Comparison of 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine-enhanced MRI in 471 patients with known or suspected renal lesions: Results of a multicenter, single-blind, interindividual, randomized clinical phase III trial

The purpose of this phase III clinical trial was to compare two different extracellular contrast agents, 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine, for magnetic resonance imaging (MRI) in patients with known or suspected focal renal lesions. Using a multicenter, single-blind, interindividual, randomized study design, both contrast agents were compared in a total of 471 patients regarding their diagnostic accuracy, sensitivity, and specificity to correctly classify focal lesions of the kidney. To test for noninferiority the diagnostic accuracy rates for both contrast agents were compared with CT results based on a blinded reading. The average diagnostic accuracy across the three blinded readers ('average reader') was 83.7% for gadobutrol and 87.3% for gadopentate dimeglumine. The increase in accuracy from precontrast to combined precontrast and postcontrast MRI was 8.0% for gadobutrol and 6.9% for gadopentate dimeglumine. Sensitivity of the average reader was 85.2% for gadobutrol and 88.7% for gadopentate dimeglumine. Specificity of the average reader was 82.1% for gadobutrol and 86.1% for gadopentate dimeglumine. In conclusion, this study documents evidence for the noninferiority of a single i.v. bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentate dimeglumine in the diagnostic assessment of renal lesions with CE-MRI

Loss of λ2³¹⁵ tarnsgene copy numbers influences the development of B1 cells.

Transgenic L2 mice contain high numbers of the lambda 2(315) immunoglobulin L chain gene in their germ line. They are characterized by an almost complete block in B2 cell development and dominance of B1 cells in their periphery. This was attributed to high transgene expression. Here, we describe a variant of such mice (L2V), which has lost half of the transgene copies. This results in decreased transgene expression. Consequently, such mice display less severe isotype exclusion and an increase in B cells expressing endogenous k light chains. In addition, the B2 cell compartment is enlarged. Nevertheless, L2V mice exhibit phosphatidylcholine (PtC) binding B cells expressing lambda L chains as well as an unaltered number of B1a cells expressing the dominating specificity usually encountered in L2 mice. Since in L2V mice transgene integration and regulation is identical to L2 mice, the correlation of decreased transgene expression and increased presence of B2 cells strongly suggests that high transgene expression is decisive for development of B1 cells in L2 mice

Development of Interleukin-17-Producing γδ T Cells Is Restricted to a Functional Embryonic Wave.

γδ T cells are an important innate source of interleukin-17 (IL-17). In contrast to T helper 17 (Th17) cell differentiation, which occurs in the periphery, IL-17-producing γδ T cells (γδT17 cells) are probably committed during thymic development. To study when γδT17 cells arise during ontogeny, we used TcrdH2BeGFP reporter mice to monitor T cell receptor (TCR) rearrangement and IL-17 production in the embryonic thymus. We observed that several populations such as innate lymphoid cells and early T cell precursors were able to produce IL-17 prior to (and thus independent of) TCR recombination. γδT17 cells were absent after transplantation of IL-17-sufficient bone marrow into mice lacking both Il17a and Il17f. Also, γδT17 cells were not generated after genetic restoration of defective Rag1 function in adult mice. Together, these data suggested that these cells developed exclusively before birth and subsequently persisted in adult mice as self-renewing, long-lived cells