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Biomedical subjects

Y Murawaki

Publications and source records attributed to Y Murawaki.

At least 19 recordsLinked to original sources
PubMed1999

Clinical usefulness of serum tissue inhibitor of metalloproteinases (TIMP)-2 assay in patients with chronic liver disease in comparison with serum TIMP-1.

Tissue inhibitors of metalloproteinases (TIMPs) are involved in liver fibrosis through impaired matrix degradation. Previous studies showed that the serum level of TIMP-1 was increased in patients with chronic liver disease, reflecting the liver TIMP-1 level, and that it is useful for assessing liver fibrosis. An enzyme immunoassay for TIMP-2 is now available. In this study, we examined the clinical usefulness of this serum TIMP-2 test for liver fibrosis in patients with chronic liver disease, in comparison with the serum TIMP-1 test. The serum TIMP-2 concentration was 61 +/- 13 ng/ml in healthy controls (n = 32), and 18% higher in the group of chronic active hepatitis (CAH) patients (n = 34), 64% higher in the liver cirrhosis (LC) group (n = 33) and 44% higher in the hepatocellular carcinoma (HCC) group (n = 61), and similar to the control level in the chronic persistent hepatitis (CPH) group (n = 23). In contrast, the serum TIMP-1 concentration was 155 +/- 17 ng/ml in the healthy controls, 18% higher in CPH, 35% in CAH, 63% higher in LC and 92% higher in HCC. The serum TIMP-2 level was related to the histological degrees of both periportal necrosis and liver fibrosis, as well as to the serum TIMP-1 level. However, the relationships for TIMP-2 were weaker compared to those of serum TIMP-1. These results suggest that compared to the serum TIMP-1 level, changes in the serum TIMP-2 level in chronic liver disease are less liver-specific, and the serum TIMP-2 level is less useful in the assessment of liver fibrosis in chronic liver disease.

Adult↗
PubMed1999

Clinical usefulness of serum matrix metalloproteinase-2 concentration in patients with chronic viral liver disease.

BACKGROUND/AIMS: The production of matrix metalloproteinase (MMP)-2 was reported to be increased in chronically diseased livers. Our aims in the present study were to elucidate the clinical usefulness of the serum MMP-2 concentration in chronic viral liver disease. METHODS: We measured serum MMP-2 concentrations with a sandwich enzyme immunoassay in 62 patients with chronic hepatitis, 35 patients with liver cirrhosis, 55 patients with hepatocellular carcinoma and 24 healthy individuals. The assay detects proMMP-2 and proMMP-2 complexed with tissue inhibitor of metalloproteinase-2, but not active forms of MMP-2. The liver MMP-2 content was also measured in autopsied cirrhotic and non-cirrhotic livers. Gelatin zymography and gel filtration chromatography were carried out using the serum. RESULTS: The serum MMP-2 concentration was significantly increased in the liver cirrhosis and hepatocellular carcinoma patients, but not in the patients with chronic hepatitis. There was no significant difference in the serum MMP-2 level between the liver cirrhosis and hepatocellular carcinoma groups. In the patients with chronic viral liver disease, serum MMP-2 concentration showed the best correlation with the degree of liver fibrosis and with serum hyaluronate level. The zymography of serum showed the majority of MMP-2 in serum exists as a proMMP-2. The chromatography of serum revealed a single peak at the position of about 90 kDa corresponding to an MMP-2 complexed with tissue inhibitor of metalloproteinases-2. The liver MMP-2 content was markedly increased in the cirrhotic livers compared with the non-cirrhotic livers, and was positively correlated with the liver collagen content. When investigating the utility of the serum MMP-2 test for differentiating liver cirrhosis from chronic hepatitis, the utility of serum MMP-2 was equal to that of serum hyaluronate, which is known as the best current test for diagnosing liver cirrhosis. CONCLUSIONS: The serum MMP-2 concentration reflects mainly the amount of proMMP-2 complexed with tissue inhibitor of metalloproteinase-2. The serum MMP-2 level was markedly increased in cirrhotic patients, and may be explained by an overproduction in the cirrhotic liver. In the clinical state, the measurement of serum MMP-2 was as useful a test for diagnosing liver cirrhosis as is the serum hyaluronate level.

