Biomedical subjects

M Unoura

Publications and source records attributed to M Unoura.

At least 37 records · Page 2Linked to original sources

PubMed1995

Clinical pathoepidemiology of hepatocellular carcinoma in Japan.

There has been a rapid increase in the number of patients with hepatocellular carcinoma (HCC) in Japan. This may be the result of an increased number of patients with hepatitis C virus (HCV)-related liver disease, and of prolonged survival of these patients due to improvement in the management of cirrhosis. Indeed, 96% of recent HCC patients admitted to our hospital were related to viral hepatitis B or C, and HCV infection accounted for three-fourths of these cases. Since most HCCs develop in the course of chronic liver disease, it is important to identify high risk groups for HCC development and to detect small HCCs early. We have established a screening method by combining various imaging studies and the measurement of serum alpha-fetoprotein; this combination has markedly increased the detection of small HCCs less than 2 cm in diameter. Multiple HCCs can occur in the same patient, either simultaneously or successively. Partly for this reason, the cumulative recurrence rate of HCC is very high even after surgical resection. In order to determine whether such HCCs arise from the common or different clonal origins, we have utilized the restriction landmark genomic scanning method. It remains to be clarified whether HCV plays a direct role in hepatocarcinogenesis, and whether antiviral treatments such as interferon eventually will decrease the incidence of HCC among patients with chronic HCV infection.

Adult↗

PubMed1994

Detection of the putative E2 protein of hepatitis C virus in human liver.

The question was asked whether a predicted envelope protein, considered to be processed from the polyprotein precursor encoded by the putative E2/NS1 region of the hepatitis C virus (HCV) genome, may be observed in HCV-infected humans. Two polyclonal antibodies against recombinant E2/NS1 proteins were prepared and their reactivity tested against liver extracts from HCV-infected patients by immunoblotting analysis. A band corresponding to a size of 44 kDa was detected in liver extracts from patients who were positive for the HCV-specific antibody anti-C100-3 but not in liver extracts from patients who did not have anti-C100-3 antibody. Additionally, no band was detected using preimmune sera or antisera which had been preabsorbed with recombinant E2/NS1 proteins. Deglycosylation studies demonstrated that the 44 kDa protein was a glycosylated form of a 38 kDa protein which corresponds to the predicted molecular weight of the putative E2/NS1 protein. These results suggest that the 44 kDa protein is a product of the E2/NS1 region. Frequent observation of the 44 kDa band in cases of chronic active hepatitis C suggests a correlation between the expression of this protein and the progression of hepatitis.

Adult↗

PubMed1994

Different genotypes of hepatitis C virus are associated with different severity of chronic liver disease.

The presence of the "Japanese type" NS4 region was investigated in two series of patients (53 from Italy and 58 from Japan) with hepatitis C virus (HCV)-related chronic liver disease. The two populations were homogeneous as regard to age, male/female ratio, histological diagnosis, and serum aminotransferase activities. Genomic amplification was carried out by "nested" polymerase chain reaction (PCR) with a pair of primers synthesized according to the sequence of JK-1 isolated in Japan. The presence of viral replication was confirmed further by PCR amplification of the 5'NC region. The NS4 region of the Japanese strain was detected in 24 sera (45%) from Italy and in 44 (71%) from Japan. NS4-positive patients were significantly older and showed an ALT serum level significantly lower (P < 0.01) than NS4 negative cases in each group. Cirrhosis was significantly (P < 0.0007) more common in NS4-positive than in NS4-negative patients. The HCV genotype was subsequently obtained according to Okamoto. All the NS4-positive patients were infected by Type II, whereas in NS4-negative patients all four genotypes were present though Type II still constituted the majority. Cirrhosis was associated exclusively with Type II both in NS4-positive and -negative subjects. These data indicate that, although the positivity for NS4 "Japanese" region seems to be associated with a more aggressive liver disease, the most prevalent Type II predicts more specifically those who are likely to develop cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

PubMed1994

Efficiency of oxetanocin-G, a novel nucleoside against the woodchuck hepatitis virus.

