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F Cremers

Publications and source records attributed to F Cremers.

14 recordsLinked to original sources
PubMed2006

Design of a computer-controlled multileaf collimator for advanced electron radiotherapy.

A multileaf collimator for electrons (eMLC) has been designed that fulfils the technical requirements for providing advanced irradiation techniques with electrons. In the present work, the basic design parameters of leaf material, leaf height, leaf width and number of leaves as well as leaf overtravel and leaf shape were determined such that an eMLC with motorized leaves can be manufactured by a company specialized in MLC technology. For this purpose, a manually driven eMLC with variable source-to-collimator distance (SCD) was used to evaluate the chosen leaf specification and investigate the impact of the SCD on the off-axis dose distribution. In order to select the final SCD of the eMLC, a compromise had to be found between maximum field size, minimum beam penumbra and necessary distance between eMLC and isocentre to eliminate patient realignments during gantry rotation. As a result, the eMLC is placed according to the target position at 72 and 84 cm SCD, respectively. This feature will be achieved by interchangeable distance holders. At these SCDs, the corresponding maximum field sizes at 100 cm source-to-isocentre distance are 20 x 20 cm and 17 x 17 cm, respectively. Finally, the off-axis dose distribution at the maximum opening of the eMLC was improved by fine-tuning the settings of the accelerator jaws and introducing trimmer bars above the eMLC. Following this optimization, a prototype eMLC consisting of 2 x 24 computer-controlled brass leaves is manufactured by 3D Line Medical Systems.

Biophysical Phenomena↗
PubMed2006

Evaluation of GafChromic EBT prototype B for external beam dose verification.

The capability of the new GafChromic EBT prototype B for external beam dose verification is investigated in this paper. First the general characteristics of this film (dose response, postirradiation coloration, influence of calibration field size) were derived using a flat-bed scanner. In the dose range from 0.1 to 8 Gy, the sensitivity of the EBT prototype B film is ten times higher than the response of the GafChromic HS, which so far was the GafChromic film with the highest sensitivity. Compared with the Kodak EDR2 film, the response of the EBT is higher by a factor of 3 in the dose range from 0.1 to 8 Gy. The GafChromic EBT almost does not show a temporal growth of the optical density and there is no influence of the chosen calibration field size on the dose response curve obtained from this data. A MatLab program was written to evaluate the two-dimensional dose distributions from treatment planning systems and GafChromic EBT film measurements. Verification of external beam therapy (SRT, IMRT) using the above-mentioned approach resulted in very small differences between the planned and the applied dose. The GafChromic EBT prototype B together with the flat-bed scanner and MatLab is a successful approach for making the advantages of the GafChromic films applicable for verification of external beam therapy.

Calibration↗
PubMed2004

Performance of electronic portal imaging devices (EPIDs) used in radiotherapy: image quality and dose measurements.

The aim of our study was to compare the image and dosimetric quality of two different imaging systems. The first one is a fluoroscopic electronic portal imaging device (first generation), while the second is based on an amorphous silicon flat-panel array (second generation). The parameters describing image quality include spatial resolution [modulation transfer function (MTF)], noise [noise power spectrum (NPS)], and signal-to-noise transfer [detective quantum efficiency (DQE)]. The dosimetric measurements were compared with ionization chamber as well as with film measurements. The response of the flat-panel imager and the fluoroscopic-optical device was determined performing a two-step Monte Carlo simulation. All measurements were performed in a 6 MV linear accelerator photon beam. The resolution (MTF) of the fluoroscopic device (f 1/2 = 0.3 mm(-1)) is larger than of the amorphous silicon based system (f 1/2 = 0.21 mm(-1)), which is due to the missing backscattered photons and the smaller pixel size. The noise measurements (NPS) show the correlation of neighboring pixels of the amorphous silicon electronic portal imaging device, whereas the NPS of the fluoroscopic system is frequency independent. At zero spatial frequency the DQE of the flat-panel imager has a value of 0.008 (0.8%). Due to the minor frequency dependency this device may be almost x-ray quantum limited. Monte Carlo simulations verified these characteristics. For the fluoroscopic imaging system the DQE at low frequencies is about 0.0008 (0.08%) and degrades with higher frequencies. Dose measurements with the flat-panel imager revealed that images can only be directly converted to portal dose images, if scatter can be neglected. Thus objects distant to the detector (e.g., inhomogeneous dose distribution generated by a modificator) can be verified dosimetrically, while objects close to a detector (e.g., a patient) cannot be verified directly and must be scatter corrected prior to verification. This is justified by the response of the flat-panel imaging device revealing a strong dependency at low energies.

