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Sample records for body irradiated baboons

  1. Revisiting Biomarkers of Total-Body and Partial-Body Exposure in a Baboon Model of Irradiation.

    Science.gov (United States)

    Valente, Marco; Denis, Josiane; Grenier, Nancy; Arvers, Philippe; Foucher, Barbara; Desangles, François; Martigne, Patrick; Chaussard, Hervé; Drouet, Michel; Abend, Michael; Hérodin, Francis

    2015-01-01

    In case of a mass casualty radiation event, there is a need to distinguish total-body irradiation (TBI) and partial-body irradiation (PBI) to concentrate overwhelmed medical resources to the individuals that would develop an acute radiation syndrome (ARS) and need hematologic support (i.e., mostly TBI victims). To improve the identification and medical care of TBI versus PBI individuals, reliable biomarkers of exposure could be very useful. To investigate this issue, pairs of baboons (n = 18) were exposed to different situations of TBI and PBI corresponding to an equivalent of either 5 Gy 60Co gamma irradiation (5 Gy TBI; 7.5 Gy left hemibody/2.5 right hemibody TBI; 5.55 Gy 90% PBI; 6.25 Gy 80% PBI; 10 Gy 50% PBI, 15 Gy 30% PBI) or 2.5 Gy (2.5 Gy TBI; 5 Gy 50% PBI). More than fifty parameters were evaluated before and after irradiation at several time points up to 200 days. A partial least square discriminant analysis showed a good distinction of TBI from PBI situations that were equivalent to 5 Gy. Furthermore, all the animals were pooled in two groups, TBI (n = 6) and PBI (n = 12), for comparison using a logistic regression and a non parametric statistical test. Nine plasmatic biochemical markers and most of hematological parameters turned out to discriminate between TBI and PBI animals during the prodromal phase and the manifest illness phase. The most significant biomarkers were aspartate aminotransferase, creatine kinase, lactico dehydrogenase, urea, Flt3-ligand, iron, C-reactive protein, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the early period, and Flt3-ligand, iron, platelet count, hemoglobin, monocyte count, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the ARS phase. These results suggest that heterogeneity could be distinguished within a range of 2.5 to 5 Gy TBI.

  2. Revisiting Biomarkers of Total-Body and Partial-Body Exposure in a Baboon Model of Irradiation.

    Directory of Open Access Journals (Sweden)

    Marco Valente

    Full Text Available In case of a mass casualty radiation event, there is a need to distinguish total-body irradiation (TBI and partial-body irradiation (PBI to concentrate overwhelmed medical resources to the individuals that would develop an acute radiation syndrome (ARS and need hematologic support (i.e., mostly TBI victims. To improve the identification and medical care of TBI versus PBI individuals, reliable biomarkers of exposure could be very useful. To investigate this issue, pairs of baboons (n = 18 were exposed to different situations of TBI and PBI corresponding to an equivalent of either 5 Gy 60Co gamma irradiation (5 Gy TBI; 7.5 Gy left hemibody/2.5 right hemibody TBI; 5.55 Gy 90% PBI; 6.25 Gy 80% PBI; 10 Gy 50% PBI, 15 Gy 30% PBI or 2.5 Gy (2.5 Gy TBI; 5 Gy 50% PBI. More than fifty parameters were evaluated before and after irradiation at several time points up to 200 days. A partial least square discriminant analysis showed a good distinction of TBI from PBI situations that were equivalent to 5 Gy. Furthermore, all the animals were pooled in two groups, TBI (n = 6 and PBI (n = 12, for comparison using a logistic regression and a non parametric statistical test. Nine plasmatic biochemical markers and most of hematological parameters turned out to discriminate between TBI and PBI animals during the prodromal phase and the manifest illness phase. The most significant biomarkers were aspartate aminotransferase, creatine kinase, lactico dehydrogenase, urea, Flt3-ligand, iron, C-reactive protein, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the early period, and Flt3-ligand, iron, platelet count, hemoglobin, monocyte count, absolute neutrophil count and neutrophil-to-lymphocyte ratio for the ARS phase. These results suggest that heterogeneity could be distinguished within a range of 2.5 to 5 Gy TBI.

  3. Schistosoma mansoni: parasitology and immunology of baboons vaccinated with irradiated cryopreserved schistosomula

    International Nuclear Information System (INIS)

    Young baboons (Papio cynocephalus) were vaccinated with γ-irradiated (500 Gy) cryopreserved Puerto Rican strain schistosomula of S. mansoni. Protection against heterologous, normal Kenyan Strain S. mansoni challenge infection was erratic and partial; and two putative correlates of immunity, reduced worm fecundity and change in worm location (anterior shift) were not observed. However, immunization of baboons with this vaccine resulted in a stimulated immune system. Both cellular and humoral anamnesis were demonstrable in vaccinated-challenged baboons. Schistosome infection-associated IgM hypergammaglobulinemia was also greatly reduced in vaccinated-challenged baboons. However IgG antibodies to adult, egg, and cercarial antigens were increased after challenge infection in preimmunized baboons. Vaccination appears to have resulted in a redirection of the immune system into anti-parasite channels, but this more specific immune response was insufficient to confer good protection against challenge infection in this experiment. The dampening effect of the vaccine on the hypergammaglobulinemia of schistosomiasis is another candidate for a possible ''anti-pathogenesis'' effect of irradiated schistosome larval vaccines. (author)

  4. Schistosoma mansoni: parasitology and immunology of baboons vaccinated with irradiated cryopreserved schistosomula

    Energy Technology Data Exchange (ETDEWEB)

    Damian, R.T.; Powell, M.R.; Roberts, M.L. (Georgia Univ., Athens (USA). Dept. of Zoology); Clark, J.D. (Georgia Univ., Athens (USA). Lab. Animal Medicine); Stirewalt, M.A.; Lewis, F.A. (Biomedical Research Inst., Rockville, MD (USA))

    1985-06-01

    Young baboons (Papio cynocephalus) were vaccinated with ..gamma..-irradiated (500 Gy) cryopreserved Puerto Rican strain schistosomula of S. mansoni. Protection against heterologous, normal Kenyan Strain S. mansoni challenge infection was erratic and partial; and two putative correlates of immunity, reduced worm fecundity and change in worm location (anterior shift) were not observed. However, immunization of baboons with this vaccine resulted in a stimulated immune system. Both cellular and humoral anamnesis were demonstrable in vaccinated-challenged baboons. Schistosome infection-associated IgM hypergammaglobulinemia was also greatly reduced in vaccinated-challenged baboons. However IgG antibodies to adult, egg, and cercarial antigens were increased after challenge infection in preimmunized baboons. Vaccination appears to have resulted in a redirection of the immune system into anti-parasite channels, but this more specific immune response was insufficient to confer good protection against challenge infection in this experiment. The dampening effect of the vaccine on the hypergammaglobulinemia of schistosomiasis is another candidate for a possible ''anti-pathogenesis'' effect of irradiated schistosome larval vaccines.

  5. Segmental pancreatic allograft survival in baboons treated with combined irradiation and cyclosporine: a preliminary report

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    du Toit, D.F.; Heydenrych, J.J.; Smit, B.; Louw, G.; Zuurmond, T.; Laker, L.; Els, D.; Weideman, A.; Wolfe-Coote, S.; van der Merwe, E.A.

    1985-04-01

    The present study was undertaken to evaluate the effectiveness of cyclosporine (CS) alone, total lymphoid irradiation (TLI) alone, and CS in combination with total body irradiation (TBI) in suppressing segmental pancreatic allograft rejection in totally pancreatectomized outbred chacma baboons. The administration of CS 25 mg/kg/day and 50 mg/ kg/day resulted in mean graft survival of 21.5 days and 24.5 days, respectively. CS 85 mg/kg/day resulted in median graft survival of 9 days. There was a wide daily fluctuation of CS serum trough levels exhibited between primates receiving the same oral dose. TBI in excess of 300 rads resulted in irreversible bone marrow suppression. Modest results were achieved in recipients of TBI-76 rads (38 x 2 rads), with median graft survival of 21 days, results not different from recipients treated with CS. TLI recipients of 600 rads (150 x 4 rads) resulted in median pancreatic graft survival of 16 days. TBI together with oral CS administration exhibited no synergistic or additive effect and a single peroperative donor-specific blood transfusion did not enhance pancreatic allograft survival in this model. However, of 10 primates receiving TBI 100 rads (50 x 2 rads) and CS 25 mg/kg/day administered orally indefinitely, four remained normoglycemic for more than 60 days. TBI 100 rads (50 x 2 rads) together with oral and parenteral CS resulted in necrotizing enterocolitis in four of six recipients.

  6. Body composition and cardiometabolic disease risk factors in captive baboons (Papio hamadryas sp.): sexual dimorphism.

    Science.gov (United States)

    Higgins, Paul B; Rodriguez, Perla J; Voruganti, V Saroja; Mattern, Vicki; Bastarrachea, Raul A; Rice, Karen; Raabe, Timothy; Comuzzie, Anthony G

    2014-01-01

    Baboons (Papio hamadryas sp.) exhibit significant sexual dimorphism in body size. Sexual dimorphism is also exhibited in a number of circulating factors associated with risk of cardiometabolic disease. We investigated whether sexual dimorphism in body size and composition underlie these differences. We examined data from 28 male and 24 female outdoor group-housed young adult baboons enrolled in a longitudinal observational study of cardiometabolic disease risk factors. Animals were sedated with ketamine HCl (10 mg/kg) before undergoing venous blood draws, basic body measurements, and dual-energy X-ray absorptiometry body composition scans. Percentage glycated hemoglobin A1c (%HbA1c ) was measured in whole blood. Serum samples were analyzed for glucose, insulin, C-peptide, high-density lipoprotein, and triglyceride concentrations. Males were heavier and had greater body length and lean tissue mass than females. Females had a greater body fat percentage relative to males (10.8 ± 6.4 vs. 6.9 ± 4.0, P = 0.01). Although C-peptide, fasting glucose, and %HbA1c did not differ between the sexes, females had greater fasting insulin and triglyceride compared to their male counterparts. Insulin and percentage body fat were significantly correlated in males (r = 0.61, P = 0.001) and to a lesser extent in females (r = 0.43, P = 0.04). Overall, relations between adiposity and fasting insulin and fasting triglyceride were stronger in males. After accounting for differences in percentage body fat, fasting insulin and triglyceride were no longer statistically different between males and females. Despite stronger correlations between relative adiposity and insulin and triglyceride in males, the higher fasting insulin and triglyceride of female baboons may be underlain by their greater relative body fat masses.

  7. Whole body [{sup 11}C]-dihydrotetrabenazine imaging of baboons: biodistribution and human radiation dosimetry estimates

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    Murthy, Rajan [Columbia University College of Physicians and Surgeons, Department of Psychiatry, New York, NY (United States); New York State Psychiatric Institute, Department of Neuroscience, Division of Brain Imaging, New York, NY (United States); Harris, Paul; Leibel, Rudolph [Columbia University College of Physicians and Surgeons, Department of Medicine, New York, NY (United States); Simpson, Norman; Parsey, Ramin [Columbia University College of Physicians and Surgeons, Department of Psychiatry, New York, NY (United States); Van Heertum, Ronald [Columbia University College of Physicians and Surgeons, Department of Radiology, New York, NY (United States); New York State Psychiatric Institute, Department of Neuroscience, Division of Brain Imaging, New York, NY (United States); Mann, J.J. [Columbia University College of Physicians and Surgeons, Department of Psychiatry, New York, NY (United States); Columbia University College of Physicians and Surgeons, Department of Radiology, New York, NY (United States); New York State Psychiatric Institute, Department of Neuroscience, Division of Brain Imaging, New York, NY (United States)

    2008-04-15

    Vesicular monoamine transporter type 2 abundance quantified using the radiotracer [{sup 11}C]-dihydrotetrabenazine (DTBZ) has been used to study diagnosis and pathogenesis of dementia and psychiatric disorders in humans. In addition, it may be a surrogate marker for insulin-producing pancreatic beta cell mass, useful for longitudinal measurements using positron emission tomography to track progression of autoimmune diabetes. To support the feasibility of long-term repeated administrations, we estimate the biodistribution and dosimetry of [{sup 11}C]-DTBZ in humans. Five baboon studies were acquired using a Siemens ECAT camera. After transmission scanning, 165-210 MBq of [{sup 11}C]-DTBZ were injected, and dynamic whole body emission scans were conducted. Time-activity data were used to obtain residence times and estimate absorbed radiation dose according to the MIRD model. Most of the injected tracer localized to the liver and the lungs, followed by the intestines, brain, and kidneys. The highest estimated absorbed radiation dose was in the stomach wall. The largest radiation dose from [{sup 11}C]-DTBZ is to the stomach wall. This dose estimate, as well as the radiation dose to other radiosensitive organs, must be considered in evaluating the risks of multiple administrations. (orig.)

  8. Whole body [11C]-dihydrotetrabenazine imaging of baboons: biodistribution and human radiation dosimetry estimates

    International Nuclear Information System (INIS)

    Vesicular monoamine transporter type 2 abundance quantified using the radiotracer [11C]-dihydrotetrabenazine (DTBZ) has been used to study diagnosis and pathogenesis of dementia and psychiatric disorders in humans. In addition, it may be a surrogate marker for insulin-producing pancreatic beta cell mass, useful for longitudinal measurements using positron emission tomography to track progression of autoimmune diabetes. To support the feasibility of long-term repeated administrations, we estimate the biodistribution and dosimetry of [11C]-DTBZ in humans. Five baboon studies were acquired using a Siemens ECAT camera. After transmission scanning, 165-210 MBq of [11C]-DTBZ were injected, and dynamic whole body emission scans were conducted. Time-activity data were used to obtain residence times and estimate absorbed radiation dose according to the MIRD model. Most of the injected tracer localized to the liver and the lungs, followed by the intestines, brain, and kidneys. The highest estimated absorbed radiation dose was in the stomach wall. The largest radiation dose from [11C]-DTBZ is to the stomach wall. This dose estimate, as well as the radiation dose to other radiosensitive organs, must be considered in evaluating the risks of multiple administrations. (orig.)

  9. Dosimetry of total body irradiation

    International Nuclear Information System (INIS)

    In the treatment of disseminated malignancies an improvement in the curability and reduction of complication rates require high precision total body irradiation (TBI) and correct reporting of relevant treatment parameters. Optimal TBI dosimetry is the basis. Radiooncological and radiobiological requirements as well as the special physical situation have to be considered. To review the efforts of medical physicists, highlights from TBI workshops and publications are summarized. Additionally, dosimetric data from 34 European radiooncological centres contributing to the recent ESTRO inquiry on TBI are analysed. The topics are: absorbed dose and dose monitor calibration, determination of absolute and relative doses, dose ratios, attenuation data and heterogeneity corrections; TBI dose calculation methods regarding patient position, beam incidence, body shape and thickness, lung size and density; methods of TBI treatment planning including calculated dose modification and of TBI quality assurance. In conclusion, the following recommendations can be given: TBI dosimetry shall be performed under TBI conditions, close to the real treatment situation. The absorbed dose to water must be determined. The dose monitor should be calibrated against dose measurements at the centre of a water equivalent phantom of TBI equivalent size and typical thickness. Photon fluence profiles have to be measured with small phantoms. Influences on the local dose must be investigated systematically. A reproducible AP/PA TBI technique should be used. The TBI dose shall be specified to mid-abdomen and reported in units of gray. The single and total dose and the dose rate to the lungs, the number of fractions and the treatment time schedule must be stated. In vivo dosimetry is required if non-reliable TBI techniques are used. An international TBI dosimetry intercomparison could assist these efforts to improve the treatment of acute leukaemia. (author). 89 refs, 3 figs, 13 tabs

  10. Investigation of the retention and distribution of americium-241 in the baboon and the enhanced removal of americium-241 from the body by diethylenetriaminepentaacetic acid (DTPA)

    International Nuclear Information System (INIS)

    Experiments were performed to study the metabolism and distribution of intravenously administered 241Am in the adult and juvenile baboon; in addition, decorporation therapy using Na3-CaDTPA was performed on selected baboons to assess the efficacy of this drug in removing systemic burdens of 241Am from this primate species. Determination of the kinetics of 241Am was accomplished principally by in vivo methodologies and by radiochemical analysis of 241Am activity of biological material. The use of Na3-CaDTPA as a therapeutic agent for the removal of 241Am from the body proved to be an effective form of treatment in the case of early administration. (U.S.)

  11. Implantation of total body irradiation in radiotherapy

    International Nuclear Information System (INIS)

    Before implementing a treatment technique, the characteristics of the beam under irradiation conditions must be well acknowledged and studied. Each one of the parameters used to calculate the dose has to be measured and validated before its utilization in clinical practice. This is particularly necessary when dealing with special techniques. In this work, all necessary parameters and measurements are described for the total body irradiation implementation in facilities designed for conventional treatments that make use of unconventional geometries to generate desired enlarged field sizes. Furthermore, this work presents commissioning data of this modality at Hospital das Clinicas of Sao Paulo using comparison of three detectors types for measurements of entrance dose during total body irradiation treatment. (author)

  12. Tissue air ratio in total body irradiation

    International Nuclear Information System (INIS)

    On the basis of dose readings in 102 patients treated with total body irradiation (TBI), a 'tissue air ratio (TAR) curve' has been produced. It could be useful to precalculate treatment time in TBI, for dose prescription to a specific point, provided the same source (60Co) and treatment setting (lateral irradiation; 3 m source-axis distance; reference point at thighs bifurcation, neat the perineum) is used. The TAR curve produced, and the formula relating tissue depth to TAR value, are presented, and compared to preexisting data for 'magna fields' treatments. This curve is exponential, and in semilog representation becomes straight, as every classic TAR curve; it is lower than others, reflecting non full-scatter situation in patient irradiation. (orig.)

  13. Pitch (F0) and formant profiles of human vowels and vowel-like baboon grunts: The role of vocalizer body size and voice-acoustic allometry

    Science.gov (United States)

    Rendall, Drew; Kollias, Sophie; Ney, Christina; Lloyd, Peter

    2005-02-01

    Key voice features-fundamental frequency (F0) and formant frequencies-can vary extensively between individuals. Much of the variation can be traced to differences in the size of the larynx and vocal-tract cavities, but whether these differences in turn simply reflect differences in speaker body size (i.e., neutral vocal allometry) remains unclear. Quantitative analyses were therefore undertaken to test the relationship between speaker body size and voice F0 and formant frequencies for human vowels. To test the taxonomic generality of the relationships, the same analyses were conducted on the vowel-like grunts of baboons, whose phylogenetic proximity to humans and similar vocal production biology and voice acoustic patterns recommend them for such comparative research. For adults of both species, males were larger than females and had lower mean voice F0 and formant frequencies. However, beyond this, F0 variation did not track body-size variation between the sexes in either species, nor within sexes in humans. In humans, formant variation correlated significantly with speaker height but only in males and not in females. Implications for general vocal allometry are discussed as are implications for speech origins theories, and challenges to them, related to laryngeal position and vocal tract length. .

  14. Total body irradiation with a sweeping beam

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    Pla, M.; Chenery, S.G.; Podgorsak, E.B.

    1983-01-01

    A technique for total body irradiation, in which the patient lies in the prone or supine position in the beam of a conventional column mounted 4 MV linear accelerator, is described. A sufficiently large radiation field is obtained by rotating the beam in a vertical plane about the source (i.e., sweeping beam) at a source-to-skin distance of 190 cm on the vertical axis. The variation of the midplane dose is less than +lt. slash-5% in parallel-opposed beams, when attenuators are placed over the region containing the lungs and bolus is employed around the head and legs. The percentage depth dose for the sweeping beam is identical to that of a stationary beam for the same collimator setting and source-to-skin distance. A method for monitoring the dose to the patient by means of a thimble ionization chamber located on the vertical beam axis is outlined. The average dose rates used are between 5 and 10 cGy/min. The design and placement of lung attenuators is simple. The treatment technique with the sweeping beam requires minimal modification of a treatment unit and can be applied on any unit which has a head swivel option.

  15. Total body irradiation in bone marrow transplantation

    International Nuclear Information System (INIS)

    Total body irradiation was used in 22 patients as part of their conditioning regimen for bone marrow transplantation. Nine patients with acute leukemia received 1000 cGy TBI in addition with chemotherapy. None of them survived and the main cause of death was interstitial pneumonitis (50%). 4 patients received 1000 cGy with a lung shielding of 500 cGy. Two patients with acute leukemia died of leukemia and sepsis, two patients had aplastic anemia, one is surviving, the other died of severe GVHD and infectious complications. Nine patients with severe aplastic anemia strongly immunized by previous blood transfusions received 800 cGy TBI with a lung shielding of 400 cGy. No rejection was observed and 7 patients (63%) are currently alive. One patient died of interstitial pneumonitis probably related to CMV infection, one of subacute necrotizing hepatitis, two of severe acute GVHD. It is concluded from this study that TBI remains the best immunosuppressive conditioning regimen even in strongly immunized patients. It may be a contributing factor of the incidence and severity of interstitial pneumonitis. A reduction of the dose of the lung to 400-500 cGy seems to decrease the severity of this complication

  16. Total body irradiation: current indications; L`irradiation corporelle totale: les indications actuelles

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    Giraud, P.; Danhier, S.; Dubray, B.; Cosset, J.M. [Institut Curie, 75 - Paris (France)

    1998-05-01

    The choice of dose and fractionation for total body irradiation is made difficult by the large number of considerations to be taken into account. The outcome of bone marrow transplantation after total body irradiation can be understood in terms of tumor cell killing, engraftment, and normal tissue damage, each of these endpoints being influenced by irradiation-, disease-, transplant-, and patient- related factors. Interpretation of clinical data is further hampered by the overwhelming influence of logistic constraints, the small numbers of randomized studies, and the concomitant variations in total dose and fraction size or dose rate. So far, three cautious conclusions can be drawn in order to tentatively adapt the total body irradiation schedule to clinically-relevant situations. Firstly, the organs at risk for normal tissue damage (lung, liver, lens, kidney) are protected by delivering small doses per fraction at low dose rate. This suggests that, when toxicity is at stake (e.g. in children), fractionated irradiation should be preferred, provided that inter-fraction intervals are long enough. Secondly, fractionated irradiation should be avoided in case of T-cell depleted transplant, given the high risk of graft rejection in this setting. An alternative would be to increase total (or fractional) dose of fractionated total body irradiation, but this approach is likely to induce more normal tissue toxicity. Thirdly, clinical data have shown higher relapse rates in chronic myeloid leukemia after fractionated or low dose rate total body irradiation, suggesting that fractionated irradiation should not be recommended, unless total (or fractional) dose is increased. Total body irradiation-containing regimens, primarily cyclophosphamide / total body irradiation, are either equivalent to or better than the chemotherapy-only regimens, primarily busulfan / cyclophosphamide. Busulfan / cyclophosphamide certainly represents a reasonable alternative, especially in patients who

  17. Total body irradiation for bone marrow transplantation

    International Nuclear Information System (INIS)

    Purpose/Objective: The primary goal of this course is to develop an understanding of the rationale for the use of total body irradiation (TBI) as a component of cytoreduction for bone marrow transplantation, the techniques used, and the results of changing important parameters, such as dose, dose rate, and fractionation. Materials and Methods: Basic radiobiological principles relevant to TBI are reviewed; in particular, emphasis is placed on cell and animal studies which suggest means of optimizing TBI delivery to achieve maximum tumor cell kill and immunosuppression along with minimal normal tissue damage. Techniques utilized at various centers are described, with some discussion of achieving homogeneity, as well as inhomogeneity when desired with partial shielding or 'boosting'. A review of clinical studies, both randomized and non-randomized, is done; these are then interpreted in terms of potential optimization of the TBI parameters. Finally, comparison of TBI-containing regimens with chemotherapy-only regimens is done. Results: Radiobiological studies suggest a potential advantage for fractionated TBI over single dose TBI. Clinical studies support this view: highly fractionated regimens have allowed higher total doses to be used to increase malignant cell kill and immunosuppression without increasing toxicity. Randomized studies of TBI combined with VP-16 or cyclophosphamide versus busulfan combined with cyclophosphamide have either shown an advantage with TBI (in acute myelocytic leukemia in first remission) or no difference (in chronic myelogenous leukemia, chronic phase). Conclusion: TBI has been an effective component of cytoreductive regimens for marrow transplantation in patients with malignant disease, especially leukemias, which constitute 73% of all marrow transplants worldwide. Evidence supports fractionated TBI, to doses ≥ 13 Gy, when compared with single dose TBI. Randomized studies support the continued use of TBI in AML, and suggest that

  18. Comparative studies in the cellular immunostimulation by whole body irradiation

    International Nuclear Information System (INIS)

    The effect of the cellular immune response by total body irradiation was investigated. The transplant survival (skin grafts) was determined as immune parameter. Donors were colony bred Wistar rats and recipients were colony bred Sprague Dawley rats. The investigations were carried out with irradiated rats and with rats irradiated after thymectomy and/or adrenalectomy as well as with animals without irradiation. A single total-body irradiation (1 and 2 Gy) was administered. The skin graft survival in irradiated rats was significant shorter (radiogenic immunostimulation) than in unirradiated rats; there were no significant differences between the operated (thymectomy and/or adrenalectomy) and not operated animals. Including precedent examinations this radiogenic immunostimulation is caused by relativly selective inactivation of T-suppressor cells. (orig.)

  19. Development of a new method of whole body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kishi, Kazushi (Wakayama Medical Coll. (Japan))

    1989-08-01

    A new method of whole body irradiation was developed using a linear accelerator linked to microprocessor. By this modified arc technique, a total body photon irradiation and a total skin electron irradiation were practical for narrow room. Approximative calculations were deviced for dose distribution. Dosimetric results were consistent with those previosly calculated. Local doses in lungs, neck and other areas were easily adjustable with arrangements of pre-set dose rate. In total skin electron irradation, six predeterminated postures and 'make up' irradiation were necessary to dose homogeneity over 'shady area' such as axillae. Clinically, a large arteriovenous malformation in an arm decreased with normalization of plethysmogram after treatment, and remarkable reductions of mycosis fungoides tumor were observed. This new method of total skin electron irradiation and total body photon therapy will clinically expand with the progress of bone marrow transplantation. (author).

  20. Acute and delayed toxicities of total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Deeg, H.J.

    1983-12-01

    Total body irradiation is being used with increasing frequency for the treatment of lymphopoietic malignancies and in preparation for marrow transplantation. Acute toxicities include reversible gastroeneritis, mucositis, myelosuppression alopecia. As the success of treatment improves and more patients become long-term survivors, manifestations of delayed and chronic toxicity become evident. These include impairment of growth and development, gonadal failure and sterility, cataract formation and possibly secondary malignancies. The contribution of total body irradiation to the development of pneumonitis and pulmonary fibrosis is still poorly understood. Some of these changes are reversible or correctable, whereas others are permanent. Nevertheless, until equally effective but less toxic regimens become available, total body irradiation appears to be the treatment of choice to prepare patients with leukemia for marrow transplantation.

  1. Total body irradiation and allogeneic bone-marrow transplantation

    International Nuclear Information System (INIS)

    The aim of the present study is to present the first case in the Bulgarian oncological practice of total-body irradiation (TBI) followed by allogeneic transplantation of hemopoietic peripheral steam cells from a haploidentical family donor to a patient with acute lymphoblastic leukemia. The patient was a 10-year old boy with a verified non-Hodgkin lymphoma - IV clinical stage (leukemia-lymphoma syndrome) with initial mediastinal and bone-marrow engagement. After the disease recurrence the patient was hospitalized in the Transplantation Department of the Specialized Pediatric Hospital for Active Treatment of Oncological Diseases for realizing allogeneic transplantation. The application of the conditioning regime includes Melphalan, Fludarabine, ATG and TBI with 5x2 Gy. The patient was discharged on the 30th day in a good general condition with compensated haematological parameters and stable function of the transplant, and with instructions for the control check-ups and examinations each 14 days till the day + 100. The TBI method applied by the team was simple for realization and did not require special equipment. The patient received irradiation by a vertical radiation beam in a small procedure room in a comfortable spinal and prone position, which allowed the realization of sufficiently homogeneous dose in the body and effective lung protection. The irradiation time was acceptable, compared with the time for the application of horizontal radiation beams at large distances. (authors)

  2. Total Body Irradiation with Step Translation and Dynamic Field Matching

    Directory of Open Access Journals (Sweden)

    Ho-Hsing Chen

    2013-01-01

    Full Text Available The purpose of this study is to develop a total body irradiation technique that does not require additional devices or sophisticated processes to overcome the space limitation of a small treatment room. The technique aims to deliver a uniform dose to the entire body while keeping the lung dose within the tolerance level. The technique treats the patient lying on the floor anteriorly and posteriorly. For each AP/PA treatment, two complementary fields with dynamic field edges are matched over an overlapped region defined by the marks on the body surface. A compensator, a spoiler, and lung shielding blocks were used during the treatment. Moreover, electron beams were used to further boost the chest wall around the lungs. The technique was validated in a RANDO phantom using GAFCHROMIC films. Dose ratios at different body sites along the midline ranged from 0.945 to 1.076. The dose variation in the AP direction ranged from 96.0% to 104.6%. The dose distribution in the overlapped region ranged from 98.5% to 102.8%. Lateral dose profiles at abdomen and head revealed 109.8% and 111.7% high doses, respectively, at the body edges. The results confirmed that the technique is capable of delivering a uniform dose distribution to the midline of the body in a small treatment room while keeping the lung dose within the tolerance level.

  3. Total body irradiation in hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Fundagul Andic

    2014-06-01

    Full Text Available Total body irradiation is used in conjunction with chemotherapy as a conditioning regimen in the treatment of many disease such as leukemia, myelodysplastic syndrome, aplastic anemia, multiple myeloma and lymphoma prior to the hematopoetic stem cell transplantation. The main purposes of the hematopoetic stem cell transplantation are eradication of the recipient bone marrow and any residual cancer cells, creation of space in the receipient bone marrow for donor hematopoetic stem cells, and immunosuppression to prevent rejection of donor stem cells in the case of an allotransplant. [Archives Medical Review Journal 2014; 23(3.000: 398-410

  4. Computer-based anthropometrical system for total body irradiation.

    Science.gov (United States)

    Sánchez-Nieto, B; Sánchez-Doblado, F; Terrón, J A; Arráns, R; Errazquin, L

    1997-05-01

    For total body irradiation (TBI) dose calculation requirements, anatomical information about the whole body is needed. Despite the fact that video image grabbing techniques are used by some treatment planning systems for standard radiotherapy, there are no such systems designed to generate anatomical parameters for TBI planning. The paper describes an anthropometrical computerised system based on video image grabbing which was purpose-built to provide anatomical data for a PC-based TBI planning system. Using software, the system controls the acquisition and digitalisation of the images (external images of the patient in treatment position) and the measurement procedure itself (on the external images or the digital CT information). An ASCII file, readable by the TBI planning system, is generated to store the required parameters of the dose calculation points, i.e. depth, backscatter tissue thickness, thickness of inhomogeneity, off-axis distance (OAD) and source to skin distance (SSD). PMID:9246868

  5. Response of adrenal gland to whole body 60Co irradiation

    International Nuclear Information System (INIS)

    Whole body of the adult albino rates was exposed to 60Co radiation in a single dose of 600 R. Following irradiation the adrenal serotonin level was found higher till the end of 8th week except a fall on 14th day, whereas the blood 5HT level remained lower than the normal except a slight rise at the end of 1st week and dropped down at 14 days followed by a further rise. The blood catecholamine level was found increased at the end of 14th day followed by a fall at 4th and 8th weeks, but the levels were moving round the normal value. The histological studies of adrenal gland showed degranulation and hypertrophy of adrenal cortex and medullary cells at various intervals of post-irradiation. On the whole it is observed that maximum changes in the level of biogenic amines take place within 14 days after irradiation, and maximum rate of mortality also coincide with this period. Thus bringing out the fact that adrenal bioamines play an important role in the vital activities of the animals. (author)

  6. Whole body irradiation by high energy electron for mycosis fungoides

    Energy Technology Data Exchange (ETDEWEB)

    Koga, Kenji; Nishikawa, Kiyoshi; Wakuta, Yuhji; Asada, Keiko; Murai, Nobuko; Watanabe, Katsushi; Takada, Takuo

    1985-02-01

    Five patients with mycosis fungoides were treated with whole body irradiation by high energy electron. They were irradiated by a linear accelerator (ML-15MIII, Mitsubishi Company) with the electron of 8 MeV, using the acrylics decelerator at the window to reduce the electron energy. Source skin distance was 150 cm and three beams with a separation of 60 cm were used. The dose distribution at the skin surface was within homogeneity of +-7.5%. The 2 patients have been alive without evidence of disease for 2 years, and 1 year and half after the treatment, respectively. Three patients were dead; two of the dead were associated with pancytopenia, one irradiated 6 times for 2 years and 4 months and the other 3 times for 2 years. The remaining one patient developed the brain metastasis without skin lesions 6 months later. Our results suggest that mycosis fungoides is curable in infiltrative stage, but not in tumorous stage. Some discussion on the problem of this treatment technique and haematological changes caused by the contaminated X-ray as well as high energy electron were made, reviewing the pertinent literatures on the device to reduce the contaminated X-ray. (author).

  7. Total body irradiation in France in the past twenty years

    International Nuclear Information System (INIS)

    A review of the activity and techniques of total body irradiation (TBI) in France in the last 20 years is presented. In order to have on overall view of the activity and techniques of total body irradiation in France, the group of cancer centre radiation oncologists sent a questionnaire to all the cancer centres or public hospitals radiotherapy departments dealing with this treatment. Thirty-six questionnaires were sent and thirty-one departments answered. Three departments do not offer this treatment. Five departments did not answer. Results, therefore, concern the activity of the 28 departments that agreed to give detailed and clear answers. A total of 10 630 TBIs have been documented, 850 to 900 TBI have been done each year since 1995. Single fraction TBIs are used in only five centres and are being progressively abandoned. For Multiple-fraction TBIs, the techniques described here are the ones used in 1999, at the time the questionnaires were sent. A majority (98%) of the teams used linear accelerators. The collected data are synthesised in tables. Nowadays, single fraction TBIs are only indicated in exceptional cases, Most of the TBIs are fractionated in six twice-daily fractions with pulmonary shielding to limit the dose between 6 and 11 Gy depending on departments' protocols and pathologies. (author)

  8. Biological basis of total body irradiation; Bases biologiques de l`irradiation corporelle totale

    Energy Technology Data Exchange (ETDEWEB)

    Dubray, B.; Helfre, S.; Dendale, R.; Cosset, J.M. [Institut Curie, 75 - Paris (France). Dept. d`Oncologie-Radiotherapie; Giraud, P. [Hopital Tenon, 75 - Paris (France). Service de Radiotherapie

    1999-03-01

    A comprehensive understanding of the radiobiological bases of total body irradiation (TBI) is made difficult by the large number of normal and malignant tissues that must be taken into account. In addition, tissue responses to irradiation are also sensitive to associated treatments, type of graft and a number of patient characteristics. Experimental studies have yielded a large body of data, the clinical relevance of which still requires definite validation through randomized trials. Fractionated TBI schemes are able to reduce late normal tissue toxicity, but the ultimate consequences of the fractional dose reduction do not appear to be equivocal. Thus, leukemia and lymphoma cells are probably more radio-biologically heterogeneous than previously thought, with several cell lines displaying relatively high radioresistance and repair capability patterns. The most primitive host-type hematopoietic stem cells are likely to be at least partly protected by TBI fractionation and may hamper late engraftment. Similarly, but with possibly conflicting consequences on the probability of engraftment, the persistence of a functional marrow stroma may also be fractionation-sensitive, while higher rejection rates have been reported after T-depletion grafts and fractionated TBI. in clinical practice (as for performance of relevant clinical trials), the influence of these results are rather limited by the heavy logistic constraints created by a sophisticated and time-consuming procedure. Lastly, clinicians are now facing an increasing incidence of second cancers, at least partly induced by irradiation, which jeopardize the long-term prospects of otherwise cured patients. (authors)

  9. Early Energetic Particle Irradiation of the HED Parent Body Regolith

    Science.gov (United States)

    Bogard, D. D.; Garrison, D. H.; Rao, M. N.

    1996-01-01

    Previous studies have shown that many individual grains within the dark phase of the Kapoeta howardite were irradiated with energetic particles while residing on the surface of the early HED regolith. Particle tracks in these grains vary in density by more than an order of magnitude and undoubtedly were formed by energetic heavy (Fe) ions associated with early solar flares. Early Irradiation of HED Regolith: Concentrations of excess Ne alone are not sufficient to decide between competing galactic and solar irradiation models. However, from recent studies of depth samples of oriented lunar rocks, we have shown that the cosmogenic 21-Ne/22-Ne ratio produced in feldspar differs substantially between Galactic Cosmic Radiation (GCR) and solar protons, and that this difference is exactly that predicted from cross-section data. Using Ne literature data and new isotopic data we obtained on acid-etched, separated feldspar from both the light and dark phases of Kapoeta, we derive 21-Ne/22-Ne = 0.80 for the recent GCR irradiation and 21-Ne/22-Ne = 0.68 for the early regolith irradiation. This derived ratio indicates that the early Ne production in the regolith occurred by both galactic and solar protons. If we adopt a likely one-component regolith model in which all grains were exposed to galactic protons but individual grains had variable exposure to solar protons, we estimate that this early GCR irradiation lasted for about 3-6 m.y. More complex two-component regolith models involving separate solar and galactic irradiation would permit this GCR age to be longer. Higher-energy solar protons would permit the GCR to be longer. Higher-energy solar protons would permit the GCR age to be shorter. Further, cosmogenic 126(Xe) in Kapoeta dark is no more than a factor of about 2 higher than that observed in Kapoeta light. Because 126(Xe) can only be formed by galactic protons and not solar protons, these data support a short GCR irradiation for the HED regolith. This would also be

  10. Total body irradiation in non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Between October 1972 and August 1977, low-dose fractionated total body irradiation (TBI), 150 to 300 rad,, was selected for 48 patients with previously untreated non-Hodgkin's lumphoma staged II, III, and IV. In 63% of the patients the disease had a nodular pattern; there were no patients with diffuse histiocytic lymphoma. All but 2 patients responded to TBI. The 4-year acutarial survival was 71% for the nodular group and 57% for the diffuse group. There were no acute symptoms during the course of treatment and no mortality associated with the treatment. Seventeen per cent of the patients developed transient platelet counts less than 30,000/mm3. Four required hospitilization for correction of thrombocytopenia and/or infection. The majority of patients who failed more than 3 months after initial complete remission were placed back in remission with either chemotherapy, TBI, or local irradiation. Patients with persistent disease after TBI showed a less favorable response with chemotherapy. A selected group of 15 patients in relapse after chemotherapy or localized radiotherapy were treated with TBI. Eleven responded to treatment, while 4 showed no useful response. The median survival for this group was slightly over 2 years. Twenty percent developed transient platelet counts less than 30,000/mm3

  11. Development of a translating bed for total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Connors, S.; Scrimger, J.; Logus, W.; Johnson, L.; Schartner, E. (Cross Cancer Institute, Edmonton (Canada))

    1988-12-01

    Total body irradiation is used to prepare a patient for bone marrow transplantation. Traditional techniques often sacrifice dose uniformity for patient comfort and ease of treatment. A method has been developed using a translational bed under a cobalt 60 photon beam. The bed and controller were designed and built on site. A bolused patient lying in the bed is moved at constant speed through the beam. Using this technique, dose homogeneity is optimized by the use of bolus, extended source-skin distance, adequate field size and use of anterior/posterior fields. The dose rate represents a compromise between a value high enough to keep treatment times tolerable by the patient and one that is sufficiently low to avoid treatment complications. The value of 50 cGy/min which was used meets these requirements. Extensive phantom measurements have shown that the dose homogeneity can be obtained to within an acceptable limit of +/- 5%.

  12. In vivo dosimetry with silicon diodes in total body irradiation

    International Nuclear Information System (INIS)

    The aim of this work is the characterization and application of silicon diode detectors for in vivo dosimetry in total body irradiation (TBI) treatments. It was evaluated the diode response with temperature, dose rate, gantry angulations and field size. A maximum response variation of 2.2% was obtained for temperature dependence. The response variation for dose rate and angular was within 1.2%. For field size dependence, the detector response increased with field until reach a saturation region, where no more primary radiation beam contributes for dose. The calibration was performed in a TBI setup. Different lateral thicknesses from one patient were simulated and then the calibration factors were determined by means of maximum depth dose readings. Subsequent to calibration, in vivo dosimetry measurements were performed. The response difference between diode readings and the prescribed dose for all treatments was below 4%. This difference is in agreement as recommended by the International Commission on Radiation Units and Measurements (ICRU), which is ±5%. The present work to test the applicability of a silicon diode dosimetry system for performing in vivo dose measurements in TBI techniques presented good results. These measurements demonstrated the value of diode dosimetry as a treatment verification method and its applicability as a part of a quality assurance program in TBI treatments. - Highlights: ► Characterization of a silicon diode dosimetry system. ► Application of the diodes for in vivo dosimetry in total body irradiation treatments. ► Implementation of in vivo dosimetry as a part of a quality assurance program in radiotherapy

  13. Predation as a determinant of minimum group size in baboons.

    Science.gov (United States)

    Bettridge, Caroline M; Dunbar, R I M

    2012-01-01

    Predation risk places a pressure on animals to adopt mechanisms by which they reduce their individual risk of being preyed on. However, a consensus on methods of determining predation risk has yet to be reached. One of the most widespread ways in which animals respond to predation risk is by living in groups. Minimum permissible group size is the smallest group size that animals are able to live in, given the habitat-specific predation risk they face. We explore ways in which predation risk can be measured and analyse its effect on minimum observed group size in baboons. Using data on predator density, habitat composition and baboon body size, we investigate the impact of the components of predation risk on baboon group size, and derive an equation that best predicts minimum group size. Minimum group size in baboons is related to predator density and female body mass. Both of these elements can, in turn, be estimated from environmental variables. These findings present support for the argument that group living in primates is a response to predation risk and offer potentially new ways of investigating carnivore and primate ecology. PMID:23363593

  14. Modeling a radiotherapy clinical procedure: total body irradiation.

    Science.gov (United States)

    Esteban, Ernesto P; García, Camille; De La Rosa, Verónica

    2010-09-01

    Leukemia, non-Hodgkin's lymphoma, and neuroblastoma patients prior to bone marrow transplants may be subject to a clinical radiotherapy procedure called total body irradiation (TBI). To mimic a TBI procedure, we modified the Jones model of bone marrow radiation cell kinetics by adding mutant and cancerous cell compartments. The modified Jones model is mathematically described by a set of n + 4 differential equations, where n is the number of mutations before a normal cell becomes a cancerous cell. Assuming a standard TBI radiotherapy treatment with a total dose of 1320 cGy fractionated over four days, two cases were considered. In the first, repopulation and sub-lethal repair in the different cell populations were not taken into account (model I). In this case, the proposed modified Jones model could be solved in a closed form. In the second, repopulation and sub-lethal repair were considered, and thus, we found that the modified Jones model could only be solved numerically (model II). After a numerical and graphical analysis, we concluded that the expected results of TBI treatment can be mimicked using model I. Model II can also be used, provided the cancer repopulation factor is less than the normal cell repopulation factor. However, model I has fewer free parameters compared to model II. In either case, our results are in agreement that the standard dose fractionated over four days, with two irradiations each day, provides the needed conditioning treatment prior to bone marrow transplant. Partial support for this research was supplied by the NIH-RISE program, the LSAMP-Puerto Rico program, and the University of Puerto Rico-Humacao.

  15. Patterns of patient specific dosimetry in total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Akino, Yuichi [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202 (United States); Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871 (Japan); McMullen, Kevin P.; Das, Indra J. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana 46202 (United States)

    2013-04-15

    Purpose: Total body irradiation (TBI) has been used for bone marrow transplant for hematologic and immune deficiency conditions. The goal of TBI is to deliver a homogeneous dose to the entire body, with a generally accepted range of dose uniformity being within {+-}10% of the prescribed dose. The moving table technique for TBI could make dose uniform in whole body by adjusting couch speed. However, it is difficult to accurately estimate the actual dose by calculation and hence in vivo dosimetry (IVD) is routinely performed. Here, the authors present patterns of patient-specific IVD in 161 TBI patients treated at our institution. Methods: Cobalt-60 teletherapy unit (Model C9 Cobalt-60 teletherapy unit, Picker X-ray Corporation) with customized moving bed (SITI Industrial Products, Inc., Fishers, IN) were used for TBI treatment. During treatment, OneDose{sup TM} (Sicel Technology, NC) Metal Oxide-silicon Semiconductor Field Effect Transistor detectors were placed at patient body surface; both entrance and exit side of the beam at patient head, neck, mediastinum, umbilicus, and knee to estimate midplane dose. When large differences (>10%) between the prescribed and measured dose were observed, dose delivery was corrected for subsequent fractions by the adjustment of couch speed and/or bolus placement. Under IRB exempt status, the authors retrospectively analyzed the treatment records of 161 patients who received TBI treatment between 2006 and 2011. Results: Across the entire cohort, the median {+-} SD (range) percent variance between calculated and measured dose for head, neck, mediastinum, umbilicus, and knee was -2.3 {+-} 10.2% (-66.2 to +35.3), 1.1 {+-} 11.5% (-62.2 to +40.3), -1.9 {+-} 9.5% (-66.4 to +46.6), -1.1 {+-} 7.2% (-35.2 to +42.9), and 3.4 {+-} 12.2% (-47.9 to +108.5), respectively. More than half of treatments were within {+-}10% of the prescribed dose for all anatomical regions. For 80% of treatments (10%-90%), dose at the umbilicus was within {+-}10

  16. Optimization of total body irradiation: the match between (maximal) leukemic cell kill and (minimal) late effects

    NARCIS (Netherlands)

    Harteveld, M.L. van

    2007-01-01

    Optimization of total body irradiation: the match between (maximal) leukemic cell kill and (minimal) late effects: In this thesis, cataract formation and renal dysfunction as late effects of high-dose total body irradiation (TBI) as part of the conditioning before hematological stem cell transplanta

  17. Total body irradiation: present and future; Irradiation corporelle totale: present et avenir

    Energy Technology Data Exchange (ETDEWEB)

    Zilli, T.; Miralbell, R.; Ozsahin, M. [Hopitaux Universitaires de Geneve, Service de Radio-Oncologie (Switzerland); Ozsahin, M. [Centre Hospitalier Universitaire Vaudois, Service de Radio-Oncologie, Lausanne (Switzerland)

    2009-09-15

    Total body irradiation (T.B.I.) has an established role as preparative regimen for bone-marrow transplantation in the treatment of hematological malignancies. Many randomized trials demonstrated that the clinical outcomes obtained from the association of T.B.I. and cyclophosphamide are equivalent, or, sometimes, better than those based on chemotherapeutic agents. Despite the therapeutic progress of the last years, and the consequent improvement in the overall survival, this preparative regimen remains always associated with a relatively high rate of acute and late toxicity. In this article, we review the actual indications of T.B.I. in clinical practice, and analyze the technological progress in this domain. We focus on the hypothesis that a selective irradiation of the hematopoietic or lymphoid organs is actually possible with intensity-modulated radiotherapy. Technical limits and preliminary results in terms of acute and late toxicities of intensity-modulated T.B.I. are analyzed. With these new technologies, treatment-related toxicity is not anymore a major limiting factor in the preparative regimens for bone-marrow transplantation, allowing for a larger spectrum of T.B.I. indications, a possible extension to patients older than 50 years, or a dose escalation. Preliminary results warrant, however, further evaluation in clinical trials to better assess the impact of this new approach on disease control and the long-term toxicity. (authors)

  18. In vivo dosimetry with silicon diodes in total body irradiation

    Science.gov (United States)

    Oliveira, F. F.; Amaral, L. L.; Costa, A. M.; Netto, T. G.

    2014-02-01

    The aim of this work is the characterization and application of silicon diode detectors for in vivo dosimetry in total body irradiation (TBI) treatments. It was evaluated the diode response with temperature, dose rate, gantry angulations and field size. A maximum response variation of 2.2% was obtained for temperature dependence. The response variation for dose rate and angular was within 1.2%. For field size dependence, the detector response increased with field until reach a saturation region, where no more primary radiation beam contributes for dose. The calibration was performed in a TBI setup. Different lateral thicknesses from one patient were simulated and then the calibration factors were determined by means of maximum depth dose readings. Subsequent to calibration, in vivo dosimetry measurements were performed. The response difference between diode readings and the prescribed dose for all treatments was below 4%. This difference is in agreement as recommended by the International Commission on Radiation Units and Measurements (ICRU), which is ±5%. The present work to test the applicability of a silicon diode dosimetry system for performing in vivo dose measurements in TBI techniques presented good results. These measurements demonstrated the value of diode dosimetry as a treatment verification method and its applicability as a part of a quality assurance program in TBI treatments.

  19. Bone markers after total body irradiation in childhood.

    Science.gov (United States)

    Couto-Silva, A-C; Trivin, C; Espérou, H; Michon, J; Baruchel, A; Souberbielle, J-C; Brauner, R

    2010-03-01

    Total body irradiation (TBI) can cause short stature because of decreased growth hormone (GH) and skeletal abnormalities. To evaluate the plasma concentrations of markers of bone formation (osteocalcin and procollagen type 1 amino-terminal propeptide, P1NP) and resorption (carboxy-terminal telopeptide, CTX), in patients (n=65) who had been given TBI at 6.6+/-0.4 years were evaluated at 9.8+/-0.4 years. Patients given single 10 Gy or fractionated 12 Gy TBI had similar characteristics, except that plasma insulin-like growth factor (IGF-1) was lower in those given a single 10 Gy. Seven had lower osteocalcin and two had higher CTX than controls. Bone markers (as zs) were positively correlated (osteocalcin with P1NP, rho=0.42, P=0.0007; osteocalcin with CTX, rho=0.3, Pirradiated when young (P=0.0002) or given single TBI lost more height between TBI and adult height. Most TBI patients had normal bone formation and resorption markers. Thus, impaired bone turnover is probably not the cause of their short stature and poor response to GH.

  20. Virtual bolus for total body irradiation treated with helical tomotherapy.

    Science.gov (United States)

    Moliner, Gilles; Izar, Françoise; Ferrand, Régis; Bardies, Manuel; Ken, Soléakhéna; Simon, Luc

    2015-11-08

    Intensity-modulated radiation therapy (IMRT) for total body irradiation (TBI) is practiced in several centers using the TomoTherapy System. In this context the planning target volume (PTV) is the entire body including the skin. A safety margin in the air surrounding the body should be added to take into account setup errors. But using inverse planning, over-fluence peak could be generated in the skin region to insure dose homogeneity. This work proposes to study the performance of the use of a virtual bolus (VB). A VB is a material placed on the skin surface during planning, but absent for the real treatment. The optimal VB that compensates large setup errors without introducing a high-dose increase or hot spots for small setup errors was determined. For two cylindrical phantoms, 20VBs with different densities, thicknesses or designs were tested. Dose coverage of the PTV (V95%) in the presence of simulated setup errors was computed to assess the VB performance. A measure of the dose increase in the phantom center due to the absence of the VB during treatment was also achieved. Finally, the fluence peak at the phantom edge was measured in complete buildup conditions using a large phantom and a detector matrix. Using these VBs, simulated setup errors were compensated to a minimum value of 2.6 and 2.1 cm for small and large phantom, respectively (and only 1.2 and 1.7 cm with no VB). An optimal double-layer VB was found with a density of 0.4 kg.m(-3) and a total thickness of 8mm; an inner layer of 5 mm was declared as the target for the treatment planning system and an additional layer of 3 mm was added to avoid the over-fluence peak. Using this VB, setup errors were compensated up to 2.9 cm. The dose increase was measured to be only +1.5% at the phantom center and over-fluence peak was strongly decreased.

  1. Delayed renal dysfunction after total body irradiation in pediatric malignancies.

    Science.gov (United States)

    Watanabe Nemoto, Miho; Isobe, Koichi; Togasaki, Gentaro; Kanazawa, Aki; Kurokawa, Marie; Saito, Makoto; Harada, Rintaro; Kobayashi, Hiroyuki; Ito, Hisao; Uno, Takashi

    2014-09-01

    The purpose of this study was to retrospectively evaluate the incidence of delayed renal dysfunction after total body irradiation (TBI) in long-term survivors of TBI/hematopoietic stem cell transplantation (HSCT). Between 1989 and 2006, 24 pediatric patients underwent TBI as part of the conditioning regimen for HSCT at Chiba University Hospital. Nine patients who survived for more than 5 years were enrolled in this study. No patient had any evidence of renal dysfunction prior to the transplant according to their baseline creatinine levels. The median age at the time of diagnosis was 6 years old (range: 1-17 years old). The follow-up period ranged from 79-170 months (median: 140 months). Renal dysfunction was assessed using the estimated glomerular filtration rate (eGFR). The TBI dose ranged from 8-12 Gy delivered in 3-6 fractions over 2-3 d. The patients were treated with linear accelerators in the supine position, and the radiation was delivered to isocentric right-left and left-right fields via the extended distance technique. The kidneys and the liver were not shielded except in one patient with a left adrenal neuroblastoma. No patient required hemodialysis. The eGFR of four patients (44.4%) progressively decreased. The remaining patients did not demonstrate any eGFR deterioration. Only one patient developed hypertension. By evaluating the changes in eGFR, renal dysfunction among long-term survivors of TBI/HSCT could be detected. Our results suggested that the TBI schedule of 12 Gy in 6 fractions over three consecutive days affects renal function.

  2. Influence of whole-body irradiation on calcium and phosphate homeostasis in the rat

    International Nuclear Information System (INIS)

    Previous irradiation studies have revealed marked alterations in calcium metabolism. Moreover, the maintenance of calcium homeostasis with parathyroid hormone or calcium salts has been reported to reduce radiation lethality. Therefore, the present study was designed to evaluate the influence of irradiation on calcium homeostasis in the rat. Nine hundred rad of whole-body irradiation produced a significant depression of both plasma calcium and phosphate at 4 days postirradiation. This effect of irradiation was observed to be dose-dependent over a range of 600 to 1200 rad, and possibly related to irradiation-induced anorexia. The physiological significance of these observations is discussed

  3. Cross-placental transfer of 2434Cm in the baboon

    International Nuclear Information System (INIS)

    An adult female baboon was injected with 1.36 μCi 2434Cm approximately four months after the onset of pregnancy. Forty-five days subsequent to the injection, the fetus was delivered by Caesarean section and the individual organs assayed for their 2434Cm contents. The soft tissues, placenta and skeleton were found to contain 0.03, 1.11, and 0.42% respectively of the mother's body burden

  4. Immunologic changes after loco-regional radiotherapy and fractionated total body irradiation (TBI) in mice

    International Nuclear Information System (INIS)

    The immunologic effects of fractionated irradiation to both hind limbs and the tail of adult mice were investigated. A dose of 34 Gy given in 17 fractions of 2 Gy, 1 fraction per day, 5 days per week, was delivered with a 60Co source. A significant decrease of the total splenocyte count and of the PHA(phytohemagglutinin)-induced proliferation of T cells was found immediately after irradiation. Both parameters normalized within 30 days after irradiation. Immediately after irradiation, the MLC (mixed lymphocyte culture) was supranormal, dropped to 45% 1 week later, and normalized within 1 month after radiotherapy. The NK (natural killer) activity was significantly decreased only the first week after loco-regional irradiation, while the LAK (lymphokine activated killer) activity was not altered at all. The percentage of goat-anti-mouse+ cells (mainly B lymphocytes) was not changed immediately after loco-regional irradiation, but rose to supranormal values (175% of control level) 3 months after irradiation. A persistent decrease of the percentage and the absolute numbers of the Lyt2+ cells (= CD8+ cells, suppressor/cytotoxic phenotype) was observed up to 3 months after irradiation, while the percentage of L3T4+ cells (= CD4+ cells, helper phenotype) remained normal for the total follow-up. No differences in allogeneic skin graft survival could be demonstrated between irradiated and control animals. The observed immunological effects could not be explained by the scatter irradiation to the whole body as total body irradiation (TBI) administered in a dose and dose rate similar to the scatter dose did not result in persistent immunologic changes. No dose-rate effect could be demonstrated in a low dose fractionated total body irradiation schedule. A total body irradiation similar to the scatter dose in humans did not result in significant immunologic changes

  5. Cardiac injury after 10 gy total body irradiation: indirect role of effects on abdominal organs.

    Science.gov (United States)

    Lenarczyk, Marek; Lam, Vy; Jensen, Eric; Fish, Brian L; Su, Jidong; Koprowski, Stacy; Komorowski, Richard A; Harmann, Leanne; Migrino, Raymond Q; Li, X Allen; Hopewell, John W; Moulder, John E; Baker, John E

    2013-09-01

    The objective of this study was to determine whether radiation-induced injury to the heart after 10 Gy total body irradiation (TBI) is direct or indirect. Young male WAG/RijCmcr rats received a 10 Gy single dose using TBI, upper hemi-body (UHB) irradiation, lower hemi-body (LHB) irradiation, TBI with the kidneys shielded or LHB irradiation with the intestines shielded. Age-matched, sham-irradiated rats served as controls. The lipid profile, kidney injury, heart and liver morphology and cardiac function were determined up to 120 days after irradiation. LHB, but not UHB irradiation, increased the risk factors for cardiac disease as well as the occurrence of cardiac and kidney injury in a way that was quantitatively and qualitatively similar to that observed after TBI. Shielding of the kidneys prevented the increases in risk factors for cardiac disease. Shielding of the intestines did not prevent the increases in risk factors for cardiac disease. There was no histological evidence of liver injury 120 days after irradiation. Injury to the heart from irradiation appears to be indirect, supporting the notion that injury to abdominal organs, principally the kidneys, is responsible for the increased risk factors for and the occurrence of cardiac disease after TBI and LHB irradiation.

  6. Hematological Effects of Total or Partial Irradiation of the Human Body

    International Nuclear Information System (INIS)

    Many studies have been devoted to hematological effects of total body irradiation in various animal species, but there are few human data. In addition, the origin of these documents limited value. It is indeed, sometimes accidentally irradiated subjects, including irradiation was not uniform and that the dosimetry performed a posteriori, is random, sometimes irradiated patients or for the treatment of cancer or to suppress immunological reactions so that a transplant of tissue or an organ transplant, and one may wonder if the reactions such subjects are similar to those of normal subjects. Documents valid for partial irradiation of a human body by a single session even fewer and almost all relate to accidental irradiation

  7. Characteristics of a Teflon rod antenna for millimeter and submillimeter wave irradiation on living bodies

    OpenAIRE

    TATSUKAWA, Toshiaki; Doi, Akitaka; TERANAKA, Masato; Takashima, Hitoshi; Goda, Fuminori; Idehara, Toshitaka; Ogawa, Isamu; KANEMAKI, Tomohiro; NISHIZAWA, Seiji; NAMBA, Tunetoyo

    2003-01-01

    The development of a millimeter and submillimeter wave catheter for irradiation on living bodies using a Teflon rod dielectric antenna is described. The power sources of electromagnetic wave are an Impatt oscillator (90 GHz, 0.3 W) and gyrotron (302 GHz, 30 W). Irradiation tests using various Teflon rod dielectric antennas were performed on beef livers. Irradiation results were considered by microwave theory and ray optics.

  8. Change in the mineralization of the healing bone callus after whole-body irradiation in mice

    International Nuclear Information System (INIS)

    The delayed consolidation of diaphysial long-bone fractures in mice subjected to whole-body X-irradiation is expressed biochemically by a faulty mineralization of the repair callus. This deficiency is proportional to the irradiation intensity and is not corrected by previous administration of cycteamine

  9. Total body irradiation as a form of preparation for bone marrow transplantation

    International Nuclear Information System (INIS)

    The history of total body irradiation and bone marrow transplantation is surprisingly old. Following the success of Thomas et al. in the 1970s, bone marrow transplantation appeared to be the sole curative treatment modality for high-risk leukemia. A supralethal dose of total body irradiation was widely accepted as a form of preparation for bone marrow transplantation. In this paper, I described the present status of bone marrow transplantation for leukemia patients in Japan based on the IVth national survey. Since interstitial pneumonitis was one of the most life threatening complications after bone marrow transplantation, I mentioned the dose, dose-rate and fraction of total body irradiation in more detail. In addition, I dealt with some problems of the total body irradiation, such as dose prescription, compensating contour as well as inhomogeneity, and shielding for the highrisk organs. (author) 82 refs

  10. Whole-body irradiation transiently diminishes the adrenocorticotropin response to recombinant human interleukin-1α

    International Nuclear Information System (INIS)

    Recombinant human interleukin-1α (rhIL-1α) has significant potential as a radioprotector and/or treatment for radiation-induced hematopoietic injury. Both IL-1 and whole-body ionizing irradiation acutely stimulate the hypothalamic-pituitary-adrenal axis. We therefore assessed the interaction of whole-body irradiation and rhIL-1α in altering the functioning of the axis in mice. Specifically, we determined the adrenocorticotropin (ACTH) and corticosterone responses to rhIL-1α administered just before and hours to days after whole-body or sham irradiation. Our results indicate that whole-body irradiation does not potentiate the rhIL-1α-induced increase in ACTH levels at the doses used. In fact, the rhIL-1α-induced increase in plasma ACTH is transiently impaired when the cytokine is administered 5 h after, but not 1 h before, exposure to whole-body irradiation. The ACTH response may be inhibited by elevated corticosterone levels after whole-body irradiation, or by other radiation-induced effects on the pituitary gland and hypothalamus. 36 refs., 3 figs

  11. Whole-body irradiation transiently diminishes the adrenocorticotropin response to recombinant human interleukin-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Perlstein, R.S.; Mehta, N.R.; Neta, R.; Whitnall, M.H. [Armed Forces Radiobiology Research Institute, Bethesda, MD (United States); Mougey, E.H. [Walter Reed Army Institute of Research, Washington, DC (United States)

    1995-03-01

    Recombinant human interleukin-1{alpha} (rhIL-1{alpha}) has significant potential as a radioprotector and/or treatment for radiation-induced hematopoietic injury. Both IL-1 and whole-body ionizing irradiation acutely stimulate the hypothalamic-pituitary-adrenal axis. We therefore assessed the interaction of whole-body irradiation and rhIL-1{alpha} in altering the functioning of the axis in mice. Specifically, we determined the adrenocorticotropin (ACTH) and corticosterone responses to rhIL-1{alpha} administered just before and hours to days after whole-body or sham irradiation. Our results indicate that whole-body irradiation does not potentiate the rhIL-1{alpha}-induced increase in ACTH levels at the doses used. In fact, the rhIL-1{alpha}-induced increase in plasma ACTH is transiently impaired when the cytokine is administered 5 h after, but not 1 h before, exposure to whole-body irradiation. The ACTH response may be inhibited by elevated corticosterone levels after whole-body irradiation, or by other radiation-induced effects on the pituitary gland and hypothalamus. 36 refs., 3 figs.

  12. Physical exercise tolerance in patients with chronic lymphoproliferative diseases after whole-body therapeutic gamma irradiation

    International Nuclear Information System (INIS)

    It is stated that physical workability remains practically at the initial level after a course of fractionated whole-body therapeutic gamma irradiation at the integral doze of 1 Gy obtained during two weeks and at the integral dose of 2 Gy obtained during 4 weeks. Tendency to decrease of systolic arterial pressure (AP) is noted under fractionated whole-body therapeutic gamma irradiation at the integral dose of 1 Gy that should be necessarily taken into account under irradiation of patients with reduced AP and patients receiving hypotensive preparations for accompanying arterial hypertension

  13. Chronic blood irradiation: a new approach

    International Nuclear Information System (INIS)

    Extracorporeal irradiation of blood is beneficial in suppressing early rejection of renal allografts and in treating chronic lymphocytic leukemia. Previously, nearly all blood irradiation has involved brief intermittent exposures with high dose rates. The small amount of data available involving chronic irradiation suggests that doses given chronically at lower rates are more effective in suppressing graft rejection. However, no suitably portable device has been available to permit chronic irradiation. This work has been directed toward developing a fully portable irradiator. After preliminary testing of a variety of source materials, 170Tm was selected for its favorable beta energy, low cost, and compatibility with the fabrication requirements. The body of the irradiator is cast from polyfurfuryl alcohol with subsequent high-temperature conversion to vitreous carbon. By sequential layering of the alcohol and suspending of 169Tm2O3 in the midlayer, a unit is produced without any radiation exposure and with the source material contained on both a macro and a micro scale. Exposure of the unit to reactor neutrons produces 170Tm without activation of the vitreous carbon. A 170Tm irradiator giving a transit dose of 16 rads (100 ml/min flow) was connected in a carotid--jugular shunt on a 20-kg goat. Lymphocyte levels decreased to about 15 percent of the preexposure level during the first week and thereafter slowly rose to about 50 percent of preexposure levels 2 months after exposure. Reciprocal skin grafts made at the end of irradiation (12 days) were rejected at 12 days on the nonirradiated control and at 24 days on the irradiated goat. These results are consistent with data reported on chronically irradiated baboons even though the dose rate for the present test was only about one-fourth that for the baboons

  14. Physical aspects of total body irradiation as practised at Tuebingen

    International Nuclear Information System (INIS)

    From the outset it has been our overriding aim: administer the medically prescribed dose as correctly as possible to the patient. Both method and dosages we have taken over from the so-called Seattle technique. Only in the single fraction-irradiation (E) the dose rate of the linac (Philips SL 75/20 or SL 75/10) was reduced to 0.07 Gy/min. The report describes how the TBI was realized. (orig./HP)

  15. Baboon feeding ecology informs the dietary niche of Paranthropus boisei.

    Directory of Open Access Journals (Sweden)

    Gabriele A Macho

    Full Text Available Hominins are generally considered eclectic omnivores like baboons, but recent isotope studies call into question the generalist status of some hominins. Paranthropus boisei and Australopithecus bahrelghazali derived 75%-80% of their tissues' δ(13C from C4 sources, i.e. mainly low-quality foods like grasses and sedges. Here I consider the energetics of P. boisei and the nutritional value of C4 foods, taking into account scaling issues between the volume of food consumed and body mass, and P. boisei's food preference as inferred from dento-cranial morphology. Underlying the models are empirical data for Papio cynocephalus dietary ecology. Paranthropus boisei only needed to spend some 37%-42% of its daily feeding time (conservative estimate on C4 sources to meet 80% of its daily requirements of calories, and all its requirements for protein. The energetic requirements of 2-4 times the basal metabolic rate (BMR common to mammals could therefore have been met within a 6-hour feeding/foraging day. The findings highlight the high nutritional yield of many C4 foods eaten by baboons (and presumably hominins, explain the evolutionary success of P. boisei, and indicate that P. boisei was probably a generalist like other hominins. The diet proposed is consistent with the species' derived morphology and unique microwear textures. Finally, the results highlight the importance of baboon/hominin hand in food acquisition and preparation.

  16. Detective mice assess relatedness in baboons using olfactory cues.

    Science.gov (United States)

    Célérier, Aurélie; Huchard, Elise; Alvergne, Alexandra; Féjan, Delphine; Plard, Floriane; Cowlishaw, Guy; Raymond, Michel; Knapp, Leslie A; Bonadonna, Francesco

    2010-05-01

    The assessment of relatedness may be crucial in the evolution of socio-sexual behaviour, because it can be associated with fitness benefits mediated by both nepotism and inbreeding avoidance. In this context, one proposed mechanism for kin recognition is 'phenotype matching'; animals might compare phenotypic similarities between themselves and others in order to assess the probability that they are related. Among cues potentially used for kin discrimination, body odours constitute interesting candidates that have been poorly investigated in anthropoid primates so far, because of a mixture of theoretical considerations and methodological/experimental constraints. In this study, we used an indirect approach to examine the similarity in odour signals emitted by related individuals from a natural population of chacma baboons (Papio ursinus). For that purpose, we designed an innovative behavioural tool using mice olfactory abilities in a habituation-discrimination paradigm. We show that: (i) mice can detect odour differences between individuals of same sex and age class in another mammal species, and (ii) mice perceive a higher odour similarity between related baboons than between unrelated baboons. These results suggest that odours may play a role in both the signalling of individual characteristics and of relatedness among individuals in an anthropoid primate. The 'biological olfactometer' developed in this study offers new perspectives to the exploration of olfactory signals from a range of species. PMID:20400623

  17. Type 2 Diabetes is a Delayed Late Effect of Whole-Body Irradiation in Nonhuman Primates

    Science.gov (United States)

    Kavanagh, Kylie; Dendinger, Michael D.; Davis, Ashley T.; Register, Thomas C.; DeBo, Ryne; Dugan, Greg; Cline, J. Mark

    2015-01-01

    One newly recognized consequence of radiation exposure may be the delayed development of diabetes and metabolic disease. We document the development of type 2 diabetes in a unique nonhuman primate cohort of monkeys that were whole-body irradiated with high doses (6.5–8.4 Gy) 5–9 years earlier. We report here a higher prevalence of type 2 diabetes in irradiated monkeys compared to age-matched nonirradiated monkeys. These irradiated diabetic primates demonstrate insulin resistance and hypertriglyceridemia, however, they lack the typical obese presentation of primate midlife diabetogenesis. Surprisingly, body composition analyses by computed tomography indicated that prior irradiation led to a specific loss of visceral fat mass. Prior irradiation led to reductions in insulin signaling effectiveness in skeletal muscle and higher monocyte chemoattractant protein 1 levels, indicative of increased inflammation. However, there was an absence of large defects in pancreatic function with radiation exposure, which has been documented previously in animal and human studies. Monkeys that remained healthy and did not become diabetic in the years after irradiation were significantly leaner and smaller, and were generally smaller and younger at the time of exposure. Irradiation also resulted in smaller stature in both diabetic and nondiabetic monkeys, compared to nonirradiated age-matched controls. Our study demonstrates that diabetogenesis postirradiation is not a consequence of disrupted adipose accumulation (generalized or in ectopic depots), nor generalized pancreatic failure, but suggests that peripheral tissues such as the musculature are impaired in their response to insulin exposure. Ongoing inflammation in these animals appears to be a consequence of radiation exposure and can interfere with insulin signaling. The reasons that some animals remain protected from diabetes as a late effect of irradiation are not clear, but may be related to body size. The translational

  18. Effects of total body irradiation on functions of small intestinal intraepithelial lymphocytes

    International Nuclear Information System (INIS)

    Objective: To explore the characteristics of intestinal mucosal immunity after gamma irradiation. Methods: The number, proliferation activity, cytotoxic activity of small intestinal intraepithelial lymphocytes (IELs), and the TNF-α and TGF-β concentrations in supernatant of cultured IELs were studied using IELs freshly isolated from whole small intestine of Kunming strain mice after 3,8 and 12 Gy total body 60Co γ-irradiation. Results: (1) The number of IELs in small intestinal mucosa of all irradiated mice significantly decreased at 8 h, reaching the lowest level at 48-72 h post-irradiation, then began to rise, but it still did not return to its normal level on day 15. (2) The proliferation activity and cytotoxic activity of IELs isolated from irradiated mice were reduced sharply. They followed the same pattern of decreasing at 8h, reaching the lowest level at 48-72 h post-irradiation, then began to rise, but it did not return to their normal levels on day 15. (3) The TNF-α and TGF-β concentrations in supernatant of cultured IELs isolated from irradiated mice were elevated at 8h, reaching their peak at 48-72 h. Conclusion: The decrease in number and important functions of IELs is one of the factors damaging the intestinal mucosal immunity barrier after total body irradiation

  19. The effects of 3Gy total body irradiation on mouse intestinal intraepithelial lymphocytes' number and functions

    International Nuclear Information System (INIS)

    To explore the characteristics of intestinal mucosal immunity after radiation injury, IEL number, proliferation activity, cytotoxic activity as well as the TNF-α and TGF-β concentrations of supernatant of cultured IEL were studied using IEL freshly isolated from whole small intestine of Kunming strain mice received 3Gy total body 60Co γ-ray irradiation. The proliferation activity, cytotoxic activity as well as the number of IEL in small intestinal mucosa were significantly decreased at 8h post-irradiation, reaching lowest level at 72h. The TNF-α and TGF-β concentrations of supernatant of cultured IEL isolated from irradiated mice were elevated at 8h, reaching peak at 72h. The decrease in number and functions of IEL may play an important role in the damage intestinal mucosal immunity barrier after total body irradiation

  20. Seed size selection by olive baboons.

    Science.gov (United States)

    Kunz, Britta Kerstin; Linsenmair, Karl Eduard

    2008-10-01

    Seed size is an important plant fitness trait that can influence several steps between fruiting and the establishment of a plant's offspring. Seed size varies considerably within many plant species, yet the relevance of the trait for intra-specific fruit choice by primates has received little attention. Primates may select certain seed sizes within a species for a number of reasons, e.g. to decrease indigestible seed load or increase pulp intake per fruit. Olive baboons (Papio anubis, Cercopithecidae) are known to select seed size in unripe and mature pods of Parkia biglobosa (Mimosaceae) differentially, so that pods with small seeds, and an intermediate seed number, contribute most to dispersal by baboons. We tested whether olive baboons likewise select for smaller ripe seeds within each of nine additional fruit species whose fruit pulp baboons commonly consume, and for larger seeds in one species in which baboons feed on the seeds. Species differed in fruit type and seed number per fruit. For five of these species, baboons dispersed seeds that were significantly smaller than seeds extracted manually from randomly collected fresh fruits. In contrast, for three species, baboons swallowed seeds that were significantly longer and/or wider than seeds from fresh fruits. In two species, sizes of ingested seeds and seeds from fresh fruits did not differ significantly. Baboons frequently spat out seeds of Drypetes floribunda (Euphorbiaceae) but not those of other plant species having seeds of equal size. Oral processing of D. floribunda seeds depended on seed size: seeds that were spat out were significantly larger and swallowed seeds smaller, than seeds from randomly collected fresh fruits. We argue that seed size selection in baboons is influenced, among other traits, by the amount of pulp rewarded per fruit relative to seed load, which is likely to vary with fruit and seed shape.

  1. Type 2 Diabetes is a Delayed Late Effect of Whole-Body Irradiation in Nonhuman Primates

    OpenAIRE

    Kavanagh, Kylie; Dendinger, Michael D.; Davis, Ashley T.; Register, Thomas C.; DeBo, Ryne; Dugan, Greg; Cline, J. Mark

    2015-01-01

    One newly recognized consequence of radiation exposure may be the delayed development of diabetes and metabolic disease. We document the development of type 2 diabetes in a unique nonhuman primate cohort of monkeys that were whole-body irradiated with high doses (6.5–8.4 Gy) 5–9 years earlier. We report here a higher prevalence of type 2 diabetes in irradiated monkeys compared to age-matched nonirradiated monkeys. These irradiated diabetic primates demonstrate insulin resistance and hypertrig...

  2. Behavior of peripheral reticulocytes following whole-body irradiation and stimulation of the bone marrow

    International Nuclear Information System (INIS)

    The relative reticulocyte content and the average Fe uptake of peripheral reticulocytes were investigated in rats after blood loss and whole-body irradiation as well as after a combined treatment for a time of 15 days. The acute loss of blood caused a rapid increase of cellular uptake within 24 hours, whereas after irradiation a considerable diminution could be observed. In addition to a direct stimulation or inhibition of bone marrow activity a direct influence of blood loss and irradiation on reticulocytes is discussed. (author)

  3. Four cases of protracted whole body irradiation (Algerian accident 1978)

    International Nuclear Information System (INIS)

    A 25 Ci iridium-192 source accidentally lost was introduced in a room where among others four young female patients (14 - 20 years old) one of them pregnant were irradiated during 4/5 weeks, 6/8 hours daily, cumulating skin doses in the range of 2500r and mean medullary doses in the range of 1250r. They developed a very protracted infections and haemorragic syndrome during which they were treated successfully by haematologic compensatory therapy with enormous quantities of packed isolated blood cells (R.B.C., W.B.C., platelets) and massive antibiotic, antimycotic and hydro-electrolytic therapy. The dosimetric (physical and biological) problems are discussed and the clinical and biological data are given in detail

  4. Comparing responses of four ungulate species to playbacks of baboon alarm calls.

    Science.gov (United States)

    Kitchen, Dawn M; Bergman, Thore J; Cheney, Dorothy L; Nicholson, James R; Seyfarth, Robert M

    2010-11-01

    A growing body of evidence suggests that a wide range of animals can recognize and respond appropriately to calls produced by other species. Social learning has been implicated as a possible mechanism by which heterospecific call recognition might develop. To examine whether familiarity and/or shared vulnerability with the calling species might influence the ability of sympatric species to distinguish heterospecific alarm calls, we tested whether four ungulate species (impala: Aepyceros melampus; tsessebe: Damaliscus lunatus; zebra: Equus burchelli; wildebeest: Connochaetes taurinus) could distinguish baboon (Papio hamadryas ursinus) alarm calls from other loud baboon calls produced during intra-specific aggressive interactions ('contest' calls). Overall, subjects' responses were stronger following playback of alarm calls than contest calls. Of the species tested, impala showed the strongest responses and the greatest difference in composite response scores, suggesting they were best able to differentiate call types. Compared with the other ungulate species, impala are the most frequent associates of baboons. Moreover, like baboons, they are susceptible to both lion and leopard attacks, whereas leopards rarely take the larger ungulates. Although it seems possible that high rates of association and/or shared vulnerability may influence impala's greater ability to distinguish among baboon call types, our results point to a stronger influence of familiarity. Ours is the first study to compare such abilities among several community members with variable natural histories, and we discuss future experiments that would more systematically examine development of these skills in young ungulates.

  5. Deep Learning of Orthographic Representations in Baboons

    OpenAIRE

    Thomas Hannagan; Ziegler, Johannes C.; Stéphane Dufau; Joël Fagot; Jonathan Grainger

    2014-01-01

    What is the origin of our ability to learn orthographic knowledge? We use deep convolutional networks to emulate the primate's ventral visual stream and explore the recent finding that baboons can be trained to discriminate English words from nonwords [1]. The networks were exposed to the exact same sequence of stimuli and reinforcement signals as the baboons in the experiment, and learned to map real visual inputs (pixels) of letter strings onto binary word/nonword responses. We show that th...

  6. Patient dose analysis in total body irradiation through in vivo dosimetry

    OpenAIRE

    Ganapathy, K.; Kurup, P. G. G.; Murali, V.; M. Muthukumaran; Bhuvaneshwari, N.; Velmurugan, J.

    2012-01-01

    Total body irradiation (TBI) is a special radiotherapy technique, administered prior to bone marrow transplantation. Due to the complex nature of the treatment setup, in vivo dosimetry for TBI is mandatory to ensure proper delivery of the intended radiation dose throughout the body. Lithium fluoride (LiF) TLD-100 chips are used for the TBI in vivo dosimetry. Results obtained from the in vivo dosimetry of 20 patients are analyzed. Results obtained from forehead, abdomen, pelvis, and mediastinu...

  7. Changes in serum amylase and its isoenzymes after whole body irradiation

    International Nuclear Information System (INIS)

    A study was carried out to assess the effect of total body irradiation on pancreatic and parotid isoenzymes of amylase in patients about to undergo bone-marrow transplantation who had received high-dose cyclophosphamide. Twelve patients were studied, enzyme activity being measured before and at various times after total body irradiation. Serum total amylase activity rose rapidly within 12 hours of irradiation to a maximum at 36 hours, returning to normal by six days; most of the increase was derived from salivary damage, with a much smaller pancreatic component. These results confirm that radiation produces acute changes in amylase activity, which may be of use in assessing radiation-induced damage. (author)

  8. FORMATION BY IRRADIATION OF AN EXPANDED, CELLULAR, POLYMERIC BODY

    Science.gov (United States)

    Charlesby, A.; Ross, M.

