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D R Olsen

Publications and source records attributed to D R Olsen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Inverse dose-rate effect due to pre-mitotic accumulation during continuous low dose-rate irradiation of cervix carcinoma cells.

PURPOSE: To investigate the radiation sensitivity of asynchronous and synchronized cancer cervix cells irradiated with low dose rates. MATERIALS AND METHODS: Cells were exposed to 60Co gamma-rays at dose rates ranging from 0.33 to 0.94 Gy/h. Synchronized cells were obtained by collecting detached mitotic cells after a shaking procedure. Cell survival was measured as the ability of cells to form colonies. Cell-cycle distributions were calculated by computer analysis of a DNA histogram recorded by flow cytometry. RESULTS: Irradiation of asynchronous cells at either 0.33 or 0.86 Gy/h resulted in exponential dose-survival curves with equal alpha-values, i.e. same radiation sensitivity, when dose-survival data for irradiation periods less than 20h were considered. However, the radiation sensitivity was higher by a factor of two when analysing dose-survival data for irradiation periods exceeding 20h. This increase in radiation sensitivity occurred when 80% of the cells accumulated in a pre-mitotic stage of the cell cycle. Irradiation of synchronized cell populations confirmed that these cells were a factor of two more sensitive to radiation in G2 than in G1. CONCLUSIONS: An inverse dose-rate effect, i.e. more efficient inactivation of cells at lower rather than at higher dose rates, was observed for radiation doses exceeding 7 Gy due to pre-mitotic accumulation of cells during low dose-rate irradiation.

Brachytherapy↗
PubMed1999

Measurement of dose rate at the interface of cell culture medium and glass dishes by means of ESR dosimetry using thin films of alanine.

Previous studies on human cervical cancer cells (NHIK 3025) have indicated that the cells, when X-irradiated in suspension, appeared to be more radiosensitive than when they were irradiated attached to glass dishes. However, this result depends on dosimetry, which is difficult in the situation where cells are attached to glass dishes due to backscattering electrons at the glass-liquid interface. Recently developed dosimetry that is based on detection of radiation-induced stable radicals in alanine and uses ESR spectroscopy offers a possibility for more relevant dosimetry at the glass-liquid interface than the previous estimates of doses based on Fricke dosimetry. Thin alanine films (>/=10 microm) were used to measure dose at the interface by irradiating the films while they were placed tightly against the bottom of dishes and covered with 1 mm of wax simulating the medium above cells. Fricke dosimetry was also performed, with different depths of Fricke solution in the dishes, to elucidate the contribution to the dose delivered by backscattering electrons at the glass-liquid interface. A dose rate of 1.9 Gy/min was measured with a thin layer (0.2-0.3 mm) of Fricke solution in petri dishes made of glass. However, this estimate appears to be too high, due to a contribution to dose by short-ranged electrons generated when the X rays passed through a steel lid 4.5 cm above the dishes. Dosimetry using alanine films resulted in dose rates of 1.15 and 0.87 Gy/min at the interfaces of glass-liquid and plastic- liquid, respectively. Hence there is a significant contribution to dose from backscattering electrons on dishes made of glass. The reason for our previous observation of a difference in radiosensitivity between cells irradiated in suspension and cells irradiated attached to glass appears to be a lack of accurate dosimetry at the glass-liquid interface.

Alanine↗
PubMed1998

Expression of eukaryotic proteins in soluble form in Escherichia coli.

At the optimum temperature for its growth (37 degrees C), Escherichia coli tends to accumulate heterologous proteins in insoluble form. Fusion protein technology has been used to increase the solubility of overexpressed proteins in this organism, but with variable degrees of success. Fusion to a mutant form of DsbA (DsbAmut) confers higher levels of solubility to heterologous proteins in a reproducible way, even when E. coli is grown at 37 degrees C. We have shown this to be true with a diverse sample of eukaryotic proteins: IGF-I, IGFBP-3, 3C proteinase, TGF beta-2, sTGF beta-RII, BDNF, GDNF, mEGFBP, leptin, and GFP. In addition, we have investigated the effects of charge average and proline content on the solubility of DsbAmut fusions. Coexpression of a protein prolyl isomerase [cyclophilin (L-)] and modification of selected asparagine residues to aspartic acid appear to have beneficial effects on the accumulation of soluble heterologous proteins.

