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M Scholz

Publications and source records attributed to M Scholz.

At least 55 records · Page 3Linked to original sources
PubMed2003

The increased biological effectiveness of heavy charged particles: from radiobiology to treatment planning.

The increased biological effectiveness of heavy charged particle beams like e.g., carbon ions in the tumor volume in comparison to the lower effectiveness in the surrounding healthy tissue represents one of the major rationales for their application in tumor therapy. This increased effectiveness also characterizes the advantage of heavier ions compared to proton beams. The increased effectiveness has to be taken into account in treatment planning in order to estimate the corresponding photon equivalent doses in normal and tumor tissues, thus allowing a link e.g., to normal tissue dose limits in conventional photon therapy. Due to the complex dependencies of RBE on parameters like dose, beam energy, LET, atomic number and cell or tissue type, the relevant RBEs cannot be solely determined from experimental data. Therefore, within the framework of the pilot project of tumor therapy with carbon ions performed at GSI Darmstadt, treatment planning is based on a biophysical model, which has been extensively tested. The paper first summarizes the essential systematic dependencies of RBE on different parameters like e.g., dose, LET, atomic number and cell type. The basic principle of the biophysical model is then introduced, and special emphasis is given to the application of the model to in vivo and clinical endpoints. Model predictions are compared to experimental data in vitro and in vivo. Finally, the implementation of the biophysical model in the treatment planning procedure is presented. The biological verification of the whole treatment planning procedure is explained and examples of patient treatment plans are given.

Animals↗
PubMed2003

Biological imaging of heavy charged-particle tracks.

The immunocytochemical response to DNA damage induced by low-energy bismuth and carbon ions was investigated in normal human fibroblasts. Inside the nuclei, the traversing charged particles lead to the accumulation of proteins related to DNA lesions and repair along the ion trajectories. Irradiation under a standard geometric setup with the beam direction perpendicular to the cell monolayer generates spots of these proteins as described previously for MRE11B (hMre11), CDKN1A (p21) and PCNA (Jakob et al., Int. J. Radiat. Biol. 78, 75-88, 2002). Here we present data obtained with a new irradiation geometry characterized by a small angle between the beam direction and the monolayer of cells. This new irradiation geometry leads to the formation of protein aggregates in the shape of streaks stretching over several micrometers in the x/y plane, thus facilitating the analysis of the fluorescence distributions along the particle trajectories. Measurements of fluorescence intensity along the ion tracks in double- and triple-stained samples revealed a strict spatial correlation for the occurrence of CDKN1A and MRE11B clusters. In addition, immunostained gamma-H2AX is used as a marker of double-strand breaks (DSBs) to visualize the localized induction of these lesions along the particle paths. A clear coincidence of CDKN1A and gamma-H2AX signals within the ion-induced streaks is observed. Also for PCNA, which mainly associates with lesions processed by excision repair, a strict colocalization with the MRE11B aggregations was found along the ion trajectories, despite the higher estimated yield of this type of lesions compared to DSBs. Strikingly similar patterns of protein clusters are generated not only for the various proteins studied but also using different ion species from carbon to bismuth, covering LET values ranging from about 300 to 13600 keV/microm and producing estimated DSB densities differing by a factor around 45. The patterns of protein clustering along the very heavy-ion trajectories appear far more heterogeneous than expected based on idealized DSB distributions arising from model calculations. The results suggest that additional factors like compaction or confined movement of chromatin are responsible for the observed clustering of proteins.

Bismuth↗
PubMed2002

[The value of natriuretic peptides NT-pro-BNP and BNP for the assessment of left-ventricular volume and function. A prospective study of 150 patients].

