A HOX complex, a repressor element and a 50 bp sequence confer regional specificity to a DPP-responsive enhancer.

A central theme during development and homeostasis is the generation of cell type-specific responses to the action of a limited number of extant signaling cascades triggered by extracellular ligands. The molecular mechanisms by which information from such signals are integrated in responding cells in a cell-type specific manner remain poorly understood. We have undertaken a detailed characterization of an enhancer that is regulated by DPP signaling and by the homeotic protein Labial and its partners, Extradenticle and Homothorax. The expression driven by this enhancer (lab550) and numerous deletions and point mutants thereof was studied in wild-type and mutant Drosophila embryos as well as in cultured cells. We find that the lab550 enhancer is composed of two elements, a Homeotic Response Element (HOMRE) and a DPP Response Element (DPPRE) that synergize. None of these two elements can reproduce the expression of lab550, either with regard to expression level or with regard to spatial restriction. The isolated DPPRE of lab550 responds extremely weakly to DPP. Interestingly, we found that the inducibility of this DPPRE is weak because it is tuned down by the action of a repressor element. This repressor element and an additional 50 bp element appear to be crucial for the cooperation of the HOMRE and the DPPRE, and might tightly link the DPP response to the homeotic input. The cooperation between the different elements of the enhancer leads to the segmentally restricted activity of lab550 in the endoderm and provides a mechanism to create specific responses to DPP signaling with the help of a HOX protein complex.

Expression of the blistered/DSRF gene is controlled by different morphogens during Drosophila trachea and wing development.

The Drosophila serum response factor (DSRF) is expressed in the precursors of the terminal tracheal cells and in the future intervein territories of the third instar wing imaginal disc. Dissection of the DSRF regulatory region reveals that a single enhancer element, which is under the control of the fibroblast growth factor (FGF)-receptor signalling pathway, is sufficient to induce DSRF expression in the terminal tracheal cells. In contrast, two separate enhancers direct expression in distinct intervein sectors of the wing imaginal disc. One element is active in the central intervein sector and is induced by the Hedgehog signalling pathway. The other element is under the control of Decapentaplegic and is active in two separate territories, which roughly correspond to the intervein sectors flanking the central sector. Hence, each of the three characterized enhancers constitutes a molecular link between a specific territory induced by a morphogen signal and the localized expression of a gene required for the final differentiation of this territory.

Multiple requirements for the receptor serine/threonine kinase thick veins reveal novel functions of TGF beta homologs during Drosophila embryogenesis.

Differentiation of distinct cell types at specific locations within a developing organism depends largely on the ability of cells to communicate. A major class of signalling proteins implicated in cell to cell communication is represented by members of the TGF beta superfamily. A corresponding class of transmembrane serine/threonine kinases has recently been discovered that act as cell surface receptors for ligands of the TGF beta superfamily. The product of the Drosophila gene decapentaplegic (dpp) encodes a TGF beta homolog that plays multiple roles during embryogenesis and the development of imaginal discs. Here we describe the complex expression pattern of thick veins (tkv), which encodes a receptor for dpp. We make use of tkv loss-of-function mutations to examine the consequences of the failure of embryonic cells to respond to dpp and/or other TGF beta homologs. We find that while maternal tkv product allows largely normal dorsoventral pattering of the embryo, zygotic tkv activity is indispensable for dorsal closure of the embryo after germ band retraction. Furthermore, tkv activity is crucial for patterning the visceral mesoderm; in the absence of functional tkv gene product, visceral mesoderm parasegment 7 cells fail to express Ultrabithorax, but instead accumulate Antennapedia protein. The tkv receptor is therefore involved in delimiting the expression domains of homeotic genes in the visceral mesoderm. Interestingly, tkv mutants fail to establish a proper tracheal network. Tracheal braches formed by cells migrating in dorsal or ventral directions are absent in tkv mutants. The requirements for tkv in dorsal closure, visceral mesoderm and trachea development assign novel functions to dpp or a closely related member of the TGF beta superfamily.

Inhibitory action of transforming growth factor beta on endothelial cells.

In the present study, we show that transforming growth factor beta (TGF-beta) strongly inhibits fibroblast growth factor-induced proliferation and motility of bovine endothelial cells in tissue culture. TGF-beta also prevents the phorbol ester-induced invasion of capillary endothelial cells into collagen matrices--i.e., blocks angiogenesis in vitro. TGF-beta promotes the incorporation of fibronectin into the extracellular matrix of endothelial cells and stimulates the secretion of other proteins--mainly of 55- and 180-kDa components. We show furthermore that endothelial cells express TGF-beta receptors similar in size to those of other tissue culture cell lines: a 280-kDa complex is present in subconfluent cells, and 85- and 72-kDa protein bands are seen in confluent cells. The various effects of TGF-beta on endothelial cells suggest that these cells are an important target of TGF-beta during wound healing and angiogenesis.

[Intravenous injections of dissolved pentazocin tablets (Fortalgesic)--a new aspect of drug abuse in our country?]. / Intravenöse Injektion von aufgelösten Pentazocin- Tabletten (Fortalgesic)- ein neuer Aspekt des Drogenmissbrauchs auch bei uns?

A first case is reported of illicit intravenous injection of pentazocine tablets recognized in a country other than the USA. The pulmonary complications of i.v. drug abuse in general and in particular the hazards of injection of aqueous suspensions of pharmaceutical preparations intended for oral consumption, with embolization of abundant insoluble foreign material, are discussed. Diagnostic, therapeutic and prophylactic procedures are suggested.

Unusual pulmonary vascular lesions after intravenous injections of microcrystalline cellulose. A complication of pentazocine tablet abuse.

We present the morphological features of a case of fatal pulmonary granulomatosis from illicit intravenous injections of microcrystalline cellulose derived from pentazocine tablets. Extensive foreign body granulomas were found in the lumena and walls of pulmonary vessels and in the pulmonary interstitium. Previously unreported gaps containing foreign material were found in the walls of medium-sized muscular pulmonary arteries. This peculiar finding is discussed in the light of the possible mechanisms involved in the removal of embolized foreign material.

[Postoperative stress hemorrhage: ineffective prevention with pepsin inhibitor and deglycyrrhizinized licorice extract. Prospective study]. / Postoperative Stressblutung: unwirksame Prophylaxe mit einem Pepsininhibitor und einem glycyrrhizinsäurefreien Süssholzextrakt. Prospektive Studien

A double blind controlled study on prophylaxis of postoperative gastrointestinal bleeding from stress lesions was performed. Both tragant sulfate, a pepsin inhibitor, and deglycyrrhizinized liquorice extract proved to be without prophylactic effect.

[A prospective study of post-operative bleeding from stress lesions. I. Epidemiology (author's transl)]. / Prospektive Studien über die postoperative Stressblutung. I. Epidemiologie

Among 5776 patients operated on under general anaesthesia there was an increased risk of postoperative gastro-intestinal bleeding from stress lesions among those aged over 70 years, after major surgery, or with complications such as hypovolaemia, septicaemia or respiratory failure (n = 551). In this group of patients the incidence of fatal haemorrhage was 0.5%. Stress lesions were a certain cause of bleeding from the gastro-intestinal tract in 5.1% and a probable one in 5.1%. Time of year, sex, past history of peptic ulcer, or anticoagulation did not increase the risk of bleeding.