Base Sequence↗
PubMed1997

External beam abdominal radiotherapy in patients with seminoma stage I: field type, testicular dose, and spermatogenesis.

PURPOSE: To establish a predictive model for the estimation of the gonadal dose during adjuvant para-aortic (PA) or dog leg (DL: PA plus ipsilateral iliac) field radiotherapy in patients with testicular seminoma. METHODS AND MATERIALS: The surface gonadal dose was measured in patients with seminoma Stage I receiving PA or DL radiotherapy. Sperm cell analysis was performed before and 1 year after irradiation. PA and DL radiotherapy were simulated in the Alderson phantom while we measured the dose to the surface and middle of an artificial testicle, varying its position within realistic anatomical constraints. The symphysis-to-testicle distance (STD), field length, and thickness of the patient were experimental variables. The developed mathematical model was validated in subsequent patients. RESULTS: The mean gonadal dose in patients was 0.09 and 0.32 Gy after PA and DL irradiation, respectively (p < 0.001). DL radiotherapy, but not PA irradiation led to significant reduction of the sperm count 1 year after irradiation. The gonadal dose-reducing effect of PA irradiation was confirmed in the Alderson phantom. A significant correlation was found between the STD and the gonadal dose during DL irradiation. A mathematical model was established for calculation of the gonadal dose and confirmed by measurements in patients. CONCLUSIONS: During radiotherapy of seminoma, the gonadal dose decreases with increasing STD. It is possible to predict the individual gonadal dose based on delivered midplane dose and STD.

Abdomen↗
PubMed1997

Combined modality treatment including intraoperative radiotherapy in locally advanced and recurrent rectal cancer.

BACKGROUND: Treatment of locally advanced and recurrent rectal cancer usually has a high local recurrence rate and poor survival. Promising results have been reported by combined external radiotherapy, extensive surgery and intraoperative radiotherapy (IORT). METHODS: One hundred fifteen patients with locally advanced rectal cancers fixed to the pelvic wall or locally recurrent rectal cancers underwent preoperative external radiotherapy with 46-50 Gy. Six to 8 weeks later radical pelvic surgery was attempted, and was combined with intraoperative electron beam radiotherapy (15-20 Gy) in 66 patients. The patients were followed closely to evaluate complication rate, local and distant recurrence rate and survival. RESULTS: Surgery with no macroscopic tumour remaining was obtained in 65% of the patients with no postoperative deaths. Pelvic infection was the major complication (21%). Although the observation time is short (3-60 months), the local recurrence rate seems low (22%) and survival seems promising (about 60% at 4 years) in patients with complete tumour resection, in contrast to patients with residual tumour (none living at 4 years). CONCLUSIONS: The combined modality treatment with preoperative external radiotherapy and extensive pelvic surgery with IORT is sufficiently promising to start a randomized trial on the clinical value of IORT as a boost treatment in the multidisciplinary approach to this disease.

Adult↗
PubMed1997

Determination of 3D dose distribution from intracavitary brachytherapy of cervical cancer by MRI of irradiated ferrous sulphate gel.

BACKGROUND AND PURPOSE: MRI ferrous sulphate gel dosimetry has proven to be a valuable method for assessment of dose delivered in teletherapy. The intention of this study was to investigate ferrous sulphate gel as a possible dosimeter for intracavitary brachytherapy applications. MATERIALS AND METHODS: A plastic duplicate of a cervix ring applicator set was submerged in Fe2(+)-infused gelatin gel. The gel was subsequently irradiated by a stepwise moving 192Ir source, using automatic afterloading equipment (Microselectron, Nucletron-Oldelft International BV, Veenendaal, The Netherlands). A 3D dose distribution was reconstructed from MR images of the gel. RESULTS: The gel dose measurements were found to be of the same accuracy as TLD measurements. Isodose curves based on gel dosimetry and isodose curves computed by a dose planning system were generally less than 2 mm apart. MR images showing the position of the applicator set in a patient during treatment were used to obtain images describing patient anatomy in the sagittal and ring planes of the applicator set. Isodose curves computed from the gel measurements were then superimposed on these images, illustrating one possible way of linking dosimetrical and anatomical data. CONCLUSIONS: Our study shows that MRI ferrous sulphate gel dosimetry is a useful tool for studies of dose distributions in brachytherapy and their relation to critical organs. Possible improvements of the gel dosimeter lie in reducing the diffusion of ferric ions and increasing the radiation sensitivity of the gel.

