What Practitioners Should Understand About Bovine Lymphosarcoma

Bovine lymphosarcoma (BLS) is a common neoplasm found in both dairy and beef cattle. It is important for veterinarians, dairy producers and beef producers to gain a thorough understanding of BLS. The \u27first step in understanding BLS is to define the disease. Bovine leukosis, bovine leukemia, bovine lymphoma, and malignant lymphoma are misnomers that add confusion and frustration in understanding the disease process of BLS. There are currently four distinct forms of BLS: calf form, thymic form, skin form, and adult or bovine leukemia virus (BLV) associated form. In understanding these forms of BLS it is important to know what clinical signs to look for, how to make the diagnosis, the treatment options and recommendations for prevention and control

Llama Failure to Thrive Syndrome

The llama (Lama glama) presents today\u27s veterinarian with all the difficulties and medical uncertainties of treating a new species. Both the rapid increase in their numbers in the United States, and their relatively high monetary values have contributed to their recent significance in veterinary medicine. Complexities encountered by the veterinarian begin with llama anatomy and physiology, both of which are somewhat different \u27from what is seen in common domestic species such as the equine, bovine, or ovine. Thus, it is not surprising that some llama diseases present uniquely and are poorly understood and researched at this time. An important condition which belongs in this category is the failure to thrive syndrome of llamas (FTS)

Pharmacologic Characterization of Cl-996, a New Angiotensin Receptor Antagonist

Mg II, angiotensin II; Cl-996, 4-[2-(1-oxo-2,2,2-trrnuoroethyl)-1H-pyrrol-1-yq-2-propyl-1-[(2'-(1H-tetrazol-5-yl)biphen-4-yl)

c-Jun N-Terminal Kinase 1 Is Required for Toll-Like Receptor 1 Gene Expression in Macrophages

P. 5027-5034The regulation of innate immune responses to pathogens occurs through the interaction of Toll-like receptors (TLRs) with pathogen-associated molecular patterns and the activation of several signaling pathways whose contribution to the overall innate immune response to pathogens is poorly understood. We demonstrate a mechanism of control of murine macrophage responses mediated by TLR1/2 heterodimers through c-Jun N-terminal kinase 1 (JNK1) activity. JNK controls tumor necrosis factor alpha production and TLR-mediated macrophage responses to Borrelia burgdorferi, the causative agent of Lyme disease, and the TLR1/TLR2-specific agonist PAM3CSK4. JNK1, but not JNK2, activity regulates the expression of the tlr1 gene in the macrophage cell line RAW264.7, as well as in primary CD11b cells. We also show that the proximal promoter region of the human tlr1 gene contains an AP-1 binding site that is subjected to regulation by the kinase and binds two complexes that involve the JNK substrates c-Jun, JunD, and ATF-2. These results demonstrate that JNK1 regulates the response to TLR1/2 ligands and suggest a positive feedback loop that may serve to increase the innate immune response to the spirocheteS

The JNK Pathway Regulates the In Vivo Deletion of Immature CD4+CD8+ Thymocytes

The extracellular signal-regulated kinase (ERK), the c-Jun NH2-terminal kinase (JNK), and p38 MAP kinase pathways are triggered upon ligation of the antigen-specific T cell receptor (TCR). During the development of T cells in the thymus, the ERK pathway is required for differentiation of CD4−CD8− into CD4+CD8+ double positive (DP) thymocytes, positive selection of DP cells, and their maturation into CD4+ cells. However, the ERK pathway is not required for negative selection. Here, we show that JNK is activated in DP thymocytes in vivo in response to signals that initiate negative selection. The activation of JNK in these cells appears to be mediated by the MAP kinase kinase MKK7 since high levels of MKK7 and low levels of Sek-1/MKK4 gene expression were detected in thymocytes. Using dominant negative JNK transgenic mice, we show that inhibition of the JNK pathway reduces the in vivo deletion of DP thymocytes. In addition, the increased resistance of DP thymocytes to cell death in these mice produces an accelerated reconstitution of normal thymic populations upon in vivo DP elimination. Together, these data indicate that the JNK pathway contributes to the deletion of DP thymocytes by apoptosis in response to TCR-derived and other thymic environment– mediated signals

What Practitioners Should Understand About Bovine Lymphosarcoma

Bovine lymphosarcoma (BLS) is a common neoplasm found in both dairy and beef cattle. It is important for veterinarians, dairy producers and beef producers to gain a thorough understanding of BLS. The 'first step in understanding BLS is to define the disease. Bovine leukosis, bovine leukemia, bovine lymphoma, and malignant lymphoma are misnomers that add confusion and frustration in understanding the disease process of BLS. There are currently four distinct forms of BLS: calf form, thymic form, skin form, and adult or bovine leukemia virus (BLV) associated form. In understanding these forms of BLS it is important to know what clinical signs to look for, how to make the diagnosis, the treatment options and recommendations for prevention and control.</p

c-Jun N-Terminal Kinase 1 Is Required for Toll-Like Receptor 1 Gene Expression in Macrophages▿

The regulation of innate immune responses to pathogens occurs through the interaction of Toll-like receptors (TLRs) with pathogen-associated molecular patterns and the activation of several signaling pathways whose contribution to the overall innate immune response to pathogens is poorly understood. We demonstrate a mechanism of control of murine macrophage responses mediated by TLR1/2 heterodimers through c-Jun N-terminal kinase 1 (JNK1) activity. JNK controls tumor necrosis factor alpha production and TLR-mediated macrophage responses to Borrelia burgdorferi, the causative agent of Lyme disease, and the TLR1/TLR2-specific agonist PAM3CSK4. JNK1, but not JNK2, activity regulates the expression of the tlr1 gene in the macrophage cell line RAW264.7, as well as in primary CD11b+ cells. We also show that the proximal promoter region of the human tlr1 gene contains an AP-1 binding site that is subjected to regulation by the kinase and binds two complexes that involve the JNK substrates c-Jun, JunD, and ATF-2. These results demonstrate that JNK1 regulates the response to TLR1/2 ligands and suggest a positive feedback loop that may serve to increase the innate immune response to the spirochete