BACKGROUND AND OBJECTIVE: An early detection of patients with left-ventricular (LV) dysfunction is essential for effective treatment of congestive heart failure. The B-type natriuretic peptide (BNP) was described as a strong diagnostic parameter of LV-dysfunction. Aim of this study was to compare the diagnostic value of BNP and the aminoterminal part of pro-BNP (NT-pro-BNP) within an heterogenous patient population. SUBJECTS AND METHODS: NT-pro-BNP and BNP were measured in 150 hospitalized cardiologic patients (age-median 64 years, 109 male versus 41 female). The values were correlated with clinical and haemodynamic parameters of the invasively determined LV-function. RESULTS: Patients with pathologic haemodynamic values of the LV-function had significantly higher NT-pro-BNP and BNP levels than patients with normal haemodynamic parameters. In our study population a severe systolic LV-dysfunction (ejectionfraction EF<40 %) could be detected with a sensitivity and specifity of 100 % and 64 % by NT-pro-BNP and 100 % and 45 % by BNP. Sensitivity and specifity for the detection of any systolic dysfunction (EF<60 %) and of a systolic or diastolic dysfunction, respectively, were 94 %, 37 % and 88 %, 41 % for NT-pro-BNP (94 %, 40 % and 84 %, 44 % for BNP). The corresponding negative predictive values were 100 %, 96 % and 71 % for NT-pro-BNP and 100 %, 96 % and 68 % for BNP. CONCLUSION: NT-pro-BNP and BNP were highly sensitive diagnostic parameters with a very good negative predictive value for LV-dysfunction. Because of the uncomplicated measurement, they could be used effectively to rule out LV-dysfunction in cardiovascular high risk patients by general practitioners.

Adult↗
PubMed2002

Calculation of the x-ray film response to heavy charged particle irradiation.

A model was developed to calculate the response of films to heavy ion irradiation as a function of particle type and energy. It is based on the local effect model and was extended to be applied to the non-homogeneous target of photographic emulsions. The calculation was performed for protons and carbon ions in the energy range from 2 to 430 MeV u(-1). The calculated film responses are in very good agreement with experimental data. Based on this model calculation a data base of film responses was set up. This enables a three-dimensional dose verification with films in the heavy ion tumour therapy project at GSI, Darmstadt.

Carbon↗
PubMed2002

Dose-dependent effects of combined IGF-I and TGF-beta1 application in a sheep cervical spine fusion model.

Combined IGF-I and TGF-beta1 application by a poly-(D,L-lactide) (PDLLA) coated interbody cage has proven to promote spine fusion. The purpose of this study was to determine whether there is a dose-dependent effect of combined IGF-I and TGF-beta1 application on intervertebral bone matrix formation in a sheep cervical spine fusion model. Thirty-two sheep underwent C3/4 discectomy and fusion. Stabilisation was performed using a titanium cage coated with a PDLLA carrier including no growth factors in group 1 ( n=8), 75 micro g IGF-I plus 15 micro g TGF-beta1 in group 2 ( n=8), 150 micro g IGF-I plus 30 micro g TGF-beta1 in group 3 ( n=8) and 300 micro g IGF-I plus 60 micro g TGF-beta1 in group 4 ( n=8). Blood samples, body weight and temperature were analysed. Radiographic scans were performed pre- and postoperatively and after 1, 2, 4, 8, and 12 weeks. At the same time points, disc space height and intervertebral angle were measured. After 12 weeks, the animals were killed and fusion sites were evaluated using quantitative computed tomographic (CT) scans to assess bone mineral density, bone mineral content and bony callus volume. Biomechanical testing was performed and range of motion, and neutral and elastic zones were determined. Histomorphological and histomorphometrical analysis were carried out and polychrome sequential labelling was used to determine the time frame of new bone formation. In comparison to the group without growth factors (group 1), the medium- and high-dose growth factor groups (groups 3 and 4) demonstrated a significantly higher bony callus volume on CT scans, a higher biomechanical stability, an advanced interbody bone matrix formation in histomorphometrical analysis, and an earlier bone matrix formation on fluorochrome sequence labelling. Additionally, the medium- and high-dose growth factor groups (groups 3 and 4) demonstrated a significantly higher bony callus volume, a higher biomechanical stability in rotation, and an advanced interbody bone matrix formation in comparison to the low-dose growth factor group (group 2). No significant difference could be determined between the medium- and the high-dose growth factor groups (groups 3 and 4, respectively). The local application of IGF-I and TGF-beta1 by a PDLLA-coated cage significantly improved results of interbody bone matrix formation in a dose-dependent manner. The best dose-response relationship was achieved with the medium growth factor dose (150 micro g IGF-I and 30 micro g TGF-beta1). With an increasing dose of these growth factors, no further stimulation of bone matrix formation was observed. Although these results are encouraging, safety issues of combined IGF-I and TGF-beta1 application for spinal fusion still have to be addressed.

Animals↗
PubMed2002

[Proper Weight Loss with Intelligence (MIRA). 2 programs for weight reduction in general practice trial].

