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Biomedical subjects

S Takase

Publications and source records attributed to S Takase.

At least 199 records · Page 11Linked to original sources

Acetaldehyde metabolism in different aldehyde dehydrogenase-2 genotypes.

In order to clarify the relationships between acetaldehyde (Ac-CHO) metabolism and low Km (mitochondrial) aldehyde dehydrogenase (ALDH2) genotypes, hepatic ALDH2 activity was determined and serial changes of blood Ac-CHO levels after ethanol administration were analyzed in the individuals homozygous for the normal ALDH2 genes, heterozygous for the normal and mutant ALDH2 genes, and homozygous for the mutant ALDH2 genes. Genomic DNA was extracted from white blood cells and genotyping of ALDH2 was performed using the polymerase chain reaction technique and slot blot hybridization with synthesized oligonucleotide probes specific to the normal and mutant ALDH2 genes. ALDH2 activity was not detectable in the liver in two cases of the mutant homozygote. In four out of eight cases of the heterozygote, hepatic ALDH2 activity was measurable, although the activity was lower compared with that in the normal homozygote. Blood ethanol levels after alcohol administration were not different among the three different ALDH2 genotypes. Blood Ac-CHO levels after drinking of alcohol were significantly higher in the heterozygotes and the mutant homozygotes than in the normal homozygotes. The levels after a moderate amount of ethanol (0.8 g/kg of body weight) in a case of the mutant homozygote were not different from those of the heterozygotes. However, the levels after a small amount of ethanol (0.1 g/kg of body weight) were significantly higher in the mutant homozygotes than in the heterozygotes. These results indicate that hepatic ALDH2 activity is lacking completely, and metabolism of Ac-CHO in the liver is severely impaired in the homozygotes of the mutant ALDH2 genes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗

Effects of various dietary protein contents on vitamin A status of rats exposed to prolonged immobilization through suspension.

The investigation was carried out to clarify the effects of various dietary protein contents on vitamin A status of rats exposed to prolonged immobilization through suspension. A rat wearing a special jacket to which metal chains were attached, was suspended for 10 days as an analogy of simulated weightlessness. Five groups of suspended rats were fed on the diets containing various amounts of casein (5, 10, 20, 40 and 60, w/w%), while control group received the 20% casein diet. Through suspending animals, a decrease in body weight gain and increase in adrenal weights occurred. Serum albumin concentration of the suspended rats fed on the 10, 20, 40 and 60% diets were the same as that of the control rats. The suspended rats showed lowered serum retinol concentrations and elevated hepatic retinyl palmitate contents without noticeable differences between the diets. The hepatic retinol levels were not clearly affected. In the suspended rats, testicular levels of retinyl palmitate and retinol significantly decreased as compared with the control. These parameters' alterations did not relate to serum albumin concentration and were independent of dietary protein levels. The results suggest that stress state may cause suppression of releasing hepatic vitamin A, resulting in a lowered serum retinol concentration, being independent of nutritional status of protein.

Adrenal Glands↗

WF-2421, a new aldose reductase inhibitor produced from a fungus, Humicola grisea.

WF-2421 is a novel aldose reductase inhibitor produced by Humicola grisea. WF-2421 was purified from the culture filtrate by successive ion exchange chromatography and the chemical structure was assigned to be alpha-formamido-5'-(2-formamido-1-hydroxyethyl)- beta,2',6-trihydroxy-3-biphenylpropanoic acid (1) on the basis of spectroscopic evidence. The IC50 value of WF-2421 was 3 x 10(-8) M against partially purified aldose reductase of rabbit lens.

Aldehyde Reductase↗

Different types of chronic hepatitis in alcoholic patients: does chronic hepatitis induced by alcohol exist?

