Aplastic Crisis as Primary Manifestation of Systemic Lupus Erythematosus

Aplastic crisis is an unusual feature of systemic lupus erythematosus (SLE). We report the case of a 54-year-old woman presenting with both (extravascular) Coombs-positive hemolytic anemia and laboratory findings of bone marrow hyporegeneration with concomitant severe neutropenia. A bone marrow biopsy confirmed aplastic crisis. Diagnostic work-up revealed soaring titers of autoantibodies (anti-nuclear, anti-double-stranded DNA, anti-cardiolipin-IgM, and anti-beta 2-glykoprotein-IgM antibodies), indicating a connective tissue disease as the most plausible reason for bone marrow insufficiency. As the criteria for SLE were fulfilled, we initiated an immunosuppressive therapy by steroids, which led to a rapid complete hematologic and clinical remission in our patient. In this case, we could report on one of the rare cases of SLE-induced aplastic crisis showing that this condition can be entirely reversed by immunosuppressive treatment and that SLE-induced aplastic crisis yields a good prognosis. In conclusion, in a case of aplastic crisis, physicians should be aware that SLE can be a rare cause that is accessible to specific treatment

Anomalous Dimensions and Non-Gaussianity

We analyze the signatures of inflationary models that are coupled to strongly interacting field theories, a basic class of multifield models also motivated by their role in providing dynamically small scales. Near the squeezed limit of the bispectrum, we find a simple scaling behavior determined by operator dimensions, which are constrained by the appropriate unitarity bounds. Specifically, we analyze two simple and calculable classes of examples: conformal field theories (CFTs), and large-N CFTs deformed by relevant time-dependent double-trace operators. Together these two classes of examples exhibit a wide range of scalings and shapes of the bispectrum, including nearly equilateral, orthogonal and local non-Gaussianity in different regimes. Along the way, we compare and contrast the shape and amplitude with previous results on weakly coupled fields coupled to inflation. This signature provides a precision test for strongly coupled sectors coupled to inflation via irrelevant operators suppressed by a high mass scale up to 1000 times the inflationary Hubble scale.Comment: 40 pages, 10 figure

Single beat 3D echocardiography for the assessment of right ventricular dimension and function after endurance exercise: Intraindividual comparison with magnetic resonance imaging

<p>Abstract</p> <p>Background</p> <p>Our study compares new single beat 3D echocardiography (sb3DE) to cardiovascular magnetic resonance imaging (CMR) for the measurement of right ventricular (RV) dimension and function immediately after a 30 km run. This is to validate sb3DE against the "gold standard" CMR and to bring new insights into acute changes of RV dimension and function after endurance exercise.</p> <p>Methods</p> <p>21 non-elite male marathon runners were examined by sb3DE (Siemens ACUSON SC2000, matrix transducer 4Z1c, volume rates 10-29/s), CMR (Siemens Magnetom Avanto, 1,5 Tesla) and blood tests before and immediately after each athlete ran 30 km. The runners were not allowed to rehydrate after the race. The order of sb3DE and CMR examination was randomized.</p> <p>Results</p> <p>Sb3DE for the acquisition of RV dimension and function was feasible in all subjects. The decrease in mean body weight and the significant increase in hematocrit indicated dehydration. RV dimensions measured by CMR were consistently larger than measured by sb3DE.</p> <p>Neither sb3DE nor CMR showed a significant difference in the RV ejection fraction before and after exercise. CMR demonstrated a significant decrease in RV dimensions. Measured by sb3DE, this decrease of RV volumes was not significant.</p> <p>Conclusion</p> <p>First, both methods agree well in the acquisition of systolic RV function. The dimensions of the RV measured by CMR are larger than measured by sb3DE. After exercise, the RV volumes decrease significantly when measured by CMR compared to baseline.</p> <p>Second, endurance exercise seems not to induce acute RV dysfunction in athletes without rehydration.</p

TRPC4/TRPC5 channels mediate adverse reaction to the cancer cell cytotoxic agent (-)-Englerin A

(-)-Englerin A (EA) is a natural product which has potent cytotoxic effects on renal cell carcinoma cells and other types of cancer cell but not non-cancer cells. Although selectively cytotoxic to cancer cells, adverse reaction in mice and rats has been suggested. EA is a remarkably potent activator of ion channels formed by Transient Receptor Potential Canonical 4 and 5 proteins (TRPC4 and TRPC5) and TRPC4 is essential for EA-mediated cancer cell cytotoxicity. Here we specifically investigated the relevance of TRPC4 and TRPC5 to the adverse reaction. Injection of EA (2 mg.kg⁻¹ i.p.) adversely affected mice for about 1 hour, manifesting as a marked reduction in locomotor activity, after which they fully recovered. TRPC4 and TRPC5 single knockout mice were partially protected and double knockout mice fully protected. TRPC4/TRPC5 double knockout mice were also protected against intravenous injection of EA. Importance of TRPC4/TRPC5 channels was further suggested by pre-administration of Compound 31 (Pico145), a potent and selective small-molecule inhibitor of TRPC4/TRPC5 channels which did not cause adverse reaction itself but prevented adverse reaction to EA. EA was detected in the plasma but not the brain and so peripheral mechanisms were implicated but not identified. The data confirm the existence of adverse reaction to EA in mice and suggest that it depends on a combination of TRPC4 and TRPC5 which therefore overlaps partially with TRPC4-dependent cancer cell cytotoxicity. The underlying nature of the observed adverse reaction to EA, as a consequence of TRPC4/TRPC5 channel activation, remains unclear and warrants further investigation

Pig α₁-Acid Glycoprotein: Characterization and First Description in Any Species as a Negative Acute Phase Protein.