    1958-12-01

    The treatment of polymeric esters of methacrylic acid having a softening polnt above 40 icient laborato C to form an expanded cellular mass with a smooth skin is discussed. The disclosed method comprises the steps of subjecting the body at a temperature below the softenpoint to a dose of at least 5 x lO/sup 6/ roentgen of gamma radiation from cobalt-60 source until its average molecular weight is reduced to a value within the range of 3 x lO/sup 5/ to 10/sup 4/, and heating at a temperature within the range of 0 to lO icient laborato C above its softening point to effect expansion.

  9. Bone Marrow Transplantation, 20 years of experience with total body irradiation in the 'Hermanos Ameijeiras' hospital

    International Nuclear Information System (INIS)

    Using Total Body Irradiation (ICT) for bone marrow transplants is indicated in several hematological malignancies such as Acute and Chronic Myeloid Leukemia, Acute Lymphocytic Leukemia, Lymphoma and Myelodysplastic Syndrome. The odds of survival with this procedure than those obtained with standard treatments in this type of condition, ensuring a better life expectancy for these patients. (Author)

  10. A SIMPLIFIED IN VIVO DOSLMETRY FOR TOTAL BODY IRRADIATION PRIOR TO BONE MARROW TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    肖泽久

    1994-01-01

    For TBI (total body irradiation) prior to BMT (bone marrow transplantation) and in order to guarantee exact treatment, it is necessary to perfect is vivo dosimetry to detect any deviation of the treatment and to verify the dose dis-tribution. A simplified and convenient transmission type in vivo dosimetry and problems are introduced and discussed.

  11. Whole-body irradiation technique: physical aspects; Tecnica de irradiacion corporal total: aspectos fisicos

    Energy Technology Data Exchange (ETDEWEB)

    Venencia, D.; Bustos, S.; Zunino, S. [Instituto Privado de Radioterapia. Obispo Oro 425. Cordoba 5000 (Argentina)

    1998-12-31

    The objective of this work has been to implement a Total body irradiation technique that fulfill the following conditions: simplicity, repeatability, fast and comfortable positioning for the patient, homogeneity of the dose between 10-15 %, short times of treatments and In vivo dosimetric verifications. (Author)

  12. Epizootic pertussis focus of hamadryad baboons

    Directory of Open Access Journals (Sweden)

    A. Yu. Medkova

    2015-01-01

    Full Text Available The absence of an adequate experimental animal model makes difficult study of immunity against whooping cough and its pathogenesis. Experimental whooping cough reported by us earlier in pubescent non-human primates of the Old World was accompanied by specific clinical and laboratory marks in the absence of cough. The possibility of pertussis modelling while experimental whooping cough in impuberal hamadryad baboons was investigated. In the process of selection of monkeys for the further studies for perfecting of experimental model for pertussis research unexpectedly were detected specific pertussis antibodies in impuberal hamadryad baboons.The aim of the study: revealing of source of infection and transmission of pertussis to hamadryad baboons and investigation of response of antibody-positive impuberal hamadryad baboons to secondary contagion by B. pertussis bacteria while experimental infection.Results. 18 veterinary checked, somatically healthy hamadryad baboons of various gender managed in two neighboring cages. Specific pertussis IgM and IgG antibodies were found in blood serum of all the animals and one of the monkey keepers. By real-time PCR in nasopharyngeal swabs of the monkey keeper and three 7- and 9-month-old hamadryad baboons were registered single B. pertussis genom equivalents. Seropositive impuberal hamadryad baboons were experimentally challenged by virulent B. pertussis 475 strain. Quantity of B. pertussis genom equivalents and percentage of IgM and IgG antibodies in impuberal hamadryad baboons after experimental infection were detected. These results were comparable with such received after secondary experimental challenge of monkeys by B. pertussis. Humoral immuneresponse was characterized by booster effect and rapid B. pertussis elimination.Conclusion. The case of transmission of B.pertussis bacteria to hamadryad baboons by natural contagion and epizootic focus of pertussis in apery conditions

  13. Booster irradiation to the spleen following total body irradiation. A new immunosuppressive approach for allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Graft rejection presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, after conditioning exactly as for leukemia patients, it was shown that over 99% of the residual host clonable T cells are concentrated in the spleen on day 5 after completion of cytoreduction. We have now corroborated these findings in a mouse model. After 9-Gy total body irradiation (TBI), the total number of Thy-1.2+ cells in the spleen reaches a peak between days 3 and 4 after TBI. The T cell population is composed of both L3T4 (helper) and Lyt-2 (suppressor) T cells, the former being the major subpopulation. Specific booster irradiation to the spleen (5 Gy twice) on days 2 and 4 after TBI greatly enhances production of donor-type chimera after transplantation of T cell-depleted allogeneic bone marrow. Similar enhancement can be achieved by splenectomy on day 3 or 4 after TBI but not if splenectomy is performed 1 day before TBI or 1 day after TBI, strengthening the hypothesis that, after lethal TBI in mice, the remaining host T cells migrate from the periphery to the spleen. These results suggest that a delayed booster irradiation to the spleen may be beneficial as an additional immunosuppressive agent in the conditioning of leukemia patients, in order to reduce the incidence of bone marrow allograft rejection

  14. Behavioural consequences of an 8 Gy total body irradiation in mice: Regulation by interleukin-4

    Energy Technology Data Exchange (ETDEWEB)

    Van der Meeren, A.; Lebaron-Jacobs, L. [Inst. de Protection et de Surete Nucleaire, Dept. de Protection de la sante de l' Homme et de Dosimetrie, Section Autonome de Radiobiologie Appliquee a la Medecine, IPSN, Fontenay-aux-Roses (France)

    2001-02-01

    The effects of an 8 Gy {gamma} total body irradiation (TBI) on exploration and locomotion activities as well as temperature were studied in C57BL6/J mice. Survival, body weight, and blood cell counts were also assessed in irradiated mice treated with placebo or interleukin (IL)-4. The efficacy of IL-4 treatment on improvement in exploration activity was evaluated. The study was carried out from 3 h to 30 days following exposure. Our results showed a biphasic response to irradiation concerning the exploration activity of mice. Irradiated mice had reduced activity as early as 3 h after exposure, with recovery of activity within 24 h. The exploration activity again decreased 4 days after irradiation and the recovery occurred slowly after day 17. IL-4 ameliorated the exploration status in mice in both phases. The locomotion activity was studied using a telemetry apparatus. A similar pattern to that of the exploration data was observed, with a minimal activity observed between days 13 and 17. A radiation-induced hypothermia was also noticed over the same time period. (author)

  15. Protective Role Of Fresh Pomegranate Against Oxidative Damage In Whole Body Gamma Irradiated Male Albino Rats

    International Nuclear Information System (INIS)

    Twenty four male albino rats, body weight 100-130 g, were used to evaluate the protective role of fresh pomegranate fruit intake for 30 days on the damage induced by single dose of 6 Gy whole body gamma irradiation. The rats were randomly and equally divided into four groups: group (1): control, group (2): irradiated with 6 Gy, group (3): pomegranate for 30 days and group (4): pomegranate for 30 days followed by 6 Gy whole body irradiation. At the end of the experiment, all rats were sacrificed after 12 hours fasting then sera were separated for the determination of sugar, total antioxidant, lipid profile and liver and kidney functions. Results showed that gamma radiation caused significant decline (P<0.05) in serum total antioxidant, total protein, albumin, HDL-C and blood glucose with significant elevation (P<0.05) in other hepato-renal markers in addition to serum total cholesterol, triglycerides and LDL-C. These changes were significantly attenuated in irradiated animals pre-treated with whole fresh pomegranate fruit leading to the conclusion that pre-intake of pomegranate fruit had a radio- protective effect. This protection of this whole fruit may be due to the increased total antioxidant level leading to free radical scavenging

  16. Study on Fractionated Total Body Irradiation before Hematopoietic Stem Cell Transplantation

    Institute of Scientific and Technical Information of China (English)

    Tong Fang; Bo Liu; Hong Gao

    2009-01-01

    OBJECTIVE To observe the dose and the complications from total body irradiation before hematopoietic stem cell transplantation.METHODS This study involved 312 patients with total body irradiation before hematopoietic stem cell transplantation. They were entered into the treated research from May 1999 to October 2005. All patients had Received the irradiation from 60Co of an absorbed dose rate of (5.2 ± 1.13) cGy/min. The total dose of TBI was 7~12 Gy, 1 f/d × 2 d. A high-dose rate group (≥ 10 Gy) included 139 cases and a low-dose rate group (< 10 Gy) included 173 cases.RESULTS The probability of acute gastrointestinal reactions in the high-dose rate group was more compared with that in the low-dose rate group. The differences for other reactions, such as hematopoietic reconstitution and graft survival rate, between the two groups were insignificant.CONCLUSION Using fractional total body irradiation at a dose rate of 5 cGy/min, with a total dose of 7~12 Gy, 1 f/d x 2 d, with the lung receiving under 7.5 Gy is a safe and effective pretreatment for hematopoietic stem cell transplantation.

  17. Low Dietary Protein Status Potentiating Risk of Health Hazard in Whole Body Gamma Irradiated Rats

    International Nuclear Information System (INIS)

    Investigations were planned to assess the changes in certain biochemical parameters as affected by the synergistic effect of exposure to fractionated doses of rays and / or feeding on different protein levels. The date showed that animals kept on normal or low protein diet exhibited a significant decrease in serum total protein and glucose. Also , a significant increase was recorded in insulin level in rats exposed at the radiation dose level of 20 Gy. Exposure to cumulative doses of irradiation has aggrevated the hyperglycemic effect of high protein diet with a significant and marked increase of insulin at all the applied doses. Animals fed normal high or low protein diet were found to exert significant decreases in T3, T4 while a significant increase in TSH of high protein group occurred as a result of exposure to cumulative doses of gamma-irradiation. Rats kept on low protein diet exhibited losses in body weight, hypercholesterolemia, low levels of phospholipids and triglycerides as compared with the normal protein diet group. In contrast high protein diet group showed no serious effects. Irradiation has potentiated body weight losses, hypotriglyceridemia and hypercholesterolemia in animal group fed low protein diet with a significant increase in serum phospholipids due to the higher radiation dose of 20 Gy. Protein deficiency acted synergistically with gamma irradiation and increased the susceptibility of body organs to radiation damage. Such findings contributed to the knowledge which stimulated the decrease of the internationally recognized occupational dose limits from 50 down to 20 m Sv (ICRP 1991)

  18. Effect of whole body gamma irradiation on delayed hypersensitivity to dinitrofluorobenzene in CBA mice

    International Nuclear Information System (INIS)

    Effect of whole body γ-irradiation of CBA mice on the subsequent development of delayed hypersensitivity (DH) response to 2,4 dinitrofluorobenzene (DNFB) was studied. Mice were irradiated with 60Co-γrays 24 hr prior to the first epicutaneous sensitization with DNFB. Mice irradiated at doses up to 1.08 Gy showed unaltered DH response. Increasing doses resulted in progressive suppression of DH response and the D50 was 3.86 Gy. Marked reduction in the number of lymph node cells was observed in irradiated, sensitized as well as unsensitized mice. This could be due to interphase death of precursor cells (antigen-sensitive cells), resulting in lower number of effector lymphocytes for DH(Tsub(DH)). Furthermore, the maximum DH response in irradiated, sensitized mice was obtained later on in comparison with the controls. The effector lymphocytes from irradiated sensitized mice were, however, functionally unimpaired. It was observed that the radiation-induced suppression of DH to DNFB in these mice could be partly due to the damage to antigen sensitive cells and also to the cells other than effector lymphocytes which participated in the inflammatory reaction. (author)

  19. Final height and gonad function after total body irradiation during childhood.

    Science.gov (United States)

    Couto-Silva, A-C; Trivin, C; Esperou, H; Michon, J; Baruchel, A; Lemaire, P; Brauner, R

    2006-09-01

    Short stature and gonad failure can be a side effect of total body irradiation (TBI). The purpose of the study was to evaluate the factors influencing final height and gonad function after TBI. Fifty young adults given TBI during childhood were included. Twenty-seven had been treated with growth hormone (GH). Those given single 10 Grays (Gy) or fractionated 12 Gy TBI had similar characteristics, GH peaks, final heights and gonad function. After the end of GH treatment, 11/20 patients evaluated had GH peak >10 microg/l. Final height was irradiated (Pirradiation, taking into account the GH peak. The plasma FSH and inhibin B concentrations may predict sperm function.

  20. Whole body surface electron irradiation in the treatment of mycosis fungoides

    Energy Technology Data Exchange (ETDEWEB)

    Lo, T.C.M.; Salzman, F.A.; Moschella, S.L.; Tolman, E.L.; Wright, K.A.

    1979-02-01

    The records of 200 patients with generalized cutaneous mycosis fungoides treated with whole body surface electron irradiation were reviewed. Type of skin lesion appeared to be the most important factor with respect to both survival and generalized skin disease-free interval. High-dose irradiation did not seem to influence prognosis significantly compared with a relatively conservative dose. The cure rate for the entire group was 7%. For a more homogeneous dose distribution, the eight-field technique is now used instead of the original four-field method. A new formula is proposed to standardize the reporting of doses.

  1. He-Ne Laser Auricular Irradiation Plus Body Acupuncture for Treatment of Acne Vulgaris in 36 Cases

    Institute of Scientific and Technical Information of China (English)

    Sun Lihong

    2006-01-01

    In order to observe the therapeutic effects of He-Ne laser auricular irradiation plus body acupuncture for acne vulgaris, 68 cases of acne vulgaris were randomly divided into a treatment group of 36 cases treated with He-Ne laser auricular irradiation plus body acupuncture, and a control group of 32 cases treated with body acupuncture only. The results showed that the cure rate was 77.8% in the treatment group and 46.9% in the control group (P<0.05), indicating that He-Ne laser auricular irradiation plus body acupuncture may exhibit better effects for acne vulgaris.

  2. The carcinogenic risk of high dose total body irradiation in non-human primates

    International Nuclear Information System (INIS)

    High dose total body irradiation (TBI) in combination with chemotherapy, followed by rescue with bone marrow transplantation (BMT), is increasingly used for the treatment of haematological malignancies. With the increasing success of this treatment and its current introduction for treating refractory autoimmune diseases the risk of radiation carcinogenesis is of growing concern. Studies on turnout induction in non-human primates are of relevance in this context since the response of this species to radiation does not differ much from that in man. Since the early sixties, studies have been performed on acute effects in Rhesus monkeys and the protective action of bone marrow transplantation after irradiation with X-rays (average total body dose 6.8 Gy) and fission neutrons (average dose 3.4 Gy). Of those monkeys, which were irradiated and reconstituted with autologous bone marrow, 20 animals in the X-irradiated group and nine animals in the neutron group survived more than 3 years. A group of 21 non-irradiated Rhesus monkeys of a comparable age distribution served as controls. All animals were regularly screened for the occurrence of neoplasms. Complete necropsies were performed after natural death or euthanasia. At post-irradiation intervals of 4-21 years an appreciable number of tumours was observed. In the neutron irradiated group eight out of nine animals died with one or more malignant tumours. In the X-irradiated group this fraction was 10 out of 20. The tumours in the control group, in seven out of the 21 animals, appeared at much older a-e compared with those in the irradiated cohorts. The histogenesis of the tumours was diverse with a preponderance of renal carcinoma, sarcomas among which osteosarcormas, and malignant glomus tumours in the irradiated groups. When corrected for competing risks, the carcinogenic risk of TBI in the Rhesus monkeys is similar to that derived from the studies of the Japanese atomic bomb survivors. The increase of the risk by a

  3. Optimum combination of targeted 131I and total body irradiation for treatment of disseminated cancer

    International Nuclear Information System (INIS)

    Purpose: Radiobiological modeling was used to explore optimum combination strategies for treatment of disseminated malignancies of differing radiosensitivity and differing patterns of metastatic spread. The purpose of the study was to derive robust conclusions about the design of combination strategies that incorporate a targeting component. Preliminary clinical experience of a neuroblastoma treatment strategy, which is based upon general principles obtained from modelling, is briefly described. Methods and Materials: The radiobiological analysis was based on an extended (dose-rate dependent) formulation of the linear quadratic model. Radiation dose and dose rate for targeted irradiation of tumors of differing size was in part based on microdosimetric considerations. The analysis was applied to several tumor types with postulated differences in the pattern of metastatic spread, represented by the steepness of the slope of the relationship between numbers of tumors present and tumor diameter. The clinical pilot study entailed the treatment of five children with advanced neuroblastoma using a combination of 131I metaiodobenzylguanidine (mIBG) and total body irradiation followed by bone marrow rescue. Results: The theoretical analysis shows that both intrinsic radiosensitivity and pattern of metastatic spread can influence the composition of the ideal optimum combination strategy. High intrinsic radiosensitivity generally favors a high proportion of targeting component in the combination treatment, while a strong tendency to micrometastatic spread favors a major contribution by total body irradiation. The neuroblastoma patients were treated using a combination regimen with an initially low targeting component (2 Gy whole body dose from targeting component plus 12 Gy from total body irradiation). The treatment was tolerable and resulted in remissions in excess of 9 months in each of these advanced neuroblastoma patients. Conclusions: Radiobiological analysis, which

  4. Establishment of a mouse model of 70% lethal dose by total-body irradiation.

    Science.gov (United States)

    Ryu, Seung-Hyun; Park, Jong-Hyung; Jeong, Eui-Suk; Choi, Soo-Young; Ham, Seung-Hoon; Park, Jin-Il; Jeon, Hee-Yeon; Kim, Jun-Young; Yoo, Ran-Ji; Lee, Yong-Jin; Woo, Sang-Keun; Choi, Yang-Kyu

    2016-06-01

    Whereas increasing concerns about radiation exposure to nuclear disasters or side effects of anticancer radiotherapy, relatively little research for radiation damages or remedy has been done. The purpose of this study was to establish level of LD70/30 (a lethal dose for 70% of mice within 30 days) by total-body γ irradiation (TBI) in a mouse model. For this purpose, at first, 8-week-old male ICR and C57BL/6N mice from A and B companies were received high dose (10, 11, 12 Gy) TBI. After irradiation, the body weight and survival rate were monitored for 30 days consecutively. In next experiment, 5-week-old male ICR and C57BL/6N mice from B company were received same dose irradiation. Results showed that survival rate and body weight change rate in inbred C57BL/6N mice were similar between A and B company. In ICR mice, however, survival rate and body weight change rate were completely different among the companies. Significant difference of survival rate both ICR and C57BL6N mice was not observed in between 5-week-old and 8-week-old groups receiving 10 or 12 Gy TBI. Our results indicate that the strain and age of mice, and even purchasing company (especially outbred), should be matched over experimental groups in TBI experiment. Based on our results, 8-week-old male ICR mice from B company subjected to 12 Gy of TBI showed LD70/30 and suitable as a mouse model for further development of new drug using the ideal total-body irradiation model.

  5. Establishment of a mouse model of 70% lethal dose by total-body irradiation.

    Science.gov (United States)

    Ryu, Seung-Hyun; Park, Jong-Hyung; Jeong, Eui-Suk; Choi, Soo-Young; Ham, Seung-Hoon; Park, Jin-Il; Jeon, Hee-Yeon; Kim, Jun-Young; Yoo, Ran-Ji; Lee, Yong-Jin; Woo, Sang-Keun; Choi, Yang-Kyu

    2016-06-01

    Whereas increasing concerns about radiation exposure to nuclear disasters or side effects of anticancer radiotherapy, relatively little research for radiation damages or remedy has been done. The purpose of this study was to establish level of LD70/30 (a lethal dose for 70% of mice within 30 days) by total-body γ irradiation (TBI) in a mouse model. For this purpose, at first, 8-week-old male ICR and C57BL/6N mice from A and B companies were received high dose (10, 11, 12 Gy) TBI. After irradiation, the body weight and survival rate were monitored for 30 days consecutively. In next experiment, 5-week-old male ICR and C57BL/6N mice from B company were received same dose irradiation. Results showed that survival rate and body weight change rate in inbred C57BL/6N mice were similar between A and B company. In ICR mice, however, survival rate and body weight change rate were completely different among the companies. Significant difference of survival rate both ICR and C57BL6N mice was not observed in between 5-week-old and 8-week-old groups receiving 10 or 12 Gy TBI. Our results indicate that the strain and age of mice, and even purchasing company (especially outbred), should be matched over experimental groups in TBI experiment. Based on our results, 8-week-old male ICR mice from B company subjected to 12 Gy of TBI showed LD70/30 and suitable as a mouse model for further development of new drug using the ideal total-body irradiation model. PMID:27382380

  6. Increased sensitivity of C. parvum treated mice to ionizing whole body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Basic, I.; Withers, R.H.; Kastelan, A.; Milas, L.

    1977-04-13

    We have investigated whether C. parvum (CP)-induced stimulation of hematopoiesis affects the survival of mice exposed to the whole body irradiation (WBI). C3Hf/Bu mice treated with CP exhibit an increased hematopoietic colony forming activity in their spleens and blood, but not in their bone marrow, as determined by the exogenous spleen colony assay. Also, CP-treated C3Hf/Bu as well as CBA mice show an increase in their endogenous colonies. This increased hematopoietic activity caused by CP treatment did not protect mice from the consequences of the WBI ranging from 650 to 950 rads. In fact, more mice died if they had been treated with CP. A decrease in the number of erythrocytes was more pronouned in mice treated with CP and irradiation than in those given irradiation alone.

  7. Tissue air ratio in total body irradiation. An in vivo evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Scarpati, D.; Mancini, G.; Corvo, R.; Franzone, P.

    1989-01-01

    On the basis of dose readings in 102 patients treated with total body irradiation (TBI), a 'tissue air ratio (TAR) curve' has been produced. It could be useful to precalculate treatment time in TBI, for dose prescription to a specific point, provided the same source (/sup 60/Co) and treatment setting (lateral irradiation; 3 m source-axis distance; reference point at thighs bifurcation, neat the perineum) is used. The TAR curve produced, and the formula relating tissue depth to TAR value, are presented, and compared to preexisting data for 'magna fields' treatments. This curve is exponential, and in semilog representation becomes straight, as every classic TAR curve; it is lower than others, reflecting non full-scatter situation in patient irradiation. (orig.).

  8. Dose-effect relationships in total body irradiation on the healing of cutaneous wounds

    Institute of Scientific and Technical Information of China (English)

    冉新泽; 程天民; 林远; 屈纪富; 刘都户; 艾国平; 阎国和; 王文昌; 许汝福

    2003-01-01

    ObjectiveTo study the effects of dosages of total body irradiation on the healing process of cutaneous wounds and to observe the changes of wound area at different periods after injury.star rats. The single dosage varied from 1 to 8 Gy. Within 1 h after irradiation, two whole thickness circular cutaneduced on the back of the animals (combined injury groups). Same wounds were produced on rats with no irradiation (single wound group). Wound healing was observed at different points after injury. ResultsAfter total body irradiation with the dose of 1,2,3,4,5,6, 7 or 8 Gy, the wound healing was obviously retarded as the dosages increased. The wound area remained was larger in the large dosage groups than in the small dosage groups. Seven days after injury, there was 33.5% wound surface left unhealed in the single wound group, whereas in the combined injury groups, 35.4%, 38.1%, 41.6%, 48.8%, 53.9%, 63.7%, 69.2% and 73.9% of the wound surfaces remained unhealed, respectively. Statistical analysis showed marked correlations between the varioustimes after total body irradiation and various dosages to the percentage of unhealed wound surface. Nine dose-effect relation formulae were deduced according to the statistical results.ConclusionsIn soft tissue trauma combined with radiation injury, the delay of wound healingis related to the dose of radiation inflicted. It is also related to the time between injury and time of observation.

  9. Sesamol attenuates cytogenetic damages in bone marrow cells of whole body gamma irradiated mice

    International Nuclear Information System (INIS)

    Whole body radiation exposure cause damages to all vital organs and bone marrow is the most sensitive. Pre-treatment with antioxidant as single prophylactic dose is expected to lower induction of damages in bone marrow. In the present study we have focused on sesamol, a dietary antioxidant mediated radioprotection in bone marrow cells of gamma irradiated mice and compared with melatonin. Male C57BL/6 mice were intraperitoneally administered with sesamol (10 and 20 mg/kg body) and after 30 minutes exposed to whole body gamma radiation using 60Co Teletherapy unit. Mice were injected with 0.2 ml of a metaphase arresting agent (0.05% colchicine) intra-peritoneally 3 hours prior to sacrifice (24 hrs. post-irradiation). Bone marrow cells were flushed out from femurs of each animal and processed for chromosomal aberration assay. Another set of experiment without colchicine injection was performed to access the DNA damage in bone marrow using alkaline comet assay. At least 100 metaphases per animal were scored under light microscope to record various aberrations and total chromosomal aberrations (TCA) was calculated. Similar measurements were performed with melatonin for comparing the efficacy of sesamol. Gamma irradiation has increased the chromatid type aberrations (break formation, fragment) and chromosomal type aberrations (ring formation, acentric) in bone marrow cells. The results have shown significant (p< 0.001) increase in TCA of irradiated mice than control. While pre-treatment of sesamol and melatonin 10 mg/kg significantly (p<0.05) reduced the TCA. The extend of protection has increased at 20 mg/kg significantly (p<0.001) as evident from the reduced TCA compared to irradiated group. Interestingly, sesamol and melatonin have shown similar extent of reduction of TCA. Thus sesamol has demonstrated strong ability to protect bone marrow at low dosage. These investigations on sesamol mediated protection in bone marrow are likely to benefit development of

  10. Predictive models of insulin resistance derived from simple morphometric and biochemical indices related to obesity and the metabolic syndrome in baboons

    OpenAIRE

    Bastarrachea Raúl A; Davalli Alberto; Casiraghi Francesca; Sorice GianPio; Tejero M Elizabeth; Leland M Michelle; Lopez-Alvarenga Juan C; Guardado-Mendoza Rodolfo; Gastaldelli Amalia; Chavez Alberto O; Comuzzie Anthony G; DeFronzo Ralph A; Folli Franco

    2009-01-01

    Abstract Background Non-human primates are valuable models for the study of insulin resistance and human obesity. In baboons, insulin sensitivity levels can be evaluated directly with the euglycemic clamp and is highly predicted by adiposity, metabolic markers of obesity and impaired glucose metabolism (i.e. percent body fat by DXA and HbA1c). However, a simple method to screen and identify obese insulin resistant baboons for inclusion in interventional studies is not available. Methods We st...

  11. DNA damage focus analysis in blood samples of minipigs reveals acute partial body irradiation.

    Directory of Open Access Journals (Sweden)

    Andreas Lamkowski

    Full Text Available Radiation accidents frequently involve acute high dose partial body irradiation leading to victims with radiation sickness and cutaneous radiation syndrome that implements radiation-induced cell death. Cells that are not lethally hit seek to repair ionizing radiation (IR induced damage, albeit at the expense of an increased risk of mutation and tumor formation due to misrepair of IR-induced DNA double strand breaks (DSBs. The response to DNA damage includes phosphorylation of histone H2AX in the vicinity of DSBs, creating foci in the nucleus whose enumeration can serve as a radiation biodosimeter. Here, we investigated γH2AX and DNA repair foci in peripheral blood lymphocytes of Göttingen minipigs that experienced acute partial body irradiation (PBI with 49 Gy (± 6% Co-60 γ-rays of the upper lumbar region. Blood samples taken 4, 24 and 168 hours post PBI were subjected to γ-H2AX, 53BP1 and MRE11 focus enumeration. Peripheral blood lymphocytes (PBL of 49 Gy partial body irradiated minipigs were found to display 1-8 DNA damage foci/cell. These PBL values significantly deceed the high foci numbers observed in keratinocyte nuclei of the directly γ-irradiated minipig skin regions, indicating a limited resident time of PBL in the exposed tissue volume. Nonetheless, PBL samples obtained 4 h post IR in average contained 2.2% of cells displaying a pan-γH2AX signal, suggesting that these received a higher IR dose. Moreover, dispersion analysis indicated partial body irradiation for all 13 minipigs at 4 h post IR. While dose reconstruction using γH2AX DNA repair foci in lymphocytes after in vivo PBI represents a challenge, the DNA damage focus assay may serve as a rapid, first line indicator of radiation exposure. The occurrence of PBLs with pan-γH2AX staining and of cells with relatively high foci numbers that skew a Poisson distribution may be taken as indicator of acute high dose partial body irradiation, particularly when samples are available

  12. Enhancement of committed hematopoietic stem cell colony formation by nandrolone decanoate after sublethal whole body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Gallicchio, V.S.; Chen, M.G.; Watts, T.D.

    1984-11-01

    The ability of an anabolic steroid, nandrolone decanoate, to increase committed topoietic stem cell (CFU-gm, CFU-e, and BFU-e) colony formation after sublethal irradiation was evaluated. Immediately after receiving whole body irradiation and on the next two days, each mouse was injected intraperitoneally with nandrolone decanoate (1.25 mg) in propylene glycol. Irradiated control mice received only propylene glycol. Compared to controls, drug-treated mice showed marked peripheral blood leukocytosis and more stable packed red cell volume. Drug-treated mice also demonstrated increased erythropoiesis, as CFU-e/BFU-e concentrations from both marrow (9% to 581%) and spleen (15% to 797%) were elevated. Granulopoiesis was increased similarly, as CFU-gm concentrations from marrow (38% to 685%) and spleen (9% to 373%) were elevated. These results demonstrate that nandrolone decanoate enhances hematopoietic stem cell recovery after sublethal whole body irradiation. This suggests that following hematopoietic suppression, nandrolone decanoate may stimulate the recovery of hematopoiesis at the stem cell level and in peripheral blood.

  13. Anorexia in rats after protracted whole-body irradiation with low doses

    International Nuclear Information System (INIS)

    In our experiments, carried out hitherto, concerning the effect of incorporated and radioactive substances, weight behaviour and food uptake have proved to be a sensitive test. With regard to these experiments and the half-life of the radionuclides used, it is reported about trial series in Wistar rats. These rats were applied, with Co-60 gamma irradiation, different whole-body doses protracted over 48 hours. A total of 32 groups of experimental animals (20 animals each) was exposed to irradiation doses of lethal, medium lethal, and sublethal ranges, control and pseudo-irradiation series included. The experiments were carried out under observance of constant irradiation and attitude conditions, night and day changes, as conditioned by the season, included. Even in the inferior sublethal range (12 to 24 R), a significant trend of decreased food uptake is registered. This trend remains for a short period after the end of irradiation, but then it returns to normal conditions. Furthermore, a new decrease with subsequent increase seems to become evident - about ten days after termination of the radiotherapy (especially after several hundred R); report about these items will be made later on. (orig.)

  14. Effects of supralethal total body irradiation and bone marrow reconstitution upon immunologic memory

    International Nuclear Information System (INIS)

    The transplantation of bone marrow from prospectively selected genotypically and pedigree DLA-identical donors into supralethally irradiated littermate and nonlittermate recipients within the Copperstown beagle colony has regularly resulted in the establishment of long-term chimerism, with no evidence of graft-versus-host disease in the recipients. It has been demonstrated that irradiated recipients exhibit significant decreases in their ability to muster primary immunological responses during the first months after reconstitution with bone marrow. Beyond the documented capacity of preirradiation blood transfusions to interfere with subsequent engraftment of allogeneic marrow, however, there have been no systematic studies of the possible effects of irradiation and bone marrow transplantation upon immunologic memory. The present study was designed in order to assess this question in greater detail, with particular regard to the effects of irradiation and bone marrow reconstitution upon host sensitization to skin allografts. The results indicate that, within the experimental limitations described, the state of sensitivity produced by first set skin allograft rejection is not affected significantly by supralethal total body irradiation and reconstitution of the recipient with allogeneic bone marrow

  15. Kidney and lung injury in irradiated rats protected from acute death by partial-body shielding

    International Nuclear Information System (INIS)

    Ninety-six CD-1 male rats were exposed to gamma-ray doses (0-25 Gy) in increments of 5 Gy. One femur, the surgically exteriorized GI tract, and the oral cavity were shielded during irradiation to protect against acute mortality from injury to the hematopoietic system, small intestine, and oral cavity. In addition, the thoraxes of half of the animals from each dose group were shielded. At approximately monthly intervals from 2 to 10 months after irradiation the hematocrit, plasma urea nitrogen (PUN), and 51Cr-EDTA clearance were measured. During the study 20 thorax-shielded and 19 thorax-irradiated animals died. All rats whose thoraxes received 25 Gy irradiation and three out of seven rats whose thoraxes received 20 Gy died 1 to 3 months postirradiation with massive pleural fluid accumulation. Shielding the thoraxes prevented this mode of death at these doses. Kidney injury was judged to be the primary cause of death of all thorax-shielded animals and 15- and 20-Gy thorax-irradiated animals. Animals with kidney damage had elevated PUN and reduced 51Cr-EDTA clearance and hematocrits. The relative merits of each of these end points in assessing radiation-induced kidney injury after total-body exposure are discussed

  16. Insulin-Like Growth Factor 1 Mitigates Hematopoietic Toxicity After Lethal Total Body Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Dunhua; Deoliveira, Divino; Kang, Yubin; Choi, Seung S. [Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Li, Zhiguo [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Chao, Nelson J. [Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States); Department of Pathology, Duke University Medical Center, Durham, North Carolina (United States); Department of Immunology, Duke University Medical Center, Durham, North Carolina (United States); Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Chen, Benny J., E-mail: chen0032@mc.duke.edu [Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Department of Medicine, Duke University Medical Center, Durham, North Carolina (United States)

    2013-03-15

    Purpose: To investigate whether and how insulin-like growth factor 1 (IGF-1) mitigates hematopoietic toxicity after total body irradiation. Methods and Materials: BALB/c mice were irradiated with a lethal dose of radiation (7.5 Gy) and treated with IGF-1 at a dose of 100 μg/dose intravenously once a day for 5 consecutive days starting within 1 hour after exposure. Survival and hematopoietic recovery were monitored. The mechanisms by which IGF-1 promotes hematopoietic recovery were also studied by use of an in vitro culture system. Results: IGF-1 protected 8 of 20 mice (40%) from lethal irradiation, whereas only 2 of 20 mice (10%) in the saline control group survived for more than 100 days after irradiation. A single dose of IGF-1 (500 μg) was as effective as daily dosing for 5 days. Positive effects were noted even when the initiation of treatment was delayed as long as 6 hours after irradiation. In comparison with the saline control group, treatment with IGF-1 significantly accelerated the recovery of both platelets and red blood cells in peripheral blood, total cell numbers, hematopoietic stem cells, and progenitor cells in the bone marrow when measured at day 14 after irradiation. IGF-1 protected both hematopoietic stem cells and progenitor cells from radiation-induced apoptosis and cell death. In addition, IGF-1 was able to facilitate the proliferation and differentiation of nonirradiated and irradiated hematopoietic progenitor cells. Conclusions: IGF-1 mitigates radiation-induced hematopoietic toxicity through protecting hematopoietic stem cells and progenitor cells from apoptosis and enhancing proliferation and differentiation of the surviving hematopoietic progenitor cells.

  17. Technical modifications in hyperfractionated total body irradiation for T-lymphocyte deplete bone marrow transplant

    International Nuclear Information System (INIS)

    The Medical College of Wisconsin implemented a major bone marrow transplant (BMT) program in July 1985. The type of transplants to be focused on were allogeneic T-lymphocyte deplete. Total body irradiation (TBI) was initially patterned after the Memorial method. Patients received total body irradiation in a sitting position at a dose rate of 20-25 cGy/minute with 50% attenuation lung blocks used both anterior/posterior and posterior/anterior. Electron boosting was utilized for the ribs beneath the lung blocks. Occasionally, lower extremity boosting was required because of the sitting position. A dose of 14 Gy was chosen since T-lymphocyte deplete bone marrow transplant data suggest the need for higher total doses to consistently obtain engraftment. This dose was given in 3 equal daily fractions over 3 days following conditioning chemotherapy. Six of 11 patients treated in this manner developed lethal pulmonary events. In response to the pulmonary toxicity, partial lung shielding was increased to 60% attenuation. In the next 107 patients receiving this program of total body irradiation there was a reduced incidence of fatal pulmonary events (10 cases of fatal idiopathic interstitial pneumonitis and 12 cases of fatal pulmonary infections) after a median follow-up of 9 months. This was an obvious improvement over the initial group. A significant level of hepato-renal toxicity was also observed with 14 Gy total body irradiation when no liver or kidney blocking was used. Of the first 20 patients treated, three cases of fatal veno-occlusive disease resulted. Subsequently, a 10% attenuation right sided liver block was added. Five of 98 patients treated with this block have developed fatal hepatic dysfunction, (median follow-up of 7.2 months)

  18. An Acute Transverse Myelitis Attack after Total Body Irradiation: A Rare Case

    OpenAIRE

    Ali Unal; Bulent Eser; Mustafa Cetin; Cigdem Pala; Serife Cingoz; Celalettin Eroglu; Serdar Sivgin; Leylagul Kaynar; Afra Yildirim; Muzaffer Keklik

    2013-01-01

    Total body irradiation (TBI) combined with chemotherapy is widely used as a pretreatment regimen of bone marrow transplantation (BMT) in hematologic disorders. Late complications related to TBI as part of the conditioning regimen for hematopoietic stem cell transplantation have been revealed. Acute transverse myelitis (ATM) is a neurological syndrome characterized by disorder of motor, sensorial, and autonomic nerves, and tracts at medulla spinalis, which is resulted from involvement of spina...

  19. Late effects on gonadal function of cyclophosphamide, total-body irradiation, and marrow transplantation

    International Nuclear Information System (INIS)

    One hundred thirty-seven patients had gonadal function evaluated 1-11 years after marrow transplantation. All 15 women less than age 26 and three of nine older than age 26 who were treated with 200 mg/kg cyclophosphamide recovered normal gonadotropin levels and menstruation. Five have had five pregnancies resulting in three live births, one spontaneous abortion, and one elective abortion. Three of 38 women who were prepared with 120 mg/kg cyclophosphamide and 920-1200 rad total-body irradiation had normal gonadotropin levels and menstruation. Two had pregnancies resulting in one spontaneous and one elective abortion. Of 31 men prepared with 200 mg/kg cyclophosphamide, 30 had normal luteinizing hormone levels, 20 had normal follicle-stimulating hormone levels, and 10 of 15 had spermatogenesis. Four have fathered five normal children. Thirty-six of 41 men prepared with 120 mg/kg cyclophosphamide and 920-1750 rad total-body irradiation had normal luteinizing hormone levels, ten had normal follicle-stimulating hormone levels, and 2 of 32 studied had spermatogenesis. One has fathered two normal children. It was concluded that cyclophosphamide does not prevent return of normal gonadal function in younger women and in most men. Total-body irradiation prevents return of normal gonadal function in the majority of patients

  20. Plutonium gastrointestinal absorption by adults baboons

    International Nuclear Information System (INIS)

    Gastrointestinal absorption of plutonium was investigated in baboons after ingestion of plutonium solution (oxidation states III; IV; V; VI), and plutonium incorporated in soya bean and winkles. We studied the effects of oxidation state and ingested mass for masses ranging from 0.35 μg to 51.6 x 10+3 μg (4 x 10-2 to 7776 μg of plutonium per kg of body weight). No clear increase in plutonium retention was shown for concentrations of plutonium smaller than 1 μg/kg. From 1 μg/kg to 1 mg/kg no effects of mass or oxidation state was observed and the mean fractional retention value was 10-4. For ingested masses higher than 1 mg/kg the fractional retention values respectively increased for Pu(V) and Pu(III) to (0.9 + 0.2) x 10-2 and (7.4+ 4.1) x 10-4 of the ingested mass. This increase might be due to the weak hydrolysis of these oxidation states which would increase gastrointestinal absorption by decrease of hydroxide formation. The fraction of plutonium retained after ingestion of soya bean was (3.0 + 0.5) x 10-4 about 3 fold higher than the value for 238 Pu nitrate solution. No clear increase in plutonium retention was shown after ingestion of winkles containing 238 Pu. In conclusion, except for high masses of ingested Pu, the retention of which could reach 1% of the ingested dose, our results show that the gastrointestinal transfer factor of 10-4 proposed by ICRP for gastrointestinal absorption of soluble form of Pu is acceptable, but 10-3 would provide better safety margin

  1. A tethering system for direct measurement of cardiovascular function in the caged baboon

    Science.gov (United States)

    Byrd, L. D.

    1979-01-01

    A device suitable for the continuous measurement of physiological activity in large, conscious monkeys has permitted the direct recording of systemic arterial blood pressure and heart rate in caged baboons. The device comprises a lightweight fiberglass backpack, retained in place on the baboon by a thoracic elastic band and shoulder straps, and a flexible stainless steel tether connecting the pack to an electrocannular slip-ring in the top center of the baboon's cage. A chronically indwelling arterial catheter inserted retrograde into the abdominal aorta via the internal iliac artery and connected to a small pressure transducer on the pack provides direct measurement of blood pressure and heart rate. Body fluids can be sampled or drugs administered via an indwelling catheter in the inferior vena cava. Electrical and fluid connections between the fiberglass pack and recording and infusion equipment located outside the cage pass through the flexible tether and remain protected from the subject. The reliability of the tethering system has been demonstrated in physiological, pharmacological, and behavioral experiments with baboons.

  2. Mitigating effects of hUCB-MSCs on the hematopoietic syndrome resulting from total body irradiation.

    Science.gov (United States)

    Shim, Sehwan; Lee, Seung Bum; Lee, Jong-geol; Jang, Won-Suk; Lee, Sun-Joo; Park, Sunhoo; Lee, Seung-Sook

    2013-04-01

    This study evaluated the clinical and pathologic effects of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in the recovery from total body irradiation by comparing it with the effects of granulocyte-colony stimulating factor (G-CSF), an efficacious drug in the treatment of acute bone marrow radiation syndrome. BALB/c mice were treated with G-CSF or hUCB-MSCs after they were irradiated with 7 Gy cobalt-60 γ-rays. Circulating blood counts, histopathologic changes in the bone marrow, and plasma level of Flt-3L and transforming growth factor (TGF-β1) were monitored in the postirradiation period. Hematologic analysis revealed that the peripheral leukocyte counts were markedly increased in the hUCB-MSCs-treated group, whereas G-CSF-treated mice did not recover significantly. Moreover, differential counts showed that hUCB-MSC treatment has regenerative effects on white blood cells, lymphocytes, and monocytes compared with the irradiated group. Treatment with hUCB-MSCs or G-CSF significantly increased immunoreactivity of Ki-67 until 3 weeks after total body irradiation. However, at 3 weeks, the number of Ki-67 immunoreactive cells significantly increased in the hUCB-MSCs-treated group compared with the G-CSF-treated group. Furthermore, hUCB-MSC treatment significantly modulated plasma levels of the hematopoietic cytokines Flt-3L and TGF-β1, whereas G-CSF treatment failed to decrease the plasma Flt-3L levels at 2 weeks after irradiation. Based on the differences in circulating blood cell reconstitution and cell density of bone marrow, the authors suggest that MSC treatment is superior to G-CSF treatment for hematopoietic reconstitution following sublethal dose radiation exposure.

  3. Lymphoid and Myeloid Recovery in Rhesus Macaques Following Total Body X-Irradiation.

    Science.gov (United States)

    Farese, Ann M; Hankey, Kim G; Cohen, Melanie Veirs; MacVittie, Thomas J

    2015-11-01

    Recovery from severe immunosuppression requires hematopoietic stem cell reconstitution and effective thymopoiesis to restore a functional immune cell repertoire. Herein, a model of immune cell reconstitution consequent to potentially lethal doses of irradiation is described, which may be valuable in evaluating potential medical countermeasures. Male rhesus macaques were total body irradiated by exposure to 6.00 Gy 250 kVp x-radiation (midline tissue dose, 0.13 Gy min), resulting in an approximate LD10/60 (n = 5/59). Animals received medical management, and hematopoietic and immune cell recovery was assessed (n ≤ 14) through 370 d post exposure. A subset of animals (n ≤ 8) was examined through 700 d. Myeloid recovery was assessed by neutrophil and platelet-related parameters. Lymphoid recovery was assessed by the absolute lymphocyte count and FACS-based phenotyping of B- and T-cell subsets. Recent thymic emigrants were identified by T cell receptor excision circle quantification. Severe neutropenia, lymphopenia, and thrombocytopenia resolved within 30 d. Total CD3+ cells μL required 60 d to reach values 60% of normal, followed by subsequent slow recovery to approximately normal by 180 d post irradiation. Recovery of CD3+4+ and CD3+8+ cell memory and naïve subsets were markedly different. Memory populations were ≥ 100% of normal by day 60, whereas naïve populations were only 57% normal at 180 d and never fully recovered to baseline post irradiation. Total (CD20+) B cells μL were within normal levels by 77 d post exposure. This animal model elucidates the variable T- and B-cell subset recovery kinetics after a potentially lethal dose of total-body irradiation that are dependent on marrow-derived stem and progenitor cell recovery, peripheral homeostatic expansion, and thymopoiesis.

  4. Enhanced responses to tumor immunization following total body irradiation are time-dependent.

    Directory of Open Access Journals (Sweden)

    Adi Diab

    Full Text Available The development of successful cancer vaccines is contingent on the ability to induce effective and persistent anti-tumor immunity against self-antigens that do not typically elicit immune responses. In this study, we examine the effects of a non-myeloablative dose of total body irradiation on the ability of tumor-naïve mice to respond to DNA vaccines against melanoma. We demonstrate that irradiation followed by lymphocyte infusion results in a dramatic increase in responsiveness to tumor vaccination, with augmentation of T cell responses to tumor antigens and tumor eradication. In irradiated mice, infused CD8(+ T cells expand in an environment that is relatively depleted in regulatory T cells, and this correlates with improved CD8(+ T cell functionality. We also observe an increase in the frequency of dendritic cells displaying an activated phenotype within lymphoid organs in the first 24 hours after irradiation. Intriguingly, both the relative decrease in regulatory T cells and increase in activated dendritic cells correspond with a brief window of augmented responsiveness to immunization. After this 24 hour window, the numbers of dendritic cells decline, as does the ability of mice to respond to immunizations. When immunizations are initiated within the period of augmented dendritic cell activation, mice develop anti-tumor responses that show increased durability as well as magnitude, and this approach leads to improved survival in experiments with mice bearing established tumors as well as in a spontaneous melanoma model. We conclude that irradiation can produce potent immune adjuvant effects independent of its ability to induce tumor ablation, and that the timing of immunization and lymphocyte infusion in the irradiated host are crucial for generating optimal anti-tumor immunity. Clinical strategies using these approaches must therefore optimize such parameters, as the correct timing of infusion and vaccination may mean the difference

  5. Influence of radioprotectors on total body weight evolution and on oxygen consumption in lethal dose irradiated animals. (Preliminary study)

    International Nuclear Information System (INIS)

    Comparison of total body weight evolution and oxygen consumption in lethal dose irradiated animals, protected by various well known radioprotective substances, isolated or in mixture, with evolution and consumption of non protected animals irradiated at the same dose and with these of check animals

  6. Short-term endocrine consequences of total body irradiation and bone marrow transplantation in children treated for leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Ryalls, M.; Tait, D.M.; Meller, S.T. (Royal Marsden Hospital, Sutton (United Kingdom)); Spoudeas, H.A.; Hindmarsh, P.C.; Brook, C.G.D. (Middlesex Hospital, London (United Kingdom)); Matthews, D.R. (Radcliffe Infirmary, Oxford (United Kingdom). Diabetes Research Lab.)

    1993-02-01

    We studied 24-h hormone profiles and hormonal responses to insulin-induced hypoglycaemia prospectively in 23 children of similar age and pubertal stage, nine of whom had received prior cranial irradiation and fourteen of whom had not before and 6-12 months after total body irradiation (TBI) for bone marrow transportation in leukaemia. (Author).

  7. Whole body UVA irradiation lowers systemic blood pressure by release of nitric oxide from intracutaneous photolabile nitric oxide derivates

    NARCIS (Netherlands)

    Opländer, C.; Volkmar, C.M.; Paunel-Görgülü, A.; van Faassen, E.E.H.; Heiss, C.

    2009-01-01

    Rationale: Human skin contains photolabile nitric oxide derivates like nitrite and S-nitroso thiols, which after UVA irradiation, decompose and lead to the formation of vasoactive NO. Objective: Here, we investigated whether whole body UVA irradiation influences the blood pressure of healthy volunte

  8. Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy

    International Nuclear Information System (INIS)

    Mitochondrial DNA (mtDNA) alterations, including mtDNA copy number and mtDNA 4977 bp common deletion (CD), are key indicators of irradiation-induced damage. The relationship between total body irradiation (TBI) treatment and mtDNA alterations in vivo, however, has not been postulated yet. The aim of this study is to analyze mtDNA alterations in irradiated human peripheral lymphocytes from acute lymphoblastic leukemia (ALL) patients as well as to take them as predictors for radiation toxicity. Peripheral blood lymphocytes were isolated from 26 ALL patients 24 hours after TBI preconditioning (4.5 and 9 Gy, respectively). Extracted DNA was analyzed by real-time PCR method. Average 2.31 times mtDNA and 0.53 fold CD levels were observed after 4.5 Gy exposure compared to their basal levels. 9 Gy TBI produced a greater response of both mtDNA and CD levels than 4.5 Gy. Significant inverse correlation was found between mtDNA content and CD level at 4.5 and 9 Gy (P = 0.037 and 0.048). Moreover, mtDNA content of lymphocytes without irradiation was found to be correlated to age. mtDNA and CD content may be considered as predictive factors to radiation toxicity

  9. Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy

    Directory of Open Access Journals (Sweden)

    Ji Fuyun

    2011-10-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA alterations, including mtDNA copy number and mtDNA 4977 bp common deletion (CD, are key indicators of irradiation-induced damage. The relationship between total body irradiation (TBI treatment and mtDNA alterations in vivo, however, has not been postulated yet. The aim of this study is to analyze mtDNA alterations in irradiated human peripheral lymphocytes from acute lymphoblastic leukemia (ALL patients as well as to take them as predictors for radiation toxicity. Methods Peripheral blood lymphocytes were isolated from 26 ALL patients 24 hours after TBI preconditioning (4.5 and 9 Gy, respectively. Extracted DNA was analyzed by real-time PCR method. Results Average 2.31 times mtDNA and 0.53 fold CD levels were observed after 4.5 Gy exposure compared to their basal levels. 9 Gy TBI produced a greater response of both mtDNA and CD levels than 4.5 Gy. Significant inverse correlation was found between mtDNA content and CD level at 4.5 and 9 Gy (P = 0.037 and 0.048. Moreover, mtDNA content of lymphocytes without irradiation was found to be correlated to age. Conclusions mtDNA and CD content may be considered as predictive factors to radiation toxicity.

  10. Optimized total body irradiation for induction of renal allograft tolerance through mixed chimerism in cynomolgus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Kimikawa, Masaaki; Kawai, Tatsuo; Ota, Kazuo [Tokyo Women`s Medical Coll. (Japan)

    1996-12-01

    We previously demonstrated that a nonmyeloablative preparative regimen can induce mixed chimerism and renal allograft tolerance between MHC-disparate non-human primates. The basic regimen includes anti-thymocyte globulin (ATG), total body irradiation (TBI, 300 cGy), thymic irradiation (TI, 700 cGy), splenectomy, donor bone marrow (DBM) infusion, and posttransplant cyclosporine therapy (CYA, discontinued after 4 weeks). To evaluate the importance and to minimize the toxicity of irradiation, kidney allografts were transplanted with various manipulations of the irradiation protocol. Monkeys treated with the basic protocol without TBI and TI did not develop chimerism or long-term allograft survival. In monkeys treated with the full protocol, all six monkeys treated with two fractionated dose of 150 cGy developed chimerism and five monkeys appeared tolerant. In contrast, only two of the four monkeys treated with fractionated doses of 125 cGy developed chimerism and only one monkey survived long term. The degree of lymphocyte depletion in all recipients was proportional to the TBI dose. The fractionated TBI regimen of 150 cGy appears to be the most consistently effective regimen for establishing donor bone marrow cell engraftment and allograft tolerance. (author)

  11. Early biochemical changes in rat lungs following whole-body exposure to external ionizing irradiation

    International Nuclear Information System (INIS)

    Some biochemical and cytological parameters were followed up in broncho-alveolar lavage fluid and in lung homogenate from albino rats, exposed to single whole-body ionizing irradiation with 4, 8, and 15 Gy. Infectious complications were ruled out by addition of 2 g/l tetracycline in the drinking water before and after irradiation. Dose-dependent increase in the number of cells and lactatedehydrogenase and acid phosphate activities in the broncho-alveolar lavage fluid was observed on the first day and a tendency toward decrease in the period between the 5th and 15th day. These parameters are of the definite value as early diagnostic tests in radiation lung injury. These is evidence of inhibition of the antioxidative protective system in this organ - a dose-dependent decrease in the enzymatic activities of superoxyde dismutase and glucose-6-phosphatedehydrogenase and in the content of nonprotein sulfhydryl groups in the pulmonary homogenate

  12. Meningioma: The role of a foreign body and irradiation in tumor formation

    Energy Technology Data Exchange (ETDEWEB)

    Saleh, J.; Silberstein, H.J.; Salner, A.L.; Uphoff, D.F. (Hartford Hospital, CT (USA))

    1991-07-01

    A case of meningioma is reported. At the age of 18 years, the patient had undergone insertion of a Torkildsen shunt through a posteroparietal burr hole for obstructive hydrocephalus secondary to a tumor of the pineal region, of which no biopsy had been made. After the hydrocephalus was relieved, he underwent irradiation of the tumor. Thirty years later, he was treated for an intracranial meningioma wrapped around the shunt. The tumor followed the shunt in all of its intracranial course. Microscopy disclosed pieces of the shunt tube within the meningioma. The role of a foreign body and irradiation in the induction of meningiomas is discussed, and a comprehensive review of the literature is presented. 47 references.

  13. Antimutagenic and redox regulatory activities of curcumin in whole body γ - irradiated mice

    International Nuclear Information System (INIS)

    the aim of the current study is understanding the redox regulatory activity ( pro- and anti-oxidant properties) and mutagenic burden following whole body -irradiation with special reference to its control by curcumin in mice. the antimutagenic effects of curcumin; diferuloylmethane ( C21 H20 O6) were evaluated in vitro using chromosomal aberration assay in male mice,induced after-exposure to 3 Gy γ-rays that is a known mutagenic and carcinogenic agent, when curcumin was given at a dose of 400 mmol/kg body wt through gastric intubation for 5 following days either before-, after-or both before and after-exposure, the incidence of aberrant cells and aberration types (mostly chromatids, breaks and fragments) reduced with curcumin dosage as compared to irradiated group. the cellular biochemical changes were estimated using liver tissue damage marker enzymes: alkaline phosphatase (ALP) and γ -glutamyl transferase (GGT), pro-oxidant: xanthine oxidase (XO), lipid per oxidative indices: thiobarbituric acid reactive substances (TBARS) and hydroperoxide (HP. the non-enzymatic antioxidant : glutathione (GSH) and the enzymatic antioxidants: superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). TBARS ,HP,XO and liver marker enzymes were increased significantly , whereas the levels of GSH and the enzymatic antioxidants were significantly depleted in -irradiated groups. curcumin-treatment either before-, after-or both before and after -irradiation has attenuated the liver toxic effects of radiation obvious by reducing the levels of tbars and HP and diminished the increases of the activity of XO and liver marker enzymes. it has also re sued the depletion of the non enzymatic -and the enzymatic-antioxidant status.conclusion:curcumin has anti-oxidant potential against -rays-induced chromosomal mutations and redox imbalance regulatory status

  14. Partial body irradiation of small laboratory animals with an industrial X-ray tube

    Energy Technology Data Exchange (ETDEWEB)

    Frenzel, Thorsten; Kruell, Andreas [Universitaetsklinikum Hamburg-Eppendorf, Hamburg (Germany). Bereich Strahlentherapie; Grohmann, Carsten; Schumacher, Udo [Universitaetsklinikum Hamburg-Eppendorf, Hamburg (Germany). Inst. fuer Anatomie und Experimentelle Morphologie

    2014-07-01

    Dedicated precise small laboratory animal irradiation sources are needed for basic cancer research and to meet this need expensive high precision radiation devices have been developed. To avoid such expenses a cost efficient way is presented to construct a device for partial body irradiation of small laboratory animals by adding specific components to an industrial X-ray tube. A custom made radiation field tube was added to an industrial 200 kV X-ray tube. A light field display as well as a monitor ionization chamber were implemented. The field size can rapidly be changed by individual inserts of MCP96 that are used for secondary collimation of the beam. Depth dose curves and cross sectional profiles were determined with the use of a custom made water phantom. More components like positioning lasers, a custom made treatment couch, and a commercial isoflurane anesthesia unit were added to complete the system. With the accessories described secondary small field sizes down to 10 by 10 mm{sup 2} (secondary collimator size) could be achieved. The dosimetry of the beam was constructed like those for conventional stereotactical clinical linear accelerators. The water phantom created showed an accuracy of 1 mm and was well suited for all measurements. With the anesthesia unit attached to the custom made treatment couch the system is ideal for the radiation treatment of small laboratory animals like mice. It was feasible to shrink the field size of an industrial X-ray tube from whole animal irradiation to precise partial body irradiation of small laboratory animals. Even smaller secondary collimator sizes than 10 by 10 mm{sup 2} are feasible with adequate secondary collimator inserts. Our custom made water phantom was well suited for the basic dosimetry of the X-ray tube.

  15. Predictive models of insulin resistance derived from simple morphometric and biochemical indices related to obesity and the metabolic syndrome in baboons

    Directory of Open Access Journals (Sweden)

    Bastarrachea Raúl A

    2009-04-01

    Full Text Available Abstract Background Non-human primates are valuable models for the study of insulin resistance and human obesity. In baboons, insulin sensitivity levels can be evaluated directly with the euglycemic clamp and is highly predicted by adiposity, metabolic markers of obesity and impaired glucose metabolism (i.e. percent body fat by DXA and HbA1c. However, a simple method to screen and identify obese insulin resistant baboons for inclusion in interventional studies is not available. Methods We studied a population of twenty baboons with the euglycemic clamp technique to characterize a population of obese nondiabetic, insulin resistant baboons, and used a multivariate linear regression analysis (adjusted for gender to test different predictive models of insulin sensitivity (insulin-stimulated glucose uptake = Rd using abdominal circumference and fasting plasma insulin. Alternatively, we tested in a separate baboon population (n = 159, a simpler model based on body weight and fasting plasma glucose to predict the whole-body insulin sensitivity (Rd/SSPI derived from the clamp. Results In the first model, abdominal circumference explained 59% of total insulin mediated glucose uptake (Rd. A second model, which included fasting plasma insulin (log transformed and abdominal circumference, explained 64% of Rd. Finally, the model using body weight and fasting plasma glucose explained 51% of Rd/SSPI. Interestingly, we found that percent body fat was directly correlated with the adipocyte insulin resistance index (r = 0.755, p Conclusion In baboons, simple morphometric measurements of adiposity/obesity, (i.e. abdominal circumference, plus baseline markers of glucose/lipid metabolism, (i.e. fasting plasma glucose and insulin provide a feasible method to screen and identify overweight/obese insulin resistant baboons for inclusion in interventional studies aimed to study human obesity, insulin resistance and type 2 diabetes mellitus.

  16. Predictive models of insulin resistance derived from simple morphometric and biochemical indices related to obesity and the metabolic syndrome in baboons

    Science.gov (United States)

    Chavez, Alberto O; Gastaldelli, Amalia; Guardado-Mendoza, Rodolfo; Lopez-Alvarenga, Juan C; Leland, M Michelle; Tejero, M Elizabeth; Sorice, GianPio; Casiraghi, Francesca; Davalli, Alberto; Bastarrachea, Raúl A; Comuzzie, Anthony G; DeFronzo, Ralph A; Folli, Franco

    2009-01-01

    Background Non-human primates are valuable models for the study of insulin resistance and human obesity. In baboons, insulin sensitivity levels can be evaluated directly with the euglycemic clamp and is highly predicted by adiposity, metabolic markers of obesity and impaired glucose metabolism (i.e. percent body fat by DXA and HbA1c). However, a simple method to screen and identify obese insulin resistant baboons for inclusion in interventional studies is not available. Methods We studied a population of twenty baboons with the euglycemic clamp technique to characterize a population of obese nondiabetic, insulin resistant baboons, and used a multivariate linear regression analysis (adjusted for gender) to test different predictive models of insulin sensitivity (insulin-stimulated glucose uptake = Rd) using abdominal circumference and fasting plasma insulin. Alternatively, we tested in a separate baboon population (n = 159), a simpler model based on body weight and fasting plasma glucose to predict the whole-body insulin sensitivity (Rd/SSPI) derived from the clamp. Results In the first model, abdominal circumference explained 59% of total insulin mediated glucose uptake (Rd). A second model, which included fasting plasma insulin (log transformed) and abdominal circumference, explained 64% of Rd. Finally, the model using body weight and fasting plasma glucose explained 51% of Rd/SSPI. Interestingly, we found that percent body fat was directly correlated with the adipocyte insulin resistance index (r = 0.755, p < 0.0001). Conclusion In baboons, simple morphometric measurements of adiposity/obesity, (i.e. abdominal circumference), plus baseline markers of glucose/lipid metabolism, (i.e. fasting plasma glucose and insulin) provide a feasible method to screen and identify overweight/obese insulin resistant baboons for inclusion in interventional studies aimed to study human obesity, insulin resistance and type 2 diabetes mellitus. PMID:19389241

  17. Feasibility of intrafraction whole-body motion tracking for total marrow irradiation

    Science.gov (United States)

    Sharma, Manju; Santos, Troy Dos; Papanikolopoulos, Nikolaos P.; Hui, Susanta Kumar

    2011-05-01

    With image-guided tomotherapy, highly targeted total marrow irradiation (TMI) has become a feasible alternative to conventional total body irradiation. The uncertainties in patient localization and intrafraction motion of the whole body during hour-long TMI treatment may pose a risk to the safety and accuracy of targeted radiation treatment. The feasibility of near-infrared markers and optical tracking system (OTS) is accessed along with a megavoltage scanning system of tomotherapy. Three near-infrared markers placed on the face of a rando phantom are used to evaluate the capability of OTS in measuring changes in the markers' positions as the rando is moved in the translational direction. The OTS is also employed to determine breathing motion related changes in the position of 16 markers placed on the chest surface of human volunteers. The maximum uncertainty in locating marker position with the OTS is 1.5 mm. In the case of normal and deep breathing motion, the maximum marker position change is observed in anterior-posterior direction with the respective values of 4 and 12 mm. The OTS is able to measure surface changes due to breathing motion. The OTS may be optimized to monitor whole body motion during TMI to increase the accuracy of treatment delivery and reduce the radiation dose to the lungs.

  18. Changes in plasma apolipoproteins following whole-body irradiation in rabbit

    Energy Technology Data Exchange (ETDEWEB)

    Feliste, R. (INSERM, Toulouse, France); Dousset, N.; Carton, M.; Douste-Blazy, L.

    1981-09-01

    Male New Zealand white rabbits were whole-body-irradiated with a linear electron accelerator at 800 rad (LD/sub 50/ in 30 days). This treatment induced a pronounced hypertriglyceridemia. The apoprotein composition of very low density lipoproteins (VLDL, d < 1.006 g/ml) and high-density lipoproteins (HDL, d = 1.063 - 1.21 g/ml) from irradiated rabbits was studied and compared to those of normal rabbits. Significant changes were observed in both very low density apolipoproteins and high-density apolipoproteins. (1) In the VLDL fraction from irradiated rabbits, there appeared in high proportion two apolipoproteins with electrophoretic mobility in urea/polyacrylamide gels similar to apoA-I and A-II but which were distinctly different in their apparent molecular weights, their isoelectric points, and their amino acid composition from these latter proteins. These proteins had apparent molecular weights of about 10,000. They focused into three bands with pI values of 6.1, 6.4, and 6.6. Their amino acid composition was characterized by a very low content of threonine and serine and a high content of aspartic acid, glycine, alanine, and arginine. In addition, a marked increase of an apolipoprotein with an apparent molecular weight of about 43,000 and with an amino acid composition similar to rat apoA-IV was also observed in rabbit VLDL after irradiation. Apolipoprotein C constituents with slowmobility decreased significantly. (2) The irradiated rabbit HDL apolipoproteins showed an important increase of the proteins with molecular weight 10,000 and isoelectric points 6.1, 6.4, and 6.6. Compared to normal rabbit HDL apolipoproteins, a significant decrease of apoA-IV occurred. These modifications were also observed with lower radiation doses (200 and 400 rad).

  19. An experimental model of acute encephalopathy after total body irradiation in the rat: effect of Ginkgo biloba extract (EGb 761)

    International Nuclear Information System (INIS)

    To define the therapeutic effect of Ginkgo biloba extract (EGb 761) in an experimental model of acute encephalopathy following total body irradiation in rats. Ninety four-month-old rats received 4.5 Gy total body irradiation (TBI) at day 1 while 15 rats received sham irradiation. A behavioural study based on a conditioning test of negative reinforcement, the one-way avoidance test, was performed test, was performed after irradiation. Orally treatment was started one day (study A) or twenty two days (study B) after irradiation and repeated daily for twelve days. In the irradiated group, three subgroups were defined according to the treatment received: EGb 761 (50 mg/kg), EGb 761 (100 mg/kg), water. This work comprised two consecutive studies. In study A (45 rats) the one-way avoidance test was administered daily from day 7 to day 14. In study B (45 rats) the behavioural test was performed from day 28 to day 35. Study A (three groups of 15 rats): following TBI, irradiated rats treated with water demonstrated a significant delay in a learning the one-way avoidance test in comparison with sham-irradiated rats (P < 0.0002) or irradiated rats treated with EGb 761 (50 mg/kg; P < 0.007) or EGb 761 (100 mg/kg; P < 0.0002). The irradiated rats, treated with EGb 761 (50 or 100 mg/kg) did not differ from the sham-irradiated controls. Study B (three groups of 15 rats): the irradiated rats, treated with water of EGb 761 (50 or 100 mg/kg) did not differ from the sham-irradiated controls. (authors)

  20. Idiopathic interstitial pneumonia following bone marrow transplantation: the relationship with total body irradiation

    International Nuclear Information System (INIS)

    Interstitial pneumonia is a frequent and often fatal complication of allogenic bone marrow transplantation. Thirty to 40 percent of such cases are of unknown etiology and have been labelled as cases of idiopathic interstitial pneumonia. Idiopathic cases are more commonly associated with the use of total body irradiation; their occurrence appears to be independent of immunosupression or graft versus host disease. Evidence is presented from the literature suggesting that the development of idiopathic interstitial pneumonia is related to the absolute absorbed dose of radiation to lung. The similarity of idiopathic pneumonia to radiation pneumonitis seen in a different clinical setting is described

  1. An Acute Transverse Myelitis Attack after Total Body Irradiation: A Rare Case

    Directory of Open Access Journals (Sweden)

    Muzaffer Keklik

    2013-01-01

    Full Text Available Total body irradiation (TBI combined with chemotherapy is widely used as a pretreatment regimen of bone marrow transplantation (BMT in hematologic disorders. Late complications related to TBI as part of the conditioning regimen for hematopoietic stem cell transplantation have been revealed. Acute transverse myelitis (ATM is a neurological syndrome characterized by disorder of motor, sensorial, and autonomic nerves, and tracts at medulla spinalis, which is resulted from involvement of spinal cord. In this paper, we presented an ATM attack developed after TBI in a patient with acute lymphoblastic leukemia (ALL as it is a rarely seen case.

  2. Basal Cell Skin Cancer after Total-Body Irradiation and Hematopoietic Cell Transplantation

    OpenAIRE

    Schwartz, Jeffrey L.; Kopecky, Kenneth J.; Robert W. Mathes; Leisenring, Wendy M; Friedman, Debra L.; Deeg, H. Joachim

    2009-01-01

    Previous studies identified radiation therapy as a key modifier of basal cell carcinoma (BCC) risk in survivors of hematopoietic cell transplantation (HCT). In the present analysis, risk of BCC was analyzed in relation to age at transplant, attained age, race, total-body irradiation (TBI), and radiation fractionation in 6,306 patients who received HCT at ages 0–65 years after conditioning regimens with (n = 3870) or without (n = 2436) TBI, and who were followed from 100 days to 36.2 years aft...

  3. Total body irradiation with volumetric modulated arc therapy: Dosimetric data and first clinical experience

    International Nuclear Information System (INIS)

    To implement total body irradiation (TBI) using volumetric modulated arc therapy (VMAT). We applied the Varian RapidArc™ software to calculate and optimize the dose distribution. Emphasis was placed on applying a homogenous dose to the PTV and on reducing the dose to the lungs. From July 2013 to July 2014 seven patients with leukaemia were planned and treated with a VMAT-based TBI-technique with photon energy of 6 MV. The overall planning target volume (PTV), comprising the whole body, had to be split into 8 segments with a subsequent multi-isocentric planning. In a first step a dose optimization of each single segment was performed. In a second step all these elements were calculated in one overall dose-plan, considering particular constraints and weighting factors, to achieve the final total body dose distribution. The quality assurance comprised the verification of the irradiation plans via ArcCheck™ (Sun Nuclear), followed by in vivo dosimetry via dosimeters (MOSFETs) on the patient. The time requirements for treatment planning were high: contouring took 5–6 h, optimization and dose calculation 25–30 h and quality assurance 6–8 h. The couch-time per fraction was 2 h on day one, decreasing to around 1.5 h for the following fractions, including patient information, time for arc positioning, patient positioning verification, mounting of the MOSFETs and irradiation. The mean lung dose was decreased to at least 80 % of the planned total body dose and in the central parts to 50 %. In two cases we additionally pursued a dose reduction of 30 to 50 % in a pre-irradiated brain and in renal insufficiency. All high dose areas were outside the lungs and other OARs. The planned dose was in line with the measured dose via MOSFETs: in the axilla the mean difference between calculated and measured dose was 3.6 % (range 1.1–6.8 %), and for the wrist/hip-inguinal region it was 4.3 % (range 1.1–8.1 %). TBI with VMAT provides the benefit of satisfactory dose

  4. Comparison between combination chemotherapy and total body irradiation plus combination chemotherapy in non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Thirty-nine untreated patients with either lymphocytic or nodular mixed/nodular histiocytic non-Hodgkin's lymphoma, stage II-IV, were randomized to treatment with total body irradiation (TBI), 100 rads in 10 fractions over 12 days, plus combination chemotherapy with either cyclophosphamide, vincristine and prednisone (CVP) or cyclophosphamide, vincristine, procarbazine and prednisone (C-MOPP) or to treatment with combination chemotherapy (CVP or C-MOPP) alone. Remission rate and duration were comparable for both treatment groups; thus the use of both treatment modalities ab initio provides no therapeutic advantage

  5. Animal models of bronchopulmonary dysplasia. The preterm baboon models

    OpenAIRE

    Yoder, Bradley A.; Coalson, Jacqueline J.

    2014-01-01

    Much of the progress in improved neonatal care, particularly management of underdeveloped preterm lungs, has been aided by investigations of multiple animal models, including the neonatal baboon (Papio species). In this article we highlight how the preterm baboon model at both 140 and 125 days gestation (term equivalent 185 days) has advanced our understanding and management of the immature human infant with neonatal lung disease. Not only is the 125-day baboon model extremely relevant to the...

  6. The behaviour of the endocrinological parameters cortisol, testosterone, growth hormone and prolactin after UVA and UVB whole-body irradiation

    International Nuclear Information System (INIS)

    With two groups, each with 8 healthy subjects UV whole-body irradiation was carried out with uniformly 30 J/cm2 UVA or respectively UVB at the level of the individual minimal erythema dose. Every subject received serial irradiations once a day for four days. The determination of the serum hormone level was accomplished by means of radioimmunoassays. The results show a weakly significant decline of cortisol 4 and 24 hours after 2 serial UVB irradiations. 3,5 and 7 days after the end of the irradiation series the cortisol values have increased, but by the seventh day statistically only weakly significant. With UVA irradiation there was also a weakly significant increase in cortisol levels three days after the end of the irradiation series. The serum levels of the other hormones showed no statistically significant changes. (orig./MG)

  7. Preweaning food intake influences the adiposity of young adult baboons.

    OpenAIRE

    Lewis, D. S.; Bertrand, H A; McMahan, C.A.; McGill, H. C.; Carey, K D; Masoro, E J

    1986-01-01

    The hypothesis that preweaning nutrition influences adult fat cell number and adiposity was tested in baboons. Newborn baboons were fed Similac formulas with caloric densities of 40.5 kcal (underfed), 67.5 kcal (fed normally), and 94.5 kcal (overfed) per 100 g formula. From weaning (16 wk) until necropsy at 5 yr of age all baboons were fed the same diet. At necropsy, fat cell number and fat cell size in 10 fat depots were measured. Female baboons overfed as infants had markedly greater fat de...

  8. Fetal liver transplantation in 2 patients with acute leukaemia after total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lucarelli, G.; Izzi, T.; Porcellini, A.; Delfini, C.; Galimberti, M.; Moretti, L.; Polchi, P.; Agostinelli, F.; Andreani, M.; Manna, M. (Haematological Department, Pesaro Hospital, Pesaro, Italy)

    1982-01-01

    2 patients with acute leukaemia in relapse were transplanted with fetal liver cells following a conditioning regimen of cyclophosphamide (120 mg/kg) and total body irradiation (1000 r). Each patient achieved a remission with haematopoietic recovery that was rapid in one case and delayed in the other. In one case there was evidence of chimerism as demonstrated by the presence of the XYY karyotype of the donor fetus in 20 % of marrow metaphases, by the presence of double Y bodies in the peripheral blood, by the appearance of new HLA-antigens, and by red cell isoenzyme phenotypes of donor origin. In the second case there was prompt haemotopoietic recovery and the appearance of red cell isoenzyme phenotypes of donor origin. Survival was 153 and 30 d, respectively, and both patients died of interstitial pneumonia without evidence of graft versus host disease.

  9. The relationship between the alkaline phosphatase network and the haematopoiesis in mice subjected to whole-body irradiation

    Directory of Open Access Journals (Sweden)

    Almohamad Khaled M.

    2014-08-01

    Full Text Available Purpose: To investigate the relationship between the alkaline phosphatase (ALP network of the marrow stroma and the haematopoietic regeneration after mice whole-body irradiation. Materials and methods: Three groups of mice were irradiated with a non-lethal ionising radiation dose: the fi rst one received an intraperitoneal injection of Levamisole, ALP inhibitor, 24 h before irradiation; the second one received an intraperitoneal injection of Lisinopril, haematopoiesis inhibitor, 24 h before irradiation; the third was left untreated, but irradiated. The fourth group, untreated and not irradiated, was the control. The total surface occupied by ALP positive processes, revealed by means of ALP cytochemistry in the marrow area, was evaluated semi-quantitively. Nucleated bone marrow cells were also counted. Results: ALP network began to increase 24 h after irradiation to reach a maximum after 72 h, when the bone marrow was almost become completely empty of the haematopoietic cells. This increase advances the haematopoietic recovery. This process was substantially delayed when the mice were injected with Levamisole 24 h before irradiation. On the contrary, ALP network increased strongly since the fi rst day after irradiation when the mice were injected with Lisinopril 24 h before irradiation. Conclusions: These data have indicated that the haematopoietic recovery and repopulation of the bone marrow were advanced by the ALP network recovery.

  10. Protective Effect Of Avocado Oil Against Biochemical And Histological Changes In Whole Body Gamma Irradiation In Albino Rats

    International Nuclear Information System (INIS)

    Avocado oil, extracted from the pulp of the fruit, is rich in poly-unsaturated fatty acids, linoleic, linolenic, oleic acids and the monounsaturated fatty acid. It also contains B-sitosterol, B-carotene, lecithin, minerals and vitamins A, C, D and E. Avocado oil lowers the blood levels of serum lipids and has antioxidant properties as a free radical scavenger. Male albino rats were divided into 5 groups. 1- Control group: rats not subjected to any treatment, 2- Avocado treated group: rats received avocado oil (0.1 ml/kg/day) via intraperitoneal injection during 21 days, 3- Irradiated group: rats were whole body gamma irradiated with 7 Gy, 4- Avocado + irradiated group: rats received avocado oil for 21 days then exposed to whole body gamma irradiation with 7 Gy and 5- Radiation + avocado group: rats were exposed to 7 Gy whole body gamma irradiation then received avocado oil for 21 days. Avocado oil (0.1 ml/kg/day) was given to rats, receiving a standard diet, for 21 days before exposure to 7 Gy whole body gamma irradiation then the treatment was continued for 10 days after irradiation. Several investigations were carried out such as superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), lipid profile and blood sugar. High significant increase in MDA was observed and treatment with avocado before irradiation caused significant increase in GSH, CAT and SOD and significant decrease in MDA as compared to the irradiated groups. The results also showed that treatment with avocado oil significantly diminished the radiation-induced alterations observed in the levels of lipid profile and glucose. The results demonstrated that whole body gamma irradiated rats showed significant increase in alanine aminotransferase (ALT), aspartate amino-transferase (AST), alkaline phosphatase (ALP) and glucose. By studying the lipid profile, significant increases in cholesterol, triglycerides and LDL-C levels were recorded while significant decrease was

  11. Blood-brain barrier permeability after gamma whole-body irradiation: an in vivo microdialysis study

    Energy Technology Data Exchange (ETDEWEB)

    Diserbo, M.; Agin, A.; Lamproglou, I.; Mauris, J.; Staali, F.; Multon, E.; Amourette, C

    2002-07-01

    The effects of total-body irradiation on the permeability of rat striatal blood-brain barrier (BBB) to [{sup 3}H]{alpha}-aminoisobutyric acid (AIBA) and [{sup 14}C] sucrose were investigated using the microdialysis technique. Seven days, 3 and 6 weeks, and 3, 5, and 8 months after gamma exposure at a dose of 4.5 Gy, no modification of the permeability to both [{sup 3}H]AIBA and [{sup 14}C] sucrose was observed. But, in the course of the initial syndrome, we observed a significant but transient increase in the BBB permeability to the two markers between 3 and 17 h after exposure. A secondary transient 'opening' of the BBB to [{sup 14}C] sucrose was noticed about 28 h following irradiation without the corresponding increase in BBB permeability to [{sup 3}H]AIBA. On the contrary, the transport of [{sup 3}H]AIBA through the BBB was decreased between 33 and 47 h postradiation. In conclusion, our experiments showed early modifications of BBB permeability after a moderate-dose whole-body exposure. Confirmation of these results with other tracers, in another experimental model or in humans, would have clinical applications for designing appropriate pharmacotherapy in radiotherapy and treatment of accidental overexposure. (author)

  12. Dose calculation method with 60-cobalt gamma rays in total body irradiation

    CERN Document Server

    Scaff, L A M

    2001-01-01

    Physical factors associated to total body irradiation using sup 6 sup 0 Co gamma rays beams, were studied in order to develop a calculation method of the dose distribution that could be reproduced in any radiotherapy center with good precision. The method is based on considering total body irradiation as a large and irregular field with heterogeneities. To calculate doses, or doses rates, of each area of interest (head, thorax, thigh, etc.), scattered radiation is determined. It was observed that if dismagnified fields were considered to calculate the scattered radiation, the resulting values could be applied on a projection to the real size to obtain the values for dose rate calculations. In a parallel work it was determined the variation of the dose rate in the air, for the distance of treatment, and for points out of the central axis. This confirm that the use of the inverse square law is not valid. An attenuation curve for a broad beam was also determined in order to allow the use of absorbers. In this wo...

