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Biomedical subjects

R Nadrowitz

Publications and source records attributed to R Nadrowitz.

13 recordsLinked to original sources

Analysis of mouse brain using a clinical 1.5 T scanner and a standard small loop surface coil.

With increasing numbers of in vivo experiments in the field of neuroscience, the interest in methods for in vivo imaging of animal brains as small as those of mice has increased. Because highly specialized small bore scanners with high field strengths are not commonly available, clinical magnetic resonance imaging (cMRI) scanners have been used in the past to image rat and more recently also mouse brains in combination with specifically developed RF coils. These studies have demonstrated that imaging of small animal brains is feasible, and that tumor volumes measured by cMRI correlate well with histological tumor volume analysis. This protocol describes the cMRI settings at 1.5 T for imaging of mouse brain with resolutions up to 120 x 120 microm using an inexpensive, commercially available small loop surface coil. This allows easy establishment of a small animal MRI facility without the need for cost intensive dedicated small animal scanners or special custom made coils. In this study, we demonstrate high-resolution imaging of intracranial xenografts in a mouse glioma model and monitor the treatment effect of external field irradiation by cMRI.

Anesthesia↗

Early immunohistochemical and functional markers indicating radiation damage of the parotid gland.

In order to evaluate the correlation between functional impairment and changes in the expression pattern of immunohistochemical antibodies in the early phase of radiation-induced dysfunction of salivary glands, eight rabbits were scintigraphically examined prior to and 24 h after irradiation with 15 Gy. The parotid glands were studied using HE-staining, Ki-67, alpha-smooth muscle actin (ASMA) and tenascin-C antibodies at every scintigraphic examination. The results demonstrated a significant alteration in the 99mTc-pertechnetate uptake in all irradiated glands. HE-staining showed no relevant impairment of salivary gland tissue in this early phase. Immunohistochemically, we observed a marked re-distribution of ASMA and tenascin-C as well as a reduction of the proliferating rate of acinar cells. This immunohistochemical change correlated with the functional impairment manifested scintigraphically. This study proves the possibility to assess disorders of salivary gland function with immunohistological antibodies as early as 24 h after irradiation and yields the prerequisites to prove the effects of radioprotective agents on salivary gland tissues.

Actins↗

[Overexpression of NPM-ALK induces different types of malignant lymphomas in IL-9 transgenic mice].

Anaplastic large cell lymphoma (ALCL) comprises approximately 25 % of all non-Hodgkin lymphomas in children and young adults. 40% of these tumours have a translocation t(2;5)(p23;q35), which fuses the nucleophosmin gene (NPM) to the anaplastic lymphoma kinase gene (ALK) resulting in a hybrid protein which contributes to the pathogenensis of ALCL. To further analyse the transforming activity in an animal model, a cDNA encoding the protein product, NPM-ALK, was incorporated into a retrovirus construct and introduced into mouse bone marrow progenitors by infection. In a bone marrow gene transfer and transplantation protocol the hematopoietic compartments of lethally irradiated IL-9 transgenic mice were reconstituted with npm-alk infected progenitor cells. IL-9 transgenic mice were chosen, because IL-9, a pleiotropic T helper 2 cytokine, is expressed in most cases of human ALCL and was shown to have an oncogenic potential at least on T cells. Reconstituted mice developed NPM-ALK positive lymphomas including lymphoblastic lymphomas of T-cell type (T-LB), mature and immature plasmacytoma (PZ) and plasmoblastic/anaplastic diffuse large B-cell lymphoma after 10-30 weeks. The combined overexpression of NPM-ALK and IL-9 exerts cooperative oncogenic activity in the transformation of murine lymphoid cells leading to accelerated and enhanced development of T-LB. Many animals developed plasmacytic/plasmoblastic neoplasms, of which the most aggressive tumours share many features with human anaplastic/plasmoblastic diffuse large B-cell lymphoma.

Animals↗

Backscatter dose from metallic materials due to obliquely incident high-energy photon beams.

If metallic material is exposed to ionizing radiation of sufficient high energy, an increase in dose due to backscatter radiation occurs in front of this material. Our purpose in this study was to quantify these doses at variable distances between scattering materials and the detector at axial beam angles between 0 degree (zero angle in beams eye view) and 90 degrees. Copper, silver and lead sheets embedded in a phantom of perspex were exposed to 10 MV-bremsstrahlung. The detector we developed is based on the fluorescence property of pyromellitic acid (1,2,4,5 benzenetetracarboxylic acid) after exposure to ionizing radiation. Our results show that the additional doses and the corresponding dose distribution in front of the scattering materials depend quantitatively and qualitatively on the beam angle. The backscatter dose increases with varying beam angle from 0 degree to 90 degrees up to a maximum at 55 degrees for copper and silver. At angles of 0 degree and 55 degrees the integral backscatter doses over a tissue-equivalent depth of 2 mm are 11.2% and 21.6% for copper and 24% and 28% for silver, respectively. In contrast, in front of lead there are no obvious differences of the measured backscatter doses at angles between 0 degree and 55 degrees. With a further increase of the beam angle from 55 degrees to 90 degrees the backscatter dose decreases steeply for all three materials. In front of copper a markedly lower penetrating depth of the backscattered electrons was found for an angle of 0 degree compared to 55 degrees. This dependence from the beam angle was less pronounced in front of silver and not detectable in front of lead. In conclusion, the dependence of the backscatter dose from the angle between axial beam and scattering material must be considered, as higher scattering doses have to be considered than previously expected. This may have a clinical impact since the surface of metallic implants is usually curved.

Biophysical Phenomena↗

[Dosimetry using pyromellitic acid and trimellitic acid. Part 1].

