Proteolytic processing of HIV gp160 to produce gp120 and gp41 is performed by PC enzymes. This process is a prerequisite for the virus infectivity, since both gp120 and gp41 participate in the virus HIV-1 entry mechanism. The structure of the gp120/gp41 junction remains to be elucidated, and the structural features required for molecular recognition between HIV-1 gp160 and proteolytic enzymes have not been clarified. Furin is the best PC candidate for the gp160 proteolytic processing known to date. In previous studies on model peptides, we have shown the relevance of an N-terminal helix for the proper recognition of the gp160 processing site by furin. Here we analyze the effect of point mutations in peptides lacking a regular N-terminal helix. To this end, we present the structure-activity characterization of three peptide analogues of the HIV gp160 processing site that all present mutations in proline at positions P3 and/or P2', while sharing the same N-terminal sequence, containing helix-breaking D-amino acids. Conformational analysis of the peptides was carried out in solution by NMR techniques, and furin's efficiency in cleaving them was measured. Structural findings are presented and discussed in relation to the different exhibited activity.

Transcripts for interleukin (IL) 15 were detected in the gastric mucosal samples of 5/5 (100%) patients with no evidence of Helicobacter pylori infection and in 4/14 (28%) H. pylori-infected patients (P<0.05). Both IL-15 mRNA and IL-15 protein were detected in 1/6 (17%) patients who successfully underwent H. pylori eradication therapy, before treatment and in 5/6 (83%) cases after eradication. Even though a parallel significant (P<0.03) improvement of gastritis score occurred after eradication, the severity of gastritis did not differ according to the mucosal IL-15 expression among H. pylori-infected patients, irrespective of the CagA serology. This study demonstrates, for the first time, that transcripts for IL-15 are expressed in the human gastric mucosa. Changes occurring during H. pylori colonisation and after eradication raise the hypothesis that H. pylori may down-regulate IL-15 expression in the gastric mucosa.

In this study the seroepidemiology of H. pylori and Epstein-Barr virus was compared in the same setting. A sample of 705 subjects completed a structured questionnaire. A serum sample was drawn from each subject and assayed for H. pylori IgG. Antibodies to Epstein-Barr virus were determined in a subgroup of 466 subjects. Cross-tabulation of data showed that 274 (58.8%) subjects were seropositive and 20 (4.3%) were seronegative for both infections, 17 (3.6%) were seropositive for H. pylori, and 155 (33.3%) were seropositive for Epstein-Barr virus (odds ratio=2.08, 95% confidence interval: 1.008-4.3). Nevertheless, the agreement between H. pylori and Epstein-Barr virus seropositivity was no better than chance (kappa=0.067) and the age-related seroprevalence curve of Epstein-Barr virus was similar in H. pylori seropositive and seronegative subjects. Furthermore, multiple logistic regression analysis did not show any risk factor shared by both infections. The findings of this study do not support the hypothesis that H. pylori and Epstein-Barr virus share a common mode of transmission. It can be speculated that the oral cavity may not be an important reservoir for H. pylori.

Editor—Brenner et al conclude that alcohol consumption may have a protective effect against infection with Helicobacter pylori.1 H pylori infection is commonly acquired during childhood and spontaneous elimination may occur, usually in young children and elderly people, but it may be acquired and eliminated spontaneously throughout adulthood.2 Drinking alcohol is usually an adult habit, and if alcohol does have a protective effect against infection with H pylori we can assume that it eradicates the infection rather than prevents it. Alcohol consumption may therefore have a role only in those few people in whom spontaneous elimination of the bacterium is thought to have occurred.2 If alcohol does protect against H pylori infection then the number of years for which it has been consumed is probably important, and not just the amount consumed, particularly when overall consumption is low. Brenner et al do not, however, give data on lifetime alcohol consumption in their series. Finally, socioeconomic factors in childhood, such as low social class, manual occupation of the parents, and measures of crowding have been consistently identified as major risk factors for infection with H pylori,3 but they were not adjusted for in the multivariate analysis in the authors’ study. We recently conducted a seroepidemiological study of H pylori infection in 705 residents in the rural town of Ciro, a wine producing centre in southern Italy.4 A structured questionnaire was administered to all subjects. The table shows data on alcohol consumption and its relation to H pylori seropositivity. The seroprevalence of infection was 63% (446/705) overall and was slightly higher in wine drinkers (70% (58/83) than in non-drinkers (62% (388 of 622)). By contrast, H pylori seropositivity was reduced in subjects who reported a lifetime alcohol consumption higher than 456 kg ethanol (64%, (27/42) v 76% (31 of 41)). The differences were not significant in a univariate or a multivariate analysis. Serological testing for H pylori has been validated, with tests indicating active infection being used as a reference.5 Since spontaneous elimination of the bacterium is uncommon,2 a positive result of a serological test for H pylori should be considered as evidence of active infection when no specific antimicrobial treatment has been given. We believe that wine consumption is not a protective factor against H pylori. Different demographic and clinical variables may account for discrepancies in findings.

