biomarkers, Tumor↗
PubMed2000

Inhibitory effects of clozapine and other antipsychotic drugs on noradrenaline transporter in cultured bovine adrenal medullary cells.

The effects of clozapine and other antipsychotic drugs on noradrenaline (NA) transport were examined in cultured bovine adrenal medullary cells and in transfected Xenopus laevis oocytes expressing the bovine NA transporter. Incubation of adrenal medullary cells with clozapine (30-1000 ng/ml) inhibited desipramine (DMI)-sensitive uptake of [3H]NA in a concentration-dependent manner (IC50=110 ng/ml or 336 nM). Other antipsychotic drugs such as haloperidol, chlorpromazine, and risperidone also decreased [3H]NA uptake (IC50= 144, 220, and 210 ng/ml or 383, 690, and 512 nM, respectively). Eadie-Hofstee analysis showed that clozapine reduced V(max) of uptake of [3H]NA and increased K(m). Furthermore, clozapine inhibited specific binding of [3H]DMI to plasma membranes isolated from bovine adrenal medulla (IC50=48 ng/ml or 146 nM). Scatchard plot analysis of [3H]DMI binding revealed that clozapine decreased both B(max) and K(d). Other antipsychotic drugs, including haloperidol, chlorpromazine, and risperidone, also reduced [3H]DMI binding to the membranes. In transfected Xenopus oocytes expressing the bovine NA transporter, clozapine inhibited [3H]NA uptake in a concentration-dependent manner similar to that observed in adrenal medullary cells. These results suggest that clozapine and haloperidol directly inhibit transport of NA by acting on the site of an NA transporter that influences both substrate transport and binding of tricyclic antidepressants.

Adrenal Medulla↗
PubMed2000

Significant changes in transrectal ultrasonic measurements of the prostate in relation to the degree of rectal wall distension.

The present study was conducted to reveal the possible changes in transrectal ultrasonic measurements of the prostate in relation to the degree of rectal wall distension. When analyzed together for 51 men, all measurements but area changed statistically significantly as the rectal wall was distended by a balloon covering a probe. Ultrasonic measurements concerning the prostatic shape changed more remarkably than those concerning its size. More importantly, changes in ultrasonic measurements were much more remarkable in patients with a healthy prostate than in those with an advanced BPH. These results suggest that possible changes in prostatic shape with the rectal wall distension has to be taken into account when evaluating transrectal prostatic ultrasonograms in terms of changes in shape, especially in patients with a healthy prostate. This is also the case when the diagnosis of BPH is made based on the change in shape, such as presumed circle area ratio, which is a parameter representing the roundness of the horizontal sonogram of the prostate.

Adult↗
PubMed2000

Systemic administration of adenosine A(2A) receptor antagonist reverses increased GABA release in the globus pallidus of unilateral 6-hydroxydopamine-lesioned rats: a microdialysis study.

The ability of adenosine A(2A) receptor antagonists to exhibit antiparkinsonian activity has recently been reported, but the mechanisms of action are still unknown. Since A(2A) receptors have been localized to GABAergic striatopallidal neurons, it is probable that these antagonists affect the activity of these neurons. In the present study, extracellular GABA basal levels were increased in the ipsilateral striatum and globus pallidus following a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. The A(2A) receptor-selective antagonist KW-6002 (3mg/kg, p.o.) caused a marked and sustained decrease of extracellular GABA levels in the globus pallidus of the 6-hydroxydopamine-lesioned rats, whereas no changes in GABA levels were observed in the globus pallidus of the non-lesioned rats. Microinjection of the A(2A) receptor agonist CGS21680 (0.005-0.5 microg) into the striatum of non-lesioned animals increased GABA concentrations in the globus pallidus, which was abolished by the voltage-dependent Na(+) channel blocker tetrodotoxin (1 micromol/l) delivered locally to the globus pallidus via the dialysis membrane. Furthermore, intrapallidal infusion of CGS21680 (10 micromol/l) also increased GABA levels in the globus pallidus. These data indicate that GABA release from striatopallidal neurons is regulated through A(2A) receptors in both the striatum and globus pallidus. The reversal of the 6-hydroxydopamine-induced increase in pallidal GABA levels by KW-6002 suggests that the antiparkinsonian effects of A(2A) receptor antagonists occur on the striatopallidal neurons.

Adenosine↗
PubMed2000

Manganese superoxide dismutase gene polymorphism and schizophrenia: relation to tardive dyskinesia.

There has been increasing evidence that deranged superoxide dismutase (SOD) activities might be a risk factor for schizophrenia and/or tardive dyskinesia (TD). In the present study, we investigated the genetic association between a functional polymorphism (Ala-9Val) in the human manganese (Mn) SOD gene and schizophrenia or TD (192 schizophrenics: 39 with TD and 153 without TD; 141 controls). No significant differences in the allelic or genotypic distribution between schizophrenics and controls were observed. However, we did find a significant difference in genotypic distribution between schizophrenics with and those without TD (p =. 03). Moreover, decreased -9Ala (mutant) allele was found among patients with TD (p =.02; odds ratio = 0.29; 95% confidence interval = 0.10-0.83). In conjunction with previous findings of increased free radicals and decreased SOD activities in TD subjects, these results suggest that the -9Ala (high activity) MnSOD allele may play a role in protecting against susceptibility to TD in schizophrenics.

Age Distribution↗