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Biomedical subjects

J Nakamura

Publications and source records attributed to J Nakamura.

At least 181 records · Page 10Linked to original sources
PubMed1998

Apolipoprotein E regulatory region genotype in schizophrenia.

Clinical observations indicate that a proportion of patients with schizophrenia experience cognitive impairment, which suggests that a neurodegenerative basis might be involved in the etiology of schizophrenia. Apolipoprotein E (ApoE), which has been confirmed to be genetically associated with Alzheimer's disease, is thus highlighted as a candidate gene for schizophrenia. Recently, novel functional polymorphisms in the ApoE transcriptional regulatory region have been found. To investigate whether these polymorphisms are associated with the risk of schizophrenia, we genotyped 144 patients with schizophrenia and 134 controls for two polymorphisms (-491A/T and -219G/T). No significant positive associations between both polymorphisms and schizophrenia were observed. Our findings exclude the regulatory region of the ApoE gene as a locus that might confer increased susceptibility to schizophrenia.

Apolipoproteins E↗
PubMed1998

Effects of propionyl-L-carnitine on cardiac dysfunction in streptozotocin-diabetic rats.

The effects of orally administered propionyl-L-carnitine on cardiac dysfunction in rats with streptozotocin-induced diabetes were investigated. Wistar male rats were divided into four groups: untreated normal, propionyl-L-carnitine (daily for 4 weeks with 3 g/kg orally) -treated normal, untreated diabetic, propionyl-L-carnitine-treated diabetic. Four weeks after streptozotocin administration, plasma lipid levels were increased and myocardial carnitine content was decreased in untreated diabetic rats. These changes were significantly reversed by the propionyl-L-carnitine treatment. Assessment of cardiac function with isolated perfused working hearts revealed a depression of left ventricular developed pressure as well as both maximum positive and negative dP/dt in untreated diabetic as compared with that in normal hearts. Cardiac function at the higher left atrial filling pressures in the propionyl-L-carnitine-treated diabetic rats was improved significantly compared to that in untreated hearts. The data thus suggest that oral administration of propionyl-L-carnitine can reduce abnormalities of cardiac function, correlated with a significant increase in myocardial carnitine content and improved lipid metabolism in terms of lowered plasma lipids.

Administration, Oral↗
PubMed1998

Distribution of glycoproteins with beta-N-acetylgalactosaminylated N-linked sugar chains among bovine tissues.

Only a small number of glycoproteins has been reported to contain N-linked sugar chains with GalNAcbeta1-->4GlcNAc structure. Our previous studies showed that most glycoproteins from bovine milk fat globule membranes contain beta-N-acetylgalactosaminylated N-linked sugar chains [Sato et al., J. Biochem. 114 (1993) 890-900]. In order to study how widely this glycosylation occurs, lectin blot analysis of membrane glycoproteins from 12 bovine tissues was performed using Wistaria floribunda agglutinin (WFA), which interacts with oligosaccharides terminating with N-acetylgalactosamine. The WFA-positive bands were detected in samples from most tissues except for intestine although the number and reactivity of bands to lectin varied among the tissues. Upon pretreatment of blotted filters with Bacillus beta-N-acetylgalactosaminidase or N-glycanase, no lectin binding was observed. WFA-agarose column chromatography of oligosaccharides released by hydrazinolysis from membrane glycoproteins of bovine tissues except for intestine revealed that a few to 18% of the released oligosaccharides bind and are eluted from the column with 100 mM N-acetylgalactosamine. These results indicate that many glycoproteins from a variety of bovine tissues contain N-linked sugar chains with GalNAcbeta1-->4GlcNAc structure, suggesting a wider occurrence of this glycosylation in bovine tissues.

Acetylgalactosamine↗
PubMed1998

Highly sensitive apurinic/apyrimidinic site assay can detect spontaneous and chemically induced depurination under physiological conditions.

