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Biomedical subjects

S Takase

Publications and source records attributed to S Takase.

At least 163 records · Page 9Linked to original sources

Genetic factors related to the development of carcinoma in digestive organs in alcoholics.

Heavy drinkers do not always develop alcoholic liver disease or cancer of the digestive organs, indicating that genetic factors may be involved. Recently, the presence of genetic polymorphisms of cytochrome P4502E1 (2E1) was confirmed. The genotype of 2E1 was separated into three types; type A which is homozygous for the c1 gene, type B which is heterozygous for the c1 and c2 genes, and type C which is homozygous for the c2 genes. In the present study the relationship between genotypes of 2E1 and digestive diseases, including alcoholic liver disease, was analyzed. In healthy controls, the prevalence of types A, B and C was 69%, 31% and 0%, respectively. In patients with esophageal cancer, four out of five patients (80%) were type B, and the prevalence of type B was significantly higher than that in normal controls. These results suggest that the c2 gene of 2E1 may be related to the development of esophageal cancer. In patients with gastric disease, the prevalence of types A and B was 72% and 28%, respectively. In patients with large bowel disease, the prevalence of type A was 83-100%, significantly higher than that in healthy controls. These results suggest that the c2 gene of 2E1 may not be related to the development of large bowel disease. However, the possibility should be considered that the c1 gene of 2E1 may link to its development. In this study, the relationship between the genotype of 2E1 and alcoholic liver disease was also analyzed. All patients with alcoholic liver disease, including one hepatoma, had the c2 gene but not the c1 gene. The frequency of the c2 gene was quite different from that in non-alcoholic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗

The relationship between the development of alcoholic liver and pancreatic diseases and the induction of gamma glutamyl transferase.

It is well known that the responses of serum gamma glutamyl transferase (GGT) to chronic alcohol drinking are different depending on the individual. In order to clarify the genetic backgrounds in the development of alcoholic liver and pancreatic diseases, the relationships between serum GGT response and alcoholic liver and pancreatic diseases in heavy drinkers were studied. The responses of GGT to alcohol drinking were classified into three groups: non-response, mild-response and hyperresponse. In alcoholic liver disease, non-responders were scarcely found and the response of GGT tended to increase in parallel with the progression of liver disease, when the hepatitis C virus (HCV) marker-positive patients were excluded. The differences in GGT levels between just after and at 4 weeks after abstinence in the HCV marker-negative patients were significantly higher than those in the HCV marker-positive patients. The rate of decrease in GGT activities during 4 weeks following abstinence was significantly higher in the HCV marker-negative patients than in the HCV marker-positive patients, indicating higher GGT induction in the HCV marker-positive patients. All patients with alcoholic pancreatitis, but without liver disease, were non-responders. All patients, except one, with severe pancreatitis were also non-responders. In alcoholic pancreatic disease, GGT induction correlated negatively with the development of pancreatitis. These results suggested that genetic polymorphism of GGT may link with the induction of GGT by alcohol drinking, and consequently link with the development of alcoholic liver and pancreatic diseases.

Adult↗

Effects of alcohol on the replication of hepatitis C virus.

We have reported that hepatitis C virus (HCV) RNA encoding the NS5 region (HCV-NS5) became negative following abstinence in some patients with alcoholic liver disease (ALD). In order to clarify the relationship between alcohol misuse (abuse) and the replication of HCV, serial changes of HCV-NS5 and the titer of HCV (HCV-titer) in blood after abstinence were studied in 11 male patients with ALD. Disappearance of HCV-NS5 after abstinence was found in five out of 11 patients (45%) and HCV-titer in blood decreased in all of these cases. In one patient, HCV-NS5 became positive and HCV-titers increased again following resumption of alcohol misuse. The etiology of liver disease in heavy drinkers was subdivided into three categories: alcohol alone, alcohol and HCV, and HCV alone, according to the diagnostic criteria of the Japanese research group for ALD. The etiology in four patients was a combination of alcohol and HCV, and was HCV alone in the remaining seven patients. In all four patients of the alcohol and HCV group, and one out of seven patients in the HCV alone group, HCV-NS5 became negative and HCV-titer decreased after abstinence. The decrease in HCV-titer was not related to the HCV genotypes. These results suggest that alcohol misuse may enhance the replication of HCV.

Adult↗

Effects of ethanol and acetaldehyde on the contraction of cultured Ito cells.

