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Biomedical subjects

A Takada

Publications and source records attributed to A Takada.

At least 577 records · Page 32Linked to original sources
PubMedDate not supplied

Effects of ethanol on experimental hepatocarcinogenesis.

Although primary hepatoma is not very frequent in alcoholics, the incidence of hepatoma in cases of hepatitis B infection combined with heavy alcohol drinking is high. In the present study, the effects of chronic alcohol administration on the development of chemical-induced hepatic cancer in rats were analyzed. In 70% hepatectomized Wistar strain male rats, a single dose (1 mg per 100 gm body weight) of diethylnitrosamine was injected intraperitoneally. Eight weeks after the injection, 20% alcohol-10% sucrose solution (diethylnitrosamine-alcohol group), 0.1% sodium phenobarbital solution (diethylnitrosamine-phenobarbital group), 10% sucrose solution (diethylnitrosamine-sucrose group) or tap water (diethylnitrosamine-alone group) was given as drinking water for 32 weeks. The numbers of visible nodules per liver were significantly greater in the diethylnitrosamine-alcohol and diethylnitrosamine-phenobarbital groups compared to the diethylnitrosamine-alone and diethylnitrosamine-sucrose groups. The numbers of enzyme-altered foci which were positive to gamma-glutamyl transpeptidase staining per square centimeter of liver section were also greater in the diethylnitrosamine-alcohol and diethylnitrosamine-phenobarbital groups than in the diethylnitrosamine-alone and diethylnitrosamine-sucrose groups, although the numbers of nodules and enzyme-altered foci were significantly larger in the diethylnitrosamine-phenobarbital group than in the diethylnitrosamine-alcohol group. The enzyme-altered foci areas calculated by gamma-glutamyl transpeptidase staining were significantly larger in the diethylnitrosamine-alcohol and diethylnitrosamine-phenobarbital groups than in the diethylnitrosamine-alone and diethylnitrosamine-sucrose groups. Histologically, visible nodules observed in diethylnitrosamine-phenobarbital and diethylnitrosamine-alcohol groups showed characteristic features of neoplastic nodules. These results indicate that alcohol has a promoter action on the development of chemically induced hepatic cancer like phenobarbital.

Animals↗
PubMedDate not supplied

Induction of cystine transport activity in isolated rat hepatocytes by sulfobromophthalein and other electrophilic agents.

The uptake of cystine in isolated rat hepatocytes was enhanced after incubation of the cells with sulfobromophthalein. The enhancement was time- and dose-dependent, with a lag of about 6 hr, and an approximately 4-fold increase in the activity occurred after 24 hr with 0.2 mM sulfobromophthalein. Actinomycin D or cycloheximide completely blocked the time-related increase in the uptake. The enhanced activity of cystine uptake was almost entirely Na+-independent and inhibited by some anionic amino acids, such as glutamate. The uptake of glutamate was also enhanced by sulfobromophthalein. It is concluded that sulfobromophthalein induces the activity of the Na+-independent, anionic amino acid transport system (System x-c) which mediates the transport of cystine. Some other electrophilic agents also enhanced the cystine uptake. The glutathione level of hepatocytes was rapidly reduced by sulfobromophthalein to about 10% of the control level at 6 hr, but at 12 hr it began to rise. It seems likely that this restoration resulted from the induced activity of the cystine uptake because inhibitors of the cystine uptake blocked the restoration and because the uptake of other sulfur amino acids was not enhanced significantly by sulfobromophthalein. System x-c may thus participate in the detoxication of electrophilic agents in hepatocytes.

Animals↗
PubMedDate not supplied

Characterization of desmin-positive rat liver sinusoidal cells.

