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E Schreiber

Publications and source records attributed to E Schreiber.

At least 19 recordsLinked to original sources
PubMed2005

Monte Carlo simulation of large electron fields.

Accurate simulation of large electron fields may lead to improved accuracy in Monte Carlo treatment planning while simplifying the commissioning procedure. We have used measurements made with wide-open jaws and no electron applicator to adjust simulation parameters. Central axis depth dose curves and profiles of 6-21 MeV electron beams measured in this geometry were used to estimate source and geometry parameters, including those that affect beam symmetry: incident beam direction and offset of the secondary scattering foil and monitor chamber from the beam axis. Parameter estimation relied on a comprehensive analysis of the sensitivity of the measured quantities, in the large field, to source and geometry parameters. Results demonstrate that the EGS4 Monte Carlo system is capable of matching dose distributions in the largest electron field to the least restrictive of 1 cGy or 1 mm, with D(max) of 100 cGy, over the full energy range. This match results in an underestimation of the bremsstrahlung dose of 10-20% at 15-21 MeV, exceeding the combined experimental and calculational uncertainty in this quantity of 3%. The simulation of electron scattering at energies of 15-21 MeV in EGS4 may be in error. The recently released EGSnrc/BEAMnrc system may provide a better match to measurement.

Computer Simulation↗
PubMed2004

High plasma ropivacaine concentrations after fascia iliaca compartment block in children.

BACKGROUND: The pharmacokinetic profile of local anaesthetics is influenced by the mode of administration. We sought to compare the pharmacokinetics of two doses of ropivacaine after fascia iliaca compartment (FIC) block in children. METHODS: In this prospective, double-blind study, children received an FIC block as a part of their anaesthetic management during elective orthopaedic surgery on the thigh. They were randomized to receive ropivacaine 0.7 ml x kg(-1) using either a 0.375% or 0.5% solution. Venous blood samples were drawn up to 6 h after injection. Plasma concentrations of ropivacaine were measured by gas-liquid chromatography. RESULTS: Six children (10.2 (range 5-15) yr, 35.6 (sd 10) kg were included. FIC block provided satisfactory peroperative pain relief. No signs of toxicity were observed, but high maximal plasma concentrations (C(max) 4.33-5.6 microg ml(-1)), were observed for three of four patients in the ropivacaine 0.5% group. The two patients in the 0.375% group showed values within the safe range (C(max) 0.66 and 0.98 microg ml(-1) respectively). Even though no toxic effects were observed, these results led us to discontinue the study. CONCLUSIONS: The administration of ropivacaine 3.5 mg x kg(-1) can be associated with sustained high plasma concentrations of ropivacaine, outside the tolerable range. In view of these results, we recommend the use of lower ropivacaine dosage during FIC block in children.

Adolescent↗
PubMed2000

Genotypic characterization of Salmonella typhi by amplified fragment length polymorphism fingerprinting provides increased discrimination as compared to pulsed-field gel electrophoresis and ribotyping.

Amplified fragment length polymorphism (AFLP) is a recently developed, PCR-based high resolution fingerprinting method that is able to generate complex banding patterns which can be used to delineate intraspecific genetic relationships among bacteria. In the present study, AFLP was evaluated for its usefulness in the molecular typing of Salmonella typhi in comparison to ribotyping and pulsed-field gel electrophoresis (PFGE). Six S. typhi isolates from diverse geographic areas (Malaysia, Indonesia, India, Chile, Papua New Guinea and Switzerland) gave unique, heterogeneous profiles when typed by AFLP, a result which was consistent with ribotyping and PFGE analysis. In a further study of selected S. typhi isolates from Papua New Guinea which caused fatal and non-fatal disease previously shown to be clonally related by PFGE, AFLP discriminated between these isolates but did not indicate a linkage between genotype with virulence. We conclude that AFLP (discriminatory index=0.88) has a higher discriminatory power for strain differentiation among S. typhi than ribotyping (DI=0.63) and PFGE (DI=0.74).

DNA Fingerprinting↗
PubMed1999

Evaluation of AFLP, a high-resolution DNA fingerprinting method, as a tool for molecular subtyping of enterohemorrhagic Escherichia coli O157:H7 isolates.

