HIV-1 gp41 envelope IgA is frequently elicited after transmission but has an initial short response half-life.

Prevention of HIV-1 transmission at mucosal surfaces will likely require durable pre-existing mucosal anti-HIV-1 antibodies (Abs). Defining the ontogeny, specificities and potentially protective nature of the initial mucosal virus-specific B-cell response will be critical for understanding how to induce protective Ab responses by vaccination. Genital fluids from patients within the earliest stages of acute HIV-1 infection (Fiebig I-VI) were examined for multiple anti-HIV specificities. Gp41 (but not gp120) Env immunoglobulin (Ig)A Abs were frequently elicited in both plasma and mucosal fluids within the first weeks of transmission. However, shortly after induction, these initial mucosal gp41 Env IgA Abs rapidly declined with a t(½) of ∼2.7 days. B-cell-activating factor belonging to the TNF family (BAFF) was elevated immediately preceding the appearance of gp41 Abs, likely contributing to an initial T-independent Ab response. HIV-1 transmission frequently elicits mucosal HIV-1 envelope-specific IgA responses targeted to gp41 that have a short half-life.

Approach to salvage antiretroviral therapy in heavily antiretroviral-experienced HIV-positive adults.

Despite dramatic declines in HIV-associated morbidity and mortality as a result of highly active antiretroviral therapy, management of heavily treatment-experienced patients remains complex and challenging. Treatment response rates with subsequent antiretroviral regimens are lower than with initial antiretroviral therapy. Additionally, increased mortality has been associated with multidrug-resistant HIV. We review data relevant to management of such patients and offer a systematic approach to constructing a salvage antiretroviral regimen.

An outbreak of methicillin resistant Staphylococcus aureus infection in a rugby football team.

Outbreaks of infection caused by methicillin resistant Staphylococcus aureus are common in hospitals and nursing homes, but until now none have been reported in the community. This is a report of an outbreak involving five members of a rugby football team.

Survey of operating theatres in Great Britain and Ireland.

A survey of operating theatres in Great Britain and Ireland by postal questionnaire was undertaken to determine the number of non-ventilated theatres in use, the number of designated theatres for specialist surgery and how and when bacterial sampling is conducted. Replies were received from 147 centres covering 438 operating theatre suites. Eighty-seven (59%) centres contained three or fewer suites and only 32% did not have a designated theatre for any specialist surgery. One hundred and seventy-three (40%) theatre suites were built over 20 years ago and 28 non-ventilated theatres were identified, mainly used for minor surgery (e.g. removal of 'lumps'). Four percent of plenum and 9% of ultraclean theatres are never monitored bacteriologically and settle plates are used in 72 (49%) centres. This survey suggests there is some confusion over the indications for bacteriological monitoring and what constitutes acceptable standards. The use of non-ventilated theatres, except for the most minor of procedures, is of some concern and should be phased out.

Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation.

OBJECTIVE: To investigate the association between gastric cancer and prior infection with Helicobacter pylori. DESIGN: Case-control comparison of prevalence of IgG antibodies to H pylori in blood samples collected prospectively, before diagnosis of gastric cancer in the cases. Presence of H pylori antibody (greater than 10 micrograms IgG/ml) determined by enzyme linked immunosorbent assay (ELISA). SUBJECTS: 29 men with a subsequent diagnosis of gastric cancer and 116 aged matched controls selected from over 22,000 middle aged men participating in two ongoing cohort studies (the British United Provident Association study and the Caerphilly collaborative heart disease study), who had provided blood samples during 1975-1982. RESULTS: 20 of the 29 cases (69%) and 54 of the 116 controls (47%) were positive for H pylori specific antibody. The median specific IgG concentration was significantly higher in the cases than controls (90 micrograms/ml v 3.6 micrograms/ml, p less than 0.01). The estimated odds ratio for the risk of gastric cancer in those with a history of infection with H pylori was 2.77 (95% confidence interval 1.04 to 7.97, 2p = 0.039). CONCLUSIONS: H pylori infection may be an important cause of gastric cancer; between 35% and 55% of all cases may be associated with such an infection.

Estimation of prevalence of Helicobacter pylori infection in an asymptomatic elderly population comparing [14C] urea breath test and serology.

