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  • 1
    Electronic Resource
    Electronic Resource
    Genetic Segregation of Spontaneous Erosive Arthritis and Generalized Autoimmune Disease in the BXD2 Recombinant Inbred Strain of Mice (2005)
    Oxford, UK; Malden, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 61 (2005), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The BXD2 strain of mice is one of approximately 80 BXD recombinant inbred (RI) mouse strains derived from an intercross between C57BL/6J (B6) and DBA/2J (D2) strains. We have discovered that adult BXD2 mice spontaneously develop generalized autoimmune disease, including glomerulonephritis (GN), increased serum titres of rheumatoid factor (RF) and anti-DNA antibody, and a spontaneous erosive arthritis characterized by mononuclear cell infiltration, synovial hyperplasia, and bone and cartilage erosion. The features of lupus and arthritis developed by the BXD2 mice segregate in F2 mice generated by crossing BXD2 mice with the parental B6 and D2 strains. Genetic linkage analysis of the serum levels of anti-DNA and RF by using the BXD RI strains shows that the serum titers of anti-DNA and RF were influenced by a genetic locus on mouse chromosome (Chr) 2 near the marker D2Mit412 (78 cm, 163 Mb) and on Chr 4 near D4Mit146 (53.6 cm, 109 Mb), respectively. Both loci are close to the B-cell hyperactivity, lupus or GN susceptibility loci that have been identified previously. The results of our study suggest that the BXD2 strain of mice is a novel model for complex autoimmune disease that will be useful in identifying the mechanisms critical for the immunopathogenesis and genetic segregation of lupus and erosive arthritis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0300-9475.2005.01548.x
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  • 2
    Electronic Resource
    Electronic Resource
    Defective Clearance of Adenovirus in IRF-1–/– Mice Associated with Defects in NK and T Cells but not Macrophages (2004)
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Scandinavian journal of immunology 60 (2004), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0300-9475.2004.01461.x
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  • 3
    Electronic Resource
    Electronic Resource
    Cellular Mechanism of Thymic Involution (2003)
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 57 (2003), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.2003.01206.x
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  • 4
    Electronic Resource
    Electronic Resource
    Genetic Dissection of Age-Related Changes of Immune Function in Mice (2001)
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 54 (2001), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.2001.00943.x
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  • 5
    Electronic Resource
    Electronic Resource
    Erratum (2003)
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 58 (2003), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.2003.01307_58_1.x
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  • 6
    Electronic Resource
    Electronic Resource
    Different Role of Apaf-1 in Positive Selection, Negative Selection and Death by Neglect in Foetal Thymic Organ Culture (2002)
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 56 (2002), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.2002.01120.x
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  • 7
    Electronic Resource
    Electronic Resource
    Ultrastructure of transplant glomerulopathy (1980)
    Oxford, UK : Blackwell Publishing Ltd
    Histopathology 4 (1980), S. 0 
    Details
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Thirty-one specimens of tissue were obtained from 15 renal allografts 3–96 months after transplantation and studied by light, electron and in some cases also by immunofluorescence microscopy. All patients had a degree of renal insufficiency and almost all had proteinuria and moderate hypertension; nephrotic syndrome was present in one and hematuria in two. On histological examination one patient showed cellular proliferation suggestive of glomerulonephritis (recurrent or de novo) and another patient had numerous crescents. The most frequent glomerular lesion was widening of the lamina rara interna with subendothelial accumulation of finely granular material, formation of new subendothelial basement membrane and deposition of microfibrils and fine filaments. The mesangial changes were mainly those of mesangiolysis and mesangial sclerosis with deposition of mesangial matrix and microfibrils, but little cellular proliferation. Fragmented red blood cells were seen in nearly half of the patients. In another seven patients the lesion resembled focal segmental glomerulosclerosis. This combination of changes termed transplant glomerulopathy leads to diffuse glomerular sclerosis. Arterial intimal thickening and occasionally also thrombosis produced ischaemic changes in the kidney and in the glomeruli and contributed significantly to the process of transplant rejection.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2559.1980.tb02931.x
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  • 8
    Electronic Resource
    Electronic Resource
    Expression of epidermal growth factor receptor in head and neck cancers correlates with clinical progression: a multicentre immunohistochemical study in the Asia–Pacific region (2002)
    Oxford, UK : Blackwell Science Ltd
    Histopathology 41 (2002), S. 0 
    Details
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2559.2002.01436.x
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  • 9
    Electronic Resource
    Electronic Resource
    Fish oil supplementation attenuates free radical generation in short-term coronary occlusion-reperfusion in cholesterol-fed rabbits
    Amsterdam : Elsevier
    Prostaglandins 47 (1994), S. 307-317 
    Details
    ISSN: 0090-6980
    Keywords: Fish oil ; coronary occlusion-reperfusion ; free radical ; hypercholesterolemia ; lipid peroxidation ; prostanoid metabolism
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0090-6980(94)90025-6
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  • 10
    Electronic Resource
    Electronic Resource
    Effects of acute exercise on the changes of lipid profiles and peroxides, prostanoids, and platelet activation in hypercholesterolemic patients before and after treatment
    Amsterdam : Elsevier
    Prostaglandins 48 (1994), S. 157-174 
    Details
    ISSN: 0090-6980
    Keywords: Hypercholesterolemia ; lipid peroxides ; lipid profiles ; platelet activation ; pravastatin ; prostanoids ; treadmill exercise
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0090-6980(94)90016-7
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