The amplified fragment-length polymorphism (AFLPTM) technique is based on the selective PCR amplification of restriction fragments. We investigated the utility of AFLP in the molecular subtyping of enterohemorrhagic Escherichia coli serotype O157:H7 isolates. We analyzed a total of 46 isolates of E. coli O157:H7 along with other serotypes, O26:H11, 0114:H19 and 0119:NT. Isolates of E. coli O157:H7 derived from the same outbreak showed an identical AFLP-banding pattern and were subtyped into the same group, giving results almost consistent with those of a pulsed-field gel electrophoresis (PFGE) study, while other serotypes showed clearly different patterns from those of E. coli O157:H7. These results suggest that the AFLP technique has potential as an alternative tool for the molecular epidemiology of E. coli O157:H7.

Bacterial Typing Techniques↗
PubMed1998

Analysis of spatial distributions of cellular molecules during mechanical stressing of cell surface receptors using confocal microscopy.

Confocal laser scanning microscopy represents a suitable technique to study the localization of cellular components in three dimension. The authors used this technique to analyse cellular events related to mechanical stimulation of integrin receptors on the cell surface. By performing optical sections the distribution of integrin receptors on the apical surface of an osteoblastic cell was determined. Concerning intracellular compartimentalization of signal transduction events, it was demonstrated that mechanical stimulation of integrins induced their linkage to the cytoskeleton. Cytoskeletally associated proteins like vinculin and talin accumulated in the vicinity of the site where the mechanical stress was applied to integrins on the cell surface. Optical sections revealed that clustering of these proteins proceeded to the base of the cell with gradually decreasing extent. In summary, it was demonstrated that the local distribution of cellular components is an important factor in mechanically induced signal transduction.

Humans↗
PubMed1997

N-Oct 5 is generated by in vitro proteolysis of the neural POU-domain protein N-Oct 3.

The neural POU-domain proteins N-Oct 3 and N-Oct 5 were first identified in electrophoretic mobility retardation assays through their ability to bind to the octamer sequence ATGCAAAT. These two N-Oct factors are detected in extracts from tumor-derived and normal neural cells. They are present differentially, however, in extracts from melanocytes and melanoma cells: N-Oct 3 is present in extracts from both melanocytes and melanoma cells, whereas N-Oct 5 is more evident in extracts from metastatic melanoma cells. We show here that a cDNA encoding N-Oct 3 directs synthesis of both the N-Oct 3 and N-Oct 5 proteins and that the N-Oct 5 protein in neural and melanoma-cell extracts is also related to N-Oct 3. N-Oct 5, however, is apparently not expressed in vivo: It is not detected if cells are rapidly lysed in SDS or if extracts are prepared with a cocktail of protease inhibitors that includes the serine-protease inhibitor 4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF). These data suggest that N-Oct 5 is a specific in vitro proteolytic cleavage product of N-Oct 3 and is not directly related to melanocyte malignancy.

Animals↗
PubMed1996

Stimulation of integrin receptors using a magnetic drag force device induces an intracellular free calcium response.

Mechanical loading of cells is of fundamental relevance in physiological processes and induces several functional responses in cells. Integrins, a family of adhesion receptors, which are responsible for the interaction with the extracellular matrix, may play a role in transmission of mechanical signals into cells. The osteogenic cell line U-2 OS expresses different integrin subunits which are uniformly distributed over the cell surface. We applied defined physical forces on individual integrin receptor subunits using paramagnetic microbeads coated with anti-integrin antibodies. Application of an inhomogeneous magnetic field consequently leads to a mechanical stress on the receptor. Intracellular Ca2+ increased when the alpha 2 or the beta 1 integrin subunits were stressed, whereas mechanical loading of the transferrin receptor had a significantly lower effect. This result indicates that forces specifically exerted to individual integrin receptors induce signal transduction pathways.

Calcium↗
PubMed1995

Isolation of the human genomic brain-2/N-Oct 3 gene (POUF3) and assignment to chromosome 6q16.

N-Oct 3 is a human POU domain transcription factor that binds to the octamer sequence ATGCAAAT. The protein is expressed in the central nervous system during development and in adult brain. We have isolated and characterized genomic clones encoding the human N-Oct 3 gene (HGMW-approved symbol POUF3). Comparison of the structure of these clones with the N-Oct 3 cDNA revealed that POUF3 is an intronless gene. Sequencing of 650 bp of the promoter region showed 84% sequence identity of POUF3 with its murine homologue, the brain-2 (designated brn-2) gene. Whereas both POUF3 and brn-2 lack a TATA box, consensus sequences for AP-2, GCF, and SP1 transcription factors were identified within the highly conserved 5'-flanking region. These sequences may play a crucial role for the tissue-specific transcription activation of the POUF3 gene. Southern blotting and in situ hybridization localized the human POUF3 gene to chromosome 6q16.

