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- Andersson, K, et al.
(författare)
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Effect of a-fluoromethylhistidine-evoked histamine depletion on ultrastructure of endocrine cells in acid-producing mucosa of stomach in mouse, rat and hamster
- 1996
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Ingår i: Cell and Tissue Research. - 1432-0878. ; 286:3, s. 84-375
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Tidskriftsartikel (refereegranskat)abstract
- The oxyntic mucosa of the mammalian stomach is rich in endocrine cells, such as ECL cells, A-like cells, somatostatin cells, D1/P cells and, in some species, enterochromaffin cells. The various endocrine cell types can be distinguished on the basis of their characteristic cytoplasmic granules and vesicles. The ECL cells contain numerous large secretory vesicles and relatively few, small electron-dense granules and small clear microvesicles. We have suggested that in the rat the ECL cells contain most of the gastric histamine with the secretory vesicles as the major histamine storage site in these cells. alpha-Fluoromethylhistidine is an irreversible inhibitor of histidine decarboxylase, the histamine-forming enzyme. We have previously shown that this enzyme inhibitor depletes histamine from the ECL cells in the rat and reduces the number of secretory vesicles in the cytoplasm. In the present study, we have examined whether alpha-fluoromethylhistidine affects the ECL cells in other species and whether it affects other types of endocrine cells in the oxyntic mucosa of the rat. Mice, rats and hamsters were treated with the inhibitor (3 mg/kg per h) via minipumps subcutaneously for 24 h. This treatment lowered the oxyntic mucosal histamine concentration by 65-90% and the number and volume density of the secretory vesicles by 85-95% in the ECL cells of the three species examined. In contrast, the number and volume density of granules and microvesicles were not greatly affected. No evidence was found for an effect of alpha-fluoromethylhistidine on A-like cells, somatostatin cells or D1/P cells of the rat stomach, suggesting that, unlike the ECL cells, they do not contain histamine.
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| 4. |
- Bian, Zhao
(författare)
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Nucleator-driven assembly of curli organelles and their pathophysiological role in E. coli septic shock
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The understanding of how polymeric surface structures are assembled in bacteria is one of general interests, which can provide insight into details of macromolecule interactions, and study how proteins fold into domains as assembly modules for building organelles. Protein-protein interactions in various subcellular compartments lead to the assembly of fimbriae at bacterial cell surfaces. Many clinical Salmonella and E. coli isolates as well as certain strains of E. coli K 12, express fibrillar surface structures, which are thin, irregular and highly aggregated, denoted curli. So far, six csg genes have been identified and their products are all involved in the assembly of curli. Among these, CsgA is a major subunit protein of curli. The co-transcribed CsgB protein shows high sequence homology to CsgA with 49% similarity and 30% identity. Part 1 of the present study demonstrates that curli are assembled on the bacterial cell surface following a distinct novel pathway, the extracellular nucleator/precipitation pathway, in which CsgB serves as a nucleator for the polymerization of secreted soluble CsgA at the microbial cell surface. CsgB is also present along the length of curli fibers as a minor component, to create branching of such fibrillar structures. The current data suggest that CsgB is translocated through the outer membrane, however, unlike CsgA (secreted in a soluble form), is insoluble on the bacterial surface. When overexpressed, CsgB is able to precipitate by itself resulting in short polymers. When both native proteins are expressed, CsgB is believed, by protein-protein interactions, to convey a conformational alteration upon CsgA, leading to heteropolymeric wild type curli fibers. The innate immune system interplays intimately with the adaptive immune system. The innate responses induced by microbial patterns, may at times be so dramatic that they are the major cause of the individual's symptoms. A good example is septic shock, which is the consequence of an over-activation of host cells by bacterial products, characterized by hypotension, by vasodilatation and increased vasopermeability. Bacterial extracellular proteins often play important roles in bacterial virulence, as they can interact with host factors directly. Curli are able to bind a series of host proteins, such as fibronectin, laminin, plasminogen, human contact phase proteins and MHC class I molecules. It has been shown that curliated E. coli and Salmonella are capable of activating the contact phase system in human plasma allowing for an anticoagulation effect and generation of the cellular mediator bradykinin. It has therefore been speculated that curli may play a role during septic shock in man. Part 2 of the present work documents that more than 50% of E. coli isolates from blood cultures of patients with sepsis are able to express curli at 37O C in vitro. Curliated E. coli induce in vitro a massive expression of pro-inflammatory cytokines (IL-6, IL-8 and TNF-alpha) in human macrophages, and an overproduction of nitric oxide in vascular smooth muscle cells by inducing NOS2, as compared to the isogenic mutants bacteria-infected cells, lacking CsgA and/or CsgB proteins. In vivo, a higher level of plasma NO (nitrite/nitrate) is detected in mice after challenged intraperitoneally with 5x108 CFU viable E. coli expressing curli proteins (CsgA/CsgB). In contrast, no elevation of plasma NO was found in mice treated with an E. coli csgBA mutant. The overproduction of NO is closely associated with a dramatic fall in blood pressure in conscious wild type mice, so characteristic of septic shock. The blood pressure remains stable in infected NOS2-deficient mice, following an 8 h period of observation. An increased heart rate, a transient decrease in body temperature and a loss of gross activity are seen in all mice irrespective of curli expression. We therefore, conclude that curli as a conserved surface organelle on E. coli may serve as pattern recognition molecules that contribute to the pathophysiological symptoms and changes associated with E. coli septic shock in man.
