Biomedical subjects

M Hoch

Publications and source records attributed to M Hoch.

At least 19 recordsLinked to original sources

PubMed2006

[Evidence-based medicine and vesicoureteral reflux].

Vesicoureteral reflux (VUR) remains one of the most controversial subjects in paediatric urology. Much literature has been published on VUR, making the understanding of this anomaly and its treatments quite opaque. Evidence-Based Medicine (EBM) should be helpful to clarify the various VUR approaches contained in the 6224 titles found on Medline using the keywords "vesicoureteral reflux" and "vesicoureteric reflux". These articles were critically reviewed and graded according to EBM scorings, with regard to their methodological designs. This review of VUR literature suggests that most of our knowledge is based on publications with a low level of evidence, and that EBM lacks arguments to support recommendations for VUR diagnostic and treatment. It appears yet that antenatal dilatation of the urinary tract and symptomatic urinary tract infections (UTI) justify VUR screening. Surgery should be discussed in recurrent UTIs or deterioration of renal function. There is no consensus in case of persistent asymptomatic VUR regarding indication and duration of antibio-prophylaxis, and selection of radical treatment.

Antibiotic Prophylaxis↗

PubMed2006

[Quantification of right ventricular function in congenital heart disease: correlation of 3D echocardiography and MRI as complementary methods].

PURPOSE: In congenital heart disease, the exact determination of the right ventricular function is of high importance for therapeutic and especially surgical planning. The aim of this study was to correlate the parameters of the right ventricular function in MRI and 3D echocardiography to determine the agreement of both modalities. MATERIALS AND METHODS: In 18 patients suffering from congenital heart disease, 3D echocardiography was performed using a Philips Sonos 7500 system. In MRI short axis slices with a 4-mm distance were acquired using an SSFP sequence on a Siemens Sonata or Symphony System. Volumetry for both modalities was performed on an external workstation (Tomtec) using the EchoView software. RESULTS: Enddiastolic and endsystolic volumes showed a highly significant correlation with coefficients of 0.996 and 0.990, respectively. In echocardiography there was a systematic slight underestimation of enddiastolic volumes and overestimation of endsystolic volumes. The Wilcoxon test did not show significant differences between the volumes and ejection fractions assessed by both modalities. CONCLUSION: There is an excellent correlation in the quantification of right ventricular volumes in MRI and 3D echocardiography, which allows a comparison of acquired volumes in clinical follow-up.

Adolescent↗

PubMed2005

Heart failure in pediatric patients.

Paradigms in understanding heart failure have changed as the knowledge of pathophysiology and its molecular basis has deepened. In the chronic compensated state of heart failure recent research has focussed on the body's regulatory mechanisms. Today heart failure is understood as a complex interplay of hemodynamic and neurohormonal factors. In pediatrics a large variety of heterogeneous conditions cause heart failure. Some require special therapeutic approaches such as the infusion of prostaglandin for ductal patency, the careful maintenance of balance between systemic and pulmonary circulations or operative treatment. In newborns with critical congenital lesions and in patients in the postoperative period management of acute heart failure becomes important. Chronic heart failure as it is understood today is present in patients with cardiomyopathies and in an increasing number of pediatric patients after palliative surgery. In heart failure due to left-to-right shunts a similar activation of compensatory neurohormonal mechanisms as in adults with chronic heart failure was found. In small clinical trials treatment of these activated compensatory mechanisms with angiotensin-converting enzyme inhibitors and beta-blockers showed beneficial effects in pediatric patients. However large clinical multicenter trials as performed in the adult population should be conducted.

Adrenergic beta-Antagonists↗

PubMed2004

Modeling interactions at the tributyltin-kaolinite interface.

