UNLABELLED: It has been suggested that establishing Helicobacter pylori infection status is irrelevant prior to H. pylori eradication treatment in chronic duodenal ulcer, as virtually all may benefit from therapy. OBJECTIVE: The aim of the present study was (i) to determine the prevalence of active H. pylori infection in patients with proven chronic duodenal ulcer on long-term H2-antagonist prophylactic treatment and whether knowledge of this would influence the use of eradication therapy and (ii) to assess other factors which might influence the clinical diagnosis or H. pylori status, such as non-steroidal and antibiotic use. METHODS: One hundred and forty-five patients receiving long-term H2-antagonists for chronic duodenal ulcer were recruited. Their case records and a prescribing database were reviewed. Patients underwent endoscopy with biopsies for rapid urease test, histology and H. pylori culture. Serum was immunoblotted and an enzyme-linked immunosorbent assay for H. pylori was performed. RESULTS: Of the 145 patients, 128 (88%) were H. pylori biopsy positive. Twelve of the 17 H. pylori biopsy-negative patients had anti-H. pylori immunoglobulin G (IgG) antibodies and 10 of the 17 H. pylori-negative patients had previously received antibiotics for other indications. Nine patients were exposed to non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) and one had additional aspirin exposure. CONCLUSION: Only 11.7% of patients on maintenance treatment for chronic duodenal ulcer had no current infection with H. pylori, although more than 70% of these had serological evidence of previous infection. Confirmation of active infection may be indicated where there is a history of NSAID or antibiotic exposure and may result in more precise targeting of eradication therapy, thus avoiding unnecessary and potentially hazardous treatment.

Adult↗

PubMed1997

Telephone interviews: a cost-effective way to select faculty.

The telephone interviewing process was a very positive experience for the interviewers. It gave us the opportunity to collaborate together to determine how best to represent our own peers and find future peers. With minimal expense, it expedited the process of filling our positions. The efficiency and thoroughness of the interview process allowed us to fill the positions by holding only three on-campus interviews which were shorter (less than one day in length in one case) and within budgetary allotments.

Cost-Benefit Analysis↗

PubMed1996

Alternative splicing of the human IgA Fc receptor CD89 in neutrophils and eosinophils.

Receptors for the Fc portion of IgA (Fc alpha R) trigger important immunological elimination processes against IgA-coated targets. Investigation of human Fc alpha R (CD89) transcripts in neutrophils, eosinophils and a monocyte-like cell line, THP-1, with the use of reverse transcriptase PCR, Northern blotting and RNase protection analysis, has provided evidence in these cell types for at least two distinct transcripts generated by alternative splicing. The cDNAs derived from the two major transcripts of both neutrophils and eosinophils have been cloned and sequenced. For both cell types, the larger clone represents the previously described full-length receptor, whereas the second, shorter, splice variant lacks the entire second, membrane-proximal, Ig-like domain. Stable CHO-K1 transfectants have been obtained for both full-length and truncated variant neutrophil receptors. Whereas the full-length receptor is recognized by a panel of five anti-Fc alpha R monoclonal antibodies (mAbs), the shorter variant is bound weakly by only two of the antibodies, suggesting that the epitopes recognized by the majority of the mAbs lie at least in part in the second Ig-like domain of Fc alpha R. Both full-length and splice variant forms of the receptor bind secretory IgA, but the weak binding to serum IgA seen with the full-length receptor is not evident with the shorter variant. Alternative splicing might therefore serve as a means of diversifying Fc alpha R structure and function.

Alternative Splicing↗

PubMed1996

CD66: role in the regulation of neutrophil effector function.

Neutrophils express several heavily glycosylated carcinoembryonic antigen (CEA)-related glycoproteins (CD66 antigens) which have been implicated in adhesion to E-selectin and as receptors for the lectins galectin 3 and bacterial type-1 fimbriae. The role of the CD66 antigens in neutrophil effector function was examined using non-cross-reacting and cross-reacting domain-mapped CD66 monoclonal antibody (mAb), which recognize epitopes on biliary glycoprotein (BGP; CD66a), CEA gene family member 6 (CGM6; CD66b), nonspecific cross-reacting antigen 90 (NCA90; CD66c) or CGM1 (CD66d). We show that BGP-specific mAb which recognize an AB-domain epitope strongly augment adhesion to fibrinogen by an Fc receptor- and beta2 integrin-dependent mechanism. Co-ligation of BGP with the glycophosphatidylinositol (GPI)-anchored CGM6 and NCA90 also caused increased beta2 integrin-mediated adhesion, receptor clustering and priming of formyl-Met-Leu-Phe (fMLP)-induced oxidant production by neutrophils, but only a small change in expression of L-selectin and CR3 compared to the chemotactic peptide fMLP. Ligation of CGM6 or NCA90 alone did not cause activation of the neutrophil in any of the assays used and did not cause priming of fMLP-induced oxidant production even when a secondary cross-linking reagent was used. We propose that specific cross-linking of neutrophil BGP with CGM6 and NCA90 contributes significantly to the regulation of neutrophil function during neutrophil recruitment.