Equipment Failure Analysis↗
PubMed2000

Non-syndromic autosomal dominant progressive non-specific mid-frequency sensorineural hearing impairment with childhood to late adolescence onset (DFNA21).

An autosomal dominant trait of progressive, non-syndromic, non-specific mid-frequency sensorineural hearing impairment was identified in a Dutch family. Many affected family members (n = 21) were identified, among whom seven out of nine relatives aged < 30 years do not show pure mid-frequency hearing impairment, which suggests variable expression. Regression analysis was used to evaluate the age-related hearing threshold data in a cross-sectional analysis in 24 affected patients and in a longitudinal analysis in five of these. At all frequencies, progression in hearing impairment (i.e. the regression coefficient) was significant and fairly similar: the pooled value was about 1.0 dB/y. There was no significant (i.e. not =0 dB) offset threshold (i.e. Y intercept at age 0) found at any frequency. The regression lines could be pooled for the low frequencies (0.25-0.5 kHz) and the mid/high frequencies (1-8 kHz) and this produced apparent onset ages of about 3 and 4 years and annual threshold increases of 0.75 and 1.1 dB/y, respectively. In most patients there is a relatively late onset age (maximum in the range of at least 25-45 years). However, based on the longitudinal analysis of a patient from the age of 4 years onwards in some patients sensorineural hearing impairment might be congenital/prelingual. Oculo-vestibular function was found to be normal. Results from linkage studies tentatively position the underlying gene defect telomeric to the repositioned DFNA13 locus at chromosome 6p21-22.

Adult↗
PubMed1995

The epidermal growth factor.

Epidermal growth factor (EGF) is a single polypeptide of 53 amino acid residues which is involved in the regulation of cell proliferation. Egf exerts its effects in the target cells by binding to the plasma membrane located EGF receptor. The EGF receptor is a transmembrane protein tyrosine kinase. Binding of EGF to the receptor causes activation of the kinase and subsequently receptor autophosphorylation. The autophosphorylation is essential for the interaction of the receptor with its substrates. These bind to the receptor by the so-called SH2 domains. The signal transduction pathways activated by EGF include the phosphatidylinositol pathway, leading to activation of protein kinase C and to increase in the intracellular Ca2+ concentration, and to the ras pathway leading to MAP kinase activation. Recently the cytoplasm has been implicated as playing an important role in EGF induced signal transduction. The EGF receptor has been demonstrated to be an actin-binding protein. In addition EGF causes a rapid actin depolymerisation and the formation of membrane ruffles. In particular these membrane ruffles have been shown to act as the first site of signal transduction after EGF binding, and thus may be considered as signal transduction structures. Finally evidence has been presented suggesting a positive role for EGF and/or the receptor in the nucleus.

Amino Acid Sequence↗
PubMed1995

Linkage analysis in a Dutch family with X-linked recessive congenital stationary night blindness (XL-CSNB).

Linkage analysis has been performed in a large Dutch pedigree with X-linked recessive congenital stationary night blindness (CSNB) by utilizing 16 DNA markers from the proximal short arm of the human X chromosome (Xp21.1-11.2). Thirteen polymorphic markers are at least partially informative and have enabled pairwise and multipoint linkage analysis. For three loci, i.e. DXS228, the monoamine oxidase B gene and the Norrie disease gene (NDG), multipoint linkage studies have yielded maximum lod scores of > 3.0 at a recombination fraction of zero. Analysis of recombination events has enabled us to rule out the possibility that the underlying defect in this family is allelic to RP3; the gene defect could also be excluded from the proximal part of the region known to carry RP2. Linkage data are consistent with a possible involvement of the NDG but mutations in the open reading frame of this gene have not been found.