One of the most prevalent lesions in DNA is the apurinic/apyrimidinic (AP) site, which is derived from the cleavage of the N-glycosyl bond by DNA glycosylase or by spontaneous depurination. AP sites are repaired by AP endonucleases during the process of base excision repair; however, an imbalance in this DNA repair system may cause mutations as well as cell death. We have established a sensitive and convenient slot-blot method to detect AP sites in genomic DNA using a novel aldehyde reactive probe (ARP), which reacts with the aldehydic group of ring-opened AP sites. The reaction of 1 mM of ARP with 15 microg of genomic DNA containing AP sites at 37 degrees C was completed within 1 min. The AP site-ARP complex was remarkably stable during incubation in TE buffer, even at 100 degrees C for 60 min. The sensitivity of this assay enables detection of 2.4 AP sites per 10(7) bases. By using this ARP-slot-blot assay, the rate of spontaneous depurination of calf thymus DNA was determined. Under physiological conditions, AP sites were increased at 1.54 AP sites/10(6) nucleotides/day (9000 AP sites/cell/day). This highly sensitive assay allows us to determine the endogenous level of AP sites in genomic DNA, as well as to investigate whether DNA-damaging agents cause imbalances of base excision/AP endonuclease repair in vivo and in vitro.

B-Lymphocytes↗
PubMed1998

Adenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys.

Treatment of Parkinson's disease with L-dopa therapy leads to long-term complications, including loss of drug efficacy and the onset of dyskinesia. Adenosine A2A receptors in striatum are selectively localized to GABAergic output neurons of the striato-pallidal pathway and may avoid such problems. The novel adenosine A2A receptor antagonist KW-6002 has been examined for antiparkinsonian activity in MPTP-treated primates. Oral administration of KW-6002 reversed motor disability in MPTP-treated common marmosets in a dose-dependent manner. However, KW-6002 only modestly increased overall locomotor activity and did not cause abnormal movement, such as stereotypy. The ability of KW-6002 to reverse motor disability was maintained on repeated daily administration for 21 days, and no tolerance was observed. KW-6002 induced little or no dyskinesia in MPTP-treated primates previously primed to exhibit dyskinesia by prior exposure to L-dopa. These results suggest that selective adenosine A2A receptor antagonists represent a new class of antiparkinsonian agents that improve disability without producing hyperactivity and without inducing dyskinesia.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1998

Application of capillary electrophoresis for the determination of inorganic ions in trace explosives and explosive residues.

Capillary electrophoresis was developed for the analysis of low explosive residue, because a significant amount of inorganic anions and cations remain after deflagration. Certain high explosives, such as emulsion explosives, produce a vast quantity of inorganic ions after a blast and can readily be analyzed using capillary electrophoresis. Often, trace amounts of explosive residues may be present on physical evidence submitted in criminal cases. Trace amounts of inorganic ions such as nitrate, chlorate, and ammonium may be detected using capillary electrophoresis owing to the low detection limit of these species. The utility of capillary electrophoresis in the analysis of explosive residues is in its ability to simultaneously analyze trace explosives and ionic products present on physical evidence.

Anions↗
PubMed1998

Inhibition of azoxymethane initiated colon tumor and aberrant crypt foci development by bovine lactoferrin administration in F344 rats.

The influence of bovine lactoferrin (bLf) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). In experiment I, 2% and 0.2% bLf, and Bifidobacterium longum (B. longum) as a positive control at 3% were given in the diet for 4 weeks, along with two s.c. 15 mg/kg injections of AOM on days 1 and 8. The numbers of aberrant crypt foci (ACF) were decreased by both treatments. Similar results were obtained in experiment II of 13 weeks duration. In experiment III, animals were given three weekly injections of AOM and then received 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bovine lactoferricin (bLfcin) for 36 weeks. No effects indicative of toxicity were noted, but significant reduction in both the incidence and number of adenocarcinomas of the large intestine was observed with almost all the treatments. Thus, the incidences of colon adenocarcinomas in the groups receiving 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bLfcin were 15%, 25%, 26.3% and only 10%, respectively, in contrast to the 57.5% control value (p < 0.01). ACF values also exhibited reduced development. Investigation of beta-glucuronidase revealed decrease in the cecal contents of animals receiving bLf. In addition, demonstration of enhancement of NK activity by bLf indicated that its inhibitory effects could have been related to elevated immune cytotoxicity.

