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Biomedical subjects

G Toda

Publications and source records attributed to G Toda.

At least 91 records · Page 5Linked to original sources

Association of restriction fragment-length polymorphisms in the alcohol dehydrogenase 2 gene with alcoholic brain atrophy.

Alcohol abuse can induce brain atrophy, but it only occurs in some alcoholics. To investigate whether genetic polymorphism of alcohol-metabolizing enzymes [including alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)] was related to alcoholic brain atrophy, we determined restriction fragment-length polymorphisms of the ADH2 and ALDH2 genes in 77 male alcoholics. Computed tomography was used to determine the severity of brain atrophy. Digestion with MaeIII and MboII after polymerase chain reaction amplification showed that the ADH2(1) gene frequency was significantly higher in patients with brain atrophy than in those without brain atrophy (chi 2 = 9.274, p < 0.01), whereas no significant association was observed between brain atrophy and the ALDH2 gene Multivariate analysis (including age, total alcohol intake, liver cirrhosis, and ADH2 genotype) showed that the ADH2(1)/ADH2(1) genotype was associated with alcoholic brain atrophy. These findings suggest that the ADH2(1) allele may be associated with alcoholic brain atrophy.

Adult↗

Effects of cimetidine on blood ethanol levels after alcohol ingestion and genetic polymorphisms of sigma-alcohol dehydrogenase in Japanese.

Administration of cimetidine, an H2-receptor antagonist increases blood alcohol concentrations. This has been attributed to decreased gastric first-pass metabolism of ethanol caused by cimetidine's inhibitory effect on gastric alcohol dehydrogenase (sigma-ADH) activity. Molecular studies on sigma-ADH showed that a point mutation might occur at position 287 (G --> T) of the sigma-ADH gene in Japanese deficient type of sigma-ADH activity. To clarify the relationship between first-pass metabolism of ethanol and polymorphism of sigma-ADH, we analyzed the nucleotide sequence at positions 287 and 294 of sigma-ADH in 11 individuals who were administered ethanol orally before and after treatment with cimetidine. Higher blood ethanol levels after cimetidine administration were found in 4 of 11 cases (group A), whereas high blood ethanol levels were observed in 7 of 11 cases (B group), irrespective of cimetidine administration. Genetic polymorphisms at position 287 and 294 were not observed in all subjects. Even in 59 Japanese men with various alcoholic liver diseases, no polymorphisms at position 287 were observed by restriction-length polymorphisms with Avail digestion after polymerase chain reaction.

Adult↗

Splenectomy-reduced hepatic injury induced by ischemia/reperfusion in the rat.

In the present study, we investigated the role of the spleen in experimental hepatic ischemia/reperfusion in the rat. After a 90-min period of ischemia in the left and middle hepatic lobes, the ischemia was released and the liver was reperfused for up to 24 h. Plasma alanine aminotransferase reached a peak 3 h after the onset of reperfusion, and gradually decreased thereafter. A histological examination revealed evidence of hepatocellular necrosis and degeneration, especially 24 h after the onset of reperfusion. In addition, there was a noticeable accumulation of polymorphonuclear cells in the liver following ischemia/reperfusion. A splenectomy performed just prior to ischemia/reperfusion reduced both biochemical and histological hepatocellular injury. The number of polymorphonuclear cells in the liver following ischemia/reperfusion was significantly reduced in rats subjected to splenectomy, suggesting that the increase in polymorphonuclear cells may contribute to liver injury. The number of mononuclear cells also increased in the marginal zones of the spleen following ischemia/reperfusion, and appeared to be derived from the splenic monocyte/macrophage population, based on immunohistochemical studies. The spleen plays an important role in the pathogenesis of hepatic ischemia/reperfusion injury and the splenic monocyte/ macrophage population contributes to liver damage.

Alanine Transaminase↗

Coronary angiographic finding of thrombus in the left atrial appendage.

PURPOSE: The value of coronary angiography in the diagnosis of thrombus in the left atrial appendage (LAA) was retrospectively analyzed. MATERIAL AND METHODS: The study covers 34 patients in whom coronary angiography showed coronary neovascularity in LAA with coronary artery-left atrial fistula indicating LAA thrombus. All 34 patients underwent transthoracic echocardiography within one week of coronary angiography. Open-heart surgery was undertaken 2-31 months after angiography in 28 patients. RESULTS: Coronary neovascularity and coronary artery-left atrial fistula arose from the left circumflex artery in 28 patients, and from the left circumflex artery and the right coronary artery in the remaining 6 patients. By echocardiography, LAA thrombus was detected in only one of the 34 patients. In 18 of the 28 patients who underwent open-heart surgery, LAA thrombus was found at surgery to have resolved. CONCLUSION: Coronary angiography is useful in the diagnosis of LAA thrombus, and coronary neovascularity and fistula formation may indicate that the thrombus can spontaneously resolve.

Adult↗

Intraocular hemorrhage developing during interferon therapy.

A 43-year-old man with chronic active hepatitis C was treated with interferon-beta (IFN-beta) at a dosage of 6 x 10(6) IU/day for a planned 6-week period. Ocular hyperemia, ophthalmalgia, and increased intraocular pressure in the right eye developed 20 days after the start of treatment. Intraocular pressure remained high, even after discontinuation of IFN therapy, laser therapy, and iridectomy. Two days later, the right eye was removed because perforation had occurred. The ocular symptoms that developed in this case were thought to have been caused and exacerbated by IFN administration.

Adult↗

[A basic study on gastric emptying test using barium grains and effect of drugs on gastric emptying in rats].