Biomarkers↗
PubMed1999

Serum matrix metalloproteinase-1 in patients with chronic viral hepatitis.

BACKGROUND AND AIMS: Previously we found that serum matrix metalloproteinase (MMP)-1 activity decreased with progression of chronic liver disease. Our objectives in the present study were to observe the change in the serum MMP-1 protein concentration using recently developed specific enzyme immunoassays for MMP-1 and MMP-1 complexed with tissue inhibitor of metalloproteinases (TIMP)-1 and to elucidate the clinical usefulness of the serum MMP-1 test in chronic viral hepatitis. We measured the serum concentrations of MMP-1 and MMP-1/TIMP-1 complex using these immunoassays in 64 patients with histologically characterized chronic viral hepatitis. RESULTS: Serum MMP-1 concentration was inversely related to the histological severity of chronic hepatitis (P< 0.0001). It was closely associated with the histological degree of periportal necrosis (P< 0.0001), intralobular necrosis (P< 0.005), portal inflammation (P<0.0001) and liver fibrosis (P< 0.05). The serum concentration of MMP-1/TIMP-1 complex was also related to the histological severity of chronic hepatitis (P< 0.0001). It was associated with the degree of portal inflammation (P< 0.05), but not with the degree of periportal necrosis, intralobular necrosis or liver fibrosis. As serum MMP-1 level was closely associated with the histological degree of necroinflammation, we examined the ability of the serum MMP-1 test to differentiate active and inactive forms of hepatitis with a receiver operating curve. The results were compared with those of serum procollagen type III N-peptide (PIIINP) test. We found that the serum MMP-1 test was superior to the serum PIIINP test in assessing liver necroinflammation. CONCLUSIONS: In addition to the previously reported changes in enzyme activity, MMP-1 proteins in serum decreased during histological progression of chronic hepatitis. The serum MMP-1 test may be useful clinically to differentiate active and inactive types of hepatitis in patients with chronic viral hepatitis.

Biomarkers↗
PubMed1999

Prognosis for pedunculated hepatocellular carcinoma.

We retrospectively compared the outcome of 13 patients at our institution and that of 163 reported cases of pedunculated hepatocellular carcinoma (HCC) with that of conventional HCC subdivided by tumor diameter (group A: less than 2 cm; group B: 2-5 cm, group C: more than 5 cm). The survival of patients with pedunculated HCC in the 163 reported cases was no different from that of group B, but less favorable than in group A (p < 0.01) and more favorable than in group C (p < 0.01). Among the 163 patients with pedunculated HCC, the 113 cases of surgically treated patients had higher survival than the 21 patients treated with transcatheter arterial embolization (n = 16) or transcatheter arterial infusion chemotherapy (n = 5) (p < 0.01) and than 29 conservatively treated patients (p < 0.001). A total of 70 patients out of 163 (42%) died within 1 year after diagnosis. Additionally, almost all cases of pedunculated HCC showed histologically moderately or poorly differentiated characteristics according to Edmondson and Stainer's classification or the WHO classification. These results suggest that pedunculated HCC has not a favorable prognosis if appropriate surgical resection has not been performed very early within a few months because of its rapid progressive nature.

Adult↗
PubMed1998

Plasma transforming growth factor-beta 1 concentrations in patients with chronic viral hepatitis.