Antibodies, Monoclonal↗

PubMed1996

Anti-tumor promoting activity of canventol and its synthetic analogs through inhibition of protein isoprenylation.

Canventol, a synthetic compound, is a new inhibitor of tumor promotion on mouse skin by okadaic acid. We previously reported that canventol acts by inhibiting both protein isoprenylation and tumor necrosis factor-alpha (TNF-alpha) release. In this study we examined the potencies of 10 newly synthesized canventol analogs through their effect on mevalonate metabolism, and then examined 3 representative analogs for inhibition of protein isoprenylation. Since canventol in vitro did not directly inhibit farnesyl protein transferase or geranylgeranyl protein transferase-I, the effects of canventol and its synthetic analogs on the fate of [3H]mevalonate in cells were studied. Canventol at 500 microM changed the ratio of newly synthesized sterols (cholesterol and lathosterol) to ubiquinones from 0.7 to 8.2 in NIH/3T3 cells which had previously been labeled with [3H]mevalonate, suggesting that the altered pattern of mevalonate metabolism is associated with inhibition of protein isoprenylation in the cells. We named this ratio the inhibition of protein isoprenylation index (IPI index). The 10 analogs showed a wide range of IPI indices. Two analogs, S3 and S9 had effects similar to, or stronger than, canventol. Three analogs, C44, C46 and C47, with lower IPI indices, inhibited tumor promotion on mouse skin slightly less than canventol itself did. This study shows that inhibition of protein isoprenylation in the cells, indicated by an increase in the IPI index, is a new biomarker for estimating inhibition of tumor promotion.

3T3 Cells↗

PubMed1995

IgM monoclonal antibodies recognizing Fc alpha R but not Fc gamma RIII trigger a respiratory burst in neutrophils although both trigger an increase in intracellular calcium levels and degranulation.

The role of IgG receptor, Fc gamma RIII, in the triggering of neutrophil functions has been controversial. Here we show that IgM monoclonal antibodies, Leu 11b and 1D3, recognizing Fc gamma RIII, bind to human neutrophils triggering an increase in intracellular calcium concentration and release of myeloperoxidase upon degranulation but do not trigger a respiratory burst detectable as lucigenin-enhanced chemiluminescence. Although many fewer molecules of IgM monoclonal antibody, MY43, recognizing Fc alpha R, bind to the same cells they trigger a much greater increase in intracellular calcium concentration, release of myeloperoxidase and a strong respiratory burst. Since the respiratory bursts triggered by IgG and IgA are equivalent, this demonstrates that Fc gamma RII is responsible for the IgG-mediated response. IgM monoclonal antibody MC2, recognizing the abundant neutrophil cell-surface carbohydrate CD15, also triggers a small rise in intracellular calcium but no respiratory burst.

Acridines↗

PubMed1995

Distinct oligosaccharide content of rheumatoid arthritis-derived immune complexes.

OBJECTIVE: To investigate the association between glycosylation and immune complex formation in various disease groups. METHODS: Immune complexes and IgG were isolated from serum and their carbohydrate content evaluated in a dot-blot assay using specifically binding lectins. RESULTS: Significantly more N-acetylglucosamine was detected in complexes from patients with rheumatoid arthritis (RA) than in those from patients with systemic lupus erythematosus, Crohn's disease, or infectious endocarditis, or from normal controls (P < 0.001). The immune complex concentration in the circulation was strongly associated with N-acetylglucosamine levels (P < 0.001 by chi-square analysis). CONCLUSION: The composition of immune complexes from RA patients is distinct in carbohydrate content from those found in other disease groups.

Acetylglucosamine↗

PubMed1995

CD66-dependent neutrophil activation: a possible mechanism for vascular selectin-mediated regulation of neutrophil adhesion.