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| 6. |
- Carlsson, Jörgen, et al.
(författare)
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Conjugate chemistry and cellular processing of EGF-dextran
- 1999
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 38:3, s. 313-321
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Tidskriftsartikel (refereegranskat)abstract
- Conjugates with specific binding to the epidermal growth factor receptor, EGFR, of interest for radionuclide based imaging and therapy were prepared using mouse epidermal growth factor, mEGF, and dextran. In one type of conjugate, mEGF was coupled to dextran by reductive amination in which the free amino group on the mEGF N-terminal reacted with the aldehyde group on the reductive end of dextran. The end-end coupled conjugate could be further activated by the cyanopyridinium agent CDAP, thereby introducing tyrosines to the dextran part. In the other type of conjugate, the cyanylating procedure using CDAP was applied, first to activate dextran and then allowing for the amino terminus of mEGF to randomly attach to the dextran. In the latter case, radionuclide-labelled tyrosines or glycines could be added in the same conjugation step. All types of mEGF-dextran conjugates had EGFR-specific binding since the binding could be displaced by an excess of non-radioactive mEGF. The conjugates were to a large extent internalized in the test cells and the associated radioactivity was retained intracellularly for different times depending on both the type of cells and conjugate applied. Different intracellular 'traffic routes' for the radionuclides are discussed as well as applications for both imaging and therapy.
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| 7. |
- Chen, DA, et al.
(författare)
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ECL cell morphology
- 1998
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Ingår i: The Yale journal of biology and medicine. - 0044-0086. ; 71:3-4, s. 217-231
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Dahlqvist, Per, et al.
(författare)
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Environmental enrichment alters nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression after middle cerebral artery occlusion in rats
- 1999
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Ingår i: Neuroscience. - 1873-7544 .- 0306-4522. ; 93:2, s. 527-535
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Tidskriftsartikel (refereegranskat)abstract
- Housing rats in an enriched environment after focal brain ischemia improves functional outcome without changes in infarct volume, suggesting neuroplastic changes outside the lesion. In this study, permanent occlusion of the middle cerebral artery was followed by housing in an enriched or a standard environment. Nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression were determined by in situ hybridization two to 30 days after middle cerebral artery occlusion. Stroke induced a decrease in nerve growth factor-induced gene A messenger RNA expression in cortical areas outside the ischemic lesion and in the CA1 subregion of the hippocampus two to three days after ischemia. This decrease was more prolonged with environmental enrichment, lasting until 20 days. However, 30 days after focal cerebral ischemia, environmental enrichment increased nerve growth factor-induced gene A expression compared to standard housing. A reduction of hippocampal glucocorticoid receptor (type II) messenger RNA two to 12 days after stroke in standard housed rats was restored by environmental enrichment. These data suggest that improved functional outcome induced by environmental enrichment after middle cerebral artery occlusion is associated with dynamically altered expression of nerve growth factor-induced gene A messenger RNA in brain regions outside the ischemic lesion, and sustained levels of hippocampal glucocorticoid receptor messenger RNA expression.
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