[C1-esterase inhibitor in ACE inhibitor-induced severe angioedema of the tongue]. / C1-Esterase-Inhibitor bei ACE-Hemmer-induziertem schwerem Angioödem der Zunge.

Angio-oedema are often massive but temporary swellings of the soft tissue of the face or the throat, which can also affect other regions of the human body (e.g. the skin or internal organs). An oedema of the face and throat represents a life-threatening situation. Apart from the clinical condition of the patient and detailed knowledge of the medical history (incl. medical applications), the treatment should depend on the different pathogenesis. In this reported case, we describe the severe clinical development of an angio-oedema under a long-term treatment with an ACE-inhibitor, which in the end was only successfully treated with the application of a C1 inhibitor concentrate.

MyoD stimulates delta-1 transcription and triggers notch signaling in the Xenopus gastrula.

The Notch signaling cascade is involved in many developmental decisions, a paradigm of which has been the selection between epidermal and neural cell fates in both invertebrates and vertebrates. Notch has also been implicated as a regulator of myogenesis, although its precise function there has remained controversial. Here we show that the muscle-determining factor MyoD is a direct, positive regulator of the Notch ligand Delta-1 in prospective myoblasts of the pre-involuted mesoderm in Xenopus gastrulae. Injection of a dominant MyoD repressor variant ablates mesodermal Delta-1 expression in vivo. Furthermore, MyoD-dependent Delta-1 induction is sufficient to activate transcription from promoters of E(spl)-related genes in a Notch-dependent manner. These results indicate that a hallmark of neural cell fate determination, i.e. the feedback loop between differentiation promoting basic helix-loop-helix proteins and the Notch regulatory circuitry, is conserved in myogenesis, supporting a direct involvement of Notch in muscle determination.

Temporal restriction of MyoD induction and autocatalysis during Xenopus mesoderm formation.

In Xenopus, the activation of the myogenic determination factors MyoD and Myf-5 in the muscle-forming region of the embryo occurs in response to mesoderm-inducing factors (MIFs). Different members of the FGF, TGF-beta, and Wnt protein families have been implicated in this process, but how MIFs induce the myogenic regulators is not known. For MyoD, the induction process may serve to locally stabilize a transient burst of ubiquitous transcription at the midblastula transition, possibly by triggering MyoD's autocatalytic loop. Here we have sought to distinguish separate activating functions during MyoD induction by analyzing when MyoD responds to different MIF signaling or to MyoD autoactivation. We show that MyoD induction depends on the developmental age of the induced cells, rather than on the type or time point of inducer application. At the permissive time, de novo MyoD induction by Activin requires less than 90 min, arguing for an immediate response, rather than a series of inductive events. MyoD autoactivation is direct, but subject to the same temporal restriction as MyoD induction by MIF signaling. Further evidence implicating MyoD autocatalysis as an essential component of the induction process comes from the observation that both autocatalysis and induction of MyoD are selectively repressed by a dominant-negative MyoD mutant. In summary, our observations let us conclude that MyoD's expression domain in the embryo results from an interplay of timed changes in cellular competence, pleiotropic signaling pathways, and autocatalysis.

The globular domain of histone H1 is sufficient to direct specific gene repression in early Xenopus embryos.

One molecule of a linker histone such as histone H1 is incorporated into every metazoan nucleosome [1]. Histone H1 has three distinct structural domains: the positively charged amino-terminal and carboxy-terminal tails are separated by a globular domain that is similar to the winged-helix motif found in sequence-specific DNA-binding proteins [2]. The globular domain interacts with DNA immediately contiguous to that wrapped around the core histones [3,4], whereas the tail domains are important for the compaction of nucleosomal arrays [5]. Experiments in vivo indicate that histone H1 does not function as a global transcriptional repressor, but instead has more specific regulatory roles [6-9]. In Xenopus, maternal stores of the B4 linker histone that are assembled into chromatin during the early cleavage divisions are replaced by somatic histone H1 during gastrulation [10]. This transition in chromatin composition causes the repression of genes encoding oocyte-type 5S rRNAs, and restricts the competence of ectodermal cells to differentiate into mesoderm [6,9-11]. Here, we demonstrate that the globular domain of histone H1 is sufficient for directing gene-specific transcriptional repression and for restricting the mesodermal competence of embryonic ectoderm. We discuss our results in the context of specific structural roles for this domain in the nucleosome.

Somatic linker histones cause loss of mesodermal competence in Xenopus.

In Xenopus, cells from the animal hemisphere are competent to form mesodermal tissues from the morula through to the blastula stage. Loss of mesodermal competence at early gastrula is programmed cell-autonomously, and occurs even in single cells at the appropriate stage. To determine the mechanism by which this occurs, we have been investigating a concomitant, global change in expression of H1 linker histone subtypes. H1 histones are usually considered to be general repressors of transcription, but in Xenopus they are increasingly thought to have selective functions in transcriptional regulation. Xenopus eggs and embryos at stages before the midblastula transition are deficient in histone H1 protein, but contain an oocyte-specific variant called histone B4 or H1M. After the midblastula transition, histone B4 is progressively substituted by three somatic histone H1 variants, and replacement is complete by early neurula. Here we report that accumulation of somatic H1 protein is rate limiting for the loss of mesodermal competence. This involves selective transcriptional silencing of regulatory genes required for mesodermal differentiation pathways, like muscle, by somatic, but not maternal, H1 protein.