Hematopoietic Acute Radiation Syndrome (Bone marrow syndrome, Aplastic Anemia): Molecular Mechanisms of Radiation Toxicity.

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Popov, Dmitri

Key Words: Aplastic Anemia (AA), Pluripotential Stem Cells (PSC) Introduction: Aplastic Anemia (AA) is a disorder of the pluripotential stem cells involve a decrease in the number of cells of myeloid, erythroid and megakaryotic lineage [Segel et al. 2000 ]. The etiology of AA include idiopathic cases and secondary aplastic anemia after exposure to drugs, toxins, chemicals, viral infections, lympho-proliferative diseases, radiation, genetic causes, myelodisplastic syndromes and hypoplastic anemias, thymomas, lymphomas. [Brodskyet al. 2005.,Modan et al. 1975., Szklo et al. 1975]. Hematopoietic Acute Radiation Syndrome (or Bone marrow syndrome, or Radiation-Acquired Aplastic Anemia) is the acute toxic syndrome which usually occurs with a dose of irradiation between 0.7 and 10 Gy (70- 1000 rads), depending on the species irradiated. [Waselenko et al., 2004]. The etiology of bone morrow damage from high-level radiation exposure results depends on the radiosensitivity of certain bone marrow cell lines. [Waselenko et al. 2004] Aplastic anemia after radiation exposure is a clinical syndrome that results from a marked disorder of bone marrow blood cell production. [Waselenko et al. 2004] Radiation hematotoxicity is mediated via genotoxic and other specific toxic mechanisms, leading to aplasia, cell apoptosis or necrosis, initiation via genetic mechanisms of clonal disorders, in cases such as the acute radiation-acquired form of AA. AA results from radiation injury to pluripotential and multipotential stem cells in the bone marrow. The clinical signs displayed in reticulocytopenia, anemia, granulocytopenia, monocytopenia, and thrombocytopenia. The number of marrow CD34+ cells (multipotential hematopoietic progenitors) and their derivative colony-forming unit{granulocyte-macrophage (CFU-GM) and burst forming unit {erythroid (BFU{E) are reduced markedly in patients with AA. [Guinan 2011, Brodski et al. 2005, Beutler et al.,2000] Cells expressing CD34 (CD34+ cell) are normally

Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation

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Yamamoto, Tetsuo; Kinoshita, Manabu; Shinomiya, Nariyoshi; Hiroi, Sadayuki; Sugasawa, Hidekazu; Majima, Takashi; Seki, Shuhji; Matsushita, Yoshitaro; Saitoh, Daizoh

2010-01-01

While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome. (author)

Pure red cell aplasia in a simultaneous pancreas-kidney transplantation patient: inside the erythroblast

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Francesca Labbadia

2012-09-01

Full Text Available A case of pure red cell aplasia in a simultaneous kidney-pancreas transplant recipient on immunosuppressive therapy is reported here. The patient presented with anemia unresponsive to erythropoietin treatment. Bone marrow cytomorphology was highly suggestive of parvovirus pure red cell aplasia, which was confirmed with serology and polymerase chain reaction positive for parvovirus B19 DNA in peripheral blood. After the administration of intravenous immunoglobulin the anemia improved with a rising number of the reticulocytes.

CD19 CAR-targeted T cells induce long-term remission and B Cell Aplasia in an immunocompetent mouse model of B cell acute lymphoblastic leukemia.

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Marco L Davila

Full Text Available Although many adults with B cell acute lymphoblastic leukemia (B-ALL are induced into remission, most will relapse, underscoring the dire need for novel therapies for this disease. We developed murine CD19-specific chimeric antigen receptors (CARs and an immunocompetent mouse model of B-ALL that recapitulates the disease at genetic, cellular, and pathologic levels. Mouse T cells transduced with an all-murine CD3ζ/CD28-based CAR that is equivalent to the one being used in our clinical trials, eradicate B-ALL in mice and mediate long-term B cell aplasias. In this model, we find that increasing conditioning chemotherapy increases tumor eradication, B cell aplasia, and CAR-modified T cell persistence. Quantification of recipient B lineage cells allowed us to estimate an in vivo effector to endogenous target ratio for B cell aplasia maintenance. In mice exhibiting a dramatic B cell reduction we identified a small population of progenitor B cells in the bone marrow that may serve as a reservoir for long-term CAR-modified T cell stimulation. Lastly, we determine that infusion of CD8+ CAR-modified T cells alone is sufficient to maintain long-term B cell eradication. The mouse model we report here should prove valuable for investigating CAR-based and other therapies for adult B-ALL.

I-131 therapy for hyperthyroidism in carbimazole induced acute aplastic anaemia

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Jenkin, B.A.; Van Every, B.; Kelly, M.J.

1998-01-01

Full text: We present a case of a 39 year old previously well woman who developed carbimazole-induced acute aplastic anaemia. Following 6 weeks of carbimazole for Grave's disease she presented with fever, sore throat and lethargy and was found to be pancytopaenic. Haemoglobin fell to 79g/l (normal>120g/l), neutrophils to an undetectable level and platelets to 4,000/ml (normal>150,000/ml). From the MIRD schema it was estimated that a therapeutic dose of 444 MBq (12mCi) to treat her hyperthyroidism would deliver a red marrow radiation dose of about 30 mSv, at least an order of magnitude below any expected demonstrable deleterious effect on the marrow. Subsequently a dose of 444 MBq of I-131 was given and within 2 weeks the marrow had begun to recover, eventually to normal. This case would support the use of 1-131 for hyperthyroidism in carbimazole-induced marrow aplasia, even in profoundly depressed marrow

I-131 therapy for hyperthyroidism in carbimazole induced acute aplastic anaemia

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Jenkin, B.A.; Van Every, B.; Kelly, M.J. [Alfred Hospital, Prahran, VIC (Australia). Nuclear Medicine Department

1998-06-01

Full text: We present a case of a 39 year old previously well woman who developed carbimazole-induced acute aplastic anaemia. Following 6 weeks of carbimazole for Grave`s disease she presented with fever, sore throat and lethargy and was found to be pancytopaenic. Haemoglobin fell to 79g/l (normal>120g/l), neutrophils to an undetectable level and platelets to 4,000/ml (normal>150,000/ml). From the MIRD schema it was estimated that a therapeutic dose of 444 MBq (12mCi) to treat her hyperthyroidism would deliver a red marrow radiation dose of about 30 mSv, at least an order of magnitude below any expected demonstrable deleterious effect on the marrow. Subsequently a dose of 444 MBq of I-131 was given and within 2 weeks the marrow had begun to recover, eventually to normal. This case would support the use of 1-131 for hyperthyroidism in carbimazole-induced marrow aplasia, even in profoundly depressed marrow

Individual differences in post radiation regeneration of the bone marrow in nonuniform irradiation (experimental investigation)

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Kalandarova, M.P.

1980-01-01

Reparative regeneration in bone marrow of sternum and iliac bone in each of 20 dogs was studied after single and two-time total X-ray irradiation. Extreme dose rates in bodies differed 5 and 8 times. It was shown that bone marrow repair did not depend on its composition before irradiation. Dogs whose bone narrow was rich of cellular elements before irradiation had both active and sharply reduced bone marrow regeneration after single and two-time irradiation in 0.75-1.45 Gy doses (sternum). Animals with a poor total cellular composition of bone marrow of sternum before irradiation also had differences in the course of reparative processes: in some of them they were considerably pronoUnced and in others bone marrow aplasia lasted for one month. IndiVidual differences in the bone marrow (iliac bone) irradiated with 1.85-3.2 Gy doses were less marked during the reparative regeneration

Radioprotection against radiation induced bone marrow syndrome by a semi-synthetic derivative of chlorophyll

International Nuclear Information System (INIS)

Suryavanshi, Shweta; Sharma, Deepak; Checker, Rahul; Santosh Kumar, S.; Sainis, Krishna B.

2014-01-01

A plethora of biological properties have been attributed to chlorophyllin (CHL), the water soluble derivative of the green plant pigment chlorophyll. Several studies are available describing its ability to modify genotoxic effects. It has been shown that administration CHL to human lymphopenic individuals led to the recovery and restoration of the immune system and also inhibited aflatoxin B1-DNA binding in individuals residing in high risk exposure to this liver carcinogen. The present study is aimed at establishing radioprotective efficacy of CHL against ionizing radiation induced hematopoietic syndrome. CHL offered complete protection against whole body irradiation (WBI, 7 Gy) induced mortality in mice. This observation was supported by increase in the number of macroscopic endogenous colonies enumerated on the surface of the spleens taken from CHL+WBI group as compared to WBI group. Radioprotection by CHL was found to be mediated by increasing the frequency of hematopoietic stem cells (HSCs) as evaluated by side population assay. Administration of CHL induced G1 arrest in bone marrow cells, increased number of granulocytes and neutrophils in the peripheral blood. At the molecular level, activation of ERK was observed in bone marrow cells obtained from CHL administered mice. In conclusion, CHL mediated radioprotection was attributed to increased stem cell numbers, G1 arrest in bone marrow cells, increased neutrophil numbers and ERK activation. (author)

Effects of ionizing radiation on differentiation of murine bone marrow cells into mast cells

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Murakami, Sho; Yoshino, Hironori; Ishikawa, Junya; Yamaguchi, Masaru; Tsujiguchi, Takakiyo; Nishiyama, Ayaka; Yokoyama, Kouki; Kashiwakura, Ikuo

2015-01-01

Mast cells, immune effector cells produced from bone marrow cells, play a major role in immunoglobulin E–mediated allergic responses. Ionizing radiation affects the functions of mast cells, which are involved in radiation-induced tissue damage. However, whether ionizing radiation affects the differential induction of mast cells is unknown. Here we investigated whether bone marrow cells of X-irradiated mice differentiated into mast cells. To induce mast cells, bone marrow cells from X-irradiated and unirradiated mice were cultured in the presence of cytokines required for mast cell induction. Although irradiation at 0.5 Gy and 2 Gy decreased the number of bone marrow cells 1 day post-irradiation, the cultured bone marrow cells of X-irradiated and unirradiated mice both expressed mast cell–related cell-surface antigens. However, the percentage of mast cells in the irradiated group was lower than in the unirradiated group. Similar decreases in the percentage of mast cells induced in the presence of X-irradiation were observed 10 days post irradiation, although the number of bone marrow cells in irradiated mice had recovered by this time. Analysis of mast cell function showed that degranulation of mast cells after immunoglobulin E–mediated allergen recognition was significantly higher in the X-irradiated group compared with in the unirradiated group. In conclusion, bone marrow cells of X-irradiated mice differentiated into mast cells, but ionizing radiation affected the differentiation efficiency and function of mast cells. (author)

Protracted radiation-induced alterations in hematopoietic repair and recovery

International Nuclear Information System (INIS)

Seed, T.M.; Fritz, T.E.

1997-01-01

Pathologic predisposition of beagle dogs under chronic, low daily dose (7.5 cGy day -1 ) whole-body gamma irradiation has been studied relative to molecular repair and hematopoietic competency. Molecular repair, assessed by a microscopy-based unscheduled DNA synthesis (UDS) response, was measured within proliferative and nonproliferative marrow myeloid elements of dogs with markedly different hematopoietic capacities (low capacity, aplasia-prone [AA + ] versus high capacity, myeloproliferative disease-prone [MPD + ]) under protracted radiation stress. Results indicated that protracted exposure elicited a net increase in UDS-repair capacity that was largely independent of exposure duration. This enhanced capacity resulted from the increased strength of the UDS signal together with an expanded number of positively responding cells. The combined response was strong in primitive blasts and weak in more differentiated myelocytic cells. The UDS repair response of the MPD + dogs was significantly greater than that of the AA + animals and was clearly modified relative to the controls. These results suggest that both resiliency and pathologic potential of the hematopoietic system under protracted radiation stress is, in part, associated with an augmentable DNA repair within the more primitive myeloid marrow elements. (author)

THE PURE RED BLOOD CELL APLASIA IN RENAL TRANSPLANT RECIPIENT

OpenAIRE

B. T. Dzumabaeva; L. S. Birjukova; L. B. Kaplanskaya; D. P. Maksimov

2011-01-01

The pure red blood cell aplasia of renal transplant recipients caused by parvovirus B19 (PB19) is characterized by persistent anemia which resistant to erythropoietin therapy, lack of reticulocytes, bone marrow hypoplasia, and clinically accompanied by severe recurrent bacterial, fungal and viral infection. In case of reactivation PB19 it is necessarv, first of all, eliminate the causes activation of this virus and to cancel or reduce the dose of drugs which depressed the normal hematopoiesis...

The role of diclofenack on inducing of aplasia cutis congenita: a case report

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Pajaziti, Laura; Rexhepi, Syzana; Shatri-Mu?a, Ylfete; Ferizi, Mybera

2009-01-01

Background Aplasia cutis congenita is a disorder where e newborn child is missing skin from certain areas. It is a rare condition with no particular race or sex more at risk. May occur by itself or be associated with other physical syndromes or disorders. A classification system exists for aplasia cutis congenital consisting of 9 groups, based on the number and location of the skin defects and the presence or absence of other malformations. Causes of aplasia congenital could be heredity, tera...

Sister chromatid exchanges in the bone marrow cells of in vivo rats induced by gamma radiation and chemical mutagens

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Rodriguez R, R.G.

1981-01-01

Sister chromatid exchanges (SCE) in the bone marrow of in vivo rats induced by gamma radiation doses and by the chemical mutagens, mitomycin C (MMC), cyclophosphamide (CP), and sulphonate-methylmethane (SMM), were studied. The purpose was to evaluate the sensitivity and reproducibility of a simplified SCE in vivo detecting system developed in our laboratory and to compare the results obtained with those reported elsewhere. Simplification consisted in administering the amounts of 5-bromo-2'-deoxyuridine (BrdU) necessary to observe the SCE, after first adsorbing the BrdU in activated carbon and then injecting it interperitoneally, into the rats. The results were a longer time in vivo ADN incorporation without convulsions in the rats, and a reduction in the time course as compared to other methods. We observed a basal rate of 3.6+-0.37 SCE/cell and that: 0.44 Gy of gamma radiation induced 7.7+-0.73 SCE/cell; 1.6 μg/g of MMC induced 8.1+-1.20 SCE/cell; 5 μg/g of CP induced 8.25+-1.5 SCE/cell, 40 μg/g of SMM induced 22.0+-5 SCE/cell and 380 μg/g of sulphonate-ethylmethane induced 8.6+-1.2 SCE/cell. This showed that all the agents were capable of inducing SCE in the bone marrow cells of rats in vivo under our conditions. We noted a greater induced efficiency for gamma radiation than the obtained by other investigators and a relatively similar efficiency in the case of chemical mutagens as reported in other studies. (author)

Medical management of accidentally exposed individuals

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Nenot, J.C.

1998-01-01

Bone marrow aplasia is one of the main syndromes following a high dose accidental radiation exposure. Whilst transfusion and bone marrow transplantation have been used with some success starting with the first treatments of accident victims, other therapeutic strategies are needed. With the development of experimental and clinical haematology, promising new approaches to the treatment of aplasia have appeared. New trends for the treatment of haemopoietic injury based on bone marrow transplantation rely on new sources of compatible donor cells, such as cord blood, on the selection of immature haemopoietic cells and on new transplant regimens. Haemopoietic growth factors stimulate the proliferation and/or differentiation of haemopoietic progenitors and, possibly, stem cells. Furthermore, they act on the functions of mature cells. Currently, they have specific uses in haematology related to their role in the regulation of growth and in the differentiation of haemopoietic progenitor cells. Growth factors have already been used for the treatment of accidental radiation induced aplasia and lessons have been learned from their medical management and followup. (author)

Medical management of accidentally exposed individuals

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Nenot, Jean-Claude [CEA Centre d`Etudes de Fontenay-aux-Roses, 92 (France). Inst. de Protection et de Surete Nucleaire

1997-12-31

Bone marrow aplasia is one of the main syndromes following a high dose accidental radiation exposure. Although both transfusion and bone marrow transplantation have been used with some success since the first treatments of patients, other therapeutic strategies are needed. New promising approaches of the treatment of aplasia have appeared with the development of experimental and clinical hematology. Some new trends for the treatment of the hematopoietic injury based on bone marrow transplantation rely on new sources of compatible donor cells, such as cord blood, on the selection of immature haemopoietic cells and on new transplant regimens. The hematopoietic growth factors stimulate proliferation and/or differentiation of hematopoietic progenitors and possibly stem cells. Furthermore, they act on the functions of mature cells. They have now specific uses in hematology, related to their role in the regulation of growth and differentiation of hematopoietic progenitor cells. Some growth factors have already been used for the treatment of accidental radiation-induced aplasia and lessons have been learned from their medical management and follow-up. (author) 30 refs.

Radiological protection effect on vanillin derivative VND3207 radiation-induced cytogenetic damage in mouse bone marrow cells

International Nuclear Information System (INIS)

Wang Chuangao; Wang Li; Zhou Pingkun; Wang Zhongwen; Hu Yongzhe; Jin Haiming; Zhang Xueqing; Chen Ying

2010-01-01

Objective: To study the protection of vanillin derivative VND3207 on the cytogenetic damage of mouse bone marrow cell induced by ionizing radiation. Methods: BALB/c mice were randomly divided into five groups: normal control group, 2 Gy dose irradiation group, and three groups of 2 Gy irradiation with VND3207 protection at doses of 10, 50 and 100 mg/kg, respectively. VND3207 was given by intragastric administration once a day for five days. Two hours after the last drug administration, the mice were irradiated with 2 Gy γ-rays. The changes of polychromatophilic erythroblasts micronuclei (MN), chromosome aberration (CA) and mitosis index (MI) of mouse bone marrow cells were observed at 24 and 48 h after irradiation. Results: Under the protection of VND3207 at the dosages 10, 50, 100 μmg/kg, the yields of poly-chromatophilic erythroblasts MN and CA of bone marrow cells were significantly decreased (t=2.36-4.26, P<0.05), and the marrow cells MI remained much higher level compared with the irradiated mice without drug protection (t=2.58, 2.01, P<0.05). The radiological protection effect was drug dose-dependent, and the administration of VND3207 at the dosage of 100 mg/kg resulted in reduction by 50 % and 65% in the yields of MN and CA, respectively. Conclusions: VND3207 had a good protection effect of on γ-ray induced cytogentic damage of mouse bone marrow cells. (authors)

Pure red cell aplasia following autoimmune hemolytic anemia: An enigma

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M Saha

2013-01-01

Full Text Available A 26-year-old previously healthy female presented with a 6-month history of anemia. The laboratory findings revealed hemolytic anemia and direct antiglobulin test was positive. With a diagnosis of autoimmune hemolytic anemia (AIHA, prednisolone was started but was ineffective after 1 month of therapy. A bone marrow trephine biopsy revealed pure red cell aplasia (PRCA showing severe erythroid hypoplasia. The case was considered PRCA following AIHA. This combination without clear underlying disease is rare. Human parvovirus B19 infection was not detected in the marrow aspirate during reticulocytopenia. The patient received azathioprine, and PRCA improved but significant hemolysis was once again documented with a high reticulocyte count. The short time interval between AIHA and PRCA phase suggested an increased possibility of the evolution of a single disease.

Radiation-induced aneusomic clones in bone marrow of rats

International Nuclear Information System (INIS)

Kohno, Sei-Ichi; Ishihara, Takaaki

1976-01-01

Wistar rats 3 months old were given a single whole-body X-irradiation with 700 R. They were killed 9.3 months, on average, after irradiation. From the bone marrows of the 23 irradiated rats, 54 clones of cells with radiation-induced chromosome abnormalities ranging from 3.3 to 78.3% in size were obtained. Karyotype analysis at the banding level showed that 43 out of the 54 clones had balanced chromosome constitutions and that the remaining 11 clones were unbalanced. The 43 balanced clones consisted of 33 clones with reciprocal translocations, 6 with inversions and 4 with both translocations and inversions. The 11 unbalanced clones were made up of 7 aneuploid clones and 4 pseudo-diploid clones. Of the 54 clones, 15 were large with frequencies of more than 25%. Contrary to general belief that cells with unbalanced chromosome constitutions have less capacity to proliferate than those with balanced ones, 8 of the 15 large clones, especially all, except 1, of the largest 6 clones were unbalanced, either aneuploid or pseudo-diploid

THE PURE RED BLOOD CELL APLASIA IN RENAL TRANSPLANT RECIPIENT

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B. T. Dzumabaeva

2011-01-01

Full Text Available The pure red blood cell aplasia of renal transplant recipients caused by parvovirus B19 (PB19 is characterized by persistent anemia which resistant to erythropoietin therapy, lack of reticulocytes, bone marrow hypoplasia, and clinically accompanied by severe recurrent bacterial, fungal and viral infection. In case of reactivation PB19 it is necessarv, first of all, eliminate the causes activation of this virus and to cancel or reduce the dose of drugs which depressed the normal hematopoiesis germs, thus to reduce the pancytopenia associating complications in this population. 

Radio protective effect of black mulberry extract on radiation-induced damage in bone marrow cells and liver in the rat

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Ghasemnezhad Targhi, Reza; Homayoun, Mansour; Mansouri, Somaieh; Soukhtanloo, Mohammad; Soleymanifard, Shokouhozaman; Seghatoleslam, Masoumeh

2017-01-01

Ionizing radiation by producing free radicals induces tissue oxidative stress and has clastogenic and cytotoxic effects. The radio protective effect of black mulberry extract (BME) has been investigated on liver tissue and bone marrow cells in the rat. Intraperitoneal (ip) administration of 200 mg/kg BME three days before and three days after 3 Gy and 6 Gy gamma irradiation significantly reduced the frequencies of micro nucleated polychromatic erythrocytes (MnPCEs) and micro nucleated norm chromatic erythrocyte (MnNCEs) and increased PCE/PCE+NCE ratio in rat bone marrow compared to the non-treated irradiated groups. Moreover, this concentration of BME extract decreased the level of malondialdehyde (MDA) and superoxide dismutase (SOD), as well as enhanced the total thiol content and catalase activity in rat's liver compared to the non-treated irradiated groups. It seems that BME extract with antioxidant activity reduced the genotoxicity and cytotoxicity induced by gamma irradiation in bone marrow cells and liver in the rat.

Imaging Radiation-Induced Gastrointestinal, Bone Marrow Injury and Recovery Kinetics Using 18F-FDG PET.

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Tang, Tien T; Rendon, David A; Zawaski, Janice A; Afshar, Solmaz F; Kaffes, Caterina K; Sabek, Omaima M; Gaber, M Waleed

2017-01-01

Positron emission tomography using 18F-Fluro-deoxy-glucose (18F-FDG) is a useful tool to detect regions of inflammation in patients. We utilized this imaging technique to investigate the kinetics of gastrointestinal recovery after radiation exposure and the role of bone marrow in the recovery process. Male Sprague-Dawley rats were either sham irradiated, irradiated with their upper half body shielded (UHBS) at a dose of 7.5 Gy, or whole body irradiated (WBI) with 4 or 7.5 Gy. Animals were imaged using 18F-FDG PET/CT at 5, 10 and 35 days post-radiation exposure. The gastrointestinal tract and bone marrow were analyzed for 18F-FDG uptake. Tissue was collected at all-time points for histological analysis. Following 7.5 Gy irradiation, there was a significant increase in inflammation in the gastrointestinal tract as indicated by the significantly higher 18F-FDG uptake compared to sham. UHBS animals had a significantly higher activity compared to 7.5 Gy WBI at 5 days post-exposure. Animals that received 4 Gy WBI did not show any significant increase in uptake compared to sham. Analysis of the bone marrow showed a significant decrease of uptake in the 7.5 Gy animals 5 days post-irradiation, albeit not observed in the 4 Gy group. Interestingly, as the metabolic activity of the gastrointestinal tract returned to sham levels in UHBS animals it was accompanied by an increase in metabolic activity in the bone marrow. At 35 days post-exposure both gastrointestinal tract and bone marrow 18F-FDG uptake returned to sham levels. 18F-FDG imaging is a tool that can be used to study the inflammatory response of the gastrointestinal tract and changes in bone marrow metabolism caused by radiation exposure. The recovery of the gastrointestinal tract coincides with an increase in bone marrow metabolism in partially shielded animals. These findings further demonstrate the relationship between the gastrointestinal syndrome and bone marrow recovery, and that this interaction can be studied

Imaging Radiation-Induced Gastrointestinal, Bone Marrow Injury and Recovery Kinetics Using 18F-FDG PET.

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Tien T Tang

Full Text Available Positron emission tomography using 18F-Fluro-deoxy-glucose (18F-FDG is a useful tool to detect regions of inflammation in patients. We utilized this imaging technique to investigate the kinetics of gastrointestinal recovery after radiation exposure and the role of bone marrow in the recovery process. Male Sprague-Dawley rats were either sham irradiated, irradiated with their upper half body shielded (UHBS at a dose of 7.5 Gy, or whole body irradiated (WBI with 4 or 7.5 Gy. Animals were imaged using 18F-FDG PET/CT at 5, 10 and 35 days post-radiation exposure. The gastrointestinal tract and bone marrow were analyzed for 18F-FDG uptake. Tissue was collected at all-time points for histological analysis. Following 7.5 Gy irradiation, there was a significant increase in inflammation in the gastrointestinal tract as indicated by the significantly higher 18F-FDG uptake compared to sham. UHBS animals had a significantly higher activity compared to 7.5 Gy WBI at 5 days post-exposure. Animals that received 4 Gy WBI did not show any significant increase in uptake compared to sham. Analysis of the bone marrow showed a significant decrease of uptake in the 7.5 Gy animals 5 days post-irradiation, albeit not observed in the 4 Gy group. Interestingly, as the metabolic activity of the gastrointestinal tract returned to sham levels in UHBS animals it was accompanied by an increase in metabolic activity in the bone marrow. At 35 days post-exposure both gastrointestinal tract and bone marrow 18F-FDG uptake returned to sham levels. 18F-FDG imaging is a tool that can be used to study the inflammatory response of the gastrointestinal tract and changes in bone marrow metabolism caused by radiation exposure. The recovery of the gastrointestinal tract coincides with an increase in bone marrow metabolism in partially shielded animals. These findings further demonstrate the relationship between the gastrointestinal syndrome and bone marrow recovery, and that this

Radiation-induced enlargement of granulocytic and macrophage progenitor cells in mouse bone marrow

Energy Technology Data Exchange (ETDEWEB)

Metcalf, D; Johnson, G R; Wilson, J [Walter and Eliza Hall Inst. of Medical Research, Parkville (Australia)

1977-01-01

The peak sedimentation velocity of C/sub 57/BL mouse bone marrow progenitors of granulocytes and macrophages (GM-colony-forming cells, GM-CFC's) increased from 4.3 mm/h to 7 to 8 mm/h by 2 days after 250 rad whole body irradiation and slowly returned to normal over the next 3 weeks. Preliminary irradiation and/or endotoxin injection did not prevent this radiation-induced change. Some change in sedimentation velocity was seen with as little as 100 rad irradiation. Neither buoyant density nor cell cycle changes could account for the sedimentation velocity data which therefore indicate a major volume increase in the GM-CFC's. This size enlargement affected all subpopulations of GM-CFC's which consequently maintained their size relationship with one another.

Ionizing Radiation Stimulates Expression of Pro-Osteoclastogenic Genes in Marrow and Skeletal Tissue

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Alwood, J. S.; Shahnazari, M.; Chicana, B.; Schreurs, A. S.; Kumar, A.; Bartolini, A.; Shirazi-Fard, Y.; Globus, R. K.

2015-01-01

Exposure to ionizing radiation can cause rapid mineral loss and increase bone-resorbing osteoclasts within metabolically-active, cancellous-bone tissue leading to structural deficits. To better understand mechanisms involved in rapid, radiation-induced bone loss, we determined the influence of total-body irradiation on expression of select cytokines known both to stimulate osteoclastogenesis and contribute to inflammatory bone disease. Adult (16wk), male C57BL/6J mice were exposed to either 2Gy gamma rays (137Cs, 0.8Gy/min) or heavy ions (56Fe, 600MeV, 0.50-1.1Gy/min); this dose corresponds to either a single fraction of radiotherapy (typical total dose is =10Gy) or accumulates over long-duration, interplanetary missions. Serum, marrow, and mineralized tissue were harvested 4hrs-7d later. Gamma irradiation caused a prompt (2.6-fold within 4hrs) and persistent (peaking at 4.1-fold within 1d) rise in the expression of the obligate osteoclastogenic cytokine, receptor activator of nuclear factor kappaB-ligand (Rankl) within marrow cells over controls. Similarly, Rankl expression peaked in marrow cells within 3d of iron exposure (9.2-fold). Changes in Rankl expression induced by gamma irradiation preceded and overlapped with a rise in expression of other pro-osteoclastic cytokines in marrow (e.g., monocyte chemotactic protein-1 increased 11.9-fold, tumor necrosis factor-alpha increased 1.7- fold over controls). Marrow expression of the RANKL decoy receptor, osteoprotegerin (Opg), also rose after irradiation (11.3-fold). The ratio Rankl/Opg in marrow was increased 1.8-fold, a net pro-resorption balance. As expected, radiation increased a serum marker of resorption (tartrate resistant acid phosphatase) and led to cancellous bone loss (16% decrease in bone volume/total volume) through reduced trabecular struts. We conclude that total-body irradiation (gamma or heavy-ion) caused temporal, concerted regulation of gene expression within marrow and mineralized tissue for

Bone marrow transplantation in miniature swine: I. Autologous and SLA matched allografts

International Nuclear Information System (INIS)

Pennington, L.R.; Pescovitz, M.D.; Popitz, F.; Sachs, D.H.; Sakamoto, K.

1986-01-01

We developed a successful bone marrow transplant protocol in MHC-inbred miniature swine (MS). Three groups of MS were studied: irradiation controls, autologous bone marrow transplants and SLA matched bone marrow allografts. One day prior to irradiation, all animals underwent Hickman catheter placement via the external jugular vein. Bone marrow was harvested by direct mechanical removal of marrow from four long bones in Groups 2 and 3 one day prior to irradiation. All animals received 900 rads of midline body radiation from a Cobalt-60 source, were treated 1 g of cephalothin IV bid from day 1 to 14, 20 mg of genetamicin IV bid, from day 4 through 14 and 250 to 350 ml of fresh, irradiated whole blood from blood group identical donors on days 7, 11 and 14. Bone marrow was filtered, washed, stored overnight at 4 C and reinfused one to six hr after irradiation. Engraftment was defined by return of the peripheral WBC to 1000/mm 3 . All six animals in Group 1 died of aplasia between days 7 and 12. Marrow engrafted in eight of 12 animals in Group 2 and 7 of 10 animals in Group 3. This model provides a means to study the biological characteristics of bone marrow transplantation in immunologically well characterized large animals and should prove useful as a model for bone marrow transplants in man

Patterns of bone-marrow scintigraphy

International Nuclear Information System (INIS)

Touya, J.J.; Lee, G.S.; Narvaez, M.; Marciano, D.

1977-01-01

111 In-transferrin, radiocolloid and bone scans were performed within one week on 105 from more than 250 scanned patients with different haematological disorders. All patients had complete haematological workups and confirmed final diagnoses. From the comparison of the 111 In-transferrin marrow scan with the radiocolloid marrow scan and bone scan, eight basic patterns of localized or generalized disorders in the bone marrow cell production were delineated. The first pattern was called a cold area and two sub-patterns were distinguished in it. A cold area in the erythropoietic and reticuloendothelial scans associated with cold or normal areas in the bone scan corresponded to radiation damage of the marrow or multiple myeloma; a cold area in both marrow scans with a hot area in the bone scan to tumour, infarct and bone trauma. The second pattern was called a hot area. A hot area in the two marrow scans with a normal bone scan was observed in islands of active bone-marrow. Hot areas in both 111 In-transferrin and bone scan associated with a cold area in the radiocolloid scan were observed in tumours growing in bones with or without little active bone marrow. Hot areas on the three scans were observed in osteomyelitis of bones of the extremities. The third pattern was bone-marrow expansion, which was observed in hereditary haemolytic anaemias, in myeloproliferative disorders and in patients with bone-marrow damage following irradiation. The fourth pattern was saturation of the serum iron-binding capacity and it was manifested by increased activity in the kidneys in the 111 In-transferrin scan. The fifth pattern was bone-marrow failure which consists of decreased accumulation in the marrow and increased accumulation in the liver of marrow-seeking agents associated with normal bone scan. The sixth pattern, pure red cell aplasia, was characterized by less accumulation of 111 In-transferrin than radiocolloid in the bone marrow. The seventh pattern, bone-marrow siderosis

Reduction of radiation-induced damage to salivary gland by bone marrow derived stem cells

International Nuclear Information System (INIS)

Coppes, R.P.; Wierenga, P.K.; Kampinga, H.H.; De Hann, G.

2003-01-01

marrow-derived cells home to severely damaged salivary glands after transplantation/mobilisation. Hence, BMSC transplantation could become a promising modality to ameliorate radiation-induced complications in salivary glands after radiotherapy

Experimental hypoplastic marrow failure in the mouse

International Nuclear Information System (INIS)

Kubota, K.; Mizoguchi, H.; Miura, Y.; Kano, S.; Takaku, F.

1978-01-01

In order to study the pathogenesis of aplastic anemia in man, hemopoietic stem cells were investigated in 'aplastic mice' the aplasia being induced by the immunological method. C3H/He(H-2sup(k), Mlssup(c)) received 600 rad whole body x-irradiation followed by the transplantation of 10 7 lymph node cells prepared from B10.BR mice (H-2sup(k), Mlssup(b)). The C3H/He mice developed pancytopenia and marrow hypoplasia 21 days after these treatments. The total number of nucleated cells, CFU-S and CFU-C in the marrow and the wet weight and CFU-C of the spleen were markedly reduced. These findings are consistent with those of aplastic anemia in man and the model may provide a useful tool for the investigation of the pathogenesis of this anemia. Control mice that received irradiation only recovered from the damage 21 days later, while control mice that received lymph node cells only showed no hematological changes. (author)

Echinacea and Parsley Oil Ameliorate the Changes Induced by gamma-radiation in Uterus, Ovaries and Bone Marrow of Female Rats

International Nuclear Information System (INIS)

Ramadan, F.L.; Othman, A.

2013-01-01

The aim of the present study was to evaluate the role of Echinacea and parsley oil some biochemical, histological and bone marrow abnormalities, induced by g-irradiation exposure. Echinacea and parsley oil were orally administrated to female rats (50 mg /100 g b.wt./ day and 0.2 ml/100g b.wt./day, respectively) 7 days before and during exposure to radiation for 3 weeks since female rats were submitted to fractionated whole body gamma-radiation 1 Gy every week up to 3 Gy total dose. The results obtained revealed that treatment with Echinacea and parsley oil induced significant amelioration to the harmful effect of radiation on red blood corpuscles (RBCs), white blood corpuscles (WBCs), haemoglobin concentration (Hb), calcium level (Ca), in addition to estradiol (E2) and progesterone (p4) hormones in serum. Moreover, the treatment with Echinacea and parsley oil diminished the increase in urea, uric acid, creatinine and alkaline phosphatase (ALP) levels recorded in the serum of irradiated rats. Our findings demonstrated that exposure to g-radiation caused an increase in the apoptotic cells, while the treatment with Echinacea and parsley oil decreased the apoptotic cells and increased the alive cells in the bone marrow of female rats. Histological observations of the ovary and uterus sections showed that radiation induced deformation in the follicular tissue, dis organization of granulosa cells, abnormal Graafian follicle which appeared without ova, haemorrhage, dilated blood vessels and vacuolation ovarian tissue. Also, the uterus of female rats showed increase in endometrium thickness, decreased muscularis thickness and muscle fibres appeared with pyknotic nuclei. All these changes were obviously improved in animals supplied with echinacea and parsley oil. It could be concluded that Echinacea and parsley oil could be useful and adjunct for maintaining the integrity of biochemical changes, restored the original histological architecture of the ovary and uterus and

Mechanical Loading Attenuates Radiation-Induced Bone Loss in Bone Marrow Transplanted Mice

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Govey, Peter M.; Zhang, Yue; Donahue, Henry J.

2016-01-01

Exposure of bone to ionizing radiation, as occurs during radiotherapy for some localized malignancies and blood or bone marrow cancers, as well as during space travel, incites dose-dependent bone morbidity and increased fracture risk. Rapid trabecular and endosteal bone loss reflects acutely increased osteoclastic resorption as well as decreased bone formation due to depletion of osteoprogenitors. Because of this dysregulation of bone turnover, bone’s capacity to respond to a mechanical loading stimulus in the aftermath of irradiation is unknown. We employed a mouse model of total body irradiation and bone marrow transplantation simulating treatment of hematologic cancers, hypothesizing that compression loading would attenuate bone loss. Furthermore, we hypothesized that loading would upregulate donor cell presence in loaded tibias due to increased engraftment and proliferation. We lethally irradiated 16 female C57Bl/6J mice at age 16 wks with 10.75 Gy, then IV-injected 20 million GFP(+) total bone marrow cells. That same day, we initiated 3 wks compression loading (1200 cycles 5x/wk, 10 N) in the right tibia of 10 of these mice while 6 mice were irradiated, non-mechanically-loaded controls. As anticipated, before-and-after microCT scans demonstrated loss of trabecular bone (-48.2% Tb.BV/TV) and cortical thickness (-8.3%) at 3 wks following irradiation. However, loaded bones lost 31% less Tb.BV/TV and 8% less cortical thickness (both pbones also had significant increases in trabecular thickness and tissue mineral densities from baseline. Mechanical loading did not affect donor cell engraftment. Importantly, these results demonstrate that both cortical and trabecular bone exposed to high-dose therapeutic radiation remain capable of an anabolic response to mechanical loading. These findings inform our management of bone health in cases of radiation exposure. PMID:27936104

UMF-synthetase activity in rat tissue extracts with the bone 4 marrow form of radiation sickness

International Nuclear Information System (INIS)

Levitova, E.N.; Koshcheenko, N.N.; Romantsev, E.F.

1986-01-01

Whole-body γ-irradiation of rats with a dose inducing bone marrow radiation syndrome caused phase organospecific chages in UMP-synthase activity. Disturbances of enzymic activity in the bone marrow and spleen well correlated with the dynamics of interphase and reproductive cell death. In brain extracts, UMP biosynthesis from orotic acid did not undergo essential changes

Autologous cell therapy as a new approach to treatment of radiation-induced bone marrow aplasia: preliminary study in a baboon model

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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)

Acute radiation syndrones and their management

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Cronkite, E.P.

1988-01-01

Radiation syndromes produced by large doses of ionizing radiation are divided into three general groups depending on dose of radiation and time after exposure. The CNS syndrome requires many thousands of rad, appears in minutes to hours, and kills within hours to days. The GIS appears after doses of a few hundred to 2000 rad. It is characterized by nausea, vomiting, diarrhea, and disturbances of water and electrolyte metabolism. It has a high mortality in the first week after exposure. Survivors will then experience the HS as a result of marrow aplasia. Depending on dose, survival is possible with antibiotic and transfusion therapy. The relationship of granulocyte depression to mortality in dogs and human beings is illustrated. The role of depth dose pattern of mortality of radiation exposure is described and used as an indication of why air exposure doses may be misleading. The therapy of radiation injury is described based on antibiotics, transfusion therapy, and use of molecular regulators. The limited role of matched allogenic bone marrow transplants is discussed. 52 refs., 13 figs.

Acute radiation syndrones and their management

International Nuclear Information System (INIS)

Cronkite, E.P.

1988-01-01

Radiation syndromes produced by large doses of ionizing radiation are divided into three general groups depending on dose of radiation and time after exposure. The CNS syndrome requires many thousands of rad, appears in minutes to hours, and kills within hours to days. The GIS appears after doses of a few hundred to 2000 rad. It is characterized by nausea, vomiting, diarrhea, and disturbances of water and electrolyte metabolism. It has a high mortality in the first week after exposure. Survivors will then experience the HS as a result of marrow aplasia. Depending on dose, survival is possible with antibiotic and transfusion therapy. The relationship of granulocyte depression to mortality in dogs and human beings is illustrated. The role of depth dose pattern of mortality of radiation exposure is described and used as an indication of why air exposure doses may be misleading. The therapy of radiation injury is described based on antibiotics, transfusion therapy, and use of molecular regulators. The limited role of matched allogenic bone marrow transplants is discussed. 52 refs., 13 figs

Incidental finding of cutaneous meningeal heterotopia in aplasia cutis congenita.

Science.gov (United States)

Kenyon, Katharine; Zedek, Daniel; Sayed, Christopher

2016-07-01

Aplasia cutis congenita and cutaneous meningeal heterotopia are both rare congenital conditions that most commonly occur on the scalp and may appear clinically and histologically similar. A subtype of aplasia cutis congenita, membranous aplasia cutis congenita, and cutaneous meningeal heterotopia are both proposed to result from neural tube closure errors. However, neither non-membranous nor membranous aplasia cutis congenita are known to occur together with cutaneous meningeal heterotopia in the same lesion. We report the incidental finding of cutaneous meningeal heterotopia within a lesion of aplasia cutis congenita. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The study on the preparation of rhIL-6 and its effects on recovery of mice from radiation-induced hematopoietic aplasia

International Nuclear Information System (INIS)

Yang Jicheng; Zhang Yun; Sheng Weihua

1997-08-01

The E coil highly expressing rhIL-6 constructed by our department was fermented and rhIL-6 products were extracted and purified. The specific activity of the purified rhIL-6 products reached 4.83 x 10 8 IU/mg. The rhIL-6 products were used to treat BALB/c mice injured by 60 Co irradiation for six days (2 μg/big/each). The results showed that the bleeding time, coagulation time and prothrombin time of the rhIL-6 treatment group were significantly shorter than those of the control group (P<0.01), the platelet count and WBC increased by 130% and 165% in the treatment group as compared with the control, the numbers of CFU-Mix cultured in vitro and CFU-s in spleen were significantly higher than those in the control group (P<0.01). These results suggest that rhIL-6 exerts beneficial effects on the recovery of mice from radiation-induced injuries of hematopoietic stem/progenitor cells, and thus helps recovery from radiation injury of bone marrow and hematopoietic function. (17 refs., 4 figs., 5 tabs.)

Recovery From Radiation-induced Bone Marrow Damage by HSP25 Through Tie2 Signaling

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Lee, Hae-June [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kwon, Hee-Chung [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Chung, Hee-Yong [College of Medicine, Hanyang University, Seoul (Korea, Republic of); Lee, Yoon-Jin [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yun-Sil, E-mail: yslee0425@ewha.ac.kr [College of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Woman' s University, Seoul (Korea, Republic of)

2012-09-01

Purpose: Whole-body radiation therapy can cause severe injury to the hematopoietic system, and therefore it is necessary to identify a novel strategy for overcoming this injury. Methods and Materials: Mice were irradiated with 4.5 Gy after heat shock protein 25 (HSP25) gene transfer using an adenoviral vector. Then, peripheral blood cell counts, histopathological analysis, and Western blotting on bone marrow (BM) cells were performed. The interaction of HSP25 with Tie2 was investigated with mouse OP9 and human BM-derived mesenchymal stem cells to determine the mechanism of HSP25 in the hematopoietic system. Results: HSP25 transfer increased BM regeneration and reduced apoptosis following whole-body exposure to ionizing radiation (IR). The decrease in Tie2 protein expression that followed irradiation of the BM was blocked by HSP25 transfer, and Tie2-positive cells were more abundant among the BM cells of HSP25-transferred mice, even after IR exposure. Following systemic RNA interference of Tie2 before IR, HSP25-mediated radioprotective effects were partially blocked in both mice and cell line systems. Stability of Tie2 was increased by HSP25, a response mediated by the interaction of HSP25 with Tie2. IR-induced tyrosine phosphorylation of Tie2 was augmented by HSP25 overexpression; downstream events in the Tie2 signaling pathway, including phosphorylation of AKT and EKR1/2, were also activated. Conclusions: HSP25 protects against radiation-induced BM damage by interacting with and stabilizing Tie2. This may be a novel strategy for HSP25-mediated radioprotection in BM.

Assessment of evolutive and prognostic indicators applied to accidental overexposure to ionizing radiation

International Nuclear Information System (INIS)

Morera Carrillo, M. de Lourdes; Cardenas, J.; Dubner, D.; Perez, M. del Rosario; Gisone, P.

2001-01-01

The acute radiation syndrome has been characterized in different ways that involve risk for life and health of the people overexposed to ionizing radiations. This work intends to test a therapeutical total body irradiation (TBI) model as conditioning to bone marrow transplantation. With the purpose of evaluating the applicability of several biological indicators in accidental overexposures, a study was carried out in 46 patients undergoing TBI receiving doses between 10 Gy and 12 Gy. The following parameters were assessed: lipo peroxyde plasmatic levels (TBARS) and total plasma antioxidant activity, reticulocyte maturity index (RMI) and charges in lymphocyte subpopulations. These data suggest that TBARS could provide an useful evolutive indicator in accidental overexposed patients and RMI is an early indicator of bone marrow recovery after radioinduced aplasia

Role of marrow architecture and stromal cells in the recovery process of aplastic marrow of lethally irradiated rats parabiosed with healthy litter mates

International Nuclear Information System (INIS)

Hayashi, K.; Kagawa, K.; Awai, M.; Irino, S.

1986-01-01

Bone marrow aplasia was induced in rats by whole body lethal irradiation (1,000 rads by x-ray), and rats died of irradiation injury within 7 days. Correlative studies at light (LM), transmission (TEM) and scanning electron microscopy (SEM) demonstrated swelling of endothelial and reticular cells and hemorrhage due to detachment of sinus endothelial cells on days 1 and 2. With time, structural recovery occurred without hemopoietic recovery. Reticular cells developed small intracytoplasmic lipid droplets on days 3 and 4. This resulted in fatty aplastic marrow within 7 days. On the other hand, in the marrow of irradiated rats parabiosed with healthy mates by aortic anastomosis, hemopoiesis was initiated by adhesion of nucleated blood cells to fine cytoplasmic pseudopods of fat-stored cells on days 1 and 2 after parabiosis. On days 3 to 5, reticular cells with large lipid droplets and fine pseudopods increased, then hemopoietic foci became clear and extensive. On day 8 after parabiosis, the aplastic bone marrow recovered completely both its structure and hemopoietic activity. Thus, hemopoietic recovery in lethally irradiated marrow begins with recovery of vascular endothelial cells, re-establishment of sinusoidal structure, and morphological and functional recoveries of reticular cells from fat-storage cells by releasing intracytoplasmic lipid droplets. Marrow stromal cells, namely reticular, fat-storage and fibroblastoid cells, share a common cellular origin, and regain their structure and function when fat-storage cells and fibroid cells are placed in contact with hemopoietic precursor cells

Bone marrow ablation with Ho-166 pharmaceuticals as preparation for bone marrow transplants

International Nuclear Information System (INIS)

Parks, N.J.; Kawakami, T.; Avila, M.; White, R.; Cain, G.; Moore, P.F.

1991-01-01

Bone marrow ablation is required preparation for leukemia patients where bone marrow transplantation is to be the therapeutic modality. Presently, the total body irradiation that is used produces appreciable morbidity in terms of radiation sickness, but an evenly distributed dose to marrow. The authors have shown in Beagles that bone-seeking radiolanthanide (Ho-166, t 1/2 = 25 h, 1.8 MeB beta, carrier added) phosphonic acid chelates can be used to completely ablate bone marrow with little morbidity. The research plan, incorporating bone marrow ablation with bone-seeking radionuclides and in vitro purging of aspirated leukemic marrow for use in autologous marrow transplants, is presented. Phosphonic acid complexes of Sm-153 also localize in the skeleton and have found use in the palliation of bone pain. However, the dose distribution is uneven because these radiopharmaceuticals distribute according to available surface; 2-4 times the skeletal average in trabecular vs cortical bone. Thus, the marrow dose can vary. The authors' research group and the Radiation Interactions Division of NIST have announced the discovery that beta radiation-induced excited electrons are trapped in the hydroxyapatite mineral of bone and provide a potential direct dosimetric method for marrow dose when combined with routine bone marrow (and included bone) biopsies. The overall research plan sets the hypothesis that reduced morbidity marrow ablation can be successfully followed by bone marrow transplantation (BMT) with autologous marrow purged in vitro by antibody-targeted alpha emitters

Protection of radiation-induced damage to the hematopoietic system, small intestine and salivary glands in rats by JNJ7777120 compound, a histamine H4 ligand.

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Diego J Martinel Lamas

Full Text Available Based on previous data on the histamine radioprotective effect on highly radiosensitive tissues, in the present work we aimed at investigating the radioprotective potential of the H4R ligand, JNJ7777120, on ionizing radiation-induced injury and genotoxic damage in small intestine, salivary glands and hematopoietic tissue. For that purpose, rats were divided into 4 groups. JNJ7777120 and JNJ7777120-irradiated groups received a daily subcutaneous JNJ7777120 injection (10 mg/kg starting 24 h before irradiation. Irradiated groups received a single dose of 5 Gy on whole-body using Cesium-137 source and were sacrificed 3 or 30 days after irradiation. Tissues were removed, fixed, stained with hematoxylin and eosin or PAS staining and histological characteristics were evaluated. Proliferative and apoptotic markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate DNA damage. Submandibular gland (SMG function was evaluated by methacholine-induced salivation. Results indicate that JNJ7777120 treatment diminished mucosal atrophy and preserved villi and the number of crypts after radiation exposure (240±8 vs. 165±10, P<0.01. This effect was associated to a reduced apoptosis and DNA damage in intestinal crypts. JNJ7777120 reduced radiation-induced aplasia, preserving medullar components and reducing formation of micronucleus and also it accelerated bone marrow repopulation. Furthermore, it reduced micronucleus frequency in peripheral blood (27±8 vs. 149±22, in 1,000 erythrocytes, P<0.01. JNJ7777120 completely reversed radiation-induced reduced salivation, conserving glandular mass with normal histological appearance and reducing apoptosis and atrophy of SMG. JNJ7777120 exhibits radioprotective effects against radiation-induced cytotoxic and genotoxic damages in small intestine, SMG and hematopoietic tissues and, thus, could be of clinical value for patients undergoing radiotherapy.

Effect of nephrotoxic drugs on the development of radiation nephropathy after bone marrow transplantation

International Nuclear Information System (INIS)

Lawton, C.A.; Fish, B.L.; Moulder, J.E.

1994-01-01

Chronic renal failure is a significant cause of late morbidity in bone marrow transplant patients whose conditioning regimen includes total body irradiation (TBI). Radiation is a major cause of this syndrome (bone marrow transplant nephropathy), but it may not be the only cause. These studies use a rat syngeneic bone marrow transplant model to determine whether nephrotoxic agents used in conjunction with bone marrow transplantation (BMT) could be enhancing or accelerating the development of radiation nephropathy. Rats received 11-17 Gy TBI in six fractions over 3 days followed by syngeneic bone marrow transplant. In conjunction with the bone marrow transplants, animals received either no drugs, cyclosporine, amphotericin, gentamicin, or busulfan. Drugs were given in schedules analogous to their use in clinical bone marrow transplantation. Drug doses were chosen so that the drug regimen alone caused detectable acute nephrotoxicity. Animals were followed for 6 months with periodic renal function tests. Gentamicin had no apparent interactions with TBI. Amphotericin increased the incidence of engraftment failure, but did not enhance radiation nephropathy. Cyclosporin with TBI caused late morbidity that appeared to be due to neurological problems, but did not enhance radiation nephropathy. Busulfan resulted in a significant enhancement of radiation nephropathy. Of the nephrotoxins used in conjunction with bone marrow transplantation only radiation and busulfan were found to be risk factors for bone marrow transplant nephropathy. 34 refs., 4 figs., 2 tabs

The role of diclofenack on inducing of aplasia cutis congenita: a case report.

Science.gov (United States)

Pajaziti, Laura; Rexhepi, Syzana; Shatri-Muça, Ylfete; Ferizi, Mybera

2009-10-12

Aplasia cutis congenita is a disorder where e newborn child is missing skin from certain areas. It is a rare condition with no particular race or sex more at risk. May occur by itself or be associated with other physical syndromes or disorders. A classification system exists for aplasia cutis congenital consisting of 9 groups, based on the number and location of the skin defects and the presence or absence of other malformations. Causes of aplasia congenital could be heredity, teratogenic substances, placental infarcts, intrauterine infections, ectodermal dysplasias etc. Diagnosis is made based on the clinical findings. Prognosis depends of the other organs malfunction level and lesions size. Our case was an 22 months old Albanian girl, who was recommended to dermatology for a consultation by a pediatric surgeon because of the changes she had on her parietal part of the scalp with missing hair areas. The child has stenosis congenita ani and to her was installed stoma. In order to investigate other accompanied anomalies of the disease, there are made specific consults by neurologist, orthopedist, cardiologist, nephrologists and citogenetics. It was found out a minor visual discoordination, Sy Floppy, Digiti V superductus pedis bill. Laxitas articularum generalisata. It was a great challenge for us to find out that during the first trimester of the pregnancy (unplanned pregnancy), her mother used Diclofenac. Since there is limited information regarding to teratogenic effects of diclofenac, we considered it interesting to present this case.

[Morphogenesis of vaginal aplasia. Therapeutic deductions].

Science.gov (United States)

Minh, H N; Smadja, A; Belaisch, J

1985-01-01

On the basis of the studies of the embryogenesis of the vagina, the authors consider that malformations classically described as being partial aplasia should not be separated from the total absence of the vagina. The important feature is the association of a functioning or non functioning uterus with the absence of the vagina. They believe that it is incorrect to describe the pouch of menstrual retention associated with a functioning uterus as "haematocolpos" and that is not justified to describe the cup-shaped vestibular depression as "hemi-vagina". According to the authors, although vaginal aplasia with a functioning uterus forming a pouch of menstrual retention constitutes an absolute indication for surgery, surgery is not justified in cases of vaginal aplasia with a non functioning uterus. If Frank's method fails in these cases, the patient or the couple should be referred to a sexologist, as women with this anomaly retain a perfect femininity, although unable to conceive.

Pulmonary Aplasia in an Adult : A Case Report

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Nurettin Yiyit

2016-01-01

Full Text Available Pulmonary aplasia is a rare congenital anomaly in which there are absence of pulmonary vessels, bronchus and parenchyma. It is distinguished from pulmonary agenesis by the presence of rudimentary stump bronchus. Patients are usually diagnosed in childhood. Patients without additional anomaly and the patients with mild disease can be diagnosed in adulthood. The left lung was not observed at the chest X-ray of 19-year-old male patient with respiratory distress in exercise. Left lung aplasia was diagnosed by computed tomography and ventilation perfusion scintigraphy. The patients with lung aplasia have an increased risk of infections. Therefore the follow-up of the patients is important.

Elimination of acute muelogenous leukemic cells from marrow and tumor suspensions in the rat with 4-hydroperoxycyclophosphamide

International Nuclear Information System (INIS)

Sharkis, S.J.; Santos, G.W.; Colvin, M.

1980-01-01

Cell suspensions of normal rat marrow mixed with rat acute myelogenous leukemic cells were prepared and incubated in vitro with graded doses of 4-hydroperoxycyclophosphamide (4HC). The cell suspensions were injected into rats prepared with a lethal dose of total body irradiation. Animals injected with these cells survived fatal irradiation induced aplasia. In a dose related manner 4HC was able to purge tumor cells from the cell mixtures. Thus, animals given cell suspensions incubated with the lower doses of 4HC showed prolonged survived before death from leukemia and animals given cell suspensions incubated with higher doses of 4HC survival lethal irradiation without the subsequent appearance of leukemia. These studies clearly establish that tumor cells may be eliminated from normal marrow suspensions without completely destroying the pluripotent stem cells

Adaptive response to ionizing radiation in bone marrow mouse cells (CFU-s) in vivo. Oxygen effect

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Saenko, A.S.; Semina, O.V.; Semenets, T.N.; Smirnova, S.G.; Orlova, N.V. [Russian Academy of Medical Sciences, Kaluga Region (Russian Federation). Medical Radiological Research Centre

1997-03-01

An acute gamma-irradiation of mice in small doses of 0.003-0.05 Gy results in elevated radioresistance of bone marrow CFU-s to challenge dose of 1.5 Gy. Hypoxia during exposure to conditioning dose abolishes or strongly decreases AR in CFU-s of mice marrow. Ascorbic acid and menadione induce cross-adaptation of mouse bone marrow CFU-s to action of gamma-radiation. The increase radioresistance was observed during 4 days after orally administration of vitamins C and K in doses of 1 mg and 0.06 mg/animal, accordingly, AR in Lewis lung carcinoma cells did not be observed in two independent experiments. (authors)

Adaptive response to ionizing radiation in bone marrow mouse cells (CFU-s) in vivo. Oxygen effect

International Nuclear Information System (INIS)

Saenko, A.S.; Semina, O.V.; Semenets, T.N.; Smirnova, S.G.; Orlova, N.V.

1997-01-01

An acute gamma-irradiation of mice in small doses of 0.003-0.05 Gy results in elevated radioresistance of bone marrow CFU-s to challenge dose of 1.5 Gy. Hypoxia during exposure to conditioning dose abolishes or strongly decreases AR in CFU-s of mice marrow. Ascorbic acid and menadione induce cross-adaptation of mouse bone marrow CFU-s to action of gamma-radiation. The increase radioresistance was observed during 4 days after orally administration of vitamins C and K in doses of 1 mg and 0.06 mg/animal, accordingly, AR in Lewis lung carcinoma cells did not be observed in two independent experiments. (authors)

Supplementation of bone marrow aspirate-derived platelet-rich plasma for treating radiation-induced ulcer after cardiac fluoroscopic procedures: A preliminary report

Directory of Open Access Journals (Sweden)

Soh Nishimoto

2012-01-01

Full Text Available Background: The frequency of encountering radiodermatitis caused by X-ray fluoroscopic procedures for ischaemic heart disease is increasing. In severe cases, devastating ulcers with pain, for which conservative therapy is ineffective, emerge. Radiation-induced ulcers are notorious for being difficult to treat. Simple skin grafting often fails because of the poor state of the wound bed. A vascularized flap is a very good option. However, the non-adherence of the well-vascularized flap with the irradiated wound bed is frequently experienced. Aim: To ameliorate the irradiated wound bed, bone marrow-derived platelet-rich plasma (bm-PRP was delivered during the surgery. Materials and Methods: Four patients with severe cutaneous radiation injury accompanied by unbearable pain after multiple fluoroscopic procedures for ischaemic heart disease were treated. Wide excision of the lesion and coverage with a skin flap supplemented with bm-PRP injection was performed. Results: All patients obtained wound closure and were relieved from pain. No complication concerning the bone marrow aspiration and delivery of bm-PRP was observed. Conclusions: Supplementation of bm-PRP can be an option without major complications, time, and cost to improve the surgical outcome for irradiated wounds.

Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

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Benkő, Klára; Pintye, Éva; Szabó, Boglárka; Géresi, Krisztina; Megyeri, Attila; Benkő, Ilona

2008-12-01

To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of γ—irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD50 values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

Effect of Rosiglitazone on Radiation Damage in Bone Marrow Hemopoiesis

International Nuclear Information System (INIS)

Benko', Klara; Pintye, Eva; Szabo, Boglarka; Geresi, Krisztina; Megyeri, Attila; Benko, Ilona

2008-01-01

To study radiobiological effects and drugs, which can modify radiation injury, has an importance if we would like to avoid harmful effects of radiation due to emergency situations or treat patients with malignant diseases by radiotherapy. During the long treatment schedules patients may be treated by not only anticancer but many other drugs because of accompanying diseases. These drugs may also modify radiobiological effects. Rosiglitazone pre-treatment proved to be myeloprotective and accelerated recovery of 5-fluorouracil-damaged bone marrow in our previous experiments. Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects in radiation-damaged hemopoiesis. Bone marrow damage was precipitated by total body irradiation (TBI) using single increasing doses (2-10 Gy) of γ--irradiation in groups of mice. Lethality was well correlated with damage in hemopoiesis measured by cellularity of bone marrow (LD 50 values were 4.8 and 5.3 gray respectively). Rosiglitazone, an insulin-sensitizing drug, had no significant effect on bone marrow cellularity. Insulin resistance associated with obesity or diabetes mellitus type 2 is intensively growing among cancer patients requiring some kind of radiotherapy. Therefore it is important to know whether drugs used for their therapy can modify radiation effects.

Trapezius aplasia: indications for a dual developmental origin of the trapezius muscle

NARCIS (Netherlands)

Nooij, Linda S.; Oostra, Roelof-Jan

2006-01-01

Aplasia of the trapezius muscle is a rarely encountered, mostly asymptomatic anomaly. We report a case of isolated unilateral complete trapezius aplasia that was noticed during a dissection course. Apart from isolated cases, trapezius aplasia may occur in different combinations with other muscle

Low-dose radiation-induced adaptive response in bone marrow cells of mice

International Nuclear Information System (INIS)

Farooqi, Zeba; Kesavan, P.C.

1993-01-01

Using bone marrow cells of whole body irradiated mice, the cytogenetic adaptive response induced by low conditioning doses of gamma-rays was investigated. The conditioning doses (0.025 and 0.05 Gy) were given at a dose-rate of 1.67 Gy/min. The challenging dose of 1 Gy was given at a dose-rate of 0.045 Gy/s. The challenging dose was given at different time intervals after the conditioning dose. The time intervals between the conditioning dose and challenging dose were 2, 7.5, 13, 18.5 and 24 h. When the time interval between the conditioning dose and the challenging dose was 2 h, both conditioning doses (0.025 and 0.05 Gy) reduced the frequency of MNPCEs and chromosomal aberrations in the bone marrow cells. The data collected at different time intervals (7.5, 13, 18.5 h) reveal that the radioadaptive response persisted for a longer time when the lower conditioning dose (0.025 Gy) was given. With the higher conditioning dose (0.05 Gy), the radioadaptive response disappeared after a time interval of 13 h. When the time interval between the conditioning dose and the challenging doses was 18.5 or 24 h, only the lower conditioning dose appeared effective in inducing the radioadaptive response

Postirradiation bone marrow damage in chickens

International Nuclear Information System (INIS)

Skardova, I.; Ojeda, F.