Tributyltin (TBT) is a common pollutant in natural environments and the interaction with mineral surfaces largely determine its solubility, speciation, bioavailability, and transport in aqueous systems. The present work aimed at quantifying the TBT adsorption using kaolinite and a kaolinite-rich sediment as sorbent materials. Experiments were conducted under conditions that are important from an environmental perspective. Proton adsorption data were determined for kaolinite as a function of pH and electrolyte concentrations to ascertain intrinsic acidity constants and site density values. The pH(zpc) of kaolinite sample KGa was determined at 4.9 by surface titration. The generalized diffused double layer model (DLM) was used to quantify both, proton and TBT adsorption. Following intrinsic acidity and TBT binding constants resulting from the TBT/kaolinite system were used: >SOH ==> >SO- + H+, logK = -5.4; >SOH + H+ ==> SOH2+, logK = 4.6; >XNa + H ==> XH + Na+, logK(X/H+) = -1.1; >SO- + TBT+ ==> >SOTBT, logK = 3.5; >XNa + TBT+ ==> Na+, logK(X/TBT) = 1.0. All surface-active variable charge sites on kaolinite, namely >AlOH and >SiOH are grouped and collectively refer to as >SOH in this paper. >XNa refers to ion exchange sites. Modeling of TBT adsorption onto kaolinite was conducted distinguishing selective (high affinity) sites (>S(S)OH) in addition to non-selective sites (>SOH). The inclusion of >S(S)OH was essential in order to quantify TBT adsorption successfully, while the inclusion of >XNa was optional. The reduction of surface coverage values by a 10-fold TBT adsorption modeling is in agreement with the results of molecular model calculations of the system. Parameters calculated for the monophase kaolinite were subsequently used to quantify the TBT adsorption onto kaolinite-rich sediment.

Adsorption↗

PubMed2003

The superior epigastric artery does not pass through Larrey's space (trigonum sternocostale).

The passage of the superior epigastric artery (SEA), the terminal branch of the internal thoracic artery (ITA), through the inferior orifice of the thorax differs in different reports. According to some, it passes through Larrey's space (trigonum sternocostale), therefore through a diaphragmatic orifice, but according to others it passes in front of the diaphragm and the transverse abdominal muscle. The aim of this study was to determine the position of the SEA in its thoracoabdominal segment. We carried out a series of 14 dissections (10 on embalmed cadavers and 4 on unembalmed cadavers), and a study of images from the Visible Human Project. Dissections always led to the same conclusions. After having dissected the trigonum sternocostale, we observed that no vascular element was present in the space, which was obstructed downwards by the parietal peritoneum and limited forwards by the aponeurosis of the transverse abdominal muscle. Inferior digitations of transversus thoracis were joined with the transversus abdominis. The SEA passed in front of the plane formed by these two muscles while the sternal and costal parts of the diaphragm were behind this plane. Whatever the level of the section of the Visible Human Project, there was always a musculoaponeurotic plane between Larrey's space and the superior epigastric artery and both veins. Larrey's space, or trigonum sternocostale, was limited medially by the lateral border of the sternal part of the diaphragm, laterally by the medial border of the costal part of the diaphragm, and anteriorly by the musculoaponeurotic plane formed by the transversus thoracis above and the transversus abdominis, below without a clear boundary between those muscles. The SEA, the terminal branch of the ITA, passed in front of this musculoaponeurotic plane.

Diaphragm↗

PubMed2002

[Evolution of the nervous system].

This review tries to establish a synthesis between the comparative/morphological approach and the molecular analysis of ontogenetic processes in development and evolution. We use the formation of the nervous system in metazoans as a paradigm to point out that highly conserved molecular mechanisms may be responsible to generate tissues and organ systems in bilateria. We discuss the conserved role of the Hox genes in anterior- posterior patterning, the function of the Achaete-scute genes and of the Notch/Delta signalling cascade in determining neural fates and the role of the BMP-4/Dpp-signalling pathway in positioning the neuroectoderm along the dorso-ventral axis of vertebrates and insects. We try to demonstrate that the evolution of complex body structures is based on modifying ontogenetic processes.

Animals↗

PubMed2002

[Phylogeny and evolution of hormone systems].

