Presence of Yersinia enterocolitica in tissues of orally-inoculated pigs and the tonsils and feces of pigs at slaughter. (49/2559)

In order to study the early events associated with infection of swine by Yersinia enterocolitica, 42 five-week-old crossbred piglets were inoculated per os with approximately 10(8) Y. enterocolitica O:3. Groups of 5 animals (and one negative control) were euthanized 30 min, 3, 6, 12, 24, 48 and 72 h following the infection. Palatine tonsils, retropharyngeal and mesenteric lymph nodes, esophagus, duodenum, jejunum, ileum (and Peyer's patches), stomach, liver, spleen and feces (from colon) were collected and analyzed for the presence of Y. enterocolitica by standard bacteriological procedures. Natural infections were also analyzed, as a complementary study, by taking one-gram samples of fecal material and tonsils from 291 pig carcasses less than 3 h after slaughter and culturing them for Y. enterocolitica using a cold enrichment technique. Within 30 min, Yersinia enterocolitica O:3 was already present at most sites. The presence of Y. enterocolitica in the liver of 3 out of 10 animals and also in the spleen of 3 out of 10 piglets, within the first 3 h postinfection, but not at later times (with one exception), probably indicated a transient bacteremia accompanying the initial stages of infection. The tonsils were colonized in most animals (13/20) as the bacteria remained present from 12 to 72 h postinfection, while only 4 out of 20 fecal samples were found to be positive over the same period. Up to 10(4) colony-forming units of Y. enterocolitica per gram of tonsil and fecal material were recovered. Finally, among the 291 animals sampled at the abattoir, a total of 79 were found positive, 70 of the tonsils sampled were positive, and bacteria were recovered in 17 fecal samples. It is therefore suggested that palatine tonsils are the most reliable tissue for the indication of an infection/colonization by Y. enterocolitica O:3 in swine and that the removal of this tissue during the slaughter process should be considered in order to minimize the possibility of contamination of meat products.  (+info)

Initiation of mammalian liver development from endoderm by fibroblast growth factors. (50/2559)

The signaling molecules that elicit embryonic induction of the liver from the mammalian gut endoderm or induction of other gut-derived organs are unknown. Close proximity of cardiac mesoderm, which expresses fibroblast growth factors (FGFs) 1, 2, and 8, causes the foregut endoderm to develop into the liver. Treatment of isolated foregut endoderm from mouse embryos with FGF1 or FGF2, but not FGF8, was sufficient to replace cardiac mesoderm as an inducer of the liver gene expression program, the latter being the first step of hepatogenesis. The hepatogenic response was restricted to endoderm tissue, which selectively coexpresses FGF receptors 1 and 4. Further studies with FGFs and their specific inhibitors showed that FGF8 contributes to the morphogenetic outgrowth of the hepatic endoderm. Thus, different FGF signals appear to initiate distinct phases of liver development during mammalian organogenesis.  (+info)

The effects of fibroblast growth factors on ischemic kidney, liver and gut injuries. (51/2559)

OBJECTIVE: To explore the possibility of reducing reperfusion injuries of internal organ with acidic and basic fibroblast growth factors (aFGF and bFGF). METHODS: Two kinds of ischemia and reperfusion animal models were used in this study. In rat model of superior mesenteric artery (SMA) occlusion, microvascular clamp was placed on the root of SMA to cut off the blood flow for 45 minutes, and then the clamp was removed. In rat model of bilateral renal ischemia and reperfusion, both renal arteries were clipped to get complete cessation of blood flow for 60 minutes, then the blood flow was allowed to return. At the onset of reperfusion, the doses of 4.0 micrograms/rat of bFGF in SMA occluded rats or 2.6 micrograms/rat of aFGF in rats with acute renal injury were administered through the jugular vein. The liver and renal function examination, tissue bacterial study and histopathological evaluation were done to evaluate the treatment results. RESULTS: The functional impairment of ischemic liver, gut and kidney were reduced with venous administration of aFGF or bFGF at the onset of reperfusion. The results of pathological and tissue bacterial examination supported the assertion of significant protective effects of FGFs. CONCLUSIONS: The protective effects of FGFs may come from the non-mitogenic effects of FGFs at the early and the mitogenic effects at the late stage of tissue repair. These results indicate a potential for clinical use of FGFs as a therapeutic modality in ischemic visceral organ injuries in the future.  (+info)

Induction of the mesendoderm in the zebrafish germ ring by yolk cell-derived TGF-beta family signals and discrimination of mesoderm and endoderm by FGF. (52/2559)

