Biomedical subjects

C Martens

Publications and source records attributed to C Martens.

At least 19 recordsLinked to original sources

PubMed2001

Combining the advantages of step-and-shoot and dynamic delivery of intensity-modulated radiotherapy by interrupted dynamic sequences.

PURPOSE: A hybrid between step-and-shoot and dynamic operation, called interrupted dynamic sequences, was investigated for prostate intensity-modulated radiotherapy (IMRT) delivered by a multisegment close-in technique. The new delivery mode was compared to the step-and-shoot mode concerning dose distribution. METHODS AND MATERIALS: Segments suitable for dynamic transition were selected using a system of segment classes. Transitions were only allowed between two segments of the same class, keeping intended sharp in-field dose gradients unchanged. Delivery was performed by an Elekta SLiplus (Crawley, UK) linear accelerator equipped with a dynamic multileaf collimator (MLC). Because no modeling of the dose during the transitions is made, accurate dose measurements were performed. Dose profiles were measured using a linear ion chamber array (LA48, PTW-Freiburg). The suitability of this detector for measurements in sharp dose gradients was investigated first. In addition, field flatness was examined for segments with a low monitor unit (MU) count. Uncertainties in dose output were investigated using an ionization chamber (30001, PTW-Freiburg). RESULTS: Because linear array measured penumbrae are only slightly broader (< or = 0.4 mm for MLC collimated field) than those obtained using a diamond detector, the array is a good device for profile measurements. Uncertainties related with the use of low MU beam segments are very small (< 1% for segments of minimum 3 MU), giving no contra-evidence for the step-and-shoot mode. Interrupted dynamic sequences are shown to introduce only small dosimetric differences as compared to the step-and-shoot delivery. CONCLUSION: Both delivery modes, step-and-shoot and interrupted dynamic sequences, result in similar dose distributions for the forward planned prostate class solution.

Humans↗

PubMed2001

RNA polymerase II and TBP occupy the repressed CYC1 promoter.

Saccharomyces cerevisiae CYC1 gene expression has been studied in great detail with regard to the response to oxygen availability and carbon source. In the absence of oxygen and the presence of glucose, the CYC1 gene is completely repressed. Chromatin structure is thought to play an important role in CYC1 gene regulation, as nucleosome depletion results in 94-fold derepression. In addition, the CYC1 core promoter has been used extensively in hybrid constructs to study activation by heterologous transcription factors. Therefore, we set out to map the chromatin structure of the CYC1 promoter and determine its role in CYC1 gene regulation. We report here that the repressed CYC1 promoter contains no positioned nucleosomes over the core promoter. However, we did find TFIID and RNA polymerase II bound in a complex on the repressed promoter. These results indicate that recruitment of TFIID and RNA polymerase II are not rate-limiting steps in CYC1 activation.

Chromatin↗

PubMed2001

Improved delivery efficiency for step and shoot intensity modulated radiotherapy using a fast-tuning magnetron.

The delivery efficiency of step and shoot intensity modulated radiotherapy (IMRT) has been improved by the installation of fast-tuning magnetrons into three travelling wave linear accelerators. The IMRT delivery efficiency and the beam start-up performance have been compared before and after installation. Start-up and inter sub-field times were reduced by an average of 3.0 s. A typical start-up time from depression of the start button to beam on is now around 4 s. Delivery efficiency for a variety of clinical and quality control prescriptions was improved by an average of 30.7% (range 7.4-60.9%), depending on a complex combination of the number of sub-fields, distance moved by leaves and dose rate. For the oldest accelerator (7 years old), dosimetric accuracy was significantly improved for low dose sub-fields. The dose output was within 2% for a 1 monitor unit (MU) sub-field and 1% for a 2 MU sub-field. The two newer accelerators displayed similar or better dose characteristics even before fast-tuning magnetron installation. Beam symmetries and flatnesses were acceptable at all energies and dose rates, and showed no obvious degradation in low dose sub-fields. It is recommended that fast-tuning magnetrons are adopted for accelerators of this design performing step and shoot IMRT.