1994-01-01

The frequency of bone marrow damage induced by the continuous gamma irradiation was studied. Effect of dose rate and level of cumulated doses of radiation was evaluated in clinical and hematological examinations and bone marrow damage was determined by chromosome aberrations in anaphase. The regulative ability of hematopoiesis of many cytokines are discussed. Positive regulators are inducers of cell proliferation, and negative regulators are inducers of apoptosis /programmed cell death/. Birds corresponding with similarities in thymus-T and bursal-B cells appear to be an interesting model for studying the possible participation of apoptosis in radiation disease. Our recent experimental studies continue to progress in this direction. (author) 17 refs.; 3 figs.; 2 tabs

Aplasia cutis congenita, skull defect, brain heterotopia, and intestinal lymphangiectasia

NARCIS (Netherlands)

Bonioli, Eugenio; Hennekam, Raoul C.; Spena, Gianantonio; Morcaldi, Guido; Di Stefano, Antonio; Serra, Giovanni; Bellini, Carlo

2005-01-01

We describe a female infant with a previously unreported combination of manifestations characterized by aplasia cutis, skull defect, brain heterotopia, mild congenital lymphedema, and intestinal lymphangiectasia. The association of intestinal lymphangiectasia and aplasia cutis, and the association

Radionuclide imaging of bone marrow in hematologic systemic disease

Energy Technology Data Exchange (ETDEWEB)

Kessel, F.; Hahn, K.; Gamm, H.

1987-02-01

Radionuclide imaging studies of the bone marrow were carried out in 164 patients suffering from hematologic systemic disease. One third of 90 patients with Hodgkin lymphoma (HL) or Non Hodgkin lymphoma (NHL) displayed a pathological distribution pattern representing bone marrow expansion. In HL there were 17% accumulation defects caused by metastases in contrast to only 7% in NHL. Among 30 patients with chronic myelocytic leukemia bone marrow expansion was found in 60%, bone marrow displacement and aplasia 10%. Focal bone marrow defects were found in 3 patients. All patients with primary polycythemia rubra vera displayed a pathologic bone marrow distribution pattern as well as splenomegaly. All patients with acute myelocytic leukemia (AML) and one patient with an acute lymphatic leukemia (ALL) had a pathological distribution pattern with bone marrow expansion and displacement. Focal bone marrow defects were not seen. Multiple myeloma with bone marrow expansion was found in 6 of 12 patients and focal accumulation defects were found in 40%, the latter lesions being not visible or equivocal on skeletal imaging studies. Pathological changes in liver and spleen were found in a high percentage of the total collective. The results document the important clinical value of bone marrow scintigraphy among the hematologic diseases studied.

Bone marrow transplantation rescues intestinal mucosa after whole body radiation via paracrine mechanisms

International Nuclear Information System (INIS)

Chang, Ya Hui; Lin, Li-Mei; Lou, Chi-Wen; Chou, Chuan-Kai; Ch’ang, Hui-Ju

2012-01-01

Purpose: Our previous study reveals bone marrow transplantation (BMT) recruits host marrow-derived myelomonocytic cells to radiation-injured intestine, enhancing stromal proliferation, leading secondarily to epithelial regeneration. In this study, we propose BMT ameliorates intestinal damage via paracrine mechanisms. Materials and methods: Angiogenic cytokines within the intestinal mucosa of mice after whole body irradiation (WBI) with or without BMT were measured by cytokine array and ELISA. BM conditioned medium (BMCM) with or without treatment with neutralizing antibodies to angiogenic cytokines were continuously infused into mice for three days after radiation. Carrageenan was used to deplete myelomonocytic cells of mice. Results: BMT increased VEGF, bFGF and other angiogenic and chemotactic cytokines in the intestinal mucosa within 24 h after WBI. Infusion of BMCM ameliorated radiation-induced intestinal damage with improved stromal activity and prolonged survival of mice. Neutralization of bFGF, PDGF and other angiogenic cytokines within BMCM abolished the mitigating effect to the intestine. Pretreatment of carrageenan to recipient mice reversed some of the cytokine levels, including VEGF, bFGF and IGF within the intestinal mucosa after BMT. Conclusions: Our result suggests BMT recruits host myelomonocytic cells and enhances intestinal stroma proliferation after radiation by secreting cytokines enhancing angiogenesis and chemotaxis. Host myelomonocytic cells further uplift the paracrine effect to enhance intestinal mucosal recovery.

MRI appearance of radiation-induced changes of normal cervical tissues

International Nuclear Information System (INIS)

Noemayr, A.; Lell, M.; Bautz, W.; Sweeney, R.; Lukas, P.

2001-01-01

Irradiation causes specific MRI changes in anatomic morphology and signal intensity. To avoid misinterpretation, it is important to consider the potential radiation changes of normal tissue in MRI. The aim of this study was to describe the detected radiation effects on normal cervical tissues in MRI. Pretreatment and posttreatment MRI of 52 patients with primary neck tumors were evaluated retrospectively. The MR imaging was performed before initiating radiotherapy and at the end of the treatment period. Patients underwent follow-up studies within 24 months after the end of irradiation. Edema was the main radiation-induced effect. It was detected in the epiglottis, larynx, pharynx wall, retro- and parapharyngeal space, salivary glands, muscles, and subcutaneous tissue. In some cases the bone marrow of the mandible showed edema, due to osteonecrosis. We additionally detected fluid accumulation in the mastoid cells. Radiation caused volume reduction of the parotid gland, thickening of the pharynx wall, and fatty degeneration of bone marrow. Magnetic resonance imaging is an excellent method of depicting radiation-induced changes of normal tissue. Especially T2-weighted sequences allow the detection of even slight edema. It is important to be aware of the most common radiation-induced changes in MRI and to take them into account when assessing an examination. (orig.)

Hereditary Factors Involved in Radiation-Induced Leukaemogenesis

International Nuclear Information System (INIS)

Duplan, J.F.

1969-01-01

The hereditary factors involved in radiation-induced leukaemogenesis were studied in pure AKR and C57BL strains, their first-generation hybrids and their back-crosses. It is known that the heredity of spontaneous lymphoid leukaemias is attributable to hereditary factors, of which only some are chromosomal, and the same situation can be considered to exist as regards the heredity of radiation-induced leukoses. In order to identify the various chromosomal and non-chromosomal factors concerned, three types of experiment were conducted with the pure strains and with each of the crosses, intended to evaluate (a) the incidence of spontaneous lymphoid leukoses, (b) the incidence of radiation-induced leukoses and (c) the inhibition of radioleukaemo- genesis by the injection of isogenic haematopoietic cells. The results show that the main non-chromosomal factor is the leukaemogenic Gross virus (VG) in the case of the AKR strain and the radioleukaemia virus (VRL) in that of the C57BL strain; these two agents are transmitted by the mother to her progeny. The VG may be responsible for radioleukaemias as well as for spontaneous leukoses, but the VRL does not produce spontaneous leukaemias even in back-crosses possessing a substantial fraction of the AKR genome, which is particularly conducive to leukaemogenesis. Restoration using C57BL bone marrow brings about a distinct inhibition of leukaemogenesis in all animals deriving from crossings for which this material is histocompatible; AKR marrow, however, never exhibits any restorative activity. Three hypotheses may be put forward to explain these results. The first is that C57BL bone marrow contains many more precursor elements than AKR marrow, these cells being necessary for inhibition of the leukaemogenic process. The second hypothesis is that the AKR strain lacks a factor which is essential for the utilization of these precursors. Finally the third hypothesis, which seems the least probable, is that AKR cells are much more

Bone marrow transplantation for treatment of radiation disease. Problems involved

International Nuclear Information System (INIS)

Fliedner, T.M.

1992-01-01

Transplantation of bone marrow cells still is one of the major means available for treatment of radiation injuries. The decisive indication is the diagnostic of irreversible damage to the hemopoietic stem cells, which becomes manifest about 5 or 6 days after exposure, by severe granulocytopenia and simultaneous, progressive thrombopenia. The radiation dose provoking such severe injury is estimated to be at least 9-10 Gy of homogeneous whole-body irradiation. Preparatory measures for transplantation include proof of tissue compatibility of donor and patient, sufficient immunosuppression prior to and/or after irradiation and bone marrow transplantation. The donor's marrow should be free of T-cells. In spite of preparatory treatment, complications such as immunological reactions or disturbance of organ functions are to be very probable. These are treated according to therapy protocols. (orig./MG) [de

Prevention of gamma radiation induced anaemia in mice by diltiazem

International Nuclear Information System (INIS)

Nunia, V.; Goyal, P.K.

2004-01-01

Intraperitoneal administration of diltiazem (DTZ), half an hour prior to whole body gamma irradiation (2.5, 5.0, and 7.5 Gy), showed the protection of animals from radiation-induced anaemia. Radiation exposure significantly (p<0.001) reduced the number of pro- and normoblasts in bone marrow and red blood cell (RBC) counts, hemoglobin (Hb), hematocrit (Hct), and erythropoietin (EPO) level in blood, but increased myeloid/erythroid ratio. At all the radiation doses, the maximum decrease in these values was noted on the 3rd day, followed by a gradual recovery from the 7th day, but it was not recorded as normal even until the end of experimentation. In animals pretreated with DTZ, these values were measured higher at all the time periods in comparison to corresponding control, and these were almost normal at the last autopsy interval only at 2.5 Gy radiation dose. DTZ maintained the higher EPO level in blood, which acted on bone marrow and spleen colony forming unit for erythroblast (CFU-E), and stimulated such cells to produce RBCs. These results confirm that DTZ has the potency to alter anaemic condition favorably through the protection of bone marrow stem cells, and subsequently it maintains the higher number of pro-and normoblasts in bone marrow, RBC counts, Hb, Hct percentage, and EPO level in blood and the lower myeloid/erythroid ratio in bone marrow. (author)

Amelioration of radiation-induced pulmonary fibrosis by a water-soluble bifunctional sulfoxide radiation mitigator (MMS350).

Science.gov (United States)

Kalash, Ronny; Epperly, Michael W; Goff, Julie; Dixon, Tracy; Sprachman, Melissa M; Zhang, Xichen; Shields, Donna; Cao, Shaonan; Franicola, Darcy; Wipf, Peter; Berhane, Hebist; Wang, Hong; Au, Jeremiah; Greenberger, Joel S

2013-11-01

A water-soluble ionizing radiation mitigator would have considerable advantages for the management of acute and chronic effects of ionizing radiation. We report that a novel oxetanyl sulfoxide (MMS350) is effective both as a protector and a mitigator of clonal mouse bone marrow stromal cell lines in vitro, and is an effective in vivo mitigator when administered 24 h after 9.5 Gy (LD100/30) total-body irradiation of C57BL/6NHsd mice, significantly improving survival (P = 0.0097). Furthermore, MMS350 (400 μM) added weekly to drinking water after 20 Gy thoracic irradiation significantly decreased: expression of pulmonary inflammatory and profibrotic gene transcripts and proteins; migration into the lungs of bone marrow origin luciferase+/GFP+ (luc+/GFP+) fibroblast progenitors (in both luc+ marrow chimeric and luc+ stromal cell line injected mouse models) and decreased radiation-induced pulmonary fibrosis (P < 0.0001). This nontoxic and orally administered small molecule may be an effective therapeutic in clinical radiotherapy and as a counter measure against the acute and chronic effects of ionizing radiation.

In vivo persistence of sister chromatid exchanges (SCE) induced by gamma rays in mouse bone marrow cells

International Nuclear Information System (INIS)

Morales-Ramirez, P.; Vallarino-Kelly, T.; Rodriguez-Reyes, R.

1984-01-01

The sister chromatid exchange (SCE) frequencies induced in bone marrow cells by in vivo irradiation with gamma rays before or after bromodeoxyuridine (BrdUrd) incorporation were compared. The frequency of SCE at different postirradiation times was also measured in bone marrow cells in vivo, irradiated before BrdUrd incorporation. Increased sensitivity to SCE induction by radiation was found in cells after BrdUrd incorporation for one cycle when compared with cells irradiated before BrdUrd incorporation. The increased SCE frequency persisted for at least 72 hr after the initial irradiation, implying that the gamma ray-induced lesion(s) capable of eliciting an SCE are persistent and cannot be easily repaired

Aplasia irreversible por el tratamiento con mesilato de Imatinib en una leucemia mieloide crónica: Presentación de un caso Irreversible aplasia due to the treatment with imatinib mesilate in a chronic myeloid leukemia: A case report

Directory of Open Access Journals (Sweden)

Olga Agramonte Llanes

2007-04-01

Full Text Available Se presenta una paciente de 45 años de edad diagnosticada en marzo de 1984 como una leucemia mieloide crónica Ph + , BCR/ABL positivo, que llevó tratamiento con busulfán, hidroxiurea, interferón y arabinósido de citosina durante 15 años. En marzo del 2003 se diagnosticó fase de transformación y en abril se comenzó la administración de Imatinib en dosis de 600mg diarios. Evolutivamente presentó dolores óseos ligeros, edema palpebral y en el día 35 pancitopenia severa, que provocó la suspensión del tratamiento. Se tomaron muestras para medulograma y biopsia de médula ósea y se diagnosticó una aplasia medular severa. Se administró tratamiento con antibioticoterapia de amplio espectro, hemoderivados y factor estimulador de colonias granulocíticas. A pesar de estas medidas terapéuticas, la paciente falleció a los 46 días de suspendido el tratamiento con Imatinib, con un cuadro clínico de aplasia medular irreversible y distrés respiratorio, complicaciones atribuibles al ImatinibA 45-year-old female patient who was diagnosed chronic myeloid leukemia Ph+ in March 1984, and had treatment with busulfan, hydroxyurea, interferon and cytosine arabinoside during 15 years is presented. In March 2003, the transformation stage was diagnosed and, in April, she began to receive imatinib at daily doses of 600 mg. Evolutively, she had mild bone pain, palpebral edema and, on the 35th day, severe pancytopenia that caused the suspension of the treatment. Bone marrow samples were taken by aspiration and biopsy, and a severe medular aplasia was diagnosed. Treatment with wide-spectrum antibiotic therapy, hemoderivates, and granulocyte colony-stimulating factor was applied. In spite of these therapeutic measures, the patient died 46 days after interrupting the treatment with imatinib, with a clinical picture of irreversible medular aplasia and respiratory distress, complications attributable to Imatinib

Characteristics of monolayer culture of bone marrow cells of rats bearing 239Pu-induced osteosarcoma

International Nuclear Information System (INIS)

Bukhtoyarova, Z.M.; Lemberg, V.K.

1984-01-01

The report is concerned with a monolayer culture of bone marrow cells of rats in which optimal blastogenic dose (92.5 kBq/kg) induced osteosarcoma. The cell culture showed an enhanced rate of fibroblast-like cell proliferation (increased number of mitoses and symplasts and larger colonies of cells), apparent signs of radiation in ury (pathologic mitoses, chromosome aberrations and gaps) as well as an increase in ploidy. Diffusion chamber measurements demonstrated osteogenic precursor-cells in osteosarcoma-bearing rats to be highly capable of bone formation. This relatively high ability seems to occur outside bone marrow as well

Hemopoietic stem cell niches, recovery from radiation and bone marrow transfusions

International Nuclear Information System (INIS)

Cronkite, E.P.; Carsten, A.L.; Brecher, G.; Feinendegen, L.

1979-01-01

Studies were conducted on the appearance of cells in recipient bone marrow with chromosome markers after bone marrow transfusion to recipients that had different treatments. Investigators tried to replete the bone marrow CFV spleen at various times after recovery from maximal sublethal doses of x radiation or during continuous exposure to tritiated water. Studies were made on the effect of diverse treatments on the acceptance of bone marrow transfusions as shown by chromosomal markers. Results showed that the bone marrow of animals rescued by transfusion of 4 x 10 6 bone marrow cells will accept from 0 to 25% of the second transfusion of bone marrow cells given one to 4 months after the first transfusion and examined 2 to 3 weeks after the second transfusion. This may be due to the second transfusion filling up empty niches

Radiation toxicity in dogs

International Nuclear Information System (INIS)

Norris, W.P.

1975-01-01

Progress is reported on studies of the effects of continuous (22 hr/day), whole-body γ-irradiation in the pure-bred beagle dog. Dogs were exposed continuously until death at one of four different exposure rates ranging from 5 to 35 R/day. The study is still 2441 days (approximately 6.7 yr) of irradiation. The experiment has narrowed to the dogs receiving 5 R/day and the controls. A group of dogs receiving one of these relatively low daily exposure rates may exhibit remarkably varied responses, both in survival times in the γ field and in ultimate causes of death. The basis for these large differences in responses of individual dogs remains mostly unexplained, but is presumed to reside in their genetic composition. The composite result in the study, however, demonstrates an orderly, step-wise appearance of clinical end points resulting from radiation-induced damage to the blood-forming tissues. About one-half the dogs exposed continuously to 10 R/day develop bone marrow aplasia and die of anemia, while the other one-half develop bone marrow hyperplasias and die of malignancies, usually myelogenous leukemias. In dogs exposed at rates greater than 10 R/day, aplastic bone marrows predominate; while hyperplastic responses are the dominant cause of death at 5 R/day. Only among the most recent deaths of dogs exposed continuously to either 10 or 5 R/day, have there appeared terminal causes of death unrelated to hematopoietic injury. These causes (degenerative and/or inflammatory disease and cancers of tissue other than bone marrow) suggest that we are now beginning to define the combinations of exposure rate and time of exposure that allow expressions of damage by tissues outside the hematopoietic system. (U.S.)

Influence of cigarette smoke and green tea on radiation-induced micronucleated polychromatic erythrocytes

International Nuclear Information System (INIS)

Gao Yong; Hao Enzhu; Ni Yanbo

2006-01-01

Objective: To observe the effects of cigarette smoke and green tea on radiation-induced bone marrow cell mutation, and to provide scientific information for prevention and treatment of radiation damage. Methods: There were 8 groups in the factorial experiment design with 3 factors at 2 levels. Mice were randomly divided into each group. There were 8 mice in each group. Mice in seven experimental groups were exposed to cigarette smoke, green tea, radiation or their mixtures respectively. One group was treated as the blank control group. The frequencies of micrnucleated polychromatic erythrocytes (MPCE) were scored by single blinded method. The data were analyzed with factorial experiments analysis of variance using SAS 8.0. Results: Analysis of variance showed that radiation, cigarette smoke and green tea were independently significant factors (P<0.01). Interactions between cigarette smoke and radiation or between green tea and radiation were statistically significant (P<0.01). Conclusion: Radiation and cigarette smoke can cause bone marrow cell mutations independently. There is synergistic effect between cigarette smoke and radiation. Green tea can inhibit radiation-induced cell mutation. (authors)

Role of whole bone marrow, whole bone marrow cultured cells, and mesenchymal stem cells in chronic wound healing.

Science.gov (United States)

Rodriguez-Menocal, Luis; Shareef, Shahjahan; Salgado, Marcela; Shabbir, Arsalan; Van Badiavas, Evangelos

2015-03-13

Recent evidence has shown that bone marrow cells play critical roles during the inflammatory, proliferative and remodeling phases of cutaneous wound healing. Among the bone marrow cells delivered to wounds are stem cells, which can differentiate into multiple tissue-forming cell lineages to effect, healing. Gaining insight into which lineages are most important in accelerating wound healing would be quite valuable in designing therapeutic approaches for difficult to heal wounds. In this report we compared the effect of different bone marrow preparations on established in vitro wound healing assays. The preparations examined were whole bone marrow (WBM), whole bone marrow (long term initiating/hematopoietic based) cultured cells (BMC), and bone marrow derived mesenchymal stem cells (BM-MSC). We also applied these bone marrow preparations in two murine models of radiation induced delayed wound healing to determine which had a greater effect on healing. Angiogenesis assays demonstrated that tube formation was stimulated by both WBM and BMC, with WBM having the greatest effect. Scratch wound assays showed higher fibroblast migration at 24, 48, and 72 hours in presence of WBM as compared to BM-MSC. WBM also appeared to stimulate a greater healing response than BMC and BM-MSC in a radiation induced delayed wound healing animal model. These studies promise to help elucidate the role of stem cells during repair of chronic wounds and reveal which cells present in bone marrow might contribute most to the wound healing process.

Histogenesis of mouse sarcomas induced by implantation of polyvinyl chloride film in radiation chimeras

International Nuclear Information System (INIS)

Mojzhess, T.G.; Prigozhina, E.L.

1976-01-01

Sarcomas were induced in CBA/CBA-T6T6 mouse radiation chimeras by implantation of polyvinyl chloride film subcutaneously 13 months after irradiation and injection of donor's bone marrow. Of the 12 tumors studied 11 had the recipient's karyotype and one the donor's. The formation of connective-tissue cells from bone-marrow precursors thus, evidently does not play an essential role in the histogenesis of sarcomas induced by plastics

Thioredoxin mitigates radiation-induced hematopoietic stem cell injury in mice

Directory of Open Access Journals (Sweden)

Pasupathi Sundaramoorthy

2017-11-01

Full Text Available Abstract Background Radiation exposure poses a significant threat to public health. Hematopoietic injury is one of the major manifestations of acute radiation sickness. Protection and/or mitigation of hematopoietic stem cells (HSCs from radiation injury is an important goal in the development of medical countermeasure agents (MCM. We recently identified thioredoxin (TXN as a novel molecule that has marked protective and proliferative effects on HSCs. In the current study, we investigated the effectiveness of TXN in rescuing mice from a lethal dose of total body radiation (TBI and in enhancing hematopoietic reconstitution following a lethal dose of irradiation. Methods We used in-vivo and in-vitro methods to understand the biological and molecular mechanisms of TXN on radiation mitigation. BABL/c mice were used for the survival study and a flow cytometer was used to quantify the HSC population and cell senescence. A hematology analyzer was used for the peripheral blood cell count, including white blood cells (WBCs, red blood cells (RBCs, hemoglobin, and platelets. Colony forming unit (CFU assay was used to study the colongenic function of HSCs. Hematoxylin and eosin staining was used to determine the bone marrow cellularity. Senescence-associated β-galactosidase assay was used for cell senescence. Western blot analysis was used to evaluate the DNA damage and senescence protein expression. Immunofluorescence staining was used to measure the expression of γ-H2AX foci for DNA damage. Results We found that administration of TXN 24 h following irradiation significantly mitigates BALB/c mice from TBI-induced death: 70% of TXN-treated mice survived, whereas only 25% of saline-treated mice survived. TXN administration led to enhanced recovery of peripheral blood cell counts, bone marrow cellularity, and HSC population as measured by c-Kit+Sca-1+Lin– (KSL cells, SLAM + KSL cells and CFUs. TXN treatment reduced cell senescence and radiation-induced

Assessment of evolutive and prognostic indicators applied to accidental overexposure to ionizing radiation; Evaluacion de indicadores pronosticos y evolutivos aplicables a situaciones accidentales de sobreexposicion a radiaciones ionizantes

Energy Technology Data Exchange (ETDEWEB)

Morera Carrillo, M. de Lourdes; Cardenas, J. [Centro de Proteccion y Higiene de las Radiaciones, La Habana (Cuba); Dubner, D.; Perez, M. del Rosario; Gisone, P. [Autoridad Regulatoria Nuclear, Buenos Aires (Argentina). Lab. de Radiopatologia; Carnot, J. [Hospital Clinico Quirurgico Hermanos Ameijeiras, La Habana (Cuba)

2001-07-01

The acute radiation syndrome has been characterized in different ways that involve risk for life and health of the people overexposed to ionizing radiations. This work intends to test a therapeutical total body irradiation (TBI) model as conditioning to bone marrow transplantation. With the purpose of evaluating the applicability of several biological indicators in accidental overexposures, a study was carried out in 46 patients undergoing TBI receiving doses between 10 Gy and 12 Gy. The following parameters were assessed: lipo peroxyde plasmatic levels (TBARS) and total plasma antioxidant activity, reticulocyte maturity index (RMI) and charges in lymphocyte subpopulations. These data suggest that TBARS could provide an useful evolutive indicator in accidental overexposed patients and RMI is an early indicator of bone marrow recovery after radioinduced aplasia.

Bone marrow adipocytes as negative regulators of the hematopoietic microenvironment

Science.gov (United States)

Naveiras, Olaia; Nardi, Valentina; Wenzel, Pamela L.; Fahey, Frederic; Daley, George Q.

2009-01-01

Osteoblasts and endothelium constitute functional niches that support hematopoietic stem cells (HSC) in mammalian bone marrow (BM) 1,2,3 . Adult BM also contains adipocytes, whose numbers correlate inversely with the hematopoietic activity of the marrow. Fatty infiltration of hematopoietic red marrow follows irradiation or chemotherapy and is a diagnostic feature in biopsies from patients with marrow aplasia 4. To explore whether adipocytes influence hematopoiesis or simply fill marrow space, we compared the hematopoietic activity of distinct regions of the mouse skeleton that differ in adiposity. By flow cytometry, colony forming activity, and competitive repopulation assay, HSCs and short-term progenitors are reduced in frequency in the adipocyte-rich vertebrae of the mouse tail relative to the adipocyte-free vertebrae of the thorax. In lipoatrophic A-ZIP/F1 “fatless” mice, which are genetically incapable of forming adipocytes8, and in mice treated with the PPARγ inhibitor Bisphenol-A-DiGlycidyl-Ether (BADGE), which inhibits adipogenesis9, post-irradiation marrow engraftment is accelerated relative to wild type or untreated mice. These data implicate adipocytes as predominantly negative regulators of the bone marrow microenvironment, and suggest that antagonizingmarrow adipogenesis may enhance hematopoietic recovery in clinical bone marrow transplantation. PMID:19516257

Experimental study of low dose radiation stimulate the haematogenesis reconstitution of the recipient after bone marrow transplantation in mice

International Nuclear Information System (INIS)

Zhang Liyuan; Yang Shun; Zhang Ye; Zhang Mingzhi; Jiang Jiagui; Jiang Jianping

2007-01-01

Objective: To investigate if low dose radiation can stimulate the haematogenesis reconstitution of the recipient after bone marrow transplantation in mice. Methods: Bone marrow cells were irradiated in vitro by different low dose radiation and then cultured in vitro. 3 H-TdR incorporation was used to measure the reproductive activity of cells, and then the radiation dose with the best stimulating effect was determined. The donator myeloid cells were exposed to low dose radiation before the recipient mice received bone marrow transplantation; then the irradiated myeloid cells were infused to the recipient; and lastly, the counts of peripheral blood cells (PBC) and bone marrow mononuclear cells (BMMNC) were monitored in order to observe the effect of low dose radiation on haematogenesis reconstitution of the recipient animal after bone marrow transplantation. Results: The reproductive activity of the bone marrow cells irradiated by 6 and 8 cGy could be improved significantly in vitro. When the recipient mice received bone marrow transplantation of the myeloid cells after low dose radiation, the counts of BMMNC and PBC were higher than those in the control group (P<0.05). Conclusions: Low dose radiation can stimulate the haematogenesis reconstitution of the recipient after bone marrow transplantation. (authors)

Antigenotoxic potential of Asparagus racemosus root extract against electron beam radiation induced micronuclei formation in Swiss albino mice

International Nuclear Information System (INIS)

Bhandary, B. Satheesh Kumar; Sharmila, K.P.; Suchetha Kumari, N.; Bhat, Vadish S.; Shetty, Jayaram; Peter, Alex John; Jose, Jerish M.; Fernandes, Ronald

2016-01-01

To evaluate the antigenotoxic potential of Asparagus Racemosus Root ethanolic extract (ARE) against electron beam radiation induced micronuclei formation in Swiss albino mice. Micronucleus assay was performed in the bone marrow of Swiss albino mice according to the method of Hosseinimehr et al., 2003. The experimental animals were orally administered 200 mg/kg body weight of ARE once daily for 15 consecutive days. At the end of experimental period, the animals were euthanized and the bone marrow was collected from the femur. Control (C), Radiation control (RC) and drug control (DC) group was also maintained. The number of radiation induced Micronucleated Polychromatic Erythrocytes (MnPCE) and Micronucleated Normochromatic Erythrocytes were decreased in the ARE treated mice which was statistically significant (p<0.05) compared to radiation control group. Present findings demonstrate the antigenotoxic potential of ARE against electron beam radiation induced micronuclei formation which may be attributed to scavenging of radiation-induced free radicals

Protective effect of zingerone, a dietary compound against radiation induced damage

International Nuclear Information System (INIS)

Satish Rao, B.S.; Rao, Nageshwar

2012-01-01

The radioprotective potential of phenolic alkanone, Zingerone (ZO) was investigated using human peripheral blood lymphocytes as well as Chinese hamster fibroblast (V79) cells growing in vitro and in vivo by using Swiss albino mice exposed to gamma radiation. In the in vivo studies, mice were administered with ZO (10-100 mg/kg b.wt), once daily for five consecutive days. One hour after the last administration of ZO on the fifth day, animals were whole body exposed to 10 Gy gamma radiations. The radioprotective potential was assessed using animal survival, haemopoietic stem cell survival (CFU) assay, mouse bone marrow micronucleus test, histological observations of intestinal and bone marrow damage. Effect of ZO pretreatment on radiation-induced changes in glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation (LPx) levels was also analyzed. ZO treatment resulted increase in the LD50/30 by 1.8 Gy (dose reduction factor = 1.2). The number of spleen colonies after whole body irradiation of mice (4.5 or 7.5 Gy) was increased when ZO was administered 1 h prior to irradiation. The histological observations indicated a decline in the villus height and crypt number with an increase in goblet and dead cell population in the irradiated group, which was normalized by pretreatment with ZO. A significant (p < 0.001) reduction in micronucleated polychromatic, normochromatic erythrocytes, increased PCE/NCE ratio, increase in the GSH, GST, SOD, CAT and decreased LPx levels were observed in ZO by pretreated group when compared to the irradiated animals. Our in vitro and in vivo studies demonstrate the potential of ZO in mitigating radiation-induced cytotoxic, genotoxicity, apoptosis in cell culture and animal mortality, cytogenetic damage, intestinal and bone marrow protection in vivo. Radioprotective potential of ZO may be attributed to the inhibition radiation-induced decline in the endogenous antioxidant levels

Right pulmonary aplasia, aberrant left pulmonary artery, and bronchopulmonary sequestration with an esophageal bronchus

International Nuclear Information System (INIS)

Lee, Peter; McCauley, Roy; Westra, Sjirk; Baba, Timothy

2006-01-01

Pulmonary aplasia and bronchopulmonary foregut malformations in which a patent communication between the foregut and the pulmonary system is present are rare congenital abnormalities. Pulmonary aplasia associated with a pulmonary sling is an even rarer abnormality. We report a unique case of right pulmonary aplasia, aberrant left pulmonary artery, and bronchopulmonary sequestration with an esophageal bronchus diagnosed by multidetector helical CT. (orig.)

Diabetes Mellitus Induces Bone Marrow Microangiopathy

NARCIS (Netherlands)

Oikawa, Atsuhiko; Siragusa, Mauro; Quaini, Federico; Mangialardi, Giuseppe; Katare, Rajesh G.; Caporali, Andrea; van Buul, Jaap D.; van Alphen, Floris P. J.; Graiani, Gallia; Spinetti, Gaia; Kraenkel, Nicolle; Prezioso, Lucia; Emanueli, Costanza; Madeddu, Paolo

2010-01-01

Objective-The impact of diabetes on the bone marrow (BM) microenvironment was not adequately explored. We investigated whether diabetes induces microvascular remodeling with negative consequence for BM homeostasis. Methods and Results-We found profound structural alterations in BM from mice with

Hemopoietic stem cell niches, recovery from radiation and bone marrow transfusions

International Nuclear Information System (INIS)

Cronkite, E.P.; Carsten, A.L.; Brecher, G.

1979-01-01

The long term hematologic effects of single whole body sublethal X-ray exposure, 525 rad, and the low level chronic exposure from 137 Cs gamma ray and ingested HTO were investigated in mice. The single X-ray exposure had early severe effect on bone marrows both in terms of total cellularity and the number of pluripotent stem cells. How do animals maintain normal cellularity in the absence of a normal number of the pluripotent stem cells[ The following 3 different mechanisms may be involved: additional division in the cytologically identifiable divisible pool of bone marrows; shortening of cycle time allowing more divisions in the same time with great amplification of a small number of colony-forming unit spleens; and the recruitment of G 0 stem cells into proliferation. The reduction in the number of bone marrow stem cells might be attributed to stromal injury in the marrows such that they cannot support as many stem cells as those before the radiation exposure. As an alternate to the ''niche'' hypothesis, the injury to the stem cell pool such that self-replication was not sufficient to restore normal cell concentration is a possibility. The time sequence of the transfusion of marrows may be important to the ultimate effect. Attempts to fill empty niches 10 and 12 weeks after a single and severe radiation injury may be impossible due to stromal changes which in effect have eliminated the niches. The bone marrows of animals rescued by the transfusion of 4 x 10 6 bone marrow cells will accept 0 to 25% of the second transfusion of 4 x 10 7 cells. (Yamashita, S.)

Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen

International Nuclear Information System (INIS)

Sharabi, Y.; Sachs, D.H.

1989-01-01

The use of allogeneic bone marrow transplantation as a means of inducing donor-specific tolerance across MHC barriers could provide an immunologically specific conditioning regimen for organ transplantation. However, a major limitation to this approach is the toxicity of whole body irradiation as currently used to abrogate host resistance and permit marrow engraftment. The present study describes methodology for abrogating host resistance and permitting marrow engraftment without lethal irradiation. Our preparative protocol involves administration of anti-CD4 and anti-CD8 mAbs in vivo, 300-rad WBI, 700-rad thymic irradiation, and unmanipulated fully MHC-disparate bone marrow. B10 mice prepared by this regimen developed stable mixed lymphohematopoetic chimerism without any clinical evidence of graft-vs.-host disease. Engraftment was accompanied by induction of specific tolerance to donor skin grafts (B10.D2), while third-party skin grafts (B10.BR) were promptly rejected. Mice treated with the complete regimen without bone marrow transplantation appeared healthy and enjoyed long-term survival. This study therefore demonstrates that stable mixed chimerism with donor-specific tolerance can be induced across an MHC barrier after a nonlethal preparative regimen, without clinical GVHD and without the risk of aplasia

Tetanus after allogeneic bone-marrow transplantation

International Nuclear Information System (INIS)

Kendra, J.R.; Halil, O.; Barrett, A.J.; Selwyn, S.

1982-01-01

A brief report is presented of a case of tetanus after allogeneic bone-marrow transplantation complicated by radiation-induced pneumonitis. A 30-year-old army sergeant received a bone-marrow transplant from his brother for the treatment of a granulocytic sarcoma after local radiotherapy to the tumour. Six years earlier he had sustained an open, compound fracture of the left tibia and fibula while on army exercise. At the time a pin and plate had been inserted and booster anti-tetanus administered. Bone-marrow transplantation was performed after total body irradiation. Cyclosporin A was given against graft-versus-host disease. Fifty four days after transplantation tetanus was diagnosed and death followed 14 days later. Necropsy disclosed radiation-induced pneumonitis, but no organisms were cultured from the lungs or the old fracture site. It is suggested that spores were incorporated into the wound site before surgery and that oxygenation around the plate became compromised after transplantation, permitting germination of dormant spores, immunosuppression allowing development of the disease. (U.K.)

Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.

Science.gov (United States)

Bär, Christian; Povedano, Juan Manuel; Serrano, Rosa; Benitez-Buelga, Carlos; Popkes, Miriam; Formentini, Ivan; Bobadilla, Maria; Bosch, Fatima; Blasco, Maria A

2016-04-07

Aplastic anemia is a fatal bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia. The disease can be hereditary or acquired and develops at any stage of life. A subgroup of the inherited form is caused by replicative impairment of hematopoietic stem and progenitor cells due to very short telomeres as a result of mutations in telomerase and other telomere components. Abnormal telomere shortening is also described in cases of acquired aplastic anemia, most likely secondary to increased turnover of bone marrow stem and progenitor cells. Here, we test the therapeutic efficacy of telomerase activation by using adeno-associated virus (AAV)9 gene therapy vectors carrying the telomerase Tert gene in 2 independent mouse models of aplastic anemia due to short telomeres (Trf1- and Tert-deficient mice). We find that a high dose of AAV9-Tert targets the bone marrow compartment, including hematopoietic stem cells. AAV9-Tert treatment after telomere attrition in bone marrow cells rescues aplastic anemia and mouse survival compared with mice treated with the empty vector. Improved survival is associated with a significant increase in telomere length in peripheral blood and bone marrow cells, as well as improved blood counts. These findings indicate that telomerase gene therapy represents a novel therapeutic strategy to treat aplastic anemia provoked or associated with short telomeres. © 2016 by The American Society of Hematology.

Prevention of radiation-induced chromosomal aberrations in bone marrow of mice by Indian medicinal plant, Alstonia scholaris

International Nuclear Information System (INIS)

Jahan, Swafiya; Ranuchaudhary; Goyal, P.K.

2007-01-01

for chromosomal study and were autopsied between 12 hrs to 30 days and chromosomal preparations were made from their bone marrow. Chromosomal aberrations including aberrant cells, chromatid breaks, centric rings, chromosomal exchanges, dicentrics and acentric fragments were scored higher at early intervals (12 hrs and 24 hrs) but later decreased gradually towards normalcy at the last autopsy interval. The pattern of change in chromosomal aberrations is almost similar as irradiated control but their frequency is found to be significantly lesser in Alstonia treated irradiated animals. From the results it is concluded that such plant extract has the potentiality to reduce radiation-induced cytogenetic lesions

Survival of bone marrow-engrafted mice subsequent to protection from lethal radiation by WR 2721

International Nuclear Information System (INIS)

Kinnamon, K.E.; Ketterling, L.L.; Ledney, G.D.; Lorenz, G.B.; Mioduszewski, R.J.; Stampfli, H.F.

1980-01-01

For the first time data are presented for animals treated with bone marrow cells after lethal radiation exposure while protected with WR 2721 (the single radioprotective chemical compound with the highest known dose reduction factor). The LD 50 30 (lethal dose to 50% in 30 days) for mice exposed to whole-body 60 Co radiation was elevated from 824 +- 8 rad in unprotected and untreated mice to (a) 1181 +- 33 rad in animals which received syngeneic bone marrow cells after exposure; (b) 1342 +- 27 rad in animals which received WR 2721 before radiation exposure; and (c) 1608 +- 33 rad in animals receiving both the radioprotective agent before exposure and bone marrow engraftment after exposure

Increased radiosensitivity and radiation-induced apoptosis in SRC-3 knockout mice

International Nuclear Information System (INIS)

Jin Jie; Wang Yu; Xu Yang; Chen Shilei; Wang Junping; Ran Xinze; Su Yongping; Wang Jin

2014-01-01

Steroid receptor coactivator-3 (SRC-3), a multifunctional transcriptional coactivator, plays an important role in regulation of cell apoptosis in chemoresistant cancer cells. However, its role in radiation-induced apoptosis in hematopoietic cells is still unclear. In this study, we used SRC-3 knockout (SRC-3 -/- ) mice to assess the role of SRC-3 in radiation-induced hematopoietic injury in vivo. After a range of doses of irradiation, SRC-3 -/- mice exhibited lower counts of peripheral blood cells and bone marrow (BM) mononuclear cells and excessive BM depression, which resulted in a significantly higher mortality compared with wildtype mice. Moreover, BM mononuclear cells obtained from SRC-3 -/- mice showed a remarkable increase in radiation-induced apoptosis. Collectively, our data demonstrate that SRC-3 plays a role in radiation-induced apoptosis of BM hematopoietic cells. Regulation of SRC-3 might influence the radiosensitivity of hematopoietic cells, which highlights a potential therapeutic target for radiation-induced hematopoietic injury. (author)

Therapeutic approaches of hematopoietic syndrome after serious accidental global irradiation. Ex vivo expansion interest of hematopoietic cells

International Nuclear Information System (INIS)

Thierry, D.

1994-01-01

Aplasia is one of the main syndrome, appearing after one global accidental irradiation by one ionizing radiation source. The hematopoietic syndrome is characterized by a peripheric blood cell number fall; the cell marrow is reduced too

Bone marrow cytology in Hiroshima atomic bomb survivors 5 years following exposure

International Nuclear Information System (INIS)

Oesterle, S.N.; Finch, S.C.

1978-11-01

Bone marrow aspiration smears obtained from 35 individuals, 5 years following exposure to the Hiroshima atomic bomb, were intensively evaluated for radiation related cytologic abnormalities. No definite radiation related changes were observed, but some findings were very suggestive. The most interesting of these was the occurrence of internuclear bridges joining erythroid precursors in the marrow smears of seven (20%) of the heavily exposed survivors. Although not specific it is likely that this lesion is indicative of residual stem cell damage and some degree of ineffectual erythropoiesis. The bone marrow morphologic lesions may be good markers of residual radiation damage but they are too infrequent in their occurrence to be of value as a biologic dosimeter. The findings in this study also suggest that a gradual disappearance of radiation induced late bone marrow changes continues for periods of 3 to 5 years or more following high dose acute radiation exposure. (author)

Allogeneic radiation chimeras induced in SPF mice

International Nuclear Information System (INIS)

Sado, Toshihiko; Kamisaku, Hitoko

1977-01-01

During the past two decades much has been learned concerning the immunobiology of bone marrow chimeras induced in experimental animals as well as in man. However, from the basic as well as clinical points of view, there still remain many unsolved questions yet to be resolved. In this presentation, we discussed some of our recent results on the immunobiology of radiation chimeras induced in specific-pathogen-free (SPF) mice. These included the following: (a) contribution of graft versus host reaction (GVHR) as well non- GVHR mediated immunologic mechanism(s) to the expression of immunologic dysfunctions observed in allogeneic and certain semiallogeneic chimeras, (b) existence of immunoregulatory mechanism as a basis for the apparent lack of immunologic reactivity (tolerance) to the host- as well as to the donor-type alloantigens in situ in successful allogeneic bone marrow chimeras, and (c) the effect of microflora of the environment on the stability of such immunoregulatory mechanisms and its possible mechanism of action. (auth.)

Inhibiting TGFβ1 has a protective effect on mouse bone marrow suppression following ionizing radiation exposure in vitro

International Nuclear Information System (INIS)

Zhang Heng; Yan Hao; Wang Xinzhuo; Niu Jingxiu; Wang Hui; Wang Yingai; Meng Aimin; Li Jin

2013-01-01

Ionizing radiation (IR) causes not only acute tissue damage but also residual bone marrow (BM) suppression. The induction of residual BM injury is primarily attributable to the induction of reactive oxygen species (ROS) pressure in hematopoietic cells. In this study, we examined if SB431542, a transforming growth factor β1 (TGFβ1) inhibitor, can mitigate IR-induced BM suppression in vitro. Our results showed that treatment with SB431542 protected mice bone marrow mononuclear cells (BMMNCs), hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) from IR-induced suppression using cell viability assays, clonogenic assays and competitive repopulation assays. Moreover, expression of gene-related ROS production in hematopoietic cells was analyzed. The expression of NADPH oxidative 1 (NOX1), NOX2 and NOX4 was increased in irradiated BMMNCs, and that of NOX2 and NOX4 was reduced by SB431542 treatment. Therefore, the results from this study suggest that SB431542, a TGFβ1 inhibitor, alleviates IR-induced BM suppression at least in part via inhibiting IR-induced NOX2 and NOX4 expression. (author)

Effect of Apis mellifera bee venom and gamma radiation on bone marrow cells of wistar rats treated in vivo

International Nuclear Information System (INIS)

Varanda, E.A.; Takahashi, C.S.; Soares, A.E.E.; Barreto, S.A.J.

1992-01-01

To determine whether the venom of Apis mellifera can exert a radioprotective effect, by reducing the frequency of chromosomal aberrations induced by radiation, five different experiments were performed on bone marrow cells of Wistar rats. Animals weighing about 100 g were injected intraperitoneally with different venom concentrations (1.0 or 0.5 μ1) 1 or 24 h before, or 30 min after being submitted to three or four Gy of gamma radiation, and sacrificed 24 h after the last treatment. (author)

Late radiation damage in bone, bone marrow and brain vasculature, with particular emphasis upon fractionation models

International Nuclear Information System (INIS)

Pitkaenen, Maunu.

1986-04-01

X-ray induced changes in rat and human bone and bone marrow vasculature and in rat brain vasculature were measured as a function of time after irradiation and absorbed dose. The absorbed dose in the organ varied from 5 to 25 Gy for single dose irradiations and from 19 to 58 Gy for fractionated irradiations.The number of fractions varied from 3 to 10 for the rats and from 12 to 25 for the human. Blood flow changes were measured using an ''1''2''5I antipyrine or ''8''6RbCl extraction technique. The red blood cell (RBC) volume was examined by ''5''1Cr labelled red cells. Different fractionation models have been compared. Radiation induced reduction of bone and bone marrow blood flow were both time and dose dependent. Reduced blood flow 3 months after irradiation would seem to be an important factor in the subsequent atrophy of bones. With a single dose of 10 Gy the bone marrow blood flow returned to the control level by 7 months after irradiation. In the irradiated bone the RBC volume was about same as that in the control side but in bone marrow the reduction was from 32 to 59%. The dose levels predicted by the nominal standard dose (NSD) formula produced about the same damage to the rat femur seven months after irradiation when the extraction of ''8''6Rb chloride and the dry weight were concerned as the end points. However, the results suggest that the NSB formula underestimates the late radiation damage in bone marrow when a small number of large fractions are used. In the irradiated brains of the rats the blood flow was on average 20.4% higher compared to that in the control group. There was no significant difference in brain blood flow between different fractionation schemes. The value of 0.42 for the exponent of N corresponds to the average value for central nervous system tolerance in the literature. The model used may be sufficiently accurate for clinical work provided the treatment schemes used do not depart too radically from standard practice

Hematopoiesis stimulation test by interleukin 1α gene transfer in the Cynomolgus macaque: application to secondary medullary aplasia from an accidental irradiation

International Nuclear Information System (INIS)

De Revel, Th.

2002-12-01

After a description of the context of medullary aplasia (haematological radiobiology, radiation acute syndrome, therapeutic care), and an overview of knowledge about the interleukin-1 and medullary stroma cells, this research thesis aims at investigating therapeutic alternatives for radio-accidental aplasia. More precisely, it aims at defining means to get cytokines which are efficient for haematopoiesis. Interleukin-1 is chosen for its properties and tests are performed on a macaque with two approaches for gene transfer: an ex vivo transfer by retroviral vector enabling an integration in the target cell genome, and an in situ transfer by adeno-viral vector directly applied in the animal osseous medulla

Radiation-Induced Leukemia at Doses Relevant to Radiation Therapy: Modeling Mechanisms and Estimating Risks

Science.gov (United States)

Shuryak, Igor; Sachs, Rainer K.; Hlatky, Lynn; Mark P. Little; Hahnfeldt, Philip; Brenner, David J.

2006-01-01

Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. Methods: To extend the model to radiation-induced leukemias, we analyzed in addition to cellular initiation, inactivation, and proliferation a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors v^ ho were subjected to much lower radiation doses. Results: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low

Investigating the Abscopal Effects of Radioablation on Shielded Bone Marrow in Rodent Models Using Multimodality Imaging.

Science.gov (United States)

Afshar, Solmaz F; Zawaski, Janice A; Inoue, Taeko; Rendon, David A; Zieske, Arthur W; Punia, Jyotinder N; Sabek, Omaima M; Gaber, M Waleed

2017-07-01

The abscopal effect is the response to radiation at sites that are distant from the irradiated site of an organism, and it is thought to play a role in bone marrow (BM) recovery by initiating responses in the unirradiated bone marrow. Understanding the mechanism of this effect has applications in treating BM failure (BMF) and BM transplantation (BMT), and improving survival of nuclear disaster victims. Here, we investigated the use of multimodality imaging as a translational tool to longitudinally assess bone marrow recovery. We used positron emission tomography/computed tomography (PET/CT), magnetic resonance imaging (MRI) and optical imaging to quantify bone marrow activity, vascular response and marrow repopulation in fully and partially irradiated rodent models. We further measured the effects of radiation on serum cytokine levels, hematopoietic cell counts and histology. PET/CT imaging revealed a radiation-induced increase in proliferation in the shielded bone marrow (SBM) compared to exposed bone marrow (EBM) and sham controls. T 2 -weighted MRI showed radiation-induced hemorrhaging in the EBM and unirradiated SBM. In the EBM and SBM groups, we found alterations in serum cytokine and hormone levels and in hematopoietic cell population proportions, and histological evidence of osteoblast activation at the bone marrow interface. Importantly, we generated a BMT mouse model using fluorescent-labeled bone marrow donor cells and performed fluorescent imaging to reveal the migration of bone marrow cells from shielded to radioablated sites. Our study validates the use of multimodality imaging to monitor bone marrow recovery and provides evidence for the abscopal response in promoting bone marrow recovery after irradiation.

Congenital aplasia of the optic chiasm and esophageal atresia: a case report

Directory of Open Access Journals (Sweden)

Madonia Maurizio

2011-08-01

Full Text Available Abstract Introduction The complete absence of the chiasm (chiasmal aplasia is a rare clinical condition. Hypoplasia of the optic nerve and congenital nystagmus are almost invariably associated characteristics. Microphthalmos or anophthalmos are common features in chiasmal aplasia, while central nervous system abnormalities are less frequent. Esophageal atresia can be isolated or syndromic. In syndromic cases, it is frequently associated with cardiac, limb, renal or vertebral malformations and anal atresia. More rarely, esophageal atresia can be part of anophthalmia-esophageal-genital syndrome, which comprises anophthalmia or microphthalmia, genital abnormalities, vertebral defects and cerebral malformations. Here, a previously unreported case of chiasmal aplasia presenting without microphthalmos and associated with esophageal atresia is described. Case presentation Aplasia of the optic chiasm was identified in a Caucasian Italian 8-month-old boy with esophageal atresia. An ultrasound examination carried out at 21 weeks' gestation revealed polyhydramnios. Intrauterine growth retardation, esophageal atresia and a small atrial-septal defect were subsequently detected at 28 weeks' gestation. Repair of the esophageal atresia was carried out shortly after birth. A jejunostomy was carried out at four months to facilitate enteral feeding. The child was subsequently noted to be visually inattentive and to be neurodevelopmentally delayed. Magnetic resonance imaging revealed chiasmal aplasia. No other midline brain defects were found. His karyotype was normal. Conclusion If achiasmia is a spectrum, our patient seems to depict the most severe form, since he appears to have an extremely severe visual impairment. This is in contrast to most of the cases described in the literature, where patients maintain good--or at least useful-- visual function. To the best of our knowledge, the association of optic nerve hypoplasia, complete chiasmal aplasia, esophageal

CT and MR Imagings of Semicircular Canal Aplasia

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Shin, Chung Hee; Hong, Hyun Sook; Yi, Beom Ha; Cha, Jang Gyu; Park, Seong Jin; Kim, Dae Ho; Lee, Hae Kyung; Kim, Shi Chan [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of)

2009-07-15

To evaluate the clinical, CT and MR imaging findings of semicircular canal (SCC) aplasia and to evaluate if a correlation exists between these findings and the associated anomalies or syndromes. This study retrospectively reviewed the CT and MRI findings of five patients with SCC aplasia. The CT and MR findings were analyzed for SCC, direction of facial nerve canal, cochlea, vestibule, oval or round window, middle ear ossicles, and internal auditory canal (IAC). The subjects included three boys and two girls ranging in age from one to 120 months (mean age; 51 months). Four of the subjects had the CHARGE syndrome, and one had the Goldenhar syndrome. Moreover, four subjects had sensorineural hearing loss and one had combined hearing loss. The course of the facial nerve canal was abnormal in all five cases. Moreover, trapped cochlea and dysplastic modiolus were each observed in one case. Four subjects had atresia of the oval window; whereas ankylosis of the ossicles was present in three subjects. IAC stenosis was present in one patient with the CHARGE syndrome. The aberrant course of the facial nerve canal, atresia of the oval window, and abnormal ossicles were frequently associated in patients with SCC aplasia. In addition, the Goldenhar and CHARGE syndromes were also commonly associated syndromes.

Is the primary event in radiation-induced chronic myelogenous leukemia the induction of the t(9; 22) translocation

Energy Technology Data Exchange (ETDEWEB)

Holmberg, M. (Swedish Radiation Protection Inst., Stockholm (Sweden))

1992-05-18

The probability that ionizing radiation induces a t(9;22) reciprocal translocation with its break points confined to the same regions as the break points for the Philadelphia (Ph') translocation in chronic myelogenous leukemia (CML) has been calculated to be 7 x 10[sup -12] per cell and gray. This figure was used to estimate the number of individuals among the atomic bomb survivors at Hiroshima and Nagasaki with such an induced translocation. For 9196 atomic bomb survivors who received a mean organ dose equivalent to bone marrow of 0.85 sievert, the estimate is done that the number of individuals with a radiation-induced t(9;22) translocation in one of the pluripotent stem cells in bone marrow is of the order of 50. The observed number of affected individuals with CML within the same cohort is 18. Even if the estimate of the number of individuals has relatively large errors, this indicates that the primary event in the radiation-induced CML cases can be a radiation-induced t(9;22) reciprocal translocation. (Author).

Absorbed dose to active red bone marrow from diagnostic and therapeutic uses of radiation

International Nuclear Information System (INIS)

Solomon, S.B.

1980-06-01

The bone-marrow dose arising from radiological procedures as carried out in Australia have been determined as part of a survey of population doses. This paper describes the method of calculation of the radiation doses to the active bone marrow from diagnostic radiography, fluoroscopy and radiotherapy. The results of the calculations are compared with the results of other models of bone-marrow dose for a number of diagnostic X-ray procedures

Dose rate and fractionation: Relative importance in radiation for bone marrow transplantation

International Nuclear Information System (INIS)

Tarbell, N.J.; Rosenblatt, M.; Mauch, P.; Hellman, S.

1987-01-01

The optimal dose rate and fractionation schedules for total body irradiation (TBI) in bone marrow transplantation (BMT) are presently unknown. This study compares several fractionation and dose rate schedules that are currently in clinical use. C/sub 3/H/HeJ were given TBI and the bone marrow survival fraction was calculated using the CFU's assay. Irradiation was given as low dose rate (LDR) at 5 cGy/min or high dose rate (HDR) at 80 cGy/min, in single fraction (SF) and fractionated (FX) regimens. These results indicate no increase in survival for the normal bone marrow stem cells with fractionation either at high or low dose-rates. In fact, fractionation seemed to decrease the bone marrow survival over single fraction radiation

Origanum vulgare leaf extract protects mice bone marrow cells against ionizing radiation

Directory of Open Access Journals (Sweden)

Reza Ghasemnezhad Targhi

2016-11-01

Full Text Available Objective: Ionizing radiation produces free radicals which induce DNA damage and cell death. Origanum vulgare leaf extract (OVLE is a natural compound and its capability of scavenging free radicals and its antioxidant activity have been demonstrated by many researchers. In this study, using micronucleus assay, radioprotective effect of OVLE against clastogenic and cytotoxic effect of gamma irradiation has been investigated in mice bone marrow cells. Materials and Methods: OVLE was injected intraperitoneally to the BALB/c mice 1hr prior to gamma irradiation (3Gy at the doses of 100 and 200 mg/kg. Twenty four hours after irradiation or treatment, animals were killed and smears were prepared from the bone marrow cells. The slides were stained with May Grunwald–Giemsa method and analyzed microscopically. The frequency of micronucleated polychromatic erythrocytes (MnPCEs, micronucleated normochromatic erythrocyte (MnNCEs and cell proliferation ratio PCE/PCE+NCE (polychromatic erythrocyte/polychromatic erythrocyte + normochromatic erythrocyte were calculated. Results: The results showed that gamma irradiation (3Gy increased the frequency of MnPCEs, MnNCEs and  reduced the PCE/PCE+NCE ratio in mice bone marrow compared to the non-irradiated control group (p< 0.0001. Injection of OVLE significantly reduced the frequency of MnPCEs (p< 0.0001 and MnNCEs (p< 0.05 and increased the PCE/PCE+NCE ratio as compared to the irradiated control group (p< 0.05. Conclusion: It seems that OVLE with its antioxidant properties and its capability of scavenging free radicals and reactive oxygen species can reduce the cytotoxic effects of gamma irradiation in mice bone marrow cells.

MarCell trademark software for modeling bone marrow radiation cell kinetics

International Nuclear Information System (INIS)

Hasan, J.S.; Jones, T.D.; Morris, M.D.

1997-01-01

Differential equations were used to model cellular injury, repair, and compensatory proliferation in the irradiated bone marrow. Recently, that model was implemented as MarCell trademark, a user-friendly MS-DOS computer program that allows users from a variety of technical disciplines to evaluate complex radiation exposure. The software allows menu selections for different sources of ionizing radiation. Choices for cell lineages include progenitor, stroma, and malignant, and the available species include mouse, rat, dog, sheep, swine, burro, and man. An attractive feature is that any protracted irradiation can be compared with an equivalent prompt dose (EPD) in terms of cell kinetics for either the source used or for a reference such as 250 kVp x rays or 60 Co. EPD is used to mean a dose rate for which no meaningful biological recovery occurs during the period of irradiation. For human as species, output from MarCell trademark includes: risk of 30-day mortality; risk of whole-body cancer and leukemia based either on radiation-induced cytopenia or compensatory cell proliferation; cell survival and repopulation plots as functions of time or dose; and 4-week recovery following treatment. copyright 1997 American Association of Physicists in Medicine

3'-deoxy-3'-[18F]fluorothymidine PET Quantification of Bone Marrow Response to Radiation Dose

International Nuclear Information System (INIS)

McGuire, Sarah M.; Menda, Yusuf; Boles Ponto, Laura L.; Gross, Brandie; Buatti, John; Bayouth, John E.

2011-01-01

Purpose: The purpose of this study was to quantify the relationship of bone marrow response to radiation dose, using 3'-deoxy-3'-[ 18 F]fluorothymidine ([ 18 F]FLT)-labeled uptake quantified in positron-emission tomography (PET) scans. Methods and Materials: Pre- and post-Week 1 treatment [ 18 F]FLT PET images were registered to the CT images used to create the radiation treatment plan. Changes in [ 18 F]FLT uptake values were measured using profile data of standardized uptake values (SUVs) and doses along the vertebral bodies located at a field border where a range of radiation doses were present for 10 patients. Data from the profile measurements were grouped into 1 Gy dose bins from 1 to 9 Gy to compare SUV changes for all patients. Additionally, the maximum pretreatment, the post-Week 1 treatment, and the dose values located within the C6-T7 vertebrae that straddled the field edge were measured for all patients. Results: Both the profile and the individual vertebral data showed a strong correlation between SUV change and radiation dose. Relative differences in SUVs between bins >1 Gy and 18 F]FLT PET images for identifying active bone marrow and monitoring changes due to radiation dose. Additionally, the change in [ 18 F]FLT uptake observed in bone marrow for different weekly doses suggests potential dose thresholds for reducing bone marrow toxicity.

Dose to red bone marrow of infants, children and adults from radiation of natural origin

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Kendall, G M [Childhood Cancer Research Group, University of Oxford, 57 Woodstock Road, Oxford OX2 6HJ (United Kingdom); Fell, T P; Harrison, J D [Health Protection Agency, Radiation Protection Division, CRCE, Chilton, Didcot OX11 0RQ, Oxon (United Kingdom)], E-mail: Gerald.Kendall@ccrg.ox.ac.uk

2009-06-15

Natural radiation sources contribute much the largest part of the radiation exposure of the average person. This paper examines doses from natural radiation to the red bone marrow, the tissue in which leukaemia is considered to originate, with particular emphasis on doses to children. The most significant contributions are from x-rays and gamma rays, radionuclides in food and inhalation of isotopes of radon and their decay products. External radiation sources and radionuclides other than radon dominate marrow doses at all ages. The variation with age of the various components of marrow dose is considered, including doses received in utero and in each year up to the age of 15. Doses in utero include contributions resulting from the ingestion of radionuclides by the mother and placental transfer to the foetus. Postnatal doses include those from radionuclides in breast-milk and from radionuclides ingested in other foods. Doses are somewhat higher in the first year of life and there is a general slow decline from the second year of life onwards. The low linear energy transfer (LET) component of absorbed dose to the red bone marrow is much larger than the high LET component. However, because of the higher radiation weighting factor for the latter it contributes about 40% of the equivalent dose incurred up to the age of 15.

Bone marrow scintigraphy with 111In-chloride

International Nuclear Information System (INIS)

Fujishima, Mamoru; Hiraki, Yoshio; Takeda, Yoshihiro; Kohno, Yoshihiro; Niiya, Harutaka; Aono, Kaname; Yorimitsu, Seiichi; Takahashi, Isao

1988-01-01

Bone marrow scintigraphy with indium chloride ( 111 In) was performed in fifty-one patients with the hematological diseases. The results of the investigation were that 1) in all patients, as well as in patients with aplastic anemia, no correlation was there between the degree of the indium chloride accumulation and peripheral blood counts, 2) in patients with aplastic anemia and pure red cell aplasia (PRCA) a tendency to reduction in uptake of indium chloride in bone marrow, 3) in patients with these two good correlation between the degree of indium chloride accumulation and histology of the erythroid bone marrow, but in patients with chronic myelocytic leukemia (CML) and atypical leukemia no correlation between the two, so it seemed unlikely that indium chloride should reflect the effective production of erythrocytes, 4) four patients with leukemia were studied with indium chloride bone marrow imaging two times to evaluate their responses to chemotherapy, and peripheral expansion was no change or reduced in two patients with acute myelocytic leukemia (AML) and one patient with acute lymphocytic leukemia (ALL) who obtained complete remission, but on the other hand, it enlarged in one patient with acute myelocytic leukemia who obtained partial remission, and 5) in two patients with chronic myelocytic leukemia it enlarged up to the ankle joints, which was considerably specific. (author)

High incidence of recurrent copy number variants in patients with isolated and syndromic Müllerian aplasia.

