Hideo Kojima

Detection of Hepatitis C Virus RNA in Sera and Liver Tissues of Non-A, Non-B Hepatitis Patients Using the Polymerase Chain Reaction

Sera obtained from patients with non‐A, non‐B hepatitis were examined for the presence of hepatitis C virus (HCV) genome by using the reverse transcription‐polymerase chain reaction assay, as well as for antibody to HCV (anti‐HCV) by using an enzyme‐linked immunosorbent assay (ELISA). We also examined the presence of HCV RNA in liver tissue obtained by surgical resection of hepatocellular carcinoma. Among 33 patients, HCV RNA was detectable in 21 (64%), and the antibody was also positive in 21 (64%). Eighteen (55%) patients were positive for both assays. The two assays gave inconsistent results in 3 patients who were positive for HCV RNA but negative for anti‐HCV, and in 3 other patients who were negative for HCV RNA and positive for anti‐HCV. HCV RNA was also detected in 6 out of 10 non‐cancerous liver tissue specimens and in 3 out of 7 tumor tissue specimens. Using the polymerase chain reaction, the HCV genome was detected directly in many specimens obtained from patients with non‐A, non‐B hepatitis, suggesting the presence of replicating virus in patients positive for anti‐HCV. In addition, the differing results of the two assay systems suggest that the application of both is important for evaluation of the status of HCV infection.

A retrospective study of hepatitis C virus carriers in a local endemic town in Japan. A possible presence of asymptomatic carrier.

Chronic hepatitis, cirrhosis, and hepatocellular carcinoma are the accepted sequelae of chronic hepatitis C virus (HCV) infection. However, the real natural history of HCV infection is not still well understood. To approach this problem, we investigated 91 individuals positive for antibodies against HCV (anti-HCV), who have received annual liver function examination in a local town known to have had high carrier rates of hepatitis B virus (HBV) and HCV. Among the 91 anti-HCV-positive individuals, 63 had undertaken the annual examination more than five times in the past 14 years. We analyzed retrospectively the past liver function test results of these 63 subjects and evaluated their present virological status by determining HCV genotypes and estimating quantity of HCV RNA in the sera. Among the 63 subjects, 50 (79.4%) had HCV RNA in the serum and 40 (80%) of the 50 subjects with HCV RNA had abnormal alanine aminotransferase or aspartate aminotransferase level more than once in their records. However, the other 10 (20%) had no abnormal levels during the period examined. Six of 50 (12%) had ultrasonographic findings suggestive of cirrhosis. Thus, HCV-infected individuals in this area did not seem to have progressive liver diseases. Considering the advanced ages of the individuals examined (mean 64 years old), we may have observed a stage in the natural history of HCV infection in which viremia persists in most individuals and the tendency to progress to serious chronic liver disease is mild.

Localization of hepatitis A virus in marmoset liver tissue during the acute phase of experimental infection

SummaryElectron microscopic and virological studies of marmoset liver tissue with acute infection of hepatitis A virus (HAV), especially in the earlier stages of infection, were carried out to characterize the maturation process of HAV. Four marmosets were inoculated intravenously with HAV suspension and sacrificed 1 week, 2 weeks, 3 weeks and 4 weeks after inoculation respectively. Hepatitis A antigen (HAAg) in 10% liver homogenates of marmosets was examined by radioimmunoassay and a large amount of HAAg was detected in the liver homogenate of two marmosets sacrificed 2 weeks and 3 weeks after inoculation respectively. The histodiagnosis of the marmoset sacrificed 2 weeks after HAV inoculation was normal. However, many clusters of virus-like particles about 27 nm in diameter, in both “solid” and “empty” forms were found, mainly in vesicles of Kupffer cells by electron microscopy. In the animal that developed mild hepatitis 3 weeks after inoculation HAV-like particles were found in vesicles of hepatocytes by electron microscopy. By immune electron microscopy using peroxidase-conjugated anti-hepatitis A antibody, HAAg was detected on the particles present within the cytoplasmic vesicles of Kupffer cells or hepatocytes and on the surrounding membrane of the vesicles which contained HAV-like particles.