Applying the MIRA (German acronym for losing weight intelligently) concept, weight-losing programs were tested for guideline conformity and suitability in practice. The core of the concept comprises instruments for the analysis and evaluation of quality criteria for weight-reduction programs. A total of 116 men and women participated in the BCM program of PreCon GmbH & Co. KG, and the "Ich nehme ab" (l'm slimming) program (designed as a self-help aid) of the Deutsche Gesellschaft für Ernährung (German Society for Nutrition), and received counseling over a period of one year. Initial results of follow-up at 40 weeks showed a weight reduction of at least 5% in 66% of all participants, and at least 10% in 24%. The weight loss correlated with the number of counselings. On the basis of the 89 questionnaires evaluated to date, quality of life as measured by the IWQOL-Lite score showed an improvement in 80% of the subjects. These preliminary results indicate that the MIRA concept would appear to be a suitable quality control tool for obesity treatment programs.

Adult↗
PubMed2002

Comparison of BMP-2 and combined IGF-I/TGF-ss1 application in a sheep cervical spine fusion model.

Growth factors have proven to promote spine fusion. However, no comparative evaluation of growth factors in spinal fusion has yet been performed. The purpose of this study was to compare the efficacy and safety of combined IGF-I and TGF-ss1 application with BMP-2 application and autologous cancellous bone graft at an early time point in a sheep cervical spine fusion model. Thirty-two sheep underwent C3/4 discectomy and fusion. They were divided into four groups, according to their treatment: group 1, titanium cage ( n=8); group 2, titanium cage filled with autologous cancellous iliac crest bone grafts ( n=8); group 3, titanium cage coated with a poly-(D,L-lactide) (PDLLA) carrier including BMP-2 (5% w/w) ( n=8); group 4, titanium cage coated with a PDLLA carrier including IGF-I (5% w/w) and TGF-ss1 (1% w/w) ( n=8). Blood samples, body weight and temperature were analysed. Radiographic scans were performed pre- and postoperatively and after 1, 2, 4, 8 and 12 weeks. At the same time points, disc space height and intervertebral angle were measured. After 12 weeks, the animals were killed and fusion sites were evaluated using functional radiographic views in flexion and extension. Quantitative computed tomographic scans were performed to assess bone mineral density, bone mineral content and bony callus volume. Biomechanical testing was carried out and the values for range of motion, and neutral and elastic zone were determined. Histomorphological and histomorphometrical analysis were performed and polychrome sequential labelling was used to determine the time frame of new bone formation. The results showed that, in comparison to the group treated with the cage alone (group 1), the cage plus BMP-2 group (group 3) and the cage plus IGF-I and TGF-ss1 group (group 4) demonstrated a significantly higher fusion rate in radiographic findings, a higher biomechanical stability, a more advanced interbody fusion in histomorphometrical analysis, and an accelerated interbody fusion on fluorochrome sequence labelling. In comparison to the bone graft group (group 2), the BMP-2 (group 3) and IGF-I/TGF-ss1 group (group 4) showed significantly less residual motion on functional radiographic evaluation, higher bone mineral density of the callus and higher biomechanical stability in extension, rotation and bending. The BMP-2 group showed significantly less residual motion on functional radiographic evaluation and higher intervertebral bone matrix formation on fluorochrome sequence labelling at 9 weeks in comparison to the IGF-I/TGF-ss1 group. In contrast, the IGF-I/TGF-ss1 group showed a significantly higher bone mineral density of the callus than the BMP-2 group. In comparison to the autologous cancellous bone graft group, both growth factors (BMP-2 and combined IGF-I and TGF-ss1) significantly improved the biomechanical results of interbody fusion. No systemic side effects were observed for either growth factor. On the basis of these preliminary results, it would appear that combined IGF-I/TGF-ss1 application yields equivalent results to BMP-2 application at an early time point in anterior sheep cervical spine fusion.

Animals↗
PubMed2002

Leukocyte filtration fails to limit functional neutrophil activity during cardiac surgery.