Oxetanocin-G (OXT-G), a potent antiviral agent, is a novel nucleoside isolated from the culture filtrate of Bacillus megaterium. We investigated the antiviral effect of oral administration of OXT-G for five days on woodchuck hepatitis virus (WHV), in vivo, using 12 woodchucks. Woodchucks were randomized into each of four treatment groups according to the dose of OXT-G. Two out of six woodchucks treated with 1.0 or 2.0 mg/kg/day of OXT-G died. After treatment with OXT-G, serum levels of WHV-DNA significantly decreased in all woodchucks. However, the antiviral effect was only partial and levels of serum WHV-DNA returned after the cessation of treatment. The amount of viral replicative intermediates was decreased in livers of woodchucks treated with OXT-G. Although further study of the toxicity of this compound would be essential before studies in man can be carried out, OXT-G has potent antiviral activity against WHV and may deserve evaluation as an antiviral agent in the treatment of chronic hepatitis B infections in humans.

Animals↗

PubMed1994

The role of hepatitis C virus in hepatocellular carcinoma in Japan.

Increasing numbers of patients with hepatocellular carcinoma (HCC) have been reported in Japan. In this paper, we investigated the role of hepatitis C virus (HCV) in HCC and the reason for the increase, using patients admitted to our university hospital from 1945 to 1992. 99 (73%) of 135 patients with HCC were positive for anti-HCV. Prospective studies demonstrated that 22 of 158 (14%) patients with chronic hepatitis C, and 31 of 70 (44%) cirrhotic patients with anti-HCV developed to HCC during the follow-up period (10.1 +/- 3.3 and 7.3 +/- 3.5 years, respectively). Prolonged survival of cirrhotic patients during past decades would also contribute to the increasing number of HCC cases as well as the number of HCV infections in Japan.

Carcinoma, Hepatocellular↗

PubMed1994

[Prediction of the outcome of IFN therapy in type C chronic hepatitis from serological grouping of hepatitis C virus].

We investigated the relationship between serological grouping of hepatitis C virus and the response to IFN therapy in type C chronic hepatitis. In group I, responders were low (28%) with a high incidence of recurrence of HCV-RNA (72%). By contrast, in group II, responders were high (62%) and recurrence of HCV-RNA (17%) was low. Serological grouping of hepatitis C virus is useful in the prediction of the outcome of IFN therapy in type C chronic hepatitis.

Chronic Disease↗

PubMed1994

[Autoimmune hepatitis with hepatitis C virus markers (anti HCV antibody or HCV-RNA) and interferon therapy].

Autoimmune hepatitis (AIH) with hepatitis C virus (HCV) markers are seen frequently after the establishment of the method to detect HCV markers. According to the mechanism of the liver injury, we divide these cases of AIH with HCV markers to three groups; 1) the cases of AIH with HCV infection incidentally, 2) the cases of AIH triggered by HCV infection, and 3) the cases of chronic hepatitis C with immunological abnormalities. As far as we don't have any markers to differentiate these cases, we now think we should treat such cases with steroids at first before administering interferon, when we are not sure about the mechanism of the liver injury, because interferon is thought to be more risky than steroid for the cases who may have immunological abnormalities.

Autoimmune Diseases↗

PubMed1994

Hepatitic bile duct injuries in chronic hepatitis C: histopathologic and immunohistochemical studies.