Classically hormones are defined as molecules that are secreted by endocrine glandular or neurosecretory cells into the blood stream and transported to their target tissue where they induce physiological processes at very low concentrations. Studies on the potential origin and the evolution of cell-to-cell communication systems suggest that exocrine pheromones (food signals and toxins) might have been the primitive bioregulatory molecules of unicellular organisms for chemical communication with each other and with the biosphere. The broad distribution and the structural diversity of pheromones suggests that these molecules and their receptors were predecessor modules of cell communication systems in metazoa. Neurosecretory cells, as we find them in Cnidarians, possibly served as basic modules for the evolution of neurohormonal systems of higher animals. Studies on genetic model organisms, such as Drosophila or the mouse, have demonstrated that chemical communication between neighbouring or more distant cells does not just involve endocrine and neurosecretory cells, but also unexpectedly tissues and organs such as the heart or the adipose tissue (e. g. the leptin signalling pathway). Comparative endocrinology could show that molecular components of hormonal systems represent signalling networks that are generally used during cellular communication processes and the differentiation of cell types during ontogenesis. Some of their functions are evolutionarily conserved, others not, as disscussion on steroid hormones and the prolactin signalling pathway will demonstrate.

Animals↗

PubMed2001

Control of endoreduplication domains in the Drosophila gut by the knirps and knirps-related genes.

Endoreduplication cycles that lead to an increase of DNA ploidy and cell size occur in distinct spatial and temporal patterns during Drosophila development. Only little is known about the regulation of these modified cell cycles. We have investigated fore- and hindgut development and we present evidence that the Drosophila knirps and knirps-related genes are key components to spatially restrict endoreduplication domains. Our lack and gain-of-function experiments show that knirps and knirps-related which encode nuclear orphan receptors transcriptionally repress S-phase genes of the cell cycle required for DNA replication and that this down-regulation is crucial for gut morphogenesis. Furthermore, we demonstrate that both genes are activated in overlapping expression domains in the fore- and hindgut in response to Wingless and Hedgehog activities emanating from epithelial signaling centers that control the regionalization of the gut tube. Our results provide a novel link between morphogen-dependent positional information and the spatio-temporal regulation of cell cycle activity in the gut.

Animals↗

PubMed2001

Gastrointestinal development in the Drosophila embryo requires the activity of innexin gap junction channel proteins.

Cell to cell communication plays an essential role during pattern formation and morphogenesis of the diverse tissues and organs of the body. In invertebrates, such as the fruitfly Drosophila, the direct communication of closely apposed cells is mediated by gap junctions which are composed of oligomers of the innexin family of transmembrane channel proteins. Few data exist about the developmental role of the eight innexin genes which have been found in the Drosophila genome. We have investigated the role of the innexin 2 and ogre genes during gastrointestinal development of the fly embryo. Our findings suggest that innexins are involved in the formation of the proventriculus, an organ that develops at the foregut/midgut boundary by migration of primordial cells and subsequent infolding of epithelial tissue layers.

Animals↗

PubMed2000

dtrap-1 encodes a novel member of the heat shock super family of proteins and is expressed in derivatives of all three germ layers during Drosophila embryogenesis.

Heat shock proteins (Hsps) comprise a highly conserved superfamily of proteins that are required for stress tolerance in living cells. At physiological conditions, these proteins act as chaperones during protein folding and protein assembly processes (Parsell and Lindquist, 1993. Annu. Rev. Genet. 27, 427-496). Members of the subfamily of Hsp90 proteins were shown to be additionally involved in the presentation and structural modification of components of diverse cellular signal transduction pathways including steroid hormone reception and regulatory kinase activities (Pratt, 1993. J. Biol. Chem. 268, 21455-21458); Cutforth et al., 1994. Cell 77, 1027-1036; van der Straten et al., 1997. EMBO J. 16, 1961-1997; Hunter and Poon, 1997. Trends Cell Biol. 7, 157-161). We have identified a Drosophila gene, called dtrap-1, which encodes a Hsp of a novel subfamily that is related to the Hsp90 family of proteins. During oogenesis dtrap-1 is expressed in nurse cells and its transcripts accumulate in the oocyte. The maternal transcripts remain in the egg but rapidly degrade during early embryogenesis, except in the posterior pole region. Zygotic expression is initiated after the onset of gastrulation showing dynamic patterns of transcripts in the developing mid- and hindgut as well as a subset of mesoderm derivatives.

