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Biomedical subjects

C Sato

Publications and source records attributed to C Sato.

At least 145 records · Page 8Linked to original sources

Gene expressions of c-met and hepatocyte growth factor in chronic liver disease and hepatocellular carcinoma.

BACKGROUND/AIMS: The roles of c-met proto-oncogene and hepatocyte growth factor in human livers have not been shown. METHODS: Gene expressions of both c-met and hepatocyte growth factor were quantified in livers with chronic active hepatitis and in cirrhotic livers with hepatocellular carcinoma as well as in normal controls, using competitive reverse transcription polymerase chain reaction. RESULTS: C-met expression was significantly increased in chronic active hepatitis compared with control livers, and c-met expression in chronic active hepatitis correlated with serum alanine aminotransferase levels. Hepatocyte growth factor expression was increased in some patients with chronic active hepatitis compared with controls, and there was a significant correlation between c-met expression and hepatocyte growth factor expression. On the other hand, in hepatocellular carcinoma tissues, c-met expression was increased in some cases, while that in the surrounding non-carcinomatous tissues was similar to normal controls. Hepatocyte growth factor expression was not detected in the hepatocellular carcinoma tissues and was low in the surrounding non-carcinomatous tissues. CONCLUSIONS: These findings suggest that hepatocyte growth factor may be involved in the regeneration of hepatocytes via paracrine mechanism in chronic active hepatitis, while in regulation of c-met expression in hepatocellular carcinoma tissues may be independent of hepatocyte growth factor stimulation.

Alanine Transaminase↗

Effects of additional administration of colchicine in ursodeoxycholic acid-treated patients with primary biliary cirrhosis: a prospective randomized study.

BACKGROUND/AIMS: Although ursodeoxycholic acid is effective for the treatment of primary biliary cirrhosis, some patients do not respond to this treatment. The objective of the present study was to investigate the effects of additional administration of colchicine in ursodeoxycholic acid-treated patients with primary biliary cirrhosis. METHODS: Twenty-two patients with primary biliary cirrhosis treated with ursodeoxycholic acid (600 mg/day) for 30 months were randomly assigned to two groups: group 1, colchicine (1 mg/day) and ursodeoxycholic acid (n = 10); group 2, ursodeoxycholic acid alone (n = 12). RESULTS: In group 1, there were significant decreases in mean serum levels of alkaline phosphatase, total bilirubin, gamma-glutamyltranspeptidase, alanine aminotransferase, aspartate aminotransferase, and IgM, and these changes were more remarkable in those who responded poorly to ursodeoxycholic acid. In contrast, there were no significant changes in those values in group 2. CONCLUSIONS: Additional administration of colchicine to ursodeoxycholic acid may be beneficial for patients with primary biliary cirrhosis, especially those who respond poorly to ursodeoxycholic acid. It is necessary, however, to further confirm the efficacy of colchicine by examining histological changes and following the patients for longer periods.

Aged↗

Sequential changes in full-length genomes of hepatitis B virus accompanying acute exacerbation of chronic hepatitis B.

BACKGROUND/AIM: During the course of persistent hepatitis B virus infection, viral replication markedly decreases after acute exacerbation of liver inflammation accompanied by emergence of antihepatitis B e antibody (anti-HBe) and/or anti-hepatitis B surface antibody (anti-HBs). In some cases, however, persistent viral replication continues even after such exacerbation with or without HBeAg/anti-HBe seroconversion. The aim of the present study was to investigate the extent of genetic variations of HBV in this phenomenon. METHODS: Full-length HBV genomes were amplified by polymerase chain reaction from sera of three patients before and after acute exacerbation and were directly sequenced. RESULTS: In the whole genomes of 3215 nucleotides, only six nucleotide mutations for six amino acid substitutions (2 in the surface gene, 2 in the X gene, 1 in the core gene and 1 in the polymerase gene) were observed in patient 1, 15 mutations for 14 amino acid substitutions (1 in the pre-core codon 28, 4 in the surface gene, 4 in the core gene and 5 in the polymerase gene) were observed in patient 2, and 5 mutations for 6 amino acid substitutions (2 in the surface gene, 2 in the X gene, pre-core stop codon mutation and 1 in the polymerase gene) were observed in patient 3. Substitution in the a determinant of the surface gene, which encodes target epitopes for neutralizing antibodies, as well as those in the pre-core/core gene, which encodes epitopes for cytotoxic T cells, were mainly found. CONCLUSION: HBV that remained after the emergence of anti-HBe and anti-HBs are considered to possess mutations in epitopes for both humoral and cellular immunity. These mutant HBV may be involved in the pathogenesis of persistent hepatic injury after acute exacerbation.

