Usefulness of blood irradiation before transfusion to avoid transfusion associated graft versus host disease (TA-GVHD)

International Nuclear Information System (INIS)

Takahashi, Koki

1997-01-01

We summarize the pathology of the transfusion associated graft versus host disease (TA-GVHD) and examine the usefulness of the blood irradiation before transfusion as more widely used prophylaxis. The symptom of TA-GVHD was as follows: after (asymptomatic phase) for 1 to 2 weeks after blood transfusion, pyrexia and erythema appeared. Furthermore, hepatic disorder, diarrhea and bloody stool occurred. In no longer time, pancytopenia by aplastic crisis of the bone marrow appeard, and severe granulocytopenia occurred. Finally, by the complication with severe infectious disease such as septicemia, almost all the patients died with in 3 to 4 weeks after blood transfusion. TA-GVHD was found in some patients without immune deficiency syndrome. The cause of the frequent occurrence of the disease in Japan was shown by the probability of the one-way matching analysis. As the countermeasure of TA-GVHD, we examined the effectiveness of the blood irradiation before transfusion under the consideration of the safety and the emergency. After the responder cells were beforehand irradiated with various doses of radiation (X-ray or g-ray), the proliferative response was investigated through the uptake of 3 H-thymidine, and we obtained 15-50 Gy as the optimum dose of the radiation. We discuss the establishment of the countermeasure for the TA-GVHD and the formation of the nationwide support system for TV-GVHD (K.H.). 33 refs

Homecare-based motor rehabilitation in musculoskeletal chronic graft versus host disease

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A Tendas

2011-01-01

Full Text Available Chronic graft versus host disease (cGVHD is a frequent complication of allogeneic stem cell transplantation. Extensive musculoskeletal and skin involvement may induce severe functional impairment, disability and quality of life deterioration. Physical rehabilitation is recommended as ancillary therapy in these forms, but experiences are sparse. A 39-year-old man affected by musculoskeletal and skin chronic graft versus host disease (cGVHD was treated with a homecare-based motor rehabilitation program during palliation for disease progression. Significant functional improvement was obtained. Motor rehabilitation should be strongly considered for patients with musculoskeletal cGVHD, both in the palliative and in the curative phase of disease.

Prevention of transfusion-associated graft-versus-host disease by irradiation: technical aspect of a new ferrous sulphate dosimetric system.

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Lucas Sacchini Del Lama

Full Text Available Irradiation of whole blood and blood components before transfusion is currently the only accepted method to prevent Transfusion-Associated Graft-Versus-Host-Disease (TA-GVHD. However, choosing the appropriate technique to determine the dosimetric parameters associated with blood irradiation remains an issue. We propose a dosimetric system based on the standard Fricke Xylenol Gel (FXG dosimeter and an appropriate phantom. The modified dosimeter was previously calibrated using a (60Co teletherapy unit and its validation was accomplished with a (137Cs blood irradiator. An ionization chamber, standard FXG, radiochromic film and thermoluminescent dosimeters (TLDs were used as reference dosimeters to determine the dose response and dose rate of the (60Co unit. The dose distributions in a blood irradiator were determined with the modified FXG, the radiochromic film, and measurements by TLD dosimeters. A linear response for absorbed doses up to 54 Gy was obtained with our system. Additionally, the dose rate uncertainties carried out with gel dosimetry were lower than 5% and differences lower than 4% were noted when the absorbed dose responses were compared with ionization chamber, film and TLDs.

Prevention of Transfusion-Associated Graft-versus-Host Disease by Irradiation: Technical Aspect of a New Ferrous Sulphate Dosimetric System

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Del Lama, Lucas Sacchini; de Góes, Evamberto Garcia; Petchevist, Paulo César Dias; Moretto, Edson Lara; Borges, José Carlos; Covas, Dimas Tadeu; de Almeida, Adelaide

2013-01-01

Irradiation of whole blood and blood components before transfusion is currently the only accepted method to prevent Transfusion-Associated Graft-Versus-Host-Disease (TA-GVHD). However, choosing the appropriate technique to determine the dosimetric parameters associated with blood irradiation remains an issue. We propose a dosimetric system based on the standard Fricke Xylenol Gel (FXG) dosimeter and an appropriate phantom. The modified dosimeter was previously calibrated using a 60Co teletherapy unit and its validation was accomplished with a 137Cs blood irradiator. An ionization chamber, standard FXG, radiochromic film and thermoluminescent dosimeters (TLDs) were used as reference dosimeters to determine the dose response and dose rate of the 60Co unit. The dose distributions in a blood irradiator were determined with the modified FXG, the radiochromic film, and measurements by TLD dosimeters. A linear response for absorbed doses up to 54 Gy was obtained with our system. Additionally, the dose rate uncertainties carried out with gel dosimetry were lower than 5% and differences lower than 4% were noted when the absorbed dose responses were compared with ionization chamber, film and TLDs. PMID:23762345

Inhibition of protein geranylgeranylation and farnesylation protects against graft-versus-host disease via effects on CD4 effector T cells.

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Hechinger, Anne-Kathrin; Maas, Kristina; Dürr, Christoph; Leonhardt, Franziska; Prinz, Gabriele; Marks, Reinhard; Gerlach, Ulrike; Hofmann, Maike; Fisch, Paul; Finke, Jürgen; Pircher, Hanspeter; Zeiser, Robert

2013-01-01

Despite advances in immunosuppressive regimens, acute graft-versus-host disease remains a frequent complication of allogeneic hematopoietic cell transplantation. Pathogenic donor T cells are dependent on correct attachment of small GTPases to the cell membrane, mediated by farnesyl- or geranylgeranyl residues, which, therefore, constitute potential targets for graft-versus-host disease prophylaxis. A mouse model was used to study the impact of a farnesyl-transferase inhibitor and a geranylgeranyl-transferase inhibitor on acute graft-versus-host disease, anti-cytomegalovirus T-cell responses and graft-versus-leukemia activity. Treatment of mice undergoing allogeneic hematopoietic cell transplantation with farnesyl-transferase inhibitor and geranylgeranyl-transferase inhibitor reduced the histological severity of graft-versus-host disease and prolonged survival significantly. Mechanistically, farnesyl-transferase inhibitor and geranylgeranyl-transferase inhibitor treatment resulted in reduced alloantigen-driven expansion of CD4 T cells. In vivo treatment led to increased thymic cellularity and polyclonality of the T-cell receptor repertoire by reducing thymic graft-versus-host disease. These effects were absent when squalene production was blocked. The farnesyl-transferase inhibitor and geranylgeranyl-transferase inhibitor did not compromise CD8 function against leukemia cells or reconstitution of T cells that were subsequently responsible for anti-murine cytomegalovirus responses. In summary, we observed an immunomodulatory effect of inhibitors of farnesyl-transferase and geranylgeranyl-transferase on graft-versus-host disease, with enhanced functional immune reconstitution. In the light of the modest toxicity of farnesyl-transferase inhibitors such as tipifarnib in patients and the potent reduction of graft-versus-host disease in mice, farnesyl-transferase and geranylgeranyl-transferase inhibitors could help to reduce graft-versus-host disease significantly without

Acute Graft Versus Host Disease: A Comprehensive Review.

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Nassereddine, Samah; Rafei, Hind; Elbahesh, Ehab; Tabbara, Imad

2017-04-01

Acute graft versus host disease (aGVHD) remains the second leading cause of death following allogeneic hematopoietic stem cell transplant (AHSCT). Over the last five years, the progress in understanding the pathophysiology of this immune based-process helped redefine graft versus host reaction and opened new possibilities for novel preventive and therapeutic approaches. The evolution in the field of immunology widened the horizons for hematopoietic stem cell transplant leading to the availability of different stem cell sources for potential graft and incorporation of novel conditioning regimens. There is conflicting data about the impact of the graft source and the conditioning regimen used in the process of AHSCT on the incidence of aGVHD. Many studies have reported increased risk of chronic GVHD (cGVHD) and to a less extent aGVHD with the use of peripheral blood stem cell and bone marrow compared to umbilical cord stem cell. The conditioning regimen, either myeloablative, non-myeloablative or reduced intensity may have different impact on the incidence of GVHD. Several preventive modalities have been adopted by different transplant centers but, to date, there is no standardized regimen. As for treatment, immunosuppression using steroids remains the first line of intervention. Several novel therapeutic options are being investigated for treatment of steroid-refractory aGVHD including the use of mesenchymal stem cells, anti thymocyte globulin and extra corporeal photophoresis. This review discusses the pathophysiology, risk factors, clinical features, and advances in the diagnosis, prevention and treatment of aGVHD. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Vulvovaginal Graft-Versus-Host Disease.

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Kornik, Rachel I; Rustagi, Alison S

2017-09-01

Vulvovaginal chronic graft-versus-host disease (cGVHD) is an underrecognized complication of stem cell transplantation. Early recognition may prevent severe sequelae. Genital involvement is associated with oral, ocular, and skin manifestations. Treatment includes topical immunosuppression, dilator use, and adjuvant topical estrogen. Clinical and histologic features may mimic other inflammatory vulvar conditions. In the right clinical context, these findings are diagnostic of chronic GVHD. Female recipients of allo-hematopoietic stem cell transplantation (HCT) are at higher risk of condylomas, cervical dysplasia, and neoplasia. The National Institutes of Health publishes guidelines for the diagnosis, grading, management, and supportive care for HCT patients by organ system. Copyright © 2017 Elsevier Inc. All rights reserved.

Transfusion-associated graft-versus-host disease

International Nuclear Information System (INIS)

Rappeport, J.M.

1990-01-01

The clinical pathologic syndrome of graft-versus-host disease (GVHD) is usually a sequela of bone marrow transplantation. This disorder occurs as a result of recognition by engrafted donor-derived lymphocytes of foreign recipient transplantation antigens. GVHD may also result from engraftment of lymphocytes from other sources, including (1) transfusion of lymphocytes containing blood components, (2) transplacental maternal fetal transfusion, and (3) passive transfer of lymphocytes in solid organ transplantation. The recipients are usually severely immunodeficient and thus incapable of rejecting the transfused lymphocytes. This syndrome may, however, also develop in immunologically competent patients receiving blood products from individuals with histocompatibility antigens not recognized as foreign. 58 refs

Early and late oral features of chronic graft-versus-host disease

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Alessandra Oliveira Ferrari Gomes

2014-01-01

Full Text Available Background: Chronic graft-versus-host disease is a serious complication of allogeneic hematopoietic cell transplantation, and the mouth is one of the affected sites. Objective: The aim of this study was to evaluate the oral features of this disease after hematopoietic cell transplantation. Methods: This was a cross-sectional multicenter study that enrolled patients submitted to transplantation. Oral evaluations used the National Institutes of Health criteria, salivary flow rates, and the range of mouth opening. Pain and xerostomia were evaluated through a visual analogue scale. Patients were divided into two groups based on the transplantation time (up to one year and more than one year. Results: Of the 57 evaluated recipients, 44 had chronic graft-versus-host disease: ten (22.72% in the group with less than one year after transplantation, and 34 (77.27% in the group with more than one year after transplantation. Lichenoid/hyperkeratotic plaques, erythematous lesions, xerostomia, and hyposalivation were the most commonly reported oral features. Lichenoid/hyperkeratotic plaques were significantly more common in patients within the first year after the transplant. The labial mucosa was affected more in the first year. No significant changes occurred in the frequency of xerostomia, hyposalivation, and reduced mouth opening regarding time after transplantation. Conclusion: Oral chronic graft-versus-host disease lesions were identified early in the course of the disease. The changes observed in salivary gland function and in the range of mouth opening were not correlated with the time after transplantation.

Preventing transfusion-associated graft-versus-host disease: state of the art

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Fast LD

2015-01-01

Full Text Available Loren D Fast Division of Hematology/Oncology, Rhode Island Hospital and Warren Alpert School of Medicine at Brown University, Providence, RI, USA Abstract: The transfer of pathogens and the induction of immune responses are deleterious consequences that can result from the transfusion of blood products. Transfusion-associated graft-versus-host disease (TA-GVHD, the most severe immune consequence, occurs when recipient immune responses are incapable of effectively eliminating donor leukocytes, permitting unabated responses of the donor T lymphocytes. Currently, prevention of TA-GVHD is routinely accomplished by exposing blood products to γ-irradiation in order to prevent donor T cell proliferation. Alternative protocols are being developed to meet the challenges associated with the use of γ-irradiation. Use of pathogen reduction protocols, which interfere with nucleic acid replication by modifying nucleic acids, are increasing. Comparison of pathogen reduction protocols with γ-irradiation have found that both protocols are equally effective in preventing T lymphocyte proliferation and GVHD responses when testing in both in vitro and in vivo models. The potential use of pathogen reduction protocols to treat whole blood prior to separation into its components could provide a cost-effective method for preventing TA-GVHD in the future. Keywords: blood transfusion, GVHD, pathogen reduction, irradiation

Fototerapia na doença enxerto contra hospedeiro Phototherapy in the graft versus host disease

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Ida Duarte

2008-10-01

Full Text Available FUNDAMENTOS: A doença enxerto contra hospedeiro é um dos obstáculos ao sucesso do transplante de medula óssea, e o envolvimento cutâneo é freqüente. A fototerapia é utilizada devido à intensa atividade imunomoduladora local, sendo opção terapêutica adjuvante para as lesões cutâneas resistentes à terapia convencional. OBJETIVO: Realizar análise descritiva do tratamento da doença enxerto contra hospedeiro com fototerapia (Puva ou UVB de faixa estreita. MÉTODOS: Foram atendidos nove pacientes com manifestação cutânea da doença enxerto contra hospedeiro aguda ou crônica. Seis foram tratados com Puva, terapia de primeira escolha, e três com UVB de faixa estreita. As sessões foram realizadas três vezes por semana, e a resposta terapêutica avaliada após 12 sessões. RESULTADOS: Todos os pacientes com doença enxerto contra hospedeiro aguda mostraram melhora, com desaparecimento do eritema e do edema. Naqueles com doença crônica, observaram-se involução das lesões liquenóides e melhora da mobilidade daqueles com a forma esclerodermiforme. Dois pacientes apresentaram doença de evolução grave e foram a óbito. CONCLUSÃO: A fototerapia mostrou-se efetiva no tratamento das manifestações cutâneas da doença enxerto contra hospedeiro aguda e crônica. A Puva permite o controle da doença, podendo a UVB de faixa estreita ser opção para pacientes impossibilitados de usar medicação sistêmica.BACKGROUND: Graft versus host disease is one of the obstacles to successful bone marrow transplantation. It often affects the skin. Phototherapy has been used because of its strong local immunomodulatory activity and it is an option for adjuvant therapy for skin lesions of graft versus host disease resistant to conventional therapy. OBJECTIVE: To make a descriptive analysis of treating graft versus host disease with phototherapy (PUVA or narrowband UVB. Methods - Nine patients with cutaneous manifestation of acute or chronic

Economic evaluation of posaconazole versus fluconazole prophylaxis in patients with graft-versus-host disease (GVHD) in the Netherlands

NARCIS (Netherlands)

J.P. Jansen (Jeroen); A.K. O'Sullivan (Amy); P.J. Lugtenburg (Pieternella); L.F.R. Span (Lambert); J.J.W.M. Janssen (Jeroen); W.B. Stam (Wiro)

2010-01-01

textabstractThe objective of this study was to evaluate the cost-effectiveness of posaconazole versus fluconazole for the prevention of invasive fungal infections (IFI) in graft-versus-host disease (GVHD) patients in the Netherlands. A decision analytic model was developed based on a double-blind

Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

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Sydney X Lu

Full Text Available Allogeneic bone marrow transplantation (allo-BMT is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT activity are limited by graft-versus-host-disease (GVHD. Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1 is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models.We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT in mouse models. In vivo, Ceacam1(-/- T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi, CD62L(lo. Additionally, Ceacam1(-/- CD8 T cells had greater expression of the gut-trafficking integrin α(4β(7, though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/- recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/- mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+ lymphoma model was improved in animals receiving Ceacam1(-/- vs. control T cells.We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the

Chronic graft-versus-host disease in the rat radiation chimera. III. Immunology and immunopathology in rapidly induced models

International Nuclear Information System (INIS)

Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

1983-01-01

Although chronic graft-versus-host disease (GVHD) frequently develops in the long-term rat radiation chimera, we present three additional models in which a histologically similar disease is rapidly induced. These include adoptive transfer of spleen and bone marrow from rats with spontaneous chronic GVHD into lethally irradiated rats of the primary host strain; sublethal irradiation of stable chimeras followed by a booster transplant; and transfer of spleen cells of chimeras recovering from acute GVHD into second-party (primary recipient strain) or third-party hosts. Some immunopathologic and immune abnormalities associated with spontaneous chronic GVHD were not observed in one or more of the induced models. Thus, IgM deposition in the skin, antinuclear antibodies, and vasculitis appear to be paraphenomena. On the other hand, lymphoid hypocellularity of the thymic medulla, immaturity of splenic follicles, and nonspecific suppressor cells were consistently present in the long term chimeras, and in all models. These abnormalities therefore may be pathogenetically important, or closely related to the development of chronic GVHD

Pneumatosis cystoides interstitialis: A complication of graft-versus-host disease. A report of two cases.

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Laskowska, Katarzyna; Burzyńska-Makuch, Małgorzata; Krenska, Anna; Kołtan, Sylwia; Chrupek, Małgorzata; Nawrocka, Elżbieta; Lasek, Władysław; Serafin, Zbigniew

2012-04-01

Pneumatosis cystoides intestinalis (PCI) is a rare disorder characterized by the presence of multiple gas collections in the subserosal or submucosal intestinal wall of the large or small intestine. We report two cases of PCI in the course of chronic graft-versus-host disease. A 5-year-old girl was treated for acute lymphoblastic leukemia. Twenty-four months after the hematopoietic stem cell transplantation, in the course of graft-versus-host disease, she developed subcutaneous emphysema of the right inguinal and pudendal region. PCI was diagnosed based on a CT examination. A 3-year-old boy was treated for juvenile myelomonocytic leukemia. Fourteen months after the hematopoietic stem cell transplantation he presented with an increased severity of intestinal symptoms, including intermittent bleeding from large intestine. PCI was diagnosed based on a CT exam and was confirmed by a colonoscopy. Pneumatosis cystoides interstitialis in the course of chronic graft-versus-host disease has a heterogeneous clinical presentation that does not correlate with results of imaging. CT is a method of choice to diagnose PCI. In patients with PCI, the presence of free air in the peritoneal cavity does not confirm an intestinal perforation.

Pneumatosis cystoides interstitialis: A complication of graft-versus-host disease. A report of two cases

International Nuclear Information System (INIS)

Laskowska, Katarzyna; Burzyńska-Makuch, Małgorzata; Krenska, Anna; Kołtan, Sylwia; Chrupek, Małgorzata; Nawrocka, Elżbieta; Lasek, Władysław; Serafin, Zbigniew

2012-01-01

Pneumatosis cystoides intestinalis (PCI) is a rare disorder characterized by the presence of multiple gas collections in the subserosal or submucosal intestinal wall of the large or small intestine. We report two cases of PCI in the course of chronic graft-versus-host disease. A 5-year-old girl was treated for acute lymphoblastic leukemia. Twenty-four months after the hematopoietic stem cell transplantation, in the course of graft-versus-host disease, she developed subcutaneous emphysema of the right inguinal and pudendal region. PCI was diagnosed based on a CT examination. A 3-year-old boy was treated for juvenile myelomonocytic leukemia. Fourteen months after the hematopoietic stem cell transplantation he presented with an increased severity of intestinal symptoms, including intermittent bleeding from large intestine. PCI was diagnosed based on a CT exam and was confirmed by a colonoscopy. Pneumatosis cystoides interstitialis in the course of chronic graft-versus-host disease has a heterogeneous clinical presentation that does not correlate with results of imaging. CT is a method of choice to diagnose PCI. In patients with PCI, the presence of free air in the peritoneal cavity does not confirm an intestinal perforation

Chronic graft versus host disease and nephrotic syndrome

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Samia Barbouch

2014-01-01

Full Text Available Disturbed kidney function is a common complication after bone marrow transplantation. Recently, attention has been given to immune-mediated glomerular damage related to graft versus host disease (GVHD. We describe a 19-year-old woman who developed membranous glomerulonephritis after bone marrow transplantation (BMT. Six months later, she developed soft palate, skin and liver lesions considered to be chronic GVHD. Fifteen months after undergoing BMT, this patient presented with nephrotic syndrome. A renal biopsy showed mem-branous glomerulonephritis associated with a focal segmental glomerulosclerosis. She was started on corticosteroid treatment with good outcome.

Use of the National Institutes of Health Consensus Guidelines Improves the Diagnostic Sensitivity of Gastrointestinal Graft-Versus-Host Disease.

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Cardona, Diana M; Detweiler, Claire J; Shealy, Michael J; Sung, Anthony D; Wild, Daniel M; Poleski, Martin H; Balmadrid, Bryan L; Cirrincione, Constance T; Howell, David N; Sullivan, Keith M

2018-04-26

- Graft-versus-host disease of the gastrointestinal tract is a common complication of hematopoietic stem cell transplant associated with significant morbidity and mortality. Accurate diagnosis can be difficult and is a truly clinicopathologic endeavor. - To assess the diagnostic sensitivity of gastrointestinal graft-versus-host disease using the 2015 National Institutes of Health (NIH) histology consensus guidelines and to analyze histologic findings that support the guidelines. - Patients with allogeneic hematopoietic stem cell transplants were identified via a retrospective search of our electronic medical record from January 1, 2005, to January 1, 2011. Endoscopies with available histology were reviewed by 2 pathologists using the 2015 NIH guidelines. The clinical diagnosis was used as the gold standard. A nontransplant set of endoscopic biopsies was used as a control. - Of the 250 total endoscopies, 217 (87%) had a clinical diagnosis of gastrointestinal graft-versus-host disease. Use of the NIH consensus guidelines showed a sensitivity of 86% and a specificity of 65%. Thirty-seven of 58 (64%) cases with an initial false-negative histopathologic diagnosis were diagnosed as graft-versus-host disease on our review. - Use of the NIH histology consensus guidelines results in a high sensitivity and specificity, thereby decreasing false-negatives. Additionally, use of the NIH guidelines aids in creating uniformity and diagnostic clarity. Correlation with clinical and laboratory findings is critical in evaluating the differential diagnosis and to avoid false-positives. As expected, increased apoptosis with decreased inflammation was associated with a pathologic diagnosis of graft-versus-host disease and supports the NIH guidelines.

Graft-versus-host reaction and immune function. III. Functional pre-T cells in the bone marrow of graft-versus-host-reactive mice displaying T cell immunodeficiency

International Nuclear Information System (INIS)

Seddik, M.; Seemayer, T.A.; Lapp, W.S.

1986-01-01

Studies were performed to determine whether pre-T cells develop normally in the bone marrow of mice displaying thymic dysplasia and T cell immunodeficiency as a consequence of a graft-versus-host (GVH) reaction. GVH reactions were induced in CBAxAF1 mice by the injection of A strain lymphoid cells. To test for the presence of pre-T cells in GVH-reactive mice, bone marrow from GVH-reactive mice (GVHBM) was injected into irradiated syngeneic F1 mice and 30-40 days later thymic morphology and function were studied. Morphology studies showed nearly normal thymic architectural restoration; moreover, such glands contained normal numbers of Thy-1-positive cells. Functional pre-T cells were evaluated by transferring thymocytes from the irradiated GVHBM-reconstituted mice into T-cell-deprived mice. These thymocytes reconstituted allograft reactivity, T helper cell function and Con A and PHA mitogen responses of T-cell-deprived mice. These results suggest that the pre-T cell population in the bone marrow is not affected by the GVH reaction. Therefore, the T cell immunodeficiency associated with the GVH reaction is not due to a deficiency of pre-T cells in the bone marrow but is more likely associated with GVH-induced thymic dysplasia

Use of telecobalt-therapy in transfusion-associated graft-versus-host disease

International Nuclear Information System (INIS)

Goes, Evamberto Garcia de

1999-08-01

The transfusion-associated Graft-Versus-Host Disease (TA-GVHD) is prevented through the irradiation of blood components before transfusion. This work started with a diagnostic about blood irradiation practices in Brazil, through the application of a questionnaire to 56 regional blood centers, and showed that the majority of the regional blood centers have no means to irradiate their own blood components. This survey have also shown that 62,5% of the regional blood centers have local facilities to irradiate their own blood components, through the use of telecobalt-therapy services. Assuming the use of telecobalt-therapy equipment as an alternative solution to the Brazilian blood irradiation problem, the development of an appropriate technique allowed a good quality for irradiated blood. A prototype of a thermic box was made in acrylic and foam, and an automated system of data acquisition, kept the temperature of blood components bellow 6 deg C, during irradiation. Phantoms built using polystyrene plastic represented blood volume routinely irradiated by the regional blood centers. The distribution of doses on the phantoms volumes determined with LiF-100 thermoluminescent dosimeters, were represented in terms of isodoses curves. The doses distributions on the phantom with higher dimensions, 30 x 30 x 20 cm, changed from a minimum relative dose of 80% up to a maximum of 106%. An investigation concerning effects of Cobalt-60 gamma radiation on red blood cells, irradiated and stored, showed increase in potassium levels, up to the tenth day, in blood units irradiated at 3,00 cGy. Surveillance of the reduction in the capacity of T-Cells proliferation as a function of dose, using Limiting Dilution Analysis, showed that a minimum of 2,500 cGy is necessary to prevent TA-GVHD. Methodology developed in this work guarantee good quality for blood irradiated with telecobalt-therapy equipment, a valid alternative for Brazilian institutions which have available only this technique

The Role of Programmed Cell Death Ligand-1 (PD-L1/CD274) in the Development of Graft versus Host Disease

Science.gov (United States)

Al-Chaqmaqchi, Heevy; Sadeghi, Behnam; Abedi-Valugerdi, Manuchehr; Al-Hashmi, Sulaiman; Fares, Mona; Kuiper, Raoul; Lundahl, Joachim

2013-01-01

Programmed cell death ligand-1 (PD-L1/CD274) is an immunomodulatory molecule involved in cancer and complications of bone marrow transplantation, such as graft rejection and graft-versus-host disease. The present study was designed to assess the dynamic expression of this molecule after hematopoietic stem cell transplantation in relation to acute graft-versus-host disease. Female BALB/c mice were conditioned with busulfan and cyclophosphamide and transplanted with either syngeneic or allogeneic (male C57BL/6 mice) bone marrow and splenic cells. The expression of PD-L1 was evaluated at different time points employing qPCR, western blot and immunohistochemistry. Allogeneic- but not syngeneic-transplanted animals exhibited a marked up-regulation of PD-L1 expression in the muscle and kidney, but not the liver, at days 5 and 7 post transplantation. In mice transplanted with allogeneic bone marrow cells, the enhanced expression of PD-L1 was associated with high serum levels of IFNγ and TNFα at corresponding intervals. Our findings demonstrate that PD-L1 is differently induced and expressed after allogeneic transplantation than it is after syngeneic transplantation, and that it is in favor of target rather than non-target organs at the early stages of acute graft-versus-host disease. This is the first study to correlate the dynamics of PD-L1 at the gene-, protein- and activity levels with the early development of acute graft-versus-host disease. Our results suggest that the higher expression of PD-L1 in the muscle and kidney (non-target tissues) plays a protective role in skeletal muscle during acute graft-versus-host disease. PMID:23593203

Functional clonal deletion versus suppressor cell-induced transplantation tolerance in chimeras prepared with a short course of total-lymphoid irradiation

International Nuclear Information System (INIS)

Slavin, S.; Morecki, S.; Weigensberg, M.; Bar, S.; Weiss, L.

1986-01-01

Allogeneic bone marrow (BM) chimeras induced by infusion of BM cells into recipients conditioned with total lymphoid irradiation (TLI) were shown to develop humoral and cell-mediated tolerance to host and donor-type alloantigens by a number of in vitro and in vivo assays. Spleen cells of tolerant chimeras exhibited suppressive activity of mixed lymphocyte reaction (MLR). MLR suppression was not abrogated by depletion of Lyt-2 cells, and neither could Lyt-2-positive cells sorted from the spleens of tolerant chimeras suppress MLR or attenuate graft-versus-host reactivity in vivo. Likewise, specifically unresponsive spleen cells obtained from chimeras could not be induced to respond in MLR against tolerizing host-type cells following depletion of Lyt-2 or passage through a nylon-wool column. Tolerance of chimera spleen cells to host alloantigens, best documented by permanent survival of donor-type skin allografts, could be adoptively transferred into syngeneic recipients treated by heavy irradiation but not into untreated or mildly irradiated recipients. Adoptive transfer of tolerance seemed to be associated with experimental conditions favoring engraftment of tolerant cells rather than suppression of host reactivity. We speculate that although host and/or donor-derived suppressor cells may be operating in reducing the pool of specific alloreactive clones by blocking cell proliferation in response to allogeneic challenge, the final outcome in tolerant chimeras is actual or functional deletion of alloreactive clones

Reduction of fatal graft-versus-host disease by 3H--thymidine suicide of donor cells cultured with host cells

International Nuclear Information System (INIS)

Cheever, M.A.; Einstein, A.B. Jr.; Kempf, R.A.; Fefer, A.

1977-01-01

The effect of the tritiated thymidine ( 3 H-TdR) suicide technique on the ability of donor cells to induce fatal graft-versus-host disease (GVHD) was studied. C57BL/6 (H-2/sup b/) spleen cells were stimulated in vitro with irradiated BALB/c (H-2/sup d/) Moloney lymphoma cells in mixed culture and 3 H-TdR of high-specific activity added to eliminate proliferating cells. The ability of such cells to induce fatal GVHD was assayed by injecting them i.v. into adult BALB/c mice immunosuppressed with cyclophosphamide (180 mg/kg). These cells induced fatal GVHD in fewer mice (52 percent) than did C57BL/6 cells cultured with BALB/c lymphoma cells but without 3 H-TdR (87 percent) and C57BL/6 cells cultured with irradiated C57BL/6 cells with (95 percent) or without 3 H-TdR (86 percent). Thus, the 3 H-TdR suicide technique greatly diminished the ability of cells to induce lethal GVHD

Cartilage grafting in facial reconstruction with special consideration of irradiated grafts

International Nuclear Information System (INIS)

Donald, P.J.

1986-01-01

The search for the perfect facial implant for reconstruction of the face continues. Cartilage, once thought to be an undesirable graft material because of its propensity for absorption, has regained popularity in the past decade. Various preparation techniques have been employed to ensure graft sterility and diminished absorption. An improved understanding of cartilage structure and physiology has shed considerable light on the host-graft relationship. Gamma irradiation is a time-honored method of preservation. An experiment was undertaken to investigate the physiology of irradiated cartilage grafts following prolonged implantation on the facial skeleton of sheep and dog. Merthiolate preserved grafts were used as controls. Direct observation, histochemical techniques, autoradiography, and transmission electron micrography were used to determine chondrocyte viability and matrix composition. It was surprising to note that following implantation of 16 to 72 months, complete resorption was seen in 87.7% of the irradiated grafts and in 43.8% of the Merthiolate stored controls. Many of the grafts acquired chondrocytes from the host and produced new proteoglycan matrix as well as undergoing some degree of ossification. A comparison to the clinical situation in humans is made. 98 references

IL-35 mitigates murine acute graft-versus-host disease with retention of graft-versus-leukemia effects.

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Liu, Y; Wu, Y; Wang, Y; Cai, Y; Hu, B; Bao, G; Fang, H; Zhao, L; Ma, S; Cheng, Q; Song, Y; Liu, Y; Zhu, Z; Chang, H; Yu, X; Sun, A; Zhang, Y; Vignali, D A A; Wu, D; Liu, H

2015-04-01

IL-35 is a newly discovered inhibitory cytokine secreted by regulatory T cells (Tregs) and may have therapeutic potential in several inflammatory disorders. Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation and caused by donor T cells and inflammatory cytokines. The role of IL-35 in aGVHD is still unknown. Here we demonstrate that IL-35 overexpression suppresses CD4(+) effector T-cell activation, leading to a reduction in alloreactive T-cell responses and aGVHD severity. It also leads to the expansion of CD4(+)Foxp3(+) Tregs in the aGVHD target organs. Furthermore, IL-35 overexpression results in a selective decrease in the frequency of Th1 cells and an increase of IL-10-producing CD4(+) T cells in aGVHD target tissues. Serum levels of TNF-α, IFN-γ, IL-6, IL-22 and IL-23 decrease and IL-10 increases in response to IL-35. Most importantly, IL-35 preserves graft-versus-leukemia effect. Finally, aGVHD grade 2-4 patients have decreased serum IL-35 levels comparing with time-matched patients with aGVHD grade 0-1. Our findings indicate that IL-35 has an important role in reducing aGVHD through promoting the expansion of Tregs and repressing Th1 responses, and should be investigated as the therapeutic strategy for aGVHD.

GRAFT VERSUS HOST DISEASE- ORAL PRESENTATION

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Pradeep P. S

2017-09-01

Full Text Available BACKGROUND Graft-versus-host disease (GVHD is described as a potentially life-threatening complication caused by allogeneic haematopoietic cell transplantation. It is an exaggerated manifestation of a normal inflammatory mechanism in which donor lymphocytes encounter foreign antigens in an atmosphere that promote inflammation. 90% of the patients show oral features in case of cGVHD. Oral mucosal lesions and salivary gland dysfunction are the main oral features of chronic GVHD. Trismus or reduction of the mouth opening due to the perioral deposition of collagen is also commonly seen. Purpose of this review is to understand pathophysiology of oral presentations of GVHD. MATERIALS AND METHODS Review related to GVHD pathophysiology, oral lesions after haematopoietic cell transplant encompassed literature from 1966 through 2015. Review of Medline/PubMed Journals were done. RESULTS It is difficult to describe the pathophysiology of oral manifestations because there is no well accepted definition. CONCLUSION Larger well-designed clinical studies are needed to understand the pathobiology of oral cGVHD and determine best treatments for this disease.

Altered T-cell entry and egress in the absence of Coronin 1A attenuates murine acute graft versus host disease.

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Fulton, LeShara M; Taylor, Nicholas A; Coghill, James M; West, Michelle L; Föger, Niko; Bear, James E; Baldwin, Albert S; Panoskaltsis-Mortari, Angela; Serody, Jonathan S

2014-06-01

Acute graft-versus-host disease (aGvHD) is a major limitation to the use of allogeneic stem cell transplantation for the treatment of patients with relapsed malignant disease. Previous work using animals lacking secondary lymphoid tissue (SLT) suggested that activation of donor T cells in SLT is critically important for the pathogenesis of aGvHD. However, these studies did not determine if impaired migration into, and more importantly, out of SLT, would ameliorate aGvHD. Here, we show that T cells from mice lacking Coronin 1A (Coro 1A(-/-)), an actin-associated protein shown to be important for thymocyte egress, do not mediate acute GvHD. The attenuation of aGvHD was associated with decreased expression of the critical trafficking proteins C-C chemokines receptor type 7 (CCR7) and sphingosine 1 phosphate receptor on donor T cells. This was mediated in part by impaired activation of the canonical NF-κB pathway in the absence of Coro 1A. As a result of these alterations, donor T cells from Coro 1A(-/-) mice were not able to initially traffic to SLT or exit SLT after BM transplantation. However, this alteration did not abrogate the graft-versus-leukemia response. Our data suggest that blocking T-cell migration into and out of SLT is a valid approach to prevent aGvHD. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Treatment of whole blood with riboflavin plus ultraviolet light, an alternative to gamma irradiation in the prevention of transfusion-associated graft-versus-host disease?

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Fast, Loren D; Nevola, Martha; Tavares, Jennifer; Reddy, Heather L; Goodrich, Ray P; Marschner, Susanne

2013-02-01

Exposure of blood products to gamma irradiation is currently the standard of care in the prevention of transfusion-associated graft-versus-host disease (TA-GVHD). Regulatory, technical, and clinical challenges associated with the use of gamma irradiators are driving efforts to develop alternatives. Pathogen reduction methods were initially developed to reduce the risk of microbial transmission by blood components. Through modifications of nucleic acids, these technologies interfere with the replication of both pathogens and white blood cells (WBCs). To date, systems for pathogen and WBC inactivation of products containing red blood cells are less well established than those for platelets and plasma. In this study, the in vitro and in vivo function of WBCs present in whole blood after exposure to riboflavin plus ultraviolet light (Rb-UV) was examined and compared to responses of WBCs obtained from untreated or gamma-irradiated blood by measuring proliferation, cytokine production, activation, and antigen presentation and xenogeneic (X-)GVHD responses in an in vivo mouse model. In vitro studies demonstrated that treatment of whole blood with Rb-UV was as effective as gamma irradiation in preventing WBC proliferation, but was more effective in preventing antigen presentation, cytokine production, and T-cell activation. Consistent with in vitro findings, treatment with Rb-UV was as effective as gamma irradiation in preventing X-GVHD, a mouse model for TA-GVHD. The ability to effectively inactivate WBCs in fresh whole blood using Rb-UV, prior to separation into components, provides the transfusion medicine community with a potential alternative to gamma irradiation. © 2012 American Association of Blood Banks.

Incidence and Pattern of Graft-versus-Host Disease in Patients Undergoing Allogeneic Transplantation after Nonmyeloablative Conditioning with Total Lymphoid Irradiation and Antithymocyte Globulin

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Lauren Veltri

2013-01-01

Full Text Available Nonmyeloablative (NMA conditioning with total lymphoid irradiation and antithymocyte globulin (TLI/ATG has been shown to protect against acute graft-versus-host disease (GVHD. We report here our institutional experience with allogeneic transplantation following NMA conditioning with TLI/ATG (. GVHD prophylaxis consisted of a combination of a calcineurin inhibitor and mycophenolate mofetil. Median patient age was 59 years. The median followup of surviving patients is 545 days. One patient experienced primary graft rejection. The median time to neutrophil engraftment was 18 days and platelet engraftment was 9.5 days. The cumulative incidence (CI of grade II–IV acute GVHD at day +100 was 28.6% and 38.1% at day +180. The CI for grade III-IV acute GVHD was 28.6% at day +180. CI of chronic GVHD was 45.2% at 1 year. The CI of disease relapse was 9.5% at 1 year. The rate of nonrelapse mortality (NRM was 0% at day +100 and only 9.5% at 1 year. The overall and progression free survival at 1 year was 81% and 80.4%, respectively. Our limited, retrospective data show encouraging relapse and NRM rates with TLI/ATG-based NMA conditioning, but with higher than previously reported rates of acute and chronic GVHD, underscoring the need for novel strategies designed to effectively prevent GVHD.

Unraveling the Mechanisms of Cutaneous Graft-Versus-Host Disease

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Pedro Santos e Sousa

2018-05-01

Full Text Available The skin is the most common target organ affected by graft-versus-host disease (GVHD, with severity and response to therapy representing important predictors of patient survival. Although many of the initiating events in GVHD pathogenesis have been defined, less is known about why treatment resistance occurs or why there is often a permanent failure to restore tissue homeostasis. Emerging data suggest that the unique immune microenvironment in the skin is responsible for defining location- and context-specific mechanisms of injury that are distinct from those involved in other target organs. In this review, we address recent advances in our understanding of GVHD biology in the skin and outline the new research themes that will ultimately enable design of precision therapies.

An update on the clinical utility of extracorporeal photopheresis in the treatment of graft-versus-host disease

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Salem B

2017-03-01

Full Text Available Baheyeldin Salem,1,2 Jennifer Webb,3 David Alex Jacobsohn1,2 1Blood and Marrow Transplant Program, 2Department of Paediatrics, 3Department of Transfusion Medicine, Children’s National Health System, Washington, DC, USA Abstract: Graft-versus-host disease (GVHD continues to be a major complication following allogeneic hematopoietic cell transplantation (allo-HCT with high morbidity and mortality. Corticosteroids are the first-line treatment for GVHD; however, a substantial number of patients go on to require second-line treatment where no single therapeutic modality has been proven to be the most effective. Extracorporeal photopheresis (ECP is an efficient and established therapy for cutaneous T-cell lymphoma, GVHD, rejection after solid organ transplantation and various autoimmune diseases. Although large randomized trials are limited, there is compelling cumulative data on the efficacy of ECP for GVHD, and the response rates, especially for cutaneous involvement, are encouraging. ECP has an excellent safety profile, a well-documented steroid-sparing effect, proven survival benefit and overall quality-of-life improvement. In many institutions, ECP is commonly regarded as the preferred second-line treatment for GVHD. Keywords: GVHD, ECP, immunosuppressive therapy, IST, apheresis, steroid-refractory ­graft-versus-host disease, hematopoietic cell transplantation, graft versus leukemia effect

Prevention of graft-versus-host-disease with preserved graft-versus-leukemia-effect by ex vivo and in vivo modulation of CD4(+) T-cells.

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Fricke, Stephan; Hilger, Nadja; Fricke, Christian; Schönfelder, Uta; Behre, Gerhard; Ruschpler, Peter; Boldt, Andreas; Oelkrug, Christopher; Sack, Ulrich; Emmrich, Frank

2014-06-01

This is the first report showing that an epitope-specific ex vivo modulation of an allogeneic hematopoietic stem cell graft by the anti-human CD4 antibody MAX.16H5 IgG1 simultaneously facilitates the anti-tumor capacity of the graft (Graft-versus-leukemia effect, GvL) and the long-term suppression of the deleterious side effect Graft-versus-host-disease (GvHD). To distinguish and consolidate GvL from GvHD, the anti-human CD4 antibody MAX16.H5 IgG1 was tested in murine GvHD and tumor models. The survival rate was significantly increased in recipients receiving a MAX.16H5 IgG1 short-term (2 h) pre-incubated graft even when tumor cells were co-transplanted or when recipient mice were treated by MAX.16H5 IgG1 before transplantation. After engraftment, regulatory T-cells are generated only supporting the GvL effect. It was also possible to transfer the immune tolerance from GvHD-free recipient chimeras into third party recipient mice without the need of reapplication of MAX.16H5 IgG1 anti-human CD4 antibodies. These findings are also benefical for patients with leukemia when no matched related or unrelated donor is available and provides a safer allogeneic HSCT, which is more effective against leukemia. It also facilitates allogeneic (stem) cell transplantations for other indications (e.g., autoimmune-disorders).

Cell-mediated immunity to histocompatibility antigens : controlling factors, with emphasis on Graft-versus-host reactions in mice

NARCIS (Netherlands)

H. Bril (Herman)

1984-01-01

textabstractGraft-versus-Host (GvH) disease is characterized by weight loss, diarrhea, skin lesions, hypofunction of the immune system with concomitant infections, etc. This syndrome is potentially lethal. GvH reactions, which underly this disease, may occur when immunocompetent T lymphocytes are

Animal experimental model of a graft-versus-host (GVH) reaction after allogenic transplantation of bone marrow in lethally irradiated mice

International Nuclear Information System (INIS)

Schwenke, H.; Muench, S.; Haubold, S.; Weber, B.

1977-01-01

The graft-versus-host (GVH) disease represents a serious still unsolved problem in the human allogenic transplantation of bone marrow. An experimental model of GVH reaction after an allogenic transplantation of bone marrow in the adult mouse has been worked out as a prerequisite for further studies on the therapeutic influence of this syndrome. 3 groups have been formed out of 82 lethally X-irradiated C57 Bl mice. The non-transplanted control group died to a hundred per cent within 12 days. While out of the 2nd group treated with syngenic bone marrow 55 per cent survived from the 22nd day, 30 per cent of the third animal group, allogenicly transplanted with histoincompatible AKR donor marrow developed a chronic GVH syndrome. The following symptoms were observed: retardation, alterations of the skin, diarrhea, edemas of the legs, failing increase of leukocytes in blood and proliferation of lymphocytes in bone marrow of about 60 per cent (18 per cent in syngenically transplanted animals), in lacking proliferation of hematopoiesis. The increase of liver and especially spleen index is not characteristic in comparison with the syngenically transplanted group, since in the latter there is also an increase of the values on account of a strong hematopoetic proliferation. The model is suitable and sufficiently well characterized for the performance of further experimental studies. (author)

Quality of life of patients with graft-versus-host disease (GvHD post-hematopoietic stem cell transplantation

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Sibéli de Fátima Ferraz Simão Proença

Full Text Available Abstract OBJECTIVE Assessing the quality of life of adult patients with hematological cancer in the 100 days after transplantation of hematopoietic stem cells and verifying whether the variable graft-versus-host disease (GvHD is predictive of worse results. METHOD An observational correlational and quantitative study with 36 adult participants diagnosed with hematologic cancer who underwent hematopoietic stem cell transplantation from September 2013 to June 2015. RESULT The mean age was 37 years, 52.78% were female, and 61.11% were diagnosed with leukemia. Quality of life scores showed a significant impact between pre-transplantation and pre-hospital discharge, and also within the 100 days post-transplantation. The statistical analysis between the scores for the groups with and without GvHD showed a significant difference between the presence of the complication and worse results. CONCLUSION Quality of life is altered as a result of hematopoietic stem cells transplantation, especially in patients who have graft-versus-host disease.

Pathogenic mechanisms of Acute Graft versus Host Disease

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Ferrara James L.M.

2002-01-01

Full Text Available Graft-versus-host-disease (GVHD is the major complication of allogeneic Bone Marrow Transplant (BMT. Older BMT recipients are a greater risk for acute GVHD after allogeneic BMT, but the causes of this association are poorly understood. Using well-characterized murine BMT models we have explored the mechanisms of increased GVHD in older mice. GVHD mortality and morbidity, and pathologic and biochemical indices were all worse in old recipients. Donor T cell responses were significantly increased in old recipients both in vivo and in vitro when stimulated by antigen-presenting cells (APCs from old mice. In a haploidential GVHD model, CD4+ donor T cells mediated more severe GVHD in old mice. We confirmed the role of aged APCs in GVHD using bone marrow chimera recipient created with either old or young bone marrow. APCs from these mice also stimulated greater responses from allogeneic cells in vitro. In a separate set of experiments we evaluated whether alloantigen expression on host target epithelium is essential for tissue damage induced by GVHD. Using bone marrow chimeras recipients in which either MHC II or MHC I alloantigen was expressed only on APCs, we found that acute GVHD does not require alloantigen expression on host target epithelium and that neutralization of tumor necrosis factor-alpha and interleukin-1 prevents acute GVHD. These results pertain to CD4-mediated GVHD and to a lesser extent in CD8-mediated GVHD, and confirm the central role of most APCs as well as inflammatory cytokines.

Syngeneic graft-versus-host disease: a report of two cases and literature review.

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Latif, T; Pohlman, B; Kalaycio, M; Sobecks, R; Hsi, E D; Andresen, S; Bolwell, B J

2003-09-01

Rappeport et al first reported the clinical syndrome of graft-versus-host disease (GVHD) in syngeneic bone marrow transplant patients. Recently, there have been more reports of a GVHD-like syndrome in syngeneic bone marrow transplant patients (SGVHD) that may result in significant clinical morbidity. A total of 17 cases of SGVHD in syngeneic bone marrow transplant patients have been reported to date in the medical literature. The current report reviews these cases and presents two additional cases of severe SGVHD that have occurred at our institution.

[NKT cells and graft-versus-host disease-review].

Science.gov (United States)

Zhao, Lei; Hao, Sha; Yuan, Wei-Ping; Cheng, Tao

2013-10-01

NKT cells (nature killer T cells), as a regulatory cellular compartment in the immune system, express cell surface markers of T cells and NK cells. It secretes a variety of cytokines that stimulate specific antigens. Through regulating the balance of Th1/Th2, the NKT cells play an important role in prevention and treatment of graft-versus-host disease (GVHD). Its antitumor and anti-infectious effects serve as a basis of its application in allogeneic hematopoietic stem cell transplantation. A better understanding of the biological and immunological features of NKT cell, as well as its specific immune regulatory mechanisms, will further justify the rationales of using NKT cells in the management of GVHD for patients. In this review, the biologic properties, classification, differentiation and development, immune activation of NKT cells as well as the NKT cells and GVHD including the related mechanisms of prevention and treatment of GVHD with NKT cells, NKT cells and tumors, NKT cells and infection, and NKT cells and clinical GVHD are summarized.

Mesenchymal Stromal Cells: What Is the Mechanism in Acute Graft-Versus-Host Disease?

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Neil Dunavin

2017-07-01

Full Text Available After more than a decade of preclinical and clinical development, therapeutic infusion of mesenchymal stromal cells is now a leading investigational strategy for the treatment of acute graft-versus-host disease (GVHD. While their clinical use continues to expand, it is still unknown which of their immunomodulatory properties contributes most to their therapeutic activity. Herein we describe the proposed mechanisms, focusing on the inhibitory activity of mesenchymal stromal cells (MSCs at immunologic checkpoints. A deeper understanding of the mechanism of action will allow us to design more effective treatment strategies.

Efficacy and Safety of Topical Corticosteroids for Management of Oral Chronic Graft versus Host Disease

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Elsaadany, Basma Abdelaleem; Ahmed, Eman Magdy; Aghbary, Sana Maher Hasan

2017-01-01

Background. Oral chronic graft versus host disease (cGVHD) is a major complication in transplantation community, a problem that can be addressed with topical intervention. Topical corticosteroids are the first line of treatment although the choice remains challenging as none of the available treatments is supported by strong clinical evidence. Objective. This systematic review aims to determine the clinical efficacy and safety of topical corticosteroids for the management of the mucosal alter...

Role of mobile passenger lymphocytes in the rejection of renal and cardiac allografts in the rat. A passenger lymphocyte-mediated graft-versus-host reaction amplifies the host response

International Nuclear Information System (INIS)

van Vrieshilfgaarde, R.; Hermans, P.; Terpstra, J.L.; van Breda Viresman, P.J.

1980-01-01

It is demonstrated that passenger lymphocytes migrate out of rat renal allografts into host spleens in a radioresistant fashion. These mobile passenger lymphocytes within BN kidney and heart transplants are immunocompetent, since they elicit a graft-versus-host (GVH) reaction in the spleens of (LEW x BN)F2 hybrid hosts. The greater GVH reaction in (LEW x BN)F1 recipients of BN kidneys reflects the greater number of mobile passenger lymphocytes in the kidney when compared to the heart. The mobile passenger lymphocytes within BN renal allografts also cause a proliferative response in the spleens of the LEW hosts as well as an accelerated rejection of BN renal allografts when compared to BN cardiac allografts, for the differences between BN kidney and heart, both in terms of splenomegaly elicited in LEW as well as tempo of rejection, are abolished by total body x-irradiation of the donor with 900 rad. Results indicate that a mobile passenger lymphocyte mediated GVH reaction in the central lymphoid organs of the host augments the host response to allogenic kidneys and contributes materially to first-set renal allograft rejection; this GVH reaction on the other hand is not conspicuously present in LEW recipients of BN cardiac allografts and has therefore little effect on first-set cardiac allograft rejection

Steroid treatment of acute graft-versus-host disease grade I: a randomized trial

OpenAIRE

Bacigalupo, Andrea; Milone, Giuseppe; Cupri, Alessandra; Severino, Antonio; Fagioli, Franca; Berger, Massimo; Santarone, Stella; Chiusolo, Patrizia; Sica, Simona; Mammoliti, Sonia; Sorasio, Roberto; Massi, Daniela; Van Lint, Maria Teresa; Raiola, Anna Maria; Gualandi, Francesca

2017-01-01

Patients with acute graft-versus-host disease (GvHD) grade I were randomized to an observation arm (n=85) or to a treatment arm (n=86) consisting of 6-methylprednisolone 1 mg/kg/day, after stratification for age and donor type. The primary end point was development of grade II–IV GvHD. The cumulative incidence of grade II–IV GvHD was 50% in the observation arm and 33% in the treatment arm (P=0.005). However, grade III–IV GvHD was comparable (13% vs. 10%, respectively; P=0.6), and this was tru...

The effect of total body irradiation dose and chronic graft-versus-host disease on leukaemic relapse after allogeneic bone marrow transplantation

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Frassoni, F; Bacigalupo, A [Ospedale San Martino (Italy). Centro Trapianti Midollo Osseo; Scarpati, D [Univ. di Genova (Italy). Ist. di Radiologia; and others

1989-10-01

One-hundred and five patients undergoing allo-geneic bone marrow transplantation (BMT) for acute myeloid leukaemia (AML) (n=61) and chronic myeloid leukaemia (n=44) were analysed for risk factors associated with relapse. All patients received marrow from an HLA identical sibling after preparation with cyclophosphamide 120 mg/kg and total body irradiation (TBI) 330 cGy on each of the three days prior to transplantation. A multivariate Cox analysis indicated that a lower TBI dose (less than 990 cGy) was the most significant factor associated with relapse and the second most important factor associated with recurrence of leukaemia was the absence of chronic graft-versus-host-disease (cGvHD). Actuarial relapse incidence was 62%, 28% and 18% for patients with no, limited or extensive chronic GvHD respectively. However, chronic GvHD had no significant impact on survival. Combined stratification for TBI dose and cGvHD showed that the dose effect of TBI on relapse was evident both in patients with and without cGvHD. Chronic GvHD influenced the risk of relapse only in patients receiving less than 990 cGy. These results suggest that a higher dose of TBI, within this schedule, produced long-term disease-free survival in the majority of AMLs and CMLs. Minor radiobiological side effects were experienced, but a small reduction of the dose may significantly increase the risk of relapse. (author).

The effect of total body irradiation dose and chronic graft-versus-host disease on leukaemic relapse after allogeneic bone marrow transplantation

International Nuclear Information System (INIS)

Frassoni, F.; Bacigalupo, A.; Scarpati, D.

1989-01-01

One-hundred and five patients undergoing allo-geneic bone marrow transplantation (BMT) for acute myeloid leukaemia (AML) (n=61) and chronic myeloid leukaemia (n=44) were analysed for risk factors associated with relapse. All patients received marrow from an HLA identical sibling after preparation with cyclophosphamide 120 mg/kg and total body irradiation (TBI) 330 cGy on each of the three days prior to transplantation. A multivariate Cox analysis indicated that a lower TBI dose (less than 990 cGy) was the most significant factor associated with relapse and the second most important factor associated with recurrence of leukaemia was the absence of chronic graft-versus-host-disease (cGvHD). Actuarial relapse incidence was 62%, 28% and 18% for patients with no, limited or extensive chronic GvHD respectively. However, chronic GvHD had no significant impact on survival. Combined stratification for TBI dose and cGvHD showed that the dose effect of TBI on relapse was evident both in patients with and without cGvHD. Chronic GvHD influenced the risk of relapse only in patients receiving less than 990 cGy. These results suggest that a higher dose of TBI, within this schedule, produced long-term disease-free survival in the majority of AMLs and CMLs. Minor radiobiological side effects were experienced, but a small reduction of the dose may significantly increase the risk of relapse. (author)

Mesenchymal stromal cells in the antimicrobial host response of hematopoietic stem cell recipients with graft-versus-host disease--friends or foes?

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Balan, A; Lucchini, G; Schmidt, S; Schneider, A; Tramsen, L; Kuçi, S; Meisel, R; Bader, P; Lehrnbecher, T

2014-10-01

Mesenchymal stromal cells (MSCs) are multipotent cells, which exhibit broad immunosuppressive activities. Moreover, they may be administered irrespectively of human leukocyte antigen (HLA) compatibility, without inducing life-threatening immunological reactions, as they express no HLA class II and limited HLA class I antigens under resting conditions. These characteristics have made MSC an appealing candidate for cell therapy after hematopoietic stem cell transplantation (HSCT), for example, for treatment of graft-versus-host disease (GvHD) or for graft rejection prevention/treatment in allogeneic HSCT recipients. Unfortunately, information regarding the effect of MSC infusion on the host response to infectious agents is scarce, and study results on infectious complications in patients receiving MSC are conflicting. The present review focuses on the available data from in vitro studies and animal models regarding the interaction of MSC with bacterial, viral and fungal pathogens. In a clinical part, we present the current information on infectious complications in allogeneic HSCT recipients who had received MSCs as prophylaxis or treatment of GvHD disease.

Graft rejection as a Th1-type process amenable to regulation by donor Th2-type cells through an interleukin-4/STAT6 pathway.

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Mariotti, Jacopo; Foley, Jason; Ryan, Kaitlyn; Buxhoeveden, Nicole; Kapoor, Veena; Amarnath, Shoba; Fowler, Daniel H

2008-12-01

Graft rejection has been defined as the mirror image of graft-versus-host disease, which is biologically characterized primarily as a Th1-type process. As such, we reasoned that graft rejection would represent a Th1 response amenable to Th2 modulation. Indeed, adoptive transfer of host Th1-type cells mediated rejection of fully MHC-disparate murine bone marrow allografts more effectively than host Th2-type cells. Furthermore, STAT1-deficient host T cells did not differentiate into Th1-type cells in vivo and failed to mediate rejection. We next hypothesized that donor Th2 cell allograft augmentation would prevent rejection by modulation of the host Th1/Th2 balance. In the setting of donor Th2 cell therapy, host-anti-donor allospecific T cells acquired Th2 polarity, persisted posttransplantation, and did not mediate rejection. Abrogation of rejection required donor Th2 cell IL-4 secretion and host T-cell STAT6 signaling. In conclusion, T cell-mediated marrow graft rejection primarily resembles a Th1-type process that can be abrogated by donor Th2 cell therapy that promotes engraftment through a novel mechanism whereby cytokine polarization is transferred to host T cells.

Marked in Vivo Donor Regulatory T Cell Expansion via Interleukin-2 and TL1A-Ig Stimulation Ameliorates Graft-versus-Host Disease but Preserves Graft-versus-Leukemia in Recipients after Hematopoietic Stem Cell Transplantation.

Science.gov (United States)

Wolf, Dietlinde; Barreras, Henry; Bader, Cameron S; Copsel, Sabrina; Lightbourn, Casey O; Pfeiffer, Brent J; Altman, Norman H; Podack, Eckhard R; Komanduri, Krishna V; Levy, Robert B

2017-05-01

Regulatory T cells (Tregs) are critical for self-tolerance. Although adoptive transfer of expanded Tregs limits graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT), ex vivo generation of large numbers of functional Tregs remains difficult. Here, we demonstrate that in vivo targeting of the TNF superfamily receptor TNFRSF25 using the TL1A-Ig fusion protein, along with IL-2, resulted in transient but massive Treg expansion in donor mice, which peaked within days and was nontoxic. Tregs increased in multiple compartments, including blood, lymph nodes, spleen, and colon (GVHD target tissue). Tregs did not expand in bone marrow, a critical site for graft-versus-malignancy responses. Adoptive transfer of in vivo-expanded Tregs in the setting of MHC-mismatched or MHC-matched allogeneic HSCT significantly ameliorated GVHD. Critically, transplantation of Treg-expanded donor cells facilitated transplant tolerance without GVHD, with complete sparing of graft-versus-malignancy. This approach may prove valuable as a therapeutic strategy promoting transplantation tolerance. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Skin ulcers related to chronic graft-versus-host disease: clinical findings and associated morbidity.

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Jachiet, M; de Masson, A; Peffault de Latour, R; Rybojad, M; Robin, M; Bourhis, J-H; Xhaard, A; Dhedin, N; Sicre de Fontbrune, F; Suarez, F; Barete, S; Parquet, N; Nguyen, S; Ades, L; Rubio, M-T; Wittnebel, S; Bagot, M; Socié, G; Bouaziz, J-D

2014-07-01

According to the National Institutes of Health classification of chronic graft-versus-host disease (cGVHD), skin ulcers after allogeneic haematopoietic stem-cell transplantation (HSCT) are recorded as having the maximal severity score but published data are scarce. To describe skin ulcers related to cGVHD with an emphasis on clinical findings, associated morbidity, management and evolution. A multicentre retrospective analysis was carried out of patients with a diagnosis of cGVHD skin ulcers. All 25 patients included in the study had sclerotic skin cGVHD and 21 had lichenoid skin lesions associated with the sclerotic skin lesions. Thirteen patients had severe cGVHD without considering the skin, because of the involvement of an extracutaneous organ by cGVHD. The median time from HSCT to the onset of ulcers was 44 months. In addition to scleroderma, initial skin lesions at the site of ulcers were bullous erosive lichen in 21 patients and bullous erosive morphoea in four patients. Fifteen patients had an inaugural oedema. Ulcers were mostly bilateral with a predilection for the lower limbs. They were frequently colonized but few infections occurred. Four patients died during a median follow-up period of 55 months. Chronic graft-versus-host disease skin ulcers occur in patients with sclerodermatous skin cGVHD, are associated with severe cGVHD, often start with bullous lichenoid lesions or bullous morphoea and seem to cause more morbidity than mortality, given the low rate of mortality observed in our series of patients. © 2014 British Association of Dermatologists.

The Role of B Cell Targeting in Chronic Graft-Versus-Host Disease

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Ruben Rhoades

2017-10-01

Full Text Available Chronic graft-versus-host disease (cGVHD is a leading cause of late morbidity and mortality following allogeneic stem cell transplantation. Current therapies, including corticosteroids and calcineurin inhibitors, are only effective in roughly 50% of cases; therefore, new treatment strategies are under investigation. What was previously felt to be a T cell disease has more recently been shown to involve activation of both T and B cells, as well as a number of cytokines. With a better understanding of its pathophysiology have come more expansive preclinical and clinical trials, many focused on B cell signaling. This report briefly reviews our current understanding of cGVHD pathophysiology and reviews clinical and preclinical trials with B cell-targeted agents.

Protection of lethally irradiated mice with allogeneic fetal liver cells: influence of irradiation dose on immunologic reconstitution

International Nuclear Information System (INIS)

Tulunay, O.; Good, R.A.; Yunis, E.J.

1975-01-01

After lethal irradiation long-lived, immunologically vigorous C3Hf mice were produced by treatment with syngeneic fetal liver cells or syngeneic newborn or adult spleen cells. Treatment of lethally irradiated mice with syngeneic or allogeneic newborn thymus cells or allogeneic newborn or adult spleen cells regularly led to fatal secondary disease or graft-versus-host reactions. Treatment of the lethally irradiated mice with fetal liver cells regularly yielded long-lived, immunologically vigorous chimeras. The introduction of the fetal liver cells into the irradiated mice appeared to be followed by development of immunological tolerance of the donor cells. The findings suggest that T-cells at an early stage of differentiation are more susceptible to tolerance induction than are T-lymphocytes at later stages of differentiation. These investigations turned up a perplexing paradox which suggests that high doses of irradiation may injure the thymic stroma, rendering it less capable of supporting certain T-cell populations in the peripheral lymphoid tissue. Alternatively, the higher and not the lower dose of irradiation may have eliminated a host cell not readily derived from fetal liver precursors which represents an important helper cell in certain cell-mediated immune functions, e.g., graft-versus-host reactions, but which is not important in others, e.g., allograft rejections. The higher dose of lethal irradiation did not permit development or maintenance of a population of spleen cells that could initiate graft-versus-host reactions but did permit the development of a population of donor cells capable of achieving vigorous allograft rejection

Ocular manifestations of graft-versus-host disease

Science.gov (United States)

Nassar, Amr; Tabbara, Khalid F.; Aljurf, Mahmoud

2013-01-01

Allogeneic hematopoietic stem cell transplantation (HSCT) has evolved over the past two decades to become the standard of care for hematologic and lymphoid malignancies. Major ocular complications after allogeneic HSCT have been increasing in number and severity. Graft-versus-host disease (GVHD) remains a major cause of ocular morbidity after allogeneic HSCT. The main objective of this review is to elucidate the ocular complications in patients developing GVHD following HSCT. Ocular complications secondary to GVHD are common and include dry eye syndrome, acquisition of ocular allergy from donors with allergic disorders. Eyelid changes may occur in GVHD leading to scleroderma-like changes. Patients may develop poliosis, madarosis, vitiligo, lagophthalmos, and entropion. The cornea may show filamentary keratitis, superficial punctate keratitis, corneal ulcers, and peripheral corneal melting which may lead to perforation in severe cases. Scleritis may also occur which can be anterior or posterior. Keratoconjunctivis sicca appears to be the most common presentation of GVHD. The lacrimal glands may be involved with mononuclear cell infiltration of both the major and accessory lacrimal glands and decrease in tear production. Severe dry eye syndrome in patients with GVHD may develop conjunctival scarring, keratinization, and cicatrization of the conjunctiva. Therapy of GVHD includes systemic immunosuppression and local therapy. Surgical treatment in refractory cases includes surgical intervention to improve the manifestation of GVHD of the eye. This may include tarsorrhapy, prose lenses, punctal occlusions and corneal transplantation. PMID:24227989

Graft-versus-host disease is enhanced by selective CD73 blockade in mice.

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Long Wang

Full Text Available CD73 functions as an ecto-5'-nucleotidase to produce extracellular adenosine that has anti-inflammatory and immunosuppressive activity. We here demonstrate that CD73 helps control graft-versus-host disease (GVHD in mouse models. Survival of wild-type (WT recipients of either allogeneic donor naïve CD73 knock-out (KO or WT T cells was similar suggesting that donor naïve T cell CD73 did not contribute to GVHD. By contrast, donor CD73 KO CD4(+CD25(+ regulatory T cells (Treg had significantly impaired ability to mitigate GVHD mortality compared to WT Treg, suggesting that CD73 on Treg is critical for GVHD protection. However, compared to donor CD73, recipient CD73 is more effective in limiting GVHD. Pharmacological blockade of A2A receptor exacerbated GVHD in WT recipients, but not in CD73 KO recipients, suggesting that A2 receptor signaling is primarily implicated in CD73-mediated GVHD protection. Moreover, pharmacological blockade of CD73 enzymatic activity induced stronger alloreactive T cell activity, worsened GVHD and enhanced the graft-versus-leukemia (GVL effect. These findings suggest that both donor and recipient CD73 protects against GVHD but also limits GVL effects. Thus, either enhancing or blocking CD73 activity has great potential clinical application in allogeneic bone marrow transplants.

Photobiomodulation Therapy Alleviates Tissue Fibroses Associated with Chronic Graft-Versus-Host Disease: Two Case Reports and Putative Anti-Fibrotic Roles of TGF-

NARCIS (Netherlands)

Epstein, Joel B.; Raber-Durlacher, Judith E.; Huysmans, Marie-Charlotte; Schoordijk, Maria C. E.; Cheng, Jerry E.; Bensadoun, Rene-Jean; Arany, Praveen R.

2018-01-01

Objective: Patients who receive allogeneic hematopoietic stem cell transplantation may experience oral complications due to chronic graft-versus-host disease (cGVHD). The manifestations may include progressive sclerosis-like changes that may involve various body sites, including the oropharynx.

A case of membranous nephropathy as a manifestation of graft-versus-host disease

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Jae Hyun Han

2013-03-01

Full Text Available Nephrotic syndrome (NS rarely occurs after hematopoietic stem cell transplantation (HSCT as a late manifestation of graft-versus-host disease (GVHD. Herein, we report a case of HSCT-associated membranous nephropathy in a female patient with aplastic anemia. The patient received an allogeneic HSCT from her human leukocyte antigen-identical brother following myeloablative conditioning chemotherapy. NS occurred 21 months after HSCT without any concurrent features of chronic GVHD. The patient was treated with prednisolone and cyclosporine after renal biopsy confirmed membranous nephropathy, and achieved complete remission. Our report contradicts previous assumptions that concomitant chronic GVHD is responsible for the development of NS, suggesting that NS can develop as a new, independent manifestation of GVHD.

Clinical approach in the management of oral chronic graft-versus-host disease (cGVHD) in a series of specialized medical centers

DEFF Research Database (Denmark)

Elad, Sharon; Jensen, Siri Beier; Raber-Durlacher, Judith E

2015-01-01

BACKGROUND: The oral cavity is frequently affected in chronic graft-versus-host disease (cGVHD), with variable clinical presentations. The literature on the effective management of patients suffering from oral cGVHD is limited. OBJECTIVE: The objective of this study was to assess the clinical app...

Human regulatory T cells control xenogeneic graft-versus-host disease induced by autologous T cells in RAG2-/-gammac-/- immunodeficient mice.

NARCIS (Netherlands)

Mutis, T; Rijn, R.S. van; Simonetti, E.R.; Aarts-Riemens, T.; Emmelot, M.E.; Bloois, L. van; Martens, A.; Verdonck, L.F.; Ebeling, S.B.

2006-01-01

PURPOSE: Effective prevention of graft-versus-host disease (GvHD) is a major challenge to improve the safety of allogeneic stem cell transplantation for leukemia treatment. In murine transplantation models, administration of naturally occurring CD4+CD25+ regulatory T cells (Treg) can prevent GvHD.

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

Photobiomodulation therapy alleviates tissue fibroses associated with chronic Graft-Versus-Host Disease : Two case reports and putative anti-fibrotic roles of TGF-β

NARCIS (Netherlands)

Epstein, J.B.; Raber-Durlacher, J.E.; Huysmans, M.C.; Schoordijk, M.C.E.; Cheng, J.E.; Bensadoun, R.J.; Arany, P.R.