OBJECTIVE AND DESIGN: The beneficial effects of leukocyte filtration on the outcome of cardiac surgery with cardiopulmonary bypass (CPB) is probably due to the limitation of pathogenesis mediated by over-stimulated neutrophils. However, the influence of leukocyte filtration on the functional neutrophil activity has not been studied in detail. Therefore, by using different filtration timing strategies we determined neutrophil effector functions before and after the filter passage as well as blood surrogate markers for neutrophil activation. METHODS: We randomly assigned 80 cardiac surgery patients to four groups (n = 20 each) without (1) and with three different filtration timing strategies (II-IV). As functional end points neutrophil phagocytic activity and oxidative burst upon ex vivo stimulation with E.coli were analyzed from blood of 31 patients whereas polymorphonuclear elastase (PMNE), myeloperoxidase, and malondialdehyde (MDA), a marker for lipid peroxidation was determined in plasma samples from 80 patients. Blood was harvested immediately before and behind the filter (Pall LG6) at different times during CPB. RESULTS: We found that none of the filtration strategies either reduced the number of neutrophils capable of eliciting phagocytic activity and oxidative burst or the activity per cell. In contrast, PMNE and MPO levels in peripheral venous blood were found to be significantly increased in groups II-IV compared with group I throughout the entire filtration period in all patients. MDA was not enhanced in the filter groups. CONCLUSIONS: Our results show that the leukocyte depletion filter in the arterial line of the heart-lung machine failed to limit neutrophil stimulation but rather augmented PMNE plasma levels. We speculate that augmented PMNE and MPO levels mainly stem from neutrophils that are captured within the mesh of the leukocyte filter.

Aged↗
PubMed2002

Perioperative monitoring of indocyanine green clearance and plasma disappearance rate in patients undergoing liver transplantation.

INTRODUCTION: Indocyanine green (ICG) elimination tests have been repeatedly suggested as an early predictor of graft function in patients with liver transplantation. Conventionally, ICG clearance (ClICG) is measured by a series of blood samples with subsequent laboratory analysis. More recently bedside techniques have become available to measure ICG concentrations in vivo and in addition to ClICG, the plasma disappearance rate of ICG (PDRICG) is increasingly being used. The aim of this study was to assess and to compare the normal time courses of ClICG and PDRICG in liver transplant recipients. METHODS: ClICG and PDRICG were measured perioperatively and at various times up to 24 h after liver transplantation. The bedside transpulmonary indicator dilution technique with an arterial fiberoptic-thermistor catheter was used to assess the ICG concentration time curve together with total circulating blood volume (Vd circ). RESULTS: Similar patterns of the time courses of ClICG and PDRICG with a fast recovery of ICG elimination in the early reperfusion period were observed. Compared to healthy subjects, ClICG was supranormal and PDRICG was slightly subnormal. In this study, Vd circ was increased at baseline and remained increased during surgery. CONCLUSIONS: PDRICG and ClICG are well suited to monitor onset and maintenance of graft function in patients undergoing liver transplantation. The PDRICG values measured tend to be relatively lower than ClICG because of an increased blood volume in these patients. By knowing these differences it is justified to monitor liver function in a very simple manner with PDRICG.

Adult↗
PubMed2002

[Experimental fusion of the sheep cervical spine. Part I: Effect of cage design on interbody fusion].

INTRODUCTION: There has been a rapid increase in the use of interbody fusion cages as an adjunct to spondylodesis, although experimental data are lacking. A sheep cervical spine interbody fusion model was used to determine the effect of different cage design parameters (endplate-implant contact area, maximum contiguous pore) on interbody fusion. MATERIAL AND METHOD: IN VITRO EVALUATION: 24 sheep cadaver specimens (C2-C5) were tested in flexion, extension, axial rotation, and lateral bending with a nondestructive flexibility method using a nonconstrained testing apparatus. Four different groups were examined: (1) control group (intact) ( n=24), (2) autologous tricortical iliac crest bone graft ( n=8), (3) Harms cage ( n=8), and (4) SynCage-C ( n=8). IN VIVO EVALUATION: 24 sheep underwent C3/4 discectomy and fusion: group 1: autologous tricortical iliac crest bone graft ( n=8), group 2: Harms cage filled with autologous cancellous iliac crest bone grafts ( n=8), and group 3: SynCage-C filled with autologous cancellous iliac crest bone grafts ( n=8). Radiographic scans were performed pre- and postoperatively and after 1, 2, 4, 8, and 12 weeks, respectively. At the same time points, disc space height (DSH), height index (HI), intervertebral angle (IVA), and endplate angle (EA) were measured. After 12 weeks the animals were killed and fusion sites were evaluated using biomechanical testing in flexion, extension, axial rotation, and lateral bending. Additionally, histomorphological and histomorphometrical analyses were performed. RESULTS: Over a 12-week period the cage groups showed significantly higher values for DSH, HI, IVA, and EA compared to the bone graft. In vivo stiffness was significantly higher for the tricortical iliac crest bone graft and Harms cage than in vitro stiffness. However, there was no difference between in vitro and in vivo stiffness of the SynCage-C. Histomorphometrical evaluation showed a more progressed bone matrix formation in the Harms cage group than in both other groups. CONCLUSION: The parameter endplate-implant contact area was not able to determine subsidence of cages. In contrast, the maximum contiguous pore of a cage significantly correlates with interbody bone matrix formation inside the cage. Additionally, there was no correlation between in vitro and in vivo stiffness of interbody fusion cages. Therefore, biomechanical in vitro studies are not able to determine in vivo outcome of fusion cages. Animal experimental evaluations of interbody fusion cages are essential prior to clinical use.