Science.gov (United States)

Nik-Zainal, Serena; Strick, Reiner; Storer, Mekayla; Huang, Ni; Rad, Roland; Willatt, Lionel; Fitzgerald, Tomas; Martin, Vicki; Sandford, Richard; Carter, Nigel P; Janecke, Andreas R; Renner, Stefan P; Oppelt, Patricia G; Oppelt, Peter; Schulze, Christine; Brucker, Sara; Hurles, Matthew; Beckmann, Matthias W; Strissel, Pamela L; Shaw-Smith, Charles

2011-03-01

Congenital malformations involving the Müllerian ducts are observed in around 5% of infertile women. Complete aplasia of the uterus, cervix, and upper vagina, also termed Müllerian aplasia or Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, occurs with an incidence of around 1 in 4500 female births, and occurs in both isolated and syndromic forms. Previous reports have suggested that a proportion of cases, especially syndromic cases, are caused by variation in copy number at different genomic loci. In order to obtain an overview of the contribution of copy number variation to both isolated and syndromic forms of Müllerian aplasia, copy number assays were performed in a series of 63 cases, of which 25 were syndromic and 38 isolated. A high incidence (9/63, 14%) of recurrent copy number variants in this cohort is reported here. These comprised four cases of microdeletion at 16p11.2, an autism susceptibility locus not previously associated with Müllerian aplasia, four cases of microdeletion at 17q12, and one case of a distal 22q11.2 microdeletion. Microdeletions at 16p11.2 and 17q12 were found in 4/38 (10.5%) cases with isolated Müllerian aplasia, and at 16p11.2, 17q12 and 22q11.2 (distal) in 5/25 cases (20%) with syndromic Müllerian aplasia. The finding of microdeletion at 16p11.2 in 2/38 (5%) of isolated and 2/25 (8%) of syndromic cases suggests a significant contribution of this copy number variant alone to the pathogenesis of Müllerian aplasia. Overall, the high incidence of recurrent copy number variants in all forms of Müllerian aplasia has implications for the understanding of the aetiopathogenesis of the condition, and for genetic counselling in families affected by it.

Survival of allografts from bone marrow donors in temporary dog radiation chimeras

International Nuclear Information System (INIS)

Vriesendorp, H.M.

Complete radiation chimeras accept indefinitely a skin or a kidney graft from the bone marrow (BM) donor. The advantages of this method of inducing graft acceptance are that it does not require the use of toxic post-operative immunosuppressive agents and that the immune reactivity against antigens other than the ones carried by the BM donor remains intact. The disadvantages of this approach are that supralethal total body irradiation (TBI) causes toxicity and that allogeneic BM cells can cause lethal Graft versus Host reactions. Attempts were made to diminish the significance of these disadvantages by using lower dose TBI and giving fewer BM cells. It is shown that, in dogs, 7.5 Gy TBI followed by 4 X 10 8 BM cells.kg -1 body weight of a DLA identical sibling leads to the development of complete radiation chimeras. The exclusive presence of donor type haemopoiesis can be demonstrated by determinations of 'informative' genetic markers, i.e., markers that show different genotypes in donor and recipient. (Auth.)

Characterization of changes in composition and function of erythrocyte membrane proteins in patients with bone marrow form of acute radiation sickness

International Nuclear Information System (INIS)

Li Jinying; Wei Shanjian; Hu Xiaojian

1998-01-01

Objective: The delayed effect of radiation on erythrocyte membrane protein, the composition and function of the membrane proteins in five patients with bone marrow form of acute radiation sickness (ARS) were follow up at six years after the Shanghai 60 Co irradiation accident. Methods: Percoll centrifugation, SDS-polyacrylamide gel electrophoresis, and analysis of NO 2 - transport rate and DIDS inhibition rate were performed. Results: The injuries of the membrane proteins induced by radiation, characterized by reduced content of band 8 and declined anion transport function of band 3 protein remained the same as initially observed. The further study showed that the inhibition of DIDS on the anion transport of the ARS erythrocytes was decreased and the transport time for NO 2 - by band 3 was significantly prolonged in younger erythrocytes than those in middle-or old-aged cells. Conclusion: It is suggested that the radiation damage to erythrocyte membrane proteins might occur at the stage of erythropoiesis in bone marrow. The exo-facial site in band 3 may be changed after radiation, which could result in the abnormalities in anion transport. It is believed that the aging of erythrocytes might be present in advanced stage of ARS

SU-F-R-55: Early Detection of Treatment Induced Bone Marrow Injury During Chemoradiation Therapy Using Quantitative CT

Energy Technology Data Exchange (ETDEWEB)

Chen, X; Song, Y; Erickson, B; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

2016-06-15

Purpose: Acute hematologic toxicity associated with bone marrow injury is a common complication of chemoradiation therapy (CRT) for pelvic malignancies. In this work, we investigate the feasibility of using quantitative CT to detect bone marrow injury during CRT. Methods: Daily CTs were acquired during routine CT-guided radiation therapy using a CT-on-rails for 15 cervical cancer patients. All patients treated with a radiation dose of 45.0 to 50.4 Gy in 1.8 Gy/fraction along with chemotherapy. For each patient, the contours of bone marrow were generated in L4, L5 and sacrum on the first daily CT and then populated to other daily CTs by rigid registration using MIM (MIM Software Inc., Cleveland, OH) with manual editing if possible. A series of CT texture parameters, including Hunsfield Unit (HU) histogram, mean HU, entropy, energy, in bone marrow contours were calculated using MATLAB on each daily CT and were correlated with the completed blood counts (CBC) collected weekly for each patient. The correlations were analyzed with Pearson correlation tests. Results: For all patient data analyzed, mean HU in bone marrow decreased during CRT delivery. From the first to the last fraction the average mean HU reduction is 58.1 ± 13.6 HU (P<0.01). This decrease can be observed as early as after first 5 fractions and is strongly associated with the changes of most CBC quantities, such as the reductions of white and blood cell counts (r=0.97, P=0.001). The reduction of HU is spatially varied. Conclusion: Chemoradiation induced bone marrow injury can be detected during the delivery of CRT using quantitative CT. Chemoradiation results in reductions in mean HU, which are strongly associated with the change in the pretrial blood cell counts. Early detection of bone marrow injury with commonly available CT opens a door to improve bone marrow sparing, reducing risk of hematologic toxicity.

Phenotypic characterization of early events of thymus repopulation in radiation bone marrow chimeras

International Nuclear Information System (INIS)

Sharrow, S.O.; Singer, A.; Hammerling, U.; Mathieson, B.J.

1983-01-01

The phenotype of murine thymocytes repopulating the thymus of radiation bone marrow chimeras shortly after irradiation and bone marrow reconstitution was analyzed by immunofluorescence and flow microfluorometry. Thymuses in these chimeras, while essentially devoid of lymphoid cells at day 7, were repopulated by days 10 to 12 after irradiation. It was found that this initial repopulation arose from a radioresistant intrathymic precursor that expanded to an almost complete complement of host-type thymocytes. However, these host-derived thymocytes were unusual in that they were relatively deficient in Lyt 1+2- and peanut agglutinin ''dull'' cells as compared with normal thymocytes. Donor bone-marrow-derived cells first appeared in the irradiated chimeric thymuses between days 12 and 15 after irradiation and bone marrow transfer. By day 19, chimeric thymuses contained more than 98% donor cells. This course was identical for three chimeric combinations, each made across different genetic barriers. In contrast to the cells that populate the fetal thymus during normal ontogeny, the first donor bone-marrow-derived cells that can be detected within the irradiated chimeric thymuses already expressed phenotypically normal adult T cell subpopulations in that they contained significant numbers both of Lyt 1+2- and of Lyt 1+2+ thymocytes. Thus, the Lyt phenotype of donor cells that initially repopulate an adult thymus after irradiation is markedly different from the Lyt phenotype of cells that initially populate the fetal thymus. The differences between adult and fetal thymic development that are observed in radiation bone marrow chimeras may be important in our understanding of T cell differentiation in these animals

Protective effect of a non specific inflammation on bone marrow protein synthesis in irradiated mice

International Nuclear Information System (INIS)

Herodin, F.; Roques, P.; Court, L.

1988-01-01

Gamma radiations exert a decrease in mouse bone marrow total protein synthesis. A non-specific inflammatory process induced with polyacrylamide microbeads stimulates spleen and marrow protein synthesis and protects the medullar protein synthesis in irradiated mice [fr

Visual and quantitative approach to bone marrow foci of increased glucose uptake on PET/CT in a case of aplastic anaemia

Energy Technology Data Exchange (ETDEWEB)

Cicone, F. [Sant' Andrea Hospital, Univ. La Sapienza, Rome (Italy). Nuclear Medicine Dept.; Centre Hospitalier Univ. Vaudois (Switzerland). Nuclear Medicine; Lausanne Univ. (Switzerland); Stalder, M. [Institut Central des Hopitaux Valaisans, Sion (Switzerland). Service of Hematology; Cairoli, A. [Centre Hospitalier Univ. Vaudois (Switzerland). Service of Hematology; Lausanne Univ. (Switzerland); Bischof Delaloye, A.; Prior, J.O. [Centre Hospitalier Univ. Vaudois (Switzerland). Nuclear Medicine; Lausanne Univ. (Switzerland); Geiger, D.

2010-07-01

This case report shows the clinical impact of a FDG-PET/CT in the assessment of bone marrow (BM) of a patient with aplastic anemia. The feasibility of a quantitative approach to BM intensities on FDG-PET is also discussed. In the authors' opinion, a deeper understanding of the factors that might independently affect FDG uptake and the definition of normal ranges of BM SUV (standardized uptake value) might help to interpret PET/CT images. Further research is needed to understand the physio-pathological basis of FDG uptake in BM and the potential value of its quantification. The analysis of the bone marrow on PET/CT is an interesting field of research. A PET/CT scan contributed to differential diagnosis in a patient with suspected bone marrow aplasia for guiding bone marrow biopsies.

Visual and quantitative approach to bone marrow foci of increased glucose uptake on PET/CT in a case of aplastic anaemia

International Nuclear Information System (INIS)

Cicone, F.; Stalder, M.; Bischof Delaloye, A.; Prior, J.O.; Geiger, D.

2010-01-01

This case report shows the clinical impact of a FDG-PET/CT in the assessment of bone marrow (BM) of a patient with aplastic anemia. The feasibility of a quantitative approach to BM intensities on FDG-PET is also discussed. In the authors' opinion, a deeper understanding of the factors that might independently affect FDG uptake and the definition of normal ranges of BM SUV (standardized uptake value) might help to interpret PET/CT images. Further research is needed to understand the physio-pathological basis of FDG uptake in BM and the potential value of its quantification. The analysis of the bone marrow on PET/CT is an interesting field of research. A PET/CT scan contributed to differential diagnosis in a patient with suspected bone marrow aplasia for guiding bone marrow biopsies.

Genetics of Müllerian aplasia

OpenAIRE

Sandbacka, Maria

2013-01-01

Müllerian aplasia (MA) is a rare congenital disorder of the female reproductive tract. It involves loss of a functional uterus and upper two thirds of the vagina, resulting in infertility and need of treatment to enable normal sex life. Skeletal and renal structural abnormalities, such as scoliosis and renal agenesis are often associated with MA. The patients are otherwise healthy females with normal secondary sex characteristics and karyotype (46,XX). However, psychosocial problems are often...

A methodology for incorporating functional bone marrow sparing in IMRT planning for pelvic radiation therapy

International Nuclear Information System (INIS)

McGuire, Sarah M.; Menda, Yusuf; Boles Ponto, Laura L.; Gross, Brandie; Juweid, Malik; Bayouth, John E.

2011-01-01

Background and purpose: The purpose of this study was to design a radiation therapy treatment planning approach that would spare hematopoietically active bone marrow using [ 18 F]FLT PET imaging. Materials and methods: We have developed an IMRT planning methodology to incorporate functional PET imaging using [ 18 F]FLT scans. Plans were generated for two simulated cervical cancer patients, where pelvic active bone marrow regions were incorporated as avoidance regions based on the ranges: SUV4 ≥ 4; 4 > SUV3 ≥ 3; and 3 > SUV2 ≥ 2. Dose objectives were set to reduce bone marrow volume that received 10 (V 10 ) and 20 (V 20 ) Gy. Results: Active bone marrow regions identified by [ 18 F]FLT with an SUV ≥ 2, SUV ≥ 3, and SUV ≥ 4 represented an average of 43.0%, 15.3%, and 5.8%, respectively of the total osseous pelvis for the two cases studied. Improved dose-volume histograms for all identified bone marrow SUV volumes and decreases in V 10 , and V 20 were achieved without clinically significant changes to PTV or OAR doses. Conclusions: Incorporation of [ 18 F]FLT PET in IMRT planning provides a methodology to reduce radiation dose to active bone marrow without compromising PTV or OAR dose objectives in pelvic malignancies.

Effects of bone marrow or mesenchymal stem cell transplantation on oral mucositis (mouse) induced by fractionated irradiation

International Nuclear Information System (INIS)

Schmidt, M.; Haagen, J.; Noack, R.; Siegemund, A.; Gabriel, P.; Doerr, W.

2014-01-01

Oral mucositis is a severe and dose limiting early side effect of radiotherapy for head-and-neck tumors. This study was initiated to determine the effect of bone marrow- and mesenchymal stem cell transplantation on oral mucositis (mouse tongue model) induced by fractionated irradiation. Daily fractionated irradiation (5 x 3 Gy/week) was given over 1 (days 0-4) or 3 weeks (days 0-4, 7-11, 14-18). Each protocol was terminated (day 7 or 21) by graded test doses (5 dose groups, 10 animals each) in order to generate complete dose-effect curves. The incidence of mucosal ulceration, corresponding to confluent mucositis grade 3 (RTOG/EORTC), was analyzed as the primary, clinically relevant endpoint. Bone marrow or mesenchymal stem cells were transplanted intravenously at various time points within these fractionation protocols. Transplantation of 6 x 10 6 , but not of 3 x 10 6 bone marrow stem cells on day -1, +4, +8, +11 or +15 significantly increased the ED 50 values (dose, at which an ulcer is expected in 50% of the mice); transplantation on day +2, in contrast, was ineffective. Mesenchymal stem cell transplantation on day -1, 2 or +8 significantly, and on day +4 marginally increased the ED 50 values. Transplantation of bone marrow or mesenchymal stem cells has the potential to modulate radiation-induced oral mucositis during fractionated radiotherapy. The effect is dependent on the timing of the transplantation. The mechanisms require further investigation. (orig.)

Reconstruction of bilateral tibial aplasia and split hand-foot syndrome in a father and daughter.

Science.gov (United States)

Al Kaissi, Ali; Ganger, Rudolf; Klaushofer, Klaus; Grill, Franz

2014-01-01

Tibial aplasia is of heterogeneous aetiology, the majority of reports are sporadic. We describe the reconstruction procedures in two subjects - a daughter and father manifested autosomal dominant (AD) inheritance of the bilateral tibial aplasia and split hand-foot syndrome. Reconstruction of these patients required multiple surgical procedures and orthoprosthesis was mandatory. The main goal of treatment was to achieve walking. Stabilization of the ankle joint by fibular-talar-chondrodesis on both sides, followed by bilateral Brown-procedure at the knee joint level has been applied accordingly. The outcome was with improved function of the deformed limbs and walking was achieved with simultaneous designation of orthotic fitting. This is the first study encompassing the diagnosis and management of a father and daughter with bilateral tibial aplasia associated with variable split hand/foot deformity without foot ablation. Our patients showed the typical AD pattern of inheritance of split-hand/foot and tibial aplasia.

Radiation-Induced Changes in Some Biochemical Parameters of the Haemopoietic Tissue of Rabbits

Energy Technology Data Exchange (ETDEWEB)

Izak, G.; Karsai, A.; Eylon, L. [Haematology Research Laboratory, Hadassah University Hospital (Israel); Hebrew University-Hadassah Medical School, Jerusalem (Israel)

1968-08-15

Bone-marrow and reticulocyte suspensions obtained from rabbits following massive haemorrhage were irradiated by a cobalt source with doses ranging between 1000-10 000 rad. The radiation-induced injury to the nucleic acid synthesizing apparatus and to the haem-and protein-producing activity of the bone-marrow cells, as well as the damage to the haemoglobin synthesizing system of the reticulocytes, was investigated shortly after exposure. The amino-acid incorporation activity into protein was substantially reduced, together with all the other parameters measured in the bone-marrow cells, while globin synthesis was not affected at the same radiation dose in the reticulocytes. On the other hand, incorporation of haem precursors into protoporphyrin and of radio iron into protoporphyrin was inhibited both in the nucleated erythroid precursors and in the reticulocytes, more so in the former than in the latter. The implications of these findings and possible means to repair the biochemical injury are discussed. (author)

Aplasia medular após transplante hepático em pediatria Aplastic anemia after pediatric liver transplantation

Directory of Open Access Journals (Sweden)

Marlene P. Garanito

2009-01-01

Full Text Available A aplasia de medula é uma das mais raras (Aplastic anemia (AA is one of the rarest (<1% and most serious complications of liver transplantation for fulminant non-A, non-B and non-C hepatitis. It was first described in 1987 by Stock; the mechanism involved is an immunologically mediated condition secondary to an unknown viral infection. The disease is associated with a dismal prognosis. Spontaneous recovery from acquired AA is very rare however some patients (50-70% recover after immunosuppressive therapy, such as Cyclosporin A (CsA and Antithymocyte globulin (ATG, even after liver transplantation. Another treatment option is bone marrow transplantation. We report on a child who developed AA following liver transplantation for fulminant viral hepatitis that was treated with intensive immunosuppression including CsA and ATG and achieved complete recovery.

Primary observation on adherent function of bone marrow stromal cells in mice post combined radiation-burn injury

International Nuclear Information System (INIS)

Chen Xinghua; Luo Chengji; Guo Chaohua; Wang Ping; Deng Xuecai

1999-01-01

Objective: To investigate the adherent function of bone marrow stromal cells in hematopoietic inductive microenvironment post combined radiation-burn injury. Methods: The expression of cell adhesion molecules including vascular cell adhesion molecule-1 (VCAM-1), fibro-connection (Fn), laminin (Ln) and collagen type IV (Col IV) on bone marrow stromal cells cultured in vitro was detected by flow cytometry and the binding capacity of bone marrow mononuclear cells to stromal cell adherence layer was tested by cell binding assay and cell binding blocking assay respectively from mice treated with 5.0 Gy γ-ray 15% of total body surface area (TBSA), third-degree burn injury and combined irradiation-burn injury, respectively. Results: 1. The expression levels of molecules mentioned above in burn-injured mice were the highest. The molecules levels in control mice were greater than those in radiation-injured mice, which were lower than those in mice with combined radiation-burn injury. 2. The binding capacity of stromal cell adherence layer in burn-injured mice was greater than that in control mice, and significantly increased from 3 to 7 days post injury as compared with that in controls, radiation-injured mice and combined radiation-burn-injured mice, respectively (P < 0.05-0.01). Contrarily, the capacity of binding in the radiation-injured and combined radiation-burn-injured mice was the lowest from 3 to 7 days post injury. 3. The binding rate of bone marrow mononuclear cells to stromal cell adherence layer descended in different degrees after pre-treatment with monoclonal antibodies directed to VCAM-1, Fn, Ln, or Col IV respectively or VCAM-1 combined with anti-Fn, anti-Ln or anti-Col IV, respectively, in stromal cell adherence layer. Conclusion: The damage of cell adherent function for bone marrow hematopoietic inductive microenvironment post combined radiation-burn injury might be one of the important factors in hematopoietic disorder in combined radiation-burn injury

Migration of bone marrow cells to the thymus in sublethally irradiated mice

International Nuclear Information System (INIS)

Varlet, Andree; Lenaerts, Patrick; Houben-Defresne, M.P.; Boniver, Jacques

1982-01-01

In sublethally irradiated mice, thymus repopulation is due first to the proliferation of surviving thymocytes followed by the multiplication of bone marrow derived prothymocytes. The migration of bone marrow cells to the thymus after a single sublethal whole-body X irradiation was studied by using fluorescein isothiocyanate as a cell marker. Irradiation increases the permissiveness of the thymus to the immigration of bone marrow cells. Furthermore, the post-Rx regenerating bone marrow cells exhibit migration capacities greater than the normal ones. The radiation induced changes in the bone marrow thymus interaction might play an important role in thymus regeneration after sublethal irradiation [fr

Melanin-Covered Nanoparticles for Protection of Bone Marrow During Radiation Therapy of Cancer

International Nuclear Information System (INIS)

Schweitzer, Andrew D.; Revskaya, Ekaterina; Chu, Peter; Pazo, Valeria; Friedman, Matthew; Nosanchuk, Joshua D.; Cahill, Sean; Frases, Susana; Casadevall, Arturo; Dadachova, Ekaterina

2010-01-01

Purpose: Protection of bone marrow against radiotoxicity during radioimmunotherapy and in some cases external beam radiation therapy such as hemi-body irradiation would permit administration of significantly higher doses to tumors, resulting in increased efficacy and safety of treatment. Melanin, a naturally occurring pigment, possesses radioprotective properties. We hypothesized that melanin, which is insoluble, could be delivered to the bone marrow by intravenously administrated melanin-covered nanoparticles (MNs) because of the human body's 'self-sieving' ability, protecting it against ionizing radiation. Methods and Materials: The synthesis of MNs was performed via enzymatic polymerization of 3,4-dihydroxyphenylalanine and/or 5-S-cysteinyl-3,4-dihydroxyphenylalanine on the surface of 20-nm plain silica nanoparticles. The biodistribution of radiolabeled MNs in mice was done at 3 and 24 h. Healthy CD-1 mice (Charles River Laboratories International, Inc., Wilmington, MA) or melanoma tumor-bearing nude mice were given MNs intravenously, 50 mg/kg of body weight, 3 h before either whole-body exposure to 125 cGy or treatment with 1 mCi of 188 Re-labeled 6D2 melanin-binding antibody. Results: Polymerization of melanin precursors on the surface of silica nanoparticles resulted in formation of a 15-nm-thick melanin layer as confirmed by light scattering, transmission electron microscopy, and immunofluorescence. The biodistribution after intravenous administration showed than MN uptake in bone marrow was 0.3% and 0.2% of injected dose per gram at 3 and 24 h, respectively, whereas pre-injection with pluronic acid increased the uptake to 6% and 3% of injected dose per gram, respectively. Systemic MN administration reduced hematologic toxicity in mice treated with external radiation or radioimmunotherapy, whereas no tumor protection by MNs was observed. Conclusions: MNs or similar structures provide a novel approach to protection of bone marrow from ionizing radiation based

Allogeneic bone marrow grafts in genotyped swine

International Nuclear Information System (INIS)

Vaiman, M.

1974-01-01

The proof of a major histocompatibility complex (MHC) called SL-A enabled to promote bone marrow allografts. A study of the response to that kind of graft in irradiated pig states a number of interesting points. Bone marrow allografting complies with the rule of tissular compatibility with the major histocompatibility complex. The taking of SL-A incompatible bone marrow allografts could not be achieved under the experimental conditions. In spite of the high doses of radiation, 950 to 1050 rads, higher than 1.5 LD 100%, recipients were capable of rejecting their grafts, regularly. SL-A identify ensured 100%, initial achievement. However, animals developed regular fatal disease within a fairly short time. This development could by no means, be ascribed to the sole sequealae of radiation sickness since autografted animals at equal or even higher doses, showed none of the symptome. Assumption of a chronic graft-vs-host reactions, induced by the minor histocompatible systems, was put foreward, but should be confirmed histopathologically [fr

Single inhalation exposure to 90SrCl2 in the Beagle dog: early hematological effects

International Nuclear Information System (INIS)

Gillett, N.; Muggenburg, B.A.; Hahn, F.F.; Boecker, B.B.; Rebar, A.H.; McClellan, R.O.

1985-01-01

Young adult Beagle dogs were exposed once to aerosols containing 90 SrCl 2 to obtain initial body burdens ranging from 2.5 to 250 uCi 90 Sr/kg body weight and subsequently observed throughout their life span. All of the dogs are now dead. The primary cause of death over the entire length of the study was radiation-induced osteosarcomas. However, six dogs died at less than 30 days after exposure as a result of a radiation-induced bone marrow aplasia. Review of hematological parameters of all dogs showed a similar, consistent, and often dramatic pancytopenia in those animals having a long-term retained burden of greater than 10 uCi 90 Sr/kg. The hematologic changes were similar to those seen in people exposed to high doses of whole body external radiation. 4 references, 1 figure, 1 table

Capacity of bone marrow colony forming unit-fibroblasts in vitro from mice with combined radiation-burn injury

International Nuclear Information System (INIS)

Chen Xinghua; Luo Chengji; Guo Chaohua; Wang Ping

1999-01-01

Objective: To investigate the capacity of bone marrow colony forming unit-fibroblasts (CFU-F) from mice with combined radiation-burn injury. Methods: Mice were treated with 5.0 Gy γ-ray radiation alone, 15% total body surface area (TBSA) III degree burn alone or combined radiation-burn. The numbers of CFU-Fs were assayed by Dexter's method. Results: The numbers of CFU-Fs from mice with radiation and combined radiation-burn injury were significantly decreased, compared with those of controls and mice with burn injury alone (P<0.05-0.01). conclusion: The results reveal that the repairing process of bone marrow stromal cells from mice with radiation injury and combined radiation-burn injury is slow, and the combined radiation-burn injury inflicted on the stromal cells possesses the characteristic of radiation injury

Study on preventive and therapeutic effect of Chinese medicinal herbal extracts on rat with bone marrow injury induced by radiation exposure

International Nuclear Information System (INIS)

Guo Jun; Chen Baotian; Meng Hua; Liu Wenchao; Xie Wei; Sheng Rong

2006-01-01

Objective: To examine the effect of Chinese medicinal herbal extracts, Danggui (Radix angelicae sinensis), Chuanxiong (Rhizoma chuanxiong), Huangqi (Radix astragali), and Danshen (Radix salviae miltiorrhizae) on rats with bone marrow injury induced with whole-body gamma-ray exposure. Methods: Sixty male rats were randomly divided into three groups, control group, model group (irradiation only with no administration of the extracts), and drug treatment group (irradiation and administration of Chinese medicinal herbal extracts). Rats were irradiated with 6 Gy cobolt-60 gamma rays after administration of the extracts for two weeks. The number of marrow nucleate cells was counted, and VEGF and PDGF expression were measured with Western blot method on the 7th day since the irradiation. Results: Bone marrow nucleate cells and VEGF and PDGF expression in bone marrow cells in the model group were significantly lower than those in the control group (P<0.01), and these values in the drug treatment group were significantly higher than those in the model group (P<0.01 or P<0.05). Conclusion: The extracts of Chuanxiong, Danggui, Huangqi, and Danshen can be used to prevent from ration bone marrow injury in rats. (authors)

Reconstruction of bilateral tibial aplasia and split hand-foot syndrome in a father and daughter

Directory of Open Access Journals (Sweden)

Ali Al Kaissi

2014-01-01

Full Text Available Background: Tibial aplasia is of heterogeneous aetiology, the majority of reports are sporadic. We describe the reconstruction procedures in two subjects - a daughter and father manifested autosomal dominant (AD inheritance of the bilateral tibial aplasia and split hand-foot syndrome. Materials and Methods: Reconstruction of these patients required multiple surgical procedures and orthoprosthesis was mandatory. The main goal of treatment was to achieve walking. Stabilization of the ankle joint by fibular-talar-chondrodesis on both sides, followed by bilateral Brown-procedure at the knee joint level has been applied accordingly. Results: The outcome was with improved function of the deformed limbs and walking was achieved with simultaneous designation of orthotic fitting. Conclusion: This is the first study encompassing the diagnosis and management of a father and daughter with bilateral tibial aplasia associated with variable split hand/foot deformity without foot ablation. Our patients showed the typical AD pattern of inheritance of split-hand/foot and tibial aplasia.

Radiation block of bone marrow cell mitoses and the effect of insulin

Energy Technology Data Exchange (ETDEWEB)

Barkalaya, A I

1976-01-01

Insulin (0.15 - 0.2 units/kg) has been administered to white rats immediately after the exposure to 750 R, at the background of hypercorticoidism. This resulted in the inhibition of the development of the post-irradiation-stress-hyperglycemia; and the mitotic index of the bone marrow cells at the time of the mitosis block was higher than in the control irradiated rats. Insulin administration at the peak of radiation sickness during hypercorticoidism levelled hyperglycemia, stimulated the mitotic activity of cells of the bone marrow and the regeneration of the latter.

Monte Carlo simulation of age-dependent radiation dose from alpha- and beta-emitting radionuclides to critical trabecular bone and bone marrow targets

Science.gov (United States)

Dant, James T.; Richardson, Richard B.; Nie, Linda H.

2013-05-01

Alpha (α) particles and low-energy beta (β) particles present minimal risk for external exposure. While these particles can induce leukemia and bone cancer due to internal exposure, they can also be beneficial for targeted radiation therapies. In this paper, a trabecular bone model is presented to investigate the radiation dose from bone- and marrow-seeking α and β emitters to different critical compartments (targets) of trabecular bone for different age groups. Two main issues are addressed with Monte Carlo simulations. The first is the absorption fractions (AFs) from bone and marrow to critical targets within the bone for different age groups. The other issue is the application of 223Ra for the radiotherapy treatment of bone metastases. Both a static model and a simulated bone remodeling process are established for trabecular bone. The results show significantly lower AFs from radionuclide sources in the bone volume to the peripheral marrow and the haematopoietic marrow for adults than for newborns and children. The AFs from sources on the bone surface and in the bone marrow to peripheral marrow and haematopoietic marrow also varies for adults and children depending on the energy of the particles. Regarding the use of 223Ra as a radionuclide for the radiotherapy of bone metastases, the simulations show a significantly higher dose from 223Ra and its progeny in forming bone to the target compartment of bone metastases than that from two other more commonly used β-emitting radiopharmaceuticals, 153Sm and 89Sr. There is also a slightly lower dose from 223Ra in forming bone to haematopoietic marrow than that from 153Sm and 89Sr. These results indicate a higher therapy efficiency and lower marrow toxicity from 223Ra and its progeny. In conclusion, age-related changes in bone dimension and cellularity seem to significantly affect the internal dose from α and β emitters in the bone and marrow to critical targets, and 223Ra may be a more efficient

Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage

Directory of Open Access Journals (Sweden)

Jie Deng

2018-04-01

Full Text Available Oxidative DNA damage in bone marrow cells is the main side effect of chemotherapy drugs including cyclophosphamide (CTX. However, not all antioxidants are effective in inhibiting oxidative DNA damage. In this study, we report the beneficial effect of carnosine (β-alanyl-l-histidine, a special antioxidant with acrolein-sequestering ability, on CTX-induced bone marrow cell suppression. Our results show that carnosine treatment (100 and 200 mg/kg, i.p. significantly inhibited the generation of reactive oxygen species (ROS and 8-hydroxy-2′-deoxyguanosine (8-oxo-dG, and decreased chromosomal abnormalities in the bone marrow cells of mice treated with CTX (20 mg/kg, i.v., 24 h. Furthermore, carnosine evidently mitigated CTX-induced G2/M arrest in murine bone marrow cells, accompanied by reduced ratios of p-Chk1/Chk1 and p-p53/p53 as well as decreased p21 expression. In addition, cell apoptosis caused by CTX was also suppressed by carnosine treatment, as assessed by decreased TUNEL-positive cell counts, down-regulated expressions of Bax and Cyt c, and reduced ratios of cleaved Caspase-3/Caspase-3. These results together suggest that carnosine can protect murine bone marrow cells from CTX-induced DNA damage via its antioxidant activity. Keywords: Carnosine, Cyclophosphamide, Oxidative DNA damage, Sister chromatid exchange, Apoptosis, Cell cycle arrest

Aspergillosis in immunocompromised children acute myeloid leukemia and bone marrow aplasia.: Report of two cases Aspergilose em crianças imunocomprometidas com leucemia mielóide aguda e aplasta de medula óssea: Registro de 2 casos

Directory of Open Access Journals (Sweden)

Maria Zilda de Aquino

1994-10-01

Full Text Available Two cases of Aspergillosis in immunocompromised children are reported. Both were caused by Aspergillns flavus. Early diagnosis and treatment led to the remission of the process. One patient had acute myeloid leukemia; the fungus was isolated from the blood. The other patient with bone marrow aplasia, presented an invasive aspergillosis of the paranasal sinuses with dissemination of fungal infection; the diagnosis was obtained by histology and culture of biopsied tissue from a palatal ulceration.No presente trabalho são registrados dois casos de aspergilose em crianças imunocomprometidas. O estudo micológico completo identificou Aspergillus flavus como agente dos dois processos. A presença cada vez mais frequente da aspergilose invasiva deve-se ao número crescente de pacientes imunocomprometidos, muitos com hemopatias graves submetidos à quimioterapia. O diagnóstico precoce em um dos casos possibilitou remissão do processo. Tratava-se de paciente com leucemia mielóide aguda, tendo sido isolado o fungo do sangue circulante. O segundo caso evoluiu para óbito, com infecção fúngica generalizada.

Identification of high-risk patients with aplastic anaemia in selection for allogeneic 0one-marrow transplantation.

Science.gov (United States)

Lohrmann, H P; Kern, P; Niethammer, D; Heimpel, H

1976-09-25

Of 75 patients with asplastic anaemia treated between 1968 and 1975, 33 were retrospectively considered as potential candidates for allogenegic bone-marrow transplantation on the basis of their age and severity of marrow failure. The prognosis of these patients with conservative treatment was assessed from parameters obtained at the time of the initial diagnosis. Initial peripheral-blood granulocyte or platelet concentrations were not of porgnostic value. In contrast, initial reticulocyte concentrations, allowed separation of the patients into two groups with poor and good prognosis. Low initial reticulocyte concentrations (less than 10 000/mu1) indicated those patients at extremely high risk of succumbing to their marrow aplasia (there were no survivors 36 months after disgnosis). In contrast, 75% of those patients with more than 10 000 reticulocytes per mu1 at diagnosis survived for 3 years. Initial peripheral-blood reticulocyte concentrations thus appear to indicate the extent of the marrow failure in aplastic anaemia more accurately than granulocytes or platelets. Low initial reticulocyte concentrations may indicate, among patients with severe aplastic anaemia, those for whom allogeneic bone-marrow transplantation should be seriously considered; patients with higher initial reticulocyte concentrations may benefit from conservation treatment.

Pyloric atresia epidermolysis bullosa aplasia cutis syndrome: a case ...

African Journals Online (AJOL)

Pyloric atresia epidermolysis bullosa aplasia cutis syndrome: a case report and literature ... skin over the right leg from the knee joint up to the middle of the right foot. ... Examination indicated no signs of child abuse; the parents refused an ...

Cell therapy with bone marrow mononuclear cells in elastase-induced pulmonary emphysema.

Science.gov (United States)

Longhini-Dos-Santos, Nathalia; Barbosa-de-Oliveira, Valter Abraão; Kozma, Rodrigo Heras; Faria, Carolina Arruda de; Stessuk, Talita; Frei, Fernando; Ribeiro-Paes, João Tadeu

2013-04-01

Emphysema is characterized by destruction of alveolar walls with loss of gas exchange surface and consequent progressive dyspnea. This study aimed to evaluate the efficiency of cell therapy with bone marrow mononuclear cells (BMMC) in an animal model of elastase-induced pulmonary emphysema. Emphysema was induced in C57Bl/J6 female mice by intranasal instillation of elastase. After 21 days, the mice received bone marrow mononuclear cells from EGFP male mice with C57Bl/J6 background. The groups were assessed by comparison and statistically significant differences (p pulmonary emphysema.

Evaluation of Functional Marrow Irradiation Based on Skeletal Marrow Composition Obtained Using Dual-Energy Computed Tomography

Energy Technology Data Exchange (ETDEWEB)

Magome, Taiki [Department of Radiological Sciences, Faculty of Health Sciences, Komazawa University, Tokyo (Japan); Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota (United States); Department of Radiology, The University of Tokyo Hospital, Tokyo (Japan); Froelich, Jerry [Department of Radiology, University of Minnesota, Minneapolis, Minnesota (United States); Takahashi, Yutaka [Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota (United States); Department of Radiation Oncology, Osaka University, Osaka (Japan); Arentsen, Luke [Department of Therapeutic Radiology, University of Minnesota, Minneapolis, Minnesota (United States); Holtan, Shernan; Verneris, Michael R. [Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota (United States); Brown, Keenan [Mindways Software Inc, Austin, Texas (United States); Haga, Akihiro; Nakagawa, Keiichi [Department of Radiology, The University of Tokyo Hospital, Tokyo (Japan); Holter Chakrabarty, Jennifer L. [College of Medicine, Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Giebel, Sebastian [Department of Bone Marrow Transplantation, Comprehensive Cancer Center M. Curie-Sklodowska Memorial Institute, Gliwice (Poland); Wong, Jeffrey [Department of Radiation Oncology, Beckman Research Institute, City of Hope, Duarte, California (United States); Dusenbery, Kathryn [Department of Therapeutic Radiology, University of Minnesota, Minneapolis, Minnesota (United States); Storme, Guy [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Brussels (Belgium); Hui, Susanta K., E-mail: shui@coh.org [Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota (United States); Department of Therapeutic Radiology, University of Minnesota, Minneapolis, Minnesota (United States); Department of Radiation Oncology, Beckman Research Institute, City of Hope, Duarte, California (United States)

2016-11-01

Purpose: To develop an imaging method to characterize and map marrow composition in the entire skeletal system, and to simulate differential targeted marrow irradiation based on marrow composition. Methods and Materials: Whole-body dual energy computed tomography (DECT) images of cadavers and leukemia patients were acquired, segmented to separate bone marrow components, namely, bone, red marrow (RM), and yellow marrow (YM). DECT-derived marrow fat fraction was validated using histology of lumbar vertebrae obtained from cadavers. The fractions of RM (RMF = RM/total marrow) and YMF were calculated in each skeletal region to assess the correlation of marrow composition with sites and ages. Treatment planning was simulated to target irradiation differentially at a higher dose (18 Gy) to either RM or YM and a lower dose (12 Gy) to the rest of the skeleton. Results: A significant correlation between fat fractions obtained from DECT and cadaver histology samples was observed (r=0.861, P<.0001, Pearson). The RMF decreased in the head, neck, and chest was significantly inversely correlated with age but did not show any significant age-related changes in the abdomen and pelvis regions. Conformity of radiation to targets (RM, YM) was significantly dependent on skeletal sites. The radiation exposure was significantly reduced (P<.05, t test) to organs at risk (OARs) in RM and YM irradiation compared with standard total marrow irradiation (TMI). Conclusions: Whole-body DECT offers a new imaging technique to visualize and measure skeletal-wide marrow composition. The DECT-based treatment planning offers volumetric and site-specific precise radiation dosimetry of RM and YM, which varies with aging. Our proposed method could be used as a functional compartment of TMI for further targeted radiation to specific bone marrow environment, dose escalation, reduction of doses to OARs, or a combination of these factors.

The characters and developments of therapy and research of neutron-induced acute radiation sickness

International Nuclear Information System (INIS)

Wang Xinru; Luo Qingliang; Wang Baoqing; Dong Shukui

2003-01-01

Neutron radiation will exert seriously lesions on body and lead to acute radiation sickness (ARS). Neutron induced ARS is characterized by complicated symptoms of gastrointestinal, high earlier death rate and lacking of specially therapeutic approaches. The primarily curable method is to treat patients with comprehensive means such as anti-infection, anti-bleeding and blood infusion, et. Cytokines can improve the hematopoietic functions of bone marrow. With the rapid development of the molecular biology and the emergence of cytokines such as recombinant human interleukin-11 that could help the regeneration of the gastrointestinal mucosa, neutron-induced ARS will be treated with new methods

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.)

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

International Nuclear Information System (INIS)

Nagata, Shuji; Shen, Robert K.; Laack, Nadia N.; Inwards, Carrie Y.; Wenger, Doris E.; Amrami, Kimberly K.

2013-01-01

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.)

Growth of transplantable melanoma and leukaemia and prevention of virus-induced leukaemia in long lived radiation chimeras constructed with unmanipulated bone marrow

International Nuclear Information System (INIS)

Pierpaoli, W.

1985-01-01

Haemopoietic radiation chimeras across the H-2 barrier (BALB/c → C57B1/6; H-2sup(d) → H-2sup(b) chimeras and vice versa) have been studied for their capacity to suppress the growth, or to reject, transplantable B16 melanotic melanoma and radiation leukaemia virus-induced, transplantable leukaemia. Also, radiation leukaemia virus (RadLV) obtained from the thymus of leukaemic C57B1/6 mice was injected i.p. into established chimeras (H-2sup(d) → H-2sup(b)). As expected, long lived, graft versus host disease free allogeneic chimeras constructed with intact bone marrow were unable to reject the tumours both when recipients were BALB/c → C57B1/6 or C57B1/6 → BALB/c chimeras. However, inoculation of a large number of immunocompetent cells from normal BALB/c mice into BALB/c → C57B1/6 chimeras failed to promote a rejection of the tumours. On the contrary, the same amount of syngeneic (BALB/c) immunocompetent cells prevented growth of melanoma when transferred into athymic nude BALB/c mice, while the tumour grew unimpaired in untreated athymic nude BALB/c mice. The same type of H-2sup(d) → H-2sup(b) chimeras displayed complete resistance to inoculation of leukaemogenic H-2sup(b) restricted RadLV while all H-2sup(b) → H-2sup(b), syngeneically reconstituted mice developed disseminated leukaemia. (author)

Modulation of Radiation Injury in Pregnant Rats by Bone Marrow Transplantation

International Nuclear Information System (INIS)

Hussein, E.M.; Abd Rabu, M.A.

2011-01-01

This Work aims to point out the influence of bone marrow transplantation (BMT) in protection of irradiated pregnant rats and suppression of oxidative stress. BMT was administered to rats, 1 h post gamma irradiation at the dose level of 2 Gy given at the 7th or 14th day of gestation. Rats were examined after 20 days from gestation to detect the physiological parameters of the mother and number of implantation sites and resorption as well as length of foetuses and tails. Pregnant rats irradiated at the 7th and 14th day of gestation showed reduction in live foetuses and length of foetuses and their tails and significant decrease in erythrocytes (RBCs), leucocytes (WBCs), haemoglobin content (Hb), and hematocrit percentage (Ht). Irradiation-induced an elevation in aldosterone and a drop in calcium (Ca). Glutathione levels showed significant decreases in blood while the content of serum thiobarbituric acid reactive substance (TBARS) showed significant increases. Lipid profile exhibited an increase in the concentrations of total cholesterol (TC), triglycerides (TG) and low lipoproteins cholesterol (LDL-C) with a significant decrease in high lipoproteins cholesterol (HDL-C) in both groups. BMT to irradiated pregnant rats induced significant amelioration in radiation- induced changes. BMT was shown to be effective in reducing physiological disorders and oxidative stress in pregnant rats reflected on minimizing embryonic injuries

Radiation-induced changes of the developing nervous system of amphibians

International Nuclear Information System (INIS)

Schneider, M.

1986-01-01

The nervous system of amphibians (Xenopus laevis and Bufo) is of an outstanding sensitivity against irradiation in the early periods of its tissue induction and development. This is descriptively shown by various pathological disturbances. Irradiated series showed a protracted course of development. The brains obtains lower relative weights and diminished absolute lengths although the body weight remained nearly constant. The distribution of pigmentation in the brains of treated animals was changed. This indicated radiation-induced disturbances. Further, the significance of pigmentation pattern for a distinct evaluation of histological effects is also confirmed by a coincidence between the gross visible anomalies of the brain and the number of pigment-sites. Examples of malformation are given by aplasias, hypoplasias, hyperplasias up to cases of cyclopia. In the peripheral nervous system of Xenopus the neuromuscular junctions of the musculus interhyoideus were examined. The majority of neural endplates in the irradiated cases showed a loss of Schwann cells. As a consequence a diffusion of the transmitter acetylcholine in the endplate-region must be suggested. Accordingly, the morphological compensation reaction was seen in a thickening and sprouting. (orig.)

Role of prothymocytes in radiation induced thymic lymphoma

International Nuclear Information System (INIS)

Bekkum, D.W. van; Knaan, S.; Boersma, W.J.A.

1982-01-01

The authors report a marked decrease in the prothymocyte/HSC ratio in the bone marrow of mice after four weekly fractionated radiation exposures which is similar to that observed in regenerating bone marrow following transplantation. Experimental results indicate that the actual efficiency of regenerating bone marrow in the prevention of leukaemia may quite possibly be much less than one-third of that of normal bone marrow. Present data seem to support the idea that the prothymocyte is the effective cell type responsible for the protection against leukaemogenesis. (Auth.)

Umbelliferone suppresses radiation induced DNA damage and apoptosis in hematopoietic cells of mice

International Nuclear Information System (INIS)

Jayakumar, S.; Bhilwade, H.N.; Chaubey, R.C.

2012-01-01

Radiotherapy is one of the major modes of treatment for different types of cancers. But the success of radiotherapy is limited by injury to the normal cells. Protection of the normal cells from radiation damage by radioprotectors can increase therapeutic efficiency. These radioprotectors can also be used during nuclear emergency situations. Umbelliferone (UMB) is a wide spread natural product of the coumarin family. It occurs in many plants from the Apiaceae family. In the present study radioprotective effect of UMB was investigated in vitro and in vivo. Anti genotoxic effect of Umbelliferone was tested by treating the splenic lymphocytes with various doses of UMB (6.5 μM - 50 μM) prior to radiation (6Gy) exposure. After the radiation exposure, extent of DNA damage was assessed by comet assay at 5 mm and two hours after radiation exposure. At both the time points, it was observed that the pretreatment of UMB reduced the radiation induced DNA damage to a significant extent in comparison to radiation control. UMB pretreatment also significantly reduced the radiation induced apoptosis enumerated by propidium iodide staining assay. Results of clonogenic survival assay using intestinal cell line showed that pretreatment with UMB significantly protected against radiation induced loss of colony forming units. To assess the anti genotoxic role of umbelliferone in vivo two different doses of UMB (20 mg/Kg and 40 mg/Kg of body weight) were injected into Swiss mice or with vehicle and exposed to radiation. Thirty minutes after the radiation comet assay was performed in peripheral leukocytes. Frequency of micro nucleated erythrocytes was scored in bone marrow cells. It was observed that UMB alone did not cause any significant increase in DNA damage in comparison to control. Animals which are exposed to radiation alone showed significant increase in DNA damage and micronuclei frequency. But animals treated with UMB prior to the radiation exposure showed significant decrease

[Risk factors for teeth aplasia and hypoplasia in cleft lip and palate children].

Science.gov (United States)

Korolenkova, M V; Starikova, N V; Ageeva, L V

2016-01-01

The aim of the study was to assess the significance of environmental risk factors for teeth aplasia and hypoplasia in cleft lip and palate children. Two hundred and forty-seven cleft lip and palate (CLP) children were enrolled in the study including 105 (42.5%) with bilateral CLP and 57.5% with unilateral CLP. The mean age was 11.2±4.9 years. Teeth condition was assessed clinically and radiologically. The impact of risk factors for teeth anomalies was analyzed by retrospective data obtained from computer database (absence of preoperative orthopedic treatment, palatal defects after primary palatoplasty and type of primary procedures). Surgical trauma by early periosteoplasty (at the age of 3-4 months), excessive scarring and tissue traction due to absence of early orthopedic treatment and palatal defect were associated with significantly higher incidence of incisors hypoplasia (both developmental enamel defects and microdentia) and aplasia of central incisors not seen in the other study subgroups. Incisors aplasia and hypoplasia in CLP patients do not always have disembryogenic origin but may depend on external environmental factors, including surgical trauma.

Is the thrombopoietin assay useful for differential diagnosis of thrombocytopenia? Analysis of a cohort of 160 patients with thrombocytopenia and defined platelet life span.

Science.gov (United States)

Gouin-Thibault, I; Cassinat, B; Chomienne, C; Rain, J D; Najean, Y; Schlageter, M H

2001-09-01

Thrombopoietin (TPO), the major hormone controlling platelet production, has been measured in thrombocytopenias with discordant results. The aim of our work was to assess the value of the TPO assay for differential diagnosis of thrombocytopenias in a large cohort of patients classified according to the results of their platelet isotopic study. We measured TPO (R&D Systems) in serum of 160 thrombocytopenic patients referred to our department for platelet life span isotopic studies. We classified patients as follows: (a) idiopathic or autoimmune thrombocytopenia group (ITP; patients with increased platelet destruction and shortened platelet life span; n = 67); (b) pure genetic thrombocytopenia group (patients with decreased platelet production, normal platelet life span, and without bone marrow aplasia; n = 55); (c) bone marrow aplasia group (BM; patients with decreased platelet production, normal platelet life span, and bone marrow aplasia; n = 13). In patients with pure genetic thrombocytopenia, TPO (median, 55 ng/L) was not different from TPO in patients with ITP (median, 58 ng/L) or controls (n = 54; median, 51 ng/L). Only in patients with bone marrow aplasia was TPO significantly higher (median, 155 ng/L) and negatively correlated to the platelet count (r(2) = 0.5014). Although the median serum TPO is increased in thrombocytopenia with decreased platelet production from bone marrow aplasia, it does not differentiate patients with pure genetic thrombocytopenia from those with ITP.

Protection of radiation induced DNA and membrane damages by total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst.

Science.gov (United States)

Smina, T P; Maurya, D K; Devasagayam, T P A; Janardhanan, K K

2015-05-25

The total triterpenes isolated from the fruiting bodies of Ganoderma lucidum was examined for its potential to prevent γ-radiation induced membrane damage in rat liver mitochondria and microsomes. The effects of total triterpenes on γ-radiation-induced DNA strand breaks in pBR 322 plasmid DNA in vitro and human peripheral blood lymphocytes ex vivo were evaluated. The protective effect of total triterpenes against γ-radiation-induced micronuclei formations in mice bone marrow cells in vivo were also evaluated. The results indicated the significant effectiveness of Ganoderma triterpenes in protecting the DNA and membrane damages consequent to the hazardous effects of radiation. The findings suggest the potential use of Ganoderma triterpenes in radio therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L. [Dept.of Radiation Oncology, Henry Ford Health System, Detroit (United States)

2014-09-15

To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

International Nuclear Information System (INIS)

Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L.

2014-01-01

To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

Expression of MDM2 in an acute lymphocytic leukemia mice model induced by γ-radiation

International Nuclear Information System (INIS)

Huang Yuecheng; Cai Jianming; Han Ling; Gao Fu; Cui Jianguo; Gao Jianguo

2004-01-01

Objective: To investigate the role of the MDM 2 in the process of carcinogenesis induced by γ-rays and its molecular mechanisms. Methods: Animal model of radiation-induced leukemia was established by γ-irradiation. According to the histological and morphological results, mice tissues were divided into three groups: cancerization group, incancerization group and control group. Expression of MDM 2 protein and mRNA in thymus/bone marrow was detected with Western blot and in situ hybridization (ISH), respectively. The authors also examined the protein phosphorylation level of MDM 2 protein by immunoprecipitation (IP). PCR-SSCP was performed to detect gene mutation. Results: A mice leukemia model was successfully established as verified by pathological findings and confirmed by transplantation test in nude mice. The protein expression in thymus/bone marrow in irradiation groups was significantly higher than that in controls (P 2 was found to be hyper-phosphorylated in the cancerization group as compared with other groups. No gene mutation was detected by SSCP/silver-staining assay in the tumor samples. Conclusion: MDM 2 may be involved in the development and progression of leukemia induced by γ-irradiation. The over-expression but not gene mutation may be responsible for malignant transformation induced by radiation. Phosphorylation is at least partly attributed to activation of MDM 2

Radiation-induced mouse chimeras: a cellular analysis of the major lymphoid compartments, factors affecting lethal graft versus host disease and host-tumor interactions

International Nuclear Information System (INIS)

Almaraz, R.

1981-01-01

The major lymphoid compartments of allogeneic bone marrow chimeras were evaluated for the extent of cell chimerism and distribution of Thy 1 and la bearing cells. These chimeras contained lymphoid cell primarily of donor origin. The bone marrow compartment was a mixture of host and donor origin cells. The distribution of Thy 1 and la bearing cells was similar as in normal mice. The effect of adult thymectomy alone or followed by whole-body irradiation and bone marrow reconstitution on the distribution of the Thy 1 positive cells was also investigated. Thymectomy with or without WBI and bone marrow reconstitution significantly lowered the number of Thy 1 bearing cells in the blood and spleen. The number of la bearing cells did not appear to be affected by thymectomy. The role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation induced fully allogeneic mouse chimeras was studied. Mice reconstituted with allogeneic bone marrow from bled donors had a statistically lower incidence of GVHD than those reconstituted with bone marrow from unbled donors. Addition of mature peripheral lymphocytes from blood to the reconstituting bone marrow cells from bled donors reduplicated the high incidence of lethal GVHD. It was demonstrated that the bone marrow of mice not exsanguinated prior to harvesting of bone marrow contained significant numbers of peripheral contaminating cells in the harvested bone marrow. The role of suppressor cell elimination in resisting tumor growth was investigated using radiation induced mouse chimeras. Local effects of irradiation alone at the site of tumor inoculation could account for this lack of growth

Activity of carbohydrate metabolism enzymes of bone marrow cells of rats affected by radiation

International Nuclear Information System (INIS)

Sukhomlinov, B.F.; Grinyuk, Yu.S.; Sibirnaya, N.A.; Starikovich, L.S.; Khmil', M.V.

1990-01-01

The influence of ionizing radiation (154.8 mC/kg on activity of some carbohydrate metabolism dehydrogenases in cells of the whole and fractionated rat bone marrow has been investigated. Different glucose metabolism units differently responded to radiation, the highest radiation response being exhibited by pentosophosphate cycle processes. The pattern of changes in the enzyme activity of different myelocaryocyte populations was shown to depend directly on the functional specilization of cells and the energy exchange types predominated in them

Chromosomal aberrations in the bone marrow cells of mice induced by accelerated {sup 12}C{sup 6+} ions

Energy Technology Data Exchange (ETDEWEB)

Ma Xiaofei [Department of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); School of Nuclear Science and Technology, Lanzhou University, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Zhang Hong, E-mail: zhangh@impac.ac.cn [Department of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Wang Zhenhua; Min Xianhua; Liu Yang; Wu Zhenhua [Department of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Sun Chao [Department of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate University of Chinese Academy of Sciences, Beijing 100049 (China); Hu Bitao [School of Nuclear Science and Technology, Lanzhou University, Lanzhou 730000 (China)

2011-11-01

Highlights: {yields} 220 MeV/u {sup 12}C{sup 6+} ions is 1.5 times more effective than X-rays in inducing chromosomal aberration in bone marrow cell. {yields} The ratio of dose averaged liner energy transfer is approach the RBE. {yields} {sup 12}C{sup 6+} ions could induce severe mitosis delay. {yields} The cell cycle is not recovered 72 h following irradiation. - Abstract: The whole bodies of 6-week-old male Kun-Ming mice were exposed to different doses of {sup 12}C{sup 6+} ions or X-rays. Chromosomal aberrations of the bone marrow (gaps, terminal deletions and breaks, fragments, inter-chromosomal fusions and sister-chromatid union) were scored in metaphase 9 h after exposure, corresponding to cells exposed in the G{sub 2}-phase of the first mitosis cycle. Dose-response relationships for the frequency of chromosomal aberrations were plotted both by linear and linear-quadratic equations. The data showed that there was a dose-related increase in the frequency of chromosomal aberrations in all treated groups compared to controls. Linear-quadratic equations were a good fit for both radiation types. The compound theory of dual radiation action was applied to decipher the bigger curvature (D{sup 2}) of the dose-response curves of X-rays compared to those of {sup 12}C{sup 6+} ions. Different distributions of the five types of aberrations and different degrees of homogeneity were found between {sup 12}C{sup 6+} ion and X-ray irradiation and the possible underlying mechanism for these phenomena were analyzed according to the differences in the spatial energy deposition of both types of radiation.

High incidence of recurrent copy number variants in patients with isolated and syndromic Mullerian aplasia

OpenAIRE

Nik-Zainal , Serena; Strick , Reiner; Storer , Mekayla; Huang , Ni; Rad , Roland; Willatt , Lionel; Fitzgerald , Tomas; Martin , Vicki; Sandford , Richard; Carter , Nigel P; Janecke , Andreas; Renner , Stefan; Oppelt , Patricia G; Oppelt , Peter; Schulze , Christine

2011-01-01

Abstract Background: Congenital malformations involving the Mullerian ducts are observed in around 5% of infertile women. Complete aplasia of the uterus, cervix, and upper vagina, also termed Mullerian aplasia or Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome occurs with an incidence of around 1 in 4,500 female births, and occurs in both isolated and syndromic forms. Previous reports have suggested that a proportion of cases, especially syndromic cases, are caused by variation in c...

Pathological changes after bone marrow and skin allograft transplantation in rats inflicted with severe combined radiation-burn injury

International Nuclear Information System (INIS)

Zheng Huaien; Cheng Tianmin; Yan Yongtang

1994-01-01

Bone marrow and skin allografts from the same donor were transplanted to rats inflicted with 8 Gy γ-radiation combined with third degree burns of 15% body surface area within 6 hr post injury. Pathological changes of hematopoietic tissues and skin allografts were studied. All injured controls died within 7 days post injury without bone marrow regeneration; 50% of treated rats survived with living skin allografts on 50th day post injury. On days 100 and 480 post operation, grafted skin still survived well on recipients with normal ultrastructure. Epidermic cells of skin allografts proliferated on day 5, developed and repaired on day 10. Histological structure of the skin returned to normal on day 30 post operation. The regeneration of bone marrow appeared on 5th day, increased markedly on day 10, and almost completed on day 15 after bone marrow transplantation. However, the regeneration of lymphocytes in cortex of spleen and lymph nodes did not appear until day 15 of BMT. The results show that bone marrow and skin allograft transplantation at early time post injury in most severe combined radiation-burn injury have tremendous beneficial effects, and the skin allograft can survive for a long time

Possible mechanisms of chromosomal aberrations: VII. Comparative dynamics of sister chromatid disjunction and realization of radiation-induced chromosomal aberrations during mitosis

International Nuclear Information System (INIS)

Lebedeva, L.I.; Akhmamet'eva, E.M.

1994-01-01

An increase in radiation-induced chromosomal aberrations during c-metaphase sister chromatid disjunction was demonstrated in murine bone marrow cells exposed to a total γ-irradiation at 0.5 Gy. Caffeine (Cf) treatment during mitosis partially suppressed the chromatid disjunction rate and increased the number of radiation-induced aberrations in this mitosis. Nalidixic acid (NA) treatment of c-metaphase cells completely suppressed chromatid disjunction and the realization of induced aberrations. Topoisomerase 2 was assumed to be involved during mitosis in both processes

Cytokinetic Analysis of Slowly Renewing Bone-Marrow Cells after Administration of Nitrogen Mustard

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Haas, R.; Fliedner, T. M.; Stehle, H. [Abteilung fuer Klinische Physiologie der Universitaet Ulm, Ulm/Donau, Federal Republic of Germany (Germany)

1968-08-15

The continuous or repeated administration of tritiated thymidine into pregnant rats during organogenesis provides a method for the complete labelling of newborn rats. If these are continuously injected with tritiated thymidine for the first four weeks after birth, the fraction of labelled cells of all organs and cell-renewal systems is still 100% If completely labelled animals are sacrificed at regular intervals after the discontinuance of thymidine administration, one can distinguish two groups of cells with distinct differences in their cell renewal. While the reticular cells A and B, the endothelial cells and the bone-marrow lymphocytes belong to a slowly proliferating group of cells, the differentiated myelopoietic and erythropoietic cells of the bone marrow proliferate rapidly. That labelled erythropoietic or myelopoietic cells are not found later than 6-10 days after discontinuance of tritated thymidine injection in these animals argues strongly against the hypothesis that under normal steady-state conditions a G{sub 0} fraction exists in the bone-marrow, from which stem cells are deviated into the differentiated cell pools by adequate stimuli. The administration of nitrogen mustard in a dose sufficient to cause bone-marrow aplasia neither destroys nor stimulates the reticular cells and endothelial cells of the bone-marrow matrix. These cells retain their label and remain present in normal numbers throughout the period of observation after nitrogen mustard treatment: The only cell type in the marrow that changes its labelling intensity after nitrogen mustard administration is the marrow lymphocyte. The decrease in the fraction and intensity of labelled bone-marrow lymphocytes precedes the rapid regeneration of nitrogen mustard aplastic bone-marrow. This cell type, in our opinion, would be the only cell to qualify as a stem cell, although positive evidence is still lacking. (author)

Radiation effect on the generation and expression of bone marrow stromal cells

International Nuclear Information System (INIS)

Xu Xiaoya; Jin Weilao; Gao Jianjun; Zhou Yi; Sheng Hui

2009-01-01

In order to investigate focal flushing dose radiation effect on the generation, differentiation and gene expression of bone marrow stromal cells the femoral head of rats was irradiated at 30 Gy by 137 Cs γ-rays (dose rate: 0.83 Gy/min). Then the bone marrow stromal cells (BMSCs) was cultured. The ability of proliferation and colony formation was observed and the expression level of Cbf-α1, PPAR-γ, VEGF-a and KDR was detected by RT-PCR technology in two weeks later. It has been found that after partly irradiated by 137 Cs γ-rays the proliferation and the number of colony of BMSCs in irradiated group decreases obviously meanwhile the expression level of Cbf-α1, PPAR-γ and VEGF-a in irradiated BMSCs obviously decreases by 18.98 %, 9.46 %, 57.34 % and 5.56 % respectively compared to the normal BMSCs (p<0.05). It shows that the focal great radiation could damage the BMSCs and depress the generation, differentiation and the expression of the related genes obviously. (authors)

Associação entre aplasia segmentar de veia safena magna e varizes em membros inferiores avaliada pelo ecocolor Doppler

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Amélia Cristina Seidel

2015-09-01

Full Text Available ResumoContextoHá diferenças individuais no diâmetro da veia safena magna (VSM em membros normais e doentes; sendo possível a identificação dessas alterações pelo ecocolor Doppler.ObjetivoAvaliar a associação da aplasia segmentar da VSM com a presença de varizes e/ou insuficiência da mesma em membros inferiores, usando o ecocolor Doppler em pacientes com clínica de doença venosa crônica (DVC.Métodos1.408 pacientes com queixas compatíveis de DVC de membros inferiores, sendo 1.286 do sexo feminino, com idade entre 17 e 85 anos, examinados com ecocolor Doppler. Foram incluídos aqueles com classificação CEAP clínica C0 a C4. Pela avaliação clínica, a amostra foi distribuída em grupo A, pacientes com varizes, e grupo B, aqueles sem varizes. O ecocolor Doppler determinou se havia aplasia da VSM pela análise do seu trajeto no compartimento safeno e presença de veias varicosas nos diferentes sítios. Para estatística, foram considerados os testes Qui-quadrado ou Exato de Fisher e uma análise de resíduos em tabelas, com nível de significância de 5%.ResultadosNo grupo A houve 479 (83,9% de VSM insuficientes, 169 (38,2% com aplasia e 71 (80,7% com insuficiência e aplasia associadas. No grupo B, houve 92 (16,1% de VSM insuficientes, 273 (61,8% com aplasia e 17 (19,3% com insuficiência e aplasia associadas.ConclusãoA aplasia segmentar da VSM ocorre mais em membros inferiores que não apresentam varizes e/ou insuficiência da mesma, mas considerando-se a presença da associação de aplasia e insuficiência, houve maior incidência no grupo de membros que apresentavam varizes.

