PubMed Health⌕ Search

Biomedical subjects

K Ameno

Publications and source records attributed to K Ameno.

At least 37 records · Page 2Linked to original sources

CYP2D6 HhaI genotype and the neuroleptic malignant syndrome.

To investigate the relationship between CYP2D6 genotypes (reported to be associated with the susceptibilities to Parkinson's disease and multisystem atrophy) and the possible susceptibility to neuroleptic malignant syndrome (NMS) and subacute myelo-optico-neuropathy (SMON), we analyzed the CYP2D6 gene by polymerase chain reaction and restriction fragment length polymorphism in Japanese schizophrenia patients with a history of NMS. There was no significant difference in the frequency of the poor metabolizer genotype of CYP2D6 between the cases with a history of NMS and controls (p > 0.05). The frequency of the mutation located at the HhaI site in exon 6 of CYP2D6 in the cases was higher, but not significantly (p > 0.05; the mutated allele frequency was 0.25), than that in the controls, schizophrenia patients without NMS (0.11) and healthy controls (0.09). The frequency (0.10) of the HhaI mutation type in patients with a diagnosis of SMON was also not significantly higher than in healthy controls. These results suggest that the poor metabolizer and HhaI polymorphism of CYP2D6 may not be a useful molecular marker for predicting the onset of NMS and SMON.

Adult↗

[Relationship between alcoholism and HTR2 MspI polymorphism].

We investigated the human serotonin receptor, HTR2 genotype among 73 alcoholics. We found that there might not be a significant difference between alcoholics and controls in the frequency of HTR2 C1/C2 gene (MspI polymorphism). This result suggested that the HTR2 C1/C2 gene might not be associated with the risk factor for developing alcohol dependence. Further studies are required to determine whether or not a novel serotonin receptor polymorphism reflects pathogenesis of alcoholism.

Adult↗

[Acetaldehyde adducts in the cerebral cortex of long-term ethanol-fed mice].

It is assumed that the acetaldehyde binds to the proteins after the consumption of ethanol to form an adduct. Such acetaldehyde adducts are related to organ diseases. We examined 8-week-old female BALB/cAJcl mice which had been on a liquid diet for six months. The alcohol-fed mice's liquid diet comprised vitamins, minerals, amino acid and a ethanol solution. The five groups of mice examined were 1.5% ethanol-fed, 2% ethanol-fed, 2.5% ethanol-fed, 3% ethanol-fed, and 3.5% ethanol-fed mice respectively. All mice fed by 2.5% or more ethanol died within a month. Tissue samples were taken from the 1.5% and 2% ethanol-fed mice to investigate the distribution of acetaldehyde adducts in various organs. We demonstrated the immunohistochemical staining of the cerebral cortex and liver from the ethanol-fed mice with antibodies against acetaldehyde adducts. In the 2% ethanol-fed mice, the protein epitope related to acetaldehyde was found in the cerebral cortex and the liver. There was a significant difference in the amount of cell degeneration between the 1.5% and 2% ethanol-fed mice. The results suggest that the neurotoxicity of ethanol starts to cause serious cell degeneration in concentrations of more than 1.5%. The neurotoxicity of ethanol in the cerebral cortex was found to be more prominent than in the liver, resulting in more cell degeneration.

Acetaldehyde↗

Combined toxicity of methanol and formic acid: two cases of methanol poisoning.

Two fatalities caused by methanol ingestion are presented. Quantitative analysis of methanol and formic acid using head-space gas chromatography showed concentrations of methanol and formic acid in the femoral blood of each subject of 2.19 mg/ml and 0.41 mg/ml, and 1.96 mg/ml and 0.38 mg/ml, respectively. We concluded that death was due to methanol ingestion and the mechanism causing death involved the combined effects of the anesthetic action of methanol itself and metabolic acidosis by formic acid. Forensic toxicokinetic analysis indicated that both victims had ingested about 100 g of methanol or more.

Adult↗

Relationship between alcoholism and CYP2E1 C/D polymorphism.

The genotypes of the CYP2E1 loci of 35 alcoholic and 130 nonalcoholic (healthy controls) Japanese were investigated to determine the relationship between CYP2E1 (C/D) polymorphism and susceptibility to alcohol dependence. There was a significant (d.f. = 1, chi2 = 11.0, p < 0.001) difference in the CYP2E1 C gene frequency between alcohol dependents (0.41) and controls (0.28), suggesting that the C gene of CYP2E1 may be related to the risk of developing alcoholism in Japanese, whereas the frequency of the D gene was higher among controls than alcoholics. Healthy Japanese controls showed a significantly (d.f. = 1, chi2 = 30.1, p < 0.001) higher frequency of the C allele than Swedish healthy controls (0. 10) did.