Magnetics↗

PubMed2001

The value of the LA48 linear ion chamber array for characterization of intensity-modulated beams.

In this paper the performance of the LA48 linear ion chamber array (PTW, Freiburg, Germany) for characterization of intensity-modulated (IM) beams was investigated. First, some elementary properties were explored. A series of beam penumbras and output factors for small rectangular fields were measured at 6 and 18 MV, and the results were compared with data obtained using a diamond detector. The energy and dose rate dependence of the array response were examined, and the leakage current was assessed. In a second step, profiles were measured for two clinically delivered IM beams and for a dynamic wedge. The interplay between the sharpening of the penumbra by the upper metal electrode plate of the array and the volume averaging of the 4 x 4 mm ion chamber elements results in precise measurements, even in regions of high dose gradient. It is true, however, that the metal electrodes imply a small energy spectrum dependence in the array response. The dose rate dependence is found to be negligible. All of this makes, the LA48 linear array a suitable device for analysing dose distributions of clinical IM beams.

Dose-Response Relationship, Radiation↗

PubMed2000

Benefit of emergency haemorrhoidectomy: a comparison with results after elective operations.

OBJECTIVE: To compare the outcome of emergency and elective haemorrhoidectomy. DESIGN: Retrospective study. SETTING: Teaching hospital, Belgium. SUBJECT: 104 patients who had haemorrhoidectomy for acutely ulcerated or strangulated haemorrhoids, and 545 who had elective haemorrhoidectomy. RESULTS: Early complications (26/104, 25%), reoperation (7/104, 7%) and late anal stenosis (7/104, 7%) were more common after emergency than elective haemorrhoidectomy, for which the corresponding figures were 74/545 (3.6%), 9 (1.7%) and 1/545 (0.2%). Late outcome was similar for the two groups. CONCLUSIONS: Emergency haemorrhoidectomy is indicated for the treatment of the acute complications of haemorrhoids.

Acute Disease↗

PubMed2000

The value of the PinPoint ion chamber for characterization of small field segments used in intensity-modulated radiotherapy.

Volume averaging and lack of electronic equilibrium complicate accurate dosimetry of small photon fields. In this paper the performance of the PinPoint ion chamber for characterizing small fields used in intensity-modulated radiotherapy (IMRT) was investigated and the results were compared with those obtained using the Markus ion chamber and a diamond detector. Sharp beam penumbras were measured for a 5 x 5 cm field defined using a cerrobend block mounted on the accelerator head. In addition, output factors were measured for a 6 MV photon beam and a variety of small rectangular fields collimated widthwise using the multileaf collimator (MLC) in combination with the back-up jaws. From this study, a reference field of 5 x 5 cm and a measuring depth of 5 cm are recommended. This is related to the over-response of the PinPoint chamber to low-energy Compton scattered photons, an effect that was investigated rigorously and turned out to limit the scope of this ionization chamber. However, taking into account some limitations, the PinPoint chamber is an excellent detector for output measurements in small fields down to 2 cm. In profile measurements the chamber causes a broadening of the measured penumbras but its spatial resolution is superior to that of the Markus chamber.

Calibration↗

PubMed1999

A generic particle-based nonradioactive homogeneous multiplex method for high-throughput screening using microvolume fluorimetry.