  13. Lung autophagic response following exposure of mice to whole body irradiation, with and without amifostine

    Energy Technology Data Exchange (ETDEWEB)

    Zois, Christos E. [Department of Radiotherapy - Oncology, Democritus University of Thrace, Alexandroupolis 68100 (Greece); Giatromanolaki, Alexandra [Department of Pathology, Democritus University of Thrace, Alexandroupolis (Greece); Kainulainen, Heikki [Department of Biology of Physical Activity, University of Jyvaeskylae (Finland); Botaitis, Sotirios [Department of Experimental Surgery, Democritus University of Thrace, Alexandroupolis (Greece); Torvinen, Sira [Department of Biology of Physical Activity, University of Jyvaeskylae (Finland); Simopoulos, Constantinos [Department of Experimental Surgery, Democritus University of Thrace, Alexandroupolis (Greece); Kortsaris, Alexandros [Department of Biochemistry, Democritus University of Thrace, Alexandroupolis (Greece); Sivridis, Efthimios [Department of Pathology, Democritus University of Thrace, Alexandroupolis (Greece); Koukourakis, Michael I., E-mail: targ@her.forthnet.gr [Department of Radiotherapy - Oncology, Democritus University of Thrace, Alexandroupolis 68100 (Greece)

    2011-01-07

    Research highlights: {yields} We investigated the effect 6 Gy of WBI on the autophagic machinery of normal mouse lung. {yields} Irradiation induces dysfunction of the autophagic machinery in normal lung, characterized by decreased transcription of the LC3A/Beclin-1 mRNA and accumulation of the LC3A, and p62 proteins. {yields} The membrane bound LC3A-II protein levels increased in the cytosolic fraction (not in the pellet), contrasting the patterns noted after starvation-induced autophagy. {yields} Administration of amifostine, reversed all the LC3A and p62 findings, suggesting protection of the normal autophagic function. -- Abstract: Purpose: The effect of ionizing irradiation on the autophagic response of normal tissues is largely unexplored. Abnormal autophagic function may interfere the protein quality control leading to cell degeneration and dysfunction. This study investigates its effect on the autophagic machinery of normal mouse lung. Methods and materials: Mice were exposed to 6 Gy of whole body {gamma}-radiation and sacrificed at various time points. The expression of MAP1LC3A/LC3A/Atg8, beclin-1, p62/sequestosome-1 and of the Bnip3 proteins was analyzed. Results: Following irradiation, the LC3A-I and LC3A-II protein levels increased significantly at 72 h and 7 days. Strikingly, LC3A-II protein was increased (5.6-fold at 7 days; p < 0.001) only in the cytosolic fraction, but remained unchanged in the membrane fraction. The p62 protein, was significantly increased in both supernatant and pellet fraction (p < 0.001), suggesting an autophagosome turnover deregulation. These findings contrast the patterns of starvation-induced autophagy up-regulation. Beclin-1 levels remained unchanged. The Bnip3 protein was significantly increased at 8 h, but it sharply decreased at 72 h (p < 0.05). Administration of amifostine (200 mg/kg), 30 min before irradiation, reversed all the LC3A and p62 findings on blots, suggesting restoration of the normal autophagic function

  14. Changes of pulmonary function in patients treated with bone marrow transplantation after total body irradiation

    International Nuclear Information System (INIS)

    Changes of pulmonary functions were studied with time in 10 patients who underwent bone marrow transplantation (BMT) after total body irradiation (TBI, total lung dose, 3 to 12 Gy; dose rate, 5.3 to 10.0 cGy/min). Regardless of the total lung dose and the dose rate of irradiation or the period after BMT, the percent vital capacity (%VC) and the ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1.0%) were kept within normal limits, whereas the diffusion capacity of carbon monoxide (%DLco) tended to decrease within 100 days after BMT in all of our patients. From the possibility that respiratory insufficiency will rapidly occur due to infection, it seems unfavorable for the patients to return to routine life during this period after BMT, even if in states without any clinical manifestations. It was found that the %DLco began to decrease prior to the onset of interstitial pneumonia (IP) and that the degree was more marked in patients who progressed to IP than in those who did not. Therefore, it is possible to predict the occurrence of IP by frequently measuring pulmonary function. In patients with IP, the %DLco rapidly improved with steroid administration, and it tended to improve gradually even after discontinuing the administration of the drug. But regardless of the total lung dose and dose rate of irradiation, the %DLco in patients with chronic graft-versus-host disease (GVHD) did not recover completely when compared with that in patients without chronic GVHD. Thus, it is considered that this persistant pulmonary dysfunction is caused mainly by chronic GVHD rather than by irradiation. (author)

  15. Late ophthalmological complications after total body irradiation in non-human primates

    Science.gov (United States)

    Niemer-Tucker, M. M.; Sterk, C. C.; de Wolff-Rouendaal, D.; Lee, A. C.; Lett, J. T.; Cox, A.; Emmanouilidis-van der Spek, K.; Davelaar, J.; Lambooy, A. C.; Mooy, C. M.; Broerse, J. J.

    1999-01-01

    PURPOSE: To investigate the long-term effects of total body irradiation (TBI) on the incidence and time course of ocular complications. MATERIALS AND METHODS: Rhesus monkeys treated with TBI photon doses up to 8.5 Gy and proton doses up to 7.5 Gy were studied at intervals up to 25 years post-irradiation. They were compared with control groups with a similar age distribution. Cataract formation and ocular fundus lesions were scored according to a standardized protocol. Fluorescein angiography and histopathology was performed in selected animals. RESULTS: Cataract formation occurred after a latent period of 3-5 years. Significant cataract induction was observed for photon-doses of 8 and 8.5 Gy and beyond 20 years after proton irradiation. The severity of the lesions represents significant impairment of vision and would require cataract surgery if similar results occurred in human bone marrow transplant patients. Fluorescein angiography demonstrated a normal pattern of retinal vessels in 13 out of 14 animals (93%) from the irradiated group and in eight out of nine animals (89%) from the control group. No additional lesions apart from age-related degenerative changes could be demonstrated. Histological evaluation revealed no radiation-associated vasculopathy. CONCLUSIONS: Radiation alone for doses up to 8.5 Gy of photons does not carry a potential risk for fundus pathology, whereas clinically important cataract induction should be anticipated within 5 years after photon doses of 8.0 and 8.5 Gy and proton doses in excess of 2.5 Gy.

  16. Establishment of Early Endpoints in Mouse Total-Body Irradiation Model

    Science.gov (United States)

    Gulani, Jatinder; King, Gregory; Hieber, Kevin; Chappell, Mark; Ossetrova, Natalia

    2016-01-01

    Acute radiation sickness (ARS) following exposure to ionizing irradiation is characterized by radiation-induced multiorgan dysfunction/failure that refers to progressive dysfunction of two or more organ systems, the etiological agent being radiation damage to cells and tissues over time. Radiation sensitivity data on humans and animals has made it possible to describe the signs associated with ARS. A mouse model of total-body irradiation (TBI) has previously been developed that represents the likely scenario of exposure in the human population. Herein, we present the Mouse Intervention Scoring System (MISS) developed at the Veterinary Sciences Department (VSD) of the Armed Forces Radiobiology Research Institute (AFRRI) to identify moribund mice and decrease the numbers of mice found dead, which is therefore a more humane refinement to death as the endpoint. Survival rates were compared to changes in body weights and temperatures in the mouse (CD2F1 male) TBI model (6–14 Gy, 60Co γ-rays at 0.6 Gy min-1), which informed improvements to the Scoring System. Individual tracking of animals via implanted microchips allowed for assessment of criteria based on individuals rather than by group averages. From a total of 132 mice (92 irradiated), 51 mice were euthanized versus only four mice that were found dead (7% of non-survivors). In this case, all four mice were found dead after overnight periods between observations. Weight loss alone was indicative of imminent succumbing to radiation injury, however mice did not always become moribund within 24 hours while having weight loss >30%. Only one survivor had a weight loss of greater than 30%. Temperature significantly dropped only 2–4 days before death/euthanasia in 10 and 14 Gy animals. The score system demonstrates a significant refinement as compared to using subjective assessment of morbidity or death as the endpoint for these survival studies. PMID:27579862

  17. Establishment of Early Endpoints in Mouse Total-Body Irradiation Model.

    Science.gov (United States)

    Koch, Amory; Gulani, Jatinder; King, Gregory; Hieber, Kevin; Chappell, Mark; Ossetrova, Natalia

    2016-01-01

    Acute radiation sickness (ARS) following exposure to ionizing irradiation is characterized by radiation-induced multiorgan dysfunction/failure that refers to progressive dysfunction of two or more organ systems, the etiological agent being radiation damage to cells and tissues over time. Radiation sensitivity data on humans and animals has made it possible to describe the signs associated with ARS. A mouse model of total-body irradiation (TBI) has previously been developed that represents the likely scenario of exposure in the human population. Herein, we present the Mouse Intervention Scoring System (MISS) developed at the Veterinary Sciences Department (VSD) of the Armed Forces Radiobiology Research Institute (AFRRI) to identify moribund mice and decrease the numbers of mice found dead, which is therefore a more humane refinement to death as the endpoint. Survival rates were compared to changes in body weights and temperatures in the mouse (CD2F1 male) TBI model (6-14 Gy, 60Co γ-rays at 0.6 Gy min-1), which informed improvements to the Scoring System. Individual tracking of animals via implanted microchips allowed for assessment of criteria based on individuals rather than by group averages. From a total of 132 mice (92 irradiated), 51 mice were euthanized versus only four mice that were found dead (7% of non-survivors). In this case, all four mice were found dead after overnight periods between observations. Weight loss alone was indicative of imminent succumbing to radiation injury, however mice did not always become moribund within 24 hours while having weight loss >30%. Only one survivor had a weight loss of greater than 30%. Temperature significantly dropped only 2-4 days before death/euthanasia in 10 and 14 Gy animals. The score system demonstrates a significant refinement as compared to using subjective assessment of morbidity or death as the endpoint for these survival studies.

  18. Establishment of Early Endpoints in Mouse Total-Body Irradiation Model.

    Science.gov (United States)

    Koch, Amory; Gulani, Jatinder; King, Gregory; Hieber, Kevin; Chappell, Mark; Ossetrova, Natalia

    2016-01-01

    Acute radiation sickness (ARS) following exposure to ionizing irradiation is characterized by radiation-induced multiorgan dysfunction/failure that refers to progressive dysfunction of two or more organ systems, the etiological agent being radiation damage to cells and tissues over time. Radiation sensitivity data on humans and animals has made it possible to describe the signs associated with ARS. A mouse model of total-body irradiation (TBI) has previously been developed that represents the likely scenario of exposure in the human population. Herein, we present the Mouse Intervention Scoring System (MISS) developed at the Veterinary Sciences Department (VSD) of the Armed Forces Radiobiology Research Institute (AFRRI) to identify moribund mice and decrease the numbers of mice found dead, which is therefore a more humane refinement to death as the endpoint. Survival rates were compared to changes in body weights and temperatures in the mouse (CD2F1 male) TBI model (6-14 Gy, 60Co γ-rays at 0.6 Gy min-1), which informed improvements to the Scoring System. Individual tracking of animals via implanted microchips allowed for assessment of criteria based on individuals rather than by group averages. From a total of 132 mice (92 irradiated), 51 mice were euthanized versus only four mice that were found dead (7% of non-survivors). In this case, all four mice were found dead after overnight periods between observations. Weight loss alone was indicative of imminent succumbing to radiation injury, however mice did not always become moribund within 24 hours while having weight loss >30%. Only one survivor had a weight loss of greater than 30%. Temperature significantly dropped only 2-4 days before death/euthanasia in 10 and 14 Gy animals. The score system demonstrates a significant refinement as compared to using subjective assessment of morbidity or death as the endpoint for these survival studies. PMID:27579862

  19. Early micro-rheological consequences of single fraction total body low-dose photon irradiation in mice.

    Science.gov (United States)

    Szluha, Kornelia; Lazanyi, Kornelia; Furka, Andrea; Kiss, Ferenc; Szabo, Imre; Pintye, Eva; Miko, Iren; Nemeth, Norbert

    2014-01-01

    Despite of the studies on widespread biological effects of irradiation, surprisingly only little number of papers can be found dealing with its in vivo hemorheological impact. Furthermore, other studies suggested that low-dose irradiation might differ from high-dose in more than linear ways. On Balb/c Jackson female adult mice hematological and hemorheological impacts of total body irradiation were investigated 1 hour following 0.002, 0.005, 0.01, 0.02, 0.05 and 0.1 Gy dose irradiation. In case of 0.01 Gy further groups were analyzed 30 minutes, 2, 4, 6, 24 and 48 h after irradiation. According to the results, it seems that the dose-dependent changes of blood micro-rheological parameters are not linear. The irradiation dose of 0.01 Gy acted as a point of 'inflexion', because by this dose we found the most expressed changes in hematological parameters, as well as in red blood cell aggregation, deformability and osmoscan data. The time-dependent changes showed progressive decrease in pH, rise in lactate concentration, further decrease in erythrocyte aggregation index and deformability, with moderate shifting of the optimal osmolarity point and modulation in membrane stability. As conclusion, low-dose total body irradiation may cause micro-rheological changes, being non-linearly correlated with the irradiation dose.

  20. Immunological network activation by low-dose rate irradiation. Analysis of cell populations and cell surface molecules in whole body irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Ina, Yasuhiro; Sakai, Kazuo [Central Research Inst. of Electric Power Industry, Low Dose Radiation Research Center, Komae, Tokyo (Japan)

    2003-07-01

    The effects of low-dose rate whole body irradiation on biodefense and immunological systems were investigated using female C57BL/6 (B6) mice. These B6 mice were exposed continuously to {gamma}-rays from a {sup 137}Cs source in the long-term low-dose rate irradiation facility at CRIEPI for 0 - 12 weeks at a dose rate of 0.95 mGy/hr. In the bone marrow, thymus, spleen, lymph nodes, and peripheral blood of the irradiated mice, changes in cell populations and cell surface molecules were examined. The cell surface functional molecules (CD3, CD4, CD8, CD19, CD45R/B220, ICAM-1, Fas, NK-1.1, CXCR4, and CCR5), and activation molecules (THAM, CD28, CD40, CD44H, CD70, B7-1, B7-2, OX-40 antigen, CTLA-4, CD30 ligand, and CD40 ligand) were analyzed by flow cytometry. The percentage of CD4{sup +} T cells and cell surface CD8 molecule expressions on the CD8{sup +} T cells increased significantly to 120-130% after 3 weeks of the irradiation, compared to non-irradiated control mice. On the other hand, the percentage of CD45R/B220{sup +} CD40{sup +} B cells, which is one of the immunological markers of inflammation, infection, tumor, and autoimmune disease, decreased significantly to 80-90% between the 3rd to 5th week of irradiation. There was no significant difference in other cell population rates and cell surface molecule expression. Furthermore, abnormal T cells bearing mutated T cell receptors induced by high-dose rate irradiation were not observed throughout this study. These results suggest that low-dose rate irradiation activates the immunological status of the whole body. (author)

  1. Anti-tumor immunological mechanisms of low dose whole-body irradiation in the protocol of tumor generadiotherapy

    International Nuclear Information System (INIS)

    Objective: To investigate the immunologic enhancement of low dose whole-body irradiation in mice bearing Lewis lung carcinoma (LLC) under recombinant plasmid pEgr-IL18-B7.1 gene-radiotherapy. Methods: LLC cells were implanted subcutaneously in the right-hind leg of C57BL/6J mice. The pEgr-IL18- B7.1 recombinant plasmids mediated by polyethylenimine were injected locally into tumors of the mice with gene- radiotherapy, and then the tumors received different therapeutic regimens containing local irradiation with 2 Gy and whole-body irradiation with 0.075 Gy, respectively. Cytotoxic activity of CTL and NK were detected with isotope labeling of 3H-TdR. The secretion activities of TNF-α and IFN-γ were detected with ELISA. The anti-tumor immunological effects of low dose whole-body irradiation in protocol of gene-radiotherapy on the tumor-bearing mice were observed. Results: Compared with conventional repeated high dose local irradiation, single high dose local irradiation in combination with repeated low dose whole-body irradiation could enhance the cytotoxic activity of CTL and NK, and increase the secretion of TNF-α and IFN-γ under pEgr-IL18-B7.1 gene-radiotherapy. Conclusions: Low dose whole-body irradiation superimposed upon a local high dose could significantly enhance the anti-tumor effect in the protocol of gene-radiotherapy through promoting the cytotoxic activity of CTL and NK, and up-regulating the expression of TNF-α and IFN-γ. (authors)

  2. Deep learning of orthographic representations in baboons.

    Science.gov (United States)

    Hannagan, Thomas; Ziegler, Johannes C; Dufau, Stéphane; Fagot, Joël; Grainger, Jonathan

    2014-01-01

    What is the origin of our ability to learn orthographic knowledge? We use deep convolutional networks to emulate the primate's ventral visual stream and explore the recent finding that baboons can be trained to discriminate English words from nonwords. The networks were exposed to the exact same sequence of stimuli and reinforcement signals as the baboons in the experiment, and learned to map real visual inputs (pixels) of letter strings onto binary word/nonword responses. We show that the networks' highest levels of representations were indeed sensitive to letter combinations as postulated in our previous research. The model also captured the key empirical findings, such as generalization to novel words, along with some intriguing inter-individual differences. The present work shows the merits of deep learning networks that can simulate the whole processing chain all the way from the visual input to the response while allowing researchers to analyze the complex representations that emerge during the learning process.

  3. Deep learning of orthographic representations in baboons.

    Science.gov (United States)

    Hannagan, Thomas; Ziegler, Johannes C; Dufau, Stéphane; Fagot, Joël; Grainger, Jonathan

    2014-01-01

    What is the origin of our ability to learn orthographic knowledge? We use deep convolutional networks to emulate the primate's ventral visual stream and explore the recent finding that baboons can be trained to discriminate English words from nonwords. The networks were exposed to the exact same sequence of stimuli and reinforcement signals as the baboons in the experiment, and learned to map real visual inputs (pixels) of letter strings onto binary word/nonword responses. We show that the networks' highest levels of representations were indeed sensitive to letter combinations as postulated in our previous research. The model also captured the key empirical findings, such as generalization to novel words, along with some intriguing inter-individual differences. The present work shows the merits of deep learning networks that can simulate the whole processing chain all the way from the visual input to the response while allowing researchers to analyze the complex representations that emerge during the learning process. PMID:24416300

  4. Deep learning of orthographic representations in baboons.

    Directory of Open Access Journals (Sweden)

    Thomas Hannagan

    Full Text Available What is the origin of our ability to learn orthographic knowledge? We use deep convolutional networks to emulate the primate's ventral visual stream and explore the recent finding that baboons can be trained to discriminate English words from nonwords. The networks were exposed to the exact same sequence of stimuli and reinforcement signals as the baboons in the experiment, and learned to map real visual inputs (pixels of letter strings onto binary word/nonword responses. We show that the networks' highest levels of representations were indeed sensitive to letter combinations as postulated in our previous research. The model also captured the key empirical findings, such as generalization to novel words, along with some intriguing inter-individual differences. The present work shows the merits of deep learning networks that can simulate the whole processing chain all the way from the visual input to the response while allowing researchers to analyze the complex representations that emerge during the learning process.

  5. Deep Learning of Orthographic Representations in Baboons

    Science.gov (United States)

    Hannagan, Thomas; Ziegler, Johannes C.; Dufau, Stéphane; Fagot, Joël; Grainger, Jonathan

    2014-01-01

    What is the origin of our ability to learn orthographic knowledge? We use deep convolutional networks to emulate the primate's ventral visual stream and explore the recent finding that baboons can be trained to discriminate English words from nonwords [1]. The networks were exposed to the exact same sequence of stimuli and reinforcement signals as the baboons in the experiment, and learned to map real visual inputs (pixels) of letter strings onto binary word/nonword responses. We show that the networks' highest levels of representations were indeed sensitive to letter combinations as postulated in our previous research. The model also captured the key empirical findings, such as generalization to novel words, along with some intriguing inter-individual differences. The present work shows the merits of deep learning networks that can simulate the whole processing chain all the way from the visual input to the response while allowing researchers to analyze the complex representations that emerge during the learning process. PMID:24416300

  6. Effects of 8 Gy whole body irradiation on number and functions of small intestinal intraepithelial lymphocytes (IELs)

    International Nuclear Information System (INIS)

    Objective: To explore the characteristics of intestinal mucosal immunity after radiation injury. Methods: Number, proliferation activity, cytotoxicity of IEL as well as the TNF-α and TGF-β concentrations in supernatant of cultured IELs were studied using freshly isolated IELs from whole small intestine of Kunming strain mice whole-body irradiated with 8 Gy 60Co rays. Results: The proliferation activity, cytotoxicity as well as the number of IELs in small intestinal mucosa were significantly decreased from 8h and reached the lowest level at 72 h post-irradiation. The TNF-α and TGF-β concentrations in supernatant of cultured IELs isolated from irradiated mice elevated at 8h and reached the peak values at 72h. Conclusion: The decrease in number and important factions of IELs might be one of the reasons which damage the intestinal mucosal immunity barrier after whole body irradiation

  7. Bronchial neuroendocrine elements in late post-radiation stage in humans after total body irradiation

    International Nuclear Information System (INIS)

    It is not known how long-term total body irradiation affects the neuroendocrine cells (Nc) and peptidergic innervation in the bronchial wall. This study examined, by immunohistochemical and radioimmunoassay (RIA) techniques, the distribution of NC and neuropeptide-containing nerve fibres in the large bronchi of Chernobyl nuclear accident cleanup workers displaying pulmonary fibrosis and metaplastic epithelium. Bronchial mucous and submucous layers from 16 Chernobyl patients and 6 control subjects were examined by conventional light microscopy and immunohistochemical techniques for determination of protein gene product 9.5 (PGP), chromogranin A, chromogranin A and B (CAB), calcitonin gene-related peptide (CGRP), calcitonin, vasoactive intestinal peptide (VIP), gastrin-releasing peptide (GRP), helospectin I, neuropeptide Y (NPY), pituitary adenylate cyclase activating peptide (PACAP), serotonin (5-hydroxyltryptamine, 5-HT), and substance P (SP). Additionally, bronchial biopsies from 6 Chernobyl cleanup workers and 3 control patients were examined by RIA for VIP and NPY/peptideYY-Ievels. The Chernobyl patients were examined 10 years after exposure during the cleanup works in the Chernobyl Atomic Electric Power Station. PGP immunoreactive nerve fibres appeared to be more frequent in the bronchial wall after long term irradiation as compared with controls. However, no specific alterations in the amounts of NPY-, PACAP-, helospectin-, SP- and CGRP-immunoreactive nerve fibres were seen in bronchi of control and Chernobyl patients. 5-HT -immunoreactive NC appeared to be more numerous in normal bronchial epithelium adjacent to metaplastic epithelium, in which numerous CAB- immunoreactive NC were seen in Chernobyl patients. RIA for VIP and NPY/PYY showed individual variations in the levels of these peptides in the bronchial tissue. In two cases (one Chernobyl patient and one control patient) there was a high concentration of VIP in parallel with a high concentration of NPY

  8. Comparison of total body irradiation-based or non-total body irradiation-based conditioning regimens for allogeneic stem cell transplantation in pediatric leukemia patients

    Directory of Open Access Journals (Sweden)

    Sang Jeong Kim

    2010-04-01

    Full Text Available Purpose : This study aims to compare the outcome of total body irradiation (TBI- or non-TBI-containing conditioning regimens for leukemia in children. Methods : We retrospectively evaluated 77 children conditioned with TBI (n=40 or non-TBI (n=37 regimens, transplanted at Chonnam National University Hospital between January 1996 and December 2007. The type of transplantation, disease status at the time of transplant, conditioning regimen, engraftment kinetics, development of graft-versus-host disease (GVHD, complications, cause of deaths, overall survival (OS, and event-free survival (EFS were compared between the 2 groups. Results : Among 34 patients with acute lymphoblastic leukemia (ALL, 28 (82.4% were in the TBI group, while 72.7% (24/33 of patients with myeloid leukemia were in the non-TBI group. Although the 5-year EFS of the 2 groups was similar for all patients (62% vs 63%, the TBI group showed a better 5-year EFS than the non-TBI group when only ALL patients were analyzed (65% vs 17%; P =0.005. In acute myelogenous leukemia patients, the non-TBI group had better survival tendency (73% vs 38%; P=0.089. The incidence of GVHD, engraftment, survival, cause of death, and late complications was not different between the 2 groups. Conclusion : The TBI and non-TBI groups showed comparable results, but the TBI group showed a significantly higher 5-year EFS than the non-TBI group in ALL patients. Further prospective, randomized controlled studies involving larger number of patients are needed to assess the late-onset complications and to compare the socioeconomic quality of life.

  9. Development and clinical application of a length-adjustable water phantom for total body irradiation.

    Science.gov (United States)

    Chen, Zhi-Wei; Yao, Sheng-Yu; Zhang, Tie-Ning; Zhu, Zhen-Hua; Hu, Zhe-Kai; Lu, Xun

    2012-08-01

    A new type of water phantom which would be specialised for the absorbed dose measurement in total body irradiation (TBI) treatment is developed. Ten millimetres of thick Plexiglas plates were arranged to form a square cube with 300 mm of edge length. An appropriate sleeve-type piston was installed on the side wall, and a tabular Plexiglas piston was positioned inside the sleeve. By pushing and pulling the piston, the length of the self-made water phantom could be varied to meet the required patients' physical sizes. To compare the international standard water phantom with the length-adjustable and the Plexiglas phantoms, absorbed dose for 6-MV X ray was measured by an ionisation chamber at different depths in three kinds of phantoms. In 70 cases with TBI, midplane doses were metered using the length-adjustable and the Plexiglas phantoms for simulating human dimensions, and dose validation was synchronously carried out. There were no significant statistical differences, p > 0.05, through statistical processing of data from the international standard water phantom and the self-designed one. There were significant statistical differences, p body width. Obviously, the difference had a positive correlation with the body width. The results proved that the new length-adjustable water phantom is more accurate for simulating human dimensions than Plexiglas phantom.

  10. Patient dose analysis in total body irradiation through in vivo dosimetry

    Directory of Open Access Journals (Sweden)

    K Ganapathy

    2012-01-01

    Full Text Available Total body irradiation (TBI is a special radiotherapy technique, administered prior to bone marrow transplantation. Due to the complex nature of the treatment setup, in vivo dosimetry for TBI is mandatory to ensure proper delivery of the intended radiation dose throughout the body. Lithium fluoride (LiF TLD-100 chips are used for the TBI in vivo dosimetry. Results obtained from the in vivo dosimetry of 20 patients are analyzed. Results obtained from forehead, abdomen, pelvis, and mediastinum showed a similar pattern with the average measured dose from 96 to 97% of the prescription dose. Extremities and chest received a dose greater than the prescription dose in many instances (more than 20% of measurements. Homogeneous dose delivery to the whole body is checked by calculating the mean dose with standard deviation for each fraction. Reasons for the difference between prescription dose and measured dose for each site are discussed. Dose homogeneity within ±10% is achieved using our in-house TBI protocol.

  11. In pediatric leukemia, dose evaluation according to the type of compensators in total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Yeon [Dongnam Inst. of Radiological and Medical science, Busan (Korea, Republic of); Kim, Chang Soo; Kim, Jung Hoon [Dept. of Radiological Science, College of Health Science, Catholic University of Busan, Busan (Korea, Republic of)

    2015-04-15

    Total body irradiation (TBI) and chemotherapy are the pre-treatment method of a stem cell transplantations of the childhood leukemia. in this study, we evaluate the Quantitative human body dose prior to the treatment. The MCNPX simulation program evaluated by changing the material of the tissue compensators with imitation material of pediatric exposure in a virtual space. As a result, first, the average skin dose with the material of the tissue compensators of Plexiglass tissue compensators is 74.60 mGy/min, Al is 73.96 mGy/min, Cu is 72.26 mGy/min and Pb 67.90 mGy/min respectively. Second, regardless of the tissue compensators material that organ dose were thyroid, gentile, digestive system, brain, lungs, kidneys higher in order. Finally, the ideal distance between body compensator and the patient were 50 cm aparting each other. In conclusion, tissue compensators Al, Cu, Pb are able to replace of the currently used in Plexiglass materials.

  12. Stimulation of hematopoietic stem cells by interferon inducer in nonhuman primates receiving fractionated total body irradiation

    International Nuclear Information System (INIS)

    Interferon response and hematopoietic stem cells (spleen colony forming units-CFU-S) were studied in rhesus monkeys subjected to fractionated total body irradiation (FTBI). An interferon inducer, a nuclease resistant complex of polyinosinic-polycytidylic acid with poly-L-lysine and carboxmethylcellulose[-poly(ICLC)] was used. Poly(ICLC) at 3.75 mg/m2 was given I.V. to 7 monkeys, 5 of which, starting 24 hours later, received 50 rad of 4 MV X rays twice a week for 2.5 weeks (total of 250 rad). Another group of 4 monkeys received FTBI only. Although the initial interferon response was similar in both groups treated with poly(ICLC)-800 international units (IU), the animals receiving FTBI showed reduced interferon levels after 100 rad. These animals, however, did not develop the hyporesponsiveness to subsequent poly(ICLC) injections that was observed in non-irradiated monkeys. Stabile interferon response (30-100 IU) in the FTBI group paralleled the prolonged persistence of the drug in their serum. Bone marrow (BM) aspirates from animals receiving FTBI and poly(ICLC) contained more CFU-S per 106 nucleated cells than those treated with poly(ICLC) alone or FTBI alone. FTBI with and without poly(ICLC) led to thrombocytopenia and leukopenia. Lower white blood cell (WBC) count was found in irradiated animals treated with poly(ICLC). Partial alopecia was observed in animals receiving poly(ICLC). Two animals--one in the poly(ICLC) and FTBI group and the other receiving FTBI alone, died with thrombocytopenia and leukopenia

  13. Neuro-immune response and sleep studies after whole body irradiation with high-LET particles

    International Nuclear Information System (INIS)

    In order to investigate the biological effects of galactic rays on astronaut cerebral functions after space flight, mice were exposed to different heavy ions (HZE) in whole-body conditions at doses comparable to the galactic flux: 12C, 16O and 20Ne (95 MeV/u, at 42-76 mGy). Animals were also exposed to 42 mGy of 60Co radiation for comparison with HZE. The neuro-immune response, evaluated by interleukin-I (IL-1) measurement, showed that this cytokine was produced 3 h after irradiation by 16O or 60Co. In contrast, neither 12C (56.7 mGy) nor 20Ne (76 mGy) induced IL-1 production. However, immunohistochemical staining of 12C-irradiated mouse brain tissue showed 2 months later a marked inflammatory reaction in the hippocampus and a diffuse response in parenchyma. Sleep studies were realized before and after exposure to 42 mGy of 16O and 76 mGy of 20Ne: only the 20Ne radiation displayed a small effect. A slight decrease in paradoxical sleep, corresponding to a reduction in the number of episodes of paradoxical sleep, was manifested between 8 and 22 days after exposure. Exposure to 12C and 16O induced no changes either in cellularity of spleen or thymus, or in caspase 3 activity (as much as four months after irradiation). Taken together, these data indicate that the CNS could be sensitive to heavy ions and that responses to HZE impact depend on the nature of the particle, the dose threshold and the time delay to develop biological processes. Differences in responses to different HZE highlight the complex biological phenomena to which astronauts are submitted during space flight. (authors)

  14. Stimulation of hematopoietic stem cells by interferon inducer in nonhuman primates receiving fractionated total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lvovsky, E.A. (George Washington Univ. Medical Center, Washington, DC); Levine, P.H.; Bengali, Z.; Leiseca, S.A.; Cicmanec, J.L.; Robinson, J.E.; Bautro, N.; Levy, H.B.; Scott, R.M.

    1982-10-01

    Interferon response and hematopoietic stem cells (spleen colony forming units--CFU-S) were studied in rhesus monkeys subjected to fractionated total body irradiation (FTBI). An interferon inducer, a nuclease resistant complex of polyinosinic-polycytidylic acid with poly-L-lysine and carboxmethylcellulose(-poly(ICLC)) was used. Poly(ICLC) at 3.75 mg/m/sup 2/ was given I.V. to 7 monkeys, 5 of which, starting 24 hours later, received 50 rad of 4 MV X rays twice a week at 2.5 weeks (total of 250 rad). Another group of 4 monkeys received FTBI only. Although the initial interferon response was similar in both groups treated wih poly(ICLC)--800 international units (IU), the animals that receiving FTBI showed reduced interferon levels after 100 rad. These animals, however, did not develop the hyporesponsiveness to subsequent poly(ICLC) injections that was observed in non-irradiated monkeys. Stabile interferon response (30-100 IU) in the FTBI group paralleled the prolonged persistence of the drug in their serum. Bone marrow (BM) aspirates from animals receiving FTBI and poly(ICLC) contained more CFU-S per 10/sup 6/ nucleated cells than those treated with poly(ICLC) along or FTBI with and without poly(ICLC) lead to thrombocytopenia and leukopenia. Lower white blood cell (WBC) count was found in irradiated animals treated with poly(ICLC). Partial alopecia was observed in animals receiving poly(ICLC). Two animals--one in the poly(ICLC) and FTBI group and the other receiving FTBI along, died with thrombocytopenia and leukopenia.

  15. Neuroimmune response and sleep studies after whole body irradiation with high-LET particles

    Science.gov (United States)

    Marquette, C.; Mathieu, J.; Bertho, J.-M.; Galonnier, M.; Wysoki, J.; Maubert, C.; Balanzat, E.; Gerbin, R.; Aigueperse, J.; Clarençon, D.

    2009-10-01

    In order to investigate the biological effects of galactic rays on astronaut cerebral functions after space flight, mice were exposed to different heavy ions (HZE) in whole-body conditions at doses comparable to the galactic flux: 12C, 16O and 20Ne (95 MeV/u, at 42-76 mGy). Animals were also exposed to 42 mGy of 60Co radiation for comparison with HZE. The neuroimmune response, evaluated by interleukin-1 (IL-1) measurement, showed that this cytokine was produced 3 h after irradiation by 16O or 60Co. In contrast, neither 12C (56.7 mGy) nor 20Ne (76 mGy) induced IL-1 production. However, immunohistochemical staining of 12C-irradiated mouse brain tissue showed 2 months later a marked inflammatory reaction in the hippocampus and a diffuse response in parenchyma. Sleep studies were realized before and after exposure to 42 mGy of 16O and 76 mGy of 20Ne: only the 20Ne radiation displayed a small effect. A slight decrease in paradoxical sleep, corresponding to a reduction in the number of episodes of paradoxical sleep, was manifested between 8 and 22 days after exposure. Exposure to 12C and 16O induced no changes either in cellularity of spleen or thymus, or in caspase 3 activity (as much as four months after irradiation). Taken together, these data indicate that the CNS could be sensitive to heavy ions and that responses to HZE impact depend on the nature of the particle, the dose threshold and the time delay to develop biological processes. Differences in responses to different HZE highlight the complex biological phenomena to which astronauts are submitted during space flight.

  16. Neuro-immune response and sleep studies after whole body irradiation with high-LET particles

    Energy Technology Data Exchange (ETDEWEB)

    Marquette, C.; Bertho, J.M.; Wysoki, J.; Maubert, C.; Gerbin, R.; Aigueperse, J. [IRSN, F-92260 Fontenay Aux Roses, (France); Mathieu, J.; Galonnier, M.; Clarencon, D. [CRSSA, Dept Radiobiol and Radiopathol, F-38700 La Tronche, (France); Balanzat, E. [CEA, DSM, CIRIL, Ganil, Caen, (France)

    2009-07-01

    In order to investigate the biological effects of galactic rays on astronaut cerebral functions after space flight, mice were exposed to different heavy ions (HZE) in whole-body conditions at doses comparable to the galactic flux: {sup 12}C, {sup 16}O and {sup 20}Ne (95 MeV/u, at 42-76 mGy). Animals were also exposed to 42 mGy of {sup 60}Co radiation for comparison with HZE. The neuro-immune response, evaluated by interleukin-I (IL-1) measurement, showed that this cytokine was produced 3 h after irradiation by {sup 16}O or {sup 60}Co. In contrast, neither {sup 12}C (56.7 mGy) nor {sup 20}Ne (76 mGy) induced IL-1 production. However, immunohistochemical staining of {sup 12}C-irradiated mouse brain tissue showed 2 months later a marked inflammatory reaction in the hippocampus and a diffuse response in parenchyma. Sleep studies were realized before and after exposure to 42 mGy of {sup 16}O and 76 mGy of {sup 20}Ne: only the {sup 20}Ne radiation displayed a small effect. A slight decrease in paradoxical sleep, corresponding to a reduction in the number of episodes of paradoxical sleep, was manifested between 8 and 22 days after exposure. Exposure to {sup 12}C and {sup 16}O induced no changes either in cellularity of spleen or thymus, or in caspase 3 activity (as much as four months after irradiation). Taken together, these data indicate that the CNS could be sensitive to heavy ions and that responses to HZE impact depend on the nature of the particle, the dose threshold and the time delay to develop biological processes. Differences in responses to different HZE highlight the complex biological phenomena to which astronauts are submitted during space flight. (authors)

  17. Dosimetry and verification of Co total body irradiation with human phantom and semiconductor diodes.

    Science.gov (United States)

    Allahverdi, Mahmoud; Geraily, Ghazale; Esfehani, Mahbod; Sharafi, Aliakbar; Haddad, Peyman; Shirazi, Alireza

    2007-10-01

    Total Body Irradiation (TBI) is a form of radiotherapy used for patients prior to bone marrow or stem cell transplant to destroy any undetectable cancer cells. The dosimetry characteristics of a (60)Co unit for TBI were studied and a simple method for the calculation of the prescribed dose for TBI is presented. Dose homogeneity was verified in a human phantom. Dose measurements were made in water phantom (30 × 30 × 30 cm(3)), using farmer ionization chamber (0.6 cc, TM30010, PTW) and a parallel plate ionization chamber (TM23343, PTW). Point dose measurements for AP/PA irradiation were measured in a human phantom using silicon diodes (T60010L, PTW). The lung dose was measured with an ionization chamber (0.3 cc, TM31013). The validity of the proposed algorithm was checked at TBI distance using the human phantom. The accuracy of the proposed algorithm was within 3.5%. The dose delivered to the mid-lobe of the lung was 14.14 Gy and it has been reduced to 8.16 Gy by applying the proper shield. Dose homogeneity was within ±7% for all measured points. The results indicate that a good agreement between the total prescribed and calculated midplane doses can be achieved using this method. Therefore, it could be possible to use calculated data for TBI treatments.

  18. Effect of whole body neutron irradiation on certain enzyme activities in different brain areas in mice

    International Nuclear Information System (INIS)

    Male swiss albino mice were exposed to whole-body irradiation by fast neutrons of 14 MeV average energy. Two single doses of 0.08 sievert and 0.16 sievert were used, corresponding to fluences of 1.27 X 108 and 2.54 X 108 n/cm2 respectively. Two enzymes were assessed in different layers of the cerebrum and cerebellum of mouse brain. Changes in the activities of acid phosphatase (ACP) and succinic dehydrogenase (SDH) were taken to measure alterations in lysosomal and mitochondrial functions respectively. The degrees of lysosomal affection in different layers of the cerebrum were not uniform, while changes in A activity were very prominent in certain layers (e.g. external pyramidal layer, polymorphous cells layer and white matter), they were practically absent in others (e.g. internal pyramidal layer). Stronger effect was noted in the tissue layers of the cerebellum. The activity of SDH decreased as result of fast neutron irradiation. The response was more apparent for this enzyme than for ACP. This indicates more liability for a decrease in energy metabolism with consequent effect on behavioural and physiological functions under central nervous system control. 4 figs., 4 tabs

  19. Total Body Irradiation for Allogeneic Bone Marrow Transplantation in Chronic Myelogenous Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Su Mi; Choi, Ihl Bohng; Kang, Ki Mun; Kim, In Ah; Shinn, Kyung Sub; Kim, Choon Choo; Kim, Dong Jip [Catholic University College of Medicine, Seoul (Korea, Republic of)

    1994-06-15

    Between July 1987 and December 1992, we treated 22 patients with chromic myelogenous leukemia; 14 in the chronic phase and 8 with more advanced disease. All were received with allogeneic bone marrow transplantation from HLA-identical sibling donors after a total body irradiation (TBI) cyclophosphamide conditioning regimen. Patients were non-randomly assigned to either 1200 cGy/6 fractions/3 days (6 patients) or 1320 cGy/8 fractions/4 days (16 patients) by dose of TBI. Of the 22 patients, 8 were prepared with cyclophosphamide alone, 14 were conditioned with additional adriamycin or daunorubicin. To prevent graft versus host disease, cyclosporine was given either alone or in conjunction with methotrexate. The actuarial survival and leukemic-free survival at four years were 58.5% and 41.2%, respectively, and the relapse rate was 36% among 22 patients. There was a statistically significant difference in survival between the patients in chronic phase and more advanced phase (76% vs 33%, p=0.05). The relapse rate of patients receiving splenectomy was higher than that of patients receiving splenic irradiation (50% vs 0%, p=0.04). We conclude that the probability of cure is highest if transplantation is performed while the patient remains in the chronic phase.

  20. Allogeneic bone marrow transplantation in adults after fractionated body irradiation and high dose cyclophosphamide

    International Nuclear Information System (INIS)

    The authors present short and long-term results of allogeneic bone marrow transplantation after hyper-fractionated total body irradiation and high dose cyclophosphamide in ten patients treated for leukaemia during th period 1985-89. Three patients died from complications connected to the transplantation, while seven are living free from leukaemia 18 to 59 months after transplantation. Two patients need treatment for chronic graft versus host disease. Allogeneic bone marrow transplantation is expensive and risky. Close cooperation between clinicians and laboratory specialists is essential. The treatment increases long term survival and probably cures certain patients with leukaemia. Some of the patients will need treatment for chronic graft versus host disease and other late sequelae. 19 refs., 2 tabs

  1. Simple technique for fabrication of shielding blocks for total body irradiation at extended treatment distances

    Directory of Open Access Journals (Sweden)

    Ravichandran R

    2009-01-01

    Full Text Available Techniques are being standardized in our department for total body irradiation (TBI with six MV photons in linear accelerator for preconditioning to bone marrow transplantation (BMT. Individualized shields with low melting point alloy are to be fabricated for shielding critical organs such as lungs, kidneys etc. A method to mount diminished dimension of shields in a tray at 3.75m is designed in the department for a teletreatment distance of four meters with magna field with A simulator image taken with the patient′s midplane (MP at one meter distance is used to mark the dimensions of lung, scaled down by a factor of 3.75/4.0. These lung dimensions are reprinted from the digital simulator image for making the shield. The methodology of the technique using digitized minification in radiography is the first of its kind to be used for shield cutting in magna field radiotherapy.

  2. Low-dose total body irradiation versus combination chemotherapy for lymphomas with follicular growth pattern.

    Science.gov (United States)

    Meerwaldt, J H; Carde, P; Burgers, J M; Monconduit, M; Thomas, J; Somers, R; Sizoo, W; Glabbeke, M V; Duez, N; de Wolf-Peeters, C

    1991-10-01

    The treatment of Non-Hodgkin's lymphomas with follicular growth pattern and advanced stage of disease remains controversial. Treatments varying from no initial treatment up to aggressive combination chemotherapy have been advocated. The EORTC Lymphoma Cooperative Group has performed a randomized prospective trial comparing short duration low dose total body irradiation (TBI) vs combination chemotherapy (CHVmP) + consolidation radiotherapy. Ninety-three patients were entered; of 84 evaluable patients, 44 received TBI and 40 CHVmP. Complete remission (CR) rates were 36%--TBI and 55%--CHVmP, but overall response rates were identical, 76 versus 69%. No significant difference in freedom from progression or survival was observed. No unexpected toxicity was seen. Although numbers are small, we cannot conclude that aggressive combination chemo-radiotherapy resulted in a better survival. Our analysis confirms that there is a constant risk of relapse. Other approaches should be explored if survival benefit is the ultimate goal in treatment of this patient population.

  3. Interstitial pneumonitis after allogeneic bone marrow transplantation following total body irradiation

    International Nuclear Information System (INIS)

    The records of 40 patients who received allogeneic bone marrow transplantation (BMT) at Hyogo College of Medicine under the same conditioning regimen using cyclophosphamide and total body irradiation (TBI) from January 1984 to August 1989 were analyzed. The dose rate of TBI was 10 cGy per minute, and the total dose was 10 Gy (2.5 Gy daily for 4 days). Interstitial pneumonitis (IP) occurred in 13 of 40 patients, and was fatal in five patients. The probability of developing IP during the first year was 31%. We performed univariate analysis on the following factors but did not find any significant risk factors for IP: age and sex of patient, sex mismatch, ABO mismatch, grade of acute graft-versus-host disease, post immunosuppression regimen, and number of marrow cells transfused. (author)

  4. Half body irradiation of patients with multiple bone metastases: A phase II trial

    DEFF Research Database (Denmark)

    Berg, Randi; Yilmaz, Mette; Høyer, Morten;

    2009-01-01

    AIM OF STUDY: The primary aim of this study was to evaluate the effect of half-body irradiation (HBI) on pain and quality of life in cancer patients with multiple bone metastases. The secondary aim was to evaluate side effects of the treatment. PATIENTS AND METHODS: A total of 44 patients received...... lower (n = 37), upper (n = 5), or sequential HBI (n = 2). The dose for lower HBI was 8 Gy in one fraction and for upper HBI 7 Gy in one fraction, with reduction of the lung dose to 6 Gy in one fraction by partial shielding. The majority of patients (n = 41) were males with prostate cancers (93...... after treatment. RESULTS: Relief of pain was observed in 76% of the patients receiving HBI with 8.8% of the patients experiencing complete pain relief with no residual pain in the treated field. For most patients, the pain relief was lasting throughout the follow-up period. About one third...

  5. Effects of chronic whole-body gamma irradiation on cell mediated immunity

    International Nuclear Information System (INIS)

    The whole blood lymphocyte stimulation test has been used to estimate the effects of chronic, whole-body, gamma irradiation in the dog. At lower dose levels, 0.07 and 0.33 R/day to cumulative dose of about 50 and 250 R, there was no change in cell mediated immunity. Dogs at high dose levels were affected. Dogs which succumbed to aplastic anemia at high doses had reduced immunological responses. Dogs which survived these high doses showed a temporary depression. When aplastic anemia was initially noted, there was a differential response to PHA and Con-A stimulation. The response to the former mitogen was profoundly reduced, but Con-A stimulated cells were unaffected, indicative of the development of radioresistant cell lines. As the dogs progressed toward aplastic anemia, all T lympocytes were negatively affected

  6. Chondrosarcoma arising within a radiation-induced osteochondroma several years following childhood total body irradiation: Case report

    Energy Technology Data Exchange (ETDEWEB)

    Nagata, Shuji [Kurume University Hospital, Department of Radiology, Fukuoka (Japan); Shen, Robert K. [Mayo Clinic, Department of Surgery, Rochester, MN (United States); Laack, Nadia N. [Mayo Clinic, Department of Radiation Oncology, Rochester, MN (United States); Inwards, Carrie Y. [Mayo Clinic, Department of Pathology, Rochester, MN (United States); Wenger, Doris E.; Amrami, Kimberly K. [Mayo Clinic, Department of Radiology, Rochester, MN (United States)

    2013-08-15

    Malignant degeneration arising in radiation-induced osteochondromas is extremely rare. We report a case of a 34-year-old man with a chondrosarcoma arising from an osteochondroma of the left posterior eighth rib that developed following total body irradiation received as part of the conditioning regimen prior to bone marrow transplantation at age 8. To our knowledge, this is only the fourth reported case of a chondrosarcoma arising within a radiation-induced osteochondroma and the first case occurring following childhood total body irradiation. (orig.)

  7. Sesamol attenuates genotoxicity in bone marrow cells of whole-body γ-irradiated mice.

    Science.gov (United States)

    Kumar, Arun; Selvan, Tamizh G; Tripathi, Akanchha M; Choudhary, Sandeep; Khan, Shahanshah; Adhikari, Jawahar S; Chaudhury, Nabo K

    2015-09-01

    Ionising radiation causes free radical-mediated damage in cellular DNA. This damage is manifested as chromosomal aberrations and micronuclei (MN) in proliferating cells. Sesamol, present in sesame seeds, has the potential to scavenge free radicals; therefore, it can reduce radiation-induced cytogenetic damage in cells. The aim of this study was to investigate the radioprotective potential of sesamol in bone marrow cells of mice and related haematopoietic system against radiation-induced genotoxicity. A comparative study with melatonin was designed for assessing the radioprotective potential of sesamol. C57BL/6 mice were administered intraperitoneally with either sesamol or melatonin (10 and 20mg/kg body weight) 30 min prior to 2-Gy whole-body irradiation (WBI) and sacrificed after 24h. Total chromosomal aberrations (TCA), MN and cell cycle analyses were performed using bone marrow cells. The comet assay was performed on bone marrow cells, splenocytes and lymphocytes. Blood was drawn to study haematological parameters. Prophylactic doses of sesamol (10 and 20mg/kg) in irradiated mice reduced TCA and micronucleated polychromatic erythrocyte frequency in bone marrow cells by 57% and 50%, respectively, in comparison with radiation-only groups. Sesamol-reduced radiation-induced apoptosis and facilitated cell proliferation. In the comet assay, sesamol (20mg/kg) treatment reduced radiation-induced comets (% DNA in tail) compared with radiation only (P < 0.05). Sesamol also increased granulocyte populations in peripheral blood similar to melatonin. Overall, the radioprotective efficacy of sesamol was found to be similar to that of melatonin. Sesamol treatment also showed recovery of relative spleen weight at 24h of WBI. The results strongly suggest the radioprotective efficacy of sesamol in the haematopoietic system of mice. PMID:25863274

  8. Comparison of 32P therapy and sequential hemibody irradiation (HBI) for bony metastases as methods of whole body irradiation

    International Nuclear Information System (INIS)

    We report a retrospective study of 15 patients with prostate carcinoma and diffuse bone metastases treated with sodium 32P for palliation of pain at Downstate Medical Center and Kings County Hospital from 1973 to 1978. The response rates, duration of response, and toxicities are compared with those of other series of patients treated with 32P and with sequential hemibody irradiation. The response rates and duration of response are similar with both modalities ranging from 58 to 95% with a duration of 3.3 to 6 months with 32P and from 75 to 86% with a median duration of 5.5 months with hemibody irradiation. There are significant differences in the patterns of response and in the toxicities of the two treatment methods. Both methods cause significant bone marrow depression. Acute radiation syndrome, radiation pneumonitis, and alopecia are seen with sequential hemibody irradiation and not with 32P, but their incidence can be reduced by careful treatment planning. Hemibody irradiation can provide pain relief within 24 to 48 h, while 32P may produce an initial exacerbation of pain. Lower hemibody irradiation alone is less toxic than either upper hemibody irradiation or 32P treatment

  9. Comparison of /sup 32/P therapy and sequential hemibody irradiation (HBI) for bony metastases as methods of whole body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Aziz, H.; Choi, K.; Sohn, C.; Yaes, R.; Rotman, M.

    1986-06-01

    We report a retrospective study of 15 patients with prostate carcinoma and diffuse bone metastases treated with sodium /sup 32/P for palliation of pain at Downstate Medical Center and Kings County Hospital from 1973 to 1978. The response rates, duration of response, and toxicities are compared with those of other series of patients treated with /sup 32/P and with sequential hemibody irradiation. The response rates and duration of response are similar with both modalities ranging from 58 to 95% with a duration of 3.3 to 6 months with /sup 32/P and from 75 to 86% with a median duration of 5.5 months with hemibody irradiation. There are significant differences in the patterns of response and in the toxicities of the two treatment methods. Both methods cause significant bone marrow depression. Acute radiation syndrome, radiation pneumonitis, and alopecia are seen with sequential hemibody irradiation and not with /sup 32/P, but their incidence can be reduced by careful treatment planning. Hemibody irradiation can provide pain relief within 24 to 48 h, while /sup 32/P may produce an initial exacerbation of pain. Lower hemibody irradiation alone is less toxic than either upper hemibody irradiation or /sup 32/P treatment.

  10. Biochemical and histological changes in whole body gamma-irradiated rats feed on wheat, barely and corn bran

    International Nuclear Information System (INIS)

    The present work aims to study the effect of adding 3 different of dietary fibers (wheat, barley or corn bran) to normal balanced diet on liver function, blood, cholesterol, triglycerides and blood glucose level to counteract their elevation in whole body gamma irradiation rats. The experimental diets (balanced diet + fibre additive) were fed for 4 weeks. Samples (blood and tissue) were collected at intervals of times 7, 14 and 28 days post exposure to single dose (7 Gy) gamma irradiation. The control group consumed a fibre diet for 4 weeks, but not irradiated. The minimum aspartate amino-transferase (AST) and alanine aminotransferase (ALT) activities and the lowest blood total cholestrol, triglycerides and blood glucose were observed in rats (irradiated and non-irradiated rats) fed on wheat bran experimental diet (barley or corn bran). It could be concluded that wheat fibers were more effective, as compared with other fibers contained in balanced diet, in improving the investigated parameters observed after whole body gamma irradiation exposure

  11. Protective Effects of Ibuprofen and L-Carnitine Against Whole Body Gamma Irradiation-Induced Duodenal Mucosal Injury

    Directory of Open Access Journals (Sweden)

    Meryem Akpolat

    2011-03-01

    Full Text Available Objective: Ibuprofen and L-carnitine have been demonstrated to provide radioprotective activity to the hamster against whole body sublethal irradiation. The purpose of this study is to test those antioxidant drugs, each of which has the capacity of inhibiting mucosal injury, as topical radioprotectants for the intestine. Material and Methods: The male hamsters were divided into the following four groups (n=6: group 1: control group, received saline, 1 ml/100 g by gavage, as placebo. Group 2: irradiated-control group, received whole body irradiation of 8 Gy as a single dose plus physiological saline. The animals in groups 3 and 4 were given a daily dose of 10 mg/kg of ibuprofen and 50 mg/kg of L-carnitine for 15 days respectively, before irradiation with a single dose of 8 Gy. Twenty-four hours after radiation exposure, the hamsters were sacrificed and samples were taken from the duodenum, and the histopatological determinations were carried out. Results: Morphologically, examination of the gamma irradiated duodenum revealed the presence of shortening and thickening of villi and flattening of enterocytes, massive subepithelial lifting. Pretreatment of ibuprofen and L-carnitine with irradiation reduced these histopathological changes. Conclusion: Ibuprofen and L-carnitine administrated by the oral route may be a good radioprotector against small intestinal damage in patients undergoing radiotherapy.

  12. A simplified technique for delivering total body irradiation (TBI) with improved dose homogeneity

    Energy Technology Data Exchange (ETDEWEB)

    Yao Rui; Bernard, Damian; Turian, Julius; Abrams, Ross A.; Sensakovic, William; Fung, Henry C.; Chu, James C. H. [Department of Radiation Oncology, Rush University Medical Center, 500 South Paulina Street, Chicago, Illinois 60612 (United States); Sections of Hematology and Stem Cell Transplantation, Division of Hematology/Oncology, Rush University Medical Center, 500 South Paulina Street, Chicago, Illinois 60612 (United States); Department of Radiation Oncology, Rush University Medical Center, 500 South Paulina Street, Chicago, Illinois 60612 (United States)

    2012-04-15

    Purpose: Total body irradiation (TBI) with megavoltage photon beams has been accepted as an important component of management for a number of hematologic malignancies, generally as part of bone marrow conditioning regimens. The purpose of this paper is to present and discuss the authors' TBI technique, which both simplifies the treatment process and improves the treatment quality. Methods: An AP/PA TBI treatment technique to produce uniform dose distributions using sequential collimator reductions during each fraction was implemented, and a sample calculation worksheet is presented. Using this methodology, the dosimetric characteristics of both 6 and 18 MV photon beams, including lung dose under cerrobend blocks was investigated. A method of estimating midplane lung doses based on measured entrance and exit doses was proposed, and the estimated results were compared with measurements. Results: Whole body midplane dose uniformity of {+-}10% was achieved with no more than two collimator-based beam modulations. The proposed model predicted midplane lung doses 5% to 10% higher than the measured doses for 6 and 18 MV beams. The estimated total midplane doses were within {+-}5% of the prescribed midplane dose on average except for the lungs where the doses were 6% to 10% lower than the prescribed dose on average. Conclusions: The proposed TBI technique can achieve dose uniformity within {+-}10%. This technique is easy to implement and does not require complicated dosimetry and/or compensators.

  13. Inability of donor total body irradiation to prolong survival of vascularized bone allografts: Experimental study in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez del Pino, J.; Benito, M.; Randolph, M.A.; Weiland, A.J. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (USA))

    1990-07-01

    At the present time, the toxic side effects of recipient immunosuppression cannot be justified for human non-vital organ transplantation. Total body irradiation has proven effective in ablating various bone-marrow-derived and endothelial immunocompetent cellular populations, which are responsible for immune rejection against donor tissues. Irradiation at a dose of 10 Gy was given to donor rats six days prior to heterotopic transplantation of vascularized bone allografts to host animals. Another group of recipient rats also received a short-term (sixth to fourteenth day after grafting), low dose of cyclosporine. Total body irradiation was able merely to delay rejection of grafts across a strong histocompatibility barrier for one to two weeks, when compared to nonirradiated allografts. The combination of donor irradiation plus cyclosporine did not delay the immune response, and the rejection score was similar to that observed for control allografts. Consequently, allograft viability was quickly impaired, leading to irreversible bone damage. This study suggest that 10 Gy of donor total body irradiation delivered six days prior to grafting cannot circumvent the immune rejection in a vascularized allograft of bone across a strong histocompatibility barrier.

  14. Gene Expression Changes in Mouse Intestinal Tissue Following Whole-Body Proton or Gamma-Irradiation

    Science.gov (United States)

    Purgason, Ashley; Zhang, Ye; Mangala, Lingegowda; Nie, Ying; Gridley, Daila; Hamilton, Stanley R.; Seidel, Derek V.; Wu, Honglu

    2014-01-01

    Crew members face potential consequences following exposure to the space radiation environment including acute radiation syndrome and cancer. The space radiation environment is ample with protons, and numerous studies have been devoted to the understanding of the health consequences of proton exposures. In this project, C57BL/6 mice underwent whole-body exposure to 250 MeV of protons at doses of 0, 0.1, 0.5, 2 and 6 Gy and the gastrointestinal (GI) tract of each animal was dissected four hours post-irradiation. Standard H&E staining methods to screen for morphologic changes in the tissue showed an increase in apoptotic lesions for even the lowest dose of 0.1 Gy, and the percentage of apoptotic cells increased with increasing dose. Results of gene expression changes showed consistent up- or down- regulation, up to 10 fold, of a number of genes across exposure doses that may play a role in proton-induced oxidative stress including Gpx2. A separate study in C57BL/6 mice using the same four hour time point but whole-body gamma-irradiation showed damage to the small intestine with lesions appearing at the smallest dose of 0.05 Gy and increasing with increasing absorbed dose. Expressions of genes associated with oxidative stress processes were analyzed at four hours and twenty-four hours after exposure to gamma rays. We saw a much greater number of genes with significant up- or down-regulation twenty-four hours post-exposure as compared to the four hour time point. At both four hours and twenty-four hours post-exposure, Duox1 and Mpo underwent up-regulation for the highest dose of 6 Gy. Both protons and gamma rays lead to significant variation in gene expressions and these changes may provide insight into the mechanism of injury seen in the GI tract following radiation exposure. We have also completed experiments using a BALB/c mouse model undergoing whole-body exposure to protons. Doses of 0, 0.1, 1 and 2 Gy were used and results will be compared to the work mentioned

  15. Investigation on using high-energy proton beam for total body irradiation (TBI).

    Science.gov (United States)

    Zhang, Miao; Qin, Nan; Jia, Xun; Zou, Wei J; Khan, Atif; Yue, Ning J

    2016-01-01

    This work investigated the possibility of using proton beam for total body irradia-tion (TBI). We hypothesized the broad-slow-rising entrance dose from a monoen-ergetic proton beam can deliver a uniform dose to patient with varied thickness. Comparing to photon-based TBI, it would not require any patient-specific com-pensator or beam spoiler. The hypothesis was first tested by simulating 250 MeV, 275 MeV, and 300 MeV protons irradiating a wedge-shaped water phantom in a paired opposing arrangement using Monte Carlo (MC) method. To allow ± 7.5% dose variation, the maximum water equivalent thickness (WET) of a treatable patient separation was 29 cm for 250 MeV proton, and > 40 cm for 275 MeV and 300 MeV proton. The compared 6 MV photon can only treat patients with up to 15.5 cm water-equivalent separation. In the second step, we simulated the dose deposition from the same beams on a patient's whole-body CT scan. The maximum patient separation in WET was 23 cm. The calculated whole-body dose variations were ± 8.9%, ± 9.0%, ± 9.6%, and ± 14% for 250 MeV proton, 275 MeV proton, 300 MeV proton, and 6 MV photon. At last, we tested the current machine capability to deliver a monoenergetic proton beam with a large uniform field. Experiments were performed on a compact double scattering single-gantry proton system. With its C-shaped gantry design, the source-to-surface distance (SSD) reached 7 m. The measured dose deposition curve had 22 cm relatively flat entrance region. The full width half maximum field size was measured 105 cm. The current scatter filter had to be redesigned to produce a uniform intensity at such treatment distance. In con-clusion, this work demonstrated the possibility of using proton beam for TBI. The current commercially available proton machines would soon be ready for such task. PMID:27685117

  16. Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small intestine

    Directory of Open Access Journals (Sweden)

    Y. Guney

    2007-10-01

    Full Text Available We investigated the day-night differences in intestinal oxidative-injury and the inflammatory response following total body (TB or abdominopelvic (AP irradiation, and the influence of melatonin administration on tissue injury induced by radiation. Rats (male Wistar, weighing 220-280 g in the irradiated groups were exposed to a dose of 8 Gy to the TB or AP region in the morning (resting period - 1 h after light onset or evening (activity span - 13 h after light onset. Vehicle or melatonin was administered immediately before, immediately after and 24 h after irradiation (10, 2.0 and 10 mg/kg, ip, respectively to the irradiated rats. AP (P < 0.05 and TB (P < 0.05 irradiation applied in the morning caused a significant increase in thiobarbituric acid reactive substance (TBARS levels. Melatonin treatment in the morning (P < 0.05 or evening (P < 0.05 decreased TBARS levels after TB irradiation. After AP irradiation, melatonin treatment only in the morning caused a significant decrease in TBARS levels (P < 0.05. Although we have confirmed the development of inflammation after radiotherapy by histological findings, neither AP nor TB irradiation caused any marked changes in myeloperoxidase activity in the morning or evening. Our results indicate that oxidative damage is more prominent in rats receiving TB and AP irradiation in the morning and melatonin appears to have beneficial effects on oxidative damage irrespective of the time of administration. Increased neutrophil accumulation indicates that melatonin administration exerts a protective effect on AP irradiation-induced tissue oxidative injury, especially in the morning.

  17. Suppression of delayed-type hypersensitivity to oxazolone in whole-body-irradiated mice and protection by WR-2721

    International Nuclear Information System (INIS)

    The effect of whole-body irradiation on cellular immunity, as measured in vivo by delayed-type hypersensitivity (DTH) to oxazolone, was determined in CD2F1 mice. DTH, determined by changes in ear swelling after challenge with oxazolone, was significantly depressed in irradiated mice (500-900 rad of 60Co) in a dose-dependent fashion when animals were irradiated after sensitization and before challenge with oxazolone. Administration of WR-2721 30 min before irradiation (2 days after sensitization) resulted in protection against suppression of DTH, which was dependent on drug and radiation dose. An effective dose of WR-2721 provided an approximate dose-modifying factor of 1.3. The data suggest that WR-2721 interacts with cells involved in that DTH response and that WR-2721 may be useful in protecting against radiation-induced decrements in cell-mediated immunity

  18. The effects of whole-body irradiation on the serum levels and kinetics of thyroid hormones in rats

    International Nuclear Information System (INIS)

    The effects of a single whole-body dose of X-rays on the serum levels and kinetics of thyroid hormones in rats were studied. The influence of radiation-induced anorexia was monitored by using pair fed control groups. A dose of 800 rad caused a reduction in T4 levels and 750 rad had a similar effect on T3; in each case the control group showed a smaller reduction. The kinetic results indicated that, in the control groups, the early reduction in hormone concentrations was caused by decreased production, whereas, in the irradiated groups, it was caused by a change in the distribution of the hormone; however the continuing reduction in hormone levels in the irradiated rats appeared to result from decreased production. The results suggest that the thyroid system may play an active part in the early metabolic changes which follow whole-body irradiation. (author)

  19. In vivo dosimetry for total body irradiation: five-year results and technique comparison.

    Science.gov (United States)

    Patel, Reshma P; Warry, Alison J; Eaton, David J; Collis, Christopher H; Rosenberg, Ivan

    2014-07-08

    The aim of this work is to establish if the new CT-based total body irradiation (TBI) planning techniques used at University College London Hospital (UCLH) and Royal Free Hospital (RFH) are comparable to the previous technique at the Middlesex Hospital (MXH) by analyzing predicted and measured diode results. TBI aims to deliver a homogeneous dose to the entire body, typically using extended SSD fields with beam modulation to limit doses to organs at risk. In vivo dosimetry is used to verify the accuracy of delivered doses. In 2005, when the Middlesex Hospital was decommissioned and merged with UCLH, both UCLH and the RFH introduced updated CT-planned TBI techniques, based on the old MXH technique. More CT slices and in vivo measurement points were used by both; UCLH introduced a beam modulation technique using MLC segments, while RFH updated to a combination of lead compensators and bolus. Semiconductor diodes were used to measure entrance and exit doses in several anatomical locations along the entire body. Diode results from both centers for over five years of treatments were analyzed and compared to the previous MXH technique for accuracy and precision of delivered doses. The most stable location was the field center with standard deviations of 4.1% (MXH), 3.7% (UCLH), and 1.7% (RFH). The least stable position was the ankles. Mean variation with fraction number was within 1.5% for all three techniques. In vivo dosimetry can be used to verify complex modulated CT-planned TBI, and demonstrate improvements and limitations in techniques. The results show that the new UCLH technique is no worse than the previous MXH one and comparable to the current RFH technique.

  20. Taxonomy Icon Data: Doguera baboon [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available Doguera baboon Papio anubis Chordata/Vertebrata/Mammalia/Theria/Eutheria/Primate Papio_anub...is_L.png Papio_anubis_NL.png Papio_anubis_S.png Papio_anubis_NS.png http://biosciencedbc.jp/taxonomy..._icon/icon.cgi?i=Papio+anubis&t=L http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Papio+anubis&t=NL http://...biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Papio+anubis&t=S http://biosciencedbc.jp/taxonomy_icon/icon.cgi?i=Papio+anubis&t=NS ...

  1. COMPROMISING EFFECT OF LOW DOSE-RATE TOTAL-BODY IRRADIATION ON ALLOGENEIC BONE-MARROW ENGRAFTMENT

    NARCIS (Netherlands)

    VANOS, R; KONINGS, AWT; DOWN, JD

    1993-01-01

    The protraction of total body irradiation (TBI) to a continuous low dose-rate has been investigated for its effect on donor marrow engraftment in murine bone marrow transplant (BMT) models of varying histocompatibility. Three different BMT combinations were used: syngeneic [B6-Gpi-1a --> B6-Gpi-1b],

  2. Renal histopathology of a baboon model with type 2 diabetes.

    Science.gov (United States)

    Rincon-Choles, Hernan; Abboud, Hanna E; Lee, Shuko; Shade, Robert E; Rice, Karen S; Carey, K Dee; Comuzzie, Anthony G; Barnes, Jeffrey L

    2012-10-01

    Naturally occurring type 2 diabetes has been found in a colony of baboons. Ongoing characterization of the baboon colony maintained at the Southwest National Primate Research Center has revealed a significant range of glucose sensitivity with some animals clearly diabetic.   Seven baboons, four with diabetes and three without diabetes, underwent histopathological investigation. Three diabetic animals were diagnosed using fasting blood glucose, hemoglobin A1C, and intravenous glucose tolerance test, and a fourth one was known to have hyperglycemia. One control baboon and three baboons with diabetes had microalbuminuria. On kidney biopsy, diabetic baboons had thickening of the glomerular basement membrane and mesangial matrix expansion compared to controls. Immunohistochemistry showed the diabetic animals had increased mesangial expression of cellular fibronectin ED-A. Two diabetic animals with microalbuminuria had evidence of mesangiolysis with the formation of an early nodule. One diabetic animal had a Kimmestiel-Wilson nodule. We conclude that the baboon represents a useful primate model of diabetes and nephropathy that resembles the nephropathy associated with type 2 diabetes in humans.

  3. Acute Radiation Syndrome Severity Score System in Mouse Total-Body Irradiation Model.

    Science.gov (United States)

    Ossetrova, Natalia I; Ney, Patrick H; Condliffe, Donald P; Krasnopolsky, Katya; Hieber, Kevin P

    2016-08-01

    Radiation accidents or terrorist attacks can result in serious consequences for the civilian population and for military personnel responding to such emergencies. The early medical management situation requires quantitative indications for early initiation of cytokine therapy in individuals exposed to life-threatening radiation doses and effective triage tools for first responders in mass-casualty radiological incidents. Previously established animal (Mus musculus, Macaca mulatta) total-body irradiation (γ-exposure) models have evaluated a panel of radiation-responsive proteins that, together with peripheral blood cell counts, create a multiparametic dose-predictive algorithm with a threshold for detection of ~1 Gy from 1 to 7 d after exposure as well as demonstrate the acute radiation syndrome severity score systems created similar to the Medical Treatment Protocols for Radiation Accident Victims developed by Fliedner and colleagues. The authors present a further demonstration of the acute radiation sickness severity score system in a mouse (CD2F1, males) TBI model (1-14 Gy, Co γ-rays at 0.6 Gy min) based on multiple biodosimetric endpoints. This includes the acute radiation sickness severity Observational Grading System, survival rate, weight changes, temperature, peripheral blood cell counts and radiation-responsive protein expression profile: Flt-3 ligand, interleukin 6, granulocyte-colony stimulating factor, thrombopoietin, erythropoietin, and serum amyloid A. Results show that use of the multiple-parameter severity score system facilitates identification of animals requiring enhanced monitoring after irradiation and that proteomics are a complementary approach to conventional biodosimetry for early assessment of radiation exposure, enhancing accuracy and discrimination index for acute radiation sickness response categories and early prediction of outcome. PMID:27356057

  4. Effect of a whole-body gamma irradiation on glycemia and ATP blood level in rats

    International Nuclear Information System (INIS)

    An attempt was made to establish possible correlations, during gamma irradiation, between glucose and ATP. The variations in their blood levels were studied, using specific enzymatic methods. The results obtained after a low dose irradiation (150 roentgens) demonstrated an increase of glycemia during the hours following the irradiation and a parallel decrease of ATP blood level

  5. Effects of a granulocyte colony stimulating factor, Neulasta, in mini pigs exposed to total body proton irradiation

    Science.gov (United States)

    Sanzari, Jenine K.; Krigsfeld, Gabriel S.; Shuman, Anne L.; Diener, Antonia K.; Lin, Liyong; Mai, Wilfried; Kennedy, Ann R.

    2015-04-01

    Astronauts could be exposed to solar particle event (SPE) radiation, which is comprised mostly of proton radiation. Proton radiation is also a treatment option for certain cancers. Both astronauts and clinical patients exposed to ionizing radiation are at risk for loss of white blood cells (WBCs), which are the body's main defense against infection. In this report, the effect of Neulasta treatment, a granulocyte colony stimulating factor, after proton radiation exposure is discussed. Mini pigs exposed to total body proton irradiation at a dose of 2 Gy received 4 treatments of either Neulasta or saline injections. Peripheral blood cell counts and thromboelastography parameters were recorded up to 30 days post-irradiation. Neulasta significantly improved WBC loss, specifically neutrophils, in irradiated animals by approximately 60% three days after the first injection, compared to the saline treated, irradiated animals. Blood cell counts quickly decreased after the last Neulasta injection, suggesting a transient effect on WBC stimulation. Statistically significant changes in hemostasis parameters were observed after proton radiation exposure in both the saline and Neulasta treated irradiated groups, as well as internal organ complications such as pulmonary changes. In conclusion, Neulasta treatment temporarily alleviates proton radiation-induced WBC loss, but has no effect on altered hemostatic responses.

  6. Hippophae leaf extract (SBL-1) countered radiation induced dysbiosis in jejunum of total body 60Cobalt gamma - irradiated mice

    International Nuclear Information System (INIS)

    Single dose of SBL-1 administered at the rate 30 mg/kg body weight (b.w.) 30 min prior to whole body 60Co-gamma-irradiation at lethal dose (10 Gy), rendered >90% survival in comparison to zero survival in the non-SBL-1 treated 60Co-gamma-irradiated (10 Gy) mice population (J Herbs Spices Med Plants, 2009; 15(2): 203-215). Present study investigated the effect of SBL-1 on jejunal microbiota in lethally irradiated mice. Study was performed with inbred Swiss albino Strain 'A' male mice (age 9 weeks) weighing 28±2 g. The animals were maintained under controlled environment at 26±2℃; 12 h light/dark cycle and offered standard animal food (Golden feed, Delhi) as well as tap water ad libitum. Metagenomic DNA was extracted, purified and quantified from jejunum of the mice. Universal primers (27f and 1492r) were used to amplify the 16S rRNA DNA from the metagenomic DNA. Amplicons were sequenced, vector contamination and chimeras were removed. The sequences (GenBank Accession No: KF681283 to KF681351) were taxonomically classified by using Sequence Match program, Ribosomal Database Project as well as by nucleotide-BLAST (E-value: 10, database: 16S rRNA gene sequences, Bacteria and Archea). Phylogenetic Tree was prepared using MEGA 5.2 package, using maximum likelihood algorithm after sequence alignment by MUSCLE. Thermus aquaticus was used as out-group to construct rooted tree. Branch stability was assessed by bootstrap analysis. Untreated animals and the animals treated with SBL-1 had 100% Lactobacillus; 60Co gamma-irradiated animals had 55% Cohaesibacter (Alphaproteobacteria); 27% Mycoplasma (Tenericutes) and only 18% Lactobacillus; animals treated with SBL-1 prior to irradiation had 89% Lactobacillus and 11% Clostridium. This study demonstrated that treatment with SBL-1 at radioprotective doses before total body irradiation with lethal dose (10 Gy) countered the jejunal dysbiosis. (author)

  7. Fractionated half body irradiation for palliation of multiple symptomatic bone metastases from solid tumors

    International Nuclear Information System (INIS)

    This was a phase I-II nonrandomized study that explored the toxicity and response of fractionated half-body irradiation (F-HBI) in patients with multiple symptomatic osseous metastases. The patients had no premedication and received 10 Gy in 5 fractions with a dose rate of 15 cGy/min. At the Cancer Institute Hospital, 9 patients were treated by this technique (1 upper and lower F-HBI, 6 upper F-HBI, 2 lower F-HBI). All patients were female and had adenocarcinomas (8 breast and 1 lung). Adverse effects were myelosuppression, vomiting and partial alopecia. But hematologic toxicity was treated with blood transfusion or G-CSF. All toxicity was transient, and no pneumonitis nor radiation-related deaths occurred. When given as palliation, F-HBI was found to relieve pain in 80% of the patients. In 10% of the patients the pain relief was complete. The mean time to achieve pain relief in responders after F-HBI was 9 days. The pain relief was long-lasting and continued without need of reirradiation for 40% of the remaining patient's life. This treatment modality appears to be well tolerated and effective in patients with multiple symptomatic osseous metastases. The optimal indications, dose and fractionation for F-HBI should be further explored in randomized trials. (author)

  8. Conditioning with total body irradiation for autologous bone marrow transplantation in patients with advanced neuroblastoma

    International Nuclear Information System (INIS)

    We administered a combination of chemotherapy, autologous bone marrow purged with magnet immunobeads and total body irradiation (TBI) for advanced neuroblastoma (NB). The effect of TBI was retrospectively studied with regard to hematological recovery and complications after autologous bone marrow transplantation (A-BMT). The bone marrow was engrafted in all patients, both recipients and non-recipients of TBI. In patients receiving TBI, the average number or days after A-BMT required for the white blood cell count to exceed 1,000/μl, the neutrophile count to exceed 500/μl and the platelet count to exceed 5.0 x 104/μl was 15.0±6.5, 16.0±6.4 and 59.7±24.4, respectively. In patients not receiving TBI, the corresponding figures were 12.2±6.2, 12.9±6.9 and 43.2±17.8 days, respectively. During hematological recovery after A-BMT, there was no statistical difference between patients having received TBI and those who did not receive TBI. Hemolytic uremic syndrome (HUS) was observed in four patients while receiving TBI, but no HUS developed after shielding the kidney from TBI. In terms or engraftment and complications, A-BMT can be performed on patients receiving TBI as safely as on those patients not receiving TBI. (author)

  9. Clinical application of glass dosimeter for in vivo dose measurements of total body irradiation treatment technique

    Energy Technology Data Exchange (ETDEWEB)

    Rah, Jeong-Eun; Hwang, Ui-Jung; Jeong, Hojin; Lee, Sang-Yeob; Lee, Doo-Hyun; Shin, Dong Ho; Yoon, Myonggeun; Lee, Se Byeong [Proton Therapy Center, National Cancer Center, 809 Madu-dong, Ilsan-gu, Goyang-si, Gyeonggi-do, 410-769 (Korea, Republic of); Lee, Rena [Department of Radiation Oncology, Mokdong Hospital, Ewha Womans University College of Medicine (Korea, Republic of); Park, Sung Yong, E-mail: cool_park@ncc.re.k [Proton Therapy Center, National Cancer Center, 809 Madu-dong, Ilsan-gu, Goyang-si, Gyeonggi-do, 410-769 (Korea, Republic of)

    2011-01-15

    The commercially available glass dosimeter (model GD-301) was investigated for its dosimetric characteristics, in order to evaluate its use for in vivo dosimetry. We specifically assessed overall precision of dosimetric dose data in patients who received treatment with the total body irradiation (TBI). Uniformity obtained in this study was within 1.2% (1 SD). The dose-response was linear in the range of 0.5-10 Gy with R of 0.999. Dose rate, SSD, field size, angular and energy dependence were found to be within 3.0%. In vivo skin dosimetry for TBI was performed for 3 patients. For all patients, the glass dosimeter was exposed and measured dose recorded for one fraction in addition to conventional used TLD and MOSFET. Overall uncertainty of the glass dosimeter for in vivo dose measurement was estimated at 2.4% (68.3% confidence level). The measured doses of the glass dosimeter were well within {+-}5.0% of the prescription dose at all sites expect mediastinum of one patient, for which it is within {+-}5.7%. Agreement of measured doses between glass dosimeter and TLD, MOSFET was within {+-}6.3% and {+-}6.6%, respectively. Results show that the glass dosimeter can be used as an accurate and reproducible dosimeter for TBI treatment skin dose measurements. The glass dosimeter is a practical alternative to TLD or MOSFET as an in vivo dosimeter.

