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Biomedical subjects

H Suwaki

Publications and source records attributed to H Suwaki.

At least 55 records · Page 3Linked to original sources
PubMed1995

CYP2E1 and ALDH2 genotypes and alcohol dependence in Japanese.

The genotypes of the CYP2E1 and ALDH2 loci of alcoholic (alcohol dependence) and nonalcoholic (healthy) Japanese were investigated to examine the relationship between the polymorphism of CYP2E1 (C1/C2) and ALDH2 (ALDH2*1/ALDH2*2), and the susceptibility to alcoholism. There was no significant difference in C2 gene frequency between alcoholics (0.19) and nonalcoholics (controls) (0.20), whereas there was a significant difference in ALDH2 allele frequency, suggesting that, in Japanese, the C2 genotype of CYP2E1 may have nothing to do with the risk of developing alcohol dependence. However, the ALDH2*1 allele may influence drinking behavior and the development of alcohol dependence. Furthermore, racial interethnic differences in the frequency of the mutated allele of the CYP2E1 gene (C2) were found, like the ALDH2 gene. Japanese healthy controls showed a significantly higher frequency of the C2 allele than did Swedish healthy controls (0.05; reported by Persson et al., FEBS Lett. 319:207-211, 1993).

Alcohol Drinking↗
PubMed1995

[The ethanol elimination pharmacokinetics--the effects of genotypes of ALDH2 and CYP2E1 on the ethanol metabolism].

The effect of CYP2E1 upon the blood ethanol level was investigated. Blood ethanol concentrations in 4 volunteers whose ADH 2, ADH 3 and ALDH 2 genotypes were identical, were determined after intravenous administrations of 0.20 g/kg of ethanol by gas chromatography. The predicting 95% confidence bounds determined on regression analysis of these data suggested that after venous injection of ethanol, the blood ethanol concentration in a volunteer normal homozygous for CYP2E1 (C1/C1) is higher than that heterozygous (C1/C2). And beta 60 (the blood ethanol concentration-time curve) of the subject heterozygous for CYP2E1 (C1/C2) was higher than that normal homozygous (C1/C1). It is possible that the C2 allele corresponding to the higher CYP2E1 activity may affect the ethanol metabolism.

Aldehyde Dehydrogenase↗
PubMed1995

[Association between alcoholics and the genotypes of ALDH2, ADH2, ADH3 as well as P-4502E1].

We examined the genotypes of ALDH2, ADH2, ADH3 and P-4502E1 loci of alcoholics and nonalcoholics. Also we compared the frequencies of the homozygous ALDH2*1/1 genotype and heterozygous ALDH2*1/2 genotypes in alcoholics. Our study reported differences in the allelic frequencies of ALDH2, ADH2 and ADH3 loci between alcoholics and nonalcoholics. For alcoholics, it was indicated that ADH2 and ADH3 plays an important role for alcoholism. For genotypes of P-4502E1, no significant difference was observed between alcoholics and nonalcoholics. Alcoholics with the heterozygous ALDH2*1/2 genotype had significantly higher frequency of the ADH2*1 than that of alcoholics with ALDH2*1/1 genotype. Concerning the alcoholics with the heterozygous ALDH2*1/2 genotype, we assumed that ADH2*1 plays a role for the development of alcoholism.

Alcohol Dehydrogenase↗
PubMed1994

Correspondence of increased debrisoquine 4-monooxygenase activity with seizure-susceptibility in Mongolian gerbils.

Four drug-metabolizing activities in Wistar rat and Mongolian gerbil liver microsomes were investigated to clarify the biochemical basis of convulsions. No significant associations were observed between the susceptibility to the tonic-clonic seizures in Mongolian gerbils and the drug-metabolizing enzymatic activities of p-nitroanisole O-demethylase, aminopyrine demethylase and benzo[a]pyrene-3-monooxygenase. However, a significant association was observed with the debrisoquine 4-monooxygenase (cytochrome P-450db1-linked monooxygenase system) activity, which is known to metabolize exogenous and endogenous parkinsonism-inducing neurotoxins such as MPTP and TIQ, and to activate carcinogens during the detoxication of xenobiotics. The mean activity of debrisoquine 4-monooxygenase in the seizure-sensitive group (male, 380; female, 350 pmol/h/mg protein) remained significantly higher (about 4-5 times) than that in the seizure-resistant group (male, 90; female, 80 pmol/h/mg protein). More Mongolian gerbils were extensive metabolizers of debrisoquine in the seizure-sensitive group than in the seizure-resistant group. These results suggest a possibility that the cytochrome P-450db1-linked monooxygenase system may activate the potential neurotoxins which are associated with tonic-clonic seizures in the Mongolian gerbil.