Hepatic sinusoidal lining cells were isolated from mature male rats (12 months old) and cultured in order to clarify the characteristics of the Ito cells (fat-storing cells). Desmin staining was used as a marker in the isolation of the Ito cells, and a highly purified desmin-positive cell fraction was obtained. Less than 10% of the desmin-positive cells were positive for vitamin A auto-fluorescence. However, the number of vitamin A-positive cells increased with vitamin A treatment, and they extended to over half of the desmin-positive cells by the first week of vitamin A treatment. The cultured Ito cells were positive for both desmin and vimentin stainings. On the other hand, Kupffer and endothelial cells were positive only with vimentin staining. Ito cells lost their fat droplets after repeated subculturing. The electron microscopic features of the Ito cells became similar to those of myofibroblasts, except for the absence of dense bodies, indicating that the Ito cells may have possibly transformed into myofibroblasts. Collagen fibers were occasionally found in the extracellular space. These results indicate that Ito cells retain both their myogenic and fibrogenic properties, and that lipocytes or myofibroblasts may be desmin-positive cells which maintain specific functions. Furthermore, staining of the intermediate filaments is useful in the identification of Ito cells, and a highly purified Ito cell fraction can be easily obtained using desmin staining as a marker.

Animals↗
PubMedDate not supplied

Comparison of ballooned hepatocytes in alcoholic and non-alcoholic liver injury in rats.

Ballooned hepatocytes are commonly observed in alcoholic and sometimes in non-alcoholic liver diseases. To clarify whether pathogenesis of this change is different in alcoholic and non-alcoholic liver diseases, changes of the livers in rats fed alcohol with pyrazole for 12 weeks were compared with those of CCl4 treated rats. Both groups of rats showed marked ballooning of the hepatocytes in the centrolobular area. Immunohistochemically, the ballooned hepatocytes in alcohol-pyrazole treated rats reacted strongly with transferrin and albumin staining. However, staining reaction of the ballooned hepatocytes in the CCl4 treated rats was slight. In alcohol-pyrazole treated rats, hepatic microtubules were significantly decreased. Retention of transferrin and albumin were found only in the ballooned hepatocytes of alcohol-pyrazole treated rats. However, in the CCl4 treated rats, neither microtubular alteration nor retention of the exportable proteins was observed. These findings indicate that the pathogenesis of ballooning of hepatocytes is different in alcoholic and non-alcoholic liver injuries. In alcoholic liver injury, microtubular alteration may lead to retention of protein and ballooning of hepatocytes by interfering with the hepatic secretion of proteins.

Animals↗
PubMedDate not supplied

Biochemical markers of chronic alcoholism.

Usefulness of several biochemical markers for the monitoring of chronic alcoholism were studied. Among generally used markers, only gamma-GTP showed a significant difference between alcoholic and non-alcoholic liver diseases. Serum glutamate dehydrogenase (GDH) activity was significantly high in alcoholic liver disease. When the ratios of GDH to ornithine carbamyl transferase (OCT) were calculated, differences between alcoholic and non-alcoholic liver diseases became clearer without overlapping of any value. Serum desialo-transferrin was found in about 60% of the alcoholics, and disappeared by abstinence. Microheterogeneity of serum protein was also found in other glycoproteins. Serum prealbumin level was significantly high in alcoholics without severe liver disease. Acetaldehyde dehydrogenase (ALDH) activity of erythrocytes was significantly low in alcoholics, and gradually increased after abstinence. These results indicate that microheterogeneity of glycoproteins, serum prealbumin level and erythrocyte ALDH activity are good markers of alcohol abuse, and serum GDH/OCT ratio is the most sensitive marker of alcoholic liver injury. Serum gamma-GTP activity is a good marker of both conditions.

Alanine Transaminase↗
PubMedDate not supplied

Hepatic aldehyde dehydrogenase isoenzymes: differences with respect to species.

Although changes in the acetaldehyde (Ac-CHO) oxidizing system in the liver are important for understanding the pathogenesis of alcoholic liver injury, interspecies differences of hepatic aldehyde dehydrogenase (ALDH: 1.2.1.3) isozymes have not yet been sufficiently studied. In the present study, the character and subcellular distribution of hepatic ALDH isozymes in male animals such as the Rhesus monkey, domestic cow, albino rabbit and Wistar strain rat were analyzed and compared with those in humans. The optimal pH for ALDH isozymes in human liver was 9.5, while those of monkey, cow, rabbit and rat were 9.0, 9.0, 8.5 and 8.5, respectively. In human liver, low Km ALDH activity was distributed mainly in the cytosol, while the corresponding activity was selectively distributed in the mitochondria in rat liver. The distribution patterns of low Km ALDH in the other animals were similar to those of the rat. In microsomes, low Km ALDH activity was very low or almost negligible in the livers of all species. These results indicate that Ac-CHO degrades mainly in the cytosol in the human liver, whereas, in the other species, it occurs in the mitochondria. This suggests that results obtained with experimental animals cannot be applied directly to humans. It is also suggested that degradation of the Ac-CHO produced in the microsomes may be slow in all species.

