Differential gene expression of bone marrow-derived CD34+ cells is associated with survival of patients suffering from myelodysplastic syndrome

One feature of the molecular pathology of myelodysplastic syndromes (MDS) is aberrant gene expression. Such aberrations may be related to patient survival, and may indicate to novel diagnostic and therapeutic targets. Therefore, we aimed at identifying aberrant gene expression that is associated with MDS and patient survival. Bone marrow-derived CD34+ hematopoietic progenitor cells from six healthy persons and 16 patients with MDS were analyzed on cDNA macroarrays comprising 1,185 genes. Thereafter, our patients were followed-up for 54 months. We found differential expression of genes that were hitherto unrecognized in the context of MDS. Differential expression of 10 genes was confirmed by quantitative real-time RT-PCR. Hierarchical cluster analysis facilitated the separation of CD34+ cells of normal donors from patients with MDS. More importantly, it also distinguished MDS-patients with short and long survival. Scrutinizing our cDNA macroarray data for genes that are associated with short survival, we found, among others, increased expression of six different genes that encode the proteasome subunits. On the other hand, the most differentially down-regulated gene was IEX-1, which encodes an anti-apoptotic protein. We confirmed its decreased expression on RNA and protein level in an independent validation set of patient samples. The presented data broadens our notion about the molecular pathology of MDS and may lend itself to better identify patients with short survival. Furthermore, our findings may help to define new molecular targets for drug development and therapeutic approaches for patients with poor prognosis.     

Characterization of the Cryptosporidium antigens from sporulated oocysts of Cryptosporidium parvum.

The antigenic constituents of sporulated Cryptosporidium parvum oocyst antigens were characterized with antisera from mice immunized against C. parvum. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver staining defined the major proteins. Six of seven lectins used recognized as many as 15 bands. The lectins concanavalin A, Dolichos biflorus, and wheat germ agglutinin showed strong activity against the same eight bands with molecular weights ranging from 72,000 to greater than 100,000. An enzyme-linked immunosorbent assay was used to detect antibody to C. parvum. Antibody binding was significantly decreased by heat and enzymatic treatment with trypsin, protease, and mixed glycosidases. C. parvum antigens were further defined by the reactivity of immune sera with a C. parvum sonicate preparation separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrophoretically transferred to nitrocellulose paper. Antisera from orally infected mice consistently recognized four antigens with molecular weights ranging from 72,000 to greater than 100,000. These antigens also bound concanavalin A. Treatment of the antigen preparation with mixed glycosidases reduced the reactivity of antisera with most antigens with molecular weights greater than 60,000. The data suggest that the antigenic composition of C. parvum is complex and that carbohydrates alone or in association with lipids or proteins may be important in the immune response to C. parvum.     

Impact of human myelin on the maturation and function of human monocyte-derived dendritic cells

Macrophages and dendritic cells (DC) play an important role in the immunopathology of multiple sclerosis. We analyzed the impact of human myelin on monocyte-derived DC and describe their immunostimulatory capacity. Cells were grown on myelin and stimulated with LPS or a defined maturation cocktail. DC activation was analyzed by the expression of cell surface markers and the secretion of cytokines and chemokines. The immunostimulatory capacity of DC was assessed by allogeneic mixed-leukocyte reactions via proliferation. Additionally, their ability to bias T cells towards Th1, Th17 or Treg differentiation was investigated. We found that phagocytosis of myelin impaired the activation of DC, displayed by an impaired ability to stimulate allogeneic T cells, an increased production of TGF-β1 and a diminished upregulation of CCR7 but did not affect the differentiation into T helper cell subsets. We hypothesize that myelin influences DC activation and plays a pivotal role in balancing immunity and tolerance.     

Effect of short-term digoxin treatment on ouabain-sensitive sodium transport of erythrocytes

In hemodialyzed patients, the serum albumin concentration determined by the bromcresol purple (BCP) method was lower than that determined by an immunological method. The degree of underestimation appeared to be well correlated to the serum concentration of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), a major endogenous ligand substance present in uremic serum. CMPF inhibited in vitro the binding of BCP to serum protein and human serum albumin. Our results suggest that CMPF is a major interferent in the underestimation of the serum albumin concentration by the BCP method in uremia.     

Level of Digitalization in Germany: Results of the Diabetes Digitalization and Technology (D.U.T) Report 2020

Background:New diagnostic and therapeutic technologies are increasingly changing the treatment of people with diabetes (PWD), along with increased usage of digital tools. To date, however, there is little data to which level and how diabetologists and PWD implement digitalization. Also, not much is known about the view of diabetologists on the current status and future developments in this respect.Method:In an online survey, diabetologists working in clinics and practices across Germany provided responses regarding their view on digitalization and the adoption of new technologies in diabetology to 56 questions. These comments reflect the opinion of several experts about the current importance and use of specific digital/technological topics.Results:Overall, 326 diabetologists took part in the survey. They reported a positive attitude (75.8%) toward new technologies and digitalization, and they see more advantages rather than disadvantages. Younger age of the diabetologists was significantly associated with a more positive attitude (r = −0.176; P < .01), and there was no gender effect (P = .738). On average, in each practice, 5.5% of PWD are using an insulin pump for therapy, 4.8% a real-time continuous glucose monitoring system, 16.9% an intermittent scanning continuous glucose monitoring system, and 0.3% an automated insulin delivery (AID) system. With respect to digitalization, the three most important current topics are software for glucose data analysis (average rank on a scale from one to six, with one being the most important: 2.4), compatibility with other systems (2.9), and AID systems (3.8)).Conclusions:This survey, which is going to be repeated annually, showed that the diabetologists who participated predominantly have a positive attitude toward new technologies and digital applications and were aware of the associated advantages. However, perceived disadvantages need to be addressed to enable wider adoption of new technologies and digital solutions.