Chromosome Mapping↗
PubMed1994

Expression pattern of parathyroid hormone/parathyroid hormone related peptide receptor mRNA in mouse postimplantation embryos indicates involvement in multiple developmental processes.

In this paper we describe the cloning of the mouse Parathyroid Hormone/Parathyroid Hormone related Peptide Receptor (PTH/PTHrPR) cDNA and expression of its mRNA during mouse postimplantation development from day 5.5 until day 15.5 post coitum (p.c.). In support of a model from previous studies, in which parietal endoderm differentiation is regulated by the interaction of the PTH/PTHrPR and Parathyroid Hormone related Peptide (PTHrP), high levels of PTH/PTHrPR mRNA levels were detected in developing parietal endoderm from day 5.5 p.c. and onwards. In the embryo proper, PTH/PTHrPR mRNA expression was mainly detected at sites of epithelium/mesenchyme interactions, starting at day 9.5 p.c. in the epithelium of the intestine and later in the mesenchyme of the lung, the epithelium of meso- and metanephric tubuli, the dermis and at all sites where bone formation takes place. The complexity of the PTH/PTHrPR expression pattern suggests tight developmental regulation and indicates multiple roles in embryogenesis for the receptor and its ligands, not only in extraembryonic tissue but also in the formation of various organs.

Animals↗
PubMed1992

Norrie disease is caused by mutations in an extracellular protein resembling C-terminal globular domain of mucins.

A candidate gene for Norrie disease, an X-linked disorder characterized by blindness, deafness and mental disturbances, was recently isolated and found to contain microdeletions in numerous patients. No strong homologies were identified. By studying the number and spacing of cysteine residues, we now detect homologies between the Norrie gene product and a C-terminal domain which is common to a group of proteins including mucins. Three newly-characterized missense mutations, replacing evolutionarily conserved cysteines or creating new cysteine codons, emphasize the functional importance of these sites. These findings and the clinical features of this disorder suggest a possible role for the Norrie gene in neuroectodermal cell-cell interaction.

Adult↗
PubMed1992

Mutations in the candidate gene for Norrie disease.

Recently, we and others have isolated a candidate gene for X linked Norrie disease (ND) which was found to be deleted or disrupted in several patients. As a prerequisite for the identification of point mutations in the ND gene we have established the exon-intron structure of this gene. In 17 unrelated patients and 15 controls, PCR products derived from the promoter region, exons 1 and 2 as well as the coding part of exon 3 were analysed with the single strand conformation polymorphism (SSCP) technique. In 12 patients altered PCR fragments were detected which were studied in detail by direct sequencing. Eleven different mutations were found, and all but one are likely to give rise to significant structural changes in the predicted protein. These findings, and the absence of functionally relevant base changes in healthy controls, emphasize the causal role of this candidate gene in Norrie disease and pave the way for reliable diagnosis and carrier detection.

Base Sequence↗
PubMed1991

Choroideremia: linkage analysis with physically mapped close DNA-markers.

We report linkage studies in 18 choroideremia (TCD) families using four closely linked polymorphic markers. Probe pZ11, which is known to be deleted in several unrelated patients with TCD, showed no recombinations (zeta max 15.63 at theta = 0.00). In contrast, one recombination was observed with DXS367, which is also physically very close to TCD. Loci DXS95 and DXYS69 each showed more than one recombination with TCD. Moreover, these analyses revealed a double crossover between TCD and DXYS1, changing the previously reported very close linkage to a recombination fraction of 0.04 with a lod score of 9.93. Multipoint linkage analysis placed TCD proximal to DXS95-DXYS69 and very close to DXS367-pZ11 with almost identical multipoint lod score maxima either proximal to DXS367 (zeta max = 23.43) or proximal to pZ11 (zeta max = 23.36). These results provide a refined linkage map around TCD and will also be useful in DNA diagnostics of the disease.