Animals↗
PubMed2002

[Experimental fusion of the sheep cervical spine. Part II: Effect of growth factors and carrier systems on interbody fusion].

INTRODUCTION: A sheep cervical spine interbody fusion model was used to determine the effect of different carriers and growth factors on interbody bone matrix formation. The purpose of this study was to compare the efficacy and safety of combined IGF-I and TGF-beta1 application with BMP-2 application in spinal fusion. Additionally, a new poly (D, L-lactide) carrier system was compared to a collagen sponge carrier. METHOD: Forty sheep underwent C3/4 discectomy and fusion: group 1: titanium cage ( n=8), group 2: titanium cage coated with a PDLLA carrier (n=8), group 3: titanium cage coated with a PDLLA carrier including BMP-2 ( n=8), group 4: titanium cage with a collagen carrier including BMP-2 ( n=8), and group 5: titanium cage coated with a PDLLA carrier including IGF-I and TGF-beta1 ( n=8). Blood samples, body weight, and temperature were analyzed. Radiographic scans were performed pre- and postoperatively and after 1, 2, 4, 8, and 12 weeks, respectively. At the same time points, disc space height (DSH) and intervertebral angle (IVA) were measured. After 12 weeks the animals were killed and fusion sites were evaluated using functional radiographic views in flexion and extension. Quantitative computed tomographic scans (QCT) were performed to assess bone mineral density (BMD), bone mineral content (BMC), and bony callus volume (BCV). Biomechanical testing was carried out in flexion, extension, axial rotation, and lateral bending. Range of motion (ROM), neutral zone (NZ), and elastic zone (EZ) were determined. Histomorphological and histomorphometrical analyses were performed and polychrome sequential labeling was used to determine the time frame of new bone formation. RESULTS: In comparison to the non-coated cages, all PDLLA-coated cages showed significantly higher values for BMD of the callus and bone volume/total volume ratio. In comparison to the cage groups (groups 1 and 2), the cage plus BMP-2 (groups 3 and 4) and the cage plus IGF-I and TGF-beta1 group (group 5) demonstrated a significantly higher fusion rate in radiographic findings, a higher biomechanical stability, an advanced interbody fusion in histomorphometric analysis, and an accelerated interbody fusion on fluorochrome sequence labeling. BMP-2 application by the PDLLA carrier system (group 3) demonstrated significantly higher bony callus volume than BMP-2 application by a collagen sponge carrier (group 4). The BMP-2 group (group 3) showed significantly lower residual motion on functional radiographic evaluation and higher intervertebral bone matrix formation on fluorochrome sequence labeling at 9 weeks in comparison to the IGF-I/TGF-beta1 group (group 5). In contrast, the IGF-I/TGF-beta1 group (group 5) showed a significantly higher bone mineral density of the callus than the BMP-2 group (group 3). CONCLUSION: PDLLA coating of cervical spine interbody fusion cages as a delivery system for growth factors was effective and safe. In comparison to the collagen sponge carrier, the new PDLLA carrier system was able to improve results of interbody bone matrix formation. Both growth factors (BMP-2 and combined IGF-I and TGF-beta1) significantly accelerated results of interbody fusion. Based on these preliminary results, the combined IGF-I/TGF-beta1 application yields results equivalent to BMP-2 application at an early time in anterior sheep cervical spine fusion.

Animals↗
PubMed2002

Effects of induction of anaesthesia with sufentanil and positive-pressure ventilation on the intra- to extrathoracic volume distribution.