Animals↗
PubMed1998

The incidence and characteristics of silent cerebral infarction in elderly diabetic patients: association with serum-soluble adhesion molecules.

The purpose of this study was to investigate the relationship between complications arising from silent cerebral infarction (SCI) and changes in the levels of serum-soluble adhesion molecules in 82 elderly diabetic patients aged 60 years and older. SCI was found in 43 % of the 82 patients, with incidence increasing in relation to age. The prevalence of SCI was higher in subjects with hypertension, poor metabolic control and increased fibrinolysis. The levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (sE-selectin) were higher in diabetic patients than in non-diabetic subjects (p < 0.05, p < 0.001, and p < 0.05, respectively). Also, sICAM-1 and sVCAM-1 were found at increased levels in diabetic patients with SCI compared to those without SCI (p < 0.01 and p < 0.05, respectively). In particular, the level of sICAM-1 was increased in patients with SCI due to perforating arterial occlusion, while the level of sVCAM-1 was increased in patients with SCI due to cortical arterial occlusion. However, no significant difference was found in sE-selectin levels. Overall average of the intima and media thickness (IMT) of the common carotid arteries increased with age. IMT proved to be greater in patients with SCI than in patients without SCI (p < 0.05), and showed a weak but significant positive correlation with sVCAM-1, while no correlation was found with either sICAM-1 or sE-selectin levels. In conclusion, measurement of serum adhesion molecules may be useful for diagnosing the early stages of brain damage and for prophylactic treatment which may prevent the onset or progression of SCI.

Aged↗
PubMed1998

Bilateral tactile agnosia: a case report.

This study reports a 64-year-old right-handed male who manifested bilateral tactile recognition deficits. They were diagnosed as bilateral tactile agnosia, since the patient showed difficulty in semantic association of objects despite preserved hylognosis and morphognosis. The patient had a bilateral lesion in the subcortical region of the angular gyrus. The case reported by Endo et al. (1992) had a right hand tactile agnosia due to a subcortical lesion in the left angular gyrus. Our findings support Endo's hypothesis that tactile agnosia occurs when the somatosensory association cortex is disconnected from the semantic memory store located in the inferior temporal lobe by a subcortical lesion of the angular gyrus. We suggest that the extent of the lesion in the tactual-semantic pathway is related to the severity of tactile agnosia and the types of the tactile naming errors.

Agnosia↗
PubMed1998

cDNA cloning and predicted primary structure of scallop sarcoplasmic reticulum Ca(2+)-ATPase.

Sarcoplasmic reticulum (SR) Ca(2+)-ATPase of the scallop cross-striated adductor muscle was purified with deoxycholate and digested with lysyl endopeptidase for sequencing of the digested fragments. Overlapping cDNA clones of the ATPase were isolated by screening the cDNA library with an RT-PCR product as a hybridization probe, which encodes the partial amino acid sequence of the ATPase. The predicted amino acid sequence of the ATPase contained all the partial sequences determined with the proteolytic fragments and consisted of the 993 residues with approximately 70% overall sequence similarity to those of the SR ATPases from rabbit fast-twitch and slow-twitch muscles. An outline of the structure of the scallop ATPase molecule is predicted to mainly consist of ten transmembrane and five 'stalk' domains with two large cytoplasmic regions as observed with the rabbit ATPase molecules. The sequence relationship between scallop and other sarco/endoplasmic reticulum-type Ca(2+)-ATPases is discussed.

Amino Acid Sequence↗
PubMed1998

Pharmacokinetic models to evaluate radiolabeling reagents for protein radiopharmaceuticals.