Aplasia Cutis Congénita: Presentación de un caso

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Rosa María Alonso Uría

1998-06-01

Full Text Available Se reportó el caso de un recién nacido, hijo de madre secundigesta, con una malformación congénita del cuero cabelludo, del tipo aplasia cutis congénita. Se describieron las características clínicas de ésta, su evolución, pronóstico y tratamiento. Se hizo énfasis en el cuidado y la prevención de las complicaciones, fundamentalmente infecciosas, en este tipo de neonatosThe case of a newborn, son of a secundigravida, with a congenital malformation of the scalp denominated aplasia cutis congenita is reported. Its clinical characteristics, evolutions, prognosis and treatment are described. Emphasis is made on the care and prevention of the complications, mainly infectious, in this type of neonates

In vitro radiation response studies on bone marrow fibroblasts (CFU-F) obtained from normal and chronically irradiated dogs

International Nuclear Information System (INIS)

Klein, A.K.; Stitzel, K.A.; Greenberg, B.; Woo, L.

1984-01-01

The radiation resistance of bone marrow fibroblasts as measured by their proliferative potential was evaluated in chronically irradiated dogs. Bone marrows were obtained from eight dogs that had been chronically irradiated beginning at 21 days of gestation or after birth and eight age-matched controls. Of these irradiated dogs, four were either preleukemic or exhibited frank acute nonlymphocytic leukemia. The other four were clinically normal but demonstrated abnormalities in their marrow that could be attributed to radiation effects and/or other pathologic changes. Fibroblasts from six of the irradiated dogs were significantly more radioresistant than those of their controls. Five of these six dogs subsequently succumbed to hematopathologic disease, while the two irradiated dogs with normal fibroblasts remained clinically normal, suggesting that this observed radioresistance may be linked to the disease process. (author)

Bone marrow-derived thymic antigen-presenting cells determine self-recognition of Ia-restricted T lymphocytes

International Nuclear Information System (INIS)

Longo, D.L.; Kruisbeek, A.M.; Davis, M.L.; Matis, L.A.

1985-01-01

The authors previously have demonstrated that in radiation-induced bone marrow chimeras, T-cell self-Ia restriction specificity appeared to correlate with the phenotype of the bone marrow-derived antigen-presenting (or dendritic) cell in the thymus during T-cell development. However, these correlations were necessarily indirect because of the difficulty in assaying thymic function directly by adult thymus transplant, which has in the past been uniformly unsuccessful. They now report success in obtaining functional T cells from nude mice grafted with adult thymuses reduced in size by treatment of the thymus donor with anti-thymocyte globulin and cortisone. When (B10 Scn X B10.D2)F1 nude mice (I-Ab,d) are given parental B10.D2 (I-Ad) thymus grafts subcutaneously, their T cells are restricted to antigen recognition in association with I-Ad gene products but not I-Ab gene products. Furthermore, thymuses from (B10 X B10.D2)F1 (I-Ab,d)----B10 (I-Ab) chimeras transplanted 6 months or longer after radiation (a time at which antigen-presenting cell function is of donor bone marrow phenotype) into (B10 X B10.D2)F1 nude mice generate T cells restricted to antigen recognition in association with both I-Ad and I-Ab gene products. Thymuses from totally allogeneic bone marrow chimeras appear to generate T cells of bone marrow donor and thymic host restriction specificity. Thus, when thymus donors are radiation-induced bone marrow chimeras, the T-cell I-region restriction of the nude mice recipients is determined at least in part by the phenotype of the bone marrow-derived thymic antigen presenting cells or dendritic cells in the chimeric thymus

Therapeutic efficacy of inosine against radiation-induced damage at cellular, biochemical and chromosomal levels in swiss albino mice

International Nuclear Information System (INIS)

El-Shamy, E.; Sallam, M. H.

2010-01-01

Inosine has been used for treatment of various diseases and disorders in medicine. Modulator effect of inosine against γ radiation-induced histological alterations in testis, reduced glutathione (GSH), lipid peroxidation (LPO), acid and alkaline phosphatases activities (AP and ALP) and chromosomal aberrations (CA) in mice was studied at various experimental intervals between 1 and 30 days. Mice exposed to 8 Gy γ-rays showed acute radiation sickness including marked testis histological changes and chromosomal aberrations (CA) in bone marrow cells with 100 % mortality within 22 days. When inosine was given orally at a dose of 80 mg/ kg body wt for 15 consecutive days after exposure to γ-rays, death in radiation + inosine group was reduced to 70 % at 30 days. The radiation - dose reduction factor (DRF) was 1.43. There was significantly lesser degree of damage to testis tissue architecture and various cell populations including spermatogonia, spermatids and leydig cells. Correspondingly, a significant decrease in the LPO and increase in the GSH levels were observed in testis of radiation + inosine group. Similarly, a significant decrease in level of AP and increase in level of ALP were observed. Inosine treatment significantly prevented γ-rays-induced CA frequency in bone marrow cells.

Pure red cell aplasia following irradiation of an asymptomatic thymoma

International Nuclear Information System (INIS)

Shibata, Kazuo; Masaoka, Akira; Mizuno, Takeo; Ichimura, Hideki

1982-01-01

An unusual case of pure red-cell aplasia (PRCA) developed sixteen days after irradiation of an asymptomatic thymoma. After removal of the encapsulated thymoma there was no improvement in the anemia, and no response to adrenocortical and anabolic steroid hormones or immunosuppressive agents. (author)

Effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

International Nuclear Information System (INIS)

Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

1983-01-01

Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. 51 Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras

Countermeasures for Space Radiation Induced Malignancies and Acute Biological Effects

Science.gov (United States)

Kennedy, Ann

The hypothesis being evaluated in this research program is that control of radiation induced oxidative stress will reduce the risk of radiation induced adverse biological effects occurring as a result of exposure to the types of radiation encountered during space travel. As part of this grant work, we have evaluated the protective effects of several antioxidants and dietary supplements and observed that a mixture of antioxidants (AOX), containing L-selenomethionine, N-acetyl cysteine (NAC), ascorbic acid, vitamin E succinate, and alpha-lipoic acid, is highly effective at reducing space radiation induced oxidative stress in both in vivo and in vitro systems, space radiation induced cytotoxicity and malignant transformation in vitro [1-7]. In studies designed to determine whether the AOX formulation could affect radiation induced mortality [8], it was observed that the AOX dietary supplement increased the 30-day survival of ICR male mice following exposure to a potentially lethal dose (8 Gy) of X-rays when given prior to or after animal irradiation. Pretreatment of animals with antioxidants resulted in significantly higher total white blood cell and neutrophil counts in peripheral blood at 4 and 24 hours following exposure to doses of 1 Gy and 8 Gy. Antioxidant treatment also resulted in increased bone marrow cell counts following irradiation, and prevented peripheral lymphopenia following 1 Gy irradiation. Supplementation with antioxidants in irradiated animals resulted in several gene expression changes: the antioxidant treatment was associated with increased Bcl-2, and decreased Bax, caspase-9 and TGF-β1 mRNA expression in the bone marrow following irradiation. These results suggest that modulation of apoptosis may be mechanistically involved in hematopoietic system radioprotection by antioxidants. Maintenance of the antioxidant diet was associated with improved recovery of the bone marrow following sub-lethal or potentially lethal irradiation. Taken together

Unilateral aplasia of both cruciate ligaments

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Liem Dennis

2010-02-01

Full Text Available Abstract Aplasia of both cruciate ligaments is a rare congenital disorder. A 28-year-old male presented with pain and the feeling of instability of his right knee after trauma. The provided MRI and previous arthroscopy reports did not indicate any abnormalities except cruciate ligament tears. He was referred to us for reconstruction of both cruciate ligaments. The patient again underwent arthroscopy which revealed a hypoplasia of the medial trochlea and an extremely narrow intercondylar notch. The tibia revealed a missing anterior cruciate ligament (ACL footprint and a single bump with a complete coverage with articular cartilage. There was no room for an ACL graft. A posterior cruciate ligament could not be identified. The procedure was ended since a ligament reconstruction did not appear reasonable. A significant notch plasty if not a partial resection of the condyles would have been necessary to implant a ligament graft. It is most likely that this would not lead to good knee stability. If the surgeon would have retrieved the contralateral hamstrings at the beginning of the planned ligament reconstruction a significant damage would have occurred to the patient. Even in seemingly clear diagnostic findings the arthroscopic surgeon should take this rare abdnormality into consideration and be familiar with the respective radiological findings. We refer the abnormal finding of only one tibial spine to as the "dromedar-sign" as opposed to the two (medial and a lateral tibial spines in a normal knee. This may be used as a hint for aplasia of the cruciate ligaments.

Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells.

Science.gov (United States)

Zhao, Yi; Zhan, Yuxia; Burke, Kathleen A; Anderson, W French

2005-04-01

Ionizing radiation-induced myeloablation can be rescued via bone marrow transplantation (BMT) or administration of cytokines if given within 2 hours after radiation exposure. There is no evidence for the existence of soluble factors that can rescue an animal after a lethal dose of radiation when administered several hours postradiation. We established a system that could test the possibility for the existence of soluble factors that could be used more than 2 hours postirradiation to rescue animals. Animals with an implanted TheraCyte immunoisolation device (TID) received lethal-dose radiation and then normal bone marrow Lin- cells were loaded into the device (thereby preventing direct interaction between donor and recipient cells). Animal survival was evaluated and stem cell activity was tested with secondary bone marrow transplantation and flow cytometry analysis. Donor cell gene expression of five antiapoptotic cytokines was examined. Bone marrow Lin- cells rescued lethally irradiated animals via soluble factor(s). Bone marrow cells from the rescued animals can rescue and repopulate secondary lethally irradiated animals. Within the first 6 hours post-lethal-dose radiation, there is no significant change of gene expression of the known radioprotective factors TPO, SCF, IL-3, Flt-3 ligand, and SDF-1. Hematopoietic stem cells can be protected in lethally irradiated animals by soluble factors produced by bone marrow Lin- cells.

Chronic renal failure due to unilateral renal agenesis and total renal dysplasia (=aplasia)

International Nuclear Information System (INIS)

Kroepelin, T.; Ziupa, J.; Wimmer, B.

1983-01-01

Three adult patients with unilateral renal agenesis/total dysplasia (= aplasia) and with an early chronic renal failure are presented. One patient had renal agenesis without ureter bud and ureteric ostium on one side, and reflux pyelonephritis on the other; one had small compact total renal dysplasia (= aplasia) on one side, while chronic uric acid nephropathy (chronic renal disease as a cause of gout) was diagnosed on the other; the third patient had a total large multicystic dysplasia on one side, and on the other a segmental large multicystic dysplasia. Radiological steps and radiodiagnostic criteria are discussed and the combination of urogenital and extraurogenital anomalies is referred to. (orig.)

Effect of insulin on the mitotic activity of bone marrow cells after irradiation. [Gamma radiation, rats

Energy Technology Data Exchange (ETDEWEB)

Barkalaya, A I

1976-02-01

A total of 236 white rats were given a whole-body gamma dose of 750 R. Part of the rats were given a subcutaneous insulin injection of 0.2 units/kg. After 10, 20, 30 min, 1, 2, 3, 5, 8, 10 and 12 hours the mitotic index was determined in both groups of rats in the bone marrow of the femur. The content of glucose and insulin in the blood was determined. The mitotic index was found to be higher on administering insulin. The use of insulin in radiation sickness intensifies the mitotic activity of bone marrow cells and stimulates the recovery of bone marrow hematopoiesis. 5 references.

Vermian aplasia and hypoplasia

International Nuclear Information System (INIS)

Fitz, C.R.

1990-01-01

This paper reports vermian aplasia or hypoplasia unrelated to Dandy-Walker complex or Joubert syndrome. Vermian hypoplasia is most commonly associated with the malformations of Dandy-Walker cyst or variant. There have been few reports of familial vermian anomaly (Joubert syndrome) with episodes of polypnea and apnea. Five patients with vermian hypoplasia or absence were prospectively discovered among 1,130 children undergoing brain MR imaging. Ages ranged from 2 mo to 15 y at the time of discovery: The abnormalities were poorly defined in three patients who had previously undergone CT. There was no common link in these patients with a variable number of other systemic, brain, or facial abnormalities. No unifying symptoms were identified. Two patients had the MR imaging appearance of Joubert syndrome, but none had the cyclical respiratory symptoms usually associated with this syndrome

Liver late effects of ionizing radiation; Effets tardifs des radiations sur le foie

Energy Technology Data Exchange (ETDEWEB)

Mornex, F.; Ramuz, O. [Centre Hospitalier Universitaire Lyon-Sud, 69 - Pierre-Benite (France); Gerard, F. [Laboratoire Marcel-Merieux, 69 - Lyon (France); Van Houtte, P. [Institut Bordet, Brussels (Belgium)

1997-12-01

Until recently, the liver was classified as a radioresistant organ, although it is in fact highly radiosensitive. The realization that the whole liver could be treated safety only with low doses of radiation led to the conclusion that radiation therapy had an extremely limited role in the treatment of intrahepatic malignancies. A resurgence of interest has been observed with the advent of conformal radiotherapy and the introduction of bone marrow transplantation with total body irradiation. The radiation-induced liver disease, often called radiation hepatitis, is a syndrome characterized by the development of anicteric ascites, approximately 2 weeks to 4 months after hepatic irradiation. Immediate tolerance is generally surprisingly good, and the subacute radiation injury is followed by a complete asymptomatic healing, although the late lesions may be associated with signs of chronic radiation hepatitis. Radiation hepatitis must be distinguished from chemo-radiation-induced-hepatitis occurring in patients undergoing bone marrow transplantation and total body irradiation. Both syndromes demonstrate the same pathological lesion: veno-occlusive disease. The main treatment for radiation hepatitis is diuretics, although soma advocate steroids for severe cases. (authors)

Pure Red Cell Aplasia Associated with Good Syndrome

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Masayuki Okui

2017-04-01

Full Text Available Pure red cell aplasia (PRCA and hypogammaglobulinemia are paraneoplastic syndromes that are rarer than myasthenia gravis in patients with thymoma. Good syndrome coexisting with PRCA is an extremely rare pathology. We report the case of a 50-year-old man with thymoma and PRCA associated with Good syndrome who achieved complete PRCA remission after thymectomy and postoperative immunosuppressive therapy, and provide a review of the pertinent literature.

Anterior Pituitary Aplasia in an Infant with Ring Chromosome 18p Deletion

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Edward J. Bellfield

2016-01-01

Full Text Available We present the first reported case of an infant with 18p deletion syndrome with anterior pituitary aplasia secondary to a ring chromosome. Endocrine workup soon after birth was reassuring; however, repeat testing months later confirmed central hypopituitarism. While MRI reading initially indicated no midline defects, subsequent review of the images confirmed anterior pituitary aplasia with ectopic posterior pituitary. This case demonstrates how deletion of genetic material, even if resulting in a chromosomal ring, still results in a severe syndromic phenotype. Furthermore, it demonstrates the necessity of close follow-up in the first year of life for children with 18p deletion syndrome and emphasizes the need to verify radiology impressions if there is any doubt as to the radiologic findings.

Extraskeletal and intraskeletal new bone formation induced by demineralized bone matrix combined with bone marrow cells

International Nuclear Information System (INIS)

Lindholm, T.S.; Nilsson, O.S.; Lindholm, T.C.

1982-01-01

Dilutions of fresh autogenous bone marrow cells in combination with allogeneic demineralized cortical bone matrix were tested extraskeletally in rats using roentgenographic, histologic, and 45 Ca techniques. Suspensions of bone marrow cells (especially diluted 1:2 with culture media) combined with demineralized cortical bone seemed to induce significantly more new bone than did demineralized bone, bone marrow, or composite grafts with whole bone marrow, respectively. In a short-term spinal fusion experiment, demineralized cortical bone combined with fresh bone marrow produced new bone and bridged the interspace between the spinous processes faster than other transplantation procedures. The induction of undifferentiated host cells by demineralized bone matrix is further complemented by addition of autogenous, especially slightly diluted, bone marrow cells

Diabetes mellitus induces bone marrow microangiopathy

Science.gov (United States)

Oikawa, Atsuhiko; Siragusa, Mauro; Quaini, Federico; Mangialardi, Giuseppe; Katare, Rajesh G.; Caporali, Andrea; van Buul, Jaap D.; van Alphen, Floris P.J.; Graiani, Gallia; Spinetti, Gaia; Kraenkel, Nicolle; Prezioso, Lucia; Emanueli, Costanza; Madeddu, Paolo

2010-01-01

Objective The impact of diabetes on the bone marrow (BM) microenvironment was not adequately explored. We investigated whether diabetes induces microvascular remodeling with negative consequence for BM homeostasis. Methods and results We found profound structural alterations in BM from type-1 diabetic mice, with depletion of the hematopoietic component and fatty degeneration. Blood flow (fluorescent microspheres) and microvascular density (immunohistochemistry) were remarkably reduced. Flow cytometry verified the depletion of MECA-32pos endothelial cells (ECs). Cultured ECs from BM of diabetic mice showed higher levels of oxidative stress, increased activity of the senescence marker β-galactosidase, reduced migratory and network-formation capacities and increased permeability and adhesiveness to BM mononuclear cells. Flow cytometry analysis of lineageneg c-Kitpos Sca-1pos (LSK) cell distribution along an in vivo Hoechst-33342 dye perfusion gradient documented that diabetes depletes LSK cells predominantly in the low-perfused part of the marrow. Cell depletion was associated to increased oxidative stress, DNA damage and activation of apoptosis. Boosting the anti-oxidative pentose phosphate pathway by benfotiamine supplementation prevented microangiopathy, hypoperfusion and LSK cell depletion. Conclusions We provide novel evidence for the presence of microangiopathy impinging on the integrity of diabetic BM. These discoveries offer the framework for mechanistic solutions of BM dysfunction in diabetes. PMID:20042708

Mitigation of radiation induced hematopoietic injury via regulation of Nrf-2 and increasing hematopoietic stem cells

International Nuclear Information System (INIS)

Patwardhan, R.S.; Sharma, Deepak; Checker, Rahul; Santosh Kumar, S.

2014-01-01

Therapeutic doses of ionizing radiation (IR) that can be delivered to tumors are restricted due to radiation induced damage to surrounding normal tissues thereby limiting the effectiveness of radiotherapy. Strategies to develop agents that selectively protect normal cells yielded limited success in the past. There is pressing need to develop safe, syndrome specific and effective radiation countermeasures to prevent or mitigate the harmful consequences of radiation exposure. Survival of bone marrow stem cells (HSCs) play a key role in protecting against IR induced hematopoietic injury. Many studies have shown manipulation of HSC frequency and/or survival as principal mechanism of radioprotection. It is known that, Nrf-2 plays crucial role in HSC survival and maintenance under oxidative stress conditions. In the present study, we have investigated the radioprotective ability of a flavonoid baicalein (5,6,7-trihydroxyflavone), extracted from the root of Scutellaria baicalensis Georgi, a medicinal plant traditionally used in Oriental medicine. There are numerous reports showing anti-inflammatory, anti-apoptotic, anti-oxidant, anti-cancer, anti-microbial, anti-mutagenic and neuroprotective properties of baicalein. Based on these reports, we have investigated the ability of baicalein to protect against radiation induced hematopoietic injury. Baicalein administration to mice protected against WBI induced mortality. Interestingly, the stem cell frequency increased in bone marrow cells obtained from baicalein administered mice as compared to vehicle treated mice. Baicalein treatment led to increased phospho-Nrf-2 levels in lineage negative BM-MNC. Administration of mice with Nrf-2 inhibitor prior to baicalein treatment led to significant abrogation of radioprotective ability of baicalein. This result suggests that, Nrf-2 may be playing a key role in baicalein mediated radioprotection. Here, we have shown that baicalein administration augments stem cell frequency, induces

Irradiation of the red bone marrow and the health implications ...

African Journals Online (AJOL)

The physiology and function of the bone is looked at as to the role in housing bone marrow. The bone marrow and particularly the red bone marrow is discussed. Sources of radiation are discussed and the health implications highlighted for caution and for study or evaluation. Key Words: Bone marrow, Irradiation, Radiation, ...

Comparative study of internal contamination of different radiators in skeleton on induction of mutagenic effect in bone marrow cells

International Nuclear Information System (INIS)

Zhu Shoupeng; Wang Liuyi; Yang Weidong

1990-10-01

The purpose of the present study was to ascertain comparative retention of 134 Cs or 147 Pm in skeleton on induction of chromosome aberrations and PCE's micronucleus formation in bone marrow cells. Results indicated that after iv signal nuclide 134 Cs, through 7 weeks observation, the retention data in skeleton could be well described by an exponential expression. Experiments indicated that the retention value and the absorption dose of 147 Pm in skeleton were significantly higher in comparison with 134 Cs. Both internal contamination of 134 Cs or 147 Pm could induce chromosome aberrations and PCE's micronucleus formation in bone marrow cells. Among the type of chromosome aberrations of bone marrow cells induced by 134 Cs or 147 Pm included gap, chromatid breakage, chromosome breakage and translocation. Moreover, the chromosome aberration rates were elevated when the intake of radioactivity of 134 Cs or 147 Pm were enlarged. At the same time, chromosome fragment of bone marrow cells also induced by 134 Cs or 147 Pm only through high radioactive contamination. Studies showed that chromosome translocation was appeared only through high radioactivity of 147 Pm contamination. By comparing with 1 '4 7 Pm, however, the induction of chromosome aberrations and PCE's micronucleus formation rates on bone marrow cells induced by 134 Cs was quite low

Sequential changes in bone marrow architecture during continuous low dose gamma irradiation

International Nuclear Information System (INIS)

Seed, T.M.; Chubb, G.T.; Tolle, D.V.

1981-01-01

Beagles continuously exposed to low daily doses (10 R) of whole-body 60 Co ν-radiation are prone to develop either early occurring aplasstic anemia or late occurring myeloproliferative disorders. In this study, we have examined by a combination of light microscopy and scanning and transmission electron microscopy the sequential changes in the morphology of biopsied rib bone marrow of continuously irradiated dogs that developed either aplastic anemia, myelofibrosis, or myelogenous leukemia. Characteristic modifications of key elements of marrow architecture have been observed during preclinical and clinical phases of these hemopathological conditions. These architectural changes during preclinical phases appear to be related to the pathological progression to each of the radiation-induced hemopathological end points

Apoptosis of bone marrow leukemia cells in mice after low dose radiation at different time

International Nuclear Information System (INIS)

Li Guangyu; Yu Mingming; Li Xianjun; Liu Zhixiang

2007-01-01

Objective: To investigate the apoptosis of bone marrow leukemia cell in mice after low dose radiation (LDR) at different time and the experimental basis for LDR auxiliary therapy on leukemia. Methods: WEHI-3 cells were injected into BALB/c mice through tail veins to make an experimental mice model of myelornonocytic leukemia. 60 leukemia mice models were divided half-and half. 30 mice models in experimental group were irradiated with LDR of 75mGy at the same time while the others 30 in the control group were not. 6 mice models with LDR and 6 mice models without LDR would be killed at the time the 1st day, the 2nd day, the 3rd day, the 5th day- and the l0th day after LDR in order to extract bone marrow samples. The apoptosis percentage of leukemia cells in bone marrow was examined. Results: The apoptosis percentage of leukemia cells in experimental group was increasing after LDR and went to top on the 2nd day and the 3rd day. The apoptosis percentage of leukemia cells was remarkably different between experimental and control group, all P<0.05. Conclusion: LDR could significantly increase the apoptosis percentage of bone marrow leukemia cells in mice. Its mechanism is remarkably different in kill and wound of big dose radiation to tumour cells. It is probably related to of the increase immune exciting response as to promote some cytokine secretion, in leukemia mice. (authors)

Action of the poison of Apis mellifera bee and gamma radiation on bone marrow cells of Wistar rats and on lymphocytes of human peripheral blood

International Nuclear Information System (INIS)

Varanda, E.A.

1987-01-01

''In vivo'' and ''in vitro'' experiments are performed to determine the radioprotective action of the poison of Apis mellifera bees. The frequency of chromosome aberrations, induced by gamma radiation, is studied in two assays: ''in vivo'' in bone marrow cells from Wistar rats and ''in vitro'' in human peripheral blood lymphocyte cultures. The sister chromatid exchanges (SCE) are studied in the ''in vitro'' assays. (M.A.C.) [pt

Effect of 2-mercaptopropionylglycine (MPG) on the radiation-induced chromosome aberrations in the bone marrow of mice

International Nuclear Information System (INIS)

Uma, D.P.; Gupta, R.

1984-01-01

The radioprotective effect of MPG, a SH compound used clinically as detoxicating agent, was investigated in vivo on adult whole-body exposed mice to 3 Gy of 60 Co radiation 15 to 20 min after a single i.p. injection of MPG. Animals pretreated with colchicine were autopsied at various intervals from 2 to 28 days and bone marrow metaphases were scored. Significantly less number of cells were found to carry aberrations in the MPG-treated animals at 24 hr as compared to the non-drug treated irradiated ones. However, at all the other earlier and later intervals, both groups of animals showed approximately the same frequency of aberrant cells. It appears that MPG protection to the chromosome is at the reparation stage rather than at the initial stage of breakage. (author)

Effects of radiations on bone marrow

International Nuclear Information System (INIS)

Tubiana, M.; Frindel, E.; Croizat, H.; Parmentier, C.

1979-01-01

After total body irradiation for kidney transplant, the initial decrease of circulating blood cells is more rapid, the nadir is reached sooner and the regeneration occurs earlier when the doses are higher than a few hundred rads. The LD 50 in man seems to be higher than 450 rads. The in vivo and in vitro assays of hemopoietic stem cells have greatly increasedd the understanding of acute and late effects. Multipotential stem cells are very radiosensitive, furthermore the differentiation of the surviving stem cells is accelerated after irradiation. This results in a severe depletion of the stem cell compartment. When this stem cell number falls below a critical value, the stem cell no longer differentiates till the completion of the regeneration of the stem cell compartment. Stem cell proliferation is regulated by inhibitors and stimulators. Release of stimulators by irradiated bone marrow has been demonstrated. Severe sequellae are observed after irradiation of animal and human bone marrow. They seem to be due either to the damage of the stromal cell or to the stem cell population. In patients, four compensating mechanisms are observed after a regional bone marrow irradiation: stimulation of non irradiated bone marrow, extension of hemopoietic areas, regeneration of irradiated bone marrow when the irradiated volume is large and increase in the amplification factor resulting in an increase in the output of mature cells for one stem cell input. Assay of progenitor cells provides useful information and a reduction in their number is still observed many years after a large regional irradiation

Gene therapy strategy to reduced bone marrow aplasia: evaluation in cynomolgus macaque exposed to a gamma total body irradiation

International Nuclear Information System (INIS)

Becard, N.

2003-01-01

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) [fr

Bone marrow stem cells assuage radiation-induced damage in a murine model of distraction osteogenesis: A histomorphometric evaluation.

Science.gov (United States)

Zheutlin, Alexander R; Deshpande, Sagar S; Nelson, Noah S; Kang, Stephen Y; Gallagher, Kathleen K; Polyatskaya, Yekaterina; Rodriguez, Jose J; Donneys, Alexis; Ranganathan, Kavitha; Buchman, Steven R

2016-05-01

The purpose of this study is to determine if intraoperatively placed bone marrow stem cells (BMSCs) will permit successful osteocyte and mature bone regeneration in an isogenic murine model of distraction osteogenesis (DO) following radiation therapy (XRT). Lewis rats were split into three groups, DO only (Control), XRT followed by DO (xDO) and XRT followed by DO with intraoperatively placed BMSCs (xDO-BMSC). Coronal sections from the distraction site were obtained, stained and analyzed via statistical analysis with analysis of variance (ANOVA) and subsequent Tukey or Games-Howell post-hoc tests. Comparison of the xDO-BMSC and xDO groups demonstrated significantly improved osteocyte count (87.15 ± 10.19 vs. 67.88 ± 15.38, P = 0.00), and empty lacunae number (2.18 ± 0.79 vs 12.34 ± 6.61, P = 0.00). Quantitative analysis revealed a significant decrease in immature osteoid volume relative to total volume (P = 0.00) and improved the ratio of mature woven bone to immature osteoid (P = 0.02) in the xDO-BMSC compared with the xDO group. No significant differences were found between the Control and xDO-BMSC groups. In an isogenic murine model of DO, BMSC therapy assuaged XRT-induced cellular depletion, resulting in a significant improvement in histological and histomorphometric outcomes. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Aplasia pura de serie roja post-trasplante alogeneico de células progenitoras hematopoyeticas ABO incompatible

Directory of Open Access Journals (Sweden)

E. Bulliorsky

2002-12-01

Full Text Available El trasplante alogeneico de células progenitoras hematopoyéticas (TCPH con incompatibilidad ABO entre el donante y el receptor puede en ocasiones asociarse a trastornos en la progenie eritroide desarrollada a partir de la médula ósea trasplantada, caracterizado por un funcionamiento tardío, inadecuado e incompleto de la misma. En este contexto, la aplasia pura de serie roja es la complicación más severa. Se han intentado tratamientos para la aplasia pura de serie roja post-TCPH con eritropoyetina o plasmaféresis, con relativo éxito. Algunos autores han informado también la utilización de globulina antilinfocitaria, asumiendo que dicha aplasia selectiva de la serie roja en la médula ósea trasplantada es mediada por un mecanismo inmune. En este trabajo se describe un paciente portador de una leucemia aguda en quien se realizó un TCPH alogeneico (ABO incompatible con su donante. Teniendo niveles bajos de aglutininas contra el grupo sanguíneo de la donante, desarrolló una aplasia pura de serie roja post - TCPH. La misma no mejoró con tratamiento con eritropoyetina o con un refuerzo de progenitores hematopoyéticos de sangre periférica de la misma donante (boost, resolviéndose totalmente luego de un tratamiento exitoso con globulina antilinfocitaria de origen equino.

[Bilateral deep venous thrombosis and vena cava aplasia treated with local thrombolysis

DEFF Research Database (Denmark)

Pelta, A.M.; Jørgensen, Maja; Just, Sven Richardt Lundgren

2008-01-01

In this case report the treatment of a young man with bilateral iliaco-femoral DVT and vena cava aplasia is presented. The patient was treated with catheter-directed thrombolysis; the catheters were introduced in the thrombus of both legs via v. popliteae. The treatment led to almost complete thr...... thrombus resolution and no valvular incompetence at three months follow-up. In our opinion this treatment should be offered even in complex cases of acute proximal deep venous thrombosis Udgivelsesdato: 2008/5/19......In this case report the treatment of a young man with bilateral iliaco-femoral DVT and vena cava aplasia is presented. The patient was treated with catheter-directed thrombolysis; the catheters were introduced in the thrombus of both legs via v. popliteae. The treatment led to almost complete...

Tissue expansion for correction of baldness in aplasia cutis congenita

NARCIS (Netherlands)

Beekmans, S.J.A.; Don Griot, J.P.W.; Niessen, F.B.; Mulder, J.W.

2009-01-01

Aplasia cutis is a congenital absence of the skin, usually presenting on the scalp. In 20% of all cases, part of the skull is also absent. A residual area of baldness may still be present some years after surgical or conservative treatment. It is possible to excise the scarred hairless region and

β -carotene effect the induction of the sister chromatid exchanges (ICH) by gamma radiation in mouse radiosensibilized osseous marrow cells In vivo

International Nuclear Information System (INIS)

Morales R, P.; Cruz V, V.L.

1997-01-01

The effect of β- carotene over the ICH radioinduction in radiosensibilized with BrdU osseous marrow cells of mouse was determined In vivo. The treatment with 50 μg β carotene per se induces a significant increment in the ICH frequency and the pre or post-treatment with the same dose causes an additive effect in the ICH frequency produced by 0.62 Gy of gamma radiation. This implies that β- carotene does not have radioprotective activity, under conditions which was developed this experiment. (Author)

Restoration of Respiratory Gases and Acid-base Balance of Blood of Gamma Irradiated Rats Through Bone Marrow Transplantation

International Nuclear Information System (INIS)

Eissa, S.M.; Roushdy, H.M.; Khamis, F. I.; Abu-Zeid, N.M.

2000-01-01

The present investigation aimed at elucidating the role played by bone marrow transplantation as a biological treatment against the deleterious effect of ionizing radiation. The parameters tested were PO2; PCO2; TCO2 and acid base balance encountering pH and (HCO3) in blood. Investigations were conducted 1,3,7,14 and 21 days post whole body gamma exposure at the dose levels 2 and 6 Gy. The data obtained showed highly significant changes in all tested parameters after whole body gamma irradiation. A higher depressant effect was more pronounced after exposure to higher radiation dose. Bone marrow transplantation to irradiated rats resulted in partial restoration or the radiation induced changes in both PO2 and PCO2 as recorded on the first week post treatment and succeeded to ameliorate the radiation induced changes in pH values and (HCO3) in blood

The effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

International Nuclear Information System (INIS)

Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

1983-01-01

Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. 51 Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras. These results raise the possibility that the fulminant GVHD seen in human marrow transplantation is in part due to the major contamination of bone marrow with peripheral blood that results from the techniques currently used for human bone marrow harvest

Overview of cobalt-60 external irradiation study

International Nuclear Information System (INIS)

Stitzel, K.; Shifrine, M.; Wilson, F.

1980-01-01

Work this year has continued to define the immunohematological effects of radiation exposure in Davis beagles over 50 days of age. One case of myeloproliferative disease occurred in one of the animals exposed to 4 R/day, and cases of bone marrow aplasia occurred in the 11 R/day, 4 R/day, and 2 R/day groups. Use of bone marrow transplantation has revealed a profound difference in the mechanism of aplasia induction in dogs which are susceptible to low doses (less than 2000 R exposure at 11 R/day) and dogs which are able to survive in the radiation field for long periods (greater than 3000 R at 11 R/day or 1800 R at 2 R/day). In the latter animals damage occurs to the hematopoietic stromal microenvironment or some other regulatory mechanism which directs the differentiation of the hematopoietic stem cells into the specific end cell pathways (i.e. thrombocytes, red cells neutrophils). In the animals which develop radiation disease after low total exposure, the damage appears to be to the hematopoietic stem cells themselves. This implies that in some animals the stem cells are resistant to massive doses of continuous whole body irradiation, relative to the dose rate

Radiation nephritis following total-body irradiation and cyclophosphamide in preparation for bone marrow transplantation

International Nuclear Information System (INIS)

Bergstein, J.; Andreoli, S.P.; Provisor, A.J.; Yum, M.

1986-01-01

Two children prepared for bone marrow transplantation with total-body irradiation and cyclophosphamide developed hypertension, microscopic hematuria, proteinuria, diminished renal function, and anemia six months after transplantation. Light microscopy of the kidneys revealed mesangial expansion, glomerular capillary wall thickening, and lumenal thrombosis. Electron microscopy demonstrated widening of the subendothelial space due to the deposition of amorphous fluffy material. In one patient, immunofluorescence microscopy revealed glomerular capillary wall deposition of fibrin and immunoglobulins. The clinical and histologic findings support the diagnosis of radiation nephritis. Patients prepared for bone marrow transplantation with total-body irradiation and cyclophosphamide should be followed closely after transplantation for the development of hypertension, proteinuria, and renal insufficiency

Extended flow cytometry characterization of normal bone marrow progenitor cells by simultaneous detection of aldehyde dehydrogenase and early hematopoietic antigens: implication for erythroid differentiation studies

Directory of Open Access Journals (Sweden)

Pascariello Caterina

2008-05-01

Full Text Available Abstract Background Aldehyde dehydrogenase (ALDH is a cytosolic enzyme highly expressed in hematopoietic precursors from cord blood and granulocyte-colony stimulating factor mobilized peripheral blood, as well as in bone marrow from patients with acute myeloblastic leukemia. As regards human normal bone marrow, detailed characterization of ALDH+ cells has been addressed by one single study (Gentry et al, 2007. The goal of our work was to provide new information about the dissection of normal bone marrow progenitor cells based upon the simultaneous detection by flow cytometry of ALDH and early hematopoietic antigens, with particular attention to the expression of ALDH on erythroid precursors. To this aim, we used three kinds of approach: i multidimensional analytical flow cytometry, detecting ALDH and early hematopoietic antigens in normal bone marrow; ii fluorescence activated cell sorting of distinct subpopulations of progenitor cells, followed by in vitro induction of erythroid differentiation; iii detection of ALDH+ cellular subsets in bone marrow from pure red cell aplasia patients. Results In normal bone marrow, we identified three populations of cells, namely ALDH+CD34+, ALDH-CD34+ and ALDH+CD34- (median percentages were 0.52, 0.53 and 0.57, respectively. As compared to ALDH-CD34+ cells, ALDH+CD34+ cells expressed the phenotypic profile of primitive hematopoietic progenitor cells, with brighter expression of CD117 and CD133, accompanied by lower display of CD38 and CD45RA. Of interest, ALDH+CD34- population disclosed a straightforward erythroid commitment, on the basis of three orders of evidences. First of all, ALDH+CD34- cells showed a CD71bright, CD105+, CD45- phenotype. Secondly, induction of differentiation experiments evidenced a clear-cut expression of glycophorin A (CD235a. Finally, ALDH+CD34- precursors were not detectable in patients with pure red cell aplasia (PRCA. Conclusion Our study, comparing surface antigen expression of

Telomerase deficiency in bone marrow-derived cells attenuates angiotensin II-induced abdominal aortic aneurysm formation.

Science.gov (United States)

Findeisen, Hannes M; Gizard, Florence; Zhao, Yue; Cohn, Dianne; Heywood, Elizabeth B; Jones, Karrie L; Lovett, David H; Howatt, Deborah A; Daugherty, Alan; Bruemmer, Dennis

2011-02-01

Abdominal aortic aneurysms (AAA) are an age-related vascular disease and an important cause of morbidity and mortality. In this study, we sought to determine whether the catalytic component of telomerase, telomerase reverse transcriptase (TERT), modulates angiotensin (Ang) II-induced AAA formation. Low-density lipoprotein receptor-deficient (LDLr-/-) mice were lethally irradiated and reconstituted with bone marrow-derived cells from TERT-deficient (TERT-/-) mice or littermate wild-type mice. Mice were placed on a diet enriched in cholesterol, and AAA formation was quantified after 4 weeks of Ang II infusion. Repopulation of LDLr-/- mice with TERT-/- bone marrow-derived cells attenuated Ang II-induced AAA formation. TERT-deficient recipient mice revealed modest telomere attrition in circulating leukocytes at the study end point without any overt effect of the donor genotype on white blood cell counts. In mice repopulated with TERT-/- bone marrow, aortic matrix metalloproteinase-2 (MMP-2) activity was reduced, and TERT-/- macrophages exhibited decreased expression and activity of MMP-2 in response to stimulation with Ang II. Finally, we demonstrated in transient transfection studies that TERT overexpression activates the MMP-2 promoter in macrophages. TERT deficiency in bone marrow-derived macrophages attenuates Ang II-induced AAA formation in LDLr-/- mice and decreases MMP-2 expression. These results point to a previously unrecognized role of TERT in the pathogenesis of AAA.

Bone marrow dosimetry for monoclonal antibody therapy

International Nuclear Information System (INIS)

Bigler, R.E.; Zanzonico, P.B.; Leonard, R.

1986-01-01

Immunoglobulins must permeate through the basement membrane of capillaries in order to enter the extracellular space (ECS) of tissue. Since the process is quite slow, the blood plasma activity in various organs contributes considerably to the radiation dose of the dose-limiting tissues. In bone marrow the basement membrane is absent and the blood circulation is functionally open. Therefore, blood plasma and marrow ECS maintain equal concentrations of labeled immunoglobulins. A combination of factors including intravenous administration, slow absorption into most tissues, slow breakdown and elimination of labeled immunoglobulin, and rapid entry into bone marrow ECS as well as known radiosensitivity of marrow led the authors to expect this tissue would prove to be the primary tissue at risk for systemic monoclonal antibody therapy. They have developed and applied in a Phase I clinical study of 131 I labeled CEA antibody a procedure for estimation of radiation dose to red bone marrow. Serieal measurements of blood plasma and total body retention are carried out. Binding of labeled antibody to the cellular components of blood is verified to be very low. They have observed bone marrow depression at doses greater than 400 rad. If no special procedures are used to reconstitute marrow after radiation treatment, this level represents a much greater than generally recognized limitation to radiolabeled monoclonal antibody therapy. 25 references, 4 tables

Bone marrow scintigraphy with /sup 111/In-chloride. A clinical value for the hematological diseases

Energy Technology Data Exchange (ETDEWEB)

Fujishima, Mamoru; Hiraki, Yoshio; Takeda, Yoshihiro; Kohno, Yoshihiro; Niiya, Harutaka; Aono, Kaname; Yorimitsu, Seiichi; Takahashi, Isao

1988-10-01

Bone marrow scintigraphy with indium chloride (/sup 111/In) was performed in fifty-one patients with the hematological diseases. The results of the investigation were that 1) in all patients, as well as in patients with aplastic anemia, no correlation was there between the degree of the indium chloride accumulation and peripheral blood counts, 2) in patients with aplastic anemia and pure red cell aplasia (PRCA) a tendency to reduction in uptake of indium chloride in bone marrow, 3) in patients with these two good correlation between the degree of indium chloride accumulation and histology of the erythroid bone marrow, but in patients with chronic myelocytic leukemia (CML) and atypical leukemia no correlation between the two, so it seemed unlikely that indium chloride should reflect the effective production of erythrocytes, 4) four patients with leukemia were studied with indium chloride bone marrow imaging two times to evaluate their responses to chemotherapy, and peripheral expansion was no change or reduced in two patients with acute myelocytic leukemia (AML) and one patient with acute lymphocytic leukemia (ALL) who obtained complete remission, but on the other hand, it enlarged in one patient with acute myelocytic leukemia who obtained partial remission, and 5) in two patients with chronic myelocytic leukemia it enlarged up to the ankle joints, which was considerably specific.

Lung damage following bone marrow transplantation. II. The contribution of cyclophosphamide

International Nuclear Information System (INIS)

Varekamp, A.E.; de Vries, A.J.; Zurcher, C.; Hagenbeek, A.

1987-01-01

The effect of high-dose cyclophosphamide (Cy), either alone or in combination with irradiation, upon the development of interstitial pneumonitis (IP) after bone marrow transplantation (BMT) was investigated in a Brown Norway rat model. The parameters that were examined included ventilation rate, mortality, and histopathology. No damage to the lungs was observed in rats given Cy alone in supralethal dosages plus BMT, and mortality resulted from severe aplasia of hemopoietic and lymphoid tissues with multifocal hemorrhages, secondary infections, and sepsis. Two separate periods of mortality were observed within the first 180 days following whole thorax irradiation with a high dose rate (HDR; 0.8 Gy/min) or a low dose rate (LDR; 0.05 Gy/min). The addition of Cy prior to irradiation resulted in an increased mortality in the first period (before day 100) in all experimental groups. The influence of Cy on mortality at 180 days however, was different for the HDR and LDR experiments. The LD50-180 after HDR irradiation, dose range 8 to 18 Gy, was not significantly altered by the addition of Cy (100 mg/kg) 1 day prior to irradiation, whereas Cy (100 mg/kg) 1 day prior to LDR irradiation, dose range: 16 to 24 Gy, caused an enhancement of radiation damage with a decrease of the LD50-180 by 1.33 Gy. The dose modification factor (DMF) was 1.07. This enhancement was no longer significant after splitting up the dose of Cy in two dosages of 50 mg/kg given on 2 consecutive days prior to irradiation with a LDR. The extrapolation of the data in this rat model to available dose-response curves on IP after BMT and radiation pneumonitis in humans, implied that non-infectious IP is a radiation pneumonitis that is only slightly enhanced by Cy

Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in Radiation Therapy Planning

International Nuclear Information System (INIS)

Campbell, Belinda A.; Callahan, Jason; Bressel, Mathias; Simoens, Nathalie; Everitt, Sarah; Hofman, Michael S.; Hicks, Rodney J.; Burbury, Kate; MacManus, Michael

2015-01-01

Purpose: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)–positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. Methods and Materials: The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Results: Fifty-one patients were studied: 67% male; median age 68 (range, 31-87) years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. Conclusions: This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interindividual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow; in such cases, individual FLT-PET scans may be required

Distribution Atlas of Proliferating Bone Marrow in Non-Small Cell Lung Cancer Patients Measured by FLT-PET/CT Imaging, With Potential Applicability in Radiation Therapy Planning

Energy Technology Data Exchange (ETDEWEB)

Campbell, Belinda A., E-mail: Belinda.Campbell@petermac.org [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Callahan, Jason [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Bressel, Mathias [Centre for Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne (Australia); Simoens, Nathalie [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Everitt, Sarah [Radiotherapy Services, Peter MacCallum Cancer Centre, East Melbourne (Australia); Hofman, Michael S.; Hicks, Rodney J. [Centre for Molecular Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Burbury, Kate [Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne (Australia); MacManus, Michael [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia)

2015-08-01

Purpose: Proliferating bone marrow is exquisitely sensitive to ionizing radiation. Knowledge of its distribution could improve radiation therapy planning to minimize unnecessary marrow exposure and avoid consequential prolonged myelosuppression. [18F]-Fluoro-3-deoxy-3-L-fluorothymidine (FLT)–positron emission tomography (PET) is a novel imaging modality that provides detailed quantitative images of proliferating tissues, including bone marrow. We used FLT-PET imaging in cancer patients to produce an atlas of marrow distribution with potential clinical utility. Methods and Materials: The FLT-PET and fused CT scans of eligible patients with non-small cell lung cancer (no distant metastases, no prior cytotoxic exposure, no hematologic disorders) were reviewed. The proportions of skeletal FLT activity in 10 predefined bony regions were determined and compared according to age, sex, and recent smoking status. Results: Fifty-one patients were studied: 67% male; median age 68 (range, 31-87) years; 8% never smokers; 70% no smoking in the preceding 3 months. Significant differences in marrow distribution occurred between sex and age groups. No effect was detected from smoking in the preceding 3 months. Using the mean percentages of FLT uptake per body region, we created an atlas of the distribution of functional bone marrow in 4 subgroups defined by sex and age. Conclusions: This atlas has potential utility for estimating the distribution of active marrow in adult cancer patients to guide radiation therapy planning. However, because of interindividual variation it should be used with caution when radiation therapy risks ablating large proportions of active marrow; in such cases, individual FLT-PET scans may be required.

Protection of nucleated bone marrow cells of mice against effect of radiation-induced micronucleus formation by using polysaccharides extracted from 'Zi Zhi' (a ganoderma)

International Nuclear Information System (INIS)

Chu Fang; Luo Houliang; Luo Gui; Chen Shunle; Liu Zhifang

1988-01-01

This paper describes the influence of polysaccharides extracted from 'Zi Zhi' (Ganoderma Sinese Zhao, Xu et Zhang) on the frequency of micronucleated cells induced by 60 Co gamma irradiation at different doses in bone marrow of mice. These polysaccharides of 'Zi Zhi' were shown to be of ability to protect nucleated bone marrow cells from micronucleus formation in irradiated mice. For Swiss mice, a dose reduction factor (DRF) was found to be 1.72 in the range of 0 to 4.728 Gy and for LACA mice, to be 1.73 in the range of 0 to 3.152 Gy. Such findings indicate that these polysaccharides are comparable to L-cysteine in their effeciency of protection

A method for calculating effective lifetime risk of radiation-induced cancer from screening mammography

International Nuclear Information System (INIS)

Ali, R.M.; England, A.; McEntee, M.F.; Hogg, P.

2015-01-01

Purpose: To propose a method for evaluating the effective lifetime risk of radiation-induced cancer from screening mammography and to present initial data for the UK National Breast Screening Programme. Material and methods: The imaging was undertaken using a Hologic Selenia full field digital mammographic unit. The proposed method utilises an ATOM phantom containing thermoluminescent dosimeters and a perspex-polyethylene breast phantom to measure organ doses during a standard four view screening mammogram. Effective dose was calculated and effective risk was modelled for a range of client ages. The total lifetime effective risk was then calculated for the UK national screening programme. Calculation of effective risk includes the radiation dose to examined and contralateral breasts in addition to other body organs; this is an advantage over the mean glandular dose. Results: The contralateral breast, thyroid, thymus, brain, lung, salivary glands, and bone marrow all receive more than 1 μGy radiation dose during screening mammography. A major difference exists for total effective lifetime risk of radiation-induced cancer between clients with average and high breast cancer risk. Differences are attributed to the commencement age of screening and time interval between screens. Conclusion: This study proposes a method to evaluate effective lifetime risk of radiation-induced cancer from screening mammography in order to compare different mammography screening programmes. - Highlights: • We proposed a method for the calculation of radiation-induced cancer from screening mammography. • We measured the radiation absorbed dose of different organs during screening mammography. • There are major differences between mammography screening programme categories with regard to radiation effective risk.

Congenital diaphragmatic hernia with concurrent aplasia of the pericardium in a foal.

Science.gov (United States)

Tăbăran, Alexandru-Flaviu; Nagy, Andras Laszlo; Cătoi, Cornel; Morar, Iancu; Tăbăran, Alexandra; Mihaiu, Marian; Bolfa, Pompei

2015-12-30

In veterinary medicine congenital abnormalities of the diaphragm and pericardium are rare, idiopathic malformations, being reported mainly in dogs. This report documents an unusual case of developmental defects in a foal consisting of diaphragmatic hernia concurrent with pericardial aplasia. Following a normal delivery, a full term, female Friesian stillborn foal with the placenta was presented for necropsy. External morphological examination indicated a normally developed foal. At necropsy, a large oval defect (approximately 20 × 15 cm in size) was observed in the left-dorsal side of the diaphragm (left lumbocostal triangle). This defect allowed the intestinal loops, spleen and partially the liver to translocate into the thorax. The loops of the left ascending colon, including the pelvic flexure and partially the small intestine covered the cranial and dorsal posterior parts of the heart due to the complete absence of the left pericardium. The remaining pericardium presented as a white, semi-transparent strip, partially covering the right side of the heart. The left lung and the main bronchus were severely hypoplastic to approximately one-fifth the size of their right homologue. The intermediate part of the liver, containing mainly the enlarged quadrate lobe was translocated in the thorax, severely enlarged and showed marked fibrosis. Histologically in the herniated lobes we diagnosed hepatic chronic passive congestion, telangiectasia and medial hypertrophy of blood vessels. Concomitant malformation involving diaphragmatic hernia and pericardial aplasia in horses have not been previously reported. Moreover, this is the first case describing pericardial aplasia in horse.

Leishmania donovani infection induces anemia in hamsters by differentially altering erythropoiesis in bone marrow and spleen.

Directory of Open Access Journals (Sweden)

William P Lafuse

Full Text Available Leishmania donovani is a parasite that causes visceral leishmaniasis by infecting and replicating in macrophages of the bone marrow, spleen, and liver. Severe anemia and leucopenia is associated with the disease. Although immune defense mechanisms against the parasite have been studied, we have a limited understanding of how L. donovani alters hematopoiesis. In this study, we used Syrian golden hamsters to investigate effects of L. donovani infection on erythropoiesis. Infection resulted in severe anemia and leucopenia by 8 weeks post-infection. Anemia was associated with increased levels of serum erythropoietin, which indicates the hamsters respond to the anemia by producing erythropoietin. We found that infection also increased numbers of BFU-E and CFU-E progenitor populations in the spleen and bone marrow and differentially altered erythroid gene expression in these organs. In the bone marrow, the mRNA expression of erythroid differentiation genes (α-globin, β-globin, ALAS2 were inhibited by 50%, but mRNA levels of erythroid receptor (c-kit, EpoR and transcription factors (GATA1, GATA2, FOG1 were not affected by the infection. This suggests that infection has a negative effect on differentiation of erythroblasts. In the spleen, erythroid gene expression was enhanced by infection, indicating that the anemia activates a stress erythropoiesis response in the spleen. Analysis of cytokine mRNA levels in spleen and bone marrow found that IFN-γ mRNA is highly increased by L. donovani infection. Expression of the IFN-γ inducible cytokine, TNF-related apoptosis-inducing ligand (TRAIL, was also up-regulated. Since TRAIL induces erythroblasts apoptosis, apoptosis of bone marrow erythroblasts from infected hamsters was examined by flow cytometry. Percentage of erythroblasts that were apoptotic was significantly increased by L. donovani infection. Together, our results suggest that L. donovani infection inhibits erythropoiesis in the bone marrow by

Models for radiation-induced tissue degeneration and conceptualization of rehabilitation of irradiated tissue by cell therapy

International Nuclear Information System (INIS)

Phulpin, Berengere

2011-01-01

Radiation therapy induced acute and late sequelae within healthy tissue included in the irradiated area. In general, lesions are characterized by ischemia, cell apoptosis and fibrosis. In this context, cell therapy using bone marrow mesenchymal stem cells (BMSC) might represent an attractive new therapeutic approach, based partly on their angiogenic ability and their involvement in the natural processes of tissue repair. The first part of this work consisted in the development of experimental mouse model of radio-induced tissue degeneration similar to that occurring after radiotherapy. The aim was to better understand the physiopathological mechanisms of radiation-induced tissue damage and to determine the best treatment strategy. The second part of this work investigated the feasibility of autologous BMSC therapy on the murine model of radiation previously established with emphasis on two pre-requisites: the retention of the injected cells within the target tissue and the evaluation of the graft on bone metabolism. This preclinical investigation in a mouse model constitutes an essential step allowing an evaluation of the benefit of cell therapy for the treatment of radiation-induced tissue injury. Data from these studies could allow the proposal of clinical studies [fr

New radiation mitigators to reduce bone marrow death of mice by post-irradiation administration

International Nuclear Information System (INIS)

Anzai, Kazunori

2009-01-01

We have found recently that heat-treated mineral yeast preparations and water-soluble analogs of vitamin E are potent radiation mitigator to reduce bone marrow death of mice by post-irradiation administration. When administered immediately after whole-body X-irradiation (7.5 Gy), both Zn-yeast and γ-tocopherol dimethylglycine ester (TDMG) significantly increased the viability of mice from 0% (control) to more than 90% (treated). Zn-yeast did not inhibit the tumor-regulation by γ-rays but even sensitize the radiation effect in mice xenografts of HeLa cells. (author)

Congenital aplasia of the semicircular canals.

Science.gov (United States)

Satar, Bulent; Mukherji, Suresh K; Telian, Steven A

2003-05-01

To describe the underrecognized inner ear malformation characterized by complete aplasia of the labyrinthine semicircular canals associated with a relatively well-formed cochlea, to investigate its relationship with known syndromic forms of hearing loss, and to hypothesize regarding the potential embryopathogenesis of this anomaly. A retrospective case review consisting of cases of sensorineural hearing loss with radiographic evidence demonstrating agenesis of the semicircular canals associated with a cochlea that was either morphologically normal or sufficiently well developed to accommodate the full insertion of a cochlear implant electrode. Cases were identified by computerized tomography findings that identified the anomaly under study. Departments of otolaryngology and radiology in a tertiary referral center, with a large cochlear implant program serving over 800 patients, more than half of whom are children. Fifteen patients with the anomaly under study were identified. Each patient underwent a complete otologic examination, audiometric studies, and high resolution computerized tomography of the temporal bone in axial and coronal planes. The bony morphology of the cochlea, round and oval windows, vestibule, semicircular canals, and vestibular aqueduct, and the course of the facial nerve were examined. Auditory findings and otologic treatment are presented. Of the 15 identified patients, 4 were nonsyndromic, 9 had CHARGE association (Coloboma of the eye, congenital Heart defects, choanal Atresia, mental and/or growth Retardation, Genital hypoplasia, and Ear anomalies and/or deafness), 1 met criteria for Noonan's syndrome, and one had features of both these syndromes. Although the cochlea was present in all cases, the cochlear morphology was usually abnormal in the CHARGE association patients. Of the 20 ears in the CHARGE subjects, only 3 ears (15%) were seen to have completely normal development of the cochlea in both the basal and upper turns. The others

Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells on the radiation-induced GI syndrome

Energy Technology Data Exchange (ETDEWEB)

Shim, Se Hwan; Jang, Won Suk; Lee, Sun Joo; Park, Eun Young; Kim, Youn Joo; Jin, Sung Ho; Park, Sun Hoo; Lee, Seung Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2011-05-15

The gastrointestinal (GI) tract is one of the most radiosensitive organ systems in the body. Radiation-induced GI injury is described as destruction of crypt cell, decrease in villous height and number, ulceration, and necrosis of intestinal epithelium. Studies show that mesenchymal stem cells (MSCs) treatment may be useful in the repair or regeneration of damaged organs including bone, cartilage, or myocardium. MSCs from umbilical cord blood (UCB) have many advantages because of the immature nature of newborn cells compared to bone marrow derived MSCs. Moreover, UCB-MSCs provide no ethical barriers for basic studies and clinical applications. In this study, we explore the regeneration capability of human UCB-MSCs after radiation-induced GI injury

Dose rate-dependent marrow toxicity of TBI in dogs and marrow sparing effect at high dose rate by dose fractionation.

Science.gov (United States)

Storb, R; Raff, R F; Graham, T; Appelbaum, F R; Deeg, H J; Schuening, F G; Sale, G; Seidel, K

1999-01-01

We evaluated the marrow toxicity of 200 and 300 cGy total-body irradiation (TBI) delivered at 10 and 60 cGy/min, respectively, in dogs not rescued by marrow transplant. Additionally, we compared toxicities after 300 cGy fractionated TBI (100 cGy fractions) to that after single-dose TBI at 10 and 60 cGy/min. Marrow toxicities were assessed on the basis of peripheral blood cell count changes and mortality from radiation-induced pancytopenia. TBI doses studied were just below the dose at which all dogs die despite optimal support. Specifically, 18 dogs were given single doses of 200 cGy TBI, delivered at either 10 (n=13) or 60 (n=5) cGy/min. Thirty-one dogs received 300 cGy TBI at 10 cGy/min, delivered as either single doses (n=21) or three fractions of 100 cGy each (n=10). Seventeen dogs were given 300 cGy TBI at 60 cGy/min, administered either as single doses (n=5) or three fractions of 100 cGy each (n=10). Within the limitations of the experimental design, three conclusions were drawn: 1) with 200 and 300 cGy single-dose TBI, an increase of dose rate from 10 to 60 cGy/min, respectively, caused significant increases in marrow toxicity; 2) at 60 cGy/min, dose fractionation resulted in a significant decrease in marrow toxicities, whereas such a protective effect was not seen at 10 cGy/min; and 3) with fractionated TBI, no significant differences in marrow toxicity were seen between dogs irradiated at 60 and 10 cGy/min. The reduced effectiveness of TBI when a dose of 300 cGy was divided into three fractions of 100 cGy or when dose rate was reduced from 60 cGy/min to 10 cGy/min was consistent with models of radiation toxicity that allow for repair of sublethal injury in DNA.

In vivo study of the adaptive response induced by radiation of different types

International Nuclear Information System (INIS)

Klokov, D.Yu.; Zaichkina, S.I.; Rozanova, O.M.; Aptikaeva, G.F.; Akhmadieva, A.Kh.; Smirnova, E.N.; Surkenova, G.N.; Kuzin, A.M.

2000-01-01

Low doses of X- and gamma-rays are known to induce the adaptive response (AR), i.e. a reduction in the damage caused by subsequent high doses. Using micronucleus test, we investigated the in vivo induction of AR in mouse bone marrow cells by low doses of radiation of different types. In our experiments we used low-LET gamma-radiation, high-LET secondary radiation from 70 GeV protons and secondary biogenic radiation. The latter is a novel type of radiation discovered only recently. Secondary biogenic radiation is known to be induced in biological objects after exposure to radiation and thought to be responsible for stimulating and protecting effects in cells in response to external irradiation. To expose mice to the secondary biogenic radiation, animals were housed in plastic cages containing gamma-irradiated oat seeds as bedding and food for 2 weeks before challenging with a high dose (1.5 Gy at a dose rate of 1 Gy/min) of 60 Co gamma-radiation. It was found that the yield of cytogenetic damage in mice exposed to both secondary biogenic and gamma-radiation was significantly reduced as compared to that in animals exposed to the challenge dose alone, i.e. the AR was induced. Pretreatment of animals with a low dose of gamma-radiation (0.1 Gy at a dose rate of 0.125 Gy/min) also induced the AR. In contrast, preliminary exposure of mice to a low dose (0.09 Gy at a dose rate of 1 Gy/min) of secondary radiation from 70 GeV protons induced no AR, suggesting that triggering the cascade of events leading to the AR induction depends on the DNA single-strand to double- strand breaks ratio. The precise mechanisms underlying the AR are of great importance since the phenomenon of AR can be used for medical benefits and in assessment of risks for carcinogens. But they have not been elucidated well at present. Taken together, our results suggest the crucial role of particular types of initial DNA lesions and the secondary biogenic radiation induced in cells in response to external

Regeneration of blood-forming organs after autologous leukocyte transfusion in lethally irradiated dogs. II. Distribution and cellularity of the marrow in irradiated and transfused animals

International Nuclear Information System (INIS)

Calvo, W.; Fliedner, T.M.; Herbst, E.; Huegl, E.; Bruch, C.