2018-01-01

Objective: Patients who receive allogeneic hematopoietic stem cell transplantation may experience oral complications due to chronic graft-versus-host disease (cGVHD). The manifestations may include progressive sclerosis-like changes that may involve various body sites, including the oropharynx.

Free and microvascular bone grafting in the irradiated dog mandible

International Nuclear Information System (INIS)

Altobelli, D.E.; Lorente, C.A.; Handren, J.H. Jr.; Young, J.; Donoff, R.B.; May, J.W. Jr.

1987-01-01

Microvascular and free rib grafts were placed in 4.5 cm defects in an edentate mandibular body defect 18 to 28 days after completion of 50 Gy of irradiation from a 60 Co source. The animals were sacrificed from two to forty weeks postoperatively and evaluated clinically, radiographically, and histologically. There was a marked difference in the alveolar mucosal viability with the two grafts. Mucosal dehiscence was not observed over any of the microvascular grafts, but was present in seven-eighths of the free grafts. Union of the microvascular bone graft to the host bone occurred within six weeks. In contrast, after six weeks the free graft was sequestered in all the animals. An unexpected finding with both types of graft was the marked subperiosteal bone formation. This bone appeared to be derived from the host bed, stabilizing and bridging the defects bilaterally. The results suggest that radiated periosteum may play an important role in osteogenesis

Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius.

Science.gov (United States)

Socié, Gérard; Schmoor, Claudia; Bethge, Wolfgang A; Ottinger, Hellmut D; Stelljes, Matthias; Zander, Axel R; Volin, Liisa; Ruutu, Tapani; Heim, Dominik A; Schwerdtfeger, Rainer; Kolbe, Karin; Mayer, Jiri; Maertens, Johan A; Linkesch, Werner; Holler, Ernst; Koza, Vladimir; Bornhäuser, Martin; Einsele, Hermann; Kolb, Hans-Jochem; Bertz, Hartmut; Egger, Matthias; Grishina, Olga; Finke, Jürgen

2011-06-09

Previous randomized graft-versus-host disease (GVHD)-prophylaxis trials have failed to demonstrate reduced incidence and severity of chronic GVHD (cGVHD). Here we reanalyzed and updated a randomized phase 3 trial comparing standard GVHD prophylaxis with or without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before transplantation from unrelated donors. The cumulative incidence of extensive cGVHD after 3 years was 12.2% in the ATG-F group versus 45.0% in the control group (P < .0001). The 3-year cumulative incidence of relapse and of nonrelapse mortality was 32.6% and 19.4% in the ATG-F group and 28.2% and 33.5% in the control group (hazard ratio [HR] = 1.21, P = .47, and HR = 0.68, P = .18), respectively. This nonsignificant reduction in nonrelapse mortality without increased relapse risk led to an overall survival rate after 3 years of 55.2% in the ATG-F group and 43.3% in the control group (HR = 0.84, P = .39, nonsignificant). The HR for receiving immunosuppressive therapy (IST) was 0.31 after ATG-F (P < .0001), and the 3-year probability of survival free of IST was 52.9% and 16.9% in the ATG-F versus control, respectively. The addition of ATG-F to standard cyclosporine, methotrexate GVHD prophylaxis lowers the incidence and severity of cGVHD, and the risk of receiving IST without raising the relapse rate. ATG-F prophylaxis reduces cGVHD morbidity.

Use of telecobalt-therapy in transfusion-associated graft-versus-host disease; Uso da telecobaltoterapia na prevencao da doenca enxerto-versus-hospedeiro associada a transfusao

Energy Technology Data Exchange (ETDEWEB)

Goes, Evamberto Garcia de

1999-08-01

The transfusion-associated Graft-Versus-Host Disease (TA-GVHD) is prevented through the irradiation of blood components before transfusion. This work started with a diagnostic about blood irradiation practices in Brazil, through the application of a questionnaire to 56 regional blood centers, and showed that the majority of the regional blood centers have no means to irradiate their own blood components. This survey have also shown that 62,5% of the regional blood centers have local facilities to irradiate their own blood components, through the use of telecobalt-therapy services. Assuming the use of telecobalt-therapy equipment as an alternative solution to the Brazilian blood irradiation problem, the development of an appropriate technique allowed a good quality for irradiated blood. A prototype of a thermic box was made in acrylic and foam, and an automated system of data acquisition, kept the temperature of blood components bellow 6 deg C, during irradiation. Phantoms built using polystyrene plastic represented blood volume routinely irradiated by the regional blood centers. The distribution of doses on the phantoms volumes determined with LiF-100 thermoluminescent dosimeters, were represented in terms of isodoses curves. The doses distributions on the phantom with higher dimensions, 30 x 30 x 20 cm, changed from a minimum relative dose of 80% up to a maximum of 106%. An investigation concerning effects of Cobalt-60 gamma radiation on red blood cells, irradiated and stored, showed increase in potassium levels, up to the tenth day, in blood units irradiated at 3,00 cGy. Surveillance of the reduction in the capacity of T-Cells proliferation as a function of dose, using Limiting Dilution Analysis, showed that a minimum of 2,500 cGy is necessary to prevent TA-GVHD. Methodology developed in this work guarantee good quality for blood irradiated with telecobalt-therapy equipment, a valid alternative for Brazilian institutions which have available only this technique

Advance in Targeted Immunotherapy for Graft-Versus-Host Disease

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Lingling Zhang

2018-05-01

Full Text Available Graft-versus-host disease (GVHD is a serious and deadly complication of patients, who undergo hematopoietic stem cell transplantation (HSCT. Despite prophylactic treatment with immunosuppressive agents, 20–80% of recipients develop acute GVHD after HSCT. And the incidence rates of chronic GVHD range from 6 to 80%. Standard therapeutic strategies are still lacking, although considerable advances have been gained in knowing of the predisposing factors, pathology, and diagnosis of GVHD. Targeting immune cells, such as regulatory T cells, as well as tolerogenic dendritic cells or mesenchymal stromal cells (MSCs display considerable benefit in the relief of GVHD through the deletion of alloactivated T cells. Monoclonal antibodies targeting cytokines or signaling molecules have been demonstrated to be beneficial for the prevention of GVHD. However, these remain to be verified in clinical therapy. It is also important and necessary to consider adopting individualized treatment based on GVHD subtypes, pathological mechanisms involved and stages. In the future, it is hoped that the identification of novel therapeutic targets and systematic research strategies may yield novel safe and effective approaches in clinic to improve outcomes of GVHD further. In this article, we reviewed the current advances in targeted immunotherapy for the prevention of GVHD.

T-cell chimerism is valuable in predicting early mortality in steroid-resistant acute graft-versus-host disease after myeloablative allogeneic cell transplantation

DEFF Research Database (Denmark)

Minculescu, Lia; Madsen, Hans O.; Sengeløv, Henrik

2014-01-01

The main aim of this study was to evaluate the impact of early T-cell chimerism status on the incidence and clinical course of acute graft-versus-host disease (aGVHD) in allogeneic transplant recipients after myeloablative conditioning. Of 62 patients, 38 (61%) had complete T-cell donor chimerism...

[Mesenchymal stromal cells in the treatment of graft-versus-host disease: where do we stand?].

Science.gov (United States)

Schüle, Silke; Berger, André

2015-11-01

Medicinal products based on mesenchymal stromal cells (MSC) are expected to have a therapeutic benefit in a variety of conditions and, accordingly, are being tested in many clinical studies. The treatment and prevention of graft-versus-host disease (GVHD) is one of the world's most widely studied MSC therapy concepts. So far, one MSC medicinal product has been approved for the treatment of GvHD. This article gives an overview of the particular features related to the production of MSC-based medicinal products, the state of non-clinical research, and the clinical development status of MSCs and the associated challenges, especially in the context of GvHD.

Increased incidence of murine graft-versus-host disease after allogeneic bone marrow transplantation by previous infusion of syngeneic bone marrow cells

International Nuclear Information System (INIS)

Waer, M.; Ang, K.K.; van der Schueren, E.; Vandeputte, M.

1984-01-01

Different groups of BALB/c mice received supralethal total-body irradiation (TBI; 8.5 Gy, day 0). When 30 x 10(6) allogeneic (C57B1) bone marrow (BM) cells were infused with or without 10 x 10(6) syngeneic (BALB/c) bM cells on day 1, many animals (60%) died from graft-versus-host disease (GVHD). Typing of peripheral blood leukocytes for donor antigens showed that, respectively, 22/22 and 17/21 of the mice in both groups became chimeric. When syngeneic bone marrow was given on day 1 and allogeneic bone marrow on day 2 after TBI, a similar number of animals (21/23) became chimeric, but GVHD occurred more frequently in this group (25/26 mice, P less than 0.01). When the syngeneic bone marrow cells were replaced by spleen cells, or when the transplantation of allogeneic bone marrow was delayed till days 3 or 6 after TBI, almost all mice rejected the allogeneic BM graft and became long-term survivors. BALB/c mice receiving 30 x 10(6) C57B1 BM cells after 17 daily fractions of 0.2 Gy of total lymphoid irradiation (TLI), showed a high incidence of chimerism (15/17) and in none of the latter animals was GVHD observed. Despite the high incidence of GVHD in the mice receiving allogeneic BM after TBI and syngeneic BM transplantation, as compared with mice prepared with TLI which do not develop GVHD, suppressor cells were as easily induced after TBI and syngeneic BM transplantation as after TLI

Reduced intensity haplo plus single cord transplant compared to double cord transplant: improved engraftment and graft-versus-host disease-free, relapse-free survival

Science.gov (United States)

van Besien, Koen; Hari, Parameswaran; Zhang, Mei-Jie; Liu, Hong-Tao; Stock, Wendy; Godley, Lucy; Odenike, Olatoyosi; Larson, Richard; Bishop, Michael; Wickrema, Amittha; Gergis, Usama; Mayer, Sebastian; Shore, Tsiporah; Tsai, Stephanie; Rhodes, Joanna; Cushing, Melissa M.; Korman, Sandra; Artz, Andrew

2016-01-01

Umbilical cord blood stem cell transplants are commonly used in adults lacking HLA-identical donors. Delays in hematopoietic recovery contribute to mortality and morbidity. To hasten recovery, we used co-infusion of progenitor cells from a partially matched related donor and from an umbilical cord blood graft (haplo-cord transplant). Here we compared the outcomes of haplo-cord and double-cord transplants. A total of 97 adults underwent reduced intensity conditioning followed by haplo-cord transplant and 193 patients received reduced intensity conditioning followed by double umbilical cord blood transplantation. Patients in the haplo-cord group were more often from minority groups and had more advanced malignancy. Haplo-cord recipients received fludarabine-melphalan-anti-thymocyte globulin. Double umbilical cord blood recipients received fludarabine-cyclophosphamide and low-dose total body irradiation. In a multivariate analysis, haplo-cord had faster neutrophil (HR=1.42, P=0.007) and platelet (HR=2.54, Pdisease (HR=0.26, Pdisease (HR=0.06, Pdisease-free, relapse-free survival was superior with haplo-cord (HR 0.63, P=0.002) but not overall survival (HR=0.97, P=0.85). Haplo-cord transplantation using fludarabine-melphalan-thymoglobulin conditioning hastens hematopoietic recovery with a lower risk of relapse relative to double umbilical cord blood transplantation using the commonly used fludarabine-cyclophosphamide-low-dose total body irradiation conditioning. Graft-versus-host disease-free and relapse-free survival is significantly improved. Haplo-cord is a readily available graft source that improves outcomes and access to transplant for those lacking HLA-matched donors. Trials registered at clinicaltrials.gov identifiers 00943800 and 01810588. PMID:26869630

Fetal hypothalamic transplants into brain irradiated rats: Graft morphometry and host behavioral responses

International Nuclear Information System (INIS)

Pearlman, S.H.; Rubin, P.; White, H.C.; Wiegand, S.J.; Gash, D.M.

1990-01-01

This study was designed to test the hypothesis that neural implants can ameliorate or prevent some of the long-term changes associated with CNS irradiation. Using a rat model, the initial study focused on establishing motor, regulatory, and morphological changes associated with brain radiation treatments. Secondly, fetal hypothalamic tissue grafts were placed into the third ventricle of rats which had been previously irradiated. Adult male Long Evans rats received one of three radiation doses (15, 22.5, ampersand 30 Gy) or no radiation. Three days after irradiation, 7 animals in each dose group received an embryonic day 17 hypothalamic graft into the third ventricle while the remaining 8-9 animals in each group received injections of vehicle solution (sham). Few changes were observed in the 15 and 22.5 Gy animals, however rats in the 30 Gy treatment group showed stereotypic and ambulatory behavioral hyperactivity 32 weeks after irradiation. Regulatory changes in the high dose group included decreased growth rate and decreased urine osmolalities, but these measures were extremely variable among animals. Morphological results demonstrated that 30 Gy irradiated animals showed extensive necrosis primarily in the fimbria, which extended into the internal capsule, optic nerve, hippocampus, and thalamus. Hemorrhages were found in the hippocampus, thalamus, and fimbria. Defects in the blood-brain barrier also were evident by entry of intravascularly injected horseradish peroxidase into the parenchyma of the brain. Animals in the 30 Gy grafted group showed fewer behavioral changes and less brain damage than their sham grafted counterparts. Specifically, activity measures were comparable to normal levels, and a dilute urine was not found in the 30 Gy implanted rats. Morphological changes support these behavioral results since only two 30 Gy implanted rats showed necrosis

Characterization of Regulatory Dendritic Cells That Mitigate Acute Graft-versus-Host Disease in Older Mice Following Allogeneic Bone Marrow Transplantation

OpenAIRE

Scroggins, Sabrina M.; Olivier, Alicia K.; Meyerholz, David K.; Schlueter, Annette J.

2013-01-01

Despite improvements in human leukocyte antigen matching and pharmacologic prophylaxis, acute graft-versus-host disease (GVHD) is often a fatal complication following hematopoietic stem cell transplant (HSCT). Older HSCT recipients experience significantly increased morbidity and mortality compared to young recipients. Prophylaxis with syngeneic regulatory dendritic cells (DCreg) in young bone marrow transplanted (BMT) mice has been shown to decrease GVHD-associated mortality. To evaluate thi...

Clinical-Grade-Expanded Regulatory T Cells Prevent Graft-versus-Host Disease While Allowing a Powerful T Cell-Dependent Graft-versus-Leukemia Effect in Murine Models.

Science.gov (United States)

Del Papa, Beatrice; Ruggeri, Loredana; Urbani, Elena; Baldoni, Stefano; Cecchini, Debora; Zei, Tiziana; Iacucci Ostini, Roberta; Crescenzi, Barbara; Carotti, Alessandra; Pierini, Antonio; Sportoletti, Paolo; Di Bartolomeo, Paolo; Falzetti, Franca; Mecucci, Cristina; Velardi, Andrea; Martelli, Massimo F; Di Ianni, Mauro

2017-11-01

We developed a good manufacturing practices-compatible expansion protocol to improve number and purity of regulatory T cells (Tregs) available for clinical trials. Six clinical-grade separation procedures were performed, followed by expansion with high-dose interleukin (IL)-2, anti-CD3/anti-CD28 TCR stimulation, and rapamycin for 19 days achieving a median of 8.5-fold (range, 6.25 to 13.7) expansion. FOXP3 expression was stably maintained over the culture period, while the percentage of CD127 was significantly reduced. The in vitro suppression assay showed a strong Mixed Lymphocytes Reaction inhibition. In vitro amplification did not induce any karyotypic modification. To evaluate the graft-versus-host disease (GVHD)/graft-versus-leukemia (GVL) bifunctional axis, expanded Tregs and conventional T cells (Tcons) were tested in NOD/SCID/IL2Rgnull mice injected with primary acute myeloid leukemia (AML) cells, AML cell line, acute lymphoid leukemia Philadelphia cell line, or Burkitt-like lymphoma cell line. All mice that received leukemia cells together with expanded Tregs and Tcons were rescued from leukemia and survived without GVHD, showing that Treg expansion procedure did not compromise GVHD control and the strong Tcon-mediated GVL activity. This report might represent the basis for treating high-risk leukemia and/or relapsed/refractory leukemia patients with high-dose Treg/Tcons. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Graft versus host disease in a rat small bowel transplant model after T-cell depleted donor specific bone marrow infusion

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Bakonyi Neto Alexandre

2003-01-01

Full Text Available Low cytoreductive regimen of irradiation associated to unmodified bone marrow infusion (UBM does not prevent the occurrence of graft versus host disease (GVHD after transplant. PURPOSE: In this study we evaluated the potential advantages of a long-term immunossupression and T-cell depleted bone marrow infusion (TCDBMI in preventing the occurrence of GVHD after small bowel transplantation (SBTx. METHODS: Heterotopic SBTX was performed with Lewis rats as recipients and DA as donors and distributed into 5 groups according to the irradiation, duration of immunossupression and the use of UBM or TCDBMI: G1 (n=6, without irradiation and G2 (n=9, G3 (n=4, G4 (n=5 and G5 (n=6 was given 250 rd of irradiation. Groups 1,2,4 and G3 and 5 were infused with 100 x 10(6 UBM and TCDBM respectively. Animals in G1, 2, 3 were immunossupressed with 1mg/ FK506/Kg/IM for 5 days and G4 and G5 for 15 days. Anti CD3 monoclonal antibodies and immunomagnetic beads were used for T-cell depletion.Animals were examined for rejection, GVHD, chimerism characterization and ileal and skin biopsies. RESULTS: Minimal to mild rejection was observed in all groups; however, GVHD were present only in irradiated groups. Long-term immunossupression changed the severity of GVHD in G4 and G5. Rejection was the cause of death in G1 while GVHD in G2, 3, 4 and 5, not avoided by the use of TCDBMI. Total chimerism and T-cell chimerism was statistically higher in irradiated groups when compared to G1. CONCLUSION: Extended immunossupression associated to low dose of irradiation decrease the severity of GVHD, not avoided by the use of TCDBMI.

Pulp Obliteration in a Patient with Sclerodermatous Chronic Graft-versus-Host Disease.

Science.gov (United States)

Gomes, Camilla Borges Ferreira; Treister, Nathaniel Simon; Miller, Brian; Armand, Philippe; Friedland, Bernard

2016-04-01

Dental pulp calcification is a common finding associated with localized dental trauma, genetic disorders, and systemic inflammatory diseases. Chronic graft-versus-host disease (cGVHD) is a frequent complication after allogeneic hematopoietic cell transplantation (allo-HCT) characterized by immune-mediated injury to the skin, mouth, eyes, liver, and other tissues, resulting in significant disability and reduced quality of life. We report a patient with sclerodermatous cGVHD who presented with general pulp calcification in all teeth 5 years after allo-HCT. A review of full mouth dental radiographs obtained just before allo-HCT revealed normal-appearing pulp chambers. Based on prior reports of generalized pulp calcification associated with progressive systemic sclerosis, we hypothesized that the etiology was likely related to the presence of cGVHD with associated vascular and fibrotic tissue changes within the pulp vasculature. Clinicians should consider cGVHD in the differential diagnosis of generalized pulp calcification. Copyright © 2016 American Association of Endodontists. All rights reserved.

New Insight for the Diagnosis of Gastrointestinal Acute Graft-versus-Host Disease

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Florent Malard

2014-01-01

Full Text Available Allogeneic stem cell transplantation (allo-SCT is a curative therapy for different life-threatening malignant and nonmalignant hematologic disorders. Graft-versus-host disease (GVHD remains a major source of morbidity and mortality following allo-SCT, which limits the use of this treatment in a broader spectrum of patients. Early diagnostic of GVHD is essential to initiate treatment as soon as possible. Unfortunately, the diagnosis of GVHD may be difficult to establish, because of the nonspecific nature of the associated symptoms and of the numerous differential diagnosis. This is particularly true regarding gastrointestinal (GI acute GVHD. In the recent years many progress has been made in medical imaging test and endoscopic techniques. The interest of these different techniques in the diagnosis of GI acute GVHD has been evaluated in several studies. With this background we review the contributions, limitations, and future prospect of these techniques in the diagnosis of GI acute GVHD.

High incidence of chronic graft-versus-host disease after myeloablative allogeneic stem cell transplantation for chronic lymphocytic leukemia in Sweden: graft-versus-leukemia effect protects against relapse.

Science.gov (United States)

Machaczka, Maciej; Johansson, Jan-Erik; Remberger, Mats; Hallböök, Helene; Lazarevic, Vladimir Lj; Wahlin, Björn Engelbrekt; Omar, Hamdy; Wahlin, Anders; Juliusson, Gunnar; Kimby, Eva; Hägglund, Hans

2013-12-01

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment option for eligible patients with chronic lymphocytic leukemia (CLL). However, it is known that cure of CLL is only possible if a graft-versus-leukemia effect is present. Between 1994 and 2007, 48 adults underwent allo-SCT for poor-risk CLL in Sweden. Of these, ten (21%) patients aged 24-53 years (median: 46 years) received myeloablative conditioning (MAC), based on TBI and cyclophosphamide. All MAC patients had refractory, poorly controlled CLL before allo-SCT (partial remission in 9/10 patients and progressive disease in one). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II-IV was 30%. Nine patients developed chronic GVHD; extensive in four. Rates of nonrelapse mortality at 1, 3 and 10 years were 0, 10 and 20%, respectively. Two patients relapsed 36 and 53 months after transplantation. Six patients were still alive after a median follow-up time of 11.5 years (range 5.9-13.7). The probabilities of relapse-free and overall survival from 1, 3 and 5 years after transplantation were 100, 90 and 70%, and 100, 90 and 80%, respectively. Nevertheless, our analysis of long-term outcome after MAC allo-SCT for CLL suggests that younger patients with poorly controlled CLL may benefit from MAC allo-SCT.

Prediction of graft-versus-host disease in humans by donor gene-expression profiling.

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Chantal Baron

2007-01-01

Full Text Available BACKGROUND: Graft-versus-host disease (GVHD results from recognition of host antigens by donor T cells following allogeneic hematopoietic cell transplantation (AHCT. Notably, histoincompatibility between donor and recipient is necessary but not sufficient to elicit GVHD. Therefore, we tested the hypothesis that some donors may be "stronger alloresponders" than others, and consequently more likely to elicit GVHD. METHODS AND FINDINGS: To this end, we measured the gene-expression profiles of CD4(+ and CD8(+ T cells from 50 AHCT donors with microarrays. We report that pre-AHCT gene-expression profiling segregates donors whose recipient suffered from GVHD or not. Using quantitative PCR, established statistical tests, and analysis of multiple independent training-test datasets, we found that for chronic GVHD the "dangerous donor" trait (occurrence of GVHD in the recipient is under polygenic control and is shaped by the activity of genes that regulate transforming growth factor-beta signaling and cell proliferation. CONCLUSIONS: These findings strongly suggest that the donor gene-expression profile has a dominant influence on the occurrence of GVHD in the recipient. The ability to discriminate strong and weak alloresponders using gene-expression profiling could pave the way to personalized transplantation medicine.

Allogeneic hematopoietic cell transplantation in first remission abrogates poor outcomes associated with high-risk pediatric acute myeloid leukemia.

Science.gov (United States)

Burke, Michael J; Wagner, John E; Cao, Qing; Ustun, Celalettin; Verneris, Michael R

2013-07-01

Despite remission rates of approximately 85% for children diagnosed with acute myeloid leukemia (AML), greater than 40% will die from relapsed disease. Patients with poor-risk molecular/cytogenetics and/or inadequate response to up-front therapy are typically considered high-risk (HR) and historically have poor outcomes with chemotherapy alone. We investigated whether allogeneic hematopoietic cell transplantation (allo-HCT) with best available donor in first remission (CR1) would abrogate the poor outcomes associated with HR AML in children and young adults treated with chemotherapy. We reviewed the outcomes of 50 consecutive children and young adults (ages 0 to 30 years) with AML who received a myeloablative allo-HCT between 2001 and 2010. Thirty-six patients (72%) were HR, defined as having FLT3-ITD mutations, 11q23 MLL rearrangements, chromosome 5 or 7 abnormalities, induction failure, and/or having persistent disease. The majority of patients received cyclophosphamide and total body irradiation conditioning, and graft-versus-host-disease (GVHD) prophylaxis was cyclosporine based. Transplantation outcomes for HR patients were compared to standard-risk patients, with no significant differences observed in overall survival (72% versus 78%, P = .72), leukemia-free survival (69% versus 79%, P = .62), relapse (11% versus 7%, P = .71), or treatment-related mortality (17% versus 14%, P = .89). Children and young adults with HR-AML have comparable outcomes to standard-risk patients following allo-HCT in CR1. Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Blood irradiation: Rationale and technique

International Nuclear Information System (INIS)

Lewis, M.C.

1990-01-01

Upon request by the local American Red Cross, the Savannah Regional Center for Cancer Care irradiates whole blood or blood components to prevent post-transfusion graft-versus-host reaction in patients who have severely depressed immune systems. The rationale for blood irradiation, the total absorbed dose, the type of patients who require irradiated blood, and the regulations that apply to irradiated blood are presented. A method of irradiating blood using a linear accelerator is described

The Role of MicroRNAs in Myeloid Cells during Graft-versus-Host Disease

Directory of Open Access Journals (Sweden)

Sophia Chen

2018-01-01

Full Text Available The successful treatment of various hematologic diseases with allogeneic hematopoietic cell transplantation is often limited by the occurrence of graft-versus-host disease (GvHD. Several microRNAs (miRs have recently been shown to impact the biology of GvHD by regulating pro- as well as anti-inflammatory target genes. There is increasing evidence that a single miR can have different effects by preferentially targeting certain genes depending on the cell type that the miR is analyzed in. This review will focus on the role of miRs in myeloid cells during the development of acute and chronic GvHD and autoimmune diseases. Because miRs act on the expression of multiple target genes and may thereby influence the immune system at different functional levels, they are potentially attractive targets for the modification of allogeneic immune responses using miR mimics and inhibitors.

Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia

DEFF Research Database (Denmark)

Baron, F; Labopin, M; Niederwieser, D

2012-01-01

This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk...... of relapse (hazards ratio (HR)=0.7, P=0.02) translating into a trend for better overall survival (OS; HR=1.3; P=0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR=0.4, P...

The prevalence and prognostic value of concomitant eosinophilia in chronic graft-versus-host disease after allogeneic stem cell transplantation

DEFF Research Database (Denmark)

Mortensen, Katrine Brandt; Gerds, Thomas Alexander; Bjerrum, Ole Weis

2014-01-01

The prognostic significance of eosinophilia after myeloablative allogeneic stem cell transplantation (ASCT) remains to be established. Patients, whom developed chronic graft-versus-host disease (cGVHD) after ASCT, were included (n = 142). Eosinophil count was analyzed at cGVHD onset. We observed...... no significant association between EO and the grade of cGVHD, thrombocytopenia, nor extensive skin involvement. Importantly, we observed no significant association between cGVHD with concomitant eosinophilia and long-term clinical outcomes, and subgroup analyses revealed a considerable confounding effect...

Pharmacogenetics of steroid-responsive acute graft-versus-host disease.

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Arora, Mukta; Weisdorf, Daniel J; Shanley, Ryan M; Thyagarajan, Bharat

2017-05-01

Glucocorticoids are central to effective therapy of acute graft-versus-host disease (GVHD). However, only about half of the patients respond to steroids in initial therapy. Based on postulated mechanisms for anti-inflammatory effectiveness, we explored genetic variations in glucocorticoid receptor, co-chaperone proteins, membrane transporters, inflammatory mediators, and variants in the T-cell receptor complex in hematopoietic cell transplant recipients with acute GVHD requiring treatment with steroids and their donors toward response at day 28 after initiation of therapy. A total of 300 recipient and donor samples were analyzed. Twenty-three SNPs in 17 genes affecting glucocorticoid pathways were included in the analysis. In multiple regression analysis, donor SNP rs3192177 in the ZAP70 gene (O.R. 2.8, 95% CI: 1.3-6.0, P=.008) and donor SNP rs34471628 in the DUSPI gene (O.R. 0.3, 95% CI: 0.1-1.0, P=.048) were significantly associated with complete or partial response. However, after adjustment for multiple testing, these SNPs did not remain statistically significant. Our results, on this small, exploratory, hypothesis generating analysis suggest that common genetic variation in glucocorticoid pathways may help identify subjects with differential response to glucocorticoids. This needs further assessment in larger datasets and if validated could help identify subjects for alternative treatments and design targeted treatments to overcome steroid resistance. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Idelalisib-induced colitis and skin eruption mimicking graft-versus-host disease.

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Hammami, Muhammad Bader; Al-Taee, Ahmad; Meeks, Marshall; Fesler, Mark; Hurley, M Yadira; Cao, Dengfeng; Lai, Jin-Ping

2017-04-01

Idelalisib is a selective inhibitor of the delta isoform of phosphatidylinositol 3-kinase which was approved by the United States Federal Drug Administration in 2014 for the treatment of relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Drug-induced injury of the gastrointestinal tract is a relatively frequent but usually under-recognized disease entity. We report the case of a 56-year-old male with a history of relapsed follicular lymphoma status post allogenic bone marrow transplant who developed severe diarrhea with a skin eruption mimicking graft-versus-host disease (GVHD) 6 months after starting idelalisib. He underwent a colonoscopy demonstrating a grossly normal-appearing colon and terminal ileum. Biopsies taken during the procedure revealed mild active ileitis, colitis, and proctitis with frequent epithelial apoptosis, and focal intra-epithelial lymphocytosis. Skin biopsies revealed sub-acute spongiotic dermatitis suggestive of either contact dermatitis or an eczematous drug reaction. Symptoms were attributed to idelalisib given their resolution with withdrawal of the drug in conjunction with the skin and colonic biopsies. High clinical suspicion and awareness of the histological features of idelalisib-associated colitis is important to distinguish it from potential mimickers such as GVHD and infectious colitis.

Serum Vitamin A Levels May Affect the Severity of Ocular Graft-versus-Host Disease.

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Tong, Jiefeng; Hu, Renjian; Zhao, Yingying; Xu, Yang; Zhao, Xiaoying; Jin, Xiuming

2017-01-01

Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established therapeutic option for a range of inherited and acquired hematological disorders. However, graft-versus-host disease (GVHD) remains the leading cause of non-relapse mortality in allogeneic HSCT recipients. Ocular involvement occurs in up to 80% of chronic GVHD patients. In our cases, the diagnosis of vitamin A deficiency was suspected for GVHD patients. Serum vitamin A measurements were conducted to confirm clinical suspicions. Our study revealed significant decrease in serum levels of vitamin A in chronic liver GVHD patients. Although there have been many studies evaluating ocular manifestations in patients with GVHD, the present study is, to our knowledge, the first to study the relationship between vitamin A and ocular manifestations of GVHD in humans. Our data suggest that vitamin A deficiency affects the severity of ocular GVHD in adults.

Dose uniformity estimations in the blood irradiator

International Nuclear Information System (INIS)

George, J.R.

2002-01-01

Use of irradiated blood in transfusions is recognized as the most effective way of preventing Graft Versus Host Disease (GVHD). This paper shows the study carried out in the dose rate variation for various source arrangements for optimising the source-sample chamber geometry, during the development of the Blood Irradiator, Bl-2000

Emerging technologies for oral diagnostics: lessons from chronic graft-versus-host disease

Science.gov (United States)

Mays, Jacqueline W.; Ambatipudi, Kiran S.; Bassim, Carol W.; Melvin, James E.

2013-05-01

Saliva is a protein-rich oral fluid that contains information about systemic and oral-specific disease pathogenesis and diagnosis. Technologies are emerging to improve detection of protein components of human saliva for use not only in biomarker discovery, but also for the illumination of pathways involved in oral disease. These include the optimization of liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analysis of saliva in health and disease. Downstream of saliva component identification and validation comes the complex task of connecting salivary proteomic data to biological function, disease state, and other clinical patient information in a meaningful way. Augmentation of database information with biological expertise is crucial for effective analysis of potential biomarkers and disease pathways in order to improve diagnosis and identify putative therapeutic targets. This presentation will use LC-MS/MS analysis of saliva from chronic Graft-versus-Host disease (cGVHD) patients to illustrate these principles, and includes a discussion of the complex clinical and diagnostic issues related to proteomics and biomarker research in cGVHD.

[Ocular graft-versus-host disease: An often misdiagnosed etiology of dry eye syndrome].

Science.gov (United States)

Moyal, L; Adam, R; Akesbi, J; Rodallec, F T; Nordmann, J-P

2017-02-01

To report a case of severe ocular graft-versus-host disease (GVHD) after cataract surgery. Observational case report. We describe the case of a 59-year-old man with postoperative corneal ulcer on his only functional eye. His past history reported allogenic bone marrow transplant. His visual acuity (VA) was limited to hand motions. Slit lamp examination revealed diffuse conjunctival hyperemia, severe blepharitis, Meibomian dysfunction, total corneal opacification with epithelial and stromal keratitis and neovascular invasion. Because of the severe dry eye symptoms and history of allogenic hematological stem cell transplantation, ocular GVHD was diagnosed. Functional and anatomical improvement occurred rapidly with topical cyclosporine 2%, with improved VA after treatment. With any severe dry eye syndrome in the context of allogenic bone marrow transplant, ocular GVHD must be considered. For planned ocular surgery, we recommend adding cyclosporine 0.1% treatment before and after surgery to prevent severe ocular GVHD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Total lymph-node irradiation and pretreatment with cyclophosphamide in preparation for bone-marrow grafting for aplastic anaemia

International Nuclear Information System (INIS)

Jansen, J.; Zwaan, F.E.; Noordijk, E.M.

1981-01-01

Bone-marrow transplantation (BMT), using bone marrow from an HLA-identical brother or sister constitutes the treatment of choice in most young patients with severe aplastic amaemia. The cases are described of 6 patients who were prepared for grafting by administration of cyclophosphamide (4 days, 50 mg/kg body weight day) and total lymph-node irradiation (750 rad in a single dose). One patient died on the 26th day after BMT from a disseminated Aspergillus infection, and another on the 28th day from the consequences of graft-versus-host disease (GVH disease). One patient recovered after an episode of GVH disease. Two patients developed no complications after the grafting. One female patient, who for the lack of an HLA-identical brother or sister had been grafted with bone marrow of her father whose HLA-phenotype was identical, was normalized haematologically but developed chronic GVH disease of the skin. This method of preparation for BMT for aplastic anaemia reduces the risk of rejection of the bone marrow to a minimum, and may well reduce the frequency and severity of GVH disease. (Auth.)

Vitamin A-coupled liposomes containing siRNA against HSP47 ameliorate skin fibrosis in chronic graft-versus-host disease.

Science.gov (United States)

Yamakawa, Tomohiro; Ohigashi, Hiroyuki; Hashimoto, Daigo; Hayase, Eiko; Takahashi, Shuichiro; Miyazaki, Miyono; Minomi, Kenjiro; Onozawa, Masahiro; Niitsu, Yoshiro; Teshima, Takanori

2018-03-29

Chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (SCT) is characterized by multiorgan fibrosis and profoundly affects the quality of life of transplant survivors. Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, plays a critical role in collagen synthesis in myofibroblasts. We explored the role of HSP47 in the fibrotic process of cutaneous chronic GVHD in mice. Immunohistochemical analysis showed massive fibrosis with elevated amounts of collagen deposits and accumulation of F4/80 + macrophages, as well as myofibroblasts expressing HSP47 and retinol-binding protein 1 in the skin after allogeneic SCT. Repeated injection of anti-colony-stimulating factor (CSF-1) receptor-blocking antibodies significantly reduced HSP47 + myofibroblasts in the skin, indicating a macrophage-dependent accumulation of myofibroblasts. Vitamin A-coupled liposomes carrying HSP47 small interfering RNA (siRNA) (VA-lip HSP47) delivered HSP47 siRNA to cells expressing vitamin A receptors and knocked down their HSP47 in vitro. Intravenously injected VA-lip HSP47 were specifically distributed to skin fibrotic lesions and did not affect collagen synthesis in healthy skin. VA-lip HSP47 knocked down HSP47 expression in myofibroblasts and significantly reduced collagen deposition without inducing systemic immunosuppression. It also abrogated fibrosis in the salivary glands. These results highlight a cascade of fibrosis in chronic GVHD; macrophage production of transforming growth factor β mediates fibroblast differentiation to HSP47 + myofibroblasts that produce collagen. VA-lip HSP47 represent a novel strategy to modulate fibrosis in chronic GVHD by targeting HSP47 + myofibroblasts without inducing immunosuppression. © 2018 by The American Society of Hematology.

Therapeutic effects of hydrogen on chronic graft-versus-host disease.

Science.gov (United States)

Qian, Liren; Liu, Xiaopeng; Shen, Jianliang; Zhao, Defeng; Yin, Wenjie

2017-10-01

The incidence of chronic graft-versus-host disease (cGVHD) is rising recent years, which has been the leading cause of non-transplantation mortality post allogenetic hematopoietic stem cell transplantation (HSCT). Imbalance of inflammatory cytokines and fibrosis plays critical roles in the pathogenesis of cGVHD. Recent studies showed that molecular hydrogen has anti-inflammatory, antioxidant, anti-fibrosis effects. Therefore, we hypothesized that molecular hydrogen may have therapeutic effects on cGVHD. To determine whether hydrogen could protect mice from cGVHD in an MHC-incompatible murine bone marrow transplantation (BMT) model, survival rates of mice were calculated, and skin lesions were also evaluated after BMT. This article demonstrated that administration of hydrogen-rich saline increased survival rate of cGVHD mice. Administration of hydrogen-rich saline after transplantation also reduced skin lesions of cGVHD mice. Previously, we reported the therapeutic effects of hydrogen on acute GVHD. However, there was no report on the therapeutic effects of hydrogen on cGVHD mice. It is suggested that hydrogen has a potential as an effective and safe therapeutic agent on cGVHD. This study will provide new ideas on the treatment of cGVHD and has important theoretical values. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial

NARCIS (Netherlands)

Choi, S.W.; Braun, T.; Chang, L.; Ferrara, J.L.; Pawarode, A.; Magenau, J.M.; Hou, G.; Beumer, J.H.; Levine, J.E.; Goldstein, S.; Couriel, D.R.; Stockerl-Goldstein, K.; Krijanovski, O.I.; Kitko, C.; Yanik, G.A.; Lehmann, M.H.; Tawara, I.; Sun, Y; Paczesny, S.; Mapara, M.Y.; Dinarello, C.A.; Dipersio, J.F.; Reddy, P.

2014-01-01

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a barrier to more widespread application of allogeneic haemopoietic stem-cell transplantation. Vorinostat is an inhibitor of histone deacetylases and was shown to attenuate GVHD in preclinical models. We aimed to study the safety and

A murine model of graft-versus-host disease induced by allogeneic bone marrow transplantation

International Nuclear Information System (INIS)

Hu Jiangwei; Jin Jiangang; Ning Hongmei; Yu Liquan; Feng Kai; Chen Hu; Wang Lisha

2007-01-01

Objective: To establish the model of graft-versus-host disease (GVHD) in mice with allogeneic bone marrow transplantation. Methods: Bone marrow cells were combined with spleen cells of male donor C57BL/6 mice according to different proportions, then were transfused into female postradiation recipient BALB/c mice. General state, life span and histopathology of the recipient mice and detected chimera were observed. Results and Conclusion:The recipient mice groups which accepted above 5 x 10 6 donor spleen cells developed acute GVHD after different peroids of time. The GVHD model in mice after allo-BMT was successfully established. The transfusion of 5 x 10 6 -5 x 10 7 spleen cells may be adequate to establish the murine model of GVHD for the prevention and treatment of GVHD. The number of murine spleen cells can be chosen according to the experimental requirement. (authors)

Serum Vitamin A Levels May Affect the Severity of Ocular Graft-versus-Host Disease

Directory of Open Access Journals (Sweden)

Jiefeng Tong

2017-06-01

Full Text Available Allogeneic hematopoietic stem cell transplantation (HSCT is a well-established therapeutic option for a range of inherited and acquired hematological disorders. However, graft-versus-host disease (GVHD remains the leading cause of non-relapse mortality in allogeneic HSCT recipients. Ocular involvement occurs in up to 80% of chronic GVHD patients. In our cases, the diagnosis of vitamin A deficiency was suspected for GVHD patients. Serum vitamin A measurements were conducted to confirm clinical suspicions. Our study revealed significant decrease in serum levels of vitamin A in chronic liver GVHD patients. Although there have been many studies evaluating ocular manifestations in patients with GVHD, the present study is, to our knowledge, the first to study the relationship between vitamin A and ocular manifestations of GVHD in humans. Our data suggest that vitamin A deficiency affects the severity of ocular GVHD in adults.

Total lymphoid irradiation

International Nuclear Information System (INIS)

Anon.

1980-01-01

An outline review notes recent work on total lymphoid irradiation (TLI) as a means of preparing patients for grafts and particularly for bone-marrow transplantation. T.L.I. has proved immunosuppressive in rats, mice, dogs, monkeys and baboons; when given before bone-marrow transplantation, engraftment took place without, or with delayed rejection or graft-versus-host disease. Work with mice has indicated that the thymus needs to be included within the irradiation field, since screening of the thymus reduced skin-graft survival from 50 to 18 days, though irradiation of the thymus alone has proved ineffective. A more lasting tolerance has been observed when T.L.I. is followed by an injection of donor bone marrow. 50% of mice treated in this way accepted allogenic skin grafts for more than 100 days, the animals proving to be stable chimeras with 50% of their peripheral blood lymphocytes being of donor origin. Experiments of a similar nature with dogs and baboons were not so successful. (U.K.)

The Green Tea Catechin Epigallocatechin Gallate Ameliorates Graft-versus-Host Disease.

Directory of Open Access Journals (Sweden)

Sabine Westphal

Full Text Available Allogeneic hematopoetic stem cell transplantation (allo-HSCT is a standard treatment for leukemia and other hematologic malignancies. The major complication of allo-HSCT is graft-versus-host-disease (GVHD, a progressive inflammatory illness characterized by donor immune cells attacking the organs of the recipient. Current GVHD prevention and treatment strategies use immune suppressive drugs and/or anti-T cell reagents these can lead to increased risk of infections and tumor relapse. Recent research demonstrated that epigallocatechin gallate (EGCG, a component found in green tea leaves at a level of 25-35% at dry weight, may be useful in the inhibition of GVHD due to its immune modulatory, anti-oxidative and anti-angiogenic capacities. In murine allo-HSCT recipients treated with EGCG, we found significantly reduced GVHD scores, reduced target organ GVHD and improved survival. EGCG treated allo-HSCT recipients had significantly higher numbers of regulatory T cells in GVHD target organs and in the blood. Furthermore, EGCG treatment resulted in diminished oxidative stress indicated by significant changes of glutathione blood levels as well as glutathione peroxidase in the colon. In summary, our study provides novel evidence demonstrating that EGCG ameliorates lethal GVHD and reduces GVHD-related target organ damage. Possible mechanisms are increased regulatory T cell numbers and reduced oxidative stress.

Reacción de ingerto versus huésped: de la comprensión a la utilización de un fenómeno biológico Graft versus host reation: from comprehension to utilization of a biological phenomenon

Directory of Open Access Journals (Sweden)

Jorge Eliécer Ossa Londoño

1999-01-01

Full Text Available La enfermedad de injerto versus huésped es una de las complicaciones con mayor mortalidad que se presentan después de un trasplante, usualmente de médula ósea, o después de una transfusión sanguínea.- Los principales órganos blanco son la piel. el hígado, el tracto gastrointestinal y el sistema inmune. Sin embargo. la apreciación de esta enfermedad ha venido cambiando a medida que avanza la comprensión de la inmunología de trasplantes. pues se ha visto que puede tener resultados benéficos como son un efecto antireucémico y un aumento de la tolerancia a los trasplantes. Graft versus host disease is one of the complications with greater lethality after transplantation, usually of bone marrow, or after blood transfusion. Organs involved include skin, liver, gastrointestinal tract and the immune system. However, the conception of graft versus host disease has been changing as comprehension of transplant immunology has advanced, since it has been demonstrated that it can have beneficial results as an antileucemic response and because of an increased tolerance to grafts.

Steroid treatment of acute graft-versus-host disease grade I: a randomized trial.

Science.gov (United States)

Bacigalupo, Andrea; Milone, Giuseppe; Cupri, Alessandra; Severino, Antonio; Fagioli, Franca; Berger, Massimo; Santarone, Stella; Chiusolo, Patrizia; Sica, Simona; Mammoliti, Sonia; Sorasio, Roberto; Massi, Daniela; Van Lint, Maria Teresa; Raiola, Anna Maria; Gualandi, Francesca; Selleri, Carmine; Sormani, Maria Pia; Signori, Alessio; Risitano, Antonio; Bonifazi, Francesca

2017-12-01

Patients with acute graft- versus -host disease (GvHD) grade I were randomized to an observation arm (n=85) or to a treatment arm (n=86) consisting of 6-methylprednisolone 1 mg/kg/day, after stratification for age and donor type. The primary end point was development of grade II-IV GvHD. The cumulative incidence of grade II-IV GvHD was 50% in the observation arm and 33% in the treatment arm ( P =0.005). However, grade III-IV GvHD was comparable (13% vs 10%, respectively; P =0.6), and this was true for sibling and alternative donor transplants. Moderate/severe chronic GvHD was also comparable (17% vs 9%). In multivariate analysis, an early interval between transplant and randomization (versus 26% ( P =0.2), relapse-related mortality 25% versus 21%, and actuarial survival was 51% versus 41% ( P =0.3) in the observation and treatment arms, respectively. In multivariate analysis, advanced disease phase, older age and an early onset of GvHD were significant negative predictors of survival, independent of the randomization arm. In conclusion, steroid treatment of acute grade I GvHD prevents progression to grade II but not to grade III-IV GvHD, and there is no effect on non-relapse mortality and survival. Patients treated with steroids are at a higher risk of developing infections and have more adverse events. ( Trial registered as EUDTRACT 2008-000413-29 ). Copyright© 2017 Ferrata Storti Foundation.

MR findings in patients with disabling musculocutaneous chronic graft-versus-host disease

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Horger, M.; Boss, A.; Claussen, C.D. [Eberhard-Karls-University, Department of Diagnostic Radiology, Tuebingen (Germany); Bethge, W.; Faul, C.; Vogel, W. [Eberhard-Karls-University, Department of Internal Medicine-Oncology, Tuebingen (Germany); Fierlbeck, G. [Eberhard-Karls-University, Department of Dermatology, Tuebingen (Germany); Bornemann, A. [Eberhard-Karls-University, Insitute for Brain Research, Tuebingen (Germany)

2008-10-15

To describe musculocutaneous MR-findings responsible for disability in chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT). Between June 2005 and February 2008, we performed whole-body musculoskeletal magnetic resonance imaging (MRI; n = 12) or regional MRI (n = 4) in 16 consecutive patients presenting with disabling sclerodermatous cGVHD (e.g., skin edema, fixed deep dermal sclerosis, joint contractures, painful muscular contractures, or myalgia). In all patients, MRI showed musculocutaneous abnormalities reflecting different degrees of inflammation and collagen tissue involvement of the skin (n = 10), subcutaneous fat tissue (n = 13), muscle fasciae (n = 16), subfascial muscular septae (n = 6), or findings compatible with myositis (n = 3). The most frequently involved muscle fasciae comprised those of the vastus lateralis muscle (n = 12), biceps femoris muscle (n = 11), gastrocnemius medialis muscle (n = 8), serratus anterior muscle, and latissimus dorsi muscle (each, n = 5). Increased signal of involved tissues on STIR-images and fat-saturated postgadolinium T1-weighted images represented the most frequent MR-signal abnormalities. MR imaging of musculocutaneous cGVHD allows accurate evaluation including assessment of deep tissue infiltration and assists in the differential diagnosis. (orig.)

MR findings in patients with disabling musculocutaneous chronic graft-versus-host disease

International Nuclear Information System (INIS)

Horger, M.; Boss, A.; Claussen, C.D.; Bethge, W.; Faul, C.; Vogel, W.; Fierlbeck, G.; Bornemann, A.

2008-01-01

To describe musculocutaneous MR-findings responsible for disability in chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT). Between June 2005 and February 2008, we performed whole-body musculoskeletal magnetic resonance imaging (MRI; n = 12) or regional MRI (n = 4) in 16 consecutive patients presenting with disabling sclerodermatous cGVHD (e.g., skin edema, fixed deep dermal sclerosis, joint contractures, painful muscular contractures, or myalgia). In all patients, MRI showed musculocutaneous abnormalities reflecting different degrees of inflammation and collagen tissue involvement of the skin (n = 10), subcutaneous fat tissue (n 13), muscle fasciae (n = 16), subfascial muscular septae (n = 6), or findings compatible with myositis (n = 3). The most frequently involved muscle fasciae comprised those of the vastus lateralis muscle (n = 12), biceps femoris muscle (n = 11), gastrocnemius medialis muscle (n = 8), serratus anterior muscle, and latissimus dorsi muscle (each, n = 5). Increased signal of involved tissues on STIR-images and fat-saturated postgadolinium T1-weighted images represented the most frequent MR-signal abnormalities. MR imaging of musculocutaneous cGVHD allows accurate evaluation including assessment of deep tissue infiltration and assists in the differential diagnosis. (orig.)

Local graft irradiation in renal transplant rejection

International Nuclear Information System (INIS)

Kawamura, Masashi; Kataoka, Masaaki; Itoh, Hisao

1990-01-01

From 1977 to 1988, of 142 renal transplantations, seven recipients (4.9%) received local graft irradiation following rejective reaction refractory to antirejection medical managements. Concurrent with the administration of pulsed high dose methylprednisolone and other antirejection medical managements, the graft was irradiated with a total dose of 6.0 Gy-150 cGy per fraction every other day at the midplane of the graft using two opposing portals of 4MX Linac. The fields were defined by palpation and echography. All patients had improvements in serum creatinine on the 10th day after beginning the irradiation. Four patients with peripheral lymphocytosis during the irradiation combined with pulsed high dose methylprednisolone improved in renal functions. On the other hand, out of 3 patients with lymphcytopenic changes, in two the transplanted graft was removed due to deteriorations, and the other patient is currently suffering from chronic rejection. Local graft irradiation can be useful in maintaining a rejective graft and reversing its functions in some patients whose rejective reaction failed to respond to the antirejection medical managements. (author)

Presentations and treatment of childhood scleroderma: localized scleroderma, eosinophilic fasciitis, systemic sclerosis, and graft-versus-host disease.

Science.gov (United States)

Hedrich, Christian Michael; Fiebig, Barbara; Hahn, Gabriele; Suttorp, Meinolf; Gahr, Manfred

2011-07-01

Juvenile scleroderma is a rare connective tissue disease that involves the skin and subcutaneous tissue. Among all presentations of juvenile scleroderma, localized scleroderma (JLSc) is the most frequent, followed by systemic disease (JSSc) and eosinophilic fasciitis (EF). In posttransplantation chronic graft-versus-host disease (GvHD), scleroderma-like skin involvement can occur. Systemic forms of juvenile scleroderma and GvHD can affect the internal organs, such as the lungs, the gastrointestinal tract, the heart, and kidneys and cause disability and severe, sometimes lethal, complications. Here, the authors give an overview of different presentations of juvenile scleroderma. They report their experience with the different forms and presentations of scleroderma, diagnostic workups, treatment, and outcome of all forms of childhood scleroderma in the context of the existing literature.

Thoracic air-leakage syndrome in allogeneic stem cell transplant recipients as a late complication of chronic graft-versus-host disease: A case report

Energy Technology Data Exchange (ETDEWEB)

Park, Jae Wook; Kim, Song Soo; Jo, Daeg Yeon; Yun, Hwan Jung; Lee, Hyo Jin; Kim, Jin Hwan [Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon (Korea, Republic of)

2016-08-15

Air-leakage syndrome associated with graft-versus-host disease (GVHD) is a rare complication, but it is also reported as an independent predictor of a worse survival rate after stem cell transplantation. We report two cases of air-leakage syndrome associated with GVHD after allogeneic stem cell transplantation in acute leukemia patients who presented with spontaneous pneumomediastinum and subcutaneous emphysema, and finally death due to respiratory failure seven to eight months later.

Lethal graft-versus-host disease: modification with allogeneic cultured donor cells

International Nuclear Information System (INIS)

Mauch, P.; Lipton, J.M.; Hamilton, B.; Obbagy, J.; Kudisch, M.; Nathan, D.; Hellman, S.

1984-01-01

The use of the bone marrow culture technique was studied as a means to prepare donor marrow for bone marrow transplantation to avoid lethal graft-versus-host disease (GVHD). Preliminary experiments demonstrated the rapid loss of theta-positive cells in such cultures, so that theta-positive cells were not detected after 6 days. Initial experiments in C3H/HeJ (H-2k, Hbbd) recipients prepared with 900 rad demonstrated improved survival when 3-day cultured C57BL/6 (H-2b, Hbbs) donor cells were used in place of hind limb marrow for transplantation. However, hemoglobin typing of recipient animals revealed only short-term donor engraftment, with competitive repopulation of recipient marrow occurring. Subsequent experiments were done in 1,200-rad prepared recipients, with long-term donor engraftment demonstrated. The majority of 1,200-rad prepared animals receiving cultured allogeneic cells died of GVHD, but animals receiving 28-day cultured cells had an improved 90-day survival and a delay in GVHD development over animals receiving hind limb marrow or marrow from shorter times in culture. In addition, animals receiving anti-theta-treated, 3-day nonadherent cells had an improved survival (44%) over animals receiving anti-theta-treated hind limb marrow (20%). These experiments demonstrate modest benefit for the use of cultured cells in bone marrow transplantation across major H-2 histocompatibility complex differences

Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong graft-versus-leukemia effects across MHC barriers in full chimeras

OpenAIRE

Ghosh, Arnab; Koestner, Wolfgang; Hapke, Martin; Schlaphoff, Verena; Länger, Florian; Baumann, Rolf; Koenecke, Christian; Cornberg, Markus; Welte, Karl; Blazar, Bruce R.; Sauer, Martin G.

2009-01-01

Antigen-presenting cells (APCs) of host origin drive graft-versus-leukemia (GVL) effects but can also trigger life-threatening graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) across major histocompatibility complex (MHC) barriers. We show that in vitro priming of donor lymphocytes can circumvent the need of recipient-derived APCs in vivo for mediating robust GVL effects and significantly diminishes the risk of severe GVHD. In vitro, generated and expanded T cel...

Acute graft-versus-host disease of the gut: considerations for the gastroenterologist.

Science.gov (United States)

Naymagon, Steven; Naymagon, Leonard; Wong, Serre-Yu; Ko, Huaibin Mabel; Renteria, Anne; Levine, John; Colombel, Jean-Frederic; Ferrara, James

2017-12-01

Haematopoietic stem cell transplantation (HSCT) is central to the management of many haematological disorders. A frequent complication of HSCT is acute graft-versus-host disease (GVHD), a condition in which immune cells from the donor attack healthy recipient tissues. The gastrointestinal system is among the most common sites affected by acute GVHD, and severe manifestations of acute GVHD of the gut portends a poor prognosis in patients after HSCT. Acute GVHD of the gastrointestinal tract presents both diagnostic and therapeutic challenges. Although the clinical manifestations are nonspecific and overlap with those of infection and drug toxicity, diagnosis is ultimately based on clinical criteria. As reliable serum biomarkers have not yet been validated outside of clinical trials, endoscopic and histopathological evaluation continue to be utilized in diagnosis. Once a diagnosis of gastrointestinal acute GVHD is established, therapy with systemic corticosteroids is typically initiated, and non-responders can be treated with a wide range of second-line therapies. In addition to treating the underlying disease, the management of complications including profuse diarrhoea, severe malnutrition and gastrointestinal bleeding is paramount. In this Review, we discuss strategies for the diagnosis and management of acute GVHD of the gastrointestinal tract as they pertain to the practising gastroenterologist.

Defecation of a colon cast as a rare presentation of acute graft-versus-host disease

International Nuclear Information System (INIS)

Al Ashgar, Hamad; Peedikayil, Musthafa; Chaudhri, Naeem; AlGhamdi, Abdulmonem

2009-01-01

Diffuse involvement of the gastrointestinal tract by graft versus host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplant (HSCT). Gastrointestinal GVHD usually presents 3 or more weeks after HSCT and is characterized by profuse diarrhea, anorexia, nausea, vomiting, abdominal pain and gastrointestinal bleeding. We report a case of a 23 year old male who had undergone allogeneic HSCT and presented with bloody diarrhea on the 90th day post-HSCT. On the fourth day of admission, the patient passed per rectum a 27-cm long pinkish colored fleshy material recognized as a colon cast. Sigmoidoscopy showed a congested and erythematous rectum with the remaining portion of the colon cast attached to the proximal part of the sigmoid colon. A biopsy from the rectal wall was suggestive of grade 4 GVHD. The patient was treated with methylprednisolone, cyclosporine and mycophenolate mofetil, with a partial response (diarrhea and abdominal pain improved), but then he developed multiple other medical complications and died after 3 months. (author)

Viral infections in acute graft-versus-host disease: a review of diagnostic and therapeutic approaches.

Science.gov (United States)

Tong, Lana X; Worswick, Scott D

2015-04-01

While immunosuppressive therapy for acute graft-versus-host disease (aGVHD) advances, viral reactivation has been found to be an increasingly common complication in these patients. Dermatologists may often be consulted on inpatient services for evaluation. We investigated the literature for the role of viral infections in aGVHD and review the current evidence regarding management. Articles in the public domain regarding aGVHD, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, hepatitis viruses, parvovirus B19, and respiratory viruses were included. Dermatologic findings vary between different viral antigens, and some infections may be a marker for the development of aGVHD or worsen prognosis. The heterogeneous cohorts of the studies reviewed often preclude direct comparison between results. The relationship between viral reactivation and aGVHD may be bidirectional and is worthy of further exploration. Additional studies are needed to determine appropriate prophylaxis and treatment. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Pentraxin 3 plasma levels at graft-versus-host disease onset predict disease severity and response to therapy in children given haematopoietic stem cell transplantation

OpenAIRE

Dander, Erica; De Lorenzo, Paola; Bottazzi, Barbara; Quarello, Paola; Vinci, Paola; Balduzzi, Adriana; Masciocchi, Francesca; Bonanomi, Sonia; Cappuzzello, Claudia; Prunotto, Giulia; Pavan, Fabio; Pasqualini, Fabio; Sironi, Marina; Cuccovillo, Ivan; Leone, Roberto

2016-01-01

Acute Graft-versus-Host Disease (GvHD) remains a major complication of allogeneic haematopoietic stem cell transplantation, with a significant proportion of patients failing to respond to first-line systemic corticosteroids. Reliable biomarkers predicting disease severity and response to treatment are warranted to improve its management. Thus, we sought to determine whether pentraxin 3 (PTX3), an acute-phase protein produced locally at the site of inflammation, could represent a novel acute G...

Small hypoxia-primed mesenchymal stem cells attenuate graft-versus-host disease

KAUST Repository

Kim, YongHwan

2018-05-22

Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their immunosuppressive capacity. Here, we show that Small MSCs primed with Hypoxia and Calcium ions (SHC-MSCs) exhibit enhanced stemness and immunomodulatory functions for treating allogeneic conflicts. Compared with naïve cultured human umbilical cord blood-derived MSCs, SHC-MSCs were resistant to passage-dependent senescence mediated via the monocyte chemoattractant protein-1 and p53/p21 cascade and secreted large amounts of pro-angiogenic and immunomodulatory factors, resulting in suppression of T-cell proliferation. SHC-MSCs showed DNA demethylation in pluripotency, germline, and imprinted genes similarly to very small embryonic-like stem cells, suggesting a potential mutual relationship. Genome-wide DNA methylome and transcriptome analyses indicated that genes related to immune modulation, cell adhesion, and the cell cycle were up-regulated in SHC-MSCs. Particularly, polo-like kinase-1 (PLK1), zinc-finger protein-143, dehydrogenase/reductase-3, and friend-of-GATA2 play a key role in the beneficial effects of SHC-MSCs. Administration of SHC-MSCs or PLK1-overexpressing MSCs significantly ameliorated symptoms of graft-versus-host disease (GVHD) in a humanized mouse model, resulting in significantly improved survival, less weight loss, and reduced histopathologic injuries in GVHD target organs compared with naïve MSC-infused mice. Collectively, our findings suggest that SHC-MSCs can improve the clinical treatment of allogeneic conflicts, including GVHD.

Characteristics of histocompatibility barriers in congenis strains of mice. III. Passive enhancement of skin allografts in x-irradiated hosts

International Nuclear Information System (INIS)

Cantrell, J.L.; Kaliss, N.; Hildemann, W.H.

1975-01-01

Passive immunological enhancement of skin allografts was investigated in three donor-host combinations of congenic mice disparate at non-H-2 loci. Serum against the graft donor was derived from mice that had received donor strain lymphoid cells as neonates, and thereby were rendered specifically tolerant of a skin allograft. We refer to this serum as ''allograft-tolerant'' serum. Each strain combination was chosen to provide only two non-H-2 histoincompatibilities present in the donor and absent in the host. The differences are categorized as immunogenetically strong, moderate, or weak, on the basis of skin allograft survival times. With passively administered allograft-tolerant serum, significantly prolonged graft survivals were noted for the weakest combination only. Combined treatment with sublethal x-irradiation and allograft-tolerant serum significantly prolonged graft survival in both the moderate and weak combinations, with the largest effect present in the weakest disparity. A hyperimmune alloantiserum (produced in adults) directed against the graft donor prolonged allograft survival in the strongest disparity when given in combination with irradiation. In this combination, graft survival time was increased in hosts exposed to x-ray alone, but joint treatment with x-ray and the alloantiserum gave the largest increment. In contrast, combined treatment with the serum and an antithymocyte alloantiserum did not affect graft survival times. Treatment with both radiation and antithymocyte serum did not prolong graft survival beyond that in mice given only x-radiation. Immunological enhancement with central inhibition is assumed as the mechanism underlying prolonged graft survival, and it is suggested that a population of thymus-derived killer cells, sensitive to x-irradiation, is required for normal graft rejection. (U.S.)

In vitro regulation of immunoglobulin synthesis after marrow transplantation. I. T-cell and B-cell deficiencies in patients with and without chronic graft-versus-host disease

International Nuclear Information System (INIS)

Lum, L.G.; Seigneuret, M.C.; Storb, R.F.; Witherspoon, R.P.; Thomas, E.D.

1981-01-01

Twenty-four patients with aplastic anemia or acute leukemia were treated by marrow grafts from HLA-identical donors after conditioning with high doses of cyclophosphamide and/or today body irradiation. They were studied between 4 and 63 mo (median 14.2) after transplantation. Seventeen patients had chronic graft-versus-host disease (C-GVHD) and 7 were healthy. They were studied for defects in their T- and B-cell function using and indirect hemolytic plaque assay for Ig production after 6 days of culture in the presence of pokeweek mitogen. T or B cells from the patients with or without C-GVHD were cocultured with T or B cells from their HLA-identical marrow donors or unrelated normal controls. Intrinsic B-cell defects, lack of helper T-cell activity, and suppressor T-cell activity were more frequently found in patients with C-GVHD than in healthy patients. Fifteen of the 17 patients with C-GVHD showed on or more defects in their T-and B-cell function compared to only 3 of the 7 patients without C-GVHD. None of the healthy controls, including the marrow donors, showed defects in their T- and B-cell functions. These in vitro findings may be helpful in assessing the process of immune reconstitution and the immunologic aberration found after human marrow transplantation

Ocular manifestations of graft-versus-host disease: 10 years’ experience

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Lin X

2015-07-01

Full Text Available Xihui Lin, Harrison Dwight Cavanagh Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USA Purpose: To evaluate the ocular presentation, treatment, and clinical course of graft-versus-host disease (GVHD. Design: Retrospective case series. Participants: Two hundred and forty-nine patients with systemic GVHD were included in the study. Methods: Ocular and systemic data were collected from 2003 to 2013. Main outcome measures: Mortality, visual acuity, and response of ocular symptoms. Results: Sixty-four patients had ocular manifestations (25.7%. At presentation, the mean age was 44.5 years and mean latency was 16.4 months. The most common presentations were keratoconjunctivitis sicca, cataract, blepharitis, ocular hypertension, and filamentary keratitis. Visual acuity at presentation was 20/49; at the worst point in the disease was 20/115; and at most recent visit was 20/63. When topical anti-inflammatory drops were used in addition to tears, 54.3% of patients’ ocular symptoms stabilized. When autologous serum was used in addition, 80% stabilized. The overall 10-year mortality of GVHD was 29.7%. For those with ocular involvement, it was 21.9%. Conclusion: Systemic GVHD has a high mortality rate, but ocular involvement does not suggest a worse prognosis. The main ocular presentations were keratoconjunctivitis sicca, cataracts, and ocular hypertension. Dry eyes in this population were very severe with overall worsening in visual acuity. However, with a step-wise approach involving topical anti-inflammatory medications and autologous serum tears, ocular symptoms do improve. It is important to monitor these patients closely, as they are prone to serious ocular complications such as corneal perforation and endophthalmitis. Keywords: dry eye, keratitis, corneal ulceration

Studies of blood irradiator application

International Nuclear Information System (INIS)

Li Wenhong; Lu Yangqiao

2004-01-01

Transfusion is an important means for medical treatment, but it has many syndromes such as transfusion-associated graft-versus-host disease, it's occurrence rate of 5% and above 90% death-rate. Now many experts think the only proven method is using blood irradiator to prevent this disease. It can make lymphocyte of blood product inactive, so that it can not attack human body. Therefore, using irradiation blood is a trend, and blood irradiator may play an important role in medical field. This article summarized study of blood irradiator application, including the meaning of blood irradiation, selection of the dose for blood irradiation and so on

IL-17 Genetic and Immunophenotypic Evaluation in Chronic Graft-versus-Host Disease

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Renata Gonçalves Resende

2014-01-01

Full Text Available Although interleukin-17 (IL-17 is a recently discovered cytokine associated with several autoimmune diseases, its role in the pathogenesis of chronic graft-versus-host disease (cGVHD was not established yet. The objective of this study was to investigate the association of IL17A and IL17F genes polymorphisms and IL-17A and IL-17F levels with cGVHD. IL-17A expression was also investigated in CD4+ T cells of patients with systemic cGVHD. For Part I of the study, fifty-eight allo-HSCT recipients and donors were prospectively studied. Blood samples were obtained to determine IL17A and IL17F genes polymorphisms. Cytokines levels in blood and saliva were assessed by ELISA at days +35 and +100 after HSCT. In Part II, for the immunophenotypic evaluation, eight patients with systemic cGVHD were selected and the expression of IL-17A was evaluated. We found association between recipient AA genotype with systemic cGVHD. No association was observed between IL-17A levels and cGVHD. Lower IL-17A levels in the blood were associated with AA genotype. In flow cytometry analysis, decreased expression of IL-17A was observed in patients with cGVHD after stimulation. In conclusion, IL-17A may have an important role in the development of systemic cGVHD.

Abrogation of Early Apoptosis Does Not Alter Late Inhibition of Hippocampal Neurogenesis After Irradiation

International Nuclear Information System (INIS)

Li Yuqing; Aubert, Isabelle; Wong, C. Shun

2010-01-01

Purpose: Irradiation of the adult brain results in acute apoptosis of neural progenitors and vascular endothelial cells, as well as late dysfunction of neural progenitors and inhibition of neurogenesis. We sought to determine whether the early apoptotic response has a causative role in late inhibition of neurogenesis after cranial irradiation. Methods and Materials: Using a genetic approach with p53 and smpd1 transgenic mice and a pharmacologic approach with basic fibroblast growth factor (bFGF) to abrogate the early apoptotic response, we evaluated the late inhibition of neurogenesis in the hippocampal dentate gyrus after cranial irradiation. Results: In dentate gyrus, subgranular neural progenitors underwent p53-dependent apoptosis within 24 h after irradiation. Despite a near abrogation of neural progenitor apoptosis in p53-/- mice, the reduction in newborn neurons in dentate gyrus at 9 weeks after irradiation in p53-/- mice was not different from that observed in wildtype controls. Endothelial cell apoptosis after radiation is mediated by membrane damage initiated by activation of acid sphingomyelinase (ASMase). Deletion of the smpd1 gene (which encodes ASMase) attenuated the apoptotic response of endothelial cells. At 9 weeks after irradiation, the inhibition of hippocampal neurogenesis was not rescued by ASMase deficiency. Intravenous administration of bFGF protected both endothelial cells and neural progenitors against radiation-induced apoptosis. There was no protection against inhibition of neurogenesis at 9 weeks after irradiation in bFGF-treated mice. Conclusion: Early apoptotic death of neural progenitors, endothelial cells, or both does not have a causative association with late inhibition of neurogenesis after irradiation.