The effects of ethanol (Et-OH) and acetaldehyde (Ac-CHO) on the contraction of cultured Ito cells were studied using a time-interval videotape recorder (VTR). Ito cells were isolated from Wistar rats and cultured for 4 days. The motion of the cells was recorded by VTR and the sequential changes of the surface area of the each cell were evaluated by an image analyzer. No contraction of Ito cells was observed after incubation with Et-OH (100 mM) or Ac-CHO (500 microM) alone. Ten nanomoles endothelin-1 (ET-1) caused Ito cells to contract gradually. Pre-incubation of ET-1 with Ac-CHO at 37 degrees C for 1 hr inhibited the contraction of Ito cells completely. This inhibition was not seen in pre-incubation of ET-1 with Et-OH. In addition, the Ito cells which were pre-cultured with Ac-CHO for 6 hr did not contract at all after incubation with ET-1. In the isoelectric focusing of ET-1, a band was clearly seen at pI 4.6 after the treatment with Et-OH as well as non-treated ET-1. Two extra bands of ET-1 appeared in the anodic side of the gel after treatment with Ac-CHO, indicating the conformational changes of ET-1. These results indicated that the contraction of Ito cells induced by ET-1 was inhibited completely by Ac-CHO. This inhibitory effect of Ac-CHO was thought to be caused by binding Ac-CHO to ET-1 itself or to ET-1 receptors.

Acetaldehyde↗

Feeding medium-chain triglycerides to rats decreases degradation of sucrase-isomaltase complex in the jejunum.

We demonstrated previously that feeding a diet containing medium-chain triglycerides (MCT) to rats causes an increase in the sucrase activity in jejunum relative to diets containing long-chain triglycerides (LCT). To explore the mechanism whereby MCT affect jejunal sucrase activity, 7-wk-old rats were fed a high LCT diet for 7 d, and then they were force-fed either the high LCT diet, a high MCT diet or a high carbohydrate (alpha-methylglucoside) diet for the subsequent 12 h. Feeding the high carbohydrate diet produced significantly greater sucrase and isomaltase activities in both upper and lower jejunum than feeding the LCT diet. Feeding the high MCT diet led to significantly greater sucrase activity in the lower jejunum, but isomaltase activity was not elevated. Rocket immunoelectrophoresis revealed that in the lower jejunum of the rats fed the high MCT diet the proportion of sucrase-isomaltase complex to its degradation product (i.e., isomaltase monomer) was elevated, suggesting that dietary MCT affects sucrase activity by retardation of degradation of sucrase-isomaltase. Because the amounts of total bile acids in the upper jejunum were 50% lower in rats fed the high MCT diet relative to animals fed the high LCT diet, it is likely that MCT feeding decreases secretion of bile into the lumen, which in turn decreases degradation of the sucrase subunit of the sucrase-isomaltase complex.

Animals↗

Induction and distribution of cellular retinol-binding protein, type two during villus-crypt development in the chick duodenum.

Between day 18 of embryogenesis and 1 day posthatch, a rapid and remarkable (over 10-fold) increase in cellular retinol-binding protein, type two (CRBP(II)) levels occurred in the lower portion of duodenal villi of the chick. With further postnatal growth and concomitant with initiation of food intake, CRBP(II) levels increased over 2-fold in the mid-villus enterocytes. The results suggest that a first induction of CRBP(II) occurs in differentiating lower villus enterocytes during the perinatal period and is followed by marked increases in mid-villus cells. These quantitative change in the distribution and levels of CRBP(II) are probably related to the appearance of retinol in the duodenal lumen.

Animals↗

Maltitol-induced increase of transepithelial transport of calcium in rat small intestine.

To gain an insight into a mechanism whereby maltitol increases intestinal absorption of calcium, we evaluated transepithelial calcium transport of everted segments of rat small intestine by comparing the values in the presence of maltitol with the values in the presence of maltose. In jejunal segments, no significant difference in the rate of calcium transport was seen between the incubations in the medium containing 100 mM maltitol and in the medium containing 100 mM maltose, regardless of the calcium concentrations in the mucosal-side medium. By contrast, the everted ileal segments incubated in the presence of maltitol exhibited two-fold greater transepithelial calcium transport than did the segments incubated in the presence of maltose at a high (10 mM) concentration of calcium, whereas at a low (0.5 mM) concentration of calcium, maltitol did not produce a significant effect. With the conditions in which intestinal alpha-glucosidases were inhibited using the medium containing Tris or acarbose, a slight (40%) but significant increase of calcium transport was again observed in the segments incubated in the medium containing maltitol as compared with the medium containing maltose. The results suggest that maltitol enhances the rate of transepithelial calcium transport in the lower part of small intestine by modulating the passive diffusion of calcium, and that not only the nature of low digestibility, but also some other nature(s) of maltitol might be responsible for the maltitol-induced increase of ileal calcium transport.

Animals↗

WB2838 [3-chloro-4-(2-amino-3-chlorophenyl)-pyrrole]: non-steroidal androgen-receptor antagonist produced by a Pseudomonas.