1976-01-01

Dogs were given transfusions of cryopreserved autologous mononuclear blood leukocytes after 1200 roentgens (R) (midline dose) whole-body x-irradiation. Bone marrow repopulation was studied by means of histomorphological methods at days 9 and 10 after transfusion of an average of 3 x 10 9 , 7 x 10 9 , 13 x 10 9 , and 31 x 10 9 cells. The return of marrow cellularity to normal values was related to the number of cells transfused. With low cell doses (3 x 10 9 and 7 x 10 9 ), the marrow regeneration at 10 days was focal. There were groups of cells (colonies) showing either erythropoiesis, myelopoiesis, or megakaryocytopoiesis in the osteal niches of the trabecular bones. Frequently such niches were seen showing complete cellular recovery next to niches with complete aplasia. With higher cell doses, all niches showed hemopoietic regeneration, and the cellularity approached normal values. No hemopoietic regeneration was observed in those skeletal parts that do not show hemopoiesis, even under normal circumstances

Stem cells rejuvenate radiation-impaired vasculogenesis in murine distraction osteogenesis.

Science.gov (United States)

Deshpande, Sagar S; Gallagher, Kathleen K; Donneys, Alexis; Nelson, Noah S; Guys, Nicholas P; Felice, Peter A; Page, Erin E; Sun, Hongli; Krebsbach, Paul H; Buchman, Steven R

2015-03-01

Radiotherapy is known to be detrimental to bone and soft-tissue repair. Bone marrow stromal cells have been shown to enhance bone regeneration during distraction osteogenesis following radiation therapy. The authors posit that transplanted bone marrow stromal cells will significantly augment the mandibular vascularity devastated by radiation therapy. Nineteen male Lewis rats were split randomly into three groups: distraction osteogenesis only (n = 5), radiation therapy plus distraction osteogenesis (n = 7), and radiation therapy plus distraction osteogenesis with intraoperative placement of 2 million bone marrow stromal cells (n = 7). A mandibular osteotomy was performed, and an external fixator device was installed. From postoperative days 4 through 12, rats underwent a gradual 5.1-mm distraction followed by a 28-day consolidation period. On postoperative day 40, Microfil was perfused into the vasculature and imaging commenced. Vascular radiomorphometric values were calculated for regions of interest. An analysis of variance with post hoc Tukey or Games-Howell tests was used, dependent on data homogeneity. Stereologic analysis indicated significant remediation in vasculature in the bone marrow stromal cell group compared with the radiation therapy/distraction osteogenesis group. Each of five metrics idicated significant improvements from radiation therapy/distraction osteogenesis to the bone marrow stromal cell group, with no difference between the bone marrow stromal cell group and the distraction osteogenesis group. Bone marrow stromal cells used together with distraction osteogenesis can rejuvenate radiation-impaired vasculogenesis in the mandible, reversing radiation therapy-induced isotropy and creating a robust vascular network. Bone marrow stromal cells may offer clinicians an alternative reconstructive modality that could improve the lifestyle of patients with hypovascular bone.

Lithium attenuates lead induced toxicity on mouse non-adherent bone marrow cells.

Science.gov (United States)

Banijamali, Mahsan; Rabbani-Chadegani, Azra; Shahhoseini, Maryam

2016-07-01

Lead is a poisonous heavy metal that occurs in all parts of environment and causes serious health problems in humans. The aim of the present study was to investigate the possible protective effect of lithium against lead nitrate induced toxicity in non-adherent bone marrow stem cells. Trypan blue and MTT assays represented that exposure of the cells to different concentrations of lead nitrate decreased viability in a dose dependent manner, whereas, pretreatment of the cells with lithium protected the cells against lead toxicity. Lead reduced the number and differentiation status of bone marrow-derived precursors when cultured in the presence of colony stimulating factor (CSF), while the effect was attenuated by lithium. The cells treated with lead nitrate exhibited cell shrinkage, DNA fragmentation, anion superoxide production, but lithium prevented lead action. Moreover, apoptotic indexes such as PARP cleavage and release of HMGB1 induced by lead, were protected by lithium, suggesting anti-apoptotic effect of lithium. Immunoblot analysis of histone H3K9 acetylation indicated that lithium overcame lead effect on acetylation. In conclusion, lithium efficiently reduces lead toxicity suggesting new insight into lithium action which may contribute to increased cell survival. It also provides a potentially new therapeutic strategy for lithium and a cost-effective approach to minimize destructive effects of lead on bone marrow stem cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

[Bilateral deep venous thrombosis and vena cava aplasia treated with local thrombolysis

DEFF Research Database (Denmark)

Pelta, A.M.; Jørgensen, Maja; Just, Sven Richardt Lundgren

2008-01-01

In this case report the treatment of a young man with bilateral iliaco-femoral DVT and vena cava aplasia is presented. The patient was treated with catheter-directed thrombolysis; the catheters were introduced in the thrombus of both legs via v. popliteae. The treatment led to almost complete...

Protective role of Carica papaya (Linn.) in electron beam radiation induced hematological and cytogenetic damages in Swiss albino mice

International Nuclear Information System (INIS)

Yogish Somayaji, T.; Suchetha Kumari, N.

2014-01-01

Carica papaya (Linn.) is known to possess various biomedical applications. It has remarkable antioxidant properties. The main objective of the study was to evaluate the leaf extracts of Carica papaya (Linn.) on hematologic and cytogenetic changes occurring due to irradiation of mice to sub-lethal doses of Electron Beam Radiation (EBR). Analysis of hematological changes occurring due to irradiation of mice to sub-lethal doses of EBR, and the effects of Carica papaya (Linn.) extract on the same. The Assessment of hematopoietic stress by spleen colony forming unit and spleen body weight index. The analysis of cell proliferation and immunomodulation with response to the effects of Carica papaya (Linn.) extract by estimation of IL-6. The estimation of serum total antioxidants, lipid peroxidation and analyzing the activities of enzymes like SOD, ALP, and AST. Male Swiss albino mice were fed orally with papaya aqueous leaf extract for 15 days. They were irradiated with a whole body dose of 6 Gy Electron Beam radiation. The mice were dissected for liver, kidney, bone marrow, spleen and brain. The hematological studies were done using blood cell count in an automated cell counter. The biochemical estimations like urea, creatinine, SGOT, SGPT, Total Protein, Albumin, Bilirubin were done using the serum and homogenates. The total antioxidant capacity, the antioxidant enzymes were estimated. The Interleukin-6 levels were estimated in serum to assess immune modulation. The results show a decrease in the hematological parameters in radiated animals. The papaya treated groups have shown modulation in the hematological parameters. The extract has also reduced the suppression of the bone marrow induced by radiation. The radiation induced liver damage is also reduced in papaya treated groups. The aqueous extract of Carica papaya (Linn.) has shown protective effects in electron beam radiation induced tissue damages in Swiss Albino mice (author)

Radiation myelopathy; Myelopathie postradique

Energy Technology Data Exchange (ETDEWEB)

Rafai, M.A.; Boulaajaj, F.Z.; Amriss, O.; El Moutawakil, B.; Slassi, I. [Explorations Fonctionnelles, CHU Ibn Rochd, Service de Neurologie, Quartier des Hopitaux (Morocco); Rafai, M.A. [Faculte de Medecine et de Pharmacie, Lab. des Neurosciences Cliniques, Casablanca (Morocco)

2009-12-15

The post radiation induced myelopathy is a very serious complication, developing months or years after the irradiation of tumors localized near the marrow. It is rare if the radiation dose is inferior to 50 Gy. We report the case of a patients treated for a cavum cancer occurring one year after the radiotherapy with a stable evolution. (N.C.)

Nicaraven attenuates radiation-induced injury in hematopoietic stem/progenitor cells in mice.

Directory of Open Access Journals (Sweden)

Miho Kawakatsu

Full Text Available Nicaraven, a chemically synthesized hydroxyl radical-specific scavenger, has been demonstrated to protect against ischemia-reperfusion injury in various organs. We investigated whether nicaraven can attenuate radiation-induced injury in hematopoietic stem/progenitor cells, which is the conmen complication of radiotherapy and one of the major causes of death in sub-acute phase after accidental exposure to high dose radiation. C57BL/6 mice were exposed to 1 Gy γ-ray radiation daily for 5 days in succession (a total of 5 Gy, and given nicaraven or a placebo after each exposure. The mice were sacrificed 2 days after the last radiation treatment, and the protective effects and relevant mechanisms of nicaraven in hematopoietic stem/progenitor cells with radiation-induced damage were investigated by ex vivo examination. We found that post-radiation administration of nicaraven significantly increased the number, improved the colony-forming capacity, and decreased the DNA damage of hematopoietic stem/progenitor cells. The urinary levels of 8-oxo-2'-deoxyguanosine, a marker of DNA oxidation, were significantly lower in mice that were given nicaraven compared with those that received a placebo treatment, although the levels of intracellular and mitochondrial reactive oxygen species in the bone marrow cells did not differ significantly between the two groups. Interestingly, compared with the placebo treatment, the administration of nicaraven significantly decreased the levels of the inflammatory cytokines IL-6 and TNF-α in the plasma of mice. Our data suggest that nicaraven effectively diminished the effects of radiation-induced injury in hematopoietic stem/progenitor cells, which is likely associated with the anti-oxidative and anti-inflammatory properties of this compound.

Study on bone marrow mesenchymal stem cells in repairing of radiation induced acute liver injury of rats

International Nuclear Information System (INIS)

Bao Yongxing; Lou Fan; Zhao Huarong; Zhu Huhu; Ma Yan; Wen Hao

2010-01-01

Objective: To investigate the role of mesenchymal stem cells in the repair of radiation induced liver injury. Methods: 12 female SD rats were irradiated with 20 Gy 6 MV X-rays on the right lobe of the liver, to establish the model of radiation induced liver injury. The rats were divided randomly into two groups as invention group and control group, and transplanted with 1 ml male mesenchymal suspension or 1 ml normal saline in 4 hours after radiotherapy. The morphological changes of liver were observed. The existence of sex determining gene Y(SRY) and the level of alpha-smooth muscle actin (a-SMA) were detected. Results: Some injury of right lobe liver in two groups were observed, and the injury degree of right lobe liver in intervention group were lower than that of control group. The amount of SRY positive cells in the right lobe liver of intervention group was higher than that in the left lobe liver (t = 3.77, P <0.05). The positive expression rate of a-SMA in right lobe liver of intervention group was lower than that of control group. Conclusions: Acute radiation induced liver injury could lead BMSCs' homing in order to decrease the degree of liver fibrosis. (authors)

In vitro radiation studies on Ewing's sarcoma cell lines and human bone marrow: application to the clinical use of total body irradiation (TBI)

International Nuclear Information System (INIS)

Kinsella, T.J.; Mitchell, J.B.; McPherson, S.; Miser, J.; Triche, T.; Glatstein, E.

1984-01-01

Patients with Ewing's sarcoma who present with a central axis or proximal extremity primary and/or with metastatic disease have a poor prognosis despite aggressive combination chemotherapy and local irradiation. In this high risk group of patients, total body irradiation (TBI) has been proposed as a systemic adjuvant. To aid in the design of a clinical TBI protocol, the authors have studied in the in vitro radiation response of two established cell lines of Ewing's sarcoma and human bone marrow CFUc. The Ewing's lines showed a larger D 0 and anti-n compared to the bone marrow CFU. No repair of potentially lethal radiation damage (PLDR) was found after 4.5 Gy in plateau phase Ewing's sarcoma cells. A theoretical split dose survival curve for both the Ewing's sarcoma lines and human bone marrow CFUc using this TBI schedule shows a significantly lower surviving fraction (10 -4 -10 -5 ) for the bone marrow CFUc. Based on these in vitro results, two 4.0 Gy fractions separated by 24 hours is proposed as the TBI regimen. Because of the potentially irreversible damage to bone marrow, autologous bone marrow transplantation following the TBI is felt to be necessary. The details of this clinical protocol in high risk Ewing's sarcoma patients are outlined

Cytogenetic adaptive response induced by pre-exposure in human lymphocytes and marrow cells of mice

International Nuclear Information System (INIS)

Zhang Lianzhen; Deng Zhicheng

1993-01-01

The cytogenetic adaptive response induced by pre-exposure in human lymphocytes and marrow cells of mice were studied. The results of this study showed that human lymphocytes in vitro and mouse marrow cells in vivo can become adapted to low-level irradiation from 3 H-TdR or exposure to a low dose of X-or γ-irradiation, so that they become less sensitive to the chromosomal damage effects of subsequent exposures. (4 tabs.)

Reduced supportive capacity of bone marrow stroma upon chemotherapy is mediated via changes in glycosaminoglycan profile

NARCIS (Netherlands)

Zweegman, Sonja; Kessler, Floortje L.; Kerkhoven, Ron M.; Heimerikx, Mike; Celie, Johanna W. A. M.; Janssen, Jeroen J. W. M.; Huijgens, Peter C.; Drager, Angelika M.; van den Born, Jacob

High dose chemotherapy and radiation have been found to impair the hematopoiesis-supportive capacity of bone marrow stroma. We now provide evidence for an important role of chemotherapy-induced alterations in stromal glycosaminoglycans (GAGs) in reduction of the supportive properties of stromal

Aged garlic extract modulates the oxidative modifications induced by γ-rays in mouse bone marrow and erythrocytes cells

International Nuclear Information System (INIS)

Tawfik, S.S.; Elshamy, E.; Sallam, M.H.

2006-01-01

Gamma-ray generate hydroxyl radicals in cells and induce cellular DNA damage which leads to genotoxicity and chromosomes aberrations. The radioprotective and therapeutic efficacy of aged garlic extract (AGE) was investigated with micronucleus method as a reliable method for the detection of chromosomes damage induced by chemical and radiation. The frequency of micronuclei found in bone marrow erythroblast cells of the Protected and treated groups with 1.0 ml/20 g body wt/day for 10 consecutive days were significantly much lower than that of the exposed groups to γ-irradiation without protection or treatment. In addition, the enzyme activities of mouse erythrocyte antioxidant defense mechanism: superoxide dismutase (SOD), glutathione peroxidase (GSH-P x ) and glutathione reductase (GSH-R) were markedly decreased after irradiation while in protected and treated groups with Age showed significant increase but did not reach the control level except for Gash-R activity of protected group

Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells.

Science.gov (United States)

Pustovalova, Margarita; Astrelina, Тatiana A; Grekhova, Anna; Vorobyeva, Natalia; Tsvetkova, Anastasia; Blokhina, Taisia; Nikitina, Victoria; Suchkova, Yulia; Usupzhanova, Daria; Brunchukov, Vitalyi; Kobzeva, Irina; Karaseva, Тatiana; Ozerov, Ivan V; Samoylov, Aleksandr; Bushmanov, Andrey; Leonov, Sergey; Izumchenko, Evgeny; Zhavoronkov, Alex; Klokov, Dmitry; Osipov, Andreyan N

2017-11-21

Mechanisms underlying the effects of low-dose ionizing radiation (IR) exposure (10-100 mGy) remain unknown. Here we present a comparative study of early (less than 24h) and delayed (up to 11 post-irradiation passages) radiation effects caused by low (80 mGy) vs intermediate (1000 mGy) dose X-ray exposure in cultured human bone marrow mesenchymal stem cells (MSCs). We show that γН2АХ foci induced by an intermediate dose returned back to the control value by 24 h post-irradiation. In contrast, low-dose irradiation resulted in residual γН2АХ foci still present at 24 h. Notably, these low dose induced residual γН2АХ foci were not co-localized with рАТМ foci and were observed predominantly in the proliferating Кi67 positive (Кi67+) cells. The number of γН2АХ foci and the fraction of nonproliferating (Кi67-) and senescent (SA-β-gal+) cells measured at passage 11 were increased in cultures exposed to an intermediate dose compared to unirradiated controls. These delayed effects were not seen in the progeny of cells that were irradiated with low-dose X-rays, although such exposure resulted in residual γН2АХ foci in directly irradiated cells. Taken together, our results support the hypothesis that the low-dose IR induced residual γH2AХ foci do not play a role in delayed irradiation consequences, associated with cellular senescence in cultured MSCs.

Radiation-induced apoptosis

International Nuclear Information System (INIS)

Ohyama, Harumi

1995-01-01

Apoptosis is an active process of gene-directed cellular self-destruction that can be induced in many cell types via numerous physiological and pathological stimuli. We found that interphasedeath of thymocytes is a typical apoptosis showing the characteristic features of apoptosis including cell shrinkage, chromatin condensation and DNA degradation. Moderate dose of radiation induces extensive apoptosis in rapidly proliferating cell population such as the epithelium of intestinal crypt. Recent reports indicate that the ultimate form of radiation-induced mitotic death in several cells is also apoptosis. One of the hallmarks of apoptosis is the enzymatic internucleosomal degradation of chromatin DNA. We identified an endonuclease responsible for the radiation-induced DNA degradation in rat thymocytes. The death-sparing effects of interrupting RNA and protein synthesis suggested a cell genetic program for apoptosis. Apoptosis of thymocytes initiated by DNA damage, such as radiation and radio mimetic substance, absolutely requires the protein of p53 cancer suppresser gene. The cell death induced by glucocorticoid, or aging, has no such requirement. Expression of oncogene bcl-2 rescues cells from the apoptosis. Massive apoptosis in radiosensitive cells induced by higher dose radiation may be fatal. It is suggested that selective apoptotic elimination of cells would play an important role for protection against carcinogenesis and malformation through removal of cells with unrepaired radiation-induced DNA damages. Data to evaluate the significance of apoptosis in the radiation risk are still poor. Further research should be done in order to clarify the roles of the cell death on the acute and late effects of irradiation. (author)

Dominance and persistence of donor marrow in long-lived allogeneic radiation chimeras obtained with unmanipulated bone marrow

International Nuclear Information System (INIS)

Pierpaoli, W.; Maestroni, G.J.M.

1983-01-01

Allogeneic, H-2-incompatible irradiation chimeras (H-2sup(d) → H-2sup(b)) constructed with normal, unmanipulated bone marrow and with marrow-derived factors live long and do not manifest a GvH disease. Their response to primary immunization is deficient but their alloreactivity is normal. This chimeric allotolerance cannot be passively transferred from chimeric donors to normal irradiated recipients. Passive transfer of both donor- or recipient-type immuno-competent T-cells into the chimeric mice does not lead to syngeneic reconstitution, rejection of the engrafted marrow or GvH disease, and the mice maintain permanently their chimerism. This new model demonstrates that chimerism is not eradicable in long-lived chimeras reconstituted with unmanipulated bone marrow, and that the bone marrow itself plays a dominant role in maintenance of chimerism. (Auth.)

Effects of low dose radiation combined with cyclophosphamide on tumor cell apoptosis, cell cycle and proliferation of bone marrow in tumor-bearing mice

International Nuclear Information System (INIS)

Yu Hongsheng; Fei Conghe; Shen Fangzhen; Liang Jun

2004-01-01

Objective: To study the effect of low dose radiation (LDR) combined with cyclophosphamide on tumor cell apoptosis, cell cycle, and proliferation of bone marrow in mice tumor-bearing mice. Methods: Kunming strain male mice were implanted with S180 sarcoma cells in the left hind leg subcutaneously as an experimental animal model. Five and 8 days after implantation, the mice were given 75 mGy whole-body γ-ray radiation and CTX(300 mg/kg) by intraperitoneal injection 36 hour after LDR. All mice were sacrificed to measure the tumor volume, tumor cell apoptosis, and cell cycle; the proliferation of bone marrow was analyzed by flow cytometry. Results: Tumor growth was significantly slowed down in the treated groups. The apoptosis of tumor cells increased significantly after LDR. The tumor cells were arrested in G 1 phase in CTX and CTX+LDR groups, more significantly in the latter group than in the former group. Concentration of bone marrow cells and proliferation index in CTX + LDR group were higher than those in CTX group, although concentration of bone marrow cells in CTX and CTX+LDR groups were much lower than that in normal mice. Conclusion: Low dose radiation combined with cyclophosphamide causes more significant G 1 -phase arrest than cyclophosphamide alone and enhances anti-tumor effect markedly. At the same time LDR significantly protects hematopoietic function of bone marrow, which is of practical significance as an adjuvant chemotherapy

Fat Composition Changes in Bone Marrow During Chemotherapy and Radiation Therapy

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Carmona, Ruben; Pritz, Jakub [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Bydder, Mark [Department of Radiology, University of California San Diego Medical Center, San Diego, California (United States); Gulaya, Sachin; Zhu, He; Williamson, Casey W. [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Welch, Christian S. [Department of Radiology, University of California San Diego Medical Center, San Diego, California (United States); Vaida, Florin [Biostatistics and Bioinformatics, Department of Family and Preventive Medicine, University of California San Diego Medical Center, San Diego, California (United States); Bydder, Graeme [Department of Radiology, University of California San Diego Medical Center, San Diego, California (United States); Mell, Loren K., E-mail: lmell@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

2014-09-01

Purpose: To quantify changes in bone marrow fat fraction and determine associations with peripheral blood cell counts. Methods and Materials: In this prospective study, 19 patients received either highly myelotoxic treatment (radiation therapy plus cisplatin, 5-fluorouracil mitomycin C [FU/MMC], or cisplatin/5-FU/cetuximab) or less myelotoxic treatment (capecitabine-radiation therapy or no concurrent chemotherapy). Patients underwent MR imaging and venipuncture at baseline, midtreatment, and posttreatment visits. We performed mixed effects modeling of the mean proton density fat fraction (PDFF[%]) by linear time, treatment, and vertebral column region (lumbar [L]4-sacral [S]2 vs thoracic [T]10-L3 vs cervical[C]3-T9), while controlling for cumulative mean dose and other confounders. Spearman rank correlations were performed by white blood cell (WBC) counts versus the differences in PDFF(%) before and after treatment. Results: Cumulative mean dose was associated with a 0.43% per Gy (P=.004) increase in PDFF(%). In the highly myelotoxic group, we observed significant changes in PDFF(%) per visit within L4-S2 (10.1%, P<.001) and within T10-L3 (3.93%, P=.01), relative to the reference C3-T9. In the less myelotoxic group, we did not observe significant changes in PDFF(%) per visit according to region. Within L4-S2, we observed a significant difference between treatment groups in the change in PDFF(%) per visit (5.36%, P=.04). Rank correlations of the inverse log differences in WBC versus the differences in PDFF(%) overall and within T10-S2 ranged from 0.69 to 0.78 (P<.05). Rank correlations of the inverse log differences in absolute neutrophil counts versus the differences in PDFF(%) overall and within L4-S2 ranged from 0.79 to 0.81 (P<.05). Conclusions: Magnetic resonance imaging fat quantification is sensitive to marrow composition changes that result from chemoradiation therapy. These changes are associated with peripheral blood cell counts. This study supports a

Fat Composition Changes in Bone Marrow During Chemotherapy and Radiation Therapy

International Nuclear Information System (INIS)

Carmona, Ruben; Pritz, Jakub; Bydder, Mark; Gulaya, Sachin; Zhu, He; Williamson, Casey W.; Welch, Christian S.; Vaida, Florin; Bydder, Graeme; Mell, Loren K.

2014-01-01

Purpose: To quantify changes in bone marrow fat fraction and determine associations with peripheral blood cell counts. Methods and Materials: In this prospective study, 19 patients received either highly myelotoxic treatment (radiation therapy plus cisplatin, 5-fluorouracil mitomycin C [FU/MMC], or cisplatin/5-FU/cetuximab) or less myelotoxic treatment (capecitabine-radiation therapy or no concurrent chemotherapy). Patients underwent MR imaging and venipuncture at baseline, midtreatment, and posttreatment visits. We performed mixed effects modeling of the mean proton density fat fraction (PDFF[%]) by linear time, treatment, and vertebral column region (lumbar [L]4-sacral [S]2 vs thoracic [T]10-L3 vs cervical[C]3-T9), while controlling for cumulative mean dose and other confounders. Spearman rank correlations were performed by white blood cell (WBC) counts versus the differences in PDFF(%) before and after treatment. Results: Cumulative mean dose was associated with a 0.43% per Gy (P=.004) increase in PDFF(%). In the highly myelotoxic group, we observed significant changes in PDFF(%) per visit within L4-S2 (10.1%, P<.001) and within T10-L3 (3.93%, P=.01), relative to the reference C3-T9. In the less myelotoxic group, we did not observe significant changes in PDFF(%) per visit according to region. Within L4-S2, we observed a significant difference between treatment groups in the change in PDFF(%) per visit (5.36%, P=.04). Rank correlations of the inverse log differences in WBC versus the differences in PDFF(%) overall and within T10-S2 ranged from 0.69 to 0.78 (P<.05). Rank correlations of the inverse log differences in absolute neutrophil counts versus the differences in PDFF(%) overall and within L4-S2 ranged from 0.79 to 0.81 (P<.05). Conclusions: Magnetic resonance imaging fat quantification is sensitive to marrow composition changes that result from chemoradiation therapy. These changes are associated with peripheral blood cell counts. This study supports a

The Mitigating Effect of Citrullus colocynthis (L. Fruit Extract against Genotoxicity Induced by Cyclophosphamide in Mice Bone Marrow Cells

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Mohammad Shokrzadeh

2013-01-01

Full Text Available Possible genoprotective effect of Citrullus colocynthis (L. (CCT fruits extract against cyclophosphamide- (CP-induced DNA damage in mice bone marrow cells was evaluated using micronucleus assay, as an index of induced chromosomal damage. Mice were preadministered with different doses of CCT via intraperitoneal injection for 7 consecutive days followed by injection with CP (70 mg/kg b.w. 1 hr after the last injection of CCT. After 24 hr, mice were scarified to evaluate the frequency of micronucleated polychromatic erythrocytes (MnPCEs. In addition, the number of polychromatic erythrocytes (PCEs among 1000 normochromatic erythrocytes (NCEs per animal was recorded to evaluate bone marrow. Pretreatment with CCT significantly reduced the number of MnPCEs induced by CP in bone marrow cells (P<0.0001. At 200 mg/kg, CCT had a maximum chemoprotective effect and reduced the number of MnPCEs by 6.37-fold and completely normalized the mitotic activity. CCT also led to marked proliferation and hypercellularity of immature myeloid elements after mice were treated with CP and mitigated the bone marrow suppression. Our study revealed that CCT has an antigenotoxic effect against CP-induced oxidative DNA damage in mice. Therefore, it could be used concomitantly as a supplement to protect people undergoing chemotherapy.

Resistance to infection with Eimeria vermiformis in mouse radiation chimeras is determined by donor bone-marrow cells

International Nuclear Information System (INIS)

Joysey, H.S.; Wakelin, D.; Rose, M.E.

1988-01-01

The course of infection with Eimeria vermiformis was determined in BALB/b, BALB/c, and C57BL/10ScSn (B10) mice and in radiation chimeras prepared from the H-2-compatible BALB/b and B10 mice. The BALB strains, irrespective of H-2 haplotype, were resistant, the B10 mice were susceptible, and in the chimeras infection was characterized by the genotype of the donated bone-marrow cells and not by the phenotype of the recipient. Thus, the genetic control of relative resistance or susceptibility to infection with this parasite is expressed through bone-marrow-derived cells

Genetic topics in radiation protection

Energy Technology Data Exchange (ETDEWEB)

Traut, H [Muenster Univ. (F.R. Germany). Inst. fuer Strahlenbiologie

1976-01-01

The effects of mutations induced by ionizing radiation on human health can be subdivided into decrease of general viability, malformations and embryonic death. Reasons are given for the recommendation why a man whose gonads had been exposed to radiation should refrain from procreation for a couple of months. An analysis of the frequency of chromosome aberrations induced in lymphocytes can provide an estimate of the dose received during an accidental exposure. Radiation induced chronic myeloid leukaemia is probably based on the induction of an aberration involving chromosome 22 in a bone marrow cell (deletion, translocation). The relationship between the frequency of radiation induced point mutations and the DNA content of the genome of the species studied so far is discussed.

Recurrence of thymoma with pleural invasion in a patient with myasthenia gravis and pure red blood cell aplasia: a case report

International Nuclear Information System (INIS)

Rodriguez, Sonia Pilar; Zuluaga, Claudia Patricia; Uriza, Luis Felipe C; Sanchez M, Jully Mariana

2008-01-01

Thymoma are thymic tumors that arise from epithelial cells, they have different morphological characteristics. It is known for its association with autoimmune diseases such as myasthenia gravis, pure red cell aplasia, systemic lupus erythematosus, or hipogamaglobulinemia pemphigus foliaceus. The association thymoma-myasthenia gravis-pure red cell aplasia is a rare one; there will be a case report with the corresponding discussion and review of the literature

Bone marrow transplantation - a field in continuous development

International Nuclear Information System (INIS)

Pfeffer, P.F.

1975-01-01

The symptoms of the radiation syndrome are described briefly and the Vinca accident in 1958 is used as an illustration of the application of bone marrow transplantation as a treatment in radiation accidents. Thereafter the immunological problems arising when a permanent substitution of donor marrow is required are discussed. Greatest experience in bone marrow transplantation has been had in the treatment of aplastic anemia and acute leukemia. In these cases the recipient's bone marrow cells must be killed by whole body irradiation or by cyclophosphamide to preclude graft-host reaction. The removal of marrow from the donor and transplanting in the recipient are described, as is the progress of the patient in a typical case. The graft-host reaction is then discussed, as is the danger of secondary infections. In conclusion the long term results are evaluated and the future developments of the treatment discussed. (JIW)

Protective Effect of Anthocyanins from Lingonberry on Radiation-induced Damages

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Shuang-Qi Tian

2012-12-01

Full Text Available There is a growing concern about the serious harm of radioactive materials, which are widely used in energy production, scientific research, medicine, industry and other areas. In recent years, owing to the great side effects of anti-radiation drugs, research on the radiation protectants has gradually expanded from the previous chemicals to the use of natural anti-radiation drugs and functional foods. Some reports have confirmed that anthocyanins are good antioxidants, which can effectively eliminate free radicals, but studies on the immunoregulatory and anti-radiation effects of anthocyanins from lingonberry (ALB are less reported. In this experiment, mice were given orally once daily for 14 consecutive days before exposure to 6 Gy of gamma-radiation and were sacrificed on the 7th day post-irradiation. The results showed that the selected dose of extract did not lead to acute toxicity in mice; while groups given anthocyanins orally were significantly better than radiation control group according to blood analysis; pretreatment of anthocyanins significantly (p < 0.05 enhanced the thymus and spleen indices and spleen cell survival compared to the irradiation control group. Pretreatment with anthocyanins before irradiation significantly reduced the numbers of micronuclei (MN in bone marrow polychromatic erythrocytes (PCEs. These findings indicate that anthocyanins have immunostimulatory potential against immunosuppression induced by the radiation.

Transfer of innate resistance and susceptibility to Leishmania donovani infection in mouse radiation bone marrow chimaeras

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Crocker, P.R.; Blackwell, J.M.; Bradley, D.J. (London School of Hygiene and Tropical Medicine (UK))

1984-07-01

Reciprocal radiation bone marrow chimaeras were made between H-2-compatible strains of mice innately resistant or susceptible to visceral leishmaniasis. In initial experiments, susceptibility but not resistance to Leishmania donovani could be transferred with donor bone marrow into irradiated recipients. In subsequent experiments it was possible to transfer both resistance and susceptibility. This was achieved either by selecting more radiosensitive mouse strains as susceptible recipients, or alternatively by increasing the irradiation dose for the susceptible recipients used in the initial experiments. Using the higher irradiation dose, successful transfer of resistance and susceptibility between congenic mice carrying the Lshsup(r) and Lshsup(s) alleles on the more radioresistant B10 genetic background provided firm evidence that the results obtained in this study were specifically related to expression of the Lsh gene. It is concluded that Lsh gene-controlled resistance and susceptibility to L. donovani is determined by bone marrow-derived cells. The cell type(s) involved is likely to be of the macrophage lineage.

Transfer of innate resistance and susceptibility to Leishmania donovani infection in mouse radiation bone marrow chimaeras

International Nuclear Information System (INIS)

Crocker, P.R.; Blackwell, J.M.; Bradley, D.J.

1984-01-01

Reciprocal radiation bone marrow chimaeras mere made between H-2-compatible strains of mice innately resistant or susceptible to visceral leishmaniasis. In initial experiments, susceptibility but not resistance to Leishmania donovani could be transferred with donor bone marrow into irradiated recipients. In subsequent experiments it was possible to transfer both resistance and susceptibility. This was achieved either by selecting more radiosensitive mouse strains as susceptible recipients, or alternatively by increasing the irradiation dose for the susceptible recipients used in the initial experiments. Using the higher irradiation dose, successful transfer of resistance and susceptibility between congenic mice carrying the Lshsup(r) and Lshsup(s) alleles on the more radioresistant B10 genetic background provided firm evidence that the results obtained in this study were specifically related to expression of the Lsh gene. It is concluded that Lsh gene-controlled resistance and susceptibility to L. donovani is determined by bone marrow-derived cells. The cell type(s) involved is likely to be of the macrophage lineage. (author)

Acquired bleeding disorders

African Journals Online (AJOL)

B one marrow aplasia ... Laboratory approach to a suspected acquired bleeding disorder. (LER = leuko- .... lymphocytic leukaemia, and lymphoma). ... cells), a bone marrow aspirate and trephine biopsy (BMAT) is not ..... transplantation.

The acute radiation syndrome in the miniature pig Troll

International Nuclear Information System (INIS)

Siegl, R.

1986-01-01

8 animals at an average age of 230 days and an average body weight of 24.9 kg were whole-body gamma-irradiated from a cobalt-60 source with 3.0 Gy midline dose. 4 of the 8 pigs survived, the others died within day 14 and 17 after irradiation, mainly due to thrombopenia dependent hemorrhage. Hematologic examinations showed as well that the platelets decreased to a minimum on day 14 p.r. The granulocyte values and yet remarkable the lymphocyte values decreased at an earlier time. The absolute lymphocyte counts reached their lowest mark already on the first day after irradiation. The reticulocytes, which also decreased markedly on day 1 p.r., sank further on the following days, till after two weeks when they started to increase again. Furthermore 25 biochemical serum parameters have been investigated. The major pathological findings of the acute radiation sickness were the mostly heavy hemorrhages. Histological studies indicated primarily aplasia of bone marrow, intestinal mucosa damages and atrophy of lymphatic tissues. Signs for septicemia were rarely found. The investigations in Troll-pigs showed, their reactions to an irradiation of middle-lethal doses are similar to those of other pigs. Only the Vietnamese pot-bellied swine reacts differently: Profuse diarrheas already after low radiation-doses are reported. (orig./MG) [de

APLASIA CUTIS CONGÉNITA – UM CASO CLÍNICO

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Mónica Costeira

2016-07-01

Comentários: A aplasia cutis congénita é uma lesão que pode ser causadora de grande ansiedade parental, pelo que é importante ao Pediatra o seu reconhecimento e devido esclarecimento. Apesar de se tratar, na maioria das vezes, de um defeito benigno, é importante o conhecimento da sua relação com outras anomalias e síndromes de forma a otimizar a sua orientação precoce e adequada. Da mesma forma, é importante o aconselhamento genético, nos casos que assim o justifiquem.

The role of stem cells in the prevention and treatment of radiation-induced xerostomia in patients with head and neck cancer.

Science.gov (United States)

Nevens, Daan; Nuyts, Sandra

2016-06-01

Xerostomia is an important complication following radiotherapy (RT) for head and neck cancer. Current treatment approaches are insufficient and can only temporarily relieve symptoms. New insights into the physiopathology of radiation-induced xerostomia might help us in this regard. This review discusses the current knowledge of salivary gland stem cells in radiation-induced xerostomia and their value in the prevention and treatment of this complication. Salivary gland stem cell transplantation, bone marrow-derived cell mobilization, molecular regulation of parotid stem cells, stem cell sparing RT, and adaptive RT are promising techniques that are discussed in this study. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Quantifying murine bone marrow and blood radiation dose response following {sup 18}F-FDG PET with DNA damage biomarkers

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Manning, Grainne [Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 ORQ (United Kingdom); Taylor, Kristina [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON (Canada); Finnon, Paul [Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 ORQ (United Kingdom); Lemon, Jennifer A.; Boreham, Douglas R. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, ON (Canada); Badie, Christophe, E-mail: christophe.badie@phe.gov.uk [Biological Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, Oxfordshire OX11 ORQ (United Kingdom)

2014-12-15

Highlights: • Mice received either a range of {sup 18}F-FDG activities or whole body X-ray doses. • Blood samples were collected at 24 and 43 h for MN-RET and QPCR analysis. • Regression analysis showed that both types of exposure produced a linear response. • BM doses of 33 mGy ({sup 18}F-FDG) and 25 mGy X-rays were significantly higher than controls. • No significant difference between internal ({sup 18}F-FDG) and external (X-ray) was found. - Abstract: The purpose of this study was to quantify the poorly understood radiation doses to murine bone marrow and blood from whole-body fluorine 18 ({sup 18}F)-fluorodeoxyglucose (FDG) positron emission tomography (PET), by using specific biomarkers and comparing with whole body external low dose exposures. Groups of 3–5 mice were randomly assigned to 10 groups, each receiving either a different activity of {sup 18}F-FDG: 0–37 MBq or whole body irradiated with corresponding doses of 0–300 mGy X-rays. Blood samples were collected at 24 h and at 43 h for reticulocyte micronucleus assays and QPCR analysis of gene expression in peripheral blood leukocytes. Blood and bone marrow dose estimates were calculated from injected activities of {sup 18}F-FDG and were based on a recommended ICRP model. Doses to the bone marrow corresponding to 33.43 mGy and above for internal {sup 18}F-FDG exposure and to 25 mGy and above for external X-ray exposure, showed significant increases in radiation-induced MN-RET formation relative to controls (P < 0.05). Regression analysis showed that both types of exposure produced a linear response with linear regression analysis giving R{sup 2} of 0.992 and 0.999 for respectively internal and external exposure. No significant difference between the two data sets was found with a P-value of 0.493. In vivo gene expression dose–responses at 24 h for Bbc3 and Cdkn1 were similar for {sup 18}F-FDG and X-ray exposures, with significant modifications occurring for doses over 300 mGy for Bbc3

Post-irradiation treatment with OK432 can prevent radiation-induced bone marrow death

International Nuclear Information System (INIS)

Kurishita, A.; Uehara, Y.; Tohoku Univ., Sendai; Katoh, H.; Hirose, S.; Uchida, A.; Mizutani, Y.; Okada, S.; Ono, T.

1991-01-01

The radioprotective effect of OK432, a Streptocuccus haemolyticus preparation, on bone marrow death was examined in mice. The LD 50 value was increased from 7.55 Gy in controls to 8.45 Gy in mice treated once with OK432 immediately after irradiation. Multiple administration of the agent further elevated the LD 50 value to 9.56 Gy. The radioprotective effect was also apparent when multiple treatments were commenced as late as 72 h after irradiation. (author)

The hematologist and radiation casualties.

Science.gov (United States)

Dainiak, Nicholas; Waselenko, Jamie K; Armitage, James O; MacVittie, Thomas J; Farese, Ann M

2003-01-01

Since the terrorist attack of September 11, 2001, preparation by the health care system for an act of terrorism has been mandated by leaders of governments. Scenarios for terrorist acts involving radioactive material have been identified, and approaches to management (based on past experience from atomic weapons detonations and radiation accidents) have been developed. Because of their experience in managing patients with profound cytopenia and/or marrow aplasia, hematologists will be asked to play a significant role in evaluating and treating victims of mass accidental or deliberate exposure to radiation. This review provides a framework for understanding how radiation levels are quantified, how radiation alters the function of hematopoietic (and nonhematopoietic) cells and tissues, and how victims receiving a significant radiation dose can be identified and managed. In Section I, Dr. Nicholas Dainiak reviews four components of the Acute Radiation Syndrome: the hematopoietic, neurovascular, gastrointestinal and cutaneous subsyndromes. Clinical signs and symptoms are discussed for exposed individuals at the time of initial presentation (the prodromal phase) and during their course of disease (the manifest illness). In Section II, he presents clinical and laboratory methods to assess radiation doses, including time to onset and severity of vomiting, rate of decline in absolute blood lymphocyte count and the appearance of chromosome aberrations such as dicentrics and ring forms. Potential scenarios of a radiation terrorist event are reviewed, and methods for initial clinical assessment, triage, and early management of the acute radiation syndrome and its component subsyndromes are summarized. In Section III, Dr. Jamie Waselenko reviews the hematopoietic syndrome, and presents guidelines for the use of cytokine therapy, antibiotics, and supportive care that have been developed by the Strategic National Pharmaceutical Stockpile Working Group. Results of preclinical and

Age-related inflammatory bone marrow microenvironment induces ineffective erythropoiesis mimicking del(5q) MDS.

Science.gov (United States)

Mei, Y; Zhao, B; Basiorka, A A; Yang, J; Cao, L; Zhang, J; List, A; Ji, P

2018-04-01

Anemia is characteristic of myelodysplastic syndromes (MDS). The mechanisms of anemia in MDS are unclear. Using a mouse genetic approach, here we show that dual deficiency of mDia1 and miR-146a, encoded on chromosome 5q and commonly deleted in MDS (del(5q) MDS), causes an age-related anemia and ineffective erythropoiesis mimicking human MDS. We demonstrate that the ageing bone marrow microenvironment is important for the development of ineffective erythropoiesis in these mice. Damage-associated molecular pattern molecules (DAMPs), whose levels increase in ageing bone marrow, induced TNFα and IL-6 upregulation in myeloid-derived suppressor cells (MDSCs) in mDia1/miR-146a double knockout mice. Mechanistically, we reveal that pathologic levels of TNFα and IL-6 inhibit erythroid colony formation and differentially affect terminal erythropoiesis through reactive oxygen species-induced caspase-3 activation and apoptosis. Treatment of the mDia1/miR-146a double knockout mice with all-trans retinoic acid, which promoted the differentiation of MDSCs and ameliorated the inflammatory bone marrow microenvironment, significantly rescued anemia and ineffective erythropoiesis. Our study underscores the dual roles of the ageing microenvironment and genetic abnormalities in the pathogenesis of ineffective erythropoiesis in del(5q) MDS.

Adaptive responses induced in bone marrow and blood of the rats by tritium contamination

International Nuclear Information System (INIS)

Savu, D.I.; Ionescu, M.A.; Petcu, I.

2000-01-01

It has been more than a decade since the initial report on the phenomenon termed 'adaptive response to ionizing radiation'. Although a number of reports have appeared since then, the understanding of this response is still incomplete. Our group intended to investigate whether the adaptive response could be induced in vivo by low level internal tritium contamination of rats and subsequently exposed to challenging irradiations with fast neutrons or gamma rays. Two experiments were performed and analysed comparatively. In the first experiment the rats have been pre-contaminated for 3 weeks to total doses of 7 cGy and 35 cGy and subsequently irradiated to 1 Gy by fast neutrons (d(13.5)+Be). They were sacrificed after 24 hours. In the second experiment rats were exposed to high gamma irradiation (1.4 Gy) after prior contamination with tritium for 20 days to total doses of 4.4 cGy and 5.1 cGy. We followed up the modifications of two biochemical parameters: (i) the in vitro tritiated thymidine incorporation in the bone marrow cells and (ii) the reduced glutathione level in the blood cells. The thymidine incorporation assay revealed a putative adaptive reaction only for the rats preirradiated with tritiated water to 35 cGy and post-irradiated with fast neutrons. The glutathione content was found to be increased (back to the normal level) for the tritium pre-contaminated and neutron irradiated animals as compared to those exposed only to fast neutrons. The adaptive response is believed to be a protective mechanism that confers resistance to the detrimental effects of ionizing radiation. Our studies suggest that the irradiation with low conditioning doses of tritium (7; 35 cGy) is more efficient in conferring radioresistance to bone marrow and blood cells at the treatment with fast neutrons (1 Gy) than the irradiation with tritium doses of 4.4 and 5.1 cGy followed by gamma rays (1.4 Gy). (authors)

Abscopal suppression of bone marrow erythropoiesis

International Nuclear Information System (INIS)

Werts, E.D.; Johnson, M.J.; DeGowin, R.L.

1978-01-01

Abscopal responses of hemopoietic tissue, which we noted in preliminary studies of mice receiving partial-body irradiation, led us to clarify these effects. In studies reported here, one hind leg of CF-1 female mice received 1000, 5000, or 10,000 rad of x radiation. We found a persistent shift from medullary to splenic erythropoiesis preventing anemia in mice receiving 5000 or 10,000 rad. Splenectomy prior to 5000-rad irradiation resulted in anemia, which was not ameliorated by exposure to intermittent hypoxia. Despite evidence for increased levels of erythropoietin in the animals, namely, a reticulocytosis and increased erythrocyte radioiron incorporation, both 59 Fe uptake and erythroblast counts in shielded marrow remained below normal. We found 50 to 90% suppression of the growth of marrow stromal colonies (MSC) from bone marrow aspirates of the shielded and irradiated femoral marrow at 1 month and at least 20% depression of MSC at 1 year, with each dose. We conclude that: (i) high doses of x radiation to one leg of mice caused prolonged suppression of medullary erythropoiesis with splenic compensation to prevent anemia; (ii) splenectomy, anemia, and hypoxia prevented the severe abscopal depression of medullary erythropoiesis; and (iii) suppressed medullary erythropoiesis with decreased growth of MSC suggested a change in the hemopoietic microenvironment of the bone marrow

Wound trauma alters ionizing radiation dose assessment

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Kiang Juliann G

2012-06-01

Full Text Available Abstract Background Wounding following whole-body γ-irradiation (radiation combined injury, RCI increases mortality. Wounding-induced increases in radiation mortality are triggered by sustained activation of inducible nitric oxide synthase pathways, persistent alteration of cytokine homeostasis, and increased susceptibility to bacterial infection. Among these factors, cytokines along with other biomarkers have been adopted for biodosimetric evaluation and assessment of radiation dose and injury. Therefore, wounding could complicate biodosimetric assessments. Results In this report, such confounding effects were addressed. Mice were given 60Co γ-photon radiation followed by skin wounding. Wound trauma exacerbated radiation-induced mortality, body-weight loss, and wound healing. Analyses of DNA damage in bone-marrow cells and peripheral blood mononuclear cells (PBMCs, changes in hematology and cytokine profiles, and fundamental clinical signs were evaluated. Early biomarkers (1 d after RCI vs. irradiation alone included significant decreases in survivin expression in bone marrow cells, enhanced increases in γ-H2AX formation in Lin+ bone marrow cells, enhanced increases in IL-1β, IL-6, IL-8, and G-CSF concentrations in blood, and concomitant decreases in γ-H2AX formation in PBMCs and decreases in numbers of splenocytes, lymphocytes, and neutrophils. Intermediate biomarkers (7 – 10 d after RCI included continuously decreased γ-H2AX formation in PBMC and enhanced increases in IL-1β, IL-6, IL-8, and G-CSF concentrations in blood. The clinical signs evaluated after RCI were increased water consumption, decreased body weight, and decreased wound healing rate and survival rate. Late clinical signs (30 d after RCI included poor survival and wound healing. Conclusion Results suggest that confounding factors such as wounding alters ionizing radiation dose assessment and agents inhibiting these responses may prove therapeutic for radiation combined

MR examination of bone marrow variations in the spine after radiotherapy

International Nuclear Information System (INIS)

Starz, I.; Einspieler, R.; Poschauko, H.; Ebner, F.; Arian-Schad, K.; Justich, E.

1990-01-01

MR examinations of bone marrow variations in the spine after radiotherapy were performed on 24 patients in the thoracic and lumbar vertebral column. The actinically affected bone marrow showed a characteristic increase of signal intensity in T 1 -weighted sequences in the sagital plane, due to conversion of red marrow to fatty marrow. The dose in the well-defined radiation areas was between 28 and 70 Gray (Gy). The lowest dose, applied to the bone-marrow bordering on the defined radiation areas, where we still could find an increase of signal intensity, was below 2,8 to 5 Gy. MR imaging was performed between 6 and 9 month after radiotherapy. (orig.) [de

Treatment of radiation exposure and regeneration medicine. Regeneration treatment of blood vessels by transplantation of autologous marrow monocytes

International Nuclear Information System (INIS)

Nagai, Kazuhiro; Kamihira, Shimeru; Matsumaru, Ichiro; Fukushima, Takuya; Yamaguchi, Hakuichiro; Miyazaki, Yasushi; Yamachika, Shiro; Eishi, Kiyoyuki; Tomonaga, Masao

2007-01-01

Described are usefulness and future view of regenerative medicine in the treatment of radiation exposure as exemplified by the vascular regeneration by autologous marrow cell transplantation. Vascular endothelial cells (VEC), possessing a high ability to divide, are known sensitive to radiation, which gives damage of blood vessel to alter its permeability leading to apoptosis of VEC, organ/tissue injuries and final damages in the cerebral blood vessels, central nervous system and skin, the acute radiation syndrome (ARS). Authors present successful cases of patients with chronic limb ischemia in the Therapeutic Angiogenesis using Cell Transplantation Trial (TACT), to whom the treatment is conducted with transplantation of autologous marrow monocyte fraction containing endothelial progenitor cells that differentiate to VEC. As well, they touch on a case of the patient encountered in a nuclear accident, mentioning that VEC are found partly derived from the donor after heamatopoietic stem cell transplantation (HSCT). Efficacy of HSCT in a literature is reviewed and commented to be an only limited one in 31 patients of various radiation accidents. However, treatment of ARS where stem cells are target, with regenerative medicine will become more useful in future, as basic and clinical researches will provide requisite findings. (T.I.)

Significance of bone-marrow scintigraphy in aplastic anemia: concise communication

International Nuclear Information System (INIS)

Najean, Y.; Le Danvic, M.; Le Mercier, N.; Pecking, A.; Colonna, P.; Rain, J.D.

1980-01-01

Tc-99m colloid and In-111 transferrin were used in a semiquantitative scintigraphic study of bone-marrow activity in 76 patients with aplastic anemia, the majority of which were severe cases. The results are compared with other known prognostic parameters and with a predictive index formulated from a prior multiparametric analysis performed in 352 cases. In 47 cases parallel abnormality of Tc and In uptakes was noted and was well correlated with other prognostic factors. Indium uptake is apparently a good indicator of the severity of aplasia; extension of active erythroid tissue, demonstrated with this method, is correlated with prognosis. In nine cases, excessive in uptake is explained by dyserythropoiesis associated with granulo- and thrombocytopenia (Fanconi's anemia in most cases). In 20 of our patients, TcSC uptake was excessive compared with that of In and with other prognostic factors. Statistically, this phenomenon carries an unfavorable prognosis but its physiological meaning remains to be defined

Radiation-induced chromosome aberrations in bone marrow cells leading to acute myeloid leukemia in mouse

International Nuclear Information System (INIS)

Nobuhiko Ban; Tomoko Kusama

1996-01-01

It is well known that radiation-induced acute myeloid leukemia (RI-AML) in mice is charaterized by deletion and/or rearrangement of chromosome 2. While chromosome 2 has been suspected to be a target of RI-AML, radiation-sensitive site of the chromosome might be implicated in the leukemogenesis. There were few cytogenetical studies, however, focusing on chromosomal rearrangements shortly after irradiation, and little was known about the frequency and pattern of chromosome 2 aberrations during the early period. In this study, metaphase samples were prepared from whole-body irradiated mice 24 hours after irradiation, most of the cells considered to be in the first mitotic stage. Distribution of chromosomal breakpoints on the metaphase samples were analyzed to study the relationship between chromosome aberrations and RI-AML. (author)

Inhibition of the CXCL12/CXCR4-axis as preventive therapy for radiation-induced pulmonary fibrosis.

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Shu, Hui-Kuo G; Yoon, Younghyoun; Hong, Samuel; Xu, Kaiming; Gao, Huiying; Hao, Chunhai; Torres-Gonzalez, Edilson; Nayra, Cardenes; Rojas, Mauricio; Shim, Hyunsuk

2013-01-01

A devastating late injury caused by radiation is pulmonary fibrosis. This risk may limit the volume of irradiation and compromise potentially curative therapy. Therefore, development of a therapy to prevent this toxicity can be of great benefit for this patient population. Activation of the chemokine receptor CXCR4 by its ligand stromal cell-derived factor 1 (SDF-1/CXCL12) may be important in the development of radiation-induced pulmonary fibrosis. Here, we tested whether MSX-122, a novel small molecule and partial CXCR4 antagonist, can block development of this fibrotic process. The radiation-induced lung fibrosis model used was C57BL/6 mice irradiated to the entire thorax or right hemithorax to 20 Gy. Our parabiotic model involved joining a transgenic C57BL/6 mouse expressing GFP with a wild-type mouse that was subsequently irradiated to assess for migration of GFP+ bone marrow-derived progenitor cells to the irradiated lung. CXCL12 levels in the bronchoalveolar lavage fluid (BALF) and serum after irradiation were determined by ELISA. CXCR4 and CXCL12 mRNA in the irradiated lung was determined by RNase protection assay. Irradiated mice were treated daily with AMD3100, an established CXCR4 antagonist; MSX-122; and their corresponding vehicles to determine impact of drug treatment on fibrosis development. Fibrosis was assessed by serial CTs and histology. After irradiation, CXCL12 levels increased in BALF and serum with a corresponding rise in CXCR4 mRNA within irradiated lungs consistent with recruitment of a CXCR4+ cell population. Using our parabiotic model, we demonstrated recruitment of CXCR4+ bone marrow-derived mesenchymal stem cells, identified based on marker expression, to irradiated lungs. Finally, irradiated mice that received MSX-122 had significant reductions in development of pulmonary fibrosis while AMD3100 did not significantly suppress this fibrotic process. CXCR4 inhibition by drugs such as MSX-122 may alleviate potential radiation-induced lung

Inhibition of the CXCL12/CXCR4-axis as preventive therapy for radiation-induced pulmonary fibrosis.

Directory of Open Access Journals (Sweden)

Hui-Kuo G Shu

Full Text Available A devastating late injury caused by radiation is pulmonary fibrosis. This risk may limit the volume of irradiation and compromise potentially curative therapy. Therefore, development of a therapy to prevent this toxicity can be of great benefit for this patient population. Activation of the chemokine receptor CXCR4 by its ligand stromal cell-derived factor 1 (SDF-1/CXCL12 may be important in the development of radiation-induced pulmonary fibrosis. Here, we tested whether MSX-122, a novel small molecule and partial CXCR4 antagonist, can block development of this fibrotic process.The radiation-induced lung fibrosis model used was C57BL/6 mice irradiated to the entire thorax or right hemithorax to 20 Gy. Our parabiotic model involved joining a transgenic C57BL/6 mouse expressing GFP with a wild-type mouse that was subsequently irradiated to assess for migration of GFP+ bone marrow-derived progenitor cells to the irradiated lung. CXCL12 levels in the bronchoalveolar lavage fluid (BALF and serum after irradiation were determined by ELISA. CXCR4 and CXCL12 mRNA in the irradiated lung was determined by RNase protection assay. Irradiated mice were treated daily with AMD3100, an established CXCR4 antagonist; MSX-122; and their corresponding vehicles to determine impact of drug treatment on fibrosis development. Fibrosis was assessed by serial CTs and histology. After irradiation, CXCL12 levels increased in BALF and serum with a corresponding rise in CXCR4 mRNA within irradiated lungs consistent with recruitment of a CXCR4+ cell population. Using our parabiotic model, we demonstrated recruitment of CXCR4+ bone marrow-derived mesenchymal stem cells, identified based on marker expression, to irradiated lungs. Finally, irradiated mice that received MSX-122 had significant reductions in development of pulmonary fibrosis while AMD3100 did not significantly suppress this fibrotic process.CXCR4 inhibition by drugs such as MSX-122 may alleviate potential

48XXYY Syndrome in an Adult with Type 2 Diabetes Mellitus, Unilateral Renal Aplasia, and Pigmentary Retinitis.

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Zantour, Baha; Sfar, Mohamed Habib; Younes, Samia; Alaya, Wafa; Kamoun, Mahdi; Mkaouar, Emna; Jerbi, Saida

2010-01-01

A 45-year-old male was referred for diabetes mellitus. Clinical examination found a family history of multiple precocious deaths, strong consanguinity, personal history of seizures during childhood, small testicles, small penis, sparse body hair, long arms and legs, dysmorphic features, mental retardation, dysarthria, tremor, and mild gait ataxia. Investigations found pigmentary retinitis, metabolic syndrome, unilateral renal aplasia, and hypergonadotropic hypogonadism, and ruled out mitochondrial cytopathy and leucodystrophy. Karyotype study showed a 48XXYY chromosomal type. Renal aplasia and pigmentary retinitis have not been described in 48XXYY patients. They may be related to the chromosomal sex aneuploidy, or caused by other genetic aberrations in light of the high consanguinity rate in the patient's family.

48XXYY Syndrome in an Adult with Type 2 Diabetes Mellitus, Unilateral Renal Aplasia, and Pigmentary Retinitis

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Baha Zantour

2010-01-01

Full Text Available A 45-year-old male was referred for diabetes mellitus. Clinical examination found a family history of multiple precocious deaths, strong consanguinity, personal history of seizures during childhood, small testicles, small penis, sparse body hair, long arms and legs, dysmorphic features, mental retardation, dysarthria, tremor, and mild gait ataxia. Investigations found pigmentary retinitis, metabolic syndrome, unilateral renal aplasia, and hypergonadotropic hypogonadism, and ruled out mitochondrial cytopathy and leucodystrophy. Karyotype study showed a 48XXYY chromosomal type. Renal aplasia and pigmentary retinitis have not been described in 48XXYY patients. They may be related to the chromosomal sex aneuploidy, or caused by other genetic aberrations in light of the high consanguinity rate in the patient's family.

Hematopoiesis Stimulating Role of IL-12 Enabling Bone Marrow Transplantation in Irradiated Rats

International Nuclear Information System (INIS)

Ashry, O.M.; Abd el Sammad, H.; El Shahat, M.; Abou el Khier, I.

2012-01-01

Severe myelosuppression is a common side effect of radiotherapy or chemotherapy. As a mean to stimulate the full-lineage blood cell recovery from severe myelosuppression, sublethally irradiated animals were used to evaluate immunological effect of interleukin IL-12 in bone marrow transplanted animals. Isologous bone marrow (BM), from the same inbred strain, were given to male rats, 1 hour post whole body gamma irradiation at a single dose level of 5 Gy and subcutaneous injection of 100 ng/ml IL-12. Irradiation induced a significant drop in haematological values, blood glutathione(GSH) as well as bone marrow viability associated with a significant elevation of serum malondialdehyde (MDA). Related to immunological data, tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) also recorded a significant depression. Irradiated animals receiving BM and IL-12 showed significantly elevated body and spleen weights, erythrocytes count (RBCs), hemoglobin content (Hb) and hemotocrit value (Hct %) besides, white blood cells (WBCs)and its differential count, as well as GSH, while MDA was significantly depressed as compared to the irradiated group. Bone marrow viability was significantly increased while IL-6 and TNF-α were normalized. The curative action of IL-12 enforcing significant innate response could trigger and augment adaptive immune response by bone marrow transplantation, hence improving oxidative stress. IL-12 administration is proposed as a complementary strategy to treat radiation-induced path-physiology and trapping free radicals accumulations after irradiation.

Clinical report of an extremely severe bone marrow form of acute radiation sickness

International Nuclear Information System (INIS)

Qiao Jianhui; Yu Changlin; Luo Weidong; Guo Mei; Wang Danhong; Sun Qiyun; Zhang Shi; Zhang Xigang; Li Guang; Niu Wenkai; Chen Jiankui; Li Xiaobing; Ge Feijiao; Ai Huisheng

2007-01-01

Objective: To sum up the experiences from the diagnosis and treatment of patient B subjected to an accidental 60 Co exposure on October 21st, 2004, in Jining, Shandong Province, China. Methods: Radiation dose of B was assessed by analysis of chromosome aberration and microneucleus assay, simulation test of the accident site, autopsy and electron spin resonance (ESR). The ultimate clinical diagnosis was based on analysis of irradiation dose, clinical manifestations and laboratory results. In therapeutical aspects, total environmental protection, HLA-identical allogeneic peripheral blood stem cell transplantation (PBSCT), anti- infection and protection managements of organs were given. Results: Patient B was diagnosed as extremely severe bone marrow form of acute radiation sickness (ARS). HLA-identical allogeneic PBSCT was performed on the patient from his brother on the 7th day after the accident. The hematopoietic recovery began on the 9th day after transplantation. The patient acquired permanent full donor' engraftment without graft versus host disease (GVHD), But the radiation injury was continuing and the patient complicated with polyinfection in lung, and cardiac insufficiency. On the 45th day after the accident, patient B was performed with tracheotomy and maintained ventilation with respirator. On the 75th day after the accident, patient B died of multiple organ failure. Conclusions: Early triage diagnosis and total environmental protection should be performed as soon as possible for extremely severe bone marrow form of ARS. It is very important to perform a successful HLA-identical allogeneic PBSCT, in order to extend the life time of the patient. Multiple organ injuries and infections of bacteria and fungi usually occurred on this kind of patients, so intense measures of anti-infection and protection of multiple organs should be taken. The important and difficult point in the treatment of this kind ARS might be for help the immune-reconstruction and tissue

Bone marrow-derived cells are differentially involved in pathological and physiological retinal angiogenesis in mice

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Zou, He [Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8507 (Japan); Otani, Atsushi, E-mail: otan@kuhp.kyoto-u.ac.jp [Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8507 (Japan); Oishi, Akio; Yodoi, Yuko; Kameda, Takanori; Kojima, Hiroshi; Yoshimura, Nagahisa [Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8507 (Japan)

2010-01-08

Purpose: Bone marrow-derived cells have been shown to play roles in angiogenesis. Although these cells have been shown to promote angiogenesis, it is not yet clear whether these cells affect all types of angiogenesis. This study investigated the involvement of bone marrow-derived cells in pathological and physiological angiogenesis in the murine retina. Materials and methods: The oxygen-induced retinopathy (OIR) model was used as a retinal angiogenesis model in newborn mice. To block the influence of bone marrow-derived cells, the mice were irradiated with a 4-Gy dose of radiation from a {sup 137}Cs source. Irradiation was performed in four different conditions with radio dense 2-cm thick lead disks; (1) H group, the head were covered with these discs to protect the eyes from radiation; (2) A group, all of the body was covered with these discs; (3) N group, mice were completely unshielded; (4) C group, mice were put in the irradiator but were not irradiated. On P17, the retinal areas showing pathological and physiological retinal angiogenesis were measured and compared to the retinas of nonirradiated mice. Results: Although irradiation induced leukocyte depletion, it did not affect the number of other cell types or body weight. Retinal nonperfusion areas were significantly larger in irradiated mice than in control mice (P < 0.05), indicating that physiological angiogenesis was impaired. However, the formation of tuft-like angiogenesis processes was more prominent in the irradiated mice (P < 0.05), indicating that pathological angiogenesis was intact. Conclusions: Bone marrow-derived cells seem to be differentially involved in the formation of physiological and pathological retinal vessels. Pathological angiogenesis in the murine retina does not require functional bone marrow-derived cells, but these cells are important for the formation of physiological vessels. Our results add a new insight into the pathology of retinal angiogenesis and bolster the hypothesis that

Bone marrow-derived cells are differentially involved in pathological and physiological retinal angiogenesis in mice

International Nuclear Information System (INIS)

Zou, He; Otani, Atsushi; Oishi, Akio; Yodoi, Yuko; Kameda, Takanori; Kojima, Hiroshi; Yoshimura, Nagahisa

2010-01-01

Purpose: Bone marrow-derived cells have been shown to play roles in angiogenesis. Although these cells have been shown to promote angiogenesis, it is not yet clear whether these cells affect all types of angiogenesis. This study investigated the involvement of bone marrow-derived cells in pathological and physiological angiogenesis in the murine retina. Materials and methods: The oxygen-induced retinopathy (OIR) model was used as a retinal angiogenesis model in newborn mice. To block the influence of bone marrow-derived cells, the mice were irradiated with a 4-Gy dose of radiation from a 137 Cs source. Irradiation was performed in four different conditions with radio dense 2-cm thick lead disks; (1) H group, the head were covered with these discs to protect the eyes from radiation; (2) A group, all of the body was covered with these discs; (3) N group, mice were completely unshielded; (4) C group, mice were put in the irradiator but were not irradiated. On P17, the retinal areas showing pathological and physiological retinal angiogenesis were measured and compared to the retinas of nonirradiated mice. Results: Although irradiation induced leukocyte depletion, it did not affect the number of other cell types or body weight. Retinal nonperfusion areas were significantly larger in irradiated mice than in control mice (P < 0.05), indicating that physiological angiogenesis was impaired. However, the formation of tuft-like angiogenesis processes was more prominent in the irradiated mice (P < 0.05), indicating that pathological angiogenesis was intact. Conclusions: Bone marrow-derived cells seem to be differentially involved in the formation of physiological and pathological retinal vessels. Pathological angiogenesis in the murine retina does not require functional bone marrow-derived cells, but these cells are important for the formation of physiological vessels. Our results add a new insight into the pathology of retinal angiogenesis and bolster the hypothesis that bone

Low-dose radiation (LDR) induces hematopoietic hormesis: LDR-induced mobilization of hematopoietic progenitor cells into peripheral blood circulation.