We reported an experimental study on a new non-invasive method for evaluation of gastric emptying by abdominal X-ray after administration of radiopaque barium grains. Adult male Wistar rats weighing around 200 g were used. After they were fasted for 24 hours, 1 ml of gruel mixed with 10 barium grains (1 mm diameter) was introduced into the rat stomach with a catheter. The rats were sacrificed at 30, 60, 90, 120 and 150 minutes after the introduction of the gruel. X-rays were taken at each time point and grains in the stomach were counted in the X-ray photographs. All barium grains were emptied from the stomach in 150 minutes. After incision of the abdomen, the residual gastric contents were weighed. A positive correlation was found between the grains in the stomach and the weight of the contents. We studied the effects of cisapride, scopolamine buthylbromide and enprostil on the gastric emptying time by this method. Cisapride accelerated gastric emptying, whereas scopolamine buthylbromide delayed it. A prostaglandin E2 analog, enprostil delayed the gastric emptying. This method was found to be a simple procedure which is outstanding for quantitative determination and useful in evaluating gastric emptying functions.

Animals↗

Microheterogeneity with concanavalin A affinity of serum transferrin in patients with alcoholic liver disease.

Microheterogeneity of transferrin (Tf) with concanavalin A (ConA) affinity was investigated by sensitive lectin-affinity electrophoresis and antibody-affinity blotting technique of sera obtained from patients with alcoholic liver disease (ALD) and normal subjects. Serum Tf was separated by ConA into three bands-a strongly ConA-reactive major band (C1), a weakly reactive minor band (C2), and a non-reactive trace band (C3). The C3 fraction was significantly increased in patients with ALD before alcohol abstinence, compared with normal subjects and patients with ALD after 4 weeks of abstinence. Furthermore, a significant correlation was found between the C3 fraction and serum carbohydrate-deficient transferrin or gamma-glutamyl-transpeptidase. These results indicate that the microheterogeneity of serum Tf in patients with ALD may be a more complex abnormality of elongation and processing on the glycans than merely a loss of terminal sialic acids. Determination of the C3 fraction is a useful marker for ALD.

Alcoholism↗

Genetic heterogeneity in the precore region of hepatitis B virus in hepatitis B e antigen-negative chronic hepatitis B patients: spontaneous seroconversion and interferon-induced seroconversion.

To elucidate the relationship between the clinical severity of chronic liver disease and the precore mutations in hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) carriers, mutations were investigated in the precore region of HBV DNA in 20 chronic hepatitis B patients who seroconverted either spontaneously or after the administration of alpha-interferon (IFN), and 5 asymptomatic carriers. The precore mutation with a stop codon at nucleotide 1896 was found in all patients, irrespective of the histology and in all asymptomatic carriers. The second mutation at nucleotide 1899 was found in 40% of cases studied but always followed by the first mutation at nucleotide 1896. The mixed viral infection of precore mutant and wild-type HBV virus was found in 40% of seroconverted cases after IFN treatment and in sera of HBV carriers obtained within a year after the spontaneous seroconversion. These data suggest that the precore mutants prevail over wild-type HBV in all HBeAg-negative HBV carriers within several years after the seroconversion, but their prevalence could not confine the clinical severity of chronic liver disease.

Adult↗

Occurrence of antibody against rat hepatic sinusoidal endothelial cells in sera of patients with autoimmune hepatitis.

To determine whether an antibody against hepatic sinusoidal endothelial cells was present in sera of patients with autoimmune hepatitis (AIH) type 1, we measured the serum IgG bound to the glutaraldehyde-fixed cultured rat sinusoidal endothelial cells by enzyme-linked immunosorbent assay. IgG bound to the cells was detected significantly more in patients with autoimmune hepatitis type 1 (97.1%) than in those with primary biliary cirrhosis (13.0%), chronic hepatitis C (5.9%) or B (7.9%), or healthy controls (0%). IgG-F(ab')2 fragments from autoimmune hepatitis patients also bound to the cells, and this binding was observed after absorption of the fragments with rat hepatoma cells, but not after absorption with bovine carotid endothelial cells. Culture of sinusoidal endothelial cells in the presence of IgG from AIH patients significantly reduced the number of viable attached cells. In conclusion, anti-sinusoidal endothelial cell antibody occurred in the sera from patients with autoimmune hepatitis type 1.

Animals↗

Association of a restriction fragment length polymorphism in the alcohol dehydrogenase 2 gene with Japanese alcoholic liver cirrhosis.

BACKGROUND/AIMS: The association of ADH2 polymorphisms with alcoholic liver cirrhosis has not been clearly demonstrated. METHODS: We investigated the association of two alleles in the ADH2 gene marked by restriction fragment length polymorphisms in patients with alcoholic liver cirrhosis. The ADH2 restriction fragment polymorphisms with Mae III were determined using the polymerase chain reaction on lymphocytes from 76 male Japanese alcoholics (non-cirrhotic patients; 34 cases, cirrhotic patients; 42 cases) and 60 healthy male subjects. RESULTS: The frequency of the ADH2(1)/ADH2(1) genotype was significantly higher in the alcoholics than in the healthy subjects p < 0.001). In the alcoholics, the genotype ADH2(2)/ADH2(2) was significantly more prevalent in the cirrhotic group than in the non-cirrhotic group (p < 0.05). CONCLUSIONS: These results suggest that the Mae III polymorphisms of the ADH2 gene may be associated not only with susceptibility to alcoholic liver cirrhosis, but also with the development of alcoholism in Japanese patients.

Adult↗