Bibliothek

Notizen: The antimicrobial enrofloxacin (Baytril®, Bayer) was evaluated under field conditions in the winter months for treatment of clinical Aeromonas salmonicida infections in salmonids by feeding medicated diets. Two trials in which lake trout Salvelinus namaycush were treated with enrofloxacin at 10mg/kg per d for 10d resulted in reduced mortalities when compared to non-medicated controls. A third trial in which Atlantic salmon Salmo salar were treated required 20d for the fish to consume the 10d medicated ration, due to poor feeding. This resulted in an effective dose of 5mg/kg per d for 20d. In spite of the lower feeding activity, a reduction in mortalities in medicated fish was observed. Tissue concentrations of drug were in excess of minimum inhibitory concentrations of the drug for the A. salmonicida isolates tested.

Notizen: This study compares the performance of three artificial neural network (ANN) approaches—backpropagalion, categorical learning, and probabilistic neural network—as classification tools to assist and support auditor's judgment about a client's continued financial viability into the future (going concern status). ANN performance is compared on the basis of overall error rates and estimated relative costs of misclassificaticn (incorrectly classifying an insolvent firm as solvent versus classifying a solvent firm as insolvent). When only the overall error rate is considered, the probabilistic neural network is the most reliable in classification, followed by backpropagation and categorical learning network. When the estimated relative costs of misclassification are considered, the categorical learning network is the least costly, followed by backpropagation and probabilistic neural network.

Notizen: A replication-defective adenovirus-LacZ recombinant virus (AdLacZ) was injected intravenously into IRF-1–/– mice and wild-type mice to characterize the contribution of IRF-1 to the immune-mediated clearance of Ad vector. Compared with wild-type mice, IRF-1–/– mice expressed higher levels of the LacZ gene product in the liver. After infusion of the AdLacZ, the expression of IRF-1 mRNA was upregulated in the liver of wild-type mice, but not in IRF-1–/– mice. Both spleen and liver mononuclear cells from IRF-1–/– mice initially exhibited a markedly lower number of NK, NK-T and CD8 T cells. At day 7 after the administration of AdLacZ, there was a significantly increased population of NK, NK-T and CD8 T cells in both spleen and liver, and also CD11b+ cells in liver of IRF-1–/– mice, compared with the increased in wild-type mice. As IRF-1 is an important signal for production of IFN-γ by CD8 T and NK cells as well as production of IL-12 by CD11b+ cells, we determined whether there were lower levels of these cytokines in IRF-1–/– mice after Ad challenge. Surprisingly, there were lower levels of IL-12, but higher levels of IFN-γ and IL-18 in IRF-1–/– compared with wild-type mice at day 7 after administration with AdLacZ. These results indicate that delayed clearance of Ad is associated with partial correction of defects of the NK, NK-T and CD8 T cells and increased production of IFN-γ and IL-18 in IRF-1–/– mice.

Notizen: Involution of the thymus and alterations in the development of thymocytes are the most prominent features of age-related immune senescence. We have carried out a comparative analysis of thymocyte and stroma in rapid thymic involution DBA/2 (D2) strain of mice compared with slow involution C57BL/6 (B6) strain of mice. Analysis of mice at 15 months of age suggested an age-related decrease in the thymocyte cell count, a block in the development of T cells and cortical involution in D2 mice compared with 3-month-old mice. TUNEL (terminal-deoxynucleotidyl-transferase-mediated dUTP–digoxigenin nick end labelling) staining and fluorescence-activated cell sorter (FACS) analysis showed that there was a significant increase in apoptotic cells in the cortex region of thymus in 15-month-old D2 mice compared with the same aged B6 mice. The thymocyte proliferation rate, as assessed by bromodeoxyuridine (BrdU) staining and [3H]-thymidine incorporation assay, was lower in 3-month-old D2 mice compared with the same age B6 mice. Immunohistochemical staining showed that the arrangement of MTS (mouse thymus stromal)-10+ epithelial cells and MTS-16+ connective tissue staining pattern had become disorganized in 15-month-old D2 mice but remained intact in B6 mice of the same age. These results suggest that, in D2 mice, both the thymocytes and stromal cells exhibit age-related defects, and that the genetic background of mice plays an important role in determining age-related alterations in thymic involution.

Notizen: Understanding of the genetic basis of normal and abnormal development of the immune response is an enormous undertaking. The immune response, at the most minimal level, involves interactions of antigen presenting cells (APCs), T and B cells. Each of these cells produce cell surface and soluble factors (cytokines) that affect both autocrine and paracrine functions. A second level of complexity needs to consider the development of the macrophage/monocyte lineage as well as the production of the common lymphoid precursor which undergoes distinct maturation steps in the thymus and periphery to form mature T cells as well as in BM (BM) and lymphoid organs to form mature B cells. A third level of complexity involves the immune response to infectious agents including viruses and also the response to tumour antigens. In addition, there are imbalances that predispose to decreased responses (immunodeficiencies) or increased responses (autoimmunity). A fourth level of complexity involves attempts to understand the differences in the immune response that occurs at a very young age, in adults, and at a very old age. This review will focus on the use of C57BL/6 J X DBA/2 J (BXD) recombinant inbred (RI) strains of mice to map genetic loci associated with the production of lymphoid precursors in the BM, development of T cells in the thymus, and T-cell responses to stimulation in the peripheral lymphoid organs in adult and in aged mice. Strategies to improve the power and precision in which complex traits such as the age-related immune response can be mapped is limited with the current set of 35 strains of BXD mice. Strategies to increase these strains by generating recombinant intercross (RIX) strains of mice are being developed to enable this large set of lines to detect quantitative trait loci (QTLs) with a much higher consistency and statistical power. More importantly, the resolution with which these QTLs can be mapped would be greatly improved and, in many cases, adequate to carry out direct identification of candidate genes. It is likely that, given the complexity of the immune system development, the number of cells involved in an immune response, and especially the changes in the immune system with ageing, mapping hundreds of genes will be required to fully understand age-related changes in the immune response. This review outlines ongoing and future strategies that will enable the mapping and identification of these genes.

