Of 83 patients with chronic hepatitis C who were treated with interferon (IFN), 32 patients (39%) showed the clearance of HCV RNA from serum at six months after the completion of IFN (responder). Response to IFN occurred in 14 (74%) of 19 patients infected with HCV genotype III/2a and in 6 (50%) of 12 with genotype IV/2b, more frequently than in 10 (20%) of 47 with genotype II/1b (p<0.001, p<0.05).
There were 4 patients who were infected with two HCV strains of different genotypes (II/1b+III/2a, 2 patients, II/1b+IV/2b, 2 patients). One of these 4 patients with mixed genotype responded to IFN. Titers of total and genotype-specific HCV RNA were followed subsequently in serum from these 4 patients. The decrease in HCV RNA titers was observed irrespective of HCV genotypes, as a result, antiviral effect seemed to appear stronger to minor genotype than to major genotype in patients with chronic hepatitis C who were infected with mixed genotypes.

View full abstract

Immunohistochemical study on p53 overexpression was performed by pretreatment with microwave oven heating as antigen retrieval using anti-p53 monoclonal antibody (DO-7). The materials were forty-eight formalin-fixed, paraffin-embedded tissue sections of the resected human hepatocellular carcinomas (HCCs) during recent 15 months in my department.
Nuclear staining of p53 was positive in 12/48 (25.0%) by this microwave pretreatment, while none of them was stained without this pretreatment. The results of staining by this method were significantly correlated with those on fresh-frozen tissue sections stained by conventional method (p<0.0001).
The tumor sizes of all p53 overexpression cases with this method were more than 2cm in diameter. P53 was not overexpressed in massive type of HCCs, while positive rate of p53 overexpression was significantly higher in multinodular-fused type (p<0.05). Well-differentiated type of HCCs has no p53 overexpression, while moderately and poorly differentiated ones showed significantly higher positive rate of p53 overexpression (p<0.05). HCCs of positive HCV-Ab, vp and fc-inf factor showed higher positive rate of p53 overexpression comparing with those of negative ones. Aneuploid HCCs showed higher positive rate of p53 overexpression than diploid ones. And furthermore, positive rate of strong p53 overexpression was significantly higher in HCCs of PCNA Labeling Index (PCNA LI)≥40% than those of PCNA LI<40% (p<0.05).
Only a few cells were sporadically stained with p53 in 26 out of 36 cases of negative p53 overexpression group. In these 26 cases, immunohistochemical staining was performed with anti-Lewis^Y (Le^Y) antibody (BM-1/JIMRO), which was a monoclonal antibody reactive to cells of apoptosis (programmd cell death) in the early stage of it. Then it was found that cells of positive cytoplasmic staining with BM-1/JIMRO were turned out to be identical or nearby to the cells of p53 overexpression in 22 cases (84.6%).
The results suggested that pretreatment of microwave oven heating in immunohistochemical staining of p53 was an effective antigen retrieval method in human HCC tissues and p53 overexpression shown by this method was seemed to be an useful marker of the biological malignant potentials of human HCCs. And more, p53 suggests to play a key role on induction of apoptosis in human HCCs.

View full abstract

Isoursodeoxycholic acid (iso UDCA) was investigated in serum of six patients with gall stone (GS), 22 with chronic hepatitis (CH) and 21 with compensatory liver cirrhosis (LC) during ursodeoxycholic acid (UDCA) treatment. The concentration of serum total bile acid (mean μmol/l) was 23.93 in patients with GS, 37.24 in CH and 78.73 in LC. Although UDCA was major fraction in serum bile acid, isoUDCA occupied 19.17%, 6.68% and 1.58%, respectively. The ratio of isoUDCA/(isoUDCA+UDCA) was 28.30 (mean %) in GS, 9.74 in CH and 2.55 in LC and it was decreases with the progression of liver disease. Moreover, the ratio of isoUDCA/(isoUDCA+UDCA) in serum bile acid significantly correlated with serum albumin, direct bilirubin, hepaplastin test and ICG test. These results suggest that the formation of isoUDCA from UDCA associated with liver function and it is decreased following liver dysfunction.

View full abstract

The control mechanism of albumin gene expression in carbon tetrachloride (CCl₄)-induced liver damage was investigated. Rats were injected intraperitoneally with CCl₄ (1.0ml/kg b.w.) and killed at various time intervals. The level of albumin mRNA in the liver, measured by Northern blot hybridization, was found to be 30%, 18% and 40% of the control value at 6, 12 and 24 hours after CCl₄ administration, respectively. Since the transcription rate of albumin gene, measured by a nuclear run-on assay, was decreased by 50% at 12 hours, destabilization of albumin mRNA must have also occurred in the CCl₄-poisoned liver. Gel mobility shift assay showed that DNA-binding activities of tissue-specific transcriptional factors, HNF1 and C/EBP, were decreased by 50% at 12 hours while Western blot assay indicated that the concentration of C/EBP was unchanged in CCl₄ poisoning.
These results suggest that the decrease in albumin gene expression in CCl₄-induced liver injury is due to inactivation of tissue-specific transcriptional factors such as HNF1 and C/EBP and destabilization of albumin mRNA.

View full abstract

A 51-year-old man was admitted to our hospital because of epigastric pain and fever. Ultrasonography showed a high echoic area, 2.8cm in size, beneath the liver surface of the medial segment (S4) and movable strong echoes in it. Plain CT disclosed a high density area with calcification in S4 and the lesion does not enhanced by contrast medium. Under a diagnosis of ciliated hepatic foregut cyst with stone formation, operation was performed for an associated cancer of gallbladder. During surgery, a whitish cystic lesion was disclosed in S4. The lesion was a unilocular cyst filled with gelatin like substance and contained white granules which was consintent with calcification. An analysis of the while granules disclosed calcium carbonate. Histologically, the inner surface of the cyst was lined by ciliated columnar epithelium and the cyst wall was composed of a smooth muscle band surrounded by an outer fibrous capsule. Therefore, the preoperative diagnosis was confirmed.

View full abstract

A thirty one year old female was admitted to our hospital complaining general fatigue. She repeated transient deep comas and was found to have hyperammonemia and hypercitrullinemia. In addition she also had nephrotic syndrome, type V hyper-lipidemia, fatty liver and primary hypothyroidism. Analysis of urea cycle enzymes in the biopsied liver tissue showed reductions in the activities of argininosuccinate synthetase (9.5% control level) and carbamylphosphate synthetase (25%) while ornithine transcarbamylase and argininosuccinate lyase activities remained normal. Km value for citrulline of argininosuccinate synthetase was normal. Taken together, she was diagnosed as having adult type (type II) citrullinemia combined with impaired carbamylphosphate synthetase activity. Possible relationship between such abnormalities of urea cycle enzymes and several complications as mentioned first remains to be elucidated.

View full abstract