In the course of our search for non-steroidal androgen-receptor antagonists of microbial origin, Pseudomonas sp. No. 2838 was found to produce an inhibitor of androgen binding to its receptor. This compound, named WB2838, was isolated and identified as 3-chloro-4-(2-amino-3-chlorophenyl)-pyrrole. The IC50 value of WB2838 for partially purified rat prostate cytosol receptor was 8.0 x 10(-7) M. However, the IC50 value of WB2838 against estrogen-receptor binding was about 90-fold greater than that against androgen-receptor binding. WB2838 inhibited the growth of androgen-responsive mouse mammary carcinoma SC-3 cells in the presence of 10(-8) M testosterone at IC50 value of 4.1 x 10(-7) M. This inhibition was reversed by adding 10(-5) M testosterone to the culture medium. WB2838 also showed the inhibitory activity against the growth of the ventral prostate induced by testosterone propionate in castrated immature rats. Therefore, it was concluded that WB2838 was a non-steroidal androgen-receptor antagonist.

Androgen Receptor Antagonists↗

The alcohol-altered liver membrane antibody and hepatitis C virus infection in the progression of alcoholic liver disease.

Progression of alcoholic liver disease is closely related to drinking habits. However, prognosis of alcoholic liver disease is not determined just by drinking habits, but also by other factors. In this study, the roles of alcohol-altered liver membrane antibody and hepatitis C virus infection were analyzed in alcoholic patients who were followed up for various lengths of time. Serial changes of liver histological appearance were analyzed in 39 patients with alcoholic liver disease who were followed for long periods (49.7 +/- 34.3 mo) and who underwent liver biopsy at least two times. Prognoses of 35 patients with alcoholic cirrhosis who were followed for more than 1 yr were also evaluated. Development of cirrhosis in alcoholic liver disease was significantly higher in the alcohol-altered liver membrane antibody-positive patients than in the patients negative for this antibody. On the other hand, hepatitis C virus markers were not related to development of cirrhosis. However, hepatocellular carcinoma developed more frequently in the hepatitis C virus marker-positive patients. In patients with cirrhosis, the cumulative rates of hepatocellular carcinoma development were significantly higher in the hepatitis C virus marker-positive patients than in the marker-negative patients. Cumulative survival rates in the hepatitis C virus marker-positive patients were significantly lower than rates in the hepatitis C virus marker-negative patients, even in noncancer patients. However, such differences were not observed in the alcohol-altered liver membrane antibody-positive and alcohol-altered liver membrane antibody-negative cirrhotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohols↗

[Genetic and epidemiologic studies on alcoholic liver diseases].

Polymorphic alleles of several genes such as ADH2, ALDH2, ApoB100, GST1, GST3 and ALAD were investigated from the aspect of the relationship with alcohol related diseases. DNAs were prepared from whole blood samples of 84 healthy controls (male), 70 patients (male) with alcohol related diseases and 87 patients (male) with non-alcoholic diseases. PCR technique was used for the detection of GST1 showed a good correlation to alcoholic liver diseases. The patients with alcoholic liver diseases had a higher frequency of ALDH2*1 than the healthy controls (p < 0.005). The frequencies of GST1 gene deletion in the samples were as follows: Healthy controls; 47.6%, alcoholic liver diseases (fibrosis: 75%, cirrhosis: 65.5%, hepatoma: 75%) and non-alcoholic liver diseases: 54%. The data indicated that the patients with alcoholic liver diseases had a significantly higher frequency of gene deletion than the healthy controls (p < 0.005). In addition, homozygote of ALAD1 allele detected by MpsI-RFLP showed a good correlation to alcoholic liver diseases. Thus, the genetic polymorphism of ALDH2, GST1 gene deletion and ALAD can be applied widely for the study of genetic association with alcoholic liver diseases.

Alcohol Dehydrogenase↗

[A case of chorea-acanthocytosis associated with low glycohemoglobin A1c].

We reported the first case of chorea-acanthocytosis associated with low glycohemoglobin A1c. Fasting blood sugar, daily profile of blood sugar, serum fructosamine and 75 g glucose tolerance test were all within normal limits. While abnormal hemoglobins were not detected, red blood cell half-life was sharply reduced to 13.4 days. These findings suggest that the low glycohemoglobin A1c in this case is highly ascribable to the reduction of red blood cell half-life rather than to continuous hypoglycemia. However, we can not rule out that the abnormalities of red blood cell membrane, suggested factors in this disease, may be related to the low glycohemoglobin A1c value. Further investigations on chorea-acanthocytosis cases with normal red blood cell half-life are necessary in order to elucidate whether an abnormal glycohemoglobin A1c value is a specific indication regarding this disease.

Acanthocytes↗

Retinal changes in myotonic dystrophy. Clinical and follow-up evaluation.