Science.gov (United States)

Li, Wei; Wang, Guanjun; Cui, Jiuwei; Xue, Lu; Cai, Lu

2004-11-01

The aim of this study was to investigate the stimulating effect of low-dose radiation (LDR) on bone marrow hematopoietic progenitor cell (HPC) proliferation and peripheral blood mobilization. Mice were exposed to 25- to 100-mGy x-rays. Bone marrow and peripheral blood HPCs (BFU-E, CFU-GM, and c-kit+ cells) were measured, and GM-CSF, G-CSF, and IL-3 protein and mRNA expression were detected using ELISA, slot blot hybridization, and Northern blot methods. To functionally evaluate LDR-stimulated and -mobilized HPCs, repopulation of peripheral blood cells in lethally irradiated recipients after transplantation of LDR-treated donor HPCs was examined by WBC counts, animal survival, and colony-forming units in the recipient spleens (CFUs-S). 75-mGy x-rays induced a maximal stimulation for bone marrow HPC proliferation (CFU-GM and BFU-E formation) 48 hours postirradiation, along with a significant increase in HPC mobilization into peripheral blood 48 to 72 hours postradiation, as shown by increases in CFU-GM formation and proportion of c-kit+ cells in the peripheral mononuclear cells. 75-mGy x-rays also maximally induced increases in G-CSF and GM-CSF mRNA expression in splenocytes and levels of serum GM-CSF. To define the critical role of these hematopoietic-stimulating factors in HPC peripheral mobilization, direct administration of G-CSF at a dose of 300 microg/kg/day or 150 microg/kg/day was applied and found to significantly stimulate GM-CFU formation and increase c-kit+ cells in the peripheral mononuclear cells. More importantly, 75-mGy x-rays plus 150 microg/kg/day G-CSF (LDR/150-G-CSF) produced a similar effect to that of 300 microg/kg/day G-CSF alone. Furthermore, the capability of LDR-mobilized donor HPCs to repopulate blood cells was confirmed in lethally irradiated recipient mice by counting peripheral WBC and CFUs-S. These results suggest that LDR induces hematopoietic hormesis, as demonstrated by HPC proliferation and peripheral mobilization, providing a

Radiation-induced alterations in murine lymphocyte homing patterns. I. Radiolabeling studies

International Nuclear Information System (INIS)

Crouse, D.A.; Feldbush, T.L.; Evans, T.C.

1976-01-01

In vitro x-irradiation of 51 Cr-labeled spleen, lymph node, bone marrow, or thymus cells was found to alter their subsequent in vivo distribution significantly in syngeneic BDF 1 mice. Irradiated cells demonstrated an increased distribution to the liver and a significantly lower retention in the lungs. Cells going to the lymph nodes or Peyer's patches showed a significant exposure-dependent decrease in homing following irradiation. Irradiated lymph node cells homed in greater numbers to the spleen and bone marrow, while irradiated cells from other sources showed no preferential distribution to the same tissues. Sampling host tissues at various times after irradiation and injection did not demonstrate any return to normal patterns of distribution. The alterations in lymphocyte homing observed after in vitro irradiation appear to be due to the elimination of a selective population of lymphocytes or membrane alterations of viable cells, and the detection of these homing changes is in turn dependent upon the relative numbers of various lymphoid subpopulations which are obtained from different cell sources. Radiation-induced alterations in the normal homing patterns of lymphoid cells may thus be of considerable importance in the evaluation of subsequent functional assays in recipient animals

Ionizing radiation induces apoptosis in hematopoietic stem and progenitor cells

International Nuclear Information System (INIS)

Meng, A.; Zhou, D.; Geiger, H.; Zant, G.V.

2003-01-01

The aims of this study was to determine if ionizing radiation (IR) induces apoptosis in hematopoietic stem (HSC) and progenitor cells. Lin-cells were isolated from mouse bone marrow (BM) and pretreated with vehicle or 100 μM z-VAD 1 h prior to exposure to 4 Gy IR. The apoptotic and/or necrotic responses of these cells to IR were analyzed by measuring the annexin V and/or 7-AAD staining in HSC and progenitor populations using flow cytometry, and hematopoietic function of these cells was determined by CAFC assay. Exposure of Lin-cells to IR selectively decreased the numbers of HSC and progenitors in association with an increase in apoptosis in a time-dependent manner. Pretreatment of Lin- cells with z-VAD significantly inhibited IR-induced apoptosis and the decrease in the numbers of HSC and progenitors. However, IR alone or in combination with z-VAD did not lead to a significant increase in necrotic cell death in either HSC or progenitors. In addition, pretreatment of BM cells with z-VAD significantly attenuated IR-induced reduction in the frequencies of day-7, -28 and -35 CAFC. Exposure of HSC and progenitors to IR induces apoptosis. The induction of HSC and progenitor apoptosis contributes to IR-induced suppression of their hematopoietic function

Management of unicameral bone cyst by using freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow.

Science.gov (United States)

Datta, N K; Das, K P; Alam, M S; Kaiser, M S

2014-07-01

Unicameral bone cyst is a common benign bone tumor and most frequent cause of the pathological fracture in children. We have started a prospective study for that treatment of unicameral bone cyst by using freeze dried radiation sterilized bone allograft impregnated with autogenous bone marrow in the department of Orthopaedics, Bangabandhu Sheikh Mujib Medical University (BSMMU) during May 1999 to April 2012. Aim of this study was to see Freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow a satisfactory graft material in the treatment of unicameral bone cyst as well as factors such as patients age, sex, cyst size and site of lesion influence on cyst healing. A total 35 patients of unicameral bone cyst were operated. In this study out of 35 patients, male were 22(62.86%) and female were 13(37.14). Male Female ratio 22:13(1.70:1) Age of the patients ranging from 2 years 6 month to 20 years, mean age 12.18 years more common 11 years to 20 years 29(82.86%) patients. Common bones sites involvements are proximal end of Humerus 20(57.14%), proximal end of Femur 7(20 %), proximal end of Tibia 3(8.57%), Calcanium 2(5.71%), proximal end of Ulna 1(2.86%), shaft of Radius 1(2.86%) and Phalanx 1(2.86%). Final clinical outcome of unicameral bone cyst treated by thorough curettage of cavity and tightly filled with freeze dried radiation sterilized bone allograft impregnate with autogenous bone marrow in which healed (success rate) 88.57% (31) and recurrence rate is 11.43% (4). P value is unicameral bone cyst.

Streptococcal cell wall-induced arthritis and adjuvant arthritis in F344----Lewis and in Lewis----F344 bone marrow chimeras

International Nuclear Information System (INIS)

van Bruggen, M.C.; van den Broek, M.F.; van den Berg, W.B.

1991-01-01

Streptococcal cell wall (SCW)-induced arthritis and adjuvant arthritis (AA) are rat models for chronic, erosive polyarthritis. Both models can be induced in susceptible Lewis rats, whereas F344 rats are resistant. In AA as well as in SCW arthritis, antigen-specific T lymphocytes have been demonstrated to be crucial for chronic disease. In this communication the authors describe their studies to probe the cellular mechanism responsible for the difference in susceptibility of Lewis and F344, using bone marrow chimeras. By transplanting bone marrow cells from F344 into lethally irradiated Lewis recipients, Lewis rats were rendered resistant to SCW arthritis induction. F344 rats reconstituted with Lewis bone marrow, i.e., Lewis----F344 chimeras, develop an arthritis upon SCW injection. For AA comparable results were obtained. These data suggest that both resistance and susceptibility to bacterium-induced chronic arthritis are mediated by hemopoietic/immune cells and that the recipiental environment does not influence the susceptibility to chronic joint inflammation

Radiation dose to trabecular bone marrow stem cells from 3H, 14C and selected α-emitters incorporated in a bone remodeling compartment

International Nuclear Information System (INIS)

Nie Huiling; Richardson, Richard B

2009-01-01

A Monte Carlo simulation of repeated cubic units representing trabecular bone cavities in adult bone was employed to determine absorbed dose fractions evaluated for 3 H, 14 C and a set of α-emitters incorporated within a bone remodeling compartment (BRC). The BRC consists of a well-oxygenated vascular microenvironment located within a canopy of bone-lining cells. The International Commission on Radiological Protection (ICRP) considers that an important target for radiation-induced bone cancer is the endosteum marrow layer adjacent to bone surface where quiescent bone stem cells reside. It is proposed that the active stem cells and progenitor cells located above the BRC canopy, the 'BRC stem cell niche', is a more important radiation-induced cancer target volume. Simulation results from a static model, where no remodeling occurs, indicate that the mean dose from bone and bone surface to the 50 μm quiescent bone stem cell niche, the current ICRP target, was substantially lower (two to three times lower) than that to the narrower and hypoxic 10 μm endosteum for 3 H, 14 C and α-particles with energy range 0.5-10 MeV. The results from a dynamic model indicate that the temporal α-radiation dose to active stem/progenitor cells located in the BRC stem cell niche from the material incorporated in and buried by forming bone was 9- to 111-fold greater than the dose to the quiescent bone stem cell niche. This work indicates that the remodeling portion of the bone surface, rather than the quiescent (endosteal) surface, has the greatest risk of radiation-induced bone cancer, particularly from short-range radiation, due to the elevated dose and the radiosensitizing oxygen effect.

Impact of Lutein Intervention in Mice on the Radiation Induced Clastogenic Changes

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Vidya Vasudeva

2017-10-01

Full Text Available One of the genetic effects of radiation is that it may lead to formation of single or double strand breaks in DNA which can be observed in differentially stained polychromatic or normochromatic erythrocytes (PCE and NCE respectively. In pursuit of finding a natural radioprotector to treat the radiation induced damages; lutein, a carotenoid pigment is one such approach. Swiss albino mice are administered with the compound (lutein/gallic acid/DMSO with respective controls for 15 consecutive days after which they are irradiated. The whole blood is drawn for comet assay and the femur of the leg is removed to flush out the content of the bone marrow in BSA for the micronucleus assay. The comet slides are observed under the fluorescent microscope and the PCE/NCE or micronucleated PCEs or NCEs are scored blindly. Lutein in the present study has effectively reduced the olive moment and the tail moment. However, % DNA in tail has been maintained to normal levels in comparison to its control indicating lesser extent of damage to the genetic material. The percent micronucleated NCE (MnNCE has been decreased in the group treated with lutein prior to radiation. The % MnPCE and the PCE/(PCE + NCE ratio has been increased in all the irradiated groups; however lutein treatment has not drastically increased the formation of micronuclei in comparison to its control. This indicates that lutein shows a protective effect against the radiation induced cytogenetic damages in Swiss albino mice.

The separation of a mixture of bone marrow stem cells from tumor cells: an essential step for autologous bone marrow transplantation

International Nuclear Information System (INIS)

Rubin, P.; Wheeler, K.T.; Keng, P.C.; Gregory, P.K.; Croizat, H.

1981-01-01

KHT tumor cells were mixed with mouse bone marrow to simulate a sample of bone marrow containing metastatic tumor cells. This mixture was separated into a bone marrow fraction and a tumor cell fraction by centrifugal elutriation. Elutriation did not change the transplantability of the bone marrow stem cells as measured by a spleen colony assay and an in vitro erythroid burst forming unit assay. The tumorogenicity of the KHT cells was similarly unaffected by elutriation. The data showed that bone marrow cells could be purified to less than 1 tumor cell in more than 10 6 bone marrow cells. Therefore, purification of bone marrow removed prior to lethal radiation-drug combined therapy for subsequent autologous transplantation appears to be feasible using modifications of this method if similar physical differences between human metastatic tumor cells and human bone marrow cells exist. This possibility is presently being explored

Hypoxia-Induced Mitogenic Factor (HIMF/FIZZ1/RELM?) Recruits Bone Marrow-Derived Cells to the Murine Pulmonary Vasculature

OpenAIRE

Angelini, Daniel J.; Su, Qingning; Kolosova, Irina A.; Fan, Chunling; Skinner, John T.; Yamaji-Kegan, Kazuyo; Collector, Michael; Sharkis, Saul J.; Johns, Roger A.

2010-01-01

Background Pulmonary hypertension (PH) is a disease of multiple etiologies with several common pathological features, including inflammation and pulmonary vascular remodeling. Recent evidence has suggested a potential role for the recruitment of bone marrow-derived (BMD) progenitor cells to this remodeling process. We recently demonstrated that hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELM?) is chemotactic to murine bone marrow cells in vitro and involved in pulmonary vascular remodeling ...

Regulation mechanisms of the FLT3-ligand after irradiation

International Nuclear Information System (INIS)

Prat-Lepesant, M.

2005-06-01

The hematopoietic compartment is one of the most severely damaged after chemotherapy, radiotherapy or accidental irradiations. Whatever its origin, the resulting damage to the bone marrow remains difficult to evaluate. Thus, it would be of great interest to get a biological indicator of residual hematopoiesis in order to adapt the treatment to each clinical situation. Recent results indicated that the plasma Flt3 ligand concentration was increased in patients suffering from either acquired or induced aplasia, suggesting that Flt3 ligand might be useful as a biological indicator of bone marrow status. We thus followed in a mouse model as well as in several clinical situations the variations in plasma Flt3 ligand concentration, after either homogeneous or heterogeneous irradiations. These variations were correlated to the number of hematopoietic progenitors and to other parameters such as duration and depth of pancytopenia. The results indicated that the concentration of Flt3 ligand in the blood reflects the bone marrow status, and that the follow-up of plasma Flt3 ligand concentration could give predictive information about the bone marrow function and the duration and severity of pancytopenia and thrombocytopenia. Nevertheless, the clinical use of Flt3 ligand as a biological indicator of bone marrow damage require the knowledge of the mechanisms regulating the variations in plasma Flt3 ligand concentration. We thus developed a study in the mouse model. The results indicated that the variations in plasma Flt3 ligand variations were not solely due to a balance between its production by lymphoid cells and its consumption by hematopoietic cells. Moreover, we showed that T lymphocytes are not the main regulator of plasma Flt3 ligand concentration as previously suggested, and that other cell types, possibly including bone marrow stromal cells, might be strongly implicated. These results also suggest that the Flt3 ligand is a main systemic regulator of hematopoiesis

Regulation mechanisms of the FLT3-ligand after irradiation; Mecanismes de regulation du FLT3-ligand apres irradiation

Energy Technology Data Exchange (ETDEWEB)

Prat-Lepesant, M

2005-06-15

The hematopoietic compartment is one of the most severely damaged after chemotherapy, radiotherapy or accidental irradiations. Whatever its origin, the resulting damage to the bone marrow remains difficult to evaluate. Thus, it would be of great interest to get a biological indicator of residual hematopoiesis in order to adapt the treatment to each clinical situation. Recent results indicated that the plasma Flt3 ligand concentration was increased in patients suffering from either acquired or induced aplasia, suggesting that Flt3 ligand might be useful as a biological indicator of bone marrow status. We thus followed in a mouse model as well as in several clinical situations the variations in plasma Flt3 ligand concentration, after either homogeneous or heterogeneous irradiations. These variations were correlated to the number of hematopoietic progenitors and to other parameters such as duration and depth of pancytopenia. The results indicated that the concentration of Flt3 ligand in the blood reflects the bone marrow status, and that the follow-up of plasma Flt3 ligand concentration could give predictive information about the bone marrow function and the duration and severity of pancytopenia and thrombocytopenia. Nevertheless, the clinical use of Flt3 ligand as a biological indicator of bone marrow damage require the knowledge of the mechanisms regulating the variations in plasma Flt3 ligand concentration. We thus developed a study in the mouse model. The results indicated that the variations in plasma Flt3 ligand variations were not solely due to a balance between its production by lymphoid cells and its consumption by hematopoietic cells. Moreover, we showed that T lymphocytes are not the main regulator of plasma Flt3 ligand concentration as previously suggested, and that other cell types, possibly including bone marrow stromal cells, might be strongly implicated. These results also suggest that the Flt3 ligand is a main systemic regulator of hematopoiesis

Role of bone marrow-derived CD11c+ dendritic cells in systolic overload-induced left ventricular inflammation, fibrosis and hypertrophy.

Science.gov (United States)

Wang, Huan; Kwak, Dongmin; Fassett, John; Liu, Xiaohong; Yao, Wu; Weng, Xinyu; Xu, Xin; Xu, Yawei; Bache, Robert J; Mueller, Daniel L; Chen, Yingjie

2017-05-01

Inflammatory responses play an important role in the development of left ventricular (LV) hypertrophy and dysfunction. Recent studies demonstrated that increased T-cell infiltration and T-cell activation contribute to LV hypertrophy and dysfunction. Dendritic cells (DCs) are professional antigen-presenting cells that orchestrate immune responses, especially by modulating T-cell function. In this study, we investigated the role of bone marrow-derived CD11c + DCs in transverse aortic constriction (TAC)-induced LV fibrosis and hypertrophy in mice. We observed that TAC increased the number of CD11c + cells and the percentage of CD11c + MHCII + (major histocompatibility complex class II molecule positive) DCs in the LV, spleen and peripheral blood in mice. Using bone marrow chimeras and an inducible CD11c + DC ablation model, we found that depletion of bone marrow-derived CD11c + DCs significantly attenuated LV fibrosis and hypertrophy in mice exposed to 24 weeks of moderate TAC. CD11c + DC ablation significantly reduced TAC-induced myocardial inflammation as indicated by reduced myocardial CD45 + cells, CD11b + cells, CD8 + T cells and activated effector CD8 + CD44 + T cells in LV tissues. Moreover, pulsing of autologous DCs with LV homogenates from TAC mice promoted T-cell proliferation. These data indicate that bone marrow-derived CD11c + DCs play a maladaptive role in hemodynamic overload-induced cardiac inflammation, hypertrophy and fibrosis through the presentation of cardiac self-antigens to T cells.

Radiation-induced adaptive response in the intact mouse

International Nuclear Information System (INIS)

Yonezawa, Morio

2009-01-01

The author and coworkers have revealed that radiation adaptive response (AR) is seen also in the bone marrow of the intact mouse, of which details are described here. First, SPF ICR mice were pre-irradiated (PI) with 0-0.1 Gy of X-ray and after 2 months, subsequently irradiated (SI) with 7.75 Gy. Survival rates at 30 days after SI were about 14% in mice with PI 0-0.025 Gy whereas 40% or more in animals with PI 0.05-0.1 Gy: bone marrow death was found significantly suppressed in this effective PI dose range. The death 2 weeks after SI was found also inhibited at PI 0.3-0.5 Gy. Second, PI doses and interval between PI and SI for acquiring the radio-resistance (RR) were studied and third, the PI 0.3-0.5 Gy with SI 8.0 Gy at 9-17 days later revealed that regional PI of the head (central nervous system) was found unnecessary for RR and of abdomen (systems of hemopoiesis, immunity and digestion), essential. Fourth, strain difference of RR was shown by the fact that RR was observed only in C57BL mouse as well, but neither in BALB/c nor C3H strain. Next, at 12 days after SI 4.25-6.75 Gy (PI 0.5 Gy at 14 days before), mouse spleen cells were subjected to colony formation analysis by counting the endogenous hemopoietic stem cells, which revealed that those cells were increased to about 5 times by PI. Suppression of SI-induced hemorrhage was found in mice with PI by the decreased fecal hemoglobin content. Finally, AR was similarly studied in p53 +/+ and its knockout C57BL mice and was not found in the latter animal, indicating the participation of p53 in AR of the intact mouse. Elucidation of AR mechanisms in the intact animal seems to require somewhat different aspect from that in cells. The results were controvertible to the general concept that radiation risk is proportional to cumulative dose, suggesting that low dose radiation differs from high dose one in biological effect. (K.T.)

Multiple myeloma among atomic bomb survivors in Hiroshima and Nagasaki, 1950-76: relationship to radiation dose absorbed by marrow

International Nuclear Information System (INIS)

Ichimaru, M.; Ishimaru, T.; Mikami, M.; Matsunaga, M.

1982-01-01

The relationship between atomic bomb exposure and the incidence of multiple myeloma has been examined in a fixed cohort of atomic bomb survivors and controls in the life-span study sample for Hiroshima and Nagasaki. From October 1950 to December 1976, 29 cases of multiple myeloma were confirmed in this sample. Our analysis shows that the standardized relative risk (RR) adjusted for city, sex, and age at the time of bombings (ATB) increased with marrow-absorbed radiation dose. The increased RR does not appear to differ between cities or sexes and is demonstrable only for those survivors whose age ATB was between 20 and 59 years. The estimated risk in these individuals is approximately 0.48 cases/million person-years/rad for bone marrow total dose. This excess risk did not become apparent in individuals receiving 50 rad or more in marrow total dose until 20 years or more after exposure

Radiation responses of hematopoietic-cells and inducing acute myeloid leukemia

International Nuclear Information System (INIS)

Ojima, Mitsuaki; Hirouchi, Tokuhisa

2016-01-01

Leukemia has consistently held the interest of researchers from the beginning of radiation carcinogenesis. One of the major reasons for this interest is the availability of several strains of mice that develop leukemia following radiation exposure after a short latency period that resemble those found in A-Bomb survivors. Previous studies have shown that rAML (Radiation-induced Acute Myeloid Leukemia) in mice show inactivation of Sfpi1 gene and a hemizygous deletion in chromosome 2. Leukemic stem cells in murine rAML have been reported to share some characteristics with common myeloid progenitor cells. In this review, we will discuss the possible mechanisms in the development of rAML stem cells, focusing on the alterations found in the leukemic stem cells and as well as the environment in which these leukemic stem cells are developed, such cytokine expression, as Well as alterations that may be found in other cells residing in the bone marrow. Hematopoietic stem cells respond to radiation exposure both as a single cell and as a part of the differentiating hematopoietic tissue for several months prior to its transformation to a rAML stem cell. It is however unclear how these 2 responses contribute to the development of the rAML stem cell. This review covers previous reports and examines the development of the rAML stem cell in detail. (author)

Bone marrow reconstitution of immune responses following irradiation in the leopard frog, Rana pipiens

International Nuclear Information System (INIS)

Ramirez, J.A.; Wright, R.K.; Cooper, E.L.

1983-01-01

The bone marrow of Rana is an important source of cells capable of maintaining individual viability, responding to Concanavalin A (Con A) and producing PFC against sheep erythrocyte (SRBC) antigens. Frog marrow is more effective than the spleen in maintaining life. Radiation destroys the ability of frogs to respond to SRBC immunization (lack of bone marrow and spleen PFC, serum antibody) and bone marrow/spleen cells to respond to Con A, i.e., bone marrow and spleen contain radiation-sensitive cells. Shielding one hind leg during irradiation leads to reconstitution of bone marrow/spleen PFC responses, antibody synthesis and individual viability. Our results suggest that bone marrow is: a) the source of stem cells, and b) the source of mature T- and B- lymphocytes that can recirculate within the immune system

Bone marrow-derived fibroblast growth factor-2 induces glial cell proliferation in the regenerating peripheral nervous system

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Ribeiro-Resende Victor

2012-07-01

Full Text Available Abstract Background Among the essential biological roles of bone marrow-derived cells, secretion of many soluble factors is included and these small molecules can act upon specific receptors present in many tissues including the nervous system. Some of the released molecules can induce proliferation of Schwann cells (SC, satellite cells and lumbar spinal cord astrocytes during early steps of regeneration in a rat model of sciatic nerve transection. These are the major glial cell types that support neuronal survival and axonal growth following peripheral nerve injury. Fibroblast growth factor-2 (FGF-2 is the main mitogenic factor for SCs and is released in large amounts by bone marrow-derived cells, as well as by growing axons and endoneurial fibroblasts during development and regeneration of the peripheral nervous system (PNS. Results Here we show that bone marrow-derived cell treatment induce an increase in the expression of FGF-2 in the sciatic nerve, dorsal root ganglia and the dorsolateral (DL region of the lumbar spinal cord (LSC in a model of sciatic nerve transection and connection into a hollow tube. SCs in culture in the presence of bone marrow derived conditioned media (CM resulted in increased proliferation and migration. This effect was reduced when FGF-2 was neutralized by pretreating BMMC or CM with a specific antibody. The increased expression of FGF-2 was validated by RT-PCR and immunocytochemistry in co-cultures of bone marrow derived cells with sciatic nerve explants and regenerating nerve tissue respectivelly. Conclusion We conclude that FGF-2 secreted by BMMC strongly increases early glial proliferation, which can potentially improve PNS regeneration.

Chronic restraint-induced stress has little modifying effect on radiation hematopoietic toxicity in mice

International Nuclear Information System (INIS)

Wang, Bing; Tanaka, Kaoru; Katsube, Takanori; Ninomiya, Yasuharu; Vares, Guillaume; Nakajima, Tetsuo; Nenoi, Mitsuru; Liu Qiang; Morita, Akinori

2015-01-01

Both radiation and stresses cause detrimental effects on humans. Besides possible health effects resulting directly from radiation exposure, the nuclear plant accident is a cause of social psychological stresses. A recent study showed that chronic restraint-induced stresses (CRIS) attenuated Trp53 functions and increased carcinogenesis susceptibility of Trp53-heterozygous mice to total-body X-irradiation (TBXI), having a big impact on the academic world and a sensational effect on the public, especially the residents living in radioactively contaminated areas. It is important to investigate the possible modification effects from CRIS on radiation-induced health consequences in Trp53 wild-type (Trp53wt) animals. Prior to a carcinogenesis study, effects of TBXI on the hematopoietic system under CRIS were investigated in terms of hematological abnormality in the peripheral blood and residual damage in the bone marrow erythrocytes using a mouse restraint model. Five-week-old male Trp53wt C57BL/6J mice were restrained 6 h per day for 28 consecutive days, and TBXI (4 Gy) was given on the 8th day. Results showed that CRIS alone induced a marked decrease in the red blood cell (RBC) and the white blood cell (WBC) count, while TBXI caused significantly lower counts of RBCs, WBCs and blood platelets, and a lower concentration of hemoglobin regardless of CRIS. CRIS alone did not show any significant effect on erythrocyte proliferation and on induction of micronucleated erythrocytes, whereas TBXI markedly inhibited erythrocyte proliferation and induced a significant increase in the incidences of micronucleated erythrocytes, regardless of CRIS. These findings suggest that CRIS does not have a significant impact on radiation-induced detrimental effects on the hematopoietic system in Trp53wt mice. (author)

Mutations in the thrombopoietin receptor, Mpl, in children with congenital amegakaryocytic thrombocytopenia

NARCIS (Netherlands)

van den Oudenrijn, S.; Bruin, M.; Folman, C. C.; Peters, M.; Faulkner, L. B.; de Haas, M.; von dem Borne, A. E.

2000-01-01

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder of undefined aetiology. The disease presents with severe thrombocytopenia and absence of megakaryocytes in the bone marrow. Furthermore, CAMT patients may develop bone marrow aplasia. To obtain more insight into the mechanism

Radiation-induced bystander effects in cultured human stem cells.

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Mykyta V Sokolov

2010-12-01

Full Text Available The radiation-induced "bystander effect" (RIBE was shown to occur in a number of experimental systems both in vitro and in vivo as a result of exposure to ionizing radiation (IR. RIBE manifests itself by intercellular communication from irradiated cells to non-irradiated cells which may cause DNA damage and eventual death in these bystander cells. It is known that human stem cells (hSC are ultimately involved in numerous crucial biological processes such as embryologic development; maintenance of normal homeostasis; aging; and aging-related pathologies such as cancerogenesis and other diseases. However, very little is known about radiation-induced bystander effect in hSC. To mechanistically interrogate RIBE responses and to gain novel insights into RIBE specifically in hSC compartment, both medium transfer and cell co-culture bystander protocols were employed.Human bone-marrow mesenchymal stem cells (hMSC and embryonic stem cells (hESC were irradiated with doses 0.2 Gy, 2 Gy and 10 Gy of X-rays, allowed to recover either for 1 hr or 24 hr. Then conditioned medium was collected and transferred to non-irradiated hSC for time course studies. In addition, irradiated hMSC were labeled with a vital CMRA dye and co-cultured with non-irradiated bystander hMSC. The medium transfer data showed no evidence for RIBE either in hMSC and hESC by the criteria of induction of DNA damage and for apoptotic cell death compared to non-irradiated cells (p>0.05. A lack of robust RIBE was also demonstrated in hMSC co-cultured with irradiated cells (p>0.05.These data indicate that hSC might not be susceptible to damaging effects of RIBE signaling compared to differentiated adult human somatic cells as shown previously. This finding could have profound implications in a field of radiation biology/oncology, in evaluating radiation risk of IR exposures, and for the safety and efficacy of hSC regenerative-based therapies.

Radiation-induced thermoacoustic imaging

International Nuclear Information System (INIS)

Bowen, T.

1984-01-01

This invention provides a new technique for obtaining information non-invasively on the composition and structures of a material or body by detecting radiation-induced thermoacoustic image features. This is accomplished by utilizing the acoustic wave generated by sudden thermal stress. The sudden thermal stress is induced by a pulse of radiation which deposits energy causing a rapid, but very small, rise of temperature (typically, ΔT approximately 10sup(-6) - 10sup(-5) deg C). The radiation may be ionizing radiation, such as high energy electrons, photons (x-rays), neutrons, or other charged particles or it may be non-ionizing radiation, such as R.F. and microwave electromagnetic radiation and ultrasonic radiation. The choice of radiation depends on the nature of the body to be imaged and the type of information desired

Late health effects of chronic radiation exposure of bone marrow

Energy Technology Data Exchange (ETDEWEB)

Yarmoshenko, Ilia V.; Malinovsky, Georgy P.; Konshina, Lidia G.; Zhukovsky, Michael V. [Institute of Industrial Ecology UB RAS, 620219, 20, Sophy Kovalevskoy St., Ekaterinburg (Russian Federation); Tuzankina, Irina A. [Institute of Immunology and Physiology UB RAS, 620049, 106, Pervomayskaya St., Ekaterinburg (Russian Federation)

2014-07-01

infectious etiology, which are unexpected due to low doses absorbed in those organs and tissues. To analyze the unexpected results recent findings on strong attributability of stomach, liver and cervix cancers to bacterial and viral infections was taken into account. According to IARC, stomach cancer relative risk associated with helicobacter pillory is 5.6, liver cancer relative risks associated with HBV and HCV are 23 and 17 respectively, cervix cancer relative risk associated with HPV is >100. At the same time association of lung cancer, colon cancer and some other common malignancies with infections is either not established or of low significance. To explain observed effects we suggested that excess mortality due to cancer and non-cancer diseases of infectious etiology is associated with radiation exposure of bone marrow due to Sr-90. Irradiation of hematopoietic stem cells and progenitor cells damages hematopoiesis and suppresses the immune response. Secondary immune deficiency induced by chronic radiation increases susceptibility to the bacterial and viral infections. Such late effect of radiation exposure can be considered within the concept of deterministic tissue reactions. (Under support of UB RAS project 12-P-2-1033). (authors)

Radiation-Induced Neoplasms in Beagles after Administrations of {sup 90}Sr and {sup 226}Ra

Energy Technology Data Exchange (ETDEWEB)

Goldman, M.; Dungworth, D. L.; Bulgin, M. S.; Rosenblatt, L. S.; Richards, W. P.C.; Bustad, L. K. [Radiobiology Laboratory and Department of Veterinary Pathology, University of California, Davis, CA (United States)

1969-11-15

The comparative carcinogenic efficiency of two bone-seeking radionuclides is under study in a colony of several hundred beagles. The toxicity of internally deposited alpha emitters ({sup 226}Ra and its daughters) and of beta irradiation ({sup 90}Sr) at comparable dosage rates indicates marked differences in site of appearance and mode of action in litters studied up to 7 years of age. Radiation carcinogenesis in beagles exposed to {sup 90}Sr daily from midgestation to adulthood (1.5 yr) is at present confined to dogs fed 4 {mu}Ci {sup 90}Sr/d or higher. The 20 cases constitute a spectrum of myeloproliferative disorders characterized by terminal anaemias, and ranging from myeloid metaplasia to granulocytic leukaemia. Continuous high-level {sup 90}Sr irradiation to bone and marrow from early life onward causes a thickened hypocellular bone ('pachyostosis'), some instances of myelofibrosis, and persistent mild leukopenia on which the final spectrum of terminal disoideis is superimposed. In contrast, up to 100 {mu}Cl {sup 226}Ra given intravenously (8 equally spaced injections at 14 to 18 months of age) to young adults is not a potent marrow cell carcinogen. The higher LET, shorter-range alpha particles are efficient in inducing bone cancers (14 cases) and skeletal lesions similar to those documented in watch-dial luminizers exposed to {sup 226}Ra in the early 1900's. The incidence of haematopoietic and skeletal neoplasms observed is dose-rate related, and the morphologic characteristics have several analogues in human cancer. The use of identically treated litters rather than individuals affords additional opportunity to study possible familial factors in the distribution of the neoplasms. Pathogenic evaluation at this juncture strongly indicates that continued bone and marrow irradiation in early life is more likely to induce haematopoietic neoplasms than is skeletal irradiation starting in young adulthood, which induces osseous neoplasms. (author)

Prenatal ultrasonography of trisomy 18 with radial aplasia: A case report

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Lee, Jee Young; Lee, Yeon Hee [Dankook University College of Medicine, Seoul (Korea, Republic of)

2002-06-15

Trisomy 18 (Edward syndrome) is the second most common chromosomal anomaly of the autosomal trisomy. Prenatal diagnosis of trisomy 18 is extremely important because of the complex malformations and lethal prognosis. Prenatal sonographic findings at 17 weeks of gestation showing radial aplasia with upper limb contracture, omphalocele, and suspicious esophageal atresia suggested the diagnosis and led to amniocentesis. Karyotyping revealed trisomy 18 (47 XX, +18, and characteristic autopsy findings were identified. We report a case of prenatally diagnosed trisomy 18 with a review of literatures.

Prenatal ultrasonography of trisomy 18 with radial aplasia: A case report

International Nuclear Information System (INIS)

Lee, Jee Young; Lee, Yeon Hee

2002-01-01

Trisomy 18 (Edward syndrome) is the second most common chromosomal anomaly of the autosomal trisomy. Prenatal diagnosis of trisomy 18 is extremely important because of the complex malformations and lethal prognosis. Prenatal sonographic findings at 17 weeks of gestation showing radial aplasia with upper limb contracture, omphalocele, and suspicious esophageal atresia suggested the diagnosis and led to amniocentesis. Karyotyping revealed trisomy 18 (47 XX, +18, and characteristic autopsy findings were identified. We report a case of prenatally diagnosed trisomy 18 with a review of literatures.

Effects of Zinc Compound on Body Weight and Recovery of Bone Marrow in Mice Treated with Total Body Irradiation

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Ming-Yii Huang

2007-09-01

Full Text Available This study aimed to investigate if zinc compound would have effects on body weight loss and bone marrow suppression induced by total body irradiation (TBI. ICR mice were divided randomly into two groups and treated with test or control compounds. The test compound contained zinc (amino acid chelated with bovine prostate extract, and the control was reverse osmosis pure water (RO water. One week after receiving the treatment, mice were unirradiated, or irradiated with 6 or 3 Gy by 6MV photon beams to the total body. Body weight changes were examined at regular intervals. Three and 5 weeks after the radiation, animals were sacrificed to examine the histologic changes in the bone marrow. Lower body weight in the period of 1-5 weeks after radiation and poor survival rate were found after the 6 Gy TBI, as compared with the 3 Gy groups. The median survival time after 6 Gy and 3 Gy TBI for mice given the test compound were 26 and 76 days, respectively, and the corresponding figures were 14 and 70 days, respectively, for mice given the control compound (p < 0.00001. With zinc supplement, the mean body weight in mice which received the same dose of radiation was 7-8 g heavier than in the water-supplement groups during the second and third weeks (p < 0.05. Hence, there was no statistically significant difference in survival rate between zinc and water supplement in mice given the same dose of irradiation. Histopathologically there was less recovery of bone marrow cells in the 6Gy groups compared with the 3Gy groups. In the 3 Gy water-supplement group, the nucleated cells and megakaryocytes were recovered in the fifth week when recovery was still not seen in the 6Gy group. With zinc supplement, these cells were recovered in the third week. In this study, we found that zinc is beneficial to body weight in mice treated with TBI. Histologic examination of bone marrow showed better recovery of bone marrow cells in groups of mice fed with zinc. This study

On kinetic study of blood cells and bone marrow under fractionated irradiation

International Nuclear Information System (INIS)

Teterina, V.I.

1977-01-01

To study the changes in the cellular composition of bone marrow during irradiation experiments on the guinea pigs have been carried out. Animals were subjected to fractionated irradiation; daily dose of 12 rad, total doses of 250, 500, 750, 1000 and 1500 rad, total duration of radiation of 1,2,3,4 and 6 monts. Experiments have shown that with small levels of total doses of the ionizing radiation haemopoiesis in the bone marrow reached its maximum. This led to suppression of anaemia and profound leukaemia in the peripheral blood. With the increase of total doses phase of insufficient compensation of harmful effects of radiation has been reached, which with continuing radiation may lead to the exhaustion of reserve possibilities of bone marrow and to the development of pancytopenia

Uterovaginal Anastomosis for Cases of Cryptomenorrhea Due to Cervical Atresia with Vaginal Aplasia: Benefits and Risks.

Science.gov (United States)

Zayed, M; Fouad, R; Elsetohy, K A; Hashem, A T; AbdAllah, A A; Fathi, A I

2017-12-01

The objective of this study was to assess short-term benefits and risks of utero-vaginal anastomosis done for cases of cryptomenorrhea due to cervical atresia with vaginal aplasia. Prospective study. Surgical procedures were done between December 2013 and September 2015 at the department of Obstetrics and Gynecology, Cairo University Hospital. Five patients who had cryptomenorrhea due to cervical atresia associated with vaginal aplasia were included. Utero-vaginal anastomoses were performed in 2 stages; a stage of McIndoe vaginoplasty and a stage of excision of the atretic cervical tissue and anastomosing the uterus to the neovagina. Follow-up was done by gynecological and ultrasound examination in a duration ranged from 12 to 36 months. Occurrence of regular menstrual flow and relief of the severe cyclic pain. All patients had relief of the severe cyclic pain. Four patients had regular menstrual flow. One patient developed occlusion of the track after 1 year and needed dilatation once. Three patients developed low vaginal stenosis without occlusion of the track. One patient had rectal injury repaired without causing postoperative morbidity. Uterovaginal anastomosis is a promising conservative management option for cervical atresia with vaginal aplasia, which has benefits but is not free of risks. Long-term follow-up is still needed to judge its feasibility. We recommend performing McIndoe vaginoplasty as a starting stage before the anastomosis preferably in a separate setting. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Bone marrow contribution to eosinophilic inflammation

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Denburg Judah A

1997-01-01

Full Text Available Allergen-induced bone marrow responses are observable in human allergic asthmatics, involving specific increases in eosinophil-basophil progenitors (Eo/B-CFU, measured either by hemopoietic assays or by flow cytometric analyses of CD34-positive, IL-3Ralpha-positive, and/or IL-5-responsive cell populations. The results are consistent with the upregulation of an IL-5-sensitive population of progenitors in allergen-induced late phase asthmatic responses. Studies in vitro on the phenotype of developing eosinophils and basophils suggest that the early acquisition of IL-5Ralpha, as well as the capacity to produce cytokines such as GM-CSF and IL-5, are features of the differentiation process. These observations are consistent with findings in animal models, indicating that allergen-induced increases in bone marrow progenitor formation depend on hemopoietic factor(s released post-allergen. The possibility that there is constitutive marrow upregulation of eosinophilopoiesis in allergic airways disease is also an area for future investigation.

Functional analysis of single amino-acid mutations in the thrombopoietin-receptor Mpl underlying congenital amegakaryocytic thrombocytopenia

NARCIS (Netherlands)

Tijssen, Marloes R.; di Summa, Franca; van den Oudenrijn, Sonja; Zwaginga, Jaap Jan; van der Schoot, C. Ellen; Voermans, Carlijn; de Haas, Masja

2008-01-01

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare disorder that presents with severe thrombocytopenia and absence of megakaryocytes in the bone marrow. The disease may develop into bone marrow aplasia. Genetic defects in the gene encoding the thrombopoietin (Tpo) receptor, MPL, are the

Efficient natural defense mechanisms against Listeria monocytogenes in T and B cell-deficient allogeneic bone marrow radiation chimeras. Preactivated macrophages are the main effector cells in an early phase after bone marrow transfer

International Nuclear Information System (INIS)

Roesler, J.; Groettrup, E.B.; Baccarini, M.; Lohmann-Mattes, M.L.

1989-01-01

Radiation chimeras in the early phase after bone marrow transplantation are a good model to study the efficiency of the body's nonspecific defense system represented by macrophages (M phi), polymorphonuclear cells (PMN), and NK cells. These cell types are present in large numbers in spleen and liver at that time, whereas the specific immune system represented by T and B cells is functionally deficient. We previously reported enhanced activities in vitro of M phi (and PMN) from recipient animals in an early phase after allogeneic bone marrow transfer. We here demonstrate that these activities result in enhanced spontaneous resistance against Listeria monocytogenes in vivo: CFU of L. monocytogenes in spleen and liver 48 h after infection were about 1 or 2 to 4 log steps less than in untreated control mice of donor or host haplotype. This enhanced resistance decreased over the 4-mo period after marrow transfer. Preactivated M phi were identified as the most important effector cells. Isolated from spleen and peritoneal cavity, they performed enhanced killing of phagocytosed Listeria. Such preactivated M phi occurred in recipient animals after transfer of allogeneic but not of syngeneic bone marrow. The precise mechanism of M phi activation in the allogeneic radiation chimera in the complete absence of any detectable T cell function is not clear at present. However, these preactivated M phi display an important protective effect against L. monocytogenes: chimeras could eliminate Listeria without acquisition of positive delayed-type sensitivity when infected with 10(3) bacteria. An inoculum of 5 . 10(3) L. monocytogenes resulted either in prolonged survival compared with normal mice of the recipient haplotype or in definitive survival accompanied by a positive delayed-type sensitivity

A correlative study on the frequencies of radiation-induced chromosome aberrations in somatic and germ cells of mammals

International Nuclear Information System (INIS)

Buul, P.P.W. van

1976-01-01

A series of investigations on the correlation between the frequencies of radiation-induced chromosome aberrations in somatic and germ cells of mouse and rhesus monkey is described. In the mouse the induction of reciprocal translocations in bone-marrow cells was compared with that in spermatogonia (as scored in the descending spermatocytes). In the rhesus monkey frequencies of radiation-induced chromosome aberrations in spermatogonia and peripheral blood lymphocytes were studied. Furthermore the effect of multigeneration irradiation (69 generations with 200 rads X-rays) on the sensitivity for translocation induction in spermatogonia of male mice was studied. Frequencies of dicentric chromosomes and chromosomal deletions in cultured peripheral blood lymphocytes of 5 different types of mice were determined following in vitro irradiation with doses of 100 and/or 200 rad X-rays. To obtain more insight into the processes underlying translocation induction in spermatogonia of the mouse, fractionation experiments were conducted

MRI of the marrow in the paediatric skeleton

International Nuclear Information System (INIS)

Foster, K.; Chapman, S.; Johnson, K.

2004-01-01

Magnetic resonance imaging (MRI) has greatly advanced evaluation of marrow diseases of the paediatric skeleton. As with many other aspects of paediatric radiology it is important to recognize the normal variations in the appearance of the marrow that occur in the growing child. These normal variations need to be differentiated from diseases and conditions that affect the marrow. This review describes the normal changes that occur in children with age, and the appearances of the pathological changes seen in infection, infiltration, haematological disorders, transplantation and radiation therapy

Gender difference in the neuroprotective effect of rat bone marrow mesenchymal cells against hypoxia-induced apoptosis of retinal ganglion cells.

Science.gov (United States)

Yuan, Jing; Yu, Jian-Xiong

2016-05-01

Bone marrow mesenchymal stem cells can reduce retinal ganglion cell death and effectively prevent vision loss. Previously, we found that during differentiation, female rhesus monkey bone marrow mesenchymal stem cells acquire a higher neurogenic potential compared with male rhesus monkey bone marrow mesenchymal stem cells. This suggests that female bone marrow mesenchymal stem cells have a stronger neuroprotective effect than male bone marrow mesenchymal stem cells. Here, we first isolated and cultured bone marrow mesenchymal stem cells from female and male rats by density gradient centrifugation. Retinal tissue from newborn rats was prepared by enzymatic digestion to obtain primary retinal ganglion cells. Using the transwell system, retinal ganglion cells were co-cultured with bone marrow mesenchymal stem cells under hypoxia. Cell apoptosis was detected by flow cytometry and caspase-3 activity assay. We found a marked increase in apoptotic rate and caspase-3 activity of retinal ganglion cells after 24 hours of hypoxia compared with normoxia. Moreover, apoptotic rate and caspase-3 activity of retinal ganglion cells significantly decreased with both female and male bone marrow mesenchymal stem cell co-culture under hypoxia compared with culture alone, with more significant effects from female bone marrow mesenchymal stem cells. Our results indicate that bone marrow mesenchymal stem cells exert a neuroprotective effect against hypoxia-induced apoptosis of retinal ganglion cells, and also that female cells have greater neuroprotective ability compared with male cells.

Intracranial carotid anastomosis and partial aplasia of an internal carotid artery

International Nuclear Information System (INIS)

Huber, G.

1980-01-01

A rare arterial anastomosis between the right and left interal carotid arteries at the base at the skull, with aplasia of the cervical part of the left internal carotid artery is reported. The case is unusual because, in addition to the vascular anomaly of the carotid artery, there is an aneurysm of the anterior communicating artery and bilateral renal cysts. The condition is a complex malformation syndrome caused by defective regression of the third branchial artery. Because of the characteristic angiographic aspects such a case should be called transverse carotid anastomosis. (orig.)

Intracranial carotid anastomosis and partial aplasia of an internal carotid artery

Energy Technology Data Exchange (ETDEWEB)

Huber, G.

1980-12-01

A rare arterial anastomosis between the right and left internal carotid arteries at the base at the skull, with aplasia of the cervical part of the left internal carotid artery is reported. The case is unusual because, in addition to the vascular anomaly of the carotid artery, there is an aneurysm of the anterior communicating artery and bilateral renal cysts. The condition is a complex malformation syndrome caused by defective regression of the third branchial artery. Because of the characteristic angiographic aspects such a case should be called transverse carotid anastomosis.

Pure Red Cell Aplasia and Hypogammaglobulinemia in a Patient with Thymoma

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Chen-Sung Lin

2009-01-01

Full Text Available Both pure red cell aplasia (PRCA and hypogammaglobulinemia are rarer conditions than myasthenia gravis (MG in thymoma patients. Several articles have discussed the relation between PRCA and thymoma or hypogammaglobulinemia and thymoma, and their proper treatments. Instances of both PRCA and hypogammaglobulinemia in a thymoma patient are few and reported sporadically in the literature. We discuss a 46-year-old woman with thymoma and simultaneous PRCA and hypogammaglobulinemia who achieved complete remission from PRCA after perioperative steroid administration and extended thymectomy, and review the literature.

A comparative study on the frequencies of radiation-induced chromosome aberrations in the somatic and germ cells in mouse and monkey

International Nuclear Information System (INIS)

Sobels, F.H.

1976-06-01

Two systems were mainly used for studying the relationship between radiation induced chromosome aberration frequencies in somatic and germ cells. The first consists of reciprocal translocation induced in bone-marrow cells of mice compared to reciprocal translocation induced spermatogonia (scored in descending spermatocytes) of the same mice. Dose-response curves for induced aberrations in both cell types (0-100-200-300-400-500 and 600 R X-rays) and dose rate effects indicated that (130-1.92-0.0287 R/min) of a 400 R γ-ray exposure of the two cell types mitotically dividing germ cells respond to radiation similarly to mitotic dividing germ cells. Clonal proliferation or selective elimination of aberration-carrying cells, and other post-irradiation factors can, however, cause great differences in absolute aberration frequencies. A similar study was attempted, using the rhesus monkey as a second system. Its bone-marrow cells were proved unsuitable for induced reciprocal translocations. Stimulated peripheral blood lymphocytes were studied instead. Following 100, 200 and 300 R of X-rays, the frequencies of induced dicentric chromosomes were compared to those of induced reciprocal translocations in spermatogonia. Human peripheral blood was studied similarly. It was concluded that: (a) The absolute frequencies of chromosome aberrations in somatic and germ cells of the rhesus monkey are low compared to most other mammalian species. (b) The ratio between dicentric frequencies and reciprocal translocation frequencies at 100 R and 200 R differed significantly from 4:1 reported for mouse and Chinese hamster and 2:1 for marmoset and man. (c) Although the numbers of 'effective chromosome arms' in man and rhesus monkey are similar (81 vs 83), the rhesus monkey showed at all doses a lower rate of induction of dicentrics in blood lymphocytes than man, reaching statistical significance at the 300 R level

Bone--bone marrow interactions

International Nuclear Information System (INIS)

Patt, H.M.

1976-01-01

Within medullary cavities, blood formation tends to be concentrated near bone surfaces and this raises interesting questions about hematopoietic consequences of radionuclide fixation in osseous tissue. Thus, it may be important, on the one hand, to consider the medullary radiation dose distribution as well as total marrow dose from bone-bound radioelements and, on the other, to inquire about possible hematopoietic implications of radiation damage to endosteal surfaces per se. The reasons for this are discussed

Modulation of radiation induced DNA damage by natural products in hemopoietic tissue of mice

International Nuclear Information System (INIS)

Jayakumar, S.; Bhilwade, H.N.; Chaubey, R.C.

2014-01-01

Ionizing radiation is known to induce oxidative stress through generation of ROS leading to a variety of DNA lesions. However, the most dangerous DNA lesions which are responsible for the origin of lethal effects, mutagenesis, genomic instability and carcinogenesis are the DSBs. During recent years efforts are being made to identify phytochemicals, antioxidants or neutraxeuticals which can reduce harmful effect of radiation during accidental exposure or prevent normal tissue injury during radiotherapy. In the present study, we have investigated the radioprotective role of curcumin, a dietary antioxidant, taurine, malabaricone-C, and umbelliferone, for their radioprotective properties in hemopoietic cells of mice. Groups of mice-were fed 1% of curcumin in diet for three weeks. Similarly other groups of mice were injected i.p. with 50 mg/kg body weight of taurine for five consecutive days. After the completion of the treatment mice pre-treated with curcumin and taurine were exposed to 3 Gy of gamma rays. Malabaricone-C was tested for its radiomodulation potential in vitro, in spleenocytes of mouse. Spleenocytes were isolated and treated with different concentrations (0.5-25 ìM) of malabaricone-C. Immediately after irradiation, alkaline comet assay were performed using standard procedures. Twenty four post radiation exposure mice were sacrificed for micronucleus test. Results of these studies showed significant reduction in DNA damage by curcumin. The micronucleus data showed marginal increase in the frequency of micronucleated erythrocytes in curcumin fed group as compared to the controls. Mice receiving curcumin for 3 weeks in diet followed by gamma radiation (3 Gy), showed approximately 50% reduction in the frequency of micro nucleated polychromatic erythrocytes. Pre-treatment of mice with taurine significantly (p < 0.01) reduced the frequency of gamma rays induced mn-PCEs in bone marrow tissue. Malabaricone-C at 1.5 ìM concentration showed very good protection

Radiation-induced centers in inorganic glasses

International Nuclear Information System (INIS)

Brekhovskikh, S.M.; Tyul'nin, V.A.

1988-01-01

The nature, structure and formation mechanisms of radiation-induced colour centers, EPR, luminescence, generated ionizing radiation in nonorganic oxide glasses are considered. Experimental material covering both fundamental aspects of radiation physics and glass chemistry, and aspects intimately connected with the creation of new materials with the given radiation-spectral characteristics, with possibilities to prepare radiation-stable and radiation-sensitive glasses is systematized and generalized. Considerable attention is paid to the detection of radiation-induced center binding with composition, glass structures redox conditions for their synthesis. Some new possibilities of practical application of glasses with radiation-induced centers, in particular, to record optical information are reflected in the paper

Glucocorticoids induce autophagy in rat bone marrow mesenchymal stem cells

DEFF Research Database (Denmark)

Wang, L.; Fan, J.; Lin, Y. S.

2015-01-01

Glucocorticoidinduced osteoporosis (GIOP) is a widespread clinical complication following glucocorticoid therapy. This irreversible damage to boneforming and resorbing cells is essential in the pathogenesis of osteoporosis. Autophagy is a physiological process involved in the regulation of cells...... and their responses to diverse stimuli, however, the role of autophagy in glucocorticoidinduced damage to bone marrow mesenchymal stem cells (BMSCs) remains unclear. The current study confirmed that glucocorticoid administration impaired the proliferation of BMSCs. Transmission electron microscopy...... that in response to glucocorticoid administration, induced autophagy aids to maintain proliferation and prevent apoptosis of BMSCs. Thus, it is hypothesized that autophagy may be a novel target in the treatment or prevention of osteoporosis....

Routine treatment of bilateral aplasia of upper lateral incisors by orthodontic space closure without mandibular extractions.

Science.gov (United States)

Zimmer, Bernd; Seifi-Shirvandeh, Nasrin

2009-06-01

This study aimed to gather statistically validated information on the changes in orthodontic variables in patients with bilateral upper lateral incisor aplasia treated with isolated orthodontic space closure. Data were collected from 25 (15 females, 10 males) consecutively treated, unselected adolescents [mean age at the end of treatment 16.4 years, standard deviation (SD) 1.3] after orthodontic space closure using push-and-pull mechanics (PPM). The changes in the relevant parameters were determined by comparing baseline and final lateral headfilms and casts. Following verification of normal distribution by means of a Kolmogorov-Smirnov test, a two-tailed t-test for related data was performed. SNA, ANB, OcP-NL, OcP-ML, upper space balance, overbite, overjet, bilateral molar relationship, and L1-NB changed significantly (P orthodontic space closure for bilateral upper lateral incisor aplasia using PPM can be regarded as a valid alternative to prosthetic solutions. Long-term use of Class III elastics does not lead to significant changes in relevant orthodontic parameters.

A biosafety evaluation of synchrotron radiation X-ray to skin and bone marrow: single dose irradiation study of rats and macaques.

Science.gov (United States)

Lu, Yifan; Tang, Guanghui; Lin, Hui; Lin, Xiaojie; Jiang, Lu; Yang, Guo-Yuan; Wang, Yongting

2017-06-01

Very limited experimental data is available regarding the safe dosages related to synchrotron radiation (SR) procedures. We used young rats and macaques to address bone marrow and skin tolerance to various doses of synchrotron radiation. Rats were subjected to 0, 0.5, 2.5, 5, 25 or 100 Gy local SR X-ray irradiation at left hind limb. Rat blood samples were analyzed at 2-90 days after irradiation. The SR X-ray irradiated skin and tibia were sectioned for morphological examination. For non-human primate study, three male macaques were subjected to 0.5 or 2.5 Gy SR X-ray on crus. Skin responses of macaques were observed. All rats that received SR X-ray irradiation doses greater than 2.5 Gy experienced hair loss and bone-growth inhibition, which were accompanied by decreased number of follicles, thickened epidermal layer, and decreased density of bone marrow cells (p X-ray but showed significant hair loss when the dose was raised above 2.5 Gy. The safety threshold doses of SR X-ray for rat skin, bone marrow and macaque skin are between 0.5 and 2.5 Gy. Our study provided essential information regarding the biosafety of SR X-ray irradiation.

The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate

Science.gov (United States)

Song, Guodong; Habibovic, Pamela; Bao, Chongyun; Hu, Jing; van Blitterswijk, Clemens A.; Yuan, Huipin; Chen, Wenchuan; Xu, Hockin H.K.

2013-01-01

Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched beagle dog model to investigate BMSC homing via blood circulation to participate in ectopic bone formation via osteoinductive biomaterial. BMSCs of male dogs were injected into female femoral marrow cavity. The survival and stable chimerism of donor BMSCs in recipients were confirmed with polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH). Biphasic calcium phosphate (BCP) granules were implanted in dorsal muscles of female dogs. Y chromosomes were detected in samples harvested from female dogs which had received male BMSCs. At 4 weeks, cells with Y-chromosomes were distributed in the new bone matrix throughout the BCP granule implant. At 6 weeks, cells with Y chromosomes were present in newly mineralized woven bone. TRAP positive osteoclast-like cells were observed in 4-week implants, and the number of such cells decreased from 4 to 6 weeks. These results show that osteoprogenitors were recruited from bone marrow and homed to ectopic site to serve as a cell source for calcium phosphate-induced bone formation. In conclusion, BMSCs were demonstrated to migrate from bone marrow through blood circulation to non-osseous bioceramic implant site to contribute to ectopic bone formation in a canine model. BCP induced new bone in muscles without growth factor delivery, showing excellent osteoinductivity that could be useful for bone tissue engineering. PMID:23298780

Epidermis–dermis junction as a novel location for bone marrow-derived cells to reside in response to ionizing radiation

International Nuclear Information System (INIS)

Okano, Junko; Kojima, Hideto; Katagi, Miwako; Nakae, Yuki; Terashima, Tomoya; Nakagawa, Takahiko; Kurakane, Takeshi; Okamoto, Naoki; Morohashi, Keita; Maegawa, Hiroshi; Udagawa, Jun

2015-01-01

Bone marrow-derived cells (BMDCs) can migrate into the various organs in the mice irradiated by ionizing radiation (IR). However, it may not be the case in the skin. While IR is used for bone marrow (BM) transplantation, studying with the epidermal sheets demonstrated that the BMDC recruitment is extraordinarily rare in epidermis in the mouse. Herein, using the chimera mice with BM from green fluorescent protein (GFP) transgenic mice, we simply examined if BMDCs migrate into any layers in the total skin, as opposed to the epidermal sheets, in response to IR. Interestingly, we identified the presence of GFP-positive (GFP + ) cells in the epidermis-dermis junction in the total skin sections although the epidermal cell sheets failed to have any GFP cells. To examine a possibility that the cells in the junction could be mechanically dissociated during separating epidermal sheets, we then salvaged such dissociated cells and examined its characteristics. Surprisingly, some GFP + cells were found in the salvaged cells, indicating that these cells could be derived from BM. In addition, such BMDCs were also associated with inflammation in the junction. In conclusion, BMDCs can migrate to and reside in the epidermis-dermis junction after IR. - Highlights: • Bone marrow-derived cells (BMDCs) migrate in the epidermis due to ionizing radiation (IR). • BMDCs dissociate from the epidermis-dermis junction in preparing epidermal sheets. • The doses of IR determine the location and the number of migrating BMDCs in the skin

Epidermis–dermis junction as a novel location for bone marrow-derived cells to reside in response to ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Okano, Junko, E-mail: jokano@belle.shiga-med.ac.jp [Division of Anatomy and Cell Biology, Shiga University of Medical Science, Shiga (Japan); Kojima, Hideto; Katagi, Miwako [Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Shiga (Japan); Nakae, Yuki [Department of Internal Medicine, Shiga University of Medical Science, Shiga (Japan); Terashima, Tomoya [Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Shiga (Japan); Nakagawa, Takahiko [TMK Project, Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto (Japan); Kurakane, Takeshi; Okamoto, Naoki; Morohashi, Keita [Division of Anatomy and Cell Biology, Shiga University of Medical Science, Shiga (Japan); Maegawa, Hiroshi [Department of Internal Medicine, Shiga University of Medical Science, Shiga (Japan); Udagawa, Jun [Division of Anatomy and Cell Biology, Shiga University of Medical Science, Shiga (Japan)

2015-06-12

Bone marrow-derived cells (BMDCs) can migrate into the various organs in the mice irradiated by ionizing radiation (IR). However, it may not be the case in the skin. While IR is used for bone marrow (BM) transplantation, studying with the epidermal sheets demonstrated that the BMDC recruitment is extraordinarily rare in epidermis in the mouse. Herein, using the chimera mice with BM from green fluorescent protein (GFP) transgenic mice, we simply examined if BMDCs migrate into any layers in the total skin, as opposed to the epidermal sheets, in response to IR. Interestingly, we identified the presence of GFP-positive (GFP{sup +}) cells in the epidermis-dermis junction in the total skin sections although the epidermal cell sheets failed to have any GFP cells. To examine a possibility that the cells in the junction could be mechanically dissociated during separating epidermal sheets, we then salvaged such dissociated cells and examined its characteristics. Surprisingly, some GFP{sup +} cells were found in the salvaged cells, indicating that these cells could be derived from BM. In addition, such BMDCs were also associated with inflammation in the junction. In conclusion, BMDCs can migrate to and reside in the epidermis-dermis junction after IR. - Highlights: • Bone marrow-derived cells (BMDCs) migrate in the epidermis due to ionizing radiation (IR). • BMDCs dissociate from the epidermis-dermis junction in preparing epidermal sheets. • The doses of IR determine the location and the number of migrating BMDCs in the skin.

