Helicobacter pylori isolates show greater genetic diversity than other bacterial species studied, but the basis for this phenomenon is unknown. Whether detectable genomic mutation appears within an H. pylori population during persistent colonization was investigated. Paired H. pylori populations obtained across 7- to 10-year intervals from 13 patients were characterized by use of methods including polymerase chain reaction (PCR) genotyping for cagA, vacA, iceA, recA, and IS605; random arbitrarily primed DNA (RAPD)-PCR and amplified fragment length polymorphism (AFLP) analysis; and ELISA, to determine Lewis phenotypes. Genotyping, including recA sequence analysis, revealed that initial and follow-up populations represented the same population in 11 patients (85%). Nevertheless, distinct dissimilarities were shown within each of these 11 pairs by both RAPD-PCR and AFLP analyses. During follow-up, Lewis-y levels, but not Lewis-x levels, decreased significantly. The changes detected by RAPD-PCR and AFLP indicate that genetic drift occurs within H. pylori populations over the course of years of colonization of a single host.

IgE-based evidence for an increase in IgE-mediated allergy was uncovered. The increase occurred mainly in the subgroup with no antibodies to H. pylori, which support the hypothesis that H. pylori could be one of the microbes counteracting atopy.

Stromelysin-2 is a matrix metalloproteinase that degrades in vitro several protein components relevant to wound repair such as collagens III and IV, gelatin, nidogen, laminin-1, proteoglycans, and elastin. Furthermore, it can activate other matrix metalloproteinases, such as collagenase-1 (matrix metalloproteinase-1) and collagenase-2 (matrix metalloproteinase-8), as well as 92 kDa gelatinase. The aim of this study was to determine in a large variety of wounds (normally healing dermal and mucosal wounds, suction blisters, ex vivo cultures, diabetic, decubitus, rheumatic, and venous ulcers) and keratinocyte cultures, which factors contribute to stromelysin-2 expression and how it is induced in relation to other matrix metalloproteinases. Our results show that stromelysin-2 mRNA and protein are upregulated later (at 3 d) than matrix metalloproteinase-1 in normally healing wounds and ex vivo explants, in which stromelysin-2 is invariably expressed by keratinocytes migrating over dermal matrix. The number of keratinocytes expressing stromelysin-2 was greatest in chronic inflamed diabetic and venous ulcers compared with rheumatoid and decubitus ulcers, six of which had no signal. In keratinocyte cultures, tumor necrosis factor-alpha, epidermal growth factor, and transforming growth factor-beta1 induced stromelysin-2 expression as measured by quantitative reverse transcriptase-polymerase chain reaction, whereas different matrices did not upregulate the mRNA. Immunostaining demonstrated stromal transforming growth factor-beta1 in contact with the stromelysin-2-positive keratinocytes. Our results suggest that stromelysin-2 expression is important for the normal repair process and is upregulated by cytokines rather than cell-matrix interactions. Stromelysin-2 is most likely to participate in the remodeling of the newly formed basement membrane, and is not overexpressed in retarded wound healing.

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The organism frequently colonizing the stomach of patients suffering from chronic active gastritis and peptic ulcer disease--Helicobacter pylori--possesses marked alcohol dehydrogenase (ADH) activity. Consequently, Helicobacter infection may contribute to the capacity of the stomach to metabolize ethanol and lead to increased acetaldehyde production. To study this hypothesis, we first determined ADH activity in a variety of H. pylori strains originally isolated from human gastric mucosal biopsies. ADH activity was also measured in endoscopic gastric mucosal specimens obtained from H. pylori-positive and -negative patients. Furthermore, we used a mouse model of Helicobacter infection to determine whether infected animals exhibit more gastric ethanol metabolism than noninfected controls. Most of the 32 H. pylori strains studied possessed clear ADH activity and produced acetaldehyde. In humans, gastric ADH activity of corpus mucosa did not differ between H. pylori-positive and -negative subjects, whereas in antral biopsies ADH activity was significantly lower in infected patients. In mice, gastric ADH activity was similar or even lower in infected animals than in controls, depending on the duration of infection, despite the fact that the infectious agent used--Helicobacter felis--showed ADH activity in vitro. In accordance with this, Helicobacter infection tended to decrease rather than increase gastric ethanol metabolism in mice. In humans, it remains to be established whether the observed decrease in antral ADH activity associated with H. pylori infection can lead to reduced gastric first-pass metabolism of ethanol.