Animals↗
PubMed1994

Primary brain tumors differ in their expression of octamer deoxyribonucleic acid-binding transcription factors from long-term cultured glioma cell lines.

Nervous system-specific transcription factors that bind to the octameric deoxyribonucleic acid sequence motif ATGCAAAT (or ATTTGCAT) are known as N-Oct proteins. Neurons and glia contain the ubiquitous Oct-1 protein and four polypeptide complexes termed N-Oct-2, N-Oct-3, N-Oct-4, and N-Oct-5. Previously, we showed that N-Oct proteins are differentially expressed by human neuroblastoma and glioblastoma cell lines in vitro. We have now extended this work to freshly isolated human primary and metastatic brain tumors. Contrary to brain tumor cell lines, of the five astrocytomas and three glioblastomas analyzed, all but two tumors displayed the complete N-Oct protein profile, irrespective of histopathological tumor grade. Two astrocytomas were negative for N-Oct-4. Ten of 13 ependymomas exhibited N-Oct-2, N-Oct-3, and N-Oct-4 but lacked the N-Oct-5 complex. In contrast, brain metastases of two patients with extracerebral carcinomas contained only Oct-1, and cerebral metastases from two cases of B cell lymphomas showed Oct-1 and Oct-2 complexes, the characteristic Oct protein pattern of B lymphocytes. Thus, metastatic carcinoma and lymphoma expressed a non-nervous system phenotype of Oct proteins.

Astrocytoma↗
PubMed1993

cDNA cloning of human N-Oct3, a nervous-system specific POU domain transcription factor binding to the octamer DNA motif.

Octamer transcription factors (Oct or OTF) are a subset of the POU family of transcription factors which regulate transcription of cellular and viral genes by binding to the octamer sequence motif ATGCAAAT. Neurons and astroglial cells harbour, in addition to the ubiquitous Oct 1 factor, at least four specific factors termed N-Oct 2,3,4 and 5. Here we report the cloning of a human brain-derived cDNA that encodes the N-Oct 3 protein (443 aa) which is the human counterpart of the murine brain-2 gene product. Extracts from mammalian cells transfected with an N-Oct 3 expression vector yield three octamer DNA binding complexes in the electrophoretic mobility shift assay (EMSA): N-Oct 3 and two smaller complexes comigrating with the N-Oct 5A and 5B proteins of brain extracts. We present data suggesting that the N-Oct 5A and 5B proteins are generated by alternative translation initiation at internal AUG residues which are located before the POU domain. In contrast to the putative N-Oct 5 proteins, which are transcriptionally inert, the N-Oct 3 protein activates transcription from a reporter gene promoter with an octamer sequence, when transiently expressed in HeLa cells.

Amino Acid Sequence↗
PubMed1993

Effect of dietary n-3 versus n-6 polyunsaturated fatty acids on hepatic excretion of cholesterol in the hamster.

Dietary polyunsaturated fatty acids of the n-6 and the n-3 class show differing effects on serum lipids and hepatic lipoprotein metabolism, which could be induced by alterations in hepatocellular cholesterol balance. As both fatty acid classes exert parallel effects on lipoprotein uptake and synthesis of cholesterol in the liver, we studied whether they have differing effects on the excretory pathways for cholesterol. Male Syrian hamsters were fed for 3 weeks low-cholesterol diets supplemented (9% w/w) with either saturated (coconut fat), n-6 unsaturated (safflower oil) or n-3 unsaturated fatty acids (fish oil), which shifted the serum lipid levels. N-6 unsaturated fatty acids increased both the synthesis of cholic acid (+57%; P = 0.05) and, in fistula bile, the secretion of cholesterol (+37%; P < 0.05 vs. saturated fatty acids). By contrast, n-3 unsaturated fatty acids did not enhance synthesis of cholic acid or biliary secretion of cholesterol (-30%, NS). The fatty acid pattern of biliary phospholipids was modified according to the major unsaturated fatty acids in the diet. The alterations both in phospholipid fatty acid composition and in secretory ratio of cholesterol to phospholipids and bile acids persisted during controlled secretion of taurocholic acid at increasing rates. In conclusion, hepatic excretion of cholesterol is increased on dietary n-6 unsaturated fatty acids, and low on n-3 unsaturated fatty acids. These two dietary fatty acid classes change differently the fatty acid composition of biliary phospholipids and the secretory ratio of cholesterol to phospholipids and bile acids in bile.