Pharmacokinetic models were constructed to further estimate the hepatic radioactivity levels derived from bifunctional chelating agents used for radiolabeling of proteins. Both galactosyl-neoglycoalbumin (NGA) and mannosyl-neoglycoalbumin (NMA) were labeled with (111)In using two benzyl-EDTA derivatives. Time-activity profiles for the liver with gallbladder, intestine, and blood after administration of (111)In-labeled NGAs in mice were simultaneously fitted to a multi-compartment model, and the first-order rate constants representing the disappearance from parenchymal cells were obtained. Similarly, a model composed of the blood and liver compartment was constructed, and the disappearance rate constants from nonparenchymal cells were calculated from the biodistribution studies following administrations of (111)In-labeled NMAs. Fitting curves showed good agreements with the experimental data. Each rate constant clearly distinguished the elimination rate of the respective radiometabolite from the liver cells. Thus, quantitative estimations of radiolabeling reagents were performed only by animal biodistribution studies, and the present pharmacokinetic analyses would be useful for screening of newly designed reagents for protein radiopharmaceuticals.

Albumins↗
PubMed1998

Molecular dosimetry of DNA adducts in the medaka small fish model.

Small fish models are being used with increasing frequency for carcinogenicity testing and comparative cancer research in the US, Canada and Europe. However, there is a need to further define the early biochemical events of carcinogenesis in these species. Identification and quantitation of DNA adducts can integrate all of the various factors involved in chemical exposure, uptake, distribution and biotransformation of a putative carcinogen. In the present study, Japanese medaka (Oryzias latipes) were exposed to the alkylating agent, diethylnitrosamine (DEN), in the ambient water. Liver DNA was analyzed for O6-ethylguanine (O6EG), O4-ethylthymidine (O4ET) and O2-ethylthymidine (O2ET) by the immuno-slot-blot technique, using monoclonal antibodies against each adduct of interest. While fish exposed to 10 p.p.m. DEN had liver DNA adduct concentrations at or only slightly higher than background levels, those exposed to 100 p.p.m. DEN averaged 34 and 53 pmol O6EG/micromol guanine, 15 and 41 pmol O2ET/micromol thymidine and 2 and 6 pmol O4ET/micromol thymidine at 0 and 24 h post-exposure, respectively. The results of this study show that, under these short-term exposure conditions, ethyl-DNA adducts appear to accumulate in medaka liver tissue in a sublinear (i.e. non-linear) fashion after aqueous exposure to DEN. Thus, critical DNA repair enzymes such as O6-alkylguanine DNA alkyltransferase, which are relatively efficient at lower carcinogen levels, are probably saturated at the 100 p.p.m. concentration level of DEN.

Animals↗
PubMed1998

Saliva level of free 3-methoxy-4-hydroxyphenylglycol in psychiatric outpatients with anxiety.

As a measurement of the level of anxiety in psychiatric outpatients with anxiety, we determined the saliva level of free 3-methoxy-4-hydroxyphenyleglycol (MHPG) using gas chromatography- mass spectrometry and scored the levels of anxiety with the Hamilton Anxiety Scale (HAS) in patients, before and after drug treatment with alprazolam for 1 week. The saliva level of free-MHPG at first visit to hospital was significantly higher than that of control individuals and disease control individuals and was reduced by alprazolam treatment for 1 week. There was no correlation between MHPG level and the HAS score at the first hospital visit. The MHPG levels after treatment correlated with the HAS scores. The reduction of the anxiety level as scored by the HAS correlated with the reduction of MHPG level. These results indicate that the free saliva MHPG level may be a useful indicator for assessing not only the level of anxiety, but also the response to drug treatment for anxiety in these patients.

Adult↗
PubMed1998

Circadian rhythms of hormone concentrations in alcohol withdrawal.

We investigated the circadian rhythm of hormones (cortisol, melatonin) in alcoholic patients during and 1 month after alcohol withdrawal. Patients with delirium tremens had irregular serum hormone concentration rhythms during withdrawal, which normalized after the withdrawal period. Patients without delirium tremens had normal circadian rhythms even during the withdrawal period. We speculated that the disturbance of the biological oscillator, in terms of the decline of synchronizing function or the decrease in synchronizing factors, caused abnormal circadian rhythms of hormone release during delirium tremens.

Adult↗