Commentary: a unifying mathematical hypothesis for the epidemiology of Helicobacter-associated diseases--plurality should not be assumed without necessity.
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Duodenal Ulcer↗
Biomedical subjects
Barry Marshall
Publications and source records attributed to Barry Marshall.
Helicobacter connections.
After preliminary studies in 1981, Marshall and Warren conducted a study in which the new bacterium Helicobacter pylori was cultured. In that series, 100 % of 13 patients with duodenal ulcer were found to be infected. The hypothesis that peptic ulcer was caused by a bacterial infection was not accepted without a fight. Most experts believed that Helicobacter was a harmless commensal, infecting people who had ulcers for some other reason. In response, Marshall drank a culture of Helicobacter to prove that the bacteria could infect a healthy person and cause gastritis. The truth behind peptic ulcers was revealed; that is, very young children acquired the Helicobacter organism, leading to a chronic infection which caused a lifelong susceptibility to peptic ulcers. Marshall developed new treatments for the infection and diagnostic tests which allowed the hypothesis to be evaluated and proven. After 1994 Helicobacter was generally accepted as the cause of most gastroduodenal diseases including peptic ulcer and gastric cancer. As a result of this knowledge, treatment is a simple procedure, and stomach surgery has become a rarity.
Australia↗
Targeted gene delivery to human airway epithelial cells with synthetic vectors incorporating novel targeting peptides selected by phage display.
Human airway epithelial cell targeting peptides were identified by biopanning on 1HAEo-cells, a well characterised epithelial cell line. Bound phage were recovered after three rounds of binding, high stringency washing and elution, leading to the production of an enriched phage peptide population. DNA sequencing of 56 clones revealed 14 unique sequences. Subsequent binding analysis revealed that 13 of these peptides bound 1HAEo-cells with high affinity. Three peptides, SERSMNF, YGLPHKF and PSGAARA were represented at high frequency. Three clearly defined families of peptide were identified on the basis of sequence motifs including (R/K)SM, L(P/Q)HK and PSG(A/T)ARA. Two peptides, LPHKSMP and LQHKSMP contained two motifs. Further detailed sequence analysis by comparison of peptide sequences with the SWISSPROT protein database revealed that some of the peptides closely resembled the cell binding proteins of viral and bacterial pathogens including Herpes Simplex Virus, rotavirus, Mycoplasma pneumoniae and rhinovirus, the latter two being respiratory pathogens, as well as peptide YGLPHKF having similarity to a protein of unknown function from the respiratory pathogen Legionella pneumophila. Peptides were incorporated into gene delivery formulations with the cationic lipid Lipofectin and plasmid DNA and shown to confer a high degree of transfection efficiency and specificity in 1HAEo-cells. Improved transfection efficiency and specificity was also observed in human endothelial cells, fibroblasts and keratinocytes. Therefore, on the basis of clone frequency after biopanning, cell binding affinity, peptide sequence conservation and pathogenic similarity, we have identified 3 novel peptide families and 5 specific peptides that have the potential for gene transfer to respiratory epithelium in vivo as well as providing useful in vitro transfection reagents for primary human cell types of scientific and commercial interest.
Amino Acid Sequence↗
Helicobacter pylori: past, present and future.
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Gastritis↗
Commentary: Helicobacter as the 'environmental factor' in Susser and Stein's cohort theory of peptic ulcer disease.
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Cohort Effect↗
Gastric spirochaetes: 100 years of discovery before and after Kobayashi.
The discovery of Helicobacter pylori, by Warren and Marshall in 1982, was preceded by nearly 100 years of inconspicuous publications relating to spiral bacteria, achlorhydria, gastritis, gastric urease, and antimicrobial therapy for ulcers. Japanese investigators, notably Kasai and Kobayashi, should be acknowledged for their pioneering work showing that spiral bacteria could infect many animals, could cause haemorrhagic erosions, and would be effectively cured with various antimicrobials.
Animals↗
Helicobacter pylori: 20 years on.
Helicobacters are a new genus of bacteria, inhabiting the interface between mucosa and lumen of the gut. Microaerophilic, spiral, flagellated and urease positive, they possess features necessary for colonisation of the juxtamucosal mucus environment. Helicobacter pylori is the major pathogenic species. Once attached to the gastric epithelial cells, it incites an immune response characterised histologically by the development of active gastritis and immunologically by the presence of specific IgG. Persistence of infection is ensured by attachment to tissue antigens (eg Lewis B), a vacuolating toxin (VacA) which assists the free passage of urea through epithelial cells, and a cytotoxin (CagA) which is actually injected into the epithelial cells via a Type IV secretion system. Finally, during the typical lifelong chronic infection, two important diseases occur. H. pylori alters gastric physiology to cause acid hypersecretion and peptic ulcer. Secondly, it damages the acid secreting mucosa leading to atrophic gastritis and gastric cancer risk.
Animals↗