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Biomedical subjects

N Kaneda

Publications and source records attributed to N Kaneda.

At least 91 records · Page 5Linked to original sources
PubMed1989

Experimental studies on the pharmacokinetics and therapeutic effect of cefbuperazone in biliary infection.

A study was carried out using an experimental biliary infection model to investigate the pharmacokinetic characteristics and therapeutic effect of cefbuperazone in the rabbit. Thirty rabbits were divided into three equal groups; a control group of normal animals, a group of infected animals receiving no cefbuperazone, and a group of infected animals receiving 50 mg cefbuperazone/kg intramuscularly. The experimental infection was made by direct inoculation of a suspension of E. coli into the common bile duct after ligation. The results showed that extremely high levels of cefbuperazone were achieved in bile and tissues of the biliary tract and were higher than those in the blood. Moreover, the levels were maintained at effective concentrations even after 6 hours. Viable bacterial cells from bile and the gall-bladder were barely detectable 24 and 48 hours after infection in the cefbuperazone-treated group, whilst counts remained high in the other infected group. White blood cell counts were increased at 24 hours after infection but were significantly lower in the cefbuperazone-treated group. Histological examination revealed marked inflammatory changes in the gall-bladder and bile duct of infected, untreated animals but few, mild changes only were seen in cefbuperazone-treated animals. Similarly, total bilirubin and liver enzymes were markedly increased in infected animals, but transaminases and alkaline phosphatase were significantly lower in the treated compared to the untreated group. The findings indicate, therefore, that cefbuperazone can be a useful antibiotic in biliary infection.

Animals↗
PubMed1988

Expression of four types of human tyrosine hydroxylase in COS cells.

Alternative splicing from a single gene produces four kinds of human tyrosine hydroxylase (types 1-4), which have structural diversity only in the N-terminal region. We attempted expression of the type 1-4 enzymes in COS cells and performed kinetic analyses. All had enzymatic activities. The Km values of the four types for L-tyrosine and 6-methyl-5,6,7,8-tetrahydropteridine were similar, although their relative homospecific activities were clearly different. The type 1 enzyme displayed the highest activity.

Blotting, Western↗
PubMed1988

Molecular cloning of cDNA and chromosomal assignment of the gene for human phenylethanolamine N-methyltransferase, the enzyme for epinephrine biosynthesis.

Phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28) catalyzes the synthesis of epinephrine from norepinephrine, the last step of catecholamine biosynthesis. To isolate a cDNA clone for human PNMT, we first isolated a cDNA clone for bovine adrenal medulla PNMT using mixed oligodeoxyribonucleotide probes whose synthesis was based on the partial amino acid sequence of tryptic peptides from the bovine enzyme. By screening a bovine adrenal medulla cDNA library, a cDNA clone with an insert of about 200 base pairs (bp) was isolated. This clone consisted of 84 bp of carboxyl-terminal coding region, which contained amino acid sequences corresponding to two tryptic peptides, and about 100 bp of 3'-untranslated region. Using this cDNA fragment as the probe, we screened a human pheochromocytoma cDNA library and isolated a cDNA clone with an insert of about 1.0 kilobase pairs, which contained the complete coding region of the enzyme. Northern blot analysis of human pheochromocytoma poly(A)+ RNA using this cDNA insert as the probe showed a single RNA species of about 1,000 nucleotides, suggesting that this clone is a full-length cDNA. Determination of the nucleotide sequence revealed that human PNMT consists of 282-amino acid residues with a predicted molecular weight of 30,853, including initial methionine. The amino acid sequence of the human PNMT was highly homologous (88%) to that of the bovine enzyme. Chromosomal assignment of the gene for human PNMT was carried out using mouse-human somatic cell hybrids. The PNMT gene was assigned to chromosome 17.

Amino Acid Sequence↗
PubMed1988

Inactivation of tyrosine hydroxylase in rat striatum by 1-methyl-4-phenylpyridinium ion (MPP+).

We report that 1-methyl-4-phenylpyridinium ion (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), inactivated tyrosine hydroxylase (TH) when MPP+ was directly infused into the striatum. We examined both in vitro TH activity and TH content measured by an enzyme immunoassay in the rat striatum after MPP+ was administered by an in vivo brain microdialysis probe. MPP+ caused the inhibition of TH activity but did not influence TH content in the ipsilateral striatum. These results indicate that MPP+ may cause an acute inactivation of TH after continuous exposure at the high concentrations.

1-Methyl-4-phenylpyridinium↗
PubMed1988

Nanosecond pulse fluorometry of conformational change in phenylalanine hydroxylase associated with activation.