Bone marrow transplantation in aplastic anaemia using cyclophosphamide and total lymphoid irradiation

International Nuclear Information System (INIS)

Jansen, J.; Zwaan, F.E.; Noordijk, E.M.

1980-01-01

Six patients with severe aplastic anaemia received a bone-marrow graft after conditioning with cyclophosphamide and total lymphoid irradiation (TLI). No rejections occurred. Acute graft-versus-host disease developed in 3 patients and was fatal in one. Another patient died from systemic aspergillus infection. Chronic GVHD of the skin developed in a patient who was grafted with bone marrow from her HLA-phenotypically identical father. These data suggest that conditioning with cyclophosphamide and TLI is a promising regimen. (orig.) [de

Dendritic cell chimerism in oral mucosa of transplanted patients affected by graft-versus-host disease.

Science.gov (United States)

Pérez, Claudio A; Rabanales, Ramón; Rojas-Alcayaga, Gonzalo; Larrondo, Milton; Escobar, Alejandro F; López, Mercedes N; Salazar-Onfray, Flavio; Alfaro, Jorge I; González, Fermín E

2016-02-01

Graft-versus-host disease (GVHD) is one of the main complications after haematopoietic stem cell transplantation. Clinical features of GVHD include either an acute (aGVHD) or a chronic (cGVHD) condition that affects locations such as the oral mucosa. While the involvement of the host's dendritic cells (DCs) has been demonstrated in aGVHD, the origin (donor/host) and mechanisms underlying oral cGVHD have not been completely elucidated. In this study, we intend to determine the origin of DCs present in mucosal tissue biopsies from the oral cavity of transplanted patients affected by cGVHD. We purified DCs, from oral biopsies of three patients with cGVHD, through immunobeads and subsequently performed DNA extraction. The origin of the obtained DCs was determined by PCR amplification of 13 informative short tandem repeat (STR) alleles. We also characterised the DCs phenotype and the inflammatory infiltrate from biopsies of two patients by immunohistochemistry. Clinical and histological features of the biopsies were concordant with oral cGVHD. We identified CD11c-, CD207- and CD1a-positive cells in the epithelium and beneath the basal layer. Purification of DCs from the mucosa of patients affected by post-transplantation cGVHD was >95%. PCR-STR data analysis of DCs DNA showed that 100% of analysed cells were of donor origin in all of the evaluated patients. Our results demonstrate that resident DCs isolated from the oral tissue of allotransplanted patients affected by cGVHD are originated from the donor. Further research will clarify the role of DCs in the development and/or severity of oral cGVHD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Albumin grafting on polymer surfaces by gamma-irradiation

International Nuclear Information System (INIS)

Kamath, K.R.; Park, K.; DeMeo, D.

1993-01-01

Polymeric biomaterial surfaces were modified by albumin grafting to improve their blood compatibility. Albumin molecules were functionalized by introduction of double bonds. The functionalized albumin was covalently attached to polypropylene fibers, polycarbonate, and poly(vinyl chloride) by gamma-irradiation. ESCA and ATR/FTIR analysis of the control and grafted surfaces was conducted. Albumin grafting efficiency was found to be dependent on the gamma-irradiation time and the concentration of albumin as indicated by platelet adhesion studies. The grafted albumin molecules were not displaced when exposed to blood for prolonged time period. Finally, PLEXUS oxygenators grafted with albumin using this approach showed a significant reduction in platelet adhesion when compared to control

Study on grafting glycidyl methacrylate onto HDPE membranes by pre-irradiation graft copolymerization

International Nuclear Information System (INIS)

Tong Long; Zu Jianhua; Liu Xinwen; Sun Guisheng; Yu Chunhui

2006-01-01

Glycidyl methacrylate (GMA) was grafted onto HDPE membranes by pre-irradiation method with 1.8 MeV E-beam and a kind of membranes having reactive epoxy groups was successfully synthesized. Effects of monomer concentration, reaction temperature and time and irradiation dose on the grafting yield were studied. Composition, thermo-property and surface morphology of the grafted membranes were studied by FTIR, DSC and Tapping-mode AFM, respectively. The FTIR measurements proved the synthesized copolymer is HDPE-g-GMA. The DSC results indicated the grafted HDPE's melting temperature (T m ) and heat of fusion (ΔH f ( HDPE) ) which was reduced with increasing grafting yield. The AFM images indicated that surface of the HDPE-g-GMA membranes was rougher than the virgin HDPE. (authors)

Practical dosimetric aspects of blood and blood product irradiation

International Nuclear Information System (INIS)

Fearon, T.C.; Luban, N.L.

1986-01-01

The method of choice to reduce susceptibility to transfusion-transmitted graft-versus-host disease is irradiation of allogenic blood and blood products for transfusion to immunosuppressed recipients. Optimal irradiation requires delivery of a known and homogeneous absorbed dose. The use of absorbed dose in air measured at the center of the irradiation volume without proper compensation for sample absorption can lead to approximately 20 percent underexposure. A lucite cylinder was used to provide the delivery of a homogeneous irradiation dose to blood products of different volumes by allowing rotation of the product

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

International Nuclear Information System (INIS)

Brinch, L.; Evensen, S.A.; Albrechtsen, D.; Egeland, T.; Solheim, B.G.; Rollag, H.; Naalsund, A.; Jacobsen, A.B.

1991-01-01

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

Preparation of poly(vinylbenzyl chloride)-grafted PFA film by a simultaneous irradiation grafting method

International Nuclear Information System (INIS)

Fei, Geng; Shin, Jun Hwa; Nho, Young Chang; Lee, Youn Sik

2009-01-01

In this study, PFA-g-PVBC films were prepared by a radiation grafting of vinylbenzyl chloride (VBC) monomer onto poly(tetrafluoroethylene-co-perfluoro propyl vinyl ether) (PFA) films by simultaneous irradiation method. IR, TGA, and SEM-EDX instruments were utilized to confirm the successful preparation of the grafted film. The effects of several irradiation conditions, including the dose, VBC concentration, and film thickness on the degree of grafting of PFA-g-PVBC film were investigated

Beta irradiation inhibits neo-intimal formation in vein grafts

International Nuclear Information System (INIS)

Lang Xiaoou; Ji Shenquan; Zeng Ke; Li Jun; Liu Bingbing; Ma Wenfeng; Zhang Qiang

2002-01-01

Objective: The study was to evaluate the effect of beta irradiation on intimal proliferation response in vein grafts. Methods: An autogenous vein graft model was established in 40 rats by transplanting internal branch of jugular vein to carotid artery by end-to-end anastomosis. The vein was irradiated by 32 P before anastomosis. Four dose schedules were studied: (1) control graft (nonirradiated); (2) irradiated with 8 Gy; (3) 18 Gy; and (4) 36 Gy. The grafted veins were harvested at 2 weeks after the operation. IH (intimal hyperplasia) and SMC (smooth muscle cell) proliferation were histologically and immuno-histochemically observed and analyzed by a computer digitalising system. Results: In 18 Gy and 36 Gy-irradiated grafts compared with the control, there was a significant decrease in the average intimal thickness (P 0.05). Immunohistochemical analysis of PCNA indicated decrease of positive cells in both 18 Gy and 36 Gy groups compared with 8 Gy and the control group (P 0.05) groups, and there was also no significant difference between 8 Gy and the control group (P > 0.05). Conclusion: These preliminary results demonstrate that proper dose of beta irradiation in vein graft inhibits smooth muscle cells proliferation and neo-intimal hyperplasia in rat

Granzyme A Is Required for Regulatory T-Cell Mediated Prevention of Gastrointestinal Graft-versus-Host Disease.

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Sarvari Velaga

Full Text Available In our previous work we could identify defects in human regulatory T cells (Tregs likely favoring the development of graft-versus-host disease (GvHD following allogeneic stem cell transplantation (SCT. Treg transcriptome analyses comparing GvHD and immune tolerant patients uncovered regulated gene transcripts highly relevant for Treg cell function. Moreover, granzyme A (GZMA also showed a significant lower expression at the protein level in Tregs of GvHD patients. GZMA induces cytolysis in a perforin-dependent, FAS-FASL independent manner and represents a cell-contact dependent mechanism for Tregs to control immune responses. We therefore analyzed the functional role of GZMA in a murine standard model for GvHD. For this purpose, adoptively transferred CD4+CD25+ Tregs from gzmA-/- mice were analyzed in comparison to their wild type counterparts for their capability to prevent murine GvHD. GzmA-/- Tregs home efficiently to secondary lymphoid organs and do not show phenotypic alterations with respect to activation and migration properties to inflammatory sites. Whereas gzmA-/- Tregs are highly suppressive in vitro, Tregs require GZMA to rescue hosts from murine GvHD, especially regarding gastrointestinal target organ damage. We herewith identify GZMA as critical effector molecule of human Treg function for gastrointestinal immune response in an experimental GvHD model.

Does defibrotide prophylaxis decrease the risk of acute graft versus host disease following allogeneic hematopoietic cell transplantation?

Science.gov (United States)

Tekgündüz, Emre; Kaya, Ali Hakan; Bozdağ, Sinem Civriz; Koçubaba, Şerife; Kayıkçı, Ömür; Namdaroğlu, Sinem; Uğur, Bilge; Akpınar, Seval; Batgi, Hikmetullah; Bekdemir, Filiz; Altuntaş, Fevzi

2016-02-01

There is some preliminary evidence, that veno-occlusive disease prophylaxis with defibrotide (DF) may also have a role in decreasing risk of acute graft-versus-host disease (aGvHD) by preventing tissue damage. In this study, we aimed to investigate the role of DF prophylaxis on the development of aGvHD at D+180. One hundred ninety-five consecutive adult patients receiving allogeneic HCT were retrospectively evaluated in 3 groups: no DF, DF/post-HCT (DF D+1 to D+14) and DF/pre-HCT (DF for 14 days concurrently with conditioning). The total (p: 0.057) and grades III/IV (p: 0.051) aGvHD rates at D+180 were 46.5%, 40%, 25.5% and 15.5%, 11.2%, 0% in patients on no DF, DF/post-HCT and DF/pre-HCT. DF may have a role in decreasing incidence and severity of aGvHD, especially if used concurrently with conditioning regimen. Copyright © 2016 Elsevier Ltd. All rights reserved.

Radiation Effect on Secondary Cancerization by Tumour Cell Grafts. Take of Irradiated Tumour Cells in Irradiated and Non-Irradiated Animals

Energy Technology Data Exchange (ETDEWEB)

Costachel, O.; Sandru, Gh.; Kitzulescu, I. [Oncological Institute, Bucharest (Romania)

1969-11-15

This study was designed to determine the ability of haemocytoblastoma, SME and Jensen tumours, which had been irradiated in vitro, to take in C{sub 57}BL/6 mice or Wistar rats that were whole-body irradiated at 0.4 kR and 0.6 kR respectively. It was found-that the take of tumour cell grafts irradiated in vitro increased in whole-body irradiated mice and rats but not in non-irradiated ones. When Wistar rats, that had been whole-body irradiated with 0.7 and 0.8 kR 1 - 7 months earlier and survived after treatment, were grafted with Jensen tumour cells irradiated in vitro with 3 kR they were found to develop tumours and lung metastases (in contrast to non-irradiated rats). A cross resistance against non-irradiated Jensen tumour cells was obtained in non- irradiated Wistar rats by grafting irradiated Jensen tumour cells. Chromosomal analysis showed two supplementary giant markers in the Jensen tumour cells that had been irradiated in vitro before grafting. (author)

Influence of x-irradiation on pharyngeal induction in the Planarian, Dugesia japonica japonica

International Nuclear Information System (INIS)

Asai, Etsuo

1980-01-01

Pharyngeal formation was examined in cases where normal or X-irradiated head pieces were transplanted into the postpharyngeal region of normal or irradiated worms. Transplantation experiments were carried out in four different combinations of hosts and grafts: (1) normal host and graft (control), (2) normal host and irradiated graft, (3) irradiated host and normal graft, (4) irradiated host and graft. In the first experiment, well developed pharynges were formed in the areas both anterior and posterior to the graft on the 14th day after transplantation. In the second experiment, formation of new pharynges was delayed compared with that in the first group. In the third experiment, only one pharynx developed in the area posterior to each graft in most cases. In the last experiment, no new pharynx appeared at all. From these results, the influence of X-rays on factors participating in pharyngeal induction was discussed. (author)

A Critical Appraisal of Extracorporeal Photopheresis as a Treatment Modality for Acute and Chronic Graft-Versus-Host Disease

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Hind Rafei

2017-10-01

Full Text Available Although significant advances have been made in the biologic understanding of graft-versus-host disease (GVHD and its treatment options, GVHD remains the single most challenging obstacle to the success of allogeneic hematopoietic cell transplantation (HCT due to high risk of disabling morbidity and mortality. Extracorporeal photopheresis (ECP has promising effects in controlling steroid-refractory GVHD, both acute and chronic, and it has been studied extensively. Its putative immunomodulatory mechanisms, while not immunosuppressive, position ECP as an attractive treatment strategy for GVHD patients who are already receiving global immunosuppression. However, ECP is relatively underutilized due in part to limited access and time commitment. Here, we review the recent findings on the ECP efficacy in both acute and chronic GVHD, primarily for steroid-refractory status, and we critically appraise its benefits. We also explore salient considerations on the optimal use of ECP in the treatment of refractory GVHD.

Mechanical behavior of styrene grafted PVC films by electron beam irradiation

International Nuclear Information System (INIS)

Cardoso, Jessica R.; Moura, Eduardo; Somessari, Elisabeth S.R.; Silveira, Carlos G.; Paes, Helio A.; Souza, Carlos A.; Manzoli, Jose E.; Geraldo, Aurea B.C.

2011-01-01

The polyvinyl chloride (PVC) is a technological and low cost polymer, however it presents high sensitivity to high energy irradiation because of the weakness of carbon-chloride bond face to carbon-carbon and carbon-hydrogen bonds. Grafting is a type of co-polymerization process that can allow it an increase of mechanical characteristics. The aim of this work is to evaluate the mechanical properties of styrene grafted PVC by electron beam irradiation using mutual and pre-irradiation methods to verify the mechanical resistance changes of obtained product whether grafting process is applied from non-irradiated or from pre-irradiated substrates. The irradiation procedures were performed in atmosphere air or inert atmosphere and the irradiation conditions comprised doses from 10 kGy to 100 kGy and dose rates of 2.2 kGy/s and 22.4 kGy/s. The styrene grafted samples were analyzed by gravimetry to determinate the grafting yield; the final values have been averaged from a series of three measurements. The Mid-A TR-FTIR was the spectrophotometer technique used for qualitative/semi-quantitative analysis of grafted samples. The Young's module and tensile strength of pre-irradiated and grafted PVC samples at both methods were measured at a Lloyd LXR tensile tester at a cross-head speed of 10.00 mm/min. We observed the decrease of Young's module and tensile strength with the increase of absorbed dose at pre-irradiated PVC samples. These mechanical parameters results are discussed. (author)

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

Modeling conduction in host-graft interactions between stem cell grafts and cardiomyocytes.

Science.gov (United States)

Chen, Michael Q; Yu, Jin; Whittington, R Hollis; Wu, Joseph C; Kovacs, Gregory T A; Giovangrandi, Laurent

2009-01-01

Cell therapy has recently made great strides towards aiding heart failure. However, while transplanted cells may electromechanically integrate into host tissue, there may not be a uniform propagation of a depolarization wave between the heterogeneous tissue boundaries. A model using microelectrode array technology that maps the electrical interactions between host and graft tissues in co-culture is presented and sheds light on the effects of having a mismatch of conduction properties at the boundary. Skeletal myoblasts co-cultured with cardiomyocytes demonstrated that conduction velocity significantly decreases at the boundary despite electromechanical coupling. In an attempt to improve the uniformity of conduction with host cells, differentiating human embryonic stem cells (hESC) were used in co-culture. Over the course of four to seven days, synchronous electrical activity was observed at the hESC boundary, implying differentiation and integration. Activity did not extend far past the boundary, and conduction velocity was significantly greater than that of the host tissue, implying the need for other external measures to properly match the conduction properties between host and graft tissue.

Vulvar and vaginal graft versus host disease: A healthcare clinic initiative

Directory of Open Access Journals (Sweden)

Naomi Van Dam

2017-01-01

Full Text Available Objective: In patients receiving bone marrow transplantation (BMT, their mucosa becomes altered and sclerotic changes in the female external genital organs occur. Although a few studies have specifically addressed vulvar and vaginal graft versus host disease (VVGvHD and its repercussions on the sexual health and quality of life of patients, VVGvHD can be overlooked by health practitioners. The objective of the study is to describe the initiation of a health care clinic specializing in VVGvHD in a general tertiary hospital. Methods: A VVGvHD clinic was founded as a part of BMT daycare in a joint initiative of the nursing staff and the medical director of the department and a gynecologist specializing in vulva and vaginal disease. Patients were assessed for vulvovaginal symptoms, such as dryness, burning, itching, pain to touch, pain during intercourse, and dysuria. These patients might be subsequently referred to the VVGvHD clinic according to their needs assessed by daycare nurses. Treatment guidelines were developed by the specialist gynecologist. Results: A total of 81 women aged 2–66 years (median age = 38 years visited the clinic from 2009 to 2015. Of these women, 70 received an allogeneic transplant and 11 underwent autologous transplantation before consultation in our clinic. VVGvHD was detected in 54% of the patients. Conclusions: The VVGvHD clinic was developed to fulfill the specific needs of female patients who underwent BMT. The pioneer clinic was founded as a joint effort of the multidisciplinary team. Evidence supporting the optimum treatment for this condition is insufficient. This was the main reason for performing this study to explore the clinic that was newly based in Israel. VVGvHD may be a fluctuating condition with frequent deterioration and improvement. Therefore, regular clinical examinations are necessary.

Mechanical behavior of styrene grafted PVC films by electron beam irradiation

Energy Technology Data Exchange (ETDEWEB)

Cardoso, Jessica R.; Moura, Eduardo; Somessari, Elisabeth S.R.; Silveira, Carlos G.; Paes, Helio A.; Souza, Carlos A.; Manzoli, Jose E.; Geraldo, Aurea B.C., E-mail: ageraldo@ipen.br, E-mail: jmanzoli@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2011-07-01

The polyvinyl chloride (PVC) is a technological and low cost polymer, however it presents high sensitivity to high energy irradiation because of the weakness of carbon-chloride bond face to carbon-carbon and carbon-hydrogen bonds. Grafting is a type of co-polymerization process that can allow it an increase of mechanical characteristics. The aim of this work is to evaluate the mechanical properties of styrene grafted PVC by electron beam irradiation using mutual and pre-irradiation methods to verify the mechanical resistance changes of obtained product whether grafting process is applied from non-irradiated or from pre-irradiated substrates. The irradiation procedures were performed in atmosphere air or inert atmosphere and the irradiation conditions comprised doses from 10 kGy to 100 kGy and dose rates of 2.2 kGy/s and 22.4 kGy/s. The styrene grafted samples were analyzed by gravimetry to determinate the grafting yield; the final values have been averaged from a series of three measurements. The Mid-A TR-FTIR was the spectrophotometer technique used for qualitative/semi-quantitative analysis of grafted samples. The Young's module and tensile strength of pre-irradiated and grafted PVC samples at both methods were measured at a Lloyd LXR tensile tester at a cross-head speed of 10.00 mm/min. We observed the decrease of Young's module and tensile strength with the increase of absorbed dose at pre-irradiated PVC samples. These mechanical parameters results are discussed. (author)

Grafting of acrylamide onto synthetic co polyamide by gamma irradiation

Energy Technology Data Exchange (ETDEWEB)

Hamoud, M R; Qamhieyh, E A [Chemistry Dept., College of Ibn Al-Haitham Baghdad university-Adhamiyah-Baghdad- (Iraq)

1995-10-01

Grafted copolymer was prepared by using gamma irradiation to graft acrylamide onto polymeric molecule prepared by interfacial condensation between two diamine molecules like 1,2 diamino propane and 1,6 diamino-hexane in aqueous layer with sebacoyl chloride in organic layer. The resulted co polyamide was grafted with acrylamide using gamma irradiation. The optimum conditions of grafting reaction were found, also various factors such as the effect of solvents, redox systems and the role water on the radiochemical grafting were studied. Many techniques were used in the characterization of the copolymer before and after grafting. 8 figs.,.

Graft copolimerization of hydrophilic monomers onto irradiated polypropylene fibers

International Nuclear Information System (INIS)

Sundardi, F.

1978-01-01

A method of graft copolymerization of hydrophilic monomers, such as 1-vinyl-2-pyrrolidone, acrylonitrile, acrylic acid, and acrylamide, onto irradiated polypropylene fibers has been studied. γ ray as well as electron beam were employed for the irradiation processes. Graft-copolymerization kinetics and the properties of grafted fibers have been investigated. Moisture regain, dyes absorption, and melting point of the grafted fibers were found to increase with the increasing of the degree of grafting. Polypropylene for 1-vinyl-2-pyrrolidone grafted fibers showed excellent dye absorption for almost all kinds of dyes such as direct, basic, acid, reactive, disper, and naphthol dyes. However, for polypropylene acrylic acid grafted fibers, the colorfastness to washing was found to be unsatisfactory. The colorfastness to washing for polypropylene 1-vinyl-2-pyrrolidone grafted fibers was found to be fairly good for certain types of dyes such as vat and naphthol dyes. (author)

Early dominance of irradiated host cells in the responder profiles of thymocytes from P → F1 radiation chimeras

International Nuclear Information System (INIS)

Korngold, R.; Bennink, J.R.; Doherty, P.C.

1981-01-01

The number of cells in the thymus of radiation (1000 rad) chimeras increases approximately 10-fold between 7 and 14 days after reconstitution with bone marrow. At least 50% of the cells in thymus on day 14 are of host origin and respond to virus presented in the context of both H-2/sup k/ and H-2/sup b/ when primed in irradiated, virus-infected (b x k)F 1 recipients. Strong CTL responses can be generated from thymocytes of donor origin on day 21. All evidence of a significant host thymocyte component has disappeared by day 28. The responsiveness of 14-day thymocytes is not abrogated by pretreatment of the mice used to make the chimeras with anti-thymocyte serum or by using doses of irradiation as high as 1200 rads to eliminate host components

Vision-Related Quality of Life in Patients with Ocular Graft-versus-Host Disease.

Science.gov (United States)

Saboo, Ujwala S; Amparo, Francisco; Abud, Tulio B; Schaumberg, Debra A; Dana, Reza

2015-08-01

To assess the vision-related quality of life (QOL) in a cohort of patients with ocular graft-versus-host disease (GVHD). Prospective study. Eighty-four patients diagnosed with chronic ocular GVHD. We assessed the vision-related QOL with the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). The symptoms of ocular GVHD were assessed using the Ocular Surface Disease Index (OSDI) and Symptom Assessment in Dry Eye (SANDE) questionnaires. We assessed vision-related QOL with the NEI-VFQ-25 and compared the scores obtained from patients with ocular GVHD with those from a healthy population. In the ocular GVHD population, we also evaluated the associations between the NEI-VFQ-25 and the dry eye symptoms measured by the OSDI and SANDE questionnaires, age, duration of disease, best-corrected visual acuity (BCVA), corneal fluorescein staining (CFS), tear break-up time, and Schirmer test. The mean composite NEI-VFQ-25 score in patients with ocular GVHD was 76.5±17. Compared with healthy subjects, patients with ocular GVHD reported reduced scores on all NEI-VFQ-25 subscales (each P vision (P = 0.11). The NEI-VFQ-25 composite scores significantly correlated with OSDI (R = -0.81, P vision-related QOL. This study highlights the impact of ocular GVHD on the vision-related QOL, and thus the importance of comprehensive diagnosis and treatment of this condition. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Graft-Versus-Host Disease after Liver Transplantation Complicated by Systemic Aspergillosis with Pancarditis

Directory of Open Access Journals (Sweden)

Joseph Romagnuolo

2000-01-01

Full Text Available Acute graft-versus-host disease (GVHD is a common complication after bone marrow transplantation, with characteristic rash and diarrhea being the most common features. After liver transplantation, however, this phenomenon is very rare. Most transplant patients are on a variety of medications, including immunosuppressants; therefore, the differential diagnosis of skin rash or diarrhea is broad. A 37-year-old man who underwent liver transplantation for primary biliary cirrhosis, and developed a rash and watery diarrhea, is presented. Skin and colonic biopsies confirmed acute GVHD. A pulse of intravenous steroids was given. The skin rash improved, but he developed pancytopenia. His course was complicated by central line infection, jugular and subclavian vein thrombosis, pseudomembranous colitis, recurrent bacteremia, cholestasis on total parenteral nutrition and cytomegalovirus infection. After the onset of pleuritic chest pain and clinical sepsis, spiral computed tomography scan of his chest and abdomen revealed septic infarcts in multiple organs. Despite empirical treatment with amphotericin B, he died of multiorgan dysfunction syndrome within 72 h. Autopsy revealed systemic aspergillosis with pancarditis, endocardial vegetations, and septic pulmonary, splenic, hepatic and renal infarcts. The pathogenesis and experience with this rare, but often fatal, complication of liver transplantation are reviewed. In contrast to GVHD after bone marrow transplantation, pancytopenia is common and liver dysfunction is rare. One should have a high level of suspicion in the liver transplant recipient presenting with rash and/or diarrhea.

Autologous Graft versus Host Disease: An Emerging Complication in Patients with Multiple Myeloma

Directory of Open Access Journals (Sweden)

Anu Batra

2014-01-01

Full Text Available Autologous graft versus host disease (autoGVHD is a rare transplant complication with significant morbidity and mortality. It has been hypothesized that patients with multiple myeloma might be predisposed to autoGVHD through dysregulation of the immune response resulting from either their disease, the immunomodulatory agents (IMiDs used to treat it, or transplant conditioning regimen. Hematopoietic progenitor cell (HPC products were available from 8 multiple myeloma patients with biopsy-proven autoGVHD, 16 matched multiple myeloma patients who did not develop autoGVHD, and 7 healthy research donors. The data on number of transplants prior to developing autoGVHD, mobilization regimens, exposure to proteasome inhibitors, use of IMiDs, and class I human leukocyte antigen types (HLA A and B were collected. The HPC products were analyzed by flow cytometry for expression of CD3, CD4, CD8, CD25, CD56, and FoxP3. CD3+ cell number was significantly lower in autoGVHD patients compared to unaffected controls (P=0.047. On subset analysis of CD3+ cells, CD8+ cells (but not CD4+ cells were found to be significantly lower in patients with autoGVHD (P=0.038. HLA-B55 expression was significantly associated with development of autoGVHD (P=0.032. Lower percentages of CD3+ and CD8+ T-cells and HLA-B55 expression may be predisposing factors for developing autoGVHD in myeloma.

Reversal of CD8 T-Cell–Mediated Mucocutaneous Graft-Versus-Host-Like Disease by the JAK Inhibitor Tofacitinib

Science.gov (United States)

Okiyama, Naoko; Furumoto, Yasuko; Villarroel, Vadim A; Linton, Jay T; Tsai, Wanxia L; Gutermuth, Jan; Ghoreschi, Kamran; Gadina, Massimo; O'Shea, John J; Katz, Stephen I

2014-01-01

The utility of allogeneic hematopoietic stem cell transplantation is limited by graft-versus-host disease (GVHD), a significant cause of morbidity and mortality. Patients with GVHD exhibit cutaneous manifestations with histological features of interface dermatitis followed by scleroderma-like changes. JAK inhibitors represent a class of immunomodulatory drugs that inhibit signaling by multiple cytokines. Herein we report the effects of tofacitinib in a murine model of GVHD. Oral administration of tofacitinib prevented GVHD-like disease manifested by weight loss and mucocutaneous lesions. More importantly, tofacitinib was also effective in reversing established disease. Tofacitinib diminished the expansion and activation of murine CD8 T cells in this model, and had similar effects on IL-2-stimulated human CD8 T cells. Tofacitinib also inhibited the expression of IFN-γ-inducible chemoattractants by keratinocytes, and IFN-γ-inducible cell death of keratinocytes. Tofacitinib may be an effective drug for treatment against CD8 T-cell–mediated mucocutaneous diseases in patients with GVHD. PMID:24213371

Post-Transplant Cyclophosphamide and Tacrolimus-Mycophenolate Mofetil Combination Prevents Graft-versus-Host Disease in Allogeneic Peripheral Blood Hematopoietic Cell Transplantation from HLA-Matched Donors.

Science.gov (United States)

Carnevale-Schianca, Fabrizio; Caravelli, Daniela; Gallo, Susanna; Coha, Valentina; D'Ambrosio, Lorenzo; Vassallo, Elena; Fizzotti, Marco; Nesi, Francesca; Gioeni, Luisa; Berger, Massimo; Polo, Alessandra; Gammaitoni, Loretta; Becco, Paolo; Giraudo, Lidia; Mangioni, Monica; Sangiolo, Dario; Grignani, Giovanni; Rota-Scalabrini, Delia; Sottile, Antonino; Fagioli, Franca; Aglietta, Massimo

2017-03-01

Allogeneic hematopoietic cell transplant (HCT) remains the only curative therapy for many hematologic malignancies but it is limited by high nonrelapse mortality (NRM), primarily from unpredictable control of graft-versus-host disease (GVHD). Recently, post-transplant cyclophosphamide demonstrated improved GVHD control in allogeneic bone marrow HCT. Here we explore cyclophosphamide in allogeneic peripheral blood stem cell transplantation (alloPBSCT). Patients with high-risk hematologic malignancies received alloPBSCT from HLA-matched unrelated/related donors. GVHD prophylaxis included combination post-HCT cyclophosphamide 50 mg/kg (days +3 and +4) and tacrolimus/mofetil mycophenolate (T/MMF) (day +5 forward). The primary objective was the cumulative incidence of acute and chronic GVHD. Between March 2011 and May 2015, 35 consecutive patients received the proposed regimen. MMF was stopped in all patients at day +28; the median discontinuation of tacrolimus was day +113. Acute and chronic GVHD cumulative incidences were 17% and 7%, respectively, with no grade IV GVHD events, only 2 patients requiring chronic GVHD immunosuppression control, and no deaths from GVHD. Two-year NRM, overall survival, event-free survival, and chronic GVHD event-free survival rates were 3%, 77%, 54%, and 49%, respectively. The graft-versus-tumor effect was maintained as 5 of 15 patients (33%) who received HCT with evidence of disease experienced further disease response. A post-transplant cyclophosphamide + T/MMF combination strategy effectively prevented acute and chronic GVHD after alloPBSCT from HLA-matched donors and achieved an unprecedented low NRM without losing efficacy in disease control or impaired development of the graft-versus-tumor effect. This trial is registered at clinicaltrials.gov as NCT02300571. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Mechanism of donor to host tolerance in rat bone marrow chimeras

International Nuclear Information System (INIS)

Tutschka, P.; Schwerdtfeger, R.; Slavin, R.; Santos, G.

1977-01-01

Lewis rats were conditioned with cyclophosphamide and grafted with AgB incompatible bone marrow. They were examined 250 days after transplantation and demonstrated to be healthy complete chimeras. Marrow cells from these chimeras were infused into lethally irradiated ACI, Lewis and BN recipients. Graft-versus-host disease occurred only in the BN rats. Other chimeric rats were given no treatment, busulfan, CY, or total body irradiation prior to the infusion of normal ACI BM. GvHD occurred only in animals given CY or TBI. Normal Lewis rats were conditioned with TBI and given ACI BM. In addition, they received whole blood, irradiated blood, or serum from chimeric rats. GvHD developed in all animals except those given unirradiated chimeric blood. These studies suggest that suppressor cell populations, sensitive to immunosuppression, are likely the fundamental mechanism of recovery from GvHD

Recommendations for the use of irradiated components

International Nuclear Information System (INIS)

2007-01-01

The disease 'graft-versus-host' associated with the transfusion (EIVH TA) is an adverse reaction rare but fatal, linked to the proliferation of T cells that are found in cellular components and reacting against the receptor's tissues). Gamma irradiation of cellular components is used as a prevention method because it deactivates the lymphocytes T by reducing its survival and by restraining its proliferation without producing alterations in others cells function. Recommendations for the use of gamma irradiation along with clinical indications for pediatric patients, patients with acquired immunosuppression and immunocompetent patients are given in this study. A brief description of operative aspects of irradiation procedures such as components to be irradiated, irradiation method, irradiation dose and viability of irradiated components is given [es

A colitogenic memory CD4+ T cell population mediates gastrointestinal graft-versus-host disease

Science.gov (United States)

Zhou, Vivian; Agle, Kimberle; Chen, Xiao; Beres, Amy; Komorowski, Richard; Belle, Ludovic; Taylor, Carolyn; Zhu, Fenlu; Haribhai, Dipica; Williams, Calvin B.; Verbsky, James; Blumenschein, Wendy; Sadekova, Svetlana; Bowman, Eddie; Ballantyne, Christie; Weaver, Casey; Serody, David A.; Vincent, Benjamin; Serody, Jonathan; Cua, Daniel J.; Drobyski, William R.

2016-01-01

Damage to the gastrointestinal tract is a major cause of morbidity and mortality in graft-versus-host disease (GVHD) and is attributable to T cell–mediated inflammation. In this work, we identified a unique CD4+ T cell population that constitutively expresses the β2 integrin CD11c and displays a biased central memory phenotype and memory T cell transcriptional profile, innate-like properties, and increased expression of the gut-homing molecules α4β7 and CCR9. Using several complementary murine GVHD models, we determined that adoptive transfer and early accumulation of β2 integrin–expressing CD4+ T cells in the gastrointestinal tract initiated Th1-mediated proinflammatory cytokine production, augmented pathological damage in the colon, and increased mortality. The pathogenic effect of this CD4+ T cell population critically depended on coexpression of the IL-23 receptor, which was required for maximal inflammatory effects. Non–Foxp3-expressing CD4+ T cells produced IL-10, which regulated colonic inflammation and attenuated lethality in the absence of functional CD4+Foxp3+ T cells. Thus, the coordinate expression of CD11c and the IL-23 receptor defines an IL-10–regulated, colitogenic memory CD4+ T cell subset that is poised to initiate inflammation when there is loss of tolerance and breakdown of mucosal barriers. PMID:27500496

Female genital tract graft-versus-host disease: incidence, risk factors and recommendations for management.

Science.gov (United States)

Zantomio, D; Grigg, A P; MacGregor, L; Panek-Hudson, Y; Szer, J; Ayton, R

2006-10-01

Female genital tract graft-versus-host disease (GVHD) is an under-recognized complication of allogeneic stem cell transplantation impacting on quality of life. We describe a prospective surveillance programme for female genital GVHD to better characterize incidence, risk factors and clinical features and the impact of a structured intervention policy. A retrospective audit was conducted on the medical records of all female transplant recipients surviving at least 6 months at a single centre over a 5-year period. Patients commenced topical vaginal oestrogen early post transplant with hormone replacement as appropriate for age, prior menopausal status and co-morbidities. A genital tract management programme included regular gynaecological review and self-maintenance of vaginal capacity by dilator or intercourse. The incidence of genital GVHD was 35% (95% confidence interval (CI) (25, 50%)) at 1 year and 49% (95% CI (36, 63%)) at 2 years. Topical therapy was effective in most cases; no patient required surgical intervention to divide vaginal adhesions. The main risk factor was stem cell source with peripheral blood progenitor cells posing a higher risk than marrow (hazard ratio=3.07 (1.22, 7.73), P=0.017). Extensive GVHD in other organs was a common association. We conclude that female genital GVHD is common, and early detection and commencement of topical immunosuppression with dilator use appears to be highly effective at preventing progression.

International, multi-center standardization of acute graft-versus-host disease clinical data collection: a report from the MAGIC consortium

Science.gov (United States)

Harris, Andrew C.; Young, Rachel; Devine, Steven; Hogan, William J.; Ayuk, Francis; Bunworasate, Udomsak; Chanswangphuwana, Chantiya; Efebera, Yvonne A.; Holler, Ernst; Litzow, Mark; Ordemann, Rainer; Qayed, Muna; Renteria, Anne S.; Reshef, Ran; Wölfl, Matthias; Chen, Yi-Bin; Goldstein, Steven; Jagasia, Madan; Locatelli, Franco; Mielke, Stephan; Porter, David; Schechter, Tal; Shekhovtsova, Zhanna; Ferrara, James L.M.; Levine, John E.

2015-01-01

Acute graft-versus-host disease (GVHD) remains a leading cause of morbidity and non-relapse mortality following allogeneic hematopoietic cell transplantation. The clinical staging of GVHD varies greatly between transplant centers and is frequently not agreed upon by independent reviewers. The lack of standardized approaches to handle common sources of discrepancy in GVHD grading likely contributes to why promising GVHD treatments reported from single centers have failed to show benefit in randomized multi-center clinical trials. We developed guidelines through international expert consensus opinion to standardize the diagnosis and clinical staging of GVHD for use in a large international GVHD research consortium. During the first year of use, the guidance was following discussion of complex clinical phenotypes by experienced transplant physicians and data managers. These guidelines increase the uniformity of GVHD symptom capture which may improve the reproducibility of GVHD clinical trials after further prospective validation. PMID:26386318

Wireless capsule endoscopy for diagnosis of acute intestinal graft-versus-host disease.

Science.gov (United States)

Neumann, Susanne; Schoppmeyer, Konrad; Lange, Thoralf; Wiedmann, Marcus; Golsong, Johannes; Tannapfel, Andrea; Mossner, Joachim; Niederwieser, Dietger; Caca, Karel

2007-03-01

The small intestine is the most common location of intestinal graft-versus-host disease (GVHD). EGD with duodenal biopsies yields the highest diagnostic sensitivity, but the jejunum and ileum are not accessible by regular endoscopy. In contrast, wireless capsule endoscopy (WCE) is a noninvasive imaging procedure offering complete evaluation of the small intestine. The objective was to compare the diagnostic value of EGD, including biopsies, with the results of WCE in patients with acute intestinal symptoms who received allogeneic blood stem cell transplantation and to analyze the appearance and distribution of acute intestinal GVHD lesions in these patients. An investigator-blinded, single-center prospective study. Patients with acute intestinal symptoms after allogeneic stem cell transplantation underwent both EGD and WCE within 24 hours. Clinical data were recorded during 2 months of follow-up. Fourteen consecutive patients with clinical symptoms of acute intestinal GVHD were recruited. In 1 patient, the capsule remained in the stomach and was removed endoscopically. In 7 of 13 patients who could be evaluated, acute intestinal GVHD was diagnosed by EGD with biopsies, but 3 of these would have been missed by EGD alone. In all 7 patients with histologically confirmed acute intestinal GVHD, WCE revealed typical signs of GVHD. Lesions were scattered throughout the small intestine, but were most accentuated in the ileum. This study had a small number of patients. WCE, which is less invasive than EGD with biopsies, showed a comparable sensitivity and a high negative predictive value for diagnosing acute intestinal GVHD. It may be helpful to avoid repeated endoscopic procedures in patients who have undergone stem cell transplantation.

Pre-irradiation induced emulsion graft polymerization of acrylonitrile onto polyethylene nonwoven fabric

International Nuclear Information System (INIS)

Liu Hanzhou; Yu Ming; Deng Bo; Li Linfan; Jiang Haiqing; Li Jingye

2012-01-01

Acrylonitrile has been widely used in the modification of polymers by graft polymerization. In the present work, pre-irradiation induced emulsion graft polymerization method is used to introduce acrylonitrile onto PE nonwoven fabric instead of the traditional reaction in organic solvents system. The degree of grafting (DG) is measured by gravimetric method and the kinetics of the graft polymerization is studied. The existence of the graft chains is proven by Fourier transform infrared spectroscopy (FT-IR) analysis. Thermal stability of the grafted polymer is measured by Thermogravimetric analysis (TGA). - Highlights: → Acrylonitrile is grafted onto pre-irradiated polyethylene (PE) nonwoven fabrics. → Emulsion system is applied, for the graft polymerization avoids organic solvent. → Kinetic of the pre-irradiation induced graft polymerization is studied. → Optimal condition is determined at the temperature below the b.p. of acrylonitrile.

Irradiation process of platelets and red blood cells: uncertainty values; Processo de irradiacao de bolsas contendo plaquetas e hemacias: fontes de incertezas

Energy Technology Data Exchange (ETDEWEB)

Pacifico, Leonardo, E-mail: leonardocpacifico@gmail.com [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil); Peixoto, Jose Gullherme P. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

2016-07-01

Irradiation of platelets and red blood cells is critical to prevent a disease called transfusion-associated graft versus host disease (TA-GVHD). An irradiator with source of Cesio-137 is used for this. During the irradiation process, input quantities contributing to the expanded uncertainty of the value of absorbed dose shown. The aim of our study was to identify the input quantities in the process. (author)

Osteopontin attenuates acute gastrointestinal graft-versus-host disease by preventing apoptosis of intestinal epithelial cells

International Nuclear Information System (INIS)

Kawakami, Kentaro; Minami, Naoki; Matsuura, Minoru; Iida, Tomoya; Toyonaga, Takahiko; Nagaishi, Kanna; Arimura, Yoshiaki; Fujimiya, Mineko; Uede, Toshimitsu; Nakase, Hiroshi

2017-01-01

Background and aims: Acute graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation, which often targets gastrointestinal (GI) tract. Osteopontin (OPN) plays an important physiological role in the efficient development of Th1 immune responses and cell survival by inhibiting apoptosis. The role of OPN in acute GI-GVHD is poorly understood. In the present study, we investigated the role of OPN in donor T cells in the pathogenicity of acute GI-GVHD. Methods: OPN knockout (KO) mice and C57BL/6 (B6) mice were used as donors, and (C57BL/6 × DBA/2) F1 (BDF1) mice were used as allograft recipients. Mice with acute GI-GVHD were divided into three groups: the control group (BDF1→BDF1), B6 group (B6→BDF1), and OPN-KO group (OPN-KO→BDF1). Bone marrow cells and spleen cells from donors were transplanted to lethally irradiated recipients. Clinical GVHD scores were assessed daily. Recipients were euthanized on day 7 after transplantation, and colons and small intestines were collected for various analyses. Results: The clinical GVHD score in the OPN-KO group was significantly increased compared with the B6 and control groups. We observed a difference in the severity of colonic GVHD between the OPN-KO group and B6 group, but not small intestinal-GVHD between these groups. Interferon-γ, Tumor necrosis factor-α, Interleukin-17A, and Interleukin-18 gene expression in the OPN-KO group was differed between the colon and small intestine. Flow cytometric analysis revealed that the fluorescence intensity of splenic and colonic CD8 T cells expressing Fas Ligand was increased in the OPN-KO group compared with the B6 group. Conclusion: We demonstrated that the importance of OPN in T cells in the onset of acute GI-GVHD involves regulating apoptosis of the intestinal cell via the Fas-Fas Ligand pathway. - Highlights: • A lack of osteopontin in donor cells exacerbated clinical gastrointestinal GVHD. • Donor cells lacking

Revascularization of autogenous skin grafts placed on irradiated tissue

International Nuclear Information System (INIS)

Ueda, M.; Torii, S.; Kaneda, T.; Oka, T.

1982-01-01

Vascular changes in rat skin after irradiation were examined microangiographically. Revascularization of the skin transplanted during the chronic stage after irradiation was also studied. The results obtained through these examinations revealed higher vascular densities at the acute and the subacute stages, and low values at the chronic stages compared with those of the control. Furthermore, when the skin grafts were transplanted to the irradiated beds in the chronic stage, primary revascularization was scant, and the inhibited capillary proliferation in the recipient sites prevented new vessel penetration. This explains why grafts transplanted to previously irradiated beds fail to survive

New membranes obtained by grafted irradiated PVDF foils

International Nuclear Information System (INIS)

Mazzei, R.; García Bermúdez, G.; Camporotondi, D.E.; Arbeitman, C.

2012-01-01

The present work describes a new method to produce membranes of poly(Acrylic-acid-Xmonomer) using the grafting procedure. PVDF foils irradiated with Ar + beam with energies between 30 and 150 keV were employed as substratum. Different combinations of monomers in water solutions were used: acrylic acid (AAc); acrylic acid–glycidyl methacrylate (AAc–GMA); acrylic acid–styrene (AAc–S), acrylic acid-N-isopropyl acrylamide (AAc–NIPAAm) and acrylic acid-N-isopropyl acrylamide–glycidyl methacrylate (AAc-NIPAAm–GMA). A large percentage of grafting results for specific values of: ion fluence and energy, AAc and sulfuric acid concentration, and different substrata PVDF polymorphous (alpha or beta). At a particular time of the grafting process, the poly(AAc-Xmonomer) membranes detach from the substratum and continue their grafting in the solution. This method is useful to produce increased replicated membranes of the irradiated original surface.

An early-biomarker algorithm predicts lethal graft-versus-host disease and survival.

Science.gov (United States)

Hartwell, Matthew J; Özbek, Umut; Holler, Ernst; Renteria, Anne S; Major-Monfried, Hannah; Reddy, Pavan; Aziz, Mina; Hogan, William J; Ayuk, Francis; Efebera, Yvonne A; Hexner, Elizabeth O; Bunworasate, Udomsak; Qayed, Muna; Ordemann, Rainer; Wölfl, Matthias; Mielke, Stephan; Pawarode, Attaphol; Chen, Yi-Bin; Devine, Steven; Harris, Andrew C; Jagasia, Madan; Kitko, Carrie L; Litzow, Mark R; Kröger, Nicolaus; Locatelli, Franco; Morales, George; Nakamura, Ryotaro; Reshef, Ran; Rösler, Wolf; Weber, Daniela; Wudhikarn, Kitsada; Yanik, Gregory A; Levine, John E; Ferrara, James L M

2017-02-09

BACKGROUND. No laboratory test can predict the risk of nonrelapse mortality (NRM) or severe graft-versus-host disease (GVHD) after hematopoietic cellular transplantation (HCT) prior to the onset of GVHD symptoms. METHODS. Patient blood samples on day 7 after HCT were obtained from a multicenter set of 1,287 patients, and 620 samples were assigned to a training set. We measured the concentrations of 4 GVHD biomarkers (ST2, REG3α, TNFR1, and IL-2Rα) and used them to model 6-month NRM using rigorous cross-validation strategies to identify the best algorithm that defined 2 distinct risk groups. We then applied the final algorithm in an independent test set ( n = 309) and validation set ( n = 358). RESULTS. A 2-biomarker model using ST2 and REG3α concentrations identified patients with a cumulative incidence of 6-month NRM of 28% in the high-risk group and 7% in the low-risk group ( P < 0.001). The algorithm performed equally well in the test set (33% vs. 7%, P < 0.001) and the multicenter validation set (26% vs. 10%, P < 0.001). Sixteen percent, 17%, and 20% of patients were at high risk in the training, test, and validation sets, respectively. GVHD-related mortality was greater in high-risk patients (18% vs. 4%, P < 0.001), as was severe gastrointestinal GVHD (17% vs. 8%, P < 0.001). The same algorithm can be successfully adapted to define 3 distinct risk groups at GVHD onset. CONCLUSION. A biomarker algorithm based on a blood sample taken 7 days after HCT can consistently identify a group of patients at high risk for lethal GVHD and NRM. FUNDING. The National Cancer Institute, American Cancer Society, and the Doris Duke Charitable Foundation.

Ibrutinib for chronic graft-versus-host disease after failure of prior therapy.

Science.gov (United States)

Miklos, David; Cutler, Corey S; Arora, Mukta; Waller, Edmund K; Jagasia, Madan; Pusic, Iskra; Flowers, Mary E; Logan, Aaron C; Nakamura, Ryotaro; Blazar, Bruce R; Li, Yunfeng; Chang, Stephen; Lal, Indu; Dubovsky, Jason; James, Danelle F; Styles, Lori; Jaglowski, Samantha

2017-11-23

Chronic graft-versus-host disease (cGVHD) is a serious complication of allogeneic stem cell transplantation with few effective options available after failure of corticosteroids. B and T cells play a role in the pathophysiology of cGVHD. Ibrutinib inhibits Bruton tyrosine kinase in B cells and interleukin-2-inducible T-cell kinase in T cells. In preclinical models, ibrutinib reduced severity of cGVHD. This multicenter, open-label study evaluated the safety and efficacy of ibrutinib in patients with active cGVHD with inadequate response to corticosteroid-containing therapies. Forty-two patients who had failed 1 to 3 prior treatments received ibrutinib (420 mg) daily until cGVHD progression. The primary efficacy end point was cGVHD response based on 2005 National Institutes of Health criteria. At a median follow-up of 13.9 months, best overall response was 67%; 71% of responders showed a sustained response for ≥20 weeks. Responses were observed across involved organs evaluated. Most patients with multiple cGVHD organ involvement had a multiorgan response. Median corticosteroid dose in responders decreased from 0.29 mg/kg per day at baseline to 0.12 mg/kg per day at week 49; 5 responders discontinued corticosteroids. The most common adverse events were fatigue, diarrhea, muscle spasms, nausea, and bruising. Plasma levels of soluble factors associated with inflammation, fibrosis, and cGVHD significantly decreased over time with ibrutinib. Ibrutinib resulted in clinically meaningful responses with acceptable safety in patients with ≥1 prior treatments for cGVHD. Based on these results, ibrutinib was approved in the United States for treatment of adult patients with cGVHD after failure of 1 or more lines of systemic therapy. This trial was registered at www.clinicaltrials.gov as #NCT02195869. © 2017 by The American Society of Hematology.

New membranes obtained by grafted irradiated PVDF foils

Energy Technology Data Exchange (ETDEWEB)

Mazzei, R. [Unidad de Actividades Tecnologicas y Agropecuarias, Laboratorio de Polimeros, Comision Nacional de Energia Atomica, Buenos Aires (Argentina); Universidad Tecnologica Nacional Facultad Regional, Buenos Aires (Argentina); Garcia Bermudez, G. [Gerencia de Investigacion y Aplicaciones, Laboratorio Tandar, Comision Nacional de Energia Atomica, Buenos Aires (Argentina); Escuela de Ciencia y Tecnologia, Universidad Nacional de General San Martin, Buenos Aires (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas, Buenos Aires (Argentina); Camporotondi, D.E., E-mail: camporotondi@cae.cnea.gov.ar [Unidad de Actividades Tecnologicas y Agropecuarias, Laboratorio de Polimeros, Comision Nacional de Energia Atomica, Buenos Aires (Argentina); Arbeitman, C. [Gerencia de Investigacion y Aplicaciones, Laboratorio Tandar, Comision Nacional de Energia Atomica, Buenos Aires (Argentina); Consejo Nacional de Investigaciones Cientificas y Tecnicas, Buenos Aires (Argentina); and others

2012-09-15

The present work describes a new method to produce membranes of poly(Acrylic-acid-Xmonomer) using the grafting procedure. PVDF foils irradiated with Ar{sup +} beam with energies between 30 and 150 keV were employed as substratum. Different combinations of monomers in water solutions were used: acrylic acid (AAc); acrylic acid-glycidyl methacrylate (AAc-GMA); acrylic acid-styrene (AAc-S), acrylic acid-N-isopropyl acrylamide (AAc-NIPAAm) and acrylic acid-N-isopropyl acrylamide-glycidyl methacrylate (AAc-NIPAAm-GMA). A large percentage of grafting results for specific values of: ion fluence and energy, AAc and sulfuric acid concentration, and different substrata PVDF polymorphous (alpha or beta). At a particular time of the grafting process, the poly(AAc-Xmonomer) membranes detach from the substratum and continue their grafting in the solution. This method is useful to produce increased replicated membranes of the irradiated original surface.

Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

International Nuclear Information System (INIS)

Guo, Yixian; Zhang, Lanfang; Wan, Suigui; Sun, Xuejing; Wu, Yongxia; Yu, Xue-Zhong; Xia, Chang-Qing

2014-01-01

Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT

Tolerance induction between two different strains of parental mice prevents graft-versus-host disease in haploidentical hematopoietic stem cell transplantation to F1 mice

Energy Technology Data Exchange (ETDEWEB)

Guo, Yixian; Zhang, Lanfang; Wan, Suigui; Sun, Xuejing; Wu, Yongxia [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Yu, Xue-Zhong [Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425 (United States); Xia, Chang-Qing, E-mail: cqx65@yahoo.com [Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

2014-04-18

Highlights: • Injection of UVB-irradiated iDCs induces alloantigen tolerance. • This alloantigen tolerance may be associated regulatory T cell induction. • Tolerant mice serve as bone marrow donors reduces GVHD to their F1 recipients in allo-HSCT. • Tolerance is maintained in F1 recipients for long time post HSCT. - Abstract: Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) has been employed worldwide in recent years and led to favorable outcome in a group of patients who do not have human leukocyte antigen (HLA)-matched donors. However, the high incidence of severe graft-versus-host disease (GVHD) is a major problem for Haplo-HSCT. In the current study, we performed a proof of concept mouse study to test whether induction of allogeneic tolerance between two different parental strains was able to attenuate GVHD in Haplo-HSCT to the F1 mice. We induced alloantigen tolerance in C3H mice (H-2k) using ultraviolet B (UVB) irradiated immature dendritic cells (iDCs) derived from the cultures of Balb/c bone marrow cells. Then, we performed Haplo-HSCT using tolerant C3H mice as donors to F1 mice (C3H × Balb/c). The results demonstrated that this approach markedly reduced GVHD-associated death and significantly prolonged the survival of recipient mice in contrast to the groups with donors (C3H mice) that received infusion of non-UVB-irradiated DCs. Further studies showed that there were enhanced Tregs in the tolerant mice and alloantigen-specific T cell response was skewed to more IL-10-producing T cells, suggesting that these regulatory T cells might have contributed to the attenuation of GVHD. This study suggests that it is a feasible approach to preventing GVHD in Haplo-HSCT in children by pre-induction of alloantigen tolerance between the two parents. This concept may also lead to more opportunities in cell-based immunotherapy for GVHD post Haplo-HSCT.

HY-Specific Induced Regulatory T Cells Display High Specificity and Efficacy in the Prevention of Acute Graft-versus-Host Disease.

Science.gov (United States)

Li, Jun; Heinrichs, Jessica; Haarberg, Kelley; Semple, Kenrick; Veerapathran, Anandharaman; Liu, Chen; Anasetti, Claudio; Yu, Xue-Zhong

2015-07-15

Naturally derived regulatory T cells (Tregs) may prevent graft-versus-host disease (GVHD) while preserving graft-versus-leukemia (GVL) activity. However, clinical application of naturally derived regulatory T cells has been severely hampered by their scarce availability and nonselectivity. To overcome these limitations, we took alternative approaches to generate Ag-specific induced Tregs (iTregs) and tested their efficacy and selectivity in the prevention of GVHD in preclinical models of bone marrow transplantation. We selected HY as a target Ag because it is a naturally processed, ubiquitously expressed minor histocompatibility Ag (miHAg) with a proven role in GVHD and GVL effect. We generated HY-specific iTregs (HY-iTregs) from resting CD4 T cells derived from TCR transgenic mice, in which CD4 cells specifically recognize HY peptide. We found that HY-iTregs were highly effective in preventing GVHD in male (HY(+)) but not female (HY(-)) recipients using MHC II-mismatched, parent→F1, and miHAg-mismatched murine bone marrow transplantation models. Interestingly, the expression of target Ag (HY) on the hematopoietic or nonhematopoietic compartment alone was sufficient for iTregs to prevent GVHD. Furthermore, treatment with HY-iTregs still preserved the GVL effect even against pre-established leukemia. We found that HY-iTregs were more stable in male than in female recipients. Furthermore, HY-iTregs expanded extensively in male but not female recipients, which in turn significantly reduced donor effector T cell expansion, activation, and migration into GVHD target organs, resulting in effective prevention of GVHD. This study demonstrates that iTregs specific for HY miHAgs are highly effective in controlling GVHD in an Ag-dependent manner while sparing the GVL effect. Copyright © 2015 by The American Association of Immunologists, Inc.

A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant.

Science.gov (United States)

Ronald, John A; Kim, Byung-Su; Gowrishankar, Gayatri; Namavari, Mohammad; Alam, Israt S; D'Souza, Aloma; Nishikii, Hidekazu; Chuang, Hui-Yen; Ilovich, Ohad; Lin, Chih-Feng; Reeves, Robert; Shuhendler, Adam; Hoehne, Aileen; Chan, Carmel T; Baker, Jeanette; Yaghoubi, Shahriar S; VanBrocklin, Henry F; Hawkins, Randall; Franc, Benjamin L; Jivan, Salma; Slater, James B; Verdin, Emily F; Gao, Kenneth T; Benjamin, Jonathan; Negrin, Robert; Gambhir, Sanjiv Sam

2017-06-01

A major barrier to successful use of allogeneic hematopoietic cell transplantation is acute graft-versus-host disease (aGVHD), a devastating condition that arises when donor T cells attack host tissues. With current technologies, aGVHD diagnosis is typically made after end-organ injury and often requires invasive tests and tissue biopsies. This affects patient prognosis as treatments are dramatically less effective at late disease stages. Here, we show that a novel PET radiotracer, 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine ([18F]F-AraG), targeted toward two salvage kinase pathways preferentially accumulates in activated primary T cells. [18F]F-AraG PET imaging of a murine aGVHD model enabled visualization of secondary lymphoid organs harboring activated donor T cells prior to clinical symptoms. Tracer biodistribution in healthy humans showed favorable kinetics. This new PET strategy has great potential for early aGVHD diagnosis, enabling timely treatments and improved patient outcomes. [18F]F-AraG may be useful for imaging activated T cells in various biomedical applications. Cancer Res; 77(11); 2893-902. ©2017 AACR . ©2017 American Association for Cancer Research.

Study of maleic anhydride and styrene grafted onto polypropylene induced by UV irradiation

International Nuclear Information System (INIS)

Li Zhenzhong; He Wei; Guo Hongjun; Zhang Wenxiong; Ma Yalin

2007-01-01

Maleic anhydride (MAH) and styrene (St) grafted onto polypropylene (PP) were prepared by UV irradiation. Effects of the irradiation time, monomer and initiator content on the grafting rate and melt flow rate (MFR) were studied. The results show that the optimal duration of UV irradiation is 30s. The grafting rate increases with initiator content when initiator content less than 0.6 phr, the MFR value of grafted PP reaches the highest point when benzophenone (BP) content is 0.4 phr. The content of MAH and St have an effect on the grafting rate and MFR value of the grafted PP, and the optimal contents of monomer is 4 phr. The existence of St as a comonomer reduces apparently the MFR value of grafted PP greatly. Grafted PP present significant changes in crystallization and fusion peaks, indicating differences in crystal size and formation after grafting reaction. (authors)

Albumin grafting on biomaterial surfaces using gamma-irradiation

International Nuclear Information System (INIS)

Kamath, K.R.

1993-01-01

Surface modification has been used extensively in various fields to introduce desirable surface properties without affecting the bulk properties of the material. In the area of biomaterials, the approach of surface modification offers an effective alternative to the synthesis of new biomaterials. The specific objective of this study was to modify different biomaterial surfaces by albumin grafting to improve their blood compatibility. The modified surfaces were characterized for surface-induced platelet activation and thrombus formation. This behavior was correlated with the conditions used for grafting. In particular, albumin was functionalized to introduce pendant double bonds into the molecule. The functionalized albumin was covalently attached to various surfaces, such as dimethyldichlorosilane-coated glass, polypropylene, polycarbonate, poly(vinyl chloride), and polyethylene by gamma-irradiation. Platelet adhesion and activation on these surfaces was examined using video microscopy and scanning electron microscopy. The extent of grafting was found to be dependent on the albumin concentration used for adsorption and the gamma-irradiation time. Release of the grafted albumin during exposure to blood was minimal. The albumin-grafted fibers maintained their thromboresistant properties even after storage at elevated temperatures for prolonged time periods. Finally, the approach was used to graft albumin on the PLEXUS Adult Hollow Fiber Oxygenators (Shiley). The blood compatibility of the grafted oxygenators improved significantly when compared to controls

Prevention of lethal murine graft versus host disease by treatment of donor cells with L-leucyl-L-leucine methyl ester

International Nuclear Information System (INIS)

Charley, M.; Thiele, D.L.; Bennett, M.; Lipsky, P.E.

1986-01-01

Graft vs. host disease (GVHD) remains one of the main problems associated with bone marrow transplantation. The current studies were undertaken to determine whether treatment of the donor inoculum with the anticytotoxic cell compound L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) would alter the development of GVHD in a murine model. Irradiated recipient mice transplanted with a mixture of control bone marrow and spleen cells from naive semiallogeneic donors died rapidly from GVHD, whereas the recipients of cells incubated with 250 microM Leu-Leu-OMe all survived. In addition, Leu-Leu-OMe treatment of cells obtained from donors immunized against host alloantigens resulted in significantly prolonged survival. Phenotypic characterization of spleen cells from the various groups of mice that had received Leu-Leu-OMe-treated cells and survived consistently revealed the donor phenotype. Treatment of marrow cells with 250 microM Leu-Leu-OMe appeared to have no adverse effects on stem cell function. Erythropoiesis was undiminished, as assayed by splenic 5-iodo-2'-deoxyuridine- 125 I uptake. Moreover, granulocytic and megakaryocytic regeneration were histologically equivalent in the spleens of recipients of control or Leu-Leu-OMe-treated cells. Treatment of the donor inoculum with Leu-Leu-OMe thus prevents GVHD in this murine strain combination with no apparent stem cell toxicity

Performance of a new clinical grading system for chronic graft-versus-host disease: a multicenter study.

Science.gov (United States)

Akpek, Gorgun; Lee, Stephanie J; Flowers, Mary E; Pavletic, Steven Z; Arora, Mukta; Lee, Shing; Piantadosi, Steven; Guthrie, Katherine A; Lynch, James C; Takatu, Alessandra; Horowitz, Mary M; Antin, Joseph H; Weisdorf, Daniel J; Martin, Paul J; Vogelsang, Georgia B

2003-08-01

We recently reported 3 risk factors (RFs) at diagnosis of chronic graft-versus-host disease (cGVHD) that were significantly associated with increased nonrelapse mortality. These included extensive skin involvement (ESI), thrombocytopenia (TP), and progressive type of onset (PTO). The hazard ratio (HR) for mortality of the patients with prognostic score (PS) between 0 and 2 (intermediate-risk; 1 RF) compared to those with PS 0 (favorable-risk; 0 RF) was 3.7 (95% CI, 1.4, 9.3); the HR for patients with PS equal to or more than 2 (high-risk; > 1 RF) compared with intermediate-risk group was 6.9 (3.8, 12.4). A rare presentation of TP and PTO without ESI yielded a PS of 1.8 (intermediate-risk). This paper reports the performance of the prognostic model and the individual RFs using data from an additional 1105 patients from University of Nebraska (n = 60), International Bone Marrow Transplantation Registry (n = 708), Fred Hutchinson Cancer Research Center (n = 188), and University of Minnesota (n = 149). The extent of skin involvement was quantified in 3 cohorts using the available data collected in different formats before the analysis. Although the HR for mortality of the patients in the intermediate-risk group versus those in the favorable-risk group ranged from 2.3 to 8.9 across the centers, it was between 1.6 to 6.9 for patients in the high-risk group versus those in the intermediate-risk group. Although TP itself was uniformly associated with increased risk of mortality across all test samples, ESI and PTO showed statistically significant associations with mortality in 1 and 2 cohorts, respectively. In conclusion, the model was predictive of cGVHD-specific survival, but the mortality hazard associated with ESI was lower in each of these test samples compared with the learning sample. Although the new clinical grading based on the model is promising because of its utility across multiple independent data sets, prospective validation is needed.

Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. II. Renal allographs

International Nuclear Information System (INIS)

Myburgh, J.A.; Smit, J.A.; Hill, R.R.H.; Browde, S.

1980-01-01

A modified regimen of fractionated total lymphoid irradiation and allogeneic bone marrow (BM) injection in chacma baboons produced transplantation tolerance for allografted kidneys from the BM donors, and substantial chimerism without evidence of graft-versus-host disease. Increasing the dose of nucleated BM cells injected 4-fold over that used in liver transplantation resulted consistently in normal graft function in the early weeks after transplantation. Bone marrow injection and challenge with renal allografts could be delayed for at least 3 weeks after completion of irradiation. If it can be shown that this period can be extended even further, the protocols will be relevant to the circumstances of clinical cadaveric renal transplantation

Prolongation of rat islet allograft survival by direct ultraviolet irradiation of the graft

International Nuclear Information System (INIS)

Lau, H.; Reemtsma, K.; Hardy, M.A.

1984-01-01

Ultraviolet irradiation of rat dendritic cells completely abrogated their allostimulatory capacity in a mixed lymphocyte reaction. Rat islets of Langerhans similarly irradiated remained hormonally functional when transplanted into syngeneic diabetic rats. Allogeneic transplantation across a major histocompatibility barrier of islets initially treated in vitro with ultraviolet irradiation resulted in prolonged allograft survival without the use of any immunosuppressive agents

The effect of γ-irradiation on changes of blood chemistry in RC-MAP after irradiation

International Nuclear Information System (INIS)

Hirose, Tetsuhito; Katayama, Norifumi; Okamoto, Yukiharu; Tsuda, Tadaaki; Ota, Kiichiro; Nishioka, Shingo; Tsumura, Michiyo; Yukawa, Mariko

1997-01-01

Irradiation to transfused blood is obligated to prevent from post transfusion graft-versus-host disease (PT-GVHD) by inactivation of lymphocytes. The rule of irradiated dose was not determined, it's dose being ranged from 15 to 50 Gy, but it's dose was done by each institute. We investigated an adequate dose of irradiation to blood on effects of plasma Na, potassium (K), Chloride (Cl), LDH, GOT, BUN and total protein (T.P) after irradiation of transfused blood. By comparison of plasma Na and K in non-irradiated blood, plasma K was increased and decreased in a parallelism of period of stored irradiated blood, two days after it's irradiation. Effects of Na and K levels were dose dependent. LDH level was increased in a time-dependency, but not by it's dose plasma Cl, LDH, GOT, BUN and T.P levels were not influenced. Our results indicated that the mechanism of RBC permeability after irradiation seemed to be inactivated Na-K ATPase activity in RBC cell membrane. (author)

Post irradiation effects on the graft of poly(tetrafluoroethylene-co-perfluoropropyl vinyl ether) (PFA) films

International Nuclear Information System (INIS)

Geraldes, Adriana N.; Zen, Heloisa A.; Ribeiro, Geise; Ferreira, Henrique P.; Souza, Camila P.; Parra, Duclerc F.; Lugao, Ademar B.

2009-01-01

Radiation induced grafting of monomers into fluorinated polymers was designed as an alternative route to polymer modification. In this work, grafting of styrene onto poly(tetrafluoroethylene-co-perfluoropropyl vinyl ether) (PFA) was studied. Radiation-induced grafting of styrene onto PFA films was investigated after simultaneous irradiation (in post-irradiation condition) using a 60 Co source. The films of PFA were irradiated at 20, 40, 80 and 100 kGy doses at room temperature and chemical changes were monitored after contact with styrene for grafting. The post-irradiation time was established between 7 and 28 days when films of PFA were maintained in styrene/toluene 1:1 v/v solution at room temperature. After these periods the grafting degrees were evaluated in the samples. The highest degree of grafting was achieved after 14 days. Chemical modifications were evaluated by infrared spectroscopic analysis (FTIR), thermogravimetry (TG), differential scanning calorimetry (DSC) and also by scanning electron microscopy (SEM). The degree of grafting (DOG) was determined gravimetrically. The results showed that irradiated PFA films at 100 kGy exhibited higher grafting degree. Surface analysis by SEM technique of irradiated, grafted and original films have presented an homogeneous surface. (author)

Sequential studies of cell inhibition of host fibroblasts in 51 patients given HLA-identical marrow grafts

International Nuclear Information System (INIS)

Tsoi, M.-S.; Storb, R.; Weiden, P.; Santos, E.; Kopecky, K.J.; Thomas, E.D.