Adult↗

Evidence for down-regulation of highly expressed TCR by CD4 and CD45 on non-selected CD4+CD8+ thymocytes.

Immature CD4+CD8+ double-positive (DP) thymocytes are positively selected for further development if they express TCR reacting with thymic ligands of low affinity. However, the majority of DP thymocytes express low TCR levels. This low level of TCR may be insufficient to recognize thymic ligands. To understand the basis for the low expression of TCR on DP thymocytes, we determined the density of TCR expression at various stages of their development using TCR transgenic (TCR-Tg) mice. We found that TCR expression was high in the thymocytes that had recently transited into the DP stage but then gradually decreased on DP cells if they were not selected by TCR interaction with MHC molecules. However, such TCR suppression was not observed in positively selected DP cells and in the non-selected DP cells obtained from CD45 deficient mice or from mice receiving anti-CD4 mAb. These findings suggest that the once highly expressed TCR at the DP stage is suppressed by CD45 and/or CD4 on non-selected thymocytes. Furthermore, TCR suppression is prevented by TCR-mediated signals. The maintenance of high TCR levels on positively selected DP thymocytes may facilitate their selection.

Animals↗

Fluid collection in the pericardial sinuses and recesses. Thin-section helical computed tomography observations and hypothesis.

RATIONALE AND OBJECTIVES: This study describes the thin-section helical computed tomography (CT) appearance of near-water-density structures situated posterior to the pulmonary trunk and right main pulmonary artery, and to consider the implications of these CT images. METHODS: Three-millimeter-thick helical CT scans of the mediastina of 133 patients were reviewed to determine the incidence and range of appearance of near-water-density structures situated posterior to the pulmonary trunk and right main pulmonary artery. Thin-section helical CT appearance was compared with that of fluid collection in the pericardial sinuses and recesses of patients with pericardial effusion, and with descriptions of the pericardial sinuses and recesses in the literature. RESULTS: Near-water-density structures showing varied appearance ranging from bands to mass-like densities were observed on thin-section helical CT images of 49 patients (37%) who had no obvious effusion in the pericardial cavity proper. The locations of the structures corresponded to the sites of recesses in the transverse and oblique sinuses, and their appearance was similar to that of fluid in the pericardial sinuses and recesses. CONCLUSION: Near-water-density structures situated posterior to the pulmonary trunk and right main pulmonary artery in patients without obvious pericardial effusion were concluded to be physiologic fluid collections in the recesses of the transverse and oblique sinuses.

Carcinoma, Bronchogenic↗

Ischemic hepatitis in cirrhosis. clinical features and prognostic implications.

To characterize liver dysfunction in patients with cirrhosis after variceal bleeding, we analyzed 50 cirrhotic patients who had bleeding esophageal varices with or without shock. Increases in serum total bilirubin levels by 1.5 times were observed within 24 h in 11 of 12 patients with shock who died > 4 days after hemorrhage but in only one of eight patients with shock who survived (p < 0.01). Increases in serum aspartate aminotransferase and alanine aminotransferase by 2.5 times were observed in six patients in the former group but in none of the latter (p < 0.05). In postmortem livers, hepatocellular degeneration with minimal inflammatory cell infiltration was observed. Ischemic hepatitis is frequently noted in cirrhotic patients with ruptured esophageal varices. Patients with increases in the serum level of total bilirubin and/or aminotransferases within 24 h from onset of hemorrhage should be carefully treated even if hemorrhage is controlled.