Transforming growth factor (TGF)-beta 1 is an important cytokine involved in the pathobiology of tissue fibrosis through its stimulation of the production of, and inhibition of the degradation of, extracellular matrix proteins. We examined the clinical usefulness of plasma TGF-beta 1 concentration as a marker of fibrogenesis in patients with chronic viral hepatitis. Thirty-five patients, 11 with minimal chronic hepatitis, 14 with mild chronic hepatitis and 10 with moderate chronic hepatitis and 20 healthy subjects were studied. Transforming growth factor-beta 1 concentrations in platelet-poor plasma were measured with a TGF-beta 1 enzyme-linked immunosorbent assay system kit after acid-ethanol extraction. Plasma TGF-beta 1 levels were significantly elevated in patients with mild and moderate chronic hepatitis, but not in those with minimal chronic hepatitis, compared with the levels in the controls. Plasma TGF-beta 1 levels were increased in parallel with the histological degree of necroinflammation and of liver fibrosis. Plasma TGF-beta 1 levels were positively correlated with blood levels of procollagen type III N-peptide, and 7S fragment and central triple-helix of type IV collagen. These results suggest that plasma TGF-beta 1 level is a useful marker in assessing the situation of liver active fibrogenesis in patients with chronic viral hepatitis.

Biomarkers↗
PubMed1998

Post-prandial serum hyaluronan concentration in patients with chronic liver disease.

Serum hyaluronan measurement is an option for diagnosing cirrhosis and assessing liver fibrosis, but it is of little use in the diagnosis of chronic hepatitis and compensated liver cirrhosis. It is generally known that intake of food results in elevation of the serum hyaluronan concentration. This work was designed to determine whether a change in the serum hyaluronan concentration after eating might reflect the hepatic sinusoidal endothelial cell impairment in chronic liver diseases. The chronological measurement of serum hyaluronan concentration after eating was performed after an overnight fast in 31 patients with chronic hepatitis, 31 cirrhotic patients, and 8 healthy subjects. The hyaluronan concentration in the loading test increased with the severity of the liver disease in the patients with chronic hepatitis, being significantly higher in the patients with moderate or a higher grade of necroinflammation than in those with a minimal grade, and also significantly higher in patients with stage 3 fibrosis than in those with stage 2 or less. The elevation of the concentration after eating in patients with liver cirrhosis was marked and the range did not overlap with that in patients with chronic hepatitis. Even in 14 patients with compensated liver cirrhosis whose hyaluronan concentration pre-prandially was less than 200 ng/ml, the range of the post-prandial peak concentration did not overlap with that in the chronic hepatitis patients. These results suggest that the evaluation of post-prandial serum hyaluronan concentration is potentially useful for assessing the grading of necroinflammation and staging of fibrosis in patients with chronic hepatitis, as well as for diagnosing compensated liver cirrhosis.

Biomarkers↗
PubMed1998

Molecular weight of hyaluronate in the serum of patients with chronic liver disease.

Hyaluronate in tissue and lymph is known to be heterogenous and to show a wide range of molecular weights (10(4) to 10(7) Da). Serum hyaluronate concentrations are increased under various pathophysiological conditions such as liver disease, post-gastrectomy, and after the ingestion of food. To clarify whether the chromatographic patterns of hyaluronate in serum from patients with chronic liver disease are different under these conditions, we subjected sera to chromatography using a Sephacryl S 400 HR column. The chromatograms revealed that the hyaluronate in serum was eluted as a single peak at the position corresponding to the molecular weight of blue dextran, the molecular weight being more than 2 x 10(6) Da. The patterns of the chromatogram were similar among the patients with liver disease and the healthy subject although the heights of the peaks were different. Ingestion of food and a history of gastrectomy for gastric cancer did not influence the elution patterns of serum hyaluronate. These results indicate that hyaluronate in serum has molecular weight of more than 2 x 10(6) Da, and that its elution patterns are not influenced by pathophysiological factors, such as the severity of liver disease, or history of gastrectomy or by food intake in patients with chronic liver disease.

Adult↗
PubMed1997

Serum carbohydrate-deficient transferrin in patients with nonalcoholic liver disease and with hepatocellular carcinoma.