To verify the existence of chronic hepatitis induced by alcohol, the clinicopathological features of chronic hepatitis in heavy drinkers were studied using various viral markers. Histological features of chronic active hepatitis were seen in 27 heavy drinkers. These patients were divided into four groups. The AL group (seven cases) consisted of alcoholics who were negative for both hepatitis C antibody and HBsAg; the HB group (four cases) was positive for HBsAg; the HC1 group (seven cases) was positive for hepatitis C antibody but negative for hepatitis C virus-RNA genome; and the HC2 group (nine cases) was positive both for hepatitis C antibody and hepatitis C virus-RNA genome. Serum AST and ALT activity declined during 4 wk of abstinence in most patients in the AL group and in the HC1 group. The response of serum AST and ALT to abstinence was poor in most patients in the HB group and the HC2 group. Serum desialo-transferrin and alcohol liver membrane antibodies were detected more frequently in the sera of patients in the AL group and HC1 group. A trend toward increased frequency of centrilobular ballooning existed in the AL group, but this did not reach statistical significance. These results suggest that chronic active hepatitis in patients in the AL group, in whom markers of HBV and hepatitis C virus were absent, may be caused by alcohol. Patients in the HC1 group who had hepatitis C antibody but not hepatitis C virus-RNA may represent cases where both alcohol and hepatitis C virus are involved.

Adult↗

[A case of ruptured aneurysm of Valsalva sinus into right atrium with peculiar findings on aortography].

A 24-year-old man with ruptured aneurysm of sinus of Valsalva into the right atrium originating from the noncoronary sinus is presented. On aortography through the ascending aorta the right atrium in systolic phase and the right ventricle in diastolic phase were opacified. We considered ruptured aneurysm like a streamer (wind sock) entered into the right ventricle in diastolic phase and into the right atrium in systolic phase. Post-aneurysmectomy course was uneventful, and radiographic examination revealed complete repair of the aneurysm.

Adult↗

Alcoholic liver disease in heterozygotes of mutant and normal aldehyde dehydrogenase-2 genes.

To clarify the pathogenetic role of acetaldehyde in the development of alcoholic liver disease, genotyping of aldehyde dehydrogenase-2 genes was performed and the clinical features of the alcoholic liver disease patients with different genotypes were compared. Genotyping of aldehyde dehydrogenase-2 was performed in 47 patients with alcoholic liver disease using the polymerase chain reaction and slot-blot hybridization. Of the 47 patients with alcoholic liver disease, 40 were homozygous for the normal aldehyde dehydrogenase-2 gene and the remaining seven cases were heterozygous for the normal and mutant aldehyde dehydrogenase-2 genes. No homozygote was found for the mutant aldehyde dehydrogenase-2 genes. Daily alcohol intake was less than 100 gm in all heterozygotes without relation to the type of alcoholic liver disease. On the other hand, all but four patients homozygotic for the normal aldehyde dehydrogenase-2 gene drank more than 100 gm alcohol/day. The mean daily alcohol intake in the heterozygotes was significantly lower than that in the normal homozygotes. The incidence of alcoholic fibrosis tended to be lower in the heterozygotes than in the normal homozygotes (14.2% vs. 52.5%). On the other hand, the incidence of alcoholic hepatitis and/or cirrhosis tended to be higher in the heterozygotes than in the normal homozygotes. These results indicate that alcoholic liver disease develops even with moderate amounts of alcohol intake in heterozygotes of the aldehyde dehydrogenase-2 genes, in which acetaldehyde metabolism in the liver is impaired and liver damage in the heterozygotes is more severe than that in the normal homozygotes, suggesting that habitual drinkers who are heterozygotes of the aldehyde dehydrogenase-2 genes may be at high risk for alcoholic liver disease.

Alcohol Drinking↗

Accumulation of glycoprotein in the Golgi apparatus of hepatocytes in alcoholic liver injuries.