The endoderm forms the gut and associated organs, and develops from a layer of cells which emerges during gastrula stages in the vertebrate embryo. In comparison to mesoderm and ectoderm, little is known about the signals which induce the endoderm. The origin of the endoderm is intimately linked with that of mesoderm, both by their position in the embryo, and by the molecules that can induce them. We characterised a gene, zebrafish gata5, which is expressed in the endoderm from blastula stages and show that its transcription is induced by signals originating from the yolk cell. These signals also induce the mesoderm-expressed transcription factor no tail (ntl), whose initial expression coincides with gata5 in the cells closest to the blastoderm margin, then spreads to encompass the germ ring. We have characterised the induction of these genes and show that ectopic expression of activin induces gata5 and ntl in a pattern which mimics the endogenous expression, while expression of a dominant negative activin receptor abolishes ntl and gata5 expression. Injection of RNA encoding a constitutively active activin receptor leads to ectopic expression of gata5 and ntl. gata5 is activated cell-autonomously, whereas ntl is induced in cells distant from those which have received the RNA, showing that although expression of both genes is induced by a TGF-beta signal, expression of ntl then spreads by a relay mechanism. Expression of a fibroblast growth factor (eFGF) or a dominant negatively acting FGF receptor shows that ntl but not gata5 is regulated by FGF signalling, implying that this may be the relay signal leading to the spread of ntl expression. In embryos lacking both squint and cyclops, members of the nodal group of TGF-beta related molecules, gata5 expression in the blastoderm is abolished, making these factors primary candidates for the endogenous TGF-beta signal inducing gata5.  (+info)

Fundamental signals that regulate eosinophil homing to the gastrointestinal tract. (53/2559)

The histological identification of increased eosinophils in the gastrointestinal tract occurs in numerous clinical disorders; however, there is a limited understanding of the mechanisms regulating eosinophil trafficking into this mucosal surface. The results presented in this study characterize the processes regulating eosinophil homing into the gastrointestinal tract at baseline. Eosinophils were found to be present in the lamina propria of 19-day-old embryos and germ-free adult mice at concentrations comparable to those present in non-germ-free adult mice. Furthermore, eosinophil gastrointestinal levels were not altered by increasing circulating eosinophils after pulmonary allergen challenge. Gastrointestinal eosinophil levels were partially reduced in mice deficient in recombinase activating gene-1 (RAG-1), IL-5, or the beta common chain (betac), but these reductions paralleled reductions in circulating eosinophils. In contrast, mice deficient in eotaxin had a marked reduction in gastrointestinal eosinophils but normal levels of eosinophils in the hematopoietic compartments. Furthermore, eotaxin was important for regulating eosinophil levels, even in the presence of high levels of IL-5. These investigations demonstrate eosinophil homing into the gastrointestinal tract during embryonic development occurring independently of viable intestinal flora. Furthermore, eotaxin is identified as the primary regulator of eosinophil gastrointestinal homing under homeostatic states, and may therefore have a fundamental role in innate immune responses.  (+info)

Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. (54/2559)

The beneficial actions of nonsteroid anti-inflammatory drugs (NSAID) can be associated with inhibition of cyclo-oxygenase (COX)-2 whereas their harmful side effects are associated with inhibition of COX-1. Here we report data from two related assay systems, the human whole blood assay and a modified human whole blood assay (using human A549 cells as a source of COX-2). This assay we refer to as the William Harvey Modified Assay. Our aim was to make meaningful comparisons of both classical NSAIDs and newer COX-2-selective compounds. These comparisons of the actions of >40 NSAIDs and novel COX-2-selective agents, including celecoxib, rofecoxib and diisopropyl fluorophosphate, demonstrate a distribution of compound selectivities toward COX-1 that aligns with the risk of serious gastrointestinal complications. In conclusion, this full in vitro analysis of COX-1/2 selectivities in human tissues clearly supports the theory that inhibition of COX-1 underlies the gastrointestinal toxicity of NSAIDs in man.  (+info)

Helicobacter pylori and apoptosis. (55/2559)

In an attempt to understand the diverse effects of infection with Helicobacter pylori on epithelial mucosal mass and consequent clinical outcome, the relationship between H. pylori infection and gastric epithelial cellular turnover has been investigated. Our results indicate that H. pylori increases epithelial cell proliferation and apoptosis in vivo, but that infection with bacteria of the cagA genotype leads to relatively more proliferation than apoptosis. This review explores the causes of the induction of apoptosis in gastric epithelial cells by H. pylori and the consequences of alterations in apoptosis to the maintenance of gastric mucosal homeostasis.  (+info)

Synaptic depression creates a switch that controls the frequency of an oscillatory circuit. (56/2559)

Synaptic depression is a form of short-term plasticity exhibited by many synapses. Nonetheless, the functional significance of synaptic depression in oscillatory networks is not well understood. We show that, in a recurrent inhibitory network that includes an intrinsic oscillator, synaptic depression can give rise to two distinct modes of network operation. When the maximal conductance of the depressing synapse is small, the oscillation period is determined by the oscillator component. Increasing the maximal conductance beyond a threshold value activates a positive-feedback mechanism that greatly enhances the synaptic strength. In this mode, the oscillation period is determined by the strength and dynamics of the depressing synapse. Because of the regenerative nature of the feedback mechanism, the circuit can be switched from one mode of operation to another by a very small change in the maximal conductance of the depressing synapse. Our model was inspired by experimental work on the pyloric network of the lobster. The pyloric network produces a simple motor rhythm generated by a pacemaker neuron that receives feedback inhibition from a depressing synapse. In some preparations, elimination of the synapse had no effect on the period of the rhythm, whereas in other preparations, there was a significant decrease in the period. We propose that the pyloric network can operate in either of the two modes suggested by the model, depending on the maximal conductance of the depressing synapse.  (+info)