Ménétrier-like disease in a Pointer with concurrent granulomatous gastritis, helicobacteriosis and leishmaniosis: a case report.

BACKGROUND: Ménétrier-like disease is a rare hypertrophic canine gastropathy, reported in only seven dogs. Clinical signs are vomiting, anorexia and weight loss. Macroscopically, giant cerebriform gastric mucosal folds are typically seen in the corpus and fundus of the stomach. Histopathologically, fundic mucous cell hyperplasia and loss of parietal and chief cells are typical. CASE PRESENTATION: A nine-year-old spayed female Pointer had a history of intermittent vomiting, marked weight loss and hypoalbuminaemia. A gastroduodenoscopy was performed three times within three months with macroscopic changes remaining the same. The gastric mucosa of the corpus, fundus and proximal antrum was markedly irregular, with cerebriform mucosal folds. In the first gastric biopsies, histopathology revealed a moderate granulomatous gastritis, with a severe manifestation of Helicobacter-like organisms. Treatment for Helicobacter spp. decreased the vomiting slightly. The dog was diagnosed with concurrent leishmaniosis; the conventional anti-Leishmania treatment decreased the vomiting moderately, the hypoalbuminaemia resolved and the dog gained weight back to a normal body condition. Granulomatous gastritis was not present in the gastric biopsies after these treatments. The dog increased vomiting when palliative treatment (maropitant citrate, ondansetron and esomeprazole) was discontinued, and thus, full-thickness biopsies of the stomach were taken and Ménétrier-like disease was diagnosed. The affected area was too large to be surgically removed; thus, palliative treatment was reinstated. The dog remained clinically well 39 months after the first clinical presentation. CONCLUSIONS: This is the first report of Ménétrier-like disease in a dog with a simultaneous manifestation of granulomatous gastritis, helicobacteriosis and leishmaniosis. The clinical signs decreased after treatment of helicobacteriosis and leishmaniosis, but vomiting remained probably as a sign of Ménétrier-like disease. Treatment options for dogs are surgical removal of the abnormal area or palliative treatment. In humans, promising results for a cure have been shown with cetuximab treatment, a human monoclonal antibody, but no canine antibody is commercially available yet. The dog here was doing well 39 months after first presentation, which is the longest reported survival time for Ménétrier-like disease with only palliative treatment in dogs. Full-thickness biopsies are preferred in macroscopic hypertrophic lesions of the stomach for better assessment of Ménétrier-like disease.

Fast size-determination of intact bacterial plasmids using nanofluidic channels.

We demonstrate how nanofluidic channels can be used as a tool to rapidly determine the number and sizes of plasmids in bacterial isolates. Each step can be automated at low cost, opening up opportunities for general use in microbiology labs.

Identification of CD66a and CD66b as the major galectin-3 receptor candidates in human neutrophils.

The mammalian lectin galectin-3 is a potent stimulus of human neutrophils, provided that the receptor(s) for the lectin has been mobilized to the cell surface before activation. We have recently shown that the receptors for galectin-3 are stored in intracellular mobilizable granules. Here we show supportive evidence for this in that DMSO-differentiated (neutrophil-like) HL-60 cells, which lack gelatinase and specific granules, are nonresponsive when exposed to galectin-3. Neutrophil granules were subsequently used for isolation of galectin-3 receptors by affinity chromatography. Proteins eluted from a galectin-3-Sepharose column by lactose were analyzed on SDS-polyacrylamide gels and showed two major bands of 100 and 160 kDa and a minor band of 120 kDa. By immunoblotting, these proteins were shown to correspond to CD66a (160 kDa), CD66b (100 kDa), and lysosome-associated membrane glycoprotein-1 and -2 (Lamp-1 and -2; 120 kDa). The unresponsive HL-60 cells lacked the CD66 Ags but contained the Lamps, implying that neutrophil CD66a and/or CD66b may be the functional galectin-3 receptors. This conclusion was supported by the subcellular localization of the CD66 proteins to the gelatinase and specific granules in resting neutrophils.

IgG binding to cytoskeletal intermediate filaments activates the complement cascade.

The cellular plasma membrane becomes permeable to macromolecules during the cell injury process. This results in exposure of the interior of the cell to plasma proteins and to high-affinity binding of the Fc part of IgG to intermediate filaments (Hansson, G K, Starkebaum, G A, Benditt, E P & Schwartz, S M, Proc natl acad sci USA 81 (1984) 3103). Such IgG binding could be an early step in a process that serves to eliminate the injured cell. We have now identified its effect on the complement system. Intermediate filaments were reconstituted in vitro from purified vimentin, and incubated with plasma proteins. Cross-linker experiments showed binding of the heavy chain of IgG to vimentin, indicating that the vimentin protein carries an Fc-binding site. In contrast, no direct binding of complement factor Clq to vimentin could be detected. Binding of both IgG and Clq could, however, be detected by immunofluorescence when cytoskeletons of cultured endothelial cells were incubated with fresh serum. Therefore, IgG binding to filaments in the presence of serum is accompanied by Clq binding to IgG. This was in turn followed by fixation of C4 and C3 to intermediate filaments in a process that was dependent on both Ca2+, Mg2+ and Clq, indicating that it was part of a complement activation via the classical pathway. Exposure of fresh serum to intermediate filaments also resulted in production of the anaphylatoxic complement cleavage fragment. C3a, with a dose-response relationship between the amount of filaments present and the amount of C3a generated. Chemotactic activity towards granulocytes and monocytes was also generated by exposure of serum to intermediate filaments, and this activity was dependent on the presence of complement factor C5 and on the classical complement activation cascade, implying that it was due to the C5a peptide. Exposure of the interior of the cell to plasma proteins thus results in binding of IgG to intermediate filaments and activation of the complement cascade via the classical pathway. This, in turn generates bioactive mediators which may recruit leukocytes to the injured cell (C5a) and have profound effects on vascular permeability (C3a, C5a). We propose that this is part of a scavenger mechanism for the elimination of damaged cells.