Adult↗

Lewis genotyping by the PCR-RFLP method in a Japanese population and its evaluation in forensic analysis.

Lewis phenotyping of red blood cells has many problems such as the influence of many biological conditions, the change during the period from newborn to early childhood and mistyping by non-specific anti-Lewis antibodies. Therefore, it would be useful to determine the Lewis genotype. Recently a method of Le-genotyping by PCR-RFLP was established. We determined the frequencies of Lewis genotypes in a Japanese population and discuss the applicability to paternity tests and other forensic applications. The gene frequencies of Le, le1 and le2 in the Japanese population studied were 0.7032, 0.2358 and 0.0610 respectively. Out of 12 paternity cases where paternity was excluded by other markers, 3 alleged fathers could also be excluded by Lewis genotyping. The genotype from organs of a fetus from a 3-month pregnancy was Le/Le. The determination of Lewis genotypes could play a useful role as a genetic marker in paternity tests and forensic analyses.

Asian People↗

[Acetaldehyde adducts in the cerebral cortex of ethanol-fed mice].

To investigate the neurotoxicity of acetaldehyde covalent adducts, immunohistochemical staining for acetaldehyde adducts using the antibody against acetaldehyde adducts, was performed in the cerebral cortex of ethanol-fed (withdrawal) mice. In the ethanol-fed mice, the degeneration in the cerebral cortex was found, while the protein epitope related to acetaldehyde was found in the cerebral cortex, liver and adrenal cortex. No histochemical and immunohistochemical changes in the tissues from the control mice were found. It is possible that acetaldehyde adducts may effect on the cerebral cortex as the neurotoxicity which cause psychosis such as delirium and hallucination after alcohol drinking.

Acetaldehyde↗

[Relationship between alcoholism and CYP2E1 genotypes].

The genotype of the CYP2E1 loci in 36 alcoholic and 42 non-alcoholic (healthy) Japanese were investigated to examine the relationship between the polymorphisms of CYP2E1 (C/D) and the susceptibility to alcohol dependence. There was a significant (df = 1, chi 2 = 4.39, p < 0.05) difference in CYP2E1 CD (heterozygote) genotype frequency between alcohol dependents (56%) and controls (33%), suggesting that the CD (heterozygote) genotype of CYP2E1 may have something to the risk of developing alcoholism in Japanese, whereas DD (homozygote) genotype was high among controls.

Adult↗

Forced double suicide by fire revealed by autopsy and toxicological examination: a case report.

We report here a forced double suicide by fire. Two burned bodies discovered in the debris of a house fire were identified as a father and his son by odontological findings. In the father, the concentration of carboxyhemoglobin (CO-Hb) in the left ventricle was over 90% and endrin, an organochlorine pesticide, was also detected in the stomach contents. However, 30.5% of CO-Hb in left ventricular blood and gasoline traces from an intratracheal puncture were detected in the son who had been undergoing treatment at a neuropsychiatric clinic. From these results, we determined this case to be a double suicide forced by the father in which the father set a fire with gasoline, thus burning his son to death, and then died in the fire himself after ingestion of Endrin. This case suggests the importance of integration of the results from the detailed forensic pathological and toxicological examinations and the scene investigation.

Adult↗

Application of capillary gel electrophoresis to the diagnosis of the aldehyde dehydrogenase 2 genotype.

This study dealt with the application of capillary gel electrophoresis (CGE) to diagnosis of the aldehyde dehydrogenase 2 (ALDH-2) genotype. Electrophoresis was performed on a low cross-linked polyacrylamide gel ¿3% T [g acrylamide+g Bis (N,N'-methylenebisacrylamide)], 0.5% C (g Bis/% T)¿ in 100 mM Tris-borate buffer (pH 8.3) at -10 kV with on-column UV detection (260 nm). During the PCR reaction, DNA from the wild-type allele generated a MboII restriction site, which is an amplification created restriction site. This did not occur, however, with DNA fragments from the mutant allele. Therefore, determination of the heterozygous genotype, the coexistence of wild-type and mutant alleles, was easily possible. Analysis of the MboII restriction digests of the PCR products was completed in less than 20 min, showing two peaks corresponding to fragments of 125 (cleaved) and 135 (uncleaved) base pairs (bp), respectively. On the other hand, determination of the homozygous genotype, wild-type or mutant, was difficult in one electrophoresis run. The CGE of the MboII restriction digests gave a single peak and the identification, cleaved or uncleaved, was difficult under our experimental conditions. However, the addition of aliquots of the PCR reaction mixture to the restriction digests, followed by re-electrophoresis, allowed successful diagnosis, yielding two peaks (cleaved and uncleaved) for the wild-type and one peak (uncleaved) for the mutant allele. This study demonstrated that CGE offers a high-speed, high-resolution analytical tool for determining genetic types, as compared with the conventional slab gel methodologies.

