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In this study the authors evaluated archived H&E slides of cardiac tissue from Beagles and cynomolgus macaques that were used as controls in preclinical safety studies in order to document the type and frequency of background changes present. The evaluation of 201 dogs revealed that the most common changes were the presence of myxomatous tissue and/or cartilage around the base of the heart (16%) and prominent vacuolization of Purkinje fibers (13%). Evaluation of 120 monkeys demonstrated frequent anisokaryosis and karyomegaly in cardiac myocyte nuclei (51%) and small foci of inflammatory cell infiltrates (63%). The infiltrates consisted mainly of lymphocytes, with fewer histiocytes, multinucleated giant cells and/or eosinophils. Less frequent findings in the monkeys included stratified squamous epithelial plaques on the epicardium (3%) and individual myofiber degeneration and necrosis (4%). Collection, handling and fixation artifacts were more common in the monkey hearts than the dog hearts. The documentation of these tissue changes in control animals provides an important baseline for evaluating tissues from animals receiving new chemical entities.
Keenan CM, Vidal JD. Standard morphologic evaluation of the heart in the laboratory dog and monkey. Toxicol Pathol 34(1): 67–74, 2006
Terszowski and colleagues report the phenotypic and functional characterization of the cervical thymus in adult mice. The cervical thymus is distinct from the thoracic thymus and reaches the size of a small lymph node. The tissue has a medullary-cortical architecture, stains positively for cytokeratin, and contains CD4+CD8+ double positive thymocytes as well as CD4+ and CD8+ single positive cells. Expression of Rag1, Rag2, TdT and other genes characteristic of thymopoiesis was demonstrated. In some mice the cervical thymi are paried organs, whereas in others there is only a single organ. Cervical thymi were present in 90% of BALB/c mice examined but only 50% of C57BL/6 mice. Cells from the cervical thymus could correct T cell deficiency when transplanted into nude mice. Although the presence of a thymic organ in the cervical region of mice has been suspected for some time, this is the first functional characterization of this tissue.
Terszowski G, Muller SM, Bleul CC, Blum C, Schirmbeck R, Reimann J, DuPasquier L, Amagai T, Boehm T, Rodewald HR. Evidence for a functional second thymus in mice. Science DOI 10.1126/science.1123497, published online March 2, 2006. et al.
Glomerulonephritis is a serious complication of immune-mediated disorders such as human systemic lupus erythematosus. The Wistar Kyoto (WKY) rat is used as a model of glomerulonephritis and develops glomerular crescents with full expression of the disease. Genetic analysis of WKY rats revealed that the activating Fc receptor for IgG (Fcgr3 or Fc
RIII) was a strong candidate gene for glomerulonephritis. Comparison of WKY rats to Lewis rats, which are not susceptible to glomerulonephritis, showed that Wistar rats have loss of part of exon 5 of the Fcgr3 gene. Furthermore, this shortened exon 5 was also present in spontaneously hypertensive rats and stroke-prone rats, whereas 27 other strains were similar to Lewis rats. Macrophages from WKY and related rat strains carrying the shortened exon 5 all demonstrated increased antigen-dependent cellular cytotoxicity compared with Lewis rats. The authors then tested humans with SLE and SLE-nephritis for FCGR3 polymorphisms and found an association between the presence of low FCGR3 copy number and SLE-nephritis. The authors postulate that the macrophage overactivity plays a key role in the pathogenesis of immune-mediated glomerulonephritis. The WKY rat is therefore a good model for interventional studies. This is the first report of a copy number polymorphism that appears to predispose to autoimmune disease.
Aitman TJ, Dong R, Vyse TJ, et al. Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans. Nature 439(7078): 851–855, 2006[CrossRef][Medline]
Immunohistochemical identification of specific cell types in formalin fixed, paraffin embedded tissues from various species is often limited by the availability of suitable antibodies and/or established protocols for antigen retrieval. Niku et al. report on the optimization of a panel of 31 antibodies and lectins for identifying a variety of cell types in bovine tissues. They present results for several antigen retrieval methods as well as differences between paraformaldehyde and ethanol fixation. Strong and specific staining was obtained for keratin, procollagen type I, vimentin, muscle actin, 
-smooth muscle actin, various neuronal markers, and several leukocyte markers including CD11a/18, CD11b, CD3
and CD79a. Data is also presented for detection of cleaved caspace 3 and Ki-67. The protocols and information on specific antibodies will be useful to many investigators.
Niku M, Ekman A, Pessa-Morikawa T, Iivanainen A. Identification of major cell types in paraffin sections of bovine tissues. BMC Vet Res 2:5, 2006
The UM-X7.1 Syrian hamster develops dilated cardiomyopathy and muscular dystrophy due to a defect in the delta-sarcoglycan gene. Miyata and colleagues investigated the mechanism of cardiomyocyte death to determine whether apoptosis or autophagy was the predominant mode of myocyte loss. Ultrastructural analysis showed that affected cardiomyocytes contained numerous autophagic vacuoles containing degraded cellular organelles. Apoptosis appeared to play a minor role in cardiomyocyte death in hamsters with cardiomyopathy. In addition, the authors determined that treatment with granulocyte colony-stimulating factor (G-CSF) resulted in improved survival, smaller heart size and less fibrosis than in untreated hamsters. G-CSF has been previously shown to improve cardiac function in ischemic heart disease and this study supports the notion that G-CSF may be useful in non-ischemic heart disease as well.
Miyata S, Takemura G, Kawase Y. Autophagic cardiomyocyte death in cardiomyopathic hamsters and its prevention by granulocyte colony-stimulating factor. Am J Pathol 168(2): 386–397, 2006
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