Retinal changes in myotonic dystrophy include butterfly-shaped pigmentary changes in the macula, reticular pigmentary retinal changes in the midperiphery, and peripheral atrophic polygonal-shaped changes. To assess the prevalence and progressiveness of these changes in a large series, 49 patients with myotonic dystrophy were examined. Of the eyes studied, 26 (26.6%) had butterfly-shaped macular pigmentary changes, 24 (24.5%) had reticular pigmentary retinal changes, and 43 (43.9%) had peripheral atrophic polygonal-shaped changes. Ten patients (18 eyes) had two different types at once. Visual acuity was not severely affected. Electroretinographic examination showed diminished a and b wave amplitudes in eyes with and without retinal changes. Arden ratios on the electrooculogram were normal in 13 of 14 patients tested. During the follow-up period, which exceeded 5 years, 3 of 9 patients had newly developed or enlarged, patterned changes of the pigment epithelium. These results suggest that pigmentary retinal changes in patients with myotonic dystrophy are slowly progressive.

Adolescent↗

Changes in type IV collagen content in livers of patients with alcoholic liver disease.

An increase of serum type IV collagen levels in patients with liver disease has been reported; however, the mechanisms of this increase are not yet well known. We recently developed an assay system for type IV collagen content in liver biopsy specimens. In this study, type IV collagen content in the livers and sera of patients with alcoholic liver disease and nonalcoholic liver disease was determined. Serum and hepatic type IV collagen contents were measured with a one-step sandwich enzyme immunoassay system using monoclonal antibodies for human type IV collagen. Hepatic type IV collagen content increased significantly in liver disease. In alcoholic liver disease, type IV collagen content in patients with mild fibrosis was lower than that in advanced types of alcoholic liver disease. In nonalcoholic liver disease, hepatic type IV collagen content tended to increase with the progression of fibrosis. Type IV collagen content in alcoholic liver disease was significantly higher than that in the corresponding type of nonalcoholic liver disease. Hepatic total collagen content increased significantly in parallel with the progression of fibrosis in both alcoholic liver disease and nonalcoholic liver disease. The total collagen content in each type of alcoholic liver disease was significantly lower than that in the corresponding type of nonalcoholic liver disease. The ratio of type IV collagen to total collagen content was the highest in livers showing mild fibrosis, both in alcoholic liver disease and nonalcoholic liver disease, and decreased in parallel with the progression of fibrosis. The ratio in patients with alcoholic liver disease was significantly higher than that in those with the corresponding nonalcoholic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Collagen↗

Changes in the markers related to collagen synthesis in the liver of chronically alcohol treated rats.

In order to clarify the roles of Ito cells in the development of alcoholic fibrosis, markers related to collagen synthesis in the liver were analyzed in chronically alcohol treated rats. The livers were obtained from rats fed a diet containing alcohol (alcohol group) and those fed a control diet (control group) for 4 weeks. Prolyl hydroxylase (PH) activity in the whole liver tissue did not differ in the alcohol and control groups. However, the activity in the isolated Ito cells was significantly higher in the alcohol group than in the control group. Immunoreactive PH beta-subunit contents in the liver and serum were significantly higher in the alcohol group than in the control group. Hydroxyproline contents in the liver did not differ in either groups. Immunohistochemically, type IV collagen and laminin were clearly stained along with the sinusoid in the livers of the alcohol group. However, the staining reactions were very weak in the control group. Staining reactions to types I and III collagen were very weak or almost absent in the livers of both groups. Desmin-positive cells, along with the sinusoid, increased significantly in the alcohol group, especially at the centrilobular area, suggesting that the number of Ito cell increase in the centrilobular areas of the alcohol treated rats. These results suggest that type IV collagen and laminin synthesis increase in the Ito cells of chronically alcohol treated rats, although clear evidence of hepatic fibrosis was not obtained. This increase may be related to capillarization of the sinusoids and finally to the development of perisinusoidal fibrosis in alcoholics.

Animals↗

Effects of vitamin A on collagen metabolism by cultured rat liver cells.

Conflicting results have been reported concerning the phenotypes of collagen produced by cultured Ito cells. These variations may be attributed to differences in pretreatment, i.e., with or without vitamin A to facilitate the separation of Ito cells. In the present study, the effects of vitamin A on collagen metabolism by Ito cells and hepatocytes of rats were analyzed. In cultured Ito cells, staining reactions to type I collagen increased, and those to type IV collagen and laminin decreased after pretreatment with vitamin A. The rate of collagen synthesis by Ito cells decreases significantly by treatment with vitamin A. The decrease was clearer in degraded collagen than in intact collagen. The synthesis of type I collagen increased and that of type IV collagen significantly decreased in Ito cells by treatment with vitamin A. In the hepatocytes, the staining reaction to type I collagen increased with vitamin A pretreatment. The net collagen and type III collagen synthesis in hepatocytes decreased by treatment with vitamin A. These results indicate that vitamin A modifies collagen metabolism in different cell types in different ways.

Animals↗