Torre-Muir syndrome

The Torre-Muir syndrome is a tumour syndrome characterized by multiple cutaneous and extracutaneous primary carcinomas and different sebaceous neoplasias. The visceral adenocarcinomas are mainly found in the gastrointestinal and urogenital tract. A case of Torre-Muir syndrome is described in a female patient and the different tumour localizations are demonstrated.     

Determination of structural and functional overlap/divergence of five proto-type galectins by analysis of the growth-regulatory interaction with ganglioside GM1 in silico and in vitro on human neuroblastoma cells

The growth-regulatory interplay between ganglioside GM1 on human SK-N-MC neuroblastoma cells and an endogenous lectin provides a telling example for glycan (polysaccharide) functionality. Galectin-1 is the essential link between the sugar signal and the intracellular response. The emerging intrafamily complexity of galectins raises the question on defining extent of their structural and functional overlap/divergence. We address this problem for proto-type galectins in this system: ganglioside GM1 as ligand, neuroblastoma cells as target. Using the way human galectin-1 interacts with this complex natural ligand as template, we first defined equivalent positioning for distinct substitutions in the other tested proto-type galectins, e.g., Lys63 vs. Leu60/Gln72 in galectins-2 and -5. As predicted from our in silico work, the tested proto-type galectins have affinity for the pentasaccharide of ganglioside GM1. In contrast to solid-phase assays, cell surface presentation of the ganglioside did not support binding of galectin-5, revealing the first level of regulation. Next, a monomeric proto-type galectin (CG-14) can impair galectin-1-dependent negative growth control by competitively blocking access to the shared ligand without acting as effector. Thus, the quaternary structure of proto-type galectins is an efficient means to give rise to functional divergence. The identification of this second level of regulation is relevant for diagnostic monitoring. It might be exploited therapeutically by producing galectin variants tailored to interfere with galectin activities associated with the malignant phenotype. Moreover, the given strategy for comparative computational analysis of extended binding sites has implications for the rational design of galectin-type-specific ligands.     

Activation of PDE2 and PDE5 by specific GAF ligands: delayed activation of PDE5

BACKGROUND AND PURPOSE

By controlling intracellular cyclic nucleotide levels, phosphodiesterases (PDE) serve important functions within various signalling pathways. The PDE2 and PDE5 families are allosterically activated by their substrate cGMP via regulatory so-called GAF domains. Here, we set out to identify synthetic ligands for the GAF domains of PDE2 and PDE5.

EXPERIMENTAL APPROACH

Using fluorophore-tagged, isolated GAF domains of PDE2 and PDE5, promising cGMP analogues were selected. Subsequently, the effects of these analogues on the enzymatic activity of PDE2 and PDE5 were analysed.

KEY RESULTS

The PDE2 ligands identified, 5,6-DM-cBIMP and 5,6-DCl-cBIMP, caused pronounced, up to 40-fold increases of the cAMP- and cGMP-hydrolysing activities of PDE2. The ligand for the GAF domains of PDE5, 8-Br-cGMP, elicited a 20-fold GAF-dependent activation and moreover revealed a time-dependent increase in PDE5 activity that occurred independently of a GAF ligand. Although GAF-dependent PDE5 activation was fast at high ligand concentrations, it was slow at physiologically relevant cGMP concentrations; PDE5 reached its final catalytic rates at 1 µM cGMP after approximately 10 min.

CONCLUSIONS AND IMPLICATIONS

We conclude that the delayed activation of PDE5 is required to shape biphasic, spike-like cGMP signals. Phosphorylation of PDE5 further enhances activity and conserves PDE5 activation, thereby enabling PDE5 to act as a molecular memory balancing cGMP responses to nitric oxide or natriuretic peptide signals.     

Das präoperative EKG als Routineuntersuchung bei Kindern

Objective: The aim of this study is to examine whether a routine preoperative ECG is necessary in children to assess the risks in anaesthesia and surgery. Methods: We examined the records of 3030 children anaesthetized in our hospital in 1990 and compared records of complications with preoperative ECGs. We also evaluated questionnaires on this subject which we had sent to 51 large pediatric hospitals in Germany in 1991. Results: During 3030 anaesthetic procedures there were 93 complications, 67 of which were not of cardiac origin. Of the 26 cardiac complications only 4 needed therapy (AV-Block 2°, fall in blood pressure). Preoperative ECGs were recorded in 180 cases: 152 were normal, 8 showed harmless deviations from normal and 16 were recorded because of known cardiac defects. None of the 180 children developed complications during anaesthesia. Our questionnaire was returned completed carefully by 36 of the 51 hospitals. In most hospitals a preoperative ECG is only recorded when heart disease is known or suspected. Conclusion: Routine preoperative ECGs are unnecessary in children unless there are clinical symptoms of heart disease or heart disease is suspected.     

Immunotherapy of Sepsis: Blind Alley or Call for Personalized Assessment?

Archivum Immunologiae et Therapiae Experimentalis - Sepsis is the most frequent cause of death in noncoronary intensive care units. In the past 10 years, progress has been made in the...     

Tendon interposition arthroplasty for basal joint arthrosis: 38 thumbs followed for 4 years

We reviewed 38 thumbs (35 patients) operated with a modified Burton procedure for basal joint arthrosis. There were 3 pintrack infections and 9 patients reported severe discomfort during the postoperative period in a plaster of Paris. After a follow-up of 4 (1-7) years, 28 patients rated the overall result as excellent, while 1 would not have consented to the operation if she had known the result in advance. Activities of daily living were markedly improved. Compared to the nonoperated hand, the key pinch was moderately reduced and grip strength was almost the same. The postoperative scaphometacarpal gap was 6 mm.