Interlobular bile ducts are reported to be damaged in viral hepatitis. Such damages are called hepatitic duct injuries and mimic chronic nonsuppurative destructive cholangitis of primary biliary cirrhosis. In this study, hepatitic bile duct injuries were evaluated histopathologically and immunohistochemically in 149 needle liver biopsy specimens from patients with chronic hepatitis C and compared immunohistochemically with primary biliary cirrhosis. Fifty-one of the needle biopsies from patients with chronic hepatitis C (34.2%) showed hepatitic bile duct injuries which were distributed focally in the liver and showed variable epithelial damages such as cytoplasmic swelling, vacuolation and acidophilia, nuclear pleomorphism, and loss of nuclear polarity. Some of the injured bile ducts were embedded within lymphoid aggregates, whereas others were surrounded by lymphocytes as well as other inflammatory cells to varied degrees. The majority of lymphoid cells around hepatitic bile duct injury were B- and T-cells mixed in various proportions, and activated T-cells were occasionally found within the biliary epithelial layer. Histopathologic and serial section studies disclosed that bile duct loss was rare in chronic hepatitis C. Statistical analysis revealed that advancement of chronic hepatitis and the degree of necroinflammatory processes of the liver, particularly in the portal tracts, were positively correlated with the occurrence of hepatitic bile duct injuries. Immunohistochemical studies demonstrated that, whereas strong ectopic expression of HLA-DR and enhanced expression of HLA-A,B,C, and pyruvate dehydrogenase E2-complex in biliary epithelial cells were frequently observed in chronic nonsuppurative destructive cholangitis of primary biliary cirrhosis, such unusual expressions were generally absent or mild, even if present, in bile duct injuries in chronic hepatitis C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Degree of diversity of hepatitis C virus quasispecies and progression of liver disease.

We examined the quasispecies of the hepatitis C virus genome in 28 patients with liver disease of varying severity. Nucleotide sequences of the hepatitis C virus genome spanning the region from the core to envelope were used to calculate the nucleotide diversity: 0.58% +/- 0.88% in 5 patients with acute hepatitis, 0.85% +/- 0.62% in 5 patients with chronic persistent hepatitis, 1.79% +/- 0.92% in 11 patients with chronic active hepatitis, 3.05% +/- 1.26% in 4 patients with cirrhosis and 2.71% +/- 1.47% in 3 patients with cirrhosis complicated by hepatocellular carcinoma. Thus the intrapatient variation in nucleotides increased significantly with severity of liver disease (p < 0.01), except in those cases of cirrhosis complicated by hepatocellular carcinoma. Multivariate analysis including the histology, duration of infection, age, sex, history of blood transfusion and serum level of ALT at diagnosis as variables showed that the histological finding was the strongest independent factor of the nucleotide diversity (p = 0.003). Serial analysis of the genome in three patients demonstrated that the intra-patient variation in nucleotides increased with the progression of liver disease. The magnitude of the intrapatient variation in nucleotides deduced from the observed changes in the patients was correlated with the mean serum levels of ALT. These findings suggest that the degree of diversity of HCV quasispecies is related to the progression of liver disease.

Adult↗

PubMed1994

[Psychiatric complications of interferon therapy].

We studied the psychiatric side effect of interferon (IFN) therapy to the patients with chronic hepatitis type C (n = 48) using Cornell Medical Index (CMI) and Self-Depression Scale (CMI). No patients in this study showed any overt psychiatric diseases by IFN treatment. However, scores of SDS were more increased in the patients treated with IFN-alpha (32.7 +/- 7.4 to 38.9 +/- 8.4, n = 26, p < 0.001) than in those treated with IFN-beta (33.7 +/- 9.8 to 36.0 +/- 12.4, n = 18, not significant), suggesting subclinical psychiatric abnormalities caused by IFN therapy. We should take care of psychiatric side effects on treatment of IFN, especially IFN-alpha, for chronic hepatitis. Further studies are needed.

Adult↗

PubMed1993

Sequence analysis of putative structural regions of hepatitis C virus isolated from 5 Japanese patients with hepatocellular carcinoma.

The nucleotide sequences of the 5'-portion of the HCV genome, consisting of 2672 nucleotides, were determined by analysis of clones derived from 5 different patients with liver cirrhosis and hepatocellular carcinoma. Comparison of 5 genomes and 8 isolates already reported demonstrated the significant genome diversity in the structural regions. Genetic divergence was outstanding in the envelope regions (E1 and NS1/E2, > 59.7% identity) in contrast to the sequence conservation of the 5' non-coding (> 93.8% identity) or core regions (> 82.0% identity). Although hypervariable regions were found in the NS1/E2 region as reported, hydropathicity was maintained for all clones, reflecting the biological functions of these regions.