Conformational change in rat liver phenylalanine hydroxylase associated with activation by phenylalanine or N-(1-anilinonaphth-4-yl)maleimide was investigated by measuring fluorescence spectra and fluorescence lifetimes of tryptophanyl residues as well as the probe fluorophore conjugated with SH groups of the hydroxylase. The fluorescence spectrum of tryptophan exhibited its maximum at 342 nm. It shifted by 8 nm toward longer wavelength accompanied by an increase in its intensity, by preincubation with 1 mM phenylalanine. The fluorescence intensity of tryptophan increased by 36% upon the activation. On the other hand, the binding of (6R)-L-erythro-tetrahydrobiopterin, a natural cofactor of the enzyme, induced a decrease in the fluorescence intensity by 79% without a shift of the maximum wavelength. The fluorescence lifetime of tryptophan of phenylalanine hydroxylase exhibited two components with lifetimes of 1.7 and 4.1 ns. The values of the lifetimes changed to 1.4 and 5.6 ns, respectively, upon the activation. It is considered that the change in the longer lifetime is correlated with the shift of the emission peak upon the activation. The values of both the lifetimes decreased to 0.64 and 3.6 ns upon the binding of (6R)-L-erythro-tetrahydrobiopterin, which is coincident with the decrease in the fluorescence intensity. Conjugation of N-(1-anilinonaphth-4-yl)maleimide with SH of phenylalanine hydroxylase brought about a decrease in both the fluorescence intensity and the value of the shorter lifetime of the tryptophanyl residues, while the longer lifetime remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Structure of the human tyrosine hydroxylase gene: alternative splicing from a single gene accounts for generation of four mRNA types.

Tyrosine hydroxylase (TH) is a rate-limiting enzyme for catecholamine biosynthesis. Recently, Grima et al. (Nature (1987) 326, 707-711) and we (Biochem. Biophys. Res. Commun. (1987) 146, 971-975; Nucleic Acids Res. (1987) 15, 6733) reported four similar but distinct mRNAs that encode human TH. These mRNAs are constant for the major part, but are distinguishable from one another as to the insertion/deletion of 12-bp and 81-bp sequences near the N-terminus. We isolated genomic clones encoding the human TH gene and determined the nucleotide sequence. The human TH gene is split into 14 exons. The 12-bp insertion sequence is encoded by the 3'-terminal portion of the first exon. The 81-bp insertion sequence corresponds to the second exon. Taking into consideration also the results of Southern blot analysis of human genomic DNA, we concluded that the four types of human TH mRNA are produced through alternative splicing from a single gene. Two kinds of alternative splicing are involved: the alternative use of two donor sites in the first exon, and the inclusion/exclusion of the second exon. We propose a possible secondary structure for the latter alternative splicing pathway.

Animals↗
PubMed1988

Striatal dopamine release and metabolism in sinoaortic-denervated rats by in vivo microdialysis.

The purpose of this study was to provide new evidence favoring the hypothesis that cardiovascular information from arterial baroreceptors is integrated with the nigrostriatal system that contributes to regulation of motor activity. Samples of extracellular striatal dopamine (DA) and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were collected by the technique of in vivo microdialysis and analyzed by high-performance liquid chromatography-electron capture detection. Rats were prepared with a guide tube placed in the caudate-putamen for subsequent insertion of microdialysis probes. During the 1st wk after sinoaortic denervation (SAD) or sham operation (SO), a microdialysis probe was inserted and perfused with Ringer solution at the rate of 2 microliter/min in the freely moving rats. Samples were collected every 20 min before and after injection of pargyline, 100 mg/kg ip. The results showed that SAD rats have approximately 50% less extracellular striatal DA, DOPAC, and HVA than SO rats (P less than 0.01). After blockade of monoamine oxidase activity with pargyline, striatal DA accumulated three times faster in SO than SAD rats suggesting DA synthesis is reduced in SAD rats. These data provide further evidence that the arterial baroreceptor system affects dopaminergic metabolism in the nigrostriatal system possibly as a means for integration of cardiovascular and motor activity.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Plasma biopterin levels of patients with affective disorders.

The plasma biopterin levels of 13 patients with affective disorders were measured both in the symptomatic phase and in the remission phase, and under no influence of psychotropic drugs except lithium and/or carbamazepine by high-performance liquid chromatography with fluorescence detection, and were compared with those of normal controls. The biopterin levels of patients in the symptomatic phase were elevated significantly as compared with those of normal controls, and the elevation tended to be more pronounced in the hypomanic phase than in the depressive phase. In contrast, the biopterin levels of patients in remission were not different from those of normal controls.

Adult↗
PubMed1987

Isolation of a novel cDNA clone for human tyrosine hydroxylase: alternative RNA splicing produces four kinds of mRNA from a single gene.