Serum carbohydrate-deficient transferrin (CDT) is used as a reliable and specific marker of alcohol consumption. However, recent studies have shown false-positive CDT test results in nonalcoholic liver disease. We examined the clinical significance of serum CDT in nonalcoholic liver disease, especially hepatocellular carcinoma. Serum CDT was measured in 23 teetotallers, 56 patients with alcoholic liver disease, 84 patients with viral liver disease and 67 patients with hepatocellular carcinoma, with an Axis %CDT radioimmunoassay kit, and the results were expressed as percentages of the total transferrin (%CDT). The mean serum %CDT value was increased 1.8-fold in alcoholic liver fibrosis and 3.8-fold in alcoholic liver cirrhosis compared with the teetotallers. The serum %CDT values in viral chronic hepatitis were similar to those of the teetotallers, and were increased 2.0-fold in viral liver cirrhosis. False-positive results were found in 10 (37%) of the 27 patients with viral liver cirrhosis. The mean serum %CDT value was increased 2.5-fold in hepatocellular carcinoma, and false-positive results were found in 31 (46%) of the 67 patients. The serum %CDT value was related to the severity of Child grade, the size of tumor and the grade of histological differentiation. These results suggest that the ability of serum CDT test to detect chronic alcoholism may be reduced in patients with nonalcoholic liver cirrhosis and those with hepatocellular carcinoma.

Adult↗
PubMed1997

Tissue inhibitor of metalloproteinase-1 in the liver of patients with chronic liver disease.

BACKGROUND/AIMS: Tissue inhibitor of metalloproteinase (TIMP)-1 is an important regulator of matrix metalloproteinase activity. To clarify the changes in TIMP-1 in diseased livers, we measured TIMP-1 concentrations in liver tissue samples from patients with chronic liver disease. The relationship between serum and liver levels of TIMP-1 was also examined in some patients. METHODS: The subjects were 68 patients who underwent liver biopsy. The liver TIMP-1 concentration was measured using an enzyme immunoassay after the extraction of TIMP-1 with 2 M guanidine. RESULTS: As compared with the controls (n=10), the liver TIMP-1 level was increased 2.2-fold in the 24 chronic active hepatitis 2A patients, 2.9-fold in the 10 chronic active hepatitis 2B patients and 4.1-fold in the six liver cirrhosis patients, but no significant increase was observed among the 18 chronic persistent hepatitis patients. The liver TIMP-1 levels were closely correlated with the histological degrees of periportal necrosis, portal inflammation, and liver fibrosis. When the localization of TIMP-1 was examined immunohistochemically, TIMP-1 was stained mainly in hepatocytes, and the intensity was stronger in the livers of chronic active hepatitis and liver cirrhosis patients than in those of the chronic persistent hepatitis patients. The serum TIMP-1 and liver TIMP-1 levels were significantly correlated, indicating that serum TIMP-1 could reflect the change of liver TIMP-1 in patients with chronic liver disease. CONCLUSION: Liver TIMP-1 concentration increases with progression of the liver disease, when the degradation of extracellular matrix proteins is decreased, resulting in the development of liver fibrosis.

Adult↗
PubMed1996

Collagen-binding activity of plasma vitronectin in chronic liver disease.

