Biomedical subjects

M Sata

Publications and source records attributed to M Sata.

At least 217 records · Page 12Linked to original sources

PubMed1996

Significance of serum tissue inhibitor of metalloproteinases-1 in various liver diseases.

BACKGROUND/AIMS: This study was performed to assess the significance of elevated serum tissue inhibitor of metalloproteinases-1 concentration in various liver diseases. METHODS: Tissue inhibitor of metalloproteinases-1 levels were measured in patients with various liver diseases, and were compared with serum type III procollagen-N-peptide (P III P), type IV collagen and laminin P1 levels, as well as with the histology of liver biopsy specimens. RESULTS: Mean tissue inhibitor of metalloproteinases-1 levels were significantly higher in subjects with acute viral hepatitis, cirrhosis, alcoholic hepatitis, and alcoholic cirrhosis than in the control group (p < 0.05). Serum tissue inhibitor of metalloproteinases-1 levels in the various liver diseases showed positive correlation with serum type IV collagen, P III P, and laminin P1 levels. Regarding the relationship between tissue inhibitor of metalloproteinases-1 and liver histology, serum tissue inhibitor of metalloproteinases-1 levels correlated with the degree of hepatic fibrosis and inflammation, such as focal necrosis and cell infiltration. Furthermore, elevated serum tissue inhibitor of metalloproteinases-1 levels were especially related to the cell infiltration, focal necrosis, portal fibrosis, and serum type IV collagen level. CONCLUSIONS: These findings suggest that the measurement of the serum tissue inhibitor of metalloproteinases-1 level in various liver diseases may be useful to estimate the active hepatic fibrogenesis associated with the active inflammatory stage of the liver injury.

Adult↗

PubMed1996

Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPases, inhibits the receptor-mediated endocytosis of asialoglycoproteins in isolated rat hepatocytes.

BACKGROUND/METHODS: The role of vacuolar type H(+)-ATPases (v-ATPases) and pH gradient between the endocytic compartments and cytoplasm in the endocytosis of asialoglycoproteins was morphologically investigated in isolated rat hepatocytes using bafilomycin A1, a specific inhibitor of v-ATPases. RESULTS: Fluorescent staining by acridine orange showed that bafilomycin A2 inhibited the acidification of the endocytic compartments. Uptake of gold-conjugated asialofetuin was significantly inhibited by bafilomycin A1. However, bafilomycin A1 did not significantly inhibit uptake of a fluid phase marker, horseradish peroxidase. The number of autophagic vacuoles increased after the bafilomycin A1 treatment. However, materials in the autophagic vacuoles were rapidly degraded after the removal of bafilomycin A1. CONCLUSIONS: Results suggest that: (a) v-ATPases are necessary for acidification of the endocytic compartments; (b) the pH gradient between the endocytic compartments and the cytoplasm which is generated by v-ATPases is necessary for the receptor-mediated endocytosis of asialoglycoproteins, and (c) v-ATPases may contribute to the degradation of the materials in autophagic vacuoles.

Animals↗

PubMed1996

Quantitative analysis of HCV RNA and genotype in patients with chronic hepatitis C accompanied by oral lichen planus.

Lichen planus (LP) is a common oral disorder that may represent a mucosal reaction to a variety of factors, including hepatitis C virus (HCV). To determine whether viral factors play a role in oral lichen planus (OLP) pathogenesis, we measured serum HCV RNA and determined HCV genotype in patients with chronic hepatitis C accompanied by OLP. The subjects included 43 patients with chronic hepatitis C: 23 with OLP (group 1) and 20 without OLP (group 2). Serum was collected from all subjects and used to quantify HCV RNA by the branched DNA signal amplification assay; HCV genotypes were classified by the reverse transcription-polymerase chain reaction (RT-PCR) method into types I, II, III and IV. Comparison of patient characteristics disclosed that the mean age of group 1, 60.7 years, was significantly higher (P = 0.001) than that of group 2 (46.4 years). No significant differences were seen between sexes in values of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein (T protein), albumin and gamma-globulin. There were also no significant differences in HCV RNA levels or HCV genotypes between groups. The findings suggested that OLP pathogenesis was a result of host factors rather than viral factors.

Adolescent↗

PubMed1996

Development and exacerbation of oral lichen planus during and after interferon therapy for hepatitis C.