Amino Acid Sequence↗

PubMed1993

99mTc colloid and 99mTc IDA imagings in diffuse hepatic disease.

Ninety-six patients with various diffuse hepatic diseases were observed using both 99mTc colloid and 99mTc iminodiacetic acid (IDA), focusing on the potential etiologies of the disease process as well as its chronicity and severity. The presence of acute hepatic disease was more sensitively depicted with 99mTc IDA than with 99mTc colloid. In chronic hepatic disease, on the other hand, 99mTc colloid and 99mTc IDA demonstrated a similar sensitivity. The potential etiology of the disease process (differential diagnosis) and the chronicity of the disease could be evaluated better with 99mTc colloid. Among the patients with different stages of liver cirrhosis, however, 99mTc IDA significantly discriminated the severity of the hepatic disease. These results suggest that 99mTc IDA may be used to determine the degree of functional disorder in acute hepatic disease and evaluate the severity of diffuse hepatic disease, whereas 99mTc colloid can effectively evaluate the potential etiology and chronicity of the disease.

Colloids↗

PubMed1993

Small hepatocellular carcinoma: treatment with subsegmental transcatheter arterial embolization.

The effectiveness of subsegmental transcatheter arterial embolization (TAE) therapy for small hepatocellular carcinomas (HCCs) was retrospectively analyzed. TAE was performed in 100 patients with liver cirrhosis. There was a total of 124 nodular-type HCCs less than 4 cm in diameter. TAE was performed by injecting a mixture of iodized oil and anticancer drugs followed by gelatin sponge particles or a mixture of iodized oil and absolute ethanol into the more distal branches of the subsegmental artery. Complete necrosis was seen at histologic examination in seven of 11 resected lesions. Among the remaining 113 lesions in 90 patients followed up without surgery, the 1-and 4-year local recurrence rates after TAE were 18% and 33%, respectively. The 1- and 4-year survival rates for 82 patients with Child class A or B disease were 100% and 67%, respectively. No substantial deterioration of liver function was observed. Subsegmental TAE improved the prognosis of the patients with liver cirrhosis associated with small HCCs.

Carcinoma, Hepatocellular↗

PubMed1993

Distant metastasis of hepatocellular carcinoma after successful treatment of the primary lesion.

Recent advances in both diagnosis and treatment of hepatocellular carcinoma (HCC) have improved the prognosis and changed the clinical significance of the subsequently increasing distant metastases. Of 163 patients with HCC, 76 (47%) were treated successfully. The cumulative recurrence rate in these patients was 65% after 3 years, and 82% after 5 years. Six patients with HCC in whom distant metastases were detected after successful treatment of the primary lesion, are reported. Two patients underwent curative surgical resection, and four cases were treated medically, resulting in a 31.9 to 94.3% reduction in tumor size in the CT scan image. Distant metastases without intrahepatic recurrence were diagnosed 10 to 46 months after the treatment of the primary lesions. The sites of the metastases included bone 3; lung 2; and adrenal gland 1. Distant metastases found after successful treatment of the primary lesions are of great clinical significance for the treatment of HCC.

Adrenal Gland Neoplasms↗

PubMed1993

Mixed types of chronic active hepatitis and primary biliary cirrhosis associated with the anti-phospholipid antibody syndrome: a case report.

An understanding of the pathogenesis of mixed types of chronic active hepatitis and primary biliary cirrhosis is important for the treatment of the patients. A 40-year-old Japanese woman with antiphospholipid syndrome has been treated with prednisolone for two years since she was diagnosed as having a mixed type of chronic active hepatitis and primary biliary cirrhosis. Biochemical tests for liver function were normal during treatment. Laparoscopy revealed a white liver, and histology demonstrated disappearance of the findings of piecemeal necrosis or chronic nonsuppurative destructive cholangitis in the specimen. Steroid treatment of patients with mixed types of chronic active hepatitis and primary biliary cirrhosis is controversial, since it is contra-indicated in some. Although the clinical features of the patients varies from one to another, this case suggests that the autoimmune mechanism of some patients may resemble autoimmune hepatitis rather than primary biliary cirrhosis, and treatment with steroid is effective.