Notizen: Apoptotic protease-activating factor 1 (Apaf-1) is a component of the apoptosome which is required for the activation of procaspase-9. As Apaf-1 knockout (KO) (Apaf-1-/-) mice die before birth, the role of Apaf-1 during thymic selection was investigated using 5 day foetal thymic organ culture (FTOC) of thymi obtained at gestational day 15. There was a lower ratio of CD4 single-positive (SP) to CD8 SP cells and decreased apoptosis of CD4+CD8+ (DP) thymocytes from Apaf-1-/- mice compared with wild-type. To determine if these defects resulted in increased production of neglected thymocytes, the Apaf-1-/- mice were crossed with the T-cell receptor (TCR)-α-chain KO mice. There was no difference in thymocyte development in the thymi of TCR-α-/-Apaf-1-/- and TCR-α-/-Apaf-1+/+ mice 5 days after FTOC. To determine if Apaf-1 is involved in apoptosis during death by negative or positive selection, FTOC of the thymus of Apaf-1-/- Db/HY TCR-αβ transgenic (Tg) mice was carried out. There was decreased apoptosis of the HY clonal-specific M33+ thymocytes and an increased percentage of the autoreactive CD8+M33+ thymocytes in male, but not female Apaf-1-/- Db/HY TCR Tg mice. Our data suggest that Apaf-1 is not involved in positive selection or death by neglect, but may have a partial role in negative selection during early thymic T-cell development.

Notizen: Expression of epidermal growth factor receptor in head and neck cancers correlates with clinical progression: a multicentre immunohistochemical study in the Asia–Pacific regionAims:  With ongoing efforts to target the epidermal growth factor receptor (EGFR)-mediated tumour growth in the treatment of selected human malignancies, there is a need to determine the expression levels of EGFR and to evaluate its prognostic value in various malignancies in the Asia–Pacific region.Methods and results:  A total of 172 patients with head and neck squamous cell carcinomas from Australia, Hong Kong, Singapore, and Taiwan were selected for EGFR detection. Immunohistochemical staining was performed to evaluate EGFR expression. EGFR expression was present in 88.4% (152/172) of all cases tested. Specifically, EGFR expression was found in 91.3% (42/46), 84.6% (22/26), 84.1% (37/44), 96.0% (24/25), and 87.1% (27/31) cases of head and neck squamous cell carcinomas from the oral cavity, oropharynx, nasopharynx, hypopharynx, and larynx, respectively. The results demonstrate a stronger EGFR expression in T4 tumours (P=0.017) and later clinical stages (P=0.016). No significant correlation was seen with risk factors, primary tumour site and ethnicity.Conclusions:  The majority of head and neck squamous cell carcinomas express EGFR, indicating the importance of studying the efficacy of anti-cancer therapy through this pathway. The results also show similar rates of receptor expression in head and neck squamous cell carcinoma patients from our region compared with other parts of the world.

Notizen: Aims: The histopathology of the Sauropus androgynus (SA)-constrictive bronchiolitis obliterans (BO) is still controversial. A recent report using pneumonectomy specimens showed that the major histopathology was obliterative arteriopathy with segmental necrosis of small bronchi instead of constrictive BO as previously described.Methods and results: We analysed semiquantitatively and immunohistochemically the histopathology of one pneumonectomy and four biopsies specimens of SA-associated lung disease. We found a significant number of constrictive and obliterative bronchioles 1 mm or less in diameter and segmental inflammatory destruction with complete luminal obliteration of the bronchi less than 3 mm in diameter in the pneumonectomy specimen (37% and 25%, respectively). Fibromuscular intimal sclerosis of the bronchial arteries was identified in 15% of the bronchi 4 mm or less in diameter. The inflammation in these airways was composed predominantly of T-lymphocytes, macrophages, mast cells and eosinophils. They were present throughout the evolutionary stages of the bronchiolitis ranging from early oedematous to the late fibrotic obliterative stage. Double immunohistochemical stains revealed negative proliferative cell nuclear antigen for most of the T-lymphocytes and macrophages but positive for fibroblasts.Conclusions: A more accurate histopathological designation of the SA-associated lung disease should be constrictive obliterative bronchitis/bronchiolitis, with the participation of T-lymphocytes, macrophages, mast cells, eosinophils and fibroblasts in its morphogenesis. The persistent accumulation of inflammatory cells was mediated predominantly by continued recruitment to the site of injury from the bloodstream, resulting eventually in the irreversible fibrosis of the bronchioles and the bronchi less than 3 mm in diameter. Obliterative arteriopathy is suspected of being only an indirect contributing factor.

Notizen: Abstract. Single two dimensional polymers confined to a strip are studied by Monte Carlo simulations. They are described by N-step self-avoiding random walks on a square lattice between two parallel hard walls with distance $1 \ll D \ll N^\nu$ ( $\nu = 3/4$ is the Flory exponent). For the simulations we employ the pruned-enriched-Rosenbluth method (PERM) with Markovian anticipation. We measure the densities of monomers and of end points as functions of the distance from the walls, the longitudinal extent of the chain, and the forces exerted on the walls. Their scaling with D and the universal ratio between force and monomer density at the wall are compared to theoretical predictions.