Brachytherapy↗
PubMed1997

Radiation-induced changes in phosphorus T1 values in human melanoma xenografts studied by 31P-MRS.

31P-magnetic resonance spectroscopy (MRS) has been shown to be a promising method for monitoring tumor response to radiation therapy. The purpose of the work reported here was to investigate whether the usefulness of 31P-MRS might be enhanced by measurement of spin-lattice relaxation times (T1s) in addition to resonance ratios. The work was based on the hypothesis that tumors having a high probability of being controlled locally would show shortened T1s during the treatment course due to reoxygenation and development of necrosis. BEX-t human melanoma xenografts, which show efficient reoxygenation and development of necrosis following single dose irradiation, were used as tumor models. Tumors were treated with single doses of 5.0 or 15.0 Gy and the T1s of the inorganic phosphate and nucleoside triphosphate beta resonances were measured as a function of time after irradiation by using the superfast inversion recovery method. Fractional tumor water content was determined by drying excised tumors at 50 degrees C until a constant weight was reached. The T1s in irradiated tumors were either longer than or not significantly different from those in unirradiated control tumors. The increase in the T1s following irradiation coincided in time with a radiation-induced increase in tumor water content, suggesting a causal relationship. The effects of reoxygenation and development of necrosis on T1s were probably overshadowed by the effects of tumor water content. Consequently, the usefulness of 31P-MRS in monitoring tumor response to radiation therapy might not be significantly enhanced by measurement of T1s.

Animals↗
PubMed1997

Measurement of the ferric diffusion coefficient in agarose and gelatine gels by utilization of the evolution of a radiation induced edge as reflected in relaxation rate images.

A method has been developed to determine the diffusion coefficients of ferric ions in ferrous sulphate doped gels. A radiation induced edge was created in the gel, and two spin-echo sequences were used to acquire a pair of images of the gel at different points of time. For each of these image pairs, a longitudinal relaxation rate image was derived. From profiles through these images, the standard deviations of the Gaussian functions that characterize diffusion were determined. These data provided the basis for the determination of the ferric diffusion coefficients by two different methods. Simulations indicate that the use of single spin-echo images in this procedure may in some cases lead to a significant underestimation of the diffusion coefficient. The technique was applied to different agarose and gelatine gels that were prepared, irradiated and imaged simultaneously. The results indicate that the diffusion coefficient is lower in a gelatine gel than in an agarose gel. Addition of xylenol orange to a gelatine gel lowers the diffusion coefficient from 1.45 to 0.81 mm2 h-1, at the cost of significantly lower Rl sensitivity. The addition of benzoic acid to the latter gel did not increase the Rl sensitivity.

Benzoates↗
PubMed1997

Implications of radiation induced apoptosis on calculated radial cell inactivation for a linear 192Ir source.

The cell inactivation probability as a function of the radial distance from a 4 cm linear, low dose rate (LDR) 192Ir source was calculated using a modified linear-quadratic (LQ) equation, taking into account the effect of radiation induced apoptosis. As a measure of the therapeutic range of the source, the radial distance from the midpoint of the central axis of the source to the point of 50% inactivation probability was calculated. It was found that the therapeutic range increased with increasing values of the maximal radiation induced apoptotic fraction, Fa; but only as long as the ratio between the apoptotic cell kill susceptibility, zeta, and the alpha value is larger than unity. If the ratio was smaller than unity, a decrease in therapeutic range was found. The slope of the radial cell inactivation probability curve was measured as the distance between the point of 10% and 90% inactivation probability. The slope was found to be fairly independent of the repair half-time, T(1/2), but became steeper with decreasing values of Fa.

Apoptosis↗
PubMed1997

Abutting orthogonal electron and photon beams in the head and neck region using asymmetrical photon beam edges.