1982-01-01

Thirty-four patients with leukemia, two with lymphoma and 15 with aplastic anemia, were studied sequentially between 33 and 666 days after treatment with high-dose cyclophosphamide and/or total body irradiation and marrow transplantation from HLA-identical siblings. Peripheral blood mononuclear cells from patients and normals were tested for cell inhibition (CI) of cultured skin fibroblasts from patients and donors or unrelated individuals using the microcytotoxicity assay. In addition, blocking of Cl by factors in patient serum was studied. Twenty patients were tested three or more times during the first year, 15 patients were studied twice and 16 patients once. Results showed that during the first 2 mo postgrafting, mononuclear cells from 45% of the patients had neither Cl nor blocking activities, 50% had Cl and serum blocking, and 5% had Cl without blocking. As time after transplatation elapsed, the percentage of patients without Cl gradually increased, whereas the percentage of patients with Cl with or without blocking decreased. At the end of 1 yr, 89% of the patients showed neither Cl nor blocking compared with 11% who showed Cl and blocking. This trend was significant (p < 0.005). The results were in agreement with our previus conclusion that serum-blocking factors were not important in the maintenance of the stable chimeric state. Early after grafting, there was a suggestive correlation (p < 0.08) between the in vitro finding of Cl of host fibroblasts by chimeric cells and the in vivo finding of acute graft-vs-host disease. However, there was no evidence that presence or absence of serum-blocking factors early after grafting was correlated with presence or absence of graft-vs-host disease

Beneficial Role of Low-Dose Antithymocyte Globulin in Unrelated Stem Cell Transplantation for Adult Patients with Acquired Severe Aplastic Anemia: Reduction of Graft-versus-Host Disease and Improvement of Graft-versus-Host Disease-Free, Failure-Free Survival Rate.

Science.gov (United States)

Park, Sung-Soo; Kwak, Dae Hun; Jeon, Young-Woo; Yoon, Jae-Ho; Lee, Sung-Eun; Cho, Byung-Sik; Eom, Ki-Seong; Kim, Yoo-Jin; Kim, Hee-Je; Lee, Seok; Min, Chang-Ki; Cho, Seok-Goo; Kim, Dong-Wook; Min, Woo-Sung; Lee, Jong Wook

2017-09-01

Stem cell transplantation (SCT) from an unrelated donor (URD) is often considered in patients with severe aplastic anemia (SAA) whom immunosuppressive therapy failed and matched sibling donor is not available. To reduce the incidence of graft-versus-host disease (GVHD) in URD SCT, introducting antithymocyte globulin (ATG) into the conditioning regimen has been proposed. Although ATG was shown to play a role in reducing GVHD in a cohort with diverse hematologic diseases, its role in SAA remains uncertain. The aim of this study was to determine the efficacy and toxicity of ATG in URD SCT for adult patients with SAA. We investigated 83 adult patients with SAA who underwent URD SCT between 2003 and 2014. The transplantation strategy consisted of total body irradiation (total 800 cGy) and cyclophosphamide (total 100 mg/kg to 120 mg/kg), followed by tacrolimus and a short-term methotrexate. We divided patients into 2 groups: group 1 (n = 25), which received HLA-matched (8/8) bone marrow (BM) without ATG, and group 2 (n = 58), which received SCT from either an HLA-mismatched donor or peripheral blood (PB). Thereafter, group 2 was subdivided according to ATG use into group 2A (without ATG, n = 26), which served as a historical cohort, and group 2B (with ATG, n = 32). Rabbit ATG (Thymoglobulin; Genzyme-Sanofi, Lyon, France) was used in group 2B at a dose of 2.5 mg/kg. The median age of all patients was 30 years (range, 17 to 59 years). The incidence of GVHD was significantly lower in group 2B than group 2A, as demonstrated by the rate of grade II to IV acute GVHD at day 100 (31.2% versus 61.5%, P = .003) and the rate of chronic GVHD at 3 years (21.9% versus 65.4%, P = .002). The overall survival rates of the 3 groups were similar. However, GVHD-free, failure-free survival (GFFS) was significantly higher in group 2B than group 2A (P = .034). A multivariable model identified use of ATG as an independent factor affecting grades II to IV acute

Reexamination of the role of Lyt-2-positive T cells in murine skin graft rejection

International Nuclear Information System (INIS)

LeFrancois, L.; Bevan, M.J.

1984-01-01

The authors have investigated which T cell subclass defined by cytolysis with monoclonal anti-Lyt-1.2 and anti-Lyt-2.2 antibodies is required to adoptively transfer the ability to reject skin grafts. B6.Thy-1.1 spleen cells immune to graft antigens were fractionated with antibody plus C' and transferred to adult thymectomized, irradiated, bone marrow-reconstituted (ATXBM) B6.Thy-1.2 hosts that were simultaneously grafted with BALB.B skin. The authors found that when the ATXBM hosts were used 6 wk after irradiation and marrow reconstitution, both Lyt-1-depleted and Lyt-2-depleted immune spleen cells could transfer the ability to promptly reject skin grafts. However, such ATXBM recipients of Lyt-2-depleted cells that had rejected skin grafts were found to contain graft-specific CTL that were largely of host (B6.Thy-1.2) origin. When ATXBM hosts were used for the experiment 1 wk after irradiation and marrow reconstitution, no host-derived graft-specific CTL could be detected. However, graft rejection occurred in recipients of anti-Lyt-1- or anti-Lyt-2 plus C'-treated immune cells and specific CTL were generated from spleen cells of both groups. Thus, in the absence of a host-derived response, adoptively transferred immune Lyt-2+ cells, either resistant to, or that escaped from, antibody plus C' treatment, are able to expand in response to the antigenic stimulus provided by the graft. A more complete elimination of specific T cell subclasses is therefore needed to assess the relative contribution of a particular subset to the graft rejection process

Grafting of polymer onto silica surface in the presence of γ-ray irradiated silica

International Nuclear Information System (INIS)

Tsuchida, A.; Yokoyama, R.; Takami, M.; Chen, J.; Ohta, M.; Tsubokawa, N.

2002-01-01

Complete text of publication follows. We have reported the graft polymerization of vinyl monomers initiated by surface radicals formed by the decomposition of azo and peroxide groups previously introduced onto the surface. In addition, the grafting of polymers onto carbon black has been reported by the reaction of polymer radicals with the surface. On the other hand, it is well known that the relatively stable radicals are generated on the surface by the γ-ray irradiation. In this paper, the grafting of polystyrene onto silica surface during the thermal polymerization of styrene in the presence of γ-ray irradiated silica, grafting mechanism and thermal stability of grafted polymer will be discussed. The grafting of polymers onto silica surface by irradiation of polymer-adsorbed silica was also investigated. Silica obtained from Mitsubishi Chemical Co., Japan was used after pulverization: the particle size was 0.037-0.088 mm. Irradiation was performed in Cs-137 source at room temperature. The silica was irradiated at 50 Gy with dose rate of 3.463 Gy/min. Into a polymerization tube, styrene and irradiated silica was charged and the polymerization was carried out under argon under stirring. The percentage of polystyrene grafting was determined from weight loss when polystyrene-grafted silica was heated at 600 deg C by a thermal analyzer. Untreated silica did not affect the thermal polymerization of styrene. On the contrary, the thermal polymerization of styrene was remarkably retarded in the presence of the irradiated silica at 60 deg C. Similar tendency was reported during the polymerization of vinyl monomers in the presence of carbon black. In the initial stage of the polymerization in the presence of the irradiated silica below 50 deg C, the polymerization was accelerated. During the polymerization in the presence of irradiated silica, polystyrene was grafted onto the surface: the percentage of grafting was 5-11%. The amount of polystyrene grafted onto silica

Evaluation of absorbed dose-distribution in the X-ray or gamma-irradiator for blood products

International Nuclear Information System (INIS)

Moriyama, Satoshi; Kurihara, Katsuhiko; Yokokawa, Nobuhiko; Satake, Masahiro; Juji, Takeo

2001-01-01

Irradiation of blood products abrogates the proliferation of lymphocytes present in cellular component, which is currently the only accepted methodology to prevent transfusion-associated graft versus host disease (TA-GVHD). A range of irradiation dose levels between 15 Gy and 50 Gy is being used, but the majority of facilities are employing 15 Gy. It should, however, be recognized that the delivered dose in the instrument canister might differ from the actual dose absorbed by the blood bag. This study have evaluated the actual dose distribution under practical conditions where a container was loaded with blood products or water bags, or filled with distilled water. This approach provides data that the maximum attenuation occurred when the container was completely filled with a blood-compatible material. Thus, an error of approximately 20 percent should be considered in the dose measured in the in-air condition. A dose calibration in an in-air condition may lead to substantial underexposure of the blood products. A dose distribution study using adequately prearranged exposure period verified that the absorbed dose of 15 Gy was attained at any point in the container for both linear accelerator and gamma-irradiator. The maximal difference in the absorbed dose between measured points was 1.5- and 1.6-fold for linear accelerator and gamma-irradiator, respectively. In conclusion, using blood-compatible materials, a careful dose calibration study should be employed in which the absorbed dose of 15 Gy is obtained at the point where the lowest dose could be expected. (author)

Postoperative irradiation after reconstructive surgery: comparative study of radiosensitivity between free-skin grafts and skin flaps

International Nuclear Information System (INIS)

Sumi, Y.; Ueda, M.; Kaneda, T.; Oka, T.; Torii, S.; Sakuma, S.

1984-01-01

Radiation effects after reconstructive surgery (free-skin grafts and skin flaps) were studied in the rat, and the optimum time for irradiation was determined. The radiosensitivity of both free-skin grafts and skin flaps showed the same trend depending on time of irradiation after operation. The grafts or flaps irradiated in the hypervascular stage showed severe reactions to irradiation, whereas those irradiated in the hypovascular stage showed milder reactions in gross and microangiographic observation. Vascular damage should be given primary consideration when deciding the proper time for irradiation after reconstructive surgery. In general, free-skin grafts showed more severe reactions than skin flaps, especially in the grafts irradiated in the early stage after operation. The experimental results of this study cannot be readily transferred to a clinical setting, but they suggest that postoperative irradiation could be begun 3 to 4 weeks after operation with respect to graft or flap survival, and the results of the clinical cases almost coincide with these experimental results

Allosuppression of B cells in vitro by graft-vs.-host reaction-derived T cells is caused by cytotoxic T lymphocytes

NARCIS (Netherlands)

Rozendaal, L.; Pals, S. T.; Schilham, M.; Melief, C. J.; Gleichmann, E.

1989-01-01

An acute graft-vs.-host reaction (GVHR) was induced by i.v. injection of 10(8) lymphoid cells from C57BL/10 (B10) donors (H-2b/b) into adult non-irradiated (B10 X DBA/2)F1 mice (H-2b/d). Previous experiments have established that spleen cells obtained from such GVHF1 mice suppress the primary

Allograft tolerance in pigs after fractionated lymphoid irradiation. I. Skin grafts after partial lateral irradiation and bone marrow cell grafting

International Nuclear Information System (INIS)

Vaiman, M.; Daburon, F.; Remy, J.; Villiers, P.A.; de Riberolles, C.; Lecompte, Y.; Mahouy, G.; Fradelizi, D.

1981-01-01

Experiments with pigs have been performed to establish bone marrow chimerism and skin graft tolerance between SLA genotyped animals. Recipients were conditioned by means of fractionated partial irradiation from lateral cobalt sources (partial lateral irradiation (PLI)). The head, neck, and lungs were protected with lead, the rest of the body being irradiated including the thymus, the majority of lymphoid organs with spleen, and most of the bone marrow sites

An analysis of facial nerve function in irradiated and unirradiated facial nerve grafts

International Nuclear Information System (INIS)

Brown, Paul D.; Eshleman, Jeffrey S.; Foote, Robert L.; Strome, Scott E.

2000-01-01

Purpose: The effect of high-dose radiation therapy on facial nerve grafts is controversial. Some authors believe radiotherapy is so detrimental to the outcome of facial nerve graft function that dynamic or static slings should be performed instead of facial nerve grafts in all patients who are to receive postoperative radiation therapy. Unfortunately, the facial function achieved with dynamic and static slings is almost always inferior to that after facial nerve grafts. In this retrospective study, we compared facial nerve function in irradiated and unirradiated nerve grafts. Methods and Materials: The medical records of 818 patients with neoplasms involving the parotid gland who received treatment between 1974 and 1997 were reviewed, of whom 66 underwent facial nerve grafting. Fourteen patients who died or had a recurrence less than a year after their facial nerve graft were excluded. The median follow-up for the remaining 52 patients was 10.6 years. Cable nerve grafts were performed in 50 patients and direct anastomoses of the facial nerve in two. Facial nerve function was scored by means of the House-Brackmann (H-B) facial grading system. Twenty-eight of the 52 patients received postoperative radiotherapy. The median time from nerve grafting to start of radiotherapy was 5.1 weeks. The median and mean doses of radiation were 6000 and 6033 cGy, respectively, for the irradiated grafts. One patient received preoperative radiotherapy to a total dose of 5000 cGy in 25 fractions and underwent surgery 1 month after the completion of radiotherapy. This patient was placed, by convention, in the irradiated facial nerve graft cohort. Results: Potential prognostic factors for facial nerve function such as age, gender, extent of surgery at the time of nerve grafting, preoperative facial nerve palsy, duration of preoperative palsy if present, or number of previous operations in the parotid bed were relatively well balanced between irradiated and unirradiated patients. However

Radiosensitivity of T and B lymphocytes. V. Effects of whole-body irradiation on numbers of recirculating T cells and sensitization to primary skin grafts in mice

International Nuclear Information System (INIS)

Anderson, R.E.; Williams, W.L.

1977-01-01

Whole-body exposure of mice to 50, 100, 300, or 500 rads results in an acute dose-related decrease in the number of viable recirculating T cells. The magnitude of this decrement becomes more pronounced with the passage of time. The dose-response relationship over this range of dosages appears to consist of three components: a steep drop between 0 and 50 rads, a plateau between 50 and 500 rads, and a second drop between 300 and 500 rads. The residual radioresistant cells are able to recognize a histoincompatible skin graft during the initial 5 days after irradiation. Low to moderate doses (50 to 300 rads) abrogate the partial tolerance noted in nonirradiated recipients exposed to the skin graft for 5 days and then regrafted from the same donor source 25 days after complete removal of the primary graft. A large (500 rads) dose results in prolonged graft survival in comparison with the nonirradiated group. It is suggested that the subpopulation of recirculating T cells which develops partial tolerance during a 5-day exposure to a homograft is more radiosensitive than the effector subpopulation which is involved in graft rejection

Influences of irradiation on the anastomotic sites of artificial graft

International Nuclear Information System (INIS)

Ogawa, Junichi; Inoue, Hiroshi; Koide, Shirosaku; Kawada, Shimei; Shotsu, Akira

1989-01-01

To examine the acute influences of irradiation on the anastomotic sites of EPTFE vascular grafts, experimental study was performed using canine dogs. After replacement of superior vena cava and bilateral femoral arteries with EPTFE grafts, a total of 20 to 100 Gy doses were given at the anastomotic sites of superior vena cava and right femoral artery. There were no degradation of grafts themselves or rupture in the anastomoses at cumulative anastomotic sites of superior vena cava, stenoses and/or overgrowth of granulation tissues were observed, although at those of right femoral artery, no remarkable differences were observed between dogs which received irradiation and those which did not receive. (author)

Preparation of vinyl acetate grafted natural rubber by irradiation method

Energy Technology Data Exchange (ETDEWEB)

Porntrairat, A.; Pattamaprom, C. [Center of Excellence on Natural Rubber Technology, Department of Chemical Engineering, Faculty of Engineering, Thammasat University, Pathumthani 12120 (Thailand)

2016-03-09

Improvement in properties of natural rubber could be done by several methods. In this research, gamma radiation technique, which is simple, accurate, easy to control and clean, was applied to enhance the properties of natural rubber (NR) in latex state. The purpose of this research is to study the appropriate condition for preparing grafted natural rubber latex by using irradiation method. Vinyl acetate monomers (VAc) were grafted onto natural rubber latex (NR-g-PVAc) at 0-10 kGys by gamma radiation from Cobalt-60 source at room temperature. Physical properties of grafted natural rubber such as chloroform number, swelling ratio and gel content were measured. The VAc content of NR-g-PVAc was investigated by titration and visualized by FTIR spectroscopy. The FTIR spectra of NR-g-PVAc prepared at 0-10 kGys showed characteristic peaks of the vinyl acetate confirming that VAc could be grafted onto natural rubber molecular chains effectively under appropriate irradiation conditions. From the result, radiation grafting was found to be a useful technique for grafting of vinyl acetate onto natural rubber.

Total lymphoid irradiation

International Nuclear Information System (INIS)

Sutherland, D.E.; Ferguson, R.M.; Simmons, R.L.; Kim, T.H.; Slavin, S.; Najarian, J.S.

1983-01-01

Total lymphoid irradiation by itself can produce sufficient immunosuppression to prolong the survival of a variety of organ allografts in experimental animals. The degree of prolongation is dose-dependent and is limited by the toxicity that occurs with higher doses. Total lymphoid irradiation is more effective before transplantation than after, but when used after transplantation can be combined with pharmacologic immunosuppression to achieve a positive effect. In some animal models, total lymphoid irradiation induces an environment in which fully allogeneic bone marrow will engraft and induce permanent chimerism in the recipients who are then tolerant to organ allografts from the donor strain. If total lymphoid irradiation is ever to have clinical applicability on a large scale, it would seem that it would have to be under circumstances in which tolerance can be induced. However, in some animal models graft-versus-host disease occurs following bone marrow transplantation, and methods to obviate its occurrence probably will be needed if this approach is to be applied clinically. In recent years, patient and graft survival rates in renal allograft recipients treated with conventional immunosuppression have improved considerably, and thus the impetus to utilize total lymphoid irradiation for its immunosuppressive effect alone is less compelling. The future of total lymphoid irradiation probably lies in devising protocols in which maintenance immunosuppression can be eliminated, or nearly eliminated, altogether. Such protocols are effective in rodents. Whether they can be applied to clinical transplantation remains to be seen

Effects of Thy-1+ cell depletion on the capacity of donor lymphoid cells to induce tolerance across an entire MHC disparity in sublethally irradiated adult hosts

International Nuclear Information System (INIS)

Pierce, G.E.; Watts, L.M.

1989-01-01

Thy-1+ cell depletion with anti-Thy-1.2 mAb and complement markedly reduced the capacity of C57BL/6J, H-2b bone marrow to establish mixed lymphoid chimerism and induce tolerance to C57BL/6J skin grafts across an entire MHC disparity in BALB/c, H-2d hosts conditioned with sublethal, fractionated 7.5 Gy total-body irradiation. In this model tolerance can be transferred to secondary irradiated BALB/c hosts only by cells of C57BL/6J donor, not host, genotype isolated from the spleens of tolerant hosts. Thy-1+ cell depletion abolished the capacity of C57BL/6J donor cells from tolerant BALB/c host spleens to transfer tolerance. The capacity of semiallogeneic BALB/c x C57BL/6J F1, H-2d/b donor BM and spleen cells to induce chimerism and tolerance to C57BL/6J skin grafts in BALB/c parental hosts was also reduced by Thy-1+ cell depletion. Thus the requirement for donor Thy-1+ cells cannot be explained simply on the basis of alloaggression. It is unlikely that the requisite Thy-1+ cells are nonspecific suppressor cells: Thy-1+ cell depletion had no effect on the slight but significant prolongation of third-party C3H/HeJ, H-2k skin grafts in irradiated BALB/c hosts injected with allogeneic C57BL/6J or semiallogeneic BALB/c x C57BL/6J F1 BM compared to irradiated controls injected with medium only. Furthermore, injections of semiallogeneic F1 spleen cells had no significant effect on the survival of the third-party grafts, although these cells were fully capable of inducing tolerance, and their capacity to induce tolerance was significantly reduced by Thy-1+ cell depletion. The requirement for a specific population of lymphoid cells, i.e. Thy-1+, remains unexplained but suggests that donor cells might play a role in the induction or maintenance of tolerance in this model other than merely providing a circulating source of donor antigens

Functional clonal deletion versus active suppression in transplantation tolerance induced by total-lymphoid irradiation

International Nuclear Information System (INIS)

Morecki, S.; Leshem, B.; Weigensberg, M.; Bar, S.; Slavin, S.

1985-01-01

Transplantation tolerance and stable chimerism were established in adult mice conditioned with a short course of total-lymphoid irradiation (TLI) followed by infusion of 30 X 10(6) allogeneic bone marrow cells. Spleen cells of tolerant mice could not exert a proliferative or cytotoxic response against host-type cells in vitro and were unable to induce graft-versus-host reaction in secondary host-type recipients. The degree of suppression assessed by coculturing tolerant splenocytes in vitro in the one-way mixed lymphocyte reaction was quite variable--and, in some cases, was not at all demonstrable, although tolerance was clearly maintained. Suppression, when apparent, could not be ascribed to T lymphocytes. Suppressor cells were found to bind soybean agglutinin and could be separated from the nonsuppressive cells by means of this lectin. Dissociation of the suppressive population (SBA+ cells) from that which is normally alloreactive (SBA- cells) resulted in a suppressor cell-depleted fraction that was still unable to respond to host-type cells but regained reactivity to unrelated cells. Limiting dilution analysis of chimeric splenocytes revealed markedly reduced frequencies of cytotoxic T lymphocyte precursors (CTL-P) directed against host-type cells, as compared with normal splenocytes reacting against the same target cells. This difference was accentuated when these cells were sensitized to host-type target cells prior to plating in limiting dilution cultures. In 1:1 mixing experiments of normal and chimeric splenocytes, there was no evidence of any in vitro suppressive activity to account for hyporeactivity of chimeric cells against host-type cells. Thus, maintenance of TLI-induced tolerance seemed not to be mediated primarily through an active suppressor cell mechanism

Allograft tolerance in pigs after fractionated lymphoid irradiation. II. Kidney graft after conventional total lymphoid irradiation and bone marrow cell grafting

International Nuclear Information System (INIS)

Fradelizi, D.; Mahouy, G.; de Riberolles, C.; Lecompte, Y.; Alhomme, P.; Douard, M.C.; Chotin, G.; Martelli, H.; Daburon, F.; Vaiman, M.

1981-01-01

Experiments with pigs have been performed in order to establish bone marrow chimerism and kidney graft tolerance between SLA genotyped semi-incompatible animals. Recipients were conditioned by means of conventional fractionated total lymphoid irradiation (TLI) delivered by a vertical cobalt source. The principal lymphoid regions of the pig, including thymus and spleen, were submitted to irradiation. Two protocols were tested: A = 250 cGy four times a week x 13 times (TLI) (two animals) and B = 350 cGy three times a week x 8 times (TLI) (four animals). Bone marrow cells were injected 24 h after the last irradiation. One day later, bilateral nephrectomy and the graft of one kidney from the bone marrow cell donor were performed simultaneously. Results convinced us that application of the TLI protocol to humans is not yet practicable and that further experimental work is needed

OSI-027 modulates acute graft-versus-host disease after liver transplantation in a rat model.

Science.gov (United States)

Zhi, Xiao; Xue, Fei; Chen, Wei; Liang, Chao; Liu, Hao; Ma, Tao; Xia, Xuefeng; Hu, Liqiang; Bai, Xueli; Liang, Tingbo

2017-09-01

Despite its rarity (1%-2%), acute graft-versus-host disease after liver transplantation (LT-aGVHD) has a high mortality rate (85%). A gradual decrease in regulatory T cells (Tregs) correlates with disease progression in a rat LT-GVHD model, and treatments which increase Tregs exert therapeutic effects on LT-aGVHD. In this study, LT-aGVHD model rats were treated with rapamycin (RAPA), OSI-027, or an equal quantity of vehicle. Rats treated with OSI-027 survived longer (>100 days) than those in the RAPA (70 ± 8 days) or control (24 ± 3 days) groups. Flow cytometric analysis showed that the Treg ratios in peripheral blood mononuclear cells in the OSI-027 group were higher than those in the RAPA or control groups. The proportions of donor-derived lymphocytes in the OSI-027 group were lower than those in the RAPA or control groups. Hematoxylin-eosin staining of skin tissue demonstrated less severe lymphocyte infiltration in the OSI-027 group than that in the RAPA or control groups. In vitro, OSI-027 induced differentiation of CD4 + CD25 - T cells into CD4 + CD25 + forkhead box P3 + Tregs. Furthermore, injection of OSI-027-induced donor-derived CD4 + CD25 + T cells into the peripheral blood of LT-aGVHD model rats prevented LT-aGVHD. Thus, OSI-027 is implicated as a novel method for the treatment of LT-aGVHD. Liver Transplantation 23 1186-1198 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

Segmentation of skin lesions in chronic graft versus host disease photographs with fully convolutional networks

Science.gov (United States)

Wang, Jianing; Chen, Fuyao; Dellalana, Laura E.; Jagasia, Madan H.; Tkaczyk, Eric R.; Dawant, Benoit M.

2018-02-01

Chronic graft-versus-host disease (cGVHD) is a frequent and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (HCT) and commonly affects the skin, resulting in distressing patient morbidity. The percentage of involved body surface area (BSA) is commonly used for diagnosing and scoring the severity of cGVHD. However, the segmentation of the involved BSA from patient whole body serial photography is challenging because (1) it is difficult to design traditional segmentation method that rely on hand crafted features as the appearance of cGVHD lesions can be drastically different from patient to patient; (2) to the best of our knowledge, currently there is no publicavailable labelled image set of cGVHD skin for training deep networks to segment the involved BSA. In this preliminary study we create a small labelled image set of skin cGVHD, and we explore the possibility to use a fully convolutional neural network (FCN) to segment the skin lesion in the images. We use a commercial stereoscopic Vectra H1 camera (Canfield Scientific) to acquire 400 3D photographs of 17 cGVHD patients aged between 22 and 72. A rotational data augmentation process is then applied, which rotates the 3D photos through 10 predefined angles, producing one 2D projection image at each position. This results in 4000 2D images that constitute our cGVHD image set. A FCN model is trained and tested using our images. We show that our method achieves encouraging results for segmenting cGVHD skin lesion in photographic images.

500-Gray γ-Irradiation May Increase Adhesion Strength of Lyophilized Cadaveric Split-Thickness Skin Graft to Wound Bed.

Science.gov (United States)

Wei, Lin-Gwei; Chen, Chieh-Feng; Wang, Chi-Hsien; Cheng, Ya-Chen; Li, Chun-Chang; Chiu, Wen-Kuan; Wang, Hsian-Jenn

2017-03-01

Human cadaveric skin grafts are considered as the "gold standard" for temporary wound coverage because they provide a more conductive environment for natural wound healing. Lyophilization, packing, and terminal sterilization with gamma-ray can facilitate the application of cadaveric split-thickness skin grafts, but may alter the adhesion properties of the grafts. In a pilot study, we found that 500 Gy γ-irradiation seemed not to reduce the adherence between the grafts and wound beds. We conducted this experiment to compare the adherences of lyophilized, 500-Gy γ-irradiated skin grafts to that of lyophilized, nonirradiated grafts. Pairs of wounds were created over the backs of Sprague- Dawley rats. Pairs of "lyophilized, 500-Gy γ-irradiated" and "lyophilized, nonirradiated" cadaveric split-thickness skin grafts were fixed to the wound beds. Adhesion strength between the grafts and the wound beds was measured and compared. On post-skin-graft day 7 and day 10, the adhesion strength of γ-irradiated grafts was greater than that of the nonirradiated grafts. Because lyophilized cadaveric skin grafts can be vascularized and the collagen of its dermal component can be remodeled after grafting, the superior adhesion strength of 500-Gy γ-irradiated grafts can be explained by the collagen changes from irradiation.

Cyclosporin-Methotrexate Compared with Cyclosporin-Methotrexate-Methylprednisolone Therapy for the Prophylaxis of Acute Graft-Versus Host Disease

International Nuclear Information System (INIS)

Khattab, N.F.

2010-01-01

Acute graft-versus host (GVHD) disease is a common immunologic complication, which occurs in 40-50% of the recipients of allogenic stem cell transplantation (SCT). The role of corticosteroid in the prevention of GVHD is not well established. We report here a study to determine whether the addition of methylprednisolone to the combination of cyclosporine (CSA) and methotrexate (MTX), methylp-rednisolone (MP) for the prophylaxis of acute GVHD would further decrease the incidence of acute GVHD. A group of patients (25 patients with acute myeloid leukemia (AML) and 12 patients with acute lymphocytic leukemia (ALL) that received CSA/MTX/MP started from 2004 to 2008, were compared to a historical group of patients (19 patient with acute myeloid leukemia (AML) and 12 patients with acute lymphocytic leukemia (ALL) that received GVHD prophylaxis in the form of CSA/MTX only from 1999 to 2003). The primary endpoint in this study was the develop-ment of GVHD and the secondary end point was overall and disease free survival. Both groups of patients were matched for age, sex, donor recipient sex, low risk patients and high risk patients. Although the incidence of acute GVHD in the MP -ve group was 35% versus 24% in the MP+ve group, there was no significant difference between them. The overall survival showed a significant difference between the 2 groups (p<0.05). It was 48% for the 2 drug regimen (CSA/MTX) vs. 81% for the three drug regimen (CSA/MTX/MP). There was a significant decrease in the relapse rate in patients on CSA/MTX/MP (p<0.05). In conclusion, the addition of MP (methylprednis-olone) to the combination of CSA/MTX did not affect the incidence of acute GVHD significantly in allogeneic SCT but surprisingly the incidence of survival and relapse was markedly increased and decreased respectively

Inhibition of BTK and ITK with Ibrutinib Is Effective in the Prevention of Chronic Graft-versus-Host Disease in Mice

Science.gov (United States)

Nguyen, Hung; Bastian, David; Heinrichs, Jessica; Wu, Yongxia; Liu, Chen; McDonald, Daniel G.; Pidala, Joseph; Yu, Xue-Zhong

2015-01-01

Bruton’s Tyrosine Kinase (BTK) and IL-2 Inducible T-cell Kinase (ITK) are enzymes responsible for the phosphorylation and activation of downstream effectors in the B-cell receptor (BCR) signaling and T cell receptor (TCR) signaling pathways, respectively. Ibrutinib is an FDA-approved potent inhibitor of both BTK and ITK that impairs B-cell and T-cell function. CD4 T cells and B cells are essential for the induction of chronic graft-versus-host disease (cGVHD). We evaluated these targets by testing the ability of Ibrutinib to prevent or ameliorate cGVHD, which is one of the major complications for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We found that Ibrutinib significantly alleviated cGVHD across four different mouse models, accompanied by increased long-term survival and reduced clinical score. The clinical improvements in Ibrutinib-treated recipients were associated with decreased serum-autoantibodies, costimulatory molecule activation, B-cell proliferation, and glomerulonephritis compared to vehicle controls. Ibrutinib was also able to alleviate the clinical manifestations in acute GVHD (aGVHD), where the recipients were given grafts with or without B cells, suggesting that an inhibitory effect of Ibrutinib on T cells contributes to a reduction in both aGVHD and cGVHD pathogenesis. An effective prophylactic regimen is still lacking to both reduce the incidence and severity of human cGVHD following allo-HSCT. Our study shows that Ibrutinib is an effective prophylaxis against several mouse models of cGVHD with minimal toxicity and could be a promising strategy to combat human cGVHD clinically. PMID:26348529

Inhibition of BTK and ITK with Ibrutinib Is Effective in the Prevention of Chronic Graft-versus-Host Disease in Mice.

Directory of Open Access Journals (Sweden)

Steven D Schutt

Full Text Available Bruton's Tyrosine Kinase (BTK and IL-2 Inducible T-cell Kinase (ITK are enzymes responsible for the phosphorylation and activation of downstream effectors in the B-cell receptor (BCR signaling and T cell receptor (TCR signaling pathways, respectively. Ibrutinib is an FDA-approved potent inhibitor of both BTK and ITK that impairs B-cell and T-cell function. CD4 T cells and B cells are essential for the induction of chronic graft-versus-host disease (cGVHD. We evaluated these targets by testing the ability of Ibrutinib to prevent or ameliorate cGVHD, which is one of the major complications for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT. We found that Ibrutinib significantly alleviated cGVHD across four different mouse models, accompanied by increased long-term survival and reduced clinical score. The clinical improvements in Ibrutinib-treated recipients were associated with decreased serum-autoantibodies, costimulatory molecule activation, B-cell proliferation, and glomerulonephritis compared to vehicle controls. Ibrutinib was also able to alleviate the clinical manifestations in acute GVHD (aGVHD, where the recipients were given grafts with or without B cells, suggesting that an inhibitory effect of Ibrutinib on T cells contributes to a reduction in both aGVHD and cGVHD pathogenesis. An effective prophylactic regimen is still lacking to both reduce the incidence and severity of human cGVHD following allo-HSCT. Our study shows that Ibrutinib is an effective prophylaxis against several mouse models of cGVHD with minimal toxicity and could be a promising strategy to combat human cGVHD clinically.

Quantitative computed tomography assessment of graft-versus-host disease-related bronchiolitis obliterans in children: A pilot feasibility study

International Nuclear Information System (INIS)

Kim, Hyun Gi; Shin, Hyun Joo; Kim, Myung-Joon; Lee, Mi-Jung; Kim, Yoon Hee; Sohn, Myung Hyun; Kim, Kyung Won; Lyu, Chuhl Joo

2015-01-01

To suggest a simple method that can quantify air trapping from chest CT in children with graft-versus-host disease (GVHD)-related bronchiolitis obliterans (BO). This institutional review board-approved retrospective study included eight GVHD-related BO patients (age, 6 - 17 years) who underwent both 31 CTs of variable settings and pulmonary function tests (PFT). The attenuation values of lung parenchyma in normal (An) and air trapping (Aa) areas were obtained. Individualized threshold [(An + Aa)/2] and fixed threshold of -950 HU were set for air trapping quantification. Spearman correlation analysis and generalized linear mixed models were used for statistical analysis. The mean value of individualized threshold was -830.2 ± 48.3 HU. The mean air trapping lung volume percentage with individualized threshold and -950 HU were 45.4 ± 18.9 % and 1.4 ± 1.9 %, respectively. The air trapping lung volume percentage with individualized threshold showed a significant negative correlation with the PFT of FEV1/FVC% in all data (γ = -0.795, P <.001) and in the correction of repetition (γ = -0.837, P =.010). We suggest a simple and individualized threshold attenuation setting method for air trapping quantification insusceptible to CT imaging protocols or respiratory phase control in children with GVHD-related BO. (orig.)

Utility of Endoscopic Examination in the Diagnosis of Acute Graft-versus-Host Disease in the Lower Gastrointestinal Tract

Directory of Open Access Journals (Sweden)

Kosuke Nomura

2017-01-01

Full Text Available Background and Aims. We retrospectively investigated the incidence of acute graft-versus-host disease (GVHD in the lower gastrointestinal (GI tract and the diagnostic accuracy of endoscopy. Methods. Of 1231 patients who underwent allogeneic hematopoietic stem cell transplantation between January 2005 and December 2014, 186 of whom underwent colonoscopy and biopsy and had no cytomegalovirus infection. The endoscopic findings and histologic diagnosis from these 186 patients were retrospectively analyzed. Results. Based on the histopathological findings, 171 patients were diagnosed with GVHD, accounting for 13.9% of all transplant recipients. Useful endoscopic findings for the diagnosis of GVHD were atrophy of the ileocecal valve and villous atrophy in the terminal ileum and tortoise shell-like mucosae, edema, and low vascular permeability in the colon. Even when no mucosal abnormality was observed, the incidence of GVHD was 78.9% in the terminal ileum and 75.0% in the colon. Furthermore, patients with mucosal exfoliation, although infrequent, were all diagnosed with grade 3/4 GVHD. Conclusions. It is important to perform endoscopy proactively for the early diagnosis of GVHD, and biopsy should be performed even when no abnormality is observed. In addition, because patients with mucosal exfoliation are extremely likely to have grade 3/4 GVHD, early treatment should be initiated.

Clinical laboratory markers of inflammation as determinants of chronic graft-versus-host disease activity and NIH global severity.

Science.gov (United States)

Grkovic, L; Baird, K; Steinberg, S M; Williams, K M; Pulanic, D; Cowen, E W; Mitchell, S A; Hakim, F T; Martires, K J; Avila, D N; Taylor, T N; Salit, R B; Rowley, S D; Zhang, D; Fowler, D H; Bishop, M R; Gress, R E; Pavletic, S Z

2012-04-01

Chronic graft-versus-host disease (cGVHD) remains a major cause of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently there are no accepted measures of cGVHD activity to aid in clinical management and disease staging. We analyzed clinical markers of inflammation in the sera of patients with established cGVHD and correlated those with definitions of disease activity. In all, 189 adults with cGVHD (33% moderate and 66% severe according to National Institutes of Health (NIH) global scoring) were consecutively enrolled onto a cross-sectional prospective cGVHD natural history study. At the time of evaluation, 80% were receiving systemic immunosuppression and failed a median of four prior systemic therapies (PST) for their cGVHD. Lower albumin (P<0.0001), higher C-reactive protein (P = 0.043), higher platelets (P = 0.030) and higher number of PST (P<0.0001) were associated with active disease defined as clinician's intention to intensify or alter systemic therapy due to the lack of response. Higher platelet count (P = 0.021) and higher number of PST (P<0.0001) were associated with more severe diseased defined by NIH global score. This study identified common laboratory indicators of inflammation that can serve as markers of cGVHD activity and severity.

Quantitative computed tomography assessment of graft-versus-host disease-related bronchiolitis obliterans in children: A pilot feasibility study

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyun Gi [Yonsei University College of Medicine, Department of Radiology and Research Institute of Radiological Science, Severance Children' s Hospital, Seoul (Korea, Republic of); Ajou University Medical Center, Department of Radiology, Ajou University School of Medicine, Suwon (Korea, Republic of); Shin, Hyun Joo; Kim, Myung-Joon; Lee, Mi-Jung [Yonsei University College of Medicine, Department of Radiology and Research Institute of Radiological Science, Severance Children' s Hospital, Seoul (Korea, Republic of); Kim, Yoon Hee; Sohn, Myung Hyun; Kim, Kyung Won [Yonsei University College of Medicine, Department of Pediatrics and Institute of Allergy, Severance Children' s Hospital, Seoul (Korea, Republic of); Lyu, Chuhl Joo [Yonsei University College of Medicine, Department of Pediatric Hematology and Oncology, Severance Children' s Hospital, Seoul (Korea, Republic of)

2015-10-15

To suggest a simple method that can quantify air trapping from chest CT in children with graft-versus-host disease (GVHD)-related bronchiolitis obliterans (BO). This institutional review board-approved retrospective study included eight GVHD-related BO patients (age, 6 - 17 years) who underwent both 31 CTs of variable settings and pulmonary function tests (PFT). The attenuation values of lung parenchyma in normal (An) and air trapping (Aa) areas were obtained. Individualized threshold [(An + Aa)/2] and fixed threshold of -950 HU were set for air trapping quantification. Spearman correlation analysis and generalized linear mixed models were used for statistical analysis. The mean value of individualized threshold was -830.2 ± 48.3 HU. The mean air trapping lung volume percentage with individualized threshold and -950 HU were 45.4 ± 18.9 % and 1.4 ± 1.9 %, respectively. The air trapping lung volume percentage with individualized threshold showed a significant negative correlation with the PFT of FEV1/FVC% in all data (γ = -0.795, P <.001) and in the correction of repetition (γ = -0.837, P =.010). We suggest a simple and individualized threshold attenuation setting method for air trapping quantification insusceptible to CT imaging protocols or respiratory phase control in children with GVHD-related BO. (orig.)

International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium.

Science.gov (United States)

Harris, Andrew C; Young, Rachel; Devine, Steven; Hogan, William J; Ayuk, Francis; Bunworasate, Udomsak; Chanswangphuwana, Chantiya; Efebera, Yvonne A; Holler, Ernst; Litzow, Mark; Ordemann, Rainer; Qayed, Muna; Renteria, Anne S; Reshef, Ran; Wölfl, Matthias; Chen, Yi-Bin; Goldstein, Steven; Jagasia, Madan; Locatelli, Franco; Mielke, Stephan; Porter, David; Schechter, Tal; Shekhovtsova, Zhanna; Ferrara, James L M; Levine, John E

2016-01-01

Acute graft-versus-host disease (GVHD) remains a leading cause of morbidity and nonrelapse mortality after allogeneic hematopoietic cell transplantation. The clinical staging of GVHD varies greatly between transplant centers and is frequently not agreed on by independent reviewers. The lack of standardized approaches to handle common sources of discrepancy in GVHD grading likely contributes to why promising GVHD treatments reported from single centers have failed to show benefit in randomized multicenter clinical trials. We developed guidelines through international expert consensus opinion to standardize the diagnosis and clinical staging of GVHD for use in a large international GVHD research consortium. During the first year of use, the guidance followed discussion of complex clinical phenotypes by experienced transplant physicians and data managers. These guidelines increase the uniformity of GVHD symptom capture, which may improve the reproducibility of GVHD clinical trials after further prospective validation. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Solvent effect on post-irradiation grafting of styrene onto poly(ethylene-alt-tetrafluoroethylene) (ETFE) films

Science.gov (United States)

Napoleão Geraldes, Adriana; Augusto Zen, Heloísa; Ribeiro, Geise; Fernandes Parra, Duclerc; Benévolo Lugão, Ademar

2013-03-01

Radiation-induced grafting of styrene onto ETFE films in different solvent was investigated after simultaneous irradiation (in post-irradiation condition) using a 60Co source. Grafting of styrene followed by sulfonation onto poly(ethylene-alt-tetrafluoroethylene) (ETFE) are currently studied for synthesis of ion exchange membranes. The ETFE films were immersed in styrene/toluene, styrene/methanol and styrene/isopropyl alcohol and irradiated at 20 and 100 kGy doses at room temperature. The post-irradiation time was established at 14 day and the grafting degree was evaluated. The grafted films were sulfonated using chlorosulfonic acid and 1,2-dichloroethane 20:80 (v/v) at room temperature for 5 h. The degree of grafting (DOG) was determined gravimetrically and physical or chemical changes were evaluated by differential scanning calorimeter analysis (DSC), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The ion exchange capacity (IEC) values showed the best performance of sulfonation for ETFE membranes grafted in toluene solvent. Surface images of the grafted films by SEM technique have presented a strong effect of the solvents on the films morphology.

X-ray irradiation of RC-MAP pre-stored for various numbers of days. Effect of X-ray irradiation on RC-MAP and reuse of RC-MAP after irradiation

International Nuclear Information System (INIS)

Yamada, Naotomo; Nagumo, Fumio; Kawasaki, Seiji; Matsuzaki, Miwako; Tadano, Jutaro

1995-01-01

X-ray irradiation is currently in wide use as a means of preventing post-transfusion graft-versus-host disease (PT-GVHD). In this study, we evaluated the effects of X-ray irradiation on RC-MAP pre-stored for various numbers of days, and assessed how long irradiated RC-MAP can be stored. RC-MAP was irradiated at a dosage of 15 Gy at 1, 7, 14, 21 or 28 days after blood collection. These specimens were referred to as group I, II, III, IV and V (X-ray-irradiated groups), respectively. Non-irradiated RC-MAP was used as the control. Results showed that plasma K concentration increased after X-ray irradiation. It is therefore advisable that RC-MAPs be used immediately in infants and in renal failure. However, to maximize the efficiency of blood product use, it seemed possible that groups I and II could be used within two weeks after irradiation, and group III within one week. On the basis of this increase in K concentration, however, groups IV and V plasma should be used immediately after irradiation. (author)

Preparation of antifouling ultrafiltration membranes via irradiation induced graft polymerization technique

International Nuclear Information System (INIS)

Deng Bo; Liu Zhognying; Lu Xiaofeng; Li Jingye; Yang Xuanxuan; Yu Ming; Zhang Bowu

2010-01-01

PVDF powders were irradiated in air at dose of 15 kGy by using gamma-rays. Macromolecular peroxides transformed from free radicals in the irradiated PVDF powders in air can be preserved for long-term at appropriate temperature stably. By mixing acrylic monomers with irradiated PVDF powders then the graft polymerization can be initiated by heating. Then a series of hydrophilic ultrafiltration (UF) membranes were fabricated by dissolving the PVDF-g-PAAc powders in the NMP under phase inversion method. The antifouling performances of UF membranes cast from virgin and grafted PVDF powders were compared. (authors)

Graft-versus-host reaction in small-bowel transplantation and possibilities for its circumvention.

Science.gov (United States)

Watanabe, K; Yagi, T; Iwagaki, H; Kimura, Y; Mitsuoka, N; Inagaki, M; Tanaka, S; Tanaka, N

2001-01-01

To study graft-versus-host reaction (GVHR) in small-bowel transplantation and its underlying mechanisms and to find methods for circumventing GVHR, we used an unidirectional GVHR model in which F1 Lewis (LEW) x Wistar King A (WKA) hybrid rats received small-bowel transplants from either LEW or WKA parent rats. The survival time of F1 hybrid rats that received full-length small-bowel transplantation from LEW and WKA was 16.3+/-2.1 days and 18.2+/-3.4 days, respectively. When one-quarter of LEW small bowel was transplanted to an F1 hybrid recipient, the survival time was significantly longer at 44.0+/-23.4 days compared with rats that had received full-length LEW small-bowel transplantation. The survival time of F1 hybrid rats which received an injection of high-dose (5 x 10(8) cells) LEW or WKA spleen cells was 11.9+/-4.0 days and 13.1+/-3.6 days, respectively. However, when an injection containing a low dose (1 x 108 cells) of LEW spleen cells was used, survival was > 100 days, showing significance compared with the survival of rats receiving the higher dose LEW spleen-cell injection. Both small-bowel transplantation and spleen-cell injection were compared for the effective period of recipient resistance to donor cell or small-bowel transplantation as second challenge. When the F1 rats given a quarter LEW small-bowel transplant as first challenge were treated with a high-dose of spleen cells 30 days after transplantation, they survived for > 30 days without GVHR. F1 rats that were treated with a low-dose LEW spleen-cell injection, followed 30 days later by full LEW small-bowel transplantation, had a survival time of > 100 days. These results indicate that segmental small-bowel transplantation and spleen-cell injection as first challenge may facilitate the prevention of GVHR, resulting in resistance to subsequent immunological challenge.

Efficacy of two different doses of rabbit anti-T-lymphocyte globulin to prevent graft-versus-host disease in children with haematological malignancies transplanted from an unrelated donor: a multicentre, randomised, open-label, phase 3 trial

OpenAIRE

Locatelli, Franco; Bernardo, Maria Ester; Bertaina, Alice; Rognoni, Carla; Comoli, Patrizia; Rovelli, Attilio; Pession, Andrea; Fagioli, Franca; Favre, Claudio; Lanino, Edoardo; Giorgiani, Giovanna; Merli, Pietro; Pagliara, Daria; Prete, Arcangelo; Zecca, Marco

2017-01-01

Background Although rabbit anti-T-lymphocyte globulin (ATLG) is largely used for the prevention of immunemediated complications in patients given allogeneic haemopoietic stem-cell transplantation (HSCT) from an unrelated donor, the optimum dose of this drug in children is still undefined. We aimed to test whether a higher dose of ATLG was superior to a lower dose for prevention of grade II–IV acute graft-versus-host disease (GVHD). Methods We conducted a multicentre, randomised, open-label, p...

Tolerogenic interactions between CD8+ dendritic cells and NKT cells prevent rejection of bone marrow and organ grafts.

Science.gov (United States)

Hongo, David; Tang, Xiaobin; Zhang, Xiangyue; Engleman, Edgar G; Strober, Samuel

2017-03-23

The combination of total lymphoid irradiation and anti-T-cell antibodies safely induces immune tolerance to combined hematopoietic cell and organ allografts in humans. Our mouse model required host natural killer T (NKT) cells to induce tolerance. Because NKT cells normally depend on signals from CD8 + dendritic cells (DCs) for their activation, we used the mouse model to test the hypothesis that, after lymphoid irradiation, host CD8 + DCs play a requisite role in tolerance induction through interactions with NKT cells. Selective deficiency of either CD8 + DCs or NKT cells abrogated chimerism and organ graft acceptance. After radiation, the CD8 + DCs increased expression of surface molecules required for NKT and apoptotic cell interactions and developed suppressive immune functions, including production of indoleamine 2,3-deoxygenase. Injection of naive mice with apoptotic spleen cells generated by irradiation led to DC changes similar to those induced by lymphoid radiation, suggesting that apoptotic body ingestion by CD8 + DCs initiates tolerance induction. Tolerogenic CD8 + DCs induced the development of tolerogenic NKT cells with a marked T helper 2 cell bias that, in turn, regulated the differentiation of the DCs and suppressed rejection of the transplants. Thus, reciprocal interactions between CD8 + DCs and invariant NKT cells are required for tolerance induction in this system that was translated into a successful clinical protocol. © 2017 by The American Society of Hematology.

Selective induction of cyclin B protein abrogates the G2 delay after irradiation

International Nuclear Information System (INIS)

Kao, G.; Muschel, R.J.; Maity, A.; Kunig, A.; McKenna, W.G.

1996-01-01

Purpose/Objective: Irradiation of tumor cells commonly results in G2 delay, which has been postulated to allow DNA repair and cell survival. The G2 delay after irradiation is also often marked in some cell lines by delayed expression of cyclin B protein, suggesting a role for cyclin B regulation. Investigations of these hypotheses however has been hampered by the inability to selectively perturb the G2 delay in a physiologic manner. Materials and Methods: We have devised a system, with which we are able to selectively induce cyclin B protein expression in vivo at specific points in the cell cycle, by transfecting Hela cells with an expression vector under control of a dexamethasone-inducible promoter. Experiments were subsequently performed by synchronizing, releasing, irradiating, inducing, and harvesting these cells through the cell cycle. Results: Irradiation with 5 Gy led to a pronounced G2 delay, reflected by markedly slowed progression into mitosis, concomitant with reduced expression of cyclin B protein. Induction of cyclin B after radiation in these cells abrogated the G2 delay by approximately doubling the rate at which the cells re-enter mitosis. Treatment of irradiated untransfected control cells with dexamethasone, in which cyclin B is not induced, led to minimal changes. Studies of effects of cyclin B induction on cyclin B localization (using immunofluorescence), cdc2 phosphorylation and activation will also be presented. Conclusion: This system should allow further investigations into fundamental mechanisms of cell cycle regulation after irradiation and DNA damage. This also provides direct evidence for the first time that cyclin B protein regulation may play a role in the G2 delay following irradiation in Hela cells, perhaps complementing phosphorylation events

Grafting of HEMA onto dopamine coated stainless steel by 60Co-γ irradiation method

International Nuclear Information System (INIS)

Jin, Wanqin; Yang, Liming; Yang, Wei; Chen, Bin; Chen, Jie

2014-01-01

A novel method for grafting of 2-hydroxyethyl methacrylate (HEMA) onto the surface of stainless steel (SS) was explored by using 60 Co-γ irradiation. The surface of SS was modified by coating of dopamine before radiation grafting. The grafting reaction was performed in a simultaneous irradiation condition. The chemical structures change of the surface before and after grafting was demonstrated by Fourier transform infrared (FTIR) spectrometer. The hydrophilicity of the samples was determined by water contact angle measurement in the comparison of the stainless steel in the conditions of pristine, dopamine coated and HEMA grafted. Surface morphology of the samples was characterized by atomic force microscope (AFM) and scanning electron microscope (SEM). The corrosion resistance properties of the samples were evaluated by Tafel polarization curve. The hemocompatibility of the samples were tested by platelet adhesion assay. - Highlights: • Poly-HEMA was grafted onto the surface of SS by 60 Co-γ-ray irradiation. • Pristine SS was coated by dopamine to form a dense poly-dopamine film before radiation grafting. • The biocompatibility and hydrophility of SS were improved after the grafting of HEMA

CD4+CD25highCD127low Regulatory T Cells in Peripheral Blood Are Not an Independent Factor for Chronic Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

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Jolanta B. Perz

2012-01-01

Full Text Available Background. The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation (HSCT largely relies on the graft-versus-leukemia (GVL effect. Uncontrolled graft-versus-host disease (GVHD is a feared complication of HSCT. Regulatory T cells (Treg are a subset of CD4+ T-helper cells believed to maintain tolerance after HSCT. It remains unclear whether low peripheral blood Treg have an impact on the risk for acute (aGVHD and chronic GVHD (cGVHD. Methods. In this paper we enumerated the CD4+CD25highCD127low Treg in the peripheral blood of 84 patients after at least 150 days from HSCT and in 20 healthy age-matched controls. Results. Although similar mean lymphocyte counts were found in patients and controls, CD3+CD4+ T-cell counts were significantly lower in patients. Patients also had significantly lower Treg percentages among lymphocytes as compared to controls. Patients with cGVHD had even higher percentages of Treg if compared to patients without cGVHD. In multivariate analysis, Treg percentages were not an independent factor for cGVHD. Conclusions. This paper did not show a relation between deficient peripheral blood Treg and cGVHD, therefore cGVHD does not seem to occur as a result of peripheral Treg paucity.

Effect of selective T cell depletion of host and/or donor bone marrow on lymphopoietic repopulation, tolerance, and graft-vs-host disease in mixed allogeneic chimeras (B10 + B10.D2----B10)

International Nuclear Information System (INIS)

Ildstad, S.T.; Wren, S.M.; Bluestone, J.A.; Barbieri, S.A.; Stephany, D.; Sachs, D.H.

1986-01-01

Reconstitution of lethally irradiated mice with a mixture of T cell-depleted syngeneic plus T cell-depleted allogeneic bone marrow (B10 + B10.D2----B10) leads to the induction of mixed lymphopoietic chimerism, excellent survivals, specific in vivo transplantation tolerance to subsequent donor strain skin grafts, and specific in vitro unresponsiveness to allogeneic donor lymphoid elements as assessed by mixed lymphocyte reaction (MLR) proliferative and cell-mediated lympholysis (CML) cytotoxicity assays. When B10 recipient mice received mixed marrow inocula in which the syngeneic component had not been T cell depleted, whether or not the allogeneic donor marrow was treated, they repopulated exclusively with host-type cells, promptly rejected donor-type skin allografts, and were reactive in vitro to the allogeneic donor by CML and MLR assays. In contrast, T cell depletion of the syngeneic component of the mixed marrow inocula resulted in specific acceptance of allogeneic donor strain skin grafts. Such animals were specifically unreactive to allogeneic donor lymphoid elements in vitro by CML and MLR, but were reactive to third party. When both the syngeneic and allogeneic marrow were T cell depleted, variable percentages of host- and donor-type lymphoid elements were detected in the mixed reconstituted host. When only the syngeneic bone marrow was T cell depleted, animals repopulated exclusively with donor-type cells. Although these animals had detectable in vitro anti-host (B10) reactivity by CML and MLR and reconstituted as fully allogeneic chimeras, they exhibited excellent survival and had no in vivo evidence for graft-vs-host disease. Experiments in which untreated donor spleen cells were added to the inocula in this last group suggest that the presence of T cell-depleted syngeneic bone marrow cells diminishes graft-vs-host disease and the mortality from it

Expansion of donor-reactive host T cells in primary graft failure after allogeneic hematopoietic SCT following reduced-intensity conditioning.

Science.gov (United States)

Koyama, M; Hashimoto, D; Nagafuji, K; Eto, T; Ohno, Y; Aoyama, K; Iwasaki, H; Miyamoto, T; Hill, G R; Akashi, K; Teshima, T

2014-01-01

Graft rejection remains a major obstacle in allogeneic hematopoietic SCT following reduced-intensity conditioning (RIC-SCT), particularly after cord blood transplantation (CBT). In a murine MHC-mismatched model of RIC-SCT, primary graft rejection was associated with activation and expansion of donor-reactive host T cells in peripheral blood and BM early after SCT. Donor-derived dendritic cells are at least partly involved in host T-cell activation. We then evaluated if such an expansion of host T cells could be associated with graft rejection after RIC-CBT. Expansion of residual host lymphocytes was observed in 4/7 patients with graft rejection at 3 weeks after CBT, but in none of the 17 patients who achieved engraftment. These results suggest the crucial role of residual host T cells after RIC-SCT in graft rejection and expansion of host T cells could be a marker of graft rejection. Development of more efficient T cell-suppressive conditioning regimens may be necessary in the context of RIC-SCT.

Preliminary studies on 1-vinyl-2-pyrrolidone grafting onto cellulose by pre-irradiation method

Energy Technology Data Exchange (ETDEWEB)

Severich, Patrick; Dutra, Rodrigo da Costa; Kodama, Yasko, E-mail: ykodama@ipen.br, E-mail: patrick.severich@ipen.br, E-mail: rodrigo.dutra@ipen.br [Instituto de Pesquisas Energética s e Nucleares (IPEN-CNEN/SP), São Paulo, SP (Brazil)

2017-07-01

Cellulose is considered a renewable biopolymer most abundant in nature. Better functional surfaces can be Obtained by modifying cellulose. On the other hand, poly vinyl pyrrolidone, PVP, is a synthetic nontoxic, water-soluble polymer frequently used in an extensive variety of applications including several pharmaceutical applications. Grafting 1-vinyl-2-pyrrolidone, NVP, onto polymeric cellulose can be obtained by ionizing radiation. Ionizing radiation grafting can be affected by several factors as environment, solvent, monomer concentration, temperature of graft reaction. Grafting by ionizing radiation can be performed by three methods, pre-irradiation, oxidation by peroxide and simultaneous irradiation. In this study, it was used pre-irradiation method of cellulose. Paper filter without ash, NVP without purification was used in this study. Paper samples were exposed to electron beam from Dynamitron Accelerator with radiation absorbed dose of 25 kGy. Influence of NVP concentration, temperature of reaction after irradiation on degree of grafting (DG) was studied. Also, cellulose radicals of grafted paper samples was studied by electron paramagnetic resonance using a Bruker X-band ESR at room temperature just after heating reaction. Small decrease of cellulose radicals was observed with increasing reaction temperature. It was observed DG small increase with increasing concentration of monomer in solution of water ethanol 50-50 v:v and rising temperature of reaction. Further tests using simultaneous method of grafting of NVP in cellulose paper, in water:ethanol 75:25 v:v solution, induced by gamma irradiation were performed. It was observed homopolymerization forming PVP with increasing monomer concentration. (author)

Preliminary studies on 1-vinyl-2-pyrrolidone grafting onto cellulose by pre-irradiation method

International Nuclear Information System (INIS)

Severich, Patrick; Dutra, Rodrigo da Costa; Kodama, Yasko

2017-01-01

Cellulose is considered a renewable biopolymer most abundant in nature. Better functional surfaces can be Obtained by modifying cellulose. On the other hand, poly vinyl pyrrolidone, PVP, is a synthetic nontoxic, water-soluble polymer frequently used in an extensive variety of applications including several pharmaceutical applications. Grafting 1-vinyl-2-pyrrolidone, NVP, onto polymeric cellulose can be obtained by ionizing radiation. Ionizing radiation grafting can be affected by several factors as environment, solvent, monomer concentration, temperature of graft reaction. Grafting by ionizing radiation can be performed by three methods, pre-irradiation, oxidation by peroxide and simultaneous irradiation. In this study, it was used pre-irradiation method of cellulose. Paper filter without ash, NVP without purification was used in this study. Paper samples were exposed to electron beam from Dynamitron Accelerator with radiation absorbed dose of 25 kGy. Influence of NVP concentration, temperature of reaction after irradiation on degree of grafting (DG) was studied. Also, cellulose radicals of grafted paper samples was studied by electron paramagnetic resonance using a Bruker X-band ESR at room temperature just after heating reaction. Small decrease of cellulose radicals was observed with increasing reaction temperature. It was observed DG small increase with increasing concentration of monomer in solution of water ethanol 50-50 v:v and rising temperature of reaction. Further tests using simultaneous method of grafting of NVP in cellulose paper, in water:ethanol 75:25 v:v solution, induced by gamma irradiation were performed. It was observed homopolymerization forming PVP with increasing monomer concentration. (author)

Gamma ray-irradiation in fresh allo-joint transplantation

International Nuclear Information System (INIS)

Watanabe, Hiroshi

1995-01-01

In the first of a series of experiments in rat designed to assess the efficacy of gamma ray irradiation in fresh allo-joint transplantation, it was found that the optimal gamma ray dosage was 4 Gy. At this dosage level, the irradiation rays suppressed the viability of marrow cells which had the highest antigenicity, with no injury to the bone or articular cartilage. In a second experiment, a fresh homologous knee joint was irradiated at 4 Gy and then transplanted while administering the donor's splenic cell suspension (for specific immunosuppression) and the immunosuppressive agent cyclosporine (5 mg/kg) to the recipient rat. All the rats that received a pre-irradiated knee joint graft survived until sacrificed for evaluation without showing any sign of host rejection. In these rats, bone fusion had occurred between the host bone and the graft by the 8th postoperative week. Degeneration of the articular cartilage was similar between the rats that had received a pre-irradiated graft and those that had not. These findings indicated that 4 Gy gamma ray irradiation to a graft before transplantation provided an effective means of immunosuppression. (author)

The occurrence of graft-versus-host disease is the major predictive factor for response to donor lymphocyte infusions in multiple myeloma

NARCIS (Netherlands)

Lokhorst, Henk M.; Wu, Kalung; Verdonck, Leo F.; Laterveer, Laurens L.; van de Donk, Niels W. C. J.; van Oers, Marinus H. J.; Cornelissen, Jan J.; Schattenberg, Anton V.

2004-01-01

The graft-versus-myeloma (GVM) effect of donor lymphocyte infusions (DLIs) is well established. We now report the outcome of DLI in 54 patients with relapsed myeloma following allogeneic transplantation. Twenty-eight patients (52%) responded, 19 patients (35%) with a partial response and 9 patients

Studies on the properties of poly (ethylene oxide) R-150 hydrogel films formed by irradiation graft

International Nuclear Information System (INIS)

Yang Zhanshan; Zhu Nankang; Yang Shuqin; Qiang Yizhong

1999-01-01

In order to improve the mechanical properties of poly (ethylene oxide) (PEO) hydrogel film was used as wound dressing. The chemical and physical properties of the PEO R-150 graft hydrogel film formed by blends of electron beam irradiated-PEO R-150 and poly(vinyl alcohol) (PVA) were studied. The experimental results showed that the crosslinking densities of the PEO R-150 graft hydrogel increased along with the increasing of the irradiation doses and decreased with the increasing of the blend concentrations. While the PVA graft proportions did not produce obvious effects on the crosslinking density of the graft hydrogel. The crosslinking density of the graft hydrogel were obviously lower than that of the pure PVA hydrogel. The equilibrium water content of the graft hydrogel decrease as the irradiation dose and the PVA graft proportion increased; but they increased as the blend concentration increased. The equilibrium water content of the graft hydrogel was obviously higher than those of the pure PVA hydrogel. The hardness of the PVA hydrogel film increased with the irradiation dose. The hardness of the graft hydrogel decreased with the blend concentration, whereas it increased with the PVA graft proportion. The results suggest the PVA produces a main effect on the crosslinking density of the graft hydrogel, the PEO R-150 produces a main effect on the equilibrium water content of the graft hydrogel, and the both polymers have double effects on the hardness of the graft hydrogel

The effect of X-ray irradiation on changes of blood chemistry in RC-MAP and CPD-whole blood after irradiation

International Nuclear Information System (INIS)

Hirose, Tetsuhito; Katayama, Norihumi; Okamoto, Yukiharu; Tsuda, Tadaaki; Ota, Kiichiro; Nishioka, Shingo; Tsumura, Michiyo

1997-01-01

The Japanese Welfare Ministry recommended to irradiate transfused blood in order to inactivate lymphocytes, thereby preventing from transfusion associated graft-versus-host disease (PT-GVHD). But an adequate dose of irradiation applied to various kinds of transfused blood has not yet known. We investigated the effect of a irradiation dose of 15 Gy (gray) on changes of plasma K, GOT, BUN and total protein (T.P) in RC-MAP (MAP) and CPD added whole blood (CPD) after days of storage of irradiation. There was a significant increase of potassium (K) in plasma in irradiated RC-MAP, compared with those in non-irradiated RC-MAP, after storage from day 2. Plasma K level in irradiated CPD increased more than those in non-irradiated CPD after storage at day 5. No different increases in plasma GOT, BUN and T.P levels were not shown in irradiated RC-MAP and CPD. Our data led to a conclusion that a adequate irradiated dose seemed to be different in various kinds of transfused blood to inactivate lymphocyte for the prevention of PT-GVHD. (author)

Endoscopic and Histological Findings Are Predicted by Fecal Calprotectin in Acute Intestinal Graft-Versus-Host-Disease.

Science.gov (United States)

Adam, Birgit; Koldehoff, Michael; Ditschkowski, Markus; Gromke, Tanja; Hlinka, Michal; Trenschel, Rudolf; Kordeals, Lambros; Steckel, Nina K; Beelen, Dietrich W; Liebregts, Tobias

2016-07-01

Gastrointestinal graft-versus-host-disease (GI-GVHD) is a major cause of nonrelapse mortality after hematopoietic stem cell transplantation (HSCT) necessitating endoscopic examinations and biopsies for diagnosis. Fecal calprotectin (CPT) has been widely used in gastrointestinal inflammation, but comprehensive data in GI-GVHD are lacking. We aimed to identify an association of CPT with endoscopic findings, mucosal damage and symptoms for diagnosing and monitoring acute GI-GVHD. Symptoms were prospectively evaluated in 110 consecutive HSCT recipients by standardized questionnaires and Bristol Stool Scale (BSS). CPT was assayed by ELISA. Symptom assessment and CPT were performed weekly and with onset of first symptoms. GVHD was diagnosed according to the Glucksberg criteria and by endoscopic biopsies. Patients with GI-GVHD received standard high-dose corticosteroid therapy and follow-up CPT, and symptom evaluation was performed after 28 days. Patients not responding to steroid treatment were re-evaluated by colonoscopy. GI-GVHD was diagnosed in 40 patients. Twelve patients with GI symptoms and CMV colitis and 24 patients with isolated skin GVHD were included as control subjects. CPT was significantly higher in GI-GVHD compared to skin GVHD and CMV colitis. Endoscopic findings, histological grading, abdominal cramps, diarrhea, urgency and BSS correlated with CPT. At follow-up, CPT correlated with abdominal cramps, diarrhea, urgency and BSS. In steroid refractory patients, CPT level was still significantly associated with severity of mucosal damage. CPT predicts endoscopic and histological findings in GI-GVHD and correlates with lower GI symptoms. It enables to discriminate GVHD from CMV colitis and to monitor therapeutic success.

Obtaining cherry and apple tree radiomutants by irradiation of grafts in gamma cell

International Nuclear Information System (INIS)

Chvojka, L.; Fridrich, A.

1980-01-01

The aim of the study was to obtain dwarf mutants of cherry and apple trees. Two methods of irradiation were used: a) winter grafts were irradiated with 60 Co (4-5 kR) and grafted in the crowns of adult trees or of two-year-old rootstocks; b) summer buds on mature annual shots were irradiated with 2-3 kR and grafted on two-year-old rootstocks. Thus the clones of dwarf cherry trees (cv. Napoleon's and Techlovicka) were obtained which were further tested for fruit-bearing in experimental plantations. Colour mutants of apple tree (cv. Champion) with yellow and red fruits were also obtained as well as dwarf types of trees. (author)

Blood irradiation

International Nuclear Information System (INIS)

Chandy, Mammen

1998-01-01

Viable lymphocytes are present in blood and cellular blood components used for transfusion. If the patient who receives a blood transfusion is immunocompetent these lymphocytes are destroyed immediately. However if the patient is immunodefficient or immunosuppressed the transfused lymphocytes survive, recognize the recipient as foreign and react producing a devastating and most often fatal syndrome of transfusion graft versus host disease [T-GVHD]. Even immunocompetent individuals can develop T-GVHD if the donor is a first degree relative since like the Trojan horse the transfused lymphocytes escape detection by the recipient's immune system, multiply and attack recipient tissues. T-GVHD can be prevented by irradiating the blood and different centers use doses ranging from 1.5 to 4.5 Gy. All transfusions where the donor is a first degree relative and transfusions to neonates, immunosuppressed patients and bone marrow transplant recipients need to be irradiated. Commercial irradiators specifically designed for irradiation of blood and cellular blood components are available: however they are expensive. India needs to have blood irradiation facilities available in all large tertiary institutions where immunosuppressed patients are treated. The Atomic Energy Commission of India needs to develop a blood irradiator which meets international standards for use in tertiary medical institutions in the country. (author)

Grafting of acrylic acid onto polypropylene films irradiated with argon ions

International Nuclear Information System (INIS)

Massa, G.; Mazzei, R.; Garcia Bermudez, G.; Filevich, A.; Smolko, E.

2005-01-01

Polypropylene (PP) foils were irradiated with 100 keV energy Argon ions at different fluences ranging from 10 12 up to 2 x 10 15 cm -2 and then grafted with acrylic acid (AA). The grafting yield was measured by weight difference and the structural changes on the films were analysed using Fourier transform infrared spectroscopy (FTIR). Different parameters that determined the grafting process such us fluence, grafting time and monomer concentration were analysed. The grafting reached an optimum value at 79% in aqueous solution at 30 min grafting time. The grafting yield as a function of the ion fluence plot, presented a maximum value, as previously found in a study of heavy beam on polymers

Characteristics and risk of chronic graft-versus-host disease of liver in allogeneic hematopoietic stem cell transplant recipients.