Adult↗

Improvement of peripheral blood lymphocyte subsets in primary biliary cirrhosis after ursodeoxycholic acid therapy.

Immunological abnormalities frequently observed in patients with primary biliary cirrhosis are considered to be related to the pathogenesis of this disease. We performed a prospective trial to evaluate whether immune mechanisms play a role in the effectiveness of ursodeoxycholic acid (UDCA) therapy. Fifteen female patients with primary biliary cirrhosis were followed for 1 year and were then treated with UDCA (600 mg/day) for another year. Laboratory tests, including peripheral blood lymphocyte subsets assessed by dual colour fluorescence analysis using monoclonal antibodies against respective T cell markers, were evaluated at the beginning of the study, at the start of therapy and at the end of therapy. In primary biliary cirrhosis, the proportion of cytotoxic T cells, suppressor inducer T cells and alpha beta-receptor bearing T cells were significantly lower than in healthy controls. No significant changes were observed in the proportions during the year before the therapy. These reductions, however, recovered to normal ranges after 1 year of UDCA therapy. These changes were associated with an improvement in the serum levels of aspartate aminotransferase, alkaline phosphatase, gamma-globulin and IgM. The close correlation between the improvement in the imbalance of lymphocyte subsets after the therapy and the clinical status suggests that an immunological process may play a role in the effectiveness of therapy in primary biliary cirrhosis.

Aged↗

Roles of alcohol, hepatitis virus infection, and gender in the development of hepatocellular carcinoma in patients with liver cirrhosis.

To assess the interaction of alcohol, hepatitis C virus (HCV), and hepatitis B virus (HBV) infection in hepatocarcinogenesis, we prospectively observed 449 patients with liver cirrhosis (LC) who presented to our outpatient clinics in 1 month; 164 patients with habitual drinking [alcoholic liver-liver cirrhosis (AL-LC)] who had taken > 72 g alcohol/day (HCV-positive 81 cases: HCV + AL; HCV-negative 83 cases: AL); 176 patients with HCV infection, but without alcohol intake: 34 patients with HBV infection: 6 patients with HCV and HBV coinfection; and 82 patients with liver diseases from other etiologies, such as primary biliary cirrhosis. In the HCV group, the cumulative occurrence rate of hepatocellular carcinoma (HCC) was 9%, 18%, and 23% in the first, second, and third years, respectively. In the HCV + AL group, that was 13%, 17%, and 28%, respectively. There was no difference in the HCC occurrence rate between the two groups. In the AL group, the cumulative HCC occurrence rate was only 1% during the observation period of 3 years. The occurrence rate was significantly lower in the AL group, compared with the HCV and the HCV + AL groups. In the HBV group, the cumulative occurrence rate of HCC during the observation period of 3 years was 17%, which was similar to that of the HBV + AL group, 14%. We also examined some other variables that might be related to the development of HCC. The cumulative occurrence rate of HCC in male patients was 31%, whereas that was 18% in female patients. In the HCV group, there was a significant increase of HCC occurrence rate in male patients. In contrast, no difference was observed in the HCC occurrence rate between male and female patients in the HBV group. The present study suggests that alcohol alone may not be an independent risk factor for HCC, nor does it accelerate HCC development in LC patients with HCV and HBV infection during the prospective observation of 3 years.

Adult↗

Distribution of hepatitis C virus RNA in the liver and its relation to histopathological changes.