BACKGROUND AND OBJECTIVE: Induction of general anaesthesia in combination with positive-pressure ventilation is often associated with a significant decrease of arterial pressure. A decreased preload may contribute to this phenomenon. The aim was to investigate whether a change in cardiac filling occurs following the induction of general anaesthesia with sufentanil under typical clinical conditions. METHODS: Fifteen patients scheduled for elective coronary bypass grafting were studied immediately before surgery. In addition to standard monitors, a transpulmonary double-indicator dilution technique measured in vivo intrathoracic blood volume, global end-diastolic volume and total circulating blood volume. For induction of anaesthesia 2 microg kg(-1) sufentanil was given. Measurements were performed awake and after the induction of anaesthesia, intubation and mechanical ventilation of the lungs. RESULTS: To maintain arterial pressure during the induction period within -20% of baseline pressure, on average 22 +/- 6mLkg(-1) crystalloids and 8 +/- 6mLkg(-1) colloids were given. Despite these amounts of fluid, cardiac filling was decreased, whereas circulating blood volume increased significantly. Both central venous pressure and pulmonary capillary wedge pressure increased. CONCLUSIONS: Induction of general anaesthesia with positive-pressure ventilation is regularly associated with a blood volume shift from intra- to extrathoracic compartments. Even in low-dose opioid monoanaesthesia with sufentanil--often regarded as relatively inert in haemodynamic terms--the phenomenon could be demonstrated as the primary cause of the often-observed decrease of arterial pressure. It seems, therefore, rationally justified to restore cardiac filling by generous administration of intravenous fluids, at least in patients with unaffected cardiac pump function. During induction of anaesthesia, central venous pressure and pulmonary capillary wedge pressure do not reliably indicate cardiac filling.

Adjuvants, Anesthesia↗
PubMed2002

Endoscopic treatment of chronic pancreatitis: a multicenter study of 1000 patients with long-term follow-up.

BACKGROUND AND STUDY AIMS: Endoscopic ductal decompression therapy has become an established method of treating patients with painful obstructive chronic pancreatitis. Smaller series, mostly with a medium-term follow-up period, have reported encouraging results. The present analysis presents long-term follow-up data from a large multicenter patient cohort. PATIENTS AND METHODS: Patients with painful chronic pancreatitis and with ductal obstruction due to either strictures and/or stones treated endoscopically at eight different centers underwent follow-up after 2 - 12 years (mean 4.9 years). The patients' clinical data, the rate of technical success, and complications were recorded from the charts. Follow-up data were prospectively obtained using structured questionnaires; the main parameter for evaluating treatment success was a significant reduction in pain (no pain or only weak pain). RESULTS: Follow-up data were obtained from 1018 of 1211 patients treated (84%) with mainly strictures (47%), stones (18%), or strictures plus stones (32%). At the long-term follow-up, 60% of the patients had their endotherapy completed, 16% were still receiving some form of endoscopic treatment, and 24% had undergone surgery. The long-term success of endotherapy was 86% in the entire group, but only 65% in an intention-to-treat analysis. There were no significant differences between the patient groups with regard to either strictures, stones, or both. Pancreatic function was not positively affected by endoscopic therapy. CONCLUSIONS: Endoscopic ductal decompression therapy offers relief of pain in two-thirds of the patients when it is used as the only form of treatment. One-quarter of the patients have to undergo surgery.

Adolescent↗
PubMed2002

Characterization of CDKN1A (p21) binding to sites of heavy-ion-induced damage: colocalization with proteins involved in DNA repair.

PURPOSE: To determine an association of locally accumulated CDKN1A and DNA repair proteins at the sites of heavy-ion traversals. MATERIALS AND METHODS: CDKN1A, PCNA, DNA-PK, hMre11 and Rad50 were investigated for their subnuclear localization after irradiation with heavy-ions using immunocytochemical staining and confocal laser-scanning microscopy. Human fibroblasts (normal diploid or XPA, ATM- or NBS1-deficient lines and HPV16 E6-transfected cells) were used. RESULTS: CDKN1A formed nuclear foci in G0/G1 normal human fibroblasts at the sites of particle traversal. Foci were persistent over hours and vanished after treatment with DNase-I. Formation of foci also occurred in NBS1- or ATM-deficient lines and in cells functionally abrogated for TP53. In normal fibroblasts, CDKN1A foci colocalized with particle-induced foci of the hMre11 and Rad50 proteins. However, only CDKN1A relocalization was observed in irradiated NBS1 cells. PCNA foci temporarily colocalizing with CDKN1A were also detected in normal fibroblasts after exposure to heavy-ions. In contrast, no radiation-induced subnuclear relocalization was found for DNA-PK. CONCLUSIONS: CDKN1A foci arise rapidly at sites of localized DNA damage induced by heavy-ions and are associated with the chromatin. Evidence is provided that localization of CDKN1A to foci is not dependent on functional TP53 and occurs independently of the formation of the hMre11/Rad50/NBS1 complex. The data support a yet unknown role of CDKN1A in sensing or early processing of radiation-induced DNA lesions.