Aldehyde Dehydrogenase↗

Detection of two metabolites of diquat in urine and serum of poisoned patients after ingestion of a combined herbicide of paraquat and diquat.

This report describes the identification of diquat-dipyridone and diquat-monopyridone as metabolites of diquat, and time course changes of these metabolites plus diquat and paraquat in urine and serum of three poisoned patients who ingested the combination herbicide Preeglox L (containing 5% paraquat dichloride and 7% diquat dibromide) in a suicide attempt. Diquat-dipyridone was isolated from urine and identified by electron impact mass spectrometry, thin layer chromatography and high performance liquid chromatography (HPLC). Diquat-monopyridone, diquat-dipyridone, diquat and paraquat in serum and urine were assayed by HPLC with fluorescence and UV detection. Paraquat-monopyridone as a metabolite of paraquat was not detected in any samples. These results indicate that diquat is metabolized to diquat-monopyridone and diquat-dipyridone and also that the metabolism of diquat is easier than that of paraquat in humans. The concentrations of each metabolite were always lower than that of diquat in each specimen. However, the ratios of the concentration of each metabolite against the concentration of diquat increased with the decrease of diquat concentration. The metabolism of diquat seems to lower slightly the diquat concentration.

Chromatography, High Pressure Liquid↗

Inhibitory mechanism of intestinal ethanol absorption induced by high acetaldehyde concentrations: effect of intestinal blood flow and substance specificity.

This study describes the effects of high blood acetaldehyde concentrations on the intestinal absorption of ethanol and 2-butanone using an in situ single-pass perfusion technique on the rat intestine and the colored microsphere method to measure intestinal blood flow. We found that high blood acetaldehyde concentrations inhibit intestinal ethanol absorption in an inverse proportion to peak acetaldehyde concentrations, decrease intestinal blood flow, and inhibit intestinal absorption of 2-butanone. The decrease of the intestinal blood flow, induced by high blood acetaldehyde concentrations, is a major mechanism inhibiting intestinal ethanol absorption, but other mechanisms are also thought to inhibit absorption. Therefore, inhibition by high acetaldehyde concentrations is not the only factor affecting ethanol absorption.

Acetaldehyde↗

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

The effects of the genotypes of CYP2E1, ALDH2, ADH upon the blood ethanol and acetaldehyde levels were investigated. The predicting 95% confidence bounds determined on regression analysis of the data suggested that after venous injection of ethanol, the blood ethanol and acetaldehyde concentrations in a volunteer normal homozygous for ALDH2 (ALDH2*1/1) were significantly lower than that heterozygous (ALDH2*1/2). And the blood ethanol and acetaldehyde concentrations in a volunteer with C2 allele (C1/C2) were significantly lower than that in (C1/1). However, there were no significant differences in the blood ethanol and acetaldehyde concentrations between volunteers with ADH2*1/1 and ALDH2*1/2. It is possible that the ALDH2*1 and C2 alleles may correspond to the lower blood ethanol and acetaldehyde concentrations after intravenous administrations of 0.2 g /kg of ethanol.

Adult↗

[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↗

Additional proof of reduction of ethanol absorption from rat intestine in vivo by high acetaldehyde concentrations.

We investigated intestinal ethanol absorption in rats pretreated with saline, cyanamide, 4-methylpyrazole and cyanamide + 4-methylpyrazole. The value of the absorption rate constant in the cyanamide-pretreated group with high acetaldehyde levels was the lowest among the four groups, but there were no significant differences among the remaining groups. We found that high acetaldehyde concentration itself clearly reduces intestinal ethanol absorption.

Acetaldehyde↗

Direct dissolution of gallstones with methyl tert-butyl ether (MTBE) via endoscopic transpapillary catheterization in the gallbladder (ETCG).

In a pilot study of direct dissolution therapy of gallstones with methyl tert-butyl ether (MTBE), endoscopic transpapillary catheterization in the gallbladder (ETCG) was performed. Complete dissolution was seen in 8 out of 12 (66%) patients and partial dissolution was seen in 2 (16%) patients. In one of the 8 complete dissolution patients, combined extracorporeal shock wave lithotripsy (ESWL) and dissolution therapy was carried out successfully. These 8 patients were followed up for 12-20 months with regular ultrasonography. During this period, 1 patient underwent laparoscopic cholecystectomy due to stone recurrence. Thickening of the gallbladder wall was seen in 2 patients, but there were no other complications. Using Tsuchiya's classification based on ultrasound, complete dissolution was seen in type Ia stones. This pilot study suggests that the direct dissolution of gallstones with MTBE via ETCG might be a useful and safe non-invasive treatment in patients with cholesterol stones in preserved gallbladders.

Adult↗