Animals↗
PubMed1994

Effects of microinjection of kainic acid into the nucleus tractus solitarius on fluid and NaCl absorption across the jejunum.

Effects of bilateral chemical inactivation of the nucleus tractus solitarius (NTS) by microinjection of kainic acid (KA) on fluid and NaCl absorption across the jejunum were examined in anesthetized Sprague-Dawley rats. Jejunal fluid and NaCl absorption was measured in a jejunal loop before and after the microinjection of artificial cerebrospinal fluid (aCSF) or KA into the NTS. Net fluid and NaCl absorption was not altered by a microinjection of aCSF. However, net fluid (from 1.12 +/- 0.07 to 1.66 +/- 0.06 ml/30 min) and NaCl (Na+ from 164.5 +/- 10.1 to 243.3 +/- 7.1 muEq/30 min; and Cl- from 175.9 +/- 7.5 to 260.8 +/- 6.5 muEq/30 min) absorption was significantly increased by the chemical inactivation of the NTS. To examine the efferent mechanism of the increased net absorption induced by the NTS inactivation, mesenteric nerve activity (MNA) was measured before and after the inactivation of the NTS. MNA was significantly increased by 165.9 +/- 74.2% after the bilateral inactivation of the NTS. Furthermore, absorption experiments were conducted in rats with pretreatment of atropine (acetylcholine-antagonist) or yohimbine (specific alpha 2-antagonist). In atropine treated rats, net jejunal absorption was significantly increased by the inactivation of the NTS. However, the increase in net absorption induced by the inactivation of the NTS was completely abolished by pretreatment with yohimbine. These results suggest that the NTS has a tonic suppression on jejunal absorption through alpha 2-adrenergic mechanism.

Animals↗
PubMed1994

High-rate sequential sampling of auditory brain-stem and somatosensory evoked responses in hypoxia.

We developed a high-rate sequential recording technique that allowed simultaneous measurements of both auditory brain-stem response (ABR) and somatosensory evoked potential (SEP) every 10 sec. Using this method, a transient increase in amplitude of all the ABR and SEP components in response to hypoxia in dogs could be detected. The increase in amplitude preceded the prolongation of latency. Our study showed that there were successive changes of evoked potentials in response to hypoxia. A transient increase in amplitude is the first to occur, followed by a latency prolongation and an amplitude decrease for both ABRs and SEPs.

Animals↗
PubMed1994

A study of urinary dolichols as a biological marker for alcohol abuse. Report 2: Comparison of urinary dolichols/creatinine concentrations among non-drinkers, moderate-drinkers and heavy-drinkers.

We report here the comparison of urinary dolichols/creatine (D/Cr) concentration ratios in male non-drinkers, moderate-drinkers and heavy drinkers at admission and during hospitalization, and also discuss its usefulness as a biological marker for alcohol abuse. Urine samples were collected from the following four experimental groups: non-(male and female) and moderate-drinker (male) volunteers, and alcoholic heavy-drinking patients (male) at admission for psychiatric treatment and after 9-15 days hospitalization (informed consent was obtained). Urinary dolichols were determined by high performance liquid chromatography after BondElutC18 (500 mg) extraction. Due to significant differences in urinary D/Cr concentrations between male and female groups in non-drinkers and because the heavy-drinkers available for this study were exclusively male, comparison of the value of urinary D/Cr concentration ratios was subsequently limited to male only. There were no statistical differences in urinary D/Cr concentrations in the male among non-drinkers, moderate-drinkers and heavy-drinkers at admission. The accuracy of urinary D/Cr as a biological marker for alcohol abuse, calculated using the mean +/- 2 s.d. in non- and moderate-drinkers as the normal range, is only 33.3% in heavy-drinkers at admission, while their value of gamma-GTP in serum was 88.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[The genotype of CYP2E1 and liver-derived serum enzymes].

We determined the genotypes of the CYP2E1 loci of Japanese alcoholics with or without liver dysfunction to investigate the relationship between CYP2E1 and the susceptibility to alcoholic liver-injury. In the alcoholics (DSM-III-R) with a liver dysfunction, there was a significant relationship between the serum concentration of a liver-derived serum enzyme LAP and the C2 allele of CYP2E1.