Irradiation of target volumes within the ethmoid sinus and nasal cavity region has, at our institution, been performed using one anterior electron beam, abutted to two opposing lateral photon beams, in order to exclude the orbit from the irradiated volume. However, this technique give rise to larger dose hetereogeneities within the target volume, as well as undesired hot spots in the chiasma region. To reduce the inhomogenious distribution, we have introduced asymmetrical photon beam edges to broaden the penumbra of the two opposing photon beams resembling the dose gradient of the perpendicular electron beam. The achieved reduction in dose heterogeneity, measured from the differential dose-volume-histogram, is in the order of 30-40% when applying the asymmetrical abutting technique compared with the conventional two opposing photon beam technique. As demonstrated by calculating the tumour control probability (TCP), the increase in dose homogeneity within the target volume, may be of clinical significance.

Dose-Response Relationship, Radiation↗
PubMed1997

Specification of the dose to organs at risk in external beam radiotherapy.

Reporting of the clinical relevant dose to organs at risk (OR) and other normal tissues is crucial in trials and protocols where the aim is to assess late complications and to increase the therapeutic ratio for external beam radiotherapy. The dose distribution in normal tissues and ORs are, however, most often heterogeneous, at least when more than two opposing beams are applied. To decide the most clinical relevant dose with respect to late occurring complications is therefore not a straight forward problem. In this work we discuss what parameters characterise the dose-volume-histogram (DVH) best by calculating normal tissue complication probabilities (NTCPs) by using the Lyman model and various sets of statistical parameters drawn out from the DVHs. These NTCPs are compared to NTCPs calculated from the full DVHs, when the sets of parameters are evaluated. Our calculations indicate that the NTCP based on the Lyman model is best correlated to the Dmax value for serially organised tissues such as the spinal cord. For organs, described largely as tissues organised in parallel, the Dmedian or Dmean of the DVH may be applied. Our calculations reveal that Dmean is the parameter of choice when Dmedian is quite small, but when the two parameters approach each other. Dmedian will be a better choice, using a unity volume fraction. For ORs characterised by a mixed serial and parallel functional structure, as the heart, neither Dmax, Dmedian nor Dmean may predict the actual NTCP.

Dose-Response Relationship, Drug↗
PubMed1997

Inhibition of corneal fibrosis by topical application of blocking antibodies to TGF beta in the rabbit.

Previous studies have shown that TGF beta 1 induces activation and myofibroblast transformation of cultured rabbit corneal keratocytes. To determine whether TGF beta has a similar function in vivo, we evaluated the effect of TGF beta-blocking antibodies on corneal fibrosis after lamellar keratectomy (LK) in the rabbit. A total of 51 rabbits received standard LK wounds, and eyes were treated with 50 microliters of Celluvisc/PBS, containing 10, 50, or 100 micrograms of 1D11, a mouse monoclonal anti-TGF beta-blocking antibody. Control wounds received either 100 micrograms of an irrelevant mouse monoclonal antibody or vehicle alone. At days 14, 28, 42, and 56, eyes were evaluated by in vivo confocal microscopy (CM) and the mice were killed for light microscopy (LM) and immunostaining with antibodies to human fibronectin. In vivo CM of LK wounds clearly identified a disorganized layer that contained irregularly arranged fibroblasts and reflective extracellular matrix overlying normal corneal stroma. In a subset of 11 eyes stained with 5-(4,6-dichlorotriazinyl) aminofluorescein (DTAF) immediately after injury, the thickness of the disorganized layer identified by in vivo CM significantly correlated with both anterior corneal fibrosis (r = 0.627; p < 0.025) and depth of keratocyte activation (r = 0.8980; p < 0.0005), indicating that in vivo CM can be used quantitatively to assess anterior stromal fibrosis. In eyes treated with an irrelevant monoclonal antibody, in vivo corneal fibrosis averaged 100 +/- 26 microns thick at day 14, whereas treatment with 10, 50, and 100 micrograms anti-TGF beta significantly reduced (p < 0.0005) the anterior disorganization in a dose-dependent fashion to 101 +/- 32, 45 +/- 11, and 56 +/- 18 microns, respectively. Semiquantitative measurement of anti-fibronectin staining within the wound revealed that anti-TGF beta significantly reduced the intensity of anti-fibronectin staining in the anterior 50 microns of the corneal stroma (p < 0.003). These findings indicate that TGF beta plays an important in vivo role in keratocyte activation and myofibroblast transformation. Furthermore, the in vivo use of TGF beta-blocking antibody effects may allow modulation of corneal fibrosis after refractive surgery.