To clarify the role of the hepatocytic Golgi apparatus in the accumulation of proteins in the hepatocytes of alcoholic liver disease, changes in the Golgi apparatus in human and experimental alcoholic liver injuries were analyzed. Immunoelectron microscopically, transferrin, one of the secretory glycoproteins from the liver, was retained in the smooth endoplasmic reticulum and Golgi apparatus of the hepatocytes in both human and rat alcoholic liver injuries. Biochemically, transferrin content in the Golgi fraction was clearly high in the rats with alcoholic liver injury. Desialo-glycoproteins were found in the serum of rats with alcoholic liver injuries. These results suggested that the glycosylation and secretion of hepatic glycoproteins in the Golgi apparatus were impaired in alcoholic liver injury. These abnormalities in the Golgi apparatus function may be important for the development of alcoholic liver injury.

Analysis of Variance↗

Ethanol and acetaldehyde metabolism in cultured hepatocytes from chronic alcoholic rats.

In this study the authors analyzed ethanol (Et-OH) and acetaldehyde (Ac-CHO) metabolism in cultured hepatocytes isolated from chronic alcoholic rats. Hepatocytes were isolated and cultured from two groups of rats, one was fed with a liquid diet containing Et-OH and another was pair-fed with a control diet for 4 weeks. After 48 hours of the primary culture, Et-OH was added to the culture medium at a final concentration of 5 mM with or without 2 mM 4-methyl pyrazole (Py). Serial changes of Et-OH and Ac-CHO levels in the medium for 48 hours were determined in 4 groups of the alcohol alone, alcohol-Py, control and control-Py groups. In the alcohol alone and control groups, Et-OH disappearance rates (EDR), which are roughly equivalent to Et-OH oxidation rates in the hepatocytes, were significantly higher than those in the corresponding Py treated groups. In the two alcoholic groups, the EDR was significantly higher than those in the corresponding control groups. In cultured hepatocytes, 75-80% of Ac-CHO produced from Et-OH was oxidized. The increasing rates of Ac-CHO (AcICR), a function of Ac-CHO production and oxidation rates in the hepatocytes, increased in parallel with the increase in the EDR. However, the AcICR/EDR rate, which is a parameter of the Ac-CHO oxidation rate in the hepatocytes, was not different among the 4 groups. These results indicate that the cultured cells maintain the characteristics of Et-OH metabolism in chronic alcoholic rats and may also be used for the study of Et-OH and Ac-CHO metabolism as an in vitro model.

Acetaldehyde↗

A diagnostic approach to different types of non-A non-B acute hepatitis through the evaluation of the lobular distribution of hepatocytic damage.

The activity in the serum of three hepatic mitochondrial enzymes, glutamate dehydrogenase (GDH), ornithine carbamyl transferase (OCT) and mitochondrial glutamic oxaloacetic transaminase (m-GOT), all of which show different lobular distribution in the liver, was investigated in order to clarify the usefulness of determinations of these enzymes for the diagnosis of different types of acute non-A non-B (NANB) hepatitis. In NANB hepatitis, there were two different histological types: portal and non-portal. In most portal cases, the GDH/OCT ratios were lower than 0.35, but the ratios were higher than 0.36 in all non-portal cases. The prognosis of the portal group and the short incubation group of NANB hepatitis was better than that of the non-portal and the long incubation group, respectively. The cases showing GDH/OCT ratios of less than 0.35 clearly displayed better prognoses than the cases showing high GDH/OCT ratios. These findings implied that the low GDH/OCT group may have been infected by particular viruses and that ratio determination is useful for the diagnosis of NANB hepatitis caused by different viruses.

Acute Disease↗

Developmental changes in vitamin A level and lack of retinyl palmitate in chick lungs.

