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Antibodies to the cytosolic leucocyte L1 protein (or calprotectin) were examined for reactivity with macrophages, neutrophils, and eosinophils identified by paired immunofluorescence staining in sections of normal human ileal mucosa, including Peyer's patches. Macrophages were recognised by expression of the myelomonocytic antigen CD68 (monoclonal antibody KP1). Neutrophilic granulocytes were identified by their content of neutrophil elastase, and eosinophilic granulocytes by monoclonal antibody EG2. Virtually all CD68+ macrophages in normal lamina propria and Peyer's patches were L1- and the same was true for most extravasated macrophages in normal peripheral lymph nodes. Some mesenteric lymph nodes, however, and all peripheral lymph nodes with overt pathological processes (malignant lymphoma) contained many CD68+L1+ macrophages. Numerous L1+ cells were also localised to the crypt region and to some extent beneath the villous epithelium in normal lamina propria, but they were mainly identified as EG2+ eosinophils. Such cells were remarkably scarce or absent beneath the follicle associated epithelium in the dome region of Peyer's patches, where CD68+L1- macrophages were abundant. Also subepithelial and interfollicular CD68- interdigitating dendritic cells in Peyer's patches (recognised by antibody to S-100 protein) were usually unreactive with L1 antibody. The L1 protein shows a broad spectrum of antimicrobial activities in vitro, and its putative antiproliferative properties are interesting in relation to the immunosuppression postulated to take place in lamina propria. The virtual absence of L1 producing cells beneath the follicle associated epithelium in Peyer's patches may support the immunostimulatory function of these macrophage rich structures, which are held to be crucial for induction of specific mucosal immunity.

The relative distribution of IgA and IgG subclass-producing immunocytes was examined by two-colour immunohistochemistry in normal human distal ileum including Peyer's patches (PP), regional mesenteric lymph nodes (MLN), and peripheral lymph nodes. IgA2 cells predominated slightly over IgA1 cells in the PP dome area. There was a decreasing median proportion of IgA2 cells in the order of PP (52%), distant ileal lamina propria (40%), MLN (32%), and peripheral lymph nodes (11%). The reverse was true for IgA1 cells in independent enumerations. These results support the notion that PP-derived B cells after stimulation are seeded mainly to the lamina propria of the distal gut, but that there is a substantial retention and terminal differentiation of this migrating population in regional MLN. The median subclass proportions of IgG-producing cells in the PP dome area were in independent determinations 68% IgG1, 23% IgG2, 8% IgG3, and 9% IgG4. This distribution was fairly similar to that seen in other tissue categories, except for a trend towards increased IgG1 and reduced IgG2 proportions in peripheral lymph nodes and reduced IgG1 along with increased IgG3 in normal palatine tonsils. The data suggested an association between the expression of IgG2 (and possibly IgG4) and IgA2 in intestinal mucosal immune responses.

Twenty-one patients with endoscopically confirmed recurrent ulceration after proximal gastric vagotomy entered an open trial of treatment with cimetidine, 1.0 g/day. Twenty patients completed 6 weeks' treatment, and repeat endoscopy showed ulcer healing in 18 of 20 patients. One patient's ulcer was found to be healed on X-ray examination, and the other patient had a healed ulcer after an additional 2 weeks' treatment. Eighteen of the patients with healed ulcer entered a maintenance trial of cimetidine, 400 mg at night. During the 1-year follow-up period the occurrence of symptoms led to re-endoscopy in 11 patients. Re-ulceration was confirmed in six patients (33%), and mean time to ulcer recurrence was 18.2 weeks. Ulcer recurrence was treated with an increased dose of cimetidine and antacids. All the ulcers then healed again, and the patients remained well on a maintenance dose of cimetidine, 800 mg/day. None of the patients had to be operated on during the trial. Two patients developed gynaecomastia during maintenance treatment with 400 mg cimetidine a day. No serious untoward signs or symptoms occurred that necessitated withdrawal from the trial. It seems as if recurrent ulcers after proximal gastric vagotomy respond to cimetidine treatment approximately as do peptic ulcers in unoperated patients.

The densities of IgG-, IgA-, IgM- and IgD-producing immunocytes were determined by paired immunofluorescence staining and morphometric analysis in the lamina propria of normal appendix specimens. Normal colon specimens were used as reference material, mostly paired from individual subjects. The density (median of cells/mm2 lamina propria area) of IgA immunocytes tended to be slightly higher in the appendix than in the colon (1259 vs 962) and the same held true for IgM cells (71 vs 55). Conversely, the overall density of IgG immunocytes was much higher in the appendix than in the colon (95 vs 38). A striking feature was the fact that almost 50% of all immunocytes were of the IgG isotype adjacent to lymphoid follicles. It seemed justified to conclude, therefore, that the abundance of such follicles explains the overall enrichment of IgG-producing cells in normal appendix mucosa. These immunocytes most likely represent follicle derived B cells that have reached terminal maturation locally, whereas precursors generated from less mature memory clones probably emigrate and home ubiquitously to distant sites of the gut lamina propria where they develop into IgA-producing immunocytes.

Immunohistochemistry of B cells associated with normal human Peyer's patches and solitary lymphoid follicles of the ileum, colon and appendix mucosa showed that local accumulation of IgG-producing cells is a common feature of gut-associated lymphoid tissue (GALT). These immunocytes have strikingly down-regulated J-chain expression, indicating that they belong to mature memory clones. They are located mainly in the dome areas, alongside the follicles, and to a lesser extent in the germinal centres, and are accompanied by a much smaller number of J-chain negative IgA- and IgM-producing cells. It is concluded that B cells of mature memory clones are retained in GALT, whereas relatively early counterparts with a high J chain-expressing potential probably emigrate rapidly after stimulation and seed distant secretory sites where they undergo terminal differentiation to produce mainly J chain-containing dimeric IgA.

Ninetyfive patients with endoscopically verified duodenal ulcer were randomly allocated in a double blind manner to 3 different treatments. Thirtyfive patients were treated with trimipramine 25 mg nocte, 32 patients with cimetidine 400 mg nocte and 26 patients with cimetidine 200 mg 3 times a day and 400 mg nocte (standard dose). In addition all patients got intensive antacid treatment with LinkR, 20 ml 1 and 3 hours after meals. Two patients were excluded from the trial. After 6 weeks of treatment re-endoscopy revealed healed ulcer in 35 patients (86%) in the trimipramine group, in 32 patients (85%) in the group treated with low dose of cimetidine and in 26 patients (100%) in the group treated with standard dose of cimetidine. The differences in healing rate were not significant. The time until complete relief of pain was significantly longer in the trimipramine group than in the cimetidine groups. The drugs were well tolerated but constipation was reported by 31% of the patients.