Adult↗

PubMed1993

[Hepatitis viruses and hepatocarcinogenesis].

The possible role of hepatitis viruses in hepatocarcinogenesis was summarized. Some 2769 of 3017 patients (92%) with hepatocellular carcinoma had advanced liver diseases such as chronic hepatitis or liver cirrhosis in Japan; and 129 of 135 patients (95%) tested positive for either hepatitis B surface antigen or hepatitis C virus antibodies. Therefore, most patients with hepatocellular carcinoma had chronic viral hepatitis in Japan. When 212 patients with chronic hepatitis and 115 with liver cirrhosis were followed (average 8.5 and 6 years, respectively), 23 (10.8%) and 43 (37.4%) of them were complicated with hepatocellular carcinoma, respectively. The ratio of these developing hepatocellular carcinoma was significantly higher among patients with viral infections than in those without them. Although these findings demonstrate a close relationship of hepatitis viral infections with hepatocarcinogenesis, the direct role of the virus on carcinogenesis has not been elucidated. The following issues were discussed with regard to hepatitis B virus: (1) "insertion-mutagenesis," (2) transactivation of X protein, and (3) genomic instability by viral integration. Since hepatocellular carcinoma was complicated after a long period of chronic viral hepatitis, further analyses about not only virology but changes of host chromosomal DNA during hepatitis are necessary for understanding its role.

Carcinoma, Hepatocellular↗

PubMed1993

Risk of hepatitis C virus infections through household contact with chronic carriers: analysis of nucleotide sequences.

We evaluated the risk of hepatitis C virus transmission through household contact with chronic carriers using nucleotide sequence analysis. Chronic hepatitis C patients (76 patients) were divided into two groups: familial transmission of hepatitis C virus was studied in group A (53 patients); group B (23 patients) served as nonfamilial controls for group A. Of 88 family members of group A patients, 18 (20%) had elevated serum ALT levels, 20 (23%) had antibodies against hepatitis C virus and 16 (18%) had hepatitis C virus RNA in serum. Nucleotide sequences of the region of the hepatitis C virus genome spanning the core and envelope genes were compared among the three groups. In group B, the average nucleotide sequence homology was 91.0% +/- 2.29% (a pairwise comparison was made for each of the patients; n = 253). Isolates from two family members were significantly more homologous to isolates from corresponding patients in group A than to isolates from group B patients. Of the two isolates from family members, one was from a child whose mother was a patient (97.7% homology) and one was from a spouse (98.1% homology). These results strongly suggest familial transmission of the same hepatitis C virus strain. Further studies are necessary to elucidate the route of intrafamilial transmission.

Adult↗

PubMed1993

High-risk groups and screening strategies for early detection of hepatocellular carcinoma in patients with chronic liver disease.

Characteristics of high-risk groups for hepatocellular carcinoma (HCC) in Japan were studied to establish screening strategies for early detection of the tumor. Some 93% of patients with HCC were associated with chronic liver disease. On the other hand, 67% of patients with liver cirrhosis had HCC at autopsy. Most were related to current hepatitis virus infection. An analysis of risk factors among 120 patients with chronic hepatitis revealed that age and histological findings were independent risk factors, while HBsAg, anti-HCV, sex, history of heavy drinking, history of blood transfusion were not independent risk factors. Multivariate analysis of 239 patients with liver cirrhosis demonstrated that age, positivity for HBsAg and/or anti-HCV, family history of liver disease, hepatic reserve, and a history of radical resection were independent factors related to the development of HCC. A screening schedule for cirrhotic patients was established in accordance with these results; ultrasonography was done every three months, and tumor markers measured every two months. The screening strategy proved to be effective for the early detection of HCC and improvement of the prognosis.

Aged↗