Oral lichen planus (OLP) is frequently seen in patients with hepatitis C virus (HCV) infection. To clarify the role of HCV in OLP pathogenesis, we investigated the occurrence and progression of oral lesions in chronic hepatitis C patients treated with interferon. Oral surgeons examined 24 hepatitis C patients (15 men, nine women; mean age 48.1 years) for oral lesions before, during and after interferon (IFN) treatment. OLP was observed in 16.7% (4/24). Two patients had OLP before treatment, one during and one after treatment. Those who developed OLP during or after treatment had neither improvement nor disappearance of OLP even when serum HCV RNA became negative. Leucoplakia was seen in four patients before treatment and oral cancer in one patient 6 months after completing treatment. OLP can occur, exacerbate and persist during IFN treatment for hepatitis C, even when serum HCV RNA becomes negative. The present study suggested that OLP pathogenesis in hepatitis C is due to host factors induced by HCV infection rather than direct HCV participation. Treating physicians should be aware of OLP occurrence or exacerbation by IFN treatment with hepatitis C patients, but IFN therapy is not necessarily contraindicated in these patients.

Adult↗

PubMed1996

Functional differences between hepatocytes and biliary epithelial cells in handling polymeric immunoglobulin A2 in humans, rats, and guinea pigs.

Immunoglobulin A (IgA) in bile plays an important role in preventing the biliary tract from infection. In the present study, to clarify the functional differences between hepatocytes and biliary epithelial cells (BEC) in handling polymeric IgA2 (pIgA2), the major and important IgA in bile, we have determined in different species the binding characteristics of 125I-labeled pIgA2 to tissue sections of human, rat, and guinea pig livers. We have also examined the binding and transport features of 125I-labeled and gold-labeled pIgA2 in cultured hepatocytes and cultured BEC of rat and guinea pig. Asialofetuin, an asialoglycoprotein, or an antisecretory component antibody was used for determining the binding characteristics of pIgA2 to the cells. Grains of 125I-pIgA2 were morphometrically analyzed. In tissue sections, 125I-pIgA2 was predominantly bound to rat hepatocytes as well as to human and guinea pig BEC. The binding of 125I-pIgA2 to the cells was significantly inhibited by pretreatment with an antisecretory component (SC) antibody (P < .001), but not by preloaded asialofetuin. In cultured cells, labeled pIgA2 was observed binding predominantly to rat hepatocytes and guinea pig BEC as compared with rat BEC and guinea pig hepatocytes (both P < .001), respectively, and gold particles of gold-labeled pIgA2 were localized in the tubulovesicular structures and biliary luminal spaces of those cells. These results suggested that pIgA2 was bound selectively to hepatocytes in the rat liver, and to BEC in the human and guinea pig livers, through the SC but not through an asialoglycoprotein receptor, and was transported transcellularly and secreted into bile.

Animals↗

PubMed1996

Sequence variation of the hypervariable region in HCV carriers with normal ALT levels: a comparison with symptomatic carriers.

The clinical significance of the hypervariable region (HVR) in the N-terminus of the E2/NS1 region, which encodes the putative envelope glycoprotein (gp 70) of HCV, has not yet been elucidated. We studied the relation between HVR changes and elevation of the alanine aminotransaminase (ALT) level due to liver cell injury as well as the persistence of HCV infection. Three patients (carrier group) who were HCV RNA positive and had normal ALT levels for as long as five years and three patients with high ALT levels were studied. None of the six patients had a history of treatment. HCV RNA was extracted from serum obtained from each patient in 1990 and 1995. The E2/NS1 region, including HVR-1 and HVR-2, was amplified using the RT-PCR method. PCR products were cloned and nucleotide sequences were determined using the dideoxynucleotide chain termination method. No clear correlation was found between the ALT levels and the number of nucleotide substitutions in HVR-1. The number of nucleotide substitutions in HVR-1 during the five years was greater than in other regions. Furthermore, more nucleotide substitutions occurred in the 1st and 2nd codon positions of HVR-1 than in the control region, even in the carrier group. In conclusion, HVR-1 changes are probably a more important factor in persistent viral infection than liver cell injury.

Aged↗

PubMed1996

Hepatitis C virus infection in patients with clinically diagnosed alcoholic liver diseases.