  10. Benefits of online in vivo dosimetry for single-fraction total body irradiation.

    Science.gov (United States)

    Eaton, David J; Warry, Alison J; Trimble, Rachel E; Vilarino-Varela, Maria J; Collis, Christopher H

    2014-01-01

    Use of a patient test dose before single-fraction total body irradiation (TBI) allows review of in vivo dosimetry and modification of the main treatment setup. However, use of computed tomography (CT) planning and online in vivo dosimetry may reduce the need for this additional step. Patients were treated using a supine CT-planned extended source-to-surface distance (SSD) technique with lead compensators and bolus. In vivo dosimetry was performed using thermoluminescent dosimeters (TLDs) and diodes at 10 representative anatomical locations, for both a 0.1-Gy test dose and the treatment dose. In total, 28 patients were treated between April 2007 and July 2013, with changes made in 10 cases (36%) following test dose results. Overall, 98.1% of measured in vivo treatment doses were within 10% of the prescribed dose, compared with 97.0% of test dose readings. Changes made following the test dose could have been applied during the single-fraction treatment itself, assuming that the dose was delivered in subportions and online in vivo dosimetry was available for all clinically important anatomical sites. This alleviates the need for a test dose, saving considerable time and resources.

  11. An anti-apoptotic peptide improves survival in lethal total body irradiation.

    Science.gov (United States)

    McDunn, Jonathan E; Muenzer, Jared T; Dunne, Benjamin; Zhou, Anthony; Yuan, Kevin; Hoekzema, Andrew; Hilliard, Carolyn; Chang, Katherine C; Davis, Christopher G; McDonough, Jacquelyn; Hunt, Clayton; Grigsby, Perry; Piwnica-Worms, David; Hotchkiss, Richard S

    2009-05-15

    Cell penetrating peptides (CPPs) have been used to deliver the anti-apoptotic Bcl-xL-derived BH4 peptide to prevent injury-induced apoptosis both in vitro and in vivo. Here we demonstrate that the nuclear localization sequence (NLS) from the SV40 large T antigen has favorable properties for BH4 domain delivery to lymphocytes compared to sequences based on the HIV-1 TAT sequence. While both TAT-BH4 and NLS-BH4 protected primary human mononuclear cells from radiation-induced apoptotic cell death, TAT-BH4 caused persistent membrane damage and even cell death at the highest concentrations tested (5-10 microM) and correlated with in vivo toxicity as intravenous administration of TAT-BH4 caused rapid death. The NLS-BH4 peptide has significantly attenuated toxicity compared to TAT-BH4 and we established a dosing regimen of NLS-BH4 that conferred a significant survival advantage in a post-exposure treatment model of LD90 total body irradiation.

  12. Monte Carlo optimization of total body irradiation in a phantom and patient geometry

    Science.gov (United States)

    Chakarova, R.; Müntzing, K.; Krantz, M.; Hedin, E.; Hertzman, S.

    2013-04-01

    The objective of this work is to apply a Monte Carlo (MC) accelerator model, validated by experimental data at isocentre distances, to a large-field total body irradiation (TBI) technique and to develop a strategy for individual patient treatment on the basis of MC dose distributions. Calculations are carried out using BEAMnrc/DOSXYZnrc code packages for a 15 MV Varian accelerator. Acceptable agreement is obtained between MC data and measurements in a large water phantom behind a spoiler at source-skin distances (SSD) = 460 cm as well as in a CIRS® thorax phantom. Dose distributions in patients are studied when simulating bilateral beam delivery at a distance of 480 cm to the patient central sagittal plane. A procedure for individual improvement of the dose uniformity is suggested including the design of compensators in a conventional treatment planning system (TPS) and a subsequent update of the dose distribution. It is demonstrated that the dose uniformity for the simple TBI technique can be considerably improved. The optimization strategy developed is straightforward and suitable for clinics where the TPS available is deficient to calculate 3D dose distributions at extended SSD.

  13. ACPSEM ROSG TBI working group recommendations for quality assurance in total body irradiation.

    Science.gov (United States)

    Nelligan, Raelene; Bailey, Michael; Tran, Thu; Baldwin, Zoë

    2015-06-01

    The Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) radiation oncology specialty group (ROSG) formed a series of working groups in 2011 to develop recommendations for guidance of radiation oncology medical physics practice within the Australasian setting. These recommendations are intended to provide guidance for safe work practices and a suitable level of quality control without detailed work instructions. It is the responsibility of the medical physicist to ensure that locally available equipment and procedures are sufficiently sensitive to establish compliance to these recommendations. The recommendations are endorsed by the ROSG, and have been subject to independent expert reviews. For the Australian audience, these recommendations should be read in conjunction with the tripartite radiation oncology practice standards [1, 2]. This publication presents the recommendations of the ACPSEM total body irradiation working group (TBIWG) and has been developed in alignment with other international associations. However, these recommendations should be read in conjunction with relevant national, state or territory legislation and local requirements, which take precedence over the ACPSEM recommendations. It is hoped that the users of this and other ACPSEM recommendations will contribute to the development of future versions through the ROSG of the ACPSEM. This document serves as a guideline for calibration and quality assurance of equipment used for TBI in Australasia.

  14. ACPSEM ROSG TBE working group recommendations for quality assurance in total body electron irradiation.

    Science.gov (United States)

    Nelligan, Raelene; Baldwin, Zoë; Ostwald, Trish; Tran, Thu; Bailey, Michael

    2015-09-01

    The Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) Radiation Oncology Specialty Group (ROSG) formed a series of working groups in 2011 to develop recommendations for guidance of radiation oncology medical physics practice within the Australasian setting. These recommendations are intended to provide guidance for safe work practices and a suitable level of quality control without detailed work instructions. It is the responsibility of the medical physicist to ensure that locally available equipment and procedures are sufficiently sensitive to establish compliance to these recommendations. The recommendations are endorsed by the ROSG, and have been subject to independent expert reviews. For the Australian readers, these recommendations should be read in conjunction with the Tripartite Radiation Oncology Reform Implementation Committee Quality Working Group: Radiation Oncology Practice Standards (2011), and Radiation Oncology Practice Standards Supplementary Guide (2011). This publication presents the recommendations of the ACPSEM ROSG Total Body Electron Irradiation Working Group and has been developed in alignment with other international associations. However, these recommendations should be read in conjunction with relevant national, state or territory legislation and local requirements, which take precedence over the ACPSEM recommendations. It is hoped that the users of this and other ACPSEM recommendations will contribute to the development of future versions through the Radiation Oncology Specialty Group of the ACPSEM. This document serves as a guideline for calibration and quality assurance of equipment used for TBE in Australasia.

  15. A Monte Carlo evaluation of beam characteristics for total body irradiation at extended treatment distances.

    Science.gov (United States)

    Chakarova, Roumiana; Krantz, Marcus

    2014-05-08

    The aim is to study beam characteristics at large distances when focusing on the electron component. In particular, to investigate the utility of spoilers with various thicknesses as an electron source, as well as the effect of different spoiler-to-surface distances (STSD) on the beam characteristics and, consequently, on the dose in the superficial region. A MC model of a 15 MV Varian accelerator, validated earlier by experimental data at isocenter and extended distances used in large-field total body irradiation, is applied to evaluate beam characteristics at distances larger than 400 cm. Calculations are carried out using BEAMnrc/DOSXYZnrc code packages and phase space data are analyzed by the beam data processor BEAMdp. The electron component of the beam is analyzed at isocenter and extended distances, with and without spoilers as beam modifiers, assuming vacuum or air surrounding the accelerator head. Spoiler thickness of 1.6 cm is found to be optimal compared to thicknesses of 0.8 cm and 2.4 cm. The STSD variations should be taken into account when treating patients, in particular when the treatment protocols are based on a fixed distance to the patient central sagittal plane, and also, in order to maintain high dose in the superficial region.

  16. Prospective evaluation of delayed central nervous system (CNS) toxicity of hyperfractionated total body irradiation (TBI)

    International Nuclear Information System (INIS)

    Purpose: Prospective evaluation of chronic radiation effects on the healthy adult brain using neuropsychological testing of intelligence, attention, and memory. Methods and Materials: 58 patients (43 ± 10 yr) undergoing hyperfractionated total body irradiation (TBI) (TBI, 14.4 Gy, 12 x 1.2 Gy in 4 days) before bone marrow or peripheral blood stem cell transplantation were prospectively included. Twenty-one recurrence-free long-term survivors were re-examined 6-36 months (median 27 months) after completion of TBI. Neuropsychological testing included assessment of general intelligence, attention, and memory using normative, standardized psychometric tests. Mood status was controlled, as well. Test results are given as IQ scores (population mean 100) or percentiles for attention and memory (population mean 50). Results: The 21 patients showed normal baseline test results of IQ (101 ± 13) and attention (53 ± 28), with memory test scores below average (35 ± 21). Test results of IQ (98 ± 17), attention (58 ± 27), and memory (43 ± 28) showed no signs of clinically measurable radiation damage to higher CNS (central nervous system) functions during the follow-up. The mood status was improved. Conclusion: The investigation of CNS toxicity after hyperfractionated TBI showed no deterioration of test results in adult recurrence-free patients with tumor-free CNS. The median follow-up of 27 months will be extended.

  17. Induction of systemic bone changes by preconditioning total body irradiation for bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Osamu; Okamoto, Reiko; Masaki, Hidekazu [National Centre for Child Health and Development, Department of Radiology, Tokyo (Japan); Nishimura, Gen [Tokyo Metropolitan Kiyose Children' s Hospital, Department of Radiology, Tokyo (Japan); Kumagai, Masaaki; Shioda, Yoko [National Centre for Child Health and Development, Department of Oncology, Tokyo (Japan); Nozawa, Kumiko [Saitama Children' s Medical Centre, Department of Radiology, Saitama (Japan); Kitoh, Hiroshi [Nagoya University Hospital, Department of Orthopaedic Surgery, Nagoya, Aichi (Japan)

    2009-01-15

    Preconditioning total body irradiation (TBI) prior to bone marrow transplantation (BMT) has been believed to be a safe procedure that does not cause late morbidity; yet, a recent report raises the suspicion that TBI-induced chondroosseous abnormalities do occur. To evaluate the radiological manifestations of TBI-induced skeletal alterations and their orthopaedic morbidity. Subjects included 11 children with TBI-induced skeletal changes, including 9 in our hospital and 2 in other hospitals. The former were selected from 53 children who had undergone TBI with BMT. Radiographic examinations (n=11), MRI (n=3), CT (n=2), and medical records in the 11 children were retrospectively reviewed. The skeletal alterations included abnormal epiphyseal ossification and metaphyseal fraying (8/11), longitudinal metaphyseal striations (8/11), irregular metaphyseal sclerosis (6/11), osteochondromas (4/11), slipped capital femoral epiphysis (2/10), genu valgum (3/10), and platyspondyly (2/3). MRI demonstrated immature primary spongiosa in the metaphysis. Of the 11 children, 9 had clinical symptoms. TBI can induce polyostotic and/or generalized bone changes, mainly affecting the epiphyseal/metaphyseal regions and occasionally the spine. The epi-/metaphyseal abnormalities represent impaired chondrogenesis in the epiphysis and growth plate and abnormal remodelling in the metaphysis. Generalized spine changes may lead to misdiagnosis of a skeletal dysplasia. (orig.)

  18. Benefits of online in vivo dosimetry for single-fraction total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Eaton, David J., E-mail: davideaton@nhs.net [Department of Radiotherapy, Royal Free Hospital, London (United Kingdom); Warry, Alison J. [Department of Radiotherapy Physics, University College London Hospital, London (United Kingdom); Trimble, Rachel E.; Vilarino-Varela, Maria J.; Collis, Christopher H. [Department of Radiotherapy, Royal Free Hospital, London (United Kingdom)

    2014-01-01

    Use of a patient test dose before single-fraction total body irradiation (TBI) allows review of in vivo dosimetry and modification of the main treatment setup. However, use of computed tomography (CT) planning and online in vivo dosimetry may reduce the need for this additional step. Patients were treated using a supine CT-planned extended source-to-surface distance (SSD) technique with lead compensators and bolus. In vivo dosimetry was performed using thermoluminescent dosimeters (TLDs) and diodes at 10 representative anatomical locations, for both a 0.1-Gy test dose and the treatment dose. In total, 28 patients were treated between April 2007 and July 2013, with changes made in 10 cases (36%) following test dose results. Overall, 98.1% of measured in vivo treatment doses were within 10% of the prescribed dose, compared with 97.0% of test dose readings. Changes made following the test dose could have been applied during the single-fraction treatment itself, assuming that the dose was delivered in subportions and online in vivo dosimetry was available for all clinically important anatomical sites. This alleviates the need for a test dose, saving considerable time and resources.

  19. Renal dysfunction after total-body irradiation. Significance of selective renal shielding blocks

    Energy Technology Data Exchange (ETDEWEB)

    Igaki, Hiroshi [Tokyo Metropolitan Komagome Hospital (Japan). Dept. of Radiation Center; University of Tsukuba, Ibaraki (Japan). Proton Medical Research Center; University of Tokyo (Japan). Dept. of Radiology; Karasawa, Katsuyuki [Tokyo Metropolitan Komagome Hospital (Japan). Dept. of Radiation Center; Sakamaki, Hisashi [Tokyo Metropolitan Komagome Hospital (Japan). Dept. of Hematology; Saito, Hiroshi [Tokyo Metropolitan Komagome Hospital (Japan). Dept. of Nephrology; Nakagawa, Keiichi; Ohtomo, Kuni [University of Tokyo (Japan). Dept. of Radiology; Tanaka, Yoshiaki [Nihon University School of Medicine, Tokyo (Japan). Dept. of Radiology

    2005-11-01

    Purpose: A retrospective analysis was conducted on the outcome of total-body irradiation (TBI) followed by bone marrow transplantation (BMT) on leukemia patients. Also studied was the risk of renal dysfunction after TBI/BMT with or without the use of selective renal shielding blocks. Patients and Methods: The cases of 109 leukemia patients who received TBI as a component of the conditioning regimen for their BMT were reviewed. They received 12 Gy of TBI in six fractions over 3 consecutive days. Doses to eyes and lungs were reduced to 7 Gy and 8 Gy, respectively, but customized organ shielding blocks. After March 1999, renal shielding blocks were used to constrain the renal dose to 10 Gy. The patients were followed for a median period of 16.6 months (range: 0.3-180.1 months). Results: The 2-year and 5-year overall survival rates were 55.4% and 43.2%, respectively. Renal dysfunction-free rates were different between those with and without renal shielding blocks: 100% and 78.5%, respectively, at 2 years. Overall survivals were not significantly different among these patients: 60.4% and 52.9%, respectively, at 2 years in patients with and without renal shielding blocks (p=0.53). Conclusion: The use of selective renal shielding blocks provided evidence for reducing radiation-induced renal toxicities without decreasing the overall survival rate. (orig.)

  20. Use of WR-2721 with total body irradiation in treatment of mouse lymphoma

    International Nuclear Information System (INIS)

    Efficacy of total body irradiation (TBI) in treatment of non-Hodgkin's lymphoma is limited by bone marrow radiosensitivity. WR-2721 has been shown to be an effective chemical protector of the hemotopoietic system. In this study, a spontaneous T-cell lymphoma implanted in BALB/c mice was used to determine the effect of WR-2721 on TBI of lymphoma. Mice were randomly assigned to 5 radiation dose groups (0-200 rad TBI) when the tumors reached the desired size. The experimental group received the half-maximum tolerated dose (365 mg/kg) of WR-2721/IP 30 min. before 150 rad TBI. Using tumor regrowth delay as an endpoint, WR-2721 was seen not to lessen the delay as would a tumor protector but rather to slightly increase the delay to 216 +- 9 hrs as compared with an expected value of 188 +- 20 hrs based on controls. In a subsequent experiment to determine the effect of WR-2721 alone, the experimental mice received 3 IP injections of WR-2721 (400 mg/kg/day) while the control group received saline. The geometric mean tumor regrowth delay times were 47 +- 3 hrs for the control group compared to 112 +- 10 hrs for the WR-2721 group ( p <.001). The authors conclude that WR-2721 does not give net radiation protection of this lymphoma at the doses studied and has an apparent cytotoxic effect on lymphoma that has not been previously reported

  1. Effects of low dose total body irradiation (LDTBI) and recombinant human interleukin-2 in mice

    International Nuclear Information System (INIS)

    10-16-week-old female BALB/c mice received low dose total body irradiation (LDTBI) in one fraction immediately before the beginning of treatment with recombinant human interleukin-2 (rIL-2). LDTBI prevented in a dose-dependent manner the weight increase of the spleen, liver and lungs induced by fluid extravasation provoked by rIL-2 injections. It also limited the increase of the number of mononuclear cells in the spleen induced after in vivo treatment with rIL-2. Immunofluorescence analysis of spleen cells revealed that LDTBI decreased the relative sIgM+ cell number in spleen, while the relative numbers of Lyt-1+, Thy-1+ and L3T4+ cells were increased, indicating that a T and/or NK population, radioresistant to LDTBI, could still proliferate under rIL-2 stimulation in vivo. Such lymphocytes were capable of in vitro lysis of YAC cells in a 4-hour 51Cr release assay, as well as lymphokine-activated killer (LAK) cells obtained in mice treated with rIL-2 alone. Thus, LDTBI given prior to rIL-2, yet preserving the cytotoxic capacity of the LAK cells activated by rIL-2, could prevent the vascular leak syndrome toxicity induced by rIL-2 injection. (author). tabs., figs

  2. Fractionated half body irradiation for palliation of multiple symptomatic bone metastases from solid tumors

    Energy Technology Data Exchange (ETDEWEB)

    Sekiguchi, Kenji; Hayashi, Shinya; Sunagawa, Yoshimitsu; Sougawa, Mitsuharu; Nakazawa, Masanori; Yamashita, Takashi (Japanese Foundation for Cancer Research, Tokyo (Japan). Hospital)

    1992-06-01

    This was a phase I-II nonrandomized study that explored the toxicity and response of fractionated half-body irradiation (F-HBI) in patients with multiple symptomatic osseous metastases. The patients had no premedication and received 10 Gy in 5 fractions with a dose rate of 15 cGy/min. At the Cancer Institute Hospital, 9 patients were treated by this technique (1 upper and lower F-HBI, 6 upper F-HBI, 2 lower F-HBI). All patients were female and had adenocarcinomas (8 breast and 1 lung). Adverse effects were myelosuppression, vomiting and partial alopecia. But hematologic toxicity was treated with blood transfusion or G-CSF. All toxicity was transient, and no pneumonitis nor radiation-related deaths occurred. When given as palliation, F-HBI was found to relieve pain in 80% of the patients. In 10% of the patients the pain relief was complete. The mean time to achieve pain relief in responders after F-HBI was 9 days. The pain relief was long-lasting and continued without need of reirradiation for 40% of the remaining patient's life. This treatment modality appears to be well tolerated and effective in patients with multiple symptomatic osseous metastases. The optimal indications, dose and fractionation for F-HBI should be further explored in randomized trials. (author).

  3. Calculation of midplane dose for total body irradiation from entrance and exit dose MOSFET measurements.

    Science.gov (United States)

    Satory, P R

    2012-03-01

    This work is the development of a MOSFET based surface in vivo dosimetry system for total body irradiation patients treated with bilateral extended SSD beams using PMMA missing tissue compensators adjacent to the patient. An empirical formula to calculate midplane dose from MOSFET measured entrance and exit doses has been derived. The dependency of surface dose on the air-gap between the spoiler and the surface was investigated by suspending a spoiler above a water phantom, and taking percentage depth dose measurements (PDD). Exit and entrances doses were measured with MOSFETs in conjunction with midplane doses measured with an ion chamber. The entrance and exit doses were combined using an exponential attenuation formula to give an estimate of midplane dose and were compared to the midplane ion chamber measurement for a range of phantom thicknesses. Having a maximum PDD at the surface simplifies the prediction of midplane dose, which is achieved by ensuring that the air gap between the compensator and the surface is less than 10 cm. The comparison of estimated midplane dose and measured midplane dose showed no dependence on phantom thickness and an average correction factor of 0.88 was found. If the missing tissue compensators are kept within 10 cm of the patient then MOSFET measurements of entrance and exit dose can predict the midplane dose for the patient. PMID:22298238

  4. Light Irradiation And Response Of The Living Body - Effect Of Pain Relief And Promotion Of Wound Healing -

    Science.gov (United States)

    Taguchi, Yoshio; Kurokawa, Yoshimochi; Ohara, Itaru; Ueki, Hamaichi; Inaba, Humio

    1989-09-01

    suffering from vascular disorders but was not effective in normal subjects. From a study of cellular electrophoretic mobility, irradiated G0G1 cells increased their mobility, but irradiated G2M cells decreased. These results suggested light irradiation contributed to homeostasis of living cells, tissues, and body. Experiments concerning the light sources, i.e. wave length, energy density and polarization were done. As a result, linear polarization and right circular polarization improved wound healing, but incoherent light itself did not. ,According to our studies, no distinguished differences among various kinds of wave length were noticed. And light irradiation with energy density was very effective between 2 to 6 J/cm2. We strongly suggest the role of coherency is very important to do light irradiation on the living body. In conclusion, we like to propose our new viewpoint. That is, the light irradiation should be discussed with the structure of high molecular substances in the living body.

  5. Microscopic anatomy of the baboon (Papio hamadryas) adrenal medulla.

    OpenAIRE

    al-Lami, F; Carmichael, S W

    1991-01-01

    Adrenal medullas of 2 baboons perfused with formaldehyde/glutaraldehyde and tannic acid were studied by light and electron microscopy. Tissues were postfixed in OsO4. This procedure allows identification of noradrenaline cells on the basis of a selective reaction of glutaraldehyde with noradrenaline vesicles. As positive control for noradrenaline cells, similarly treated mouse adrenal medullas were also examined. Light microscopic examination of thick sections of baboon medullas did not show ...

  6. Feto-placental adaptations to maternal obesity in the baboon

    OpenAIRE

    Farley, Darren; Tejero, Maria E; Comuzzie, Anthony G.; Higgins, Paul B.; Cox, Laura; Werner, Sherry L.; Jenkins, Susan L.; Li, Cun; Choi, Jaehyek; Dick, Edward J.; Hubbard, Gene B.; Frost, Patrice; Dudley, Donald D.; Ballesteros, Brandon; Wu, Guoyao

    2009-01-01

    Maternal obesity is present in 20–34% of pregnant women and has been associated with both intrauterine growth restriction and large-for-gestational age fetuses. While fetal and placental functions have been extensively studied in the baboon, no data are available on the effect of maternal obesity on placental structure and function in this species. We hypothesize that maternal obesity in the baboon is associated with a maternal inflammatory state and induces structural and functional changes ...

  7. Acute whole body UVA irradiation combined with nitrate ingestion enhances time trial performance in trained cyclists.

    Science.gov (United States)

    Muggeridge, David J; Sculthorpe, Nicholas; Grace, Fergal M; Willis, Gareth; Thornhill, Laurence; Weller, Richard B; James, Philip E; Easton, Chris

    2015-08-01

    Dietary nitrate supplementation has been shown to increase nitric oxide (NO) metabolites, reduce blood pressure (BP) and enhance exercise performance. Acute exposure to ultraviolet (UV)-A light also increases NO bioavailability and reduces BP. We conducted a randomized, counterbalanced placebo-controlled trial to determine the effects of UV-A light alone and in combination with nitrate on the responses to sub-maximal steady-state exercise and time trial (TT) performance. Nine cyclists (VO2max 53.1 ± 4.4 ml/kg/min) completed five performance trials comprising 10 min submaximal steady-state cycling followed by a 16.1 km TT. Following a familiarization the final four trials were preceded, in random order, by either (1) Nitrate gels (NIT) + UV-A, (2) Placebo (PLA) + UV-A, (3) NIT + Sham light (SHAM) and (4) PLA + SHAM (control). The NIT gels (2 × 60 ml gels, ~8.1 mmol nitrate) or a low-nitrate PLA were ingested 2.5 h prior to the trial. The light exposure consisted of 20 J/cm(2) whole body irradiation with either UV-A or SHAM light. Plasma nitrite was measured pre- and post-irradiation and VO2 was measured continuously during steady-state exercise. Plasma nitrite was higher for NIT + SHAM (geometric mean (95% CI), 332 (292-377) nM; P = 0.029) and NIT + UV-A (456 (312-666) nM; P = 0.014) compared to PLA + SHAM (215 (167-277) nM). Differences between PLA + SHAM and PLA + UV-A (282 (248-356) nM) were small and non-significant. During steady-state exercise VO2 was reduced following NIT + UVA (P = 0.034) and tended to be lower in NIT + SHAM (P = 0.086) but not PLA + UV-A (P = 0.381) compared to PLA + SHAM. Performance in the TT was significantly faster following NIT + UV-A (mean ± SD 1447 ± 41 s P = 0.005; d = 0.47), but not PLA + UV-A (1450 ± 40 s; d = 0.41) or NIT + SHAM (1455 ± 47 s; d = 0.28) compared to PLA + SHAM (1469 ± 52 s). These findings demonstrate that exposure to UV-A light alone does not alter the physiological responses to exercise or improve

  8. Total Body Irradiation in the "Hematopoietic" Dose Range Induces Substantial Intestinal Injury in Non-Human Primates.

    Science.gov (United States)

    Wang, Junru; Shao, Lijian; Hendrickson, Howard P; Liu, Liya; Chang, Jianhui; Luo, Yi; Seng, John; Pouliot, Mylene; Authier, Simon; Zhou, Daohong; Allaben, William; Hauer-Jensen, Martin

    2015-11-01

    The non-human primate has been a useful model for studies of human acute radiation syndrome (ARS). However, to date structural changes in various parts of the intestine after total body irradiation (TBI) have not been systematically studied in this model. Here we report on our current study of TBI-induced intestinal structural injury in the non-human primate after doses typically associated with hematopoietic ARS. Twenty-four non-human primates were divided into three groups: sham-irradiated control group; and total body cobalt-60 (60Co) 6.7 Gy gamma-irradiated group; and total body 60Co 7.4 Gy gamma-irradiated group. After animals were euthanized at day 4, 7 and 12 postirradiation, sections of small intestine (duodenum, proximal jejunum, distal jejunum and ileum) were collected and fixed in 10% formalin. The intestinal mucosal surface length, villus height and crypt depths were assessed by computer-assisted image analysis. Plasma citrulline levels were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Total bone marrow cells were counted and hematopoietic stem/progenitor cells in bone marrow were analyzed by flow cytometer. Histopathologically, all segments exhibited conspicuous disappearance of plicae circulares and prominent atrophy of crypts and villi. Intestinal mucosal surface length was significantly decreased in all intestinal segments on day 4, 7 and 12 after irradiation (P 0.05). Crypt depth was also significantly reduced in all segments on day 4, 7 and 12 after irradiation (P irradiation, consistent with intestinal mucosal injury. Both 6.7 and 7.4 Gy TBI reduced total number of bone marrow cells. And further analysis showed that the number and function of CD45(+)CD34(+) hematopoietic stem/progenitors in bone marrow decreased significantly. In summary, TBI in the hematopoietic ARS dose range induces substantial intestinal injury in all segments of the small bowel. These findings underscore the importance of maintaining the

  9. Multicolor flow cytometry analysis of blood cell subsets in patients given total body irradiation before bone marrow transplantation

    International Nuclear Information System (INIS)

    Bone marrow transplantation has often been closely linked with accidental or intentional therapeutical irradiation. In both situations, study of the radiosensitivity of human blood cell subsets is of interest. Using one-color flow cytometry analysis of B lymphocytes, T cell subsets, and natural killer cells, we previously reported that lymphocyte subsets exhibit equal radiosensitivity. Taking advantage of recent developments in the knowledge of leukocyte differentiation antigens and flow cytometry technology we undertook a study of blood cell subsets to search for rare populations exhibiting different radiosensitivity. Thirty patients, who were delivered a 12 Gy fractionated total body irradiation as part of their conditioning regimen before transplantation for malignant disorders, were studied using multicolor flow cytometry. T and B lymphocytes showed a sharp, radiation-induced decrease, with the B lymphocytes (cluster of differentiation (CD) 19+) being the most sensitive. When analyzed by multicolor flow cytometry all major lymphocyte subsets appeared equally sensitive to the in vivo irradiation. Therefore, all major lymphocyte subsets sharing the helper phenotype (naive or memory) and the cytotoxic phenotype appeared equally sensitive to in vivo whole body irradiation. In parallel, the CD34+ cell subset remained basically unchanged after whole body irradiation. Finally, the CD3-, 56+, 16+ natural killer cell subset was relatively radioresistant (91 and 74% of its initial value, after 2 and 4 Gy, respectively) as compared to other lymphocyte subsets. Our study provides evidence that T and B cell subsets seem to be highly radiosensitive in vivo. The CD34+ progenitor/stem cells and NK cells seem to be more radioresistant. This latter result might provide clues to the understanding of the pathophysiogeny of radiation-induced aplasia and of the engrafment/rejection process following bone marrow transplantation. 20 refs., 3 figs., 1 tab

  10. [Grooming and group structure in hamadryas baboons].

    Science.gov (United States)

    2010-09-01

    The results of 3-year observation on coral living hamadryas baboons transported from natural habitat in Tuapse reservation have been presented. Despite of the fact that grooming between males and females accounted for 73% of total cases of grooming in adult individual pairs, only the relationships of males with high-ranked females of their harems fully corresponded to a star-shaped sociogram. The high-ranked females were not different from all the other females either according to a total number of grooming cases with their female partners or according to a proportion of a performed and received grooming. Grooming between the related females was noted predominantly in the cases when they belonged to the same harem. Grooming between the related males accounted for 59% of all the cases of grooming between the male partners.

  11. Neoplasia in beagles that received whole-body irradiation during prenatal or postnatal development

    International Nuclear Information System (INIS)

    Sensitivity to radiation carcinogenesis is being studied in 1680 beagle dogs that received whole-body 60Co gamma radiation exposures during development. Eight treatment groups of 120 dogs each received 0.16 or 0.83 Gy at one of three prenatal (8, 28, or 55 days postcoitus) ages or at one postnatal (2 days postpartum) age. One treatment group of 120 dogs received 0.83 Gy as juveniles at 70 days postpartum, and one treatment group of 240 young adult dogs received 0.83 Gy at 365 days postpartum. Three-hundred-sixty control dogs were sham irradiated. Of the 1680 dogs, 1058 are dead. Approximately 25% of these deaths were related to malignant neoplasia. The age-related incidence of neoplasia is being evaluated. While the incidence of all neoplasms is being studied, particular emphasis is being placed on types of cancer with known susceptibility to induction by radiation such as those of breast, thyroid, and hematopoietic tissues. Neoplasms are classed as (1) incidental, i.e., those found at necropsy in dogs that died of an unrelated cause; (2) mortality independent, i.e., those seen in live dogs and removed surgically, or (3) fatal, i.e., those directly or indirectly responsible for death. Analyses of incidental tumors are done by a prevalence method, whereas analyses of mortality-independent and fatal tumors use an onset-rate or death-rate method. The results of these methods are then combined to give a composite age-related incidence of specific neoplasms. Analyses also are done on disease subgroups to attempt to delineate the effect of intercurrent disease on tumor incidence. The results of such analyses support the concept that age at exposure is an important factor in radiation carcinogenesis. 28 refs., 7 tabs

  12. Cataract after total body irradiation and bone marrow transplantation degree of visual impairment

    International Nuclear Information System (INIS)

    Purpose: To assess the degree of visual impairment as a result of cataract formation after total body irradiation (TBI) for bone marrow transplantation. Methods and Materials: The data from 93 patients who received TBI in 1 or 2 fractions as a part of their conditioning regimen for bone marrow transplantation were analyzed with respect to the degree of visual impairment as a result of cataract formation. The probability to develop severe visual impairment (SVI) was determined for all patients, and the degree of visual impairment was assessed for 56 patients with stabilized cataract, using three categories: no, mild, or severe. Results: For all 93 patients, the probability of developing a cataract causing SVI was 0.44. For allogeneic patients, it was 0.33 without and 0.71 with steroid treatment (p<0.001). All SVI-free probability curves reached a plateau distinct from the cataract-free curves. Apparently, cataracts developing late in the follow-up period rarely cause SVI. Of the patients with stabilized cataract, 32% had no visual impairment, 16% had mild, and 52% severe impairment. No or mild visual impairment was present in 61% of all patients with stable cataract and no steroid treatment compared with only 13% of the patients treated with steroids (p=0.035). Conclusion: SVI occurs in only some of the patients (52%) with stable cataract after TBI for bone marrow transplantation in 1 or 2 fractions. Steroid treatment markedly increases the probability of developing visual problems as result of a cataract after TBI

  13. Clinical tolerance of total body irradiation and allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Total body irradiation (TBI) followed by bone marrow transplantation (BMT) is well established as a part of the conditioning regimen in high dose therapy. The objective is to report the organ toxicity investigated prospectively in patients who had conditioning regimes including fractionated TBI (FTBI) and chemotherapy. From October 2002 to December 2007 18 patients received FTBI in our institution. There were 11 males and; 7 females with median age of 20 years (range 8-50). The present study includes 11 patients with initial diagnoses; acute lymphoid leukemia (ALL), 4 - acute myeloid leukemia (AML) and 3 - chronic myeloid leukemia (GML). At the time of BMT 11 patients were in complete response, 4 in progression and 3 in chronic phase. TBI was performed on a 60Co unit in alternate prone and supine position. Three patients received nonmyeloablative regimen including 'mini' TBI of 2 Gy followed by allogeneic BMT and 15 received myeloablative regimen of 10-12 Gy FTBI. The dose rate requirement was met for TBI 5-10 cGy/min. A standardized supportive therapy was administered. During the transplantation period on day 0 and +1 of the clinical protocol the realized transplantation of the donor cells pool passed without complications in 16 of the patients and was accompanied by allergic reactions in 2 patients. Induced bone-marrow aplasia was observed in all patients during the post-transplantation period. On day +14 to +24 'entgraftment' was established in 16 patients. In 2 patients till the 35th day after the transplantation no symptoms of the grafting were observed, which imposed reinfusion of donor cells pool. Seven patients developed acute GvHD, 2 patients developed idiopathic pneumonia syndrome, 1 patient developed liver toxicity, 1 - neurological and 1 - cardiovascular toxicity. FTBI is a well tolerated therapeutic regimen in high dose therapy. The observed organ toxicity in the 18 patients in similar to that cited in reference literature. (authors)

  14. Development of a metabolomic radiation signature in urine from patients undergoing total body irradiation.

    Science.gov (United States)

    Laiakis, Evagelia C; Mak, Tytus D; Anizan, Sebastien; Amundson, Sally A; Barker, Christopher A; Wolden, Suzanne L; Brenner, David J; Fornace, Albert J

    2014-04-01

    The emergence of the threat of radiological terrorism and other radiological incidents has led to the need for development of fast, accurate and noninvasive methods for detection of radiation exposure. The purpose of this study was to extend radiation metabolomic biomarker discovery to humans, as previous studies have focused on mice. Urine was collected from patients undergoing total body irradiation at Memorial Sloan-Kettering Cancer Center prior to hematopoietic stem cell transplantation at 4-6 h postirradiation (a single dose of 1.25 Gy) and 24 h (three fractions of 1.25 Gy each). Global metabolomic profiling was obtained through analysis with ultra performance liquid chromatography coupled to time-of-flight mass spectrometry (TOFMS). Prior to further analyses, each sample was normalized to its respective creatinine level. Statistical analysis was conducted by the nonparametric Kolmogorov-Smirnov test and the Fisher's exact test and markers were validated against pure standards. Seven markers showed distinct differences between pre- and post-exposure samples. Of those, trimethyl-l-lysine and the carnitine conjugates acetylcarnitine, decanoylcarnitine and octanoylcarnitine play an important role in the transportation of fatty acids across mitochondria for subsequent fatty acid β-oxidation. The remaining metabolites, hypoxanthine, xanthine and uric acid are the final products of the purine catabolism pathway, and high levels of excretion have been associated with increased oxidative stress and radiation induced DNA damage. Further analysis revealed sex differences in the patterns of excretion of the markers, demonstrating that generation of a sex-specific metabolomic signature will be informative and can provide a quick and reliable assessment of individuals in a radiological scenario. This is the first radiation metabolomics study in human urine laying the foundation for the use of metabolomics in biodosimetry and providing confidence in biomarker

  15. Retrospective, monocentric analysis of late effects after total body irradiation (TBI) in adults

    Energy Technology Data Exchange (ETDEWEB)

    Boelling, Tobias [Universitaetsklinikum Muenster (Germany). Dept. of Radiotherapy; Paracelsus Clinic Osnabrueck (Germany). Dept. of Radiotherapy; Kreuziger, David Christoph; Ernst, Iris; Elsayed, Hassan; Willich, Normann [Universitaetsklinikum Muenster (Germany). Dept. of Radiotherapy

    2011-05-15

    Purpose: Total body irradiation (TBI) is a standard treatment modality within the multidisciplinary approach for allogeneous stem cell or bone marrow transplantation. However, surviving patients are at risk for developing a variety of late sequelae. This analysis aimed to retrospectively characterize late effects after TBI in adults treated in a single center. Patients and Methods: Patients {>=} 18 years treated with fractionated TBI (4-12 Gy) between 1996 and 2008 were included in this study. Treatment data were collected retrospectively from the treating departments. Late effects were evaluated using the clinic charts and/or were obtained from the general practitioners using a standardized questionnaire. Analyses were performed by calculation of the cumulative incidences using the Kaplan-Meier method and the log rank test. Results: A total of 308 patients {>=} 18 years were treated including a TBI of whom 78 patients were excluded from further analysis due to death within less than 1 year after TBI. Patients suffered from leukemia in most cases. Late toxicity follow-up was available in 120 patients (mean age 46.1 years; range, 18-70 years) after a mean follow-up of 23 months (range, 12-96 months). The cumulative incidences (CI) at 3 years were 28% for pulmonary event, 8% for pulmonary toxicity, 25% for kidney toxicity, 8% for cataract, 17% for bone toxicity, and 10% for secondary malignancy. The CI of bone toxicity was higher in female than in male patients (p = 0.019). Conclusion: Late effects after TBI in the context of allogeneous stem cell or bone marrow transplantation can frequently be observed. Regular follow-up examinations are advised for the early registration and treatment of adverse effects. (orig.)

  16. Build-up material requirements in clinical dosimetry during total body irradiation treatments.

    Science.gov (United States)

    Butson, Martin; Pope, Dane; Haque, Mamoon; Chen, Tom; Song, Guangli; Whitaker, May

    2016-01-01

    Total body irradiation (TBI) treatments are mainly used in a preparative regimen for hematopoietic stem cell (or bone marrow) transplantation. Our standard clinical regimen is a 12 Gy/6 fraction bi-daily technique using 6MV X-rays at a large extended source to surface distance (SSD). This work investigates and quantifies the dose build-up characteristics and thus the requirements for bolus used for in vivo dosimetry for TBI applications. Percentage dose build-up characteristics of photon beams have been investigated at large extended SSDs using ionization chambers and Gafchromic film. Open field measurements at different field sizes and with differing scatter conditions such as the introduction of standard Perspex scattering plates at different distances to the measurement point were made in an effort to determine the required bolus/build-up material required for accurate determination of applied dose. Percentage surface dose values measured for open fields at 300 cm SSD were found to range from 20% up to 65.5% for fields 5 cm × 5 cm to 40 cm × 40 cm, respectively. With the introduction of 1 cm Perspex scattering plates used in TBI treatments, the surface dose values increased up to 83-90% (93-97% at 1 mm depth), depending on the position of the Perspex scattering plate compared to the measurement point. Our work showed that at least 5 mm water equivalent bolus/scatter material should be placed over the EBT3 film for accurate dose assessment for TBI treatments. Results also show that a small but measurable decrease in measured dose occurred with 5 mm water equivalent thick bolus material of areas '3 cm(2). As such, we recommend that 3 cm × 3 cm × 5 mm bolus build-up is the smallest size that should be placed over EBT3 Gafchromic film when used for accurate in vivo dosimetry for TBI applications.

  17. Build-up material requirements in clinical dosimetry during total body irradiation treatments.

    Science.gov (United States)

    Butson, Martin; Pope, Dane; Haque, Mamoon; Chen, Tom; Song, Guangli; Whitaker, May

    2016-01-01

    Total body irradiation (TBI) treatments are mainly used in a preparative regimen for hematopoietic stem cell (or bone marrow) transplantation. Our standard clinical regimen is a 12 Gy/6 fraction bi-daily technique using 6MV X-rays at a large extended source to surface distance (SSD). This work investigates and quantifies the dose build-up characteristics and thus the requirements for bolus used for in vivo dosimetry for TBI applications. Percentage dose build-up characteristics of photon beams have been investigated at large extended SSDs using ionization chambers and Gafchromic film. Open field measurements at different field sizes and with differing scatter conditions such as the introduction of standard Perspex scattering plates at different distances to the measurement point were made in an effort to determine the required bolus/build-up material required for accurate determination of applied dose. Percentage surface dose values measured for open fields at 300 cm SSD were found to range from 20% up to 65.5% for fields 5 cm × 5 cm to 40 cm × 40 cm, respectively. With the introduction of 1 cm Perspex scattering plates used in TBI treatments, the surface dose values increased up to 83-90% (93-97% at 1 mm depth), depending on the position of the Perspex scattering plate compared to the measurement point. Our work showed that at least 5 mm water equivalent bolus/scatter material should be placed over the EBT3 film for accurate dose assessment for TBI treatments. Results also show that a small but measurable decrease in measured dose occurred with 5 mm water equivalent thick bolus material of areas '3 cm(2). As such, we recommend that 3 cm × 3 cm × 5 mm bolus build-up is the smallest size that should be placed over EBT3 Gafchromic film when used for accurate in vivo dosimetry for TBI applications. PMID:27217628

  18. Patient dosimetry for total body irradiation using single-use MOSFET detectors.

    Science.gov (United States)

    Briere, Tina Marie; Tailor, Ramesh; Tolani, Naresh; Prado, Karl; Lane, Richard; Woo, Shiao; Ha, Chul; Gillin, Michael T; Beddar, A Sam

    2008-01-01

    We studied the usefulness of a new type of solid-state detector, the OneDose single-use MOSFET (metal oxide semiconductor field effect transistor) dosimeter, for entrance dose measurements for total body irradiation (TBI). The factory calibration factors supplied by the manufacturer are applicable to conventional radiotherapy beam arrangements and therefore may not be expected to be valid for TBI dosimetry because of the large field sizes and extended source-to-axis distances used. OneDose detectors were placed under a 1-cm thick bolus at the head, neck, and umbilicus of 9 patients undergoing TBI procedures. Thermoluminescent dosimeters (TLDs) were placed beside the detectors. We found that the OneDose readings differed from the TLD readings by 4.6% at the head, 1.7% at the neck, and 3.9% at the umbilicus, with corresponding standard deviations of 3.9%, 2.2%, and 2.7%. For all patient measurements, 95% of the OneDose readings fell within 3.3% +/- 6.0% of the TLD readings. Anthropomorphic phantom measurements showed differences of -0.1% at the neck and -1.2% midway between the phantom's carina and umbilicus. Our results suggest that these detectors could be used for TBI quality assurance monitoring, although TLDs should remain the standard when critical dose measurements are performed. If OneDose detectors are to be used for TBI, the use of more than one at each location is strongly recommended. Because the detectors are designed for single use, they cannot be individually calibrated. However, to obtain institution-specific correction factors for better applicability to TBI dosimetry, measurements of several detectors taken from a particular lot could also be obtained in phantom with the TBI geometry configurations used for patient treatment. PMID:19020482

  19. Accelerated recovery of hematopoiesis following sub-lethal whole body irradiation with recombinant murine interleukin-1 (IL-1)

    International Nuclear Information System (INIS)

    This communication reports the results of studies designed to investigate the ability of recombinant murine interleukin-1 (rIL-1) to enhance the recovery of hematopoiesis following administration of sub-lethal whole body irradiation (2 Gy). Mice were administered rIL-1 (100 and 500 units) i.p. Twenty-four hours later these mice were administered 2 Gy radiation. Irradiated control mice were given only phosphate buffered saline (PBS). Animals were then serially sacrificed (on days 1, 2, 4, 7, 9, and 12 following irradiation) and their peripheral blood was analyzed for indices (packed red cell volume, WBC, platelets, and differential). Femoral bone marrow was harvested and assayed for their stem cell content--erythroid (CFU-E, BFU-E), granulocyte-macrophage (CFU-GM), and megakaryocyte (CFU-MEG). Irradiated mice pretreated with rIL-1 demonstrated accelerated hematopoietic recovery as measured by higher WBC, platelets and femoral stem cell content than PBS-treated irradiated controls. These results indicate IL-1 may be an effective radioprotective agent against the hematotoxicity induced by ionizing radiation

  20. An explanation for the ability of cytotoxic drug pretreatment to reduce bone marrow related lethality of total body irradiation (TBI)

    International Nuclear Information System (INIS)

    Mice given 9 to 10 Gy total body irradiation (TBI) die a hematological death 10 to 14 days after exposure. This lethality can be avoided by pretreatment with a cytotoxic drug two days before irradiation. The best example of this is seen when 200 mg/Kg cytosine arabinoside (ara-C) is given two days before TIB. Improved survival results from an earlier onset in the recovery of marrow stem cells (CFU-s) in animals given ara-C before irradiation as compared to controls. In animals given radiation alone there is a lag phase in the recovery of CFU-s; drug pretreatment before irradiation abolishes this delay. We postulate that the cells that repopulate the CFU-s compartment after irradiation are a sub-population of the DFU-s with higher self-renewal capability, lower proliferative activity and higher radiosensitivity (D0 = .8 Gy) than the overall population D0 = 1.1 Gy). Further, we suggest that drug pretreatment alters the radiosensitivity of the first population, increasing it temporarily to that of the overall population. This may come about by ara-C triggering these CFU-s into a relatively radioresistant phase of the cell cycle. In the Lewis lung tumor ara-C pretreatment does not affect the response to radiation, even at times when the drug promotes the early recovery of the CFU-s. It would therefore seem that a potentially useful gain in the therapeutic index may result from these findings

  1. Impact of Whole Body Irradiation on the Intestinal Microbiome- Considerations for Space Flight

    Science.gov (United States)

    Karouia, Fathi; Santos, Orlando; Valdivia-Silva, Julio E.; Jones, Jeffrey; Greenberger, Joel S.; Epperly, Michael W.

    Human space travelers experience a unique environment that affects homeostasis and physiologic adaptation. Spaceflight-related changes have been reported in the musculo-skeletal, cardiovascular, neurovestibular, endocrine, and immune systems to just name a few. However, to date, radiation exposure is one of the main limiting factors for long duration space exploration missions and especially a mission to Mars. Over the past few years through advances in technology, the characterization of the microbiome has revealed a large and complex community of microorganisms living in symbiosis with the human host. However, heterogeneity of the intestinal microbial spectrum in humans has been associated with a variety of diseases and susceptibility to infectious and toxic agents. Limited information is known about the influence of space environment in general and radiation in particular on the microbiome. Furthermore, multiple spaceflight and simulated microgravity experiments have shown changes in phenotypic microbial characteristics such as microbial growth, morphology, metabolism, genetic transfer, antibiotic and stress susceptibility, and an increase in virulence factors. We now report a study of the bacterial composition of the intestine in C57BL/6NTAC mice and the types of microbes entering the body at two time points after the LD 50/30 dose of total body irradiation using microarray-based assay, G3 PhyloChip 16S rRNA, and bioinformatics methods. Bacteria and archaea taxon richness was determined at the genus level and ranged from 2 to 107 and 0 to 3 respectively. As expected, pre-exposure blood samples exhibited less bacterial and archaeal genus richness compared to all other samples. However, the study shows a significant shift in the mouse gut microbial speciation in several bacterial families, with increases in the Turicibacteraceae and Enterobacteriaceae and decreases in the Lachnospiraceae and Ruminococcaceae families. The findings most relevant to occupational

  2. Total-body irradiation with 25-MV photons in advanced non-Hodgkin's lymphoma and chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma were treated with total-body irradiation (TBI). One group was treated after chemotherapy failed, while the other group received TBI initially. TBI was ineffective against CLL after chemotherapy failed. All patients with lymphocytic lymphoma who initially responded to chemotherapy but later relapsed were helped by TBI, as were 88 percent of patients with previously untreated lymphocytic lymphomas

  3. Citrulline as a Biomarker in the Non-human Primate Total- and Partial-body Irradiation Models: Correlation of Circulating Citrulline to Acute and Prolonged Gastrointestinal Injury.

    Science.gov (United States)

    Jones, Jace W; Bennett, Alexander; Carter, Claire L; Tudor, Gregory; Hankey, Kim G; Farese, Ann M; Booth, Catherine; MacVittie, Thomas J; Kane, Maureen A

    2015-11-01

    The use of plasma citrulline as a biomarker for acute and prolonged gastrointestinal injury via exposure to total- and partial-body irradiation (6 MV LINAC-derived photons; 0.80 Gy min) in nonhuman primate models was investigated. The irradiation exposure covered gastrointestinal injuries spanning lethal, mid-lethal, and sub-lethal doses. The acute gastrointestinal injury was assessed via measurement of plasma citrulline and small intestinal histopathology over the first 15 d following radiation exposure and included total-body irradiation at 13.0 Gy, 10.5 Gy, and 7.5 Gy and partial-body irradiation at 11.0 Gy with 5% bone marrow sparing. The dosing schemes of 7.5 Gy total-body irradiation and 11.0 Gy partial-body irradiation included time points out to day 60 and day 180, respectively, which allowed for correlation of plasma citrulline to prolonged gastrointestinal injury and survival. Plasma citrulline values were radiation-dependent for all radiation doses under consideration, with nadir values ranging from 63-80% lower than radiation-naïve NHP plasma. The nadir values were observed at day 5 to 7 post irradiation. Longitudinal plasma citrulline profiles demonstrated prolonged gastrointestinal injury resulting from acute high-dose irradiation had long lasting effects on enterocyte function. Moreover, plasma citrulline did not discriminate between total-body or partial-body irradiation over the first 15 d following irradiation and was not predictive of survival based on the radiation models considered herein.

  4. Late Effects of Total-Body Gamma Irradiation on Cardiac Structure and Function in Male Rhesus Macaques.

    Science.gov (United States)

    DeBo, Ryne J; Lees, Cynthia J; Dugan, Greg O; Caudell, David L; Michalson, Kris T; Hanbury, David B; Kavanagh, Kylie; Cline, J Mark; Register, Thomas C

    2016-07-01

    Heart disease is an increasingly recognized, serious late effect of radiation exposure, most notably among breast cancer and Hodgkin's disease survivors, as well as the Hiroshima and Nagasaki atomic bomb survivors. The purpose of this study was to evaluate the late effects of total-body irradiation (TBI) on cardiac morphology, function and selected circulating biomarkers in a well-established nonhuman primate model. For this study we used male rhesus macaques that were exposed to a single total-body dose of ionizing gamma radiation (6.5-8.4 Gy) 5.6-9.7 years earlier at ages ranging from ∼3-10 years old and a cohort of nonirradiated controls. Transthoracic echocardiography was performed annually for 3 years on 20 irradiated and 11 control animals. Myocardium was examined grossly and histologically, and myocardial fibrosis/collagen was assessed microscopically and by morphometric analysis of Masson's trichrome-stained sections. Serum/plasma from 27 irradiated and 13 control animals was evaluated for circulating biomarkers of cardiac damage [N-terminal pro B-type natriuretic protein (nt-proBNP) and troponin-I], inflammation (CRP, IL-6, MCP-1, sICAM) and microbial translocation [LPS-binding protein (LBP) and sCD14]. A higher prevalence of histological myocardial fibrosis was observed in the hearts obtained from the irradiated animals (9/14) relative to controls (0/3) (P = 0.04, χ(2)). Echocardiographically determined left ventricular end diastolic and systolic diameters were significantly smaller in irradiated animals (repeated measures ANOVA, P effects including a high incidence of myocardial fibrosis, reduced left ventricular diameter and elevated systemic inflammation. Additional prospective studies are required to define the time course and mechanisms underlying radiation-induced heart disease in this model. PMID:27333082

  5. Hemi body irradiation: An economical way of palliation of pain in bone metastasis in advanced cancer

    Directory of Open Access Journals (Sweden)

    Santanu Pal

    2014-01-01

    Full Text Available Background: The primary aim of this prospective non-randomized study was to evaluate the effect of hemi-body irradiation (HBI on pain and quality of life in cancer patients with extensive bone metastases. The secondary aim was to evaluate side-effects and cost-effectiveness of the treatment. Materials and Methods: Between March 2008 and December 2010, a total of 23 (male = 14, female = 9, median age = 60 years diagnosed cases of metastatic cancer patients (prostate = 11, breast = 6, and lung = 6 received HBI, which was delivered as lower (n = 7 (dose = 8 Gy, upper (n = 8 (dose = 6 Gy, or sequential HBI (n = 8 with a Telecobalt unit (Theratron 780C. Among them, one lung cancer patient died at 2 months and one prostate cancer patient defaulted after the second follow-up. Thus, 21 patients (male = 13, female = 8, median age = 65 years (prostatic cancer = 10, breast cancer = 6, and lung cancer = 5 were followed up for a minimum of 6 months. Evaluations were performed before and at 2, 4, 8, 16, and 24 weeks after treatment. Pain evaluation was done by Visual Analogue Scale (VAS, Verbal Rating Scale (VRS, Percentage of Pain Relief (PRR, and Global Pain Score (GPS. Toxicity was assessed by CTC v-3 toxicity scores in the medical record. Assessment of oral morphine consumption was done before and after radiation using paired t-test, and correlation analysis was also done with decrease of morphine consumption and reduction of pain score using statistical analysis. Results: Response (control of pain was partial (PR in 67% and complete (CR in 22% of patients. For most patients, the pain control lasted throughout the follow-up period (6 months. From 66.66% patients requiring 13 or more Morphine (10 mg tablets per day prior to HBI, none of the patients required to consume 13 or more Morphine (10 mg tablets per day following HBI, which was correlated with significant reduction in various pain scores (P < 0.05. One way ANOVA with Dunnett′s Multiple Comparison

  6. Metabolism of endogenous surfactant in premature baboons and effect of prenatal corticosteroids

    NARCIS (Netherlands)

    Bunt, JEH; Carnielli, VP; Seidner, [No Value; Ikegami, M; Wattimena, JLD; Sauer, PJJ; Jobe, AH; Zimmermann, LJI

    1999-01-01

    We studied the synthesis of surfactant and the effect of prenatal betamethasone treatment in vivo in very preterm baboons. Ten pregnant baboons were randomized to receive either betamethasone (beta) or saline (control) 48 and 24 h before preterm delivery. The newborn baboons were intubated, treated

  7. Characterization of spontaneous bone marrow recovery after sublethal total body irradiation: importance of the osteoblastic/adipocytic balance.

    Directory of Open Access Journals (Sweden)

    Géraldine Poncin

    Full Text Available Many studies have already examined the hematopoietic recovery after irradiation but paid with very little attention to the bone marrow microenvironment. Nonetheless previous studies in a murine model of reversible radio-induced bone marrow aplasia have shown a significant increase in alkaline phosphatase activity (ALP prior to hematopoietic regeneration. This increase in ALP activity was not due to cell proliferation but could be attributed to modifications of the properties of mesenchymal stem cells (MSC. We thus undertook a study to assess the kinetics of the evolution of MSC correlated to their hematopoietic supportive capacities in mice treated with sub lethal total body irradiation. In our study, colony-forming units-fibroblasts (CFU-Fs assay showed a significant MSC rate increase in irradiated bone marrows. CFU-Fs colonies still possessed differentiation capacities of MSC but colonies from mice sacrificed 3 days after irradiation displayed high rates of ALP activity and a transient increase in osteoblastic markers expression while pparγ and neuropilin-1 decreased. Hematopoietic supportive capacities of CFU-Fs were also modified: as compared to controls, irradiated CFU-Fs significantly increased the proliferation rate of hematopoietic precursors and accelerated the differentiation toward the granulocytic lineage. Our data provide the first evidence of the key role exerted by the balance between osteoblasts and adipocytes in spontaneous bone marrow regeneration. First, (preosteoblast differentiation from MSC stimulated hematopoietic precursor's proliferation and granulopoietic regeneration. Then, in a second time (preosteoblasts progressively disappeared in favour of adipocytic cells which down regulated the proliferation and granulocytic differentiation and then contributed to a return to pre-irradiation conditions.

  8. Hepatic catalase activity after whole-body irradiation of the mouse

    International Nuclear Information System (INIS)

    Using biochemical techniques, the effect of irradiation on catalase rate of different tissues is studied. With cytochemistry, the decrease of catalase activity is studied in situ, after exposure to great ionizing radiation doses

  9. Effect of 60Co-gamma whole-body irradiation on serum amylase level

    International Nuclear Information System (INIS)

    Changes of serum amylase activity in rats, after several doses of acut 60Co-gamma irradiation as a function of time were investigated. These changes proved to be of no diagnostic value in early radiation damage. (author)

  10. Toxicities of total-body irradiation for pediatric bone marrow transplantation

    International Nuclear Information System (INIS)

    Purpose: To determine the acute and late effects, including cognitive function, of total body irradiation (TBI) and chemotherapy for bone marrow transplant (BMT) in children with immunodeficiency or hematologic disorders. Methods and Materials: At UCSF, 15 children with immunodeficiency disorders and 58 children with leukemia received chemoradiotherapy between July 1982 and November 1993 and were evaluated for toxicity. Patients with severe combined immunodeficiency disorder (SCID) received 7 Gy TBI while leukemia patients received 12 Gy TBI. Results: Eight immunodeficient patients (53%) are alive at 4 months to 11 years posttransplant. Acute toxicity was limited and treatment well tolerated. Most patients developed mild nausea and vomiting, skin rash, or erythema. Transient fever/chills, oral mucositis, and alopecia were noted in approximately 50% of patients. Seventy-three percent of patients demonstrated acute liver dysfunction, but only four (27%) developed veno-occlusive disease. All children had decreased growth velocity but normal growth hormone levels. Other endocrinologic evaluations including adrenocorticotropic hormone (ACTH), cortisol, and thyroid hormones were normal. Only one evaluable girl had delayed puberty with late onset of secondary sexual characteristics. Neuropsychological testing demonstrated an intelligence quotient (IQ) reduction between the baseline and 1 year post-BMT, with some recovery at 3 years. Only one patient developed a clinically significant cataract. Thirteen percent of patients had chronic interstitial lung disease. Four children developed exostosis. Only 1 of the 15 children developed a second malignancy (acute myelogenous leukemia) at age 5, 51 months posttransplant for SCID. For patients with leukemia, similar toxicities were observed. Twenty-nine percent disease-free survival was noted with a mean follow-up of 4.7 years. Twenty-two percent had chronic interstitial lung disease and two patients were diagnosed with cataracts

  11. Protective Effects of Hong Shan Capsule against Lethal Total-Body Irradiation-Induced Damage in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Jianzhong Li

    2015-08-01

    Full Text Available Hong Shan Capsule (HSC, a crude drug of 11 medicinal herbs, was used in clinical practice for the treatment of radiation injuries in China. In this study, we investigated its protection in rats against acute lethal total-body irradiation (TBI. Pre-administration of HSC reduced the radiation sickness characteristics, while increasing the 30-day survival of the irradiated rats. Administration of HSC also reduced the radiation sickness characteristics and increased the 30-day survival of mice after exposure to lethal TBI. Ultrastructural observation illustrated that the pretreatment of rats with HSC significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed the dramatic effect of HSC on alterations of gene expression caused by lethal TBI. Pretreatment with HSC prevented differential expression of 66% (1398 genes of 2126 genes differentially expressed in response to TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 32 pathways, such as pathways in cancer and the mitogen-activated protein kinase (MAPK signaling pathway. Our analysis indicated that the pretreatment of rats with HSC modulated these pathways induced by lethal TBI, such as multiple MAPK pathways, suggesting that pretreatment with HSC might provide protective effects on lethal TBI mainly or partially through the modulation of these pathways. Our data suggest that HSC has the potential to be used as an effective therapeutic or radio-protective agent to minimize irradiation damage.

  12. Protective Effects of Hong Shan Capsule against Lethal Total-Body Irradiation-Induced Damage in Wistar Rats.

    Science.gov (United States)

    Li, Jianzhong; Xu, Jing; Xu, Weiheng; Qi, Yang; Lu, Yiming; Qiu, Lei; Hu, Zhenlin; Chu, Zhiyong; Chai, Yifeng; Zhang, Junping

    2015-08-12

    Hong Shan Capsule (HSC), a crude drug of 11 medicinal herbs, was used in clinical practice for the treatment of radiation injuries in China. In this study, we investigated its protection in rats against acute lethal total-body irradiation (TBI). Pre-administration of HSC reduced the radiation sickness characteristics, while increasing the 30-day survival of the irradiated rats. Administration of HSC also reduced the radiation sickness characteristics and increased the 30-day survival of mice after exposure to lethal TBI. Ultrastructural observation illustrated that the pretreatment of rats with HSC significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed the dramatic effect of HSC on alterations of gene expression caused by lethal TBI. Pretreatment with HSC prevented differential expression of 66% (1398 genes) of 2126 genes differentially expressed in response to TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 32 pathways, such as pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway. Our analysis indicated that the pretreatment of rats with HSC modulated these pathways induced by lethal TBI, such as multiple MAPK pathways, suggesting that pretreatment with HSC might provide protective effects on lethal TBI mainly or partially through the modulation of these pathways. Our data suggest that HSC has the potential to be used as an effective therapeutic or radio-protective agent to minimize irradiation damage.

  13. Transition pattern and mechanism of B-lymphocyte precursors in regenerated mouse bone marrow after subtotal body irradiation.

    Directory of Open Access Journals (Sweden)

    Deping Han

    Full Text Available Little is known about the effects of ionizing radiation on the transition and the related signal transduction of progenitor B cells in the bone marrow. Thus, using an NIH Swiss mouse model, we explored the impact of ionizing radiation on the early stage of B-cell development via an examination of the transition of CLP to pro-B to pre-B cells within bone marrow as a function of radiation doses and times. Our results showed that while the total number of bone marrow lymphoid cells at different stages were greatly reduced by subtotal body irradiation (sub-TBI, the surviving cells continued to transition from common lymphoid progenitors to pro-B and then to pre-B in a reproducible temporal pattern. The rearrangement of the immunoglobulin heavy chain increased significantly 1-2 weeks after irradiation, but no change occurred after 3-4 weeks. The rearrangement of the immunoglobulin light chain decreased significantly 1-2 weeks after sub-TBI but increased dramatically after 3-4 weeks. In addition, several key transcription factors and signaling pathways were involved in B-precursor transitions after sub-TBI. The data indicate that week 2 after irradiation is a critical time for the transition from pro-B cells to pre-B cells, reflecting that the functional processes for different B-cell stages are well preserved even after high-dose irradiation.

  14. Localization of /sup 3/H-estradiol in the reproductive organs of male and female baboons

    Energy Technology Data Exchange (ETDEWEB)

    Weaker, F.J.; Sheridan, P.J.

    1982-05-01

    The uptake and retention of radiolabeled estradiol by both the male and female reproductive organs were examined in the baboon. Two male and two female baboons were injected intracardially with 1 microgram/kg body weight of /sup 3/H-estradiol and two animals, one male and one female, were injected with both labeled and 100 micrograms/kg body weight of unlabeled estradiol. One and a half hours after the injections, the animals were sacrificed and the uterus, cervix, vagina, oviduct, seminal vesicles, and prostate gland were removed and processed for autoradiography. The stratified squamous epithelia of the cervix and vagina demonstrated a light uptake of the label in the germinative, but not in the superficial cell layers. The columnar cells lining the oviduct and uterine glands were labeled, whereas the luminal epithelium of the uterus and the glandular epithelia of the seminal vesicles and prostate gland did not sequester the tritiated steroid. The interstitial cells of all the organs studied demonstrated a moderate to heavy uptake of the radioactivity, whereas the smooth muscle cells were lightly labeled except in the vagina, in which these cells displayed a moderate number of silver grains.

  15. What baboons can (not) tell us about natural language grammars.

    Science.gov (United States)

    Poletiek, Fenna H; Fitz, Hartmut; Bocanegra, Bruno R

    2016-06-01

    Rey et al. (2012) present data from a study with baboons that they interpret in support of the idea that center-embedded structures in human language have their origin in low level memory mechanisms and associative learning. Critically, the authors claim that the baboons showed a behavioral preference that is consistent with center-embedded sequences over other types of sequences. We argue that the baboons' response patterns suggest that two mechanisms are involved: first, they can be trained to associate a particular response with a particular stimulus, and, second, when faced with two conditioned stimuli in a row, they respond to the most recent one first, copying behavior they had been rewarded for during training. Although Rey et al. (2012) 'experiment shows that the baboons' behavior is driven by low level mechanisms, it is not clear how the animal behavior reported, bears on the phenomenon of Center Embedded structures in human syntax. Hence, (1) natural language syntax may indeed have been shaped by low level mechanisms, and (2) the baboons' behavior is driven by low level stimulus response learning, as Rey et al. propose. But is the second evidence for the first? We will discuss in what ways this study can and cannot give evidential value for explaining the origin of Center Embedded recursion in human grammar. More generally, their study provokes an interesting reflection on the use of animal studies in order to understand features of the human linguistic system. PMID:26026382

  16. Long-term results of total body irradiation in adults with acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Marnitz, Simone; Zich, Alexander; Budach, Volker; Jahn, Ulrich; Neumann, Oliver [Charite University Medicine, Department of Radiation Oncology, Berlin (Germany); Martus, Peter [University Tuebingen, Institute of Clinical Epidemiology and Applied Biostatistics, Tuebingen (Germany); Arnold, Renate [Charite University Medicine, Campus CVK, Department of Hematology and Oncology, Bone Marrow Transplant Unit, Berlin (Germany)

    2014-05-15

    The aim of this chart review of adult patients treated for acute lymphoblastic leukemia (ALL) with total body irradiation (TBI) was to evaluate early and late toxicity and long-term outcome. A total of 110 adult patients (34 ± 12 years) with ALL underwent TBI (6 fractions of 2 Gy for a total of 12 Gy) as a part of the treatment regimen before transplantation. Treatment-related toxicity, mortality, and hematologic outcome are reported. Mean follow-up was 70 months. The 2- and 5-year leukemia-free survival rates were 78 and 72 %, respectively. In all, 29 % (32/110) patients suffered from medullary recurrence after a median time of 7 months. Gender was the only statistically significant prognostic factor in terms of overall survival in favor of female patients. Treatment-related mortality and overall survival after 2 and 5 years were 16 and 22 %, and 60 and 52.7 %, respectively. The most frequent late reaction wascGVHD of the skin (n = 33, 30 %). In addition, 15.5 % (17/110 patients) suffered pulmonary symptoms, and 6 patients developed lung fibrosis. Eyes were frequently affected by the radiation (31/110 = 28 %); 12 of 110 patients (11 %) presented with symptoms from osteoporosis, 5 of 110 patients (4.5 %) developed hypothyreosis and 2 patients diabetes mellitus. Of the male patients, 11 % reported erectile dysfunction or loss of libido, while 2 of 36 women reported menopausal syndrome at the mean time of 28 months after treatment with requirement for substitution. No women became pregnant after treatment. No acute or late cardiac toxicities were documented in our patients. No secondary malignancies were documented. Although hematologic outcome was in the upper range of that reported in the literature, treatment-related mortality (TRM) and medullary recurrences remain a challenge. Sophisticated radiation techniques allow for decreasing toxicity to certain organs and/or dose escalation to the bone marrow in highly selected patients in order to improve therapeutic

  17. Experimental model of a combined lung lesion by selinon herbicide and external whole-body ionizing irradiation

    International Nuclear Information System (INIS)

    Wistar rats have been treated as follows: acute gamma irradiated with 4 Gy; per os poisoned with selinon 5 times weekly during 4 months at dose 2.2 mg/kg (1/20 LD50) exposed to combined treatment with both factors. The following indices of the bronchoalveolar lavage fluid (BALF) and supernatant from lung homogenate (LH) were determined in dynamics till day 60: in BALF - total cell count; activity of the lactate dehydrogenase, alkaline phosphatase, acid phosphatase, protein content; in LH - activity of superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, amounts of malonic aldehyde and protein. The results show that chronic oral introduction of selinon at small doses causes toxic lung damage. Whole-body irradiation with 4 Gy ionizing radiation fails to potentiate the biological effects recorded. 2 figs., 4 refs

  18. Effect of whole-body irradiation of mice on the number of background plaque-forming cells

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, R.E.; Lefkovits, I.; Soeederberg, A.

    1983-08-01

    Mice were exposed in whole-body fashion to several doses of radiation and killed at various times thereafter for a determination of the number of background plaque-forming cells (PFCs) as assayed on either sheep erythrocytes or bromelain-treated autologous mouse erythrocytes. Increased numbers of both types of PFC were found in the irradiated groups. These increases were dependent on radiation dose and time after exposure. They did not appear to be caused by a disruption of normal lymphocyte traffic or a switch in immunoglobulin isotype. An increased number of PFCs on bromelain-treated mouse RBCs but not on sheep RBCs were found in irradiated congenitally athymic nude mice. On the basis of this and related observations, background PFCs on bromelain-treated mouse RBCs and on sheep RBCs appear to fall under different forms of homeostatic control.

  19. Effects of whole-body x-irradiation on some aspects of collagen metabolism in the rat

    International Nuclear Information System (INIS)

    Whole-body exposure of adult rats to x rays at sublethal or lethal doses causes a decrease in hydroxyproline levels in urine and skeletal muscle. Similarly, reduction in the excretion of labeled hydroxyproline in urine following intraperitoneal injection of 14C-proline may be attributed to impaired in vivo hydroxylation of proline. Incorporation of administered 14C-proline into 14C-hydroxyproline and its distribution in different metabolic forms of collagen in skeletal muscle and skin are markedly reduced in x-irradiated rats. These suggest impaired hydroxylation of proline. However, in vitro proline hydroxylase activity in liver is not affected by radiation treatment. Decreased endogenous oxygen consumption, as observed in liver homogenates of x-irradiated rats, may be one of the factors which affect in vivo proline hydroxylation

  20. Effect of whole-body irradiation of mice on the number of background plaque-forming cells.

    Science.gov (United States)

    Anderson, R E; Lefkovits, I; Söederberg, A

    1983-08-01

    Mice were exposed in whole-body fashion to several doses of radiation and killed at various times thereafter for a determination of the number of background plaque-forming cells (PFCs) as assayed on either sheep erythrocytes or bromelain-treated autologous mouse erythrocytes. Increased numbers of both types of PFC were found in the irradiated groups. These increases were dependent on radiation dose and time after exposure. They did not appear to be caused by a disruption of normal lymphocyte traffic or a switch in immunoglobulin isotype. An increased number of PFCs on bromelain-treated mouse RBCs but not on sheep RBCs were found in irradiated congenitally athymic nude mice. On the basis of this and related observations, background PFCs on bromelain-treated mouse RBCs and on sheep RBCs appear to fall under different forms of homeostatic control.

  1. Space Weathering of airless bodies in the Solar System - Combining hypervelocity dust impacts with energetic irradiation experiments

    Science.gov (United States)

    Fiege, K.; Bennett, C.; Guglielmino, M.; Orlando, T. M.; Trieloff, M.; Srama, R.

    2015-12-01

    The chemical and mineralogical characterization of meteorites and their parent asteroids provides us with information about the processes and conditions during the formation of the inner Solar System. However, linking meteorites to their parent bodies is problematic. Astronomical observations aim to reconstruct the surface properties of these bodies primarily by visible and infrared spectra, but space weathering severely modifies the optical, compositional and physical properties of thin surface layers and thus precludes proper identification of chemistry and mineralogy. The effects of space weathering have been experimentally studied mainly with respect to ion bombardment and sputtering. Other studies aimed to simulate the influence of micrometeoroid bombardment by using laser ablation techniques. However, there is sufficient evidence that laser ablation does not realistically lead to the same effects as produced during real micrometeorite impacts. We performed micrometeorite bombardment using a 2MV dust accelerator at the Institute for Space Systems at University of Stuttgart, Germany, capable of generating impact speeds up to 100 km s-1. These results are combined with energetic irradiation experiments at the Electron and Photon Induced Chemistry on Surfaces (EPICS) laboratory at Georgia Institute of Technology, USA. By simulating highly realistic irradiation conditions, we are able to investigate the processes of particle and solar wind irradiation on solid planetary surfaces and study the formation of e.g., nanophase iron in minerals, the effects on hydrous minerals regarding their volatile budgets, or possible OH-formation in nominally anhydrous minerals and relate these to their optical properties. Using a variety of minerals, this work aims to contribute to a better understanding of the general alteration mechanisms in space environments in dependence of weathering agent and available material. We here present the results of initial comparison analysis and

  2. Erythropoiesis in mice exposed to continuous whole body irradiation of gamma-rays

    Energy Technology Data Exchange (ETDEWEB)

    Joshima, Hisamasa; Fukutsu, Kumiko; Matsushita, Satoru; Kashima, Masatoshi

    1988-09-01

    The erythropoietic effects of continuous ..gamma..-irradiation with a daily regime of 0.029, 0.083 and 0.374 Gy were studied in mice. Irradiation was performed with /sup 137/Cs ..gamma..-rays for 22 hr/day. The length of irradiation time varied from 3 to 112 days. Erythropoiesis was investigated on the basis of clearance of /sup 59/Fe from the circulation and of incorporation of /sup 59/Fe into circulating erythrocytes and erythropoietic tissue. A chemical method for the separation of heme and nonheme iron-containing fractions was employed to examine the uptake of /sup 59/Fe into both the heme and nonheme iron fractions. Daily exposure to 0.029 and 0.083 Gy caused no significant changes in erythropoiesis. Daily exposure to 0.374 Gy caused some significant changes in erythropoiesis. On day 7 of continuous irradiation, the amount of /sup 59/Fe incorporated into erythrocytes decreased, but the values returned to normal on day 14 and 28 of continuous irradiation, indicating recovery within erythropoietic tissues at earlier time. On day 56, depressed incorporation of /sup 59/Fe into erythrocytes with normal rate of disappearance of /sup 59/Fe from the circulation and increased heme level of /sup 59/Fe in the femoral marrow were observed. Results observed on day 56 may suggest the possibility of ineffective erythropoiesis during the continuous irradiation. On day 112, some mice showed almost the same changes in erythropoiesis as those mice exposed to acute X-rays radiation.

  3. Pulmonary complications of bone marrow transplantation: a comparison of total body irradiation and cyclophosphamide to busulfan and cyclophosphamide

    International Nuclear Information System (INIS)

    Purpose: To retrospectively compare the acute and long-term pulmonary toxicities of total body irradiation and busulfan in bone marrow transplantation. Methods and Materials: From March 1984 through February 1991, 144 patients received high-dose therapy with cyclophosphamide plus either total body irradiation (TBI-CY) or busulfan (BU-CY) followed by bone marrow rescue. Treatment protocols were based on disease type. Cyclophosphamide dose was 120-200 mg/kg, given in 2-4 days. Total body irradiation was given as 12 Gy in four fractions over 4 days, or 14.4 Gy in eight fractions over 4 days. Busulfan dose was 16 mg/kg given over 4 days. Results: Seventy-nine patients were treated with TBI-CY and 65 patients with BU-CY. More patients in the TBI group had allogeneic transplants (40 vs. 18). Pulmonary events occurred in 48 patients, 19 in BU-CY and 29 in TBI-CY. Of the 58 patients with allogeneic transplants, 21 (36%) developed chronic graft-vs.-host disease (GVHD), and 10 of those patients developed pulmonary complications (including 2 with obliterative bronchitis and 1 with asthma). Interstitial pneumonitis (IP) occurred in 14 patients, 12 in the TBI-CY group and 2 in the BU-CY group. Cytomegalovirus and pneumocystis infections were associated with IP in 11 of those patients. Fatal idiopathic IP occurred in one patient in each of the TBI-CY and BU-CY groups. Multivariate analysis showed that only chronic GVHD and prior bleomycin use were significant predictors of interstitial pneumonitis; no difference was seen between TBI-CY and BU-CY. Conclusions: Pulmonary complications were most commonly associated with GVHD and prior bleomycin use. The incidence of cytomegalovirus or pneumocystis carinii pneumonitis was greater in the patients receiving the TBI regimen; fatal pulmonary complications were not significantly different between TBI and nonTBI regimens

  4. Combined total body X-ray irradiation and total skin electron beam radiotherapy with an improved technique for mycosis fungoides

    International Nuclear Information System (INIS)

    Twelve consecutive patients with advanced stage mycosis fungoides (MF) were treated with combined total body X ray irradiation (TBI) and total skin electron beam radiotherapy (EBRT). Six had generalized plaque disease and dermatopathic nodes, three had tumor stage disease and node biopsy positive for mycosis fungoides, and three had erythroderma/Sezary syndrome. The treatment regimen consisted of split course total body X ray irradiation, given in twice weekly 15 cGy fractions to 75 cGy, then total skin electron beam radiation therapy given in once weekly 400 cGy fractions to a total dose of 2400 cGy. Underdosed areas and areas of greatest initial involvement were boosted 400 cGy twice weekly for an additional 1200 cGy. This was followed by a second course of total body X ray irradiation, to a total dose of 150 cGy. The total skin electron beam radiotherapy technique is a modification of an established six position EBRT technique for mycosis fungoides. Measurements to characterize the beam with and without a lexan scattering plate, demonstrated that the combination of no-plate beams produced better dose uniformity with a much higher dose rate. This improved technique is particularly advantageous for elderly and/or frail patients. Nine (75%) of the 12 patients achieved complete response (CR). The other three had significant improvement with greater than 80% clearing of their disease and resolution of symptoms. All six patients with generalized plaque disease achieved complete response and remained free of disease from 2 to 16 months. Two of three node positive patients also achieved complete response; one, with massive biopsy-documented mycosis fungoides nodal disease and deep open tumors, remained relapse-free over 2 years. Only one of the three patients with erythroderma/Sezary syndrome achieved a complete response, which was short lived

  5. Combined total body X-ray irradiation and total skin electron beam radiotherapy with an improved technique for mycosis fungoides

    Energy Technology Data Exchange (ETDEWEB)

    Halberg, F.E.; Fu, K.K.; Weaver, K.A.; Zackheim, H.S.; Epstein, E.H. Jr.; Wintroub, B.U.

    1989-08-01

    Twelve consecutive patients with advanced stage mycosis fungoides (MF) were treated with combined total body X ray irradiation (TBI) and total skin electron beam radiotherapy (EBRT). Six had generalized plaque disease and dermatopathic nodes, three had tumor stage disease and node biopsy positive for mycosis fungoides, and three had erythroderma/Sezary syndrome. The treatment regimen consisted of split course total body X ray irradiation, given in twice weekly 15 cGy fractions to 75 cGy, then total skin electron beam radiation therapy given in once weekly 400 cGy fractions to a total dose of 2400 cGy. Underdosed areas and areas of greatest initial involvement were boosted 400 cGy twice weekly for an additional 1200 cGy. This was followed by a second course of total body X ray irradiation, to a total dose of 150 cGy. The total skin electron beam radiotherapy technique is a modification of an established six position EBRT technique for mycosis fungoides. Measurements to characterize the beam with and without a lexan scattering plate, demonstrated that the combination of no-plate beams produced better dose uniformity with a much higher dose rate. This improved technique is particularly advantageous for elderly and/or frail patients. Nine (75%) of the 12 patients achieved complete response (CR). The other three had significant improvement with greater than 80% clearing of their disease and resolution of symptoms. All six patients with generalized plaque disease achieved complete response and remained free of disease from 2 to 16 months. Two of three node positive patients also achieved complete response; one, with massive biopsy-documented mycosis fungoides nodal disease and deep open tumors, remained relapse-free over 2 years. Only one of the three patients with erythroderma/Sezary syndrome achieved a complete response, which was short lived.

