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Biomedical subjects

E Sonnenberg

Publications and source records attributed to E Sonnenberg.

8 recordsLinked to original sources

Tyrosine kinase receptors in the control of epithelial growth and morphogenesis during development.

The c-ros, c-met and c-neu genes encode receptor-type tyrosine kinases and were originally identified because of their oncogenic potential. However, recent progress in the analysis of these receptors and their respective ligands indicate that they do not mediate exclusively mitogenic signals. Rather, they can induce cell movement, differentiation or morphogenesis of epithelial cells in culture. Interestingly, the discussed receptors are expressed in embryonal epithelia, whereas direct and indirect evidence shows that the corresponding ligands are produced in mesenchymal cells. In development, signals given by mesenchymal cells are major driving forces for differentiation and morphogenesis of epithelia; embryonal epithelia are generally unable to differentiate without the appropriate mesenchymal factors. The observed activities of these receptor/ligand systems in cultured cells and their expression patterns indicate that they regulate epithelial differentiation and morphogenesis also during embryogenesis and suggest thus a molecular basis for mesenchymal epithelial interactions.

Animals↗

Scatter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development.

Scatter factor/hepatocyte growth factor (SF/HGF) has potent motogenic, mitogenic, and morphogenetic activities on epithelial cells in vitro. The cell surface receptor for this factor was recently identified: it is the product of the c-met protooncogene, a receptor-type tyrosine kinase. We report here the novel and distinct expression patterns of SF/HGF and its receptor during mouse development, which was determined by a combination of in situ hybridization and RNase protection experiments. Predominantly, we detect transcripts of c-met in epithelial cells of various developing organs, whereas the ligand is expressed in distinct mesenchymal cells in close vicinity. In addition, transient SF/HGF and c-met expression is found at certain sites of muscle formation; transient expression of the c-met gene is also detected in developing motoneurons. SF/HGF and the c-met receptor might thus play multiple developmental roles, most notably, mediate a signal given by mesenchyme and received by epithelial. Mesenchymal signals are known to govern differentiation and morphogenesis of many epithelia, but the molecular nature of the signals has remained poorly understood. Therefore, the known biological activities of SF/HGF in vitro and the embryonal expression pattern reported here indicate that this mesenchymal factor can transmit morphogenetic signals in epithelial development and suggest a molecular mechanism for mesenchymal epithelial interactions.

Animals↗

Expression of the met-receptor and its ligand, HGF-SF during mouse embryogenesis.

We have determined the expression patterns of the met proto-oncogene and the gene which encodes its ligand, scatter factor/hepatocyte growth factor (HGF-SF), during mouse embryogenesis. A recurring pattern of expression was found in a variety of different organs: expression of met in specific epithelial cells, and transcripts for the HGF-SF gene in mesenchymal cells in close vicinity. Exchange of signals between mesenchymal and epithelial cell compartments are important in morphogenesis and differentiation of a variety of embryonal organs, although their molecular basis has not been elucidated. The observed expression of met and HGF-SF during development suggests that this receptor and its specific ligand might play a role in such processes. In addition to this distinct pattern, expression of met in certain epithelia and HGF-SF in the surrounding mesenchyme, we find met transcripts in neural, endothelial and muscle cells and transcripts for HGF-SF in neural and muscle tissue. In no instance did we observe both, transcripts for the receptor and the ligand, in the same cells. This suggests a paracrine mode of action for HGF-SF and its receptor during development. This exchange of signals might thus regulate a variety of processes, notably among them mesenchymal epithelial interactions.

Animals↗

Transient and locally restricted expression of the ros1 protooncogene during mouse development.

The ros1 gene was detected originally by virtue of its transforming potential; the cDNA of the human protooncogene was isolated from a tumor cell line expressing the gene ectopically. It encodes a receptor-type tyrosine specific protein kinase which is closely related to sevenless in Drosophila. Here we report the novel and remarkable in vivo expression pattern of c-ros1, which was determined in the mouse. By a combination of RNase protection and in situ hybridization, we find transient c-ros1 expression during development in the kidney, intestine and lung, coinciding with major morphogenetic and differentiation events in these organs. This temporally restricted nature of expression is unusual for tyrosine kinase receptors and suggests a role for ros1 during development. Furthermore, in kidney development c-ros1 transcripts are confined to subgroups of ureter cells known to be involved directly in inductive interactions between ureter epithelium and metanephric mesenchyme. Thus, this study implicates for the first time a tyrosine kinase receptor in mesenchymal epithelial interactions and suggests a molecular basis for these important inductive events in development.

Animals↗

Prospective microbiologic surveillance in control of nosocomial methicillin-resistant Staphylococcus aureus.

A prospective microbiological surveillance (PMS) program was developed in a comprehensive hospital-wide effort for control of nosocomial methicillin-resistant Staphylococcus aureus (MRSA). This PMS program entailed: active identification of colonized and infected patients; application of a screening microbiologic system for MRSA; isolation of colonized and infected patients; antibiotic decolonization of MRSA; and educational efforts. The PMS program was studied over three and one half years for its contribution to infection control of MRSA, early identification of nosocomial MRSA outbreaks, use of the highest yield surveillance culture sites, and cost effectiveness. Following initiation of the PMS program in December 1982, during an MRSA outbreak, the frequency of new MRSA cases declined from 14 to none by the end of a 3-month pilot study. The frequency of new MRSA cases stabilized at approximately 2 per month until October 1983, when the PMS system allowed prompt detection of a new outbreak of 11 cases. Following isolation and antibiotic decolonization, the frequency of cases again declined to 3 per month. A third outbreak in December 1985 again was promptly detected and controlled. Infection to colonization ratio decreased from a maximum of 1.5 during outbreaks to a minimum of 0.17 after outbreaks. Wounds and tracheostomy sites provided the greatest yield of detection of new cases of MRSA. During one 15-month period, 35 of the 43 new cases were detected initially at wounds and tracheostomy sites. No new MRSA cases were detected by a positive axillary or nares site alone. The estimated quarterly cost of outbreaks and infection paralleled the quarterly frequency of new MRSA cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-Benefit Analysis↗

Human figure drawings as a measure of the child's response to dental visits.

The HFD as obtained in this study was a measure of the child's response at the beginning of the dental visit. HFD scores correlate with the five other measures of the child's response as well as those measures correlate with each other. The subscore of six items was an acceptable substitute for the twenty items scoring index and was superior to any single item. The data, with respect to age, suggest that children suppress signs of overt fear and anxiety with increasing age, giving a misleading impression of older children's feelings toward their dental experience.

Anxiety↗