Administration, Topical↗
PubMed1996

Brain metastasis model in athymic nude mice using a novel MUC1-secreting human breast-cancer cell line, MA11.

The MA11 human breast-cancer cell line was established with cells isolated from a bone-marrow sample using immunomagnetic beads conjugated to the anti-MUC1 antibody BM-2. The cell line showed a selective preference for metastasising to the brain in athymic nude mice. Following injection of MA11 cells into the left ventricle of the heart, brain metastases developed in 87% (20/23) animals, with a mean latency until development of neurological symptoms of 65 days. Necropsy and histological examination revealed tumour nodules of varying sizes throughout the brain, invading both grey and white matter of both hemispheres, and with extensive involvement of the cerebellum. MRI spin-echo images indicated brain lesions in some animals that were subsequently confirmed by histology. Three mice showed small tumour nodules (1-2 mm) in the lung, and 2 had solitary lesions (< 1 mm) within the spinal cord. Metastases were not detected in bone, liver, adrenal gland, kidney, spleen or heart. The human MUC1 mucin, as determined by a europium-based immunoradiometric assay, was detected in the serum of 9/11 animals that showed histological evidence of brain metastases. The mucin could not be found in mouse serum samples taken before day 46. The concentration range of MUC1 observed was from <1 to >50 U/ml, and did not appear to correlate with the size or number of tumours as determined from histological sections. This new model provides an opportunity to study the mechanisms of clinically relevant organ-selective metastases and may be of use in evaluating novel treatment for brain metastases in breast cancer.

Aged↗
PubMed1996

Measurement of dynamic wedge angles and beam profiles by means of MRI ferrous sulphate gel dosimetry.

The purpose of this study is to examine the possible value of measuring the dose distribution in dynamic wedge photon beams using ferrous sulphate gel phantoms analysed by MRI. The wedge angles and dose profiles were measured for a field size of 70 x 70 mm2 and for dynamic wedge angles of 15 degrees, 30 degrees, 45 degrees and 60 degrees using a 15 MV photon beam generated from a Clinac 2100 CD (Varian). The dose profiles obtained from MRI ferrous sulphate gel were in good agreement with the dose measurements performed with a diode detector array. Also, the wedge angles determined from the MRI ferrous sulphate gel agreed well with the values obtained by using film dosimetry and with calculations by use of TMS (treatment planning system) (Helax, Uppsala, Sweden). The study demonstrated that MRI ferrous sulphate gel dosimetry is an adequate tool for measurements of some beam characteristics of dynamic radiation fields.

Algorithms↗
PubMed1996

Development of an experimental model for high dose rate endocavitary irradiation of the rat rectum.

Experimental data indicate a greater tolerance for endocavitary than for external beam irradiation of the normal rectal tissue in the rat. Increased tolerance has been attributed to temperature induced rectal hypoxia and a reduction of the dose to the mesentery. The general scarcity of experimental work in the field and the problems concerning hypoxia and dosimetry motivated the development of the current model. An 8 mm diameter endocavitary applicator was used for symmetrical dilatation and central introduction of the 192Ir source into the rectum of male Fischer F344 rats. Pulse oximetry and pO2-electrode readings from the intubated rectum gave no indication of radiobiological hypoxia. In vitro and in vivo thermoluminescence dosimetry (TLD) was supported by MRI based ferrous sulphate gel dosimetry. Using a 25 mm length source configuration the 90% isodose incorporated a 13 mm length segment of the rectum, and a 5.6% maximum deviation from the calculated dose was observed by the TLD and MRI based gel dosimetry. The ureters, the bladder and the skin were the only organs other than the target organ which received doses greater than 10% of the rectal dose. The model seems to be suitable for dose effect studies since endocavitary irradiation of the rat rectum can be performed without induction of local tissue hypoxia.

Animals↗