Multifocal cutaneous non-epitheliotropic B-cell lymphoma in a cat.

CASE SUMMARY: Skin tumours are the second-most common form of feline cancer after haematopoietic neoplasms and are often malignant. Cutaneous lymphoma is uncommon in cats and can be classified as epitheliotropic (typically of T-cell origin) or non-epitheliotropic (either of T-cell or B-cell origin). The present study describes a case of multifocal cutaneous non-epitheliotropic B-cell lymphoma. The skin nodules were multiple and variable in size; showed rapid progression; were alopecic and erythematous in appearance and pruritic and ulcerated; and were mostly located on the trunk. Nodule biopsies revealed the presence of uniform medium-to-large round neoplastic cells that infiltrated the dermis and subcutis. The neoplasias were consistent with a round cell cutaneous tumour and did not show evidence of epitheliotropism. Furthermore, immunohistochemical assessments indicated an immunophenotype characterised by round cells with a strong membrane and cytoplasmic positivity for the CD20 antigen, consistent with a lymphocyte of B-cell origin. RELEVANCE AND NOVEL INFORMATION: Cutaneous non-epitheliotropic B-cell lymphoma in cats is rare and was previously reported to appear as single dermal and subcutaneous masses that are variable in size and generally develop in the tarsal region. To our knowledge, this is the first report to describe multifocal cutaneous non-epitheliotropic B-cell lymphoma in a cat.

Gene expression profiles in peripheral blood mononuclear cells of chronic heart failure patients.

The present study was aimed at identifying chronic heart failure (CHF) biomarkers from peripheral blood mononuclear cells (PBMCs) in patients with ischemic (ICM) and nonischemic dilated (NIDCM) cardiomyopathy. PBMC gene expression profiling was performed by Affymetrix in two patient groups, 1) ICM (n = 12) and 2) NIDCM (n = 12) New York Heart Association (NYHA) III/IV CHF patients, vs. 3) age- and sex-matched control subjects (n = 12). Extracted RNAs were then pooled and hybridized to a total of 11 microarrays. Gene ontology (GO) analysis separated gene profiling into functional classes. Prediction analysis of microarrays (PAM) and significance analysis of microarrays (SAM) were utilized in order to identify a molecular signature. Candidate markers were validated by quantitative real-time polymerase chain reaction. We identified a gene expression profiling that distinguished between CHF patients and control subjects. Interestingly, among the set of genes constituting the signature, chemokine receptor (CCR2, CX(3)CR1) and early growth response (EGR1, 2, 3) family members were found to be upregulated in CHF patients vs. control subjects and to be part of a gene network. Such findings were strengthened by the analysis of an additional 26 CHF patients (n = 14 ICM and n = 12 NIDCM), which yielded similar results. The present study represents the first large-scale gene expression analysis of CHF patient PBMCs that identified a molecular signature of CHF and putative biomarkers of CHF, i.e., chemokine receptor and EGR family members. Furthermore, EGR1 expression levels can discriminate between ICM and NIDCM CHF patients.

The schistosome enzyme that activates oxamniquine has the characteristics of a sulfotransferase

Available evidence suggests that the antischistosomal drug oxamniquine is converted to a reactive ester by a schistosome enzyme that is missing in drug-resistant parasites. This study presents data supporting the idea that the active ester is a sulfate and the activating enzyme is a sulfotransferase. Evidence comes from the fact that the parasite extract loses its activating capability upon dialysis, implying the requirement of some dialyzable cofactor. The addition of the sulfate donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) restored activity of the dialyzate, a strong indication that a sulfotransferase is probably involved. Classical sulfotransferase substrates like beta-estradiol and quercetin competitively inhibited the activation of oxamniquine. Furthermore, these substrates could be sulfonated in vitro using an extract of sensitive (but not resistant) schistosomes. Gel filtration analysis showed that the activating factor eluted in a fraction corresponding to a molecular mass of about 32 kDa, which is the average size of typical sulfotransferase subunits. Ion exchange and affinity chromatography confirmed the sulfotransferase nature of the enzyme. Putative sulfotransferases present in schistosome databases are being examined for their possible role as oxamniquine activators.

The schistosome enzyme that activates oxamniquine has the characteristics of a sulfotransferase.

Available evidence suggests that the antischistosomal drug oxamniquine is converted to a reactive ester by a schistosome enzyme that is missing in drug-resistant parasites. This study presents data supporting the idea that the active ester is a sulfate and the activating enzyme is a sulfotransferase. Evidence comes from the fact that the parasite extract loses its activating capability upon dialysis, implying the requirement of some dialyzable cofactor. The addition of the sulfate donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) restored activity of the dialyzate, a strong indication that a sulfotransferase is probably involved. Classical sulfotransferase substrates like beta-estradiol and quercetin competitively inhibited the activation of oxamniquine. Furthermore, these substrates could be sulfonated in vitro using an extract of sensitive (but not resistant) schistosomes. Gel filtration analysis showed that the activating factor eluted in a fraction corresponding to a molecular mass of about 32 kDa, which is the average size of typical sulfotransferase subunits. Ion exchange and affinity chromatography confirmed the sulfotransferase nature of the enzyme. Putative sulfotransferases present in schistosome databases are being examined for their possible role as oxamniquine activators.

Laminar shear stress inhibits CXCR4 expression on endothelial cells: functional consequences for atherogenesis.

Laminar shear stress (LSS) represents a major athero-protective stimulus. However, the mechanisms for this effect are poorly characterized. As chemokine receptors modulate endothelial cell functions, we hypothesized that at least some LSS effects on endothelial cells (ECs) may be due to LSS-dependent changes in chemokine receptor expression and function. Exposure of Human umbilical vein endothelial cells (HUVECs) to 15 dynes/cm2/sec(-1) LSS strongly inhibited CXC chemokine receptor 4 (CXCR4) expression at the transcriptional level and impaired stromal-derived factor (SDF)-1/CXCL12-driven chemotaxis. On the contrary, low shear stress (SS; 4 dynes/cm2/sec(-1)) only marginally affected CXCR4 expression when compared with static control cells. Differently from CXCR4, the expression of SDF-1 mRNA was not affected by LSS treatment. CXCR4 overexpression induced a dose-dependent endothelial cell apoptosis that was enhanced by SDF-1 treatment and was caspase-dependent. CXCR4 overexpression inhibited the LSS-mediated antiapoptotic effect on ECs and was associated to impairment of LSS-induced ERK1/2 phosphorylation. These findings suggest that LSS-induced CXCR4 down-regulation may contribute to endothelial cell survival. Interestingly, the expression of the proatherogenic chemokines MCP-1 and IL-8 was induced by SDF-1 treatment and by CXCR4 overexpression in HUVECs. Further, the known LSS-induced inhibition of MCP-1 expression was impaired in CXCR4 overexpressing ECs. Finally, CXCR4 was abundantly expressed by human atherosclerotic plaque endothelium that is exposed to low/absent shear stress, while it was poorly expressed by minimally diseased carotid artery endothelium. In conclusion, LSS-dependent CXCR4 down-regulation may contribute to atheroprotection by favoring the integrity of the endothelial barrier and by inhibiting MCP-1 and IL-8 expression.