We have developed a novel fluorescence-based homogeneous binding assay for high-throughput screening of chemical compounds. In this assay, a Cy5- or Cy5.5-labeled ligand binds to receptor immobilized on a particle, either a bead or a cell. The resulting localized signal can be detected by a modified microvolume fluorimeter (MVF). When a molecule which competes with the labeled ligand is present, the localized fluorescence on cells or beads is reduced. Image processing software enumerates events and analyzes fluorescence intensity. We describe MVF assays for the IL-1 and IL-5 receptors. Using synthetic peptides with a range of affinities for the IL-1 receptor, we obtained IC(50) data consistent with those determined by radioligand binding assays. Because the image processing software can discriminate among events with different diameters, we were able to develop a multiplex assay, in which the IL-1R and IL-5R assays were carried out in the same well with each receptor immobilized on a different size of bead. IC(50) values generated in the multiplex assay for ligands specific to each receptor were comparable to those determined independently. Finally, similar IC(50) values were obtained in a 16-microl volume in an 864-well plate. This homogeneous, nonradioactive, miniaturizable, and multiplex-capable assay holds much promise for screening of combinatorial libraries and compound collections.

Animals↗

PubMed1999

Heterodimerization between members of the Nur subfamily of orphan nuclear receptors as a novel mechanism for gene activation.

We have recently shown that the orphan nuclear receptor Nur77 (NGFI-B) is most active in transcription when it is interacting with a cognate DNA sequence as a homodimer. Further, we have shown that the target for Nur77 dimers, the Nur response element (NurRE), is responsive to physiological stimuli in both endocrine and lymphoid cells, whereas other DNA targets of Nur77 action are not. The Nur77 subfamily also includes two related receptors, Nur-related factor 1 (Nurr1) and neuron-derived orphan receptor 1 (NOR-1). Often, more than one member of this subfamily is induced in response to extracellular signals. We now show that Nur77 and Nurr1 form heterodimers in vitro in the presence or absence of NurRE, and we have documented interactions between these proteins in vivo by using a two-hybrid system in mammalian cells. These heterodimers synergistically enhance transcription from NurRE reporters in comparison to that seen with homodimers. The naturally occurring NurRE from the pro-opiomelanocortin gene preferentially binds and activates transcription in the presence of Nur77 homo- or heterodimers, while a consensus NurRE sequence does not show this preference. Taken together, the data indicate that members of the Nur77 subfamily are most potent as heterodimers and that different dimers exhibit target sequence preference. Thus, we propose that a combinatorial code relying on specific NurRE sequences might be responsible for the activation of subsets of target genes by one of the members of the Nur77 subfamily of transcription factors.

Corticotropin-Releasing Hormone↗

PubMed1997

Atorvastatin: an effective lipid-modifying agent in familial hypercholesterolemia.

Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are the drugs of choice in heterozygous familial hypercholesterolemia (FH), which has a high risk of ischemic heart disease. An open-label study was conducted to test the efficacy and safety of atorvastatin, a new synthetic HMG-CoA reductase inhibitor in proven FH. After a 4-week placebo phase, 22 subjects were randomized to either 80 mg atorvastatin at night (n = 11) or 40 mg twice a day for 6 weeks. The two dosage groups were well matched and had no difference in lipoprotein responses. After 6 weeks, the LDL cholesterol concentration was reduced by 57%, from 8.16 +/- 1.15 to 3.53 +/- 0.99 mmol/L (P < .001). The total cholesterol concentration decreased from 9.90 +/- 1.32 to 5.43 mmol/L (P < .001). HDL cholesterol concentration increased from 1.19 +/- 0.31 to 1.49 +/- 0.43 mmol/L (P < .001). Triglyceride concentrations decreased from 1.34 +/- 0.66 to 0.88 +/- 0.36 mmol/L (P < .01). Three subjects had single, transient increases of serum transaminase of up to twice the upper limit of normal. Apolipoprotein B concentration decreased significantly by 42%. Changes in apolipoproteins AI and (a) were not statistically significant. Nondenaturing gradient gel electrophoresis revealed increases in the size of smaller LDL particles in four subjects. Plasma fibrinogen concentration increased by 44%. The drug was well tolerated. One subject withdrew for personal reasons. Atorvastatin is a powerful and safe lipid-modifying agent for LDL cholesterol; it also modifies HDL cholesterol and triglyceride concentrations, and may suffice as a single agent for many subjects with heterozygous FH.