BACKGROUND AND AIMS:Mucosal and systemic antibodies against Helicobacter pylori have been detected but their role in the natural history of Helicobacter pylori-related diseases is unclear. In this study, the levels of Helicobacter pylori IgG and IgA were related to the grade of gastritis.PATIENTS AND METHODS:A series of 152 dyspeptic patients underwent gastroscopy with biopsies. Helicobacter pylori was detected in 131 (86%) patients. Samples of serum and unstimulated saliva were collected. Helicobacter pylori IgG and IgA were measured in homogenised gastric biopsies, saliva and serum by an in-house enzyme linked immunosorbent assay.RESULTS:Levels of gastric mucosa, salivary and serum Helicobacter pylori IgG were higher (p < or = 0.01) in Helicobacter pylori positive than negative patients. Likewise, levels of gastric mucosa and serum Helicobacter pylori IgA were higher (p < 0.01) in Helicobacter pylori positive patients. Gastric mucosa, saliva and serum Helicobacter pylori antibody levels did not differ between superficial and atrophic, active and inactive Helicobacter pylori positive gastritis.CONCLUSIONS:These data indicate that gastric inflammatory changes may not necessarily be related to the antibody response against Helicobacter pylori.

An in-house enzyme-linked immunosorbent assay (ELISA) for measurement of Helicobacter pylori-specific immunoglobulin G (IgG) and IgA in saliva was evaluated by comparison with histopathologic (Giemsa staining) and biochemical (urease quick test) examination of gastric biopsy specimens obtained from 112 children referred for diagnostic gastroscopy. Serum H. pylori IgG was also measured in a subgroup of 50 children by the same ELISA. Salivary H. pylori IgG levels were significantly higher in H. pylori-positive (n = 57) than in H. pylori-negative (n = 55) children (P < 0.001). The sensitivity and specificity of the salivary IgG test were 93 and 82%, respectively; the positive and negative predictive values were 84 and 92%, respectively; and the accuracy was 87.5%, Salivary H. pylori IgA did not distinguish H. pylori-positive from H. pylori-negative children, The performance of serum H. pylori IgG was slightly (3 to 6%) better than that of salivary H. pylori IgG, The salivary IgG test can be considered a useful tool for the screening of H. pylori infection in children.

Background and aims—Recent studies have shown that the age-specific seroprevalence of H pylori infection parallels hepatitis A (HAV), suggesting similar modes of transmission. The aim of this study was to investigate the seroepidemiology ofH pylori and HAV in the same setting. Patients—A sample of 705 resident subjects (273 men, age range 1–87 years, median 50) who attended the outpatient medical centre of the rural town of Cirò, Southern Italy (11 000 inhabitants) for blood testing were recruited. Methods—All subjects completed a structured questionnaire. A serum sample was drawn from each subject and assayed for H pylori IgG by a validated in house enzyme linked immunosorbent assay. Antibodies to HAV were determined in 466 subjects (163 men, age range 1–87 years, median 49). A measure of agreement between H pylori and HAV seropositivity, the κ statistic, was used. Results—Overall, 446 (63%) subjects were seropositive for H pylori. Of the 466 subjects screened for both H pylori and HAV, 291 (62%) were seropositive for H pylori and 407 (87%) for HAV. Cross-tabulation of these data showed that 275 (59%) were seropositive and 43 (9%) seronegative for both H pylori and HAV, 16 (3%) were seropositive for H pylori, and 132 (28%) were seropositive for HAV (OR = 5.6, CI 3 to 10). There was a parallel, weakly correlated (r = 0.287) rise in the seroprevalence of the two infections with increasing age. However, the agreement between H pylori and HAV seropositivity was little better than chance (κ = 0.21) and in those aged less than 20 years it was worse than chance (κ = –0.064). Furthermore, multiple logistic regression analysis did not show any risk factor shared by both infections. Conclusions—The correlation between H pylori and HAV reflects the age-specific seroprevalence of both infections rather than a true association. This study provides evidence against a common mode of transmission of H pylori and HAV.