The collagen-binding activity of plasma vitronectin was measured in 15 control subjects and 64 subjects with chronic liver disease. The assay of collagen-binding vitronectin was performed by an enzyme immunoassay using a monoclonal antibody to human vitronectin and type I collagen from human placenta. The plasma collagen-binding vitronectin concentration (mean +/- S.D.) was 5.6 +/- 1.9 micrograms/ml in the controls, 8.3 +/- 1.1 micrograms/ml in chronic persistent hepatitis, 8.3 +/- 2.9 micrograms/ml in chronic active hepatitis, 7.8 +/- 2.9 micrograms/ml in liver cirrhosis and 8.2 +/- 2.1 micrograms/ml in hepatocellular carcinoma with cirrhosis. The percent collagen-binding vitronectin to total plasma vitronectin was 2.2 +/- 0.8% in the controls, 3.9 +/- 2.2% in chronic persistent hepatitis, 3.9 +/- 1.2% in chronic active hepatitis, 5.8 +/- 3.3% in liver cirrhosis and 4.1 +/- 1.2% in hepatocellular carcinoma with cirrhosis. The plasma collagen-binding vitronectin also correlated with the serum levels of 7S collagen and hyaluronic acid. These findings suggest that vitronectin may play an important role in the progression of liver disease and/or in hepatic fibrosis through its collagen-binding domain.

Aged↗
PubMed1996

Comparison of serum 7S fragment of type IV collagen and serum central triple-helix of type IV collagen for assessment of liver fibrosis in patients with chronic viral liver disease.

BACKGROUND/AIMS: A competitive radioimmunoassay for serum 7S fragment of type IV collagen (7S collagen) using a polyclonal antibody against 7S collagen and a sandwich enzyme immunoassay for serum central triple-helix of type IV collagen (IV collagen) using two monoclonal antibodies against the pepsin-solubilized type IV collagen may be used as diagnostic aids for liver fibrosis in clinical medicine. We compared the clinical usefulness for assessing liver fibrosis of serum 7S collagen and IV collagen tests in chronic viral liver diseases, and also examined the elution pattern of 7S collagen- and IV collagen-related antigens in serum by gel filtration analysis. METHODS: Serum 7S collagen and IV collagen levels were assayed in 151 patients with chronic viral liver disease and 30 healthy control subjects. RESULTS: Gel filtration on the Sephacryl S400HR column revealed that the 7S collagen antigenicity in serum was heterogeneous, whereas the IV collagen antigen in serum was uniform in size. Serum levels of 7S collagen and IV collagen showed increases closely correlated with the severity of liver disease. The abnormal percentage of 7S collagen in three patient groups was similar to that of IV collagen in the corresponding groups. Serum 7S collagen and IV collagen levels were strongly correlated with the histological degree of liver fibrosis; the correlation coefficients were r = +0.675 for 7S collagen and r = +0.665 for IV collagen. When we assessed the ability of each test to detect cirrhosis with a receiver operating curve, the serum 7S collagen test was a slightly better marker than the serum IV collagen test. For the detection of cirrhosis, serum 7S collagen was 83% sensitive and 88% specific at a cutoff value of 9 ng/ml, and serum IV collagen was 80% sensitive and 81% specific at a cutoff value of 160 ng/ml. CONCLUSIONS: These findings suggested that serum 7S collagen and IV collagen tests are similarly useful for assessing liver fibrosis in patients with chronic viral liver disease, although the former is slightly better for diagnosing cirrhosis than the latter.

Adult↗
PubMed1996

Serum markers for fibrosis and plasma transforming growth factor-beta 1 in patients with hepatocellular carcinoma in comparison with patients with liver cirrhosis.

In order to elucidate collagen metabolism in hepatocellular carcinoma (HCC) tissue, we compared levels of different potential markers of collagen metabolism and plasma transforming growth factor-beta 1 in patients with HCC and in patients with liver cirrhosis. Serum levels of prolyl hydroxylase and the tissue inhibitor of metalloproteinase-1 in patients with HCC were significantly higher than those in patients with liver cirrhosis and increased with the size of the HCC tumour, whereas the serum levels of procollagen type III propeptide and type IV collagen 7S domain were similar in the two groups. In HCC, the increased plasma transforming growth factor-beta 1 levels were closely correlated with serum levels of prolyl hydroxylase and the tissue inhibitor of metalloproteinase-1. These findings suggest that, in HCC tissue, the intracellular biosynthesis of collagen is enhanced, whereas the secretion of procollagen is disturbed and the degradation of collagen is suppressed by the excess production of the tissue inhibitor of metalloproteinase-1. The results also suggest that plasma transforming growth factor-beta 1 plays an important role in the altered metabolism of collagen in HCC.