Kernels of Higher Derivations in R[x, y]

Let R be an HCF-ring and R[x, y] the polynomial ring in two variables over R. In this article, we prove that the kernel of any nontrivial higher R-derivation on R[x, y] has the form R[h] for some h ∈ R[x, y].

Propagation of hepatitis A virus in hybrid cell lines derived from marmoset liver and Vero cells.

To establish monkey liver cell lines with a high susceptibility to hepatitis A virus (HAV), marmoset (Saguinus labiatus) liver cells were fused with Vero cells deficient in hypoxanthine-guanine phosphoribosyltransferase and the resulting hybrid cells were selected in HAT medium. Of four hybrid cell lines obtained (S. 1a/Ve-1 to -4), three (S. 1a/Ve-1, -3 and -4) were equally susceptible to HAV infection. When inoculated with a virus isolated from marmoset liver tissue (10% liver tissue extract) or a faecal virus (10% stool extract) from a human hepatitis A patient, all susceptible cell lines showed a significant elevation of viral antigen activity as seen in radioimmunoassay and/or immunofluorescent antibody assays, at 4 to 6 weeks post-infection (p.i.) with the liver-derived inoculum and at 6 to 8 weeks p.i. with the stool-derived inoculum. In S. 1a/Ve-1 cells, a representative of the susceptible hybrid cell lines, full adaptation of HAV (liver tissue virus concentrate) to cell culture was attained after four serial passages. Thereafter, the virus grew to a plateau titre of 10(8.5) TCID50/ml at 7 days p.i. in a growth experiment. The infected cells showed no cytopathic effects but eventually a persistent infection was established when a saturated level of virus growth was reached.

Closed Polynomials in Polynomial Rings over Unique Factorization Domains

Let R be a UFD, and let M(R, n) be the set of all subalgebras of the form R[f], where f ∈ R[x 1,…, x n ]∖R. For a polynomial f ∈ R[x 1,…, x n ]∖R, we prove that R[f] is a maximal element of M(R, n) if and only if it is integrally closed in R[x 1,…, x n ] and Q(R)[f] ∩ R[x 1,…, x n ] = R[f]. Moreover, we prove that, in the case where the characteristic of R equals zero, R[f] is a maximal element of M(R, n) if and only if there exists an R-derivation on R[x 1,…, x n ] whose kernel equals R[f].

Notes on the Kernels of Locally Finite Higher Derivations in Polynomial Rings

Let A = k[3] be the polynomial ring in three variables over a field k, and let D be a nontrivial locally finite iterative higher derivation on A. Let AD denote the kernel of D. In this note, we prove that, if chark > 0 and ML(AD) ≠ AD, then AD ≅ k[2]. As a consequence of this result, we give another proof of the cancellation theorem for k[2] over any field k of positive characteristic.

Studies on intrahepatic localization of pre-S2 antigen in various patients with chronic HBV infection.

B型慢性肝炎79例の肝生検組織87標本について連続切片を作製し,pre-S2抗原,HBs抗原ならびにHBc抗原をPAP法で検索した.87例の肝組織標本中pre-S2抗原は70例,HBs抗原は71例,HBc抗原は49例で陽性であった.肝細胞内におけるpre-S2抗原の局在様式は,HBs抗原と同様に細胞質び漫型,封入体型,膜型の3つのパターンを呈した.pre-S2抗原は,HBs抗原が染色された71標本中70標本で観察ができ,さらにそのうち69標本では,HBs抗原と同様の組織内分布および細胞内局在様式を示した.肝組織中のHBc抗原の有無およびその局在様式は,血中HBe抗原・抗体およびDNAPとの関連が認められたが,pre-S2抗原およびHBs抗原の分布ならびに局在は,HBe抗原・抗体,DNAP活性との間に関連性は認めなかった.