A non-invasive serological assay devised in this laboratory had a sensitivity and specificity of 100% as determined by culture and confirmed by histology in a group of 47 patients who had undergone endoscopy. The correlation between serology and the non-invasive [14C] breath test was very good. Only one of 24 culture positive patients was, while all 23 culture negative patients were, breath test negative. In a group of 46 healthy elderly persons, however, significant anomalies between serology and breath test were observed. Only 83% of the breath test negative persons were seronegative, while only 68% of the breath test positive persons were seropositive. These results can be explained in terms of age related atrophic gastritis and immune incompetence, causing reduced colonisation and decreased antibody production, respectively. These investigations suggest that non-invasive tests for H pylori infection may not be reliable in the elderly.

Antigenicity of fractions of Helicobacter pylori prepared by fast protein liquid chromatography and urease captured by monoclonal antibodies.

The antigenicity of Helicobacter pylori protein fractions separated by fast protein liquid chromatography size exclusion was investigated by EIA with sera from patients of well defined Helicobacter pylori status. The antigenic material of Helicobacter pylori was confined to fractions 8 and 14 to 21. Urease containing fractions (14/15) and flagella containing fractions (17/18) were identified. Fraction 8 non-specifically bound human immunoglobulin as demonstrated by the binding of Helicobacter pylori negative sera. The remaining fractions 14 to 21 when used individually as EIA antigens were 91-100% specific, however fractions 16 to 19 showed a reduced sensitivity (78%) compared with the acid extract (95%). The urease fractions were 91% sensitive. Purified urease antigen captured by antiurease monoclonal antibodies was 83% sensitive and 93.3% specific.

Investigation of the structure and localization of the urease of Helicobacter pylori using monoclonal antibodies.

The urease of Helicobacter pylori (formerly Campylobacter pylori) has been partly purified by fast protein liquid chromatography. This material contained 10 nm doughnut-like structures when examined by electron microscopy and comprised three major polypeptides (61 kDa, 56 kDa and 28 kDa). Only two of these polypeptides (61 kDa and 28 kDa) were observed in urease-containing material isolated by preparative non-denatured PAGE. Monoclonal antibodies (mAbs) were produced which were directed against two of these polypeptides (56 kDa and 28 kDa). Only mAbs directed against the 28 kDa polypeptide inhibited or captured urease activity. These results suggest that the 56 kDa polypeptide is not essential for enzyme activity. Anti-urease mAbs were used in an indirect immunogold technique to localize the enzyme at the ultrastructural level. In both prefixed bacteria and ultrathin cryosectioned bacteria the enzyme was located on the cell surface and in material apparently shed from that surface.

Geographic association of Helicobacter pylori antibody prevalence and gastric cancer mortality in rural China.

To examine the geographic association between Helicobacter pylori infection and gastric cancer, we have assessed the prevalence of IgG antibodies to H. pylori in plasma samples taken in 1983 from 1882 men, aged 35-64 years, in 46 rural counties of the People's Republic of China. The gastric cancer mortality rates in these countries in 1973-75 varied from 3 per 1,000 (cumulative rate, 0-64 years) to 69 per 1,000, while the proportions of the population positive for H. pylori antibodies (based on an average of about 41 men per county) varied from 28% to 96%. After correction for the limited number of blood samples per county, the estimated correlation between H. pylori antibody prevalence and gastric cancer mortality was 40% (p = 0.02). No other type of cancer showed a significant association with H. pylori.

Antigenic conservation of the ureases of spiral- and helical-shaped bacteria colonising the stomachs of man and animals.

A monoclonal antibody, CP11, has been produced which is directed against the ureas of Campylobacter pylori. This antibody has been used to look for antigenic cross-reactivity, in other ureolytic and non-ureolytic campylobacters, by immunohistological techniques. It has also been used to investigate the helical-shaped organisms found in the stomach of the human, monkey and cat (CS1) and the ileum of the rat (ST1). Interestingly the antibody cross-reacted with the gastric helical organisms from the human, monkey and cat but not with the rat helical organism. No cross-reactivity was observed with C. mustelae or the other ureolytic campylobacters, C. nitrofigilis and the urease positive thermophilic campylobacters. These results are discussed in relation to the phylotaxonomy of these organisms.