Counter-Radiation Balm and its Medical Properties at Radiation Injuries and Functional Disorders in Gastrointestinal Tract

International Nuclear Information System (INIS)

Melkadze, R.; Shalamberidze, M.

2006-01-01

It has been shown that the Counter-Radiation Balm (CRB) is fairly effective in normalization of secretory phenomena and eubiotic state of the digestive tract in conditions of their functional disorders induced by various causes. The CRB has normalizing effect on an intestional flora during experimental dysbacterioses, induced with irradiation and starvation. This holds true in both bone marrow- and mixed patterns of acute radiation disease (ARD). The CRB somewhat decreases a toxic constituent of ARD, increases colonization resistance of the intestine to external microbial invasions and precludes extension of intestinal area for conditionally-pathogene flora. (author)

Concurrent spinal cord and vertebral bone marrow radionecrosis 8 years after therapeutic irradiation

International Nuclear Information System (INIS)

Warscotte, L.; Sindic, C.J.M.; Duprez, T.; Lecouvet, F.E.; Lonneux, M.; Michaux, L.; Renard, L.

2002-01-01

Concurrent radionecrosis within the spinal cord and the bone marrow at the same thoracic level was observed 8 years after localized therapeutic irradiation in a patient who had undergone repeated cycles of radiotherapy, glucocorticoid treatment, and chemotherapy for a non-Hodgkin's lymphoma. Mechanisms combining radiotoxic potentialization by glucocorticoids/alkylating agents and delayed radiation-induced vasculitis involving the common arterial pathways to the spinal cord and to the vertebrae were speculated to have acted in a synergistic way. (orig.)

Reversal of acute (''malignant'') myelosclerosis by allogeneic bone marrow transplantation

International Nuclear Information System (INIS)

Wolf, J.L.; Spruce, W.E.; Bearman, R.M.; Forman, S.J.; Scott, E.P.; Fahey, J. L.; Farbstein, M.J.; Rappaport, H.; Blume, K.G.

1982-01-01

A 28-yr-old woman with acute malignant myelosclerosis received, as primary treatment, ablative chemotherapy and total body radiation therapy followed by bone marrow transplantation from her histocompatible brother. The patient is now well more than 15 mo after bone marrow transplantation, with normal peripheral blood counts, a normal bone marrow, no evidence of graft-versus-host disease, and is on no therapy. In light of the poor results obtained with conventional chemotherapy in this disease, bone marrow transplantation may represent the treatment of choice for patients who have an appropriate donor

Radiation-induced camptocormia and dropped head syndrome. Review and case report of radiation-induced movement disorders

International Nuclear Information System (INIS)

Seidel, Clemens; Kuhnt, Thomas; Kortmann, Rolf-Dieter; Hering, Kathrin

2015-01-01

In recent years, camptocormia and dropped head syndrome (DHS) have gained attention as particular forms of movement disorders. Camptocormia presents with involuntary forward flexion of the thoracolumbar spine that typically increases during walking or standing and may severely impede walking ability. DHS is characterized by weakness of the neck extensors and a consecutive inability to extend the neck; in severe cases the head is fixed in a ''chin to chest position.'' Many diseases may underlie these conditions, and there have been some reports about radiation-induced camptocormia and DHS. A PubMed search with the keywords ''camptocormia,'' ''dropped head syndrome,'' ''radiation-induced myopathy,'' ''radiation-induced neuropathy,'' and ''radiation-induced movement disorder'' was carried out to better characterize radiation-induced movement disorders and the radiation techniques involved. In addition, the case of a patient developing camptocormia 23 years after radiation therapy of a non-Hodgkin's lymphoma of the abdomen is described. In total, nine case series of radiation-induced DHS (n = 45 patients) and - including our case - three case reports (n = 3 patients) about radiogenic camptocormia were retrieved. Most cases (40/45 patients) occurred less than 15 years after radiotherapy involving extended fields for Hodgkin's disease. The use of wide radiation fields including many spinal segments with paraspinal muscles may lead to radiation-induced movement disorders. If paraspinal muscles and the thoracolumbar spine are involved, the clinical presentation can be that of camptocormia. DHS may result if there is involvement of the cervical spine. To prevent these disorders, sparing of the spine and paraspinal muscles is desirable. (orig.) [de

Influence of hyperoxia on the number of nucleated cells and oxygen tension in rat bone marrow after whole-body irradiation

International Nuclear Information System (INIS)

Zima, M.; Vodicka, I.

1987-01-01

The cell number in the femur bone marrow of rats determined three days after X-ray or gamma irradiation is inversely proportional to the dose while oxygen tension in the marrow shows direct dependence on the dose. With fractionation of the lethal dose of gamma radiation (9 Gy) into two doses with different time intervals between them, a greater number of bone marrow cells and a smaller oxygen tension are reached on the 3rd day after the second dose, reflecting the extent of bone marrow repair. A short-term hyperoxia (95% O 2 + 5% CO 2 ) lasting 20 min from the end of exposure compared with the euoxic conditions induced, on the 3rd day after the second fraction, a nonsignificant but reproducible increase in the marrow cell number and a decrease in partial oxygen tension in the distal part of femur marrow. The results obtained testify that immediate short-term hyperoxia facilitates regeneration of the marrow and that a greater number of cells accompanied by greater metabolic activity and oxygen consumption decrease the partial oxygen tension measured on the 3rd day following the last exposure. (author). 7 figs., 16 refs

Bone-marrow densitometry: Assessment of marrow space of human vertebrae by single energy high resolution-quantitative computed tomography

International Nuclear Information System (INIS)

Peña, Jaime A.; Damm, Timo; Bastgen, Jan; Barkmann, Reinhard; Glüer, Claus C.; Thomsen, Felix; Campbell, Graeme M.

2016-01-01

Purpose: Accurate noninvasive assessment of vertebral bone marrow fat fraction is important for diagnostic assessment of a variety of disorders and therapies known to affect marrow composition. Moreover, it provides a means to correct fat-induced bias of single energy quantitative computed tomography (QCT) based bone mineral density (BMD) measurements. The authors developed new segmentation and calibration methods to obtain quantitative surrogate measures of marrow-fat density in the axial skeleton. Methods: The authors developed and tested two high resolution-QCT (HR-QCT) based methods which permit segmentation of bone voids in between trabeculae hypothesizing that they are representative of bone marrow space. The methods permit calculation of marrow content in units of mineral equivalent marrow density (MeMD). The first method is based on global thresholding and peeling (GTP) to define a volume of interest away from the transition between trabecular bone and marrow. The second method, morphological filtering (MF), uses spherical elements of different radii (0.1–1.2 mm) and automatically places them in between trabeculae to identify regions with large trabecular interspace, the bone-void space. To determine their performance, data were compared ex vivo to high-resolution peripheral CT (HR-pQCT) images as the gold-standard. The performance of the methods was tested on a set of excised human vertebrae with intact bone marrow tissue representative of an elderly population with low BMD. Results: 86% (GTP) and 87% (MF) of the voxels identified as true marrow space on HR-pQCT images were correctly identified on HR-QCT images and thus these volumes of interest can be considered to be representative of true marrow space. Within this volume, MeMD was estimated with residual errors of 4.8 mg/cm 3 corresponding to accuracy errors in fat fraction on the order of 5% both for GTP and MF methods. Conclusions: The GTP and MF methods on HR-QCT images permit noninvasive

Stimulation of murine stem cell proliferation by circulating activities produced during the recovery of a radiation-induced hemopoietic injury

International Nuclear Information System (INIS)

Grande Azanedo, M.T.

1988-01-01

The proliferative activity of CFU-S, low in normal steady state, increases after treatment with different aggressors, i.e. radiation. This stimulation has been attributed in part to a local regulation system of stem cell proliferation, and at least in part to a humoral regulatory system. In the present work it has been investigated the role that circulating activities have in the CFU- S stimulation, by means of in vitro and in vivo incubation assays with diffusion chambers. The results show that bone marrow of mice irradiated with 5 Gy produces in vitro diffusible activities capable of stimulating the CFU-S proliferation. As well with this same dose circulating activities are also produced in vivo. In addition we have observed that these activities are only released during the periods of active hemopoietic regeneration that follow irradiation with moderate doses (1.5 and 5 Gy). In another set of experiments we saw that the stimulating activities are also detected in serum of mice irradiated with 5 Gy. These serum activities modify the proliferative state of very primitive precursors (12 d CFU-S). When the serum activities are added to long term bone marrow cultures the CFU-S) are also stimulated to proliferate. Finally, we observed that the radiation-induced serum activities stimulate the proliferation of bone marrow CFU-S when injected into normal mice, suggesting that such activities are involved in the regulation of CFU-S proliferation. (Author)

Contribution of radiation-induced, nitric oxide-mediated bystander effect to radiation-induced adaptive response.

Science.gov (United States)

Matsumoto, H.; Ohnishi, T.

There has been a recent upsurge of interest in radiation-induced adaptive response and bystander effect which are specific modes in stress response to low-dose low-dose rate radiation Recently we found that the accumulation of inducible nitric oxide NO synthase iNOS in wt p53 cells was induced by chronic irradiation with gamma rays followed by acute irradiation with X-rays but not by each one resulting in an increase in nitrite concentrations of medium It is suggested that the accumulation of iNOS may be due to the depression of acute irradiation-induced p53 functions by pre-chronic irradiation In addition we found that the radiosensitivity of wt p53 cells against acute irradiation with X-rays was reduced after chronic irradiation with gamma rays This reduction of radiosensitivity of wt p53 cells was nearly completely suppressed by the addition of NO scavenger carboxy-PTIO to the medium This reduction of radiosensitivity of wt p53 cells is just radiation-induced adaptive response suggesting that NO-mediated bystander effect may considerably contribute to adaptive response induced by radiation

Damage of chromosomes in mouse bone marrow cells after combined treatment with gamma radiation and cyclophosphamide

International Nuclear Information System (INIS)

Rupova, Ivanka

2008-01-01

Full text: Current approaches to successful management of malignancy include combined modalities of treatment with ionizing radiation and anticancer drugs. Together with tumor cells normal tissues and cells are also submitted to the damaging effect of these agents, creating thus a probability for development of secondary neoplastic processes. The aim of the present study was to investigate the rate of chromosome damage at different modalities of combined exposures to gamma irradiation and cyclophosphamide(CY) of mice. Chromosomal aberration frequency in metaphase bone marrow cells was used as a measure to evaluate the effect. Combination treatments with 3 Gy gamma irradiation and 20 mg/kg cyclophosphamide were given at different intervals - simultaneously or at 12 hr interval, in order to establish the conditions and factors influencing the rate of chromosome damage. The distribution of different types of chromosome aberrations, such as chromatid fragments, chromatid exchanges, chromosome fragments and chromosome exchanges was analyzed. The results showed a high synergistic effect at simultaneous treatment with both agents if assessed by the index of aberrations per cell (%). An attempt has been made to suggest a possible explanation of the effects at different combined treatments related to the type of induced chromosomal aberrations. (author)

Serial MR imaging evaluation of effects of radiation therapy on bone marrow and liver

International Nuclear Information System (INIS)

Yankelevitz, D.; Henschke, C.I.; Chu, F.; Hayt, D.B.; Whalen, J.P.; Cahill, P.T.

1989-01-01

This paper reports on baseline and serial MR imaging studies obtained on 20 patients (lung cancer and lymphoma) who were receiving radiation therapy as their only form of treatment. Quantitative and qualitative MR signal intensity measurement were made on bone marrow and liver. Additionally, changes in signal intensity were correlated with laboratory values including both complete blood count and liver function tests. The spine showed increased signal intensity on T1-weighted images. MR signal intensity increased rapidly in the first 6 weeks and continued to rise slowly thereafter. In three of 10 cases in which the liver was included in the radiotherapy field, areas of increased activity in the liver were seen on T2-weighted images. These areas were in the field of radiation and sharply demarcated from nonirradiated liver. This area of abnormality gradually returned to normal after completion of therapy

Radiation-induced instability of human genome

International Nuclear Information System (INIS)

Ryabchenko, N.N.; Demina, Eh.A.

2014-01-01

A brief review is dedicated to the phenomenon of radiation-induced genomic instability where the increased level of genomic changes in the offspring of irradiated cells is characteristic. Particular attention is paid to the problems of genomic instability induced by the low-dose radiation, role of the bystander effect in formation of radiation-induced instability, and its relationship with individual radiosensitivity. We believe that in accordance with the paradigm of modern radiobiology the increased human individual radiosensitivity can be formed due to the genome instability onset and is a significant risk factor for radiation-induced cancer

Acute human parvovirus b19 infection: cytologic diagnosis.

Science.gov (United States)

Sharada Raju, Rane; Nalini Vinayak, Kadgi; Madhusudan Bapat, Vishnuprasad; Preeti Balkisanji, Agrawal; Shaila Chandrakant, Puranik

2014-09-01

Human parvovirus B19 is highly tropic to human bone marrow and replicates only in erythroid progenitor cells. It is causative agent of transient aplastic crisis in patients with chronic haemolytic anemia. In immunocompromised patients persistent parvovirus B19 infection may develop and it manifests as pure red cell aplasia and chronic anaemia. Bone marrow is characterised morphologically by giant pronormoblast stage with little or no further maturation. We encountered a case of 6 year old HIV positive male child presented with pure red cell aplasia due to parvovirus B19 infection. Bone marrow aspiration cytology revealed giant pronormoblast with prominent intranuclear inclusions led to suspicion of parvovirus B19 infection which was confirmed by DNA PCR. This case is presented to report classical morphological features of parvovirus B19 infection rarely seen on bone marrow examination should warrant the suspicion of human parvovirus B19 infection in the setting of HIV positive patient with repeated transfusions and confirmation should be done by PCR.

T2 relaxation times of irradiated vertebral bone marrow in patients with seminoma.

Science.gov (United States)

Argiris, A; Maris, T; Vlahos, L

1997-01-01

Our purpose was to demonstrate the effects of localized radiotherapy on lumbar vertebral bone marrow with the use of quantitative MRI with measurements of T2 relaxation times. Ten patients with early stage testicular seminoma with a history of radiation therapy to a "dog-leg" field including the lumbar vertebrae underwent MR imaging of their lumbar spine using a 0.5 Tesla magnet. Five healthy subjects and two nonirradiated patients were imaged as well. The intervals from the beginning of radiotherapy to MRI examination varied from 1.5 to 52 months, and the radiation dose ranged from 3000-4200 cGy. The T2 relaxation times of the lumbar vertebral bone marrow and subcutaneous fat were calculated for each subject. Postirradiation bone marrow in irradiated seminoma patients exhibited significantly longer T2 relaxation times than nonirradiated bone marrow in controls (71.1 vs. 63.6 ms, p = 0.047, t-test). The differences between the T2 relaxation times of bone marrow and subcutaneous fat for each subject allowed for even better differentiation between irradiated patients and controls (10.4 vs. 0.4 ms, p = 0.0004, t-test). Postirradiation bone marrow had significantly longer T2 relaxation times than subcutaneous fat in irradiated patients (N = 10, 71.1 vs. 60.7 ms, p = 0.00009, t-test), while nonirradiated bone marrow had T2 relaxation times not statistically different from subcutaneous fat in nonirradiated subjects (N = 7, 63.6 vs. 63.2 ms). Measurements of T2 relaxation times of bone marrow enabled us to differentiate between irradiated seminoma patients and controls. Postirradiation bone marrow undergoes late radiation effects resulting in longer T2 relaxation times than nonirradiated bone marrow and subcutaneous fat.

Bone marrow changes adjacent to the sacroiliac joints after pelvic radiotherapy mimicking metastases on MRI

Energy Technology Data Exchange (ETDEWEB)

Kanberoglu, K.; Mihmanli, I.; Kurugoglu, S.; Ogut, G.; Kantarci, F. [Dept. of Radiology, Istanbul Univ. (Turkey)

2001-09-01

Radiation-induced changes in the sacroiliac joints mimicking metastases on MR images were evaluated. Twelve patients who received radiotherapy to the pelvic region due to pelvic malignancy were included in the study. All patients had undergone external beam radiation therapy to the pelvic region, and 2 patients received supplementary internal radiation. The changes in the sacroiliac joints were evaluated. Computed-tomography-guided core bone biopsy from the bone marrow was taken from their corresponding MR sections in 5 of the patients. T1 hypointense and T2 hyperintense areas with ill-defined margins in the bone marrow adjacent to the sacroiliac joints were observed in all patients. On bone scintigraphy all the lesions demonstrated increased activity. Other radiological modalities excluded fracture, soft tissue mass, and osseous destruction. Bone biopsies demonstrated peritrabecular fibrosis and inflammatory cell infiltration. Patients receiving radiotherapy to the pelvis may demonstrate T1 hypointense/T2 hyperintense, ill-defined postradiotherapeutic benign changes in the sacroiliac joints. In the absence of any other signs of disease progression and when the imaging pattern is typical, close radiological follow-up should be sufficient to rule out metastases. (orig.)

Squalene Selectively Protects Mouse Bone Marrow Progenitors Against Cisplatin and Carboplatin-Induced Cytotoxicity In Vivo Without Protecting Tumor Growth

Directory of Open Access Journals (Sweden)

Bikul Das

2008-10-01

Full Text Available Squalene, an isoprenoid antioxidant is a potential cytoprotective agent against chemotherapy-induced toxicity. We have previously published that squalene protects light-density bone marrow cells against cis-diamminedichloroplatinum( II (cisplatin-induced toxicity without protecting tumor cells in vitro. Here, we developed an in vivo mouse model of cisplatin and cis-diammine (cyclobutane-1,1-dicarboxylato platinum(II (carboplatin-induced toxicity to further investigate squalene-mediated LD-BM cytoprotection including the molecular mechanism behind selective cytoprotection. We found that squalene significantly reduced the body weight loss of cisplatin and carboplatin-treated mice. Light-density bone marrow cells from squalene-treated mice exhibited improved formation of hematopoietic colonies (colony-forming unit-granulocyte macrophage. Furthermore, squalene also protected mesenchymal stem cell colonies (colony-forming unit-fibroblast from cisplatin and carboplatin-induced toxicity. Squalene-induced protection was associated with decreased reactive oxygen species and increased levels of glutathione and glutathione peroxidase/glutathione-S-transferase. Importantly, squalene did not protect neuroblastoma, small cell carcinoma, or medulloblastoma xenografts against cisplatin-induced toxicity. These results suggest that squalene is a potential candidate for future development as a cytoprotective agent against chemotherapeutic toxicity.

Hematological effects: comparative studies on the radiation survival characteristics in vivo and in vitro of bone marrow-derived clonogenic populations (CFU-C and PFU-C) and some observations on bone marrow cellularity in beagles

International Nuclear Information System (INIS)

Wilson, F.D.; O'Grady, L.; Momeni, M.; Wheeling, J.A.; Klein, K.; Graham, R.; Jow, N.; Di Bartola, S.

1975-01-01

Data accumulated for the hematological effects program are reviewed. Particular emphasis is given to the effects of acute and chronic irradiation on hematopoietic progenitor populations (CFU-C, colony-forming units in culture) and ''candidate'' mesenchymal progenitors (PFU-C, plaque-forming units in culture) using methylcellulose bone marrow culture systems and both in vivo and in vitro radiation exposure protocols. Preliminary results of studies on the temporal effects of acute x-irradiation on the capacity of PFU-C to generate colony stimulating activity (CSA) are also presented. The results of such experiments are providing the basis upon which future RBE studies on a variety of nuclides will be structured. Data (including age related changes) is also presented on in vivo bone marrow cellularity determinations, as well as for marrow stem cell quantitative studies using nondestructive techniques for normal Beagles. In these studies, two techniques for correction of variable effects of hemodilution are compared. Such studies are also providing baseline data for the 60 Co hematological effects program

Absorbed bone marrow dose in certain dental radiographic techniques

International Nuclear Information System (INIS)

White, S.C.; Rose, T.C.

1979-01-01

The absorbed dose of radiation in the bone marrow of the region of the head and neck was measured during intraoral, panoramic, and cephalometric radiography. Panoramic radiography results in a dose a fifth or less than that from an intraoral survey. The use of rectangular collimation reduces the bone marrow absorbed dose from an intraoral survey by about 60%. Comparison of the doses from dental radiography with natural environmental radiation shows that an intraoral set of films results in the same total dose to the bone marrow as 65 days of background exposure. The use of rectangular collimation reduces this value to 25 days. Panoramic radiography results in significantly less irradiation, as it reduces the value to 14 days or fewer. Dental radiography thus involves exposures in the range of variation of natural environmental background values

Radioprotective effect of sulphydryl group containing triazole derivative to modulate the radiation-induced clastogenic effects

International Nuclear Information System (INIS)

Suchetha Kumari, N.; Madhu, L.N.

2012-01-01

Protection of biological systems against radiation damage is of paramount importance during accidental and unavoidable exposure to radiation. Several physico-chemical and biological factors collectively contribute to the damage caused by radiation and are, therefore, targets for developing radioprotectors. Chemicals capable of scavenging free radicals, relieving oxidative stress, promoting antioxidant activity and modulating immune response have been some of the radioprotectors extensively investigated with limited success. It has long been known that some of the most effective radioprotective agents are those which contain sulphydryl groups. The present study reports an evaluation of radical scavenging property and radioprotective property of sulphydryl group containing triazole derivative. The lethal dose of Electron beam radiation (EBR) was studied by survival assay. The dose reduction factor (DRF) of 4-amino-5-mercapto-3-methyl-1,2,4-triazole (TR1) was calculated by taking the ratio between LD 50 of EBR with and without TR1 treatment. Radical scavenging property of TR1 was assessed by DPPH radical scavenging assay. The clastogenic effects of EBR were recorded by Micronucleus test in bone marrow cells and DNA fragmentation assay in hepatic cells of mice. The survival assay results showed that 10Gy was the LD 50 of EBR. The calculated DRF for TR1 was found to be 1.2. DPPH radical scavenging assay showed a positive result when it compared with the standard glutathione. Treatment of mice with 100 mg of TR1 for 15 days before irradiation significantly (P<0.05) reduced the frequency of micronucleus formation in bone marrow cells and also reduced the DNA fragmentation in hepatic cells. The result obtained in the present study concludes that TR1 has a protective effect against the EBR-induced mortality and clastogenicity. (author)

Ghrelin Therapy Improves Survival after Whole-Body Ionizing Irradiation or Combined with Burn or Wound: Amelioration of Leukocytopenia, Thrombocytopenia, Splenomegaly, and Bone Marrow Injury

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Juliann G. Kiang

2014-01-01

Full Text Available Exposure to ionizing radiation alone (RI or combined with traumatic tissue injury (CI is a crucial life-threatening factor in nuclear and radiological events. In our laboratory, mice exposed to 60Co-γ-photon radiation (9.5 Gy, 0.4 Gy/min, bilateral followed by 15% total-body-surface-area skin wounds (R-W CI or burns (R-B CI experienced an increment of ≥18% higher mortality over a 30-day observation period compared to RI alone. CI was accompanied by severe leukocytopenia, thrombocytopenia, erythropenia, and anemia. At the 30th day after injury, numbers of WBC and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were recovered towards preirradiation levels. Only RI induced splenomegaly. RI and CI resulted in bone-marrow cell depletion. In R-W CI mice, ghrelin (a hunger-stimulating peptide therapy increased survival, mitigated body-weight loss, accelerated wound healing, and increased hematocrit. In R-B CI mice, ghrelin therapy increased survival and numbers of neutrophils, lymphocytes, and platelets and ameliorated bone-marrow cell depletion. In RI mice, this treatment increased survival, hemoglobin, and hematocrit and inhibited splenomegaly. Our novel results are the first to suggest that ghrelin therapy effectively improved survival by mitigating CI-induced leukocytopenia, thrombocytopenia, and bone-marrow injury or the RI-induced decreased hemoglobin and hematocrit.

Sequential changes in bone marrow architecture during continuous low dose gamma irradiation

International Nuclear Information System (INIS)

Seed, T.M.; Chubb, G.T.; Tolle, D.V.

1981-01-01

Beagles continuously exposed to low daily doses (10 R) of whole-body 60Co gamma-radiation are prone to develop either early occurring aplastic anemia or late occurring myeloproliferative disorders (Seed et al., 1977). In this study, we have examined by a combination of light microscopy and scanning and transmission electron microscopy the sequential changes in the morphology of biopsied rib bone marrow of continuously irradiated dogs that developed either aplastic anemia, myelofibrosis, or myelogenous leukemia. Characteristic modification of key elements of marrow architecture have been observed during preclinical and clinical phases of these hemopathological conditions. The more prominent of these changes include the following. (i) In developing aplastic anemia: severe vascular sinus and parenchymal cord compression, and focally degenerate endosteal surfaces. (ii) In developing myelofibrosis: hyperplasia of endosteal and reticular stomal elements. (iii) In developing leukemia: hypertrophy of reticular and endothelial elements in the initial restructuring of the stromal matrix and the subsequent aberrant hemopoietic repopulation of the initially depleted stromal matrix. These architectural changes during preclinical phases appear to be related to the pathological progression to each of the radiation-induced hemopathological end points

Radioprotective effects saffron and its combination with green tea against γ-radiation-induced DNA damage in Swiss albino mice

International Nuclear Information System (INIS)

Koul, Apurva; Abraham, Suresh K.

2016-01-01

Protective effects of aqueous extract of saffron (dried stigmas of Crocus sativus L.) alone and its combination with green tea against γ-radiation-induced genotoxicity and oxidative stress were investigated in Swiss albino mice. Saffron (40 mg/kg bw) alone and in combination with green tea (40 mg/kg bw) were orally administered to mice for six consecutive days, followed by exposure to γ-radiation (2.25 Gy) on 6 th day after final feeding. Antigenotoxic effect of saffron was assayed using micronucleus test in bone marrow cells which showed a significant decrease in the number of micronucleated PCEs in saffron alone and its combination with green tea pre-treated animals when compared with the radiation alone treated animals. Saffron alone and its combination with green tea pre-treated animals showed a significant decrease in lipid peroxidation levels with a significant increase in the activity of antioxidant defense system enzymes, viz. acetylcholine esterase, glutathione-S-transferase, catalase, glutathione peroxidase, glutathione reductase and non-enzymatic antioxidant (GSH), when compared with the radiation alone treated animals. Our results suggested that saffron in combination with green tea exhibits radioprotective effects against γ-radiation induced DNA damage and oxidative stress in Swiss albino mice. (author)

Concurrent spinal cord and vertebral bone marrow radionecrosis 8 years after therapeutic irradiation

Energy Technology Data Exchange (ETDEWEB)

Warscotte, L.; Sindic, C.J.M. [Department of Neurology, Universite Catholique de Louvain (Belgium); Duprez, T.; Lecouvet, F.E. [Department of Radiology and Medical Imaging, Universite Catholique de Louvain, Brussels (Belgium); Lonneux, M. [Department of Nuclear Medicine, Universite Catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels (Belgium); Michaux, L. [Department of Hematology, Universite Catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels (Belgium); Renard, L. [Department of Radiation Oncology, Universite Catholique de Louvain, Cliniques Universitaires Saint-Luc, Brussels (Belgium)

2002-03-01

Concurrent radionecrosis within the spinal cord and the bone marrow at the same thoracic level was observed 8 years after localized therapeutic irradiation in a patient who had undergone repeated cycles of radiotherapy, glucocorticoid treatment, and chemotherapy for a non-Hodgkin's lymphoma. Mechanisms combining radiotoxic potentialization by glucocorticoids/alkylating agents and delayed radiation-induced vasculitis involving the common arterial pathways to the spinal cord and to the vertebrae were speculated to have acted in a synergistic way. (orig.)

Bone marrow transplantation after the Chernobyl nuclear accident

International Nuclear Information System (INIS)

Baranov, A.; Gale, R.P.; Guskova, A.

1989-01-01

On April 26, 1986, an accident at the Chernobyl nuclear power station in the Soviet Union exposed about 200 people to large doses of total-body radiation. Thirteen persons exposed to estimated total-body doses of 5.6 to 13.4 Gy received bone marrow transplants. Two transplant recipients, who received estimated doses of radiation of 5.6 and 8.7 Gy, are alive more than three years after the accident. The others died of various causes, including burns (the cause of death in five), interstitial pneumonitis (three), graft-versus-host disease (two), and acute renal failure and adult respiratory distress syndrome (one). There was hematopoietic (granulocytic) recovery in nine transplant recipients who could be evaluated, six of whom had transient partial engraftment before the recovery of their own marrow. Graft-versus-host disease was diagnosed clinically in four persons and suspected in two others. Although the recovery of endogenous hematopoiesis may occur after exposure to radiation doses of 5.6 to 13.4 Gy, we do not know whether it is more likely after the transient engraftment of transplanted stem cells. Because large doses of radiation affect multiple systems, bone marrow recovery does not necessarily ensure survival. Furthermore, the risk of graft-versus-host disease must be considered when the benefits of this treatment are being weighed

Animal experiments to investigate biological-chemical radiation protection and the therapy of radiolesions

International Nuclear Information System (INIS)

Brueckner, V.

1974-01-01

The influence of a combined therapy of radiation protection agents and erythropoetin on the radiation-induced suppression of erythropoiesis in mice is studied with the aid of the radioiron utilization test. After whole-body irradiation with 500 R, the erythropoietic system is so severely affected that erythropoetin application alone does not yield any results. AET (significant) and Cysteamin (insignificant), on the other hand, protect the bone marrow to a certain degree. The protected bone marrow provides a better base for erythropoetin therapy than the bone marrow of the irradiated and unprotected animals. Compared to the application of radiation protection agents alone, the combined therapy with AET and erythropoetin increases the radioiron incorporation in the erythrocytes by 7.5% while the therapy with Cysteamin and erythropoetin results in a 19.3% increase. In spite of these methods, however, the radioiron incorporation rate of the control animals was not reached. (BSC/AK) [de

Effect of Leaked Radiation from Microwave Oven on Bone Marrow of Male Rats in Pre and Post Pubertal Stage

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G Jelodar

2011-01-01

Full Text Available Introduction: Increasing hematological diseases along with increased use of microwaves in different systems proposed possible correlation between them. Age of exposure to wave is also an important factor. This study was conducted to evaluate the effect of radiation leakaged from microwave oven on hemopoitic bone marrow cells at pre and post pubertal. Methods: Fourteen male mature (2 months old and 14 male immature rats(one month old were randomly divided in to four groups (control and test. Test groups were exposed, three times a day each time 30 min for 60 days, to microwaves produced by microwave oven. After sixty days, animals were sacrified and bone marrow samples were collected from femural bones. Percent of variose cells type and their morphology were evaluated in 500 cells of each smear. Results: exposure to microwave did not exert visible morphological alteration. In the immature experimental group significant decrease in percent of basophilic rubricyte, polychromatic rubricyte, meta rubricyte and all the erythroid cell types observed(P<0.05, whereas, meta myelocyte, notrophilic band, total myeloid cell types and prolifrative cells, other cell types and the myeloid/erythroid ratio significantly increased(P<0.05. In the mature group, however, a significant decrease in percent of meta rubricyte and myelocyte cells observed(P<0.05, although prolifrative cells and all other cell types were significantly increasing in this group. Conclusion: In conclusion, the radiation leaked from microwave oven in the experimental conditions had no effect on the morphology of hemopoitic bone marrow cells, though the number of these cells was altered especially in immature group.

Congenital Amegakaryocytic Thrombocytopenic Purpura (CAMT)

International Nuclear Information System (INIS)

Ghauri, R. I.; Naveed, M.; Mannan, J.

2014-01-01

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare, autosomal recessive disorder induced by mutations of the gene coding for thrombopoietin (TPO) receptor (c-MPL) despite high levels of serum TPO. Patients initially present with isolated thrombocytopenia that subsequently progresses into pancytopenia. Although the mechanisms leading to aplasia are unknown, the age of onset has been reported to depend on the severity of the c-MPL functional defect. The primary treatment for CAMT is bone marrow transplantation. This report describes a newborn girl who presented to us with symptoms of sepsis but septic profile came negative except thrombocytopenia. Bone marrow biopsy was done for thrombocytopenia which revealed amegakaryocytic thrombocytopenia. She was given prednisolone. (author)

H4 histamine receptors mediate cell cycle arrest in growth factor-induced murine and human hematopoietic progenitor cells.

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Anne-France Petit-Bertron

Full Text Available The most recently characterized H4 histamine receptor (H4R is expressed preferentially in the bone marrow, raising the question of its role during hematopoiesis. Here we show that both murine and human progenitor cell populations express this receptor subtype on transcriptional and protein levels and respond to its agonists by reduced growth factor-induced cell cycle progression that leads to decreased myeloid, erythroid and lymphoid colony formation. H4R activation prevents the induction of cell cycle genes through a cAMP/PKA-dependent pathway that is not associated with apoptosis. It is mediated specifically through H4R signaling since gene silencing or treatment with selective antagonists restores normal cell cycle progression. The arrest of growth factor-induced G1/S transition protects murine and human progenitor cells from the toxicity of the cell cycle-dependent anticancer drug Ara-C in vitro and reduces aplasia in a murine model of chemotherapy. This first evidence for functional H4R expression in hematopoietic progenitors opens new therapeutic perspectives for alleviating hematotoxic side effects of antineoplastic drugs.

Radiation-induced heart injury

International Nuclear Information System (INIS)

Suzuki, Yoshihiko; Niibe, Hideo

1975-01-01

In order to identify radiation-induced heart injury and to differentiate it from heart disease, an attempt was made to clarify post-irradiation heart injury by investigating the histological changes which occur during the internal between the irradiation and the time of demonstrable histological changes. A study was made of 83 autopsies in which most of the primary neoplasms were breast cancers, lung cancers and mediastinal tumors. In 43 of these autopsies the heart had been irradiated. Sixty eight dd-strain mice were also used for microautoradiographic study. Histological changes in the heart were observed in 27 of the 43 cases receiving irradiation. The limit of the tolerance dose to the heart for indicating histological changes was 1220 ret in humans. The latent period without histological changes was 2.7 months after initiation of radiation therapy. Greater heart injury was observed after re-irradiation or after the combined therapy of radiation and chemotherapy especially mitomycin (MMC). The histological findings after treatment with MMC were similar to those of radiation-induced heart injury. Results of the study indicate that the damage is secondary to radiation-induced changes of the vascula connective tissue. (Evans, G.)

Radioresistant canine hematopoietic cells

International Nuclear Information System (INIS)

Kawakami, T.G.; Shimizu, J.; Rosenblatt, L.S.; Goldman, M.

1987-01-01

Survival of dogs that are continuously exposed to a moderate dose-rate of gamma radiation (10 cGy/day) is dependent on the age of the dog at the time of exposure. Most dogs exposed postpartum to gamma radiation suffered from suppressed hematopoiesis and died of aplasia. On the other hand, none of the in utero-exposed dogs suffered from suppressed hematopoiesis and most became long-term survivors, tolerating 10-fold greater total dose, but dying of myeloproliferative disease (MPD). Using acute gamma irradiation of hematopoietic cells and colony forming unit cell assay (CFU), they observed that a canine hematopoietic cell line established from a myeloid leukemic dog that was a long-term survivor of continuous irradiation was approximately 4-fold more radioresistant than a hematopoietic cell line established from a dog with nonradiation-induced myeloid leukemia or hematopoietic cells from normal canine bone marrow. In utero dogs that are long-term survivors of continuous irradiation have radioresistant hematopoietic cells, and radioresistance that is a constitutive property of the cells

Neural stem cells induce bone-marrow-derived mesenchymal stem cells to generate neural stem-like cells via juxtacrine and paracrine interactions

International Nuclear Information System (INIS)

Alexanian, Arshak R.

2005-01-01

Several recent reports suggest that there is far more plasticity that previously believed in the developmental potential of bone-marrow-derived cells (BMCs) that can be induced by extracellular developmental signals of other lineages whose nature is still largely unknown. In this study, we demonstrate that bone-marrow-derived mesenchymal stem cells (MSCs) co-cultured with mouse proliferating or fixed (by paraformaldehyde or methanol) neural stem cells (NSCs) generate neural stem cell-like cells with a higher expression of Sox-2 and nestin when grown in NS-A medium supplemented with N2, NSC conditioned medium (NSCcm) and bFGF. These neurally induced MSCs eventually differentiate into β-III-tubulin and GFAP expressing cells with neuronal and glial morphology when grown an additional week in Neurobasal/B27 without bFGF. We conclude that juxtacrine interaction between NSCs and MSCs combined with soluble factors released from NSCs are important for generation of neural-like cells from bone-marrow-derived adherent MSCs

Erythrocyte stiffness during morphological remodeling induced by carbon ion radiation.

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Baoping Zhang

Full Text Available The adverse effect induced by carbon ion radiation (CIR is still an unavoidable hazard to the treatment object. Thus, evaluation of its adverse effects on the body is a critical problem with respect to radiation therapy. We aimed to investigate the change between the configuration and mechanical properties of erythrocytes induced by radiation and found differences in both the configuration and the mechanical properties with involving in morphological remodeling process. Syrian hamsters were subjected to whole-body irradiation with carbon ion beams (1, 2, 4, and 6 Gy or X-rays (2, 4, 6, and 12 Gy for 3, 14 and 28 days. Erythrocytes in peripheral blood and bone marrow were collected for cytomorphological analysis. The mechanical properties of the erythrocytes were determined using atomic force microscopy, and the expression of the cytoskeletal protein spectrin-α1 was analyzed via western blotting. The results showed that dynamic changes were evident in erythrocytes exposed to different doses of carbon ion beams compared with X-rays and the control (0 Gy. The magnitude of impairment of the cell number and cellular morphology manifested the subtle variation according to the irradiation dose. In particular, the differences in the size, shape and mechanical properties of the erythrocytes were well exhibited. Furthermore, immunoblot data showed that the expression of the cytoskeletal protein spectrin-α1 was changed after irradiation, and there was a common pattern among its substantive characteristics in the irradiated group. Based on these findings, the present study concluded that CIR could induce a change in mechanical properties during morphological remodeling of erythrocytes. According to the unique characteristics of the biomechanical categories, we deduce that changes in cytomorphology and mechanical properties can be measured to evaluate the adverse effects generated by tumor radiotherapy. Additionally, for the first time, the current study

Radiation-induced gene expression in human subcutaneous fibroblasts is predictive of radiation-induced fibrosis

DEFF Research Database (Denmark)

Rødningen, Olaug Kristin; Børresen-Dale, Anne-Lise; Alsner, Jan

2008-01-01

BACKGROUND AND PURPOSE: Breast cancer patients show a large variation in normal tissue reactions after ionizing radiation (IR) therapy. One of the most common long-term adverse effects of ionizing radiotherapy is radiation-induced fibrosis (RIF), and several attempts have been made over the last...... years to develop predictive assays for RIF. Our aim was to identify basal and radiation-induced transcriptional profiles in fibroblasts from breast cancer patients that might be related to the individual risk of RIF in these patients. MATERIALS AND METHODS: Fibroblast cell lines from 31 individuals......-treated fibroblasts. Transcriptional differences in basal and radiation-induced gene expression profiles were investigated using 15K cDNA microarrays, and results analyzed by both SAM and PAM. RESULTS: Sixty differentially expressed genes were identified by applying SAM on 10 patients with the highest risk of RIF...

Application of radiation-induced apoptosis in radiation oncology and radiation protection

International Nuclear Information System (INIS)

Crompton, N.E.A.; Emery, G.C.; Ozsahin, M.; Menz, R.; Knesplova, L.; Larsson, B.

1997-01-01

A rapid assay of the ability of lymphocytes to respond to radiation-induced damage is presented. Age and genetic dependence of radiation response have been quantified. The assay is sensitive to low doses of radiation. Its ability to assess the cytotoxic response of blood capillaries to radiation has been evaluated. (author)

Bone-marrow densitometry: Assessment of marrow space of human vertebrae by single energy high resolution-quantitative computed tomography

Energy Technology Data Exchange (ETDEWEB)

Peña, Jaime A.; Damm, Timo; Bastgen, Jan; Barkmann, Reinhard; Glüer, Claus C., E-mail: glueer@rad.uni-kiel.de [Sektion Biomedizinische Bildgebung, Klinik für Radiologie und Neuroradiologie, Christian-Albrechts-Universität zu Kiel, Campus Kiel, Kiel 24118 (Germany); Thomsen, Felix [Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional del Sur, Bahía Blanca 8000 (Argentina); Campbell, Graeme M. [Sektion Biomedizinische Bildgebung, Klinik für Radiologie und Neuroradiologie, Christian-Albrechts-Universität zu Kiel, Campus Kiel, Kiel 24118, Germany and Institut für Biomechanik, Technische Universität Hamburg-Harburg (TUHH), Hamburg 21073 (Germany)

2016-07-15

Purpose: Accurate noninvasive assessment of vertebral bone marrow fat fraction is important for diagnostic assessment of a variety of disorders and therapies known to affect marrow composition. Moreover, it provides a means to correct fat-induced bias of single energy quantitative computed tomography (QCT) based bone mineral density (BMD) measurements. The authors developed new segmentation and calibration methods to obtain quantitative surrogate measures of marrow-fat density in the axial skeleton. Methods: The authors developed and tested two high resolution-QCT (HR-QCT) based methods which permit segmentation of bone voids in between trabeculae hypothesizing that they are representative of bone marrow space. The methods permit calculation of marrow content in units of mineral equivalent marrow density (MeMD). The first method is based on global thresholding and peeling (GTP) to define a volume of interest away from the transition between trabecular bone and marrow. The second method, morphological filtering (MF), uses spherical elements of different radii (0.1–1.2 mm) and automatically places them in between trabeculae to identify regions with large trabecular interspace, the bone-void space. To determine their performance, data were compared ex vivo to high-resolution peripheral CT (HR-pQCT) images as the gold-standard. The performance of the methods was tested on a set of excised human vertebrae with intact bone marrow tissue representative of an elderly population with low BMD. Results: 86% (GTP) and 87% (MF) of the voxels identified as true marrow space on HR-pQCT images were correctly identified on HR-QCT images and thus these volumes of interest can be considered to be representative of true marrow space. Within this volume, MeMD was estimated with residual errors of 4.8 mg/cm{sup 3} corresponding to accuracy errors in fat fraction on the order of 5% both for GTP and MF methods. Conclusions: The GTP and MF methods on HR-QCT images permit noninvasive

[Aplasia cutis congenita associated with epidermolysis bullosa].

Science.gov (United States)

Muñoz-Guerrero, Félix; Muñoz-Solís, Adrián Antonio; Ornelas-Aguirre, José Manuel

2017-12-01

Aplasia cutis congenita (ACC) is a skin condition of rare presentation, this disease is characterized by absence of skin at birth and associated with facial, skin and bone skull deformities. The diagnosis is mainly clinical. Male 5 days after birth, unique product of primigravida mother and no family history of relevance. Physical examination revealed bilateral and symmetrical skin defects of both lower extremities, the disease is characterized by skin fragility, scabs, and coated pseudomembrane ulcers, decreased interdigital space between toes of the left foot, retraction of the foot and genu varum. It was handled with allograft of epidermis cultured in vitro, general wound care and clinical follow-up. ACC associated with epidermolysis bullosa is one of the rarer forms of presentation. It is necessary to rule out other skin diseases. Clinical management is recommended with biological or synthetic skin cover, infection prevention, early treatment of complications and clinical follow. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Like Father, Like Daughter-inherited cutis aplasia occurring in a family with Marfan syndrome: a case report.

Science.gov (United States)

Islam, Yasmin Florence Khodeja; Williams, Charles A; Schoch, Jennifer Jane; Andrews, Israel David

2017-01-01

We present the case of a newborn with co-occurrence of Marfan syndrome and aplasia cutis congenita (ACC) and a family history significant for Marfan syndrome and ACC in the father. This case details a previously unreported mutation in Marfan syndrome and describes a novel coinheritance of Marfan syndrome and ACC.

Radiation-induced pneumothorax

International Nuclear Information System (INIS)

Epstein, D.M.; Littman, P.; Gefter, W.B.; Miller, W.T.; Raney, R.B. Jr.

1983-01-01

Pneumothorax is an uncommon complication of radiation therapy to the chest. The proposed pathogenesis is radiation-induced fibrosis promoting subpleural bleb formation that ruptures resulting in pneumothorax. We report on two young patients with primary sarcomas without pulmonary metastases who developed spontaneous pneumothorax after irradiation. Neither patient had antecedent radiographic evidence of pulmonary fibrosis

Radiation induced sarcomas of bone following therapeutic radiation

International Nuclear Information System (INIS)

Kim, J.H.; Chu, F.C.H.; Woodward, H.Q.; Huvos, A.

1983-01-01

Because of new therapeutic trends of multi-modality and the importance of late effects, we have updated our series of radiation induced bone sarcomas seen at Memorial Sloan-Kettering Cancer Center over the past four decades. A total of 37 cases of bone sarcoma arising from normal bone in the irradiated field was analyzed. The median for latent period from irradiation to diagnosis of bone sarcoma was 11 years with a minimum latent period of four years. The median radiation dose for the bone sarcoma was 6000 rad in 6 weeks with a minimum total radiation dose of 3000 rad in 3 weeks. We have found nine patients who developed bone sarcomas in the radiation field after successful treatment of Hodgkin's disease. Criteria for radiation induced bone sarcomas and the magnitude of the risk of bone sarcomas are briefly discussed

Radiation-induced bone neoplasma in facial cranium

Energy Technology Data Exchange (ETDEWEB)

Zomer-Drozda, J; Buraczewska-Lipinska, H; Buraczewski, J [Instytut Onkologii, Warsaw (Poland)

1976-01-01

Radiation-induced bone neoplasms in the region of facial cranium account for about 40% of all radiation-induced tumours of bones, although the number of cases with lesions irradiated in this area is proportionally much lower than the number of cases treated with radiotherapy in other parts of the body. Four personal cases of radiation-induced tumours with complicated course are reported. Attention is called to the value of radiological investigations in the diagnosis of bone diseases and in differential diagnosis of radiation-induced tumours of bones.

Regulation of radiation-induced protein kinase Cδ activation in radiation-induced apoptosis differs between radiosensitive and radioresistant mouse thymic lymphoma cell lines

International Nuclear Information System (INIS)

Nakajima, Tetsuo; Yukawa, Osami; Tsuji, Hideo; Ohyama, Harumi; Wang, Bing; Tatsumi, Kouichi; Hayata, Isamu; Hama-Inaba, Hiroko

2006-01-01

Protein kinase Cδ (PKCδ) has an important role in radiation-induced apoptosis. The expression and function of PKCδ in radiation-induced apoptosis were assessed in a radiation-sensitive mouse thymic lymphoma cell line, 3SBH5, and its radioresistant variant, XR223. Rottlerin, a PKCδ-specific inhibitor, completely abolished radiation-induced apoptosis in 3SBH5. Radiation-induced PKCδ activation correlated with the degradation of PKCδ, indicating that PKCδ activation through degradation is involved in radiation-induced apoptosis in radiosensitive 3SBH5. In radioresistant XR223, radiation-induced PKCδ activation was lower than that in radiosensitive 3SBH5. Cytosol PKCδ levels in 3SBH5 decreased markedly after irradiation, while those in XR223 did not. There was no apparent change after irradiation in the membrane fractions of either cell type. In addition, basal cytosol PKCδ levels in XR223 were higher than those in 3SBH5. These results suggest that the radioresistance in XR223 to radiation-induced apoptosis is due to a difference in the regulation of radiation-induced PKCδ activation compared to that of 3SBH5. On the other hand, Atm -/- mouse thymic lymphoma cells were more radioresistant to radiation-induced apoptosis than wild-type mouse thymic lymphoma cells. Irradiated wild-type cells, but not Atm -/- cells, had decreased PKCδ levels, indicating that the Atm protein is involved in radiation-induced apoptosis through the induction of PKCδ degradation. The decreased Atm protein levels induced by treatment with Atm small interfering RNA had no effect on radiation-induced apoptosis in 3SBH5 cells. These results suggest that the regulation of radiation-induced PKCδ activation, which is distinct from the Atm-mediated cascade, determines radiation sensitivity in radiosensitive 3SBH5 cells

Radiation-induced decrease of CD8+ dendritic cells contributes to Th1/Th2 shift.

Science.gov (United States)

Liu, Hu; Li, Bailong; Jia, Xiaojing; Ma, Yan; Gu, Yifeng; Zhang, Pei; Wei, Qun; Cai, Jianming; Cui, Jianguo; Gao, Fu; Yang, Yanyong

2017-05-01

Exposure to ionizing radiation (IR) often reduce the helper T (Th) 1 like function, resulting in a Th1/Th2 imbalance, which could affect the efficacy of cancer radiotherapy. As the most potent antigen presenting cells, dendritic cells (DC) can be divided into several subsets with specialized function. However, there is no literature covering the changes of DC subsets and their roles in immune regulation in response to IR. In the present study, we were aimed to investigate the changes of DC subsets after IR and its relationship with Th1/Th2 immunity. We found a significant decrease of BDCA3+DC in the blood of patients treated with radiotherapy. CD8+DC, a mouse equivalent of human BDCA3+DC, was also found decreased in mice spleen, peripheral blood and lymph node tissues after irradiation. As CD8+DC mainly induce Th1 immunity, we tested the changes of Th1/Th2 response and found that IR caused a repression of Th1 immunity, indicating a possible role of CD8+DC in radiation-induced Th1/Th2 imbalance. We also found that a CD8+DC-inducing cytokine, Fms-like tyrosine kinase 3 ligand (FLT3 ligand), restored CD8+DC and reversed Th1/Th2 shift. And then we found that bone marrow cells from irradiated mice differentiated into less CD8+DC, which was also protected by FLT3 ligand. In conclusion, our data showed that IR induced a decrease of CD8+DC and Th1/Th2 shift, which was reversed by Flt3 ligand treatment, suggesting a novel mechanism for radiation-induced immunosuppression. Copyright © 2017. Published by Elsevier B.V.

Late-onset persistent retinal microvascular changes after bone marrow transplantation: 3-year follow-up

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Muccioli Cristina

2002-01-01

Full Text Available Purpose: To describe a case of persistent retinopathy after bone marrow transplantation in the absence of radiation therapy. Methods: Case Report. Results: A 42 year-old man developed bilateral visual loss 15 months after receiving a bone marrow transplant for acute leukemia. The patient was treated with a high dose of cyclosporin A and oral corticosteroids. No radiation therapy was given. Late-onset, multiple, bilateral cotton-wool spots developed 15 months after the bone marrow transplantation and still persist. After three years other cotton-wool spots arose in the absence of any immunosuppressive therapy. Conclusions: Bone marrow transplantation microvasculopathy of the retina may be related to certain combinations of chemotherapy drugs or immunosuppression itself and may persist in the absence of these immunosuppressive drugs.

3 cases of radiation-induced sarcoma

International Nuclear Information System (INIS)

Shiba, Keiichiro; Fukuma, Hisatoshi; Beppu, Yasuo; Hirota, Teruyuki; Shinohara, Norio.

1982-01-01

Criteria for the diagnosis of radiation-induced sarcoma have been previously described. All cases must have a history of irradiation and the second neoplasm must have arisen in the area of the radiation field. A latent period of several years must have elapsed after irradiation before clinical evidence of a second malignant neoplasm. Most important thing is that, all suspected cases must have been proved histologically. We have experienced 3 cases of radiation-induced sarcoma, they were 42-years-old man who developed an osteosarcoma of the lumbar spine at the field of postoperative irradiation for seminoma 7 years previously, 69-years-old woman who developed a malignant fibrous histiocytoma of the buttock at the field of radical radiation for uterine carcinoma 7 years previously and 59-years-old woman who developed an extraskeletal osteosarcoma of the abdominal wall at the field of postoperative irradiation for uterine sarcoma 7 years previously. The last case is very rare and only 8 cases of radiation-induced extraskeletal osteosarcoma have been reported. Since there has been a definite trend in the treatment of cancer toward employing radiation for more favorable cases, in addition to technical improvements in the administration of radiotherapy and more modern equipment, survival data may have been altered considerably in many malignant tumors. Accordingly, more radiation-induced tumors may be encountered in the future. The clinical presentation and histopathology of these radiation-induced sarcomas are presented with a review of the literature. (author)

Use of Human Cadaveric Mesenchymal Stem Cells for Cell Therapy of a Chronic Radiation-Induced Skin Lesion: A Case Report

International Nuclear Information System (INIS)

Portas, M.; Coppola, A.; Mansilla, E.; Drago, H.; Dubner, D.; Radl, A.; Di Giorgio, M.

2016-01-01

Acute and late radiation-induced injury on skin and subcutaneous tissues are associated with substantial morbidity in radiation therapy, interventional procedures and also are of concern in the context of nuclear or radiological accidents. Pathogenesis is initiated by depletion of acutely responding epithelial tissues and damage to vascular endothelial micro-vessels. Efforts for medical management of severe radiation-induced lesions have been made. Nevertheless, the development of strategies to promote wound healing, including stem cell therapy, is required. From 1997 to 2014, over 248 patients were referred to the Radio-pathology Committee of Hospital de Quemados del Gobierno de la Ciudad de Buenos Aires (Burns Hospital) for the diagnosis and therapy of radiation-induced localized lesions. As part of the strategies for the management of severe cases, there is an ongoing research and development protocol on 'Translational Clinical Trial phases I/II to evaluate the safety and efficacy of adult mesenchymal stem cells from bone marrow for the treatment of large burns and radiological lesions'. The object of this work was to describe the actions carried out by the Radio-pathology Committee of the Burns Hospital in a chronic case with more than 30 years of evolution without positive response to conventional treatments. The approach involved the evaluation of the tissular compromise of the lesion, the prognosis and the personalized treatment, including regenerative therapy. (authors)

Magnetic resonance imaging in diffuse malignant bone marrow diseases

Energy Technology Data Exchange (ETDEWEB)

Nyman, R.; Rehn, S.; Glimelius, B.; Hagberg, H.; Hemmingsson, A.; Jung, B.; Simonsson, B.; Sundstroem, C.

Twenty-four patients with malignant bone marrow involvement or polycythemia vera, 8 patients with reactive bone marrow and 7 healthy individuals were examined with spin-echo magnetic resonance imaging at 0.35 T and 0.5 T. Signs of an increased longitudinal relaxation time, T1, were found when normal bone marrow was replaced by malignant cells, polycythemia vera or reactive marrow. A shortened T1 was indicated in 4 patients in bone marrow regions treated by radiation therapy; the marrow was most likely hypocellular in these cases. The estimated T1 relaxation times were highly correlated to the cellularity of the bone marrow as assessed by histology. Among patients with close to 100% cellularity neither T1 nor T2 discriminated between the various malignancies or between malignant and reactive, non-malignant bone marrow. Characterization of tissues in terms of normalized image intensities was also attempted, the motive being to avoid approximations and uncertainties in the assessment of T1 and T2. The normalization was carried out with respect to the image of highest intensity, i.e. the proton density weighted image. The results were in agreement with those for T1 and T2. It was concluded that MRI is valuable for assessing bone marrow cellularity, but not for differentiating between various bone marrow disorders having a similar degree of cellularity.

Fatal radiation pneumonia following subclinical busulfan injury

International Nuclear Information System (INIS)

Soble, A.R.; Perry, H.

1977-01-01

A patient with polycythemia vera received a moderate dose (480 mg) of busulfan intermittently over a 6 year period and later developed Hodgkin's disease. Following split-course upper mantle, chest irradiation, he developed rapidly progressive, fatal pneumonia and bone marrow hypoplasia. It is postulated that the hyperacute organ failures (lung and bone marrow) resulted from augmentation of subclinical busulfan-induced damage of these organs by additive radiation effect. It is recommended that in patients who have had antineoplastic chemotherapy, major radiotherapy to the cervicothoracic region be accompanied by careful monitoring of respiratory and hematopoietic function, both before and during radiotherapy

Resistance to RadLV-induced leukemia: non-participation of splenic natural killer cells

International Nuclear Information System (INIS)

St-Pierre, Y.; Hugo, P.; Lemieux, S.; Lussier, G.; Potworowski, E.F.

1988-01-01

The phenotypic expression of genetically determined resistance to radiation leukemia virus (RadLV)-induced leukemia in mice has been shown to reside in the bone marrow. Because the bone marrow contains precursors of natural killer (NK) cells, known to play a role in retrovirally induced infections, and because these cells have been suggested as participating in resistance to radiation-induced leukemia, it was pertinent to establish whether their levels differed in strains of mice susceptible and resistant to leukemia. We therefore tested splenic NK cell levels in C57BL/Ka (susceptible) and B10.A(5R) (resistant) mice before viral inoculation, immediately after viral inoculation, and throughout the preleukemic period and showed that they were not different. This indicates that splenic NK cell levels have no bearing on the resistance to RadLV-induced leukemia and that other immune or non-immune mechanisms must be sought

Incidental finding of unilateral isolated aplasia of serratus anterior muscle and winged scapula on chest radiograph: A case report

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Choi, Joon Sung; Park, Hyun Jin; Ko, Jeong Min [Dept. of Radiology, St. Vincent' s Hospital, College of Medicine, The Catholic University of Korea, Suwon (Korea, Republic of)

2014-10-15

The isolated aplasia of the serratus anterior muscle with winging of scapula is very rare, and only a few cases are reported. Here, we present a case of a 30-year-old Korean male who initially presented with a left flank pain. His physical exam did not show any significant finding in his right shoulder. However, his chest radiograph showed absence of right serratus anterior muscle and slightly elevated and medially rotated right scapula. Subsequent CT scan showed the right serratus anterior muscle aplasia and medial winging of the right scapula. This case is unique in two aspects. First, the combination of abnormalities is different from the typical congenital abnormalities involving shoulder girdle, such as Sprengel deformity or Poland syndrome. Secondly, this was incidentally diagnosed with chest radiograph, without clinical impression. Careful reading of chest radiograph can help the radiologists to detect such clinically silent abnormalities.

Incidental finding of unilateral isolated aplasia of serratus anterior muscle and winged scapula on chest radiograph: A case report

International Nuclear Information System (INIS)

Choi, Joon Sung; Park, Hyun Jin; Ko, Jeong Min

2014-01-01

The isolated aplasia of the serratus anterior muscle with winging of scapula is very rare, and only a few cases are reported. Here, we present a case of a 30-year-old Korean male who initially presented with a left flank pain. His physical exam did not show any significant finding in his right shoulder. However, his chest radiograph showed absence of right serratus anterior muscle and slightly elevated and medially rotated right scapula. Subsequent CT scan showed the right serratus anterior muscle aplasia and medial winging of the right scapula. This case is unique in two aspects. First, the combination of abnormalities is different from the typical congenital abnormalities involving shoulder girdle, such as Sprengel deformity or Poland syndrome. Secondly, this was incidentally diagnosed with chest radiograph, without clinical impression. Careful reading of chest radiograph can help the radiologists to detect such clinically silent abnormalities.

Radiation-induced radical ions in calcium sulfite

Science.gov (United States)

Bogushevich, S. E.

2006-07-01

We have used EPR to study the effect of γ radiation on calcium sulfite. We have observed and identified the radiation-induced radical ions SO 2 - (iso) with g = 2.0055 and SO 2 - (orth-1) with g1 = 2.0093, g2 = 2.0051, g3 = 2.0020, identical to the initial and thermally induced SO 2 - respectively, SO 3 - (iso) with g = 2.0031 and SO 3 - (axial) with g⊥ = 2.0040, g∥ = 2.0023, identical to mechanically induced SO 3 - . We have established the participation of radiation-induced radical ions SO 3 - in formation of post-radiation SO 2 - .

Radiation- induced aneuploidy in mammalian germ cells

International Nuclear Information System (INIS)

Tease, C.

1989-01-01

The ability of ionizing radiation to induce aneuploidy in mammalian germ cells has been investigated experimentally in the laboratory mouse using a variety of cytogenetic and genetic methods. These studies have provided unambiguous evidence of induced nondisjunction in both male and female germ cells when the effect of irradiation is screened in meiotic cells or preimplantation embryos. In contrast, however, cytogenetic analyses of post-implantation embryos and genetic assays for induced chromosome gains have not found a significant radiation effect. These apparently contradictory findings may be reconciled if (a) radiation induces tertiary rather than primary trisomy, or (b) induces embryo-lethal genetic damage, such as deletions, in addition to numerical anomalies. Either or both of these explanations may account for the apparent loss during gestation of radiation-induced trisomic embryos. Extrapolating from the information so far available, it seems unlikely that environmental exposure to low doses if low dose rate radiation will result in a detectable increase in the rate of aneuploidy in the human population. (author)

Ganoderma lucidum total triterpenes prevent γ-radiation induced oxidative stress in Swiss albino mice in vivo.

Science.gov (United States)

Smina, T P; Joseph, Jini; Janardhanan, K K

2016-11-01

The in vivo radio-protective effect of total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst was evaluated using Swiss albino mice, by pre-treatment with total triterpenes for 14 days, followed by a whole body exposure to γ-radiation. The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) were analysed in liver and brain homogenates. The extent of lipid and protein peroxidation was also estimated in liver and brain homogenates after irradiation. Protection of radiation-induced DNA strand breaks in peripheral blood lymphocytes and bone marrow cells was assessed using the comet assay. Total triterpenes were highly effective in reducing the levels of lipid peroxidation and protein oxidation to near normal values in both liver and brain tissues. Total triterpenes, when administered in vivo, were also found to be successful in restoring the antioxidant enzyme activities and GSH level in liver and brain of irradiated mice. Administration of total triterpenes, prior to radiation exposure, significantly decreased the DNA strand breaks. The results of the present study thus revealed the potential therapeutic use of Ganoderma total triterpenes as an adjuvant in radiation therapy.