  6. Effect of low dose whole-body X-irradiation on the efficacy of pEgr-IL18-B7.1 gene-radiotherapy

    International Nuclear Information System (INIS)

    Objective: To observe the therapeutic effect of whole-body irradiation with low dose X-rays in mice bearing Lewis lung carcinoma under recombinant plasmid pEgr-IL18-B7.1 gene-radiotherapy. Methods: The pEgr-IL18-B7.1 recombinant plasmids mediated by polyethylenimine were injected locally into tumors of the mice with gene-radiotherapy, and then the tumors received different therapeutic regimens containing local X-irradiation with 2 Gy and whole-body X-irradiation with 0.075 Gy, respectively. The anti-tumor effects of low dose X-rays in optimizing the protocol of pEgr-IL18-B7.1 gene-radiotherapy on the tumor-bearing mice were observed. Results: As compared with repeated high dose local X-irradiation alone, single high dose local X-irradiation in combination with repeated low dose of whole-body X-irradiation showed more significant inhibition of tumor growth under pEgr-IL18-B7.1 gene-radiotherapy. Conclusions: Low dose whole-body X-irradiation superimposed upon a local high dose could significantly enhance the anti-tumor effect in the protocol of pEgr-IL18-B7.1 gene-radiotherapy. (authors)

  7. The Baboon (Papio spp. as a Model of Human Ebola Virus Infection

    Directory of Open Access Journals (Sweden)

    Gary L.White

    2012-10-01

    Full Text Available Baboons are susceptible to natural Ebola virus (EBOV infection and share 96% genetic homology with humans. Despite these characteristics, baboons have rarely been utilized as experimental models of human EBOV infection to evaluate the efficacy of prophylactics and therapeutics in the United States. This review will summarize what is known about the pathogenesis of EBOV infection in baboons compared to EBOV infection in humans and other Old World nonhuman primates. In addition, we will discuss how closely the baboon model recapitulates human EBOV infection. We will also review some of the housing requirements and behavioral attributes of baboons compared to other Old World nonhuman primates. Due to the lack of data available on the pathogenesis of Marburg virus (MARV infection in baboons, discussion of the pathogenesis of MARV infection in baboons will be limited.

  8. Total body irradiation and allogeneic bone marrow transplantation - Sofia University Hospital experience

    International Nuclear Information System (INIS)

    Aim of the study: To report the long-term outcome in patients with leukaemias, who had conditioning regimens including total body irradiation (TBI) prior to bone marrow transplantation (BMT), and to establish independent factors correlated with treatment outcome. Material and methods: Between January 2002 and December 2007, 18 patients, 11 males and 7 females with median age of 12 years (range 8-50), received TBI. Initial diagnoses were acute lymphoblastic leukaemia (ALL) 11 (61%), acute myeloid leukaemia (AML) 4 (22%), and chronic myeloid leukaemia (CML) 3 (17%). Pre-transplantation disease status was defined as remission 11 (61%), progression 4 (22%), and chronic phase 3 (17%). All the patients were conditioned with a high-dose chemoradiotherapy regimen including fractionated TBI delivering 10 to 12 Gy in 15 (73%) and a single fraction of 2 Gy in 3 (17%) of the cases. TBI was performed in alternate prone and supine positions with a 60 Co machine. In 13 (72%) patients transplantation was carried out from an HLA-identical related donor and in 5 (28%) from an unrelated donor. Seventeen allogeneic transplantations were of peripheral blood stem cells and 1 was of bone marrow stem cells. Post- transplantation clinical, biological, and functional evaluations were performed on days 30, 100, 180, at 1 year, and annually thereafter. Each evaluation included an assessment of the study end points: marrow chimerism, disease status (complete remission or relapse), survival status (alive or dead), treatment-related toxicity (TRT), treatment-related mortality (TRM) and graft-versus-host-disease (GvHD). Results: Median follow-up from BMT was 27 months (range 3-52). Sixteen patients achieved engraftment, 2 patients had primary graft failure. Seven of 18 (39%) evaluable patients developed acute GvHD, 6 (35%) patients developed chronic GvHD. At the time of reporting 9 of 18 patients remain alive and in remission. Nine patients died, 4 (22%) because of relapse and 5 (28%) because of

  9. Acute whole-body irradiation, even at moderate dose, induces alterations in blood-brain-barrier permeability

    International Nuclear Information System (INIS)

    Full text: A radiation-induced blood-brain barrier (BBB) breakdown has been evoked, but clearly demonstrated only at high doses of ionizing radiations. By using two protocols, we have searched an impairment in BBB integrity induced by moderate doses. First, the effects of irradiation on the permeability of striatal BBB to [3H]AIBA and [14C]sucrose were investigated in rats by using brain microdialysis. 32 rats, irradiated at 4.5Gy were serially experimented from 0 to 24 hours, from 24 to 48 hours and at later delays after exposure. 32 sham-irradiated rats served as controls. Second, the entry of pyridostigmine (PYR would not be expected to cross the BBB) into the brain was investigated in mice subjected to (neutron-g) exposure at 0.7Gy or 4Gy. For each dose 120 animals were irradiated and 120 sham-irradiated mice were included. At different delays after exposure, 10 mice were injected with 0.9% NaCl (control) or PYR bromide (0.1 mg/kg). Mice were killed 10min after injection and striatum, cortex and hippocampus were quickly dissected. Penetration of the drug into the brain was examined by measurement of AChE activity. Concerning microdialysis protocol, no late modification of the permeability of BBB was observed. But, in the course of the initial syndrome, we observed a transient increase of the permeability to the two markers, between the third and the 17th hour after exposure. A secondary transient 'opening' of the BBB to [14C] sucrose was noticed about 28 hours following irradiation with no modification of the permeability to [3H]AIBA. Concerning the BBB permeability to PYR, by comparing irradiated-PYR mice to sham-PYR mice, a decrease of AChE activity in the three cerebral areas was noted 48 hours after exposure at 4 Gy ; at 0.7 Gy this decrease is noted in the striatum only. In conclusion, our experiments by using two animal models, two types of radiations, and different tracers show modifications of the BBB permeability after moderate doses whole-body

  10. Survival and Neurocognitive Outcomes After Cranial or Craniospinal Irradiation Plus Total-Body Irradiation Before Stem Cell Transplantation in Pediatric Leukemia Patients With Central Nervous System Involvement

    Energy Technology Data Exchange (ETDEWEB)

    Hiniker, Susan M. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Agarwal, Rajni [Section of Stem Cell Transplantation, Department of Pediatrics, Stanford University, Stanford, California (United States); Modlin, Leslie A. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Gray, Christine C. [Division of Child and Adolescent Psychiatry, Department of Psychiatry, Stanford University, Stanford, California (United States); Harris, Jeremy P.; Million, Lynn [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Kiamanesh, Eileen F. [Cancer Clinical Trials Office, Stanford Cancer Institute, Stanford University, Stanford, California (United States); Donaldson, Sarah S., E-mail: sarah2@stanford.edu [Department of Radiation Oncology, Stanford University, Stanford, California (United States)

    2014-05-01

    Purpose: To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen. Methods and Materials: Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes. Results: All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college. Conclusion: The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy

  11. Survival and Neurocognitive Outcomes After Cranial or Craniospinal Irradiation Plus Total-Body Irradiation Before Stem Cell Transplantation in Pediatric Leukemia Patients With Central Nervous System Involvement

    International Nuclear Information System (INIS)

    Purpose: To evaluate survival and neurocognitive outcomes in pediatric acute lymphoblastic leukemia (ALL) patients with central nervous system (CNS) involvement treated according to an institutional protocol with stem cell transplantation (SCT) and a component of craniospinal irradiation (CSI) in addition to total-body irradiation (TBI) as preparative regimen. Methods and Materials: Forty-one pediatric ALL patients underwent SCT with TBI and received additional cranial irradiation or CSI because of CNS leukemic involvement. Prospective neurocognitive testing was performed before and after SCT in a subset of patients. Cox regression models were used to determine associations of patient and disease characteristics and treatment methods with outcomes. Results: All patients received a cranial radiation boost; median total cranial dose was 24 Gy. Eighteen patients (44%) received a spinal boost; median total spinal dose for these patients was 18 Gy. Five-year disease-free survival (DFS) for all patients was 67%. Those receiving CSI had a trend toward superior DFS compared with those receiving a cranial boost alone (hazard ratio 3.23, P=.14). Patients with isolated CNS disease before SCT had a trend toward superior DFS (hazard ratio 3.64, P=.11, 5-year DFS 74%) compared with those with combined CNS and bone marrow disease (5-year DFS 59%). Neurocognitive testing revealed a mean post-SCT overall intelligence quotient of 103.7 at 4.4 years. Relative deficiencies in processing speed and/or working memory were noted in 6 of 16 tested patients (38%). Pre- and post-SCT neurocognitive testing revealed no significant change in intelligence quotient (mean increase +4.7 points). At a mean of 12.5 years after transplant, 11 of 13 long-term survivors (85%) had completed at least some coursework at a 2- or 4-year college. Conclusion: The addition of CSI to TBI before SCT in pediatric ALL with CNS involvement is effective and well-tolerated. Craniospinal irradiation plus TBI is worthy

  12. Effect of intestinal microflora on the survival time of mice exposed to lethal whole-body γ irradiation

    International Nuclear Information System (INIS)

    The effect of intestinal microflora on the survival time of mice exposed to 2-kR whole-body γ irradiation was studied using germfree, monoassociated, and conventionalized ICR mice. The germfree mice were monoassociated with 1 of 11 bacterial strains, which were isolated from the fresh feces of conventional mice, 2 weeks prior to irradiation. All mice died within 3 weeks after irradiation. Monoassociation with Fusobacterium sp., Streptococcus faecalis, Escherichia coli, or Pseudomonas sp. significantly reduced the mean survival time compared to that of germfree mice. In contrast, monoassociation with Clostridium sp., Bifidobacterium pseudolongum, or Lactobacillus acidophilus significantly prolonged the mean survival time compared to that of germfree mice. This suggests that the latter organisms may perform some activity to protect the mice from radiation injury. In this histopathological autopsy examination, the main lesions were hypocellularity in hematopoietic organs and hemorrhage in various organs. Neither karyorrhexis nor desquamation of intestinal mucosal cells was observed in any mice. From these observations, it is suggested that the death of these mice was related to hematopoietic damage. Bacterial invasion into various organs was observed in conventionalized and Pseudomonas-, E. coli-, or S. faecalis-monoassociated mice but not in Clostridium-, B. pseudolongum-, L. acidophilus-, or Fusobacterium-monoassociated mice

  13. Radio-induced neuropathology: from early effects to late sequelae. Rat behavioural and metabolic studies after sublethal total body irradiation

    International Nuclear Information System (INIS)

    The radioresistance dogma of Central Nervous System (CNS) is now obsolete. Recent progress in neuroscience allow us to reconsider the radiation-induced cognitive dysfunctions observed after radiation therapy or after a nuclear accident, and to devise appropriate diagnostic and therapeutic means. We have developed a Rat model to study the effects of total body irradiation at a sublethal dose (4.5 Gy). This leads to impaired learning and memory of a task being acquired during the first month - which is prevented by administration of a radioprotector (amifostine) - while it does not appear to affect retrograde memory. Early, an apoptotic wave occurs in the sub-ventricular zone, 5 to 9 hours after exposure, while neuro-genesis is suppressed. Two days after irradiation, the metabolic study conducted by NMR HRMAS (High Resolution Magic Angle Spinning) suggests the presence of cerebral oedema and the study of brain lipids in liquid NMR confirms the membrane damages (elevated cholesterol and phospholipids). The lipid profile is then normalized while a gliosis appears. Finally, 1 month post-irradiation, the elevation of GABA, an inhibitory neurotransmitter, in 2 separate brain structures, occurs simultaneously with a taurine decrease in the hippocampus that lasts 6 months. Our integrated model allows validating bio-markers measurable in vivo NMR spectroscopy - the next experimental stage - and testing new radiation-protective agents. (author)

  14. The effect of total body irradiation and bone marrow transplantation during childhood and adolescence on growth and endocrine function

    International Nuclear Information System (INIS)

    Seventeen children with acute leukaemia and myeloproliferative disorders were investigated for growth and endocrine dysfunction. All had undergone bone marrow transplantation prepared with cyclophosphamide and single fraction total body irradiation (900-1000 cGy) between 1.5 and 3.8 (mean 2.2) years previously. The majority exhibited growth failure, of multiple aetiology. Ten patients, of whom eight had had previous prophylactic cranial irradiation, had evidence of growth hormone deficiency based on reduced growth hormone reponse to insulin induced hypoglycaemia. Three had evidence of hypothalamic damage. Gonadal failure was common. All four girls of adolescent age (10.6-14.1 years) had ovarian failure requiring sex steroid replacement. Of eight boys of adolescent age (12.3-18.3 years), two had testicular failure requiring sex steroid supplements. Both had had previous testicular irradiation. Five others had compensated gonadal failure; one had normal Leydig cell function. Abnormalities of the TSH response to TRH occurred in 10 patients but only three had overt hypothyroidism. Unlike growth hormone deficiency, gonadal and thyroid dysfunction showed no correlation with previous cranial radiotherapy. (author)

  15. Pegylated G-CSF Inhibits Blood Cell Depletion, Increases Platelets, Blocks Splenomegaly, and Improves Survival after Whole-Body Ionizing Irradiation but Not after Irradiation Combined with Burn

    Directory of Open Access Journals (Sweden)

    Juliann G. Kiang

    2014-01-01

    Full Text Available Exposure to ionizing radiation alone (radiation injury, RI or combined with traumatic tissue injury (radiation combined injury, CI is a crucial life-threatening factor in nuclear and radiological accidents. As demonstrated in animal models, CI results in greater mortality than RI. In our laboratory, we found that B6D2F1/J female mice exposed to 60Co-γ-photon radiation followed by 15% total-body-surface-area skin burns experienced an increment of 18% higher mortality over a 30-day observation period compared to irradiation alone; that was accompanied by severe cytopenia, thrombopenia, erythropenia, and anemia. At the 30th day after injury, neutrophils, lymphocytes, and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were similar to basal levels. Comparing CI and RI mice, only RI induced splenomegaly. Both RI and CI resulted in bone marrow cell depletion. It was observed that only the RI mice treated with pegylated G-CSF after RI resulted in 100% survival over the 30-day period, and pegylated G-CSF mitigated RI-induced body-weight loss and depletion of WBC and platelets. Peg-G-CSF treatment sustained RBC balance, hemoglobin levels, and hematocrits and inhibited splenomegaly after RI. The results suggest that pegylated G-CSF effectively sustained animal survival by mitigating radiation-induced cytopenia, thrombopenia, erythropenia, and anemia.

  16. Effects of food availability on serum insulin and lipid concentrations in free-ranging baboons.

    Science.gov (United States)

    Kemnitz, Joseph W; Sapolsky, Robert M; Altmann, Jeanne; Muruthi, Philip; Mott, Glen E; Stefanick, Marcia L

    2002-05-01

    The relationship between food availability and metabolic physiology was studied in groups of free-ranging baboons (Papio spp.) living in the Amboseli National Park and the Masai Mara National Reserve of Kenya. Three groups subsisted entirely on natural forage, while two other groups lived near tourist facilities and often consumed food wastes from these lodges. The refuse provided a very accessible food source with relatively high caloric density. Consumption of the refuse was associated with reduced locomotion. Sexually mature individuals from all five groups were sedated surreptitiously in the early morning and blood samples were collected. Compared to animals foraging exclusively in the wild, animals that supplemented their diet with the refuse items had two- to threefold elevations in serum insulin concentrations, as well as increased total cholesterol (C), HDL-C, and VLDL+LDL-C levels. No sex differences in physiological measures were observed except in body mass. Elevated serum insulin, and cholesterol and lipoprotein concentrations influence the development of cardiovascular disease and have been shown to be subject to dietary manipulation and exercise under controlled conditions. The present results suggest potentially deleterious effects of a highly accessible, calorically dense food source, and associated reduction of physical activity for baboons living in an otherwise natural environment.

  17. Monte Carlo efficiency calibration of a neutron generator-based total-body irradiator

    International Nuclear Information System (INIS)

    Many body composition measurement systems are calibrated against a single-sized reference phantom. Prompt-gamma neutron activation (PGNA) provides the only direct measure of total body nitrogen (TBN), an index of the body's lean tissue mass. In PGNA systems, body size influences neutron flux attenuation, induced gamma signal distribution, and counting efficiency. Thus, calibration based on a single-sized phantom could result in inaccurate TBN values. We used Monte Carlo simulations (MCNP-5; Los Alamos National Laboratory) in order to map a system's response to the range of body weights (65-160 kg) and body fat distributions (25-60%) in obese humans. Calibration curves were constructed to derive body-size correction factors relative to a standard reference phantom, providing customized adjustments to account for differences in body habitus of obese adults. The use of MCNP-generated calibration curves should allow for a better estimate of the true changes in lean tissue mass that many occur during intervention programs focused only on weight loss. (author)

  18. Animal experiments with rats as a contribution to the question of whole body irradiation

    International Nuclear Information System (INIS)

    Recovery after sublethal radiation damage was studied in the white blood count which shows a fast reaction to attacks caused by radiation. The so-called 'fractionated-dose method' was used. This method detrmines to what extent the total dose must be raised for two partial doses given at different times to produce the same amount of damage as a single irradiation. The second dose was applied after 7. days. A dose reduction by protraction of the first dose over 2 days was only found after doses of 300 to 400 rad. Regarding the anorexia connected with the radiation syndrome, no differences were found at low doses between protracted and one-time irradiation. This suggests that there is no repair. (MG)

  19. Acute central nervous system (CNS) toxicity of total body irradiation (TBI) measured using neuropsychological testing of attention functions

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to investigate acute normal tissue damage of low irradiation doses to the healthy, adult central nervous system (CNS) using neuropsychological testing of attention functions. Methods and Materials: Neuropsychological testing (IQ, attention [modified Trail-Making Test A, Digit Symbol Test, D2 Test, Wiener Determination Machine]) was used to examine 40 patients (43 ± 10 years) before and immediately after the first fraction (1.2 Gy) of hyperfractionated total body irradiation (TBI) at the University of Heidelberg. The patients received antiemetic premedication. Test results are given as mean percentiles ± standard deviation, with 50 ± 34 being normal. Thirty-eight control patients (53 ± 15 years) were studied to quantify the influence of hospitalization, stress, and repeated testing. Results: The patients showed normal baseline test results (IQ = 101 ± 14, attention = 54 ± 28) and no decrease in test results after 1.2 Gy TBI. Attention functions improved (66 ± 25) corresponding to a practice effect of repeated testing that was seen in the control group, although alternate versions of the tests were used (IQ = 104 ± 10, attention before = 42 ± 29, attention after = 52 ± 31). Conclusion: Our data show no deterioration of neuropsychologic test results acutely after 1.2 Gy whole body exposure in adult patients without CNS disease receiving antiemetic medication

  20. Citrulline as a Biomarker in the Murine Total-Body Irradiation Model: Correlation of Circulating and Tissue Citrulline to Small Intestine Epithelial Histopathology.

    Science.gov (United States)

    Jones, Jace W; Tudor, Gregory; Li, Fei; Tong, Yan; Katz, Barry; Farese, Ann M; MacVittie, Thomas J; Booth, Catherine; Kane, Maureen A

    2015-11-01

    The use of plasma citrulline as a biomarker for gastrointestinal acute radiation syndrome via exposure to total-body irradiation in a murine model was investigated. The radiation exposure covered lethal, mid-lethal, and sub-lethal gastrointestinal acute radiation syndrome. Plasma citrulline profiles were generated over the first 6 d following total-body irradiation exposure of 6-15 Gy. In addition, plasma citrulline was comprehensively evaluated in the context of matching small intestine citrulline and histopathology. Higher plasma citrulline was significantly associated with lower irradiation doses over the first 6 d following the irradiation insult. Furthermore, higher plasma citrulline was significantly associated with higher crypt survival. The correlation of the plasma citrulline to crypt survival was more robust for higher irradiation doses and for later time points. The data suggested plasma citrulline was most informative for reflecting gastrointestinal injury resulting from exposure to 9-15 Gy total-body irradiation covering time-points 2-5 d post the irradiation insult.

  1. Effect of antihistamines, disodium cromoglycate (DSCG) or methysergide on post-irradiation cerebral blood flow and mean systemic arterial blood pressure in primates after 25 Gy, whole-body, gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Cockerham, L.G.; Forcino, C.D. [Armed Forces Radiobiology Research Inst., Bethesda, MD (United States)

    1995-06-01

    Exposure to ionizing radiation causes hypotension, cerebral ischemia and release of histamine (HA) and serotonin (5-HT). To investigate the relationship among these responses, rhesus monkeys (Macaca mulatta) received physiological saline (i.v.), disodium cromoglycate (DSCG), antihistamines (AH, mepyramine and cimetidine), or methysergide (METH), then were given 25 Gy whole-body irradiation. Monkeys receiving DSCG, AH or METH had higher post-irradiation mean arterial blood pressure (MBP) than saline-treated controls. Compared to levels in controls, post-irradiation hippocampal blood flow (rCBF) levels were higher in monkeys receiving DSCG, AH or METH. Treatment with the 5-HT{sub 2} receptor antagonist methysergide was the most effective in maintaining both rCBF and MBP after irradiation. Results support the hypothesis that the irradiation-induced cerebral ischemia and, to some extent, the hypotension is mediated by serotonin through 5-HT{sub 2} receptor sites. (author) 72 refs.

  2. Effect of antihistamines, disodium cromoglycate (DSCG) or methysergide on post-irradiation cerebral blood flow and mean systemic arterial blood pressure in primates after 25 Gy, whole-body, gamma irradiation

    International Nuclear Information System (INIS)

    Exposure to ionizing radiation causes hypotension, cerebral ischemia and release of histamine (HA) and serotonin (5-HT). To investigate the relationship among these responses, rhesus monkeys (Macaca mulatta) received physiological saline (i.v.), disodium cromoglycate (DSCG), antihistamines (AH, mepyramine and cimetidine), or methysergide (METH), then were given 25 Gy whole-body irradiation. Monkeys receiving DSCG, AH or METH had higher post-irradiation mean arterial blood pressure (MBP) than saline-treated controls. Compared to levels in controls, post-irradiation hippocampal blood flow (rCBF) levels were higher in monkeys receiving DSCG, AH or METH. Treatment with the 5-HT2 receptor antagonist methysergide was the most effective in maintaining both rCBF and MBP after irradiation. Results support the hypothesis that the irradiation-induced cerebral ischemia and, to some extent, the hypotension is mediated by serotonin through 5-HT2 receptor sites. (author) 72 refs

  3. Inherently analog quantity representations in olive baboons (Papio anubis

    Directory of Open Access Journals (Sweden)

    Allison M Barnard

    2013-05-01

    Full Text Available Strong evidence indicates that non-human primates possess a numerical representation system, but the inherent nature of that system is still debated. Two cognitive mechanisms have been proposed to account for non-human primate numerical performance: (1 a discrete object-file system limited to quantities <4, and (2 an analog system which represents quantities comparatively but is limited by the ratio between two quantities. To test the underlying nature of non-human primate quantification, we asked eight experiment -naive olive baboons (Papio anubis to discriminate between number pairs containing small (<4, large (>4, or span (small vs. large numbers of food items presented simultaneously or sequentially. The prediction from the object-file hypothesis is that baboons will only accurately choose the larger quantity in small pairs, but not large or span pairs. Conversely, the analog system predicts that baboons will be successful with all numbers, and that success will be dependent on numerical ratio. We found that baboons successfully discriminated all pair types at above chance levels. In addition, performance significantly correlated with the ratio between the numerical values. Although performance was better for simultaneous trials than sequential trials, evidence favoring analog numerical representation emerged from both conditions, and was present even in the first exposure to number pairs. Together, these data favor the interpretation that a single, coherent analog representation system underlies spontaneous quantitative abilities in primates.

  4. An economic analysis of "demand" for food in baboons.

    Science.gov (United States)

    Foltin, R W

    1991-11-01

    Responding of 6 adult male baboons (Papio c. anubis) was maintained under a fixed-ratio schedule of food reinforcement during daily 22-hr experimental sessions. Completion of the ratio requirement resulted in the delivery of a single 1-g food pellet; supplemental feeding was limited to a daily fruit ration. Ratio values were increased on Mondays, Wednesdays, and Fridays according to the following schedule: 2, 4, 8, 16, 32, 64, 96, 128. Responding under each ratio value was examined four times. Under the Fixed-Ratio 2 conditions, food intake ranged between 300 and 600 g. Ratios were increased for each baboon until food intake decreased to about 100 g (20% to 30% of Fixed-Ratio 2 intake). Increasing the response cost increased total time responding and total daily responding in all baboons, but this increase in responding was not sufficient to maintain stable food intake. Baboons responded between 90 and 180 min per day. The highest running response rates were observed under the Fixed-Ratio 2 and Fixed-Ratio 4 schedules. Running rate was similar across the larger ratio values (greater than Fixed-Ratio 8) but was lower than that observed under the Fixed-Ratio 2 and Fixed-Ratio 4 schedules. Similar results were observed the four times that each fixed-ratio value was tested. Intake as a function of cost was analyzed by fitting data to the nonlinear equation proposed by Hursh, Raslear, Shurtleff, Bauman, and Simmons (1988) for "demand" functions. Demand for food was inelastic over most of the ratio values until food intake decreased to 15% to 55% of baseline. The results indicate that demand functions are appropriate for the study of food intake in baboons, but also caution that intake at the cost when demand shifts from inelastic to elastic and its relationship to maximal intake should also be included in analyses of demand for a commodity. PMID:1774538

  5. Effect of Whole-Body X-Irradiation of the Synthesis of Individual Fatty Acids in Liver Slices from Normal and Fasted Rats

    DEFF Research Database (Denmark)

    Hansen, Heinz Johs. Max; Hansen, Lisbeth Grænge; Faber, M.

    1965-01-01

    (1) Using (2-14C) acetate and (1-14C) butyrate as precursors, rat-liver fatty acids were synthesized in vitro and assayed by paper chromatography. (2) Whole-body x-irradiation induced a change in the synthetic pattern of hepatic fatty acids towards a relatively enhanced synthesis of palmitic acid....... (3) X-irradiation and fasting seem to have opposite effects on fatty-acid synthesis. X-irradiation counteracts the drop in total synthesis and the relatively enhanced synthesis of palmitoleic acid induced by fasting. The relative enhancement of palmitic-acid synthesis mentioned under (2) stands...

  6. Arabinoxylan rice bran (MGN-3/Biobran) provides protection against whole-body γ-irradiation in mice via restoration of hematopoietic tissues

    International Nuclear Information System (INIS)

    The aim of the current study is to examine the protective effect of MGN-3 on overall maintenance of hematopoietic tissue after γ-irradiation. MGN-3 is an arabinoxylan from rice bran that has been shown to be a powerful antioxidant and immune modulator. Swiss albino mice were treated with MGN-3 prior to irradiation and continued to receive MGN-3 for 1 or 4 weeks. Results were compared with mice that received radiation (5 Gy γ rays) only, MGN-3 (40 mg/kg) only and control mice (receiving neither radiation nor MGN-3). At 1 and 4 weeks post-irradiation, different hematological, histopathological and biochemical parameters were examined. Mice exposed to irradiation alone showed significant depression in their complete blood count (CBC) except for neutrophilia. Additionally, histopathological studies showed hypocellularity of their bone marrow, as well as a remarkable decrease in splenic weight/relative size and in number of megakaryocytes. In contrast, pre-treatment with MGN-3 resulted in protection against irradiation-induced damage to the CBC parameters associated with complete bone marrow cellularity, as well as protection of the aforementioned splenic changes. Furthermore, MGN-3 exerted antioxidative activity in whole-body irradiated mice, and provided protection from irradiation-induced loss of body and organ weight. In conclusion, MGN-3 has the potential to protect progenitor cells in the bone marrow, which suggests the possible use of MGN-3/Biobran as an adjuvant treatment to counteract the severe adverse side effects associated with radiation therapy

  7. Total-body irradiation and host reconstitution with stored autologous marrow: an experimental model for the induction of allogeneic unresponsiveness in large mammals. [Dogs

    Energy Technology Data Exchange (ETDEWEB)

    Rapaport, F.T.; Bachvaroff, R.J.; Dicke, K.; Santos, G.

    1979-03-01

    These results point to the capacity of suprelethal total-body irradiation and autologous bone marrow replacement to produce in the host a time-dependent privileged phase of immunologic reactivity during which exposure to alloantigens is more likely to produce unresponsiveness, rather than sensitization. The mechanisms implicated in the mediation of this phenomenon are not clear. Regardless of hypothetical interpretations, however, the current growing interest in total-body irradiation and autologous bone marrow replacement in clinical medicine, and the ease with which this approach appears to produce allogenic unresponsiveness in large mammals, raise the possibility that this method may constitute a highly promising approach to the facilitation of survival of vital transplanted organs in man. This possibility is further supported by the long-term record of the world's longest surviving renal allograft recipient, whose preoperative preparation consisted of total-body irradiation 24 hr before a kidney transplant.

  8. Effect of whole body proton or gamma irradiation on genetic damage and hematological variables

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Ji-Young; Ahn, Ji-Yeon; Yi, Jae Youn; Kang, Chang-Mo; Yun, Yeon-Sook; Song, Jie-Young [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2008-05-15

    For the purpose of cancer therapy or spaceflight with mission or simple trip, a considerable concern about the absorbed amount of radiation and its deleterious effect on physiological system, if any, has been increased. Many efforts have been dedicated to estimate the risk, however, there is very little known about the spectrum of radiations during the flight through arctic zone as well as the effects of low-dose radiation. Here, we aimed to evaluate the effect of proton or gamma-irradiation at a recommended dose limit of occupational (20mGy per year) and the standardized radio-therapeutic fraction dose (2Gy) on gastro-intestinal damages, peripheral hematology, and the frequency of micronuclei formation.

  9. Acute radiation syndrome, c.aused by single whole-body external irradiation

    International Nuclear Information System (INIS)

    The general characteristic of conceptions of the material substrate of various forms and types of radiation injuries from the moment of a wide use of radiation energy and radioactive substances up to the present time, the dependence of structural changes on the type of ionizing radiation, dose and forms of its effect, are presented. The pathological anatomy of particular manifestations of acute radiation disease in various systems of the organism is described. The attention is paid to the variant of radiation disease taking place during non-uniform general irradiation. Local and general morphological changes which develop in skin, hyperdermic fat and skeleton muscles simultaneously in the zone of massive local effect against the background of the general radiation injury, are described for the first time. Delayed alterations in blood vessels and interstitial tissue after the acute radiation disease are described as well as the pathomorphology and histochemistry of trophic disorders in the acute and delayed periods of acute radiation disease

  10. Metabolic changes in serum steroids induced by total-body irradiation of female C57B/6 mice.

    Science.gov (United States)

    Moon, Ju-Yeon; Shin, Hee-June; Son, Hyun-Hwa; Lee, Jeongae; Jung, Uhee; Jo, Sung-Kee; Kim, Hyun Sik; Kwon, Kyung-Hoon; Park, Kyu Hwan; Chung, Bong Chul; Choi, Man Ho

    2014-05-01

    The short- and long-term effects of a single exposure to gamma radiation on steroid metabolism were investigated in mice. Gas chromatography-mass spectrometry was used to generate quantitative profiles of serum steroid levels in mice that had undergone total-body irradiation (TBI) at doses of 0Gy, 1Gy, and 4Gy. Following TBI, serum samples were collected at the pre-dose time point and 1, 3, 6, and 9 months after TBI. Serum levels of progestins, progesterone, 5β-DHP, 5α-DHP, and 20α-DHP showed a significant down-regulation following short-term exposure to 4Gy, with the exception of 20α-DHP, which was significantly decreased at each of the time points measured. The corticosteroids 5α-THDOC and 5α-DHB were significantly elevated at each of the time points measured after exposure to either 1 or 4Gy. Among the sterols, 24S-OH-cholestoerol showed a dose-related elevation after irradiation that reached significance in the high dose group at the 6- and 9-month time points.

  11. A pilot study to evaluate the cost-effectiveness of ondansetron and granisetron in fractionated total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Gibbs, S.J.; Cassoni, A.M. [Middlesex Hospital, London (United Kingdom)

    1996-11-01

    The duration of the antiemetic effect of granisetron was examined in a pilot study of patients (n = 26) undergoing a standard emetogenic stimulus in the form of total body irradiation fractionated over 3-4 days, in a randomized comparison with twice-daily ondansetron. A single intravenous dose of granisetron at the onset of therapy was effective over the entire follow-up period in 50% (6/12) of patients, compared with 77% (10/13) prescribed twice-daily oral ondansetron for 3 or 4 days. The response rate within the first 24 hours from the start of irradiation was 67% (8/12) for granisetron and 77% (10/13) for ondansetron. Granisetron and ondansetron was therefore of similar efficacy within the first 24-hour period, but granisetron was less efficaceous more than 24 hours after the onset of therapy. Patients who required a second dose of granisetron did so at intervals of 12, 42, 47 and 48 hours following the first fraction of radiotherapy. The cost per patient in this study was 48 for granisetron and {sub 1}54 for ondanestron, but the dose scheduling we used cannot be recommended in view of the lower effectiveness of granisetron. (author).

  12. High-dose total body irradiation and myeloablative conditioning before allogeneic hematopoietic cell transplantation: time to rethink?

    Science.gov (United States)

    Mohty, Mohamad; Malard, Florent; Savani, Bipin N

    2015-04-01

    Over the last decade, the care of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) has significantly improved, leading to a decrease in deaths related to allo-HCT as well as improved long-term survival. However, for many patients, long-term survivorship is associated with a substantial burden of chronic morbidities. Indeed, malignant and nonmalignant late complications after allo-HCT are numerous and usually multifactorial, with all organs and tissues a potential target. In many cases, these long-term side effects are associated with the use of high-dose total body irradiation, myeloablative conditioning regimens, and the onset of chronic graft-versus-host disease. It appears to be essential to change the natural history of these late effects. This requires the introduction of improved conditioning regimens and the development of lifelong monitoring controls, patient counseling, and preventative treatment measures. This approach will allow us to pursue our efforts to improve patient outcome.

  13. Biogenic amines in brain areas of rats and response to varying dose levels of whole body gamma irradiation

    International Nuclear Information System (INIS)

    The levels of norepinephrine (NE), dopamine (DA), 5-hydroxy-tryptamine (5-HT) and 5-hydroxy-indole acetic acid (5-HIAA) were examined in the brain areas:cortex,: cerebellum, striatum and pons in rats exposed to whole body gamma-irradiation at the dose levels 6.5 and 10 Gy. The data obtained indicated that: 6.5 Gy induced in all brain areas, a slight increase in 5-HT concomitant with significant decrease in NE, DA levels, besides a significant increase in 5-HTAA in cerebellum and pons. After the dose 10 Gy the maximum excitation of 5-HT level was in striatum whereas declines in NE, DA were recorded in all brain areas. 5-HIAA displayed significant increase in cerebellum and pons and maximum decline in the cortex. 4 tab

  14. Metabolism of endogenous surfactant in premature baboons and effect of prenatal corticosteroids

    OpenAIRE

    Bunt, Jan Erik; Carnielli, Virgilio; Seidner, S.R.; Ikegami, M; Wattimena, Josias; Sauer, Pieter; Jobe, Alan; Zimmermann, Luc

    1999-01-01

    textabstractWe studied the synthesis of surfactant and the effect of prenatal betamethasone treatment in vivo in very preterm baboons. Ten pregnant baboons were randomized to receive either betamethasone (beta) or saline (control) 48 and 24 h before preterm delivery. The newborn baboons were intubated, treated with surfactant, and ventilated for 6 d. They received a 24-h infusion with the stable isotope [U-(13)C]glucose as precursor for the synthesis of palmitic acid in surfactant phosphatidy...

  15. Baboon Model of Generalized Epilepsy: Continuous Intracranial Video-EEG Monitoring with Subdural Electrodes

    OpenAIRE

    Szabó, C. Ákos; Salinas, Felipe S.; Leland, M Michelle; Caron, Jean-Louis; Hanes, Martha A.; Knape, Koyle D.; Xie, Dongbin; Williams, Jeff T.

    2012-01-01

    The baboon provides a natural non-human primate model for photosensitive, generalized epilepsy. This study describes an implantation procedure for the placement of subdural grid and strip electrodes for continuous video-EEG monitoring in the epileptic baboon to evaluate the generation and propagation of ictal and interictal epileptic discharges. Subdural grid, strip and depth electrodes were implanted in six baboons, targeting brain regions that were activated in functional neuroimaging studi...

  16. Low-dose fractionated whole-body irradiation in the treatment of advanced non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Thirty-nine patients with advanced non-Hodgkin's lymphoma (38 patients with lymphocytic lymphoma and 1 patient with mixed lymphocytic and histiocytic lymphoma) were treated by fractionated low dose whole body irradiation (WBI) with a minimum follow-up of 8 months. Twenty-eight patients had no previous treatment and the other 11 patients were in relapse after previous chemotherapy or regional radiotherapy. There were 20 and 19 patients in stages III and IV groups, respectively. The majority of patients (31) had nodular histology; diffuse lymphocytic lymphoma was present in 8 patients (Rappaport criteria) (9). Constitutional symptoms were present in 10 patients. Thirty-three (85%) attained complete remission (CR) with median duration of remission 24 months. Actuarial survival was 78% and 74% at 3 and 4 years. However, relapse free survival was 26% at 3 and 4 years. A prospective randomized trial to compare 10 vs. 15 rad per fraction of fractionated WBI schedules (the same total dose 150 rad) demonstrated no difference in response rate, response duration, and median nadir platelet or WBC counts between the two schedules. Supplement radiotherapy to bulky tumor site prevented local recurrence, but did not influence survival or duration or remission. Major toxicity was thrombocytopenia with median nadir platelet counts 77,000/mm3 (11,000 to 170,000/mm3). Five of 6 patients with diffuse lymphocytic poorly differentiated lymphoma attained CR. However, their median survival was 30 months which is much shorter than that of nodular lymphoma. Constitutional symptoms and advanced stage (stage IV) were associated with shorter duration of remission. Response of patients in relapse after WBI to subsequent chemotherapy +- local radiotherapy was CR in 50% and PR in 40%. Fractionated whole body irradiation is an excellent systemic induction agent for advanced lymphocytic and mixed lymphoma

  17. Effect of alcohol on internally deposited Am-241 in the baboon: a pilot study

    International Nuclear Information System (INIS)

    The efficacy of ethyl alcohol in enhancing the excretion of Am-241 from the baboon has been tested. Alcohol enhances Am-241 excretion via the fecal route by a factor of about 2.5. However, there is a corresponding increase in fecal volume, and no significant change in the concentration of the nuclide in the feces. Other cathartics tested caused increased fecal volumes with no change in amount of activity excreted leading to a decreased concentration of the nuclide in the feces. Alcohol is not as effective as DTPA in removing Am-241 from the body. Preliminary results suggest that alcohol has little or no enhancement effect on the decorporation capability of DTPA

  18. Electroejaculated Baboon (Papio anubis) Sperm Requires a Higher Dosage of Pentoxifylline to Enhance Motility

    OpenAIRE

    Cseh, Sandor; Chan, Philip J.; Corselli, Johannah; Bailey, Leonard L.

    2000-01-01

    Purpose: Sperm collected by electroejaculation often showpoor motility. The objective was to determine whether theaddition of the phosphodiesterase inhibitor, pentoxifylline,would stimulate electroejaculated baboon sperm motility.

  19. A Comparison of Molecular and Histopathological Changes in Mouse Intestinal Tissue Following Whole-Body Proton- or Gamma-Irradiation

    Science.gov (United States)

    Purgason, Ashley; Mangala, Lingegowda; Zhang, Ye; Hamilton, Stanley; Wu, Honglu

    2010-01-01

    There are many consequences following exposure to the space radiation environment which can adversely affect the health of a crew member. Acute radiation syndrome (ARS) involving nausea and vomiting, damage to radio-sensitive tissue such as the blood forming organs and gastrointestinal tract, and cancer are some of these negative effects. The space radiation environment is ample with protons and contains gamma rays as well. Little knowledge exists to this point, however, regarding the effects of protons on mammalian systems; conversely several studies have been performed observing the effects of gamma rays on different animal models. For the research presented here, we wish to compare our previous work looking at whole-body exposure to protons using a mouse model to our studies of mice experiencing whole-body exposure to gamma rays as part of the radio-adaptive response. Radio-adaptation is a well-documented phenomenon in which cells exposed to a priming low dose of radiation prior to a higher dose display a reduction in endpoints like chromosomal aberrations, cell death, micronucleus formation, and more when compared to their counterparts receiving high dose-irradiation only. Our group has recently completed a radio-adaptive experiment with C57BL/6 mice. For both this study and the preceding proton research, the gastrointestinal tract of each animal was dissected four hours post-irradiation and the isolated small intestinal tissue was fixed in formalin for histopathological examination or snap-frozen in liquid nitrogen for RNA isolation. Histopathologic observation of the tissue using standard H&E staining methods to screen for morphologic changes showed an increase in apoptotic lesions for even the lowest doses of 0.1 Gy of protons and 0.05 Gy of gamma rays, and the percentage of apoptotic cells increased with increasing dose. A smaller percentage of crypts showed 3 or more apoptotic lesions in animals that received 6 Gy of gamma-irradiation compared to mice

  20. Pretransplant pulmonary function tests predict risk of mortality following fractionated total body irradiation and allogeneic peripheral blood stem cell transplant

    International Nuclear Information System (INIS)

    Purpose: To determine the value of pulmonary function tests (PFTs) done before peripheral blood stem cell transplant (PBSCT) in predicting mortality after total body irradiation (TBI) performed with or without dose reduction to the lung. Methods and Materials: From 1997 to 2004, 146 consecutive patients with hematologic malignancies received fractionated TBI before PBSCT. With regimen A (n = 85), patients were treated without lung dose reduction to 13.6 gray (Gy). In regimen B (n = 35), total body dose was decreased to 12 Gy (1.5 Gy twice per day for 4 days) and lung dose was limited to 9 Gy by use of lung shielding. In regimen C (n = 26), lung dose was reduced to 6 Gy. All patients received PFTs before treatment, 90 days after treatment, and annually. Results: Median follow-up was 44 months (range, 12-90 months). Sixty-one patients had combined ventilation/diffusion capacity deficits defined as both a forced expiratory volume in the first second (FEV1) and a diffusion capacity of carbon dioxide (DLCO) <100% predicted. In this group, there was a 20% improvement in one-year overall survival with lung dose reduction (70 vs. 50%, log-rank test p = 0.042). Conclusion: Among those with combined ventilation/diffusion capacity deficits, lung dose reduction during TBI significantly improved survival

  1. Autoradiographic studies on the cell kinetics after the whole body X-irradiation. 2. Regularities of the post-irradiation death of differentiating and proliferating cells of the rat brain subependimal zone

    International Nuclear Information System (INIS)

    A wave-like character of death of proliferating and differentiating (D) cells is shown autoradiographically using 3H-thymidine introduced 60-80 min before the whole body X-ray irradiation in doses of 50, 150 or 300 R on subependymal cells of rat brain. Lethally damaged cells irradiated in G2 and S-phases, resulted in 4 peaks of death in mitosis by following the first postradiational mitotic cycle (MC). Lethally damaged cells irradiated in G1-phase lost ability for DNA synthesis as cells irradiated in a dose of 300 R did not include additionally introduced (3 hrs before death) 14C-thymidine from 12 to 17 hrs after 3H-thymidine injection. However, in the first 4 hrs after irradiation there were no cells irradiated in G1-phase among dead ones, as indirec showed the calculations of data obtained tly/ while studying Pliss lymphosarcoma. A supposition is made that the death of cells irradiated in G1-phase is attributed to mitotic phase of the first MC after irradiation. Waves of death of lethally damaged D-cells repeated the peaks of death and corresponded to the mitotic peaks of proliferating cells, which permitted to presuppose the presence of ''short cycle'' (SC) in D-cells, which have the rhythm similar to MC and their death has been attributed to the final SC phase, which corresponds to MC mitotic phase in time. According to the peaks of cell death position of one hour block independent of dose in six MC(SC) points is determined. The cells have experienced the block in the point of MC(SC) in subphase of which they were caught by irradiation. Dose effect is manifested in the number of dead cells

  2. Indirect Tumor Cell Death After High-Dose Hypofractionated Irradiation: Implications for Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery

    Energy Technology Data Exchange (ETDEWEB)

    Song, Chang W., E-mail: songx001@umn.edu [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yoon-Jin [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Griffin, Robert J. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Park, Inhwan [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Koonce, Nathan A. [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas (United States); Hui, Susanta [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Kim, Mi-Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Dusenbery, Kathryn E. [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Sperduto, Paul W. [Minneapolis Radiation Oncology and Gamma Knife Center, University of Minnesota, Minneapolis, Minnesota (United States); Cho, L. Chinsoo [Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, Minnesota (United States)

    2015-09-01

    Purpose: The purpose of this study was to reveal the biological mechanisms underlying stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS). Methods and Materials: FSaII fibrosarcomas grown subcutaneously in the hind limbs of C3H mice were irradiated with 10 to 30 Gy of X rays in a single fraction, and the clonogenic cell survival was determined with in vivo–in vitro excision assay immediately or 2 to 5 days after irradiation. The effects of radiation on the intratumor microenvironment were studied using immunohistochemical methods. Results: After cells were irradiated with 15 or 20 Gy, cell survival in FSaII tumors declined for 2 to 3 days and began to recover thereafter in some but not all tumors. After irradiation with 30 Gy, cell survival declined continuously for 5 days. Cell survival in some tumors 5 days after 20 to 30 Gy irradiation was 2 to 3 logs less than that immediately after irradiation. Irradiation with 20 Gy markedly reduced blood perfusion, upregulated HIF-1α, and increased carbonic anhydrase-9 expression, indicating that irradiation increased tumor hypoxia. In addition, expression of VEGF also increased in the tumor tissue after 20 Gy irradiation, probably due to the increase in HIF-1α activity. Conclusions: Irradiation of FSaII tumors with 15 to 30 Gy in a single dose caused dose-dependent secondary cell death, most likely by causing vascular damage accompanied by deterioration of intratumor microenvironment. Such indirect tumor cell death may play a crucial role in the control of human tumors with SBRT and SRS.

  3. Indirect Tumor Cell Death After High-Dose Hypofractionated Irradiation: Implications for Stereotactic Body Radiation Therapy and Stereotactic Radiation Surgery

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to reveal the biological mechanisms underlying stereotactic body radiation therapy (SBRT) and stereotactic radiation surgery (SRS). Methods and Materials: FSaII fibrosarcomas grown subcutaneously in the hind limbs of C3H mice were irradiated with 10 to 30 Gy of X rays in a single fraction, and the clonogenic cell survival was determined with in vivo–in vitro excision assay immediately or 2 to 5 days after irradiation. The effects of radiation on the intratumor microenvironment were studied using immunohistochemical methods. Results: After cells were irradiated with 15 or 20 Gy, cell survival in FSaII tumors declined for 2 to 3 days and began to recover thereafter in some but not all tumors. After irradiation with 30 Gy, cell survival declined continuously for 5 days. Cell survival in some tumors 5 days after 20 to 30 Gy irradiation was 2 to 3 logs less than that immediately after irradiation. Irradiation with 20 Gy markedly reduced blood perfusion, upregulated HIF-1α, and increased carbonic anhydrase-9 expression, indicating that irradiation increased tumor hypoxia. In addition, expression of VEGF also increased in the tumor tissue after 20 Gy irradiation, probably due to the increase in HIF-1α activity. Conclusions: Irradiation of FSaII tumors with 15 to 30 Gy in a single dose caused dose-dependent secondary cell death, most likely by causing vascular damage accompanied by deterioration of intratumor microenvironment. Such indirect tumor cell death may play a crucial role in the control of human tumors with SBRT and SRS

  4. Gastrointestinal transfer of neptunium (V) in newborn baboons: preliminary results

    International Nuclear Information System (INIS)

    To measure gastrointestinal neptunium absorption, baboons aged from 17 hours to 26 days were gavaged with an oral dose of 0.002 ug/kg of neptunium-239 nitrate. Absorption ranged from 3.71 to 0.113 per cent of the gavaged dose which was, 88 to 3 times higher than the values for adults. This range was reduced to 41 to 3 when doubtful results were discarded because of possible lung contamination. Absorption was expressed in terms of retention per animal at killing since collection of urine and faeces from neonates was not possible. For the same animals the skeleton/liver ratio of the neptunium burden rose continuously in the 26 dav-old baboon and reached twice the mean adult value

  5. Focused grooming networks and stress alleviation in wild female baboons.

    Science.gov (United States)

    Wittig, Roman M; Crockford, Catherine; Lehmann, Julia; Whitten, Patricia L; Seyfarth, Robert M; Cheney, Dorothy L

    2008-06-01

    We examine the relationship between glucocorticoid (GC) levels and grooming behavior in wild female baboons during a period of instability in the alpha male rank position. All females' GC levels rose significantly at the onset of the unstable period, though levels in females who were at lower risk of infanticide began to decrease sooner in the following weeks. Three factors suggest that females relied on a focused grooming network as a coping mechanism to alleviate stress. First, all females' grooming networks became less diverse in the weeks following the initial upheaval. Second, females whose grooming had already focused on a few predictable partners showed a less dramatic rise in GC levels than females whose grooming network had been more diverse. Third, females who contracted their grooming network the most experienced a greater decrease in GC levels in the following week. We conclude that close bonds with a few preferred partners allow female baboons to alleviate the stress associated with social instability.

  6. Total body irradiation for installment of arylsulfatase B activity in a cat by bone marrow transplantation

    International Nuclear Information System (INIS)

    Mucopolysaccharidosis VI is an inherited, metabolic defect in which a deficiency of arylsulfatase B, results in accumulation of glycosaminoglycans (GAG) in lysosomes. Arylsulfatase B activity was installed in an affected 2 year old siamese cat with no arylsulfatase B activity, excess urinary GAG, Alder-Reilly bodies in neutrophils, facial dysmorphia, corneal clouding, multiple epiphyseal dysplasia, and hind limb paresis. Following grafting of bone marrow from an immunologically nonreactive, female sibling with normal arylsulfatase B activity, increased arylsulfatase B activity and urinary excretion of hexuronic acid decreased by 19 days post transplantation. There were no metachromatic inclusions in circulating neutrophils, which were phenotypically female. The cat now has competent trilineage hematopoiesis, resolution of the facial dysmorphia, no corneal clouding, and improved movement of the head, neck, and mandible. The technique, sequence of hematologic recovery, and evidence of engraftment, are discussed. This may be a model for correction of mucopolysaccharidosis VI in man

  7. Relative effect of radiation dose rate on hemopoietic and nonhemopoietic lethality of total-body irradiation

    International Nuclear Information System (INIS)

    Experiments were undertaken to determine the influence of dose rate on the toxicity of total-body irrdiation (TBI) with and without syngeneic bone-marrow rescue in mice. The results showed a much greater dose-rate dependence for death from nonhemopoietic toxicity than from bone-marrow ablation, with the ratio of LD50's increasing from 1.73 at 25 cGy/min to 2.80 at 1 cGy/min. At the higher dose rates, dose-limiting nonhemopoietic toxicity resulted from late organ injury, affecting the lungs, kidneys, and liver. At 1 cGy/min the major dose-limiting nonhemopoietic toxicity was acute gastrointestinal injury. The implications of these results in the context of TBI in preparation for bone-marrow transplantation are discussed. 15 refs., 4 figs

  8. Feeding, ranging and social organisation of the Guinea baboon

    OpenAIRE

    Sharman, Martin John

    1982-01-01

    Before this study, the Guinea or Western baboon, Papio papio, was almost unknown in its natural environment. This thesis reports a nineteen-month field study of two troops of P. papio carried out in south-eastern Senegal. The monkeys were followed on foot, and aspects of their feeding, ranging and social behaviour were recorded. The troops were censused whenever possible. Both study groups, and other troops in the area, were found to be unusually large by comparison with other known troop...

  9. Genetic integration of molar cusp size variation in baboons

    OpenAIRE

    Koh, Christina; BATES, ELIZABETH; Broughton, Elizabeth; Do, Nicholas T.; Fletcher, Zachary; Mahaney, Michael C.; Hlusko, Leslea J.

    2010-01-01

    Many studies of primate diversity and evolution rely on dental morphology for insight into diet, behavior, and phylogenetic relationships. Consequently, variation in molar cusp size has increasingly become a phenotype of interest. In 2007 we published a quantitative genetic analysis of mandibular molar cusp size variation in baboons. Those results provided more questions than answers, as the pattern of genetic integration did not fit predictions from odontogenesis. To follow up, we expanded o...

  10. Growth factor treatment prior to low-dose total body irradiation increases donor cell engraftment after bone marrow transplantation in mice

    NARCIS (Netherlands)

    Noach, EJK; Ausema, A; Dillingh, JH; Dontje, B; Weersing, E; Akkerman, [No Value; Vellenga, E; Haan, GC

    2002-01-01

    Low-toxicity conditioning regimens prior to bone marrow transplantation (BMT) are widely explored. We developed a new protocol using hematopoietic growth factors prior to low-dose total body irradiation (TBI) in recipients of autologous transplants to establish high levels of long-term donor cell en

  11. THE EFFECT OF DONOR LYMPHOCYTES-T AND TOTAL-BODY IRRADIATION ON HEMATOPOIETIC ENGRAFTMENT AND PULMONARY TOXICITY FOLLOWING EXPERIMENTAL ALLOGENEIC BONE-MARROW TRANSPLANTATION

    NARCIS (Netherlands)

    DOWN, JD; MAUCH, P; WARHOL, M; NEBEN, S; FERRARA, JLM

    1992-01-01

    To study the effects of donor T lymphocytes on engraftment and graft-versus-host disease in relation to recipient total-body irradiation, we have returned small numbers of T cells to T-cell-depleted bone marrow transplanted across a minor histocompatibility barrier in mice (B10.BR --> CBA). T-cell-d

  12. Results of hematopoietic stem cell transplantation after treatment with different high-dose total-body irradiation regimens in five Dutch centers

    NARCIS (Netherlands)

    van Kempen-Harteveld, M. Loes; Brand, Ronald; Kal, Henk B.; Verdonck, Leo F.; Hofman, Pieter; Schattenberg, Anton V.; van der Maazen, Richard W.; Cornelissen, Jan J.; Eijkenboom, Wil M. H.; van der Lelie, Johannes P.; Oldenburger, Foppe; Barge, Renee M.; van Biezen, Anja; Vossen, Jaak M. J. J.; Noordijk, Evert M.; Struikmans, Henk

    2008-01-01

    Purpose: To evaluate results of high-dose total-body irradiation (TBI) regimens for hematopoietic stem cell transplantation. Methods and Materials: A total of 1,032 patients underwent TBI in one or two fractions before autologous or allogeneic hematologic stem cell transplantation for acute leukemia

  13. Antelope Predation by Nigerian Forest Baboons: Ecological and Behavioural Correlates.

    Science.gov (United States)

    Sommer, Volker; Lowe, Adriana; Jesus, Gonçalo; Alberts, Nienke; Bouquet, Yaëlle; Inglis, David M; Petersdorf, Megan; van Riel, Eelco; Thompson, James; Ross, Caroline

    2016-01-01

    Baboons are well studied in savannah but less so in more closed habitats. We investigated predation on mammals by olive baboons (Papio anubis) at a geographical and climatic outlier, Gashaka Gumti National Park (Nigeria), the wettest and most forested site so far studied. Despite abundant wildlife, meat eating was rare and selective. Over 16 years, baboons killed 7 bushbuck (Tragelaphus scriptus) and 3 red-flanked duiker (Cephalophus rufilatus), mostly still-lying 'parked' infants. Taking observation time into account, this is 1 predation per group every 3.3 months - far lower than at other sites. Some features of meat eating resemble those elsewhere; predation is opportunistic, adult males monopolize most prey, a targeted killing bite is lacking and begging or active sharing is absent. Carcass owners employ evasive tactics, as meat is often competed over, but satiated owners may tolerate others taking meat. Other features are unusual; this is only the second study site with predation records for bushbuck and the only one for red-flanked duiker. The atypical prey and rarity of eating mammals probably reflects the difficulty of acquiring prey animals when vegetation cover is dense. Our data support the general prediction of the socioecological model that environments shape behavioural patterns, while acknowledging their intraspecific or intrageneric plasticity. PMID:27287424

  14. Effect of radiation dose rate and cyclophosphamide on pulmonary toxicity after total body irradiation in a mouse model

    International Nuclear Information System (INIS)

    Purpose: Interstitial pneumonitis (IP) is still a major complication after total body irradiation (TBI) and bone marrow transplantation (BMT). It is difficult to determine the exact role of radiation in this multifactorial complication, especially because most of the experimental work on lung damage was done using localized lung irradiation and not TBI. We have thus tested the effect of radiation dose rate and combining cyclophosphamide (CTX) with single fraction TBI on lung damage in a mouse model for BMT. Methods and Materials: TBI was given as a single fraction at a high dose rate (HDR, 0.71 Gy/min) or a low dose rate (LDR, 0.08 Gy/min). CTX (250 mg/kg) was given 24 h before TBI. Bone marrow transplantation (BMT) was performed 4-6 h after the last treatment. Lung damage was assessed using ventilation rate (VR) and lethality between 28 and 180 days (LD(50(28))-180). Results: The LD50 for lung damage, ± standard error (SE), increased from 12.0 (± 0.2) Gy using single fraction HDR to 15.8 (± 0.6) Gy using LDR. Adding CTX shifted the dose-response curves towards lower doses. The LD50 values for the combined treatment were 5.3 (± 0.2) and 3.5 (± 0.2) Gy for HDR and LDR, respectively. This indicates that the combined effect of CTX and LDR was more toxic than that of combined CTX and HDR. Lung damage evaluated by VR demonstrated two waves of VR increase. The first wave of VR increase occurred after 6 weeks using TBI only and after 3 weeks in the combined CTX-TBI treatment, irrespective of total dose or dose rate. The second wave of VR elevation resembled the IP that follows localized thoracic irradiation in its time of occurrence. Conclusions: Lung damage following TBI could be spared using LDR. However, CTX markedly enhances TBI-induced lung damage. The combination of CTX and LDR is more toxic to the lungs than combining CTX and HDR

  15. Development of a portable blood irradiator for potential clinical uses

    Energy Technology Data Exchange (ETDEWEB)

    Hungate, F.P.

    1988-12-01

    This document provides an account of the development of a fully portable blood irradiator and the evaluation of its safety and efficacy when implanted in goats, sheep, a baboon and dogs. The program was initiated because the control of lymphocyte populations by irradiation is a potential method for improving success in organ or tissue transplantation and for treating a variety of blood diseases. 15 refs., 27 figs., 2 tabs.

  16. High-energy total body irradiation as preparation for bone marrow transplantation in leukemia patients: treatment technique and related complications

    International Nuclear Information System (INIS)

    Purpose: Bone marrow transplantation with conditioning regimens that include total-body irradiation (TBI) is widely used in patients with acute lymphoblastic and acute myelocytic leukemias. The major causes of death in this population are relapse of leukemia, infection, and treatment related complications. Our purpose was to achieve a homogenous radiation dose distribution and to minimize the dose to the lungs, liver, and kidneys so that the incidence of organ injury was reduced. Methods and Materials: Dose to the bone marrow, midplane, and periphery was quantified by use of thermoluminescent detectors in a bone-equivalent tissue phantom. In an effort to reduce the risk of complications, we treated relapsed or refractory leukemia patients with TBI administered in fractionated, parallel opposed large fields with 24 MV photons, using tissue compensation and partial-transmission lung shielding. Tissue toxicities were then determined. Results: Dose quantitation in bone-equivalent and tissue-equivalent phantoms demonstrated that backscatter and pair production interactions adjacent to bone increased the bone marrow dose by 6 to 11%. At an SSD of 400 cm and at patient diameters of 20 to 40 cm, the percent inhomogeneity across the phantom with 24 MV photons was 0 to 0.3%, compared to 4 to 6% for 6 MV photons. End-organ toxicities consisted of clinical interstitial pneumonitis in six patients, idiopathic interstitial pneumonitis in three patients, renal toxicity in seven patients, and veno-occlusive disease of the liver in one patient. Toxicities did not correlate with fractionation schedule. Conclusions: Total-body irradiation administered with 24 MV photons increases the dose deposition in bone marrow through pair production and backscatter interactions occurring in bone. Because percent depth dose increases with SSD, the 24 MV beam is more penetrating at a 400 cm distance than at 100 cm and dose homogeneity is improved with higher energies. Thus, the incidence of

  17. Differential effects of whole-body {gamma}-irradiation on antinociception induced by morphine and {beta}-endorphin administered intracerebroventricularly in the mouse

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.K. [Korea Atomic Energy Research Inst., Taejon (Korea, Republic of); Chung, K.M.; Park, T.W.

    2000-05-01

    Two separate lines of evidence suggested the present study. First, intracerebroventricularly (i.c.v.) administered morphine (a {mu}-opioid receptor agonist) and {beta}-endorphin (an {epsilon}-opioid receptor agonist) produce antinociception by activating different descending pain inhibitory systems. Second, {gamma}-irradiation attenuates the acute antinociceptive action of i.c.v. injected morphine, but not DPLPE (a {delta}-opioid receptor agonist), in mice. These findings prompted us to investigate the effect of {gamma}-irradiation on the antinociception produced by i.c.v. injected morphine and {beta}-endorphin in male ICR mice. In one group, mice were exposed to whole-body irradiation at a dose of 5 Gy from a {sup 60}Co {gamma}-source and the antinociceptive effects were tested 5, 30, 60,90 and 180 min after irradiation using the 1% acetic acid-induced writhing test (10 ml/kg). The antinociceptive effect was produced time-dependently and reached its maximum at 90 min after irradiation. Thus, time was fixed in the following studies. In another group, mice were irradiated with 5 Gy and tested 90 minutes later for antinociception produced by i.c.v. administration of morphine (50 and 100 ng/mouse) or {beta}-endorphin (31 ng/mouse). Irradiation significantly potentiated the antinociception produced by {beta}-endorphin. However, the antinociception produced by morphine was not affected by irradiation. These results demonstrate a differential sensitivity of {mu}- and {epsilon}-opioid receptors to {gamma}-irradiation, in addition, support the hypothesis that morphine and {beta}-endorphin administered supraspinally produce antinociception by different neuronal mechanisms. (author)

  18. High Dose-Per-Fraction Irradiation of Limited Lung Volumes Using an Image-Guided, Highly Focused Irradiator: Simulating Stereotactic Body Radiotherapy Regimens in a Small-Animal Model

    International Nuclear Information System (INIS)

    Purpose: To investigate the underlying biology associated with stereotactic body radiotherapy (SBRT), both in vivo models and image-guided, highly focal irradiation systems are necessary. Here, we describe such an irradiation system and use it to examine normal tissue toxicity in a small-animal model at lung volumes similar to those associated with human therapy. Methods and Materials: High-dose radiation was delivered to a small volume of the left lung of C3H/HeJCr mice using a small-animal stereotactic irradiator. The irradiator has a collimation mechanism to produce focal radiation beams, an imaging subsystem consisting of a fluorescent screen coupled to a charge-coupled device camera, and a manual positioning stage. Histopathologic examination and micro-CT were used to evaluate the radiation response. Results: Focal obliteration of the alveoli by fibrous connective tissue, hyperplasia of the bronchiolar epithelium, and presence of a small number of inflammatory cells are the main reactions to low-volume/high-dose irradiation of the mouse lung. The tissue response suggested a radiation dose threshold for early phase fibrosis lying between 40 and 100 Gy. The irradiation system satisfied our requirements of high-dose-rate, small beam diameter, and precise localization and verification. Conclusions: We have established an experimental model and image-guided animal irradiation system for the study of high dose per fraction irradiations such as those used with SBRT at volumes analogous to those used in human beings. It will also allow the targeting of specific anatomical structures of the thorax or ultimately, orthotopic tumors of the lung.

  19. Human ghrelin mitigates intestinal injury and mortality after whole body irradiation in rats.

    Directory of Open Access Journals (Sweden)

    Zhimin Wang

    Full Text Available Widespread use of ionizing radiation has led to the realization of the danger associated with radiation exposure. Although studies in radiation countermeasures were initiated a half century ago, an effective therapy for a radiomitigator has not been identified. Ghrelin is a gastrointestinal hormone, and administration of ghrelin is protective in animal models of injuries including radiation combined injury. To test whether ghrelin can be protective in whole body irradiaton (WBI alone, male Sprague Dawley (SD rats were treated with human ghrelin (20 nmol/rat daily for 6 days starting at either 24 h or 48 h after 10 Gray (Gy WBI and survival outcome was examined. The 10 Gy WBI produced a LD70/30 model in SD rats (30% survival in 30 days. The survival rate in rats treated with ghrelin starting at 24 h was significantly improved to 63% and when treatment was initiated at 48 h, the survival remained at 61%. At 7 days post WBI, plasma ghrelin was significantly reduced from the control value. Ghrelin treatment starting at 24 h after WBI daily for 6 days improved histological appearance of the intestine, reduced gut permeability, serum endotoxin levels and bacterial translocation to the liver by 38%, 42% and 61%, respectively at day 7 post WBI. Serum glucose and albumin were restored to near control levels with treatment. Ghrelin treatment also attenuated WBI-induced intestinal apoptosis by 62% as evidenced by TUNEL staining. The expression of anti-apoptotic cell regulator Bcl-xl was decreased by 38% in the vehicle and restored to 75% of the control with ghrelin treatment. Increased expression of intestinal CD73 and pAkt were observed with ghrelin treatment, indicating protection of the intestinal epithelium after WBI. These results indicate that human ghrelin attenuates intestinal injury and mortality after WBI. Thus, human ghrelin can be developed as a novel mitigator for radiation injury.

  20. Skin Injuries Reduce Survival and Modulate Corticosterone, C-Reactive Protein, Complement Component 3, IgM, and Prostaglandin E 2 after Whole-Body Reactor-Produced Mixed Field (n + γ-Photons) Irradiation

    OpenAIRE

    Kiang, Juliann G; Ledney, G. David

    2013-01-01

    Skin injuries such as wounds or burns following whole-body γ-irradiation (radiation combined injury (RCI)) increase mortality more than whole-body γ-irradiation alone. Wound-induced decreases in survival after irradiation are triggered by sustained activation of inducible nitric oxide synthase pathways, persistent alteration of cytokine homeostasis, and increased susceptibility to systemic bacterial infection. Among these factors, radiation-induced increases in interleukin-6 (IL-6) concentrat...

  1. Skin Inqjuries Reduce Survival and Modulate Corticosterone, C-Reactive Protein, Complement Component 3, IgM, and Prostaglandin E2 after Whole-Body Reactor-Produced Mixed Field (n + γ-Photons) Irradiation

    OpenAIRE

    Kiang, Juliann G; G. David Ledney

    2013-01-01

    Skin injuries such as wounds or burns following whole-body γ-irradiation (radiation combined injury (RCI)) increase mortality more than whole-body γ-irradiation alone. Wound-induced decreases in survival after irradiation are triggered by sustained activation of inducible nitric oxide synthase pathways, persistent alteration of cytokine homeostasis, and increased susceptibility to systemic bacterial infection. Among these factors, radiation-induced increases in interleukin-6 (IL-6) concentrat...

  2. Metabolism of endogenous surfactant in premature baboons and effect of prenatal corticosteroids

    NARCIS (Netherlands)

    J.E.H. Bunt (Jan Erik); V.P. Carnielli (Virgilio); S.R. Seidner; M. Ikegami; J.L.D. Wattimena (Josias); P.J.J. Sauer (Pieter); A.H. Jobe (Alan); L.J.I. Zimmermann (Luc)

    1999-01-01

    textabstractWe studied the synthesis of surfactant and the effect of prenatal betamethasone treatment in vivo in very preterm baboons. Ten pregnant baboons were randomized to receive either betamethasone (beta) or saline (control) 48 and 24 h before preterm delivery. Th

  3. Total body irradiation (TBI) in pediatric patients. A single-center experience after 30 years of low-dose rate irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Linsenmeier, Claudia; Thoennessen, Daniel; Negretti, Laura; Streller, Tino; Luetolf, Urs Martin [University Hospital Zurich (Switzerland). Dept. of Radiation-Oncology; Bourquin, Jean-Pierre [University Children' s Hospital Zurich (Switzerland). Dept. of Hemato-Oncology; Oertel, Susanne [University Hospital Zurich (Switzerland). Dept. of Radiation-Oncology; Heidelberg Univ. (Germany). Dept. of Radiation Oncology

    2010-11-15

    To retrospectively analyze patient characteristics, treatment, and treatment outcome of pediatric patients with hematologic diseases treated with total body irradiation (TBI) between 1978 and 2006. 32 pediatric patients were referred to the Department of Radiation-Oncology at the University of Zurich for TBI. Records of regular follow-up of 28 patients were available for review. Patient characteristics as well as treatment outcome regarding local control and overall survival were assessed. A total of 18 patients suffered from acute lymphoblastic leukemia (ALL), 5 from acute and 2 from chronic myelogenous leukemia, 1 from non-Hodgkin lymphoma, and 2 from anaplastic anemia. The cohort consisted of 15 patients referred after first remission and 13 patients with relapsed leukemia. Mean follow-up was 34 months (2-196 months) with 15 patients alive at the time of last follow-up. Eight patients died of recurrent disease, 1 of graft vs. host reaction, 2 of sepsis, and 2 patients died of a secondary malignancy. The 5-year overall survival rate (OS) was 60%. Overall survival was significantly inferior in patients treated after relapse compared to those treated for newly diagnosed leukemia (24% versus 74%; p=0.004). At the time of last follow-up, 11 patients survived for more than 36 months following TBI. Late effects (RTOG {>=}3) were pneumonitis in 1 patient, chronic bronchitis in 1 patient, cardiomyopathy in 2 patients, severe cataractogenesis in 1 patient (48 months after TBI with 10 Gy in a single dose) and secondary malignancies in 2 patients (36 and 190 months after TBI). Growth disturbances were observed in all patients treated prepubertally. In 2 patients with identical twins treated at ages 2 and 7, a loss of 8% in final height of the treated twin was observed. As severe late sequelae after TBI, we observed 2 secondary malignancies in 11 patients who survived in excess of 36 months. However, long-term morbidity is moderate following treatment with the fractionated

  4. Total body irradiation (TBI) in pediatric patients. A single-center experience after 30 years of low-dose rate irradiation

    International Nuclear Information System (INIS)

    To retrospectively analyze patient characteristics, treatment, and treatment outcome of pediatric patients with hematologic diseases treated with total body irradiation (TBI) between 1978 and 2006. 32 pediatric patients were referred to the Department of Radiation-Oncology at the University of Zurich for TBI. Records of regular follow-up of 28 patients were available for review. Patient characteristics as well as treatment outcome regarding local control and overall survival were assessed. A total of 18 patients suffered from acute lymphoblastic leukemia (ALL), 5 from acute and 2 from chronic myelogenous leukemia, 1 from non-Hodgkin lymphoma, and 2 from anaplastic anemia. The cohort consisted of 15 patients referred after first remission and 13 patients with relapsed leukemia. Mean follow-up was 34 months (2-196 months) with 15 patients alive at the time of last follow-up. Eight patients died of recurrent disease, 1 of graft vs. host reaction, 2 of sepsis, and 2 patients died of a secondary malignancy. The 5-year overall survival rate (OS) was 60%. Overall survival was significantly inferior in patients treated after relapse compared to those treated for newly diagnosed leukemia (24% versus 74%; p=0.004). At the time of last follow-up, 11 patients survived for more than 36 months following TBI. Late effects (RTOG ≥3) were pneumonitis in 1 patient, chronic bronchitis in 1 patient, cardiomyopathy in 2 patients, severe cataractogenesis in 1 patient (48 months after TBI with 10 Gy in a single dose) and secondary malignancies in 2 patients (36 and 190 months after TBI). Growth disturbances were observed in all patients treated prepubertally. In 2 patients with identical twins treated at ages 2 and 7, a loss of 8% in final height of the treated twin was observed. As severe late sequelae after TBI, we observed 2 secondary malignancies in 11 patients who survived in excess of 36 months. However, long-term morbidity is moderate following treatment with the fractionated

  5. Technique in linear accelerator total body irradiation%直线加速器全身照射技术

    Institute of Scientific and Technical Information of China (English)

    张九堂; 伍志红; 鲁旭蔚; 何金莲

    2001-01-01

    This article describes the physical, technical, and dosimetric aspects of total body irradiation (TBI) that was carried out by using 6MV X-Ray from Varian 2300 C/D Linear Accelerator at a distance of 450 cm from target to the treatment table and at a gantry angle of 270°.The dose to lung tissue was limit by setting the individual lead compensators customized before, and using DPD-510 to monitor the absorbed dose of the reference point the absorbed dose in depth of half of body will be (Din+Dout)/2 after taking treatment in both AP position and PA position.%本文介绍了在直线加速器上实行全身照射的方法,包括治疗床的设计、测量装置的制作、实验参数的测定和照射方法。SSD=450 cm,机架角为270度,患者取侧卧位,前后野和后前野对穿照射,采用分段肺屏蔽办法控制肺的吸收剂量。用多通道半导体剂量仪进行剂量全程监测作为质量控制手段进行质量控制和实现质量保证,用入射表面剂量Din与出射表面剂量Dout之和的一半即(Din+Dout)/2作为对应入射方向上体中层面的吸收剂量。

  6. Upper limit of cerebral blood flow autoregulation in experimental renovascular hypertension in the baboon

    DEFF Research Database (Denmark)

    Strandgaard, S; Jones, J V; MacKenzie, E T;

    1975-01-01

    The effect of arterial hypertension on cerebral blood flow was studied by the intracarotid 133Xe clearance method in baboons. The arterial blood pressure was raised in gradual steps with angiotensin. Baboons with renal hypertension of 8-12 weeks duration were studied along with normotensive baboons....... In initially normotensive baboons, cerebral blood flow remained constant until the mean arterial blood pressure had risen to the range of 140 to 154 mm Hg; thereafter cerebral blood flow increased with each rise in mean arterial blood pressure. In the chronically hypertensive baboons, cerebral blood flow...... remained constant until the mean arterial blood pressure had been elevated to the range of 155 to 169 mm Hg. Thus, in chronic hypertension it appears that there are adaptive changes in the cerebral circulation which may help to protect the brain from further increases in arterial blood pressure....

  7. Efficacy of fenbendazole and milbemycin oxime for treating baboons (Papio cynocephalus anubis) infected with Trichuris trichiura.

    Science.gov (United States)

    Reichard, Mason V; Wolf, Roman F; Carey, David W; Garrett, Jennifer Jane; Briscoe, Heather A

    2007-03-01

    We evaluated the efficacy of fenbendazole (FBZ) and milbemycin oxime (MO) in the treatment of baboons (Papio cynocephalus anubis) with naturally acquired Trichuris trichiura infection by comparing fecal egg count reduction (FECR) tests. We assigned 7 baboons, each singly housed and confirmed infected with T. trichiura, to treatment groups of FBZ (n=3) or MO (n=3), or as a control (n=1). All (100%) baboons that received FBZ stopped shedding T. trichiura eggs within 6 d of treatment, and fecal egg counts remained negative at 65 d after treatment. Although the number of T. trichiura eggs shed per gram of feces from 2 (67%) baboons decreased significantly after the second treatment with MO, this regimen never totally eliminated eggs of T. trichiura. The results of our study indicate that FBZ was more effective for treating baboons with T. trichiura than was MO.

  8. Radiological protection in a patient during a total body irradiation procedure; Proteccion radiologica en un paciente durante un procedimiento de TBI (irradiacion de cuerpo entero)

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez O, J. O.; Hinojosa G, J.; Gomez M, E.; Balam de la Vega, J. A. [The American British Cowdray Medical Center, I. A. P., Sur 128 No. 143, Col. Americas, 01120 Mexico D. F. (Mexico); Deheza V, J. C., E-mail: johernandezo@abchospital.co [IPN, Escuela Superior de Fisica y Matematicas, Av. Luis Enrique Erro s/n, Edificio No. 9, Unidad Profesional Adolfo Lopez Mateos, Col. Lindavista, 07738 Mexico D. F. (Mexico)

    2010-09-15

    A technique used in the Service of Radiotherapy of the Cancer Center of the American British Cowdray Medical Center (ABC) for the bone marrow transplantation, is the total body irradiation. It is known that the dose calculation, for this irradiation type, is old, since the dosimetric calculation is carried out by hand and they exist infinity of techniques for the patients irradiation and different forms of protecting organs of risk, as well as a great uncertainty in the given dose. In the Cancer Center of the ABC Medical Center, was carried out an irradiation procedure to total body with the following methodology: Computerized tomography of the patient total body (two vacuum mattresses in the following positions: dorsal and lateral decubitus), where is combined the two treatment techniques anterior-posterior and bilateral, skin delineate and reference volumes, dose calculation with the planning system Xi O of CMS, dose determination using an ionization chamber and a lung phantom IMRT Thorax Phantom of the mark CIRS and dosimetry in vivo. In this work is presented the used treatment technique, the results, statistics and the actualization of the patient clinical state. (Author)

  9. Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. I. Orthoptic liver allographs

    International Nuclear Information System (INIS)

    Fractionated total lymphoid irradiation (TLI) and allogeneic bone marrow (BM) injection have been reported to produce stable chimerism without graft-versus-host disease (GVHD) in inbred mice and rats and mongrel dogs, and transplantation tolerance for skin and heart grafts in rodents. This concept has been studied in outbred chacma baboons receiving orthotopic liver allografts with the use of five different irradiation protocols. Eight fractions of 200 rad to the whole torso, followed immediately by allogeneic BM injections, and liver grafts from the BM donors 3 to 4 weeks later resulted in markedly prolonged survivals of 63 to 106 days in four baboons (median survival of untreated controls 19 days). Only one of the four animals died directly from the effects of rejection. BM chimerism was demonstrated in two baboons. There were no clinical or histological signs of GVHD in any of the animals. Two fractions of TLI, totaling 800 rad, 23 hr apart and followed immediately by BM injection and liver grafting resulted in profound thrombocytopenia and death form intraperitoneal hemorrhage in four of five baboons. In one animal BM injection and liver transplantation were delayed for 75 days. The baboon is still alive more than 6 months later. Three groups received single doses of 300, 400, and 500 rad to the whole torso, followed by allogeneic BM injections 1 and 2 weeks later, and liver transplants from their BM donors after an additional 3 to 4 weeks. The four baboons receiving 300 rad survived for 42, 86, 123, and >180 days. Two of the four baboons receiving 400 rad died of septic intraabdominal complications with minimal or no evidence of rejection. Fourh of the five baboons receiving 500 rad died from rejection

  10. The Sequence of Cyclophosphamide and Myeloablative Total Body Irradiation in Hematopoietic Cell Transplantation for Patients with Acute Leukemia.