Human tyrosine hydroxylase (TH) cDNA was isolated by molecular cloning. Lambda gt 11 cDNA library constructed from human pheochromocytoma was screened with a synthetic 23-mer oligonucleotide complementary to rat TH mRNA. We found a novel type of cDNA clone whose N-terminal sequence is similar to but clearly distinct from each of the three types (type 1, 2 and 3) of TH cDNA reported by Grima et al. [Nature (1987) 326, 707-711]. It contains both the 12-bp insert characteristic of type 2 cDNA and the 81-bp sequence of type 3. This novel cDNA clone was designated as type 4. Southern blot analysis of human genomic DNA indicated that TH is encoded by a single gene. This suggests that the four different forms of TH mRNA are produced by alternative RNA splicing from a single primary transcript.

Adrenal Gland Neoplasms↗
PubMed1987

Presence of tetrahydroisoquinoline and 2-methyl-tetrahydroquinoline in parkinsonian and normal human brains.

1,2,3,4-Tetrahydroisoquinoline (TIQ) and 2-methyl-1,2,3,4-tetrahydroquinoline (2-Me-TQ) were identified for the first time by gas chromatography-mass spectrometry in the parkinsonian and normal human brains. TIQ, an analogue of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was markedly increased in the parkinsonian brain and could be an endogenous neurotoxin to induce Parkinson's disease.

Autopsy↗
PubMed1987

Acute effects of 1-methyl-4-phenylpyridinium ion (MPP+) on dopamine and serotonin metabolism in rat striatum as assayed in vivo by a micro-dialysis technique.

The acute effect of 1-methyl-4-phenylpyridinium ion (MPP+), a neurotoxin derived from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was examined by the in vivo micro-dialysis technique. A dialysis cannula was implanted into rat striatum, and the changes in the concentrations of dopamine (DA), 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in the perfusate every 20 min after administration of MPP+ were determined by high-performance liquid chromatography with electrochemical detection (HPLC-ED). After MPP+ administration the levels of DOPAC, HVA and 5-HIAA were markedly decreased. On the contrary the level of DA was markedly increased and reached a maximum 40 min after beginning of the MPP+ administration. By postmortem analysis of the striatal tissue MPP+ was proved to cause the inhibition of monoamine oxidase (MAO), especially MAO-B. These results suggest that the acute biochemical changes induced by MPP+ in vivo were MAO inhibition and release of DA.

1-Methyl-4-phenylpyridinium↗
PubMed1987

Total biopterin levels of plasma in patients with depression.

The total biopterin levels of plasma in 12 patients with depression were measured. They were elevated significantly as compared with those in normal controls. The plasma biopterin levels in 6 of 12 patients were measured both in the depressive and in the remissive phases. In the depressive phase the total biopterin levels were increased, whereas in the remission phase they did not differ from those in normal controls. Antidepressants did not affect the plasma biopterin levels. We speculate that the elevation of the plasma biopterin levels in patients with depression was related to the depressive state itself.

Adult↗
PubMed1987

Action of 7-ethylcamptothecin on tumor cells and its disposition in mice.

Some biological effects of camptothecin (CPT) and its new derivative 7-ethylcamptothecin (ECPT) were studied. The drugs were effective against murine leukemia; ECPT was more effective than CPT. Ip administration of ECPT or CPT gave maximum treated/control values of 325% and 232%, respectively. The drugs also inhibited the growth of KB cells in vitro, 50% effective doses of 3.5 ng/ml of ECPT and 8.6 ng/ml of CPT, indicating the stronger activity of ECPT. Pharmacokinetic studies of the drugs in mice showed that ECPT had a longer biological half-life in the terminal phase and a larger amount remained in the plasma compared with CPT. After iv administration of ECPT, the drug accumulated in the intestine, suggesting that the main route of excretion of the drug is through the biliary tract. The study on cell cycle progression by flow cytometry suggested that the main effect of both drugs on L1210 cells was the blocking of G2-M phase. These results suggest that the main reasons for the superior antitumor activity of ECPT compared with CPT are as follows: (a) ECPT had a stronger growth-inhibiting activity against tumor cells, and (b) ECPT remained in the intestinal tract for a longer time and in higher amounts when administered in vivo.

Animals↗
PubMed1986

The presence of catechol-o-methyltransferase activity in separately cultured cerebromicrovascular endothelial and smooth muscle cells.

The activity of catechol-o-methyltransferase (COMT) was investigated in cultured and propagated cerebromicrovascular endothelial and smooth muscle cells using high performance liquid chromatography and immunocytochemistry. The existence of COMT was detected in both cell types. The demonstration of this enzyme activity in the cerebromicrovascular smooth muscle cells, in addition to the endothelium, indicates that the enzymatic barrier to catecholamine is not limited to capillaries, the main constituents of the blood-brain barrier.

Animals↗