Transfusion-transmitted infections

Although the risk of transfusion-transmitted infections today is lower than ever, the supply of safe blood products remains subject to contamination with known and yet to be identified human pathogens. Only continuous improvement and implementation of donor selection, sensitive screening tests and effective inactivation procedures can ensure the elimination, or at least reduction, of the risk of acquiring transfusion transmitted infections. In addition, ongoing education and up-to-date information regarding infectious agents that are potentially transmitted via blood components is necessary to promote the reporting of adverse events, an important component of transfusion transmitted disease surveillance. Thus, the collaboration of all parties involved in transfusion medicine, including national haemovigilance systems, is crucial for protecting a secure blood product supply from known and emerging blood-borne pathogens

Patient-derived xenograft (PDX) models in basic and translational breast cancer research

Patient-derived xenograft (PDX) models of a growing spectrum of cancers are rapidly supplanting long-established traditional cell lines as preferred models for conducting basic and translational preclinical research. In breast cancer, to complement the now curated collection of approximately 45 long-established human breast cancer cell lines, a newly formed consortium of academic laboratories, currently from Europe, Australia, and North America, herein summarizes data on over 500 stably transplantable PDX models representing all three clinical subtypes of breast cancer (ER+, HER2+, and "Triple-negative" (TNBC)). Many of these models are well-characterized with respect to genomic, transcriptomic, and proteomic features, metastatic behavior, and treatment response to a variety of standard-of-care and experimental therapeutics. These stably transplantable PDX lines are generally available for dissemination to laboratories conducting translational research, and contact information for each collection is provided. This review summarizes current experiences related to PDX generation across participating groups, efforts to develop data standards for annotation and dissemination of patient clinical information that does not compromise patient privacy, efforts to develop complementary data standards for annotation of PDX characteristics and biology, and progress toward "credentialing" of PDX models as surrogates to represent individual patients for use in preclinical and co-clinical translational research. In addition, this review highlights important unresolved questions, as well as current limitations, that have hampered more efficient generation of PDX lines and more rapid adoption of PDX use in translational breast cancer research

Lymphocyte responses exacerbate angiotensin II-dependent hypertension

Activation of the immune system by ANG II contributes to the pathogenesis of hypertension, and pharmacological suppression of lymphocyte responses can ameliorate hypertensive end-organ damage. Therefore, to examine the mechanisms through which lymphocytes mediate blood pressure elevation, we studied ANG II-dependent hypertension in scid mice lacking lymphocyte responses and wild-type controls. Scid mice had a blunted hypertensive response to chronic ANG II infusion and accordingly developed less cardiac hypertrophy. Moreover, lymphocyte deficiency led to significant reductions in heart and kidney injury following 4 wk of angiotensin. The muted hypertensive response in the scid mice was associated with increased sodium excretion, urine volumes, and weight loss beginning on day 5 of angiotensin infusion. To explore the mechanisms underlying alterations in blood pressure and renal sodium handling, we measured gene expression for vasoactive mediators in the kidney after 4 wk of ANG II administration. Scid mice and controls had similar renal expression for interferon-γ, interleukin-1β, and interleukin-6. By contrast, lymphocyte deficiency (i.e., scid mice) during ANG II infusion led to upregulation of tumor necrosis factor-α, endothelial nitric oxide synthase (eNOS), and cyclooxygenase-2 (COX-2) in the kidney. In turn, this enhanced eNOS and COX-2 expression in the scid kidneys was associated with exaggerated renal generation of nitric oxide, prostaglandin E(2), and prostacyclin, all of which promote natriuresis. Thus, the absence of lymphocyte activity protects from hypertension by allowing blood pressure-induced sodium excretion, possibly via stimulation of eNOS- and COX-2-dependent pathways

The Actin-binding Protein Caldesmon Is in Spleen and Lymph Nodes Predominately Expressed by Smooth-muscle Cells, Reticular Cells, and Follicular Dendritic Cells

Reticular cells and follicular dendritic cells (FDCs) build up a framework that underlies the compartmentalization of spleens and lymph nodes. Subpopulations of reticular cells express the smooth-muscle isoform of actin, indicative of a specialized contractile apparatus. We have investigated the distribution of the actin-binding protein caldesmon in spleen and lymph nodes of mice and rats. Caldesmon modulates contraction and regulates cell motility. Alternative splicing of transcripts from a single gene results in high-molecular-mass isoforms (h-caldesmon) that are predominately expressed by smooth-muscle cells (SMCs), and low-molecular-mass isoforms (l-caldesmon) that are thought to be widely distributed in non-muscle tissues, but the distribution of caldesmon in spleen and lymph nodes has not been reported. We have performed Western blot analysis and immunohistochemistry using four different antibodies against caldesmon, among these a newly developed polyclonal antibody directed against recombinant mouse caldesmon. Western blot analysis showed the preponderance of l-caldesmon in spleen and lymph nodes. Our results from immunohistochemistry demonstrate caldesmon in SMCs, as expected, but also in reticular cells and FDCs, and suggest that the isoform highly expressed by reticular cells is l-caldesmon. In spleen of SCID mice, caldesmon was expressed by reticular cells in the absence of lymphocytes. (J Histochem Cytochem 58:183–193, 2010