    Science.gov (United States)

    Holter-Chakrabarty, Jennifer L; Pierson, Namali; Zhang, Mei-Jie; Zhu, Xiaochun; Akpek, Görgün; Aljurf, Mahmoud D; Artz, Andrew S; Baron, Frédéric; Bredeson, Christopher N; Dvorak, Christopher C; Epstein, Robert B; Lazarus, Hillard M; Olsson, Richard F; Selby, George B; Williams, Kirsten M; Cooke, Kenneth R; Pasquini, Marcelo C; McCarthy, Philip L

    2015-07-01

    Limited clinical data are available to assess whether the sequencing of cyclophosphamide (Cy) and total body irradiation (TBI) changes outcomes. We evaluated the sequence in 1769 (CyTBI, n = 948; TBICy, n = 821) recipients of related or unrelated hematopoietic cell transplantation who received TBI (1200 to 1500 cGY) for acute leukemia from 2003 to 2010. The 2 cohorts were comparable for median age, performance score, type of leukemia, first complete remission, Philadelphia chromosome-positive acute lymphoblastic leukemia, HLA-matched siblings, stem cell source, antithymocyte globulin use, TBI dose, and type of graft-versus-host disease (GVHD) prophylaxis. The sequence of TBI did not significantly affect transplantation-related mortality (24% versus 23% at 3 years, P = .67; relative risk, 1.01; P = .91), leukemia relapse (27% versus 29% at 3 years, P = .34; relative risk, .89, P = .18), leukemia-free survival (49% versus 48% at 3 years, P = .27; relative risk, .93; P = .29), chronic GVHD (45% versus 47% at 1 year, P = .39; relative risk, .9; P = .11), or overall survival (53% versus 52% at 3 years, P = .62; relative risk, .96; P = .57) for CyTBI and TBICy, respectively. Corresponding cumulative incidences of sinusoidal obstruction syndrome were 4% and 6% at 100 days (P = .08), respectively. This study demonstrates that the sequence of Cy and TBI does not impact transplantation outcomes and complications in patients with acute leukemia undergoing hematopoietic cell transplantation with myeloablative conditioning.

  11. Does total body irradiation conditioning improve outcomes of myeloablative human leukocyte antigen-identical sibling transplantations for chronic lymphocytic leukemia?

    Science.gov (United States)

    Sabloff, Mitchell; Sobecks, Ronald M; Ahn, Kwang Woo; Zhu, Xiaochun; de Lima, Marcos; Brown, Jennifer R; Inamoto, Yoshihiro; Holland, H Kent; Aljurf, Mahmoud D; Laughlin, Mary J; Kamble, Rammurti T; Hsu, Jack W; Wirk, Baldeep M; Seftel, Matthew; Lewis, Ian D; Arora, Mukta; Alyea, Edwin P; Kalaycio, Matt E; Cortes, Jorge; Maziarz, Richard T; Gale, Robert Peter; Saber, Wael

    2014-03-01

    An allogeneic hematopoietic cell transplantation from an HLA-identical donor after high-dose (myeloablative) pretransplantation conditioning is an effective therapy for some people with chronic lymphocytic leukemia (CLL). Because CLL is a highly radiosensitive cancer, we hypothesized that total body irradiation (TBI) conditioning regimens may be associated with better outcomes than those without TBI. To answer this, we analyzed data from 180 subjects with CLL receiving myeloablative doses of TBI (n = 126) or not (n = 54), who received transplants from an HLA-identical sibling donor between 1995 and 2007 and reported to the Center for International Blood & Marrow Transplant Research. At 5 years, treatment-related mortality was 48% (95% confidence interval [CI], 39% to 57%) versus 50% (95% CI, 36% to 64%); P = NS. Relapse rates were 17% (95% CI, 11% to 25%) versus 22% (95% CI, 11% to 35%); P = NS. Five-year progression-free survival and overall survival were 34% (95% CI, 26% to 43%) versus 28% (95% CI, 15% to 42%); P = NS and 42% (95% CI, 33% to 51%) versus 33% (95% CI, 19% to 48%); P = NS, respectively. The single most common cause of death in both cohorts was recurrent/progressive CLL. No variable tested in the multivariate analysis was found to significantly affect these outcomes, including having failed fludarabine. Within the limitations of this study, we found no difference in HLA-identical sibling transplantation outcomes between myeloablative TBI and chemotherapy pretransplantation conditioning in persons with CLL.

  12. Low-dose total body irradiation in non-Hodgkin lymphoma: Short- and long-term toxicity and prognostic factor

    Energy Technology Data Exchange (ETDEWEB)

    De Neve, W.J.; Lybeert, M.L.; Meerwaldt, J.H. (A.Z.-V.U.B., Brussels (Belgium))

    1990-08-01

    The toxicity of low-dose total body irradiation (LTBI), the prognostic factors related to survival and relapse-free survival, and the efficacy of treatment given for relapse after LTBI were analyzed in 68 patients with non-Hodgkin lymphoma (NHL) treated at the Rotterdamsch Radiotherapeutisch Instituut. All patients received LTBI between 1973 and 1979. The patient material was heterogeneous with respect to malignancy grade, stage, age, and therapy given before or after LTBI; the unifying principle was that all patients received LTBI and had symptomatic NHL. Analysis of prognostic variables with Cox's model revealed grade (p less than 0.001) and age (p = 0.004) as predictors for survival and grade (p less than 0.001) and dose of LTBI (p = 0.056) as predictors for relapse-free survival after LTBI. No subjective toxicity was observed during or after LTBI treatment. Hematologic toxicity was dose-limiting and was increased if patients had received cytotoxic treatment before LTBI. LTBI-related hematologic toxicity was lower in patients with low-grade NHL than in those with intermediate or high-grade NHL, was limited in time, and recovered in all patients. Patients relapsing after LTBI received a variety of therapies. Response rates were high, but of short duration, especially in intermediate or high-grade NHL. Duration of response was progressively shorter after multiple relapses.

  13. Total body irradiation and cyclophosphamide, vincristine, prednisone in the treatment of favorable prognosis non-Hodgkin's lymphomas

    International Nuclear Information System (INIS)

    A pilot study was undertaken to test the feasibility of administering total body irradiation (TBI) followed by chemotherapy with cyclophosphamide, vincristine and prednisone (CVP). Twelve patients with previously untreated Stages III to IV non-Hodgkin's lymphoma were studied. Nine patients had nodular poorly differentiated lymphocytic lymphoma and 3 had nodular mixed lymphoma. TBI was given to a total dose of 150 rad in biweekly 15 rad fractions. Reversible thrombocytopenia and neutropenia were observed and resulted in 3 attenuated courses (105 rad, 120 rad, 135 rad). No bleeding, infection or other important toxicity occurred from TBI. After a median of 45 days following TBI, all patients began CVP. Eleven patients completed 6 cycles; 1 patient refused further chemotherapy after the first cycle. Dosage adjustments made for neutropenia and thrombocytopenia were such that 83% of the planned cyclophosphamide dose was given. No bleeding, serious infections or fatalities were seen. Toxicities included parathesias, nausea and abdominal pain. At the end of chemotherapy, 6 of the 11 patients who completed 6 cycles of CVP were disease free with remissions of 3+, 4+, 7+, 11+, 14 and 20+ months. TRI + CVP delivered in the manner described is associated with acceptable toxicity

  14. Hyperfractionated high-dose total body irradiation in bone marrow transplantation for Ph{sup 1}-positive acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Kikuchi, Akira; Ebihara, Yasuhiro; Mitsui, Tetsuo [Tokyo Univ. (Japan). Hospital of the Institute of Medical Science] [and others

    1998-12-01

    In two cases of Philadelphia-positive childhood acute lymphoblastic leukemia (Ph{sup 1} ALL), we performed allogeneic bone marrow transplantation (AlloBMT) with preconditioning regimen, including hyperfractionated high-dose total body irradiation (TBI) (13.5 Gy, in 9 fractions). Their disease statuses at BMT were hematological relapse in case 1 and molecular relapse in case 2. Bone marrow donors were unrelated in case 1, and HLA was a partially mismatched mother in case 2. Regimen-related toxicity was tolerable in both cases. Hematological recovery was rapid, and engraftment was obtained on day 14 in case 1 and on day 12 in case 2. BCR/ABL message in bone marrow disappeared on day 89 in case 1 and on day 19 in case 2 and throughout their subsequent clinical courses. Although short-term MTX and Cy-A continuous infusion were used for GVHD prophylaxis, grade IV GVHD was observed in case 1 and grade III in case 2. Both cases experienced hemorrhagic cystitis because of adenovirus type 11 infection. Although case 1 died of interstitial pneumonitis on day 442, case 2 has been free of disease through day 231. AlloBMT for Ph{sup 1} ALL with preconditioning regimen including hyperfractionated high-dose TBI is considered to be worth further investigation. (author)

  15. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation

    OpenAIRE

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T.; Komorowski, Richard; Fish, Brian L; Migrino, Raymond Q.; Harmann, Leanne; Hopewell, John W.; Kronenberg, Amy; Patel, Shailendra; Moulder, John E.; Baker, John E

    2015-01-01

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days af...

  16. Recombinant human MFG-E8 attenuates intestinal injury and mortality in severe whole body irradiation in rats.

    Directory of Open Access Journals (Sweden)

    Michael A Ajakaiye

    Full Text Available The gastrointestinal (GI syndrome component of acute radiation syndrome (ARS results from depletion of immature parenchymal stem cells after high dose irradiation and contributes significantly to early mortality. It is associated with severe, irreparable damage in the GI tract and extremely low survival. There is a need for the development of viable mitigators of whole body irradiation (WBI due to the possibility of unexpected high level radiation exposure from nuclear accidents or attacks. We therefore examined the effect of recombinant human milk fat globule-EGF factor 8 (rhMFG-E8 in mitigating damage after WBI. Male Sprague-Dawley rats were exposed to 10 Gy WBI using Cesium-137 as the radiation source. The animals in the treatment group received rhMFG-E8 (166 µg/kg BW subcutaneously once a day with the first dose given 6 h after WBI. Blood and tissue samples from the ileum were collected after 3 days of treatment. A separate cohort of animals was treated for 7 days and the 21 day mortality rate was determined. Treatment with rhMFG-E8 significantly improved the survival from 31% to 75% over 21 days. Furthermore, rhMFG-E8 treatment resulted in a 36% reduction in the radiation injury intestinal mucosal damage score, corresponding to visible histological changes. MFG-E8 gene expression was significantly decreased in WBI-induced animals as compared to sham controls. Treatment with rhMFG-E8 increased p53 and p21 expression by 207% and 84% compared to untreated controls. This was accompanied by an 80% increase in the expression of anti-apoptotic cell regulator Bcl-2. p53 and p21 levels correlate with improved survival after radiation injury. These cell regulators arrest the cell after DNA damage and enable DNA repair as well as optimize cell survival. Taken together, these results indicate that rhMFG-E8 ameliorates the GI syndrome and improves survival after WBI by minimizing intestinal cell damage and optimizing recovery.

  17. Recovery of the Erythropoietin-Sensitive Stem-Cell Population following Total-Body X-Irradiation

    International Nuclear Information System (INIS)

    Erythropoietin acts upon haemopoietic stem cells to initiate their differentiation into the erythroid series. This effect may be used in polycythaemic mice to estimate changes in the erythropoietin-sensitive stem-cell population following total-body irradiation (TBR). Generally, single doses of erythropoietin, less than that needed for maximum stem-cell response, are used to estimate changes in the stem-cell population. The validity of results using this test is based upon accepting several assumptions regarding erythropoietin kinetics. These are: (a) the contribution of endogenous erythropoietin is always negligible; (b) the origin of the dose-response curve to erythropoietin alters only because of changes in stem-cell numbers; (c) the proportion of stem cells responding to a given concentration of erythropoietin is independent of stem-cell numbers; (d) the slope of the dose-response curve does not alter; and (e) competition between erythropoietin and other factors for the stem cells remains unchanged. The studies to be reported indicate that some of these assumptions m a y not always be valid. Following 150 rad TBR, changes in erythropoietin dose-response curves were not always due to changes in the size of the stem-cell population, but also due to changes in erythropoietin kinetics. Changes in erythropoietin kinetics could be corrected for by using doses of erythropoietin which at any particular time after TBR gave maximum stem-cell response; through full dose-response studies, the nature of changes in erythropoietin kinetics following TBR could be established. These studies appear to explain discrepancies in results obtained in different laboratories using the erythropoietin test. The effect of 150 rad TBR on the erythropoietin-sensitive stem-cell population is an initial depression within 30 min to 20% of normal followed by a second depression (post-irradiation dip) at about 12 h. Twenty-four hours after TBR there is a recovery to the initial depression. This

  18. Improvement of lateral position total body irradiation with ovarian shielding. Shielding block for the lung of tungsten sheets

    International Nuclear Information System (INIS)

    Bone marrow transplantation requires the prior administration of a large amount of anticancer and total body irradiation (TBI) with 12 Gy, which brings about infertility in females as the dose exceed the threshold of the pregnant function (2.5-6 Gy). This paper reports the preparation of columnar shields for ovaries of low melting point lead (Pb), and of shields of the lung-formed Pb and tungsten (W) sheet for lungs at TBI. Reported cases are from the experience of 11 patients during the period of 2007-2012, Jan. Ordinary old TBI is conducted from right/left and left/right directions at the source-skin distance (SSD) 400 cm with 10 MV X-ray (10 cGy/min) at the supine position with the lung density correction; TBI with ovarian shielding (OS) from anteroposterior and posteroanterior directions, at the lateral position, with the lung shielding (Pb); and TBI-OS, with the lung shielding (W sheet). Ovarian block shield is a Pb column of 5 cm diameter X 8 cm thickness. The Pb lung block with 0.5 cm thickness is made fitted to individual patients' lung form, of which preparation has been time-consuming and has required much labor. The W sheet is a commercially available one with 1 mm thickness, and easily usable with several sheets for shielding after cutting with a scissor so as to be fitted to individual patients' lung form. In contrast to the ordinary supine TBI, lateral TBI with the lung Pb block shielding is found for the lung dose to be reduced from 12 Gy to 10 Gy; and with the W sheet (4 mm thick) shielding, for the transmission coefficient to be virtually similar to that of Pb block (82.6 and 83.4%, respectively). The ovarian shielding is found effective for the organ dose to be reduced to about 2 Gy at 12 Gy irradiation. Preparation of W sheet is easier and more convenient for its fitting to individual patients' lung form than previous Pb block. (T.T.)

  19. The ability of filgrastim to mitigate mortality following LD50/60 total-body irradiation is administration time-dependent.

    Science.gov (United States)

    Farese, Ann M; Brown, Cassandra R; Smith, Cassandra P; Gibbs, Allison M; Katz, Barry P; Johnson, Cynthia S; Prado, Karl L; MacVittie, Thomas J

    2014-01-01

    The identification of the optimal administration schedule for an effective medical countermeasure is critical for the effective treatment of individuals exposed to potentially lethal doses of radiation. The efficacy of filgrastim (Neupogen®), a potential medical countermeasure, to improve survival when initiated at 48 h following total body irradiation in a non-human primate model of the hematopoietic syndrome of the acute radiation syndrome was investigated. Animals were exposed to total body irradiation, antero-posterior exposure, total midline tissue dose of 7.5 Gy, (target lethal dose 50/60) delivered at 0.80 Gy min, using linear accelerator-derived 6 MV photons. All animals were administered medical management. Following irradiation on day 0, filgrastim (10 μg kg d) or the control (5% dextrose in water) was administered subcutaneously daily through effect (absolute neutrophil count ≥ 1,000 cells μL for three consecutive days). The study (n = 80) was powered to demonstrate a 25% improvement in survival following the administration of filgrastim or control beginning at 48 ± 4 h post-irradiation. Survival analysis was conducted on the intention-to-treat population using a two-tailed null hypothesis at a 5% significance level. Filgrastim, initiated 48 h after irradiation, did not improve survival (2.5% increase, p = 0.8230). These data demonstrate that efficacy of a countermeasure to mitigate lethality in the hematopoietic syndrome of the acute radiation syndrome can be dependent on the interval between irradiation and administration of the medical countermeasure.

  20. Patterns of failure following total body irradiation and bone marrow transplantation with or without a radiotherapy boost for advanced neuroblastoma

    International Nuclear Information System (INIS)

    Purpose: To evaluate the patterns of failure and outcome of patients undergoing high-dose chemotherapy, total body irradiation (TBI), and bone marrow transplantation (BMT) for advanced/relapsed pediatric neuroblastoma, with emphasis on the impact of a radiotherapy boost to primary and metastatic sites. Methods and Materials: Between May 1986 and June 1993, 26 patients with advanced neuroblastoma underwent high-dose chemotherapy and TBI followed by BMT at our institution. The majority of patients were over the age of 2 years (73%) and were Stage IV at diagnosis (81%). Multiple metastatic sites were involved including bone (17), bone marrow (15), distant nodes (11), liver (5), lung (4) and brain (1). Twenty patients (77%) received cyclophosphamide (50 mg/kg x 4 days) and TBI as consolidation therapy. TBI was delivered to a total dose of 12 Gy given in 2 Gy twice daily (b.i.d.) fractions over the 3 days preceding bone marrow infusion. A local radiotherapy boost of 8-24 Gy was given to 13 out of 26 patients (50%) to the primary and/or metastatic sites immediately prior to or following induction chemotherapy according to physician judgement. Sites not amenable to a radiotherapy boost included the bone marrow, diffuse/bilateral lung involvement, and multiple bone metastases (> four sites). Results: The actuarial overall survival of the 26 patients was 40.4% at 3 and 5 years, with a progression-free survival at 5 years of 38.5%. Six patients died of transplant-related toxicity (23%). The use of cyclophosphamide as high-dose consolidation chemotherapy was significantly better than other multidrug regimens used in terms of overall survival (p < 0.0001) and progression-free survival (p = 0.0004). The presence of liver involvement prior to BMT was a significant adverse prognostic factor by multivariate analysis. Of the 20 patients surviving the transplant, 10 (50%) underwent a local radiotherapy boost. The patterns of failure were as follows: 3 out of 10 'boost' patients

  1. Calibration of semiconductors diodes for in vivo dosimetry in total body irradiation treatments; Calibracao de diodos semicondutores para dosimetria in vivo em tratamentos de irradiacao de corpo inteiro

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Fernanda F.; Costa, Alessandro M.; Ghilardi Netto, Thomaz, E-mail: ferretti.oliveira@gmail.com [Universidade de Sao Paulo (FFCLRP/USP), Ribeirao Preto, SP (Brazil). Faculdade de Ciencias e Letras. Departamento de Fisica; Amaral, Leonardo L. [Universidade de Sao Paulo (HCFMRP/USP), Ribeirao Preto, SP (Brazil). Hospital das Clinicas. Servico de Radioterapia

    2012-08-15

    This paper presents the results of in vivo dosimetry with p-type semiconductors diodes, EDP-15 (Scanditronix Wellhoefer) of two patients who underwent total body irradiation treatments, at Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto University of Sao Paulo (HCFMRP-USP). The diodes were well calibrated and the calibration factors were determined with the aid of a reference ionization chamber (FC065, IBA dosimetry, sensitive volume of 0.65 cm{sup 3}).The calibration was performed in a Total Body Irradiation (TBI) setup, using solid water phantoms. Different lateral thicknesses from one patient were simulated and then the calibration factors were determined by means of maximum depth dose readings (half of the lateral thickness). The response difference between diode readings and the prescribed dose for both treatments was below 4%. This difference is in agreement as recommended by International Commission on Radiation Units (ICRU), which is {+-}5%. (author)

  2. 5-Azacytidine stimulates fetal hemoglobin synthesis in anemic baboons.

    OpenAIRE

    DESIMONE, J.; Heller, P; Hall, L; Zwiers, D

    1982-01-01

    In an attempt to stimulate Hb F synthesis in baboons by means other than erythropoietic stress, we considered the possibility that an agent that inhibits methylation of CpG sequences in DNA may be effective. 5-Azacytidine, a cytosine analogue that cannot be methylated, is such an agent. Animals whose packed red cell volume was maintained at approximately 20% by bleeding were given 10 daily intravenous injections of the drug (6 mg/kg) in 12 days. Hb F levels in these animals started to increas...

  3. p38 MAPK Inhibitor Insufficiently Attenuates HSC Senescence Administered Long-Term after 6 Gy Total Body Irradiation in Mice

    Directory of Open Access Journals (Sweden)

    Lu Lu

    2016-06-01

    Full Text Available Senescent hematopoietic stem cells (HSCs accumulate with age and exposure to stress, such as total-body irradiation (TBI, which may cause long-term myelosuppression in the clinic. However, the methods available for long-term myelosuppression remain limited. Previous studies have demonstrated that sustained p38 mitogen-activated protein kinases (p38 MAPK activation in HSCs following exposure to TBI in mice and the administration of its inhibitor twenty-four hours after TBI may partially prevent long-term myelosuppression. However, long-term myelosuppression is latent and identified long after the administration of radiation. In this study, we investigated the effects of SB203580 (a small molecule inhibitor of p38 MAPK on long-term myelosuppression induced by TBI. Mice with hematopoietic injury were injected intraperitoneally with SB203580 every other day five times beginning 70 days after 6 Gy of 137Cs γ ray TBI. Our results at 80 days demonstrated that SB203580 did not significantly improve the TBI-induced long-term reduction of peripheral blood cell and bone marrow nucleated cell (BMNC counts, or defects in hematopoietic progenitor cells (HPCs and HSC clonogenic function. SB203580 reduced reactive oxygen species (ROS production and p-p38 expression; however, SB203580 had no effect on p16 expression in the HSCs of mice. In conclusion, these findings suggest that treatment with SB203580 70 days after TBI in mice inhibits the ROS-p38 oxidative stress pathway; however, it has no therapeutic effect on long-term myelosuppression induced by TBI.

  4. Total body irradiation for stage II-IV non-Hodgkin's lymphoma: ten-year follow-up

    Energy Technology Data Exchange (ETDEWEB)

    Mendenhall, N.P.; Noyes, W.D.; Million, R.R.

    1989-01-01

    Between 1972 and 1977, a prospective study was conducted at the University of Florida on the role of total body irradiation (TBI) in the management of stage II-IV non-Hodgkin's lymphoma (NHL). Forty-four consecutive de novo (DN) patients (including ten stage II, 18 stage III, and 16 stage IV), as well as 16 previously treated (PT) patients, were accrued. Twenty of the 44 DN patients were symptomatic at presentation. Complete clinical responses were obtained in 20 of the 27 DN patients with favorable histologies (FH), and six of the 17 with unfavorable histologies (UH). Partial responses were obtained in six patients with FH and 11 patients with UH; only one patient showed no response to TBI. By univariate analysis, PT patients showed a trend for decreased relapse-free survival (P = .066) and decreased survival (P = .093). Multivariate analysis identified the best predictors of response rate to be histology (P = .0146) and marrow involvement (P = .0854); of relapse-free survival, histology (P = .0035), and TBI dose (P = .002); and of absolute survival, age (P = .0012), histology (P = .012), and TBI dose (P = .029). Thirty of the 41 patients who relapsed underwent salvage treatment with either chemotherapy or radiation. Twenty-three of the 30 undergoing salvage therapy obtained a second complete clinical response. There were no treatment-related deaths. The most common complication was thrombocytopenia. The major late complications were myeloproliferative disorders in four patients, which occurred only after cumulative TBI doses in excess of 200 cGy.

  5. SIGN-R1 and complement factors are involved in the systemic clearance of radiation-induced apoptotic cells in whole-body irradiated mice

    International Nuclear Information System (INIS)

    Although SIGN-R1-mediated complement activation pathway has been shown to enhance the systemic clearance of apoptotic cells, the role of SIGN-R1 in the clearance of radiation-induced apoptotic cells has not been characterized and was investigated in this study. Our data indicated that whole-body γ-irradiation of mice increased caspase-3+ apoptotic lymphocyte numbers in secondary lymphoid organs. Following γ-irradiation, SIGN-R1 and complements (C4 and C3) were simultaneously increased only in the mice spleen tissue among the assessed tissues. In particular, C3 was exclusively activated in the spleen. The delayed clearance of apoptotic cells was markedly prevalent in the spleen and liver of SIGN-R1 KO mice, followed by a significant increase of CD11b+ cells. These results indicate that SIGN-R1 and complement factors play an important role in the systemic clearance of radiation-induced apoptotic innate immune cells to maintain tissue homeostasis after γ-irradiation. - Highlights: • Splenic SIGN-R1+ macrophages are activated after γ-irradiation. • C3 and C4 levels increased and C3 was activated in the spleen after γ-irradiation. • SIGN-R1 mediated the systemic clearance of radiation-induced apoptotic cells in spleen and liver

  6. SIGN-R1 and complement factors are involved in the systemic clearance of radiation-induced apoptotic cells in whole-body irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin-Yeon; Loh, SoHee; Cho, Eun-hee [Department of Biomedical Science & Technology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of); Choi, Hyeong-Jwa [Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, 215-4, 75 Nowon gil Nowon-Gu, Seoul, 139-706 (Korea, Republic of); Na, Tae-Young [College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-741 (Korea, Republic of); Nemeno, Judee Grace E.; Lee, Jeong Ik [Regenerative Medicine Laboratory, Department of Veterinary Medicine, College of Veterinary Medicine, Konkuk University, Seoul, 143-701 (Korea, Republic of); Yoon, Taek Joon [Department of Food and Nutrition, Yuhan College, Bucheon, Gyeonggi-do, 422-749 (Korea, Republic of); Choi, In-Soo [Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of); Lee, Minyoung [Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, 215-4, 75 Nowon gil Nowon-Gu, Seoul, 139-706 (Korea, Republic of); Lee, Jae-Seon [Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, 400-712 (Korea, Republic of); Kang, Young-Sun, E-mail: kangys1967@naver.com [Department of Biomedical Science & Technology, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of); Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul, 143-701 (Korea, Republic of)

    2015-08-07

    Although SIGN-R1-mediated complement activation pathway has been shown to enhance the systemic clearance of apoptotic cells, the role of SIGN-R1 in the clearance of radiation-induced apoptotic cells has not been characterized and was investigated in this study. Our data indicated that whole-body γ-irradiation of mice increased caspase-3{sup +} apoptotic lymphocyte numbers in secondary lymphoid organs. Following γ-irradiation, SIGN-R1 and complements (C4 and C3) were simultaneously increased only in the mice spleen tissue among the assessed tissues. In particular, C3 was exclusively activated in the spleen. The delayed clearance of apoptotic cells was markedly prevalent in the spleen and liver of SIGN-R1 KO mice, followed by a significant increase of CD11b{sup +} cells. These results indicate that SIGN-R1 and complement factors play an important role in the systemic clearance of radiation-induced apoptotic innate immune cells to maintain tissue homeostasis after γ-irradiation. - Highlights: • Splenic SIGN-R1{sup +} macrophages are activated after γ-irradiation. • C3 and C4 levels increased and C3 was activated in the spleen after γ-irradiation. • SIGN-R1 mediated the systemic clearance of radiation-induced apoptotic cells in spleen and liver.

  7. Allogeneic compact bone-derived mesenchymal stem cell transplantation increases survival of mice exposed to lethal total body irradiation: a potential immunological mechanism

    Institute of Scientific and Technical Information of China (English)

    Qiao Shukai; Ren Hanyun; Shi Yongjin; Liu Wei

    2014-01-01

    Background Radiation-induced injury after accidental or therapeutic total body exposure to ionizing radiation has serious pathophysiological consequences,and currently no effective therapy exists.This study was designed to investigate whether transplantation of allogeneic murine compact bone derived-mesenchymal stem cells (CB-MSCs) could improve the survival of mice exposed to lethal dosage total body irradiation (TBI),and to explore the potential immunoprotective role of MSCs.Methods BALB/c mice were treated with 8 Gy TBI,and then some were administered CB-MSCs isolated from C57BL/6 mice.Survival rates and body weight were analyzed for 14 days post-irradiation.At three days post-irradiation,we evaluated IFN-Y and IL-4 concentrations; CD4+CD25+Foxp3+ regulatory T cell (Treg) percentage; CXCR3,CCR5,and CCR7 expressions on CD3+T cells; and splenocyte T-bet and GATA-3 mRNA levels.CB-MSC effects on bone marrow hemopoiesis were assessed via colony-forming unit granulocyte/macrophage (CFU-GM) assay.Results After lethal TBI,compared to non-transplanted mice,CB-MSC-transplanted mice exhibited significantly increased survival,body weight,and CFU-GM counts of bone marrow cells (P<0.05),as well as higher Treg percentages,reduced IFN-Y,CXCR3 and CCR5 down-regulation,and CCR7 up-regulation.CB-MSC transplantation suppressed Th1 immunity.Irradiated splenocytes directly suppressed CFU-GM formation from bone marrow cells,and CB-MSC co-culture reversed this inhibition.Conclusion Allogeneic CB-MSC transplantation attenuated radiation-induced hematopoietic toxicity,and provided immunoprotection by alleviating lymphocyte-mediated CFU-GM inhibition,expanding Tregs,regulating T cell chemokine receptor expressions,and skewing the Th1/Th2 balance toward anti-inflammatory Th2 polarization.

  8. Effect of gamma irradiation on sex chromatin body appearance and the sex chromosome aberrations in the potato tuber moth, phthorimaea operculella (Lepidoptera: Gelechiidae)

    International Nuclear Information System (INIS)

    Genetic sexing technique based on the construction of a Balanced Lethal Strain (BLS) has been proposed for Phthorimaea operculella (Zeller). The isolation of female with T(W. Z) translocation is a fundamental step to develop such strain. Gamma irradiation was used to induce the requested translocations. The availability of sex-linked morphological marker is required to facilitate the detection of such mutations. Since a visible sex-linked marker has not been found in P. operculella, therefore main aim of our study was to determine the possibility of using sex heterochromatin body as a marker to identify the required translocated females. The appearance of sex heterochromatin body and the analysis of sex chromosomes in F1 females of irradiated P. operculella females were investigated. The percentage of abnormality in sex heterochromatin body in highly polyploid Malpighian tubule nuclei was increased by increasing the applied dose. Based on the appearance of this body, 3 mutant lines were isolated: elongated, small, fragmented lines. W chromosome was easily distinguished from Z chromosome when the analysis of pachytene sex chromosome bivalents of P. operculella females was carried out. The aberrations involved W chromosome directly influenced the appearance of sex heterochromatin body in highly polyploid somatic cells of the isolated mutant lines. The results showed that sex heterochromatin could be used as sex determination and cytogenetic marker in P. operculella. (Author)

  9. Mechanisms of xenogeneic baboon platelet aggregation and phagocytosis by porcine liver sinusoidal endothelial cells.

    Directory of Open Access Journals (Sweden)

    Qiang Peng

    Full Text Available BACKGROUND: Baboons receiving xenogeneic livers from wild type and transgenic pigs survive less than 10 days. One of the major issues is the early development of profound thrombocytopenia that results in fatal hemorrhage. Histological examination of xenotransplanted livers has shown baboon platelet activation, phagocytosis and sequestration within the sinusoids. In order to study the mechanisms of platelet consumption in liver xenotransplantation, we have developed an in vitro system to examine the interaction between pig endothelial cells with baboon platelets and to thereby identify molecular mechanisms and therapies. METHODS: Fresh pig hepatocytes, liver sinusoidal and aortic endothelial cells were isolated by collagenase digestion of livers and processing of aortae from GTKO and Gal+ MGH-miniature swine. These primary cell cultures were then tested for the differential ability to induce baboon or pig platelet aggregation. Phagocytosis was evaluated by direct observation of CFSE labeled-platelets, which are incubated with endothelial cells under confocal light microscopy. Aurintricarboxylic acid (GpIb antagonist blocking interactions with von Willebrand factor/vWF, eptifibatide (Gp IIb/IIIa antagonist, and anti-Mac-1 Ab (anti-α(Mβ(2 integrin Ab were tested for the ability to inhibit phagocytosis. RESULTS: None of the pig cells induced aggregation or phagocytosis of porcine platelets. However, pig hepatocytes, liver sinusoidal and aortic endothelial cells (GTKO and Gal+ all induced moderate aggregation of baboon platelets. Importantly, pig liver sinusoidal endothelial cells efficiently phagocytosed baboon platelets, while pig aortic endothelial cells and hepatocytes had minimal effects on platelet numbers. Anti-MAC-1 Ab, aurintricarboxylic acid or eptifibatide, significantly decreased baboon platelet phagocytosis by pig liver endothelial cells (P<0.01. CONCLUSIONS: Although pig hepatocytes and aortic endothelial cells directly caused

  10. Role of total body irradiation as based on the comparison of preparation regimens for allogeneic bone marrow transplantation for acute leukemia in first complete remission

    International Nuclear Information System (INIS)

    The role of total body irradiation (TBI) for allogeneic bone marrow transplantation (BMT) for acute leukemia in first complete remission was reevaluated in this study. From Japanese BMT Registry, data of 123 acute leukemia patients in first complete remission who underwent allogeneic bone marrow transplantation in 22 hospitals between 1988 and 1990 were available for the present comparative study of preparation regimens with or without total body irradiation. Two-year survivals were 77% and 51% in the TBI containing regimen group and in the non-TBI regimen group, respectively (p=0.0010). Corresponding two-year relapse rates were 16% and 37%, respectively (p=0.0197). Corresponding probabilities of developing interstitial pneumonitis were 21% and 24%, respectively (p=0.8127). The analysis of causes of death indicated that non-TBI regimen increased the incidence of septicemia and lethal organ failures, such as liver, heart, lung and other multiple sites. It was emphasized that an additional role of total body irradiation was to disperse the treatment-related toxicity in allogeneic bone marrow transplantation for acute leukemia. (orig.)

  11. Biodosimetry Based on γ-H2AX Quantification and Cytogenetics after Partial- and Total-Body Irradiation during Fractionated Radiotherapy.

    Science.gov (United States)

    Zahnreich, Sebastian; Ebersberger, Anne; Kaina, Bernd; Schmidberger, Heinz

    2015-04-01

    The aim of this current study was to quantitatively describe radiation-induced DNA damage and its distribution in leukocytes of cancer patients after fractionated partial- or total-body radiotherapy. Specifically, the impact of exposed anatomic region and administered dose was investigated in breast and prostate cancer patients receiving partial-body radiotherapy. DNA double-strand breaks (DSBs) were quantified by γ-H2AX immunostaining. The frequency of unstable chromosomal aberrations in stimulated lymphocytes was also determined and compared with the frequency of DNA DSBs in the same samples. The frequency of radiation-induced DNA damage was converted into dose, using ex vivo generated calibration curves, and was then compared with the administered physical dose. This study showed that 0.5 h after partial-body radiotherapy the quantity of radiation-induced γ-H2AX foci increased linearly with the administered equivalent whole-body dose for both tumor entities. Foci frequencies dropped 1 day thereafter but proportionality to the equivalent whole-body dose was maintained. Conversely, the frequency of radiation-induced cytogenetic damage increased from 0.5 h to 1 day after the first partial-body exposure with a linear dependence on the administered equivalent whole-body dose, for prostate cancer patients only. Only γ-H2AX foci assessment immediately after partial-body radiotherapy was a reliable measure of the expected equivalent whole-body dose. Local tumor doses could be approximated with both assays after one day. After total-body radiotherapy satisfactory dose estimates were achieved with both assays up to 8 h after exposure. In conclusion, the quantification of radiation-induced γ-H2AX foci, but not cytogenetic damage in peripheral leukocytes was a sensitive and rapid biodosimeter after acute heterogeneous irradiation of partial body volumes that was able to primarily assess the absorbed equivalent whole-body dose.

  12. Delayed Effects of Acute Radiation Exposure in a Murine Model of the H-ARS: Multiple-Organ Injury Consequent to Total Body Irradiation.

    Science.gov (United States)

    Unthank, Joseph L; Miller, Steven J; Quickery, Ariel K; Ferguson, Ethan L; Wang, Meijing; Sampson, Carol H; Chua, Hui Lin; DiStasi, Matthew R; Feng, Hailin; Fisher, Alexa; Katz, Barry P; Plett, P Artur; Sandusky, George E; Sellamuthu, Rajendran; Vemula, Sasidhar; Cohen, Eric P; MacVittie, Thomas J; Orschell, Christie M

    2015-11-01

    The threat of radiation exposure from warfare or radiation accidents raises the need for appropriate animal models to study the acute and chronic effects of high dose rate radiation exposure. The goal of this study was to assess the late development of fibrosis in multiple organs (kidney, heart, and lung) in survivors of the C57BL/6 mouse model of the hematopoietic-acute radiation syndrome (H-ARS). Separate groups of mice for histological and functional studies were exposed to a single uniform total body dose between 8.53 and 8.72 Gy of gamma radiation from a Cs radiation source and studied 1-21 mo later. Blood urea nitrogen levels were elevated significantly in the irradiated mice at 9 and 21 mo (from ∼22 to 34 ± 3.8 and 69 ± 6.0 mg dL, p irradiated controls) and correlated with glomerosclerosis (29 ± 1.8% vs. 64 ± 9.7% of total glomeruli, p irradiated controls). Glomerular tubularization and hypertrophy and tubular atrophy were also observed at 21 mo post-total body irradiation (TBI). An increase in interstitial, perivascular, pericardial and peribronchial fibrosis/collagen deposition was observed from ∼9-21 mo post-TBI in kidney, heart, and lung of irradiated mice relative to age-matched controls. Echocardiography suggested decreased ventricular volumes with a compensatory increase in the left ventricular ejection fraction. The results indicate that significant delayed effects of acute radiation exposure occur in kidney, heart, and lung in survivors of the murine H-ARS TBI model, which mirrors pathology detected in larger species and humans at higher radiation doses focused on specific organs.

  13. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation.

    Science.gov (United States)

    Lenarczyk, Marek; Su, Jidong; Haworth, Steven T; Komorowski, Richard; Fish, Brian L; Migrino, Raymond Q; Harmann, Leanne; Hopewell, John W; Kronenberg, Amy; Patel, Shailendra; Moulder, John E; Baker, John E

    2015-06-01

    The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20-120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.

  14. Effects of whole- and partial-body irradiation on circulating anterior pituitary hormones and testosterone and the relationship of these hormones to drug-metabolizing enzymes in the liver

    International Nuclear Information System (INIS)

    Doses within the range of 850 to 1500 rad given to the whole body, head, or lower-trunk region of male rats cause a marked depression in the rate of oxidative demethylation of drugs in the liver endoplasmic reticulum, 3 to 4 days after the irradiation. The V/sub max/ of the enzyme system is depressed and the K/sub m/ increased. Irradiation to the whole body, head, or lower trunk also causes a fall in the circulating levels of testosterone and luteinizing hormone (LH) and the concentrations of these hormones are markedly reduced 3 to 4 days after the irradiation. Injections of testosterone or anterior pituitary extract effectively restore the activity of the liver enzyme system after irradiation of the head or lower trunk. It is concluded that whole-body irradiation causes inhibition of drug-metabolizing enzymes in the liver by a complex series of interrelated effects on the testis, anterior pituitary, and possibly the hypothalamus

  15. Gene therapy strategy to reduced bone marrow aplasia: evaluation in cynomolgus macaque exposed to a gamma total body irradiation

    International Nuclear Information System (INIS)

    The aim of this work was to assess whether direct intra-marrow injection of an adeno-viral vector expressing human IL-1α gene stimulates hematopoiesis in healthy non-irradiated and gamma irradiated cynomolgus macaques. In the first hand, we have evaluated the feasibility of this gene therapy strategy in two healthy non-irradiated macaques. In this work, we have observed an increase of neutrophil, monocyte and platelets in the two animals treated with the therapeutic construct. This effect was associated with no abnormal clinical side effect. On the other hand, we have evaluated this strategy in non-human primate exposed to a sublethal gamma irradiation. Two of three animals treated by the therapeutic construct reduced significantly the neutropenia, thrombocytopenia and anemia radio-induced. In conclusion, this gene therapy strategy gave a similar clinical benefit comparatively to systemic administration of huIL-1α but without severe side effect. (author)

  16. Total body irradiation, busulfan and cyclophosphamide as a conditioning regimen for allogeneic bone marrow transplantation for patients with hematological malignancies

    International Nuclear Information System (INIS)

    Between May 1989 and October 1998, 44 patients with hematological malignancies received allogeneic bone marrow transplantation from HLA-matched related (n=25), unrelated (n=16) or 1 locus HLA-mismatched related donors (n=3). Busulfan (BU) (8 mg/kg) and cyclophosphamide (CY) (90 mg/kg) with fractionated total body irradiation (TBI) (12 Gy) (n=30) or BU (16 mg/kg) and CY (120 mg/kg) (n=14) were given as conditioning regimen. All patients receiving BU/CY were transplanted from related donors in first remission of acute leukemia or in first chronic phase of CML (standard risk group; S-group). For 30 patients receiving TBI/BU/CY, 13 were transplanted in standard risk and 17 were in advanced stage of hematological malignancies (high risk group; H-group); 7 in S-group and 9 in H-group transplanted from unrelated donor. Severe regimen-related toxicity was found in 10% of patients receiving TBI/BU/CY (one in standard risk group and 2 in high risk group), but not found in patients receiving BU/CY. Probability of disease free survival (DFS) at 5 years was 38% in patients receiving BU/CY, and 43% in patients receiving TBI/BU/CY (52% in S-group and 35% in H-group). For patients transplanted from related donor at standard risk, probability of DFS was higher in patients receiving TBI/BU/CY than in patients receiving BU/CY (83% vs 38%; p<0.05). For patients receiving TBI/BU/CY as preparatory regimen, probability of DFS was higher in patients transplanted from related donors than in patients transplanted from unrelated donors (63% vs 29%; p<0.05), that was due to lower rate of non-relapse mortality (8% vs 61%; p<0.001). Probability or relapse was 33% in patients receiving BU/CY, and 28% in patients receiving TBI/BU/CY (23%, in S-group and 31% even in H-group), and no significant difference was found between the three groups. We conclude that this TBI/BU/CY regimen is well tolerated and is very effective in reducing relapse and improving survival, especially in standard risk

  17. Cataracts after bone marrow transplantation: long-term follow-up of adults treated with fractionated total body irradiation

    International Nuclear Information System (INIS)

    Purpose: To determine the risk of, and risk factors for, developing cataracts after bone marrow transplantation.Methods and Materials: Four hundred and ninety-two adults who underwent bone marrow transplantation in Seattle were followed for 2 to 18 (median, 6) years. Before transplantation, patients received a preparative regimen of chemotherapy plus total body irradiation (TBI) (n = 407) or chemotherapy alone, without TBI (n = 85). TBI was administered in a single dose of 10 Gy (n = 74) or in fractionated doses totaling 12-15.75 Gy (n = 333). The risk of cataracts was determined for groups of patients with respect to the type of preparative regimen received and other pretransplant and posttransplant variables. Results: One hundred and fifty-nine patients (32%) developed cataracts between 0.5 to 11 (median, 2.3) years after transplantation. The probability of cataracts at 11 years after transplantation was 85%, 50%, 34%, and 19% for patients receiving 10 Gy of single-dose TBI, >12 Gy fractionated TBI, 12 Gy fractionated TBI, and no TBI, respectively (p 12 Gy fractionated TBI, 12 Gy fractionated TBI, or no TBI (33%, 22% and 23%, respectively). Patients given corticosteroids after transplant had a higher probability of cataracts (45%) than those without steroids (38%)(p <0.0001). In a proportional hazards regression model, the variables that were correlated with an increased probability of cataracts were single-dose TBI (relative risk (RR) = 2.46) and steroid therapy (RR = 2.34), while a decreased probability of cataracts was correlated with a nonTBI preparative regimen (RR = 0.41). The yearly hazard of developing cataracts in recipients of single-dose TBI was highest during the third year after transplantation, while in recipients of fractionated TBI, the hazard was distributed among years one through seven. The probability of cataracts in all groups reached a plateau at 7 years after transplantation, after which the development of cataracts was extremely unlikely

  18. Total body irradiation, busulfan and cyclophosphamide as a conditioning regimen for allogeneic bone marrow transplantation for patients with hematological malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Kai, Shunro; Misawa, Mahito; Hara, Hiroshi [Hyogo Coll. of Medicine, Nishinomiya (Japan)

    1999-08-01

    Between May 1989 and October 1998, 44 patients with hematological malignancies received allogeneic bone marrow transplantation from HLA-matched related (n=25), unrelated (n=16) or 1 locus HLA-mismatched related donors (n=3). Busulfan (BU) (8 mg/kg) and cyclophosphamide (CY) (90 mg/kg) with fractionated total body irradiation (TBI) (12 Gy) (n=30) or BU (16 mg/kg) and CY (120 mg/kg) (n=14) were given as conditioning regimen. All patients receiving BU/CY were transplanted from related donors in first remission of acute leukemia or in first chronic phase of CML (standard risk group; S-group). For 30 patients receiving TBI/BU/CY, 13 were transplanted in standard risk and 17 were in advanced stage of hematological malignancies (high risk group; H-group); 7 in S-group and 9 in H-group transplanted from unrelated donor. Severe regimen-related toxicity was found in 10% of patients receiving TBI/BU/CY (one in standard risk group and 2 in high risk group), but not found in patients receiving BU/CY. Probability of disease free survival (DFS) at 5 years was 38% in patients receiving BU/CY, and 43% in patients receiving TBI/BU/CY (52% in S-group and 35% in H-group). For patients transplanted from related donor at standard risk, probability of DFS was higher in patients receiving TBI/BU/CY than in patients receiving BU/CY (83% vs 38%; p<0.05). For patients receiving TBI/BU/CY as preparatory regimen, probability of DFS was higher in patients transplanted from related donors than in patients transplanted from unrelated donors (63% vs 29%; p<0.05), that was due to lower rate of non-relapse mortality (8% vs 61%; p<0.001). Probability or relapse was 33% in patients receiving BU/CY, and 28% in patients receiving TBI/BU/CY (23%, in S-group and 31% even in H-group), and no significant difference was found between the three groups. We conclude that this TBI/BU/CY regimen is well tolerated and is very effective in reducing relapse and improving survival, especially in standard risk

  19. Effects of whole-body irradiation on the degradation of 125I insulin and Na131I insulin in rabbits

    International Nuclear Information System (INIS)

    The degradation of simultaneously (i.v.) injected Na131I- and 125I-bovine insuline by rabbit blood and the urinary excretion of Na131I- and 125I-containing insulin degradation products have been investigated before and 24 h after 700 R X-ray irradiation. Also, the distribution of the two substances in the livers, kidneys, spleens, and KI-blocked thyroids was observed after irradiation. Radiation effects on the distribution of Na131I- and 125I-insulin on the livers, kidneys, and spleens of rabbits were not observed. On irradiation, there was a significant reduction of diuresis and also of the urinary excretion of 131I and 125I radioactivity. Irradiation had no influence on the distribution of Na131I-and 125I-insulin between plasma and extravascular space. The renal excretion function for water, iodide, and insulin degradation products was clearly impaired after irradiation. The same applies to the insulincatabolism by the degrading organs. The leukocyte count was reduced to about 17% during the first 4 days after irradiation. (orig./MG)

  20. GROUP DECISIONS. Shared decision-making drives collective movement in wild baboons.

    Science.gov (United States)

    Strandburg-Peshkin, Ariana; Farine, Damien R; Couzin, Iain D; Crofoot, Margaret C

    2015-06-19

    Conflicts of interest about where to go and what to do are a primary challenge of group living. However, it remains unclear how consensus is achieved in stable groups with stratified social relationships. Tracking wild baboons with a high-resolution global positioning system and analyzing their movements relative to one another reveals that a process of shared decision-making governs baboon movement. Rather than preferentially following dominant individuals, baboons are more likely to follow when multiple initiators agree. When conflicts arise over the direction of movement, baboons choose one direction over the other when the angle between them is large, but they compromise if it is not. These results are consistent with models of collective motion, suggesting that democratic collective action emerging from simple rules is widespread, even in complex, socially stratified societies.

  1. Surfactant phosphatidylcholine half-life and pool size measurements in premature baboons developing bronchopulmonary dysplasia

    NARCIS (Netherlands)

    D.J. Janssen; V.P. Carnielli (Virgilio); P.E. Cogo (Paola); S.R. Seidner; I.H.I. Luijendijk; J.L.D. Wattimena (Josias); A.H. Jobe (Alan); L.J.I. Zimmermann (Luc)

    2002-01-01

    textabstractBecause minimal information is available about surfactant metabolism in bronchopulmonary dysplasia, we measured half-lives and pool sizes of surfactant phosphatidylcholine in very preterm baboons recovering from respiratory distress syndrome and developing bronchopulmon

  2. The Possible Effect Of Tamoxifen Vs Whole Body Irradiation Treatment On Thyroid Hormones in Female Rats Bearing Mammary Tumors Chemically Induced

    International Nuclear Information System (INIS)

    Breast cancer is the most common malignancy among women in most developed and developing regions of the world. In women, this drug has tissuespecific effects, acting as an estrogen antagonist on the breast, and as an estrogen agonist on bone, lipid metabolism (increasing high-density lipoprotein cholesterol and decreasing low-density lipoprotein cholesterol), and the endometrium. Thyroid hormones act on almost all organs throughout the body and regulate the basal metabolism of the organism. Thyroid hormone can also stimulate the proliferation in vitro of certain tumor cell lines. The aim of the present study is to evaluate the significant value of tamoxifen and/or irradiation treatment on thyroid hormones in breast cancer bearing female rats. Forty two female Sprague-Dawely rats randomly divided into seven groups and the effect of tamoxifen and post-irradiation was studied on breast cancer chemically induced. The results shows a T4 and estradiol levels not T3 were altered in different experimental groups. It could be concluded that irradiation-induced changes in the composition of the mammary microenvironment promote the expression of neoplastic potential by affecting both estradiol and thyroid hormones, and tamoxifen may alter the thyroid hormones. Irradiation and tamoxifen administration may have worth effects on T4 and estradiol levels and it is recommended to further studies towards the bystander effect of radiation and tamoxifen on the tissue culture and molecular biology scale.

  3. A comparison of haemocoagulation tests in the experimental endotoxin model DIC and in rats whole-body irradiated by 250 Gy

    International Nuclear Information System (INIS)

    A comparison of results of tests performed with the endotoxin model of disseminated intravascular coagulation (DIC) and with irradiated groups of rats led to the conclusion that after whole-body irradiation with the high dose of 250 Gy, DIC occurs, in spite of the fact that the first stage, the hypercoagulation condition, can hardly be observed. In the experimental endotoxin model, an increase of activated partial thromboplastin test (APTT) values and prolongation of the thrombin time was observed up to 24 hours for two endotoxin doses. After both endotoxin doses, the fibrinogen level was transiently decreased with a subsequent increase. The fibrin monomers correspond to a decrease in the fibrinogen level. After the first dose, they were positive between the 3rd and 12th hours, and after the second dose, positivity was observed 6 hours after the application. The antithrombin III level was decreased after 12 hours for both endotoxin doses. The thrombocyte count was considerably reduced already from the 6th hour after administering endotoxin to the end of the experiment. Considerable changes in thrombocyte aggregation were observed only 3 hours after administering the second dose. When comparing the resulting values of these tests with values observed in irradiated animals, a certain agreement was found in the nature of the changes after exposure to 250 Gy. The fibrinogen level was transiently decreased 3 hours after irradiation, when considerable changes in the thrombocyte aggregation also occurred. (author) 5 figs., 17 refs

  4. Thyroxine clearance in rats within the first month after the single whole-body {gamma} - irradiation at a dose of 10Gy

    Energy Technology Data Exchange (ETDEWEB)

    Pryadko, Kirill A. [Institute of Radiobiology, National Academy of Sciences, Minsk (Belarus)

    2002-07-01

    The effects of acute whole-body {gamma} -irradiation at a dose of 10 Gy on thyroxine (T{sub 4}) plasma clearance rate (PCR) and thyroidal and blood T4 concentration ([T{sub 4}]) were examined within one month after exposure. The PCR values were measured using the bolus injection, single-compartmental approach. To eliminate the influence of radiation-induced anorexia animals were fasting for two days before the pharmacokinetic experiments. Hormone concentrations in blood and in thyroid tissue were measured by RIA. Throughout the observation period, PCR was elevated in irradiated rats with maximum at day 4 after exposure (0.56{+-}0.04 vs. 0.36{+-}0.03 ml/h100 gbw, P<0.001). [T{sub 4}] in blood was not significantly different from that in control animals. Thyroidal [T{sub 4}] was significantly decreased in irradiated animals 4 days after exposure (151.8{+-}21.7 vs. 258.8{+-}29.9 pmol/mg protein, P<0.01) and gradually increased after day 9. 10 Gy {gamma} -irradiation causes the intensification of T{sub 4} metabolism without the pronounced changes in concentration. Presumably, at early terms the rising local demand in O{sub 4} can not be compensated with the existing level of production. Alterations in the intensity of T{sub 4} metabolism are evident at least one month after exposure but they may not be detected without taking into account kinetic data.

  5. Studies on immunity to Schistosoma mansoni in vivo: whole-body irradiation has no effect on vaccine-induced resistance in mice

    Energy Technology Data Exchange (ETDEWEB)

    Vignali, D.A.A.; Bickle, Q.D.; Taylor, M.G.

    1988-02-01

    Actively immunized mice, whole-body irradiated with 650 or 525 rad., manifested comparable levels of resistance to Schistosoma mansoni compared with unirradiated, immunized mice in spite of a marked reduction in circulating leucocytes and platelets, and despite an abrogation of delayed-type hypersensitivity (DTH) (Type IV) reponse to schistosomular antigens. However, limited histopathological comparison of lung sections from irradiated and unirradiated mice 7 days post-challenge showed that cellular reactions ('foci') around parasites were similar in size and cellular composition except that in irradiated mice, eosinophils were poorly represented both in the foci and in lung tissue in general. Neither presumed immune complex-mediated (Type III, Arthus reaction) hypersensitivity nor serum anti-schistosomulum extract antibody levels were affected. The pattern of /sup 125/I-labelled schistosomular surface antigens immunoprecipitated with serum from irradiated and unirradiated mice was essentially similar. These results are consistent with antibody playing an important role in vaccine-induced immunity in mice but suggest that radiosensitive T cell function and radiosensitive cells, such as platelets and polymorphonuclear cells, including eosinophils, may not be essential.

  6. Effects of whole-body γ-irradiation on the biosynthesis of certain serum proteins. Final report, November 29, 1967--June 30, 1976

    International Nuclear Information System (INIS)

    Whole-body exposure of rats to ionizing radiations yielded an increased incorporation of labeled amino acids into serum albumin in in vivo studies suggesting a stimulation of biosynthesis. Actually this may have been caused by an elevated hepatic transport of labeled amino acids (see below). A suppressed biosynthesis of albumin was observed when the experiments were performed in vitro using liver microsomes. Impaired biosynthesis appeared to be caused by a reduced mRNA production. Irradiation stimulated the biosynthesis of acute-phase plasma proteins (stress response) and inhibited the excretion of α/sub 2u/-globulin, the sex-dependent protein of the adult male rat. Exposure of rats to γ-rays stimulated amino acid transport into the liver. This process which is Na+ and energy-dependent was studied with α-aminoisobutyric acid, cycloleucine, and L-methionine among others. After irradiation the serum glucagon and insulin, as well as hepatic cAMP levels, were elevated. Amino acid transport may be an important factor in controlling the increased gluconeogenesis and glycogenesis observed in rats following whole-body irradiation

  7. The treatment of advanced stage favorable histology non-Hodgkin's lymphoma: a preliminary report of a randomized trial comparing single agent chemotherapy, combination chemotherapy, and whole body irradiation

    International Nuclear Information System (INIS)

    Between 1975 and 1978, 51 patients with favorable histology non-Hodgkin's lymphomas, pathologic stage III-IV, were treated prospectively on a randomized treatment protocol. Treatment options were single alkylating agent chemotherapy, combination chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP), or fractionated whole body irradiation followed by low dose involved field irradiation. The median follow-up interval in this group of patients is not 41 mo. Actuarial survival is excellent, 84% at 4 yr for the entire group, with similar survival observed for each of the three treatment options. Initial complete remission rates (64%, 88%, and 71%) were not significantly different in the three treatment arms. Frequent relapse after initial remission induction was noted, however, with a freedom from relapse at 4 yr of only 25%. The toxicities of the three therapies were acceptable. Acute complications of therapy were most numerous in the group of patients treated with CVP; however, long-term hematologic depression was most commonly observed in patients treated with whole body irradiation. In general, hematologic complications were more frequent among patients who had marrow involvement and intact spleens at the time of initial therapy. The relationship of this study to other clinical trials in the management of patients with advanced stage favorable histology lymphomas and its implications for future clinical trials are discussed

  8. Effects of whole-body. gamma. -irradiation on the biosynthesis of certain serum proteins. Final report, November 29, 1967--June 30, 1976. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Neuhaus, O.W.

    1976-06-30

    Whole-body exposure of rats to ionizing radiations yielded an increased incorporation of labeled amino acids into serum albumin in in vivo studies suggesting a stimulation of biosynthesis. Actually this may have been caused by an elevated hepatic transport of labeled amino acids (see below). A suppressed biosynthesis of albumin was observed when the experiments were performed in vitro using liver microsomes. Impaired biosynthesis appeared to be caused by a reduced mRNA production. Irradiation stimulated the biosynthesis of acute-phase plasma proteins (stress response) and inhibited the excretion of ..cap alpha../sub 2u/-globulin, the sex-dependent protein of the adult male rat. Exposure of rats to ..gamma..-rays stimulated amino acid transport into the liver. This process which is Na/sup +/ and energy-dependent was studied with ..cap alpha..-aminoisobutyric acid, cycloleucine, and L-methionine among others. After irradiation the serum glucagon and insulin, as well as hepatic cAMP levels, were elevated. Amino acid transport may be an important factor in controlling the increased gluconeogenesis and glycogenesis observed in rats following whole-body irradiation.

  9. Voxel-based morphometry in epileptic baboons: Parallels to human juvenile myoclonic epilepsy.

    Science.gov (United States)

    Szabó, C Ákos; Salinas, Felipe S

    2016-08-01

    The epileptic baboon represents a natural model for genetic generalized epilepsy (GGE), closely resembling juvenile myoclonic epilepsy (JME). Due to functional neuroimaging and pathological differences between epileptic (SZ+) and asymptomatic control (CTL) baboons, we expected structural differences in gray matter concentration (GMC) using voxel-based morphometry (VBM). Standard anatomical (MP-RAGE) MRI scans using a 3T Siemens TIM Trio (Siemens, Erlangen, Germany) were available in 107 baboons (67 females; mean age 16±6years) with documented clinical histories and scalp-electroencephalography (EEG) results. For neuroimaging, baboons were anesthetized with isoflurane 1% (1-1.5 MAC) and paralyzed with vecuronium (0.1-0.3mg/kg). Data processing and analysis were performed using FSL's VBM toolbox. GMC was compared between CTL and SZ+ baboons, epileptic baboons with interictal epileptic discharges on scalp EEG (SZ+/IED+), asymptomatic baboons with abnormal EEGs (SZ-/IED+), and IED+ baboons with (IED+/PS+) and without (IED+/PS-) photosensitivity, and the subgroups amongst themselves. Age and gender related changes in gray matter volumes were also included as confound regressors in the VBM analyses of each animal group. Significant increases in GMC were noted in the SZ+/IED+ subgroup compared to the CTL group, including bilaterally in the frontopolar, orbitofrontal and anterolateral temporal cortices, while decreases in GMC were noted in the right more than left primary visual cortices and in the specific nuclei of the thalamus, including reticular, anterior and medial dorsal nuclei. No significant differences were noted otherwise, except that SZ+/IED+ baboons demonstrated increased GMC in the globus pallidae bilaterally compared to the SZ-/IED+ group. Similar to human studies of JME, the epileptic baboons demonstrated GMC decreases in the thalami and occipital cortices, suggesting secondary injury due to chronic epilepsy. Cortical GMC, on the other hand, was increased

  10. Patent ductus arteriosus ligation alters pulmonary gene expression in preterm baboons

    OpenAIRE

    Waleh, Nahid; McCurnin, Donald C.; Yoder, Bradley A.; Shaul, Philip W.; Clyman, Ronald I.

    2011-01-01

    Ibuprofen-induced ductus closure improves pulmonary mechanics and increases alveolar surface area in premature baboons compared with baboons with a persistent patent ductus arteriosus (PDA). Ibuprofen-treatment has no effect on the expression of genes that regulate pulmonary inflammation but does increase the expression of alpha-ENaC (the transepithelial sodium channel that is critical for alveolar water clearance). Although ligation eliminates the PDA, it does not improve pulmonary mechanics...

  11. Surfactant phosphatidylcholine half-life and pool size measurements in premature baboons developing bronchopulmonary dysplasia

    OpenAIRE

    Janssen, D.J.; Carnielli, Virgilio; Cogo, Paola; Seidner, S.R.; Luijendijk, I.H.I.; Wattimena, Josias; Jobe, Alan; Zimmermann, Luc

    2002-01-01

    textabstractBecause minimal information is available about surfactant metabolism in bronchopulmonary dysplasia, we measured half-lives and pool sizes of surfactant phosphatidylcholine in very preterm baboons recovering from respiratory distress syndrome and developing bronchopulmonary dysplasia, using stable isotopes, radioactive isotopes, and direct pool size measurements. Eight ventilated premature baboons received (2)H-DPPC (dipalmitoyl phosphatidylcholine) on d 5 of life, and radioactive ...

  12. DSCR9 gene simultaneous expression in placental, testicular and renal tissues from baboon (papio hamadryas

    Directory of Open Access Journals (Sweden)

    Rodriguez-Sanchez Irám

    2012-06-01

    Full Text Available Abstract Background In 2002 Takamatsu and co-workers described the human DSCR9 gene and observed that it was transcriptionally active in human testicular tissue, but no protein was identified as a product of this transcript. Similar results were obtained in chimpanzee tissue. This gene has not been detected in species other than primates, suggesting that DSCR9 is exclusively found in these mammals. Results We report evidence of DSCR9 expression in placenta, testis and kidney of baboon (Papio hamadryas. We used primers specific for DSCR9 to amplify transcripts through reverse transcription (RT coupled to polymerase chain reaction (PCR. Furthermore, PCR was used to amplify the complete DSCR9 gene from genomic DNA from three baboons. We amplified and sequenced five overlapping segments that were assembled into the 3284 bp baboon DSCR9 gene, including the putative promoter and the entire transcriptional unit (5'-UTR, CDS and 3'-UTR. Conclusions The baboon DSCR9 gene is highly similar to the human counterpart. The isolated transcripts from baboon tissues (placenta, testis and kidney of three different baboons correspond to the human orthologous gene.

  13. Effect of Fluosol-DA 20% and oxygen on response of C57BL/6 mice to whole-body irradiation

    International Nuclear Information System (INIS)

    Normal tissue effects in mice due to combinations of a perfluorochemical emulsion, Fluosol-DA 20%, 100% oxygen, and whole-body irradiation were investigated. Eight-to-10-week-old C57BL/6 male mice were injected via the tail vein with 10 ml/kg of Fluosol-DA with and without subsequent exposure to oxygen for 60 minutes. Animals then received graded doses of whole-body radiation (4 MV photons) at a dose rate of 2.85 +/- .015 Gy/minute. Using linear regression analysis, the lethal doses of radiation to 50% and 10% of the animals within 30 days in the absence of Fluosol-DA and oxygen were 8.35 Gy (95% c.l.:7.77-8.93 Gy) and 6.73 Gy (95% cl.:6.21-7.25 Gy), respectively, and were unaffected by Fluosol-DA and/or oxygen pre-treatment. However, Fluosol-DA given alone or in combination with oxygen produced increased balding and decreased graying incidence in mice within 60 days, and resulted in depressed weight gain 15 to 60 days post-treatment. Normal tissue effects due to administration of Fluosol-DA and oxygen in combination with whole-body irradiation have been demonstrated but appear minimal compared to other anti-tumor modalities currently under investigation

  14. Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or memory impairment in mice.

    Science.gov (United States)

    Wang, Bing; Tanaka, Kaoru; Ji, Bin; Ono, Maiko; Fang, Yaqun; Ninomiya, Yasuharu; Maruyama, Kouichi; Izumi-Nakajima, Nakako; Begum, Nasrin; Higuchi, Makoto; Fujimori, Akira; Uehara, Yoshihiko; Nakajima, Tetsuo; Suhara, Tetsuya; Ono, Tetsuya; Nenoi, Mitsuru

    2014-01-01

    The cause and progression of Alzheimer's disease (AD) are poorly understood. Possible cognitive and behavioral consequences induced by low-dose radiation are important because humans are exposed to ionizing radiation from various sources. Early transcriptional response in murine brain to low-dose X-rays (100 mGy) has been reported, suggesting alterations of molecular networks and pathways associated with cognitive functions, advanced aging and AD. To investigate acute and late transcriptional, pathological and cognitive consequences of low-dose radiation, we applied an acute dose of 100-mGy total body irradiation (TBI) with X-rays to C57BL/6J Jms mice. We collected hippocampi and analyzed expression of 84 AD-related genes. Mouse learning ability and memory were assessed with the Morris water maze test. We performed in vivo PET scans with (11)C-PIB, a radiolabeled ligand for amyloid imaging, to detect fibrillary amyloid beta peptide (Aβ) accumulation, and examined characteristic AD pathologies with immunohistochemical staining of amyloid precursor protein (APP), Aβ, tau and phosphorylated tau (p-tau). mRNA studies showed significant downregulation of only two of 84 AD-related genes, Apbb1 and Lrp1, at 4 h after irradiation, and of only one gene, Il1α, at 1 year after irradiation. Spatial learning ability and memory were not significantly affected at 1 or 2 years after irradiation. No induction of amyloid fibrillogenesis or changes in APP, Aβ, tau, or p-tau expression was detected at 4 months or 2 years after irradiation. TBI induced early or late transcriptional alteration in only a few AD-related genes but did not significantly affect spatial learning, memory or AD-like pathological change in mice.

  15. SU-E-T-501: Normal Tissue Toxicities of Pulsed Low Dose Rate Radiotherapy and Conventional Radiotherapy: An in Vivo Total Body Irradiation Study

    International Nuclear Information System (INIS)

    Purpose: Pulsed low dose rate radiotherapy (PLDR) is a re-irradiation technique for therapy of recurrent cancers. We have previously shown a significant difference in the weight and survival time between the mice treated with conventional radiotherapy (CRT) and PLDR using total body irradiation (TBI). The purpose of this study was to investigate the in vivo effects of PLDR on normal mouse tissues.Materials and Methods: Twenty two male BALB/c nude mice, 4 months of age, were randomly assigned into a PLDR group (n=10), a CRT group (n=10), and a non-irradiated control group (n=2). The Siemens Artiste accelerator with 6 MV photon beams was used. The mice received a total of 18Gy in 3 fractions with a 20day interval. The CRT group received the 6Gy dose continuously at a dose rate of 300 MU/min. The PLDR group was irradiated with 0.2Gyx20 pulses with a 3min interval between the pulses. The mice were weighed thrice weekly and sacrificed 2 weeks after the last treatment. Brain, heart, lung, liver, spleen, gastrointestinal, urinary and reproductive organs, and sternal bone marrow were removed, formalin-fixed, paraffin-embedded and stained with H and E. Morphological changes were observed under a microscope. Results: Histopathological examination revealed atrophy in several irradiated organs. The degree of atrophy was mild to moderate in the PLDR group, but severe in the CRT group. The most pronounced morphological abnormalities were in the immune and hematopoietic systems, namely spleen and bone marrow. Brain hemorrhage was seen in the CRT group, but not in the PLDR group. Conclusions: Our results showed that PLDR induced less toxicity in the normal mouse tissues than conventional radiotherapy for the same dose and regimen. Considering that PLDR produces equivalent tumor control as conventional radiotherapy, it would be a good modality for treatment of recurrent cancers

  16. SU-E-T-501: Normal Tissue Toxicities of Pulsed Low Dose Rate Radiotherapy and Conventional Radiotherapy: An in Vivo Total Body Irradiation Study

    Energy Technology Data Exchange (ETDEWEB)

    Cvetkovic, D; Zhang, P; Wang, B; Chen, L; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

    2014-06-01

    Purpose: Pulsed low dose rate radiotherapy (PLDR) is a re-irradiation technique for therapy of recurrent cancers. We have previously shown a significant difference in the weight and survival time between the mice treated with conventional radiotherapy (CRT) and PLDR using total body irradiation (TBI). The purpose of this study was to investigate the in vivo effects of PLDR on normal mouse tissues.Materials and Methods: Twenty two male BALB/c nude mice, 4 months of age, were randomly assigned into a PLDR group (n=10), a CRT group (n=10), and a non-irradiated control group (n=2). The Siemens Artiste accelerator with 6 MV photon beams was used. The mice received a total of 18Gy in 3 fractions with a 20day interval. The CRT group received the 6Gy dose continuously at a dose rate of 300 MU/min. The PLDR group was irradiated with 0.2Gyx20 pulses with a 3min interval between the pulses. The mice were weighed thrice weekly and sacrificed 2 weeks after the last treatment. Brain, heart, lung, liver, spleen, gastrointestinal, urinary and reproductive organs, and sternal bone marrow were removed, formalin-fixed, paraffin-embedded and stained with H and E. Morphological changes were observed under a microscope. Results: Histopathological examination revealed atrophy in several irradiated organs. The degree of atrophy was mild to moderate in the PLDR group, but severe in the CRT group. The most pronounced morphological abnormalities were in the immune and hematopoietic systems, namely spleen and bone marrow. Brain hemorrhage was seen in the CRT group, but not in the PLDR group. Conclusions: Our results showed that PLDR induced less toxicity in the normal mouse tissues than conventional radiotherapy for the same dose and regimen. Considering that PLDR produces equivalent tumor control as conventional radiotherapy, it would be a good modality for treatment of recurrent cancers.

  17. Total body 100-mGy X-irradiation does not induce Alzheimer's disease-like pathogenesis or memory impairment in mice

    International Nuclear Information System (INIS)

    The cause and progression of Alzheimer's disease (AD) are poorly understood. Possible cognitive and behavioral consequences induced by low-dose radiation are important because humans are exposed to ionizing radiation from various sources. Early transcriptional response in murine brain to low-dose X-rays (100 mGy) has been reported, suggesting alterations of molecular networks and pathways associated with cognitive functions, advanced aging and AD. To investigate acute and late transcriptional, pathological and cognitive consequences of low-dose radiation, we applied an acute dose of 100-mGy total body irradiation (TBI) with X-rays to C57BL/6J Jms mice. We collected hippocampi and analyzed expression of 84 AD-related genes. Mouse learning ability and memory were assessed with the Morris water maze test. We performed in vivo PET scans with 11C-PIB, a radiolabeled ligand for amyloid imaging, to detect fibrillary amyloid beta peptide (Aβ) accumulation, and examined characteristic AD pathologies with immunohistochemical staining of amyloid precursor protein (APP), Aβ, tau and phosphorylated tau (p-tau). mRNA studies showed significant downregulation of only two of 84 AD-related genes, Apbb1 and Lrp1, at 4 h after irradiation, and of only one gene, Il1α, at 1 year after irradiation. Spatial learning ability and memory were not significantly affected at 1 or 2 years after irradiation. No induction of amyloid fibrillogenesis or changes in APP, Aβ, tau, or p-tau expression was detected at 4 months or 2 years after irradiation. TBI induced early or late transcriptional alteration in only a few AD-related genes but did not significantly affect spatial learning, memory or AD-like pathological change in mice. (author)

  18. A pacific culture among wild baboons: its emergence and transmission.

    Directory of Open Access Journals (Sweden)

    Robert M Sapolsky

    2004-04-01

    Full Text Available Reports exist of transmission of culture in nonhuman primates. We examine this in a troop of savanna baboons studied since 1978. During the mid-1980s, half of the males died from tuberculosis; because of circumstances of the outbreak, it was more aggressive males who died, leaving a cohort of atypically unaggressive survivors. A decade later, these behavioral patterns persisted. Males leave their natal troops at adolescence; by the mid-1990s, no males remained who had resided in the troop a decade before. Thus, critically, the troop's unique culture was being adopted by new males joining the troop. We describe (a features of this culture in the behavior of males, including high rates of grooming and affiliation with females and a "relaxed" dominance hierarchy; (b physiological measures suggesting less stress among low-ranking males; (c models explaining transmission of this culture; and (d data testing these models, centered around treatment of transfer males by resident females.

  19. Social networks predict gut microbiome composition in wild baboons.

    Science.gov (United States)

    Tung, Jenny; Barreiro, Luis B; Burns, Michael B; Grenier, Jean-Christophe; Lynch, Josh; Grieneisen, Laura E; Altmann, Jeanne; Alberts, Susan C; Blekhman, Ran; Archie, Elizabeth A

    2015-01-01

    Social relationships have profound effects on health in humans and other primates, but the mechanisms that explain this relationship are not well understood. Using shotgun metagenomic data from wild baboons, we found that social group membership and social network relationships predicted both the taxonomic structure of the gut microbiome and the structure of genes encoded by gut microbial species. Rates of interaction directly explained variation in the gut microbiome, even after controlling for diet, kinship, and shared environments. They therefore strongly implicate direct physical contact among social partners in the transmission of gut microbial species. We identified 51 socially structured taxa, which were significantly enriched for anaerobic and non-spore-forming lifestyles. Our results argue that social interactions are an important determinant of gut microbiome composition in natural animal populations-a relationship with important ramifications for understanding how social relationships influence health, as well as the evolution of group living.

  20. Fetal hemoglobin reactivation in baboon and man: a short perspective.

    Science.gov (United States)

    Lavelle, D; DeSimone, J; Heller, P

    1993-01-01

    Present concepts of the mechanism of reactivation of synthesis of fetal hemoglobin (HbF) in the adult under conditions of erythropoietic stress are briefly reviewed. Since HbF can be considered an effective natural antisickling agent, the reactivation of its synthesis in patients with sickle cell anemia as a desirable therapeutic goal has been extensively explored since the discovery in 1982 that 5-azacytidine increases HbF levels in the baboon. Hydroxyurea (HU) has become the most widely used agent, although its effectiveness in increasing HbF levels and the number of F cells is highly variable. Recent investigations are cited showing that other agents such as butyrate, and the addition of recombinant hemopoietic growth factors, such as erythropoietin and stem cell factor, especially in combination with HU, offer important therapeutic possibilities. Transacting nuclear proteins are briefly discussed as possibly having a future role in the efforts of stimulating gamma-chain synthesis. PMID:7677951

  1. Succesive irradiation of the lower and upper body in non-Hodgkin lymphoma after failure of chemotherapy. Report of eight cases

    International Nuclear Information System (INIS)

    Eight patients, with stages CS IV non-Hodgkin lymphoma involving the bone marrow and secondarily resistant to chemotherapy were studied. The eight patients were managed, by external irradiation of the lower half of the body (LHBI), followed six weeks later by irradiation of the upper half of the body (UHBI). A single dose of 8.00 Grays in 6 cases and 6.00 Grays in two cases was delivered. After LHBI, 4 of 8 patients experienced nausea and emesis within the first thirty minutes. Two patients had diarrhea 24 to 48 hours after treatment. Side effects recorded after LHBI were as follows: marked tiredness in 3 cases, alopecia in 6, stomatitis in 1, oral and digestive candidiasis in 2, nausea and emesis 4, fever in 1, oral herpes simplex in 1, diarrhea in 1 and abdominal pain in 1. The dose delivered to the lungs was brought down to 6.00 Grays by interposition of attenuating lead sheets, and no postirradiation lung disease was observed. After the first radiation session, 2 of 8 patients had hemoglobin levels less than 8 g/100 ml and platelet counts less than 50 000/mm3 on the sixth and eleventh day respectively. After irradiation of the second half of the body, 3 patients developed severe medullary aplasia. Each of these patients had received 8.00 Grays. In each case, duration of the aplasia exceeded two months. Outcome was fatal in two patients, at four months and 3.5. Overall apparent clinical remission rate was 4/8

  2. Succesive irradiation of the lower and upper body in non-Hodgkin lymphoma after failure of chemotherapy. Report of eight cases

    Energy Technology Data Exchange (ETDEWEB)

    Touboul, E.; Leonard, P.; Guerin, R.A.; Merle Beral, H.; Goris, C.; Leblond-Missenard, V.; Jablonski, O.; Buscaill, A. (Centre Hospitalier Universitaire, Pitie Salpetriere, 75 - Paris (France))

    1985-04-18

    Eight patients, with stages CS IV non-Hodgkin lymphoma involving the bone marrow and secondarily resistant to chemotherapy were studied. The eight patients were managed, by external irradiation of the lower half of the body (LHBI), followed six weeks later by irradiation of the upper half of the body (UHBI). A single dose of 8.00 Grays in 6 cases and 6.00 Grays in two cases was delivered. After LHBI, 4 of 8 patients experienced nausea and emesis within the first thirty minutes. Two patients had diarrhea 24 to 48 hours after treatment. Side effects recorded after LHBI were as follows: marked tiredness in 3 cases, alopecia in 6, stomatitis in 1, oral and digestive candidiasis in 2, nausea and emesis 4, fever in 1, oral herpes simplex in 1, diarrhea in 1 and abdominal pain in 1. The dose delivered to the lungs was brought down to 6.00 Grays by interposition of attenuating lead sheets, and no postirradiation lung disease was observed. After the first radiation session, 2 of 8 patients had hemoglobin levels less than 8 g/100 ml and platelet counts less than 50 000/mm/sup 3/ on the sixth and eleventh day respectively. After irradiation of the second half of the body, 3 patients developed severe medullary aplasia. Each of these patients had received 8.00 Grays. In each case, duration of the aplasia exceeded two months. Outcome was fatal in two patients, at four months and 3.5. Overall apparent clinical remission rate was 4/8.

  3. Categorization does not promote symmetry in Guinea baboons (Papio papio).

    Science.gov (United States)

    Medam, Tiphaine; Marzouki, Yousri; Montant, Marie; Fagot, Joël

    2016-09-01

    Humans have the capacity to use stimuli interchangeably by forming equivalence classes, and this ability seems to be supported by our language system. According to Sidman and Tailby (Conditional discrimination vs. matching to sample: an expansion of the testing paradigm. J Exp Anal Behav 37:5-22, 1982), the formation of equivalence classes require that three relations are derived among the class members, and past experiments have shown that one of these relations, i.e., symmetry, corresponding to the ability to reverse a relation (if A → B, then B → A), is extremely difficult to obtain in non-human animals. Because language development and the ability to form equivalence classes both co-occur in children with an increased ability to form categories, the current study tested the idea that category learning might promote symmetry in a nonhuman primate species. In Experiment 1, twelve Guinea baboons (Papio papio) were trained to associate 60 pictures of bears and 60 pictures of cars to two category labels, before being tested in symmetry trials. In Experiment 2, symmetry was trained and tested by reversing the association order between labels and pictures, using a new set of stimuli. In both experiments, the baboons successfully demonstrated category discrimination, but had only a weak (though significant) tendency to respond in accordance with symmetry during test trials. Altogether, our results confirm that symmetry is inherently difficult in non-human animals. We discuss possible explanations for such a limitation and give reasons for thinking that the effects of categorization on symmetry should be further investigated. PMID:27278368

  4. Protection of mouse hematopoietic stem cells by a preparation of herb mixture (hemoHIM) against whole body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Jung, W. H.; Park, H. R.; Oh, H.; Jung, I. Y.; Cho, S. K. [KAERI, Taejon (Korea, Republic of)

    2002-10-01

    A preparation of herb mixture (HemoHIM) was designed from three medicinal herbs including Angelica gigantis Radix to protect gastrointestine, hematopoietic organs and immune system against radiation damage. In the present study, we investigated the radioprotective effects of HemoHIM on hematopoietic stem cells in {gamma}-irradiated mice and the underlying mechanisms. The administration of HemoHIM significantly increased the formation of endogenous spleen colony and reduced apoptosis of bone marrow cells in {gamma}-irradiated mice. These results showed that HemoHIM protected hematopoietic stem cells from irradiation. To investigate the mechanism of the protection, the effects of HemoHIM on expression of radioprotective cytokines was examined. HemoHIM increased the mRNA levels of IL-1{beta}, TNF-{alpha}, SCF and IL-6 in bone marrow cells and peritoneal macrophages in vitro. In vivo administration of HemoHIM increased the mRNA levels of IL-1{beta}, TNF-{alpha} in spleen. The examination of radical scavenging activity of HemoHIM as another mechanism revealed that HemoHIM was effective at scavenging DPPH radicals and hydroxyl radicals. From these results, it is suggested that HemoHIM exerts these radioprotective effects through the induction of radioprotective cytokines and/or through directly scavenging radicals produced by {gamma}-irradiation.