Adult↗

PubMed1997

Surgical treatment of distal biceps tendon ruptures results of a multicentric BOTA-study and review of the literature. Belgian Orthopedic Trauma Association.

Distal biceps tendon ruptures (DBTR) are relatively uncommon. This multicentric study, conducted on behalf of BOTA (Belgian Orthopedic Trauma Association), documents the complications and results after surgical treatment of 18 DBTR's. In the current series a repair with Mitek anchors was found to be a simple and reliable fixation that could be performed through a single anterior approach with minor risks of radial nerve damage. If a two-incision technique following Boyd and Anderson is used, the ulna should not be exposed in order to avoid a radioulnar synostosis; splitting the extensor muscle mass is preferable to a subperiostal ulna dissection, and the wound should always be drained to decrease the likelihood of hematoma formation.

Adult↗

PubMed1995

Florid reactive periostitis.

Florid reactive periostitis (FRP) is a benign entity, mostly involving the tubular bones of the hands and feet. It is important to distinguish FRP from malignant processes such as periosteal osteosarcoma and parosteal osteosarcoma, to give an adequate treatment and to avoid amputation of the total digit. The final diagnosis of FRP is usually based on the combination of clinical, radiological, and pathological findings. The pattern seen on the isotope bone scan can be very helpful in orienting the differential diagnosis.

Bone Neoplasms↗

PubMed1995

Bilateral posterior four-part fracture-dislocation of the shoulder.

A case of a bilateral posterior four-part fracture dislocation of the shoulder after a convulsive seizure was treated conservatively on one side, while the other shoulder was replaced by a hemiarthroplasty. A review of the literature and a treatment protocol for managing these injuries are presented. In four-part fracture-dislocations good results can be achieved with conservative treatment, but when avascular necrosis is likely to occur (delay in diagnosis or dubious relationship of the fragments after reduction) it is better to replace the humeral head.

Bone Nails↗

PubMed1995

Modulation of vindesine and doxorubicin resistance in multidrug-resistant pleural mesothelioma cells by tumor necrosis factor-alpha.

Tumor necrosis factor-alpha (TNF-alpha) has been shown to enhance the cytotoxicity of a variety of antineoplastic agents. To examine whether multidrug-resistant cells are targets of TNF-alpha, and whether TNF-alpha is capable of modulating chemoresistance of these cells, a pleural mesothelioma cell line (PXF1118L) and two multidrug-resistant sublines thereof were used as experimental models. Drug resistance of these cells was due to P-glycoprotein expression, as confirmed by (1) staining with a monoclonal antibody (MRK16) specific for human P-glycoprotein, (2) decreased accumulation of [3H]vinblastine that was reversed by verapamil, and (3) enhanced cytotoxicity of vindesine in the presence of verapamil. Parental and multidrug-resistant cells exhibited little but comparable sensitivity to TNF-alpha alone. Combining TNF-alpha with vindesine or, to a lesser extent, with doxorubicin, but not with cisplatin, resulted in greater cytotoxicity towards multidrug-resistant cells than seen for each compound alone, indicating a synergism. In contrast, TNF-alpha failed to modulate vindesine or doxorubicin cytotoxicity in parental cells. [3H]Vinblastine accumulation was unaffected by TNF-alpha, and chemoresistance was reduced by TNF-alpha also in the presence of verapamil (10 microM), indicating that TNF-alpha was acting in a way different from calcium-channel blockers. Though the molecular mechanism by which TNF-alpha was enhancing vindesine and doxorubicin cytotoxicity remained undefined in this study, the numbers of TNF-alpha binding sites on parental and on multidrug-resistant cells were similar, and P-glycoprotein expression was unmodulated during the entire 48 h incubation period. In conclusion, we show that TNF-alpha increases the cytotoxicity of anticancer drugs in multidrug-resistant tumor cells by a mechanism that differs from most chemosensitizing agents, including verapamil. Further studies will be needed to clarify the mechanism by which TNF-alpha synergizes with anticancer drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1990

Abnormal T cells from lpr mice down-regulate transcription of interferon-gamma and tumor necrosis factor-alpha in vitro.