Animals↗

PubMed1998

Krüppel acts as a developmental switch gene that mediates Notch signalling-dependent tip cell differentiation in the excretory organs of Drosophila.

Cell proliferation in the excretory organs of Drosophila, the Malpighian tubules (MT), is under the control of a neural tip cell. This unique cell is singled out from equivalent MT primordial cells in response to Notch signalling. We show that the gene Krüppel (Kr), best known for its segmentation function in the early embryo, is under the control of the Notch-dependent signalling process. Lack-of-function and gain-of-function experiments demonstrate that Kr activity determines the neural fate of tip cells by acting as a direct downstream target of proneural basic helix-loop-helix (bHLH) proteins that are restricted in response to Notch signalling. We have identified a unique cis-acting element that mediates all spatial and temporal aspects of Kr gene expression during MT development. This element contains functional binding sites for the restricted proneural bHLH factors and Fork head protein which is expressed in all MT cells. Our results suggest a mechanism in which these transcription factors cooperate to set up a unique cell fate within an equivalence group of cells by restricting the activity of the developmental switch gene Kr in response to Notch signalling.

Animals↗

PubMed1998

A modifier screen in the eye reveals control genes for Krüppel activity in the Drosophila embryo.

Irregular facets (If) is a dominant mutation of Drosophila that results in small eyes with fused ommatidia. Previous results showed that the gene Krüppel (Kr), which is best known for its early segmentation function, is expressed ectopically in If mutant eye discs. However, it was not known whether ectopic Kr activity is either the cause or the result of the If mutation. Here, we show that If is a gain-of-function allele of Kr. We then used the If mutation in a genetic screen to identify dominant enhancers and suppressors of Kr activity on the third chromosome. Of 30 identified Kr-interacting loci, two were cloned, and we examined whether they also represent components of a natural Kr-dependent developmental pathway of the embryo. We show that the two genes, eyelid (eld) and extramacrochaetae (emc), which encode a Bright family-type DNA binding protein and a helix-loop-helix factor, respectively, are necessary to achieve the singling-out of a unique Kr-expressing cell during the development of the Malpighian tubules, the excretory organs of the fly. The results indicate that the Kr gain-of-function mutation If provides a tool to identify genes that are active during eye development and that a number of them function also in the control of Kr-dependent developmental processes.

Amino Acid Sequence↗

PubMed1998

Seven-up, the Drosophila homolog of the COUP-TF orphan receptors, controls cell proliferation in the insect kidney.

Morphogenesis of the insect kidney, the Malpighian tubules, is controlled in Drosophila by a single large cell, the tip cell. It has been postulated that this cell sends out a mitogenic signal that induces the division of neighboring cells. The signal and the molecules that receive it have remained elusive. We show that the COUP-TF-related nuclear orphan receptor Seven-up is a key component that becomes induced in response to mitogenic EGF receptor signaling activity emanating from the tip cell. Seven-up in turn is capable of regulating the transcription of cell cycle regulators.

Animals↗

PubMed1998

Drosophila endoderm development requires a novel homeobox gene which is a target of Wingless and Dpp signalling.

We have identified and cloned a novel type of homeobox gene that is composed of two homeodomains and is expressed in the Drosophila endoderm. Mutant analysis reveals that its activity is required at the foregut/midgut boundary for the development of the proventriculus. This organ regulates food passage from the foregut into the midgut and forms by the infolding of ectoderm and endoderm-derived tissues. The endodermal outer wall structure of the proventriculus is collapsed in the mutants leading to a failure of the ectodermal part to invaginate and build a functional multilayered organ. Lack-of-function and gain-of-function experiments show that the expression of this homeobox gene in the proventriculus endoderm is induced in response to Wingless activity emanating from the ectoderm/endoderm boundary whereas its expression in the central midgut is controlled by Dpp and Wingless signalling emanating from the overlying visceral mesoderm.