Animals↗
PubMed1992

Human small cell lung cancer expresses the octamer DNA-binding and nervous system-specific transcription factor N-Oct 3 (brain-2).

Small cell lung cancer (SCLC) cells express several characteristics of neuronal cells, including synthesis of neuropeptides and expression of the respective receptors. Establishment and maintenance of the neuronal phenotype of SCLC may depend on expression of gene transcription factors inherent to the central nervous system. The present study shows the nervous system-specific transcription factor N-Oct 3 (brain-2) to be expressed in all 13 SCLC cell lines investigated. Furthermore, N-Oct 3 (brain-2) was also found in SCLC-derived skin metastasis. In contrast, in extracts and RNA of non-SCLC cell lines and non-SCLC tumor tissues, such as lung squamous, large cell, and adenocarcinoma, expression of N-Oct 3 (brain-2) was not detectable. These data support the concept that SCLC cells derive from the neuroectodermal cell lineage since expression of N-Oct 3 (brain-2) protein is highly abundant at the neural tube stage and in the adult restricted to the neuroectodermal cell lineage.

Carcinoma, Small Cell↗
PubMed1992

Interrelationships of bile acid and phospholipid fatty acid species with cholesterol saturation of duodenal bile in health and gallstone disease.

The relative amount of cholesterol and the fatty acid composition of phosphatidylcholines in bile can be influenced by the bile acid species secreted. To search for a contribution of secondary bile acids and of phosphatidylcholines to supersaturation of bile in gallstone disease, we compared the relative amount of cholesterol and the biliary composition of bile acids and of phospholipid fatty acids in cholecystokinin-stimulated duodenal bile of 22 female gallstone patients and 16 healthy controls and analyzed the interrelationships of these bile constituents. Gallstone patients had higher molar percentages of cholesterol than did controls (10.2 +/- 3.2 vs. 6 +/- 1.5 mol%; p less than 0.001) and demonstrated a trend toward larger fractions of deoxycholic and lithocholic acids. By linear models, variation of cholesterol saturation could be predicted (p less than 0.001) up to 53% by the bile acid pattern and up to 81% by the fatty acid pattern of phospholipids. Linear path analysis (goodness-of-fit index = 0.973) confirmed the tight relationship between phospholipid fatty acids (positive: oleic, arachidonic; negative: linoleic, palmitoleic) and the relative amount of cholesterol; more than half the influence of cholic, deoxycholic and lithocholic acids on the relative amount of cholesterol could be explained indirectly by their influence on the phospholipid fatty acid pattern. We conclude that the relationships examined by path analysis support the working hypothesis that secondary bile acids contribute to supersaturation of bile mainly by changing the fatty acid pattern of the secreted phospholipids (presumably the pattern of phosphatidylcholines), which increases the molar ratio of cholesterol/phospholipids in bile.

Adult↗
PubMed1992

Insulinotropic action of glucagonlike peptide-I-(7-37) in diabetic and nondiabetic subjects.

OBJECTIVE: Whether glucagonlike peptide-I-(7-37) (GLP-I-[7-37]), a naturally occurring intestinal peptide, is insulinotropic in nondiabetic and non-insulin-dependent (type II) diabetic subjects. RESEARCH DESIGN AND METHODS: GLP-I-(7-37) or saline placebo was infused (1-5 ng.kg-1.min-1 for 30 min) in 4 nondiabetic and 11 type II diabetic subjects in the fasting and prandial state. Glucose, insulin, and GLP-I-(7-37) levels were measured. RESULTS: GLP-I-(7-37) infusion resulted in a 3- to 10-fold increase in peak insulin levels and in insulin area under the curve in nondiabetic and diabetic subjects. In diabetic subjects, infusion concurrent with a standard meal eliminated the postprandial glucose excursion for 60 min after the meal. Insulin-releasing potency of GLP-I-(7-37) was attenuated at decreased glucose levels. CONCLUSIONS: GLP-I-(7-37) has potent insulinotropic effects in nondiabetic and diabetic subjects. Whether GLP-I-(7-37) is useful as a therapeutic medication in type II diabetes requires further investigation.

Adult↗