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Biomedical subjects

K Fukuhara

Publications and source records attributed to K Fukuhara.

10 recordsLinked to original sources
PubMed1992

Noradrenergic activation in the paraventricular nucleus during acute and chronic immobilization stress in rats: an in vivo microdialysis study.

In vivo microdialysis was used to study the effects of single (2 h) or repeated (2 h for 7 consecutive days) immobilization (IMMO) stress on extracellular fluid concentrations of norepinephrine (NE) and the deaminated metabolites of NE and dopamine, dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) in the paraventricular nucleus of conscious rats. During IMMO, NE, DHPG, and DOPAC levels increased markedly, with similar peak values and time courses in the repeatedly stressed and previously unstressed groups. NE levels during a 2-h baseline period were lower in the repeatedly stressed group than in the unstressed group (99 +/- 9 pg/ml vs. 167 +/- 13 pg/ml, P less than 0.05), whereas DHPG (1,697 +/- 263 pg/ml vs. 1,424 +/- 194 pg/ml) and DOPAC (5,989 +/- 863 pg/ml vs. 4,428 +/- 1150 pg/ml) levels tended to be higher, so that the NE/DHPG ratio at baseline was significantly lower in the repeatedly stressed group (P less than 0.05). The results indicate that IMMO stress enhances NE release, reuptake, metabolism, and synthesis in the PVN. Repeated exposure to IMMO may decrease the microdialysate NE/DHPG ratio by inhibiting exocytotic release or enhancing neuronal reuptake of NE. In either case, the results suggest that repeated exposure to stress alters the release and disposition of NE in the PVN of conscious animals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Reduction properties of nitrated naphthalenes: relationship between electrochemical reduction potential and the enzymatic reduction by microsomes or cytosol from rat liver.

The nitroreductase activities of rat liver microsomes and cytosol towards various nitrated naphthalenes (1-, 2-mononitro-, 1,3-, 1,5-, 1,7-, 1,8-dinitro-1,3,5- and 1,3,8-trinitronaphthalenes) were characterized as follows. (1) The rates of reduction of nitrated naphthalenes in either microsomal or cytosolic incubation were found to increase in the order of trinitro- > dinitro- > mono-nitronaphthalene, although, in the case of microsomal nitroreduction, trinitronaphthalenes were reduced more rapidly than in cytosol. (2) The effective cofactors, electron donors, in the nitroreduction of nitrated naphthalenes in cytosol were NADH and hypoxanthine, but not NADPH. (3) The nitrated naphthalenes with a nitro group at a beta-position appear to be more easily reduced among the various isomers. The cytosolic nitroreductase activities towards the nitrated naphthalenes were closely related to the single-electron reduction potentials measured by cyclic voltammetry and hence, there was a good relationship between the logarithm of nitroreductase activities and the electrochemical reduction potentials. In microsomes, nitroreductase activities were rather less well related to electrochemical reduction potentials.

Animals↗
PubMed1992

Mutagenicity of nitro-azabenzo[a]pyrene and its related compounds.

The mutagenicity of nitrated benzo[a]pyrene (BP) and the related compounds, 1- and 3-nitrobenzo[a]pyrene (NBP), 1- and 3-nitro-6-cyanobenzo[a]pyrene (N-6-CBP), 1- and 3-nitro-6-azabenzo[a]-pyrene (N-6-ABP), 1- and 3-nitro-6-azabenzo[a]-pyrene-N-oxide (N-6-ABPO) and 1,6- and 3,6-dinitrobenzo[a]-pyrene (DNBP), was investigated. The mutagenic activities of 3-N-6-CBP and 3-N-6-ABP were 117 and 76 times, respectively, that of 3-NBP. In addition, 3,6-DNBP was more mutagenic than 1,6-DNBP. It is suggested that the mutagenic activation differs with the position of NO2 substitution in the chemical structure. A nitro derivative with NO2 substitution at the 3 position of the aromatic ring of BP was more mutagenic than that with the substitution at the 1 or 6 position. The reducibility of DNBPs was then determined by detecting 1- or 3-amino-6-nitrobenzo[a]pyrene (A-6-NBP), a metabolite of DNBP; 3,6- and 1,6-DNBP were reduced to 3- and 1-A-6-NBP at frequencies of 958 +/- 26 and 79 +/- 8, respectively, pmole per mg of protein, when the compound was incubated anaerobically with rat liver S9 mix at 37 degrees C for 15 min. NO2 substituted at the 3 position of the aromatic ring of BP was readily reduced by a microsome enzyme to form an amino derivative. The result suggests that these compounds have a structure-activity relationship between mutagenicity and NO2 substitution of BP.

Animals↗
PubMed1992

Immunohistological analysis of P53 expression in human skin tumors.