Binding Sites↗
PubMed2002

Measurement of biological effects of high-energy carbon ions at low doses using a semi-automated cell detection system.

PURPOSE: To study the effects of low-dose, high-LET irradiation in order to detect possible deviations from a linear-quadratic dose dependence. MATERIALS AND METHODS: Experiments using charged particle irradiation were performed, in particular in the low-dose range from 0 to 2 Gy, and compared with experiments using photon radiation. The survival of V79 cells was studied by means of a semi-automated system, which allowed the detection and relocation of positions of individual cells at regular intervals. It consists of an inverted microscope equipped with a computerized stage control and image processing system. With such a technique, the precision of the survival assay is increased by avoiding the stochastic uncertainties of the conventional dilution assay. Furthermore, by means of daily observations, the system allows a detailed study of the growth kinetics of individual cells up to approximately 1 week after irradiation. RESULTS AND CONCLUSION: Up to now, high-LET experiments have been performed using mainly 100 MeV/u carbon ions (LET: 28 keV/microm). A significant hypersensitivity at low doses (0.1 Gy) has been detected for these ions. It is the first report of such a pronounced effect for charged particle irradiation. Although hypersensitivity after carbon ion irradiation apparently is in contrast to other data reported for peak pion irradiation at similar LET values, the difference might possibly be due to differences in the track structure of the particles.

Animals↗
PubMed2002

Extragonadal retroperitoneal germ cell tumor: evidence of origin in the testis.

BACKGROUND: The origin of extragonadal retroperitoneal germ cell tumors remains controversial. Whether they develop primarily in the retroperitoneum or whether they are metastases of a primary testicular tumor has long been debated. PATIENTS AND METHODS: We retrospectively analyzed 26 patients treated as having primary extragonadal retroperitoneal germ cell tumors based upon the findings of testicular palpation by the referring physician. Testicular evaluation was then extended with ultrasonographical and histological examinations. RESULTS: Biopsy of the extragonadal tumor was performed in 25 patients, confirming diagnosis of extragonadal retroperitoneal germ cell tumor. Prior to treatment patients were clinically evaluated by several physicians and the testes were not considered suspicious for testicular cancer. At urological workup, testes were found to be atrophic and/or indurated in 14 (54%) patients, enlarged in one (4%) and unremarkable in 11 (42%). Ultrasound examination of the testes in 20 patients showed pathological findings in all of them. Histology of the testis was available in 25 of 26 patients and revealed active tumor in three, intratubular germ cell neoplasia in four, scar tissue in 12, sclerosis in three, sclerosis and fibrosis in one, and fibrosis alone in two. CONCLUSIONS: So-called primary extragonadal germ cell tumors in the retroperitoneum are very likely a rare or non-existing entity and should be considered as metastases of a viable or burned-out testicular cancer until proven otherwise. All of our patients with histologically examined testes had pathological finding, 76% of which were either viable tumor or scars.

Adult↗
PubMed2002

Semiconductor and thermoluminescent dosimetry of pulsed soft X ray plasma sources.

A multichannel detection system having a dynamic range of approximately 1 x 10(-9) Gy --20 Gy was developed with the use of commercially produced Si-photodiodes and TLDs for accurate measurement of X ray energy emitted from plasma-focus facility and from laser-produced plasmas. The proof of linearity of the employed detectors accomplished by a comparison of their responses to a broad band spectrum of X rays emitted from plasmas, is reported. It is demonstrated that TLDs irradiated with no protective filter show an incorrect response due to overloading in the sub-keV range and repopulation of dosimetric peaks induced by the UV radiation. The measurement of the power of undesirable secondary X ray sources driven by the primary plasma inside the interaction chamber was performed on the basis of analysis of space dependence of X ray intensity with respect to the assumed r(-2) decrease in the intensity far away from the plasma.

Hot Temperature↗