  5. Eight week exposure to a high sugar high fat diet results in adiposity gain and alterations in metabolic biomarkers in baboons (Papio hamadryas sp.

    Directory of Open Access Journals (Sweden)

    Tejero M Elizabeth

    2010-10-01

    Full Text Available Abstract Background Baboons (Papio hamadryas Sp. develop features of the cardiometabolic syndrome and represent a clinically-relevant animal model in which to study the aetiology of the disorder. To further evaluate the baboon as a model for the study of the cardiometabolic syndrome, we developed a high sugar high fat diet and hypothesized that it could be used to induce adiposity gain and affect associated circulating biomarkers. Methods We developed a diet enriched with monosaccharides and saturated fatty acids that was composed of solid and liquid energy sources. We provided a group of baboons (n = 9 ad libitum access to this diet for 8 weeks. Concurrently, a control group (n = 6 was maintained with ad libitum access to a low sugar low fat baseline diet and normal water for 8 weeks. Body composition was determined by dual-energy X-ray absorptiometry and circulating metabolic biomarkers were measured using standard methodology before and after the 8 week study period. Results Neither body composition nor circulating biomarkers changed in the control group. Following the 8 weeks, the intervention group had a significant increase in fat mass (1.71 ± 0.98 vs. 3.23 ± 1.70 kg, p = 0.004, triglyceride (55 ± 13 vs. 109 ± 67 mg/dL, p = 0.006,, and leptin (1.19 ± 1.40 vs. 3.29 ± 2.32 ng/mL, p = 0.001 and a decline in adiponectin concentrations (33530 ± 9744 vs. 23330 ± 7863 ng/mL, p = 0.002. Percentage haemoglobin A1C (4.0 ± 0.3 vs. 6.0 ± 1.4, p = 0.002 also increased in the intervention group. Conclusions Our findings indicate that when exposed to a high sugar high fat diet, young adult male baboons develop increased body fat and triglyceride concentrations, altered adipokine concentrations, and evidence of altered glucose metabolism. Our findings are in keeping with observations in humans and further demonstrate the potential utility of this highly clinically-relevant animal model for studying diet-induced metabolic dysregulation.

  6. Metabolism and Disposition of 3,4-Methylenedioxymethamphetamine (“Ecstasy”) in Baboons after Oral Administration: Comparison with Humans Reveals Marked Differences

    OpenAIRE

    Mueller, Melanie; Goodwin, Amy K.; Ator, Nancy A; McCann, Una D.; Ricaurte, George A.

    2011-01-01

    The baboon is potentially an attractive animal for modeling 3,4-methylenedioxymethamphetamine (MDMA) effects in humans. Baboons self-administer MDMA, are susceptible to MDMA neurotoxicity, and are suitable for positron emission tomography, the method most often used to probe for MDMA neurotoxicity in humans. Because pharmacokinetic equivalence is a key feature of a good predictive animal model, we compared the pharmacokinetics of MDMA in baboons and humans. Baboons were trained to orally cons...

  7. MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total-Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats.

    Science.gov (United States)

    Li, Jianzhong; Xu, Jing; Lu, Yiming; Qiu, Lei; Xu, Weiheng; Lu, Bin; Hu, Zhenlin; Chu, Zhiyong; Chai, Yifeng; Zhang, Junping

    2016-05-17

    Matrine is an alkaloid extracted from Sophora flavescens Ait and has many biological activities, such as anti-inflammatory, antitumor, anti-fibrosis, and immunosuppressive properties. In our previous studies, the matrine derivative MASM was synthesized and exhibited potent inhibitory activity against liver fibrosis. In this study, we mainly investigated its protection against lethal total-body irradiation (TBI) in rats. Administration of MASM reduced the radiation sickness characteristics and increased the 30-day survival of rats before or after lethal TBI. Ultrastructural observation illustrated that pretreatment of rats with MASM significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed that pretreatment with MASM had a dramatic effect on gene expression changes caused by TBI. Pretreatment with MASM prevented differential expression of 53% (765 genes) of 1445 differentially expressed genes induced by TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 21 pathways, such as metabolic pathways, pathways in cancer, and mitogen-activated protein kinase (MAPK) pathways. Our data indicated that pretreatment of rats with MASM modulated these pathways induced by TBI, suggesting that the pretreatment with MASM might provide the protective effects on lethal TBI mainly or partially through the modulation of these pathways, such as multiple MAPK pathways. Therefore, MASM has the potential to be used as an effective therapeutic or radioprotective agent to minimize irradiation damages and in combination with radiotherapy to improve the efficacy of cancer therapy.

  8. MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total-Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Jianzhong Li

    2016-05-01

    Full Text Available Matrine is an alkaloid extracted from Sophora flavescens Ait and has many biological activities, such as anti-inflammatory, antitumor, anti-fibrosis, and immunosuppressive properties. In our previous studies, the matrine derivative MASM was synthesized and exhibited potent inhibitory activity against liver fibrosis. In this study, we mainly investigated its protection against lethal total-body irradiation (TBI in rats. Administration of MASM reduced the radiation sickness characteristics and increased the 30-day survival of rats before or after lethal TBI. Ultrastructural observation illustrated that pretreatment of rats with MASM significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed that pretreatment with MASM had a dramatic effect on gene expression changes caused by TBI. Pretreatment with MASM prevented differential expression of 53% (765 genes of 1445 differentially expressed genes induced by TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 21 pathways, such as metabolic pathways, pathways in cancer, and mitogen-activated protein kinase (MAPK pathways. Our data indicated that pretreatment of rats with MASM modulated these pathways induced by TBI, suggesting that the pretreatment with MASM might provide the protective effects on lethal TBI mainly or partially through the modulation of these pathways, such as multiple MAPK pathways. Therefore, MASM has the potential to be used as an effective therapeutic or radioprotective agent to minimize irradiation damages and in combination with radiotherapy to improve the efficacy of cancer therapy.

  9. 23例X线全身照射患者的照射方法及剂量学分析%The Irradiation Method and Dosimetry Analyze of 23 Patients Received X Ray Total Body Irradiation

    Institute of Scientific and Technical Information of China (English)

    张红; 邱小平; 杨振; 宾石珍

    2011-01-01

    目的:报道23例全身照射患者的照射方法,并对照射中的实时监测结果进行剂量学分析.方法:采用6MV X线对23例患者行前后对穿野分次全身照射治疗,并在照射中用多通道半导体剂量计对晶体、肺、腹部、睾丸、膝五个部位进行剂量实时监测.结果:晶体、肺、腹部、睾丸、膝五个部位的平均受照剂量分别为445.28 cGy、614.26 cGy、799.71cGy、210.21 cGy、840.74 cGy,所有患者的肺实际受照剂量均在限制剂量以内,5例患者腹部实测剂量和处方剂量的剂量偏差超出了5%.结论:患者实际受照剂量与处方剂量会存在一定偏差,为了保证患者的安全,在照射过程中进行剂量实时监测是十分必要的.%Objective: To report the irradiation method of 23 patients received total body irradiation and to analyze the dosimetry characteristics according to the result of real-time dose monitoring by semiconductor dosimeter. Methods: Fractionated-Total body irradiation by 6 MV X-Ray with anterior-posterior fields was given to 23 patients and the multi-channel semiconductor dosimeter was used for real-time monitoring to lens.lung, abdomen, testicle and knee during total body irradiation. Results: The mean actual dose of lens,lung, abdomen, testicle and knee was 445.28 cGy,614.26 cGy,799.71 cGy,210.21 cGy,840.74 cGy, respectively. The actual lung dose of all patients was within the limited dose, the deviation of the measured dose of abdomen and prescription dose of 5 patients exceeded 5%. Conclusions: There are some deviations between the actual irradiation dose of the patients and the prescription dose, so it is necessary to monitor the real-time dose in the course of irradiation to ensure the patient safety.

  10. Modeling the effective connectivity of the visual network in healthy and photosensitive, epileptic baboons.

    Science.gov (United States)

    Ákos Szabó, C; Salinas, Felipe S; Li, Karl; Franklin, Crystal; Leland, M Michelle; Fox, Peter T; Laird, Angela R; Narayana, Shalini

    2016-05-01

    The baboon provides a model of photosensitive, generalized epilepsy. This study compares cerebral blood flow responses during intermittent light stimulation (ILS) between photosensitive (PS) and healthy control (CTL) baboons using H 2 (15) O-PET. We examined effective connectivity associated with visual stimulation in both groups using structural equation modeling (SEM). Eight PS and six CTL baboons, matched for age, gender and weight, were classified on the basis of scalp EEG findings performed during the neuroimaging studies. Five H 2 (15) O-PET studies were acquired alternating between resting and activation (ILS at 25 Hz) scans. PET images were acquired in 3D mode and co-registered with MRI. SEM demonstrated differences in neural connectivity between PS and CTL groups during ILS that were not previously identified using traditional activation analyses. First-level pathways consisted of similar posterior-to-anterior projections in both groups. While second-level pathways were mainly lateralized to the left hemisphere in the CTL group, they consisted of bilateral anterior-to-posterior projections in the PS baboons. Third- and fourth-level pathways were only evident in PS baboons. This is the first functional neuroimaging study used to model the photoparoxysmal response (PPR) using a primate model of photosensitive, generalized epilepsy. Evidence of increased interhemispheric connectivity and bidirectional feedback loops in the PS baboons represents electrophysiological synchronization associated with the generation of epileptic discharges. PS baboons demonstrated decreased model stability compared to controls, which may be attributed to greater variability in the driving response or PPRs, or to the influence of regions not included in the model. PMID:25749860

  11. An experimental model of acute encephalopathy after total body irradiation in the rat: effect of Ginkgo biloba extract (EGb 761); Effet de l'extrait de Ginkgo biloba (EGb 761) chez le rat sur un modele experimental d'encephalopathie aigue apres irradiation corporelle totale

    Energy Technology Data Exchange (ETDEWEB)

    Lamproglou, I.; Bok, B. [Hopital Bichat, 75 - Paris (France); Boisserie, G.; Mazeron, J.J.; Baillet, F. [Hopital Pitie-Salpetriere, 75 - Paris (France); Drieu, K. [IHB-IPSEN, 75 - Paris (France)

    2000-06-01

    To define the therapeutic effect of Ginkgo biloba extract (EGb 761) in an experimental model of acute encephalopathy following total body irradiation in rats. Ninety four-month-old rats received 4.5 Gy total body irradiation (TBI) at day 1 while 15 rats received sham irradiation. A behavioural study based on a conditioning test of negative reinforcement, the one-way avoidance test, was performed test, was performed after irradiation. Orally treatment was started one day (study A) or twenty two days (study B) after irradiation and repeated daily for twelve days. In the irradiated group, three subgroups were defined according to the treatment received: EGb 761 (50 mg/kg), EGb 761 (100 mg/kg), water. This work comprised two consecutive studies. In study A (45 rats) the one-way avoidance test was administered daily from day 7 to day 14. In study B (45 rats) the behavioural test was performed from day 28 to day 35. Study A (three groups of 15 rats): following TBI, irradiated rats treated with water demonstrated a significant delay in a learning the one-way avoidance test in comparison with sham-irradiated rats (P < 0.0002) or irradiated rats treated with EGb 761 (50 mg/kg; P < 0.007) or EGb 761 (100 mg/kg; P < 0.0002). The irradiated rats, treated with EGb 761 (50 or 100 mg/kg) did not differ from the sham-irradiated controls. Study B (three groups of 15 rats): the irradiated rats, treated with water of EGb 761 (50 or 100 mg/kg) did not differ from the sham-irradiated controls. (authors)

  12. Thoracic re-irradiation using stereotactic body radiotherapy (SBRT) techniques as first or second course of treatment

    International Nuclear Information System (INIS)

    Background and purpose: Management for in-field failures after thoracic radiation is poorly defined. We evaluated SBRT as an initial or second course of treatment re-irradiating in a prior high dose region. Materials and methods: Thirty-three patients were treated with re-irradiation defined by the prior 30 Gy isodose line. Kaplan–Meier estimates were performed for local (LC), regional (RC), distant control (DC), and overall survival (OS). The plans when available were summed to evaluate doses to critical structures. Patient and treatment variables were analyzed on UVA for the impact on control and survival measures. Results: Median follow-up was 17 months. Treatment for sequential courses was as follows: (course1:course2) EBRT:SBRT (24 patients), SBRT:SBRT (7 patients), and SBRT:EBRT (3 patients). Median re-irradiation dose and fractionation was 50 Gy and 10 fractions (fx), with a median of 18 months (6–61) between treatments. Median OS was 21 months and 2 year LC 67%, yet LC for >1 fraction was 88% (p = 0.006 for single vs. multiple). 10 patients suffered chronic grade 2–3 toxicity (6 chest wall pain, 3 dyspnea, 1 esophagitis) and 1 grade 5 toxicity with aorta-esophageal fistula after 54 Gy in 3 fx for a central tumor with an estimated EQD2 to the aorta of 200 Gy. Conclusion: Tumor control can be established with re-irradiation using SBRT techniques for in-field thoracic failures at the cost of manageable toxicity

  13. Continuous infusion cyclophosphamide and low-dose total body irradiation is a safe and effective conditioning regimen for autologous transplant in multiple myeloma.

    Science.gov (United States)

    Byrne, M; Wingard, J R; Moreb, J S

    2013-11-01

    We present the results of a novel conditioning regimen in multiple myeloma (MM) patients undergoing tandem autologous stem cell transplant (ASCT). MM patients were enrolled in a prospective phase II clinical trial. After initial ASCT, disease response was assessed by day +100. Patients achieving very good partial remission (VGPR) were offered maintenance therapy. If patients achieved VGPR, they were offered a second ASCT using continuous intravenous cyclophosphamide (CICy) 6 g/m(2) over 4 days and low-dose total body irradiation (ldTBI) 600 rads over 2 days. Total body irradiation was replaced by melphalan 140 mg/m(2) if patients had received prior radiation. Twenty-one patients received tandem ASCT. Three patients received CICy and melphalan. Median duration of neutropenia with CICy/ldTBI was 11 days. Fifteen patients (71.4%) developed febrile neutropenia while grade 1 to 2 diarrhea was the next most common adverse event (42.9%). There was no treatment-related mortality. Four patients had entered complete remission (19%) and 6 achieved VGPR (28.6%). In conclusion, this conditioning regimen is safe and effective and may be useful in patients who do not benefit from first ASCT using more traditional conditioning regimen.

  14. Enhancement of distribution of dermal multipotent stem cells to bone marrow in rats of total body irradiation by platelet-derived growth factor-AA treatment

    International Nuclear Information System (INIS)

    Objective: To observe whether dermal multipotent stem cells (dMSCs) treated with platelet-derived growth factor-AA (PDGF-AA) could distribute more frequently to the bone marrow in rats of total body irradiation (TBI). Methods: Male dMSCs were isolated and 10 μg/L PDGF-AA was added to the culture medium and further cultured for 2 h. Then the expression of tenascin-C were examined by Western blot, and the migration ability of dMSCs was assessed in transwell chamber. The pre-treated dMSCs were transplanted by tail vein injection into female rats administered with total body irradiation, and 2 weeks after transplantation, real-time PCR was employed to measure the amount of dMSCs in bone marrow. Non-treated dMSCs served as control.Results PDGF-AA treatment increased the expression of tenascin-C in dMSCs, made (1.79 ± 0.13) × 105 cells migrate to the lower chamber under the effect of bone marrow extract, and distributed to bone marrow in TBI rats, significantly more than (1.24 ± 0.09) ×105 in non-treated dMSCs (t=8.833, P<0.01). Conclusions: PDGF-AA treatment could enhance the migration ability of dMSCs and increase the amount of dMSCs in bone marrow of TBI rats after transplantation. (authors)

  15. Total body irradiation of donors can alter the course of tolerance and induce acute rejection in a spontaneous tolerance rat liver transplantation model.

    Science.gov (United States)

    Zhang, YeWei; Zhao, HeWei; Bo, Lin; Yang, YinXue; Lu, Xiang; Sun, JingFeng; Wen, JianFei; He, Xia; Yin, GuoWen

    2012-09-01

    Liver transplantation is an established therapy for end-stage liver diseases. Graft rejection occurs unless the recipient receives immunosuppression after transplantation. This study aimed to explore the mechanism of acute rejection of liver allografts in rats pre-treated with total body irradiation to eliminate passenger lymphocytes and to define the role of CD4(+)CD25(+) regulatory T cells in the induction of immunotolerance in the recipient. Male Lewis rats were used as donors and male DA rats were recipients. Rats were randomly assigned to the following four groups: control group, homogeneity liver transplantation group, idio-immunotolerance group and acute rejection group. After transplantation, the survival time of each group, serum alanine aminotransferase, total bilirubin levels, number of Foxp3(+)CD4(+)CD25(+) regulatory T cells, expression of glucocorticoid-induced tumor necrosis factor receptor on T cell subgroups, histopathology of the hepatic graft and spleen cytotoxic T lymphocyte lytic activity were measured. In the acute rejection group, where donors were preconditioned with total body irradiation before liver transplantation, all recipients died between day 17 and day 21. On day 14, serum alanine aminotransferase increased significantly to (459.2±76.9) U L(-1), total bilirubin increased to (124.1±33.7) μmol L(-1) (Pliver graft, and thus affected the course of tolerance and induced acute rejection after liver transplantation.

  16. Increased health care utilization by survivors of childhood lymphoblastic leukemia is confined to those treated with cranial or total body irradiation: a case cohort study

    International Nuclear Information System (INIS)

    Previous studies have indicated that survivors of childhood acute lymphoblastic leukemia (ALL) have an increased morbidity measured in terms of health care utilization. However, earlier studies have several potentially important limitations. To overcome some of these, we investigated hospital contact rates, and predictors thereof, among 5-year survivors of ALL in a population-based setting, and compared them to a control cohort regarding outcome measures from a comprehensive nation-wide health register. All individuals diagnosed with ALL before the age of 18 in Southern Sweden during 1970–1999 and alive January 2007 (n = 213; male = 107) were identified through the Swedish Cancer Register. Each subject was matched to fifty controls, identified in the Swedish Population Register. All study subjects were linked to the National Hospital Register and detailed information was obtained on all hospital contacts (hospital admissions and outpatients visits) starting five years after cancer diagnosis, and the corresponding date for the controls, until 2009. The median follow-up among the 5-year survivors of ALL was 16 years (range 5–33), accruing a total of 3,527 person-years. Of the 213 5-year survivors, 105 (49.3%) had at least one hospital contact compared to 3,634 (34.1%) of the controls (p < 0.001). Survivors had more hospital contacts (3 [1–6] vs. 2 [1–4] contacts, p < 0.001) and more total days in hospital (6 [2–18] vs. 3 [1–7] days, p < 0.001) than the controls during the study period. Logistic regression analysis showed that survivors treated with cranial irradiation and/or total body irradiation (45% and 7%, respectively) had an increased risk of at least one hospital contact (OR 2.3, 95%CI; 1.5–3.6 and OR 11.0, 95%CI; 3.2–50.7, respectively), while there was no significant difference between the non-irradiated survivors and controls. We show that irradiated survivors of childhood ALL have an increased morbidity measured in terms of hospital

  17. Adoptive transfer of Mammaglobin-A epitope specific CD8 T cells combined with a single low dose of total body irradiation eradicates breast tumors.

    Science.gov (United States)

    Lerret, Nadine M; Rogozinska, Magdalena; Jaramillo, Andrés; Marzo, Amanda L

    2012-01-01

    Adoptive T cell therapy has proven to be beneficial in a number of tumor systems by targeting the relevant tumor antigen. The tumor antigen targeted in our model is Mammaglobin-A, expressed by approximately 80% of human breast tumors. Here we evaluated the use of adoptively transferred Mammaglobin-A specific CD8 T cells in combination with low dose irradiation to induce breast tumor rejection and prevent relapse. We show Mammaglobin-A specific CD8 T cells generated by DNA vaccination with all epitopes (Mammaglobin-A2.1, A2.2, A2.4 and A2.6) and full-length DNA in vivo resulted in heterogeneous T cell populations consisting of both effector and central memory CD8 T cell subsets. Adoptive transfer of spleen cells from all Mammaglobin-A2 immunized mice into tumor-bearing SCID/beige mice induced tumor regression but this anti-tumor response was not sustained long-term. Additionally, we demonstrate that only the adoptive transfer of Mammaglobin-A2 specific CD8 T cells in combination with a single low dose of irradiation prevents tumors from recurring. More importantly we show that this single dose of irradiation results in the down regulation of the macrophage scavenger receptor 1 on dendritic cells within the tumor and reduces lipid uptake by tumor resident dendritic cells potentially enabling the dendritic cells to present tumor antigen more efficiently and aid in tumor clearance. These data reveal the potential for adoptive transfer combined with a single low dose of total body irradiation as a suitable therapy for the treatment of established breast tumors and the prevention of tumor recurrence.

  18. Sex differences in the acoustic structure of vowel-like grunt vocalizations in baboons and their perceptual discrimination by baboon listeners

    Science.gov (United States)

    Rendall, Drew; Owren, Michael J.; Weerts, Elise; Hienz, Robert D.

    2004-01-01

    This study quantifies sex differences in the acoustic structure of vowel-like grunt vocalizations in baboons (Papio spp.) and tests the basic perceptual discriminability of these differences to baboon listeners. Acoustic analyses were performed on 1028 grunts recorded from 27 adult baboons (11 males and 16 females) in southern Africa, focusing specifically on the fundamental frequency (F0) and formant frequencies. The mean F0 and the mean frequencies of the first three formants were all significantly lower in males than they were in females, more dramatically so for F0. Experiments using standard psychophysical procedures subsequently tested the discriminability of adult male and adult female grunts. After learning to discriminate the grunt of one male from that of one female, five baboon subjects subsequently generalized this discrimination both to new call tokens from the same individuals and to grunts from novel males and females. These results are discussed in the context of both the possible vocal anatomical basis for sex differences in call structure and the potential perceptual mechanisms involved in their processing by listeners, particularly as these relate to analogous issues in human speech production and perception.

  19. Spontaneous disc degeneration in the baboon model: magnetic resonance imaging and histopathologic correlation.

    Science.gov (United States)

    Platenberg, R C; Hubbard, G B; Ehler, W J; Hixson, C J

    2001-10-01

    Degenerative disc disease is a major source of disability in humans. The baboon model is an excellent natural disease model to study comparable human disease, because baboons are relatively large (adult males 20-26 kg, adult females 12-17 kg), long-lived (30-45 years), well defined, easy to use, and closely related to humans. Published investigations with plain radiographs of disc degeneration in baboons indicated vertebral anatomy and changes that were remarkably similar to those seen in humans, and it would be valuable to determine if magnetic resonance imaging (MRI) and histopathologic evaluation would be useful methods for studying the model, as MRI allows multi-planar visualization of tissues without the use of intravenous contrast and it is superior for evaluating disc hydration, annulus tears, and herniations. The thoracolumbar junctions from 47 randomly selected baboons, ranging in age from 2 weeks to 34 years, were evaluated with MRI and histopathology. Excellent correlation with MRI was observed for changes in disc desiccation, height, and age (P discs seen by MRI were in baboons 14 years of age or older.

  20. Bomb-spike dating of a mummified baboon in Ludwig Cave, Namibia

    Directory of Open Access Journals (Sweden)

    Hodgins Greg

    2007-01-01

    Full Text Available In 1982 a mummified adult female baboon was discovered on a ledge in Ludwig Cave in Namibia. A toe bone was removed for dating in July 1995. AMS radiocarbon dating of bone collagen, tendon, and skin indicates a post-modern age. Application of the atomic bomb-spike calibration curve suggests death in late 1977 and an age at death of around 19 years. Baboons roost in the cave and the mummified female, along with a mummified juvenile male discovered in 2002 and three rotting corpses discovered in 1995, were probably chased by other baboons or by leopards down a ca. 6 m drop during the rainy season, and were unable to climb the steep and very slippery slope to escape. The large number of baboons trapped in the cave in less than 20 years, and mummification of two individuals on dry, dusty ledges in the cave, may explain why large numbers of baboon skeletons have been discovered in ancient bone breccias (up to 4 Ma old in a number of caves throughout Southern Africa.

  1. Human infants and baboons show the same pattern of handedness for a communicative gesture.

    Directory of Open Access Journals (Sweden)

    Helene Meunier

    Full Text Available To test the role of gestures in the origin of language, we studied hand preferences for grasping or pointing to objects at several spatial positions in human infants and adult baboons. If the roots of language are indeed in gestural communication, we expect that human infants and baboons will present a comparable difference in their pattern of laterality according to task: both should be more right-hand/left-hemisphere specialized when communicating by pointing than when simply grasping objects. Our study is the first to test both human infants and baboons on the same communicative task. Our results show remarkable convergence in the distribution of the two species' hand biases on the two kinds of tasks: In both human infants and baboons, right-hand preference was significantly stronger for the communicative task than for grasping objects. Our findings support the hypothesis that left-lateralized language may be derived from a gestural communication system that was present in the common ancestor of baboons and humans.

  2. New data on the toxicity and translocation of inhaled 239PuO2 in baboons

    International Nuclear Information System (INIS)

    In 1973-1974, baboons were exposed to a polydispersed aerosol of 239PuO2, prepared at 10000C, at the Commissariat a l'Energie Atomique in France. The data published in 1978 for these baboons were used by Bair et al (1980), for comparison with those obtained in beagles exposed to 239PuO2 at the Pacific Northwest Laboratory, USA. Since our 1978 publication, 8 baboons have died or were killed by euthanasia when moribund, and 11 were still alive when the present report was drafted. Two of the eight baboons died of lung squamous cell carcinoma at 2171 and 2528 days respectively. The remaining 6 died of fibrosis, interstitial pneumonia or diseases unrelated to Pu toxicity. The relationship observed in the eight baboons between initial lung burden and survival time shows that their lifespan was longer than expected from the data curve based on the findings for the first 1000 days. However, this increased survival time was not observed if the lifespan was expressed as a function of the average lung burden. (author)

  3. Comparison of acute mortality in baboons and dogs after inhalation of 239PuO2

    International Nuclear Information System (INIS)

    Results from experiments with baboons were compared with those from experiments with dogs to determine the relative sensitivity of the two species to acute mortality from inhaled 239PuO2. To assure a valid comparison of data developed at two laboratories, methodology differences were minimized by establishing a common pool of raw data, using the same computer programs to analyze the data, and standardizing assumptions regarding the calculation of radiation doses to lungs. Several comparison methods were used involving variations in estimating different parameters such as the concentration of plutonium in the lungs. Although nearly all comparisons suggested baboons were slightly more sensitive, none of the methods for comparing the relationship between dose and survival time showed consistently significant differences between baboons and dogs. Although the baboons were physiologically and morphologically immature when exposed to plutonium, whereas the dogs were mature, it was concluded that adult baboons and dogs are similarly sensitive to the acute effects of inhaled 239PuO2. Since only acute mortality was considered in this comparison, the results do not apply to possible late effects caused by much lower levels of plutonium than were used in these experiments

  4. S110, a novel decitabine dinucleotide, increases fetal hemoglobin levels in baboons (P. anubis

    Directory of Open Access Journals (Sweden)

    Banzon Virryan

    2010-10-01

    Full Text Available Abstract Background S110 is a novel dinucleoside analog that could have advantages over existing DNA methyltransferase (DNMT inhibitors such as decitabine. A potential therapeutic role for S110 is to increase fetal hemoglobin (HbF levels to treat β-hemoglobinopathies. In these experiments the effect of S110 on HbF levels in baboons and its ability to reduce DNA methylation of the γ-globin gene promoter in vivo were evaluated. Methods The effect of S110 on HbF and γ-globin promoter DNA methylation was examined in cultured human erythroid progenitors and in vivo in the baboon pre-clinical model. S110 pharmacokinetics was also examined in the baboon model. Results S110 increased HbF and reduced DNA methylation of the γ-globin promoter in human erythroid progenitors and in baboons when administered subcutaneously. Pharmacokinetic analysis was consistent with rapid conversion of S110 into the deoxycytosine analog decitabine that binds and depletes DNA. Conclusion S110 is rapidly converted into decitabine, hypomethylates DNA, and induces HbF in cultured human erythroid progenitors and the baboon pre-clinical model.

  5. Radioprotective and Anti-infertility Role of Resveratrol in Adult Male Rats Exposed to Whole-body ?-Irradiation

    International Nuclear Information System (INIS)

    GAMMA-Radiation destroys the process of spermatogenesis and even leads to male infertility. Moreover, seminal oxidative stress is known to end in per oxidative damage of the sperm plasma membrane and loss of its DNA integrity. Man infertility is defined as one year of regular and unprotected intercourse without conception. Plants provide a treatment option that is affordable and available for infertile couples and phyto therapy is an essential form of treatment in nowadays health system. Resveratrol (RSV) is a natural phytoalexin with a wide range of biological activities. Male rats were divided into six groups under investigation, each of six animals. Control group, two RSV groups which received intra gastric RSV (20 and 40 mg kg-1 day-1) for 7 weeks, irradiated group (2 Gy gamma-rays) and two irradiated and RSV groups which received the same preceding doses of RSV for the same period after 2 Gy gamma-rays exposure. Hormonal assay in serum; testosterone, follicular stimulating hormone (FSH) and prolactin were recorded for fertility assessment. The abnormalities occurred in the reproductive system of the irradiated rats were evaluated: Chromosomal aberration frequencies in spermatocytes, metaphase-1, sperm-head abnormalities and oxidative parameters in testes tissue; malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH) and nitric oxide (NO). Also, the findings suggest that the anti-fertility effect of melatonin was proved to be transient and reversed completely or in part at the end of the second recovery period. The results showed that RSV has a curative role against the oxidative stress involved by gamma-rays in the rats and showed a significant improvement on the male reproductive functions.

  6. A prospective study of the early clinical symptoms following a 2 Gy therapeutic whole-body irradiation; Etude prospective de la symptomatologie clinique precoce apres irradiation corporelle totale therapeutique de 2 Gy

    Energy Technology Data Exchange (ETDEWEB)

    Fizazi, K.; Chaillet, M.P.; Fourquet, A.; Jammet, P.; Cosset, J.M. [Institut Curie, 75 - Paris (France)

    1995-10-01

    Early human tolerance following total body irradiation (TBI) according to the dose received is still poorly known. Thirteen selected patients were prospectively evaluated for clinical side effects during the first 10 hours following a 2 Gy TBI prior to bone marrow transplantation. All of them but one were treated for haematological malignancies and were in clinical remission at the date of TBI. There were 10 males and 3 females, with a median age of 43 y (range 16*61) and a good performance status (WHO 0-1). They received granisetron (3 mg) injected intravenously 1 h before the time of TBI in order to prevent nausea and vomiting. The main symptoms consisted in drowsiness (69%), headache (62%), xerostomia (62%), nausea and vomiting (46%), anorexia (38%), parotid gland pain (23%) and abdominal pain (8%). Their intensity was always moderate, except for 2 patients who experimented severe vomiting. The incidence rate and the time-course of the symptoms of the prodromal phase may proved to be helpful for early clinical evaluation and triage of victims of an accidental irradiation. In particular, absence of fever at the 6{sup th} h after TBI supports the assumption of an estimated exposure dose below 2 Gy. (authors). 23 refs., 2 tabs.

  7. Olfactomedin-like 3 (OLFML3) gene expression in baboon and human ocular tissues: cornea, lens, uvea and retina

    Science.gov (United States)

    Rodríguez-Sánchez, Iràm Pablo; Garza-Rodríguez, Maria Lourdes; Mohamed-Noriega, Karim; Voruganti, Venkata Saroja; Tejero, Maria Elizabeth; Delgado-Enciso, Ivan; Ibave, Diana Cristina Perez; Schlabritz-Loutsevitch, Natalia E.; Mohamed-Noriega, Jibran; Martinez-Fierro, Margarita L; Reséndez-Pérez, Diana; Cole, Shelley A; Cavazos-Adame, Humberto; Comuzzie, Anthony G.; Mohamed-Hamsho, Jesús; Barrera-Saldaña, Hugo Alberto

    2013-01-01

    Background Olfactomedin-like is a polyfunctional polymeric glycoprotein. This family has at least four members. One member of this family is OLFML3, which is preferentially expressed in placenta but is also detected in other adult tissues including the liver and heart. However, the orthologous rat gene is expressed in the iris, sclera, trabecular meshwork, retina, and optic nerve. Methods OLFML3 amplification was performed by RT-PCR from human and baboon ocular tissues. The products were cloned and sequenced. Results We report OFML3 expression in human and baboon eye. The full CDS has 1221 bp, from which a OFR of 406 amino acid was obtained. The baboon OLFML3 gene nucleotidic sequence has 98%, and amino acidic 99% similarity with humans. Conclusions OLFML3 expression in human and baboon ocular tissues and its high similarity make the baboon a powerful model to deduce the physiological and/or metabolic function of this protein in the eye. PMID:23398349

  8. A non-Levy random walk in chacma baboons: what does it mean?

    Directory of Open Access Journals (Sweden)

    Cédric Sueur

    Full Text Available The Lévy walk is found from amoebas to humans and has been described as the optimal strategy for food research. Recent results, however, have generated controversy about this conclusion since animals also display alternatives to the Lévy walk such as the Brownian walk or mental maps and because movement patterns found in some species only seem to depend on food patches distribution. Here I show that movement patterns of chacma baboons do not follow a Lévy walk but a Brownian process. Moreover this Brownian walk is not the main process responsible for movement patterns of baboons. Findings about their speed and trajectories show that baboons use metal maps and memory to find resources. Thus the Brownian process found in this species appears to be more dependent on the environment or might be an alternative when known food patches are depleted and when animals have to find new resources.

  9. Male-driven grooming bouts in mixed-sex dyads of Kinda baboons (Papio kindae).

    Science.gov (United States)

    Weyher, Anna H; Phillips-Conroy, Jane E; Fourrier, Marc S; Jolly, Clifford J

    2014-01-01

    The behavior of the Central African Kinda baboon (Papio kindae) is not well documented. Having previously noted distinctive grooming behavior in several Kinda baboon populations, we investigated the topic more systematically in the Kafue National Park, Zambia. We recorded the duration and details of male-female dyadic interactions (approaches, withdrawals and time spent grooming) in the early morning and late afternoon. Such interactions were more often initiated by the male and terminated by the female partner. The male groomed the female more often, and longer, than she groomed him, regardless of the female's reproductive state or the presence of an infant. The bias towards male grooming was stronger in morning than evening interactions. These behaviors, whose function is not immediately obvious, and which are unlike those previously reported in baboons, further exemplify the distinctiveness of the taxon.

  10. Effects of Pre-exposure Mouse Pituitary with Low-dose 60Co γ-ray on Growth Hormone (GH) and Body Mass Induced by Subsequent High-dose Irradiation

    Institute of Scientific and Technical Information of China (English)

    ZhangHong; LiWenjian; JingXiaodong; LiuBing; MinFengling; ZhouQingming; XieYi

    2003-01-01

    The pituitary of the B6C3F1 hybrid strain mice were irradiated with 0.05 Gy of 60Co γ-ray as the pre-exposure dose (D1), and were then irradiated with 2 Gy of 60Co γ-ray as challenging irradiation dose (D2) at 4h after per-exposure. Body weight and serum growth hormone (GH) were measured at 35th day after irradiation. The results showed that irradiation of mouse testes with 2 Gy of 60Co γ-ray significantly diminished mousebody weight and level of serum GH (Table). Pre-exposure with a low-dose (0.05 Gy) of 60Co γ-ray significantly alleviated reductions of mouse body weight and level of serum GH induced by subsequent a high-dose (2 Gy) irradiation (Table). The data suggested that low-dose ionizing irradiation can induce adaptive responses to the harmful effects of pituitary by subsequent high-dose exposure.

  11. Effects of pharmacological manipulations on "demand" for food by baboons.

    Science.gov (United States)

    Foltin, R.W.

    1993-12-01

    In a study examining the effects of pharmacological manipulations on "demand" for food, responding of six adult male baboons (Papio c. anubis) was maintained under a fixed-ratio schedule of food reinforcement during daily 22h experimental sessions. Increasing the response requirement decreased daily food intake. Administration of anorectic drugs (amphetamine, fenfluramine, diethylpropion, phenmetrazine, phenylpropanolamine and mazindol) produced parallel dose-dependent downward shifts in responding at all response costs. In contrast, administration of the anxiolytic, diazepam, produced parallel dose-dependent upward shifts in responding at all response costs. Oral phencyclidine decreased intake during the first 8h of the session, but compensatory feeding later in the day eliminated this effect. Changes in pellet intake were fitted to a theoretical equation derived by Hursh et al. (1988) to describe changes in demand for a commodity. When responding increases as a result of increasing cost, demand is said to be inelastic, but when responding decreases as a result of increasing cost, demand is said to be elastic. Administration of anorectic drugs, while decreasing maximal intake at minimal cost, had no effect on the elasticity of demand for food. Similarly, diazepam increased maximal intake at minimal cost without affecting the elasticity of demand for food. The effect of anorectic drugs differs from the previously reported effects of caloric substitutes which increase the elasticity of demand for food. Thus, anorectic drugs do not function as caloric substitutes, in an economic sense, for food. PMID:11224228

  12. Wild chacma baboons (Papio ursinus) remember single foraging episodes.

    Science.gov (United States)

    Noser, Rahel; Byrne, Richard W

    2015-07-01

    Understanding animal episodic-like memory is important for tracing the evolution of the human mind. However, our knowledge about the existence and nature of episodic-like memory in non-human primates is minimal. We observed the behaviour of a wild male chacma baboon faced with a trade-off between protecting his stationary group from aggressive extra-group males and foraging among five out-of-sight platforms. These contained high-priority food at a time of natural food shortage. In 10 morning and eight evening trials, the male spontaneously visited the platforms in five and four different sequences, respectively. In addition, he interrupted foraging sequences at virtually any point on eight occasions, returning to the group for up to 2 h. He then visited some or all of the remaining platforms and prevented revisits to already depleted ones, apparently based on his memory for the previous foraging episode about food value, location, and time. Efficient use of memory allowed him to keep minimal time absent from his group while keeping food intake high. These findings support the idea that episodic-like memory offers an all-purpose solution to a wide variety of problems that require flexible, quick, yet precise decisions in situations arising from competition for food and mates in wild primates. PMID:25833223

  13. Helical tomotherapy targeting total bone marrow after total body irradiation for patients with relapsed acute leukemia undergoing an allogeneic stem cell transplant

    International Nuclear Information System (INIS)

    Background and purpose: To report our clinical experience in planning and delivering total marrow irradiation (TMI) after total body irradiation (TBI) in patients with relapsed acute leukemia undergoing an allogeneic stem-cell transplant (SCT). Materials and Methods: Patients received conventional TBI as 2 Gy BID/day for 3 days boosted the next day by TMI (2 Gy in a single fraction) and followed by cyclophosphamide (Cy) 60 mg/kg for 2 days. While TBI was delivered with linear accelerator, TMI was performed with helical tomotherapy (HT). Results: Fifteen patients were treated from July 2009 till May 2010, ten with acute myeloid leukemia, and five with acute lymphoid leukemia. At the time of radiotherapy eight patients were in relapse and seven in second or third complete remission (CR) after relapse. The donor was a matched sibling in 7 cases and an unrelated donor in 8 cases. Median organ-at-risk dose reduction with TMI ranged from 30% to 65% with the largest reduction (-50%-65%) achieved for brain, larynx, liver, lungs and kidneys. Target areas (bone marrow sites and spleen in selected cases) were irradiated with an optimal conformity and an excellent homogeneity. Follow-up is short ranging from 180 to 510 days (median 310 days). However, tolerance was not different from a conventional TBI-Cy. All patients treated with TBI/TMI reached CR after SCT. Three patients have died (2 for severe GvHD, 1 for infection) and 2 patients showed relapsed leukemia. Twelve patients are alive with ten survivors in clinical remission of disease. Conclusions: This study confirms the clinical feasibility of using HT to deliver TMI as selective dose boost modality after TBI. For patients with advanced leukemia targeted TMI after TBI may be a novel approach to increase radiation dose with low risk of severe toxicity.

  14. Distribution in pregnant mice of radioactivity after injection of 131I, and immunosuppressive effect by the whole body irradiation

    International Nuclear Information System (INIS)

    For the purpose of decreasing resistance to leprous bacilli, 100 μCi of 131I was injected subcutaneously to 2-3 week pregnant, dd-strain mice. Internal distribution of 131I was followed up by measuring radioactivity in each organ of parent mice (I-P) and fetal mice (I-F). 300 rad in all of 60Co was irradiated to 2-3 week pregnant mice (R-P) in two directions from the dorsal side of the abdomen. Immunosuppressive effect of the irradiation was evaluated in the parent mice and their offsprings (R-F) and compared with that in the 131I-treated mice using a skin graft method. It was shown that 131I of parent mice stayed in the uterus and was transmitted to their fetus through the placenta, and clarified that 131I which remained in parent mice was continually supplied to their infant mice through milk still after birth. These findings seem to explaine the result that I-F which had been affected continually by 131I had higher sensitivity to leprous bacilli than I-P. Immunosuppressive effect on a skin graft disclosed that the chief mechanisms of 131I are to decrease the function of the reticulo-endothelial system by iodine and to suppress cellular immunity by its radioactivity. The rejecting time for the mouse skin homograft in the untreated mouse was 8.8 days on the average, and the lymph node weight was 33 mg. The order of the duration in the graft survival was R-P>I-F>I-P>R-F> normal mice, while that of lymph node weights was completely inverse. Therefore, the immunosuppressive effect on I-P and I-F mice, when it is compared with normal mice, could be confirmed, and the I-F was said to be favorable further than to I-P when based on this immunity test by transplantation. (Ueda, J.)

  15. Chronic radiation injury with mice and dogs exposed to external whole-body irradiation at the Argonne National Laboratory

    International Nuclear Information System (INIS)

    This document describes studies on chronic radiation injury in experimental animals and the extrapolation of derived injury parameters to man. Most of the large studies have used mice given single, weekly, or continuous exposure to cobalt-60 gamma rays, or, more recently, single or weekly exposure to fission neutrons from the JANUS reactor. Primary measures of injury have been life shortening and the associated major pathological changes, particularly neoplastic diseases. Recent and ongoing studies compare the effects of extremely low neutron exposures with gamma irradiations delivered as a single dose or in 60 equal weekly increments. Total neutron doses range from 1 to 40 rads; gamma-ray doses range from 22.5 to 600 rads. Selected genetic studies are performed concurrently to provide a nearly complete matrix of somatic and genetic effects of these low exposures. Studies with the beagle have complemented those with mice and have shown a strong parallelism in the responses of the two species. Present exposures are at 0.3, 0.75, and 1.88 rads per day of continuous gamma irradiation to test a model for the prediction of life shortening in man which has evolved from Argonne's long-term studies. The dog offers the opportunity for longitudinal clinical evaluations that are not possible in the mouse, to develop a broader view of the neoplastic disease spectrum, and to study the mechanisms of radiation induction of leukemia. Diverse statistical approaches have been used to measure excess risk, dose-response functions, and rates of injury and repair. Actuarial statistical methods have been favored since they permit a more direct means of extrapolation to man. 50 refs., 4 figs

  16. Total body irradiation in a patient with fragile X syndrome for acute lymphoblastic leukemia in preparation for stem cell transplantation: A case report and literature review.

    Science.gov (United States)

    Collins, D T; Mannina, E M; Mendonca, M

    2015-10-01

    Fragile X syndrome (FXS) is a congenital disorder caused by expansion of CGG trinucleotide repeat at the 5' end of the fragile X mental retardation gene 1 (FMR1) on the X chromosome that leads to chromosomal instability and diminished serum levels of fragile X mental retardation protein (FMRP). Afflicted individuals often have elongated features, marfanoid habitus, macroorchidism and intellectual impairment. Evolving literature suggests the condition may actually protect from malignancy while chromosomal instability would presumably elevate the risk. Increased sensitivity to ionizing radiation should also be predicted by unstable sites within the DNA. Interestingly, in this report, we detail a patient with FXS diagnosed with acute lymphoblastic leukemia treated with induction followed by subsequent cycles of hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone) with a complete response who then was recommended to undergo peripheral stem cell transplantation. The patient underwent total body irradiation (TBI) as a component of his conditioning regimen and despite the concern of his clinicians, developed minimal acute toxicity and successful engraftment. The pertinent literature regarding irradiation of patients with FXS is also reviewed.

  17. Mitigating the Effects of Xuebijing Injection on Hematopoietic Cell Injury Induced by Total Body Irradiation with γ rays by Decreasing Reactive Oxygen Species Levels

    Directory of Open Access Journals (Sweden)

    Deguan Li

    2014-06-01

    Full Text Available Hematopoietic injury is the most common side effect of radiotherapy. However, the methods available for the mitigating of radiation injury remain limited. Xuebijing injection (XBJ is a traditional Chinese medicine used to treat sepsis in the clinic. In this study, we investigated the effects of XBJ on the survival rate in mice with hematopoietic injury induced by γ ray ionizing radiation (IR. Mice were intraperitoneally injected with XBJ daily for seven days after total body irradiation (TBI. Our results showed that XBJ (0.4 mL/kg significantly increased 30-day survival rates in mice exposed to 7.5 Gy TBI. This effect may be attributable to improved preservation of white blood cells (WBCs and hematopoietic cells, given that bone marrow (BM cells from XBJ-treated mice produced more granulocyte-macrophage colony forming units (CFU-GM than that in the 2 Gy/TBI group. XBJ also decreased the levels of reactive oxygen species (ROS by increasing glutathione (GSH and superoxide dismutase (SOD levels in serum and attenuated the increased BM cell apoptosis caused by 2 Gy/TBI. In conclusion, these findings suggest that XBJ enhances the survival rate of irradiated mice and attenuates the effects of radiation on hematopoietic injury by decreasing ROS production in BM cells, indicating that XBJ may be a promising therapeutic candidate for reducing hematopoietic radiation injury.

  18. {sup 18}F-FDG uptake by spleen helps rapidly predict the dose level after total body irradiation in a Tibetan minipig model

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yu Jue; Gu, Wei Wang [Southern Medical University, Department of Laboratory Animal Center, Guangzhou, Guangdong (China); Wu, Shao Jie; Guo, Kun Yuan; Chen, Chi [Southern Medical University, Department of Hematology, Zhujiang Hospital, Guangzhou, Guangdong (China); Xie, Qiang; Cai, Liang [Chinese People' s Armed Police Forces, Department of Oncology and PET/CT, Guangdong Provincial Corp Hospital, Guangzhou, Guangdong (China); Zou, Fei [Southern Medical University, School of Public Health and Tropical Medicine, Guangzhou, Guangdong (China)

    2012-09-15

    To investigate whether {sup 18}F- FDG uptake can be applied in dosimetry to facilitate the rapid and accurate evaluation of individual radiation doses after a nuclear accident. Forty-eight Tibetan minipigs were randomised into a control group (n = 3) and treatment groups (n = 45). {sup 18}F-FDG combined positron-emission tomography and computed tomography (PET/CT) were carried out before total body irradiation (TBI) and at 6, 24 and 72 h after receiving TBI doses ranging from 1 to 11 Gy. Spleen tissues and blood samples were also collected for histological examination, apoptosis and blood analysis. Mean standardised uptake values (SUVs) of the spleen showed significant differences between the experimental and the control groups. Spleen SUV at 6 h post-irradiation showed significant correlation with radiation dose; Spearman's correlation coefficient was 0.97 (P < 0.01). Histological observations showed that damage to the splenic lymphocyte became more severe with an increase in the radiation dose. Moreover, apoptosis was one of the major routes of splenic lymphocyte death, which was also confirmed by flow cytometry analysis. In the Tibetan minipig model, radiation doses have a close relationship with the {sup 18}F-FDG uptake of the spleen. This finding suggests that {sup 18}F-FDG PET/CT may be useful for the rapid detection of individual radiation doses. (orig.)

  19. Autologous stem cell transplantation following high-dose whole-body irradiation of dogs - influence of cell number and fractionation regimes

    International Nuclear Information System (INIS)

    The acute radiation syndrome after a single dose of 1600 R (approx. 12-14 Gy in body midline) and after fractionated irradiation with 2400 R (approx. 18-20 Gy) was studied with regard to fractionation time and to the number of bone marrow cells infused. The acute radiation syndrome consisted of damage to the alimentary tract and of damage to the hemopoietic system. Damage of hemopoiesis was reversible in dogs which had been given a sufficient amount of hemopoietic cells. Furthermore changes in skin and in the mucous membranes occurred. Hemopoietic recovery following infusion of various amounts of bone marrow was investigated in dogs which were irradiated with 2400 R within 7 days. Repopulation of bone marrow as well as rise of leukocyte and platelet counts in the peripheral blood was taken as evidence of complete hemopoietic reconstitution. The results indicate that the acute radiation syndrom following 2400 R TBI and autologous BMT can be controlled by fractionation of this dose within 5 or 7 days. The acute gastrointestinal syndrome is aggravated by infusion of a lesser amount of hemopoietic cells. However, TBI with 2400 R does not require greater numbers of hemopoietic cells for restoration of hemopoiesis. Thus, the hemopoiesis supporting tissue can not be damage by this radiation dose to an essential degree. Longterm observations have not revealed serious late defects which could represent a contraindication to the treatment of malignent diseases with 2400 R of TBI. (orig./MG)

  20. Effects of whole body γ irradiation on skin wound cells and the repaired-promoting action of W11-a12

    International Nuclear Information System (INIS)

    Objective: To study the effects of 6 Gy whole body γ irradiation on components of wound cells and the repair-promoting action of W11-a12, an extract from Periplaneta americana. Methods: After mice were received 6 Gy gamma ray irradiation, the area of healing range in wound cross section, the cellular infiltration of wound and the content of basic fibroblast growth factor (bFGF) in wound epithelial cells were observed and the healing-promoting effect of W11-a12 on the radiation-impaired wound was investigated. Results: The area of healing range in cross section was decreased, various infiltrated cells were all inhibited by radiation, but the range of inhibition was more or less different, and the descending order of severity was as follows: macrophages, vascular endothelial cells, fibroblasts and epithelial cells. The content of bFGF in epithelial cells was decreased. W11-a12 had beneficial heal-promoting effect on radiation-impaired wound: it increased cellular infiltration and promoted synthesis and secretion of bFGF in epithelial cells. Conclusion: The depletion of wound cells is mainly responsible for the healing deficits of radiation-impaired skin wound and W11-a12 enhances cell migration and proliferation and promotes synthesis and secretion of bFGF in epithelial cells

  1. A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia

    International Nuclear Information System (INIS)

    We retrospectively compared the outcome in patients in the EBMT database transplanted for acute leukaemia from January 1987 to January 1994 who received busulphan and cyclophosphamide (BU/CY) as a pretransplant regimen versus those who received cyclophosphamide and total-body irradiation (CY-TBI). The patients were matched for type of transplant (autologous bone marrow transplantation (ABMT) versus allogenic (BMT)), diagnosis (acute lymphoblast leukaemia (ALL) ora cute myeloid leukaemia (AML)), status (early first complete remission, CR-1) versus intermediate (second or later remission, first relapse)), age, FAB classification for AML, prevention of graft-versus-host disease and year of transplantation. BU/CY and CY/TBI as pretransplant regimens gave similar results in all situations, except ABMT for ALL intermediate stages with more than 2 years from diagnosis to transplantation, where a lower RI and a higher LFS were associated with CY/TBI. (author)

  2. Clinical evaluation of bone marrow transplantation using total body irradiation and induction chemotherapy. Treatment results during twelve years at our hospital and some problems on the therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Toshiki; Koga, Sukehiko; Kikukawa, Kaoru; Okamoto, Masataka; Miyazaki, Hitoshi; Kojima, Hiroshi; Esaki, Kohji [Fujita Health Univ., Toyoake, Aichi (Japan). School of Medicine

    2000-10-01

    We performed sixty patients with hematological malignancies the total body irradiation prior to bone marrow transplantation (TBI-BMT) from 1988 to 2000. We delivered our each patient hyperfractionated TBI consisting of 2 fractions of 3 Gy per day for 2 consecutive days following induction chemotherapy. It proved that TBI-BMT was a valuable treatment method for hematological malignancies which have poor prognosis. About the cumulative survival rate, patients of first remission were better outcome than patients beyond second remission. However, the therapy remained some problems which were the prophylaxis of GVHD for HLA-matched unrelated recipients. And we have to consider a new maintenance procedure to prevent relapse from transplanted donor cell. (author)

  3. Bomb-spike dating of a mummified baboon in Ludwig Cave, Namibia

    OpenAIRE

    Hodgins Greg; Brook George A.; Marais Eugene

    2007-01-01

    In 1982 a mummified adult female baboon was discovered on a ledge in Ludwig Cave in Namibia. A toe bone was removed for dating in July 1995. AMS radiocarbon dating of bone collagen, tendon, and skin indicates a post-modern age. Application of the atomic bomb-spike calibration curve suggests death in late 1977 and an age at death of around 19 years. Baboons roost in the cave and the mummified female, along with a mummified juvenile male discovered in 2002 and three rotting corpses discovered i...

  4. High Prevalence of Antibodies against the Bacterium Treponema pallidum in Senegalese Guinea Baboons (Papio papio.

    Directory of Open Access Journals (Sweden)

    Sascha Knauf

    Full Text Available The bacterium Treponema pallidum is known to cause syphilis (ssp. pallidum, yaws (ssp. pertenue, and endemic syphilis (ssp. endemicum in humans. Nonhuman primates have also been reported to be infected with the bacterium with equally versatile clinical manifestations, from severe skin ulcerations to asymptomatic. At present all simian strains are closely related to human yaws-causing strains, an important consideration for yaws eradication. We tested clinically healthy Guinea baboons (Papio papio at Parc National Niokolo Koba in south eastern Senegal for the presence of anti-T. pallidum antibodies. Since T. pallidum infection in this species was identified 50 years ago, and there has been no attempt to treat non-human primates for infection, it was hypothesized that a large number of West African baboons are still infected with simian strains of the yaws-bacterium. All animals were without clinical signs of treponematoses, but 18 of 20 (90% baboons tested positive for antibodies against T. pallidum based on treponemal tests. Yet, Guinea baboons seem to develop no clinical symptoms, though it must be assumed that infection is chronic or comparable to the latent stage in human yaws infection. The non-active character is supported by the low anti-T. pallidum serum titers in Guinea baboons (median = 1:2,560 versus serum titers that are found in genital-ulcerated olive baboons with active infection in Tanzania (range of medians among the groups of initial, moderate, and severe infected animals = 1:15,360 to 1:2.097e+7. Our findings provide evidence for simian infection with T. pallidum in wild Senegalese baboons. Potentially, Guinea baboons in West Africa serve as a natural reservoir for human infection, as the West African simian strain has been shown to cause sustainable yaws infection when inoculated into humans. The present study pinpoints an area where further research is needed to support the currently on-going second WHO led yaws eradication

  5. SU-E-T-515: Field-In-Field Compensation Technique Using Multi-Leaf Collimator to Deliver Total Body Irradiation (TBI) Dose

    Energy Technology Data Exchange (ETDEWEB)

    Lakeman, T [The State University of New York at Buffalo (United States); Wang, IZ [The State University of New York at Buffalo (United States); Roswell Park Cancer Institute, Buffalo, NY (United States)

    2014-06-01

    Purpose: Total body irradiation (TBI) uses large parallel-opposed radiation fields to suppress the patient's immune system and eradicate the residual cancer cells in preparation of recipient for bone marrow transplant. The manual placement of lead compensators has been used conventionally to compensate for the varying thickness through the entire body in large-field TBI. The goal of this study is to pursue utilizing the modern field-in-field (FIF) technique with the multi-leaf collimator (MLC) to more accurately and efficiently deliver dose to patients in need of TBI. Method: Treatment plans utilizing the FIF technique to deliver a total body dose were created retrospectively for patients for whom CT data had been previously acquired. Treatment fields include one pair of opposed open large fields (collimator=45°) with a specific weighting and a succession of smaller fields (collimator=90°) each with their own weighting. The smaller fields are shaped by moving MLC to block the sections of the patient which have already received close to 100% of the prescribed dose. The weighting factors for each of these fields were calculated using the attenuation coefficient of the initial lead compensators and the separation of the patient in different positions in the axial plane. Results: Dose-volume histograms (DVH) were calculated for evaluating the FIF compensation technique. The maximum body doses calculated from the DVH were reduced from the non-compensated 179.3% to 148.2% in the FIF plans, indicating a more uniform dose with the FIF compensation. All calculated monitor units were well within clinically acceptable limits and exceeded those of the original lead compensation plan by less than 50 MU (only ~1.1% increase). Conclusion: MLC FIF technique for TBI will not significantly increase the beam on time while it can substantially reduce the compensator setup time and the potential risk of errors in manually placing lead compensators.

  6. SU-E-T-515: Field-In-Field Compensation Technique Using Multi-Leaf Collimator to Deliver Total Body Irradiation (TBI) Dose

    International Nuclear Information System (INIS)

    Purpose: Total body irradiation (TBI) uses large parallel-opposed radiation fields to suppress the patient's immune system and eradicate the residual cancer cells in preparation of recipient for bone marrow transplant. The manual placement of lead compensators has been used conventionally to compensate for the varying thickness through the entire body in large-field TBI. The goal of this study is to pursue utilizing the modern field-in-field (FIF) technique with the multi-leaf collimator (MLC) to more accurately and efficiently deliver dose to patients in need of TBI. Method: Treatment plans utilizing the FIF technique to deliver a total body dose were created retrospectively for patients for whom CT data had been previously acquired. Treatment fields include one pair of opposed open large fields (collimator=45°) with a specific weighting and a succession of smaller fields (collimator=90°) each with their own weighting. The smaller fields are shaped by moving MLC to block the sections of the patient which have already received close to 100% of the prescribed dose. The weighting factors for each of these fields were calculated using the attenuation coefficient of the initial lead compensators and the separation of the patient in different positions in the axial plane. Results: Dose-volume histograms (DVH) were calculated for evaluating the FIF compensation technique. The maximum body doses calculated from the DVH were reduced from the non-compensated 179.3% to 148.2% in the FIF plans, indicating a more uniform dose with the FIF compensation. All calculated monitor units were well within clinically acceptable limits and exceeded those of the original lead compensation plan by less than 50 MU (only ~1.1% increase). Conclusion: MLC FIF technique for TBI will not significantly increase the beam on time while it can substantially reduce the compensator setup time and the potential risk of errors in manually placing lead compensators

  7. High-dose total-body irradiation and autologous marrow reconstitution in dogs: dose-rate-related acute toxicity and fractionation-dependent long-term survival

    International Nuclear Information System (INIS)

    Beagle dogs treated by total-body irradiation (TBI) were given autologous marrow grafts in order to avoid death from marrow toxicity. Acute and delayed non-marrow toxicities of high single-dose (27 dogs) and fractionated TBI (20 dogs) delivered at 0.05 or 0.1 Gy/min were compared. Fractionated TBI was given in increments of 2 Gy every 6 hr for three increments per day. Acute toxicity and early mortality (<1 month) at identical total irradiation doses were comparable for dogs given fractionated or single-dose TBI. With single-dose TBI, 14, 16, and 18 Gy, respectively, given at 0.05 Gy/min, 0/5, 5/5, and 2/2 dogs died from acute toxicity; with 10, 12, and 14 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 5/5 dogs died acutely. With fractionated TBI, 14 and 16 Gy, respectively, given at 0.1 Gy/min, 1/5, 4/5, and 2/2 dogs died auctely. Early deaths were due to radiation enteritis with or without associated septicemia (29 dogs; less than or equal to Day 10). Three dogs given 10 Gy of TBI at 0.1 Gy/min died from bacterial pneumonia; one (Day 18) had been given fractionated and two (Days 14, 22) single-dose TBI. Fifteen dogs survived beyond 1 month; eight of these had single-dose TBI (10-14 Gy) and all died within 7 months of irradiation from a syndrome consisting of hepatic damage, pancreatic fibrosis, malnutrition, wasting, and anemia. Seven of the 15 had fractionated TBI, and only one (14 Gy) died on Day 33 from hepatic failure, whereas 6 (10-14 Gy) are alive and well 250 to 500 days after irradiation. In conclusion, fractionated TBI did not offer advantages over single-dose TBI with regard to acute toxicity and early mortality; rather, these were dependent upon the total dose of TBI. The total acutely tolerated dose was dependent upon the exposure rate; however, only dogs given fractionated TBI became healthy long-term survivors

  8. Changes of arterial blood pressure, heart rate, internal body temperature, and blood acido-basic balance in the unanaesthetized rabbit following whole-body gamma irradiation at a mean absorbed dose of 250 rads

    Energy Technology Data Exchange (ETDEWEB)

    Dufour, R.; Court, L.

    1973-09-01

    The general effects of whole-body gamma -irradiation at a mean absorbed dose of 250 rads were studied simultaneously in the unanaesthetized rabbit for 48 hours. They occurred early, with the following characteristics: arterial blood pressure decreased steadily as early as the 2nd hour and reached its minimum value on the 5th hour with a decrease of about 14%; it remained low during the following two days. Heart rate increased during the first hour, was the highest by the end of the second hour, and resumed normal value on the 24th hour. Internal body temperature increased during the 1st hour and was maximum by the end of the 2nd hour, with a mean increase of 1.2 deg C; hyperthermia steadily decreased between the 4th and the 6th hours and had completely disappeared by the 24th hour. Respiratory alkalosis is shown in the acido-basic balance by a raise of pH, a decrease of PCO/sub 2/ and arterial blood bicarbonates. These various changes seem to indicate a double origin, both central and peripheral. (FR)

  9. Inferential reasoning and modality dependent discrimination learning in olive baboons (Papio hamadryas anubis).

    Science.gov (United States)

    Schmitt, Vanessa; Fischer, Julia

    2009-08-01

    Apes use inferential reasoning by exclusion to locate food both in the visual and auditory domain. To test whether olive baboons (Papio hamadryas anubis) show similar abilities as the apes object choice experiments with differing information about food located in 1 of 2 cups were conducted in the visual and auditory modality. Although all baboons (N = 7) were able to locate the reward when they had previously seen it, they failed to make use of auditory cues or arbitrary acoustic signals. When only partial information was given (i.e., only 1 cup was opened) 4 of the baboons were apparently able to infer the location of the reward by reasoning, whereas the other 3 may have adopted an alternative strategy ("avoid the empty cup"). In addition, 3 of the baboons were able to use arbitrary visual markers to locate the food reward. The results suggest that inferential reasoning is not restricted to apes but is shared with Old World monkeys. Furthermore, they also highlight some important differences in the processing of auditory versus visual information in operant conditioning settings.

  10. The average baboon brain: MRI templates and tissue probability maps from 89 individuals.

    Science.gov (United States)

    Love, Scott A; Marie, Damien; Roth, Muriel; Lacoste, Romain; Nazarian, Bruno; Bertello, Alice; Coulon, Olivier; Anton, Jean-Luc; Meguerditchian, Adrien

    2016-05-15

    The baboon (Papio) brain is a remarkable model for investigating the brain. The current work aimed at creating a population-average baboon (Papio anubis) brain template and its left/right hemisphere symmetric version from a large sample of T1-weighted magnetic resonance images collected from 89 individuals. Averaging the prior probability maps output during the segmentation of each individual also produced the first baboon brain tissue probability maps for gray matter, white matter and cerebrospinal fluid. The templates and the tissue probability maps were created using state-of-the-art, freely available software tools and are being made freely and publicly available: http://www.nitrc.org/projects/haiko89/ or http://lpc.univ-amu.fr/spip.php?article589. It is hoped that these images will aid neuroimaging research of the baboon by, for example, providing a modern, high quality normalization target and accompanying standardized coordinate system as well as probabilistic priors that can be used during tissue segmentation. PMID:26975558

  11. Methoxychlor and its metabolites inhibit growth and induce atresia of baboon antral follicles.

    Science.gov (United States)

    Gupta, Rupesh K; Aberdeen, Graham; Babus, Janice K; Albrecht, Eugene D; Flaws, Jodi A

    2007-08-01

    Methoxychlor (MXC), an organochlorine pesticide, inhibits growth and induces atresia of antral follicles in rodents. MXC metabolites, mono-OH MXC (mono-OH) and bis-OH MXC (HPTE), are thought to be more toxic than the parent compound. Although studies have examined effects of MXC in rodents, few studies have evaluated the effects of MXC in primates. Therefore, the present study tested the hypothesis that MXC, mono-OH, and HPTE inhibit growth and induce atresia of baboon antral follicles. To test this hypothesis, antral follicles were isolated from adult baboon ovaries and cultured with vehicle (dimethylsulfoxide; DMSO), MXC (1-100 micro g/ml), mono-OH (0.1-10 micro g/ml), or HPTE (0.1-10 micro g/ml) for 96 hr. Growth was monitored at 24 hr intervals. After culture, follicles were processed for histological evaluation of atresia. MXC, mono-OH, and HPTE significantly inhibited follicular growth and increased atresia compared to DMSO. Moreover, the adverse effects of MXC and its metabolites on growth and atresia in baboon antral follicles were observed at lower (100-fold) doses than those causing similar effects in rodents. These data suggest that MXC and its metabolites inhibit growth and induce atresia of baboon antral follicles, and that primate follicles are more sensitive to MXC than rodent follicles.

  12. Carbon-11 labelled ketamine-synthesis, distribution in mice and PET studies in baboons

    Energy Technology Data Exchange (ETDEWEB)

    Shiue, C.-Y.; Vallabhahosula, Shankar; Wolf, Alfred P.; Dewey, Stephen L.; Fowler, Joanna S.; Schlyer, David J.; Arnett, Carroll D.; Zhou Yiguo

    1997-02-01

    No-carrier-added (NCA)[{sup 11}C]({+-})-ketamine (2a) and its enantiomers (+)-2b and (-)-2c were synthesized by methylation of the corresponding norketamine (1a-c) with [{sup 11}C]H{sub 3}I in an overall radiochemical yield of 20% (EOB) with specific activities of 0.35-0.45 Ci/{mu}mole at EOB in a synthesis time of 40 min from EOB. Compound 2a was metabolized rapidly in mouse brain and labeled metabolites appeared in baboon plasma. PET studies of compounds 2a-c in a baboon showed that influx of compounds 2a-c into the brain was high for the first few min but radioactivity then declined rapidly. Although the retention of radioactivity in the baboon striatum was not significantly different for 2a-c 20 min post-injection, graphical analysis of time-activity data for each enantiomer and for the racemate in baboon striatum suggested that (+)-ketamine may interact with receptors slightly more effectively than its (-)-enantiomer or racemate. However, due to its rapid metabolism in the brain and a similar uptake in the striatum and cerebellum, [{sup 11}C]ketamine may not be an ideal tracer for studying NMDA receptor with PET.

  13. Sarcoglycan complex in masseter and sternocleidomastoid muscles of baboons: an immunohistochemical study

    Directory of Open Access Journals (Sweden)

    G. Cutroneo

    2015-06-01

    Full Text Available The sarcoglycan complex consists of a group of single-pass transmembrane glycoproteins that are essential to maintain the integrity of muscle membranes. Any mutation in each sarcoglycan gene causes a series of recessive autosomal dystrophin-positive muscular dystrophies. Negative fibres for sarcoglycans have never been found in healthy humans and animals. In this study, we have investigated whether the social ranking has an influence on the expression of sarcoglycans in the skeletal muscles of healthy baboons. Biopsies of masseter and sternocleidomastoid muscles were processed for confocal immunohistochemical detection of sarcoglycans. Our findings showed that baboons from different social rankings exhibited different sarcoglycan expression profiles. While in dominant baboons almost all muscles were stained for sarcoglycans, only 55% of muscle fibres showed a significant staining. This different expression pattern is likely to be due to the living conditions of these primates. Sarcoglycans which play a key role in muscle activity by controlling contractile forces may influence the phenotype of muscle fibres, thus determining an adaptation to functional conditions. We hypothesize that this intraspecies variation reflects an epigenetic modification of the muscular protein network that allows baboons to adapt progressively to a different social status.

  14. Rank and grooming reciprocity among females in a mixed-sex group of captive hamadryas baboons

    NARCIS (Netherlands)

    Leinfelder, I.; Vries, Han de; Deleu, R.; Nelissen, M.

    2001-01-01

    In a mixed-sex, captive group of hamadryas baboons (Papio hamadryas hamadryas) we investigated whether female grooming relationships are affected by their dominance ranks. Seyfarths [1977] grooming for support model and Barrett et al.s [1999] biological market model both predict that in primate grou

  15. The Application of Flow Cytometry to Examine Damage Clearance in Stem Cells From Whole-Body Irradiated Mice

    Energy Technology Data Exchange (ETDEWEB)

    Marples, Brian; Kovalchuk, Olga; McGonagle, Michele; Martinez, Alvaro; Wilson, George, D.

    2010-02-26

    The bone marrow contains many types of cells. Approximately 1-2% of these cells are critical for life, these are the so-called ‘bone marrow stem cells’ which divide indefinitely to produce platelets, red blood cells and white blood cells. Death of the bone marrow stem cells results in a diminished ability of the organism to make new blood cell components and can be fatal without medical intervention, such as a bone marrow transplant. Bone marrow stem cells are considered to be particularly sensitive to radiation injury. Therefore, it is important to understand how these cells response to total body radiation exposure and how these cells can be protected from radiation damage. The aim of this project was to determine if these critical cells in the bone marrow are susceptible to short-term and long-term injury after a whole-body exposure to a sub-lethal low dose of ionizing radiation. The overall aims were to determine if the extent of injury produced by the sub-lethal radiation exposure would be cleared from the stem cells and therefore present no long- term genetic risk to the organism, or if the radiation injury persisted and had an adverse long-term consequences for the cell genome. This research question is of interest in order to define the risks to exposed persons after occupational, accidental or terrorism-related sub-lethal low-dose radiation exposures. The novel aspect of this project was the methodology used to obtain the bone marrow stem cell-like cells and examining the outcomes of sub-lethal low-dose radiation in a mammalian animal model. Four radiation treatments were used: single treatments of 0.01Gy, 0.1 Gy, 1 Gy and ten treatments of 0.1 Gy given over 10 days. Bone marrow stem cell-like cells were then harvested 6 hours, 24 hours and 24 days later. The levels of radiation-induced cell death, damage to DNA and permanent changes to cellular DNA were measured in the isolated stem cell-like cells after each radiation treatment and time point and

  16. [French experience in paediatric total body irradiation: A study from the radiotherapy committee of the Société française des cancers de l'enfant (SFCE)].

    Science.gov (United States)

    Demoor-Goldschmidt, C; Supiot, S; Claude, L; Carrie, C; Mazeron, R; Helfré, S; Alapetite, C; Jouin, A; Coche, B; Padovani, L; Muracciole, X; Bernier, V; Vigneron, C; Noël, G; Leseur, J; Le Prisé, É; Stefan, D; Habrand, J L; Kerr, C; Bondiau, P Y; Ruffier, A; Chapet, S; Mahé, M A

    2016-06-01

    A survey was conducted in 2015 in France on the care of children in radiotherapy services. We present the results for total body irradiation in children, a specific technique of radiation treatment, which needs dedicated controls for this particular population. Of the 17 centres interviewed, 16 responded, and 13 practiced total body irradiation. Patients are positioned in lateral decubitus in 11 centres and supine/prone in two centres. Doses used for total body irradiation in myeloablative bone marrow transplantation are the same in all centres (12Gy); treatments are always fractionated. Lung shielding is positioned to limit the dose at an average of 8Gy with extremes ranging from 6 to 10Gy. The shape of the shieldings varies depending on departments' protocol, with a smaller size in case of mediastinal mass. Four centres have experience of total body irradiation under general anaesthesia, despite twice-daily fractions. In total, practice is relatively homogeneous throughout France and is inspired by the knowledge obtained in adults.

  17. Time-course of micronucleated erythrocytes in response to whole-body gamma irradiation in a model mammalian species, the bank vole (Clethrionomys glareolus, Schreber).

    Science.gov (United States)

    Smolich, Igor I; Savina, Natalya V; Ryabokon, Nadezhda I

    2011-01-01

    The time course of the formation of micronucleated polychromatic (MNPCEs) and normochromatic erythrocytes (MNNCEs) in the bone marrow of the bank vole (Clethrionomys glareolus, Schreber), a model mouse-like species, was studied using the standard micronucleus test at 0, 6, 12, 18, 24, 30, 36 and 48 hr following whole-body acute γ-irradiation at a dose of 0.5 Gy. Based on the existing literature on laboratory mice, it was suggested that such a dose will not have significant effect on erythroid cell proliferation in the bank vole and hence on the time course of the rise of micronucleated cells. In total, ∼905,000 polychromatic (PCEs) and normochromatic erythrocytes (NCEs) from 82 adult bank voles were analyzed. Although the mean frequencies of MNNCEs were too low to allow for the correct assessment of their time course, an analysis of PCEs showed an increasing rate of MNPCE appearance at 6 hr that reached a maximum at 18-24 hr after irradiation and subsequently decreased. Because the kinetics of MNPCEs reflects the process of erythropoiesis, the current results regarding the time points of appearance of radiation-induced MNPCEs provide the first information on the prolongation of one of the terminal stages of erythrocyte formation in bank vole specimens, namely the stage of maturation of PCEs from erythroblasts. Moreover, the observed time-course data, as well as the low-background frequencies of MNPCEs and characteristic level of PCEs response to radiation, showed similarities between the two model species: bank vole (this study) and laboratory mice (literature data).

  18. Pleistocene aridification cycles shaped the contemporary genetic architecture of Southern African baboons.

    Directory of Open Access Journals (Sweden)

    Riashna Sithaldeen

    Full Text Available Plio-Pleistocene environmental change influenced the evolutionary history of many animal lineages in Africa, highlighting key roles for both climate and tectonics in the evolution of Africa's faunal diversity. Here, we explore diversification in the southern African chacma baboon Papio ursinus sensu lato and reveal a dominant role for increasingly arid landscapes during past glacial cycles in shaping contemporary genetic structure. Recent work on baboons (Papio spp. supports complex lineage structuring with a dominant pulse of diversification occurring 1-2Ma, and yet the link to palaeoenvironmental change remains largely untested. Phylogeographic reconstruction based on mitochondrial DNA sequence data supports a scenario where chacma baboon populations were likely restricted to refugia during periods of regional cooling and drying through the Late Pleistocene. The two lineages of chacma baboon, ursinus and griseipes, are strongly geographically structured, and demographic reconstruction together with spatial analysis of genetic variation point to possible climate-driven isolating events where baboons may have retreated to more optimum conditions during cooler, drier periods. Our analysis highlights a period of continuous population growth beginning in the Middle to Late Pleistocene in both the ursinus and the PG2 griseipes lineages. All three clades identified in the study then enter a state of declining population size (Nef through to the Holocene; this is particularly marked in the last 20,000 years, most likely coincident with the Last Glacial Maximum. The pattern recovered here conforms to expectations based on the dynamic regional climate trends in southern Africa through the Pleistocene and provides further support for complex patterns of diversification in the region's biodiversity.

  19. Comparative analysis of acute leukemia hematopoietic stem cell transplantation in single body irradiation and fractionated total body irradiation mode%急性白血病造血干细胞移植前单次全身照射与分次全身照射模式的对比分析

    Institute of Scientific and Technical Information of China (English)

    赵奇; 马骁; 周菊英; 秦颂兵

    2015-01-01

    目的 对比单次全身照射(single total body irradiation,STBI)8 Gy和分次全身照射(fractionated total body irradiation,FTBI) 12 Gy两种不同的全身照射模式,探讨合适的造血干细胞移植前全身照射(total body irradiation,TBI)方案.方法 回顾性分析苏州大学附属第一医院2003-04-05-2010-07-10确诊的160例急性白血病患者资料,所有患者均接受移植前TBI预处理,70例患者进行STBI 8 Gy照射,90例患者行FTBI 12 Gy照射,2次/d,2 Gy/次,连续照射3d,2次间隔6h,比较不同方案的急性期毒副作用、造血重建时间、移植存活率、间质性肺炎(interstitial pneumonia,IP)和急性移植物抗宿主病(acute graft-versus host disease,aGVHD)的发生情况.结果 STBI 8 Gy照射组和FTBI 12 Gy照射组胃肠道反应(恶心、呕吐)发生率分别为61.4%(43/70)和40.0%(36/90),x2=7.223,P=0.006;口腔黏膜炎分别为71.4%(50/70)和45.6%(41/90),x2=10.746,P=0.001;腮腺炎分别为64.3%(45/70)和48.9%(44/90),x2=3.782,P=0.037.两组上述毒副作用相比差异有统计学意义.STBI 8 Gy组中性粒细胞造血重建时间、血小板造血重建时间、移植存活率和Ⅲ~Ⅳ度aGVHD的发生率分别为13.84士3.84、16.69±4.70、95.7%(67/70)和14.3%(10/70),FTBI12 Gy组分别为14.31±3.79、17.43±5.26、95.6%(86/90)和16.7%(15/90),两组相比差异无统计学意义.IP发生率FTBI 12 Gy照射组为4.4%(4/90),STBI 8 Gy照射组为14.3%(10/70).多因素Logistic回归分析显示,IP的发生与照射方案和剂量率有关,与性别、年龄、干细胞来源和腮腺炎无关.结论 FTBI 12 Gy方案与STBI 8 Gy方案相比可减轻急性期毒副作用,减轻肺部放射损伤,而造血重建时间、移植存活率和aGVHD的发生两种方案相比差异无统计学意义.采用FTBI 12 Gy方案,吸收剂量率控制在4~6 cGy/min,肺中位剂量控制在<8 Gy,对比STBI 8 Gy方案是安全、有效的造血干细胞移植预处理方案.%OBJECTIVE To

  20. Dosimetric analysis for photon and electron beams in Whole body irradiation; Analisis dosimetrico para haces de fotones y electrones en irradiacion corporal total

    Energy Technology Data Exchange (ETDEWEB)

    Hurtado G, M. [Posgrado. Fisica Medica Radiologica. Universidad Nacional de Colombia, Bogota. Instituto Nacional de Cancerologia. Instituto Regional de Cancer de la Orinoquia. Hospital Regional de Villavicencio, Meta (Colombia)

    1998-12-31

    To initiate the Whole body irradiation as an alternative for the treatment of the hematological diseases, leukemia and assistant for the osseous marrow transplantation, it may be taken account the application of International Protocols about control and quality assurance. It is established the intercomparison by the different dosimetric methods: cylindrical ionization chambers and parallel plane, radiographic emulsion film, semiconductor diodes (Mosfet transistors) and TLD-100 thermoluminescent crystals, obtained measurements for 140 x 140 cm{sup 2} fields and large distances 340 cm respect conventional fields in Radiotherapy. The in vitro dosimetry was realized at the Universal Anthropomorphic puppet Alderson Rando basically with the cylindrical crystals (1 mm diameter) of TLD-100 lithium fluoride. It was obtained the dose value with a 0.6 cm{sup 3} cylindrical ionization chamber and the Farmer electrometer for Whole body irradiation (ICT) with photons for electrons and were obtained values with the Markus plane parallel camera. Knowing the dose rate value to the source-surface distance DFS= 80 cm, it was calibrated the crystals with the reference radiation beam of {sup 60} Co for obtaining the response curve: Dose vs. Tl lecture. It was characterized the 10 % of the total population for 300 crystals for applying the statistics corresponding. The luminescence curve obtained of Gaussian form was considered satisfactory by its stability during the pre-anneal lecture and anneal process, getting the main peak lecture at 300 Centigrade according to assigned parameters at lecture equipment TLD Harshaw model 4500. The results indicate the functional dependence with the distance DFS= 340 cm for the following depth PPD, the relations TMR and TPR, the TAR is not calculated by the increment of the dispersion in air. The penumbra increment indicates an increase of the radiation field respect of luminous field. The dispersion angle q{sub 1} respect at the field central axis

  1. Road and Street Centerlines, Baboon Peak, Published in 2007, 1:24000 (1in=2000ft) scale, Iron County.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — , published at 1:24000 (1in=2000ft) scale, was produced all or in part from Other information as of 2007. It is described as 'Baboon Peak'. The extent of these data...