The serum protein α1-acid glycoprotein (AGP), also known as orosomucoid, is generally described as an archetypical positive acute phase protein. Here, porcine AGP was identified, purified and characterized from pooled pig serum. It was found to circulate as a single chain glycoprotein having an apparent molecular weight of 43 kDa by SDS-PAGE under reducing conditions, of which approximately 17 kDa were accounted for by N-bound oligosaccharides. Those data correspond well with the properties of the protein predicted from the single porcine AGP gene (ORM1, Q29014 (UniProt)), containing 5 putative glycosylation sites. A monoclonal antibody (MAb) was produced and shown to quantitatively and specifically react with all microheterogenous forms of pig AGP as analyzed by 2-D electrophoresis. This MAb was used to develop an immunoassay (ELISA) for quantification of AGP in pig serum samples. The adult serum concentrations of pig AGP were in the range of 1-3 mg/ml in a number of conventional pig breeds while it was lower in Göttingen and Ossabaw minipigs (in the 0.3 to 0.6 mg/ml range) and higher in young (2-5 days old) conventional pigs (mean: 6.6 mg/ml). Surprisingly, pig AGP was found to behave as a negative acute phase protein during a range of experimental infections and aseptic inflammation with significant decreases in serum concentration and in hepatic ORM1 expression during the acute phase response. To our knowledge this is the first description in any species of AGP being a negative acute phase protein

Radionuclide imaging of bone marrow disorders

Noninvasive imaging techniques have been used in the past for visualization the functional activity of the bone marrow compartment. Imaging with radiolabelled compounds may allow different bone marrow disorders to be distinguished. These imaging techniques, almost all of which use radionuclide-labelled tracers, such as 99mTc-nanocolloid, 99mTc-sulphur colloid, 111In-chloride, and radiolabelled white blood cells, have been used in nuclear medicine for several decades. With these techniques three separate compartments can be recognized including the reticuloendothelial system, the erythroid compartment and the myeloid compartment. Recent developments in research and the clinical use of PET tracers have made possible the analysis of additional properties such as cellular metabolism and proliferative activity, using 18F-FDG and 18F-FLT. These tracers may lead to better quantification and targeting of different cell systems in the bone marrow. In this review the imaging of different bone marrow targets with radionuclides including PET tracers in various bone marrow diseases are discussed

Traits associated with innate and adaptive immunity in pigs: heritability and associations with performance under different health status conditions

There is a need for genetic markers or biomarkers that can predict resistance towards a wide range of infectious diseases, especially within a health environment typical of commercial farms. Such markers also need to be heritable under these conditions and ideally correlate with commercial performance traits. In this study, we estimated the heritabilities of a wide range of immune traits, as potential biomarkers, and measured their relationship with performance within both specific pathogen-free (SPF) and non-SPF environments. Immune traits were measured in 674 SPF pigs and 606 non-SPF pigs, which were subsets of the populations for which we had performance measurements (average daily gain), viz. 1549 SPF pigs and 1093 non-SPF pigs. Immune traits measured included total and differential white blood cell counts, peripheral blood mononuclear leucocyte (PBML) subsets (CD4+ cells, total CD8α+ cells, classical CD8αβ+ cells, CD11R1+ cells (CD8α+ and CD8α-), B cells, monocytes and CD16+ cells) and acute phase proteins (alpha-1 acid glycoprotein (AGP), haptoglobin, C-reactive protein (CRP) and transthyretin). Nearly all traits tested were heritable regardless of health status, although the heritability estimate for average daily gain was lower under non-SPF conditions. There were also negative genetic correlations between performance and the following immune traits: CD11R1+ cells, monocytes and the acute phase protein AGP. The strength of the association between performance and AGP was not affected by health status. However, negative genetic correlations were only apparent between performance and monocytes under SPF conditions and between performance and CD11R1+ cells under non-SPF conditions. Although we cannot infer causality in these relationships, these results suggest a role for using some immune traits, particularly CD11R1+ cells or AGP concentrations, as predictors of pig performance under the lower health status conditions associated with commercial farms

A Novel PAN/Apple Domain-Containing Protein from Toxoplasma gondii: Characterization and Receptor Identification

Toxoplasma gondii is an intracellular parasite that invades nucleated cells, causing toxoplasmosis in humans and animals worldwide. The extremely wide range of hosts susceptible to T. gondii is thought to be the result of interactions between T. gondii ligands and receptors on its target cells. In this study, a host cell-binding protein from T. gondii was characterized, and one of its receptors was identified. P104 (GenBank Access. No. CAJ20677) is 991 amino acids in length, containing a putative 26 amino acid signal peptide and 10 PAN/apple domains, and shows low homology to other identified PAN/apple domain-containing molecules. A 104-kDa host cell-binding protein was detected in the T. gondii lysate. Immunofluorescence assays detected P104 at the apical end of extracellular T. gondii. An Fc-fusion protein of the P104 N-terminus, which contains two PAN/apple domains, showed strong affinity for the mammalian and insect cells evaluated. This binding was not related to protein-protein or protein-lipid interactions, but to a protein-glycosaminoglycan (GAG) interaction. Chondroitin sulfate (CS), a kind of GAG, was shown to be involved in adhesion of the Fc-P104 N-terminus fusion protein to host cells. These results suggest that P104, expressed at the apical end of the extracellular parasite, may function as a ligand in the attachment of T. gondii to CS or other receptors on the host cell, facilitating invasion by the parasite