We have examined the role of CD66 in the modulation of neutrophil adhesion and effector function. Engagement of neutrophil CD66 with anti-carcinoembryonic antigen (anti-CEA) Ig results in activation-associated phenomena including shape change, activation of beta 2-integrins, and priming of the respiratory burst. Anti-CEA Ig-treated neutrophils underwent transient shape change distinct from that induced by formyl-Met-Leu-Phe (fMLP). fMLP stimulated beta 2-integrin up-regulation and 70% loss of L-selectin, whereas only low-level up-regulation of the beta 2-integrins, without loss of L-selectin, occurred with anti-CEA Ig. Anti-CEA F(ab')2 fragments and whole Ig augmented beta 2-integrin-dependent adhesion. Anti-CEA Ig-induced beta 2-integrin activation was transient, whereas fMLP-induced activation persisted longer. Although they did not cause a significant increase in respiratory burst activity, CEA Ig and F(ab')2 fragments of antibody primed neutrophils so that the subsequent fMLP-induced respiratory burst was significantly increased.

Amino Acid Sequence↗

PubMed1995

Cleavage of IgG and IgA in vitro and in vivo by the urinary tract pathogen Proteus mirabilis.

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Bacterial Proteins↗

PubMed1995

The binding of monomeric IgA to myeloid Fc alpha R: evidence for receptor re-cycling and determination of its affinity.

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Antibodies, Anti-Idiotypic↗

PubMed1995

The detection of raised levels of IgM to Proteus mirabilis in sera from patients with rheumatoid arthritis.

An analysis by ELISA of 100 rheumatoid factor (RF)-positive sera selected at random from a collection of sera from patients with various auto-immune diseases and joint pains, and 100 RF-negative sera from the same collection matched by patient age and gender, showed that the RF-positive sera had highly significantly (p < 0.0001) raised levels of IgM antibody, but not IgG antibody, to Proteus mirabilis over those of the RF-negative sera. This response was subsequently found to be associated with sera from patients who clinically had rheumatoid arthritis (RA). Sera from the RA patients had significantly greater amounts (p = 0.026) of IgM antibody to P. mirabilis than to the other organisms tested and these values were also highly significantly different (p < 0.0001) from P. mirabilis IgM antibody levels in matched RF-negative sera. Sera from RA patients also had significantly greater amounts of IgA to P. mirabilis (p < 0.0001) and greater amounts of IgM to Escherichia coli (p < 0.0001) and Klebsiella pneumoniae (p < 0.0001) than those in matched RF-negative sera. Other classes of antibody to these organisms and all classes of antibody to Pseudomonas aeruginosa were not raised in the sera of RA patients over those of RF-negative controls. The IgM response in RA patients was not specific for only one O serotype of P. mirabilis but was associated with all 11 different O serotypes of P. mirabilis tested and those of other Proteus spp. Moreover, the IgM antibodies to Proteus spp. appeared to be independent from C-reactive protein and RF.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP-Binding Cassette Transporters↗

PubMed1995

The diversity of leucocyte IgA receptors.

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Animals↗

PubMed1994

Unaggregated serum IgA binds to neutrophil Fc alpha R at physiological concentrations and is endocytosed but cross-linking is necessary to elicit a respiratory burst.

My43 is a monoclonal antibody directed against Fc alpha Rs on monocytes that also recognizes neutrophil (PMN) Fc alpha Rs and is able to elicit a respiratory burst in purified cells. It appears to be directed against the immunoglobulin A (IgA) binding site of Fc alpha Rs or an epitope in close proximity, since IgA and My43 compete for binding to PMNs. My43 immunoblotted Fc alpha R that had been affinity purified from PMN membranes and immunoprecipitated a 50-70 kDa protein from radiolabeled PMN membranes, apparently identical to that purified on IgA-Sepharose. These results suggest the presence of a single class of Fc alpha R on PMNs. Binding of unaggregated monomeric or dimeric serum IgA to Fc alpha Rs on PMNs occurs at physiological concentrations, suggesting that in vivo Fc alpha Rs are saturated with ligand. This binding does not elicit a respiratory burst. Purified PMNs do not express surface IgA, since receptor-bound IgA is lost from the cell surface by endocytosis at room temperature although not at 4 degree C. Rapid endocytosis of receptor-bound IgA has been demonstrated by flow cytometry and confocal microscopy. Unoccupied receptor that is able to bind IgA or My43 is subsequently reexpressed. Cross-linking of surface-bound IgA using F(ab')2 anti-alpha chain antibodies triggers an oxidative burst. After internalization of the surface IgA the same F(ab')2 anti-alpha chain antibodies do not trigger the burst.

Endocytosis↗