  2. Experimental infections of baboons (Papio spp. and vervet monkeys (Cercopithecus aethiops with Trichinella zimbabwensis and successful treatment with ivermectin

    Directory of Open Access Journals (Sweden)

    S. Mukaratirwa

    2008-08-01

    Full Text Available Experimental Trichinella zimbabwensis infections were established in three baboons (Papios p.and four vervet monkeys (Cercopithecuase thiops and the clinical-pathological manifestations assessed. The infected animals showed clinical signs ranging from fever, diarrhoea, periorbitaol edema and muscular pain in varying degrees. One baboon became blind due to the infection. Levels of creatinine phosphokinase and lactated ehydrogenase increased to reach a peak on Day 42 post-infection(pifor both baboons and monkeys. Blood parameters such as packed cell volume, levels of red blood cells and white blood cells did not change significantly from the normal ranges except for the levels of eosinophils which peaked above the normal ranges at Day 28 and 56 pi in baboons and at Day 56 pi in monkeys.

  3. Brucella papionis sp. nov., isolated from baboons (Papio spp.).

    Science.gov (United States)

    Whatmore, Adrian M; Davison, Nicholas; Cloeckaert, Axel; Al Dahouk, Sascha; Zygmunt, Michel S; Brew, Simon D; Perrett, Lorraine L; Koylass, Mark S; Vergnaud, Gilles; Quance, Christine; Scholz, Holger C; Dick, Edward J; Hubbard, Gene; Schlabritz-Loutsevitch, Natalia E

    2014-12-01

    Two Gram-negative, non-motile, non-spore-forming coccoid bacteria (strains F8/08-60(T) and F8/08-61) isolated from clinical specimens obtained from baboons (Papio spp.) that had delivered stillborn offspring were subjected to a polyphasic taxonomic study. On the basis of 16S rRNA gene sequence similarities, both strains, which possessed identical sequences, were assigned to the genus Brucella. This placement was confirmed by extended multilocus sequence analysis (MLSA), where both strains possessed identical sequences, and whole-genome sequencing of a representative isolate. All of the above analyses suggested that the two strains represent a novel lineage within the genus Brucella. The strains also possessed a unique profile when subjected to the phenotyping approach classically used to separate species of the genus Brucella, reacting only with Brucella A monospecific antiserum, being sensitive to the dyes thionin and fuchsin, being lysed by bacteriophage Wb, Bk2 and Fi phage at routine test dilution (RTD) but only partially sensitive to bacteriophage Tb, and with no requirement for CO2 and no production of H2S but strong urease activity. Biochemical profiling revealed a pattern of enzyme activity and metabolic capabilities distinct from existing species of the genus Brucella. Molecular analysis of the omp2 locus genes showed that both strains had a novel combination of two highly similar omp2b gene copies. The two strains shared a unique fingerprint profile of the multiple-copy Brucella-specific element IS711. Like MLSA, a multilocus variable number of tandem repeat analysis (MLVA) showed that the isolates clustered together very closely, but represent a distinct group within the genus Brucella. Isolates F8/08-60(T) and F8/08-61 could be distinguished clearly from all known species of the genus Brucella and their biovars by both phenotypic and molecular properties. Therefore, by applying the species concept for the genus Brucella suggested by the ICSP

  4. Fetal baboon sex specific outcomes in adipocyte differentiation at 0.9 gestation in response to moderate maternal nutrient reduction

    OpenAIRE

    Tchoukalova, Yourka D.; Krishnapuram, Rashmi; White, Ursula A.; Burk, David; Fang, Xiaobing; Nijland, Mark J.; Nathanielsz, Peter W.

    2013-01-01

    Objective To investigate in vitro adipocyte differentiation in baboon fetuses in response to reduced maternal nutrition. Design Cross-sectional comparison of adipocyte differentiation in normally grown fetuses and fetuses of pregnant baboons fed 70% control global diet from 30 days of pregnancy to term. Subjects Control (CTR) fetuses of ad libitum fed mothers (5 females and 5 males) and fetuses of mothers fed the 70% global diet eaten by CTR (MNR, 5 females and 5 males). The expression of gen...

  5. Histological changes in the penis of the Chacma baboon--a model to study aging penile vascular impotence.

    Science.gov (United States)

    Bornman, M S; du Plessis, D J; Ligthelm, A J; van Tonder, H J

    1985-01-01

    Light and scanning electron microscopy was performed on the penes of Chacma baboons to establish their suitability as animal model for studying vascular impotence. Analogous aging penile vascular changes were found in man, and a fibrous trabeculopathy with intertrabecular senechiae was demonstrated. Considering the corresponding changes, the Chacma baboon could thus be regarded suitable for studying the pathophysiology of aging penile vascular changes. PMID:3981618

  6. Cortisol responses to immobilization with Telazol or ketamine in baboons (Papio cynocephalus/anubis) and rhesus macaques (Macaca mulatta)

    OpenAIRE

    Bentson, K L; Capitanio, J P; Mendoza, S P

    2003-01-01

    Little is known about the influence of Telazol on cortisol or of anesthetic agents on immunological measures, and reports of ketamine's effect on cortisol are inconsistent. We measured effects of Telazol, ketamine and blood sampling on cortisol in male rhesus macaques and male savannah baboons. We also obtained leukocyte counts in the macaques. In macaques, Telazol reduced cortisol in the morning but not in the afternoon; ketamine had no effect on cortisol in these animals. In baboons, cortis...

  7. Hunting, food subsidies, and mesopredator release: the dynamics of crop-raiding baboons in a managed landscape

    OpenAIRE

    Taylor, RA; Ryan, SJ; Brashares, JS; Johnson, LR

    2016-01-01

    The establishment of protected areas or parks has become an important tool for wildlife conservation. However, frequent occurrences of human-wildlife conflict at the edges of these parks can undermine their conservation goals. Many African protected areas have experienced concurrent declines of apex predators alongside increases in both baboon abundance and the density of humans living near the park boundary. Baboons then take excursions outside of the park to raid crops for food, conflicting...

  8. SU-C-213-04: Application of Depth Sensing and 3D-Printing Technique for Total Body Irradiation (TBI) Patient Measurement and Treatment Planning

    International Nuclear Information System (INIS)

    Purpose: To develop and validate an innovative method of using depth sensing cameras and 3D printing techniques for Total Body Irradiation (TBI) treatment planning and compensator fabrication. Methods: A tablet with motion tracking cameras and integrated depth sensing was used to scan a RANDOTM phantom arranged in a TBI treatment booth to detect and store the 3D surface in a point cloud (PC) format. The accuracy of the detected surface was evaluated by comparison to extracted measurements from CT scan images. The thickness, source to surface distance and off-axis distance of the phantom at different body section was measured for TBI treatment planning. A 2D map containing a detailed compensator design was calculated to achieve uniform dose distribution throughout the phantom. The compensator was fabricated using a 3D printer, silicone molding and tungsten powder. In vivo dosimetry measurements were performed using optically stimulated luminescent detectors (OSLDs). Results: The whole scan of the anthropomorphic phantom took approximately 30 seconds. The mean error for thickness measurements at each section of phantom compare to CT was 0.44 ± 0.268 cm. These errors resulted in approximately 2% dose error calculation and 0.4 mm tungsten thickness deviation for the compensator design. The accuracy of 3D compensator printing was within 0.2 mm. In vivo measurements for an end-to-end test showed the overall dose difference was within 3%. Conclusion: Motion cameras and depth sensing techniques proved to be an accurate and efficient tool for TBI patient measurement and treatment planning. 3D printing technique improved the efficiency and accuracy of the compensator production and ensured a more accurate treatment delivery

  9. SU-C-213-04: Application of Depth Sensing and 3D-Printing Technique for Total Body Irradiation (TBI) Patient Measurement and Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Lee, M; Suh, T [Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Research Institute of Biomedical Engineering, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of); Han, B; Xing, L [Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA (United States); Jenkins, C [Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA (United States); Department of Mechanical Engineering, Stanford University, Palo Alto, CA (United States)

    2015-06-15

    Purpose: To develop and validate an innovative method of using depth sensing cameras and 3D printing techniques for Total Body Irradiation (TBI) treatment planning and compensator fabrication. Methods: A tablet with motion tracking cameras and integrated depth sensing was used to scan a RANDOTM phantom arranged in a TBI treatment booth to detect and store the 3D surface in a point cloud (PC) format. The accuracy of the detected surface was evaluated by comparison to extracted measurements from CT scan images. The thickness, source to surface distance and off-axis distance of the phantom at different body section was measured for TBI treatment planning. A 2D map containing a detailed compensator design was calculated to achieve uniform dose distribution throughout the phantom. The compensator was fabricated using a 3D printer, silicone molding and tungsten powder. In vivo dosimetry measurements were performed using optically stimulated luminescent detectors (OSLDs). Results: The whole scan of the anthropomorphic phantom took approximately 30 seconds. The mean error for thickness measurements at each section of phantom compare to CT was 0.44 ± 0.268 cm. These errors resulted in approximately 2% dose error calculation and 0.4 mm tungsten thickness deviation for the compensator design. The accuracy of 3D compensator printing was within 0.2 mm. In vivo measurements for an end-to-end test showed the overall dose difference was within 3%. Conclusion: Motion cameras and depth sensing techniques proved to be an accurate and efficient tool for TBI patient measurement and treatment planning. 3D printing technique improved the efficiency and accuracy of the compensator production and ensured a more accurate treatment delivery.

  10. Single administration of p2TA (AB103, a CD28 antagonist peptide, prevents inflammatory and thrombotic reactions and protects against gastrointestinal injury in total-body irradiated mice.

    Directory of Open Access Journals (Sweden)

    Salida Mirzoeva

    Full Text Available The goal of this study was to elucidate the action of the CD28 mimetic peptide p2TA (AB103 that attenuates an excessive inflammatory response in mitigating radiation-induced inflammatory injuries. BALB/c and A/J mice were divided into four groups: Control (C, Peptide (P; 5 mg/kg of p2TA peptide, Radiation (R; total body irradiation with 8 Gy γ-rays, and Radiation + Peptide (RP; irradiation followed by p2TA peptide 24 h later. Gastrointestinal tissue damage was evaluated by analysis of jejunum histopathology and immunohistochemistry for cell proliferation (Cyclin D1 and inflammation (COX-2 markers, as well as the presence of macrophages (F4/80. Pro-inflammatory cytokines IL-6 and KC as well as fibrinogen were quantified in plasma samples obtained from the same mice. Our results demonstrated that administration of p2TA peptide significantly reduced the irradiation-induced increase of IL-6 and fibrinogen in plasma 7 days after exposure. Seven days after total body irradiation with 8 Gy of gamma rays numbers of intestinal crypt cells were reduced and villi were shorter in irradiated animals compared to the controls. The p2TA peptide delivery 24 h after irradiation led to improved morphology of villi and crypts, increased Cyclin D1 expression, decreased COX-2 staining and decreased numbers of macrophages in small intestine of irradiated mice. Our study suggests that attenuation of CD28 signaling is a promising therapeutic approach for mitigation of radiation-induced tissue injury.

  11. Subclinical pulmonary function defects following autologous and allogeneic bone marrow transplantation: relationship to total body irradiation and graft-versus-host disease

    International Nuclear Information System (INIS)

    Pulmonary function results pre- and post-transplant, to a maximum of 4 years, were analyzed in 98 patients with haematological disorders undergoing allogeneic (N = 53) or autologous bone marrow transplantation (N = 45) between 1982 and 1988. All received similar total body irradiation based regimens ranging from 9.5 Gy as a single fraction to 14.4 Gy fractionated. FEV1/FVC as a measure of airway obstruction showed little deterioration except in patients experiencing graft-versus-host disease in whom statistically significant obstructive ventilatory defects were evident by 6 months post-transplant (p less than 0.01). These defects appeared to be permanent. Restrictive ventilatory defects, as measured by reduction in TLC, and defects in diffusing capacity (DLCO and KCO) were also maximal at 6 months post-transplant (p less than 0.01). Both were related, at least in part, to the presence of GVHD (p less than 0.01) or use of single fraction TBI with absorbed lung dose of 8.0 Gy (p less than 0.05). Fractionated TBI resulted in less marked restricted ventilation and impaired gas exchange, which reverted to normal by 2 years, even when the lung dose was increased from 11.0 Gy to between 12.0 and 13.5 Gy. After exclusion of patients with GVHD (30% allografts) there was no significant difference in pulmonary function abnormalities between autograft and allograft recipients

  12. Comparison of outcomes of allogeneic transplantation for chronic myeloid leukemia with cyclophosphamide in combination with intravenous busulfan, oral busulfan, or total body irradiation.

    Science.gov (United States)

    Copelan, Edward A; Avalos, Belinda R; Ahn, Kwang Woo; Zhu, Xiaochun; Gale, Robert Peter; Grunwald, Michael R; Hamadani, Mehdi; Hamilton, Betty K; Hale, Gregory A; Marks, David I; Waller, Edmund K; Savani, Bipin N; Costa, Luciano J; Ramanathan, Muthalagu; Cahn, Jean-Yves; Khoury, H Jean; Weisdorf, Daniel J; Inamoto, Yoshihiro; Kamble, Rammurti T; Schouten, Harry C; Wirk, Baldeep; Litzow, Mark R; Aljurf, Mahmoud D; van Besien, Koen W; Ustun, Celalettin; Bolwell, Brian J; Bredeson, Christopher N; Fasan, Omotayo; Ghosh, Nilanjan; Horowitz, Mary M; Arora, Mukta; Szer, Jeffrey; Loren, Alison W; Alyea, Edwin P; Cortes, Jorge; Maziarz, Richard T; Kalaycio, Matt E; Saber, Wael

    2015-03-01

    Cyclophosphamide (Cy) in combination with busulfan (Bu) or total body irradiation (TBI) is the most commonly used myeloablative conditioning regimen in patients with chronic myeloid leukemia (CML). We used data from the Center for International Bone Marrow Transplantation Research to compare outcomes in adults who underwent hematopoietic cell transplantation for CML in first chronic phase after myeloablative conditioning with Cy in combination with TBI, oral Bu, or intravenous (i.v.) Bu. Four hundred thirty-eight adults received human leukocyte antigen (HLA)-matched sibling grafts and 235 received well-matched grafts from unrelated donors (URD) from 2000 through 2006. Important differences existed between the groups in distribution of donor relation, exposure to tyrosine kinase inhibitors, and year of transplantation. In multivariate analysis, relapse occurred less frequently among patients receiving i.v. Bu compared with TBI (relative risk [RR], .36; P = .022) or oral Bu (RR, .39; P = .028), but nonrelapse mortality and survival were similar. A significant interaction was detected between donor relation and the main effect in leukemia-free survival (LFS). Among recipients of HLA-identical sibling grafts, but not URD grafts, LFS was better in patients receiving i.v. Bu (RR, .53; P = .025) or oral Bu (RR, .64; P = .017) compared with TBI. In CML in first chronic phase, Cy in combination with i.v. Bu was associated with less relapse than TBI or oral Bu. LFS was better after i.v. or oral Bu compared with TBI.

  13. Opportunistic virus DNA levels after pediatric stem cell transplantation: serostatus matching, anti-thymocyte globulin, and total body irradiation are additive risk factors.

    Science.gov (United States)

    Kullberg-Lindh, C; Mellgren, K; Friman, V; Fasth, A; Ascher, H; Nilsson, S; Lindh, M

    2011-04-01

    Viral opportunistic infections remain a threat to survival after stem cell transplantation (SCT). We retrospectively investigated infections caused by cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus type 6 (HHV6), or adenovirus (AdV) during the first 6-12 months after pediatric SCT. Serum samples from 47 consecutive patients were analyzed by quantitative real-time polymerase chain reaction assay. DNAemia at any time point occurred for CMV in 47%, for EBV in 45%, for HHV6 in 28%, and for AdV in 28%. Three patients (6.3%) died of CMV-, EBV-, or AdV-related complications 4, 9, and 24 weeks after SCT, respectively, representing 21% of total mortality. These 3 cases were clearly distinguishable by DNAemia increasing to high levels. Serum positivity for CMV immunoglobulin G in either recipient or donor at the time of SCT, total body irradiation, and anti-thymocyte globulin conditioning were independent risk factors for high CMV or EBV DNA levels. We conclude that DNAemia levels help to distinguish significant viral infections, and that surveillance and prophylactic measures should be focused on patients with risk factors in whom viral complications rapidly can become fatal.

  14. Safety and efficacy of total body irradiation, cyclophosphamide, and cytarabine as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with acute lymphoblastic leukemia.

    Science.gov (United States)

    Mori, Takehiko; Aisa, Yoshinobu; Kato, Jun; Yamane, Akiko; Nakazato, Tomonori; Shigematsu, Naoyuki; Okamoto, Shinichiro

    2012-04-01

    Disease relapse still greatly interferes with the success of allogeneic hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia (ALL). This study retrospectively evaluated the long-term safety and efficacy of a conditioning regimen consisting of total body irradiation (TBI; 12 Gy), cyclophosphamide (CY; 60 mg kg(-1) , two doses), and high-dose cytarabine (Ara-C; 2 g m(-2) ; four doses) for patients with ALL. Fifty-five patients (median age: 31-years old) were evaluated. Stem cells were from human leukocyte antigen-identical siblings in 22 patients and from alternative donors in 33. There were no cases of early death before engraftment, and 100-day transplant-related mortality was 7.3%. With a median follow-up period of 9.6 years, 5-year overall and disease-free survival were 63.2% (95% CI: 46.5-79.9%) and 63.6% (95% CI: 47.1-80.1%) in patients with complete remission, respectively, both of which were significantly higher than the values of 27.3% (95% CI: 8.7-46.0%) and 22.7% (95% CI: 5.3-40.1%) for patients in advanced stages (P < 0.01). These results suggest that TBI and CY (TBI-CY) plus Ara-C could be a feasible and effective conditioning regimen for adult patients with ALL both in remission and in advanced stages, and a future study to compare this combination therapy with TBI-CY is required.

  15. Effect of a non lethal whole-body gamma irradiation on the spontaneous and evoked electroencephalographic activities of the adult rabbit

    International Nuclear Information System (INIS)

    The whole of the experimental methods described (animal preparation, achievement of a precise physiological technique, dosimetry, biological information processing) allowed us to follow the changes for 15 days in the spontaneous and evoked electroencephalogram activities of rabbits submitted to a non-lethal 400 rads whole-body gamma-irradiation. Behavioural troubles, changes in the arousal state and the spontaneous electrical activity of the neo-cortex and hippocampus were noticed constantly together with an enhanced cortical excitability, and the appearance of elements of the paroxystic series sometimes in contrast with a general decrease in amplitude. After a visual stimulus the general morphology of evoked activities at the level of the primary visual areas and hippocampus was unchanged, but enhanced latencies and delays, less systematic modifications in amplitudes seemed to show out a direct effect of radiations on the nervous system and sensorial activities; these troubles seemed to occur independently from the basic electrical activity. As a whole, the changes observed were usually transitory and varied with each individual. Finally an assumption is made to explain the mechanism of arousal troubles and the general evolution of spontaneous electrical activity in the brain. (author)

  16. Effects of total body irradiation-based conditioning allogenic sem cell transplantation for pediatric acute leukemia: A single-institution study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Moo; Choi, Eun Kyung; Kim, Jong Hoon [Dept.of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); and others

    2014-09-15

    To evaluate the effects of total body irradiation (TBI), as a conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT), in pediatric acute leukemia patients. From January 2001 to December 2011, 28 patients, aged less than 18 years, were treated with TBI-based conditioning for allo-SCT in our institution. Of the 28 patients, 21 patients were diagnosed with acute lymphoblastic leukemia (ALL, 75%) and 7 were diagnosed with acute myeloid leukemia (AML, 25%). TBI was completed 4 days or 1 day before stem cell infusion. Patients underwent radiation therapy with bilateral parallel opposing fields and 6-MV X-rays. The Kaplan-Meier method was used to calculate survival outcomes. The 2-year event-free survival and overall survival rates were 66% and 56%, respectively (71.4% and 60.0% in AML patients vs. 64.3% and 52.4% in ALL patients, respectively). Treatment related mortality rate were 25%. Acute and chronic graft-versus-host disease was a major complication; other complications included endocrine dysfunction and pulmonary complications. Common complications from TBI were nausea (89%) and cataracts (7.1%). The efficacy and toxicity data in this study of TBI-based conditioning to pediatric acute leukemia patients were comparable with previous studies. However, clinicians need to focus on the acute and chronic complications related to allo-SCT.

  17. Allogeneic bone marrow transplantation with conditioning regimen to total body irradiation + thiotepa + melphalan for 35 patients with high-risk leukemia

    International Nuclear Information System (INIS)

    Thirty-five children with high-risk leukemia received an allogeneic bone marrow transplantation (BMT) following a pre-conditioning regimen consisting of total body irradiation, thiotepa and melphalan. Twenty-one patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 acute undifferentiated leukemia, 2 acute mixed lineage leukemia, 2 myelodysplastic syndrome and 2 juvenile chronic myeloid leukemia. Sixteen patients received BMT while in complete remission (CR), but 19 were not in CR. Eighteen patients received transplants from HLA-matched related donors, 15 from unrelated donors and 2 from HLA-mismatched related donors. Cyclosporin±methotrexate was used for graft-versus-host disease (GVHD) prophylaxis in the BMTs from related donors and tacrolimus±prednisolone in the BMTs from unrelated donors. Transplant-related death occurred in 12 patients; 5 acute GVHD, 4 infections (3 fungal infections, 1 Cytomegalovirus pneumonia), 1 intracranial haemorrhage and 2 chronic GVHD. Relapses were observed in 6 patients (69, 168, 175, 222, 275 and 609 days post BMT). Event-free survival rate at 2 years is 38.1% in CR patients and 36.9% in nonCR patients. (author)

  18. A Phase II Trial of Adjuvant Low-dose Total Body Irradiation in non-Hodgkin's Lymphoma Patients following Standard CHOP

    Energy Technology Data Exchange (ETDEWEB)

    Safwat, Akmal; Bayoumi, Yasser; Akkoush, Hany; Mahmoud, Hossam K. [Aarhus Univ. Hospital (Denmark). Medical Oncology Dept.

    2004-07-01

    Because survival results achieved in aggressive NHL with the standard CHOP are not very satisfactory, we investigated adding adjuvant low-dose total body irradiation (LTBI) to standard CHOP in a phase II trial. Thirty-six patients were included between September 1999 and September 2001. All patients were in documented complete remission (CR) after the end of their standard CHOP. LTBI started 4-6 weeks following the last CHOP course and was given in two courses, each with 4 daily fractions of 0.2 Gy, separated by 2 weeks of rest. Patients with bulky disease received involved-field radiotherapy on initial bulky sites starting 4-6 weeks after the last LTBI fraction. Primary end points were disease-free survival (DFS) and overall survival (OS) and the secondary end point was toxicity. The toxicities of LTBI were temporary thrombocytopenia and leucopenia (requiring no transfusions or treatment with growth factors). The 3-year DFS was 61%{+-}9% and the overall survival was 87{+-}6%. Univariate analysis showed time to achieve CR, and whether the patient got LTBI-induced haematological toxicity to be 2 significant prognostic factors affecting DFS. The use of adjuvant LTBI in patients with aggressive NHL in CR after standard chemotherapy is a feasible, non-toxic treatment that is worthy of testing in a future phase III trial.

  19. The estimation of lung dose from mid-perineum ionization chamber measurements in total body irradiations: A quality control check on dose delivery

    International Nuclear Information System (INIS)

    A series of patients (eleven males and eight females) receiving total body irradiation prior to bone marrow transplantation was monitored during treatment by recording the dose from an ionization chamber placed between the thighs in the mid-perineal region. The treatment was delivered by opposed lateral 6 MV photon beams. The patient was encompassed by the radiation field with the maximum collimator opening at a distance of 3.49 m from the X-ray focus to the patient mid-line. An analysis was made of the measured dose and the calculated percentage average lung dose for each patient in the series to seek a correlation between measured doses and patients' anatomical data so that estimates of delivered lung doses could be made. Whilst a global factor can be applied to measured dose to predict lung dose, it is concluded that perineal dose measurements distal to the region where dose is prescribed (mean lung dose) are sub-optimal for checks on target dose delivery. Entrance and exit dose measurements at the level of dose prescription (in the thorax) are preferable for more accurate predictions and quality control checks. 6 refs., 1 tab., 2 figs

  20. The estimation of lung dose from mid-perineum ionization chamber measurements in total body irradiations: A quality control check on dose delivery

    Energy Technology Data Exchange (ETDEWEB)

    Cross, P. [Saint Vincent`s Hospital, Darlinghurst, NSW (Australia)

    1995-11-01

    A series of patients (eleven males and eight females) receiving total body irradiation prior to bone marrow transplantation was monitored during treatment by recording the dose from an ionization chamber placed between the thighs in the mid-perineal region. The treatment was delivered by opposed lateral 6 MV photon beams. The patient was encompassed by the radiation field with the maximum collimator opening at a distance of 3.49 m from the X-ray focus to the patient mid-line. An analysis was made of the measured dose and the calculated percentage average lung dose for each patient in the series to seek a correlation between measured doses and patients` anatomical data so that estimates of delivered lung doses could be made. Whilst a global factor can be applied to measured dose to predict lung dose, it is concluded that perineal dose measurements distal to the region where dose is prescribed (mean lung dose) are sub-optimal for checks on target dose delivery. Entrance and exit dose measurements at the level of dose prescription (in the thorax) are preferable for more accurate predictions and quality control checks. 6 refs., 1 tab., 2 figs.

  1. Allogeneic bone marrow transplantation with conditioning regimen to total body irradiation + thiotepa + melphalan for 35 patients with high-risk leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Yumura-Yagi, Keiko; Inoue, Masami; Okamura, Takayuki [Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi (Japan)] [and others

    1997-06-01

    Thirty-five children with high-risk leukemia received an allogeneic bone marrow transplantation (BMT) following a pre-conditioning regimen consisting of total body irradiation, thiotepa and melphalan. Twenty-one patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 acute undifferentiated leukemia, 2 acute mixed lineage leukemia, 2 myelodysplastic syndrome and 2 juvenile chronic myeloid leukemia. Sixteen patients received BMT while in complete remission (CR), but 19 were not in CR. Eighteen patients received transplants from HLA-matched related donors, 15 from unrelated donors and 2 from HLA-mismatched related donors. Cyclosporin{+-}methotrexate was used for graft-versus-host disease (GVHD) prophylaxis in the BMTs from related donors and tacrolimus{+-}prednisolone in the BMTs from unrelated donors. Transplant-related death occurred in 12 patients; 5 acute GVHD, 4 infections (3 fungal infections, 1 Cytomegalovirus pneumonia), 1 intracranial haemorrhage and 2 chronic GVHD. Relapses were observed in 6 patients (69, 168, 175, 222, 275 and 609 days post BMT). Event-free survival rate at 2 years is 38.1% in CR patients and 36.9% in nonCR patients. (author)

  2. A single whole-body low dose X-irradiation does not affect L1, B1 and IAP repeat element DNA methylation longitudinally.

    Directory of Open Access Journals (Sweden)

    Michelle R Newman

    Full Text Available The low dose radioadaptive response has been shown to be protective against high doses of radiation as well as aging-induced genomic instability. We hypothesised that a single whole-body exposure of low dose radiation would induce a radioadaptive response thereby reducing or abrogating aging-related changes in repeat element DNA methylation in mice. Following sham or 10 mGy X-irradiation, serial peripheral blood sampling was performed and differences in Long Interspersed Nucleic Element 1 (L1, B1 and Intracisternal-A-Particle (IAP repeat element methylation between samples were assessed using high resolution melt analysis of PCR amplicons. By 420 days post-irradiation, neither radiation- or aging-related changes in the methylation of peripheral blood, spleen or liver L1, B1 and IAP elements were observed. Analysis of the spleen and liver tissues of cohorts of untreated aging mice showed that the 17-19 month age group exhibited higher repeat element methylation than younger or older mice, with no overall decline in methylation detected with age. This is the first temporal analysis of the effect of low dose radiation on repeat element methylation in mouse peripheral blood and the first to examine the long term effect of this dose on repeat element methylation in a radiosensitive tissue (spleen and a tissue fundamental to the aging process (liver. Our data indicate that the methylation of murine DNA repeat elements can fluctuate with age, but unlike human studies, do not demonstrate an overall aging-related decline. Furthermore, our results indicate that a low dose of ionising radiation does not induce detectable changes to murine repeat element DNA methylation in the tissues and at the time-points examined in this study. This radiation dose is relevant to human diagnostic radiation exposures and suggests that a dose of 10 mGy X-rays, unlike high dose radiation, does not cause significant short or long term changes to repeat element or global DNA

  3. A Prospective Phase 2 Trial of Reirradiation With Stereotactic Body Radiation Therapy Plus Cetuximab in Patients With Previously Irradiated Recurrent Squamous Cell Carcinoma of the Head and Neck

    Energy Technology Data Exchange (ETDEWEB)

    Vargo, John A. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Ferris, Robert L. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Ohr, James [Division Medical Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Clump, David A. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Davis, Kara S.; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T. [Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Bauman, Julie E.; Gibson, Michael K. [Division Medical Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Branstetter, Barton F. [Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Heron, Dwight E., E-mail: herond2@umpc.edu [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States)

    2015-03-01

    Purpose: Salvage options for unresectable locally recurrent, previously irradiated squamous cell carcinoma of the head and neck (rSCCHN) are limited. Although the addition of reirradiation may improve outcomes compared to chemotherapy alone, significant toxicities limit salvage reirradiation strategies, leading to suboptimal outcomes. We therefore designed a phase 2 protocol to evaluate the efficacy of stereotactic body radiation therapy (SBRT) plus cetuximab for rSCCHN. Methods and Materials: From July 2007 to March 2013, 50 patients >18 years of age with inoperable locoregionally confined rSCCHN within a previously irradiated field receiving ≥60 Gy, with a Zubrod performance status of 0 to 2, and normal hepatic and renal function were enrolled. Patients received concurrent cetuximab (400 mg/m{sup 2} on day −7 and then 250 mg/m{sup 2} on days 0 and +8) plus SBRT (40-44 Gy in 5 fractions on alternating days over 1-2 weeks). Primary endpoints were 1-year locoregional progression-free survival and National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 graded toxicity. Results: Median follow-up for surviving patients was 18 months (range: 10-70). The 1-year local PFS rate was 60% (95% confidence interval [CI]: 44%-75%), locoregional PFS was 37% (95% CI: 23%-53%), distant PFS was 71% (95% CI: 54%-85%), and PFS was 33% (95% CI: 20%-49%). The median overall survival was 10 months (95% CI: 7-16), with a 1-year overall survival of 40% (95% CI: 26%-54%). At last follow-up, 69% died of disease, 4% died with disease, 15% died without progression, 10% were alive without progression, and 2% were alive with progression. Acute and late grade 3 toxicity was observed in 6% of patients respectively. Conclusions: SBRT with concurrent cetuximab appears to be a safe salvage treatment for rSCCHN of short overall treatment time.

  4. Mitochondrial genome analyses suggest multiple Trichuris species in humans, baboons, and pigs from different geographical regions

    DEFF Research Database (Denmark)

    Hawash, Mohamed B. F.; Andersen, Lee O.; Gasser, Robin B.;

    2015-01-01

    BACKGROUND: The whipworms Trichuris trichiura and Trichuris suis are two parasitic nematodes of humans and pigs, respectively. Although whipworms in human and non-human primates historically have been referred to as T. trichiura, recent reports suggest that several Trichuris spp. are found...... in primates. METHODS AND FINDINGS: We sequenced and annotated complete mitochondrial genomes of Trichuris recovered from a human in Uganda, an olive baboon in the US, a hamadryas baboon in Denmark, and two pigs from Denmark and Uganda. Comparative analyses using other published mitochondrial genomes...... of Trichuris recovered from a human and a porcine host in China and from a françois' leaf-monkey (China) were performed, including phylogenetic analyses and pairwise genetic and amino acid distances. Genetic and protein distances between human Trichuris in Uganda and China were high (~19% and 15%, respectively...

  5. The Gottingen Minipig Is a Model of the Hematopoietic Acute Radiation Syndrome: G-Colony Stimulating Factor Stimulates Hematopoiesis and Enhances Survival From Lethal Total-Body γ-Irradiation

    International Nuclear Information System (INIS)

    Purpose: We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials: Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results: The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusions: These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes

  6. The Gottingen Minipig Is a Model of the Hematopoietic Acute Radiation Syndrome: G-Colony Stimulating Factor Stimulates Hematopoiesis and Enhances Survival From Lethal Total-Body γ-Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Moroni, Maria, E-mail: maria.moroni@usuhs.edu [Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Ngudiankama, Barbara F. [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland (United States); Christensen, Christine [Division of Comparative Pathology, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Olsen, Cara H. [Biostatistics Consulting Center, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Owens, Rossitsa [Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Lombardini, Eric D. [Veterinary Medicine Department, Armed Forces Research Institute of Medical Sciences, Bangkok (Thailand); Holt, Rebecca K. [Veterinary Science Department, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States); Whitnall, Mark H. [Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland (United States)

    2013-08-01

    Purpose: We are characterizing the Gottingen minipig as an additional large animal model for advanced drug testing for the acute radiation syndrome (ARS) to enhance the discovery and development of novel radiation countermeasures. Among the advantages provided by this model, the similarities to human hematologic parameters and dynamics of cell loss/recovery after irradiation provide a convenient means to compare the efficacy of drugs known to affect bone marrow cellularity and hematopoiesis. Methods and Materials: Male Gottingen minipigs, 4 to 5 months old and weighing 9 to 11 kg, were used for this study. We tested the standard off-label treatment for ARS, rhG-CSF (Neupogen, 10 μg/kg/day for 17 days), at the estimated LD70/30 total-body γ-irradiation (TBI) radiation dose for the hematopoietic syndrome, starting 24 hours after irradiation. Results: The results indicated that granulocyte colony stimulating factor (G-CSF) enhanced survival, stimulated recovery from neutropenia, and induced mobilization of hematopoietic progenitor cells. In addition, the administration of G-CSF resulted in maturation of monocytes/macrophages. Conclusions: These results support continuing efforts toward validation of the minipig as a large animal model for advanced testing of radiation countermeasures and characterization of the pathophysiology of ARS, and they suggest that the efficacy of G-CSF in improving survival after total body irradiation may involve mechanisms other than increasing the numbers of circulating granulocytes.

  7. The Ontogeny of the Endocrine Pancreas in the Fetal/Newborn Baboon

    Science.gov (United States)

    Quinn, Amy R.; Blanco, Cynthia L.; Perego, Carla; Finzi, Giovanna; La Rosa, Stefano; Capella, Carlo; Guardado-Mendoza, Rodolfo; Casiraghi, Francesca; Gastaldelli, Amalia; Johnson, Marney; Dick, Edward J.; Folli, Franco

    2013-01-01

    Background Erratic regulation of glucose metabolism including hyperglycemia is a common condition of premature infants and is associated with increased morbidity and mortality. Objective To examine histological and ultra-structural differences in the endocrine pancreas in fetal (throughout gestation) and neonatal baboons. Methods Twelve fetal baboons were delivered at 125 days (d) gestational age (GA), 140dGA, or 175dGA. Eight animals were delivered at term (185dGA); half were fed for 5d. Seventy-three non-diabetic adult baboons were used for comparison. Pancreatic tissue was studied utilizing light microscopy, confocal imaging and electron microscopy. Results The fetal and neonatal endocrine pancreas islet architecture became more organized as GA advanced. The percent areas of α-β-δ-cell type were similar within each fetal and newborn GA (NS), but were higher than the adults (P<0.05) regardless of GA. The ratio of β-cells within the islet (whole and core) increased with gestation (P<0.01). Neonatal baboons who survived for 5 days (feeding), had a 2.5-fold increase in pancreas weight compared to their counterparts euthanized at birth (P=0.01). Endocrine cells were found amongst exocrine ductal and acinar cells in 125,140 and 175dGA fetuses. Subpopulation of cells that co-expressed trypsin and glucagon/insulin show the presence of cells with mixed endo-exocrine lineage in fetuses. Conclusions The fetal endocrine pancreas has no prevalence of a of α-β-δ-cell type with larger endocrine cell percent areas than adults. Cells with mixed endocrine/exocrine phenotype occur during fetal development. Developmental differences may play a role in glucose homeostasis during the neonatal period and may have long term implications. PMID:22723715

  8. Influence of Age, Reproductive Cycling Status, and Menstruation on the Vaginal Microbiome in Baboons (Papio anubis)

    OpenAIRE

    UCHIHASHI, M.; BERGIN, I. L.; BASSIS, C. M.; HASHWAY, S. A.; Chai, D.; Bell, J. D.

    2015-01-01

    The vaginal microbiome is believed to influence host health by providing protection from pathogens and influencing reproductive outcomes such as fertility and gestational length. In humans, age-associated declines in diversity of the vaginal microbiome occur in puberty and persist into adulthood. Additionally, menstruation has been associated with decreased microbial community stability. Adult female baboons, like other non-human primates (NHPs), have a different and highly diverse vaginal mi...

  9. Sex-Dependent Cognitive Performance in Baboon Offspring Following Maternal Caloric Restriction in Pregnancy and Lactation

    OpenAIRE

    RODRIGUEZ, Jesse S.; Bartlett, Thad Q; Keenan, Kathryn E.; Nathanielsz, Peter W.; Nijland, Mark J.

    2012-01-01

    In humans a suboptimal diet during development has negative outcomes in offspring. We investigated the behavioral outcomes in baboons born to mothers undergoing moderate maternal nutrient restriction (MNR). Maternal nutrient restriction mothers (n = 7) were fed 70% of food eaten by controls (CTR, n = 12) fed ad libitum throughout gestation and lactation. At 3.3 ± 0.2 (mean ± standard error of the mean [SEM]) years of age offspring (controls: female [FC, n = 8], male [MC, n = 4]; nutrient rest...

  10. Microsomal drug-metabolizing enzymes in the olive baboon (papio anabis)

    DEFF Research Database (Denmark)

    1975-01-01

    1.1. The activity of microsomal drug-metabolizing enzymes—azo reductase, nitroreductase, p-hydroxylation, N-demethylation, O-demethylation, NADPH cytochrome c reductase and cytochrome P P-450—in the olive baboon are lower than in other animal species, e.g. mouse, rat, guinea-pig. 2. 2. The level ...... and beta-glucuronidase is present more in the lysosomal than in the microsomal fraction....

  11. Place of low-dose total body irradiation in the treatment of localized follicular non-Hodgkin's lymphoma: results of a pilot study

    International Nuclear Information System (INIS)

    Purpose: In a first prospective nonrandomized trial, 107 patients with Stage III and IV 'low-grade' lymphomas have been treated with a combination of chemotherapy and low-dose total body irradiation (LD-TBI). This study shows that this scheme of LD-TBI was very well tolerated, gave a high response rate (83%), and extended RFS. It incited us to start a pilot study on localized follicular lymphomas. Methods and Materials: From January 1986 through October 1994, 34 patients with previously untreated localized low-grade non-Hodgkin's lymphomas have been included in a prospective trial with LD-TBI followed by radical involved field radiotherapy (IF-RT). Patients received two courses of whole body irradiation of 0.75 Gy in 5 fractions and 1 week separated by a rest period of 2 weeks. After 1 month, patients were reevaluated, and received 40 Gy in 20 fractions, and 4 weeks on initially pathological lymph node areas. Eight patients have been excluded from the study: 4 after histologic review (2 centrocytic, 1 lymphocytic, 1 centroblastic) and 4 patients with Stage IV because of bone-marrow involvement. The remaining 26 patients were 11 men and 15 women, 50 years old median age (mean: 50.2; range: 35-73.5) with clinical Stage I (10 pts), II1 (8 pts), and II2 (8 pts). All patients received the planned treatment. Results: Clinical tolerance was excellent, and the hematological follow-up shows a mean nadir value of 3.9.109/1 (2.1-8.1) for leucocytes, 13.4 g/l (10.8-15.4) for hemoglobin, and 124.109/l (46-216) for platelets, with a median delay of 3.2 months. Of 26 patients, 24 achieved complete remission (CR) after the LD-TBI that was before the IF-RT. All patients, except one, were in complete remission after IF-RT. Nineteen patients remain alive without any evidence of disease, with a median follow-up of 56.2 months. Five patients relapsed; 3 of them died. Conclusion: As delivered, this schedule of LD-TBI give a very high rate of CR in localized follicular non

  12. Low-dose total body irradiation as first-line treatment of localized follicular non-Hodgkin's lymphoma. Results of a pilot study

    International Nuclear Information System (INIS)

    Purpose/Objective: In a first prospective non randomized trial, 107 patients with stage III and IV 'low-grade' lymphomas have been treated with a combination of chemotherapy and low-dose Total Body Irradiation (LD-TBI) [Richaud and Hoerni, 1992]. This study show that this scheme of LD-TBI was very well tolerated, gave a high response rate (83%) and extended RFS. It incite us to start a pilot study on localized follicular lymphomas. Materials and Methods: From January 1986 through October 1995, 34 patients with localized low-grade non-Hodgkin's lymphomas have been treated in first intention by LD-TBI followed by radical involved field radiotherapy (IF-RT). Patients received two courses of whole body irradiation of 0.75 Gy in 5 fractions and one week separated by a rest period of two weeks. After one month, patients were reevaluated and received 40 Gy in 20 fractions and 4 weeks on initially pathological lymph nodes areas. Eight patients have been excluded from the study : 4 after histologic review (2 centrocytic, 1 lymphocytic, 1 centroblastic), 4 patients were stage IV with bone marrow involvement. The remaining 26 patients were 11 male and 14 female, 50.2 years old mean age (range : 35-73.5) with clinical stage I (10 pts), II1 (8 pts) and II2 (8 pts). All patients received the planned treatment. Results: Clinical tolerance was excellent and the haematologic follow-up show a mean nadir value of(3.9.109(l (2.1-8.1))) for leucocytes, (13.4 g(l (10.8-15.4))) for haemoglobin and (124.109(l (46-216))) for platelets with a median delay of 3.2 months. Clinical complete remission was obtained after the LD-TBI and before the IF-RT for 24 out of 26 patients. All patients, excepted one, were in complete remission after IF-RT. Nineteen patients remain alive without any evidence of disease with a median follow-up of 56.2 months. Five patients relapsed : three of them died. Conclusion: As delivered, this schedule of LD-TBI give a very high rate of complete clinical remission in

  13. 20 years of experience in static intensity-modulated total-body irradiation and lung toxicity. Results in 257 consecutive patients

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, R.A.; Schultze, J.; Jensen, J.M.; Hebbinghaus, D.; Galalae, R.; Kimmig, B.N. [University Hospital of Schleswig-Holstein (UHK), Kiel (Germany). Dept. of Radiotherapy

    2007-10-15

    Purpose: To analyze lung complications after allogeneic or autologous transplantation following total-body irradiation (TBI) with compensators, so-called sIMRT (static intensity-modulated radiotherapy). Patients and Methods: Between 1983 and 1998, 257 patients with different hematologic malignancies underwent TBI in six fractions to a total dose of 12 Gy within 3 consecutive days (212 with 11 Gy lung dose) prior to allogeneic (n = 174) or autologous (n = 83) transplantation. 40 patients were < 16 years of age. Minimum follow-up time was 5 years. Median follow-up period was 110 months (13-231 months). Results: 5-year survival rate was 47.9%, 5-year tumor-related mortality 23%, 5-year treatment-related mortality 29.2% (12 Gy lung dose: 53.3% {+-} 14.6%, 11 Gy: 24.1% {+-} 5.7%). Interstitial pneumonitis (IP) developed in 28 of 257 patients (10.9% {+-} 3.8%). IP incidences in the allogeneic and autologous groups were 14.4% ({+-} 5.6%) and 3.6% (0-7.6%), respectively. IP incidences with 12/11 Gy lung dose were 22% ({+-} 12%)/8.5% ({+-} 3.7%). IP mortality was 9.3% ({+-} 3.6%). 13 of 28 patients with IP had a cytomegalovirus infection, five an acute graft-versus-host disease grade IV of the lungs. IP incidences with 12/11 Gy lung dose were 25% (9-50%)/4.2% (0.2-19.1%) in patients < 16 years, and 20.7% (9.4-37.4%) and 13.3% ({+-} 6.5%) in older patients after allogeneic transplantation. Conclusion: Compensator-generated static intensity-modulated TBI with a total dose of 12 Gy and a lung dose of 11 Gy is a modern and comfortable treatment with moderate lung toxicity, small dose inhomogeneities and little setup failure before transplantation. Especially patients < 16 years of age benefit from lung dose reduction.

  14. Allogeneic bone marrow transplantation with conditioning regimen of total body irradiation/busulfan/melphalan for 16 patients in children with high-risk leukemia and lymphoma

    International Nuclear Information System (INIS)

    We report the therapeutic results of allogeneic bone marrow transplantations (BMT) for 16 children with high-risk leukemia and lymphoma. The conditioning regimen consisted of total body irradiation (TBI) (12 Gy), busulfan (Bu) (4 mg/kg x 2 days), and melphalan (L-PAM) (70 mg/m2 x 2 or 3 days). Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporin (CsA) + methotrexate (MTX) (4 cases) and CsA + MTX-methyl-prednisolone (11 cases). Seven patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 B-cell type non-Hodgkin's lymphoma, and 1 peripheral T-cell lymphoma. Nine patients were in complete remission (CR) and 7 in non CR at BMT. Nine patients received transplants from HLA-matched related (MR) donors, 4 from HLA-mismatched related (MisR) donors, and 3 from unrelated (UR) donors. Seven of the cases, all of which were transplanted from MR, have continued complete remission for 15-47 (median 27) months. Nine patients, of which seven were transplanted from MisR/UR, died from complications from fungal pneumonia (3), cytomegalovirus pneumonitis (1), GVHD (1), rhabdomyolysis (1), lymphoproliferative disorder (1), rejection (1), and relapse (1). These results suggest that the combination of TBI, Bu, and L-PAM as a BMT regimen has a significant anti-neoplastic benefit and is considered to be useful; however, considering the high rate of fatal transplant-related complications, more refinement is required, especially for transplants from MisR and UR donors. (author)

  15. Rituximab, fludarabine, and total body irradiation as conditioning regimen before allogeneic hematopoietic stem cell transplantation for advanced chronic lymphocytic leukemia: long-term prospective multicenter study.

    Science.gov (United States)

    Michallet, Mauricette; Socié, Gerard; Mohty, Mohamad; Sobh, Mohamad; Bay, Jacques-O; Morisset, Stéphane; Labussière-Wallet, Hélène; Tabrizi, Reza; Milpied, Noel; Bordigoni, Pierre; El-Cheikh, Jean; Blaise, Didier

    2013-02-01

    To evaluate the efficacy and toxicity of reduced-intensity conditioning (RIC) combining fludarabine, low-dose total body irradiation (TBI) and rituximab before allogeneic hematopoietic stem cell transplantation (allo-HSCT) from human leucocyte antigen (HLA) identical siblings, we conducted a prospective study in patients ≤65 years old with advanced chronic lymphocytic leukemia (CLL) stage B or C in response after a salvage treatment. Conditioning included rituximab (375 mg/m² on day 5), fludarabine (30 mg/m² from day 4 to day 2), TBI (2 Gy on day 0), and rituximab (500 mg/m² on days 1 and 8). Forty patients were included, 34 (85%) were male with a median age of 54 years (range, 35-65 years), 38 (95%) were in B stage, and 2 were in stage C; only 7 patients (17%) were in complete response. Seven (17%) patients did not receive rituximab. Thirty-nine (98%) patients engrafted, 17 patients developed acute graft-versus-host disease (GVHD) grade ≥II with a cumulative incidence at 3 months of 44% (36-52) with a significant protective effect of rituximab (p = 0.02). The cumulative incidence of chronic GVHD was 29% (21-36) at 12 months for both limited and extensive forms. The median overall survival was not reached with 5-years probability of 55% (41-74). The multivariate analysis showed a positive effect of rituximab on overall survival and event-free survival (hazard ratio [HR] = 0.1 [0-0.6], p = 0.02; and HR = 0.1 [0-0.4], p = 0.035, respectively). The association of fludarabine, TBI, and rituximab is feasible, well tolerated, and allows better outcomes in advanced CLL.

  16. Tacrolimus and mycophenolate mofetil after nonmyeloablative matched-sibling donor allogeneic stem-cell transplantations conditioned with fludarabine and low-dose total body irradiation.

    Science.gov (United States)

    Nieto, Yago; Patton, Nigel; Hawkins, Timothy; Spearing, Ruth; Bearman, Scott I; Jones, Roy B; Shpall, Elizabeth J; Rabinovitch, Rachel; Zeng, Chan; Barón, Anna; McSweeney, Peter A

    2006-02-01

    We evaluated tacrolimus/mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis after a nonmyeloablative stem cell transplantation (NST) from a matched sibling donor (MSD). Thirty-two patients (median age, 57 years) with advanced hematologic malignancies, who were poor candidates for a conventional myeloablative transplantation, received fludarabine (30 mg/m(2), day -4 to day -2), total-body irradiation (TBI) (200 cGy, day 0), infusion of donor peripheral blood progenitor cells (day 0), oral tacrolimus 0.06 mg/kg twice daily (from day 3), and oral MMF at 15 mg/kg twice daily (days 0-+27). Tacrolimus was tapered from day +100 to day +180 in those patients with indolent malignancies (n = 25), and from day +35 to day +56 in those with aggressive tumors (n = 7). Regimen toxicities and myelosuppression were mild, allowing 75% of patients to have entirely outpatient transplantations. One patient (3%) experienced a nonfatal graft rejection. Rates of grades II-IV and III-IV acute GVHD were 15.6% and 3%, respectively. Acute GVHD was diagnosed at median day +78 (range, days +31-+84). Extensive chronic GVHD was observed in 10 of 24 evaluable patients (41.6%) at a median onset of day +198 (range, days +128-+277), either spontaneously (n = 5) or elicited after tumor progression (n = 5). Five patients experienced transplantation-related mortality (TRM) (15.6%) from either acute GVHD-related multiorgan failure (MOF) (n = 3) or infectious complications (n = 2). At median follow-up of 19 months (range, 2-41 months), the overall survival, progression-free survival, and disease-free survival rates are 62.5%, 50%, and 40%, respectively. In conclusion, the use of tacrolimus/MMF after MSD NST is associated with encouraging rates of GVHD control.

  17. Prospective evaluation of pulmonary function in cancer patients treated with total body irradiation, high-dose melphalan, and autologous hematopoietic stem cell transplantation

    International Nuclear Information System (INIS)

    Pulmonary function tests (standard vital capacity, SVC; total lung capacity, TLC; forced expiratory volume in 1 second-forced vital capacity ratio, FEV1/FVC; carbon monoxide transfer factor, DLCO) were prospectively evaluated in patients (median age 25 years, 13-52 years; median follow-up 20 months, 6-51 months) with Hodgkin's disease (15 patients), non-Hodgkin's lymphoma (9 patients), and inflammatory breast cancer (3 patients) treated with sequential high-dose therapy comprising the following phases over approximately 2 months: (a) cyclophosphamide (7 g/m2); (b) vincristine (1.4 mg/m2), methotrexate (8 g/m2), and cisplatinum (120 mg/m2) or etoposide (2 g/m2); (c) total body irradiation (TBI; 12.5 gy, 5 fractions over 48 hours), intravenous melphalan (120-180 mg/m2), and transplantation of autologous peripheral blood and/or bone marrow hematopoietic stem cells. Within 2 months after transplantation, 12 patients also received 25 Gy radiotherapy boost to mediastinum and clavicular regions. In vivo dosimetry evaluations of fractionated TBI treatments showed that mean radiation dose absorbed by lungs was 12.18 Gy (97.4% of TBI dose). Despite such a high radiation dose, we observed only transient and subclinical decrease of SVC, TLC, and DLCO. The decrease of SVC, TLC, and DLCO was more evident and prolonged in patients receiving radiotherapy boost. All parameters progressively recovered to normal values within 2 years after transplantation. In contrast, FEV1/FVC remained within normal limits in all patients, thus demonstrating the absence of obstructive ventilatory changes. In addition, no interstitial pneumonia was observed

  18. A comparison of single-dose and fractionated total-body irradiation on the development of pneumonitis following bone marrow transplantation

    International Nuclear Information System (INIS)

    Purpose: A review of 132 consecutive patients who received bone marrow transplant for various malignancies was conducted to determine factors associated with increased risk in developing interstitial pneumonitis (IP) as the result of total body irradiation (TBI). Twenty-four patients were excluded because 22 did not receive TBI and two had insufficient records. Methods and Materials: Patients were conditioned with TBI and various drug regimens. Eighteen patients received a single 6.0 Gy dose of x-rays. The remaining 90 were treated with three doses of 3.33 Gy separated by 24 h. All patients were followed for at least 18 months for the purposes of determining the IP incidence. Results: Twenty-seven of there 108 (25%) patients developed IP; 19 (17.6%) died. The 2-year estimated incidence of IP was 24 and 18.6% for fatal IP. The etiology was determined to be idiopathic in 12 patients, the result of cytomegalovirus in 6 patients, and caused by a variety of other infectious organisms in 9 patients. We were unable to demonstrate a statistically significant increase in IP with age (adults vs. children), dose regimen, use of methotrexate for graft-vs.-host disease prophylaxis, the presence of acute graft-vs.-host disease, time from diagnosis to transplant, or transplant type (allogeneic vs. autologous). Conclusions: The incidence of fatal IP reported here is similar to that reported by other institutions utilizing hyperfractionated TBI protocols. Our data do not support the need for hyperfractionation to reduce the risk of IP

  19. Age and sex dependence in tumorigenesis in mice by continuous low-dose-rate gamma-ray whole-body irradiation

    International Nuclear Information System (INIS)

    We investigated the dependency of sex and age in mice in the induction of neoplasms by gamma-rays from cesium-137 at a low dose rate of 0.375Gy/22h/day. Thymic lymphomas occurred significantly at the same incidence in both sexes, and more frequently when younger mice were exposed to radiation. Strain C57BL/6J mice were divided into 8 groups, which were whole-body irradiated with a total dose of 39Gy for 105 days each. The exposure was begun at 28 days of age (male:AM1, female:AF1), and then stepwise increasing the starting age by 105 days, i.e., from 133 days (AM2 and AF2), from 238 days (AM3 and AF3), and from 343 days (AM4 and AF4), respectively. Unirradiated mice served as control (UM and UF). The incidence of thymic lymphomas was about 60 % in AM1, AM2, AF1 and AF2, 40 % in AM3 and AF3 and 20 % in AF4 and AF4, demonstrating no sex dependency, but a distinct age dependency, for lymphomogenesis. It was proven that mice showed a tendency to become less susceptible to radiation induced thymic lymphoma with increasing age. Concomitantly, life-shortening also was caused, and the greater the degree of life-shortening was, the younger the mice were the start of exposure. Life-shortening was attributed to thymic lymphoma, and hemorrhage and infectious diseases due to the depletion of bone marrow cells. (author)

  20. Busulfan, cyclophosphamide and fractionated total body irradiation as a conditioning regimen for allogeneic bone marrow transplantation in patients with non-lymphocytic hematopoietic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Hiroshi [Jikei Univ., Tokyo (Japan). School of Medicine

    1996-11-01

    Allogeneic bone marrow transplantation (BMT) with the conditioning regimen of 8 mg/kg of busulfan (BUS), 120 mg/kg of cyclophosphamide (CPM) and 10 Gy of total body irradiation (TBI) was evaluated in the patients with non-lymphocytic hematopoietic malignancies. The disease distribution of the 22 patients was as follows; 14 in the standard risk group (SRG), 8 in the high risk group (HRG). SRG included the patients with acute myeloid leukemia (AML) in the first complete remission, chronic myelogenous leukemia (CML) in chronic phase and myelodysplastic syndrome with refractory anemia, while HRG included the patients with refractory AML and CML in blastic phase. The median age of patients was 33 years old (y.o.), and the median observation period was 34.5 months No relapse occurred, but 8 patients (36%) died of various complications. Ail the patients who died of interstitial pneumonitis (4 cases) were 40 y.o. and more. Acute graft-versus-host disease (GvHD) and chronic GvHD were clinically controllable. The probability of disease-free survival rate at 5 years (5y-DFS) was 50.0% in overall patients. The 5y-DFS was 57.1% in HRG (7 cases), while 54.3% in SRG (13 cases) donated from the HLA identical siblings (20 cases). In these 13 patients in SRG, the 5y-DFS was 100% in patients under 40 y.o. (6 cases), while the probability of disease-free survival rate at 3 years was 68.6% and the 5y-DFS was 0% in patients over 40 y.o. (7 cases). Our data indicate that the conditioning regimen combining BUS, CPM and TBI for allogeneic BMT is promising for the treatment of the patients of HRG and the patients under 40 y.o. in SRG. (author)

  1. Allogeneic bone marrow transplantation with conditioning regimen of total body irradiation/busulfan/melphalan for 16 patients in children with high-risk leukemia and lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Yoshihara, Takao; Fujii, Noriko [Matsushita Memorial Hospital, Moriguchi, Osaka (Japan); Naya, Mayumi [and others

    1999-02-01

    We report the therapeutic results of allogeneic bone marrow transplantations (BMT) for 16 children with high-risk leukemia and lymphoma. The conditioning regimen consisted of total body irradiation (TBI) (12 Gy), busulfan (Bu) (4 mg/kg x 2 days), and melphalan (L-PAM) (70 mg/m{sup 2} x 2 or 3 days). Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporin (CsA) + methotrexate (MTX) (4 cases) and CsA + MTX-methyl-prednisolone (11 cases). Seven patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 B-cell type non-Hodgkin`s lymphoma, and 1 peripheral T-cell lymphoma. Nine patients were in complete remission (CR) and 7 in non CR at BMT. Nine patients received transplants from HLA-matched related (MR) donors, 4 from HLA-mismatched related (MisR) donors, and 3 from unrelated (UR) donors. Seven of the cases, all of which were transplanted from MR, have continued complete remission for 15-47 (median 27) months. Nine patients, of which seven were transplanted from MisR/UR, died from complications from fungal pneumonia (3), cytomegalovirus pneumonitis (1), GVHD (1), rhabdomyolysis (1), lymphoproliferative disorder (1), rejection (1), and relapse (1). These results suggest that the combination of TBI, Bu, and L-PAM as a BMT regimen has a significant anti-neoplastic benefit and is considered to be useful; however, considering the high rate of fatal transplant-related complications, more refinement is required, especially for transplants from MisR and UR donors. (author)

  2. Improvement of registration accuracy in accelerated partial breast irradiation using the point-based rigid-body registration algorithm for patients with implanted fiducial markers

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Minoru; Yoshimura, Michio, E-mail: myossy@kuhp.kyoto-u.ac.jp; Sato, Sayaka; Nakamura, Mitsuhiro; Yamada, Masahiro; Hirata, Kimiko; Ogura, Masakazu; Hiraoka, Masahiro [Department of Radiation Oncology and Image-Applied Therapy, Kyoto University Graduate School of Medicine, Kyoto 606-8507 (Japan); Sasaki, Makoto; Fujimoto, Takahiro [Division of Clinical Radiology Service, Kyoto University Hospital, Kyoto 606-8507 (Japan)

    2015-04-15

    Purpose: To investigate image-registration errors when using fiducial markers with a manual method and the point-based rigid-body registration (PRBR) algorithm in accelerated partial breast irradiation (APBI) patients, with accompanying fiducial deviations. Methods: Twenty-two consecutive patients were enrolled in a prospective trial examining 10-fraction APBI. Titanium clips were implanted intraoperatively around the seroma in all patients. For image-registration, the positions of the clips in daily kV x-ray images were matched to those in the planning digitally reconstructed radiographs. Fiducial and gravity registration errors (FREs and GREs, respectively), representing resulting misalignments of the edge and center of the target, respectively, were compared between the manual and algorithm-based methods. Results: In total, 218 fractions were evaluated. Although the mean FRE/GRE values for the manual and algorithm-based methods were within 3 mm (2.3/1.7 and 1.3/0.4 mm, respectively), the percentages of fractions where FRE/GRE exceeded 3 mm using the manual and algorithm-based methods were 18.8%/7.3% and 0%/0%, respectively. Manual registration resulted in 18.6% of patients with fractions of FRE/GRE exceeding 5 mm. The patients with larger clip deviation had significantly more fractions showing large FRE/GRE using manual registration. Conclusions: For image-registration using fiducial markers in APBI, the manual registration results in more fractions with considerable registration error due to loss of fiducial objectivity resulting from their deviation. The authors recommend the PRBR algorithm as a safe and effective strategy for accurate, image-guided registration and PTV margin reduction.

  3. Treponema pallidum infection in the wild baboons of East Africa: distribution and genetic characterization of the strains responsible.

    Directory of Open Access Journals (Sweden)

    Kristin N Harper

    Full Text Available It has been known for decades that wild baboons are naturally infected with Treponema pallidum, the bacterium that causes the diseases syphilis (subsp. pallidum, yaws (subsp. pertenue, and bejel (subsp. endemicum in humans. Recently, a form of T. pallidum infection associated with severe genital lesions has been described in wild baboons at Lake Manyara National Park in Tanzania. In this study, we investigated ten additional sites in Tanzania and Kenya using a combination of macroscopic observation and serology, in order to determine whether the infection was present in each area. In addition, we obtained genetic sequence data from six polymorphic regions using T. pallidum strains collected from baboons at two different Tanzanian sites. We report that lesions consistent with T. pallidum infection were present at four of the five Tanzanian sites examined, and serology was used to confirm treponemal infection at three of these. By contrast, no signs of treponemal infection were observed at the six Kenyan sites, and serology indicated T. pallidum was present at only one of them. A survey of sexually mature baboons at Lake Manyara National Park in 2006 carried out as part of this study indicated that roughly ten percent displayed T. pallidum-associated lesions severe enough to cause major structural damage to the genitalia. Finally, we found that T. pallidum strains from Lake Manyara National Park and Serengeti National Park were genetically distinct, and a phylogeny suggested that baboon strains may have diverged prior to the clade containing human strains. We conclude that T. pallidum infection associated with genital lesions appears to be common in the wild baboons of the regions studied in Tanzania. Further study is needed to elucidate the infection's transmission mode, its associated morbidity and mortality, and the relationship between baboon and human strains.

  4. Autologous cell therapy as a new approach to treatment of radiation-induced bone marrow aplasia: preliminary study in a baboon model

    Energy Technology Data Exchange (ETDEWEB)

    Herodin, F.; Drouet, M. [Radiohematology Unit, Centre de Recherches du Service de Sante des Armees, La Tronche CEDEX (France)

    2002-07-01

    The sparing of viable hematopoietic stem and progenitor cells located in underexposed bone marrow territories associated with the relative radioresistance of certain stem cell populations is the rationale for autologous cell therapy consisting of ex vivo expansion of residual cells after collection postirradiation. The feasibility of this treatment mainly depends on time constraints and hematopoietic cell threshold. We showed in this study that in the absence of early-acting mobilizing agent administration, subliminar amounts of CD34{sup +} cells can be collected (1 x 10{sup 6} CD34{sup +} cells/100 mL bone marrow or for 1 L apheresis) from 6-Gy {gamma} globally irradiated baboons. Residual CD34{sup +} cells were successfully expanded in serum-free medium in the presence of antiapoptotic cytokine combination (stem cell factor + FLT-3 ligand + thrombopoietin + interleukin 3, 50 ng/mL each, i.e., 4F): K{sub CD34{sup +}} = x2.8 and x13.7 (n=2). Moreover, we demonstrated the short-term neutrophil engraftment potential of a low-size mixed expanded graft (1.5 x 10{sup 6} final CD34{sup +}cells/kg) issued from the coculture of unirradiated (20%) and 2.5-Gy in vitro irradiated (80%) CD34{sup +} cells on an allogeneic stromal cell layer in the presence of 4F. Further preclinical research needs to be performed to clearly establish this therapeutic approach that could be optimized by the early administration of antiapoptotic cytokines. (author)

  5. Analysis of prostate-specific antigen transcripts in chimpanzees, cynomolgus monkeys, baboons, and African green monkeys.

    Directory of Open Access Journals (Sweden)

    James N Mubiru

    Full Text Available The function of prostate-specific antigen (PSA is to liquefy the semen coagulum so that the released sperm can fuse with the ovum. Fifteen spliced variants of the PSA gene have been reported in humans, but little is known about alternative splicing in nonhuman primates. Positive selection has been reported in sex- and reproductive-related genes from sea urchins to Drosophila to humans; however, there are few studies of adaptive evolution of the PSA gene. Here, using polymerase chain reaction (PCR product cloning and sequencing, we study PSA transcript variant heterogeneity in the prostates of chimpanzees (Pan troglodytes, cynomolgus monkeys (Macaca fascicularis, baboons (Papio hamadryas anubis, and African green monkeys (Chlorocebus aethiops. Six PSA variants were identified in the chimpanzee prostate, but only two variants were found in cynomolgus monkeys, baboons, and African green monkeys. In the chimpanzee the full-length transcript is expressed at the same magnitude as the transcripts that retain intron 3. We have found previously unidentified splice variants of the PSA gene, some of which might be linked to disease conditions. Selection on the PSA gene was studied in 11 primate species by computational methods using the sequences reported here for African green monkey, cynomolgus monkey, baboon, and chimpanzee and other sequences available in public databases. A codon-based analysis (dN/dS of the PSA gene identified potential adaptive evolution at five residue sites (Arg45, Lys70, Gln144, Pro189, and Thr203.

  6. Mental maps in chacma baboons (Papio ursinus): using inter-group encounters as a natural experiment.

    Science.gov (United States)

    Noser, Rahel; Byrne, Richard W

    2007-07-01

    Encounters between groups of wild chacma baboons (Papio ursinus) can be viewed as a natural experiment to investigate the nature of these primates' mental representations of large-scale space. During a 16-month field study in a high population density habitat we recorded the foraging routes and the most important resources of a group of 25 individuals. Also, we estimated the locations of additional baboon groups relative to the study group. Routes were less linear, travel speed was higher, and inter-resource distances were larger when other groups were present within 500 m of the focal group; thus, the study group avoided others by taking detours. We predicted that evasive manoeuvres would be characteristic of different possible orientation mechanisms, and compared them with our observations. We analysed 34 evasive manoeuvres in detail. In an area that lacked prominent landmarks, detours were small; larger detours occurred when resources were directly visible, or in the vicinity of a hill offering conspicuous landmarks. In areas without prominent landmarks, detours were along familiar routes and waiting bouts of up to 60 min occurred; on one occasion the study group aborted their entire day's journey. We discuss these findings in the light of time and energy costs and suggest that the baboons lack the ability to compute Euclidean relations among locations, but use network maps to find their way to out-of-sight locations.

  7. 60Coγ射线半身照射对非照射区域骨髓造血组织基质细胞衍生因子1表达的影响%Influences of 60Coγray irradiation on expression stromal cell derived factor-1 in bone marrow hematopoietic tissue of non-irradiation area in left-half-body ionizing irradiated mice

    Institute of Scientific and Technical Information of China (English)

    高作文; 杨龙; 陈乐如; 娄金书; 张国强; 李开信; 程天民

    2013-01-01

    Objective To invesligale the mouse bone marrow hemalopoielic functions in non-irradiation area after irradiated by way of left-half- body. Methods The 6-8-week male Kunming strain mice were randomly divided into normal control( NC) , total-body-irradiated( TBI) , left-half-body-irradiated( LHBI) , and total-body-shield-irradia-ted( TBSI) groups. Left-half-body-irradiated group was treated with two pieces of 5 cm x 8 cm x 16 cm overlapped lead bricks shielding right-side body and irradiated with 8. 0 Gy60Coγ-ray. The leukocyte in peripheral blood and the number of bone marrow hematopoietic cells( BMHCs) were studied, the concentration of SOD, MDA in mouse serum were measured, and the expression SDF-1 in bone marrow hematopoietic tissues were observed by the Western blotting method and laser scanning confocal microscope combined with immunohistochemistry. Results In the left-half-body irradiated condition, the leucocyte in peripheral blood and the BMHCs were diminished, the concentration of MDA was increased and the SOD was decreased in the mouse serum remarkably ( compared with NC, P <0. 01) ; In non-irradiation area, the SDF-1-positive cells and the expression SDF-1 in bone marrow hematopoietic tissues were reduced significantly. Conclusion Our study suggested that the local irradiation resulted in the decrease of SDF-1-positive cells and the decline expression SDF-1 in bone marrow hematopoietic tissues in non-irradiation area, and the increase of reactive oxygen or free radicals might play an important role in the abnormal expression of SDF-1 in BMHT and the injury of hematopoietic microenvironment.%目的 探讨局部电离辐射对小鼠非照射区域骨髓造血组织基质细胞衍生因子-1(SDF-1)表达的影响.方法 将6~8周龄雄性昆明小鼠随机分为健康对照组、全身照射组、全身屏蔽照射组以及左半身照射组4组,用铅屏蔽建立半身照射模型,以8.0 Gy 60Co γ射线照射,观察小鼠外周血白细胞和骨髓有核

  8. Efficacy of fenbendazole formulated in a commercial primate diet for treating specific pathogen-free baboons (Papio cynocephalus anubis) infected with Trichuris trichiura.

    Science.gov (United States)

    Reichard, Mason V; Wolf, Roman F; Clingenpeel, Lindsay C; Doan, Sandra K; Jones, Amy N; Gray, Kristene M

    2008-11-01

    Trichuris trichiura is a common intestinal nematode parasite of captive baboons. We evaluated the efficacy of fenbendazole formulated in a commercial primate diet (FBZ-PD) for treating specific pathogen-free (SPF) baboons (Papio cynocephalus anubis) naturally infected with Trichuris trichiura. Twenty-nine baboons, housed indoors in 3 separate rooms, were fed FBZ-PD for 5 d, whereas 4 baboons housed in another isolated area served as untreated controls. The efficacy of FBZ-PD was measured as reduction in the number of T. trichiura eggs in host feces after treatment as determined by quantitative fecal flotation examination. All baboons that received FBZ-PD stopped shedding T. trichiura eggs by 7 d after initiation of treatment, and remained negative until at least 119 d after treatment. However, eggs of T. trichiura were present in the feces of 3 (10.3%) experimental baboons at 154 d after treatment. Untreated control baboons shed T. trichiura eggs throughout the entire study. Our results indicate that FBZ-PD was efficacious for treating SPF baboons infected with T. trichiura.

  9. Follow up of infection of chacma baboons with inoculum containing a and non-a genotypes of hepatitis B virus

    Institute of Scientific and Technical Information of China (English)

    Marina Baptista; Anna Kramvis; Saffie Jammeh; Jocelyn Naicker; Jacqueline S.Galpin; Michael C.Kew

    2003-01-01

    AIM: To determine whether one genotype (A or non-A genotypes of HBV) predominated over the other during the course of HBV infection.METHODS: Four baboons were inoculated with HBV. DNA was extracted from serum obtained at monthly intervals postinoculation for 52 weeks and HBV DNA was amplified using primers specific for the core region containing an insert characteristic of genotype A (nt 2 354-2 359, numbering from the EcoRI site). The amplicons were cloned into PCRScriptTM and a minimum of 15 clones per time point were sequenced in both directions.RESULTS: Both genotypes persisted for the entire followup period of 52 weeks. Genotype non-A predominated in two baboons and genotype A in one baboon. Neither genotype predominated in the fourth baboon, as shown at a 5 % level of testing.CONCLUSION: No conclusions concerning the dominance of either genotype or the natural progression or replication rates of HBV could be drawn because the pattern of the genotypes found may have been caused by sampling fluctuations at the time of DNA extraction and cloning as a result of the very low viral loads in the baboon sera.

  10. Establishment and Characterization of Baboon Embryonic Stem Cell Lines An Old World Primate Model for Regeneration and Transplantation Research

    Science.gov (United States)

    Simerly, Calvin R.; Navara, Christopher S.; Castro, Carlos A.; Turpin, Janet C.; Redinger, Carrie J.; Mich-Basso, Jocelyn D.; Jacoby, Ethan S.; Grund, Kevin J.; McFarland, David A.; Oliver, Stacie L.; Ben-Yehudah, Ahmi; Carlisle, Diane L.; Frost, Patricia; Penedo, Cecilia; Hewitson, Laura; Schatten, Gerald

    2010-01-01

    Here we have developed protocols using the baboon as a complementary alternative Old World Primate to rhesus and other macaques which have severe limitations in their availability. Baboons are not limited as research resources, they are evolutionarily closer to humans and the multiple generations of pedigreed colonies which display complex human disease phenotypes all support their further optimization an invaluable primate model. Since neither baboon assisted reproductive technologies nor baboon embryonic stem cells (ESCs) have been reported, here we describe the first derivations and characterization of baboon ESC lines from IVF-generated blastocysts. Two ESCs lines (BabESC-4 and BabESC-15) display ESC morphology, express pluripotency markers (Oct-4, hTert, Nanog, Sox-2, Rex-1, TRA1–60, TRA1–81), and maintain stable euploid female karyotypes with parentage confirmed independently. They have been grown continuously for >430 and 290 days, respectively. Teratomas from both lines have all three germ layers. Availabilities of these BabESCs represent another important resource for stem cell biologists. PMID:19393591

  11. Abrogation of bone marrow allograft resistance in mice by increased total body irradiation correlates with eradication of host clonable T cells and alloreactive cytotoxic precursors

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, E.; Lapidot, T.; Gozes, D.; Singer, T.S.; Reisner, Y.

    1987-01-15

    Host-vs-graft activity presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, conditioned exactly like leukemia patients, it was shown that residual host clonable T cells, as well as alloreactive cytotoxic precursors, were present in peripheral blood and spleen after completion of cytoreduction. We have now extended this study in a mouse model for allogeneic bone marrow transplantation. C/sub 3/H/HeJ mice were treated by 9 Gy total body irradiation (TBI), and 24 hr later their spleen cells were cultured in the presence of T cell growth factor and phytohemagglutinin according to the limit dilution procedure. After 7 days of culture the average frequency of clonable cells was 2.5 X 10(-3) compared with 37 X 10(-3) in the spleens of normal mice. The T cell derivation of the growing cells was ascertained by complement-mediated cytotoxicity with anti-Thy-1 as well as with anti-Lyt-2 and anti-Ly-3T4. In parallel, we found that the initial engraftment rate of bone marrow allograft in mice given 9 Gy TBI was lower than that found in recipients of syngeneic marrow. The initial engraftment rate was measured by the number of colony-forming units in the spleen and by splenic uptake of /sup 125/IUdR. A slight increase in TBI from 9 Gy to 11 Gy markedly reduced the difference in the number of spleen colony-forming units or the IUdR uptake between recipients of allogeneic and syngeneic bone marrow. This increase in TBI also coincided with eradication of detectable clonable T cells. Moreover, in mice transplanted with T cell-depleted bone marrow after 9 Gy TBI, we also demonstrate that cytotoxicity against donor-type target cells is present in the spleen 10 to 14 days posttransplantation, whereas in mice treated by 11 Gy TBI such alloreactivity could not be detected.

  12. Similar Survival for Patients Undergoing Reduced-Intensity Total Body Irradiation (TBI) Versus Myeloablative TBI as Conditioning for Allogeneic Transplant in Acute Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Mikell, John L., E-mail: jmikell@emory.edu [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Waller, Edmund K. [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Switchenko, Jeffrey M. [Department of Biostatistics and Bioinformatics, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Rangaraju, Sravanti; Ali, Zahir; Graiser, Michael [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Hall, William A. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Langston, Amelia A. [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Esiashvili, Natia [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Khoury, H. Jean [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Khan, Mohammad K. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2014-06-01

    Purpose: Hematopoietic stem cell transplantation (HSCT) is the mainstay of treatment for adults with acute leukemia. Total body irradiation (TBI) remains an important part of the conditioning regimen for HCST. For those patients unable to tolerate myeloablative TBI (mTBI), reduced intensity TBI (riTBI) is commonly used. In this study we compared outcomes of patients undergoing mTBI with those of patients undergoing riTBI in our institution. Methods and Materials: We performed a retrospective review of all patients with acute leukemia who underwent TBI-based conditioning, using a prospectively acquired database of HSCT patients treated at our institution. Patient data including details of the transplantation procedure, disease status, Karnofsky performance status (KPS), response rates, toxicity, survival time, and time to progression were extracted. Patient outcomes for various radiation therapy regimens were examined. Descriptive statistical analysis was performed. Results: Between June 1985 and July 2012, 226 patients with acute leukemia underwent TBI as conditioning for HSCT. Of those patients, 180 had full radiation therapy data available; 83 had acute lymphoblastic leukemia and 94 had acute myelogenous leukemia; 45 patients received riTBI, and 135 received mTBI. Median overall survival (OS) was 13.7 months. Median relapse-free survival (RFS) for all patients was 10.2 months. Controlling for age, sex, KPS, disease status, and diagnosis, there were no significant differences in OS or RFS between patients who underwent riTBI and those who underwent mTBI (P=.402, P=.499, respectively). Median length of hospital stay was shorter for patients who received riTBI than for those who received mTBI (16 days vs 23 days, respectively; P<.001), and intensive care unit admissions were less frequent following riTBI than mTBI (2.22% vs 12.69%, respectively, P=.043). Nonrelapse survival rates were also similar (P=.186). Conclusions: No differences in OS or RFS were seen between

  13. Reduced-intensity conditioning regimen using low-dose total body irradiation before allogeneic transplant for hematologic malignancies: Experience from the European Group for Blood and Marrow Transplantation

    International Nuclear Information System (INIS)

    Purpose: The high rate of toxicity is the limitation of myelobalative regimens before allogeneic transplantation. A reduced intensity regimen can allow engraftment of stem cells and subsequent transfer of immune cells for the induction of a graft-vs.-tumor reaction. Methods and Materials: The data from 130 patients (80 males and 50 females) treated between 1998 and 2003 for various hematologic malignancies were analyzed. The median patient age was 50 years (range, 3-72 years). Allogeneic transplantation using peripheral blood or bone marrow, or both, was performed in 104 (82%), 22 (17%), and 4 (3%) patients, respectively, from HLA identical sibling donors (n = 93, 72%), matched unrelated donors (n = 23, 18%), mismatched related donors (4%), or mismatched unrelated donors (6%). Total body irradiation (TBI) at a dose of 2 Gy delivered in one fraction was given to 101 patients (78%), and a total dose of 4-6 Gy was given in 29 (22%) patients. The median dose rate was 14.3 cGy/min (range, 6-16.4). Results: After a median follow-up period of 20 months (range, 1-62 months), engraftment was obtained in 122 patients (94%). Acute graft-vs.-host disease of Grade 2 or worse was observed in 37% of patients. Multivariate analysis showed three favorable independent factors for event-free survival: HLA identical sibling donor (p < 0.0001; relative risk [RR], 0.15), complete remission (p < 0.0001; RR, 3.08), and female donor to male patient (p = 0.006; RR 2.43). For relapse, the two favorable prognostic factors were complete remission (p < 0.0001, RR 0.11) and HLA identical sibling donor (p = 0.0007; RR 3.59). Conclusions: In this multicent