To investigate a cellular mode of HCV-infection in the liver and its pathological implications in relation to histopathological changes or clinical data, we studied the distribution of HCV-RNA in the livers of 21 patients with HCV-related chronic liver disease (chronic active hepatitis, 14 cases; cirrhosis, 7 cases) using the in situ hybridization technique. In situ hybridization was performed on 4% paraformaldehyde-fixed frozen sections with digoxigenin-labeled DNA probe deduced from the core region of HC-J4. In situ hybridization showed positive signals in the liver specimens of 20/21 cases. The signals were localized in the cytoplasm of hepatocytes. The distribution pattern of positive cells was individually different, whereas the pattern was identical in the right and left lobes. There were no correlations of the HCV-positive cell number with serum aminotransferase levels at biopsy or with genotypes of HCV. The positive hepatocytes were occasionally associated with infiltrating mononuclear cells, and they were sparsely distributed in the area of piecemeal necrosis. These findings suggest that factors such as host immunoreaction to the virus may be more important than its direct cytopathy in the pathogenesis of chronic hepatitis C virus infection.

Alanine Transaminase↗

Natural history of polypoid lesions in the gall bladder.

BACKGROUND: Although polypoid lesions of the gall bladder are frequently observed in asymptomatic subjects, the natural history of these lesions has never been studied using ultrasonography. AIM: The natural history of polypoid lesions of the gall bladder was investigated using ultrasonography. SUBJECTS: Among 4343 patients who presented to the outpatient clinic of Tsuchiura Kyodo General Hospital in 1988, 111 subjects were diagnosed as having polypoid lesions of the gall bladder by ultrasonography. Among these patients, two had gall bladder carcinoma. The remaining 109 subjects (58 female; age: median 54, range 25-89) were enrolled in this study. METHODS: The subjects were followed up by ultrasonography once or twice a year until 1994. RESULTS: Four patients received cholecystectomy and two patients died of other causes during the observation period. In one patient, gall bladder carcinoma was found, but its location was different from that of the pre-existing polyp. The size of the lesions did not change in 88.3% of the other 130 patients during this period, even among those in whom the initial size of the lesion exceeded 10 mm. There was no apparent correlation between the change in the diameter of the polypoid lesions and patients' sex or age. CONCLUSION: Most polypoid lesions of the gall bladder detected by ultrasonography are benign.

Aged↗

Characteristics of anti-HCV antibody-positive patients with hepatocellular carcinoma on chronic hemodialysis: recommendation of periodic ultrasonography for early detection.

We analyzed 10 patients (male:female 9:1, mean age 64.2 years) who developed hepatocellular carcinoma during the observation period of 2 years among 2,164 chronic hemodialysis patients in 23 dialysis centers. Among them, 409 patients were positive for serum anti-HCV antibodies (19%). They were all positive for serum anti-HCV antibodies but negative for HBs antigen. None of the anti-HCV antibody-negative patients developed hepatocellular carcinoma during this period. Although liver function tests of the patients were almost normal, pathological examination of the liver revealed chronic active hepatitis or cirrhosis. Periodic ultrasonographic examination is necessary for early detection of hepatocellular carcinoma in chronic hemodialysis patients with positive anti-HCV antibodies even if liver function tests are within normal ranges.

Aged↗

Non-neuronal release of ATP and inositol 1,4,5-trisphosphate accumulation evoked by P2- and M-receptor stimulation in guinea pig ileal segments.

Intracellular signal transduction involved in non-neuronal ATP release evoked by alpha, beta-methylene ATP and bethanechol was evaluated in guinea pig ileal longitudinal muscle segments. alpha, beta-methylene ATP (100 microM) and bethanechol (10 microM) evoked ATP released that reached a peak about 3 min after administration. The evoked release of ATP was markedly inhibited by neomycin and spermine, inhibitors of phospholipase C, but not by treatment with pertussis toxin. In addition, the release of ATP was almost completely suppressed by 1 mM Li+, an inhibitor of inositol monophosphatase. These inhibitors, however, did not affect the contractions of the tissue evoked by these agonists. Forskolin and phorbol 12-myristate 13-acetate, activators of adenylate cyclase and protein kinase C, respectively, failed to enhance the evoked release. The accumulation of inositol 1,4,5-triphosphate [Ins(1,4,5)P3] in the muscle segments were enhanced about 2 min after the administration of alpha, beta-methylene ATP. In the presence of 1 mM Li+, however, the enhancement of Ins(1,4,5)P3 accumulation by the P2 agonist was no longer elicited. These findings suggest that the release of ATP by receptor stimulation may result mainly from the activation of phospholipase C, which is coupled to a pertussis toxin-insensitive G-protein and subsequent accumulation of Ins(1,4,5)P3 in the smooth muscles. However, the discrepancy between the inhibitory effects of Li+ on the release of ATP and the accumulation of Ins(1,4,5)P3 to be clarified in future studies.