Alternative Splicing↗

PubMed1997

Effects of indapamide on Ca2+ entry into vascular smooth muscle cells.

Part of the antihypertensive action of indapamide has been attributed to a direct inhibitory action on Ca2+ entry into vascular smooth muscle cells. The present study has been performed to identify the possible mechanisms involved. To this end the effect of indapamide on intracellular Ca2+ activity - [Ca2+]i - has been tested under control conditions and under conditions known to increase [Ca2+]i such as osmotic cell swelling (mimicking mechanical stress), depolarization (increase of extracellular K+ concentration) and oxidative stress (H2O2). Indapamide (10 micromol/l) was without effect on control [Ca2+]i, but significantly blunted the increase of [Ca2+]i following potassium-induced depolarization or following osmotic cell swelling. It did not significantly modify the increase of [Ca2+]i induced by H2O2. The effects on cell membrane potential induced by increased [K+], osmotic cell swelling, or H2O2 were not significantly modified by indapamide (10 micromol/l). Voltage-gated Ca2+ currents were not significantly modified by 10 micromol/l indapamide, but were significantly reduced by 100 micromol/l and blunted by 1 mmol/l. In conclusion, indapamide at high concentrations (100 micromol/l) inhibits voltage-gated Ca2+ channels, an effect which blunts the increase of [Ca2+]i during depolarization of the cell membrane at increased extracellular [K+] or osmotic stress. Whether these effects at high concentrations of indapamide are relevant to the antihypertensive action, however, cannot be established from these in vitro studies.

Animals↗

PubMed1996

Gene regulation in the Drosophila embryo.

Pattern formation in Drosophila depends on hierarchical interactions between the maternal and zygotic gene activities which subdivide the embryo into increasingly smaller metameric units along the anterior posterior axis. Here we describe those genes that encode the transcription factors which control precisely the expression of subordinate transcription factors in time and space. This regulation operates through the protein-protein interactions between transcription factors bound to the cis-acting enhancers, which eventually determine the frequency of transcription initiation by polymerase II. Our data show that taking into account the multiple transcriptional activators and repressors that bind to a typical enhancer element, it is likely that the regulation of gene expression in a given cell is defined by their concentration-dependent interplay which directs target gene expression in a position-dependent fashion.

Animals↗

PubMed1996

Control of gut development by fork head and cell signaling molecules in Drosophila.

The alimentary canal of most animals can be subdivided into a fore- mid- and hindgut portion, each gut part possessing distinct physiological functions. The genetic basis underlying the formation of the different gut parts is poorly understood. Here we show that the Drosophila genes hedgehog, wingless and decapentaplegic, which encode cell signaling molecules, are required for the establishment of signaling centers that coordinate morphogenesis in the hindgut epithelium. The activation of these genes in the developing as well as in the foregut requires fork head, which encodes a transcription factor. Furthermore, we demonstrate that hedgehog and wingless activities in the gut epithelial cells are required for the expression of the homeobox gene bagpipe in the ensheathing visceral mesoderm. These results provide strong evidence that similar principles underlie Drosophila fore- and hindgut development, and that the genetic hierarchy of gut development might be conserved between Drosophila and vertebrates.

Animals↗

PubMed1996

Krüppel, a Drosophila segmentation gene, participates in the specification of neurons and glial cells.

We report that the Drosophila segmentation gene Krüppel (Kr) is expressed in neural precursor cells, neurons and glial cells at different stages of neurogenesis and that Kr mutants develop aberrant peripheral (PNS) and central (CNS) nervous systems. Expression derived from a Kr minigene rescues the segmentation defects but these embryos continue to lack most of the neural Kr activity. Phenotypic analysis of the rescued embryos indicates that, in addition to overall effects on the PNS and CNS structure via its segmentation role, Kr expression in the nervous system is functionally required for establishing particular neural and glial fates.

Animals↗