Fibrosing cholestatic hepatitis in a transplant recipient with hepatitis B virus precore mutant

A patient with hepatitis B virus (HBV) precore mutant (seropositive for hepatitis B surface antigen [HBsAg], anti-hepatitis B e antigen [HBeAg], and HBV DNA) who underwent orthotopic liver transplantation for end-stage liver disease is described. Sequencing of the HBV precore region of the pretransplant serum sample confirmed the presence of the precore stop-codon mutant (G-->A mutation in codon 1896) only. The patient received HBV immunoglobulin prophylaxis for 6 months but HBV recurred thereafter with a mild hepatitic flare, and he remained seropositive for HBsAg, anti-HBe, and HBV DNA. The initial hepatitic illness resolved in 3 months. The patient remained well for another 16 months before presenting with fibrosing cholestatic hepatitis (FCH). During his entire initial hepatitic flare, quiescent period, and final FCH phase, he remained seropositive for HBsAg, anti-HBe, and HBV DNA. Moreover, sequencing of the serum HBV DNA in final FCH phase showed the presence of the identical HBV precore mutant. Immunohistochemical staining showed extensive expression of HBsAg/pre-S1, pre-S2, and hepatitis B core antigen, but HBeAg was scarcely detectable. This case illustrates that (1) recurrence of HBV precore mutant infection can occur in liver; (2) it can give rise to FCH; and (3) hepatic accumulation of HBeAg is not essential for the development of FCH.     

Colourimetric point mutation assay: for detection of precore mutants of hepatitis B

Rats with unilateral dopamine (DA) depletions (hemiParkinson analogue rats) produced by intracerebral 6-hydroxydopamine injection are impaired in using the contralateral (bad) limbs for postural adjustments. This article examines whether the bad limbs are impaired in applying the forces required to initiate postural adjustments that anticipate and accompany voluntary movements. The rats were trained to reach for food using their good paw while standing on small platforms, each of which measured force changes produced by an individual limb. In one condition the force platforms were aligned to support the limb placement of normal rats and in the second they were aligned to permit the DA-depleted rats to use a compensatory reaching stance. It was found that the bad limbs of the DA-depleted rats produced normal supporting reactions but did not initiate adjustments in posture. Postural adjustments were initiated with the good limbs and preceded rather than accompanied the reaching movements. When constrained to use the posture of normal rats, the DA-deplete rats could not reach successfully, but when allowed to adjust their stance to increase reliance on the good limbs, reaching performance improved. Measures of ground reaction forces confirm that DA-depleted rats can support posture but cannot initiate postural adjustments with their impaired limbs.     

Nucleotide sequence of precore region of hepatitis B virus DNA in HBsAg-positive carriers in Malaysia

This study aims to describe and analyze the colonization of Aedes albopictus whose presence was detected in 1991 in the area of Sào José do Rio. Preto already colonized by the Aedes aegypti. Year and month of occurrence, counties, composition and location of larval samples, kinds of containers, average number of larvae an Breteau Index bare been analyzed from the information obtained in measurements of larval density by Superintendência de Controle de Endemias (SUCEN). The presence of Aedes albopictus was ascertained in 34 towns up to December 1994. The colonization of the area by the mosquito is still reduced showing some differences in relation to Aedes aegypti such as greater ratio outdoors, occupying container in different proportions. The average number of Aedes albopictus larvae has had influence of larvae of another species. It has showed a seasonal behavior similar to Aedes aegypti and it has moved from east to west direction.     

The precore sequence of hepatitis B virus is required for nuclear localization of the core protein

The cellular localization of the precore/core and core proteins was studied by immunofluorescence following transfection of 143 thymidine kinase-negative (TK ) and Hep-G2 cells with expression constructs containing wild-type (hepatitis B e antigen [HBeAg]-positive) and precore mutant (HBeAg-negative) sequences. Precore/core constructs with the wild-type phenotype result in strong nuclear staining, while, in contrast, constructs expressing core antigen alone have strong cytoplasmic staining. These differences in the pattern of immunofluorescence staining may be caused by expression of the precore/core protein, some of which may be translocated into the nucleus, following removal of the signal peptide. In vitro translation experiments showed that the main protein products obtained in the presence of microsomal membranes were the precore/core protein and a truncated product representing the same protein without its signal peptide. Core protein expression from the precore mutant constructs was very much reduced, indicating that translational re-initiation was not very efficient. The significance of the precore/core protein being present in the nucleus is not clear, but suggests that it may be important in the replicative cycle of the virus. Finally, HBeAg produced by some of the constructs could not be detected because amino acid substitutions affected antibody-binding epitopes.     