Adenosine Triphosphate↗

[Channel structure and functioning based on octagonal structure model].

On the basis of the sequence comparison of squid sodium channel SQSCl with those of other channels, we have proposed a tertiary structure model of the sodium channel where the transmembrane segments are octagonally aligned and the four linkers of S5-6 between segments S5 and S6 play a crucial role in the activation gate, voltage sensor and ion selective pore, which can slide, depending on membrane potentials, along inner walls consisting of segments S2 and S4 alternately. The proposed octagonal structure model is contrasted with that of Noda et al (Nature 320 : 188-192, 1986) and with Durrel and Guy (Biophys J 62 : 238-250, 1992). The octagonal structure model can explain the gating of activation and inactivation, the ion selectivity, and as well, the action mechanism of both tetrodotoxin (TTX) and a-scorpion toxin (ScTX), and be applied not only to the sodium channel, but also to the calcium channel, potassium channel, cGMP gated channel and further to the inwardly rectifying K channels. However Yan and Horn have discussed voltage dependent S4 movement in sodium channels from the accessibility of methanethiosulfonate (MTSET) to cystein residue which was substituted for the outermost arginine in IVS4 (Neuron 15 : 213-218, 1995), the neutralization of the arginine was revealed not to influence the activation of the channel. It suggest that the residue in the 3rd position of IVS4 is not a part of the voltage sensor located in the membrane. These result suggest that the change of the accessibility might be caused by the change of the covering of the residue rather than the movement of S4.

Amino Acid Sequence↗

Effect of alcohol drinking on gene expression of hepatic O6-methylguanine DNA methyltransferase in chronic liver diseases.

O6-methylguanine DNA methyltransferase (MGMT) is a repair protein that transfers methyl groups from O6-methylguanine to a cysteine acceptor in its own molecule, and restores DNA to its undamaged state. If left unrepaired, O6-methylguanine can pair with either a thymine or a cytosine, causing a C-G to T-A transition, which is considered to be one of the molecular mechanisms of both mutagenesis and carcinogenesis. The expression of MGMT mRNA in liver tissue was quantitatively assessed by the competitive reverse transcription-polymerase chain reaction method in patients with chronic liver diseases with or without alcohol drinking. MGMT mRNA expression was 1.4 +/- 0.9 pg/micrograms RNA in control livers. Its expression in chronic hepatitis was 3.8 +/- 0.7 in alcoholics and 2.7 +/- 0.8 in nonalcoholics, which were not statistically different. MGMT mRNA expression in liver cirrhosis was significantly low, compared with that in chronic hepatitis, and 0.8 +/- 0.3 in alcoholics and 0.5 +/- 0.1 in nonalcoholics, which also were not significantly different. The present study shows that MGMT mRNA was not decreased in patients with chronic liver diseases with alcohol drinking, compared with those without alcohol drinking.

Alcohol Drinking↗

Articles on AIDS in major Japanese newspapers.

People in general obtain knowledge about AIDS through the mass media. It is interesting to know how newspapers have dealt with AIDS in recent years, since newspapers are the most important mass media. The number of articles on AIDS from 1981 to 1994 was investigated in three major Japanese newspapers (Asahi, Yomiuri, and Mainichi) which are distributed nationwide. The first article appeared in 1982, and the number of articles gradually increased to a peak (total 785 articles) in 1987 when the first Japanese female patient was reported. Then, the number of articles decreased to 116 in 1989. The number of articles on AIDS in newspapers was not correlated with the reported number of patients.

Acquired Immunodeficiency Syndrome↗