PURPOSE: The intention of the study was to demonstrate that a chemical dosimeter on the basis of fluorescing acids is able to measure ionizing radiation much more sensitively than the Fricke dosimeter. MATERIALS AND METHODS: As detectors for ionizing radiation pyromellitic acid (1,2,4,5-benzene-tetracarboxylic acid) and trimellitic acid (1,2,4-benzene-tricarboxylic acid) were investigated. Both solutions were exposed to pulsed 10 MV photons. The dose rate and the radiation dose were modified according to the different questions. RESULTS: The correlation between absorbed dose and intensity of fluorescence was studied from 2 Gy up to doses of 16 Gy. Within this dose range the intensity of fluorescence of the mentioned solutions correlate with the absorbed doses in a single-valued and linear way. The fluorescence of pyromellitic acid is independent of the dose rate in the studied range from 0.6 Gy/min to 5 Gy/min. Detectors with trimellitic acid are able to quantify the absorbed energy of ionising radiation independent of the dose rate from 0.6 Gy/min on, but in contrast to pyromellitic acid only up to 3.8 Gy/min. The stability of the excitation and fluorescence spectra, the fading of the irradiated detectors, the reproducibility of the measured results and the increase of the null value of both solutions qualify for the use of these dosimeters in the clinical routine. CONCLUSIONS: If further measurements should prove the independence of the presented detectors from the kind of radiation, the radiation quality and the temperature, there is a new possibility to use the specific advantages of chemical dosimeters in a more simple way.

Benzoates↗

[The properties and potential uses of the trimesic acid dosimeter].

The trimesic acid dosimeter developed by Matthews is extremely sensitive to ionizing radiation. Tests on the characteristics of this detector show two serious differences to the Fricke dosimeter. With trimesic acid (1, 3, 5-benzentricarboacid) absorbed doses can be detected which are 1000 times smaller than with the Fricke solution. The radiochemical turnover here, as opposed to the Fricke dosimeter, is dependent on the dose rate up to 2.2 Gy/min. With high dose rates the trimesic acid dosimeter is well suitable for thin-layer dosimetry. For example in front of metallic scattering bodies (Al, Ti, Cu, Mo, Ag, W, Pb) exposed to cobalt-60-gamma, 9- and 15-MV bremsstrahlung and electron radiation with initial energies of 6.0, 8.0, 10.0 and 19.45 MeV the back scatter radiation can be measured easily.

Cobalt Radioisotopes↗

[Optimal production of murine monoclonal antibodies in ascites of syngeneic mice by a single whole body irradiation].

Hybridoma cells injected intraperitoneally into mice induce formation of ascites tumors producing ascites fluid with high levels of monoclonal antibodies. Several parameters affect the growth of the immunoglobulin-producing tumors in vivo. In the present study the average ascites tumor formation rate of 10 different hybridomas could be increased from 32% (n = 338 mice) to 77% (n = 112 mice) by only one whole body irradiation of paraffin-pretreated-Balb/c mice. Production of monoclonal antibodies was better in males because significantly (p less than 0.01) increased volume of ascites fluid. From the increased tumor formation rate in irradiated mice it is suggested that in non-irradiated recipients the tumor growth rate was lowered by immunological reactions against hybridoma cells provoked by cell surface neoantigens revealed by cell fusion and/or tumor-associated antigens of the myeloma parent cells as well as by altered antigen pattern caused by possible mutations in the myeloma cell line and/or Balb/c/K strain.

Animals↗

Decrease of glucose-induced insulin secretion of pancreatic rat islets after irradiation in vitro.

Irradiation of pancreatic rat islets up to a dose of 2.5 Gy did neither alter glucose-nor IBMX-induced insulin secretion studied in vitro. The insulin as well as glucagon content of irradiated islets were similar as in the control tissue. This was also true in islets irradiated with 25 Gy which were characterized by a decreased insulin secretion in the presence of glucose and IBMX, respectively. Since we did not find indications of an enhanced hormone output in the radiation medium, we want to suggest that higher irradiation doses affect insulin release of pancreatic islets in vitro. This observation has to be taken into account for application of radioimmunosuppression for transplantation.

Animals↗

The effect of irradiation on the development of low-dose streptozotocin diabetes in mice.

The effect of single-dose whole-body irradiation (6.0 Gy) on the development of low-dose streptozotocin diabetes in male C57 Bl/KsJ-mice was investigated. When irradiation precedes the SZ application the development of hyperglycemia could be prevented. Irradiation after SZ injections at the time of appearance hyperglycemia did not interfere with the onset of diabetes. The results underline the participation of radiosensitive immune cells as an etiologic factor of low-dose SZ diabetes.

Animals↗

Re-distribution of tenascin-C in the parotid acinar cells. An early marker of radiation-induced damage of salivary glands?

PURPOSE: In order to investigate the early changes in the expression of tenascin-C, following irradiation and the associated functional impairment of salivary glands. MATERIALS AND METHODS: Fifteen rabbits were used for the study. Five provided control parotid gland tissue and a further 10 rabbits were scintigraphically examined prior to and 24 h after 15/30 Gy. Glands were studied histologically using HE-staining and tenascin-C antibodies. RESULTS: Reduction in the salivary ejection fraction (SEF) was observed in all irradiated glands. Simultaneously, a marked re-distribution of tenascin-C expression was noticed. Reactivity detected in the intercalated, secretory ducts and perineurinal regions prior to radiation was noticed intracellularly after 24 h. Furthermore, nerves showed tenascin-C expression in the Schwann cells, but no longer perineurinally. Myofibroblasts were also observed in the stroma. CONCLUSION: This study proves the ability to predict functional disorders of salivary function as early as 24 h after radiation and provides evidence of the participation of tenascin-C in the pathological process of radiation-induced damage in salivary glands.

Animals↗