To determine the incidence of hepatitis C virus (HCV) infection in patients with alcoholic liver disease (ALD), serum samples from 252 patients with ALD were tested for anti-HCV and HCV RNA. Serial sera of these patients were collected and stored under optimal conditions to allow exact quantification of HCV RNA. Fifteen patients who visited our hospital during the same period of time with chronic HCV infections served as controls. In those with ALD, anti-HCV and HCV RNA were positive in 55.5% and 41.2%, respectively. Patients with histologically diagnosed chronic hepatitis and hepatocellular carcinoma had much higher prevalence rates of HCV RNA (84% and 100%, respectively) compared to those with fatty liver (4.3%), hepatic fibrosis (10.1%) and alcoholic hepatitis (22.2%) (P < 0.01). Although no difference in serum HCV RNA levels was observed between the patients with both ALD and chronic HCV infection and those with chronic HCV infection alone, HCV RNA levels significantly (10-fold) dropped after abstinence in nearly half of the patients (P < 0.01). These data indicate that HCV infection in patients with ALD promotes progression of liver disease, and abstinence from alcohol is associated with a reduction in serum HCV RNA levels.

Adult↗

PubMed1996

Interferon accumulation in cirrhotic rat liver.

In patients with chronic hepatitis C, the therapeutic effect of interferon (IFN) is influenced by the progression of liver disease. In a previous study, we showed that 2',5'-oligoadenylate synthetase activity in the liver homogenate was significantly lower in cirrhotic rats than in controls after injection of murine IFN. To determine the reason for this decrease, we injected IFN into rats with thioacetamide-induced cirrhosis and used microautoradiography with human lymphoblastoid interferon ([125I]LyIFN). Accumulation of [125I]LyIFN in cirrhotic rat livers was approximately half of that in control rats (2880 +/- 900 vs 5770 +/- 600 mm2, P < 0.01). In the cirrhotic rat livers there were few grains on the hepatocytes, but many on collagen fibres. These results suggest that binding of IFN to its hepatocyte receptors is hindered in the presence of cirrhosis. The decreased amount of IFN reaching hepatocytes may contribute to the poor responses to IFN seen in patients with cirrhosis.

Animals↗

PubMed1996

Higher elimination rate of hepatitis C virus among women.

The mortality rate from liver disease in H town of the Fukuoka prefecture in Japan is significantly higher in men than in women. To clarify the gender-related difference, we evaluated subjects with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in the S area of this town. A total of 824 adults participated in this study, 332 men and 492 women. The incidence of positivity for hepatitis B surface antigen (HBsAg) in serum did not differ significantly between the subjects in the S area (1.9%) and Japanese blood donors (1.5%); however, the incidence of positivity for serum antibody to hepatitis C virus (HCVAb) in the subjects (31.8%) greatly exceeded that in Japanese blood donors (1.3%). The rate of positivity for HCVAb did not differ significantly between men (28.3%) and women (34.1%), but the proportion of serum HCV RNA-positive to HCVAb-positive subjects was significantly higher in men (78.2% in men vs 67.3% in women). The incidence of elevated serum alanine aminotransferase (ALT) in subjects positive for serum HCV RNA was also significantly higher in men (77.0% in men vs 55.8% in women). These results suggest that a more frequent elimination of HCV from serum in women may explain the observed lower mortality from liver disease.

Adult↗

PubMed1996

Biological responses to administered interferon in alcoholics.

To elucidate the influence of chronic alcohol intake on interferon (IFN) therapy in patients with various diseases, 3 million units of natural IFN (nHuIFN-alpha Ly) was administered once to alcoholics, nonalcoholic chronic hepatitis C (CH-C) patients, and healthy subjects. The serial changes of serum activity of 2'-5' oligoadenylate synthetase, serum levels of beta 2-microglobulin, C-reactive protein (CRP), and body temperature were monitored. The increase in the activity of 2'-5' oligoadenylate synthetase, the response of serum-reactive protein, and body temperature after IFN administration were significantly lower in the alcoholics than those in CH-C group, and healthy subjects (control group). The serum beta 2-microglobulin level was already higher in the alcoholics before IFN administration than those of the control group and the CH-C group. These findings suggest that physiological responses to exogenous IFN in alcoholics are generally decreased. Hence, for the maximum effect of IFN therapy, it is important for patients to abstain from alcohol intake and for doctors to carefully consider the timing of initiation.

2',5'-Oligoadenylate Synthetase↗

PubMed1996

Usefulness of technetium-99m-galactosyl human serum albumin liver scintigraphy for assessment of severity of alcoholic hepatitis.