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Chien-Ting Chen

Full Text Available Chronic graft-versus-host-disease (cGvHD is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT. Among various organ-specific cGvHD, the cGvHD of liver is less well-characterized. In this study, we applied the National Institutes of Health 2014 scoring criteria of cGvHD to analyze a retrospective cohort of 362 allo-HSCT recipients focusing on cGvHD of liver. The overall incidence of liver cGvHD with a score of 3 by 1.5 years post-transplant was 5.8% (21/362. Poor outcome, in terms of overall survival (OS, were observed in patients with scores of 3 liver cGvHD, comparing to those with scores less than 3 (hazard ratio [HR] 2.037, 95% confidence interval [CI] 1.123-3.696, P = 0.019. In multivariate analysis, male gender (HR 4.004, P = 0.042 and chronic hepatitis C virus (HCV infection status (HR 19.087, P < 0.001 were statistically significant risk factors for scores of 3 liver cGvHD. Our results indicate that liver cGvHD with scores of 3 has a grave prognosis following allo-HSCT, and that HCV carrier status and male are risk factors. Early recognition of this devastating complication might help in prompt immunosuppressive therapy and reducing late poor outcome.

Platelet lysate mucohadesive formulation to treat oral mucositis in graft versus host disease patients: a new therapeutic approach.

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Del Fante, Claudia; Perotti, Cesare; Bonferoni, Maria Cristina; Rossi, Silvia; Sandri, Giuseppina; Ferrari, Franca; Scudeller, Luigia; Caramella, Carla Marcella

2011-09-01

Optimal treatment of oral mucositis (OM) due to graft versus host disease (GvHD) is currently not available. Platelet-derived growth factors (PDGFs) have high capability for tissue healing and may play a role in repairing the mucosal barrier. The aim of the present work was to develop a mucoadhesive formulation to administer platelet lysate to oral cavity prolonging contact time of platelet lysate with oral mucosa. The mucoadhesive formulation was characterized for in vitro properties (PDGF-AB concentration, mucoadhesive properties, cytotoxicity, fibroblast proliferation, wound healing). Moreover, a preliminary clinical study on seven GvHD patients with OM refractory to other therapies was conducted, to evaluate feasibility, safety, and efficacy. GVPL (mucoadhesive gel vehicle mixed with platelet lysate)showed good mucoadhesive properties; additionally, it was characterized by good biocompatibility in vitro on fibroblasts and it was able to enhance fibroblast proliferation and wound healing, maintaining the efficacy for up to 14 days following storage at 2-8°C. In vivo, clinical response was good-to-complete in five, fair in one, none in the remaining one. The in vitro results indicate that GVPL has optimal mucoadhesive and healing enhancer properties, maintained over time (up to 14 days); preliminary clinical results suggest that oral application of platelet lysate-loaded mucoadhesive formulation is feasible, safe, well tolerated, and effective. A larger controlled randomized study is needed.

Graft Copolymerization of Methyl Methacrylate Monomer onto Starch and Natural Rubber Latex Initiated by Gamma Irradiation

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S. Iskandar

2011-04-01

Full Text Available To obtain the degradable plastic, the graft copolymerization of methyl methacrylate onto starch and natural rubber latex was conducted by a simultaneous irradiation technique. Gamma-ray from cobalt-60 source was used as the initiator. The grafted copolymer of starch-polymethyl methacrylate and the grafted copolymer of natural rubber-polymethyl methacrylate were mixed in the blender, and dried it in the oven. The dried grafted copolymer mixture was then molded using hydraulic press machine. The effect of irradiation dose, composition of the grafted copolymer mixture, film forming condition and recycle effect was evaluated. The parameters observed were tensile strength, gel fraction and soil burial degradability of grafted copolymer mixture. It was found that the tensile strength of grafted copolymer mixture increased by -ray irradiation. Increasing of the grafted copolymer of natural rubber-polymethyl methacrylate content, the gel fraction and tensile strength of the grafted copolymer mixture increased. The tensile strength of the grafted copolymer mixture was increased from 18 MPa to 23 MPa after recycled (film forming reprocessed 3 times. The grafted copolymer mixture was degraded completely after soil buried for 6 months

Comparative study of navigated versus freehand osteochondral graft transplantation of the knee.

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Koulalis, Dimitrios; Di Benedetto, Paolo; Citak, Mustafa; O'Loughlin, Padhraig; Pearle, Andrew D; Kendoff, Daniel O

2009-04-01

Osteochondral lesions are a common sports-related injury for which osteochondral grafting, including mosaicplasty, is an established treatment. Computer navigation has been gaining popularity in orthopaedic surgery to improve accuracy and precision. Navigation improves angle and depth matching during harvest and placement of osteochondral grafts compared with conventional freehand open technique. Controlled laboratory study. Three cadaveric knees were used. Reference markers were attached to the femur, tibia, and donor/recipient site guides. Fifteen osteochondral grafts were harvested and inserted into recipient sites with computer navigation, and 15 similar grafts were inserted freehand. The angles of graft removal and placement as well as surface congruity (graft depth) were calculated for each surgical group. The mean harvesting angle at the donor site using navigation was 4 degrees (standard deviation, 2.3 degrees ; range, 1 degrees -9 degrees ) versus 12 degrees (standard deviation, 5.5 degrees ; range, 5 degrees -24 degrees ) using freehand technique (P standard deviation, 2.1 degrees ; range, 0 degrees -9 degrees ) versus 10.7 degrees (standard deviation, 4.9 degrees ; range, 2 degrees -17 degrees ) in freehand (P standard deviation, 2.0 degrees ; range, 1 degrees -9 degrees ) versus 10.6 degrees (standard deviation, 4.4 degrees ; range, 3 degrees -17 degrees ) with freehand technique (P = .0001). The mean height of plug protrusion under navigation was 0.3 mm (standard deviation, 0.2 mm; range, 0-0.6 mm) versus 0.5 mm (standard deviation, 0.3 mm; range, 0.2-1.1 mm) using a freehand technique (P = .0034). Significantly greater accuracy and precision were observed in harvesting and placement of the osteochondral grafts in the navigated procedures. Clinical studies are needed to establish a benefit in vivo. Improvement in the osteochondral harvest and placement is desirable to optimize clinical outcomes. Navigation shows great potential to improve both harvest

Establishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation.

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Marilène Binsfeld

Full Text Available Multiple myeloma (MM is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM effects, the use of allogeneic hematopoietic stem cell transplantation (allo-SCT remains controversial in MM. In the current study, we investigated the anti-myeloma effects of allo-SCT from B10.D2 mice into MHC-matched myeloma-bearing Balb/cJ mice, with concomitant development of chronic graft-versus-host disease (GvHD.Balb/cJ mice were injected intravenously with luciferase-transfected MOPC315.BM cells, and received an allogeneic (B10.D2 donor or autologous (Balb/cJ donor transplant 30 days later. We observed a GvM effect in 94% of the allogeneic transplanted mice, as the luciferase signal completely disappeared after transplantation, whereas all the autologous transplanted mice showed myeloma progression. Lower serum paraprotein levels and lower myeloma infiltration in bone marrow and spleen in the allogeneic setting confirmed the observed GvM effect. In addition, the treated mice also displayed chronic GvHD symptoms. In vivo and in vitro data suggested the involvement of effector memory CD4 and CD8 T cells associated with the GvM response. The essential role of CD8 T cells was demonstrated in vivo where CD8 T-cell depletion of the graft resulted in reduced GvM effects. Finally, TCR Vβ spectratyping analysis identified Vβ families within CD4 and CD8 T cells, which were associated with both GvM effects and GvHD, whereas other Vβ families within CD4 T cells were associated exclusively with either GvM or GvHD responses.We successfully established an immunocompetent murine model of graft-versus-myeloma. This is the first murine GvM model using immunocompetent mice that develop MM which closely resembles human MM disease and that are treated after disease establishment with an allo-SCT. Importantly, using TCR Vβ spectratyping, we also demonstrated the presence of GvM unique responses

Delayed erythropoiesis in irradiated rats grafted with syngeneic marrow: effects of cytotoxic drugs and iron-deficiency anemia

International Nuclear Information System (INIS)

Rodday, P.; Bennett, M.; Vitalle, J.J.

1976-01-01

Erythropoiesis in spleens of lethally irradiated Lewis rats grafted with 4-35 x 10 6 syngeneic marrow cells was inhibited or delayed during the test period of 5 days; this was in marked contrast to observations in irradiated mice. The mechanism of this inhibition was the subject of this study. Pretreatment of recipients 9 days prior to irradiation with the cytotoxic drugs cyclophosphamide (CY), busulfan (BUS), or dimethylmyleran (DMM), or the induction of iron deficiency with anemia in recipients reversed this delayed erythropoiesis. However, neither iron-deficiency anemia nor pretreatment with BUS or DMM affected the ability of irradiated recipients to reject 20 to 50 x 10 6 allogeneic marrow cells. The administration of commercial preparations of erythropoietin to hosts stimulated erythropoiesis moderately. However, proliferation of syngeneic marrow cells was not enhanced when infused into lethally irradiated spontaneous hypertensive (SH) inbred-strain rats which have high levels of endogenous erythropoietin. Finally, plasma from irradiated rats treated with phenylhydrazine to produce severe anemia was rich in erythropoietin but failed to stimulate erythropoiesis in the cell transfer system. Two hypotheses are considered

Immune reactivity after high-dose irradiation

International Nuclear Information System (INIS)

Gassmann, W.; Wottge, H.U.; von Kolzynski, M.; Mueller-Ruchholtz, W.

1986-01-01

Immune reactivity after total-body irradiation was investigated in rats using skin graft rejection as the indicator system. After sublethal irradiation with 10.5 Gy (approximately 50% lethality/6 weeks) the rejection of major histocompatibility complex allogeneic skin grafts was delayed significantly compared with nonirradiated control animals (28 versus 6.5 days). In contrast, skin grafts were rejected after 7.5 days in sublethally irradiated animals and 7 days in lethally irradiated animals if additional skin donor type alloantigens--namely, irradiated bone marrow cells--were given i.v. either simultaneously or with a delay of not more than 24 hr after the above conditioning regimen. These reactions were alloantigen-specific. They were observed in six different strain combinations with varying donors and recipients. Starting on day 2 after irradiation, i.v. injection of bone marrow gradually lost its effectivity and skin grafts were no longer rejected with uniform rapidity; skin donor marrow given on days 4 or 8 did not accelerate skin graft rejection at all. These data show that for approximately 1-2 days after high-dose total-body irradiation rats are still capable of starting a vigorous immune reaction against i.v.-injected alloantigens. The phenomenon of impaired rejection of skin grafted immediately after high-dose irradiation appears to result from the poor accessibility of skin graft alloantigens during the early postirradiation phase when vascularization of the grafted skin is insufficient

Maintenance of host leukocytes in peripheral immune compartments following lethal irradiation and bone marrow reconstitution: implications for graft versus host disease.

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Staley, Elizabeth M; Tanner, Scott M; Daft, Joseph G; Stanus, Andrea L; Martin, Steven M; Lorenz, Robin G

2013-03-01

Bone marrow reconstitution is utilized as a tool for disease treatment and as a research technique to elucidate the function of bone marrow derived cells. Clinically successful engraftment is indicated by the development of a functioning immune repertoire. In research, reconstitution is considered successful if >85% of splenic leukocytes are of donor origins. Previous work suggests that splenic reconstitution may not be indicative of reconstitution in the mucosa. We sought to evaluate mucosal reconstitution in animals following a standard bone marrow eradication and reconstitution technique. Bone marrow was harvested from adult B6.SJL donor mice (CD45.1) and injected via either the retro-orbital or intraperitoneal route into lethally irradiated B6 (CD45.2) adult or neonatal recipients respectively. The expression of CD45 by flow cytometry was used to calculate reconstitution with respect to immune compartment and cell type. In reconstituted adult animals 93.2±1.5% of splenic leukocytes expressed the donor CD45.1 antigen thus meeting the standard definition of reconstitution, however only 58.6±13.6% of intestinal lamina propria lymphocytes and 52.4±16.0% of intestinal intraepithelial lymphocytes were of donor origin, confirming splenic reconstitution fails to represent peripheral immune reconstitution. T-cells in the gastrointestinal tract are the most poorly reconstituted, while B-cells appear to be almost universally replaced by donor cells. The inadequate mucosal reconstitution was not corrected by evaluating later time points or by performing the bone marrow transfer during the neonatal period. This demonstration that substantial host T-cells remain in the intestinal mucosa after a "successful" bone marrow transplantation should cause a re-evaluation of data from research bone marrow chimera experiments, as well as the mechanisms for complications after clinical bone marrow transplantation. Copyright © 2013 Elsevier B.V. All rights reserved.

Hydrophilicity improvement of polyethersulfone membranes by grafting methacrylic acid with γ-ray irradiation

International Nuclear Information System (INIS)

Li Jing; Hou Zhengchi; Xie Leidong; Zhang Fengying; Deng Bo

2005-01-01

Grafting methyacrylic acid onto poly(ether sulfone) membranes was realized by means of simultaneous irradiation in liquids. The modified membranes with different grafting ratios were obtained by changing the concentration of methyacrylic acid. It was shown that the grafting ratio increased lineally as the monomer concentration was less than 10% and hydrophilicity of the membranes was improved with increasing grafting ratios. (authors)

Study on the properties of blend rubber prepared with grafted rubber and irradiated rubber by Gamma Rays

International Nuclear Information System (INIS)

Dafader, N. C.; Haque, M. E.; Islam, K. A.

2004-05-01

The blend rubbers were prepared by mixing γ-rays irradiated and monomer grafted rubbers. The monomers, methyl methacrylate (MMA) and styrene were used separately to prepare grafted rubber by exposure to radiation. The physico-chemical properties of the blend rubbers were evaluated. The tensile strength and elongation at break of the blend rubbers decrease whereas modulus at 500% elongation, swelling ratio and permanent set increase with the increased proportion of grafted rubber in the blend. The tear strength of the blend between irradiated and styrene grafted rubbers increases with the increased proportion of grafted rubber but that of the blend of irradiated and MMA grafted rubbers remains almost constant. The blend rubber could be used for special type of application like rubber thread, tube, catheter etc

Effects of Irradiation on Insect Host-Parasite Relationship

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Rahalkar, G. W.; Ramakrishnan, V. [Biology Division, Bhabha Atomic Research Centre, Trombay, Bombay (India)

1968-06-15

Effects of host irradiation on the development of its parasite were investigated. Females of Bracon brevicomis readily accepted irradiated larvae of tile wax moth (Galleria mellonella) and rice moth (Corcyra cephalonica) for oviposition. However, irradiated wax moth larvae adversely influenced the viability of eggs laid on them and also the survival of the parasite grubs feeding on their bodies. The female grubs were affected more than the males. Rice moth larvae, on the other hand, exerted no significant influence on the viability of parasite eggs, but adversely affected the survival of the grubs. The progeny of parents that had been reared on irradiated larvae also exhibited some developmental changes although grown on non-irradiated host larvae, and these changes were more pronounced when G. mellonella was used as the host insect. (author)

Synthesis and Characterization of Konjac Glucomannan-Graft-Polyacrylamide via γ-Irradiation

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Jie Pang

2008-03-01

Full Text Available The synthesis of konjac glucomannan-graft-polyacrylamide (KGM-g-PAM wascarried out at 25°C by γ-irradiation under a N2 atmosphere. The effects of absorbedradiation dosage and monomer concentration on grafting yield and water absorbency werestudied. The grafted copolymers were characterized using Fourier Transform Infrared(FTIR spectroscopy, nuclear magnetic resonance (NMR, x-ray diffraction (XRD,thermogravimetric analysis (TGA and gel permeation chromatography (GPC. Thegrafting yield was observed to increase with increasing absorbed dosage and monomerconcentration. Compared with the original KGM, the grafted copolymers exhibited betterthermal stability and water absorbency. The results suggest that γ-irradiation is convenientand efficient for inducing graft copolymerization of KGM and acrylamide (AM.

Pre-irradiation grafting of hydrophilic monomers onto polyethylene: Pt. 1

International Nuclear Information System (INIS)

Gargan, K.; Kronfli, E.; Lovell, K.V.

1990-01-01

An investigation was carried out to identify compounds which are suitable for use as homopolymerisation inhibitors when grafting acrylic acid or methacrylic acid onto pre-irradiated low-density polyethylene. It was found that certain transition metal compounds were able to suppress the formation of homopolymer whilst still allowing significant levels of grafting to take place. For acrylic acid the most suitable inhibitor found was ferrous sulphate, whilst cupric sulphate or potassium ferrocyanide were favoured for use with methacrylic acid. The influence of the inhibitor concentration on the degree of grafting was also investigated. (author)

Late acute graft-versus-host disease: a prospective analysis of clinical outcomes and circulating angiogenic factors.

Science.gov (United States)

Holtan, Shernan G; Khera, Nandita; Levine, John E; Chai, Xiaoyu; Storer, Barry; Liu, Hien D; Inamoto, Yoshihiro; Chen, George L; Mayer, Sebastian; Arora, Mukta; Palmer, Jeanne; Flowers, Mary E D; Cutler, Corey S; Lukez, Alexander; Arai, Sally; Lazaryan, Aleksandr; Newell, Laura F; Krupski, Christa; Jagasia, Madan H; Pusic, Iskra; Wood, William; Renteria, Anne S; Yanik, Gregory; Hogan, William J; Hexner, Elizabeth; Ayuk, Francis; Holler, Ernst; Watanaboonyongcharoen, Phandee; Efebera, Yvonne A; Ferrara, James L M; Panoskaltsis-Mortari, Angela; Weisdorf, Daniel; Lee, Stephanie J; Pidala, Joseph

2016-11-10

Late acute (LA) graft-versus-host disease (GVHD) is persistent, recurrent, or new-onset acute GVHD symptoms occurring >100 days after allogeneic hematopoietic cell transplantation (HCT). The aim of this analysis is to describe the onset, course, morbidity, and mortality of and examine angiogenic factors associated with LA GVHD. A prospective cohort of patients (n = 909) was enrolled as part of an observational study within the Chronic GVHD Consortium. Eighty-three patients (11%) developed LA GVHD at a median of 160 (interquartile range, 128-204) days after HCT. Although 51 out of 83 (61%) achieved complete or partial response to initial therapy by 28 days, median failure-free survival was only 7.1 months (95% confidence interval, 3.4-19.1 months), and estimated overall survival (OS) at 2 years was 56%. Given recently described alterations of circulating angiogenic factors in classic acute GVHD, we examined whether alterations in such factors could be identified in LA GVHD. We first tested cases (n = 55) and controls (n = 50) from the Chronic GVHD Consortium and then validated the findings in 37 cases from Mount Sinai Acute GVHD International Consortium. Plasma amphiregulin (AREG; an epidermal growth factor [EGF] receptor ligand) was elevated, and an AREG/EGF ratio at or above the median was associated with inferior OS and increased nonrelapse mortality in both cohorts. Elevation of AREG was detected in classic acute GVHD, but not chronic GVHD. These prospective data characterize the clinical course of LA GVHD and demonstrate alterations in angiogenic factors that make LA GVHD biologically distinct from chronic GVHD. © 2016 by The American Society of Hematology.

Acute and chronic graft-versus-host disease after allogeneic peripheral-blood stem-cell and bone marrow transplantation: a meta-analysis.

Science.gov (United States)

Cutler, C; Giri, S; Jeyapalan, S; Paniagua, D; Viswanathan, A; Antin, J H

2001-08-15

Controversy exists as to whether the incidence of graft-versus-host disease (GVHD) is increased after peripheral-blood stem-cell transplantation (PBSCT) when compared with bone marrow transplantation (BMT). We performed a meta-analysis of all trials comparing the incidence of acute and chronic GVHD after PBSCT and BMT reported as of June, 2000. Secondary analyses examined relapse rates after the two procedures. An extensive MEDLINE search of the literature was undertaken. Primary authors were contacted for clarification and completion of missing information. A review of cited references was also undertaken. Sixteen studies (five randomized controlled trials and 11 cohort studies) were included in this analysis. Data was extracted by two pairs of reviewers and analyzed for the outcomes of interest. Meta-analyses, regression analyses, and assessments of publication bias were performed. Using a random effects model, the pooled relative risk (RR) for acute GVHD after PBSCT was 1.16 (95% confidence interval [CI], 1.04 to 1.28; P=.006) when compared with traditional BMT. The pooled RR for chronic GVHD after PBSCT was 1.53 (95% CI, 1.25 to 1.88; P <.001) when compared with BMT. The RR of developing clinically extensive chronic GVHD was 1.66 (95% CI, 1.35 to 2.05; P <.001). The excess risk of chronic GVHD was explained by differences in the T-cell dose delivered with the graft in a meta-regression model that did not reach statistical significance. There was a trend towards a decrease in the rate of relapse after PBSCT (RR = 0.81; 95% CI, 0.62 to 1.05). Both acute and chronic GVHD are more common after PBSCT than BMT, and this may be associated with lower rates of malignant relapse. The magnitude of the transfused T-cell load may explain the differences in chronic GVHD risk.

Graft copolymerization of glycidyl methacrylate onto delignified kenaf fibers through pre-irradiation technique

International Nuclear Information System (INIS)

Sharif, Jamaliah; Mohamad, Siti Fatahiyah; Fatimah Othman, Nor Azilah; Bakaruddin, Nurul Azra; Osman, Hasnul Nizam; Güven, Olgun

2013-01-01

Glycidyl methacrylate grafted kenaf (GMA-g-Kenaf) was prepared by pre-irradiation grafting technique. Kenaf fibers were treated with different concentration of sodium chlorite solution before used as trunk polymer. Treated kenaf fibers were irradiated by electron beam followed by grafting reaction in GMA/water emulsion system. The degree of grafting was determined as a function of absorbed dose, reaction time, reaction temperature and concentration of monomer. The results showed that the lignin content was decreased from 14.3% to as low as 3.3% with the increased of sodium chlorite concentration. This was evidenced by SEM pictures which show the surface of treated kenaf fibers was cleaner and smoother compared to that of untreated one. The degree of grafting increased with the increase of absorbed dose, reaction temperature, reaction time and monomer concentration as well as with decreasing lignin content. Formation of graft copolymer was confirmed with SEM, FTIR analysis. The structural investigation by XRD showed that degree of crystallinity of graft copolymers decreased with the increase in degree of grafting. - Highlights: • We used kenaf fibers for radiation induce graft copolymerization with GMA. • Kenaf fibers was treated to remove lignin in order to increase grafting yield. • Treated kenaf fibers were graft copolymerize through preirradiation technique. • Optimum conditions for graft copolymerization of kenaf fibers were established. • Formation of graft copolymer is also confirmed with SEM, FTIR and XRD

Meniscal allograft transplantation. Part 1: systematic review of graft biology, graft shrinkage, graft extrusion, graft sizing, and graft fixation.

Science.gov (United States)

Samitier, Gonzalo; Alentorn-Geli, Eduard; Taylor, Dean C; Rill, Brian; Lock, Terrence; Moutzouros, Vasilius; Kolowich, Patricia

2015-01-01

To provide a systematic review of the literature regarding five topics in meniscal allograft transplantation: graft biology, shrinkage, extrusion, sizing, and fixation. A systematic literature search was conducted using the PubMed (MEDLINE), ScienceDirect, and EBSCO-CINAHL databases. Articles were classified only in one topic, but information contained could be reported into other topics. Information was classified according to type of study (animal, in vitro human, and in vivo human) and level of evidence (for in vivo human studies). Sixty-two studies were finally included: 30 biology, 3 graft shrinkage, 11 graft extrusion, 17 graft size, and 6 graft fixation (some studies were categorized in more than one topic). These studies corresponded to 22 animal studies, 22 in vitro human studies, and 23 in vivo human studies (7 level II, 10 level III, and 6 level IV). The principal conclusions were as follows: (a) Donor cells decrease after MAT and grafts are repopulated with host cells form synovium; (b) graft preservation alters collagen network (deep freezing) and causes cell apoptosis with loss of viable cells (cryopreservation); (c) graft shrinkage occurs mainly in lyophilized and gamma-irradiated grafts (less with cryopreservation); (d) graft extrusion is common but has no clinical/functional implications; (e) overall, MRI is not superior to plain radiograph for graft sizing; (f) graft width size matching is more important than length size matching; (g) height appears to be the most important factor influencing meniscal size; (h) bone fixation better restores contact mechanics than suture fixation, but there are no differences for pullout strength or functional results; and (i) suture fixation has more risk of graft extrusion compared to bone fixation. Systematic review of level II-IV studies, Level IV.

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

Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rγnull mice display a T-effector memory phenotype.

Science.gov (United States)

Ali, Niwa; Flutter, Barry; Sanchez Rodriguez, Robert; Sharif-Paghaleh, Ehsan; Barber, Linda D; Lombardi, Giovanna; Nestle, Frank O

2012-01-01

The occurrence of Graft-versus-Host Disease (GvHD) is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; "Hu-PBMC mice") are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null)), notably the NOD-scid IL-2Rγ(null) (NSG) and BALB/c-Rag2(null) IL-2Rγ(null) (BRG) mice, has led to improved human cell engraftment. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45(+) compartment and higher engraftment levels of CD3(+) T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (T(EM)) phenotype and high levels of cutaneous lymphocyte antigen (CLA) expression. Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting T(EM)-cell driven GvHD.

Xenogeneic graft-versus-host-disease in NOD-scid IL-2Rγnull mice display a T-effector memory phenotype.

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Niwa Ali

Full Text Available The occurrence of Graft-versus-Host Disease (GvHD is a prevalent and potentially lethal complication that develops following hematopoietic stem cell transplantation. Humanized mouse models of xenogeneic-GvHD based upon immunodeficient strains injected with human peripheral blood mononuclear cells (PBMC; "Hu-PBMC mice" are important tools to study human immune function in vivo. The recent introduction of targeted deletions at the interleukin-2 common gamma chain (IL-2Rγ(null, notably the NOD-scid IL-2Rγ(null (NSG and BALB/c-Rag2(null IL-2Rγ(null (BRG mice, has led to improved human cell engraftment. Despite their widespread use, a comprehensive characterisation of engraftment and GvHD development in the Hu-PBMC NSG and BRG models has never been performed in parallel. We compared engrafted human lymphocyte populations in the peripheral blood, spleens, lymph nodes and bone marrow of these mice. Kinetics of engraftment differed between the two strains, in particular a significantly faster expansion of the human CD45(+ compartment and higher engraftment levels of CD3(+ T-cells were observed in NSG mice, which may explain the faster rate of GvHD development in this model. The pathogenesis of human GvHD involves anti-host effector cell reactivity and cutaneous tissue infiltration. Despite this, the presence of T-cell subsets and tissue homing markers has only recently been characterised in the peripheral blood of patients and has never been properly defined in Hu-PBMC models of GvHD. Engrafted human cells in NSG mice shows a prevalence of tissue homing cells with a T-effector memory (T(EM phenotype and high levels of cutaneous lymphocyte antigen (CLA expression. Characterization of Hu-PBMC mice provides a strong preclinical platform for the application of novel immunotherapies targeting T(EM-cell driven GvHD.

Graft-copolymerization of polyethersulfone microporous membrane with electron beam simultaneous irradiation method

International Nuclear Information System (INIS)

Han Zhaolei; Meng Fanxia; Wang Yongxia; Liu Xiaoguang; Wang Rong

2010-01-01

Polyethersulfone(PES) microporous membrane was grafted with methacrylic acid under electron beam irradiation. Controlling the monomer concentration or the absorbed dose, the relationships of the degree of grafting with the monomer concentration and the absorbed dose were obtained for optimum the monomer concentration and absorbed dose. The grafted membrane was characterized by FT-IR and SEM, and the hydrophilicity contact angle of the membrane was tested. (authors)

Safety and efficacy of autologous serum eye drop for treatment of dry eyes in graft-versus-host disease.

Science.gov (United States)

Azari, Amir A; Karadag, Remzi; Kanavi, Mozhgan Rezaei; Nehls, Sarah; Barney, Neal; Kim, Kyungmann; Longo, Walter; Hematti, Peiman; Juckett, Mark

2017-06-01

To evaluate the treatment of autologous serum eye drops (ASED) on dry eyes in patients with graft-versus-host disease (GVHD). A retrospective chart review of 35 patients with a history of ocular GVHD following hematopoietic stem cell transplantation that used ASED to alleviate dry eye symptoms was performed. Patients were categorized into three different groups. If patients had available ophthalmic data before and after starting treatment was group 1 (n = 14), had available ophthalmic data after starting treatment in group 2 (n = 10) and had available ophthalmic data before treatment or did not have any data after starting treatment in group 3 (n = 11). Data were collected on patient's age, gender, primary diagnosis, visual acuity and fluorescein corneal staining were collected on individual eyes in order to evaluate the efficacy of the ASED on alleviating dry eye-related signs and symptoms. No adverse ocular effect from the ASED was found in our series (except one fungal keratitis). All patients reported either improvement (55%) or stability (45%) in their ocular symptoms upon the use of ASED. In patients with available data before and after starting treatment, the corneal staining score improved by a median of 1 (p = 0.003) and the LogMAR visual acuity had a non-significant improvement. In our study, ASED used by patients with ocular GVHD were both safe and effective. ASED should be considered in patients with GVHD who suffer from dry eyes.

PVDF multifilament yarns grafted with polystyrene induced by γ-irradiation: Influence of the grafting parameters on the mechanical properties

International Nuclear Information System (INIS)

Marmey, P.; Porte, M.C.; Baquey, Ch.

2003-01-01

The development of alternative prosthetic materials for cardiovascular applications has found growing interest due to the failure to date to be able to implement functional patent small diameter vascular grafts (diameter <5 mm). For instance, the successful implantation of small diameter polyester (PET) and expanded polytetrafluoroethylene (PTFEe) vascular grafts has not been achieved in humans. Our strategy is to work with a new multifilament yarns biomaterial, produced from polyvinylidene fluoride (PVDF), which shows suitable mechanical properties, such as a lower tensile modulus than PET and PTFEe. The required biological properties sought for (i.e. low thrombogenicity) could be achieved by 'heparin-like' surface modification treatments in order to modify the thrombogenicity levels of the polymeric materials [Ann. Biomed. Eng. 7 (1979) 429]. A four step method is necessary to achieve this 'heparin-like' surface transformation [J. Biomed. Mater. Res. 52 (2000) 119]. The first step consists in grafting polystyrene onto the PVDF surface by γ irradiation. The purpose of this study was to evaluate the influence of grafting parameters on the mechanical properties: (i) γ-ray irradiation time and (ii) grafting time of styrene monomers, which polymerize and form polystyrene bound to the PVDF surface

Graft copolymerization of N-vinyl-2-pyrrolidone onto pre-irradiated poly(vinylidene fluoride) powder

International Nuclear Information System (INIS)

Xu Chenqi; Huang Wei; Zhou Yongfeng; Yan Deyue; Chen Shutao; Huang Hua

2012-01-01

Graft copolymerization of N-vinyl-2-pyrrolidone (NVP) onto 60 Co γ-ray pre-irradiated poly (vinylidene fluoride) (PVDF) powder was investigated to find out the relationship between the degree of grafting (DG) and various factors, including monomer concentration, irradiation dose, reaction time, catalyst and so on. The DG can be calculated by comparing the amount of nitrogen element in the resulting copolymer (PVDF-g-PVP) powder with that in PVP on the basis of element analysis. The presence of PVP in the resulting PVDF powder was confirmed by the comparative studies of pristine PVDF and grafted PVDF powder through Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR), X-ray photoelectron spectroscopy (XPS), thermo gravimetric analyzer (TGA) and differential scanning calorimetry (DSC), respectively. When the reaction was performed at the monomer concentration of 20% (vol.) and the absorbed dose of 40 kGy for 3 h in water, the max. DG of 17.7% was obtained. - Highlights: ► We modify pristine PVDF powders with NVP by the pre-irradiated graft polymerization. ► The various factors influencing the degree of grafting are investigated in detail. ► The optimal condition of graft polymerization is obtained. ► The polymerization is processed at 20% (vol.) of NVP and 40kGy for 3 hours in water. ► The maximum degree of grafting is 17.7 % at such a condition.

Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong graft-versus-leukemia effects across MHC barriers in full chimeras.

Science.gov (United States)

Ghosh, Arnab; Koestner, Wolfgang; Hapke, Martin; Schlaphoff, Verena; Länger, Florian; Baumann, Rolf; Koenecke, Christian; Cornberg, Markus; Welte, Karl; Blazar, Bruce R; Sauer, Martin G

2009-04-30

Antigen-presenting cells (APCs) of host origin drive graft-versus-leukemia (GVL) effects but can also trigger life-threatening graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT) across major histocompatibility complex (MHC) barriers. We show that in vitro priming of donor lymphocytes can circumvent the need of recipient-derived APCs in vivo for mediating robust GVL effects and significantly diminishes the risk of severe GVHD. In vitro, generated and expanded T cells (ETCs) mediate anti-leukemia effects only when primed on recipient-derived APCs. Loading of APCs in vitro with leukemia cell lysate, chimerism status of the recipient, and timing of adoptive transfer after HCT are important factors determining the outcome. Delayed transfer of ETCs resulted in strong GVL effects in leukemia-bearing full chimera (FC) and mixed chimera (MC) recipients, which were comparable with the GVL/GVHD rates observed after the transfer of naive donor lymphocyte infusion (DLI). Upon early transfer, GVL effects were more pronounced with ETCs but at the expense of significant GVHD. The degree of GVHD was most severe in MCs after transfer of ETCs that had been in vitro primed either on nonpulsed recipient-derived APCs or with donor-derived APCs.

Intraoperative extracorporeal autogenous irradiated tendon grafts for functional limb salvage surgery of soft tissue sarcomas of the wrist and hand.

Science.gov (United States)

Omori, Shinsuke; Hamada, Kenichiro; Outani, Hidetatsu; Oshima, Kazuya; Joyama, Susumu; Tomita, Yasuhiko; Naka, Norifumi; Araki, Nobuhito; Yoshikawa, Hideki

2015-05-12

In patients with soft tissue sarcoma of the wrist and hand, limb salvage operation is extremely challenging for surgeons in attempting a complete tumor resection with negative surgical margins. In this study, we report four patients with soft tissue sarcoma of the wrist and hand treated by limb salvage operation with intraoperative extracorporeal autogenous irradiated tendon grafts. The patients were all male, and the mean age at the time of surgery was 45 years. Histological diagnoses included clear cell sarcoma in two patients, synovial sarcoma in one, and angiosarcoma in one. All four patients had high grade tumors, wherein three had American Joint Committee on Cancer (AJCC) stage III disease and one with AJCC stage IV disease. The tumors were resected en bloc with involved tendons. The tendons were isolated from the resected tissues, irradiated ex vivo, and re-implanted into the host tendons. In one patient, the bone was resected additionally because of tumor invasion to the bone. Hand function was evaluated using Musculoskeletal Tumor Society (MSTS) rating system. Of the four patients, three died of distant metastatic disease. The remaining patient lives and remains disease-free. The mean follow-up period was 33 months. One patient had local recurrence outside the irradiated graft at 20 months after surgery. The functional rating was 22. Lower scores were seen in patients with reconstruction of flexor tendons than extensor tendons. Limb salvage operation with intraoperative extracorporeal autogenous irradiated tendon grafts is an acceptable method in selected patients with soft tissue sarcoma of the wrist and hand.

Cellular basis of the immunohematologic defects observed in short-term semiallogeneic B6C3F1→C3H chimeras: evidence for host-versus-graft reaction initiated by radioresistant T cells

International Nuclear Information System (INIS)

Aizawa, S.; Sado, T.; Kamisaku, H.; Kubo, E.

1980-01-01

Lethally irradiated C3Hf mice reconstituted with a relatively low dose (2 x 10 6 ) of B6C3F 1 bone marrow cells (B6C3F 1 →C3Hf chimeras) frequently manifest immunohematologic deficiencies during the first month following injection of bone marrow cells. They show slow recovery of antibody-forming potential to sheep red blood cells (SRBC) as compared to that observed in syngeneic (C3Hf→C3Hf or B6C3F 1 →B6C3F 1 ) chimeras. They also show a deficiency of B-cell activity as assessed by antibody response to SRBC following further reconstitution with B6C3F 1 -derived thymus cells 1 week after injection of bone marrow cells. A significant fraction of B6C3F 1 →C3Hf chimeras was shown to manifest a sudden loss of cellularity of spleens during the second week following injection of bone marrow cells even though cellularity was restored to the normal level within 1 week. The splenic mononuclear cells recovered from such chimeras almost invariably showed strong cytotoxicity against target cells expressing donor-type specific H-2 antigens (H-2/sup b/) when assesed by 51 Cr-release assay in vitro. The effector cells responsible for the observed anti-donor specific cytotoxicity were shown to be residual host-derived T cells. These results indicate strongly that residual host T cells could develop anti-donor specific cytotoxicity even after exposure to a supralethal dose (1050 R) of radiation and that the immunohematologic disturbances observed in shortterm F 1 to parent bone marrow chimeras (B6C3F 1 →C3Hf) were due to host-versus-graft reaction (HVGR) initiated by residual host T cells. The implication of these findings on the radiobiological nature of the residual T cells and the persistence of potentially anti-donor reactive T-cell clones in long-surviving allogeneic bone marrow chimeras was discussed

Blood, blood compounds and cell cultures irradiation in clinical radiotherapy equipment: studies on ideal volume and dose

International Nuclear Information System (INIS)

Fernandes, Marco Antonio R.; Pereira, Adelino Jose; Novaes, Paulo Eduardo R.S.

1995-01-01

The authors present the technic and equipment used by the Physical Radiologic Service of Radiation Therapy Department of A.C. Camargo Hospital to irradiate blood and blood compounds. The practical routine is illustrated. The results from others Institutions are presented, discussing about the homogeneity of dose of 2000 to 3500 c Gy to all target volume, sufficient to neutralize cells responsible by graft-versus-host disease from blood transfusions. (author). 6 refs., 2 figs., 1 tab

The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

Energy Technology Data Exchange (ETDEWEB)

Easterling, K.J.; Trumble, T.E. (Yale Univ. School of Medicine, New Haven, CT (USA))

1990-10-01

Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal.

The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

International Nuclear Information System (INIS)

Easterling, K.J.; Trumble, T.E.

1990-01-01

Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal

Acrylamide graft over silicone rubber tubes by simultaneous irradiation in 60 Co source

International Nuclear Information System (INIS)

Julio, C.A.; Higa, O.Z.

1992-01-01

The synthesis of a hydrogel having silicone rubber tubes as support was carried out through the radiation grafting technique. The best conditions for the grafting development were determined in relation to the monomer and inhibitor concentration, dose rate and irradiation dose. The addition of cupric ions in the process inhibited the acrylamide homo polymerization and enhanced the grafting yield. The water content in the grafted tubes characterized the hydrophilic property of the material. (author)

Abrogation of bone marrow allograft resistance in mice by increased total body irradiation correlates with eradication of host clonable T cells and alloreactive cytotoxic precursors

International Nuclear Information System (INIS)

Schwartz, E.; Lapidot, T.; Gozes, D.; Singer, T.S.; Reisner, Y.

1987-01-01

Host-vs-graft activity presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, conditioned exactly like leukemia patients, it was shown that residual host clonable T cells, as well as alloreactive cytotoxic precursors, were present in peripheral blood and spleen after completion of cytoreduction. We have now extended this study in a mouse model for allogeneic bone marrow transplantation. C 3 H/HeJ mice were treated by 9 Gy total body irradiation (TBI), and 24 hr later their spleen cells were cultured in the presence of T cell growth factor and phytohemagglutinin according to the limit dilution procedure. After 7 days of culture the average frequency of clonable cells was 2.5 X 10(-3) compared with 37 X 10(-3) in the spleens of normal mice. The T cell derivation of the growing cells was ascertained by complement-mediated cytotoxicity with anti-Thy-1 as well as with anti-Lyt-2 and anti-Ly-3T4. In parallel, we found that the initial engraftment rate of bone marrow allograft in mice given 9 Gy TBI was lower than that found in recipients of syngeneic marrow. The initial engraftment rate was measured by the number of colony-forming units in the spleen and by splenic uptake of 125 IUdR. A slight increase in TBI from 9 Gy to 11 Gy markedly reduced the difference in the number of spleen colony-forming units or the IUdR uptake between recipients of allogeneic and syngeneic bone marrow. This increase in TBI also coincided with eradication of detectable clonable T cells. Moreover, in mice transplanted with T cell-depleted bone marrow after 9 Gy TBI, we also demonstrate that cytotoxicity against donor-type target cells is present in the spleen 10 to 14 days posttransplantation, whereas in mice treated by 11 Gy TBI such alloreactivity could not be detected

Five-Strand versus Four-Strand Hamstring Tendon Graft Technique for Anterior Cruciate Ligament Reconstruction: A Biomechanical Comparison.

Science.gov (United States)

Vaillant, Eric R; Parks, Brent G; Camire, Lyn M; Hinton, Richard Y

2017-11-01

The aim of this article is to compare diameter and stiffness, displacement, and strain in a five-strand versus four-strand hamstring graft for anterior cruciate ligament reconstruction. Eight matched pairs of lower extremities underwent four-strand or five-strand hamstring graft reconstruction. Diameter was significantly higher in the five-strand versus the four-strand construct ( p  = 0.002). No significant difference was found between the groups in construct displacement or stiffness. Significantly higher strain was observed in the inner limb versus the outer limb in the four-strand construct ( p  = 0.001) and in the inner limb versus the fifth limb in the 5-strand construct ( p  = 0.004). A fifth limb added to a four-strand hamstring graft significantly increased graft diameter but did not significantly change stiffness or displacement, suggesting that attachment of additional graft material via suture did not provide for full incorporation of the added limb into the graft at time zero. The inner limb in both constructs absorbed significantly greater load than did other limbs. The use of suture to attach additional material to a four-strand hamstring graft may not contribute to improved biomechanical qualities of the graft at time zero. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Solvent and irradiation doses effects on the ion exchange capacity of sulfonated styrene grafted PVDF

International Nuclear Information System (INIS)

Ferreira, Henrique P.; Parra, Duclerc F.; Lugao, Ademar B.

2011-01-01

Polymers exhibiting ion exchange capacity are studied for many years due to their application in several fields, such as membranes for proton exchange fuel cells, filtration membranes, heavy ions recovery and artificial muscles and sensors. Radiation induced grafting followed by sulfonation is a well-known way to obtain ion exchange polymers. Fluorinated polymers are frequently used as polymeric matrix for grafting due to their excellent physicochemical properties. Radiation induced grafting of styrene into poly (vinylidene fluoride) (PVDF) by simultaneous method in 1:1 styrene/toluene or styrene/N,N-dimethylformamide solutions was studied. Irradiations were performed under nitrogen atmosphere, room temperature and at doses of 5, 10 and 20 kGy with dose rate of 5 kGy.h -1 from a 60 Co gamma source. After washing, grafted materials were sulfonated in 10% chlorosulfonic acid/1,2-dichloroethane solutions for 4 h at room temperature. Characterization shows that increasing irradiation dose corresponds to increases in the grafting yield (GY %) gravimetrically calculated and these different solvents shows different grafting behaviors. Toluene allows no more than 3 % of grafting while DMF allows up to 55 % of grafting in the same condition. Grafting in toluene solution occurs on the surface and in DMF solution it occurs in the bulk, as confirmed by SEM. Both irradiation doses and solvent used have direct effects in the ion exchange capacities (calculated after titrations). FT-IR spectra exhibit new peaks after grafting and after sulfonation, attributed to grafted monomer and sulfonic groups attached to the styrene. DSC shows differences in thermal behavior of the polymer before and after each step. (author)

Solvent and irradiation doses effects on the ion exchange capacity of sulfonated styrene grafted PVDF

Energy Technology Data Exchange (ETDEWEB)

Ferreira, Henrique P.; Parra, Duclerc F.; Lugao, Ademar B. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2011-07-01

Polymers exhibiting ion exchange capacity are studied for many years due to their application in several fields, such as membranes for proton exchange fuel cells, filtration membranes, heavy ions recovery and artificial muscles and sensors. Radiation induced grafting followed by sulfonation is a well-known way to obtain ion exchange polymers. Fluorinated polymers are frequently used as polymeric matrix for grafting due to their excellent physicochemical properties. Radiation induced grafting of styrene into poly (vinylidene fluoride) (PVDF) by simultaneous method in 1:1 styrene/toluene or styrene/N,N-dimethylformamide solutions was studied. Irradiations were performed under nitrogen atmosphere, room temperature and at doses of 5, 10 and 20 kGy with dose rate of 5 kGy.h{sup -1} from a {sup 60}Co gamma source. After washing, grafted materials were sulfonated in 10% chlorosulfonic acid/1,2-dichloroethane solutions for 4 h at room temperature. Characterization shows that increasing irradiation dose corresponds to increases in the grafting yield (GY %) gravimetrically calculated and these different solvents shows different grafting behaviors. Toluene allows no more than 3 % of grafting while DMF allows up to 55 % of grafting in the same condition. Grafting in toluene solution occurs on the surface and in DMF solution it occurs in the bulk, as confirmed by SEM. Both irradiation doses and solvent used have direct effects in the ion exchange capacities (calculated after titrations). FT-IR spectra exhibit new peaks after grafting and after sulfonation, attributed to grafted monomer and sulfonic groups attached to the styrene. DSC shows differences in thermal behavior of the polymer before and after each step. (author)

The survey of blood irradiation equipment. About the present condition and a problem

International Nuclear Information System (INIS)

Irikawa, Tomio; Kuramitsu, Hideaki; Tanaka, Keiko; Hamamoto, Takaaki

2001-01-01

Once it shows the symptoms of post transfusion graft versus host disease, mostly all examples follow fatal progress. For this reason, generally 15-50 Gy irradiation is performed into the blood for transfusion by the ''guideline of radiation'' of the Japan society of blood transfusion as measure only in development-of-symptoms prevention. This time, the questionnaire was performed for the hospital of 100 institutions of the Chugoku and the Shikoku district, and the actual condition of management employment of blood irradiation equipment was investigated. Consequently, there was little institution in which the medical-examination radiological technologist is participating directly, and it was made clear dependent on the maker of an equipment management. (author)

Quality evaluation of blood irradiation process;Avaliacao da qualidade do processo de irradiacao de hemocomponentes

Energy Technology Data Exchange (ETDEWEB)

Goto, R.E.; Medeiros, R.B. [Universidade Federal de Sao Paulo (DDI/UNIFESP), SP (Brazil). Dept. de Diagnostico por Imagem. Coordenadoria de Fisica e Higiene das Radiacoes

2009-07-01

An adverse reaction in blood transfusion is the graft versus host disease (GVHD). This disease affects immunodeficient or immunosuppressed patients where transfused T cells proliferate and initiate a host's immune system reaction. Blood gamma irradiation is the most efficient way to inhibit lymphocyte T blastic transformation and mitotic activity and it is the most effective method to combat this disorder. However, there is no fast and effective system to analyze the dose distribution in the irradiation process and guarantee that the absorbed doses are in agreement with FDA recommendations. This study aims to establish a periodic quality control of the gammacell irradiators using radiochromic films properly calibrated. The quality control is simply and effective to combat GVHD as well as is useful to detect mechanical fails at rotation set system through the dose uniformity analysis. It was possible to verify the uniformity ranged from -72.38% to 106.33% and some blood bag received doses not compatible with recommended international threshold. (author)

Synthesis of perm-selective membranes by grafting acrylic acid into air-irradiated Teflon-FEP films

Science.gov (United States)

Bozzi, Annick; Chapiro, Adolphe

Grafting acrylic acid into air-irradiated Teflon-FEP films was investigated. Pre-irradiation doses ranged from 0.5 to 10 kGy. Grafting occurred at 45 or 60°C. Homopolymerization inhibitors, ferrous ions or methylene blue, were added to the system. It was found that after completion of the reaction, within 40-100 min, membranes were obtained with very low electric resistivities. The influence of added inhibitors, pre-irradiation dose and grafting temperature was studied. From the results it is concluded that the initiating centers in air-irradiated Teflon-FEP are, on the one hand, peroxides of structure POOP', in which P is a polymeric radical and Pprime; a small fragment, and on the other trapped PO .2 radicals. The latter only react after losing their oxygen. In the presence of polymerization inhibitors, initiation involves a redox process which reduces the overall activation energy.

Synthesis of perm-selective membranes by grafting acrylic acid into air-irradiated Teflon-FEP films

International Nuclear Information System (INIS)

Bozzi, Annick; Chapiro, Adolphe

1988-01-01

Grafting acrylic acid into air-irradiated Teflon-FEP films was investigated. Pre-irradiation doses ranged from 0.5 to 10 kGy. Grafting occurred at 45 or 60 0 C. Homopolymerization inhibitors, ferrous ions or methylene blue, were added to the system. It was found that after completion of the reaction, within 40-100 min, membranes were obtained with very low electric resistivities. The influence of added inhibitors, pre-irradiation dose and grafting temperature was studied. From the results it is concluded that the initiating centers in air-irradiated Teflon-FEP are, on the one hand, peroxides of structure POOP', in which P is a polymeric radical and P' a small fragment, and on the other hand trapped PO 2 sup(·) radicals. The latter only react after losing their oxygen. In the presence of polymerization inhibitors, initiation involves a redox process which reduces the overall activation energy. (author)

Total lymphoid irradiation and cyclophosphamide conditioning prior to bone marrow transplantation for patients with severe aplastic anemia

International Nuclear Information System (INIS)

Ramsay, N.K.; Kim, T.H.; McGlave, P.; Goldman, A.; Nesbit, M.E. Jr.; Krivit, W.; Woods, W.G.; Kersey, J.H.

1983-01-01

A preparative regimen, consisting of total lymphoid irradiation and cyclophosphamide, was utilized in 40 patients with severe aplastic anemia undergoing allogeneic marrow transplantation. This regimen was successful in decreasing rejection in these previously transfused patients, as only one patient rejected the marrow graft. Twenty-nine of the 40 transplanted patients are surviving from 1.5 to 59 mo, with a median follow-up of 24 mo. The actuarial survival rate for these heavily transfused patients with aplastic anemia is 72% at 2 yr. This preparative regimen is extremely effective in decreasing rejection following transplantation for severe aplastic anemia. Future efforts in this area must be aimed at the elimination of graft-versus-host disease and control of fatal infections

Treatment of chronic granulocytic leukemia by chemotherapy, total body irradiation and allogeneic bone marrow transplantation

Energy Technology Data Exchange (ETDEWEB)

Doney, K; Buckner, C D; Sale, G E; Ramberg, R; Boyd, C; Thomas, E D [Fred Hutchinson Cancer Research Institute; Washington Univ., Seattle (USA). School of Medicine)

1978-01-01

Fourteen patients with chronic granulocytic leukemia received bone marrow grafts from HLA identical siblings. Ten patients were in blast crisis prior to grafting, three were in an accelerated phase of their disease, and one was aplastic secondary to chemotherapy. Prior to transplant all patients were conditioned with chemotherapy including cyclophosphamide plus 1,000 rad of total body irradiation. Ten patients achieved engraftment while four died 1 to 26 days after marrow infusion without functioning grafts. Two patients reveived a second infusion of donor marrow because of delayed engraftment. Neither marrow cell dose nor presence of myelofibrosis correlated with succesful engraftment. Three out of ten engrafted patients developed graft-versus-host disease. Interstitial pneumonia occurred in seven patients. The immediate cause of death was bacterial septicemia in six patients. All evidence of leukemia disappeared in nine out of ten evaluable patients. The median survival was 43 days. One patient had a complete remission of 16 months duration.

Treatment of chronic granulocytic leukemia by chemotherapy, total body irradiation and allogeneic bone marrow transplantation

International Nuclear Information System (INIS)

Doney, K.; Buckner, C.D.; Sale, G.E.; Ramberg, R.; Boyd, C.; Thomas, E.D.; Washington Univ., Seattle

1978-01-01

Fourteen patients with chronic granulocytic leukemia received bone marrow grafts from HLA identical siblings. Ten patients were in blast crisis prior to grafting, three were in an accelerated phase of their disease, and one was aplastic secondary to chemotherapy. Prior to transplant all patients were conditioned with chemotherapy including cyclophosphamide plus 1,000 rad of total body irradiation. Ten patients achieved engraftment while four died 1 to 26 days after marrow infusion without functioning grafts. Two patients reveived a second infusion of donor marrow because of delayed engraftment. Neither marrow cell dose nor presence of myelofibrosis correlated with succesful engraftment. Three out of ten engrafted patients developed graft-versus-host disease. Interstitial pneumonia occurred in seven patients. The immediate cause of death was bacterial septicemia in six patients. All evidence of leukemia disappeared in nine out of ten evaluable patients. The median survival was 43 days. One patient had a complete remission of 16 months duration. (Author)

T-regulatory cells in chronic rejection versus stable grafts.

Science.gov (United States)

Al-Wedaie, Fatima; Farid, Eman; Tabbara, Khaled; El-Agroudy, Amgad E; Al-Ghareeb, Sumaya M

2015-04-01

Studying regulatory T cells in kidney allograft acceptance versus chronic rejection may help in the understanding of more mechanisms of immune tolerance and, in the future, may enable clinicians to induce immune tolerance and decrease the use of immunosuppressive drugs. The aim of the current study was to evaluate regulatory T cells in kidney transplant patients with stable graft versus transplant with biopsy-proven chronic rejection. The 3 groups that were studied included: kidney transplanted patients with no rejection episodes (n = 43); transplanted patients with biopsy-proven renal rejection (n = 27); and healthy age-matched nontransplanted individuals as controls (n = 42).The percentage of regulatory T cells (CD4+CD25+Foxp3+) in blood was determined by flow cytometry. The regulatory T cell percentage was significantly lower in chronic rejection patients than control or stable graft groups. No significant difference was observed in regulatory T cell percentage between the stable graft and control groups. In the stable graft group, patients on rapamycin had a significantly higher regulatory T cell percentage than patients on cyclosporine. No effect of donor type, infection, or duration after transplant was observed on regulatory T cell percentage. The results of the current study are consistent with previous studies addressing the function of regulatory T cells in inducing immunotolerance after kidney transplant. Considering the established role of regulatory T cells in graft maintenance and our observation of high regulatory T cell percentage in patients receiving rapamycin than cyclosporine, we recommend including rapamycin when possible in immunosuppressive protocols. The findings from the current study on the chronic rejection group support ongoing research of having treatment with regulatory T cells, which may constitute a novel, efficient antirejection therapy in the future.

Blood compounds irradiation process: assessment of absorbed dose using Fricke and Thermoluminescent dosimetric systems

Energy Technology Data Exchange (ETDEWEB)

Soares, Gabriela de Amorim; Squair, Peterson Lima; Pinto, Fausto Carvalho; Belo, Luiz Claudio Meira; Grossi, Pablo Andrade [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN-CNEN/MG), Belo Horizonte, MG (Brazil)], e-mail: gas@cdtn.br, e-mail: pls@cdtn.br, e-mail: fcp@cdtn.br, e-mail: lcmb@cdtn.br, e-mail: pabloag@cdtn.br

2009-07-01

The assessment of gamma absorbed doses in irradiation facilities allows the quality assurance and control of the irradiation process. The liability of dose measurements is assign to the metrological procedures adopted including the uncertainty evaluation. Fricke and TLD 800 dosimetric systems were used to measure absorbed dose in the blood compounds using the methodology presented in this paper. The measured absorbed doses were used for evaluating the effectiveness of the irradiation procedure and the gamma dose absorption inside the irradiation room of a gamma irradiation facility. The radiation eliminates the functional and proliferative capacities of donor T-lymphocytes, preventing Transfusion associated graft-versus-host disease (TA-GVHD), a possible complication of blood transfusions. The results show the applicability of such dosimetric systems in quality assurance programs, assessment of absorbed doses in blood compounds and dose uniformity assign to the blood compounds irradiation process by dose measurements in a range between 25 Gy and 100 Gy. (author)

Blood compounds irradiation process: assessment of absorbed dose using Fricke and Thermoluminescent dosimetric systems

International Nuclear Information System (INIS)

Soares, Gabriela de Amorim; Squair, Peterson Lima; Pinto, Fausto Carvalho; Belo, Luiz Claudio Meira; Grossi, Pablo Andrade

2009-01-01

The assessment of gamma absorbed doses in irradiation facilities allows the quality assurance and control of the irradiation process. The liability of dose measurements is assign to the metrological procedures adopted including the uncertainty evaluation. Fricke and TLD 800 dosimetric systems were used to measure absorbed dose in the blood compounds using the methodology presented in this paper. The measured absorbed doses were used for evaluating the effectiveness of the irradiation procedure and the gamma dose absorption inside the irradiation room of a gamma irradiation facility. The radiation eliminates the functional and proliferative capacities of donor T-lymphocytes, preventing Transfusion associated graft-versus-host disease (TA-GVHD), a possible complication of blood transfusions. The results show the applicability of such dosimetric systems in quality assurance programs, assessment of absorbed doses in blood compounds and dose uniformity assign to the blood compounds irradiation process by dose measurements in a range between 25 Gy and 100 Gy. (author)

A study of the behaviour of irradiated or unirradiated grafts in the camera aquosa of irradiated and unirradiated animals

International Nuclear Information System (INIS)

Djalali-Behzad, G.

1969-06-01

Following grafts of new born mice spinal ganglia in the 'camera aquosa' of adult mice, the authors tried hematopoietic tissue grafts in the same conditions. The growth of iso-logous and hetero-logous bone marrow in the 'camera aquosa' showed that this tissue, even after exposure to supralethal doses, was capable of survival and growth. A counter-experiment with non irradiated bone marrow grafts in the 'camera aquosa' of rats delivered 700 rads led to the conclusion that the environment, intoxicated by exposure, acted on the graft so that after vascularization it became unable to grow. (author) [fr

Predominance of granulocytopoiesis in bone marrow grafts in the omenta of mice treated with erythropoietin

International Nuclear Information System (INIS)

Meck, R.A.; Laissue, J.A.

1977-01-01

The effects of erythropoietin on the differentiation of murine bone marrow injected into the omenta of x-irradiated mice were investigated. Experimental hosts were injected with 2.5 units of erythropoietin on days 0-7 and sacrificed on day 10. Control hosts were injected with saline or sheep serum. After 10 days the grafts were > 95% granulocytic regardless of host treatment. Since these grafts contain multipotent hematopoietic stem cells and the experimental hosts were exposed to large doses of erythropoietin, the results of this experiment indicate that a specialized microenvironment is required for murine erythropoiesis in vivo. (author)

Grafting study of polysulfone polymeric membranes by gamma ray irradiation

International Nuclear Information System (INIS)

Furtado Filho, Acacio A.M.; Gomes, Ailton de S.

2011-01-01

Radiation-induced grafting of styrene poli sulfone films were investigated by simultaneous method in solution using gamma-ray from a radio nuclide 60 Co source. The gamma-ray energy of high intensity induced breaking of chemical bonds leading to free radical formation. The radical start a conventional polymerization sequence comparable with that obtained with a chemical catalyst acting as initiator. The effects of grafting conditions such as irradiation total dose, dose rate and addition of cross linking agent, were studied by means of morphology analysis, thermal degradation and crystallinity. After the grafting reaction, the membranes were submitted to an exhaustive extraction with solvent to remove the polystyrene homopolymer formed. The degree of grafting (DOG) was analyzed by percentage of weight increase. As a result, the reaction always follows the same pattern: DOG increases rapidly initially whilst propagation is the main reaction, then more slowly as termination becomes more frequent. (author)

Graft-versus-host disease and sialodacryoadenitis viral infection in bone marrow transplanted rats

International Nuclear Information System (INIS)

Rossie, K.M.; Sheridan, J.F.; Barthold, S.W.; Tutschka, P.J.

1988-01-01

The effect of a localized viral infection on the occurrence of graft-vs.-host disease (GVHD) was examined in allogeneic rat bone marrow chimeras (ACI/LEW). Animals without clinical evidence of GVHD, 62 days after bone marrow transplant, were infected in salivary and lacrimal glands with sialodacryoadenitis virus (SDAV), and sacrificed 8-25 days postinfection. Using established histologic criteria, GVHD was found more frequently in salivary and lacrimal glands of SDAV-infected chimeras than uninfected chimeras. Skin and oral mucosa, tissues not infected by the virus, showed no differences in occurrence of GVHD, suggesting that the viral infection induced only local and not systemic GVHD. GVHD and SDAV infection, which are histologically similar, were differentiated by examining tissues for SDAV antigen using immunoperoxidase technique. Histologic changes were present for at least 1 week longer than viral antigen, suggesting they represented GVHD rather than viral infection. GVHD and SDAV infection were also differentiated by looking for a histologic feature characteristic of GVHD and not found in SDAV infection (periductal lymphocytic infiltrate). This was found in SDAV-infected chimeras more frequently than uninfected chimeras, suggesting that the viral infection somehow induced GVHD. Results showed a localized increase in the occurrence of GVHD subsequent to localized viral infection

Influence of the thymus on the capacity of female mice to reject male skin grafts

International Nuclear Information System (INIS)

De Pirro, E.S.; Goldberg, E.H.

1989-01-01

The ability of female mice to reject H-Y-incompatible, but otherwise histocompatible, male skin grafts differs greatly from strain to strain, as is illustrated particularly by the C57BL strain (B6 and other sublines), termed ''H-Y rejector,'' because females invariably and promptly reject C57BL male skin, in comparison with the C3H strain, termed ''H-Y nonrejector,'' because females characteristically accept male C3H skin. To assess the extent to which the thymus governs this rejector vs. nonrejector status, two studies were made. In the first, lethally irradiated B6 (C57BL) and C3H females were restored with (B6 X C3H)F1 female cells, providing a graft-vs.-host-free milieu for differentiation of the same immunopoietic cell population in B6 vs. C3H hosts. With respect to (B6 X C3H)F1 male skin grafts, B6 hosts responded as rejectors and C3H hosts as nonrejectors, signifying that rejector vs. nonrejector status was determined by the host during immunopoiesis. That the main organ responsible for rejector vs. nonrejector determination is the thymus was shown in a second study. Previously thymectomized (B6 X C3H)F1 females received a histocompatible graft of thymus from either B6 or C3H neonatal females and were restored with donor-marked (B6-Ly-5a X C3H)F1 female cells after lethal irradiation. With respect to (B6 X C3H)F1 male skin grafts, the recipients of B6 thymus grafts responded generally as rejectors and the recipients of C3H thymus grafts responded uniformly as nonrejectors

Donor genotype in the Interleukin-7 receptor α-chain predicts risk of graft-versus-host disease and cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation

DEFF Research Database (Denmark)

Kielsen, Katrine; Enevold, Christian; Heilmann, Carsten

2018-01-01

The efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by acute and chronic graft-versus-host disease (aGVHD and cGVHD) and viral infections due to long-lasting immunodeficiency. Interleukin-7 (IL-7) is a cytokine essential for de novo T cell generation in thymus.......1-3.8, P = 0.034) and with significantly increased risk of extensive cGVHD (HR = 2.0, 95% CI = 1.1-3.6, P = 0.025) after adjustment for potential risk factors. In addition, the TT genotype was associated with a higher risk of cytomegalovirus (CMV) infection post-transplant (HR = 2.4, 95% CI = 1.2-4.3, P.......7, 95% CI = 1.2-2.3, P = 0.0027) and increased treatment-related mortality (HR = 2.3, 95% CI = 1.3-4.0, P = 0.0047), but was not associated with the risk of relapse (P = 0.35). In conclusion, the IL-7Rα rs6897932 genotype of the donor is predictive of aGVHD and cGVHD, CMV infection, and mortality...

Extracorporeal photopheresis for graft-versus-host disease: the role of patient, transplant, and classification criteria and hematologic values on outcome-results from a large single-center study.

Science.gov (United States)

Berger, Massimo; Albiani, Roberto; Sini, Bruno; Fagioli, Franca

2015-04-01

Extracorporeal photopheresis (ECP) has been shown as active therapy for graft-versus-host disease (GVHD). The aim was to ascertain the role of ECP in 71 patients with steroid-refractory or -dependent acute and chronic GVHD (aGVHD and cGVHD) with special focus on hematologic variables and GVHD staging classification. A total of 34 patients were treated for aGVHD and 37 for cGVHD. The overall response rate (ORR) for aGVHD was 65% and the complete aGVHD-free survival was 50% (95% confidence interval [CI], 36%-70%). The ORR for cGVHD response was 81% while the complete cGVHD-free survival was 50% (95% CI, 34%-73%). The aGVHD-free survival was associated with aGVHD grading (Grade II 81%, Grade III 33%, and Grade IV 0%, p ≤ 0.00) and the absence of visceral involvement (77% vs. 33%, p = 0.03). The cGVHD-free survival was associated with the female sex (67% vs. 25%, p = 0.01) and with the limited form according to the Seattle classification (67% vs. 20%, p = 0.003). No role for hematologic values or apheresis cell count was found, except for the cGVHD ORR (p = 0.037). Transplant-related mortality and overall survival were associated with ECP response 0% versus 54% (p = 0.0001) and 77% versus 45% (p = 0.03) for aGVHD patients and 7% versus 14% (p = 0.02) and 73% versus 20% (p = 0.0003) for cGVHD patients, respectively. While confirming a higher probability of GVHD responses for early GVHD, our study shows no role of hematologic values or apheresis cell count on GVHD response. © 2014 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Peroxydisulfate initiated synthesis of potato starch-graft-poly(acrylonitrile under microwave irradiation

Directory of Open Access Journals (Sweden)

2007-01-01

Full Text Available Potato starch-graft-poly(acrylonitrile could be efficiently synthesized using small concentration of ammonium peroxydisulfate (0.0014M in aqueous medium under microwave irradiation. A representative microwave synthesized graft copolymer was characterized using Fourier Transform Infrared Spectroscopy, X-ray Diffraction, Scanning Electron Microscopy and Thermogravimetric Analysis. Under microwave conditions oxygen removal from the reaction vessel was not required and the graft copolymer was obtained in high yield using very small amount of ammonium peroxydisulfate, however using the same amount of ammonium peroxydisulfate (0.0014M on thermostatic water bath no grafting was observed up to 98°C (even in inert atmosphere. Raising the concentration of the initiator to 0.24 M resulted into 10% grafting at 50 °C but in inert atmosphere.The viscosity/shear stability of the grafted starch (aqueous solution and water/saline retention ability of the microwave synthesized graft copolymer were also studied and compared with that of the native potato starch.

Modulation and Apoptosis of Neutrophil Granulocytes by Extracorporeal Photopheresis in the Treatment of Chronic Graft-Versus-Host Disease.

Directory of Open Access Journals (Sweden)

Cindy Franklin

Full Text Available Chronic graft-versus-host disease (cGVHD is a common side effect of allogeneic stem cell transplantation and a major cause of morbidity and mortality in affected patients. Especially skin, eyes and oral mucosa are affected. This can lead to pain and functional impairment. Extracorporeal photopheresis (ECP is an effective immunomodulatory therapy with minimal side effects but its mode of action is still largely unknown. The objective of the present study was to examine the effects of ECP on neutrophil granulocytes in patients with cGVHD. Analysis of leukocytes from cGVHD patients obtained from the ECP device during treatment showed that neutrophil granulocytes account for the majority of cells treated during ECP. Neutrophils from healthy donors treated in vitro with 8-methoxypsoralen and UVA light as well as neutrophils from buffy coats of patients with cGVHD treated by ECP showed increased apoptosis and decreased half-life. In remaining non-apoptotic cells chemoirradiation resulted in loss of activation markers and reduced effector functions. This was accompanied by an increase in extracellular arginase-1 activity. Additional comparison of neutrophils isolated from blood of cGVHD patients before and 24h after ECP revealed a decreased half-life and reduction of effector functions of post-ECP neutrophils ex vivo. These observations strongly suggest that ECP induces both apoptosis and physiological changes in neutrophils and that these changes also take place in vivo. This study is the first to show that ECP modulates apoptosis and inflammatory activity in neutrophil granulocytes, indicating that neutrophils may significantly contribute to the overall immunomodulatory effects attributed to this treatment.

Advanced sclerosis of the chest wall skin secondary to chronic graft-versus-host disease: a case with severe restrictive lung defect.