Aged↗
PubMed1996

Clinical significance of serum hyaluronan in patients with chronic viral liver disease.

In order to elucidate the clinical significance of serum hyaluronan in chronic viral hepatitis, serum hyaluronan concentrations were measured using a sandwich enzyme binding assay in 115 patients with chronic viral hepatitis. These findings were examined in relation to the results of laboratory liver tests, levels of serum markers for fibrosis and liver histological findings. Serum hyaluronan levels increased with the progress of liver disease, particularly in liver cirrhosis. There were no significant differences in serum hyaluronan levels among the cirrhotic patients according to Child's grade. Multivariate analysis showed that the significant independent predictors of serum hyaluronan were serum aspartate aminotransferase (P = 0.020), serum alanine aminotransferase (P = 0.008), serum cholinesterase (P < 0.001), particularly serum type IV collagen 7S domain (P < 0.0001), and the histological degree of liver fibrosis (P < 0.0001). These findings suggest that elevated serum hyaluronan levels are closely related to the severity of liver fibrosis. We assessed the predictive value of serum hyaluronan in differentiating cirrhosis from chronic hepatitis, constructing receiver operating curves; we found that serum hyaluronan was a better test for diagnosing cirrhosis than serum type IV collagen 7S domain and laboratory liver tests.

Adult↗
PubMed1995

Clinical evaluation of a monoclonal antibody to serum KM01 for the diagnosis of hepatocellular carcinoma.

In order to evaluate a monoclonal antibody KM01 which was developed in mice immunized against a human colon carcinoma cell line, serum levels of KM01 and other tumor markers were studied in patients with both hepatocellular carcinoma and liver cirrhosis and in patients with liver cirrhosis alone. The KM01 levels in the sera of 50 patients with hepatocellular carcinoma plus liver cirrhosis and 50 patients with liver cirrhosis were measured using an enzyme immunoassay method and compared with various tumor markers including alpha-fetoprotein (AFP), DUPAN-2, and protein induced vitamin K absence or antagonist-II (PIVKA-II). The mean serum level (+/- S.D.) and sensitivity of KM01 in patients with hepatocellular carcinoma plus liver cirrhosis were 734 (+/- 716) units/ml and 64%, respectively, and they were significantly higher than those of liver cirrhosis patients (P < 0.001). Three out of 9 cases showing negative serum AFP levels had positive serum KM01 levels. Although the sensitivity of serum KM01 level for hepatocellular carcinoma was inferior to serum AFP and plasma PIVKA-II values, the sensitivity of a combination assay of serum KM01 or AFP was increased to 88%. Clinical data of the patients with markedly elevated serum KM01 levels (more than 1000 units/ml) were compared with patients with moderately elevated levels (530-1000 units/ml); serum bilirubin and alkaline-phosphatase were statistically higher in the former group (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Serum markers for connective tissue turnover in patients with chronic hepatitis B and chronic hepatitis C: a comparative analysis.

BACKGROUND/AIMS: Clinical and pathological differences between chronic hepatitis B and chronic hepatitis C have now been established. METHODS: To compare hepatic connective tissue metabolism in chronic hepatitis B and C, we determined serum levels of prolyl 4-hydroxylase beta-subunit, procollagen III aminoterminal peptide, type IV collagen 7S domain, the central helix region of type IV collagen, tissue inhibitor of metalloproteinase, and hyaluronan in 55 patients with chronic hepatitis B and 83 patients with chronic hepatitis C. RESULTS: There were no significant differences in the above markers for connective tissue turnover between the chronic hepatitis B group and the chronic hepatitis C group. CONCLUSIONS: These results suggest that the accelerated connective tissue metabolism observed in chronic viral hepatitis is independent of the causative virus.

Adult↗