The immunology of primary biliary cirrhosis: the end of the beginning?

The chronic liver disease primary biliary cirrhosis (PBC) is characterised by autoreactive B‐cell and T‐cell responses directed against mitochondrial antigens. In recent years these responses have been extensively characterised and the principal PBC associated autoantigen identified as pyruvate dehydrogenase complex (PDC). The identification of anti‐PDC responses (present in over 95% of PDC patients) has given rise to important questions pertinent to our understanding of the pathogenesis of PBC. What specific role to anti‐PDC responses play in target cell damage? How and why does immune tolerance break down to as highly conserved and ubiquitously expressed self‐antigen as PDC? Why does breakdown in tolerance to an antigen present in all nucleated cells result in damage restricted to the intra‐hepatic bile ducts? In attempting to answer these key questions we have, in this review, proposed a unifying hypothesis for the pathogenesis of PBC.     

Natural history of asthma: persistence versus progression-does the beginning predict the end?

Environmental exposures during the early years and airway obstruction that develops during this time, in conjunction with genetic susceptibility, are important factors in the development of persistent asthma in childhood. Established risk factors for childhood asthma include frequent wheezing during the first 3 years, a parental history of asthma, a history of eczema, allergic rhinitis, wheezing apart from colds, and peripheral blood eosinophilia, as well as allergic sensitization to aeroallergens and certain foods. Risk factors for the development of asthma in adulthood remain ill defined. Moreover, reasons for variability in the clinical course of asthma--persistence in some individuals and progression in others--remain an enigma. The distinction between disease persistence and disease progression suggests that these are different entities or phenotypes. There is currently no consensus on whether disease progression requires either airway inflammation or airway remodeling or the combination of the two. For patients with irreversible airway obstruction, inflammation might, in part, be necessary but perhaps not entirely sufficient to induce the irreversible component, some of which could be attributed to alterations in the structure of the bronchial wall. Intervening with intermittent or daily inhaled corticosteroids in high-risk infants and children does not prevent disease progression or impaired lung growth. These findings, however, might not apply to adults, and further study in adults is needed to determine the effect of inhaled corticosteroid therapy on disease progression.     

Immunoprophylaxis of atopy: light at the end of the tunnel?

Current research in the field of atopy is directed almost exclusively towards treatment of established allergic disease. In particular, treatment has concentrated on controlling the release and actions of various mediators, such as cytokines, from the allergy effector cells at the end of the immunoinflammatory cascade. Here, Patrick Holt argues that a potentially more-effective and achievable goal may be the prevention of initial T helper 2 (Th2)-cell sensitization to environmental allergens during infancy. This might be achieved via amplification of the endogenous ‘immune deviation’ mechanism(s) that normally facilitate discrimination between pathogenic and non-pathogenic antigens at the mucosal surfaces of the body.     

Cloning of the genome of cricket paralysis virus: sequence of the 3′ end

DNA complementary to the single-stranded RNA genome of the insect picornavirus, cricket paralysis virus (CrPV), was cloned into the plasmid pBR322 by a hybrid RNA-cDNA cloning strategy. Positive CrPV-specific clones were selected by colony hybridization and characterised by restriction enzyme mapping. Overlapping clones spanning 7.5 kb of the estimated 8.5 kb genome were obtained, the largest being 7.0 kb. Comparison of the restriction enzyme map with those of mammalian picornaviruses revealed no conserved pattern of cleavage sites. The CrPV-cDNA was sequenced using the M13-dideoxy chain-terminating method although the chemical method of Maxam and Gilbert was employed to complete gaps in the sequence. The sequence of the 3′-terminal 1600 nucleotides is presented and is compared with those of mammalian picornaviruses. Computer comparisons of the CrPV sequence and those of mammalian picornaviruses revealed no significant homology between either the nucleotide or the predicted amino acid sequence of this region.     

Nucleotide and deduced amino acid sequence of the 3′ end of the BYMV-MI genome

Summary We have cloned and sequenced cDNA transcribed from the 3 1239 nucleotides of the genomic RNA of a Western Australian isolate (MI) of bean yellow mosaic potyvirus (BYMV). This sequence contains 246 nucleotides of the NIb (replicase) gene and 819 nucleotides representing the entire coding region of the viral coat protein gene, followed by a 3 non-coding region of 174 nucleotides. The coding region of the coat protein gene is identical in length (273 amino acids) to that already reported for other isolates of this virus. The sequence identities obtained for BYMV-MI and published sequences of BYMV isolates range between 85% and 92% for the coding region of the coat protein and 90% to 98% for the 3 non-coding region. Likewise, the region of the NIb gene sequenced shows 99% and 97% sequence identity in the deduced amino acid and the nucleotide sequences, respectively.     

Sequence determination of the extreme 5′ end of equine arteritis virus leader region

The extreme 5 end of the leader sequence of four equine arteritis virus (EAV) strains was obtained by using rapid amplification of cDNA end method (5 RACE), and sequenced. Seventeen more nucleotides were added upstream of the 5 end of the EAV published genomic sequence. A common feature among the analyzed EAV isolates was the presence of an AUG start codon within the added sequence and the appearance of an intraleader open reading frame (ORF) of 111 nucleotides which was predicted to encode a peptide of 37 amino acids. The role of this putative intraleader ORF has yet to be determined.