Science.gov (United States)

Ödek, Çağlar; Kendirli, Tanil; İleri, Talia; Yaman, Ayhan; Fatih Çakmakli, Hasan; Ince, Elif; İnce, Erdal; Ertem, Mehmet

2014-10-01

Pulmonary chronic graft-versus-host disease (cGvHD) is one of the most common causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (aHSCT). Herein, we describe a patient with severe restrictive lung defect secondary to cGvHD. A 21-year-old male patient was admitted to our pediatric intensive care unit (PICU) with pneumonia and respiratory distress. He had a history of aHSCT for chronic myelogeneous leukemia at the age of 17 years. Six months after undergoing aHSCT, he had developed cGvHD involving skin, mouth, eye, lung, liver, and gastrointestinal tract. At the time of PICU admission he had respiratory distress and required ventilation support. Thorax high-resolution computed tomography was consistent with bronchiolitis obliterans. Although bronchiolitis obliterans is an obstructive lung defect, a restrictive pattern became prominent in the clinical course because of the sclerotic chest wall skin. The activity of cGvHD kept increasing despite the therapy and we lost the patient because of severe respiratory distress and massive hemoptysis secondary to bronchiectasis. In conclusion, pulmonary cGvHD can present with restrictive changes related with the advanced sclerosis of the chest wall skin. Performing a fasciotomy or a scar revision for the rigid chest wall in selected patients may improve the patients ventilation.

RANTES polymorphisms and the risk of graft-versus-host disease in human leukocyte antigen-matched sibling allogeneic hematopoietic stem cell transplantation.

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Shin, Dong-Yeop; Kim, Inho; Kim, Jin Hee; Lee, Yun-Gyoo; Kang, Eun Joo; Cho, Hyeon Jin; Lee, Kyung-Hun; Kim, Hye Jin; Park, Eun-Hee; Lee, Jong-Eun; Bae, Ji-Yeon; See, Cha Ja; Yoon, Sung-Soo; Park, Sung Sup; Han, Kyou-Sup; Park, Myoung Hee; Hong, Yun-Chul; Park, Seonyang; Kim, Byoung Kook

2013-01-01

We investigated the association between RANTES (regulated upon activation, normal T cell expressed and secreted) polymorphisms and clinical outcomes in patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Three RANTES gene polymorphisms, i.e., -403G/A (rs2107538), -28C/G (rs2280788) and In1.1T/C (rs2280789), were genotyped, and the effects of the genotypes and haplotypes of RANTES on clinical outcomes were analyzed. The competing risk regression analysis was used to investigate the relationship between the polymorphisms and the cumulative risk of graft-versus-host disease (GVHD). An AGC haplotype in a recessive model showed significant harmful effects on the cumulative risk of acute GVHD and relapse-free survival (adjusted hazard ratios 2.42 and 2.71, 95% confidence intervals 1.29-4.55 and 1.30-5.64; p = 0.018 and 0.024, respectively), whereas a GCT haplotype did not. RANTES polymorphisms were not significantly associated with overall survival and the risk of chronic GVHD. This study suggests that RANTES polymorphisms might be associated with the occurrence of acute GVHD rather than of chronic GVHD and also of relapse-free survival in the patients treated with allo-HSCT. Further larger prospective investigations are needed to establish the role of RANTES polymorphisms in patients treated with allo-HSCT. Copyright © 2012 S. Karger AG, Basel.

Revision Vaginoplasty: A Comparison of Surgical Outcomes of Laparoscopic Intestinal versus Perineal Full-Thickness Skin Graft Vaginoplasty.

Science.gov (United States)

Van der Sluis, Wouter B; Bouman, Mark-Bram; Buncamper, Marlon E; Mullender, Margriet G; Meijerink, Wilhelmus J

2016-10-01

Vaginal (re)construction can greatly improve the quality of life of indicated patients. If primary vaginoplasty fails, multiple surgical approaches exist for revision. The authors compared surgical results of laparoscopic intestinal versus full-thickness skin graft revision vaginoplasty. A retrospective chart review of patients who underwent revision vaginoplasty at the authors' institution was conducted. Patient demographics, surgical characteristics, complications, hospitalization, reoperations, and neovaginal depth for both surgical techniques were recorded and compared. The authors studied a consecutive series of 50 transgender and three biological women who underwent revision vaginoplasty, of which 21 were laparoscopic intestinal and 32 were perineal full-thickness skin graft vaginoplasties, with a median clinical follow-up of 3.2 years (range, 0.5 to 19.7 years). Patient demographics did not differ significantly. There was no mortality. Two intraoperative rectal perforations (10 percent) occurred in the intestinal group versus six (19 percent) in the full-thickness skin graft group. Operative time was shorter for the full-thickness skin graft vaginoplasty group (131 ± 35 minutes versus 191 ± 45 minutes; p skin graft (81 percent) vaginoplasty procedures. A deeper neovagina was achieved with intestinal vaginoplasty (15.9 ± 1.4 cm versus 12.5 ± 2.8 cm; p skin graft vaginoplasty can be used as secondary vaginal reconstruction. Intraoperative and postoperative complications do not differ significantly, but rectal perforation was more prevalent in the full-thickness skin graft vaginoplasty group. Although the operative time of laparoscopic intestinal vaginoplasty is longer, adequate neovaginal depth was more frequently achieved than in secondary perineal full-thickness skin graft vaginoplasty. Therapeutic, III.

Hydrophilicity improvement of polyethersulfone powders by grafting acrylic acid with γ-ray simultaneous irradiation method

International Nuclear Information System (INIS)

Deng Bo; Hou Zhengchi; Zhang Fengying; Xie Leidong; Li Jing; Yang Haijun

2005-01-01

Acrylic acid was grafted to Polyethersulfone (PES) powders by liquid-phase simultaneous irradiation. Effects of grafting conditions, such as absorbed dose, volume fraction of monomer, inhibitor (Cu 2+ ) concentration, and pH of the grafting solution on degree of the grafting were investigated. Combined with gravimetric analysis, a working curve of grafting degree through FT-IR quantitative analysis was obtained. The highest grafting degree was achieved at dose of 25 kGy, volume fraction of monomer of 30% and inhibitor concentration of 0.004 mol/L. Greater degrees of the grafting could be obtained by adding increasing amount of hydrochloric acid to the system. Hydrophilicity of the grafted PES powders increased with higher degrees of the grafting. (authors)

CD24(hi)CD27⁺ and plasmablast-like regulatory B cells in human chronic graft-versus-host disease.

Science.gov (United States)

de Masson, Adèle; Bouaziz, Jean-David; Le Buanec, Hélène; Robin, Marie; O'Meara, Alix; Parquet, Nathalie; Rybojad, Michel; Hau, Estelle; Monfort, Jean-Benoît; Branchtein, Mylène; Michonneau, David; Dessirier, Valérie; Sicre de Fontbrune, Flore; Bergeron, Anne; Itzykson, Raphaël; Dhédin, Nathalie; Bengoufa, Djaouida; Peffault de Latour, Régis; Xhaard, Aliénor; Bagot, Martine; Bensussan, Armand; Socié, Gérard

2015-03-12

Interleukin 10 (IL-10)-producing B cells (regulatory B cells [Bregs]) regulate autoimmunity in mice and humans, and a regulatory role of IL-10-producing plasma cells has been described in mice. Dysfunction of B cells that maintain homeostasis may play a role in the pathogenesis of chronic graft-versus-host disease (cGVHD) after allogeneic stem cell transplantation. Here, we found a relation between decreased Breg frequencies and cGVHD severity. An impaired ability of B cells to produce IL-10, possibly linked to poor signal transducer and activator of transcription 3 and extracellular signal-regulated kinase phosphorylation, was found in patients with active cGVHD. IL-10 production was not confined to a single B-cell subset, but enriched in both the CD24(hi)CD27(+) and CD27(hi)CD38(hi) plasmablast B-cell compartments. In vitro plasmablast differentiation increased the frequency of IL-10-producing B cells. We confirmed that allogeneic transplant recipients had an impaired reconstitution of the memory B-cell pool. cGVHD patients had less CD24(hi)CD27(+) B cells and IL-10-producing CD24(hi)CD27(+) B cells. Patients with cGVHD had increased plasmablast frequencies but decreased IL-10-producing plasmablasts. These results suggest a role of CD24(hi)CD27(+) B-cell and plasmablast-derived IL-10 in the regulation of human cGVHD. © 2015 by The American Society of Hematology.

Graft copolymerization of water soluble mixed monomers onto polyethylene by the pre-irradiation method

International Nuclear Information System (INIS)

Long Fu; Tang Liming; Zhao Jin; Gao Zhenyong

1993-01-01

Grafting of water soluble mixed monomers of acrylic acid (AA)/acrylamide (Am) and acrylic acid/methacrylic acid (MA) onto polyethylene film by the pre-irradiation grafting method was investigated. The results showed that the grafting proceeded successfully with the adding of ferric salt in the solution. In the case of AA/Am system, a synergistic effect was noticed. In the case of AA/MA system, the graft percent increased with the increase in the concentration of MA in the feed ratio. Furthermore, the effects of monomer concentration, radiation dose and temperature on the grafting were also studied

1. modification of the proliferative capacity of transplanted bone marrow colony forming units by changes in the host environment

International Nuclear Information System (INIS)

Beran, M.; Tribukait, B.

1974-01-01

Regulation of the proliferation of transplanted colony forming units (CFUs) was investigated in lethally irradiated mice, pretreated by methods known to accelerate hemopoietic recovery after sublethal irradiation. Prospective recipients were exposed to either hypoxia, vinblastine or priming irradiation and at different intervals thereafter lethally irradiated and transplanted with bone marrow. Repopulation of CFUs was determined by counting the number of splenic colonies in primary recipients or by retransplantation. Regeneration of grafted CFUs was greatly accelerated and their self-renewal capacity increased in mice grafted within 2 days after hypoxia. Also the number of splenic colonies formed by grafted syngeneic CFUs as well as by C57B1 parent CFUs growing in BC3F1 hosts was significantly increased. The effect was not dependent on the seeding efficiency of CFUs and apparently resulted from hypoxia induced changes in the hosts' physiological environment. Proliferative capacity of grafted CFUs increased remarkably in hosts receiving vinblastine 2 or 4 days prior to irradiation. Priming irradiation given 6 days before main irradiation accelerated, given 2 days before impaired regeneration of CFUs. The increased rate of regeneration was not related to the cellularity of hemopoietic organs at the time of transplantation. The growth of CFUs in diffusion chambers implanted into posthypoxic mice was only slightly improved which does indicate that the accelerated regeneration of CFUs in posthypoxic mice is mainly due to the changes in the hemopoietic microenvironment. A short conditioning of transplanted CFUs by host factor(s) was sufficient to improve regeneration. The results might suggest that the speed of hemopoietic regeneration depends on the number of CFUs being induced to proliferate shortly after irradiation, rather than on the absolute numbers of CFUs available to the organism. (author)

Graft polymerization of styrene onto starch by simultaneous cobalt-60 irradiation

International Nuclear Information System (INIS)

Fanta, G.F.; Burr, R.C.; Doane, W.M.; Russell, C.R.

1977-01-01

Starch-g-polystyrene copolymers have been prepared by the simultaneous 60 Co irradiation of starch--styrene mixtures, and copolymers have been characterized with respect to weight per cent polystyrene (% add-on) and also the molecular weight and molecular weight distribution of polystyrene grafts. In a typical polymerization, 4g each of starch and styrene were blended with 1 ml water and 1.5 ml of an organic solvent; the resulting semisolid paste was irradiated to a total dose of 1 Mrad. With ethylene glycol, acetonitrile, ethanol, methanol, acetone, and dimethylformamide as the organic solvent, values for % add-on ranged from 24% to 29%. The highest % add-on (43%) and the highest conversion of styrene to grafted polymer (76%) were obtained when the organic solvent was omitted, and water alone was used. When water was also omitted, polymerization of styrene was negligible; however, graft copolymer was formed in the absence of water when either ethylene glycol or ethanol was added. Attempts were unsuccessful to achieve a % add-on greater than 43% by doubling the amount of styrene in the polymerization recipe. Mixtures of equal weights of starch and styrene are relatively nonviscous, but these mixtures thicken when either water or ethylene glycol is blended in. Reasons for this thickening action and the possible influence of thickening on the graft polymerization reaction were explored

Viability of platelets following storage in the irradiated state. A pair-controlled study

International Nuclear Information System (INIS)

Read, E.J.; Kodis, C.; Carter, C.S.; Leitman, S.F.

1988-01-01

Gamma irradiation of blood products is a standard practice recommended for the prevention of posttransfusion graft-versus-host disease in susceptible hosts. We studied the effects of irradiation on stored platelet concentrates and evaluated whether platelets could be stored for 5 days in the irradiated state without adverse effects on their viability. Using a pair-controlled design in which each of six normal subjects acted as his or her own control, we compared in vitro storage characteristics and in vivo kinetics of platelet concentrates exposed to 30 Gy and stored for 5 days with those of platelet concentrates simply stored for 5 days without irradiation. Irradiation had no significant effects on in vitro storage characteristics (platelet count, mean platelet volume, pH, and white cell count) or on in vivo kinetics, including initial recovery and mean platelet survival. Using the multiple-hit model, initial recovery was 49.6 +/- 10.8 percent, and mean platelet survival was 5.6 +/- 1.05 days for irradiated concentrates, compared with 51.3 +/- 13.0 percent and 5.9 +/- 0.50 days, respectively, for the unirradiated control concentrates. We conclude that irradiation of platelet concentrates with up to 30 Gy has no effect on their in vivo recovery or survival, and that irradiation administered before storage of platelet concentrates does not interfere with their clinical efficacy

Modification of phase transitions in swift heavy ion irradiated and MMA-grafted ferroelectric fluoro-polymers

International Nuclear Information System (INIS)

Petersohn, E.; Betz, N.; Le Moel, A.

1994-01-01

Ferroelectric polyvinylidene fluoride (β) and copolymers of vinylidene fluoride trifluoroethylene (P(VDF/TrFE)) films were irradiated with swift heavy ions and post irradiation grafted with methyl methacrylate (MMA). We have studied the influence of irradiation parameters such as the ion fluence, the type of ion and the electronic stopping power, on the melting and crystallization temperatures and the ferroelectric-paraelectric phase transitions, by differential scanning calorimetry (DSC) and dielectric measurements. The relation between the shift in the transition temperatures and the ion fluence is described by a single term equation. Ion track grafting with MMA affects the ferroelectric-paraelectric phase transitions in P(VDF/TrFE) and leads to a strong amorphization of the polymer films. The grafting in β PVDF occurs mainly on the surface of the samples and no change in the transition temperatures is observed. (authors). 12 refs., 6 figs., 2 tabs

Thiotepa-based versus total body irradiation-based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

Science.gov (United States)

Eder, Sandra; Labopin, Myriam; Arcese, William; Or, Reuven; Majolino, Ignazio; Bacigalupo, Andrea; de Rosa, Gennaro; Volin, Liisa; Beelen, Dietrich; Veelken, Hendrik; Schaap, Nicolaas P M; Kuball, Jurgen; Cornelissen, Jan; Nagler, Arnon; Mohty, Mohamad

2016-01-01

Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long-established ones. This retrospective matched-pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa-based (n = 121) or a cyclophosphamide/total body irradiation-based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling or an unrelated donor. With a median follow-up of 44 months, the outcome was similar in both groups. Acute graft-versus-host disease grade II-IV was observed in 25% after thiotepa-containing regimen versus 35% after TBI (P = 0.06). The 2-yr cumulative incidence of chronic graft-versus-host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non-relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia-free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Study on changes of the plasma cytokines in 60Co γ-ray irradiated blood and leukocyte reduction of whole blood

International Nuclear Information System (INIS)

Li Zhiqiang; Le Jiayi; Qu Yihua; Xu Wenhao

2006-01-01

Objective: To study the changes of IL-2, IL-6, IFN-γ and TNF-α in 60 Co γ-ray irradiated and leukocyte reduction of whole blood, and to understand the fever phenomenon in patients received blood transfusion. Methods: ELISA method was used to measure changes of the cytokines. Results: The plasma levels of IL-2, IL-6, IFN-γ and TNF-α did not change significantly with extending the conservation period both in 60 Co-irradiated and leukocyte reduction of whole blood. The frequency of fever decreaed obviously with transfusion of 60 Co-irradiated and leukocyte reduction of whole blood. Conclusion: 60 Co-irradiated blood can not only prevent transfusion associated graft-versus-host disease (TA-GVHD), but also decrease non-hemolytic febrile transfusion reactions (NHFTR) effectively. (authors)

Stability of radicals in electron-irradiated fluoropolymer film for the preparation of graft copolymer fuel cell electrolyte membranes

DEFF Research Database (Denmark)

Larsen, Mikkel Juul; Ma, Yue; Qian, Huan

This presentation concerns the stability of radicals generated in poly(ethylene-alt-tetra­fluoro­ethylene) (ETFE) film by electron irradiation prior to grafting of styrene onto this base material. It has been demonstrated that the grafting yield decreases as the storage time of the irradiated fil...

Differential immune response of congenic mice to ultraviolet-treated major histocompatibility complex class II-incompatible skin grafts

International Nuclear Information System (INIS)

Vermeer, B.J.; Santerse, B.; Van De Kerckhove, B.A.; Schothorst, A.A.; Claas, F.H.

1988-01-01

The influence of ultraviolet (UVB) irradiation on the survival of H-2 class II-disparate skin grafts was studied in congenic mouse strains. Isolated skin was UVB irradiated in vitro at a dose of 40 mJ/cm 2 from both sides to remove Ia immunogenicity. Immediately after irradiation the skin was transplanted onto the flank of allogeneic mice. When B10.AQR grafts were transplanted onto B10.T(6R) recipients, a significant prolongation of the survival time was observed, while 50% of the UVB-treated grafts were not rejected at all. However, in the opposite direction--i.e., B10.T(6R) grafts onto B10.AQR recipients, no significant prolongation of the survival was observed. To test whether this effect was due to a difference in susceptibility of the donor skin to UVB irradiation or to a different immune response in the recipients, (B10.T(6R) x B10.AQR) grafts were transplanted onto the parent strains. Similar results were obtained, in that UVB-treated grafts did not show a prolonged survival in B10.AQR recipients, whereas a significant prolongation (50% of the grafts survived more than 100 days) was observed in B10.T(6R) recipients. UVB-treated (B10.T(6R) x B10.AQR)F1 grafts were also transplanted onto (B10.T(6R) x C57B1/10)F1, (B10.AQR x C57B1/10)F1, (B10.T(6R) x Balb/c)F1 and (B10.AQR x Balb/c)F1 recipients--but in none of these combinations was a prolonged survival time observed. These data suggest that, in contrast to all in vitro experiments, the abrogation of the immune response by UVB treatment of the stimulator cells is, in vivo, not a general phenomenon. The genetic constitution of the responder mice seems to play an important role in determining whether or not an immune response takes place

Graft-versus-leukemia, donor selection for adoptive immunotherapy in mice

International Nuclear Information System (INIS)

LeFeber, W.P.; Truitt, R.L.; Rose, W.C.; Bortin, M.M.

1977-01-01

The optimal donor for adoptive immunotherapy would exhibit great antitumor reactivity and no antihost reactivity. Immunocompetent cells from 11 strains of mice were tested in vivo for their reactivity against a long-passage AKR acute lymphoblastic leukemia and against immunosuppressed nonleukemic AKR mice. Donor mice were syngeneic, unprimed H-2 compatible, primed H-2 compatible, congenic, or H-2 incompatible with AKR. Bioassays were used to evaluate the relative graft-vs.-leukemia (GvL) reactivity and the relative graft-vs.-host (GvH) reactivity of transplanted bone marrow and lymph-node cells from the panel of donors. No significant GvL reactivity was found when cells from syngeneic, unprimed H-2 compatible, or congenic donors were tested. H-2 compatible donors that were immunized with γ-irradiated AKR leukemic spleen cells showed modest GvL reactivity, but associated with the immunization was a disproportionate increase in acute and delayed GvH mortality. Among the H-2 mismatched donors, mice of the SJL strain appeared to most closely approach the ideal because of least intense GvH reactivity and maximal GvL reactivity. As measured in these experiments there was no correlation between the severity of GvH disease and the efficacy of the GvL reaction; GvL reactivity in unprimed donors was always associated with H-2 incompatibility; disparity between donor and recipient at H-2 did not guarantee an effective GvL reaction; and the increase in GvL reactivity obtained by immunizing H-2 compatible donors was overshadowed by the increase in GvH disease

Characterization of regulatory dendritic cells that mitigate acute graft-versus-host disease in older mice following allogeneic bone marrow transplantation.

Science.gov (United States)

Scroggins, Sabrina M; Olivier, Alicia K; Meyerholz, David K; Schlueter, Annette J

2013-01-01

Despite improvements in human leukocyte antigen matching and pharmacologic prophylaxis, acute graft-versus-host disease (GVHD) is often a fatal complication following hematopoietic stem cell transplant (HSCT). Older HSCT recipients experience significantly increased morbidity and mortality compared to young recipients. Prophylaxis with syngeneic regulatory dendritic cells (DCreg) in young bone marrow transplanted (BMT) mice has been shown to decrease GVHD-associated mortality. To evaluate this approach in older BMT recipients, young (3-4 months) and older (14-18 months) DCreg were generated using GM-CSF, IL-10, and TGFβ. Analysis of young versus older DCreg following culture revealed no differences in phenotype. The efficacy of DCreg treatment in older BMT mice was evaluated in a BALB/c→C57Bl/6 model of GVHD; on day 2 post-BMT (d +2), mice received syngeneic, age-matched DCreg. Although older DCreg-treated BMT mice showed decreased morbidity and mortality compared to untreated BMT mice (all of which died), there was a small but significant decrease in the survival of older DCreg-treated BMT mice (75% survival) compared to young DCreg-treated BMT mice (90% survival). To investigate differences between dendritic cells (DC) in young and older DCreg-treated BMT mice that may play a role in DCreg function in vivo, DC phenotypes were assessed following DCreg adoptive transfer. Transferred DCreg identified in older DCreg-treated BMT mice at d +3 showed significantly lower expression of PD-L1 and PIR B compared to DCreg from young DCreg-treated BMT mice. In addition, donor DC identified in d +21 DCreg-treated BMT mice displayed increased inhibitory molecule and decreased co-stimulatory molecule expression compared to d +3, suggesting induction of a regulatory phenotype on the donor DC. In conclusion, these data indicate DCreg treatment is effective in the modulation of GVHD in older BMT recipients and provide evidence for inhibitory pathways that DCreg and donor DC may

Characterization of regulatory dendritic cells that mitigate acute graft-versus-host disease in older mice following allogeneic bone marrow transplantation.

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Sabrina M Scroggins

Full Text Available Despite improvements in human leukocyte antigen matching and pharmacologic prophylaxis, acute graft-versus-host disease (GVHD is often a fatal complication following hematopoietic stem cell transplant (HSCT. Older HSCT recipients experience significantly increased morbidity and mortality compared to young recipients. Prophylaxis with syngeneic regulatory dendritic cells (DCreg in young bone marrow transplanted (BMT mice has been shown to decrease GVHD-associated mortality. To evaluate this approach in older BMT recipients, young (3-4 months and older (14-18 months DCreg were generated using GM-CSF, IL-10, and TGFβ. Analysis of young versus older DCreg following culture revealed no differences in phenotype. The efficacy of DCreg treatment in older BMT mice was evaluated in a BALB/c→C57Bl/6 model of GVHD; on day 2 post-BMT (d +2, mice received syngeneic, age-matched DCreg. Although older DCreg-treated BMT mice showed decreased morbidity and mortality compared to untreated BMT mice (all of which died, there was a small but significant decrease in the survival of older DCreg-treated BMT mice (75% survival compared to young DCreg-treated BMT mice (90% survival. To investigate differences between dendritic cells (DC in young and older DCreg-treated BMT mice that may play a role in DCreg function in vivo, DC phenotypes were assessed following DCreg adoptive transfer. Transferred DCreg identified in older DCreg-treated BMT mice at d +3 showed significantly lower expression of PD-L1 and PIR B compared to DCreg from young DCreg-treated BMT mice. In addition, donor DC identified in d +21 DCreg-treated BMT mice displayed increased inhibitory molecule and decreased co-stimulatory molecule expression compared to d +3, suggesting induction of a regulatory phenotype on the donor DC. In conclusion, these data indicate DCreg treatment is effective in the modulation of GVHD in older BMT recipients and provide evidence for inhibitory pathways that DCreg and

Carboxylated nanodiamonds inhibit γ-irradiation damage of human red blood cells.

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Santacruz-Gomez, K; Silva-Campa, E; Melendrez-Amavizca, R; Teran Arce, F; Mata-Haro, V; Landon, P B; Zhang, C; Pedroza-Montero, M; Lal, R

2016-04-07

Nanodiamonds when carboxylated (cNDs) act as reducing agents and hence could limit oxidative damage in biological systems. Gamma (γ)-irradiation of whole blood or its components is required in immunocompetent patients to prevent transfusion-associated graft versus host disease (TA-GVHD). However, γ-irradiation of blood also deoxygenates red blood cells (RBCs) and induces oxidative damage, including abnormalities in cellular membranes and hemolysis. Using atomic force microscopy (AFM) and Raman spectroscopy, we examined the effect of cNDs on γ-irradiation mediated deoxygenation and morphological damage of RBCs. γ-Radiation induced several morphological phenotypes, including stomatocytes, codocytes and echinocytes. While stomatocytes and codocytes are reversibly damaged RBCs, echinocytes are irreversibly damaged. AFM images show significantly fewer echinocytes among cND-treated γ-irradiated RBCs. The Raman spectra of γ-irradiated RBCs had more oxygenated hemoglobin patterns when cND-treated, resembling those of normal, non-irradiated RBCs, compared to the non-cND-treated RBCs. cND inhibited hemoglobin deoxygenation and morphological damage, possibly by neutralizing the free radicals generated during γ-irradiation. Thus cNDs have the therapeutic potential to preserve the quality of stored blood following γ-irradiation.

Comprehensive Analysis of the Activation and Proliferation Kinetics and Effector Functions of Human Lymphocytes, and Antigen Presentation Capacity of Antigen-Presenting Cells in Xenogeneic Graft-Versus-Host Disease.

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Kawasaki, Yasufumi; Sato, Kazuya; Hayakawa, Hiroko; Takayama, Norihito; Nakano, Hirofumi; Ito, Ryoji; Mashima, Kiyomi; Oh, Iekuni; Minakata, Daisuke; Yamasaki, Ryoko; Morita, Kaoru; Ashizawa, Masahiro; Yamamoto, Chihiro; Hatano, Kaoru; Fujiwara, Shin-Ichiro; Ohmine, Ken; Muroi, Kazuo; Kanda, Yoshinobu

2018-04-17

Xenogeneic graft-versus-host disease (GVHD) models in highly immunodeficient mice are currently being used worldwide to investigate human immune responses against foreign antigens in vivo. However, the individual roles of CD4 + and CD8 + T cells, and donor/host hematopoietic and nonhematopoietic antigen-presenting cells (APCs) in the induction and development of GVHD have not been fully investigated. In the present study, we comprehensively investigated the immune responses of human T cells and the antigen presentation capacity of donor/host hematopoietic and nonhematopoietic APCs in xenogeneic GVHD models using nonobese diabetic/Shi-scid-IL2rg null mice. CD4 + T cells and, to a lesser extent, CD8 + T cells individually mediated potentially lethal GVHD. In addition to inflammatory cytokine production, CD4 + T cells also supported the activation and proliferation of CD8 + T cells. Using bone marrow chimeras, we demonstrated that host hematopoietic, but not nonhematopoietic, APCs play a critical role in the development of CD4 + T cell-mediated GVHD. During early GVHD, we detected 2 distinct populations in memory CD4 + T cells. One population was highly activated and proliferated in major histocompatibility complex antigen (MHC) +/+ mice but not in MHC -/- mice, indicating alloreactive T cells. The other population showed a less activated and slowly proliferative status regardless of host MHC expression, and was associated with higher susceptibility to apoptosis, indicating nonalloreactive T cells in homeostasis-driven proliferation. These observations are clinically relevant to donor T cell response after allogeneic hematopoietic stem cell transplantation. Our findings provide a better understanding of the immunobiology of humanized mice and support the development of novel options for the prevention and treatment for GVHD. Copyright © 2018. Published by Elsevier Inc.

Post-irradiation time effects on the graft of poly(ethylene-alt-tetrafluoroethylene) (ETFE) films for ion exchange membrane application

Energy Technology Data Exchange (ETDEWEB)

Geraldes, Adriana N., E-mail: angeral@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Centro de Quimica e Meio Ambiente (CQMA), Av. Professor Lineu Prestes, 2242, 05508-900, Sao Paulo (Brazil); Zen, Heloisa A.; Ribeiro, Geise; Ferreira, Henrique P.; Souza, Camila P.; Parra, Duclerc F.; Santiago, Elisabete I.; Lugao, Ademar B. [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Centro de Quimica e Meio Ambiente (CQMA), Av. Professor Lineu Prestes, 2242, 05508-900, Sao Paulo (Brazil)

2010-03-15

Grafting of styrene followed by sulfonation onto poly(ethylene-alt-tetrafluoroethylene) (ETFE) was studied for synthesis of ion exchange membranes. Radiation-induced grafting of styrene onto ETFE films was investigated after simultaneous irradiation (in post-irradiation condition) using a {sup 60}Co source. The ETFE films were irradiated at 20 kGy dose at room temperature and chemical changes were monitored after contact with styrene for grafting. The post-irradiation time was established at 14 days when the films were remained in styrene/toluene 1:1 v/v. After this period the grafting degree was evaluated in the samples. The grafted films were sulfonated using chlorosulfonic acid and 1, 2-dichloroethane 20:80 (v/v) at room temperature for 5 h. The membranes were analyzed by infrared spectroscopy (FTIR), differential scanning calorimeter (DSC), thermogravimetric measurements (TG) and degree of grafting (DOG). The ion exchange capacity (IEC) of membranes was determined by acid-base titration and the values for ETFE membranes were achieved higher than Nafion films. Preliminary single cell performance was made using pure H{sub 2} and O{sub 2} as reactants at a cell temperature of 80 deg. C and atmospheric gas pressure. The fuel cell performance of ETFE films was satisfactory when compared to state-of-art Nafion membranes.

Post-irradiation time effects on the graft of poly(ethylene-alt-tetrafluoroethylene) (ETFE) films for ion exchange membrane application

Science.gov (United States)

Geraldes, Adriana N.; Zen, Heloísa A.; Ribeiro, Geise; Ferreira, Henrique P.; Souza, Camila P.; Parra, Duclerc F.; Santiago, Elisabete I.; Lugão, Ademar B.

2010-03-01

Grafting of styrene followed by sulfonation onto poly(ethylene-alt-tetrafluoroethylene) (ETFE) was studied for synthesis of ion exchange membranes. Radiation-induced grafting of styrene onto ETFE films was investigated after simultaneous irradiation (in post-irradiation condition) using a 60Co source. The ETFE films were irradiated at 20 kGy dose at room temperature and chemical changes were monitored after contact with styrene for grafting. The post-irradiation time was established at 14 days when the films were remained in styrene/toluene 1:1 v/v. After this period the grafting degree was evaluated in the samples. The grafted films were sulfonated using chlorosulfonic acid and 1, 2-dichloroethane 20:80 (v/v) at room temperature for 5 h. The membranes were analyzed by infrared spectroscopy (FTIR), differential scanning calorimeter (DSC), thermogravimetric measurements (TG) and degree of grafting (DOG). The ion exchange capacity (IEC) of membranes was determined by acid-base titration and the values for ETFE membranes were achieved higher than Nafion ® films. Preliminary single cell performance was made using pure H 2 and O 2 as reactants at a cell temperature of 80 °C and atmospheric gas pressure. The fuel cell performance of ETFE films was satisfactory when compared to state-of-art Nafion ® membranes.

MicroRNA-155 Modulates Acute Graft-versus-Host Disease by Impacting T Cell Expansion, Migration, and Effector Function.

Science.gov (United States)

Zitzer, Nina C; Snyder, Katiri; Meng, Xiamoei; Taylor, Patricia A; Efebera, Yvonne A; Devine, Steven M; Blazar, Bruce R; Garzon, Ramiro; Ranganathan, Parvathi

2018-06-15

MicroRNA-155 (miR-155) is a small noncoding RNA critical for the regulation of inflammation as well as innate and adaptive immune responses. MiR-155 has been shown to be dysregulated in both donor and recipient immune cells during acute graft-versus-host disease (aGVHD). We previously reported that miR-155 is upregulated in donor T cells of mice and humans with aGVHD and that mice receiving miR-155-deficient (miR155 -/- ) splenocytes had markedly reduced aGVHD. However, molecular mechanisms by which miR-155 modulates T cell function in aGVHD have not been fully investigated. We identify that miR-155 expression in both donor CD8 + T cells and conventional CD4 + CD25 - T cells is pivotal for aGVHD pathogenesis. Using murine aGVHD transplant experiments, we show that miR-155 strongly impacts alloreactive T cell expansion through multiple distinct mechanisms, modulating proliferation in CD8 + donor T cells and promoting exhaustion in donor CD4 + T cells in both the spleen and colon. Additionally, miR-155 drives a proinflammatory Th1 phenotype in donor T cells in these two sites, and miR-155 -/- donor T cells are polarized toward an IL-4-producing Th2 phenotype. We further demonstrate that miR-155 expression in donor T cells regulates CCR5 and CXCR4 chemokine-dependent migration. Notably, we show that miR-155 expression is crucial for donor T cell infiltration into multiple target organs. These findings provide further understanding of the role of miR-155 in modulating aGVHD through T cell expansion, effector cytokine production, and migration. Copyright © 2018 by The American Association of Immunologists, Inc.

Keratocyte apoptosis and not myofibroblast differentiation mark the graft/host interface at early time-points post-DSAEK in a cat model.

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Adam J Weis

Full Text Available To evaluate myofibroblast differentiation as an etiology of haze at the graft-host interface in a cat model of Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK.DSAEK was performed on 10 eyes of 5 adult domestic short-hair cats. In vivo corneal imaging with slit lamp, confocal, and optical coherence tomography (OCT were performed twice weekly. Cats were sacrificed and corneas harvested 4 hours, and 2, 4, 6, and 9 days post-DSAEK. Corneal sections were stained with the TUNEL method and immunohistochemistry was performed for α-smooth muscle actin (α-SMA and fibronectin with DAPI counterstain.At all in vivo imaging time-points, corneal OCT revealed an increase in backscatter of light and confocal imaging revealed an acellular zone at the graft-host interface. At all post-mortem time-points, immunohistochemistry revealed a complete absence of α-SMA staining at the graft-host interface. At 4 hours, extracellular fibronectin staining was identified along the graft-host interface and both fibronectin and TUNEL assay were positive within adjacent cells extending into the host stroma. By day 2, fibronectin and TUNEL staining diminished and a distinct acellular zone was present in the region of previously TUNEL-positive cells.OCT imaging consistently showed increased reflectivity at the graft-host interface in cat corneas in the days post-DSAEK. This was not associated with myofibroblast differentiation at the graft-host interface, but rather with apoptosis and the development of a subsequent acellular zone. The roles of extracellular matrix changes and keratocyte cell death and repopulation should be investigated further as potential contributors to the interface optical changes.

Novel Concept of CD4-Mediated Activation of Regulatory T Cells for the Treatment of Graft-Versus-Host Disease

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Janine Schlöder

2017-11-01

Full Text Available Allogeneic hematopoietic stem cell transplantation is the only curative treatment option for several hematological malignancies and immune deficiency syndromes. Nevertheless, the development of a graft-versus-host disease (GvHD after transplantation is a high risk and a severe complication with high morbidity and mortality causing therapeutic challenges. Current pharmacological therapies of GvHD lead to generalized immunosuppression followed by severe adverse side effects including infections and relapse of leukemia. Several novel cell-based immunomodulatory strategies for treatment or prevention of GvHD have been developed. Herein, thymus-derived regulatory T cells (tTreg, essential for the maintenance of peripheral immunologic tolerance, are in the focus of investigation. However, due to the limited number of tTreg in the peripheral blood, a complex, time- and cost-intensive in vitro expansion protocol is necessary for the production of an efficient cellular therapeutic. We demonstrated that activation of tTreg using the CD4-binding human immunodeficiency virus-1 protein gp120 leads to a substantially increased suppressor activity of tTreg without the need for additional expansion. Gp120-activated tTreg prevent GvHD development in a preclinical humanized mouse model. In addition, gp120 is not only effective in prevention but also in therapy of GvHD by suppressing all clinical symptoms and improving survival of treated mice. These data indicate that tTreg activation by gp120 is a feasible and potent strategy for significant functional improvement of tTreg as cellular therapeutic for GvHD treatment without the need of complicated, time-intensive, and expensive in vitro expansion of isolated tTreg.

Modified extracorporeal photopheresis with cells from a healthy donor for acute graft-versus-host disease in a mouse model.

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Holger Budde

Full Text Available Graft-versus-host disease (GvHD is a major challenge after hematopoietic stem cell transplantation but treatment options for patients are still limited. In many cases first-line treatment with glucocorticoids is not successful. Among second-line therapies the extracorporeal photopheresis (ECP is frequently performed, due to induction of selective tolerance instead of general immunosuppression. However, for some patients with severe acute GvHD the leukapheresis step of the ECP procedure is physically exhausting and limits the number of ECP cycles.We hypothesized that leukocytes from healthy cell donors could be used as a replacement for ECP leukocytes gained from the GvHD patient. For this purpose we used a well established mouse model of acute GvHD. The ECP therapy was based on cells with the genetic background of the initial donor of the stem cell transplantation. As a precondition we developed a protocol representing conventional ECP in mice equivalent to clinical used ECP setup.We could demonstrate that conventional, clinically derived ECP setup is able to alleviate acute GvHD. By using leukocytes obtained from healthy mice with the bone marrow donor's genetic background we could not observe a statistically significant therapeutic effect.Conventional human ECP setup is effective in the mouse model of severe acute GvHD. In addition we could not prove that ECP cells from healthy mice with bone marrow donor's genetic background are as effective as ECP cells derived from GvHD mice. Based on our findings, new questions arise for further studies, in which the cellular characteristics for ECP mediated immune tolerance are a matter of investigation.

Nonspecific suppressor elements in murine allogeneic radiation chimeras

International Nuclear Information System (INIS)

Urso, P.; Gengozian, N.

1979-01-01

Spleen cells from long-term mouse allogeneic radiation chimeras were tested for their ability to modulate the graft-versus-host (GVH) or plaque-forming cell (PFC) response of normal lymphocytes transplanted in lethally x-irradiated recipients. In vivo GVH proliferation of normal lymphocytes (syngeneic to donor cells of the chimera) against antigens of host-type in which the chimeric state had been established was reduced by chimera cells. Inhibition varied, some chimeras suppressing GVH more than others and a few not suppressing at all. The suppressive effect was abrogated if the chimera cells were treated with anti-THETA; treatment with anti-IgM did not eliminate this activity. When mixtures of normal donor lymphocytes and chimera cells were given to irradiated recipients genetically different from host or donor, reduction of donor cell GVH also occurred. Further, chimera cells reduced the GVH activity of normal host cells in irradiated recipients differing from the host at one H-2 locus and from the donor at minor histocompatibility loci. The modulating effect of spleen cells from chimeras on the PFC response by normal lymphocytes also varied. Six chimeras induced a 25 to 90% suppression, two enhanced the response, and one showed no effect. Where suppression occurred, treatment of chimera cells with anti-THETA most often, but not always, restored PFC production. Our results show that the suppressive action of splenic lymphoid cells by chimeras is highly nonspecific and variable in expression. We suggest that tolerance in chimeras may be mediated by nonspecific suppressor elements leading to unresponsiveness to a variety of antigens including SRBC

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

Anti-CD3 Antibody Ameliorates Transfusion-Associated Graft-Versus-Host Disease in a Chemotherapy-Based Mouse Model With Busulfan and Fludarabine

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Xiaofan Li

2017-05-01

Full Text Available ABSTRACT To establish a transfusion-associated graft-versus-host disease (TA-GVHD mouse model with busulfan and fludarabine for effective treatment evaluation. BALB/c (H-2d mice were injected with busulfan (15 mg/kg and fludarabine (30 mg/kg twice a day for 4 days. The mice were transfused with 106 T cell-depleted bone marrow (TCD-BM and cells in different groups 3 days after chemotherapy: syngeneic BALB/c, MHC minor mismatch DBA/2 (H-2d, or MHC major mismatch C57BL/6(H2-b. Recipient BALB/c mice were injected with either blood only or blood+splenocyte. TA-GVHD was monitored in terms of body weight loss, clinical scores, and survival. Dexamethasone (50 mg/kg, cyclophosphamide (50 mg/kg, cyclosporine A (30 mg/kg, and anti-CD3 (1 mg/kg were injected to each group to examine the treatments. Blood transfusion alone is insufficient to induce TA-GVHD in a chemotherapy-based mouse model. A MHC-mismatched TA-GVHD model can be induced by splenocyte and blood transfusion. This MHC-mismatched TA-GVHD model was resistant to dexamethasone treatment. Treatment based on anti-CD3 monoclonal antibody slightly ameliorated TA-GVHD. Treatment effectiveness was associated with T-cell depletion following activation by anti-CD3. Busulfan and fludarabine chemotherapy regimen can be used to establish a TA-GVHD mouse model. Anti-CD3 monoclonal antibody is a potential alternative to treat TA-GVHD.

Graft copolymerization of N-maleoyl-N-phthaloyl-chitosan (MAPHCS) and acrylic acid via γ-ray irradiation

International Nuclear Information System (INIS)

Mu Qing; Fang Yue'e

2006-01-01

Chitosan is a well-known abundant natural polymer with good biodegradability, biocompatibility and bioactivity. But its insolubility in common organic solvents of chitosan have hindered its utilization and basic research. N-maleoyl-N-phthaloyl-chitosan (MAPHCS), soluble in DMF or DMSO, was synthesized and characterized by Fourier transform infrared spectra analysis (FT-IR) and 1 H-NMR. The graft copolymerization of acrylic acid onto chitosan was carried out with N-maleoyl-N-phthaloyl-chitosan as intermediate in homogeneous system and initiated by γ-irradiation. The double bond of MAPHCS may be the grafting site because the grafting field was much higher than that of the graft copolymerization of acrylic acid and phthaloylchitosan via γ-ray irradiation. The chemical structure of the graft copolymer was characterized by FT-IR and 1 H-NMR. As indicated in FTIR spectra, the evidence of the stronger absorbance at 2800-3000 cm -1 for C-H and at 1720 cm -1 for carboxyl group implied significantly the successful introduction of the poly (acrylic acid) on the chitosan chain. Differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA) were also used to characterize the copolymer. Effects of synthesis variables on the graft copolymerization were studied in light of the grafting percentage. The grafting percentage increased with the dose at lower doses, and then decreased. The maximum grafting percentage was up to 132%. (authors)

Steroid-sparing effect of extracorporeal photopheresis in the therapy of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Science.gov (United States)

Ussowicz, M; Musiał, J; Mielcarek, M; Tomaszewska, A; Nasiłowska-Adamska, B; Kałwak, K; Gorczyńska, E; Mariańska, B; Chybicka, A

2013-11-01

Steroid-refractory graft-versus-host disease (GVHD) remains a challenging therapeutic problem after allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the clinical effect of extracorporeal photopheresis (ECP), and its impact on intensivity of immunosuppresive therapy in allogeneic HSCT patients. In this study 443 Therakos ECP procedures were performed in 21 patients after allogeneic HSCT with acute (aGVHD, 8 patients) or chronic (cGVHD, 13 patients) therapy-refractory GVHD. The median age at ECP onset was 20.5 years (range, 10-55). Venous access was provided by a nontunelized central venous catheter (12 patients) or 9.6-French portacath (9 patients). In the cGVHD group 9/13 patients were improved with a 4-year overall survival rate of 67.7%. ECP led to steroid discontinuation in 6 and substantial dose reduction in 5 patients. The prednisone dose equivalent per kilogram body weight decreased from 0.32 mg to 0.07 mg after therapy. Therapy of aGVHD led to complete or partial symptom remission in 3/9 subjects. The change in steroid dose in the aGVHD group was not significant, there were no long-term survivors. Portacath access was well tolerated and provided adequate blood flow rates. The ECP therapy significantly reduced the rates of remissions with steroid discontinuation among cGVHD but not aGVHD patients. Rare ECP-related complications were either catheter related or anticoagulation induced during ECP procedures. Photopheresis was a safe, effective method to treat steroid-resistant cGVHD. Copyright © 2013 Elsevier Inc. All rights reserved.

Irradiation of Eggs and Larvae of Bactrocera Carambolae (Drew and Hancock) Fruit Fly to Produce Irradiation Host for Its Parasitoids

International Nuclear Information System (INIS)

Achmad Nasroh Kuswadi; Murni lndarwatmi; Nasution, Indah Arastuti

2004-01-01

Bactrocera carambolae (Drew and Hancock) fruit fly, a major pests of commercial fruits in Indonesia, is attacked by several species of parasitoids in the field, such as by Biosteres sp. that attacks on early instar larvae and Opius sp. on late instar larvae. In order to produce irradiated host in mass rearing of both species, several dosage of gamma were tested on both eggs and larvae. Egg masses of 0.5 ml were irradiated with 0, 10, 20, 30, 40 and 50 Gy and then inoculated into artificial diet. Viability of the eggs, the larval period and the number of pupae produced were observed. About 200 third instar larvae irradiated with 0, 10, 30, 50,70 dan 90 Gy and the number and quality of the pupae developed were then observed. The results showed that the eggs irradiated with tested dosage did not reduce its viability however it reduced the survival of larvae emerged. Number of pupae produced from 0.5 ml irradiated eggs were reduced from 2740 pupae to 407, 167, 113, 53 and 44 pupae, besides the pupation delayed up to three days. Irradiation on third instars larvae did not reduce its pupation, since pupae were developed from > 85 % of irradiated larvae. However, irradiation did reduced the fly emergence from the pupae. Irradiated hosts for Biosteres sp and Opius sp can be produced by irradiating eggs however it should be evaluated since the survival rate of the larvae reduced. Irradiation of third instar larvae may produce irradiated host for Opius sp So, the use of irradiated eggs or irradiated larvae as host in the colonization of the parasitoids will insure no hosts emerged as adult. However it remain to be proved whether irradiated hosts are prefered and able to support the life of parasitoid. (author)

[Immunological mechanisms of graft versus tumor effect].

Science.gov (United States)

Ine, Shoji; Yamada, Minami; Miyamura, Koichi; Sasaki, Takeshi

2003-09-01

Lesson from hematopoietic stem cell transplantation demonstrated that donor immuno-surveillance system can eradicate tumor cells. This is so-call graft versus tumor(GVT) effect. Antigen presenting cells show peptide from minor antigen rather leukemic specific antigen in the context of major histocompatibility complex. The effector cells composed of CD8 T lymphocyte, CD4 T lymphocyte, natural killer cell and natural killer T cell. Death signal was transmitted from effector cells via granzyme/perforin system and FasL/Fas system, and recently TRAIL system seems most important for GVT effect.

Can low-dose irradiation of donor hearts before transplantation inhibit graft vasculopathy?

International Nuclear Information System (INIS)

Shirasawa, Bungo; Hamano, Kimikazu; Ito, Hiroshi; Gohra, Hidenori; Katho, Tomoe; Fujimura, Yoshihiko; Esato, Kensuke

1999-01-01

This experimental study was conducted to histopathologically determine whether the low-dose irradiation of donor hearts before transplantation can inhibit graft vasculopathy. Immediately after donor F 344 rat hearts were removed, they were treated with a single dose of radiation using 7.5 Gy, 15 Gy, or no radiation (control group). The F 344 hearts were transplanted into Lewis rats heterotopically, and cyclosporine A was injected intramuscularly for 20 days after transplantation in all groups. The hearts were harvested 90 days after transplantation, and examined for intimal thickening using elastica van Gieson staining. Severe intimal thickening was observed in both the irradiated groups, the percent intimal area of the coronary arteries was significantly increased in both these groups, to 34.3±12.9 in the 7.5 Gy group and 37.0±8.9 in the 15 Gy group, compared with 23.1±9.8 in the control group (p<0.01). In conclusion, these findings show that low-dose irradiation to donor hearts before transplantation does not inhibit graft vasculopathy. (author)

Effect of ultraviolet B irradiation on delayed-type hypersensitivity, cytotoxic T lymphocyte activity, and skin graft rejection

International Nuclear Information System (INIS)

Tamaki, K.; Iijima, M.

1989-01-01

The influence of ultraviolet B irradiation on the induction of delayed-type hypersensitivity reactions to alloantigens by epidermal cells (EC), on the generation of cytotoxic T lymphocyte activity to alloantigens, and on skin graft rejection was studied. After the skin was irradiated with UVB in vitro, EC were obtained. The EC were injected subcutaneously, and the DTH reaction was compared with that induced by non-UVB-irradiated EC. A reduction in the DTH reaction was observed (from 62% to 99.1%). CTL activity in these mice was assessed after in vitro stimulation. CTL activity in mice sensitized with UVB-irradiated EC was significantly reduced. Furthermore, mice sensitized with UVB-irradiated EC did not reject a subsequent skin allograft in an accelerated fashion, whereas mice sensitized with non-UVB-irradiated EC did. The mechanism(s) of these reactions and the clinical application of the UVB irradiation prior to grafting are discussed

Implementation of good manufacturing practices (GMP) on human blood irradiation

International Nuclear Information System (INIS)

Boghi, Claudio; Napolitano, Celia M.; Ferreira, Danilo C.; Rela, Paulo Roberto; Zarate, Herman S.

2007-01-01

The irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease), a rare but devastating adverse effect of leukocytes present in blood components for a immuno-competent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of lymphocytes. The implementation of the GMP will assure that the properly dose in a range of 25 Gy to 50 Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies to establish the GMP were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaSO 4 : Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, trace ability and calibration system. The PMMA and gafchromic dosimetric systems have shown a better performance and were adopted on establishment of GMP procedures. The irradiation tests have been done using a Gammacell 220 Irradiator. The developed GMP can be adapted for different types of gamma irradiators, allowing to set up a quality assurance program for blood irradiation. (author)

Implementation of good manufacturing practices (GMP) on human blood irradiation

Energy Technology Data Exchange (ETDEWEB)

Boghi, Claudio; Napolitano, Celia M.; Ferreira, Danilo C.; Rela, Paulo Roberto [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mails: cboghi@uol.com.br; cmnapoli@ipen.br; dancarde@ig.com.br; prela@ipen.br; Zarate, Herman S. [Comission Chilena de Energia Nuclear, Santiago (Chile)]. E-mail: hzarate@cchen.cl

2007-07-01

The irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease), a rare but devastating adverse effect of leukocytes present in blood components for a immuno-competent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of lymphocytes. The implementation of the GMP will assure that the properly dose in a range of 25 Gy to 50 Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies to establish the GMP were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaSO{sub 4}: Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, trace ability and calibration system. The PMMA and gafchromic dosimetric systems have shown a better performance and were adopted on establishment of GMP procedures. The irradiation tests have been done using a Gammacell 220 Irradiator. The developed GMP can be adapted for different types of gamma irradiators, allowing to set up a quality assurance program for blood irradiation. (author)

Good manufacturing practices (GMP utilized on human blood irradiation process

Directory of Open Access Journals (Sweden)

Cláudio Boghi

2008-01-01

Full Text Available Irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease, a rare but devastating adverse effect of leukocytes present in blood components for immunocompetent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of lymphocytes. The implementation of the GMP will assure that the properly dose in a range of 25Gy to 50Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies to establish the GMP were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaSO4: Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, trace ability and calibration system. The PMMA and gafchromic dosimetric systems have shown a better performance and were adopted on establishment of GMP procedures. The irradiation tests have been done using a Gammacell 220 Irradiator. The developed GMP can be adapted for different types of gamma irradiators, allowing to set up a quality assurance program for blood irradiation.

Kinetic investigations of graft copolymerization of sodium styrene sulfonate onto electron beam irradiated poly(vinylidene fluoride) films

Energy Technology Data Exchange (ETDEWEB)

Mahmoud Nasef, Mohamed, E-mail: mahmoudeithar@fkkksa.utm.m [Institute of Hydrogen Economy, International City Campus, Universiti Teknologi Malaysia, Jalan Semarak, 54100 Kuala Lumpur (Malaysia); Chemical Engineering Department, Faculty of Chemical and Natural Resources Engineering, Universiti Teknologi Malaysia, 81310 UTM Skudai, Johor (Malaysia); Saidi, Hamdani [Institute of Hydrogen Economy, International City Campus, Universiti Teknologi Malaysia, Jalan Semarak, 54100 Kuala Lumpur (Malaysia); Chemical Engineering Department, Faculty of Chemical and Natural Resources Engineering, Universiti Teknologi Malaysia, 81310 UTM Skudai, Johor (Malaysia); Mohd Dahlan, Khairul Zaman [Radiation Processing Technology Division, Malaysian Nuclear Agency, Bangi, 43000 Kajang, Selangor (Malaysia)

2011-01-15

Graft copolymerization of sodium styrene sulfonate (SSS) onto electron beam (EB) irradiated poly(vinylidene fluoride) (PVDF) films was investigated to find out a simple preparation process for sulfonic acid proton exchange membranes with respect to monomer concentration, absorbed dose, temperature, film thickness and storage time. The reaction order of the monomer concentration and absorbed dose of grafting was found to be 2.84 and 1.20, respectively. The overall activation energy for graft copolymerization reaction was calculated to be 11.36 kJ/mol. The initial rate of grafting was found to decrease with an increase in the film thickness. The trapped radicals in the irradiated PVDF films remained effective in initiating the reaction without considerable loss in grafting level up to 180 days, when stored under -60 {sup o}C. The presence and distribution of polystyrene sulfonate grafts in the obtained membranes were observed by Fourier transform infrared (FTIR) spectroscopic analysis, scanning optical microscope and scanning transmission electron microscopy (STEM) coupled with X-ray energy dispersive (EDX), respectively.

Recipient Immune Modulation with Atorvastatin for Acute Graft-versus-Host Disease Prophylaxis after Allogeneic Transplantation.

Science.gov (United States)

Kanate, Abraham S; Hari, Parameswaran N; Pasquini, Marcelo C; Visotcky, Alexis; Ahn, Kwang W; Boyd, Jennifer; Guru Murthy, Guru Subramanian; Rizzo, J Douglas; Saber, Wael; Drobyski, William; Michaelis, Laura; Atallah, Ehab; Carlson, Karen S; D'Souza, Anita; Fenske, Timothy S; Cumpston, Aaron; Bunner, Pamela; Craig, Michael; Horowitz, Mary M; Hamadani, Mehdi

2017-08-01

Atorvastatin administration to both the donors and recipients of matched related donor (MRD) allogeneic hematopoietic cell transplantation (allo-HCT) as acute graft-versus-host disease (GVHD) prophylaxis has been shown to be safe and effective. However, its efficacy as acute GVHD prophylaxis when given only to allo-HCT recipients is unknown. We conducted a phase II study to evaluate the safety and efficacy of atorvastatin-based acute GVHD prophylaxis given only to the recipients of MRD (n = 30) or matched unrelated donor (MUD) (n = 39) allo-HCT, enrolled in 2 separate cohorts. Atorvastatin (40 mg/day) was administered along with standard GVHD prophylaxis consisting of tacrolimus and methotrexate. All patients were evaluable for acute GVHD. The cumulative incidences of grade II to IV acute GVHD at day +100 in the MRD and MUD cohorts were 9.9% (95% confidence interval [CI], 0 to 20%) and 29.6% (95% CI,15.6% to 43.6%), respectively. The cumulative incidences of grade III and IV acute GVHD at day +100 in the MRD and MUD cohorts were 3.4% (95% CI, 0 to 9.7%) and 18.3% (95% CI, 6.3% to 30.4%), respectively. The corresponding rates of moderate/severe chronic GVHD at 1 year were 28.1% (95% CI, 11% to 45.2%) and 38.9% (95% CI, 20.9% to 57%), respectively. In the MRD cohort, the 1-year nonrelapse mortality, relapse rate, progression-free survival, and overall survival were 6.7% (95% CI, 0 to 15.4%), 43.3% (95% CI, 24.9% to 61.7%), 50% (95% CI, 32.1% to 67.9%), and 66.7% (95% CI, 49.8% to 83.6%), respectively. The respective figures for the MUD cohort were 10.3% (95% CI, 8% to 19.7%), 20.5% (95% CI, 7.9% to 33.1%), 69.2% (95% CI, 54.7% to 83.7%), and 79.5% (95% CI, 66.8% to 92.2%), respectively. No grade 4 toxicities attributable to atorvastatin were seen. In conclusion, the addition of atorvastatin to standard GVHD prophylaxis in only the recipients of MRD and MUD allo-HCT appears to be feasible and safe. The preliminary efficacy seen here warrants confirmation in

Evidence for successful acceptance of irradiated free gingival allografts in dogs

International Nuclear Information System (INIS)

Rubenstein, H.S.; Ruben, M.P.; Levy, C.; Peiser, S.

1975-01-01

Free graft samples were excised and frozen to -55 0 C. Subsequently the grafts were exposed to 2.5 x 10 6 rads of 60 Co γ-radiation. The irradiated allogeneic grafts were later reconstituted and surgically transferred to four recipient subjects. Three autogenous nonirradiated grafts were also placed as controls. The animals were killed so as to furnish healing data at 0, 3, 7, 10, and 40 days postoperatively. Fourteen allografts were evaluated. They were judged to be nonantigenic, immunologically incompetent and nonviable. However, retention of an essentially unaltered connective tissue corium may have been instrumental in supporting subsequent epithelial regeneration from adjacent host tissue, while being passively incorporated into a very dynamic receptor zone. The graft thus served as a scaffolding for connective tissue deposition and attachment. It appears that the experimental regime obviated the immunologic interference usually encountered in allografting procedures. Thus, high intensity irradiation of the graft tissue may have rendered the tissue to be immunologically tolerable. Further studies are required to ascertain the duration of the host's immunologic unresponsiveness to the alien tissue, as well as ultimate structural and biologic fate of the transplanted tissues. Experiments are now in progress which have been designed to test the extent of immunologic sensitization induced by the grafted tissue

Preclinical Testing of Antihuman CD28 Fab' Antibody in a Novel Nonhuman Primate Small Animal Rodent Model of Xenogenic Graft-Versus-Host Disease.

Science.gov (United States)

Hippen, Keli L; Watkins, Benjamin; Tkachev, Victor; Lemire, Amanda M; Lehnen, Charles; Riddle, Megan J; Singh, Karnail; Panoskaltsis-Mortari, Angela; Vanhove, Bernard; Tolar, Jakub; Kean, Leslie S; Blazar, Bruce R

2016-12-01

Graft-versus-host disease (GVHD) is a severe complication of hematopoietic stem cell transplantation. Current therapies to prevent alloreactive T cell activation largely cause generalized immunosuppression and may result in adverse drug, antileukemia and antipathogen responses. Recently, several immunomodulatory therapeutics have been developed that show efficacy in maintaining antileukemia responses while inhibiting GVHD in murine models. To analyze efficacy and better understand immunological tolerance, escape mechanisms, and side effects of clinical reagents, testing of species cross-reactive human agents in large animal GVHD models is critical. We have previously developed and refined a nonhuman primate (NHP) large animal GVHD model. However, this model is not readily amenable to semi-high throughput screening of candidate clinical reagents. Here, we report a novel, optimized NHP xenogeneic GVHD (xeno-GVHD) small animal model that recapitulates many aspects of NHP and human GVHD. This model was validated using a clinically available blocking, monovalent anti-CD28 antibody (FR104) whose effects in a human xeno-GVHD rodent model are known. Because human-reactive reagents may not be fully cross-reactive or effective in vivo on NHP immune cells, this NHP xeno-GVHD model provides immunological insights and direct testing on NHP-induced GVHD before committing to the intensive NHP studies that are being increasingly used for detailed evaluation of new immune therapeutic strategies before human trials.

Antibiotic-Induced Depletion of Anti-inflammatory Clostridia Is Associated with the Development of Graft-versus-Host Disease in Pediatric Stem Cell Transplantation Patients.

Science.gov (United States)

Simms-Waldrip, Tiffany R; Sunkersett, Gauri; Coughlin, Laura A; Savani, Milan R; Arana, Carlos; Kim, Jiwoong; Kim, Minsoo; Zhan, Xiaowei; Greenberg, David E; Xie, Yang; Davies, Stella M; Koh, Andrew Y

2017-05-01

Adult stem cell transplantation (SCT) patients with graft-versus-host-disease (GVHD) exhibit significant disruptions in gut microbial communities. These changes are associated with higher overall mortality and appear to be driven by specific antibiotic therapies. It is unclear whether pediatric SCT patients who develop GVHD exhibit similar antibiotic-induced gut microbiota community changes. Here, we show that pediatric SCT patients (from Children's Medical Center Dallas, n = 8, and Cincinnati Children's Hospital, n = 7) who developed GVHD showed a significant decline, up to 10-log fold, in gut anti-inflammatory Clostridia (AIC) compared with those without GVHD. In fact, the development of GVHD is significantly associated with this AIC decline and with cumulative antibiotic exposure, particularly antibiotics effective against anaerobic bacteria (P = .003, Firth logistic regression analysis). Using metagenomic shotgun sequencing analysis, we were able to identify specific commensal bacterial species, including AIC, that were significantly depleted in GVHD patients. We then used a preclinical GVHD model to verify our clinical observations. Clindamycin depleted AIC and exacerbated GVHD in mice, whereas oral AIC supplementation increased gut AIC levels and mitigated GVHD in mice. Together, these data suggest that an antibiotic-induced AIC depletion in the gut microbiota is associated with the development of GVHD in pediatric SCT patients. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Management of an irradiated anophthalmic socket following dermis-fat graft rejection: A case report

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Raizada Kuldeep

2008-01-01

Full Text Available Dermis-fat graft (DFG is often the only promising option in cases of severely contracted sockets. However, there is an increased risk of graft failure in irradiated sockets with decreased vascularity. In such difficult cases, repeat DFG implantation also has higher risks of graft failure. We describe an ingenious method of successful management of an irradiated anophthalmic socket following DFG infection and necrosis, with acceptable cosmetic results. At surgery, an orbital impression was taken with ophthalmic grade alginate. Based on this measurement, a custom-made stem pressure socket-expander made up of high density polymethyl methacrylate (PMMA was fitted, a week post surgery and kept in situ for six weeks. On review, the fornices had considerably deepened. The expander device was removed and the patient was now fitted with a custom-made thicker prosthesis made up of high-density PMMA. The patient has followed up for a year subsequently and the prosthesis has remained stable.

Descemet Stripping Automated Endothelial Keratoplasty for Failed Penetrating Keratoplasty: Influence of the Graft-Host Junction on the Graft Survival Rate.

Science.gov (United States)

Omoto, Takashi; Sakisaka, Toshihiro; Toyono, Tetsuya; Yoshida, Junko; Shirakawa, Rika; Miyai, Takashi; Yamagami, Satoru; Usui, Tomohiko

2018-04-01

To investigate the clinical results of Descemet stripping automated endothelial keratoplasty (DSAEK) for failed penetrating keratoplasty (PK) and the influence of the graft-host junction (GHJ) on the graft survival rate. Data were retrospectively collected on patient demographics, visual outcomes, complications, and graft survival rate for 17 eyes of 16 patients who underwent DSAEK for failed PK. The graft survival rate was compared between the eyes when divided into a bump group and a well-aligned group according to the shape of the GHJ detected on anterior segment optical coherence tomography. The most common indication for initial PK was bullous keratopathy after glaucoma surgery (35.3%). Seven eyes (41.2%) were classified into the bump group and 10 eyes (58.8%) into the well-aligned group. The mean best-ever documented visual acuity (BDVA) after DSAEK was 0.33 logMAR. Postoperatively, almost 70% of eyes achieved a BDVA that was within 0.2 logMAR of their preoperative BDVA. Graft detachment occurred in 29.4% of eyes and primary graft failure in 17.6%. All primary failures occurred in the bump group. The cumulative graft survival rate was 82.3% at 1 year, 73.2% at 2 years, and 58.6% at 3 years. Graft failure was more likely in eyes in the bump group than in those in the well-aligned group (P = 0.037, Wilcoxon test). DSAEK for failed PK had a favorable outcome in this study. However, the GHJ should be assessed carefully before performing the procedure.

PTFE grafts versus tunneled cuffed catheters for hemodialysis: which is the second choice when arteriovenous fistula is not feasible?

Science.gov (United States)

Donati, Gabriele; Cianciolo, Giuseppe; Mauro, Raffaella; Rucci, Paola; Scrivo, Anna; Marchetti, Antonio; Giampalma, Emanuela; Golfieri, Rita; Panicali, Laura; Iorio, Mario; Stella, Andrea; La Manna, Gaetano; Stefoni, Sergio

2015-02-01

Vascular access-related complications are still one of the leading causes of morbidity in hemodialysis patients. The aim of this study was to compare polytetrafluoroethylene (PTFE) grafts versus tunneled cuffed permanent catheters (TCCs) in terms of vascular access and patients' survival. An observational study was carried out with a 2-year follow-up. Eighty-seven chronic hemodialysis patients were enrolled: 31 with a PTFE graft as vascular access for hemodialysis versus 56 with a TCC. Patients' mean age was 63.8 ± 14.6 (grafts) versus 73.5 ± 11.3 years (TCCs), P = 0.001. Significantly more patients with TCC had atrial fibrillation than patients with grafts (30.3% versus 6.5%, P = 0.01). In an unadjusted Kaplan-Meier analysis, median TCC survival at 24 months was 5.4 months longer than that of PTFE grafts but not significantly (log-rank test = 1.3, P = ns). In a Cox regression analysis adjusted for age, gender, number of previous vascular accesses, diabetes, atrial fibrillation, smoking, and any complication, this lack of significant difference in survival of the vascular access between TCC and PTFE groups was confirmed and diabetes proved to be an independent risk factor for the survival of both vascular accesses considered (P = 0.02). In an unadjusted Kaplan-Meier analysis, a higher mortality was found in the TCC group than in the PTFE group at 24 months (log-rank test = 10.07, P PTFE grafts. When an arteriovenous fistula (AVF) is not possible, PTFE grafts can be considered the vascular access of second choice, whereas TCCs can be used when an AVF or PTFE graft are not feasible or as a bridge to AVF or PTFE graft creation. Copyright © 2014 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Irradiation grafting of natural rubber latex with maleic anhydride and its compatibilization of poly(lactic acid)/natural rubber blends

Science.gov (United States)

Pongsathit, Siriwan; Pattamaprom, Cattaleeya

2018-03-01

Maleic anhydride (MA) is an interesting monomer to be grafted onto natural rubber(NR) due to its potential as a compatibilizer of hydrophobic rubbers and polymers with higher polarity. So far, radiation grafting of MA onto NR in latex state has not been reported. In this study, the grafting of NR with MA in latex state was investigated by exposing the latex to cobalt-60 gamma irradiation at a fixed MA content of 9% and a varied absorbed doses from 2 to 10 kGy. The FTIR spectrometer, 1H NMR spectrometer and gel content analysis have confirmed successful grafting of MA onto NR after irradiation. The grafted NRs were then used to increase the compatibility and the impact property of PLA/NR blends. It was found that the highest impact strength of the blends was achieved when the grafting was carried out at the absorbed dose of 4 kGy.

SEVERE (GRADE III-IV ACUTE GRAFT VERSUS HOST DISEASE AFTER ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANTATION

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Irena Preložnik-Zupan

2002-09-01

Full Text Available Background. Beside greater susceptibility to infections, acute graft host disease is a consequence of the activation of donor T-cells against host antigens. Most common target organs are skin, liver and intestinal mucosis.Methods. In the 6-year period between January 1995 and December 2000, 49 patients were treated with allogeneic haematopoietic stem cell transplantation (allo-HSCT in Transplant unit, Department of Hematology, Clinical Centre Ljubljana. The standard GVHD prophylaxis regimen consisted of cyclosporine and short-course methotrexate. Severe, grade III-IV aGVHD with skin and/or gastrointestinal and/or liver involvement appeared in 16 (32% of the 49 patients.Results. Among the 16 patients with severe aGVHD, 14 had liver involvement, ten gastrointestinal and eight skin involvement. One patient had skin involvement only, the rest of them had combined involvement of two or three organ systems. Routine first-line treatment for aGVHD, given to all 16 pts with severe forms of the disease, was methylprednisolone (MP 2mg/ kg. Six patients with predominant skin involvement responded to MP. Other ten patients with mainly liver and gastrointestinal involvement needed second or even third line aGVHD treatment. These were anti-thymocyte globulin (ATG and/or monoclonal antibodies (OKT3 and/or mycophenolate mofetil (MMF and/or FK506 (tacrolimus. Seven patients died of advanced aGVHD and treatment related infection.Conclusions. Based on our experiences, we conclude that in critically ill patients with severe aGVHD, neutropenia and high risk for opportunistic infection, each day of ineffective MP therapy may have fatal consequences. Simultaneous institution of a combination of corticosteroids and a second-line drug might prove more appropriate for patients with a severe form of aGVHD.

