Noteworthy

Currently there is much interest in identifying and characterizing stem cells in various tissues. It is generally believed that stem cells have the ability to efflux Hoechst 33343. Redvers and colleagues exploited this feature and isolated the Hoechst side population (SP) of cells from the epidermis of adult mice. These cells were found to be SSC^low/K14⁺/CD34^-/Oil red O^-/c-kit^-/CD45^- keratinocytes. To test the ability of these cells to regenerate tissue in vivo the authors inoculated the SP cells into denuded rat tracheas and transplanted these tissues into SCID mice, along with various controls. Only the SP cell fractions were able to fully reconstitute normal appearing epithelium with a polarized basal layer, granular layer and stratum corneum. Further work using the Hoechst SP of cells may advance our understanding of normal epidermal development, carcinogenesis, tissue regeneration, and wound healing.

Redvers RP, Li A, Kaur P. Side population in adult murine epidermis exhibits phenotypic and functional characteristics of keratinocyte stem cells. PNAS 103:35 13168–13173, 2006

Bone marrow biopsies are commonly performed in veterinary medicine, and specimens are often fixed in 10% neutral buffered formalin followed by decalcification. Here the authors describe an alternative protocol for processing bone marrow samples, which they have named the Hammersmith Protocol. Specimens are fixed in acetic acid-zinc-formalin and decalcified in 10% formic acid-5% formaldehyde. One micron sections are cut from paraffin blocks. These sections provide excellent morphologic detail. The authors routinely use specimens prepared in this method for immunohistochemical profiling (over 80 antibodies are presented in the paper). In addition, specimens preserved in this fashion are suitable for DNA extraction as well as mRNA in situ hybridization.

Naresh KN, Lampert I, Hasserjian R. Optimal processing of bone marrow trephine biopsy: the Hammersmith Protocol. J Clin Pathol 59:9 903–911, 2006

Mutations in the adenomatosis polyposis coli (APC) gene are associated with cancers of the bowel and breast. Mice heterozygous for Apc (Apc^Min/+) develop numerous intestinal polyps at an early age and are used extensively in the study of intestinal cancer. Based on a previous observation that C57BL/6 Apc^Min/+ mice in specific pathogen-free facilities do not develop mammary tumors while those in other facilities do, the authors sought to determine the role of gut inflammation on mammary carcinogenesis in Apc^Min/+ mice. They infected Rag2^-/- Apc^Min/+ mice with Helicobacter hepaticus and observed a significant increase in mammary tumors in female mice as well as increased numbers of intestinal tumors. Tumor development could be suppressed by adoptive transfer of interleukin 10-competent T-regulatory (T_R) cells. The authors speculate that infection with enteric pathogens and the subsequent pro-inflammatory response result in enhanced potency of T_R cells that affords protection against epithelial cancer. They suggest that this phenomenon could potentially explain the increased incidence of epithelial tumors in developed countries with high levels of hygiene and decreased enteric inflammation.

Rao VP, Poutahidis T, Ge Z. Innate immune inflammatory responses against enteric bacteria Helicobacter hepaticus induces mammary adenocarcinoma in mice. Cancer Res 66:15 7395–7400, 2006

Inflammatory myopathies in the dog are a heterogeneous group of disorders that vary in terms of the distribution of affected muscles, presence of concurrent lesions in the skin or other tissues, presence of autoantibodies, and other underlying disease processes. Shelton and colleagues examined gene expression in muscle tissues from four cases of canine masticatory muscle myositis (CMMM) and four cases of canine idiopathic polymyositis (CPM) using expression microarrays. Microarray results were validated using quantitative real-time PCR and immunohistochemistry. In both types of myositis they found significant up-regulation of genes involved in macrophage and dendritic cell functions. Furthermore, they demonstrated that the complement pathway is activated in CMMM but not in CPM, and genes involved in B-cell activation and tissue remodeling were expressed at higher levels in CMMM. This work sheds light on molecular distinctions between these two myopathies and may be helpful in designing therapeutic interventions.

Shelton GD, Hoffman EP, Ghimbovschi S. Immunopathogenic pathways in canine inflammatory myopathies resemble human myositis. Vet Immunol Immunopathol 113:1–2 200–214, 2006

Complete atrioventricular (AV) block in dogs and cats is associated with a wide variety of pathologic conditions. The authors of this study examined the hearts of 13 cats with hypertrophic cardiomyopathy and complete AV block in order to characterize the histopathologic lesions in the AV conduction system. While the sinoatrial nodes and AV nodes appeared histologically similar to those of control cats, the AV bundle and bundle branches demonstrated loss of conduction fibers and replacement by fibrous tissue. The central fibrous body was also markedly fibrotic. Ten of thirteen cats had a focal area of chondrometaplastic tissue extending from the central fibrous body into the AV bundle, and in some cats bone cysts with marrow elements were present. These chondrometaplastic and osseous lesions were associated with compression of the AV bundle and reduced number of conduction fibers. Mild fibrotic changes were seen in control cats.

Kaneshige T, Machida N, Itoh H, Yamane Y. The anatomical basis of complete atrioventricular block in cats with hypertrophic cardiomyopathy. J Comp Pathol 135:1 25–31, 2006