1. Developmental changes in retinol and retinyl palmitate contents in lungs of chick embryos and posthatch chicks were investigated. 2. Remarkable changes in the lung retinol levels were found during development of chicks. Embryonic lungs 5 days prior to hatching contained the highest content of retinol. The level then declined rapidly and was lowest on 1 day before hatching. 3. Its level then rose substantially within 7 days after hatching. 4. No retinyl palmitate in chick lungs was detectable at any of the developmental stages examined, nor even in adult hen. 5. Serum retinol level changed in parallel with the lung retinol. 6. The patterns of changes in liver retinol and retinyl palmitate were remarkably different from that occurring in the lung retinol. In chick embryonic livers, the levels of them were low, followed by a rapid increase after hatching. 7. The high level and its rapid decrease of lung retinol content during development of chick embryos may be functionally connected with retinol action in embryonic lungs for cellular differentiation and maturation.

Aging↗

Effects of medium-chain triglycerides on brush border membrane-bound enzyme activity in rat small intestine.

The effects of various types of dietary fat on brush border membrane-bound enzymes in rat intestinal mucosa were examined. Four groups of five rats were pair-fed defined diets for 10 d. The control group was fed a diet containing 57% sucrose and 2% corn oil as a fixed carbohydrate reference; the three experimental groups received diets containing 57% sucrose and 2% corn oil plus 13% fat in the form of medium-chain triglycerides (MCT) or long-chain triglycerides (LCT) (either lard as a highly saturated fat or corn oil as a highly unsaturated fat). Feeding LCT compared to the control diet, decreased sucrase activity in mucosal brush borders of the duodenum and jejunum. In these segments of MCT-fed rats, sucrase activity was similar to that in the control animals. In another experiment, measuring immunoreactive sucrase-isomaltase in jejunal brush border membranes revealed that feeding a high corn oil diet, but not a high MCT diet, led to a reduction in the sucrase catalytic activity per unit weight of enzyme protein, suggesting that the degradation status of sucrase-isomaltase might be altered by the different types of dietary fats. With MCT feeding, jejunal alkaline phosphatase activity was enhanced to a large extent compared to the activity in other groups. Feeding MCT, compared to lard or corn oil, also increased microvillus phospholipids of the jejunal mucosa. These results suggest that MCT, unlike LCT, do not suppress the activity of mucosal microvillus membrane enzymes in rat small intestine.

Alkaline Phosphatase↗

Thyroid function in patients with myotonic dystrophy.

In order to investigate endocrine disturbances in patients with myotonic dystrophy (MD), 12 patients and 20 normal controls were studied. All patients were clinically euthyroid and there were no significant differences between circulating levels (mean +/- SD) of T4 (114.7 +/- 26.8 vs 129.9 +/- 28.3 nmol/l), FT4 (16.6 +/- 4.5 vs 18.4 +/- 3.8 pmol/l), T3 (1.61 +/- 0.29 vs 1.86 +/- 0.33 pmol/l), TSH (2.7 +/- 1.3 vs 2.4 +/- 1.4 mU/l), TBG (26.7 +/- 5.5 vs 27.6 +/- 4.9 mg/l), T4/T3 (84.3 +/- 18.4 vs 82.1 +/- 15.3), and FT4/FT3 (0.28 +/- 0.05 vs 0.33 +/- 0.08). Serum FT3 (4.3 +/- 1.4 pmol/l) in patients were significantly lower than those (5.3 +/- 0.9 pmol/l) in normal controls (P less than 0.02). Thyroidal 131I-uptakes (8.7 +/- 4.3%) in patients were significantly lower than those (25.8 +/- 7.4%) in controls (P less than 0.01). The mean maximal TSH responses following TRH stimulation were significantly less in patients with MD (11.4 +/- 4.5 vs 17.0 +/- 6.2 mU/l; P less than 0.02). Neither circulating thyroid microsomal nor thyroglobulin antibodies were detectable in the 11 patients tested. Serum thyroglobulin concentrations were within the normal range in all patients but one. In conclusion, it is suggested that normal levels of serum T4, T3, FT4, TSH, TBG, T4/T3 and FT4/FT3, slight but significant decrease of serum FT3, reduced TSH response to TRH and a decrease of thyroidal radioiodine uptake might be due to a slight functional failure of TSH secretion in patients with myotonic dystrophy.

Adult↗