Radiation-induced camptocormia and dropped head syndrome. Review and case report of radiation-induced movement disorders

Energy Technology Data Exchange (ETDEWEB)

Seidel, Clemens; Kuhnt, Thomas; Kortmann, Rolf-Dieter; Hering, Kathrin [Leipzig University, Department of Radiotherapy and Radiation Oncology, Leipzig (Germany)

2015-10-15

In recent years, camptocormia and dropped head syndrome (DHS) have gained attention as particular forms of movement disorders. Camptocormia presents with involuntary forward flexion of the thoracolumbar spine that typically increases during walking or standing and may severely impede walking ability. DHS is characterized by weakness of the neck extensors and a consecutive inability to extend the neck; in severe cases the head is fixed in a ''chin to chest position.'' Many diseases may underlie these conditions, and there have been some reports about radiation-induced camptocormia and DHS. A PubMed search with the keywords ''camptocormia,'' ''dropped head syndrome,'' ''radiation-induced myopathy,'' ''radiation-induced neuropathy,'' and ''radiation-induced movement disorder'' was carried out to better characterize radiation-induced movement disorders and the radiation techniques involved. In addition, the case of a patient developing camptocormia 23 years after radiation therapy of a non-Hodgkin's lymphoma of the abdomen is described. In total, nine case series of radiation-induced DHS (n = 45 patients) and - including our case - three case reports (n = 3 patients) about radiogenic camptocormia were retrieved. Most cases (40/45 patients) occurred less than 15 years after radiotherapy involving extended fields for Hodgkin's disease. The use of wide radiation fields including many spinal segments with paraspinal muscles may lead to radiation-induced movement disorders. If paraspinal muscles and the thoracolumbar spine are involved, the clinical presentation can be that of camptocormia. DHS may result if there is involvement of the cervical spine. To prevent these disorders, sparing of the spine and paraspinal muscles is desirable. (orig.) [German] In den letzten Jahren haben Bewegungsstoerungen von Wirbelsaeule und paraspinaler Muskulatur in

Bone marrow-sparing intensity-modulated radiation therapy for Stage I seminoma

International Nuclear Information System (INIS)

Zilli, Thomas; Boudreau, Chantal; Doucet, Robert; Alizadeh, Moein; Lambert, Carole; Van Nguyen, Thu; Taussky, Daniel

2011-01-01

Background. A direct association between radiotherapy dose, side-effects and secondary cancers has been described in patients with seminoma. A treatment planning study was performed in order to compare computed tomography-based traditional radiotherapy (CT-tRT) versus bone marrow-sparing intensity-modulated radiation therapy (BMS-IMRT) in patients with Stage I seminoma. Material and methods. We optimized in 10 patients a CT-tRT and a BMS-IMRT treatment plan to deliver 20 Gy to the para-aortic nodes. CT-tRT and IMRT consisted of anteroposterior-posterioranterior parallel-opposed and seven non-opposed coplanar fields using 16 and 6-MV photon energies, respectively. Dose-Volume Histograms for clinical target volume (CTV), planning target volume (PTV) and organs at risk (OARs) were compared for both techniques using Wilcoxon matched-pair signed rank-test. Results. Dmean to CTV and PTV were similar for both techniques, even if CT-tRT showed a slightly improved target coverage in terms of PTV-D95% (19.7 vs. 19.5 Gy, p 0.005) and PTV-V95% (100 vs. 99.7%, p = 0.011) compared to BMS-IMRT. BMS-IMRT resulted in a significant reduction (5.2 Gy, p = 0.005) in the Dmean to the active bone marrow (ABM). The V100% and V75% of the OARs were reduced with BMS-IMRT by: ABM-V100% = 51.7% and ABM-V75% = 42.3%; bowel-V100% = 15.7% and bowel-V75% = 16.8%; stomach-V100% = 22% and stomach-V75% = 27.7%; pancreas-V100% = 37.1% and pancreas-V75% = 35.9% (p = 0.005 for all variables). Conclusions. BMS-IMRT reduces markedly the dose to the OARs compared to CT-tRT. This should translate into a reduction in acute and long-term toxicity, as well as into the risk of secondary solid and hematological cancers

Positive indium-III bone marrow scan in metastatic breast carcinoma. Case report

International Nuclear Information System (INIS)

LaManna, M.M.; Hyzinski, M.; Swami, V.K.; Parker, J.A.

1984-01-01

Indium is generally presumed to localize in the bone marrow within the erythroid cell line. Fibrosis, inflammation, lymphoma, extended field radiation, chemotherapy, or combinations of both treatment modalities generally depress the uptake of indium by the marrow in a complex fashion. We report a case of metastatic breast carcinoma and pancytopenia in which the In-111 scan appeared qualitatively similar to a Tc-99m MDP bone scan. Findings were confirmed by bone marrow biopsy

Hereditary Factors Involved in Radiation-Induced Leukaemogenesis; Facteurs hereditaires impliques dans la radioleucemogenese

Energy Technology Data Exchange (ETDEWEB)

Duplan, J. F. [Laboratoire Pasteur, Institut du Radium, Paris (France)

1969-11-15

The hereditary factors involved in radiation-induced leukaemogenesis were studied in pure AKR and C57BL strains, their first-generation hybrids and their back-crosses. It is known that the heredity of spontaneous lymphoid leukaemias is attributable to hereditary factors, of which only some are chromosomal, and the same situation can be considered to exist as regards the heredity of radiation-induced leukoses. In order to identify the various chromosomal and non-chromosomal factors concerned, three types of experiment were conducted with the pure strains and with each of the crosses, intended to evaluate (a) the incidence of spontaneous lymphoid leukoses, (b) the incidence of radiation-induced leukoses and (c) the inhibition of radioleukaemo- genesis by the injection of isogenic haematopoietic cells. The results show that the main non-chromosomal factor is the leukaemogenic Gross virus (VG) in the case of the AKR strain and the radioleukaemia virus (VRL) in that of the C57BL strain; these two agents are transmitted by the mother to her progeny. The VG may be responsible for radioleukaemias as well as for spontaneous leukoses, but the VRL does not produce spontaneous leukaemias even in back-crosses possessing a substantial fraction of the AKR genome, which is particularly conducive to leukaemogenesis. Restoration using C57BL bone marrow brings about a distinct inhibition of leukaemogenesis in all animals deriving from crossings for which this material is histocompatible; AKR marrow, however, never exhibits any restorative activity. Three hypotheses may be put forward to explain these results. The first is that C57BL bone marrow contains many more precursor elements than AKR marrow, these cells being necessary for inhibition of the leukaemogenic process. The second hypothesis is that the AKR strain lacks a factor which is essential for the utilization of these precursors. Finally the third hypothesis, which seems the least probable, is that AKR cells are much more

Stem cell therapy for the treatment of radiation-induced normal tissue damage

International Nuclear Information System (INIS)

Chapel, A.; Benderitter, M.; Gourmelon, P.; Lataillade, J.J.; Gorin, N.C.

2013-01-01

Radiotherapy may induce irreversible damage on healthy tissues surrounding the tumour. In Europe, per year, 1.5 million patients undergo external radiotherapy. Acute adverse effect concern 80% of patients. The late adverse effect of radiotherapy concern 5 to 10% of them, which could be life threatening. Eradication of these manifestations is crucial. The French Institute of Radioprotection and Nuclear Safety (IRSN) contribute to understand effect of radiation on healthy tissue. IRSN is strongly implicated in the field of regeneration of healthy tissue after radiotherapy or radiological accident and in the clinical use of cell therapy in the treatment of irradiated patients. Our first success in cell therapy was the correction of deficient hematopoiesis in two patients. The intravenous injection of Mesenchymal Stem Cells (MSC) has restored bone marrow micro-environment after total body irradiation necessary to sustain hematopoiesis. Cutaneous radiation reactions play an important role in radiation accidents, but also as a limitation in radiotherapy and radio-oncology. We have evidenced for the first time, the efficiency of MSC therapy in the context of acute cutaneous and muscle damage following irradiation in five patients. Concerning the medical management of gastrointestinal disorder after irradiation, we have demonstrated the promising approach of the MSC treatment. We have shown that MSC migrate to damaged tissues and restore gut functions after radiation damage. The evaluation of stem cell therapy combining different sources of adult stem cells is under investigation

Radiation-induced myelopathy

Energy Technology Data Exchange (ETDEWEB)

Gaenshirt, H [Heidelberg Univ. (F.R. Germany). Neurologische Klinik

1975-10-01

12 cases of radiation-induced myelopathy after /sup 60/Co teletherapy are reported on. Among these were 10 thoracal lesions, one cerviothoracal lesion, and one lesion of the medulla oblongata. In 9 cases, Hodgkin's disease had been the primary disease, tow patients had been irradiated because of suspected vertebral metastases of cancer of the breast, and one patient had suffered from a glomus tumour of the petrous bone. The spinal doses had exceeded the tolerance doses recommended in the relevant literature. There was no close correlation between the radiation dose and the course of the disease. The latency periods between the end of the radiotherapy and the onset of the neurological symptons varied from 6 to 16 mouths and were very constant in 7 cases with 6 to 9 months. The segmental height of the lesion corresponded to the level of irradiation. The presenting symptons of radiation-induced myelopathy are buruing dysaesthesias and Brown-Sequard's paralysis which may develop into transverse lesion of the cord with paraplegia still accompanied by dissociated perception disorders. The disease developed intermittently. Disturbances of the bladder function are frequent. The fluid is normal in most cases. Myelographic examinations were made in 8 cases. 3 cases developed into stationary cases exhibiting. Brown-Sequard syndrome, while 9 patients developed transverse lesion of the cord with paraplegia. 3 patients have died; antopsy findings are given for two of these. In the pathogenesis of radiation-induced myelopathy, the vascular factor is assumed to be of decisive importance.

Bone marrow transplantation for an infant with neutrophil dysfunction

Energy Technology Data Exchange (ETDEWEB)

Camitta, B M; Quesenberry, P J; Parkman, R; Boxer, L A; Stossel, T P; Cassady, J R; Rappeport, J M; Nathan, D G [Harvard Medical School, Boston, Mass. (USA); Tufts Univ., Boston, Mass. (USA). School of Medicine)

1977-01-01

A child with severe neutrophil dysfunction and intractable infections received bone marrow transplants from histocompatible siblings. After a first transplant preceded by cyclophosphamide (CY), antithymocyte serum (ATS) and procarbazine (PCB) preconditioning, there was no evidence for engraftment and autologous marrow function rapidly returned. Cell mediated lysis showed no evidence of patient sensitization against the marrow donor suggesting that graft rejection did not cause the transplant failure. A second transplant was performed utilizing another matched sibling donor. Total body irradiation was added to CY, ATS, and PCB for preconditioning after in vitro studies of the colony forming capacity (CFUsub(c)) of the patient's marrow cells showed normal sensitivity to radiation. Full engraftment ensued with correction of granulocyte function abnormalities. The patient eventually died of intractable pulmonary disease. Experience with this child suggests that cyclophosphamide alone may be insufficient preparation for marrow transplantation in some patients with non-neoplastic hematologic disorders. Experimental and clinical data supporting this contention are reviewed.

Total body irradiation prior to bone marrow transplantation: efficacy and safety of granisetron in the prophylaxis and control of radiation-induced emesis

International Nuclear Information System (INIS)

Belkacemi, Yazid; Ozsahin, Mahmut; Pene, Francoise; Rio, Bernard; Sutton, Laurent; Laporte, Jean-Philippe; Touboul, Emmanuel; Gorin, Norbert-Claude; Laugier, Alain

1996-01-01

Purpose: Radiation-induced emisis is one of the most disturbing side effects of total body irradiation (TBI). To evaluate the efficacy and to determine the best schedule of granisetron (a selective 5-hydroxytryptamine 3 serotonin receptor antagonist) administration in the prevention of radiation-induced nausea and vomiting, we conducted a trial involving patients receiving single-dose TBI before bone marrow transplantation (BMT). Methods and Materials: Thirty-six patients with non-Hodgkin's lymphoma (n 12), multiple myeloma (n = 8), acute lymphoblastic leukemia (n = 7), acute nonlymphoblastic leukemia (n = 6), and chronic myeloid leukemia (n = 3) referred to our department between March 1992 and February 1994 were enrolled in this study to assess the efficacy of granisetron during single-dose TBI before autologous BMT (n = 26), allogeneic BMT (n = 8), or syngeneic BMT (n 2). The male-to-female ratio was 22:14 (1.57), and the mean age was 41 ± 11 years (range 16-58). Before TBI, conditioning chemotherapy consisted of cyclophosphamide (CY) alone (60 mg/kg per day on 2 successive days) in 24 patients, CY combined with other drugs in 6, and combinations without CY in 6. All patients received single-dose TBI (10 Gy administered to the midplane at L4, and 8 Gy to the lungs). The mean instantaneous and average dose rates were 0.039 ± 0.012 Gy/min (range 0.031-0.058), and 0.025-0.006 Gy/min (range 2.08-3.96), respectively. Granisetron was administered 30-45 min before TBI according to two different modalities: a total dose of 3 mg as a 5-min intravenous (i.v.) infusion (Treatment A, n = 15; 42%) or the same treatment plus 3 mg of granisetron as a 24-h continuous i.v. infusion (total dose: 6 mg, Treatment B, n = 21; 58%). Depending on the BMT teams, hyper diuresis was continued (n = 19, 53%) or suspended (n = 17, 47%) during TBI. Nausea and vomiting were assessed during the TBI session and the following 12 h, and were scored as follows: S1 = no nausea or vomiting; S2

Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? A review.

Science.gov (United States)

Lorimore, S A; Wright, E G

2003-01-01

To review studies of radiation responses in the haemopoietic system in the context of radiation-induced genomic instability, bystander effects and inflammatory-type processes. There is considerable evidence that cells that themselves are not exposed to ionizing radiation but are the progeny of cells irradiated many cell divisions previously may express a high frequency of gene mutations, chromosomal aberrations and cell death. These effects are collectively known as radiation-induced genomic instability. A second untargeted effect results in non-irradiated cells exhibiting responses typically associated with direct radiation exposure but occurs as a consequence of contact with irradiated cells or by receiving soluble signals from irradiated cells. These effects are collectively known as radiation-induced bystander effects. Reported effects include increases or decreases in damage-inducible and stress-related proteins; increases or decreases in reactive oxygen species, cell death or cell proliferation, and induction of mutations and chromosome aberrations. This array of responses is reminiscent of effects mediated by cytokines and other similar regulatory factors that may involve, but do not necessarily require, gap junction-mediated transfer, have multiple inducers and a variety of context-dependent consequences in different cell systems. That chromosomal instability in haemopoietic cells can be induced by an indirect bystander-type mechanism both in vitro and in vivo provides a potential link between these two untargeted effects and there are radiation responses in vivo consistent with the microenvironment contributing secondary cell damage as a consequence of an inflammatory-type response to radiation-induced injury. Intercellular signalling, production of cytokines and free radicals are features of inflammatory responses that have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. The

[Induction of micronuclei in peripheral blood and bone marrow reticulocytes of male mice after subchronic exposure to x-rays and bisphenol A].

Science.gov (United States)

Radzikowska, Joanna; Gajowik, Aneta; Dobrzyńska, Małgorzata

2012-01-01

Ionizing radiation and xenoestrogens are widely present in the human environment. Bisphenol A (BPA) is used to manufacture polycarbonate plastics, epoxy and polyester resins. BPA is present in a great variety of products including: baby bottles, compact disks, thermal paper, safety helmets, bullet resistant laminate, plastic windows, car parts, adhesives, protective coatings, powder paints, polycarbonate bottles and containers, the sheathing of electrical and electronic parts, dental fillings. Food and beverage cans are protected from rusting and corrosion by the application of epoxy resins as inner coatings. Human activities involving the use of radiation and radioactive materials in industry, agriculture and research cause radiation exposure in addition to natural exposure coming from cosmic rays and naturally occurring radioactive substances. The aim of the study was to estimate the effects of bisphenol A, X-rays and combined exposure to X-rays and bisphenol A on the induction of micronuclei in the peripheral blood and in bone marrow reticulocytes of laboratory mice. Pzh-Sfis male mice were exposed for 8 weeks. Animals were treated with bisphenol A diluted in drinking water (5 mg/kg bw, 10 mg/kg bw, 20 mg/kg bw), irradiated 0.05 Gy of X-rays or exposed to a combination of both (0.05 Gy + 5 mg/kg bw BPA). The samples of peripheral blood were taken at 1, 4 and 8 week following the start of exposure, whereas the bone marrow after the end of experiment, only. The induction of micronuclei in reticulocytes were evaluated by using fluorescence microscope. Bisphenol A as well as ionizing radiation stimulated induction of micronuclei in peripheral blood and bone marrow reticulocytes. After the irradiation the level of micronuclei increased, whereas after exposure to BPA decreased related to time expired from beginning of experiment. Combined exposure of ionizing radiation and bisphenol A induced significantly higher frequency of micronuclei compared to the effect

Radiation-induced polymerization and radiation effect on polymers

International Nuclear Information System (INIS)

Seguchi, Tadao

1977-12-01

The processes of radiation-induced polymerization of monomers and also radiation effects on polymers have been studied by instrumental analyses of electron spin resonance (ESR), nuclear magnetic resonance (NMR) and electron microscopy. In radiation-induced polymerization, graft-copolymerization and absorbed state polymerization were taken up. For graft-copolymerization, monomers such as methylmethacrylate and butadiene were made to react with irradiated polyethylene, and behaviors of the initiating radicals and propagating radicals were followed under the reaction by ESR. For absorbed state polymerization, acrylonitrile/zeolite and methylmethacrylate/zeolite were chosen. Absorbed monomers were irradiated at 77 0 K and polymerized at room temperature. Active species and the concentrations were measured by ESR and the yields of polymer were observed by NMR. In radiation effect on polymers, polyvinylfluoride, polyvinylidenfluoride and polytetrafluoroethylene were taken up. Active species trapped in the polymer matrixes were identified and decay and reactivity of the species were also studied. On the basis of information from the electron microscopy and x-ray analysis, radiation effects on these polymers are described. In polytetrafluoroethylene produced by radiation polymerization, the relation between morphology and polymerization conditions and also the process of crystallization during polymerization were studied. (auth.)

Study on radiation-inducible genes

Energy Technology Data Exchange (ETDEWEB)

Lim, Sang Yong; Kim, Dong Ho; Joe, Min Ho; Park, Hae Jun; Song, Hyu Npa

2012-01-15

Radiation-inducible genes of E. coli, which is a model strain for bacterial study, and Salmonella, which is a typical strain for pathogenic bacteria were compared through omic analysis. Heat shock response genes and prophage genes were induced by radiation in Salmonella, not in E. coli. Among prophage genes tested, STM2628 showed the highest activation by radiation, and approximately 1 kb promoter region was turned out to be necessary for radiation response. To screen an artificial promoter showing activation by 2 Gy, the high-throughput screening method using fluorescent MUG substrate was established. The use of bacteria as anticancer agents has attracted interest. In this study, we tried to develop tumor targeting bacteria in which the radiation-inducible promoter activate a transgene encoding a cytotoxic protein. To do this, a tumor-targeting hfq Salmonella mutant strain was constructed, and we found that its virulence decreased. For outward secretion of anticancer protein produced inside bacteria, the signal peptide of SspH1 was determined and the signal peptide was proven to be able to secrete an anticancer protein. Tumor xenograft mouse model was secured, which can be used for efficiency evaluation of bacterial tumor therapy.

Study on radiation-inducible genes

International Nuclear Information System (INIS)

Lim, Sang Yong; Kim, Dong Ho; Joe, Min Ho; Park, Hae Jun; Song, Hyu Npa

2012-01-01

Radiation-inducible genes of E. coli, which is a model strain for bacterial study, and Salmonella, which is a typical strain for pathogenic bacteria were compared through omic analysis. Heat shock response genes and prophage genes were induced by radiation in Salmonella, not in E. coli. Among prophage genes tested, STM2628 showed the highest activation by radiation, and approximately 1 kb promoter region was turned out to be necessary for radiation response. To screen an artificial promoter showing activation by 2 Gy, the high-throughput screening method using fluorescent MUG substrate was established. The use of bacteria as anticancer agents has attracted interest. In this study, we tried to develop tumor targeting bacteria in which the radiation-inducible promoter activate a transgene encoding a cytotoxic protein. To do this, a tumor-targeting hfq Salmonella mutant strain was constructed, and we found that its virulence decreased. For outward secretion of anticancer protein produced inside bacteria, the signal peptide of SspH1 was determined and the signal peptide was proven to be able to secrete an anticancer protein. Tumor xenograft mouse model was secured, which can be used for efficiency evaluation of bacterial tumor therapy

Radiation-induced cancers in man

International Nuclear Information System (INIS)

Hirose, Fumio

1978-01-01

Radiation-induced cancers in man were divided into three groups, a group in which cancers occurred after atomic bomb exposure, a group in which cancers occurred in radiologists and other medical specialists, and a group in which cancers occurred after exposure to diagnostic radiation, and they were summarized. In atomic bomb survivors leukemia, thyroid cancer, salivary gland cancer, lung cancer, and breast cancer occurred so frequently. In addition to them, mortality ratios by malignant lymphoma, stomach cancer, esophageal cancer, and by cancer of urinary tract were increased. The incidence of leukemia was decreased in those who treated radiation owing to the development of the protection of occupational exposure, and the incidence of radiation-induced cancers was decreased in patients owing to the improvement of therapy. However, a new problem has arisen as to the occurrence of cancers after medical exposure, such as various histological types of cancers after the treatment of skin diseases on the head, and breast cancer after the treatment of pneumothorax. Dose-to-effect relation, hereditary factors, effect of age, immunological influences and endocrine actions were also studied in each radiation-induced cancer. (Ichikawa, K.)

Radiation-induced cancers in man

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Hirose, F [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology

1978-07-01

Radiation-induced cancers in man were divided into three groups, a group in which cancers occurred after atomic bomb exposure, a group in which cancers occurred in radiologists and other medical specialists, and a group in which cancers occurred after exposure to diagnostic radiation, and they were summarized. In atomic bomb survivors leukemia, thyroid cancer, salivary gland cancer, lung cancer, and breast cancer occurred so frequently. In addition to them, mortality ratios by malignant lymphoma, stomach cancer, esophageal cancer, and by cancer of urinary tract were increased. The incidence of leukemia was decreased in those who treated radiation owing to the development of the protection of occupational exposure, and the incidence of radiation-induced cancers was decreased in patients owing to the improvement of therapy. However, a new problem has arisen as to the occurrence of cancers after medical exposure, such as various histological types of cancers after the treatment of skin diseases on the head, and breast cancer after the treatment of pneumothorax. Dose-to-effect relation, hereditary factors, effect of age, immunological influences and endocrine actions were also studied in each radiation-induced cancer.

The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

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Ali, Haytham; Galal, Omima; Urata, Yoshishige; Goto, Shinji; Guo, Chang-Ying; Luo, Lan; Abdelrahim, Eman; Ono, Yusuke; Mostafa, Emtethal; Li, Tao-Sheng

2014-01-01

Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit + stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days in sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit + stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit + stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms

The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

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Ali, Haytham [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Galal, Omima [Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Urata, Yoshishige; Goto, Shinji; Guo, Chang-Ying; Luo, Lan [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Abdelrahim, Eman [Department of Medical Histology, Qena Faculty of Medicine, South Valley University (Egypt); Ono, Yusuke [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Mostafa, Emtethal [Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Li, Tao-Sheng, E-mail: litaoshe@nagasaki-u.ac.jp [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

2014-09-26

Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit{sup +} stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days in sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit{sup +} stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit{sup +} stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms.

Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELM alpha recruits bone marrow-derived cells to the murine pulmonary vasculature.

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Daniel J Angelini

2010-06-01

Full Text Available Pulmonary hypertension (PH is a disease of multiple etiologies with several common pathological features, including inflammation and pulmonary vascular remodeling. Recent evidence has suggested a potential role for the recruitment of bone marrow-derived (BMD progenitor cells to this remodeling process. We recently demonstrated that hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELM alpha is chemotactic to murine bone marrow cells in vitro and involved in pulmonary vascular remodeling in vivo.We used a mouse bone marrow transplant model in which lethally irradiated mice were rescued with bone marrow transplanted from green fluorescent protein (GFP(+ transgenic mice to determine the role of HIMF in recruiting BMD cells to the lung vasculature during PH development. Exposure to chronic hypoxia and pulmonary gene transfer of HIMF were used to induce PH. Both models resulted in markedly increased numbers of BMD cells in and around the pulmonary vasculature; in several neomuscularized small (approximately 20 microm capillary-like vessels, an entirely new medial wall was made up of these cells. We found these GFP(+ BMD cells to be positive for stem cell antigen-1 and c-kit, but negative for CD31 and CD34. Several of the GFP(+ cells that localized to the pulmonary vasculature were alpha-smooth muscle actin(+ and localized to the media layer of the vessels. This finding suggests that these cells are of mesenchymal origin and differentiate toward myofibroblast and vascular smooth muscle. Structural location in the media of small vessels suggests a functional role in the lung vasculature. To examine a potential mechanism for HIMF-dependent recruitment of mesenchymal stem cells to the pulmonary vasculature, we performed a cell migration assay using cultured human mesenchymal stem cells (HMSCs. The addition of recombinant HIMF induced migration of HMSCs in a phosphoinosotide-3-kinase-dependent manner.These results demonstrate HIMF-dependent recruitment of BMD

Radiation-induced brain injury: A review

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Michael eRobbins

2012-07-01

Full Text Available Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (> 6 months to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses > 30 Gy; white matter necrosis occurs at fractionated doses > 60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain

Blood and bone marrow response following total body irradiation in patients with lymphosarcomas

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Qasim, M.M.

1977-01-01

Marrow depression and associated peripheral blood changes following fractionated T.B.I. are considerable and appear alarming. However, provided the marrow reserve is good and is not compromised by previous chemotherapy and radiation therapy, recovery occurred in all cases and appeared to be complete. Bone marrow of 3 patients with previous T.B.I. did not show recovery after the second course of T.B.I. Extreme caution is indicated when such a therapy is repeated, as this may lead to progressive marrow hypoplasia. Fractionated low dose T.B.I. could be utilized as a useful therapeutic modality in the management of disseminated lymphosarcoma provided the marrow reserve is good. (author)

Ionizing radiation induced malignancies in man

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Dutrillaux, B.

1997-01-01

Using data on gene and chromosome alterations in human cancers, it is proposed that most radiation induced cancers are a consequence of recessive mutations of tumor suppressor genes. This explains the long delay between radiation exposure and the cancer onset. As a consequence, radiation induced cancers belong to groups of tumors where no specific translocations (forming or activating oncogenes) but multiple unbalanced chromosome rearrangements (deletions unmasking recessive mutations) exist. This explains why osteosarcomas, malignant fibrous histiocytoma, chondrosarcomas are frequently induced, but not liposarcoma, Ewing sarcomas and rhabdomyosarcomas, among others. A single exception confirms this rule: papillary thyroid cancer, frequently induced in exposed children, in which structural rearrangements frequently form a RET/PTC3 fusion gene. This fusion gene is the results of the inversion of a short segment of chromosome 10, and it is assumed that such rearrangement (small para-centric inversion) can easily occur after exposure to radiations, at contrast with translocations between to genes belonging to different chromosomes. (author)

The homing of bone marrow MSCs to non-osseous sites for ectopic bone formation induced by osteoinductive calcium phosphate.

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Song, G.; Habibovic, Pamela; Bao, Chongyun; Hu, J.; van Blitterswijk, Clemens; Yuan, Huipin; Chen, W.; Xu, H.H.K.

2013-01-01

Osteoinductive biomaterials are promising for bone repair. There is no direct proof that bone marrow mesenchymal stem cells (BMSCs) home to non-osseous sites and participate in ectopic bone formation induced by osteoinductive bioceramics. The objective of this study was to use a sex-mismatched

Gonad, bone marrow and effective dose to the population of more than 90 towns and cities of Iran, arising from environmental gamma radiation

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Bahreyni Toossi, M. T.; Bayani, Sh.; Yarahmadi, M.; Aghamir, A.; Jomehzadeh, A.; Hagh Parast, M.; Tamjidi, A.

2009-01-01

Since 1996 the assessment of environmental gamma radiation dose in residential areas of Iranian towns and cities has been accomplished for 10 counties. As a practical method and based on the results of a pilot study, in order to attribute the final results to the whole residential area of a town five stations were selected for every town. The location of individual station was studied closely to comply with recommended conditions in the literature. Materials and Methods: RDS-110 was employed to measure gamma dose rate for one hour. Average annual dose rates plus conversion coefficients were employed to estimate gonad, bone marrow, equivalent and effective dose. Result: Minimum and maximum annual bone marrow and gonad dose equivalent attributed to environmental gamma are 0.24 mSvy -1 (for both tissues) and 1.44 and 1.46 mSvy -l , respectively. Conclusion: Average gonad and bone marrow doses for North Khorasan, Boshehr and Hormozgan provinces were less than the corresponding values for normal area.

Studies on hematopoietic cell apoptosis and the relative gene expression in irradiated mouse bone marrow

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Peng Ruiyun; Wang Dewen; Xiong Chengqi; Gao Yabing; Yang Hong; Cui Yufang; Wang Baozhen

2001-01-01

Objective: To study apoptosis and expressions bcl-2 and p53 in irradiated mouse bone marrow. Methods: LACA mice were irradiated with 60 Co γ-rays. By means of in situ terminal labelling, in situ hybridization and image analysis, the authors studied radiation-induced apoptosis of hematopoietic cells and the expressions of bcl-2 and p53. Results: The characteristics of apoptosis appeared in hematopoietic cells at 6 hrs after irradiation. The expression of bcl-2 was obviously decreased when apoptosis of hematopoietic cells occurred, whereas it increased in the early recovery phase; p53 protein increased during both apoptosis of hematopoietic cells and the recovery phase, and mutant type p53 DNA was positive only in the recovery phase. Conclusion: Radiation may induced apoptosis of hematopoietic cells in a dose-dependent manner; Both bcl-2 and p53 genes play an important role in apoptosis and recovery phase

Use of Human Cadaveric Mesenchymal Stem Cells for Cell Therapy of a Chronic Radiation-Induced Skin Lesion: A Case Report.

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Portas, M; Mansilla, E; Drago, H; Dubner, D; Radl, A; Coppola, A; Di Giorgio, M

2016-09-01

Acute and late radiation-induced injury on skin and subcutaneous tissues are associated with substantial morbidity in radiation therapy, interventional procedures and also are of concern in the context of nuclear or radiological accidents. Pathogenesis is initiated by depletion of acutely responding epithelial tissues and damage to vascular endothelial microvessels. Efforts for medical management of severe radiation-induced lesions have been made. Nevertheless, the development of strategies to promote wound healing, including stem cell therapy, is required. From 1997 to 2014, over 248 patients were referred to the Radiopathology Committee of Hospital de Quemados del Gobierno de la Ciudad de Buenos Aires (Burns Hospital) for the diagnosis and therapy of radiation-induced localized lesions. As part of the strategies for the management of severe cases, there is an ongoing research and development protocol on 'Translational Clinical Trial phases I/II to evaluate the safety and efficacy of adult mesenchymal stem cells from bone marrow for the treatment of large burns and radiological lesions'. The object of this work was to describe the actions carried out by the Radiopathology Committee of the Burns Hospital in a chronic case with more than 30 years of evolution without positive response to conventional treatments. The approach involved the evaluation of the tissular compromise of the lesion, the prognosis and the personalized treatment, including regenerative therapy. © World Health Organisation 2016. All rights reserved. The World Health Organization has granted Oxford University Press permission for the reproduction of this article.

Three cases of radiation-induced cancer in oral regions

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Kawamura, Hiroshi; Shinoki, Kunihiko; Endo, Yoshitaka; Fujita, Yasushi; Hayashi, Susumu

1985-01-01

Three cases of radiation-induced cancer in the oral regions were reported with relation to radiation therapy. One was the general radiation-induced cancer following radiotherapy for the hemangioma. The other two cases, which belonged in the B-1 group of Sakai and his coworker's diagnostic criteria for radiation-induced cancer, were those occurring after radiotherapy for the malignant tumors. Due to the relatively high dosage exposure by the patient in the radiotherapy it is necessary to look out the latency of the radiation-induced cancer. After radiotherapy, careful and periodical observation is important for immediate treatment in an early stage for the radiation-induced cancer to have a favorable prognosis. In addition careful observation of the changes after radiotherapy helps in discovering the precancerous lesions from the therapy. For the radiation-induced cancer, surgical treatment would be the best, however, radiation therapy is also effective in certain cases. (author)

Effects of Lycium barbarum Polysaccharides on Apoptosis, Cellular Adhesion, and Oxidative Damage in Bone Marrow Mononuclear Cells of Mice Exposed to Ionizing Radiation Injury.

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Zhou, Jing; Pang, Hua; Li, Wenbo; Liu, Qiong; Xu, Lu; Liu, Qian; Liu, Ying

2016-01-01

Lycium barbarum has been used for more than 2500 years as a traditional herb and food in China. We investigated the effects of Lycium barbarum polysaccharides (LBP) on apoptosis, oxidative damage, and expression of adhesion molecules in bone marrow mononuclear cells (BMNC) of mice injured by ionizing radiation. Kunming mice were exposed to X-rays; then mice in the LBP groups were continuously injected with various concentrations of LBP intraperitoneally for 14 days. Mice in the control group were continuously injected with normal saline (NS) by the same route for 14 days. A normal group was set up. After 1, 7, and 14 days of treatment, mice were killed and BMNC were extracted. Cell cycle, apoptosis, and the expression of adhesion molecules CD44 and CD49d were detected by flow cytometry. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were identified by colorimetric analyses. LBP significantly decreased the percentage of G0/G1 phase, apoptosis, MDA level, and expression of CD44 and CD49d and distinctly increased the activity of SOD. LBP showed a protective effect on BMNC against ionizing radiation-induced apoptosis and oxidative damage and altered the expression of adhesion molecule.

The nature and principles of the radiation-induced cancerogenesis

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Lips'ka, A.YI.; Serkyiz, Ya.Yi.

2004-01-01

The paper represents the analysis of the authors and literary data concerning the nature and principles of the radiation-induced neoplasms. The mechanisms of the radiation-induced cancerogenesis development are not clear understood. The experimental data altogether do not allow developing the mathematical model of the radiation-induced cancerogenesis at the molecular level. This model has to take into account all necessary indices including radiation factor and the state of the organism. The general principles of the radiation-induced cancerogenesis have been formulated in the present review. It is possible to use these principles in order to predict and calculate the risks of the radiation-induced neoplasms

Feasibility study of helical tomotherapy for total body or total marrow irradiation

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Hui, Susanta K.; Kapatoes, Jeff; Fowler, Jack; Henderson, Douglas; Olivera, Gustavo; Manon, Rafael R.; Gerbi, Bruce; Mackie, T. R.; Welsh, James S.

2005-01-01

Total body radiation (TBI) has been used for many years as a preconditioning agent before bone marrow transplantation. Many side effects still plague its use. We investigated the planning and delivery of total body irradiation (TBI) and selective total marrow irradiation (TMI) and a reduced radiation dose to sensitive structures using image-guided helical tomotherapy. To assess the feasibility of using helical tomotherapy (A) we studied variations in pitch, field width, and modulation factor on total body and total marrow helical tomotherapy treatments. We varied these parameters to provide a uniform dose along with a treatment times similar to conventional TBI (15-30 min). (B) We also investigated limited (head, chest, and pelvis) megavoltage CT (MVCT) scanning for the dimensional pretreatment setup verification rather than total body MVCT scanning to shorten the overall treatment time per treatment fraction. (C) We placed thermoluminescent detectors (TLDs) inside a Rando phantom to measure the dose at seven anatomical sites, including the lungs. A simulated TBI treatment showed homogeneous dose coverage (±10%) to the whole body. Doses to the sensitive organs were reduced by 35%-70% of the target dose. TLD measurements on Rando showed an accurate dose delivery (±7%) to the target and critical organs. In the TMI study, the dose was delivered conformally to the bone marrow only. The TBI and TMI treatment delivery time was reduced (by 50%) by increasing the field width from 2.5 to 5.0 cm in the inferior-superior direction. A limited MVCT reduced the target localization time 60% compared to whole body MVCT. MVCT image-guided helical tomotherapy offers a novel method to deliver a precise, homogeneous radiation dose to the whole body target while reducing the dose significantly to all critical organs. A judicious selection of pitch, modulation factor, and field size is required to produce a homogeneous dose distribution along with an acceptable treatment time. In

Effect of Transplantation of Bone Marrow Derived Mesenchymal Stem Cells and Platelets Rich Plasma on Experimental Model of Radiation Induced Oral Mucosal Injury in Albino Rats

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Basma Elsaadany

2017-01-01

Full Text Available Normal tissue damage following radiotherapy is still a major problem in cancer treatment. Therefore, the current work aimed at exploring the possible role of systemically injected bone marrow derived mesenchymal stem cells (BM-MSCs and/or locally injected platelet rich plasma (PRP in ameliorating the side effects of ionizing radiation on the rat’s tongue. Twelve rats served as control group (N and 48 rats received a single radiation dose of 13 Gy to the head and neck region; then, they were equally divided into 4 experimental groups: irradiated only (C, irradiated + MSCs (S, irradiated + (PRP (P, and combined group (PS. Animal scarification occurred in 3 and 7 days after radiation. Then, tongues were dissected and examined histologically and for expression of bcl-2 by RT-PCR. Histological examination of the treated groups (S, (P, and (PS revealed an obvious improvement in the histological structure of the tongue, compared to group (C, in addition to upregulated expression of bcl-2, indicating decreased apoptotic activity. Conclusion. BM-MSCs and PRP have shown positive effect in minimizing the epithelial atrophy of normal oral mucosa after regional radiotherapy, which was emphasized by decreasing apoptotic activity in these tissues. Nevertheless, combined use of BM-MSCs and PRP did not reveal the assumed synergetic effect in oral tissue protection.

Sequencing analysis of mutations induced by N-ethyl-N-nitrosourea at different sampling times in mouse bone marrow.

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Wang, Jianyong; Chen, Tao

2010-03-01

In our previous study (Wang et al., 2004, Toxicol. Sci. 82: 124-128), we observed that the cII gene mutant frequency (MF) in the bone marrow of Big Blue mice showed significant increase as early as day 1, reached the maximum at day 3 and then decreased to a plateau by day 15 after a single dose of carcinogen N-ethyl-N-nitrosourea (ENU) treatment, which is different from the longer mutation manifestation time and the constancy of MFs after reaching their maximum in some other tissues. To determine the mechanism underlying the quick increase in MF and the peak formation in the mutant manifestation, we examined the mutation frequencies and spectra of the ENU-induced mutants collected from different sampling times in this study. The cII mutants from days 1, 3 and 120 after ENU treatment were randomly selected from different animals. The mutation frequencies were 33, 217, 305 and 144 x 10(-6) for control, days 1, 3, and 120, respectively. The mutation spectra at days 1 and 3 were significantly different from that at day 120. Considering that stem cells are responsible for the ultimate MF plateau (day 120) and transit cells are accountable for the earlier MF induction (days 1 or 3) in mouse bone marrow, we conclude that transit cells are much more sensitive to mutation induction than stem cells in mouse bone marrow, which resulted in the specific mutation manifestation induced by ENU.

Mapping Radiation Injury and Recovery in Bone Marrow Using 18F-FLT PET/CT and USPIO MRI in a Rat Model.

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Rendon, David A; Kotedia, Khushali; Afshar, Solmaz F; Punia, Jyotinder N; Sabek, Omaima M; Shirkey, Beverly A; Zawaski, Janice A; Gaber, M Waleed

2016-02-01

We present and test the use of multimodality imaging as a topological tool to map the amount of the body exposed to ionizing radiation and the location of exposure, which are important indicators of survival and recovery. To achieve our goal, PET/CT imaging with 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) was used to measure cellular proliferation in bone marrow (BM), whereas MRI using ultra-small superparamagnetic iron oxide (USPIO) particles provided noninvasive information on radiation-induced vascular damage. Animals were x-ray-irradiated at a dose of 7.5 Gy with 1 of 3 radiation schemes-whole-body irradiation, half-body shielding (HBS), or 1-leg shielding (1LS)-and imaged repeatedly. The spatial information from the CT scan was used to segment the region corresponding to BM from the PET scan using algorithms developed in-house, allowing for quantification of proliferating cells, and BM blood volume was estimated by measuring the changes in the T2 relaxation rates (ΔR2) collected from MR scans. (18)F-FLT PET/CT imaging differentiated irradiated from unirradiated BM regions. Two days after irradiation, proliferation of 1LS animals was significantly lower than sham (P = 0.0001, femurs; P < 0.0001, tibias) and returned to sham levels by day 10 (P = 0.6344, femurs; P = 0.3962, tibias). The degree of shielding affected proliferation recovery, showing an increase in the irradiated BM of the femurs, but not the tibias, of HBS animals when compared with 1LS (P = 0.0310, femurs; P = 0.5832, tibias). MRI of irradiated spines detected radiation-induced BM vascular damage, measured by the significant increase in ΔR2 2 d after whole-body irradiation (P = 0.0022) and HBS (P = 0.0003) with a decreasing trend of values, returning to levels close to baseline over 10 d. Our data were corroborated using γ-counting and histopathology. We demonstrated that (18)F-FLT PET/CT and USPIO MRI are valuable tools in mapping regional radiation exposure and the effects of radiation on

A case of severe congenital kyphoscoliosis secondary to multiple bilateral thoracic pedicle aplasia

International Nuclear Information System (INIS)

Geoffray, Anne; Leloutre, Beatrice; Albertario, Marco; Bechard-Sevette, Nancy; Clement, Jean-Luc

2008-01-01

A 9-month-old boy with congenital kyphoscoliosis secondary to multiple bilateral thoracic pedicle aplasias is presented. This anomaly has rarely been described in the literature. Plain films showed absence of thoracic pedicles bilaterally from T2 to T9, which was better demonstrated on CT multiplanar and 3-D reformatted images. There were no neurological symptoms even though the deformity progressed rapidly. Congenital kyphosis or kyphoscoliosis is often related to spinal anomalies that are located on the anterior aspect of the vertebrae. However, posterior anomalies may also be responsible and should be recognized before neurological complications occur. (orig.)

Molecular Mechanisms That Contribute to Bone Marrow Pain

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Jason J. Ivanusic

2017-09-01

Full Text Available Pain associated a bony pathology puts a significant burden on individuals, society, and the health-care systems worldwide. Pathology that involves the bone marrow activates sensory nerve terminal endings of peripheral bone marrow nociceptors, and is the likely trigger for pain. This review presents our current understanding of how bone marrow nociceptors are influenced by noxious stimuli presented in pathology associated with bone marrow. A number of ion channels and receptors are emerging as important modulators of the activity of peripheral bone marrow nociceptors. Nerve growth factor (NGF sequestration has been trialed for the management of inflammatory bone pain (osteoarthritis, and there is significant evidence for interaction of NGF with bone marrow nociceptors. Activation of transient receptor potential cation channel subfamily V member 1 sensitizes bone marrow nociceptors and could contribute to increased sensitivity of patients to noxious stimuli in various bony pathologies. Acid-sensing ion channels sense changes to tissue pH in the bone marrow microenvironment and could be targeted to treat pathology that involves acidosis of the bone marrow. Piezo2 is a mechanically gated ion channel that has recently been reported to be expressed by most myelinated bone marrow nociceptors and might be a target for treatments directed against mechanically induced bone pain. These ion channels and receptors could be useful targets for the development of peripherally acting drugs to treat pain of bony origin.

Cell Cycle Related Differentiation of Bone Marrow Cells into Lung Cells

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Dooner, Mark; Aliotta, Jason M.; Pimental, Jeffrey; Dooner, Gerri J.; Abedi, Mehrdad; Colvin, Gerald; Liu, Qin; Weier, Heinz-Ulli; Dooner, Mark S.; Quesenberry, Peter J.

2007-12-31

Green-fluorescent protein (GFP) labeled marrow cells transplanted into lethally irradiated mice can be detected in the lungs of transplanted mice and have been shown to express lung specific proteins while lacking the expression of hematopoietic markers. We have studied marrow cells induced to transit cell cycle by exposure to IL-3, IL-6, IL-11 and steel factor at different times of culture corresponding to different phases of cell cycle. We have found that marrow cells at the G1/S interface have a 3-fold increase in cells which assume a lung phenotype and that this increase is no longer seen in late S/G2. These cells have been characterized as GFP{sup +} CD45{sup -} and GFP{sup +} cytokeratin{sup +}. Thus marrow cells with the capacity to convert into cells with a lung phenotype after transplantation show a reversible increase with cytokine induced cell cycle transit. Previous studies have shown the phenotype of bone marrow stem cells fluctuates reversibly as these cells traverse cell cycle, leading to a continuum model of stem cell regulation. The present studies indicate that marrow stem cell production of nonhematopoietic cells also fluctuates on a continuum.

PTH prevents the adverse effects of focal radiation on bone architecture in young rats.

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Chandra, Abhishek; Lan, Shenghui; Zhu, Ji; Lin, Tiao; Zhang, Xianrong; Siclari, Valerie A; Altman, Allison R; Cengel, Keith A; Liu, X Sherry; Qin, Ling

2013-08-01

Radiation therapy is a common treatment regimen for cancer patients. However, its adverse effects on the neighboring bone could lead to fractures with a great impact on quality of life. The underlying mechanism is still elusive and there is no preventive or curative solution for this bone loss. Parathyroid hormone (PTH) is a current therapy for osteoporosis that has potent anabolic effects on bone. In this study, we found that focal radiation from frequent scans of the right tibiae in 1-month-old rats by micro-computed tomography severely decreased trabecular bone mass and deteriorated bone structure. Interestingly, PTH daily injections remarkably improved trabecular bone in the radiated tibiae with increases in trabecular number, thickness, connectivity, structure model index and stiffness, and a decrease in trabecular separation. Histomorphometric analysis revealed that radiation mainly decreased the number of osteoblasts and impaired their mineralization activity but had little effects on osteoclasts. PTH reversed these adverse effects and greatly increased bone formation to a similar level in both radiated and non-radiated bones. Furthermore, PTH protects bone marrow mesenchymal stem cells from radiation-induced damage, including a decrease in number and an increase in adipogenic differentiation. While radiation generated the same amount of free radicals in the bone marrow of vehicle-treated and PTH-treated animals, the percentage of apoptotic bone marrow cells was significantly attenuated in the PTH group. Taken together, our data demonstrate a radioprotective effect of PTH on bone structure and bone marrow and shed new light on a possible clinical application of anabolic treatment in radiotherapy. Copyright © 2013 Elsevier Inc. All rights reserved.

Radiation-induced linking reactions in polyethylene

International Nuclear Information System (INIS)

Zoepfl, F.J.

1983-01-01

Three types of measurements are reported relating to chemical reactions in polyethylene induced by ionizing radiation: 1) viscometric and low-angle laser light scattering measurements to determine the effect of a radical scavenger on the yield of links; 2) calorimetric measurements to determine the effect of radiation-induced linking on the melting behavior of polyethylene; and 3) high-resolution solution carbon 13 nuclear magnetic resonance (NMR) spectrometry measurements to determine the nature of the links and the method of their formation. The NMR results present the first direct detection of radiation-induced long-chain branching (Y links) in polyethylene, and place an apparent upper limit on the yield of H-shaped crosslinks that are formed when polyethylene is irradiated to low absorbed doses. The effect of radiation-induced linking on the melting behavior of polyethylene was examined using differential scanning calorimetry (DSC). It was found that radiation-induced links do not change the heat of fusion of polythylene crystals, but decrease the melt entropy and increase the fold surface free energy per unit area of the crystals. The carbon 13 NMR results demonstrate that long-chain branches (Y links) are formed much more frequently than H-shaped crosslinks at low absorbed doses. The Y links are produced by reactions of alkyl free radicals with terminal vinyl groups in polyethylene

Genetic alterations during radiation-induced carcinogenesis

International Nuclear Information System (INIS)

Kodama, Seiji

1995-01-01

This paper reviews radiation-induced genetic alterations and its carcinogenesis, focusing on the previous in vitro assay outcome. A colony formation assay using Syrian hamster fetal cells and focus formation assay using mouse C3H10T1/2 cells are currently available to find malignant transformation of cells. Such in vitro assays has proposed the hypothesis that radiation-induced carcinogenesis arises from at least two-stage processes; i.e., that an early step induced by irradiation plays an important role in promoting the potential to cause the subsequent mutation. A type of genetic instability induced by radiation results in a persistently elevated frequency of spontaneous mutations, so-called the phenomenon of delayed reproductive death. One possible mechanism by which genetic instability arises has been shown to be due to the development of abnormality in the gene group involved in the maintenance mechanism of genome stability. Another possibility has also been shown to stem from the loss of telomere (the extremities of a chromosome). The importance of search for radiation-induced genetic instability is emphasized in view of the elucidation of carcinogenesis. (N.K.)

Combined effect of radiation and YM-881 (SMANCS) on murine tumors and bone marrow

International Nuclear Information System (INIS)

Ono, K.; Wandl, E.; Sasai, K.; Tsutsui, K.; Shibamoto, Y.; Takahashi, M.; Abe, M.; Vienna Univ.

1990-01-01

The combined effect of radiation and YM-881 (SMANCS) was studied in vitro and in vivo. When 0.25 μg/ml of YM-881 was simultaneously combined with radiation, during and after irradiation for 30 min in total, D q decreased from 3.3 Gy to 1.4 Gy without changing D 0 in the dose-survival curve of exponentially growing SCC VII tumor cells. Five or ten times administrations of 0.1 mg/kg YM-881 at an interval of 24 h did not inhibit tumor growth. However, administration of 0.1 mg/kg YM-881 just before every irradiation which was repeated five times at an interval of 24 h yielded dose modifying factors (DMFs) of 1.8-1.2 when the tumor response to treatment was evaluated by the time for the tumors to regrow to three times the original volume. Administration of YM-881 ten times just before every irradiation yielded DMFs of 1.3-1.2. Adverse effects of the combination on bone marrow were examined by spleen colony assay. After five injections of 0.1 mg/kg YM-881, the mean number of CFU-S per femur decreased to 77% of the pretreatment level, but this was not significant statistically (0.1>p>0.05). The slope of radiation response curve for CFU-S per femur was not affected by the combination. (orig.)

Imaging findings in a child with calcineurin inhibitor-induced pain syndrome after bone marrow transplant for beta thalassemia major

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Ayyala, Rama S.; Arnold, Staci D.; Bhatia, Monica; Dastgir, Jahannaz [Columbia University Medical Center, Morgan Stanley Children' s Hospital, Department of Radiology, New York, NY (United States)

2016-10-15

Calcineurin inhibitor-induced pain syndrome is an entity recognized in patients on immunosuppressive therapy after transplantation. Diagnosis is characterized by onset of pain beginning in the setting of an elevated calcineurin-inhibitor trough level. Reducing the medication dose relieves symptoms. Imaging findings can be nonspecific, including bone marrow edema and periosteal reaction. We present the unique case of calcineurin inhibitor-induced pain syndrome in a child and review the imaging findings. (orig.)

Imaging findings in a child with calcineurin inhibitor-induced pain syndrome after bone marrow transplant for beta thalassemia major

International Nuclear Information System (INIS)

Ayyala, Rama S.; Arnold, Staci D.; Bhatia, Monica; Dastgir, Jahannaz

2016-01-01

Calcineurin inhibitor-induced pain syndrome is an entity recognized in patients on immunosuppressive therapy after transplantation. Diagnosis is characterized by onset of pain beginning in the setting of an elevated calcineurin-inhibitor trough level. Reducing the medication dose relieves symptoms. Imaging findings can be nonspecific, including bone marrow edema and periosteal reaction. We present the unique case of calcineurin inhibitor-induced pain syndrome in a child and review the imaging findings. (orig.)

Thyroid dysfunction among long-term survivors of bone marrow transplantation

International Nuclear Information System (INIS)

Sklar, C.A.; Kim, T.H.; Ramsay, N.K.

1982-01-01

Thyroid function studies were followed serially in 27 long-term survivors (median 33 months) of bone marrow transplantation. There were 15 men and 12 women (median age 13 1/12 years, range 11/12 to 22 6/12 years). Aplastic anemia (14 patients) and acute nonlymphocytic leukemia (eight patients) were the major reasons for bone marrow transplantation. Pretransplant conditioning consisted of single-dose irradiation combined with high-dose, short-term chemotherapy in 23 patients, while four patients received a bone marrow transplantation without any radiation therapy. Thyroid dysfunction occurred in 10 of 23 (43 percent) irradiated patients; compensated hypothyroidism (elevated thyroid-stimulating hormone levels only) developed in eight subjects, and two patients had primary thyroid failure (elevated thyroid-stimulating hormone levels and low T4 index). The abnormal thyroid studies were detected a median of 13 months after bone marrow transplantation. The four subjects who underwent transplantation without radiation therapy have remained euthyroid (median follow-up two years). The only variable that appeared to correlate with the subsequent development of impaired thyroid function was the type of graft-versus-host disease prophylaxis employed; the irradiated subjects treated with methotrexate alone had a higher incidence of thyroid dysfunction compared to those treated with methotrexate combined with antithymocyte globulin and prednisone (eight of 12 versus two of 11, p less than 0.05). The high incidence and subtle nature of impaired thyroid function following single-dose irradiation for bone marrow transplantation are discussed

Identification of resident and inflammatory bone marrow derived cells in the sclera by bone marrow and haematopoietic stem cell transplantation.

Science.gov (United States)

Hisatomi, Toshio; Sonoda, Koh-hei; Ishikawa, Fumihiko; Qiao, Hong; Nakazawa, Takahiro; Fukata, Mitsuhiro; Nakamura, Toru; Noda, Kousuke; Miyahara, Shinsuke; Harada, Mine; Kinoshita, Shigeru; Hafezi-Moghadam, Ali; Ishibashi, Tatsuro; Miller, Joan W

2007-04-01

To characterise bone marrow derived cells in the sclera under normal and inflammatory conditions, we examined their differentiation after transplantation from two different sources, bone marrow and haematopoietic stem cells (HSC). Bone marrow and HSC from green fluorescent protein (GFP) transgenic mice were transplanted into irradiated wild-type mice. At 1 month after transplantation, mice were sacrificed and their sclera examined by histology, immunohistochemistry (CD11b, CD11c, CD45), and transmission and scanning electron microscopy. To investigate bone marrow derived cell recruitment under inflammatory conditions, experimental autoimmune uveitis (EAU) was induced in transplanted mice. GFP positive cells were distributed in the entire sclera and comprised 22.4 (2.8)% (bone marrow) and 28.4 (10.9)% (HSC) of the total cells in the limbal zone and 18.1 (6.7)% (bone marrow) and 26.3 (3.4)% (HSC) in the peripapillary zone. Immunohistochemistry showed that GFP (+) CD11c (+), GFP (+) CD11b (+) cells migrated in the sclera after bone marrow and HSC transplantation. Transmission and scanning electron microscopy revealed antigen presenting cells among the scleral fibroblasts. In EAU mice, vast infiltration of GFP (+) cells developed into the sclera. We have provided direct and novel evidence for the migration of bone marrow and HSC cells into the sclera differentiating into macrophages and dendritic cells. Vast infiltration of bone marrow and HSC cells was found to be part of the inflammatory process in EAU.

Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats

Directory of Open Access Journals (Sweden)

Jodi A. Carlson Scholz

2012-12-01

Full Text Available Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH. Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture.

48XXYY Syndrome in an Adult with Type 2 Diabetes Mellitus, Unilateral Renal Aplasia, and Pigmentary Retinitis

OpenAIRE

Zantour, Baha; Sfar, Mohamed Habib; Younes, Samia; Alaya, Wafa; Kamoun, Mahdi; Mkaouar, Emna; Jerbi, Saida

2010-01-01

A 45-year-old male was referred for diabetes mellitus. Clinical examination found a family history of multiple precocious deaths, strong consanguinity, personal history of seizures during childhood, small testicles, small penis, sparse body hair, long arms and legs, dysmorphic features, mental retardation, dysarthria, tremor, and mild gait ataxia. Investigations found pigmentary retinitis, metabolic syndrome, unilateral renal aplasia, and hypergonadotropic hypogonadism, and ruled out mitochon...

Late renal dysfunction in adult survivors of bone marrow transplantation

International Nuclear Information System (INIS)

Lawton, C.A.; Cohen, E.P.; Barber-Derus, S.W.; Murray, K.J.; Ash, R.C.; Casper, J.T.; Moulder, J.E.

1991-01-01

Until recently long-term renal toxicity has not been considered a major late complication of bone marrow transplantation (BMT). Late renal dysfunction has been described in a pediatric population status post-BMT which was attributable to the radiation in the preparatory regimen. A thorough review of adults with this type of late renal dysfunction has not previously been described. Fourteen of 103 evaluable adult patients undergoing allogeneic (96) or autologous (7) bone marrow transplantation, predominantly for leukemia and lymphomas, at the Medical College of Wisconsin (Milwaukee, WI) have had a syndrome of renal insufficiency characterized by increased serum creatinine, decreased glomerular filtration rate, anemia, and hypertension. This syndrome developed at a median of 9 months (range, 4.5 to 26 months) posttransplantation in the absence of specific identifiable causes. The cumulative probability of having this renal dysfunction is 20% at 1 year. Renal biopsies performed on seven of these cases showed the endothelium widely separated from the basement membrane, extreme thickening of the glomerular basement membrane, and microthrombi. Previous chemotherapy, antibiotics, and antifungals as well as cyclosporin may add to and possibly potentiate a primary chemoradiation marrow transplant renal injury, but this clinical syndrome is most analogous to clinical and experimental models of radiation nephritis. This late marrow transplant-associated nephritis should be recognized as a potentially limiting factor in the use of some intensive chemoradiation conditioning regimens used for BMT. Some selective attenuation of the radiation to the kidneys may decrease the incidence of this renal dysfunction

Relationship of bone marrow dose to eosinophilia following radiotherapy

International Nuclear Information System (INIS)

Murohashi, Ikuo; Gomi, Hiromichi; Nakano, Takashi; Morita, Shinroku; Arai, Tatsuo; Jinnai, Itsuro; Nara, Nobuo; Bessho, Masami; Hirashima, Kunitake.

1986-01-01

Absolute blood eosinophils were counted prior to and during radiotherapy in a total of 380 patients with carcinoma in the chest, pelvis, or abdomen. The patients were divided into 5 groups by types of cancer, and these groups differed in the irradiation sites or the sizes of radiation field. Accumulated bone marrow dose from the start of radiotherapy to the time when eosinophil count during radiotherapy reached its peak was simultaneously determined. In each group, maximum eosinophil count during radiotherapy was significantly increased compared with the value before radiotherapy. In all groups except one, the increase in eosinophil count following radiotherapy was directly proportional to the bone marrow dose. However, in the most heavily irradiated ovarian cancer group, the increase in eosinophil count was markedly lower. In contrast, neutrophils were reduced in numbers in all groups. These results suggest that bone marrow (red marrow) damage by irradiation results in eosinophilia, and that unimpaired hemopoiesis is also indispensable for such an eosinophil response. Accumulated bone marrow doses of 800 - 900 rad given during 4 weeks fractionated irradiation caused the most prominent eosinophilia. (author)

Bone marrow aspiration

Science.gov (United States)

Iliac crest tap; Sternal tap; Leukemia - bone marrow aspiration; Aplastic anemia - bone marrow aspiration; Myelodysplastic syndrome - bone marrow aspiration; Thrombocytopenia - bone marrow aspiration; Myelofibrosis - bone marrow aspiration

Radiation-induced brain injury: A review

Energy Technology Data Exchange (ETDEWEB)

Greene-Schloesser, Dana; Robbins, Mike E.; Peiffer, Ann M.; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Wheeler, Kenneth T. [Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Department of Radiology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Chan, Michael D., E-mail: mrobbins@wakehealth.edu [Department of Radiation Oncology, Wake Forest School of Medicine,, Winston-Salem, NC (United States); Brain Tumor Center of Excellence, Wake Forest School of Medicine,, Winston-Salem, NC (United States)

2012-07-19

Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their

Radiation-induced brain injury: A review

International Nuclear Information System (INIS)

Greene-Schloesser, Dana; Robbins, Mike E.; Peiffer, Ann M.; Shaw, Edward G.; Wheeler, Kenneth T.; Chan, Michael D.

2012-01-01

Approximately 100,000 primary and metastatic brain tumor patients/year in the US survive long enough (>6 months) to experience radiation-induced brain injury. Prior to 1970, the human brain was thought to be highly radioresistant; the acute CNS syndrome occurs after single doses >30 Gy; white matter necrosis occurs at fractionated doses >60 Gy. Although white matter necrosis is uncommon with modern techniques, functional deficits, including progressive impairments in memory, attention, and executive function have become important, because they have profound effects on quality of life. Preclinical studies have provided valuable insights into the pathogenesis of radiation-induced cognitive impairment. Given its central role in memory and neurogenesis, the majority of these studies have focused on the hippocampus. Irradiating pediatric and young adult rodent brains leads to several hippocampal changes including neuroinflammation and a marked reduction in neurogenesis. These data have been interpreted to suggest that shielding the hippocampus will prevent clinical radiation-induced cognitive impairment. However, this interpretation may be overly simplistic. Studies using older rodents, that more closely match the adult human brain tumor population, indicate that, unlike pediatric and young adult rats, older rats fail to show a radiation-induced decrease in neurogenesis or a loss of mature neurons. Nevertheless, older rats still exhibit cognitive impairment. This occurs in the absence of demyelination and/or white matter necrosis similar to what is observed clinically, suggesting that more subtle molecular, cellular and/or microanatomic modifications are involved in this radiation-induced brain injury. Given that radiation-induced cognitive impairment likely reflects damage to both hippocampal- and non-hippocampal-dependent domains, there is a critical need to investigate the microanatomic and functional effects of radiation in various brain regions as well as their

Aplasia Ras homologue member Ⅰ overexpression inhibits tumor growth and induces apoptosis through inhibition of PI3K/Akt survival pathways in human osteosarcoma MG-63 cells in culture.