Chronic graft-versus-host disease in the rat radiation chimera: I. clinical features, hematology, histology, and immunopathology in long-term chimeras

Energy Technology Data Exchange (ETDEWEB)

Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

1982-04-01

The clinical features, pathology, and immunopathology of chronic graft-versus-host disease (GVHD) developing in the long-term rat radiation chimera are described. At 6 to 12 months post-transplant, the previously stable ACI/LEW chimeras developed patchy to diffuse severe hair loss and thickened skin folds, and had microscopic features resembling scleroderma, Sjogren's syndrome, and chronic hepatitis. Skin histology showed dermal inflammation and acanthosis with atrophy of the appendages, with progression to dermal sclerosis. The liver revealed chronic hepatitis with bile duct injury and proliferation and periportal piecemeal necrosis. The tongue had considerable submucosal inflammation, muscular necrosis, and atrophy and arteritis. The serous salivary glands, lacrimal glands, and bronchi had lymphocytic inflammation and injury to duct, acinar, and mucosal columnar epithelium. The thymus had lymphocyte depletion of the medulla with prominent epithelium. The spleen and lymph nodes had poorly developed germinal centers but increased numbers of plasma cells. IgM was observed along the basement membrane and around the basal cells of the skin and tongue and along the basement membrane of the bile ducts. IgM was present also in the arteries of the tongue. Immunoglobulins eluted from the skin, cross-reacted with the bile duct epithelium and usually with both ACI and Lewis skin. Increased titers of speckled antinuclear antibodies were present in the serum of rats with chronic (GVHD). Chronic GVHD in the long-term rat radiation chimera is very similar to human chronic GVHD and is a potentially excellent model for autoimmune disorders including scleroderma, Sjorgren's syndrome, and chronic hepatitis.

Chronic graft-versus-host disease in the rat radiation chimera: I. clinical features, hematology, histology, and immunopathology in long-term chimeras

International Nuclear Information System (INIS)

Beschorner, W.E.; Tutschka, P.J.; Santos, G.W.

1982-01-01

The clinical features, pathology, and immunopathology of chronic graft-versus-host disease (GVHD) developing in the long-term rat radiation chimera are described. At 6 to 12 months post-transplant, the previously stable ACI/LEW chimeras developed patchy to diffuse severe hair loss and thickened skin folds, and had microscopic features resembling scleroderma, Sjogren's syndrome, and chronic hepatitis. Skin histology showed dermal inflammation and acanthosis with atrophy of the appendages, with progression to dermal sclerosis. The liver revealed chronic hepatitis with bile duct injury and proliferation and periportal piecemeal necrosis. The tongue had considerable submucosal inflammation, muscular necrosis, and atrophy and arteritis. The serous salivary glands, lacrimal glands, and bronchi had lymphocytic inflammation and injury to duct, acinar, and mucosal columnar epithelium. The thymus had lymphocyte depletion of the medulla with prominent epithelium. The spleen and lymph nodes had poorly developed germinal centers but increased numbers of plasma cells. IgM was observed along the basement membrane and around the basal cells of the skin and tongue and along the basement membrane of the bile ducts. IgM was present also in the arteries of the tongue. Immunoglobulins eluted from the skin, cross-reacted with the bile duct epithelium and usually with both ACI and Lewis skin. Increased titers of speckled antinuclear antibodies were present in the serum of rats with chronic (GVHD). Chronic GVHD in the long-term rat radiation chimera is very similar to human chronic GVHD and is a potentially excellent model for autoimmune disorders including scleroderma, Sjorgren's syndrome, and chronic hepatitis

Host influence on irradiation bioefficacy : growth and development of Spodoptera litura (Fabricius)

International Nuclear Information System (INIS)

Seth, R.K.

1995-01-01

Survival and development of Spodoptera litura(F), a polyphagous pest was ascertained on a range of host plants, common and economic in the Indian context. Castor, cotton, green gram and okra constituted the preferred host group showing significantly better growth rate (GR) and growth index (GI) than the group of less preferred host plants that included groundnut, red gram, rose leaf and rose petal. Ontogenic growth profile vis-a-vis irradiation was studied with recording of GI at L3, pupa and adult levels in response to gamma dosages administered in L1 stage. Irradiation effect on the growth index was mainly due to reduction in survival, which was further pronounced owing to delay in development. On all the preferred host plants, adult-G1 was reduced by more than 50 per cent at 40 Gy gamma dose; whereas the same dose on less preferred host plants could prevent adult emergence on ground nut and red gram, and inhibited pupa formation on rose diet. The percentage mortality of larvae exhibiting delayed development was markedly more in the less preferred host group. Dose dependent reduction was observed in the larval growth rate of L3, L5 and L6 instars on all the host plants. 20 Gy exhibited almost same intensity of adverse impact in less preferred host group as was shown by 40 Gy in preferred hosts. 20 Gy dose reduced the pupal weight and conversion ratio of treated insects significantly. Age influence was evident on irradiation efficacy on all the diets. Insects treated in the later instar had less radiosusceptibility as compared to the young irradiated larvae. Irradiation had a negative correlation with survival and weight gain during the course of development that in turn bore a positive relation with the increase in radiation dosage. Food is an important governing factor in influencing the insects survival value and developmental behaviour and may modify its intrinsic sensitivity towards irradiation stress. (author). 21 refs., 1 fig., 5 tabs

Analysis of Gel Permeation Chromatography From Irradiation Copolymer Grafting of Methylmethacrylate on to Natural Rubber

International Nuclear Information System (INIS)

Hendrana, Sunit; Purwanto, Indratmoko Hari; Karyaningsih, Ipit; Utama, MargaHerwinarni

2004-01-01

Grafting of methyl methacrylate (MMA) onto natural rubber was carried out by γ-irradiation using 60 Co source at dose rate 1 KGy/h and total dose of 5 KGy. Gel permeation chromatography (GPC) was used to analyse the grafting. The GPC's chromatogram, molecular weight and molecular weight distribution data indicate that grafting of MMA onto natural rubber and homo polymerization of MMA are the reaction mostly occurs. Meanwhile, the presence of natural rubber radical with a chain end natural rubber radical affect the PMMA homopolymer occurred

Differentiation of bone marrow cells to functional T lymphocytes following implantation of thymus grafts and thymic stroma in nude and ATxBM mice

International Nuclear Information System (INIS)

Splitter, G.A.; McGuire, T.C.; Davis, W.C.

1977-01-01

Cardiac allografts were used to compare the immunologic capacity of nude mice and adult, thymectomized, lethally irradiated, bone marrow-reconstituted (AT x BM) mice. Neither nude nor AT x BM mice were able to reject cardiac allografts of any party. However, both rejected grafts of any party following implantation of neonatal thymus or thymus from 3-week-old syngeneic mice. Irradiated syngeneic thymus grafts (800 R) were equally effective in restoring host responsiveness against allografts. In contrast, allogeneic thymus grafts restored the capacity to reject second-party heart grafts only in AT x BM mice. Second-party grafts persisted indefintely when placed on nude mice implanted with an allogeneic, unirradiated thymus graft. Third-party grafts transplanted 17 weeks after reconstitution, however, were rejected. Irradiated nude mice given normal littermate bone marrow and simultaneously grafted with second-party thymus and heart allografts also failed to reject their second-party heart grafts. The difference in ultimate capacity to respond between AT x BM and nude mice suggests that a maturational defect exists in the nude mouse environment which impedes development of precursor T lymphocytes

Effects of solvent polarity on mutual polypropylene grafting by electron beam irradiation

International Nuclear Information System (INIS)

Geraldo, A.B.C.; Moura, E.; Somessari, E.S.R.; Silveira, C.G.; Paes, H.A.; Souza, C.A.; Fernandes, W.; Manzoli, J.E.

2011-01-01

Complete text of publication follows. Copolymerization by grafting is a process largely known and the advantages of modifying polymers by radiation includes superimposition of properties related to the backbone and the grafted chains in the absence of an initiator. This process produces low byproduct levels, costs and hazards. Since polypropylene is applied in many industrial and commercial sectors, the grafting process is an alternative to improve some of its physical and chemical properties. The aim of this work was to verify the effect of distinct organic solvents on polypropylene grafting process by mutual irradiation applying absorbed doses from 30 kGy to 100 kGy at dose rates of 2.2 kGy/s and 22.4 kGy/s. All process were performed in atmosphere air presence. Styrene was the monomer grafted on polymer substrate and some non-polar and polar organic solvents, like toluene, xylene, acetone, methanol and its homologous, were used at distinct concentrations. The grafted samples were evaluated by degree of styrene grafting (gravimetric determination) and the Mid-FTIR spectrophotometry. As a general behavior, the degree of grafting increases when absorbed dose values increase in a specific solvent until a maximum dose value (50-70 kGy), after this, the degree of grafting decreases. Moreover, the grafting process have high yields when protic polar solvents are used. These results suggest the grafting process does not have dependence of substrate swelling, that is expected when a non-polar substrate and a non-polar media are in contact. The grafting, in this case, can be related to the free radical generation at protic polar solvents in a first step of process mechanism; these reactive specimens start the reaction on substrate surface to allow the accessibility of monomer species to active sites. Some reaction mechanisms are proposed.

Graft copolymerization of vinyl monomers onto nylon 6 fibers by γ-ray pre-irradiation in air

International Nuclear Information System (INIS)

Iwasaki, Tatsuo; Ueda, Yoshitsugu

1992-01-01

Vinyl acetate, methyl methacrylate, alkyl acrylates, acrylonitrile, and acrylamide, were grafted onto nylon 6 fibers by the γ-ray pre-irradiation technique, and the effects of grafting on the microstructure and the mechanical properties of the graft copolymers were investigated. According to the analysis by wide-angle X-ray diffraction, the degree of crystallization decreased by increasing the percent graft of poly(vinyl acetate) in the grafted nylon 6 films. The mechanical parameters, such as the Young's modulus and the tensile strength at break, increased with increasing percent graft up to 50%. When percent grafting was smaller than 50%, rather homogeneous amorphous materials were obtained with vinyl acetate, while heterogeneous ones were obtained with other vinyl monomers. A poly(vinyl alcohol) grafted nylon 6 was obtained effectively by saponification of poly(vinyl acetate) grafted nylon 6, the former showing higher mechanical properties than the latter. Similar behavior was observed after saponification of the poly(methyl acrylate) grafted nylon 6. (author)

Serial changes in plasma K concentration during storage of irradiation blood products

International Nuclear Information System (INIS)

Togashi, Kazue; Yamada, Keiko; Otake, Sachiko; Saito, Yukiko; Sugimura, Kazuhito; Takahashi, Hoyu

1996-01-01

Irradiation of blood products is highly effective in the prevention of transfusion-associated graft-versus-host disease (GVHD). In order to assess the safe storage period of irradiated blood products, serial changes in plasma K, red cell 2,3-diphosphoglycerate (2,3-DPG) and lactic acid concentrations of whole blood and M·A·P-added red cell concentrate (RC-M·A·P) during storage at 5degC were measured after irradiation with 137 Cs by IBL 437C (CIS bio international). Plasma K concentration did not change immediately after irradiation, but increased more rapidly and in a radiation dose-dependent manner in the irradiated products than nonirradiated products. The changes in red cell 2,3-DPG and lactic acid concentrations were not affected by irradiation but were rather dependent on the storage period after blood collection. Plasma K concentrations of whole blood and RC-M·A·P irradiated with 25 Gy increased at 5 and 3 days, respectively, to the K levels observed after the storage of nonirradiated products for 21 days. It is therefore recommended that whole blood be used within 5 days and RC-M·A·P within 3 days when stored after irradiation with 25 Gy. (author)

Current outcome of HLA identical sibling versus unrelated donor transplants in severe aplastic anemia

DEFF Research Database (Denmark)

Bacigalupo, Andrea; Socié, Gerard; Hamladji, Rose Marie

2015-01-01

We have analyzed 1448 patients with acquired aplastic anemia grafted between 2005 and 2009, and compared outcome of identical sibling (n=940) versus unrelated donor (n=508) transplants. When compared to the latter, sibling transplants were less likely to be performed beyond 180 days from diagnosis.......04). In conclusion, in multivariate analysis, the outcome of unrelated donor transplants for acquired aplastic anemia, is currently not statistically inferior when compared to sibling transplants, although patients are at greater risk of acute and chronic graft-versus-host disease. The use of peripheral blood grafts...

Synthesis of Fuel Cell Membrane: Copolymerization of Styrene on ETFE Film by Grafted pre-Irradiation

Directory of Open Access Journals (Sweden)

Yohan Yohan

2010-10-01

Full Text Available Preirradiation Grafting styrene monomer on ETFE  film has been prepared. Research has been  performed by γ-ray radiation at various total dose from 2.5 - 12.5 kGy and various dose rate from 1.3 - 1.9 kGy/hour. Irradiated copolymer is then grafted by styrene monomer in various solvent: ethanol, 2-propanol, and toluene, various concentration from 20 - 70% volume, various temperature from 50 - 90oC, and various grafting time from 2 - 12 hours. The results showed that percent of grafting is increase with increase of total dose and decrease of  rate dose. The optimum experiment conditions are obtained at total dose 10 kGy, dose rate 1,9 kGy/hour, 2-propanol solvent, 40% volume styrene, 4 hours grafting time, and 70oC grafting temperature.

Mutual irradiation grafting on indigenous aramid fiber-3 in diethanolamine and epichlorohydrin and its effect on interfacially reinforced epoxy composite

Energy Technology Data Exchange (ETDEWEB)

Xing, Lixin [School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin 150001,China (China); Department of Materials Science and Engineering, The Pennsylvania State University, University Park, PA 16802 (United States); Liu, Li, E-mail: liuli@hit.edu.cn [School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin 150001,China (China); Xie, Fei [School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin 150001,China (China); Huang, Yudong [School of Chemical Engineering and Technology, Harbin Institute of Technology, Harbin 150001,China (China); State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150001 (China)

2016-07-01

Highlights: • High energy gamma rays were used to decorate the surface of aramid fiber via mutual irradiation grafting process in two medium. • The effects of different grafting medium on aramid fiber surface were investigated through SEM, AFM, XPS, wettability and adsorption measurements. • Interfacial properties of aramid reinforced polymer composites were remarkable improved after mutual irradiation. - Abstract: The surface of indigenous aramid fiber-3 (IAF3) was decorated via mutual irradiation grafting process in diethanolamine (DEA) and epichlorohydrin (ECH), respectively, with the assist of high energy gamma rays. This modification method with great permeability produced the homogeneous and ameliorative AF3 surfaces, which were observed by the scanning electron microscopy (SEM) and atom forced microscopy (AFM). Enhanced surface free energy and reduced contact angles of irradiated AF3 verified the fabulous effectiveness of mutual irradiation without seriously injured tensile strength. The composites based on epoxy resin (ER) polymer as the matrix and irradiated IAF3 grafted DEA and ECH as the reinforcement. By capitalizing on the irradiated IAF3 which has higher wettability and adsorption on resin, the irradiated IAF3-ECH/ER composites exhibit admirable interfacial mechanical performance as compared to the pristine IAF3 contained composites. The interfacial shear strength (IFSS), interlaminar shear strength (ILSS) and flexural strength of composites were remarkable improved to 86.5, 60.13 and 511 MPa respectively, from the pristine IAF3/ER composite with IFSS of 65.9 MPa, ILSS of 48.1 MPa, and flexural strength of 479 MPa.

Mutual irradiation grafting on indigenous aramid fiber-3 in diethanolamine and epichlorohydrin and its effect on interfacially reinforced epoxy composite

International Nuclear Information System (INIS)

Xing, Lixin; Liu, Li; Xie, Fei; Huang, Yudong

2016-01-01

Highlights: • High energy gamma rays were used to decorate the surface of aramid fiber via mutual irradiation grafting process in two medium. • The effects of different grafting medium on aramid fiber surface were investigated through SEM, AFM, XPS, wettability and adsorption measurements. • Interfacial properties of aramid reinforced polymer composites were remarkable improved after mutual irradiation. - Abstract: The surface of indigenous aramid fiber-3 (IAF3) was decorated via mutual irradiation grafting process in diethanolamine (DEA) and epichlorohydrin (ECH), respectively, with the assist of high energy gamma rays. This modification method with great permeability produced the homogeneous and ameliorative AF3 surfaces, which were observed by the scanning electron microscopy (SEM) and atom forced microscopy (AFM). Enhanced surface free energy and reduced contact angles of irradiated AF3 verified the fabulous effectiveness of mutual irradiation without seriously injured tensile strength. The composites based on epoxy resin (ER) polymer as the matrix and irradiated IAF3 grafted DEA and ECH as the reinforcement. By capitalizing on the irradiated IAF3 which has higher wettability and adsorption on resin, the irradiated IAF3-ECH/ER composites exhibit admirable interfacial mechanical performance as compared to the pristine IAF3 contained composites. The interfacial shear strength (IFSS), interlaminar shear strength (ILSS) and flexural strength of composites were remarkable improved to 86.5, 60.13 and 511 MPa respectively, from the pristine IAF3/ER composite with IFSS of 65.9 MPa, ILSS of 48.1 MPa, and flexural strength of 479 MPa.

Autologous fat graft in irradiated orbit postenucleation for retinoblastoma.

Science.gov (United States)

Klinger, Francesco; Maione, Luca; Vinci, Valeriano; Lisa, Andrea; Barbera, Federico; Balia, Laura; Caviggioli, Fabio; Di Maria, Alessandra

2018-01-05

Autologous fat grafting has been extensively and successfully adopted in a number of pathologic conditions in regenerative surgery especially on irradiated fields in order to improve pain symptoms and tissue trophism promoting scar release. In the present study, we report our experience with autologous fat grafting for the treatment of postirradiation fibrosis and pain on three consecutive patients undergoing orbital enucleation for locally advanced retinoblastoma (RB) and subsequent radiotherapy. We selected three consecutive patients who underwent orbital enucleation for locally advanced RB and subsequent local radiotherapy showing severe reduction in orbital volume and eyelid length and retraction due to fibrosis, spontaneous local pain exacerbated after digital pressure with no possibility to place an ocular implant. They underwent autologous fat grafting in the orbital cavity and results were evaluated by clinical examination at 5 and 14 days, and 1, 3, 6 months, and 1 year after surgery. A significant release of scar retraction, reduction of fibrosis and orbital rim contraction together with an important improvement of pain symptoms was observed in all patients. The local changes observed enabled an ease placement of an ocular prosthetic implant (implant). No local or systemic complication occurred. Fat grafting is a promising treatment for patients showing radiotherapy related complication in the orbital area and it should be adopted by all oculoplastic surgeon in order to improve pain syndrome creating the ideal local conditions for the placement of an ocular prosthetic implant.

Cutaneous chronic graft-versus-host disease does not have the abnormal endothelial phenotype or vascular rarefaction characteristic of systemic sclerosis.

Directory of Open Access Journals (Sweden)

Jo Nadine Fleming

2009-07-01

Full Text Available The clinical and histologic appearance of fibrosis in cutaneous lesions in chronic graft-versus -host disease (c-GVHD resembles the appearance of fibrosis in scleroderma (SSc. Recent studies identified distinctive structural changes in the superficial dermal microvasculature and matrix of SSc skin. We compared the dermal microvasculature in human c-GVHD to SSc to determine if c-GVHD is a suitable model for SSc.We analyzed skin biopsies of normal controls (n = 24, patients with SSc (n = 30 and c-GVHD with dermal fibrosis (n = 133. Immunostaining was employed to identify vessels, vascular smooth muscle, dermal matrix, and cell proliferation. C-GVHD and SSc had similar dermal matrix composition and vascular smooth muscle pathology, including intimal hyperplasia. SSc, however, differed significantly from c-GVHD in three ways. First, there were significantly fewer (p = 0.00001 average vessels in SSc biopsies (9.8 when compared with c-GVHD (16.5. Second, in SSc, endothelial markers were decreased significantly (19/19 and 12/14 for VE cadherin and vWF (p = <0.0001 and <0.05, respectively. In contrast, 0/13 c-GVHD biopsies showed loss of staining with canonical endothelial markers. Third, c-GVHD contained areas of microvascular endothelial proliferation not present in the SSc biopsies.The sclerosis associated with c-GVHD appears to resemble wound healing. Focal capillary proliferation occurs in early c-GVHD. In contrast, loss of canonical endothelial markers and dermal capillaries is seen in SSc, but not in c-GVHD. The loss of VE cadherin in SSc, in particular, may be related to microvascular rarefaction because VE cadherin is necessary for angiogenesis. C-GVHD is a suitable model for studying dermal fibrosis but may not be applicable for studying the microvascular alterations characteristic of SSc.

Gamma irradiation effects on the grafting of low-density polyethylene with diethyl maleate

International Nuclear Information System (INIS)

Sanchez, Y.; Albano, C.; Karam, A.; Perera, R.; Silva, P.; Gonzalez, J.

2005-01-01

In this work, a low-density polyethylene (LDPE) was grafted with diethyl maleate (DEM) using gamma-rays from a Cobalt-60 source at different absorbed doses and monomer concentrations between 5 and 30 wt.%. This process was carried out in a decalin solution at 10 w/v% to obtain a homogeneous dispersion of the monomer into the polyethylene matrix. It was found that the grafting degree increases with the absorbed doses, as a consequence of the increased amount of energy given to the system, which made the grafting process more favorable. The grafting degree also increases with the concentration of DEM, because a higher concentration makes the insertion easier due to the increased availability of the free monomer. The highest grafting degree was obtained at 200 kGy of absorbed dose and with 30 wt.% of DEM. The melt flow index (MFI) values showed a decreasing trend as the absorbed dose was increased. This fact reveals that crosslinking and grafting are taking place simultaneously, this behavior being remarkable at higher irradiation doses. The results from thermogravimetric analysis (TGA) showed that the initial degradation temperatures remained almost unchanged with the absorbed dose

Limb regeneration from X-irradiated tails of Ambystoma mexicanum following transplantation of flank skin from region adjacent to hindlimb

International Nuclear Information System (INIS)

Hofmann, D.K.; Kleinebeckel, D.; Luther, W.

1978-01-01

In the experiments performed by W. Luther on young Ambystoma mexicanum, tails of host animals were irradiated with 2000 r. Afterwards a skin cuff was removed from the mid-tail region. From non-irradiated donor animals, square pieces of skin dorsally adjacent to both hindlimbs were grafted (either 90 0 -rotated or unrotated) to both sides of the denuded area of the irradiated host tail. After 3 weeks the tails were amputated across the skin transplants, and the structures which had regenerated from the distal portions of the tails were fixed 6-16 weeks later. Morhological and histological investigation revealed that 4 out of 12 regenerates from rotated grafts showed clear limb characteristics. (orig./AJ) [de

Wharton’s Jelly-Derived Mesenchymal Stromal Cells as a Promising Cellular Therapeutic Strategy for the Management of Graft-versus-Host Disease

Directory of Open Access Journals (Sweden)

Joseph P. McGuirk

2015-04-01

Full Text Available Allogeneic hematopoietic cell transplantation (allo-HCT, a treatment option in hematologic malignancies and bone marrow failure syndromes, is frequently complicated by Graft-versus-host disease (GVHD. The primary treatment for GVHD involves immune suppression by glucocorticoids. However, patients are often refractory to the steroid therapy, and this results in a poor prognosis. Therefore alternative therapies are needed to treat GVHD. Here, we review data supporting the clinical investigation of a novel cellular therapy using Wharton’s jelly (WJ-derived mesenchymal stromal cells (MSCs as a potentially safe and effective therapeutic strategy in the management of GVHD. Adult-derived sources of MSCs have demonstrated signals of efficacy in the management of GVHD. However, there are limitations, including: limited proliferation capacity; heterogeneity of cell sources; lengthy expansion time to clinical dose; expansion failure in vitro; and a painful, invasive, isolation procedure for the donor. Therefore, alternative MSC sources for cellular therapy are sought. The reviewed data suggests MSCs derived from WJ may be a safe and effective cellular therapy for GVHD. Laboratories investigated and defined the immune properties of WJ-MSCs for potential use in cellular therapy. These cells represent a more uniform cell population than bone marrow-derived MSCs, displaying robust immunosuppressive properties and lacking significant immunogenicity. They can be collected safely and painlessly from individuals at birth, rapidly expanded and stored cryogenically for later clinical use. Additionally, data we reviewed suggested licensing MSCs (activating MSCs by exposure to cytokines to enhance effectiveness in treating GVHD. Therefore, WJCs should be tested as a second generation, relatively homogeneous allogeneic cell therapy for the treatment of GVHD.

Distinct Biomarker Profiles in Ex Vivo T Cell Depletion Graft Manipulation Strategies: CD34+ Selection versus CD3+/19+ Depletion in Matched Sibling Allogeneic Peripheral Blood Stem Cell Transplantation.

Science.gov (United States)

Cantilena, Caroline R; Ito, Sawa; Tian, Xin; Jain, Prachi; Chinian, Fariba; Anandi, Prathima; Keyvanfar, Keyvan; Draper, Debbie; Koklanaris, Eleftheria; Hauffe, Sara; Superata, Jeanine; Stroncek, David; Muranski, Pawel; Barrett, A John; Battiwalla, Minoo

2018-03-01

Various approaches have been developed for ex vivo T cell depletion in allogeneic stem cell transplantation to prevent graft-versus-host disease (GVHD). Direct comparisons of T cell depletion strategies have not been well studied, however. We evaluated cellular and plasma biomarkers in 2 different graft manipulation strategies, CD3 + CD19 + cell depletion (CD3/19D) versus CD34 + selection (CD34S), and their associations with clinical outcomes. Identical conditions, including the myeloablative preparative regimen, HLA-identical sibling donor, GVHD prophylaxis, and graft source, were used in the 2 cohorts. Major clinical outcomes were similar in the 2 groups in terms of overall survival, nonrelapse mortality, and cumulative incidence of relapse; however, the cumulative incidence of acute GVHD trended to be higher in the CD3/19D cohort compared with the CD34S cohort. A distinct biomarker profile was noted in the CD3/19D cohort: higher levels of ST2, impaired Helios - FoxP3 + Treg reconstitution, and rapid reconstitution of naïve, Th2, and Th17 CD4 cells in the early post-transplantation period. In vitro graft replication studies confirmed that CD3/19D disproportionately depleted Tregs and other CD4 subset repertoires in the graft. This study confirms the utility of biomarker monitoring, which can be directly correlated with biological consequences and possible future therapeutic indications. Published by Elsevier Inc.

Radiobiological speculations on therapeutic total body irradiation

International Nuclear Information System (INIS)

Vriesendorp, H.M.

1990-01-01

Unexpected total body irradiation (TBI) of human beings, involved in nuclear warfare or in accidents in nuclear reactors can be lethal. In the 1950s, bone marrow transplantation was discovered as a potentially life saving procedure after TBI in the dose range of 5.0 to 12.0 Gy. Since that time, deliberate or therapeutic TBI has been used to condition patients with a lethal bone marrow disorder for bone marrow replacement. The therapeutic ratio of TBI followed by bone marrow transplantation is small. Many potentially lethal complications can occur, such as acute TBI side effects, late TBI side effects or immunological complications of bone marrow transplantation such as graft versus host disease or graft rejection. The benefits of TBI and bone marrow transplantation are that they offer a chance for cure of previously lethal bone marrow disorders. The optimal parameters for TBI remain to be defined. The review discusses the current clinical and experimental animal data, as they relate to the future definition of less toxic TBI procedures with a better therapeutic ratio. Different TBI procedures are required for patients with malignant vs. non-malignant disorders or for patients with histoincompatible vs. histocompatible bone marrow donors.77 references

Kinetic behaviour of graft copolymerisation of nitrogenous heterocyclic monomer onto EB-irradiated ETFE films

International Nuclear Information System (INIS)

Paveswari Sithambaranathan; Arshad Ahmad; Mohamed Mahmoud Nasef; Universiti Teknologi Malaysia Campus, Kuala Lumpur

2015-01-01

Kinetic behaviour of graft copolymerisation of a nitrogenous heterocyclic monomer, 4-vinylpyridine (4-VP), onto electron beam irradiated poly(ethylene-co-tetrafluoroethylene) (ETFE) films was investigated in correlation with reaction parameters (absorbed dose, monomer concentration and reaction temperature). This was established by determination of initial polymerisation rate (r p0 ), characteristic radical recombination rate (γ) and delay time (t 0 ). The orders of the dependence of the initial rate of grafting on the absorbed dose and monomer concentration were found to be 2.28 and 3.49, respectively. The effect of temperature was investigated in the range of 50-70 deg C and the activation energy was determined. The incorporation of poly(4-VP) grafts and the accompanied chemical changes in the grafted ETFE films were monitored using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, respectively. The results of the present study showed that a quantitative kinetic description for grafting of 4-VP onto ETFE can be established and the degree of grafting can be tuned by controlling the reaction parameters. (author)

Abrogation of genetically controlled resistance of mice to Treponema pallidum by irradiation

International Nuclear Information System (INIS)

Klein, J.R.; Monjan, A.A.; Hardy, P.H. Jr.; Cole, G.A.

1980-01-01

On intradermal infection, transient primary lesions, characteristic of those seen in naturally acquired human syphilis, can be produced regularly in some strains of mice but not others, indicating a genetic basis for host susceptibility. However strains of mice which normally fail to develop lesions, do so after exposure to ionising radiation. Here the importance of an intact immune system in the outcome of local infection is illustrated by the use of radiation-induced immunosuppression. The mice were exposed to lethal doses of total body irradiation from a 137 Ce source (137 rad per min), 850-1,050 rad depending on mouse strain. (UK)

The use of irradiated corneal patch grafts in pediatric Ahmed drainage implant surgery.

Science.gov (United States)

Nolan, Kaitlyn Wallace; Lucas, Jordyn; Abbasian, Javaneh

2015-10-01

To describe the use of irradiated cornea for scleral reinforcement in Ahmed glaucoma valve drainage implant (AGV) devices in children. The medical records of patients endophthalmitis, and tube/plate self-explantation. A total of 25 procedures (20 patients) met inclusion criteria. Average patient age was 70 months (range, 2 months to 17 years). Mean follow-up was 24.8 months (range, 6 months to 6.2 years). One tube experienced conjunctival exposure through two separate corneal grafts (2/25 cases [8%]), sequentially in the same eye. The first event occurred at month 3.5 after primary implantation of the tube shunt; the second erosion occurred following revision of the existing implant at month 1.5 postoperatively. There were 2 cases of auto-explantation, 2 cases of wound dehiscence, and 1 case of persistent inflammation. There were no cases of endophthalmitis or other infections. To our knowledge, this is the first report describing the use of corneal patch grafts in children. Irradiated cornea improves cosmesis and enhances visualization of the tube. The risk of tube exposure was found to be low and comparable to other materials used as a patch graft. Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

In vitro hemocompatibility of sulfonated polypropylene non-woven fabric prepared via a facile γ-ray pre-irradiation grafting method

Energy Technology Data Exchange (ETDEWEB)

Li, Rong [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Wu, Guozhong [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); School of Physical Science and Technology, ShanghaiTech University, Shanghai 200031 (China); Ye, Yin, E-mail: yeyin@sinap.ac.cn [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China)

2015-11-30

Graphical abstract: - Highlights: • Sulfonated PP{sub NWF} was successfully fabricated via γ-ray pre-irradiation-induced graft polymerization of SSS method with the aid of AAm. • Compared with the pristine PP{sub NWF}, the sulfonated PP{sub NWF} material presented outstanding hydrophilicity. • The sulfonated PP{sub NWF} exhibited good hemocompatibility. - Abstract: Sulfonated polypropylene non-woven fabric (PP{sub NWF}) was successfully prepared via γ-ray pre-irradiation-induced graft polymerization of sodium styrenesulfonate (SSS) and acrylamide (AAm). The effect of pre-irradiation dose, reaction temperature, reaction time and concentration of binary monomer on the degree of grafting (DG) was studied. The chemical structure of the original and modified PP{sub NWF} materials were investigated by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS) to confirm the successful introduction of sulfonated (−SO{sub 3}{sup −}) group. The wettability was examined via measurement of de-ionized water adsorption percentage, which demonstrated that the hydrophilicity of PP{sub NWF} was greatly enhanced after graft modification. A little amount of bovine serum albumin (BSA) adsorption and nearly no platelet adhesion on the surface of modified PP{sub NWF} and low hemolytic ratio of the modified PP{sub NWF} revealed that the sulfonated PP{sub NWF} exhibited good hemocompatibility. Besides, blood clotting time measurement indicated that the anticoagulant property of PP{sub NWF} was effectively enhanced via SSS modification. Consequently, the hydrophilicity, in vitro hemocompatibility and anticoagulant effect of PP{sub NWF} were significantly improved by γ-ray pre-irradiation-induced graft polymerization of SSS.

Radiation grafting on natural films

International Nuclear Information System (INIS)

Lacroix, M.; Khan, R.; Senna, M.; Sharmin, N.; Salmieri, S.; Safrany, A.

2014-01-01

Different methods of polymer grafting using gamma irradiation are reported in the present study for the preparation of newly functionalized biodegradable films, and some important properties related to their mechanical and barrier properties are described. Biodegradable films composed of zein and poly(vinyl alcohol) (PVA) were gamma-irradiated in presence of different ratios of acrylic acid (AAc) monomer for compatibilization purpose. Resulting grafted films (zein/PVA-g-AAc) had their puncture strength (PS=37–40 N mm −1 ) and puncture deformation (PD=6.5–9.8 mm) improved for 30% and 50% PVA in blend, with 5% AAc under 20 kGy. Methylcellulose (MC)-based films were irradiated in the presence of 2-hydroxyethyl methacrylate (HEMA) or silane, in order to determine the effect of monomer grafting on the mechanical properties of films. It was found that grafted films (MC-g-HEMA and MC-g-silane) using 35% monomer performed higher mechanical properties with PS values of 282–296 N mm −1 and PD of 5.0–5.5 mm under 10 kGy. Compatibilized polycaprolactone (PCL)/chitosan composites were developed via grafting silane in chitosan films. Resulting trilayer grafted composite film (PCL/chitosan-g-silane/PCL) presented superior tensile strength (TS=22 MPa) via possible improvement of interfacial adhesion (PCL/chitosan) when using 25% silane under 10 kGy. Finally, MC-based films containing crystalline nanocellulose (CNC) as a filling agent were prepared and irradiated in presence of trimethylolpropane trimethacrylate (TMPTMA) as a grafted plasticizer. Grafted films (MC-g-TMPTMA) presented superior mechanical properties with a TS of 47.9 MPa and a tensile modulus (TM) of 1792 MPa, possibly due to high yield formation of radicals to promote TMPTMA grafting during irradiation. The addition of CNC led to an additional improvement of the barrier properties, with a significant 25% reduction of water vapor permeability (WVP) of grafted films. - Highlights: • Irradiation of zein

Gas-phase and liquid-phase pre-irradiation grafting of AAc onto LDPE and HDPE films for pervaporation membranes

International Nuclear Information System (INIS)

Rao Zhigong; Li Guixiang; Sugo, Takanobu; Okamoto, Jiro

1992-01-01

A study has been made on gas-phase and liquid-phase pre-irradiation grafting of acrylic acid onto LDPE and HDPE films for pervaporation membranes of ethanol-water mixtures. It was found that the degree of grafting, percent volume change of grafted membranes and length of grafting chains depend on the methods of grafting, crystal state of substrate films and diffusion rate of the monomer in the films. The pervaporation characteristics of grafted membranes is influenced directly by the surface hydrophilicity of grafted membranes, temperature of the feed, degree of grafting, crosslinking of grafted chains and alkaline metal ions in the functional groups. The potassium ion exchange membrane of HDPE synthesized by gas-phase grafting has better pervaporation efficiency. At 80 wt% ethanol in the feed, 25 o C feed temperature and 70% degree of grafting a grafted membrane has a 0.65 kg/m 2 h flux and a separation factor of 20. (Author)

Graft polymerization of guar gum with acryl amide irradiated by microwaves for colonic drug delivery.

Science.gov (United States)

Shahid, Muhammad; Bukhari, Shazia Anwer; Gul, Yousra; Munir, Hira; Anjum, Fozia; Zuber, Mohammad; Jamil, Tahir; Zia, Khalid Mahmood

2013-11-01

This article is aimed to discuss the modification of guar gum through microwave irradiation by varying the time of irradiation. The characterization of the modified products was carried out using FTIR spectroscopic analysis. The FT-IR spectrum of the pure guar gum (GG) sample showed a broad peak at 3298 cm(-1) while the modified GG sample displayed a peak at 1541 cm(-1) which was absent in the crude sample. The X-ray diffraction (XRD) analysis confirmed the increase in crystallinity due to grafting of the sample with polyacrylamide (GG-g-PAM). Scanning electron microscope (SEM) images revealed that granular form of guar gum was changed into fibrillar structure after grafting. Thermo-gravimetric analysis of the modified samples was also carried out and discussed. The role of guar gum as a matrix for controlled release of drug triamcinolone was evaluated. The GG-acrylamide grafted samples presented a correlation between drug release and time of microwave exposure. The results revealed that such modified product has potential applications in colonic drug delivery system. Copyright © 2013 Elsevier B.V. All rights reserved.

Suppressor cells in transplantation tolerance II. Maturation of suppressor cells in the bone marrow chimera

International Nuclear Information System (INIS)

Tutschka, P.J.; Ki, P.F.; Beschorner, W.E.; Hess, A.D.; Santos, G.W.

1981-01-01

Histoincompatible bone marrow allografts were established in lethally irradiated rats. At various times after transplantation, the spleen cells were harvested, subjected to mixed lymphocyte cultures, and assayed for suppressor cells in vitro and in vivo by adoptive transfer studies. Alloantigen-nonspecific suppressor cells appeared in the chimera at 40 days after grafting, coinciding with the resolution of graft-versus-host disease (GVHD). At 250 days the nonspecific suppressor cells were replaced by suppressor cells specifically suppressing donor-versus-host alloantigen responses. At 720 days suppressor cells could no longer be identified by in vitro methods but were identified by in vivo adoptive transfer of transplantation tolerance. After injection of host-type antigen into chimeras, the suppressor cells could be again demonstrated by in vitro methods

Suppressor cells in transplantation tolerance. II. maturation of suppressor cells in the bone marrow chimera

International Nuclear Information System (INIS)

Tutschka, P.J.; Ki, P.F.; Beschorner, W.E.; Hess, A.D.; Santos, G.W.

1981-01-01

Histoincompatible bone marrow allografts were established in lethally irradiated rats. At various times after transplantation, the spleen cells were harvested, subjected to mixed lymphocyte cultures, and assayed for suppressor cells in vitro and in vivo by adoptive transfer studies. Alloantigen-nonspecific suppressor cells appeared in the chimera at 40 days after grafting, coinciding with the resolution of graft-versus-host disease (GVHD). At 250 days the nonspecific suppressor cells were replaced by suppressor cells specifically suppressing donor-versus-host alloantigen responses. At 720 days suppressor cells could no longer be identified by in vitro methods but were identified by in vivo adoptive transfer of transplantation tolerance. After injection of host-type antigen into chimeras, the suppressor cells could be again demonstrated by in vitro methods

A study of the behaviour of irradiated or unirradiated grafts in the camera aquosa of irradiated and unirradiated animals; Etude du comportement d'un greffon irradie ou non, transplante dans la chambre anterieure de l'oeil d'un animal irradie ou non

Energy Technology Data Exchange (ETDEWEB)

Djalali-Behzad, G [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

1969-06-01

Following grafts of new born mice spinal ganglia in the 'camera aquosa' of adult mice, the authors tried hematopoietic tissue grafts in the same conditions. The growth of iso-logous and hetero-logous bone marrow in the 'camera aquosa' showed that this tissue, even after exposure to supralethal doses, was capable of survival and growth. A counter-experiment with non irradiated bone marrow grafts in the 'camera aquosa' of rats delivered 700 rads led to the conclusion that the environment, intoxicated by exposure, acted on the graft so that after vascularization it became unable to grow. (author) [French] Apres avoir greffe des ganglions rachidiens de souriceaux nouveaux-nes dans la chambre anterieure de l'oeil de souris adultes, l'auteur a tente de greffer du tissu hematopoietique de la meme facon. La proliferation de la moelle osseuse isologue et heterologue, dans la chambre anterieure de l'oeil, lui a permis de mettre en evidence une certaine capacite de survie et de proliferation de ce tissu irradie meme a dose supraletale. Par une contre-experimentation, c'est-a-dire par la greffe de moelle non irradiee dans la chambre anterieure de rats irradies a 700 rads, il conclut que le milieu ambiant, intoxique par l'irradiation, agit sur le greffon de telle sorte que ce dernier, apres s'etre vascularise, devient depourvu de son aptitude de proliferation. (auteur)

Mesenchymal Stem Cells (MSCs) Attenuate Cutaneous Sclerodermatous Graft-Versus-Host Disease (Scl-GVHD) through Inhibition of Immune Cell Infiltration in a Mouse Model.

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Lim, Ji-Young; Ryu, Da-Bin; Lee, Sung-Eun; Park, Gyeongsin; Min, Chang-Ki

2017-09-01

Human chronic graft-versus-host disease (GVHD) shares clinical characteristics with a murine sclerodermatous GVHD model that is characterized by skin thickening and lung fibrosis. A B10.D2 → BALB/c transplant model of sclerodermatous GVHD was used to address the therapeutic effect of mesenchymal stem cells (MSCs) on the development of chronic GVHD. The clinical and pathological severity of cutaneous sclerodermatous GVHD was significantly attenuated in MSC-treated recipients relative to sclerodermatous GVHD control subjects. After MSC treatment, skin collagen production was significantly reduced, with consistent down-regulation of Tgfb expression. Effects of MSCs on molecular markers implicated in persistent transforming growth factor-β signaling and fibrosis, such as PTEN, phosphorylated Smad-2/3, and matrix metalloproteinase-1, were observed in skin tissue. MSCs neither migrate to the skin nor affect the in vivo expansion of immune effector cells, but they inhibited the infiltration of immune effector cells into skin via down-regulation of CCR4 and CCR8 expression on CD4 + T cells and CCR1 on CD11b + monocyte/macrophages. MSCs diminished expression of chemokines such as CCL1, CCL3, CCL8, CCL17, and CCL22 in skin. MSCs were also dependent on stimulated splenocytes to suppress fibroblast proliferation. Our findings indicate that MSCs attenuate the cutaneous sclerodermatous GVHD by selectively blocking immune cell migration and down-regulating chemokines and chemokine receptors. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Arresting rampant dental caries with silver diamine fluoride in a young teenager suffering from chronic oral graft versus host disease post-bone marrow transplantation: a case report.

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Chu, Chun-Hung; Lee, Angeline Hui-Cheng; Zheng, Liwu; Mei, May Lei; Chan, Godfrey Chi-Fung

2014-01-03

Rampant caries is an advanced and severe dental disease that affects multiple teeth. This case describes the management of rampant caries in a young teenager suffering from chronic oral graft versus host disease after allogeneic bone marrow transplantation. A 14-year-old Chinese boy suffering from β-thalassemia major was referred to the dental clinic for the management of rampant dental caries. An oral examination revealed pale conjunctiva, bruising of lips, and depapillation of tongue indicating an underlying condition of anemia. The poor oral condition due to topical and systemic immunosuppressants was seriously aggravated, and rampant caries developed rapidly, affecting all newly erupted, permanent teeth. The teeth were hypersensitive and halitosis was apparent. Strategies for oral health education and diet modification were given to the patient. Xylitol chewing gum was used to stimulate saliva flow to promote remineralization of teeth. Silver diamine fluoride was topically applied to arrest rampant caries and to relieve pain from hypersensitivity. Carious teeth with pulpal involvement were endodontically treated. Stainless steel crowns were provided on molars to restore chewing function, and polycarbonate crowns were placed on premolars, upper canines and incisors. This case report demonstrates success in treating a young teenager with severe rampant dental decay by contemporary caries control and preventive strategy.

Effects of actonomycin D and ultraviolet irradiation on multiplication of brome mosaic virus in host and non-host cells

International Nuclear Information System (INIS)

Maekawa, K.; Furusawa, I.; Okuno, T.

1981-01-01

The modes of multiplication of brome mosaic virus (BMV) were compared in protoplasts isolated from host and non-host plants. BMV actively multiplied in the leaves and isolated mesophyll protoplasts of barley, a host of BMV. BMV multiplication in barley protoplasts was inhibited by addition of actinomycin D immediately after inoculation or by u.v. irradiation of the protoplasts before inoculation. In contrast, although BMV could not multiply in leaves of radish and turnip (non-hosts for BMV) it multiplied at a low level in protoplasts isolated from these two plant species. Moreover, u.v. irradiation, or the addition of actinomycin D, enhanced multiplication of BMV in radish and turnip protoplasts. These results suggest that (i) in the host cells replication of BMV is dependent on cellular metabolism of nucleic acid and protein, and (ii) in the non-host cells a substance(s) inhibitory to replication of BMV is synthesized. (author)

Biomaterials and host versus graft response: A short review

Science.gov (United States)

Velnar, Tomaz; Bunc, Gorazd; Klobucar, Robert; Gradisnik, Lidija

2016-01-01

Biomaterials and biotechnology are increasing becoming an important area in modern medicine. The main aim in this area is the development of materials, which are biocompatible to normal tissue. Tissue-implant interactions with molecular, biological and cellular characteristics at the implant-tissue interface are important for the use and development of implants. Implantation may cause an inflammatory and immune response in tissue, foreign body reaction, systemic toxicity and imminent infection. Tissue-implant interactions determine the implant life-period. The aims of the study are to consider the biological response to implants. Biomaterials and host reactions to implants and their mechanisms are also briefly discussed. PMID:26894284

Ocular graft versus host disease in allogenic haematopoetic stem cell transplantation in a tertiary care centre in India

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Rehan Khan

2015-01-01

Full Text Available Background & objectives: This study was aimed to report the occurrence of ocular graft versus host disease (oGVHD in allogeneic haematopoietic stem cell transplantation (allo-HSCT patients in a tertiary care hospital setting. Methods: A cross-sectional study of ocular surface of allo-HSCT patients was done. Slit lamp biomicroscopy, symptom score, tear meniscus height, fluorescein tear break-up time, Schirmer′s test I, ocular surface staining, dry eye severity, ocular surface disease index score were done. Indications for allo-HSCT, human leukocyte antigen (HLA matching, GVHD risk factor, systemic manifestation and treatment were also noted. Results: GVHD occurred in 44.4 per cent of 54 allo-HSCT patients (mean age 26.7 ± 12 yr included in the study. GVHD risk factors identified included female gender, relapse, older age of donor, cytomagelo virus (CMV reactivation, and multiparous female donors. oGVHD was noted in 31.5 per cent with mean time to occurrence being 17.8 ± 21.9 months after the allo-HSCT and was observed in 89.5 per cent of chronic GVHD cases. Acute GVHD (oral and dermatological involvement showed a significant association with GVHD in our patients (P< 0.001, 0R 23.0, CI 6.4-82.1. Chronic GVHD was observed to be associated with the occurrence of oGVHD (dry eye (P<0.001, OR = 24.0, CI 0.02 - 0.29. Of the 34 eyes with oGHVD, dry eye of level 3 severity was seen in 16, level 2 in six, level 1 in 12 eyes. Interpretation & conclusions: GVHD occurred in 44.4 per cent of the patients studied in the present study. Acute and chronic GVHD showed a strong association with oGVHD. Dry eye disease due to chronic oGVHD was observed in 17 (31.5% of 54 allo-HSCT patient with chronic oGVHD occurring in 17 (89.4% of chronic GVHD cases in allo-HSCT patients. Our study on oGVHD in post allo-HSCT patients in tertiary care centre points towards the fact that ocular morbidity due to dry eye disease as a result of oGVHD is a cause for concern in these

Fabrication of thermo-responsive PNIPAAm-g-ETFE for cell culture dishes by pre-irradiation grafting

Science.gov (United States)

Yamahara, Yumi; Nagasawa, Naotsugu; Taguchi, Mitsumasa; Oshima, Akihiro; Washio, Masakazu

2018-01-01

Thermo-responsive templates for the cell cultivation based on Poly(tetrafluoroethylene-co-ethylene) (ETFE) were fabricated by pre-irradiation grafting of N-isoproplyacrylamide (NIPAAm) monomer by electron beam (EB) irradiation under nitrogen gas atmosphere at room temperature, and their characteristic properties were studied. The detachment of cultured HeLa cells from fabricated thermo-responsive templates were attempted. Furthermore, the reaction mechanism is proposed using ESR spectroscopy and FT-IR spectroscopy. It is confirmed that the cultured HeLa cells were detached from fabricated thermo-responsive templates at 20 °C. Water contact angle analysis indicated that obtained templates had thermo-response around 30 °C. It is suggested that the grafted polymer chains would mainly react with peroxy radicals (-CF2-CF(OO･)-) on tetrafluoroethylene unit in ETFE.

Radiation grafting on natural films

Science.gov (United States)

Lacroix, M.; Khan, R.; Senna, M.; Sharmin, N.; Salmieri, S.; Safrany, A.

2014-01-01

Different methods of polymer grafting using gamma irradiation are reported in the present study for the preparation of newly functionalized biodegradable films, and some important properties related to their mechanical and barrier properties are described. Biodegradable films composed of zein and poly(vinyl alcohol) (PVA) were gamma-irradiated in presence of different ratios of acrylic acid (AAc) monomer for compatibilization purpose. Resulting grafted films (zein/PVA-g-AAc) had their puncture strength (PS=37-40 N mm-1) and puncture deformation (PD=6.5-9.8 mm) improved for 30% and 50% PVA in blend, with 5% AAc under 20 kGy. Methylcellulose (MC)-based films were irradiated in the presence of 2-hydroxyethyl methacrylate (HEMA) or silane, in order to determine the effect of monomer grafting on the mechanical properties of films. It was found that grafted films (MC-g-HEMA and MC-g-silane) using 35% monomer performed higher mechanical properties with PS values of 282-296 N mm-1 and PD of 5.0-5.5 mm under 10 kGy. Compatibilized polycaprolactone (PCL)/chitosan composites were developed via grafting silane in chitosan films. Resulting trilayer grafted composite film (PCL/chitosan-g-silane/PCL) presented superior tensile strength (TS=22 MPa) via possible improvement of interfacial adhesion (PCL/chitosan) when using 25% silane under 10 kGy. Finally, MC-based films containing crystalline nanocellulose (CNC) as a filling agent were prepared and irradiated in presence of trimethylolpropane trimethacrylate (TMPTMA) as a grafted plasticizer. Grafted films (MC-g-TMPTMA) presented superior mechanical properties with a TS of 47.9 MPa and a tensile modulus (TM) of 1792 MPa, possibly due to high yield formation of radicals to promote TMPTMA grafting during irradiation. The addition of CNC led to an additional improvement of the barrier properties, with a significant 25% reduction of water vapor permeability (WVP) of grafted films.

Cytogenetic studies in dogs after total body irradiation and allogeneic transfusion with cryopreserved blood mononuclear cells: observations in long-term chimeras

International Nuclear Information System (INIS)

Carbonell, F.; Calvo, W.; Fliedner, T.M.; Kratt, E.; Gerhartz, H.; Koerbling, M.; Nothdurft, W.; Ross, W.M.

1984-01-01

Cytogenetic studies were performed on two dog groups after total body irradiation and allogeneic transfusion with cryopreserved blood mononuclear cells. The first group of dogs was transfused with unseparated leukocytes and suffered from graft-versus-host disease (GvHD). Cytogenetic studies demonstrated only cells of donor origin in all dogs of this group. The second group of animals was transfused with fraction 2 of a discontinuous albumin gradient. The dogs of this group did not develop GvHD, and the cytogenetic studies showed the presence of a mosaic of cells from donor and recipient origin in all of them. These results suggest that the GvHD may suppress autochthonous regeneration

Microfiltration membranes prepared from polyethersulfone powder grafted with acrylic acid by simultaneous irradiation and their pH dependence

International Nuclear Information System (INIS)

Deng Bo; Li Jingye; Hou Zhengchi; Yao Side; Shi Liuqing; Liang Guoming; Sheng Kanglong

2008-01-01

Polyethersulfone (PES) powder was grafted with acrylic acid (AAc) by simultaneous γ-ray irradiation. The kinetics of the radiation induced graft polymerization was studied and the grafted PES powder was characterized. Then, microfiltration (MF) membranes were prepared from PES-g-PAAc powder with different degrees of grafting (DG) under phase inversion method. The swelling behavior and the mean pore size of MF membranes were measured, and the filtration property was tested. The results showed that the pore size and the flux of MF membranes increased with the increase in DG. And, MF membranes' properties were dependent on the pH value

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

Homologous tracheal transplantation with grafts previously exposed to high doses of gamma radiation in dogs without immunosuppressive agents

International Nuclear Information System (INIS)

Yokomise, Hiroyasu; Inui, Kenji; Kure, Toshio; Wada, Hiromi; Itomi, Shigeki

1993-01-01

The study was designed to determine whether previous high doses irradiation of gamma radiation would contribute to tracheal transplantation with no use of immunosuppressive agents. Twenty mongrel dogs were used as experimental animals. Five rings of thoracic tracheas, which were extracted from recipients, were exposed to 20000, 50000, or 100000 cGy in each 5 dogs. Five other non-irradiated dogs served as controls. Irradiated tracheal grafts were transplanted and covered with pedicled omentum. After transplantation, no immunosuppressive agents were given to dogs. All dogs in the control group died of tracheal stenosis due to graft-host rejection within one month. All but one long-term survivor died of tracheal stenosis, as well, in both the 20000 cGy and 50000 cGy groups. In the 100000 cGy group, grafts became viable in 4 dogs, and three of these survived one year or more. In conclusion, previous irradiation with high doses of 100000 cGy allowed homologous tracheal transplantation even when no immunosuppressive agents are given. (N.K.)

Hyperfractionated total body irradiation for T-depleted HLA identical bone marrow transplants

International Nuclear Information System (INIS)

Latini, P.; Checcaglini, F.; Maranzano, E.; Aristei, C.; Panizza, B.M.; Gobbi, G.; Raymondi, C.; Aversa, F.; Martelli, M.F.

1988-01-01

Twenty patients suffering from malignant hemopathies (mean age 31.7 years) were given hyperfractionated total body irradiation (TBI) as conditioning for T-depleted HLA identical allogeneic bone marrow transplantation. At an average of 12 months (range of 4.5-22 months) follow-up there were two cases of early death and two cases (11%) of rejection. There were no cases of acute or chronic graft versus host disease nor cases of interstitial pneumonitis. The average time for durable engraftment was 22 days. Disease-free survival at 12 months was 65%. To improve the results and further reduce the percent of rejection, the authors propose intensifying the immunosuppressive conditioning by increasing the cyclophosphamide dose and that of TBI so that a total dose of 1560 cGy is reached. 35 refs.; 1 figure

Effects of grafts of single anterior pituitary glands on the incidence and type of mammary neoplasm in neutron- or γ-irradiated Fischer female rats

International Nuclear Information System (INIS)

Clifton, K.H.; Douple, E.B.; Sridharan, B.N.

1976-01-01

Three batches comprised of 48 young adult Fischer female rats each were subjected to total-body irradiation with 50 rads modified fission neutrons, or were given 600 rads 137 Cs γ-rays, or served as unirradiated controls. On the day following exposure, one-half of each batch was grafted with a single anterior pituitary gland beneath the left kidney capsule. The animals were observed for mammary neoplasia and all those that died during the experiment were autopsied. The experiment was terminated 538 +- 13 days after irradiation when all neutron-irradiated, pituitary-grafted animals had one or more mammary tumors. Only 2 of the 23 untreated rats that survived until termination of the experiment developed mammary fibroadenomas, and none had mammary carcinomas. The incidence of fibroadenomas was increased, and a single carcinoma was found in unirradiated rats with pituitary grafts. Irradiation alone caused an increase in the incidence of mammary fibroadenomas and the appearance of carcinomas. Fibroadenomas were markedly increased by the addition of pituitary grafts to irradiation. Carcinoma incidence was less markedly affected. The neutron dose of 50 rads was slightly more effective in inducing mammary neoplasms than the 600-rad dose of γ-rays

Distribution and clonality of the vα and vβ T-cell receptor repertoire of regulatory T cells in leukemia patients with and without graft versus host disease.

Science.gov (United States)

Jin, Zhenyi; Wu, Xiuli; Chen, Shaohua; Yang, Lijian; Liu, Qifa; Li, Yangqiu

2014-03-01

Graft versus host disease (GVHD) is the main complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recent data indicated that regulatory T (Treg) cells might relate to GVHD, and such functions might be mediated by certain T-cell receptor (TCR) subfamily of Treg cells. Thus, we analyzed the distribution and clonality of the TCR Vα and Vβ repertoire of Treg cells from leukemia patients with and without GVHD after allo-HSCT. Numerous TCR Vα subfamilies, including Vα1, Vα9, Vα13, Vα16-19, and Vα24-29, were absent in Treg cells after allo-HSCT. The usage numbers for the TCR Vα and Vβ subfamilies in Treg cells from patients without GVHD appeared more widely. The expression frequencies of Vα10 or Vα20 between both groups were significantly different. Moreover, the expression frequency of TCR Vβ2 subfamily in patients without GVHD was significantly higher than that in patients with GVHD. Oligoclonally expanded TCR Vα and Vβ Treg cells were identified in a few samples in both groups. Restricted utilization of the Vα and Vβ subfamilies and the absence of some important TCR rearrangements in Treg cells may be related to GVHD due to a lower regulating function of Treg subfamilies.

The morphological effect of electron irradiation on the healing of skin wounds and skin grafts in the rat

International Nuclear Information System (INIS)

Wang, Q.

1995-01-01

Current oncological practice frequently uses pre-, intra- or post-operative radiotherapy/chemotherapy. Before such treatment can begin it is imperative to establish that satisfactory wound healing will occur. Many previous studies have examined the response of wound healing to ionizing and non-ionizing radiation. In general, clinical and experimental reports indicate that ionizing radiation produces poor to difficult healing of wounds, and can even prevent healing altogether. It is for this reason that the effect of radiation on wound repair has been a long standing concern for surgeons, radiotherapists and radiobiologists. Electron irradiation produces large differences in depth-dose distributions. This enables the delivery of a constant maximal dose throughout the superficial layer of tissue, for example, the total depth of skin, with less damage in deeper tissue layers, compared to that produced by the use of electromagnetic radiation such as X-rays. It is for this reason that electron beam irradiation has been selected as a radiation source for radiation of the graft bed. To date there have been few morphological examinations of the effect of electron radiation on the healing of skin wounds in rats. A review of the literature shows no information on the use of radiation of the graft bed in skin graft surgery. In the present work the processes involved in wound repair in response to radiation were studied, morphologically, using two experimental models, incisional wounds combined with pre-operative radiation and skin autografts combined with radiation of the wound bed. In the latter case an unirradiated skin graft was surgically attached to an irradiated wound bed. Light microscopy (LM), backscattered electron imaging (BEI), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used as investigative tools. These repair processes include inflammation, re-epithelialization, re-formation of the dermo-epidermal junction, re

The morphological effect of electron irradiation on the healing of skin wounds and skin grafts in the rat

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Wang, Q

1995-07-01

Current oncological practice frequently uses pre-, intra- or post-operative radiotherapy/chemotherapy. Before such treatment can begin it is imperative to establish that satisfactory wound healing will occur. Many previous studies have examined the response of wound healing to ionizing and non-ionizing radiation. In general, clinical and experimental reports indicate that ionizing radiation produces poor to difficult healing of wounds, and can even prevent healing altogether. It is for this reason that the effect of radiation on wound repair has been a long standing concern for surgeons, radiotherapists and radiobiologists. Electron irradiation produces large differences in depth-dose distributions. This enables the delivery of a constant maximal dose throughout the superficial layer of tissue, for example, the total depth of skin, with less damage in deeper tissue layers, compared to that produced by the use of electromagnetic radiation such as X-rays. It is for this reason that electron beam irradiation has been selected as a radiation source for radiation of the graft bed. To date there have been few morphological examinations of the effect of electron radiation on the healing of skin wounds in rats. A review of the literature shows no information on the use of radiation of the graft bed in skin graft surgery. In the present work the processes involved in wound repair in response to radiation were studied, morphologically, using two experimental models, incisional wounds combined with pre-operative radiation and skin autografts combined with radiation of the wound bed. In the latter case an unirradiated skin graft was surgically attached to an irradiated wound bed. Light microscopy (LM), backscattered electron imaging (BEI), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used as investigative tools. These repair processes include inflammation, re-epithelialization, re-formation of the dermo-epidermal junction, re

Antibody-mediated suppression of grafted lymphoma. III. Evaluation of the role of thymic function, non-thymus-derived lymphocytes, macrophages, platelets, and polymorphonuclear leukocytes in syngeneic and allogeneic hosts

International Nuclear Information System (INIS)

Shin, H.S.; Hayden, M.; Langley, S.; Kaliss, N.; Smith, M.R.

1975-01-01

Syngeneic or allogeneic mice pretreated with sublethal whole-body irradiation were rendered incapable of suppressing the growth of grafted tumor cells sensitized with alloantibody. The growth of sensitized tumor cells was suppressed when they were mixed with donor effector cells from mice syngeneic or allogeneic to the recipients and then were inoculated in irradiated recipients. Three donor-host combinations were used to study the suppression of the murine lymphoma 6C3HED indigenous to C3H mice. These were C3H donor cells in C3H recipients, C57BL/6 donor cells in C3H recipients, or C57BL/6 donor cells in C57BL/6 recipients. In all three combinations, macrophages obtained from an inflammatory exudate, exudate lymphocytes not bearing theta antigen, and platelets were, in descending order of effectiveness, consistently active in restoring antibody-mediated suppression of tumor growth in irradiated hosts. Prior irradiation of the transferred lymphocytes somewhat diminished their effectiveness. Freeze-thawed or heat-killed macrophages (but not freeze-thawed platelets or lymphocytes) were effective in restoration. Peripheral blood mononuclear leukocytes and splenic lymphoid cells were not active in the recipients syngeneic to the donor cells but were active in recipients allogeneic to the donor cells. Polymorphonuclear leukocytes isolated from peripheral blood or an inflammatory exudate were not active. Intact thymic function seems unimportant since antibody-mediated suppression took place as effectively in thymectomized mice as in normal controls. (U.S.)

Low-dose ultraviolet-B irradiation of donor corneal endothelium and graft survival

International Nuclear Information System (INIS)

Dana, M.R.; Olkowski, S.T.; Ahmadian, H.; Stark, W.J.; Young, E.M.

1990-01-01

Donor rabbit corneal endothelium was pretreated with different doses of ultraviolet (UV-B) irradiation (302 nm) before grafting to test whether allograft survival could be favorably affected in comparison with untreated corneas grafted into the same recipients. Endothelial rejection was observed in 19 of 32 (59%) eyes that received no treatment compared with five of 32 (16%) eyes that received UV-B (P less than 0.001), and increasing doses of UV-B were associated with lower rejection rates (P less than 0.05). Although exposure of donor endothelium significantly reduced endothelial rejection at all doses tested, it resulted in primary graft failure in a substantial proportion of corneas treated at high doses. Class II (Ia) antigen staining of corneal tissue was present in conjunction with clinical evidence of rejection, and the magnitude of staining correlated with the histologic extent of inflammation. Scanning electron microscopy revealed various endothelial cell surface irregularities and membrane defects in high-dose UV-treated corneas. Endothelial cell cultures exposed in vitro to UV-B light showed a dose-dependent loss in cell viability. These data suggest that UV-B pretreatment of donor corneal endothelium prolongs graft survival but that toxic side effects must be carefully controlled

Polymer electrolyte membranes for fuel cells by radiation induced grafting with electron beam irradiation: state-of-the-art

International Nuclear Information System (INIS)

Nasef, M.M.; Nasef, M.M.

2010-01-01

Polymer electrolyte membranes have generated considerable interest in various fields of industrial interest due to their wide spread applications in fuel cells, batteries, electrolyzers sensors and actuators. Such diversity in applications implies a strong demand to architect the membranes towards particular properties for specific applications. Radiation induced grafting of vinyl and acrylic monomers into polymeric films, is an appealing method for producing various polymer electrolyte membranes. This method has the advantages of simplicity, controllability over the composition leading to tailored membrane properties and absence of shaping problem as preparation starts with substrate in a film form. It also has the flexibility of using various types of radiation sources such as gamma-rays and electron beam. Of all, electron beam (EB) accelerator is an advantageous source of high energy radiation that can initiate grafting reactions required for preparation of the membranes particularly when pilot scale production and commercial applications are sought. The grafting penetration can be varied from surface to bulk of membranes depending on the acceleration energy. This lecture reviews the-state of- the-art in the use of EB irradiation in preparation of composite and grafted polymer electrolyte membranes for fuel cell applications by radiation induced grafting with simultaneous irradiation and preirradiation methods. The use of simultaneous EB irradiation method was found to simplify the process and reduce the reaction time as well as the monomer consumption whereas the use of preirradiation method in a single-step route provides a shorter route to prepare polymer electrolyte membranes with improved properties and reduced cost in addition of setting basis for designing a continuous line to produce these membranes with dedicated EB facilities

Antibodies against human cytomegalovirus late protein UL94 in the pathogenesis of scleroderma-like skin lesions in chronic graft-versus-host disease.

Science.gov (United States)

Pastano, Rocco; Dell'Agnola, Chiara; Bason, Caterina; Gigli, Federica; Rabascio, Cristina; Puccetti, Antonio; Tinazzi, Elisa; Cetto, Gianluigi; Peccatori, Fedro; Martinelli, Giovanni; Lunardi, Claudio

2012-09-01

Human cytomegalovirus (hCMV) infection and its reactivation correlate both with the increased risk and with the worsening of graft-versus-host disease (GVHD). Because scleroderma-like skin lesions can occur in chronic GVHD (cGVHD) in allogeneic stem-cell transplant (HCT) patients and hCMV is relevant in the pathogenesis of systemic sclerosis (SSc), we evaluated the possible pathogenetic link between hCMV and skin cGVHD. Plasma from 18 HCT patients was tested for anti-UL94 and/or anti-NAG-2 antibodies, identified in SSc patients, by direct ELISA assays. Both donors and recipients were anti-hCMV IgG positive, without autoimmune diseases. Patients' purified anti-UL94 and anti-NAG-2 IgG binding to human umbilical endothelial cells (HUVECs) and fibroblasts was performed by FACS analysis and ELISA test. HUVECs apoptosis and fibroblasts proliferation induced by patients' anti-NAG-2 antibodies were measured by DNA fragmentation and cell viability, respectively. About 11/18 patients developed cGVHD and all of them showed skin involvement, ranging from diffuse SSc-like lesions to limited erythema. Eight of eleven cGVHD patients were positive for anti-UL94 and/or anti-NAG-2 antibodies. Remarkably, 4/5 patients who developed diffuse or limited SSc-like lesions had antibodies directed against both UL94 and NAG-2; their anti-NAG-2 IgG-bound HUVECs and fibroblasts induce both endothelial cell apoptosis and fibroblasts proliferation, similar to that induced by purified anti-UL94 and anti-NAG-2 antibodies obtained from SSc patients. In conclusion, our data suggest a pathogenetic link between hCMV infection and scleroderma-like skin cGVHD in HCT patients through a mechanism of molecular mimicry between UL94 viral protein and NAG-2 molecule, as observed in patients with SSc.

Allogeneic versus autologous derived cell sources for use in engineered bone-ligament-bone grafts in sheep anterior cruciate ligament repair.

Science.gov (United States)

Mahalingam, Vasudevan D; Behbahani-Nejad, Nilofar; Horine, Storm V; Olsen, Tyler J; Smietana, Michael J; Wojtys, Edward M; Wellik, Deneen M; Arruda, Ellen M; Larkin, Lisa M

2015-03-01

The use of autografts versus allografts for anterior cruciate ligament (ACL) reconstruction is controversial. The current popular options for ACL reconstruction are patellar tendon or hamstring autografts, yet advances in allograft technologies have made allogeneic grafts a favorable option for repair tissue. Despite this, the mismatched biomechanical properties and risk of osteoarthritis resulting from the current graft technologies have prompted the investigation of new tissue sources for ACL reconstruction. Previous work by our lab has demonstrated that tissue-engineered bone-ligament-bone (BLB) constructs generated from an allogeneic cell source develop structural and functional properties similar to those of native ACL and vascular and neural structures that exceed those of autologous patellar tendon grafts. In this study, we investigated the effectiveness of our tissue-engineered ligament constructs fabricated from autologous versus allogeneic cell sources. Our preliminary results demonstrate that 6 months postimplantation, our tissue-engineered auto- and allogeneic BLB grafts show similar histological and mechanical outcomes indicating that the autologous grafts are a viable option for ACL reconstruction. These data indicate that our tissue-engineered autologous ligament graft could be used in clinical situations where immune rejection and disease transmission may preclude allograft use.