We performed a liver scintigraphy using technetium-99m diethylene-triaminepentaacetic acid-galactosyl human serum albumin (99mTc-GSA), which images the functional liver mass through its binding to the specific receptor asialoglycoprotein receptor in patients with severe alcoholic hepatitis. Receptor index (LHL 15) was significantly lower in patients with alcoholic hepatitis, compared with controls with normal liver. Difference in the isotope uptake patterns between liver and heart varied according to the severity of liver disease, and made it possible to categorize 5 grades. Grading score could discriminate between the eventual outcome of the patients. Furthermore, single photon emission computed tomography showed the variable uptake patterns in the hepatic lobule, wherein there were no evident findings in macroscopic view at autopsy. The results of this study show the usefulness of 99mTc-GSA scintigraphy in the evaluation and prognosis of alcoholic hepatitis.

Adult↗

PubMed1996

Detection of serum HBV DNA and anti-HCV antibody in HBsAg seronegative patients with hepatocellular carcinoma in Japan.

One hundred eight patients with hepatocellular carcinoma (HCC) underwent serologic testing for HBsAg, antibodies to HBs (anti-HBs), HBc (anti-HBc) and HCV (anti-HCV), and an assay for hepatitis B virus (HBV) DNA by the polymerase chain reaction (PCR). Ten (9.3%) of the 108 patients were positive for HBsAg and 96 (88.8%) were positive for anti-HCV. Both HBsAg and anti-HCV were present in 4 (3.7%) of the 108 patients. HBV DNA was detected in the serum of all patients who were positive for HBsAg and 9 (9.2%) of the 98 patients who were HBsAg-negative. Anti-HBc was positive and anti-HBs was negative in 8 of these 9 HBsAg negative patients with HBV DNA. HBsAg, HBV DNA and anti-HCV were negative in 6 (5.5%) of the 108 patients. These results suggest that HCV is highly associated with HCC and that HBV is occasionally associated with HCC even when HBsAg is negative.

Aged↗

PubMed1996

Evaluation of interferon treatment in cirrhotic patients with hepatitis C.

The aim of this study was to examine the effects of interferon on cirrhotic patients with hepatitis C and the incidence of adverse reactions. The subjects were 35 cirrhotic patients, and 29 chronic active hepatitis patients without cirrhosis (CAH) served as controls. The cirrhotic patients received 3 or 6 million units of human lymphoblastoid interferon daily for one or two weeks and then three times a week for 22 or 23 weeks, while the CAH patients received 6 million units daily for 2 weeks and then three times a week for 14 or 16 weeks. Discontinuation of interferon treatment or dose reduction was required in the 7 cirrhotic patients. The most frequent reason was thrombocytopenia. Dose reduction alone was necessary in two CAH patients. Five cirrhotic patients (14.3%) and nine CAH patients (31.0%) were classified as complete responders to interferon treatment. In all five complete responders with cirrhosis, the hepatitis C virus RNA level before treatment was less than 5 log copies/50 microliters. The results of this study confirm the beneficial effect of interferon in selected patients with cirrhosis on basis of pre-treatment virus levels and platelet count.

Base Sequence↗

PubMed1996

Sequential interferon-alpha and beta treatment in patients with chronic hepatitis C.

To assess the effectiveness and side effects of sequential interferon (IFN)-alpha and beta treatment for patients with chronic hepatitis C, 25 patients were enrolled in a trial of this regimen. The patients were given 6 million units (MU) of natural human INF-beta daily for 2 weeks followed by 6 MU of natural human IFN-alpha three times a week for 10 to 22 weeks. Serum alanine aminotransferase (ALT) levels normalized for at least 24 weeks in 10 patients (40%), of whom 4 (40%) had no detectable serum hepatitis C virus (HCV) RNA. Three variables were significant in predicting a sustained response: a low serum HCV RNA level, a low Knodell's fibrosis score, and a low indocyanine green retention rate at 15 minutes. Elevated serum ALT and proteinurea were observed with IFN-beta treatment but these side effects were mild and disappeared when INF-beta treatment ended. While all patients completed the entire regimen, we concluded that sequential IFN-alpha and beta treatment provides no additional antiviral effects in chronic hepatitis C.

Alanine Transaminase↗

PubMed1996

Inhibitory effect of antineoplaston A10 and AS2-1 on human hepatocellular carcinoma.