We have studied the ability of isolated T cell subpopulations from the autoimmune mouse MRL/MPJ/lpr/lpr (lpr) to proliferate and to undergo changes in cytokine gene transcription in vitro, in the presence or absence of cytokines. The lpr mouse develops lupus-like symptoms and massive lymphadenopathy due to accumulation of abnormal CD4-/CD8- T lymphocytes, which are unusual in coexpressing Thy1 and B220. FACS-purified B220+/Thy1+ lpr lymph node cells showed little proliferative response to cytokines, even in the presence of PMA, and failed to proliferate in response to stimulation through the CD3/TcR complex. Polymerase chain reaction was used to examine the presence of cytokine gene transcripts in B220-/Thy1+ and B220+/Thy1+ ("abnormal") T cells, before and after in vitro culture. The high level of transcripts of IFN-gamma and TNF-alpha genes observed in freshly isolated B220+/Thy1+ cells decreased after 10 hr of in vitro culture, while levels of TNF-beta, IL-6 and TGF-beta transcripts were maintained. These results suggest that a positive stimulus for IFN-gamma and TNF-alpha gene transcription by lpr B220+/Thy1+ cells may exist in vivo but is removed upon purification of this abnormal T cell subset.

Animals↗

PubMed1990

In vivo cytokine gene expression in T cell subsets of the autoimmune MRL/Mp-lpr/lpr mouse.

Expression of cytokine genes in freshly isolated T cell subsets in the autoimmune lpr mouse has been studied to determine what factors may be produced by these cells in vivo. RNA prepared from T cell subsets from diseased lpr mice and from the normal congenic strain, MRL/n, was tested for the presence of cytokine-specific message using the polymerase chain reaction. Cells of the expanded abnormal T cell subset were shown to express genes encoding interferon (IFN)-gamma, tumor necrosis factor (TNF)-beta, TNF-alpha and interleukin (IL)6, cytokines which are associated with inflammatory immune responses. These cells may thus play an important role in exacerbation of the pathological symptoms of the systemic autoimmune disease. These cells expressed no detectable IL1, IL2, IL3, IL4 or IL5. Phenotypically normal CD4+ and CD8+ T cells from both lpr and MRL/n also contained transcripts for IFN-gamma, TNF-alpha, TNF-beta and IL6. IL2 mRNA was found almost exclusively in the CD4+ subset, indicating that the CD8+ T cells in the lpr mouse are not highly activated through their class I major histocompatibility complex molecules to produce IL2, as could occur if a virus infection was inducing autoimmunity in these mice. Similar levels of IL2 mRNA were present in the CD4+ T cells of lpr and MRL/n mice, demonstrating that these cells are not defective in IL2 production in vivo.

Animals↗

PubMed1989

The abnormal T lymphocytes in lpr mice transcribe interferon-gamma and tumor necrosis factor-alpha genes spontaneously in vivo.

The autoimmune mouse strain MRL/MPJ/lpr/lpr is characterized by accumulation of an abnormal T cell population which does not express CD4 or CD8 surface antigens. These cells were thought to be immunologically inert based on their inability to proliferate in response to a variety of T cell mitogens. We investigated the capacity of these cells to express lymphokine genes using a sensitive RNase protection assay. RNA was isolated from abnormal T cells which were purified directly from diseased animals, either as CD4-/CD8- or as fluorescence-activated cell sorter-isolated B220+/Thy-1+ cells. These RNA preparations contained no detectable interleukin (IL) 2, IL 4, IL 5 or IL 6 transcripts, but did contain transcripts of genes for interferon-gamma and tumor necrosis factor-alpha. Thus, this expanded population of abnormal cells spontaneously expresses these two lymphokines which have many interacting effects on the immune system, and may have important roles in the pathogenesis of autoimmune disease in lpr mice.

