At least two distinct epigenetic mechanisms are correlated with high-frequency “switching” for aprt phenotypic expression in mouse embryonal carcinoma stem cells

A series of clones displaying high frequency switching phenotypes for expression of the adenine phosphoribosyltransferase (aprt) gene were previously isolated from the P19 mouse embryonal carcinoma stem cell line. Most clones contained only oneaprt allele. We report here the characterization of each of these clones with regards to enzymatic activity, mRNA steady state levels, DNA methylation, and chromatin conformation. When clones were selected for resistance to the purine analog 2,6-diaminopurine, which requires markedly reduced levels of APRT enzymatic activity, two distinct classes were observed. The first class was associated with reduced or undetectable levels ofaprt mRNA, hypermethylation of the 5 CpG island, and a closed chromatin conformation within this region. When clones of this class were selected for reacquisition of APRT enzymatic activity they were found to have increased mRNA levels, a hypomethylated CpG island, and an open chromatin conformation. In contrast, the second class of clones displayed wild-type levels of mRNA, CpG island hypomethylation, and an open chromatin conformation regardless of whether they were selected for the presence or absence of APRT enzymatic activity. The implications of these results for general mechanisms of epigenetic change in somatic cells and the possibility that expression of the mouseaprt gene may be developmentally regulated are discussed.     

Gleichstrommessungen an der menschlichen Haut bei Quellung und Entquellung des Gewebes

Zusammenfassung 1. Die biophysikalischen Ursachen meßbarer Veränderungen im Verhalten des menschlichen Hautwiderstandes werden mit der Methode des Elektropermeagramms durch Aufzeichnung eines gewebsaufladenden Gleichstroms untersucht.2. Durch verschiedenartige und variierte experimentelle Versuchsanordnungen sowie klinische Beobachtungen wird nachgewiesen, daß den Schweißdrüsen weder in morphologischer noch funktioneller Beziehung ein erkennbarer Einfluß auf das Verhalten des polarisatorischen Hautwiderstandes, des Anfangs- und Endwiderstandes im Elektropermeagramm zuzuschreiben ist.3. Für Veränderungen der Hautwiderstände ist der Hydratationszustand der lebenden Epidermis im Sinne ihrer Quellung und Entquellung maßgebend.     

Fetal development in experimental uremia

Summary Uremic women on hemodialysis with metabolic bone disease (hyperparathyroidism, osteomalacia resulting from defective vitamin D metabolism) and anemia (erythropoietin deficiency) are known to give birth to infants without bone disease or anemia. Therefore, skeletal development (enchondral and desmal bone formation) and hepatic erythropoiesis were evaluated in fetuses of uremic rats. These fetuses failed to show defective mineralisation or evidence of bone disease. Bolus injection of high doses of exogenous PTH into the maternal or fetal organism did not affect fetal bone histology. In addition, no apparent defect of bone mineralisation or bone formation was found in fetuses of ricketic rats. Normal mineralisation in the offspring of uremic rats may be explained by fetal hyperphosphatemia and/or insensitivity of fetal (woven) bone mineralisation to vitamin D.Absence of fetal anemia (normal hematocrits, normal density of hematopoietic cells in the liver) in the presence of maternal anemia is presumably due to the insensitivity of fetal erythropoiesis to erythropoietin.With the support of Deutsche Forschungsgemeinschaft     

Trisomy 4 as the sole cytogenetic abnormality in a Waldenström macroglobulinemia

We report a case of Waldenstr?m macroglobulinemia with trisomy 4 as the sole cytogenetic abnormality. Trisomy 4 has been reported previously in Waldenstr?m macroglobulinemia, but only in conjunction with multiple chromosomal aberrations. Trisomy 4 has been reported in other hematologic malignancies including acute myeloid and lymphoid leukemias.