Choroideremia↗
PubMed1991

Characterization of a proteinaceous adhesin of Staphylococcus epidermidis which mediates attachment to polystyrene.

Coagulase-negative staphylococci (CoNS) have evolved into important agents of foreign body-related infections. Adhesion of causative bacteria to biomaterials is considered to be an essential step in these infections. We and others have shown that adhesion of CoNS to biomaterials may be mediated by protease-sensitive surface constituents. In the present study we expanded on these investigations by characterizing a biomaterial adhesin of Staphylococcus epidermidis 354 by using a strain-specific monoclonal antibody (MAb 36.4). MAb 36.4 was strongly and exclusively reactive with strain 354 in an enzyme-linked immunosorbent assay in which whole bacteria were used as antigens. Immunoblotting of cell wall polypeptides of strain 354 revealed strong reactivity with a 200- to 220-kDa band and a weaker reaction in the 100- to 110-kDa range. Preincubation of strain 354 with MAb 36.4 resulted in a 54 to 91% (mean +/- standard deviation, 74% +/- 14%; n = 10) inhibition of adhesion to polystyrene spheres. Fab fragments prepared from MAb 36.4 also inhibited adhesion effectively, indicating specific blocking of an adhesion antigen rather than aspecific inhibition. Immunogold electron microscopy with MAb 36.4 revealed deposition of gold particles on the cell surface and possibly also on fimbrialike surface projections. It is concluded that a surface-located protein antigen of S. epidermidis 354 recognized by MAb 36.4 acts as an adhesin mediating attachment to uncoated foreign material. It is speculated that this type of adhesion to biomaterials may play an important role in the pathogenesis of foreign body-related infections caused by CoNS.

Antibodies, Monoclonal↗
PubMed1988

In vivo import of plastocyanin and a fusion protein into developmentally different plastids of transgenic plants.

Transgenic tomato plants that constitutively express a foreign plastocyanin gene were used to study protein transport in different tissues. Normally expression of endogenous plastocyanin genes in plants is restricted to photosynthetic tissues only, whereas this foreign plastocyanin protein is found to be present in all tissues examined. The protein is transported into the local plastids in these tissues and it is processed to the mature size. We conclude that plastids of developmentally different tissues are capable of importing precursor proteins that are normally not found in these tissues. Most likely such plastids, though functionally and morphologically differentiated, have similar or identical protein import mechanisms when compared to the chloroplasts in green tissue.

Chloroplasts↗
PubMed1988

Antigenic relatedness of a strongly immunogenic 65 kDA mycobacterial protein antigen with a similarly sized ubiquitous bacterial common antigen.

In gene libraries of Mycobacterium bovis BCG, Mycobacterium tuberculosis and Mycobacterium leprae recombinants were frequently found expressing an immunodominant 65 kDa protein antigen. In this study polyclonal and monoclonal antibodies against the 65 kDa antigen were found to react with a variety of different bacteria. Furthermore it is shown that the 65 kDa mycobacterial protein belongs to the family of antigens previously designated 'common antigen' due to their presence in a large variety of bacterial species. The molecular weight of this common antigen in 17 bacterial species was determined and it varied from 59 to 65 kDa. These bacteria included Gram-negative, Gram-positive and archae-bacteria, indicating that this antigen consists of members of an evolutionary well-conserved protein family. The 65 kDa protein was located in the cytoplasmic fraction of both Escherichia coli K12 and M. bovis BCG. Its function for the bacterial cell is presently unknown. The immunological relatedness of this common antigen to the MbaA protein might indicate a role in the etiology of rheumatoid arthritis, as was recently suggested for the mycobacterial 65 kDa antigen.

Antigens, Bacterial↗