Antineoplastons, first described by Burzynski, are naturally occurring peptides and amino acid derivatives which control neoplastic growth. Antineoplaston A10 (3-pehnylacetylamino-2,6-piperidinedion) is the first chemically identified antineoplastons and when it is administered orally it is hydrolysed in pancreatic juice to phenylactylglutamine and phenylacetylisoglutamine in the ration of 4 to 1. These metabolites are water soluble and have antitumor effect, they are further degraded to pehnylacetic acid. The mixture of phenylacetylglutamine and phenylacetylisoglutamine in the ratio of 4 to 1 was formulated as Antineoplaston A10 injectable formulation. The mixture of phenylacetylglutamine and phenylacetic acid in the ratio of 1 to 4 was also shown to have antitumor effect in tissue culture study, then formulated as Antineoplaston AS2-1. The reported cytostatic inhibitory effect of A10 on human hepatocellular carcinoma cells and differentiation inducing effect of AS2-1 on various tumor cells suggest potential benefit for the treatment of human hepatocellular carcinoma since this tumor recurs frequently despite initial successful treatment. We report here the effects of Antineoplaston A10 and AS2-1 on cell proliferation, cell morphology, cell cycle, and DNA in human hepatocellular carcinoma cell lines. Both agents inhibited cell proliferation and increased the number of cells in G0 and G1 phases and Antineoplaston AS2-1 induced apoptosis, we also describe our clinical experience of a hepatocellula carcinoma (HCC) patient whose tumor, after incomplete trancathere arterial embolization (TAE) for a 7cm 7cm HCC, has been stable for more than 15 months during which time he has been taking Antineoplaston AS2-1 continuously without any serious adverse effects.

Antineoplastic Agents↗

PubMed1996

An experimental animal model of primary biliary cirrhosis induced by lipopolysaccharide and pyruvate dehydrogenase.

Previously, we found that the antibody titer belonging to the IgM class produced against the bacterial antigen (Lipid A) was elevated in sera from patients with primary biliary cirrhosis (PBC). On the other hand, the targets of the mitochondrial autoantibodies have been identified as being components of the pyruvate dehydrogenase complex (PDH). We tried to produce an experimental animal model for the investigation of the association between hepatic bile duct alteration and bacterial infection. Female C57/BL mice, aged 4 weeks, were used. An emulsion consisting of lipopolysaccharide (LPS) derived from Salmonella minnesota Re595, PDH, and Freund's adjuvant was prepared. This emulsion was subcutaneously injected on the back of the mice. The mice were divided into a control group (n = 5), a group given LPS (n = 5) alone, those given PDH alone (n = 5), and those given a combination of LPS and PDH (n = 5). The antigens were administered once a week every week with a maximum duration of administration of 24 weeks. The serum levels of IgM after 24 weeks in the LPS and LPS + PDH groups were 2.5 times higher than those in the control and PDH groups. The light microscopic findings of liver tissue revealed that infiltration of lymphocytes and plasma cells in the portal area, proliferation of the bile duct, and degeneration of the biliary epithelial cells were more prominent in the PDH and LPS + PDH groups than in the other groups. These results indicate that our animal model may be useful in investing the pathogenesis of PBC.

Animals↗

PubMed1996

A patient with chronic hepatitis C and a history of abuse of analeptic drugs, who showed hallucination and delusion with interferon administration.

We experienced a case of chronic hepatitis type C accompanied with hallucination and delusion induced by interferon (IFN) therapy positive. The case was a 47-year-old male, whose laboratory data showed positive for anti-Hepatitis C Virus (HCV) and elevated transaminase level. He was treated with 6 MU/day of natural-type IFN-alpha (HLBI). Sleeplessness and delusions of persecution developed about 2 months after the start of IFN therapy. The interview of the psychiatrist disclosed that the patient had a history of addiction to drugs, and these psychiatric symptoms were diagnosed as being of "the flashback phenomenon." These side effects were improved after the administration of psychotropics and it was suggested that we had to take care of the development of flashback phenomenon during the treatment of IFN in cases of chronic hepatitis with a history of addiction to drugs.

Delusions↗

PubMed1996

Oral cancer and hepatitis C virus (HCV): can HCV alone cause oral cancer?--a case report.

Previously, we reported the high prevalence of hepatitis C virus (HCV) infection in patients with oral cancer or oral lichen planus in Kyushu, Japan. We now report a 61-year-old man with chronic hepatitis C and no oral lesions who developed oral cancer 6 months after interferon therapy (interferon alpha [HLBI], 6 million units (MU) daily for 2 weeks and then 3 times a week for 14 weeks). This case emphasizes the need for periodic oral cavity examinations of hepatitis C patients and contributed to the investigation of oral cancer and HCV.

Hepacivirus↗