Mechanism of suppression of cell-mediated immunity by measles virus

The mechanisms underlying the profound suppression of cell-mediated immunity (CMI) accompanying measles are unclear. Interleukin-12 (IL-12), derived principally from monocytes and macrophages, is critical for the generation of CMI. Measles virus (MV) infection of primary human monocytes specifically down-regulated IL-12 production. Cross-linking of CD46, a complement regulatory protein that is the cellular receptor for MV, with antibody or with the complement activation product C3b similarly inhibited monocyte IL-12 production, providing a plausible mechanism for MV-induced immunosuppression. CD46 provides a regulatory link between the complement system and cellular immune responses.     

Prevalence of mutations in core promoter/precore region in Japanese patients with chronic hepatitis B virus infection

We examined the frequency and significance of mutations in the core promoter and precore region in 103 Japanese patients with chronic hepatitis B virus (HBV) infection. HBV DNAs from the patients' sera were amplified by polymerase chain reaction and were directly sequenced. A double mutation (T1762 A1764) in the core promoter was frequently observed in the patients regardless of HBeAg status except for asymptomatic carriers with HBeAg. Furthermore, a mutation at nucleotide 1753 from T to C or G was frequently found in anti-HBe positive patients and was often accompanied by the double mutation. The A1896 mutation was found in only about one fourth of the patients with anti-HBe. These data suggest that the patients with chronic liver diseases frequently had a double mutation regardless of HBeAg status and a mutation at nucleotide 1753 might be associated with HBeAg-negative chronic hepatitis B virus infection.     

Genotype-specific complementation of hepatitis delta virus RNA replication by hepatitis delta antigen

Characterizations of genetic variations among hepatitis delta virus (HDV) isolates have focused principally on phylogenetic analysis of sequences, which vary by 30 to 40% among three genotypes and about 10 to 15% among isolates of the same genotype. The significance of the sequence differences has been unclear but could be responsible for pathogenic variations associated with the different genotypes. Studies of the mechanisms of HDV replication have been limited to cDNA clones from HDV genotype I, which is the most common. To perform a comparative analysis of HDV RNA replication in genotypes I and III, we have obtained a full-length cDNA clone from an HDV genotype III isolate. In transfected Huh-7 cells, the functional roles of the two forms of the viral protein, hepatitis delta antigen (HDAg), in HDV RNA replication are similar for both genotypes I and III; the short form is required for RNA replication, while the long form inhibits replication. For both genotypes, HDAg was able to support replication of RNAs of the same genotype that were mutated so as to be defective for HDAg production. Surprisingly, however, neither genotype I nor genotype III HDAg was able to support replication of such mutated RNAs of the other genotype. The inability of genotype III HDAg to support replication of genotype I RNA could have been due to a weak interaction between the RNA and HDAg. The clear genotype-specific activity of HDAg in supporting HDV RNA replication confirms the original categorization of HDV sequences in three genotypes and further suggests that these should be referred to as types (i.e., HDV-I and HDV-III) rather than genotypes.     

In vitro transformation by hepatitis B virus DNA

There is strong epidemiological evidence that the hepatitis B virus (HBV) contributes to the development of hepatocellular carcinoma (HCC). In several immortalized cell lines, an in vitro transforming activity of HBV DNA and expression vectors for the viral protein X (HBx) has now been demonstrated. Furthermore, it appears as if still unknown parts of the HBV genome other than HBx contribute to the transforming activity of HBV DNA in vitro. Only one of several studies found that HBx-transgenic mouse lines develop HCC. A mouse line transgenic for the large surface protein of HBV develops HCC due to concomitant necroinflammatory infection. Growing evidence shows the importance of recombination of integrated viral DNA and cellular DNA for HCC development. A direct transforming potential of one of these viral integrates has been demonstrated. Chemical carcinogens are more effective in HBV-containing cell lines or transgenic mice.     

Identification of vertical transmission of hepatitis B virus from mother to children by direct sequencing a segment of surface gene of hepatitis B virus

Intermittent catheterization (ICP) is a well-proven effective means of urologic management for spinal cord diseased (SCD) persons who meet the following criteria: adequate low pressure bladder capacity (350-400 cc minimum), adequate hand function, unobstructed urethra and compliant, understanding, continent, cooperative patients. Time-directed (Q4 H-Q6 H), ICP-obtained volumes on twenty-one patients revealed a majority of early, unnecessary as well as some late over-distended bladder catheterizations. The PCI 5000 or "Bladder Manager", a miniaturized ultrasonic bladder volume measuring device developed by Diagnostic Ultrasound of Seattle, was evaluated. It allowed the patients to perform volume-directed ICP which results in less frequent catheterizations and prevents bladder overdistension.