Aldehyde Dehydrogenase↗
PubMedDate not supplied

Determination of aldehyde dehydrogenase isozyme activity in human liver.

As acetaldehyde (Ac-CHO) has been implicated as a cause of alcoholic liver injury, accurate knowledge concerning changes in the Ac-CHO oxidizing system in human liver is essential for the understanding of the pathogenesis. However, an assay system for aldehyde dehydrogenase (ALDH: EC 1.2, 1.3) isozymes in human biological material has not yet been established. In the present study, the assay systems for human liver ALDH isozyme activity were analyzed. In human red blood cells, in which only one type of ALDH isozyme, high Km ALDH, is present, a maximum activity was observed at a substrate concentration of over 300 microM. In human liver of the usual type in which ALDH I (low Km isozyme) was not deficient, the activity reached a first plateau at 12 microM Ac-CHO after which the activity started to increase again at 20 microM Ac-CHO and continued to increase until 5.0 mM Ac-CHO. In the liver of the unusual type, which is deficient in low Km ALDH, activity was not detected at Ac-CHO concentrations lower than 10 microM. These results indicate that the optimum substrate concentrations for the determination of ALDH isozymes are 12 microM for low Km, 300 microM for high Km and over 1 mM for very high Km ALDH isozymes. The maximum activities of these three isozymes in the liver were obtained at a pH ranging between 9.0-9.5 and at an NAD concentration of over 500 microM. From these results, it is concluded that the assay system of Blair and Bodley is applicable for the determination of ALDH isozyme activity in human biological material with the exception of determining Km values.

Aldehyde Dehydrogenase↗
PubMedDate not supplied

Effects of malotilate treatment on alcoholic liver disease.

Malotilate, a new hepatotrophic drug, improves serum transaminase levels and the markers of protein metabolism in the liver in chronic liver diseases. However, the effects of malotilate on alcoholic liver disease are not well known. In the present study, the effects of this drug on the recovery process of alcoholic liver disease after abstinence were analyzed. Many hepatic test values were significantly improved after abstinence from alcohol in both the malotilate-treated and nontreated control groups. However, the Normotest values improved significantly only in the malotilate group, and not in the control group. The improvement rates for choline esterase activity were significantly greater in the malotilate group than in the control group. Serum albumin levels significantly increased in the malotilate group but not in the control group. Changes in the serum markers of hepatic fibrogenesis were not different between the 2 groups. These results indicate that malotilate accelerates the recovery of impaired protein metabolism in alcoholic liver disease and that this drug may be useful for the treatment of alcoholic liver diseases.

Aged↗
PubMedDate not supplied

Changes in blood acetaldehyde levels after ethanol administration in alcoholics.

Serial changes in blood ethanol (Et-OH) and acetaldehyde (Ac-CHO) levels following a single oral administration of 0.8 g/kg of Et-OH were determined in order to clarify the metabolism of Ac-CHO in alcoholic liver disease (ALD). The Et-OH metabolic rate (EMR) in alcoholics either with or without liver disease was significantly higher than the rate in nonalcoholics. Peak values of blood Ac-CHO levels and the Ac-CHO/EMR ratios in ALD were significantly higher than those in subjects with nonALD or alcoholics and nonalcoholics without liver disease. In the type I aldehyde dehydrogenase isozyme deficient cases (unusual type), blood Ac-CHO levels and Ac-CHO/EMR ratios were very high and the levels remain at a plateau until 90 minutes after Et-OH administration and then decreased relatively quickly. Changes in blood Ac-CHO levels and Ac-CHO/EMR ratios in ALD were similar to those in cases of the unusual type. These results indicate that Ac-CHO metabolism in ALD is decreased relative to its production and that this decrease might be due to increased production of Ac-CHO in the nonalcohol dehydrogenase pathway located in the microsomes, in which degradation of Ac-CHO was slow.

Acetaldehyde↗