The p53 expression in various skin tumors was immunohistologically evaluated using two mouse monoclonal anti-p53 antibodies, PAb421 and PAb1801. The p53 expression was not detected in the normal epidermal cells. Nuclear staining suggested that the p53 expression was observed in 10 of 26 squamous cell carcinomas (SCCs) from 24 patients, in one undifferentiated carcinoma, one proliferating trichilemmal cyst, one malignant proliferating trichilemmal tumor and in one metastatic carcinoma of breast cancer. None off four cases of Bowen's disease (SCC in situ) showed nuclear staining. In the SCCs, five of 20 primary lesions, three of four recurrent lesions and both of two metastatic lesions had positive nuclei. There was one case of SCC in which a primary lesion was negative but a recurrent lesion was positive. Thus, p53 expression was more frequently observed in SCCs at more clinically advanced stages. This may suggest that p53 has some relevance to progression of SCC. Nuclear staining was not detected in any of the following cases: two cases of seborrheic keratosis, one eccrine poroma, one keratoacanthoma, 11 basal cell epitheliomas, two mammary Paget's disease, three genital Paget's disease, one sebaceous carcinoma, four malignant melanomas, six lymphomas, two leukemia cutis and two angiosarcomas.

Antibodies, Monoclonal↗
PubMed1992

Regulation of tyrosine hydroxylase and dopamine beta-hydroxylase mRNA levels in rat adrenals by a single and repeated immobilization stress.

Adrenal catecholamines are known to mediate many of the physiological consequences of the "fight or flight" response to stress. However, the mechanisms by which the long-term responses to repeated stress are mediated are less well understood and possibly involve alterations in gene expression. In this study the effects of a single and repeated immobilization stress on mRNA levels of the adrenal catecholamine biosynthetic enzymes, tyrosine hydroxylase and dopamine beta-hydroxylase, were examined. A repeated 2-hr daily immobilization for 7 consecutive days markedly elevated both tyrosine hydroxylase and dopamine beta-hydroxylase mRNA levels (about six- and fourfold, respectively). In contrast, tyrosine hydroxylase but not dopamine beta-hydroxylase mRNA levels were elevated immediately following a single immobilization. The elevation in tyrosine hydroxylase mRNA with a single immobilization was as high as with seven daily repeated immobilizations. This elevation was not sustained and returned toward control values 24 hr later. Both tyrosine hydroxylase and dopamine beta-hydroxylase mRNA levels were elevated immediately following two daily immobilizations to levels similar to those observed after seven immobilizations and were maintained 24 hr later. The results indicate that both tyrosine hydroxylase and dopamine beta-hydroxylase mRNA levels are elevated by stress; however, the mechanism and/or timing of their regulation are not identical.

Adrenal Glands↗
PubMed1992

The metabolism of 1,6-dinitropyrene in rat hepatocytes.

This paper reports investigations using hepatocytes to study the metabolism and DNA binding of the environmental contaminant, 1,6-dinitropyrene. Since 1,6-dinitropyrene is not believed to be mutagenic per se, metabolites were synthesized and the metabolism of 1,6-dinitropyrene was subsequently studied in rat hepatocytes. The mode of activation of dinitropyrenes is reduction of one of the nitro groups. Nitroreduction has been shown previously to be oxygen sensitive and therefore the effect of oxygen on the metabolic pattern and DNA binding was investigated by comparing results from aerobic and anaerobic conditions. The binding of [14C]1,6-dinitropyrene equivalents to rat hepatocyte DNA was increased by 15% in the presence of oxygen. Although there was little difference in the rate of 1,6-dinitropyrene metabolism, with or without O2, there was a difference in the metabolic pattern. Under anaerobic conditions there was an increase in the level of the terminal reduction product 1-amino-6-nitropyrene.

Animals↗
PubMed1991

Isolation of steroidal glycoalkaloids from Solanum incanum by two countercurrent chromatographic methods.

Using a bioassay for inhibition of plant growth and a combination of two countercurrent chromatographies: rotation locular countercurrent chromatography and droplet countercurrent chromatography, two biologically active glycosidal alkaloids, solasonine and solamargine were isolated from fresh ripe fruit of Solanum incanum. The combination of these chromatographic techniques has established an efficient isolation of polar phytochemicals of steroidal glycoalkaloids.

Carbohydrate Sequence↗
PubMed1979

Toxicological and teratological studies of 2-chloro-11-(2-dimethylaminoethoxy)-dibenzo[b,f]thiepine (zotepine), a new neuroleptic drug.

Toxicological and teratological studies of 2-chloro-11-(2-dimethylaminoethoxy)dibenzo[b,f]thiepine (zotepine) were performed in mice, rats, rabbits and dogs. There was no essential difference among mice, rats, rabbits and dogs in the acute toxicity of i.v. given zotepine. The rather small variation between intravenous and oral acute toxicity suggests the good absorption of zotepine from the gastrointestinal tract. In the subacute and chronic toxicity studies in rats, significant changes attributed to the drug were impairment of growth, alveolar proliferation in the mammary gland, decrease in uterine weight and increased number of diestrous rats. These changes were dose-dependent in the animals given 16 mg/kg or higher. Incidence of tumor in the treated groups in the 12-month study was almost the same as that in the control. In the subacute and chronic toxicity studies in dogs, abnormal quietness and abnormal gait occurred. Enlarged breasts and galactorrhea also occurred in females given 16 and 64 mg/kg in the 6-month study. Apart from these changes, one dog given 64 mg/kg had reversible hepatic dysfunction. In the teratological studies, zotepine had no adverse effects on pregnant animals and their fetuses in rats and rabbits, or reproductive performance of the F1 rats.

Animals↗