Alanine Transaminase↗
PubMed1994

A study of urinary dolichols as a biological marker for alcohol abuse. Report 1: Quantitation of urinary dolichols by high performance liquid chromatography after BondElutC18 (500 mg) cartridge extraction.

This report describes the quantitation of urinary dolichols (Dolichol-90, -95 and -100) by advanced high performance liquid chromatography (HPLC) after BondElutC18 (500 mg) cartridge column extraction. The urine sample (15 ml) mixed with heneicosaprenol as internal standard (IS, 300 ng) was adjusted to pH 3 by 0.1N hydrochloric acid (HCl). BondElutC18 (500 mg) column was preactivated by methanol (4 ml) and distilled water (4 ml), and the urine sample was applied. The column was washed by HCl-sodium acetate buffer (pH 3, 6 ml), distilled water (4 ml) and methanol (4 ml), and then eluted by 2-propanol/dichloromethane/methanol (5/3/2 by vol, 4 ml). After drying the eluted solution under nitrogen gas flow, the residue was dissolved in 60 microliters of HPLC mobile phase, and 20 microliters of the mixture was injected into the HPLC. The HPLC conditions were as follows: column, mu Bondapack C18 (Waters); mobile phase, 2-propanol/methanol (72/28 by vol), 1.0 ml/min; detection, UV at 210 nm. Recovery yields of Dolichol-90, -95 and -100 were in the range of 68-75% and the calibration curve of each dolichol was linear over the range 0.01-1.00 micrograms.

Alcoholism↗
PubMed1994

[Blood ethanol levels and the CTP2E1 C2 allele].

The effect of CYP2E1 upon the blood ethanol level was investigated. Blood ethanol concentrations in 2 volunteers whose ADH2, ADH3 and ALDH2 genotypes were identical, were determined after intravenous administrations of 0.15 g/kg of ethanol by gas chromatography. beta 60 (0.28 mg/ml/hr) of the blood ethanol concentration-time curve in one with the CYP2E1 C2 allele was higher than that (0.25 mg/ml/hr) in the other with no C2 allele. It is possible that the C2 allele may correspond to the higher CYP2E1 activity of ethanol metabolism.

Aldehyde Dehydrogenase↗
PubMed1994

[A characteristic of alcoholics with the atypical aldehyde dehydrogenase (ALDH2(2)--a relationship to other alcohol metabolizing enzymes].

The series were composed of 59 alcoholics. All the subjects fulfilled the DSM-III-R criteria for alcohol dependency. We investigated the genotype at ALDH2. 6 patients were heterozygous ALDH2(1)/ALDH2(2). We determined the genotypes at ADH2, ADH3 and P-4502E1 about 6 patients. 5 patients had ADH2(1)/ADH2(1) allele. 2 patients had P-450E1*C2. We found a genetic characteristic about alcoholics with the heterozygous ALDH2(1)/ALDH2(2) allele.

Alcohol Dehydrogenase↗
PubMed1994

[Relationship between alcoholism and genotypes of acetaldehyde-metabolizing enzymes].

The genotypes of the CYP2E1 and ALDH2 loci in alcoholic and non-alcoholic (healthy) Japanese were investigated to examine the relationship between the polymorphisms of CYP2E1 (C1/C2) and ALDH2 (ALDH2*1/ALDH2*2), and the susceptibility to alcoholism. There was no significant difference in C2 gene frequency between alcoholics (0.20) and non-alcoholics (0.19), while there was a significant difference in ALDH2 allele frequency, suggesting that the C2 allele of CYP2E1 may have nothing to the risk of developing alcoholism in Japanese, whereas the ALDH2*1 allele may influence drinking behavior and the development of alcoholism.

Alcoholism↗
PubMed1993

Effect of ceruletide on epileptogenesis in amygdaloid kindled rats.

The inhibitory effects of ceruletide (CLT), a cholecystokinin-8 (CCK)-like peptide, were investigated in the epileptogenesis in the amygdaloid kindled rats. Lower doses of CLT (20-80 micrograms/kg) inhibited the progression of kindling process. After acquiring C5 stage, a higher dose (160 micrograms/kg) was required to suppress the seizure susceptibility. These results, in light of several previous studies showing no serious side effects, suggest that CLT might be useful as an anti-epileptogenic agent for clinical usage.

Amygdala↗