PHA induced enhanced growth and precocious functional maturation of the gastrointestinal tract in suckling rats. The effects persisted if the PHA treatment started at 14 days of age, but not before, suggesting an age dependent mechanism. These findings may lead to a better understanding of gastrointestinal maturation and constitute a basis for the treatment of mammals having an immature gut.

Various Helicobacter species have been isolated from the stomach, intestinal tract and liver of a variety of mammalian and some avian species, and Helicobacter DNA has been detected in human bile and liver samples. An immunoblot assay was established to analyse serum antibody responses to non-gastric Helicobacter species in patients with autoimmune liver diseases, in comparison with healthy individuals. Sera from 36 patients with primary sclerosing cholangitis (PSC), 21 with primary biliary cirrhosis, 19 with autoimmune chronic hepatitis and 80 blood donors were analysed by immunoblot, using cell-surface proteins from Helicobacter pullorum, Helicobacter bilis and Helicobacter hepaticus as antigens. Prior to testing, sera were cross-absorbed with a whole-cell lysate of Helicobacter pylori. Antibody reactivity to various proteins of these three Helicobacter species was measured by densitometric scanning and results were processed by computer software to estimate antigenic specificity. Results were also compared with antibody response to H. pylori. For H. pullorum, reactivity to at least two of the proteins with molecular masses of 48, 45, 37, 20 and 16 kDa, for H. hepaticus, reactivity to the 76, 30 and 21 kDa proteins and for H. bilis, reactivity to the 22 and 20 kDa proteins, seemed to have high specificity. Positive immunoblot results with sera from patients with PSC to antigens of H. pullorum, H. bilis and H. hepaticus were found in 38, 22 and 25 % of cases, respectively, and from patients with other autoimmune liver diseases, in 30, 22 and 22 % of cases, respectively. Prevalence of serum antibodies to non-gastric Helicobacter species was significantly higher in patients with autoimmune chronic liver diseases than in healthy blood donors (P , 0·001). Increased antibody levels to enterohepatic Helicobacter species raise questions concerning an infectious role of these emerging bacterial pathogens in human autoimmune liver diseases. INTRODUCTIONGenetic, environmental and microbial factors are believed to play a role in the development of chronic liver diseases of presumed autoimmune aetiology, such as primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Unknown environmental factors or infectious agents could trigger an immunological reaction and an inflammatory response that result in the destruction of intra-and extrahepatic bile ducts (Lee & Kaplan, 1995;Sutton & Neuberger, 2002). No causative microbial agent has been defined clearly for humans. Normal intestinal microflora or previously unrecognized intestinal pathogens might contribute to the development of disease in susceptible hosts. More recently, DNA of different Helicobacter species was detected in human bile and gall-bladder samples, suggesting that these organisms may colonize or translocate to the biliary tract of humans and may be associated with hepatobiliary diseases (Fox et al., 1998(Fox et al., , 2001Leong & Sung, 2002; Ljungh & Wadström, 2002).Isolation of a Helicobacter species from a human liver was reported recently (...

The high prevalence of Helicobacter DNA and the positive findings by IHC in gallbladder and liver raise questions concerning an infectious role of Helicobacter in patients with chronic cholecystitis.

The ecological niches occupied by various species of Helicobacter are not yet known and the full spectrum of diseases associated with Helicobacter infections are not yet defined. Since these fastidious microaerofilic bacteria require special growth conditions new and improved molecular and serologic diagnostic methods have been developed to increase our understanding of their pathogenesis and virulence characteristics. Immunogenic cell surface proteins of Helicobacter pullorum, Helicobacter bilis, and Helicobacter hepaticus were characterised by proteomic techniques using two-dimensional electrophoresis and immunoblotting with antisera from immunised rabbits. Cross-reactivity between the three Helicobacter species were analysed after a four-step cross-absorption experiment. For H. pullorum, H. bilis and H. hepaticus 21, 13 and 27 specific immunogenic proteins, respectively, were identified. These proteins could be of important sero-diagnostic value for analyses of sera from humans, laboratory animals and for the veterinarian field.