Animals↗

PubMed1989

Expression of lymphokine genes in splenic lymphocytes of autoimmune mice.

Lymphocytes of autoimmune mice have been reported to have defective IL-2 production and proliferation in response to the mitogen concanavalin A. We have examined transcription of lymphokine genes in Con A stimulated spleen cells from both autoimmune and normal mice and found that IL-2, IL-4 and gamma-interferon (IFN gamma) were induced in all mice tested. Spleen cells were taken from young (pre-disease) or old (clinically active) MRL/lpr (lpr) and male BXSB autoimmune mice and from their normal counterparts (MRL/n, BXSB females, BALB/c and DBA/2) and stimulated with Con A. Con A induced production of IL-2, IL-4 and IFN gamma message and protein, and kinetics of induction did not vary significantly among the strains. However, in old lpr mice, levels of IL-2 protein and mRNA were about 10-fold lower than in other strains; IL-4 protein and mRNA were decreased approximately three-fold; and IFN gamma mRNA was readily detected in unstimulated cells and low but detectable levels of protein were produced constitutively. In contrast, little or no defect in IL-2 or IL-4 transcription or secretion were seen in male BXSB mice and no constitutive IFN gamma transcription was seen in this strain. These data indicate that all three lymphokine genes are activated by Con A in autoimmune mice, even though Con A-induced proliferation is defective in these mice. Furthermore, autoimmune mouse strains vary in terms of lymphokine expression: male BXSB mice display a normal lymphokine profile, whereas lpr mice show a marked imbalance of lymphokines compared to normal controls.

Animals↗

PubMed1985

Relationship among IgE-binding factors with various molecular weights.

The rat-mouse T cell hybridoma 23B6 forms IgE-binding factors on incubation with IgE. The hybridoma cells incubated with IgE contained intracellular IgE-binding factors of 60K, 30K, 14K, and 10K daltons, and secreted the 60K, 30K, and 14K IgE-binding factors. Both intracellular and extracellular IgE-binding factors of 60K and 14K daltons selectively suppressed the IgE response, whereas the 30K and 10K factors failed to do so. Reduction and alkylation of the extracellular 60K IgE-binding factors yielded fragments of 30K, 14K, and 10K daltons with IgE-binding activity, and the same treatment of the 30K "inactive" IgE-binding factor yielded the 14K and 10K fragments. Among the fragments obtained by reduction and alkylation, only the 14K IgE-binding factors selectively suppressed the IgE response. Monoclonal antibody OX 3, which recognizes an Ia determinant, bound the 60K and 30K IgE-binding factor, and the 30K fragment obtained by reduction and alkylation. None of the 14K and 10K IgE-binding factors and fragments of comparable size obtained by reduction and alkylation contained the antigenic determinant. The results indicate that 30K, 14K, and 10K IgE-binding factors are derived from the 60K precursor molecules. Transfection of COS 7 monkey kidney cells with a single cloned cDNA, 8.3, which encodes rodent IgE-binding factor, resulted in the formation of IgE-binding factors of 60K and 11K daltons. Both species of the factors had affinity for lentil lectin and selectively potentiated the IgE response, but only the 60K IgE-binding factor bound to the monoclonal anti-Ia antibody. Reduction and alkylation of the 60K IgE-binding factors from the cDNA clone yielded an 11K fragment having the same properties as the 11K IgE-binding factor, with respect to the affinity for lentil lectin, and the biologic activities. Because the cDNA clone was constructed from mRNA of 23B6 cells, it appears that the 60K IgE-binding factor molecule from 23B6 cells is composed of a single peptide chain, and that the naturally formed 30K, 14K, and 10K IgE-binding factors are formed by post-translational modification of the 60K peptide.

Animals↗