The prevalence of H. pylori infection is significantly higher in the de- veloping than in the developed countries and is closely related to low socioeconomic status.Japan is an exception among the developed coun- tries in that the prevalence of H. pylori infection in people more than 50 years old is approximately 80%.Recent reports demonstrates that its prevalence has declined in the west, especially in children.The Aim of this study was to investigate the prevalence of H. pylori infection in children and young adults in Japan.Studies in children and young adults are important in determining the epidemiology of H. pylori infection.Methods: The study population consisted of 621 (345 males) asymptomatic Japanese children and young adults between the ages of 0 and 39 years who resided in Hiroshima area.The presence of Hp infection was judged by serum IgG antibody.Results:Age (yr) Proportion positive 0-5 1/ 26 (4%) 6-10 2/ 84 (2%) 11-15 15/106 (14%) 16-20 23/161 (14%) 21-30 471154 (31%) 31-40 55/ 90 (61%)Conclusion: Our results demonstrate that the prevalence of H. pylori infection in Japan has markedly declined in children and young adults.This low prevalence is similar to that in the west and might to be linked to the declining incidence of gastric carcinoma in this country.

Aim of this study is to provide indirect evidence that human colonic mucosa harbour Helicobacter pylori. The antibody response of IgG and IgA class against Helicobacter pylori was examined in autologous homogenate of gastric and rectal endoscopic biopsies from 26 patients and in rectal samples of a further 36. All had a documented (histology and/or serology) Helicobacter pylori status. Helicobacter pylori specific IgG and IgA were measured by an in-house ELISA. In Helicobacter pylori positive patients having both gastric and rectal homogenate, mean level of Helicobacter pylori IgG and IgA was higher in gastric than in rectal samples (0.810 +/- 0.668 optical density vs 0.329 +/- 0.509 optical density for IgG, p = 0.007 and 0.660 +/- 0.477 vs 0.116 +/- 0.229 for IgA, p < 0.001, respectively). In each patient, level of the two isotypes was clearly higher in gastric than in autologous rectal sample. In the overall study population, mean level of Helicobacter pylori IgG in rectal homogenate was not significantly (p = 0.16) different between Helicobacter pylori positive (48/62, 77%, 0.243 +/- 0.388 optical density) and negative (14/62, 23%; 0.095 +/- 0.088) patients. In same material, levels of Helicobacter pylori IgA were very low and undetectable either in Helicobacter pylori positive or negative patients. Although Helicobacter pylori IgG are detectable in rectal homogenates of Helicobacter pylori positive patients, present data suggest that these antibodies may not be local in origin but rather reflect circulating response. These observations do not support the view that large bowel mucosa is colonised by Helicobacter pylori.

BACKGROUND:Chronic haemodialysis (HD) patients frequently suffer from dyspeptic symptoms and hypergastrinaemia is a common finding in these patients. Helicobacter pylori (H. pylori) infection is associated with dyspepsia and hypergastrinaemia.METHODS:The aim of this study was to determine whether H. pylori is frequently found in HD patients and to explore the relationship of H. pylori with dyspeptic symptoms and/or hypergastrinaemia in these patients. Serum H. pylori specific IgG were measured by an in-house enzyme-linked immunosorbent assay (sensitivity and specificity is 97% and 91% respectively) in 103 chronic HD patients. The patients (53 M, 50 F, mean age f60 +/- 13 years) completed a questionnaire exploring the type, frequency and intensity of dyspeptic symptoms. Fasting plasma gastrin levels were also measured. Serum and plasma samples from 103 hospital patients matched for age, sex and dyspepsia were use as controls.RESULTS:There was no significant difference in terms of serum H. pylori IgG between HD patients and controls (0.977 +/- 0.295 vs 1.046 +/- 0.306 OD respectively). The prevalence of subjects with positive serology was relatively high in both groups, but did not differ between HD patients (73%) and controls (78%). Dyspepsia was reported in 72 (70%) cases. There was no relationship between presence (and grading) of dyspepsia or type of dyspeptic symptoms and H. pylori serology. In the HD group, patients seropositive for H pylori had a significantly higher gastrinaemia than those who were seronegative: 598 +/- 413 ng/ml vs 309 +/- 252 ng/ml (P < 0.0001). The relationship between seropositivity for H. pylori and hypergastrinaemia was significant (P = 0.00038), after adjustment by multiple regression analysis for sex, age, smoking, alcohol, months on dialysis, renal function, drugs, and dyspepsia.CONCLUSIONS:Data of this study suggest that H. pylori may play a role in contributing to hypergastrinaemia of HD patients.