Osteogenic Matrix Cell Sheets Facilitate Osteogenesis in Irradiated Rat Bone

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Yoshinobu Uchihara

2015-01-01

Full Text Available Reconstruction of large bone defects after resection of malignant musculoskeletal tumors is a significant challenge in orthopedic surgery. Extracorporeal autogenous irradiated bone grafting is a treatment option for bone reconstruction. However, nonunion often occurs because the osteogenic capacity is lost by irradiation. In the present study, we established an autogenous irradiated bone graft model in the rat femur to assess whether osteogenic matrix cell sheets improve osteogenesis of the irradiated bone. Osteogenic matrix cell sheets were prepared from bone marrow-derived stromal cells and co-transplanted with irradiated bone. X-ray images at 4 weeks after transplantation showed bridging callus formation around the irradiated bone. Micro-computed tomography images at 12 weeks postoperatively showed abundant callus formation in the whole circumference of the irradiated bone. Histology showed bone union between the irradiated bone and host femur. Mechanical testing showed that the failure force at the irradiated bone site was significantly higher than in the control group. Our study indicates that osteogenic matrix cell sheet transplantation might be a powerful method to facilitate osteogenesis in irradiated bones, which may become a treatment option for reconstruction of bone defects after resection of malignant musculoskeletal tumors.

Influence of host irradiation on the bio-infectivity of Steinernema glaseri as entomopathogenic nematodes and their perpetuating parasitisation potential on a serious tropical lepidopteran pest, Spodoptera litura

Energy Technology Data Exchange (ETDEWEB)

Seth, R K [Department of Zoology, University of Delhi, Delhi (India); Barik, T K; Chauhan, S [Department of Zoology, University of Delhi, Delhi (India)

2005-07-01

IJs derived from irradiated hosts, reared on natural food, was evaluated up to two ensuing generations to understand the perpetuating potential of these entomophilous parasitoids. In the first phase the F{sub 1}-IJs harvested from parasitised irradiated hosts were evaluated for their bio-infectivity on untreated hosts, and compared with normal IJs response on treated hosts and the control (normal IJs versus untreated host). In the next phase the efficacy of F{sub 2} progeny (next generation of F{sub 1}-IJs parasitising untreated host) was ascertained on normal hosts. The time required for causing mortality was significantly higher in case of F{sub 1}-IJs as compared to F{sub 2}-IJs, which on the contrary behaved almost similar to the control. The parasitisation efficacy by normal IJs on irradiated hosts, and by F{sub 1}-IJs on untreated hosts, was evidently less than the control; whereas the F{sub 2}-IJs parasitisation response was almost equivalent to the control. A similar pattern was observed with respect to EPNs harvesting behaviour exhibited by F{sub 1}-IJs and F{sub 2}-IJs. This indicated almost revival response elicited by F{sub 2}-IJs being similar to the control, at 40 Gy and 70 Gy, although the revival response by F{sub 2}-IJs was more apparent at 40 Gy. Considering reduced mating success and adult survival at 40 Gy, this dose could also be effectively used for propagation of EPNs within sterilised host for inoculative releases. The performance of these EPNs on irradiated host and behaviour of IJs harvested from irradiated host indicated the feasibility of using entomogenous S. glaseri as an ecologically sound biocontrol component for the management of S. litura.

Radiographic features of esophageal involvement in chronic graft-vs.-host disease

International Nuclear Information System (INIS)

McDonald, G.B.; Sullivan, K.M.; Plumley, T.F.

1984-01-01

Chronic graft-vs.-host disease (GVHD) is an important late complication of allogeneic bone-marrow transplantation. It resembles several naturally occurring autoimmune diseases and involves the skin, mouth, eyes, liver, and esophagus. The radiographic findings of 14 symptomatic patients with chronic GVHD involving the esophagus were reviewed and found to include webs, ringlike narrowings, and tapering strictures in the mid and upper esophagus. Esophagoscopy revealed characteristic desquamation in the 13 patients studied, but barium studies detected this lesion in only one patient. Knowledge of the site and characteristics of esophageal involvement with chronic GVHD assists the radiologic evaluation of this disorder

A study of the behaviour of irradiated or unirradiated grafts in the camera aquosa of irradiated and unirradiated animals; Etude du comportement d'un greffon irradie ou non, transplante dans la chambre anterieure de l'oeil d'un animal irradie ou non

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Djalali-Behzad, G. [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

1969-06-01

Following grafts of new born mice spinal ganglia in the 'camera aquosa' of adult mice, the authors tried hematopoietic tissue grafts in the same conditions. The growth of iso-logous and hetero-logous bone marrow in the 'camera aquosa' showed that this tissue, even after exposure to supralethal doses, was capable of survival and growth. A counter-experiment with non irradiated bone marrow grafts in the 'camera aquosa' of rats delivered 700 rads led to the conclusion that the environment, intoxicated by exposure, acted on the graft so that after vascularization it became unable to grow. (author) [French] Apres avoir greffe des ganglions rachidiens de souriceaux nouveaux-nes dans la chambre anterieure de l'oeil de souris adultes, l'auteur a tente de greffer du tissu hematopoietique de la meme facon. La proliferation de la moelle osseuse isologue et heterologue, dans la chambre anterieure de l'oeil, lui a permis de mettre en evidence une certaine capacite de survie et de proliferation de ce tissu irradie meme a dose supraletale. Par une contre-experimentation, c'est-a-dire par la greffe de moelle non irradiee dans la chambre anterieure de rats irradies a 700 rads, il conclut que le milieu ambiant, intoxique par l'irradiation, agit sur le greffon de telle sorte que ce dernier, apres s'etre vascularise, devient depourvu de son aptitude de proliferation. (auteur)

Synergistic effects of combined immunosuppressive modulation. I. Unresponsiveness to dendritic cell-depleted renal allografts in dogs exposed to total-lymphoid irradiation

International Nuclear Information System (INIS)

Rapaport, F.T.; Meek, A.; Miura, S.; Hayashi, R.; Arnold, A.N.; Strober, S.

1988-01-01

Attenuation of the allogeneic stimulus provided by dendritic cells (DC) was achieved by irradiation of the donors, followed by their reconstitution with bone marrow from the prospective DLA-identical recipient. Following long-term (131-187 days) recovery free of graft-versus-host (GVH) disease, the chimeric kidneys were placed into the corresponding recipients; such allografts were rejected at 55, 55, and 60 days, respectively. Four other recipients were conditioned with 1750-1790 cgy of total lymphoid irradiation (TLI) and were then given a similar chimeric kidney from the corresponding partner. These allografts currently survive for 296, 295, 290, and 252 days, respectively. A third group of four dogs was exposed to TLI prior to transplantation of a normal DLA-identical kidney. These grafts were rejected at 20, 42, 46, and 242 days, respectively. Thirteen DLA-identical renal allografts transplanted into normal dogs survived for 13-38 days (mean survival time = 28.6 days). Depletion of allogeneic DC alone, or TLI alone, produced relative prolongations in allograft survival in canine recipients. Combined use of these two modalities, however, resulted in long-term allogeneic unresponsiveness in the recipients

Demonstration of clonable alloreactive host T cells in a primate model for bone marrow transplantation

International Nuclear Information System (INIS)

Reisner, Y.; Ben-Bassat, I.; Douer, D.; Kaploon, A.; Schwartz, E.; Ramot, B.

1986-01-01

The phenomenon of marrow rejection following supralethal radiochemotherapy was explained in the past mainly by non-T-cell mechanisms known to be resistant to high-dose irradiation. In the present study a low but significant number of radiochemoresistant-clonable T cells was found in the peripheral blood and spleen of Rhesus monkeys following the cytoreductive protocol used for treatment of leukemia patients prior to bone marrow transplantation. More than 95% of the clonable cells are concentrated in the spleen 5 days after transplant. The cells possess immune memory as demonstrated by the generation of alloreactive-specific cytotoxicity. The present findings suggest that host-versus-graft activity may be mediated by alloreactive T cells. It is hoped that elimination of such cells prior to bone marrow transplantation will increase the engraftment rate of HLA-nonidentical marrow in leukemia patients

The nature of the initiating centres for grafting in air-irradiated perfluoro polymers

International Nuclear Information System (INIS)

Bozzi, A.; Chapiro, A.

1987-01-01

Grafting of acrylic acid on polytetrafluoroethylene has been performed using films of the polymer gamma-irradiated in air and then treated with aqueous acrylic acid. It is concluded that the initiating centres are peroxides POOP', where P' is a small perfluorinated fragment, and also trapped peroxy radicals PO 2 radical which undergo deoxygenation. Homopolymerization is suppressed by polymerization inhibitors. (author)

Proliferation and Differentiation of Autologic and Allogenic Stem Cells in Supralethally X-Irradiated Dogs

Energy Technology Data Exchange (ETDEWEB)

Chertkov, I. L. [Department of Radiobiology, Central Institute of Haematology and Blood Transfusion, Moscow, USSR (Russian Federation)

1967-07-15

Full text: Allogenic bone marrow after transplantation into dogs irradiated with 1000 R X-rays differentiates in the normal way only for 3-4 days, afterwards transforming into lymphoid cells. This transformation is due to the antigen stimulus of the host on the grafted stem cells. The lymphoid cells, obtained from the host's blood on the 7-8th day after grafting, showed specific, immune activity under the Immune Lymphocyte Transfer test. Within a short duration of the immune response immunoblasts and immunocytes Undergo degenerative changes: destroyed mitochondria, formation of autophagic vacuoles and, finally, lysis of the cells. These changes are suggested to be the result of overloading of immune cells with antigen. Preliminary sensitization of the donor with prospective host's haemopoietic tissue does not hasten the immune transformation of haemopoiesis. Injections of bacterial pyrogen, cortisone or 6-mercaptopurine into recipients, as well as incubation of bone marrow at 37 Degree-Sign C for 2 hours, do not prevent the immune transformation. Preliminary thymectomy of the prospective recipients prevents in some of the cases immune transformation of the bone-marrow graft. The delay of allogenic bone-marrow transplantation for 5-6 days prevents in some dogs (X-irradiated with 1000 R, but not with 1200 R) the immune transformation. Transplantation of autologic bone marrow or shielding of the legs during irradiation is accompanied with good restoration of normal haemopoiesis without lymphoid transformation. (author)

Survival of dental implants in native and grafted bone in irradiated head and neck cancer patients: a retrospective analysis.

Science.gov (United States)

Buddula, Aravind; Assad, Daniel A; Salinas, Thomas J; Garces, Yolanda I

2011-01-01

To study the long-term survival of dental implants placed in native or grafted bone in irradiated bone in subjects who had received radiation for head and neck cancer. A retrospective chart review was conducted for all patients who received dental implants following radiation treatment for head and neck cancer between May 1, 1987 and July 1, 2008. Only patients irradiated with a radiation dose of 50 Gy or greater and those who received dental implants in the irradiated field after head and neck radiation were included in the study. The associations between implant survival and patient/implant characteristics were estimated by fitting univariate marginal Cox proportional hazards models. A total of 48 patients who had prior head and neck radiation had 271 dental implants placed during May 1987-July 2008. There was no statistically significant difference between implant failure in native and grafted bone (P=0.76). Survival of implants in grafted bone was 82.3% and 98.1% in maxilla and mandible, respectively, after 3 years. Survival of implants in native bone in maxilla and mandible was 79.8% and 100%, respectively, after 3 years. For implants placed in the native bone, there was a higher likelihood of failure in the maxilla compared to the mandible and there was also a tendency for implants placed in the posterior region to fail compared to those placed in the anterior region. There was no significant difference in survival when implants were placed in native or grafted bone in irradiated head and neck cancer patients. For implants placed in native bone, survival was significantly influenced by the location of the implant (maxilla or mandible, anterior or posterior).

Carboxylated nanodiamond and re-oxygenation process of gamma irradiated red blood cells

International Nuclear Information System (INIS)

Acosta-Elias, M.; Sarabia-Sainz, A.; Silva-Campa, E.; Angulo-Molina, A.; Soto-Puebla, D.; Barboza-Flores, M.; Melendrez, R.; Alvarez-Garcia, S.; Pedroza-Montero, M.; Pedroso-Santana, S.; Santacruz-Gomez, K.; Castaneda, B.

2015-01-01

Nanodiamonds (NDs) possess exceptional physical, chemical, and biological properties, which make them suitable for potential biomedical applications. They are biocompatible and their usefulness as effective Raman/fluorescence probes for labeling as well as for drug delivery has been demonstrated. Related to their biocompatibility, the interaction between NDs and red blood cells (RBCs) is of great interest. In this work, the influence of carboxylated NDs (cNDs) in the re-oxygenation capability of both γ-irradiated and stored RBCs was studied. The standard 25 Gy γ dose recommended to prevent transfusion associated graft-versus-host disease was used. A 5-day maximum storage time was used to evaluate the ''storage lesion''. The hemoglobin (Hb) oxygenation state was assessed by Raman microspectroscopy and the morphologic changes on cells were tracked by optical imaging. Our results show that irradiated RBCs have a better re-oxygenation capability and morphological recovery when they are in presence of cNDs. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Carboxylated nanodiamond and re-oxygenation process of gamma irradiated red blood cells

Energy Technology Data Exchange (ETDEWEB)

Acosta-Elias, M. [Doctorado en Nanotecnologia, Universidad de Sonora (Mexico); Sarabia-Sainz, A.; Silva-Campa, E.; Angulo-Molina, A.; Soto-Puebla, D.; Barboza-Flores, M.; Melendrez, R.; Alvarez-Garcia, S.; Pedroza-Montero, M. [Departamento de Investigacion en Fisica, Universidad de Sonora, Hermosillo (Mexico); Pedroso-Santana, S. [Doctorado en Ciencias (Fisica), Universidad de Sonora, Hermosillo (Mexico); Santacruz-Gomez, K.; Castaneda, B. [Departamento de Fisica, Universidad de Sonora, Hermosillo (Mexico)

2015-11-15

Nanodiamonds (NDs) possess exceptional physical, chemical, and biological properties, which make them suitable for potential biomedical applications. They are biocompatible and their usefulness as effective Raman/fluorescence probes for labeling as well as for drug delivery has been demonstrated. Related to their biocompatibility, the interaction between NDs and red blood cells (RBCs) is of great interest. In this work, the influence of carboxylated NDs (cNDs) in the re-oxygenation capability of both γ-irradiated and stored RBCs was studied. The standard 25 Gy γ dose recommended to prevent transfusion associated graft-versus-host disease was used. A 5-day maximum storage time was used to evaluate the ''storage lesion''. The hemoglobin (Hb) oxygenation state was assessed by Raman microspectroscopy and the morphologic changes on cells were tracked by optical imaging. Our results show that irradiated RBCs have a better re-oxygenation capability and morphological recovery when they are in presence of cNDs. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Synthesis and property characterization of cassava starch grafted poly(acrylamide-co-(maleic acid)) superabsorbent via γ-irradiation

International Nuclear Information System (INIS)

Kiatkamjornwong, Suda; Mongkolsawat, Kanlaya; Sonsuk, Manit

2004-01-01

Graft copolymerizations of acrylamide and maleic acid onto cassava starch by a simultaneous irradiation technique using γ-rays as a initiator were carried out. Various important parameters of total dose, dose rate, monomer-to-cassava starch ratio and maleic acid content were studied. Addition of 2% ww -1 diprotic acid of maleic acid into the reaction mixture yields a saponified starch graft copolymer with a water absorption in distilled water as high as 2256g g -1 of its dried weight. The water absorption of these saponified graft copolymers insaline and buffer solutions was also measured. The water absorption depends largely on the cationic type and concentration of these solutions in terms of ionic strength. This research explains a charge transfer mechanism for graft copolymerization of maleic acid and acrylamide onto cassava starch, and describes the influential parameters that affect grafting efficiency and water absorption. (author)

Hydrophilic microfiltration membranes prepared from acryl amide grafted PVDF powder by γ-rays pre-irradiation

International Nuclear Information System (INIS)

Yang Xuanxuan; Deng Bo; Yu Ming; Yu Yang; Zhang Bowu; Li Jingye

2011-01-01

Acryl amide (AAm) was grafted onto poly (vinylidene fluoride) (PVDF) powder by a γ-rays pre-irradiation induced graft polymerization technique. The DG values of the PVDF-g-PAM powder were determined by fluorine elemental analysis. Effects of grafting time on DG of PVDF-g-PAM powder at the same monomer concentration were studied. And modified powder was dissolved in NMP and added PVP as pre-forming agent. The microfiltration (MF) membranes were cast using a phase inversion method. The contact angle, degree of swelling, water flux and antifouling properties of those modified MF membranes were investigated. The results indicated that the hydrophilicity of modified MF membranes was improved obviously and the antifouling property of modified MF membranes (DG of 13%) was better than that of the pristine membrane. (authors)

Graft-Versus-Host-Disease

Science.gov (United States)

... however you can Daughter's dying wish became mother's motivation Be The Match Blog Stories Anna, transplant recipient ... any symptoms of GVHD , tell your transplant doctor right away. Chronic GVHD: Usually develops 3-6 months ...

Procedures development and methodology of control for application of good manufacture practices (GMP) on human blood irradiation

International Nuclear Information System (INIS)

Boghi, Claudio

2008-01-01

The irradiation of human blood is used to avoid the TA-GVHD (transfusion-associated graft-versus-host-disease), a rare but devastating adverse effect of leukocytes present in blood components for a immunocompetent transfusion recipients. Usually this irradiation practice is performed to a physical elimination of leukocytes. The implementation of the procedures will assure that the properly dose in a range of 25 Gy to 50 Gy will be delivered to the blood in the bag collected in a blood tissue bank. The studies of the procedures in order to establish a GMP (Good Manufacturing Practices) were developed under the guidelines of the standard ISO 11137 - Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. In this work, two dosimetric systems were used for dose mapping during the studies of irradiator qualification, loading pattern, irradiation process validation and auditing. The CaS0 4 :Dy dosimeter presented difficulties concerning to uncertainty on dose measurement, stability, traceability and calibration. The PMMA and Gafchromic dosimetric systems have shown a better performance and were adopted on studies of irradiators qualification that are necessary to implementation of GMP. The irradiation tests have been done in a Gammacell 220 irradiator. The developed procedures can be adapted for different kinds of gamma irradiators, allowing implanting a quality assurance program and a GMP for blood irradiation. (author)

Radiation-induced grafting of styrene on to LDPE films for preparation of cation exchange membranes, i. effect of grafting conditions

International Nuclear Information System (INIS)

Mohamed Mahmoud Nasef; Hamdani Saidi; Hussin Mohd Nor; Khairul Zaman Mohd Dahlan; Kamaruddin Hashim

1999-01-01

PE-g-polystyrene copolymers were prepared by simultaneous radiation-induced graft copolymerization of styrene onto low density polyethylene (LDPE) films. The effects of irradiation conditions such as monomer concentration, Mohr's salt and sulfuric acid addition, irradiation dose and dose rate were investigated. It was found that the degree of grafting increases with the monomer concentration and reaches its maximum value at styrene concentration of 80 vol %. The addition of Mohr's salt as well as sulfuric acid caused a considerable increase in the degree of grafting with various styrene concentrations. The degree of grafting also increased with the increased in irradiation dose, however it remarkably decreased with the increase in dose rate. The formation of graft copolymers was confirmed by FTIR analysis. The structural investigation of the graft copolymer was carried out by x-ray diffraction (XRD). The degree of crystallinity content was found to be decreased with the increase in the degree of grafting and influenced the mechanical properties of the graft copolymer to some extent. (Author)

Lung allograft rejection in the rat. I. Accelerated rejection caused by graft lymphocytes

International Nuclear Information System (INIS)

Prop, J.; Nieuwenhuis, P.; Wildevuur, C.R.

1985-01-01

To find out to what extent rejection of lungs differs from that of other organs, functional rejection of lung allografts was studied in five combinations of inbred rat strains. Rejection could be monitored accurately by perfusion scintigraphy, and equally well by chest roentgenography. The rejection of lung grafts was found to proceed remarkably fast, when compared with heart grafts, in combinations with strong RT1-incompatibilities. This accelerated rejection pattern could be converted into rejection at a normal pace by pretreatment of the donor with 10 Gy roentgen irradiation one day before transplantation. Donor pretreatment depleted the lung graft's bronchus-associated lymphoid tissue (BALT) of lymphocytes. When grafts were depleted of all other passenger cells as well--by retransplantation from a cyclosporine-treated intermediate host--they showed an even more reduced immunogenicity, probably because of the loss of donor-type dendritic cells. These results indicate that lymphocytes from the BALT of lung grafts are capable of accelerating the rejection response

Radiation-induced grafting of styrene on polypropylene pellets

International Nuclear Information System (INIS)

Souza, Camila P.; Ferreira, Henrique P.; Parra, Duclerc F.; Lugao, Ademar B.

2009-01-01

The changes of radiation-induced in polypropylene (PP) pellets exposed to gamma irradiation in inert atmosphere were investigated in correlation with the applied doses (10 and 50 kGy). Also, results from the grafting of styrene onto PP pellets using simultaneous irradiation at the same doses are presented. The grafting reaction was carried out using toluene as solvent, under nitrogen atmosphere and at room temperature. The properties of the irradiated and grafted PP pellets were studied using Melt Flow Index, thermal analysis (TG and DSC), and ATR-IR. The degree of grafting (DOG) for the grafted pellets was gravimetrically determined. The results showed that radiation-induced graft polymerization on pellets were successfully obtained and the influence of dose irradiated did not change the thermal properties in spite of the increase in the MFI and consequently this increase in the viscosity results an decrease the molecular mass. The MFI for grafted pellets was not achievable because the high degree of viscosity of polymer, even arising the test temperature, the polymer was not flow enough. (author)

Effect of Massive Blood Transfusion on the Therapeutic Efficiency of Homogenic Bone Marrow in Acute Radiation Illness

Energy Technology Data Exchange (ETDEWEB)

Seraphimov-Dimitrov, V.; Decheva, Z.; Nedyalkova, M. [Institute of Haematology and Blood Transfusion, Sofia (Bulgaria)

1969-07-15

Simultaneously with bone-marrow transplantation, the authors replaced the blood of the lethally irradiated recipient animals with blood from the bone-marrow donor. From experiments on dogs and rabbits it became clear that replacing 86% of the recipient's blood with blood from the bone-marrow donor considerably reduces the therapeutic effect of bone-marrow transplantation. The authors consider that the main cause of the animals' early death in experiments combining bone-marrow transplantation and massive donor blood transfusions is a secondary syndrome resulting from the graft-versus-host reaction. This does not exclude the inverse possibility - that the development of a host-versus-graft reaction is due to the presence of a massive number of antigens of the donor blood in the blood of the recipient. (author)

Induction of a glucocorticoid-sensitive F1-anti-parental mechanism that affects engraftment during graft-versus-host disease.

Science.gov (United States)

You-Ten, K E; Seemayer, T A; Wisse, B; Bertley, F M; Lapp, W S

1995-07-01

Studies have shown that graft-vs-host disease (GVHD) in animal models induces persistent elevated levels of circulating adrenal glucocorticoids. In this report, we investigated the effects of endogenous glucocorticoids on the outcome of GVHD by adrenalectomizing (ADX) unirradiated (C57BL/6 x A)F1 (B6AF1) mice before GVHD induction. GVHD was induced by injection of 20 x 10(6) A strain parental lymphoid cells into B6AF1 mice. Our results demonstrated that non-ADX recipient mice experienced features characteristic of GVHD on day 13, which became progressively more severe by days 18 to 21. The GVHD features included severe immunosuppression, reversal in the host splenic CD4+/CD8+ ratio, histopathologic lesions in different tissues, and high parental cell chimerism in the spleens and lymph nodes. In contrast, ADX F1 recipient mice experienced GVHD features on day 13 similar to their non-ADX counterparts; however, ADX animals recovered rapidly from GVHD by days 18 to 21. Flow cytometry showed that, although a relatively high frequency of parental cells was detected in the spleens and lymph nodes of ADX mice on day 13, nearly all of the parental cells in the peripheral lymphoid organs disappeared on days 18 to 21, the time of recovery from GVHD. The marked reduction of parental cells and recovery from GVHD were prevented by treating ADX F1 mice with either exogenous glucocorticoid, anti-asialoGM1, or anti-CD8, but not anti-NK1.1 Ab. These results suggest that a dramatic recovery from GVHD was induced by a cell-mediated, steroid-sensitive F1-anti-parental mechanism. The F1-anti-parental phenomenon described herein is different from classical hybrid resistance.

Localized surface grafting reactions on carbon nanofibers induced by gamma and e-beam irradiation

Energy Technology Data Exchange (ETDEWEB)

Evora, M.C., E-mail: cecilia@ieav.cta.br [Institute for Advanced Studies-IEAV/DCTA, Av. Cel Jose Alberto Albano do Amarante, 1-Putim, 12228-001 São Jose dos Campos, SP (Brazil); Araujo, J.R., E-mail: jraraujo@inmetro.gov.br [Instituto Nacional de Metrologia, Qualidade e Tecnologia, Av. Nossa Sra. das Graças, 50, 25250-020 Duque de Caxias, RJ (Brazil); Ferreira, E.H.M. [Instituto Nacional de Metrologia, Qualidade e Tecnologia, Av. Nossa Sra. das Graças, 50, 25250-020 Duque de Caxias, RJ (Brazil); Strohmeier, B.R. [Thermo Fisher Scientific, 5225 Verona Road, Madison, WI 53711 (United States); Silva, L.G.A., E-mail: lgasilva@ipen.br [Institute for Nuclear and Energy Research- IPEN, Av. Prof lineu Prestes, 2242- Cidade Universitaria, 05508-000 SP (Brazil); Achete, C.A. [Instituto Nacional de Metrologia, Qualidade e Tecnologia, Av. Nossa Sra. das Graças, 50, 25250-020 Duque de Caxias, RJ (Brazil)

2015-04-30

Graphical abstract: - Highlights: • Methodology for the functionalization of carbon nanofibers was investigated. • Two radiation sources were used to promote grafting reactions: gamma and electron beam. • We report the optimum inhibitor concentration to achieve the functionalization. • Surface of carbon nanofibers showed an increase of oxygen content after irradiation. • The radiation-induced graphitization did not damage the overall sp{sup 2} structure. - Abstract: Electron beam and gamma-ray irradiation have potential application to modify the carbon fiber nanostructures in order to produce useful defects in the graphitic structure and create reactive sites. In this study, the methodology to functionalize carbon nanofiber (CNF), via a radiation process and using acrylic acid as a source of oxygen functional groups, was investigated. The samples were submitted to a direct grafting radiation process with electron beam and gamma-ray source. Several parameters were changed such as: acrylic acid concentration, radiation dose and percentage of inhibitor necessary to achieve functionalization, with higher percentage of oxygen functional groups on CNF surface, and better dispersion. The better results achieved were when mixing CNF in a solution of acrylic acid with 6% of inhibitor (FeSO{sub 4}·7H{sub 2}O) and irradiated at 100 kGy. The samples were characterized by X-ray photoelectron spectroscopy and the surface composition (atomic%) showed a significant increase of oxygen content for the samples after irradiation. Also, the dispersion of the functionalized CNF in water was stable during months which may be a good indication that the functionalization process of CNF via ionizing radiation was successful.

Localized surface grafting reactions on carbon nanofibers induced by gamma and e-beam irradiation

International Nuclear Information System (INIS)

Evora, M.C.; Araujo, J.R.; Ferreira, E.H.M.; Strohmeier, B.R.; Silva, L.G.A.; Achete, C.A.

2015-01-01

Graphical abstract: - Highlights: • Methodology for the functionalization of carbon nanofibers was investigated. • Two radiation sources were used to promote grafting reactions: gamma and electron beam. • We report the optimum inhibitor concentration to achieve the functionalization. • Surface of carbon nanofibers showed an increase of oxygen content after irradiation. • The radiation-induced graphitization did not damage the overall sp 2 structure. - Abstract: Electron beam and gamma-ray irradiation have potential application to modify the carbon fiber nanostructures in order to produce useful defects in the graphitic structure and create reactive sites. In this study, the methodology to functionalize carbon nanofiber (CNF), via a radiation process and using acrylic acid as a source of oxygen functional groups, was investigated. The samples were submitted to a direct grafting radiation process with electron beam and gamma-ray source. Several parameters were changed such as: acrylic acid concentration, radiation dose and percentage of inhibitor necessary to achieve functionalization, with higher percentage of oxygen functional groups on CNF surface, and better dispersion. The better results achieved were when mixing CNF in a solution of acrylic acid with 6% of inhibitor (FeSO 4 ·7H 2 O) and irradiated at 100 kGy. The samples were characterized by X-ray photoelectron spectroscopy and the surface composition (atomic%) showed a significant increase of oxygen content for the samples after irradiation. Also, the dispersion of the functionalized CNF in water was stable during months which may be a good indication that the functionalization process of CNF via ionizing radiation was successful

Allogeneic marrow grafting for acute leukemia: A follow-up of long-term survivors

International Nuclear Information System (INIS)

Stewart, P.S.; Buckner, C.D.; Clift, R.A.; Sanders, J.E.; Storb, R.; Leonard, J.M.; Thomas, E.D.

1979-01-01

We have reported 100 consecutive patients with refractory acute leukemia treated with chemotherapy, total body irradiation (TBI) and marrow from an HLA identical sibling. At the time of the report 17 patients were alive after 11-53 months. All patients have now been followed more than 3 years. At the time of the last report 4 of the 17 patients had relapsed: two in the narrow, one in the central nervous system and one in the testicle. Three of these four patients have died of their disease 27, 34 and 50 months following tranplant. The patient with a solitary testicular relapse remains in complete remission 49 months after local irradiation without concomitant systemic therapy. One other patient died 26 months following transplantation from cardiopulmonary complications following multiple respiratory infections. Of the 13 surviving patients, three suffer from chronic graft-versus-host disease. Summaries of the problems encountered in these patients after the first 100 days are presented. Ten of the original 100 patients are living productive lives 36-80 months after transplantation. The data clearly demonstrate that long-term unmaintained remissions are possible in a small fraction of patients with terminal leukemia treated with various chemotherapy regimens and TBO followed by marrow transplantation. (author)

Allogeneic marrow grafting for acute leukemia: A follow-up of long-term survivors

Energy Technology Data Exchange (ETDEWEB)

Stewart, P S; Buckner, C D; Clift, R A; Sanders, J E; Storb, R; Leonard, J M; Thomas, E D [Fred Hutchinson Cancer Research Center, Division of Oncology, Department of Medicine, University of Washington School of Medicine, and U.S. Public Health Service Hospital, Seattle, Washington, USA

1979-01-01

We have reported 100 consecutive patients with refractory acute leukemia treated with chemotherapy, total body irradiation (TBI) and marrow from an HLA identical sibling. At the time of the report 17 patients were alive after 11-53 months. All patients have now been followed more than 3 years. At the time of the last report 4 of the 17 patients had relapsed: two in the narrow, one in the central nervous system and one in the testicle. Three of these four patients have died of their disease 27, 34 and 50 months following tranplant. The patient with a solitary testicular relapse remains in complete remission 49 months after local irradiation without concomitant systemic therapy. One other patient died 26 months following transplantation from cardiopulmonary complications following multiple respiratory infections. Of the 13 surviving patients, three suffer from chronic graft-versus-host disease. Summaries of the problems encountered in these patients after the first 100 days are presented. Ten of the original 100 patients are living productive lives 36-80 months after transplantation. The data clearly demonstrate that long-term unmaintained remissions are possible in a small fraction of patients with terminal leukemia treated with various chemotherapy regimens and TBO followed by marrow transplantation.

Bone marrow transplantation across major histocompatibility barriers in mice. II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

International Nuclear Information System (INIS)

Vallera, D.A.; Soderling, C.C.; Carlson, G.J.; Kersey, J.H.

1982-01-01

Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatibility barriers. Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then give to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 200-rad TLI. In TLI plus CY-conditional recipients, we have also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. Furthermore, graft failure in mice receiving normal dosages of anti-Thy-1.2 plus C-treated donor cells was not a strain-restricted phenomenon. Moreover, removal of bone marrow T cells with monoclonal anti-Lyt-1 plus complement also resulted in graft failure in TLI-conditioned recipients. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for there findings are discussed

Grafted Cellulose Based Adsorbents for Selective Separation Purposes

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Takacs, E; Wojnarovits, L [Institute of Isotopes, Hungarian Academy of Sciences, Budapest (Hungary)

2012-09-15

The effect of high energy ionizing radiation on cotton-cellulose was studied. It was found that degradation of cellulose started at low doses, below 5 kGy, resulting in decrease in the degree of polymerization. However, the mechanical properties of cotton-cellulose samples only slightly changed with the dose up to 40 kGy. Acrylate type monomers were successfully grafted to cellulose by mutual and by pre-irradiation grafting technique. With both techniques the grafting yield increased with increasing dose and monomer concentration. In the case of pre-irradiation grafting the increase in grafting time also resulted in an increase in grafting percentage. Cotton-cellulose was functionalized using pre-irradiation grafting (PIG) and simultaneous grafting (SG) of glycidyl methacrylate (GMA). The adsorption properties of this material were further enhanced by {beta}-cyclodextrin (CD) immobilization. This molecule is known for its unique ability to form inclusion complexes among others with aromatic compounds like phenols, pesticide, dyes, etc. (author)

Freeze and Thaw of CD4+CD25+Foxp3+ Regulatory T Cells Results in Loss of CD62L Expression and a Reduced Capacity to Protect against Graft-versus-Host Disease.

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Mareike Florek

Full Text Available The adoptive transfer of CD4+CD25+Foxp3+ regulatory T cells (Tregs in murine models of allogeneic hematopoietic cell transplantation (HCT has been shown to protect recipient mice from lethal acute graft-versus-host disease (GVHD and this approach is being actively investigated in human clinical trials. Here, we examined the effects of cryopreservation on Tregs. We found that freeze and thaw of murine and human Tregs is associated with reduced expression of L-selectin (CD62L, which was previously established to be an important factor that contributes to the in vivo protective effects of Tregs. Frozen and thawed murine Tregs showed a reduced capacity to bind to the CD62L binding partner MADCAM1 in vitro as well as an impaired homing to secondary lymphoid organs in vivo. Upon adoptive transfer frozen and thawed Tregs failed to protect against lethal GVHD compared with fresh Tregs in a murine model of allogeneic HCT across major histocompatibility barriers. In summary, the direct administration of adoptively transferred frozen and thawed Tregs adversely affects their immunosuppressive potential which is an important factor to consider in the clinical implementation of Treg immunotherapies.

Survival of dental implants in native and grafted bone in irradiated head and neck cancer patients: A retrospective analysis

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Aravind Buddula

2011-01-01

Full Text Available Aim: To study the long-term survival of dental implants placed in native or grafted bone in irradiated bone in subjects who had received radiation for head and neck cancer. Materials and Methods: A retrospective chart review was conducted for all patients who received dental implants following radiation treatment for head and neck cancer between May 1, 1987 and July 1, 2008. Only patients irradiated with a radiation dose of 50 Gy or greater and those who received dental implants in the irradiated field after head and neck radiation were included in the study. The associations between implant survival and patient/implant characteristics were estimated by fitting univariate marginal Cox proportional hazards models. Results: A total of 48 patients who had prior head and neck radiation had 271 dental implants placed during May 1987-July 2008. There was no statistically significant difference between implant failure in native and grafted bone (P=0.76. Survival of implants in grafted bone was 82.3% and 98.1% in maxilla and mandible, respectively, after 3 years. Survival of implants in native bone in maxilla and mandible was 79.8% and 100%, respectively, after 3 years. For implants placed in the native bone, there was a higher likelihood of failure in the maxilla compared to the mandible and there was also a tendency for implants placed in the posterior region to fail compared to those placed in the anterior region. Conclusion: There was no significant difference in survival when implants were placed in native or grafted bone in irradiated head and neck cancer patients. For implants placed in native bone, survival was significantly influenced by the location of the implant (maxilla or mandible, anterior or posterior.

Splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia

International Nuclear Information System (INIS)

Gratwohl, A.; Hermans, J.; Biezen, A.V.

1996-01-01

A total of 229 patients with chronic myeloid leukaemia (CML) in chronic phase were randomized between 1986 and 1990 to receive or not receive additional splenic irradiation as part of their conditioning prior to bone marrow transplantation (BMT). Both groups, 115 patients with and 114 patients without splenic irradiation, were very similar regarding distribution of age, sex, donor/recipient sex combination, conditioning, graft-versus-host disease (GvHD) prevention method and blood counts at diagnosis or prior to transplant. 135 patients (59%) are alive as of October 1995 with a minimum follow-up of 5 years. 52 patients have relapsed (23%), 26 patients in the irradiated, 26 patients in the non-irradiated group (n.s.) with a relapse incident at 6 years of 28%. The main risk factor for relapse was T-cell depletion as the method for GvHD prevention, and an elevated basophil count in the peripheral blood prior to transplant. Relapse incidence between patients with or without splenic irradiation was no different in patients at high risk for relapse, e.g. patients transplanted with T-cell-depleted marrows (P = n.s.) and in patients with low risk for relapse, e.g. patients transplanted with non-T-cell-depleted transplants and basophil counts 3% basophils in peripheral blood). In this patient group, relapse incidence was 11% at 6 years with splenic irradiation but 32% in the non-irradiated group (P = 0.05). Transplant-related mortality was similar whether patients received splenic irradiation or not. This study suggests an advantage in splenic irradiation prior to transplantation for CML in this subgroup of patients and illustrates the need for tailored therapy. (Author)

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

International Nuclear Information System (INIS)

Lucarelli, G.; Izzi, T.; Porcellini, A.; Delfini, C.; Galimberti, M.; Moretti, L.; Polchi, P.; Agostinelli, F.; Andreani, M.; Manna, M.; Dallapiccola, B.

1982-01-01

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

Questionnaire survey and technical guideline of blood irradiation on medical facilities

International Nuclear Information System (INIS)

Matsumoto, Mitsuhiro; Hasegawa, Hironori; Okumura, Masahiko; Sonoda, Tatsuo; Osada, Koji.

1997-01-01

We know that transfusion-associated graft versus host disease (TA-GVHD) is a serious side effect associated with blood transfusion and the onset is independent on the immunological conditions of patients. We have only prophylactic treatment against TA-GVHD. The most reliable method is to irradiate the blood for transfusion. In Japanese medical facilities, however, the risk of TA-GVHD is poorly understood and actual conditions of the blood irradiation are unclear. We sent a questionnaire to randomly selected 426 medical facilities in Japan, which had the department of radiology, to investigate the actual conditions of blood irradiation for transfusion and the problems on the irradiation dose measurement of the external apparatus for blood irradiation. The questionnaire involved 19 questions about the blood irradiation for transfusion. The survey took place for one month (June 1-June 30, 1995). Replies were obtained from a total of 306 medical facilities (72%). The results showed that blood irradiation was done by several methods in the 75% of the medical facilities, and the external irradiation apparatus was used in 83%. Some problems were shown, including irradiation period, cost of the irradiation, the operating procedure of the apparatus, requested number of the irradiation, and the request after usual hours. There was no significant problem on the irradiation dose, irradiation method, etc. We also sent a questionnaire to 74 facilities of the Red Cross Blood Center, in which the frequency of blood irradiation have increased since May, 1976. The X-ray apparatus as the external irradiation apparatus has practical advantages; lower cost, compact and out of the legal control on the ionizing radiation, however, it has some problems on the uniformity of the absorption dose when a single X-ray tube-type apparatus is used. We discuss about the possible onset of TA-GVHD or other accidents by the incorrect irradiation of the blood preparations. (K.H.)

Radiation effects on cultured human monocytes and on monocyte-derived macrophages

International Nuclear Information System (INIS)

Buescher, E.S.; Gallin, J.I.

1984-01-01

Prior to administration, leukocyte transfusions are commonly irradiated with up to 5,000 R to eliminate lymphocytes and thereby prevent graft-versus-host disease in the recipient. It has been widely believed that phagocytes are resistant to this irradiation. In a recent report, it was noted that phagocyte oxidative metabolism was compromised during preparation of white cells for transfusion. As part of the effort to examine the basis for this inhibition of phagocyte function during white cell preparation, an assessment was made of the effects of irradiation on the long-lived monocytes that have been shown to persist at inflammatory foci posttransfusion. Human monocytes were irradiated for up to 3 min, receiving 2,500-5,000 R. This irradiation damaged human monocytes, significantly decreasing their in vitro survival for the first 3 wk of culture, and growth as assessed by two-dimensional cell size measurements during the first 2 wk of culture. Despite smaller cell size, total cell protein was significantly increased over time in irradiated cultures. Extracellular release of lysozyme and beta-glucuronidase per cell was not affected by irradiation, but extracellular lactate dehydrogenase (LDH) release was significantly increased after irradiation. Irradiated monocytes killed Listeria monocytogenes at a slower rate than the nonirradiated controls. Thus, the data indicate that irradiation in doses used to prevent graft-versus-host disease in leukocyte transfusion recipients has a deleterious effect on in vitro human monocyte survival and function

Dosimetry of blood irradiator - 2000

International Nuclear Information System (INIS)

Mhatre, Sachin G.V.; Shinde, S.H.; Bhat, R.M.; Rao, Suresh; Sharma, D.N.

2008-01-01

Full text: Blood transfusion to an immunodeficient or immunosuppressed patient has a high risk involved due to occurrence of Transfusion Graft Versus Host Disease (T-GVHD). In order to eliminate this problem, blood is routinely exposed to ionizing radiation (gamma) prior to transfusion. Doses ranging from 15 Gy to 50 Gy can prevent T-GVHD. Aim of the present work was to perform dosimetry of 60 Co Blood Irradiator-2000 developed by Board of Radiation and isotope Technology (BRIT), India; using FBX dosimetric system. Dose-rate measured by FBX dosimeter was intercompared with Fricke dosimeter, which is a Reference Standard dosimeter. Experiments included measurement of dose-rate at the centre of irradiation volume, dose mapping in the central vertical plane within the irradiation volume and measurement of average dose received by blood sample using blood bags filled with FBX dosimeter by simulating actual irradiation conditions. During irradiation, the sample chamber is retracted into a cylindrical source cage, so that the sample is irradiated from all sides uniformly. Blood irradiator-2000 has sample rotation facility for increasing the dose uniformity during irradiation. The performance of this was investigated by measuring the central vertical plane dose profile in stationary state as well in rotation using the sample rotation facility (60 rpm). FBX being an aqueous dosimetric system fills container of irregular shape being irradiated hence can be used to integrate the dose over the volume. Dose-rate measured by FBX dosimeter was intercompared with Fricke dosimeter, which was in good agreement. Average dose-rate at the centre of irradiation volume and within the blood bag was measured by FBX and Fricke dosimeters. It was observed that dose profiles measured by FBX and Fricke dosimeters agreed within ± 2%. Dose uniformity within the irradiation volume was found to reduce from 21% to 17% when the sample rotation facility was used. Thus, it is suggested by the

Expression of bone morphogenic protein 2/4, transforming growth factor-β1, and bone matrix protein expression in healing area between vascular tibia grafts and irradiated bone-experimental model of osteonecrosis

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Schultze-Mosgau, Stefan; Lehner, Bernhard; Roedel, Franz; Wehrhan, Falk; Amann, Kerstin; Kopp, Juergen; Thorwarth, Michael; Nkenke, Emeka; Grabenbauer, Gerhard

2005-01-01

Purpose: For the surgical treatment of osteoradionecrosis after multimodal therapy of head-and-neck cancers, free vascular bone grafts are used to reconstruct osseous structures in the previously irradiated graft bed. Reduced, or even absent osseous healing in the transition area between the vascular graft and the irradiated graft bed represents a clinical problem. Inflammatory changes and fibrosis lead to delayed healing, triggered by bone morphogentic protein 2/4 (BMP2/4) and transforming growth factor (TGF)-β 1 . Given the well-known fibrosis-inducing activity of TGF-β 1 , an osteoinductive effect has been reported for BMP2/4. However, the influence of irradiation (RT) on this cytokine expression remains elusive. Therefore, the aim of the present in vivo study was to analyze the expression of BMP2/4, TGF-β 1 , collagen I, and osteocalcin in the transition area between the bone graft and the graft bed after RT. Methods and materials: Twenty Wistar rats (male, weight 300-500 g) were used in this study. A free vascular tibia graft was removed in all rats and maintained pedicled in the groin region. Ten rats underwent RT with 5 x 10 Gy to the right tibia, the remainder served as controls. After 4 weeks, the previously removed tibia grafts were regrafted into the irradiated (Group 1) and nonirradiated (Group 2) graft beds. The interval between RT and grafting was 4 weeks. After a 4-week osseous healing period, the bone grafts were removed, and the transition area between the nonirradiated graft and the irradiated osseous graft bed was examined histomorphometrically (National Institutes of Health imaging program) and immunohistochemically (avidin-biotin-peroxidase complex) for the expression of BMP2/4, TGF-β 1 , collagen I, and osteocalcin. Results: Absent or incomplete osseous healing of the graft was found in 9 of 10 rats after RT with 50 Gy and in 1 of 10 of the rats with nonirradiated osseous grafts. Histomorphometrically, the proportion of osseous healing in

Total lymphoid irradiation based conditioning for hematopoietic stem cell transplantation in severe aplastic anemia

International Nuclear Information System (INIS)

Lee, Yun Hee; Kim, Ji Yoon; Choi, Byung Ock; Ryu, Mi Ryeong; Chung, Su Mi

2012-01-01

To retrospectively evaluate the outcome and toxicity of total lymphoid irradiation (TLI) based conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) patients who experienced an engraftment failure from prior HSCT or were heavily transfused. Between 1995 and 2006, 20 SAA patients received TLI for conditioning of HSCT. All patients were multi-transfused or had long duration of disease. Fifteen (75%) patients had graft failure from prior HSCT. In 18 (90%) patients, the donors were human leukocyte antigen identical siblings. The stem cell source was the peripheral blood stem cell in 15 (75%) patients. The conditioning regimen was composed of antithymocyte globulin plus TLI with a median dose of 750 cGy in 1 fraction. The graft-versus-host disease (GVHD) prophylaxis used cyclosporine with methotrexate. With a median follow-up of 10.8 years, graft failures developed in 6 patients. Among them, 3 patients received their third HSCT to be engrafted finally. The Kaplan-Meier overall survival rate was 85.0% and 83.1% at 5 and 10 years, respectively. The incidence of acute and chronic GVHD was 20% and 20%, respectively. None of the patients have developed a malignancy after HSCT. In our study, TLI based conditioning in allogeneic HSCT was feasible with acceptable rates of GVHD in SAA patients who experienced graft failure from prior HSCT or was at a high risk of graft rejection. We achieved relatively better results of engraftment and survival with a long term follow-up.

Total lymphoid irradiation based conditioning for hematopoietic stem cell transplantation in severe aplastic anemia

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Lee, Yun Hee; Kim, Ji Yoon; Choi, Byung Ock; Ryu, Mi Ryeong; Chung, Su Mi [Dept. of Radiation Oncology, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

2012-12-15

To retrospectively evaluate the outcome and toxicity of total lymphoid irradiation (TLI) based conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) patients who experienced an engraftment failure from prior HSCT or were heavily transfused. Between 1995 and 2006, 20 SAA patients received TLI for conditioning of HSCT. All patients were multi-transfused or had long duration of disease. Fifteen (75%) patients had graft failure from prior HSCT. In 18 (90%) patients, the donors were human leukocyte antigen identical siblings. The stem cell source was the peripheral blood stem cell in 15 (75%) patients. The conditioning regimen was composed of antithymocyte globulin plus TLI with a median dose of 750 cGy in 1 fraction. The graft-versus-host disease (GVHD) prophylaxis used cyclosporine with methotrexate. With a median follow-up of 10.8 years, graft failures developed in 6 patients. Among them, 3 patients received their third HSCT to be engrafted finally. The Kaplan-Meier overall survival rate was 85.0% and 83.1% at 5 and 10 years, respectively. The incidence of acute and chronic GVHD was 20% and 20%, respectively. None of the patients have developed a malignancy after HSCT. In our study, TLI based conditioning in allogeneic HSCT was feasible with acceptable rates of GVHD in SAA patients who experienced graft failure from prior HSCT or was at a high risk of graft rejection. We achieved relatively better results of engraftment and survival with a long term follow-up.

Graft-versus-Leukemia Effect Following Hematopoietic Stem Cell Transplantation for Leukemia

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Anne M. Dickinson

2017-06-01

Full Text Available The success of hematopoietic stem cell transplantation (HSCT lies with the ability of the engrafting immune system to remove residual leukemia cells via a graft-versus-leukemia effect (GvL, caused either spontaneously post-HSCT or via donor lymphocyte infusion. GvL effects can also be initiated by allogenic mismatched natural killer cells, antigen-specific T cells, and activated dendritic cells of leukemic origin. The history and further application of this GvL effect and the main mechanisms will be discussed and reviewed in this chapter.

National Institutes of Health classification for chronic graft-versus-host disease predicts outcome of allo-hematopoietic stem cell transplant after fludarabine-busulfan-antithymocyte globulin conditioning regimen.

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Saillard, Colombe; Crocchiolo, Roberto; Furst, Sabine; El-Cheikh, Jean; Castagna, Luca; Signori, Alessio; Oudin, Claire; Faucher, Catherine; Lemarie, Claude; Chabannon, Christian; Granata, Angela; Blaise, Didier

2014-05-01

Abstract In 2005, the National Institutes of Health (NIH) proposed standard criteria for diagnosis, organ scoring and global assessment of chronic graft-versus-host disease (cGvHD) severity. We retrospectively reclassified cGvHD with NIH criteria in a monocentric cohort of 130 consecutive adult patients with hematological malignancies presenting cGvHD after receiving allo-hematopoietic stem cell transplant (HSCT) with a fludarabine-busulfan-antithymocyte globulin (ATG) conditioning regimen, among 313 consecutive HSCT recipients. We compared NIH and Seattle classifications to correlate severity and outcome. The follow up range was effectively 2-120 months. Forty-four percent developed Seattle-defined cGvHD (22% limited, 78% extensive forms). Using NIH criteria, there were 23%, 40% and 37% mild, moderate and severe forms, respectively, and 58%, 32% and 8% classic cGvHD, late acute GvHD and overlap syndrome. Five-year overall survival was 55% (49-61), and cumulative incidences of non-relapse mortality (NRM) and relapse/progression at 2 years were 19% (14-23) and 19% (14-24). NIH mild and moderate forms were associated with better survival compared to severe cGvHD (hazard ratio [HR] = 3.28, 95% confidence interval [CI]: 1.38-7.82, p = 0.007), due to higher NRM among patients with severe cGvHD (HR = 3.04, 95% CI: 1.05-8.78, p = 0.04) but comparable relapse risk (p = NS). In conclusion, the NIH classification appears to be more accurate in predicting outcome mostly by the reclassification of old-defined extensive forms into NIH-defined moderate or severe.

Preparation and characterization of acrylic acid-grafted poly (vinyl alcohol) hydrogel actuators using γ-ray irradiation

International Nuclear Information System (INIS)

An, Sung Jun; Lim, Youn Mook; Gwon, Hui Jeong; Kim, Yun Hye; Youn, Min Ho; Nho, Young Chang; Han, Dong Hyun; Kim, Chong Yeal

2008-01-01

Active polymer gels expand and contract in response to certain environmental stimuli, such as the application of an electric field or a change in the pH level of the surroundings. This ability to achieve large, reversible deformations with no external mechanical loading has generated much interest in the use of these gels as biomimetic actuators and artificial muscles. In this study, poly (vinyl alcohol)(PVA) grafted acrylic acid monomer (PVA-g-AAc) hydrogels were prepared by 60 Co γ-ray irradiation and their properties such as degree of grafting and weight swelling in electrostimulation as an artificial muscle and actuator were investigated

The effects of transfusion of irradiated blood upon cellular immune response in patients underwent open heart surgery

International Nuclear Information System (INIS)

Togashi, Ken-ichi; Nakazawa, Satoshi; Moro, Hisanaga; Yazawa, Masatomo; Kanazawa, Hiroshi; Hayashi, Jun-ichi; Yamazaki, Yoshihiko; Eguchi, Shoji

1989-01-01

The purpose of this paper is to demonstrate the effect of the transfusion of blood received 1500 rad exposure upon the immune response in 14 patients underwent various type of cardiac surgery. 13 patients received known amounts banked blood and irradiated fresh blood, while one patient received a lot of amounts of banked and irradiated and non-irradiated fresh blood. The authors studied the numbers of lymphocytes as well as lymphocyte subsets such as pan-T cells, B cells, helper/inducer T cells (T H/I ), cytotoxic/supressor T cells (T C/S ), active T cells, natural killer (NK) cells and NK cell activity during two weeks after surgeries. In all 14 patients, pan-T lymphocytes decreased markedly in a few days after surgeries, but increased to higher levels on the eight postoperative day than the levels preoperatively. T H/I and T C/S lymphocytes changed on the similar pattern as pan-T lymphocytes. Active T and B cells did not change significantly in two weeks. The number and activity of NK cells gave the lowest levels on the second postoperative day and did not recovery to the preoperative levels in two weeks. One patient received non-irradiated fresh blood showed the similar immune response as other 13 patients, while he gave the lower levels than others did. This patient died of graft-versus-host disease (GVHD)-like syndrome on the 36th postoperative day. It may be thought that the transfusion of irradiated blood would prevent the host from GVHD and gave the better effects on the immune response than that of non-irradiated blood following open-heart surgeries. (author)

Successful treatment of dry eye in two patients with chronic graft-versus-host disease with systemic administration of FK506 and corticosteroids.

Science.gov (United States)

Ogawa, Y; Okamoto, S; Kuwana, M; Mori, T; Watanabe, R; Nakajima, T; Yamada, M; Mashima, Y; Tsubota, K; Oguchi, Y

2001-05-01

We present two cases of severe dry eye in patients with chronic graft-versus-host disease (CGVHD) after hematopoietic stem cell transplantation (SCT) who were successfully treated by the systemic administration of FK506 and corticosteroids. A 29-year-old man with chronic myelogenous leukemia underwent SCT. Oral and lung CGVHD developed on approximately day 130, and dry eye associated with CGVHD was diagnosed on day 168. The patient began receiving cyclosporin A (150 mg/d) for the treatment of oral and lung CGVHD. Treatment with prednisolone (1 mg/kg/d) began on approximately day 300. Oral and lung GVHD improved slightly, but worsened again although systemic administration of cyclosporin A and prednisolone were continued. Cyclosporin A was discontinued, and systemic administration of FK506 was started on day 376. Forty-four days later, marked improvement in the ocular surface and other organs was observed. However, the dry eye worsened while tapering FK506, with no flare of other affected organs. A 43-year-old woman with myelodysplastic syndrome underwent SCT. She received FK506 for prophylaxis of CGVHD. She had mild dry eye before SCT. Oral and intestinal CGVHD developed, and the dry eye worsened significantly on approximately day 150 while tapering FK506. Treatment with prednisolone (1 mg/kg/d) began, and the dose of FK506 was increased. By day 240, the symptoms of dry eye and the findings of the ocular surface markedly improved, and CGVHD in other organs was completely resolved. However, the improvement in the dry eye was lost when FK506 was tapered for the second time. Systemic administration of FK506 with corticosteroids is an effective treatment of severe dry eye in patients with CGVHD, but long-term administration may be required to achieve a lasting response. These cases also suggest that further investigation into the use of topical FK506 and prednisolone as a maintenance therapy should be pursued.

Cost-Utility Analysis: Sartorius Flap versus Negative Pressure Therapy for Infected Vascular Groin Graft Managment.

Science.gov (United States)

Chatterjee, Abhishek; Macarios, David; Griffin, Leah; Kosowski, Tomasz; Pyfer, Bryan J; Offodile, Anaeze C; Driscoll, Daniel; Maddali, Sirish; Attwood, John

2015-11-01

Sartorius flap coverage and adjunctive negative pressure wound therapy (NPWT) have been described in managing infected vascular groin grafts with varying cost and clinical success. We performed a cost-utility analysis comparing sartorius flap with NPWT in managing an infected vascular groin graft. A literature review compiling outcomes for sartorius flap and NPWT interventions was conducted from peer-reviewed journals in MEDLINE (PubMed) and EMBASE. Utility scores were derived from expert opinion and used to estimate quality-adjusted life years (QALYs). Medicare current procedure terminology and diagnosis-related groups codes were used to assess the costs for successful graft salvage with the associated complications. Incremental cost-effectiveness was assessed at $50,000/QALY, and both univariate and probabilistic sensitivity analyses were conducted to assess robustness of the conclusions. Thirty-two studies were used pooling 384 patients (234 sartorius flaps and 150 NPWT). NPWT had better clinical outcomes (86.7% success rate, 0.9% minor complication rate, and 13.3% major complication rate) than sartorius flap (81.6% success rate, 8.0% minor complication rate, and 18.4% major complication rate). NPWT was less costly ($12,366 versus $23,516) and slightly more effective (12.06 QALY versus 12.05 QALY) compared with sartorius flap. Sensitivity analyses confirmed the robustness of the base case findings; NPWT was either cost-effective at $50,000/QALY or dominated sartorius flap in 81.6% of all probabilistic sensitivity analyses. In our cost-utility analysis, use of adjunctive NPWT, along with debridement and antibiotic treatment, for managing infected vascular groin graft wounds was found to be a more cost-effective option when compared with sartorius flaps.

Human mesenchymal stem cells suppress donor CD4(+) T cell proliferation and reduce pathology in a humanized mouse model of acute graft-versus-host disease.

Science.gov (United States)

Tobin, L M; Healy, M E; English, K; Mahon, B P

2013-05-01

Acute graft-versus-host disease (aGVHD) is a life-threatening complication following allogeneic haematopoietic stem cell transplantation (HSCT), occurring in up to 30-50% of patients who receive human leucocyte antigen (HLA)-matched sibling transplants. Current therapies for steroid refractory aGVHD are limited, with the prognosis of patients suboptimal. Mesenchymal stem or stromal cells (MSC), a heterogeneous cell population present in many tissues, display potent immunomodulatory abilities. Autologous and allogeneic ex-vivo expanded human MSC have been utilized to treat aGVHD with promising results, but the mechanisms of therapeutic action remain unclear. Here a robust humanized mouse model of aGVHD based on delivery of human peripheral blood mononuclear cells (PBMC) to non-obese diabetic (NOD)-severe combined immunodeficient (SCID) interleukin (IL)-2rγ(null) (NSG) mice was developed that allowed the exploration of the role of MSC in cell therapy. MSC therapy resulted in the reduction of liver and gut pathology and significantly increased survival. Protection was dependent upon the timing of MSC therapy, with conventional MSC proving effective only after delayed administration. In contrast, interferon (IFN)-γ-stimulated MSC were effective when delivered with PBMC. The beneficial effect of MSC therapy in this model was not due to the inhibition of donor PBMC chimerism, as CD45(+) and T cells engrafted successfully in this model. MSC therapy did not induce donor T cell anergy, FoxP3(+) T regulatory cells or cause PBMC apoptosis in this model; however, it was associated with the direct inhibition of donor CD4(+) T cell proliferation and reduction of human tumour necrosis factor-α in serum. © 2012 British Society for Immunology.

Radiation grafting of dimethylaminopropylacrylamide and dimethylaminopropylmethacrylamide onto polyethylene

Energy Technology Data Exchange (ETDEWEB)

Burillo, Guillermina; Oseguera, M.A. [UNAM, Inst. de Ciencias Nucleares, Mexico City (Mexico); Vazquez, Carmen; Castillo, L.P. del [UNAM, Inst. de Investigaciones en Materiales, Mexico City (Mexico)

1997-11-01

Radiation-induced grafting of dimethylaminopropylacrylamide and dimethylamino-propylmethacrylamide onto polyethylene films, by direct grafting of the vinyl monomers to a polymer by mutual irradiation, has been investigated. The kinetics of the reaction were studied at different irradiation temperatures, monomer concentration and dose rates of gamma rays, and the appropriate reaction conditions for graft polymerization were determined. The thermal and mechanical behavior of the grafted films by means of DMA, TMA, DSC and TGA were also investigated. (author).

Regulatory T Cells in Chronic Graft-Versus-Host Disease After Extracorporeal Photopheresis: Correlation With Skin and Global Organ Responses, and Ability to Taper Steroids.

Science.gov (United States)

Denney, Helen A; Whittle, Robert J; Lai, Jennifer; Jacques, Richard M; Taylor, Peter C

2017-01-01

Induction of immune tolerance by an increase in regulatory T (Treg) cells after extracorporeal photopheresis (ECP) is thought to contribute to how ECP exerts its therapeutic effect in patients with chronic graft-versus-host disease (cGvHD). We investigated whether percentages and absolute counts of Treg cells changed post-ECP, and examined correlation with response. Absolute counts and % of CD4+ T cells and Treg cells (CD4 + CD25 + FOXP3 + CD127dim/-) were evaluated using flow cytometry in 32 patients with cGvHD treated by ECP for a minimum of 3 months, and up to 12 months. CD4+ or Treg cells at baseline to 12 months post-ECP were compared with changes in skin disease scores or global organ involvement, or the ability to taper steroids, at 14, 28, and 56 weeks. Regulatory T cells % increased significantly above any overall changes in CD4+ % at 6, 9, and 12 months post-ECP. There was no statistically significant association between Treg cells and skin or steroid response, whereas a larger increase in CD4+ count from baseline to 1 to 3 months corresponded to increased odds of being able to reduce steroid dose by 50% or greater at 14 weeks. Skin and global organ responders at 28 weeks had higher median Treg cell counts 3 months post-ECP than nonresponders, as did steroid responders at 56 weeks who were 12 months post-ECP. Regulatory T cell counts and % varied greatly among cGvHD patients, and the increase post-ECP was not significant until 6 months. No clear correlation was found between Treg cells and clinical improvement, suggesting that increases in Treg cell numbers and/or proportions are not driving the mechanism leading to a response after ECP.

Refractory Graft-Versus-Host Disease-Free, Relapse-Free Survival as an Accurate and Easy-to-Calculate Endpoint to Assess the Long-Term Transplant Success.

Science.gov (United States)

Kawamura, Koji; Nakasone, Hideki; Kurosawa, Saiko; Yoshimura, Kazuki; Misaki, Yukiko; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Akahoshi, Yu; Kusuda, Machiko; Kameda, Kazuaki; Wada, Hidenori; Ishihara, Yuko; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Kimura, Shun-Ichi; Tanihara, Aki; Kako, Shinichi; Kanamori, Heiwa; Mori, Takehiko; Takahashi, Satoshi; Taniguchi, Shuichi; Atsuta, Yoshiko; Kanda, Yoshinobu

2018-02-21

The aim of this study was to develop a new composite endpoint that accurately reflects the long-term success of allogeneic hematopoietic stem cell transplantation (allo-HSCT), as the conventional graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) overestimates the impact of GVHD. First, we validated current GRFS (cGRFS), which recently was proposed as a more accurate endpoint of long-term transplant success. cGRFS was defined as survival without disease relapse/progression or active chronic GVHD at a given time after allo-HSCT, calculated using 2 distinct methods: a linear combination of a Kaplan-Meier estimates approach and a multistate modelling approach. Next, we developed a new composite endpoint, refractory GRFS (rGRFS). rGRFS was calculated similarly to conventional GRFS treating grade III to IV acute GVHD, chronic GVHD requiring systemic treatment, and disease relapse/progression as events, except that GVHD that resolved and did not require systemic treatment at the last evaluation was excluded as an event in rGRFS. The 2 cGRFS curves obtained using 2 different approaches were superimposed and both were superior to that of conventional GRFS, reflecting the proportion of patients with resolved chronic GVHD. Finally, the curves of cGRFS and rGRFS overlapped after the first 2 years of post-transplant follow-up. These results suggest that cGRFS and rGRFS more accurately reflect transplant success than conventional GRFS. Especially, rGRFS can be more easily calculated than cGRFS and analyzed with widely used statistical approaches, whereas cGRFS more accurately represents the burden of GVHD-related morbidity in the first 2 years after transplantation. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Revision Vaginoplasty: A Comparison of Surgical Outcomes of Laparoscopic Intestinal versus Perineal Full-Thickness Skin Graft Vaginoplasty

NARCIS (Netherlands)

Sluis, W.B. van der; Bouman, M.B.; Buncamper, M.E.; Mullender, M.G.; Meijerink, W.J.H.J.

2016-01-01

BACKGROUND: Vaginal (re)construction can greatly improve the quality of life of indicated patients. If primary vaginoplasty fails, multiple surgical approaches exist for revision. The authors compared surgical results of laparoscopic intestinal versus full-thickness skin graft revision vaginoplasty.

Air Pump-Assisted Graft Centration, Graft Edge Unfolding, and Graft Uncreasing in Young Donor Graft Pre-Descemet Endothelial Keratoplasty.

Science.gov (United States)

Jacob, Soosan; Narasimhan, Smita; Agarwal, Amar; Agarwal, Athiya; A I, Saijimol

2017-08-01

To assess an air pump-assisted technique for graft centration, graft edge unfolding, and graft uncreasing while performing pre-Descemet endothelial keratoplasty (PDEK) using young donor grafts. Continuous pressurized air infusion was used for graft centration, graft edge unfolding, and graft unwrinkling. Ten eyes of 10 patients underwent PDEK with donors aged below 40 years. In all eyes, the donor scrolled into tight scrolls. In all cases, the air pump-assisted technique was effective in positioning and centering the graft accurately and in straightening infolded graft edges and smoothing out graft creases and wrinkles. Endothelial cell loss was 38.6%. Postoperative best-corrected visual acuity at 6 months was 0.66 ± 0.25 in decimal equivalent. Continuous pressurized air infusion acted as a third hand providing a continuous pressure head that supported the graft and prevented graft dislocation as well as anterior chamber collapse during intraocular maneuvering. Adequate maneuvering space was available in all cases, and bleeding, if any, was tamponaded successfully in all cases. Although very young donor grafts may be used for PDEK, they are difficult to center and unroll completely before floating against host stroma. An air pump-assisted technique using continuous pressurized air infusion allows successful final graft positioning even with very young donor corneas. It thus makes surgery easier as several key steps are made easier to handle. It additionally helps in tamponading hemorrhage during peripheral iridectomy, increasing surgical space, preventing fluctuations in the anterior chamber depth, and promoting graft adherence.

Irradiation of blood, blood compounds and cell culture in equipment of radiotherapy of clinical usage. Study about volume and ideal dose

International Nuclear Information System (INIS)

Fernandes, Marco Antonio Rodrigues; Pereira, Adelino Jose; Novaes, Paulo Eduardo Ribeiro dos Santos

1996-01-01

The irradiation of blood bags with the objective of minimizing the graft-versus-host disease in the proceedings of blood transfusion has been consolidated as an indispensable step in the advances of hematopoietic system diseases therapeutics. This practice performed in the great oncological treatment centers requires appropriate equipment (cell irradiators), that due to the high coast, is inaccessible to the majority of the services. The main objective of this work is the show the technique developed by the Radiological Physics Service of the Hospital A. C. Camargo Radiation Department, using the teletherapy equipment of clinical usage available at the Institution. The literature shows that a total dose of 2000 to 3500 c Gy must be administered to all target volume to get an ideal dose/volume relation that proportionates better therapeutic results, neutralizing the cells which are causative of post transfusion reactions of rejection, without prejudicing the other cells that are necessary to the maintenance and preservation of the transplanted person's hematopoietic system functions. With the technic developed for optimization of the irradiation. it is possible to conclude that the utilization of radiotherapy equipment of clinical usage for blood irradiation, substituting cells irradiators, is a good option, permitting safe transfusion of products irradiated with adequate dose. (author)

Impact of Donor Epstein-Barr Virus Serostatus on the Incidence of Graft-Versus-Host Disease in Patients With Acute Leukemia After Hematopoietic Stem-Cell Transplantation: A Study From the Acute Leukemia and Infectious Diseases Working Parties of the European Society for Blood and Marrow Transplantation.

Science.gov (United States)

Styczynski, Jan; Tridello, Gloria; Gil, Lidia; Ljungman, Per; Hoek, Jennifer; Iacobelli, Simona; Ward, Katherine N; Cordonnier, Catherine; Einsele, Hermann; Socie, Gerard; Milpied, Noel; Veelken, Hendrik; Chevallier, Patrice; Yakoub-Agha, Ibrahim; Maertens, Johan; Blaise, Didier; Cornelissen, Jan; Michallet, Mauricette; Daguindau, Etienne; Petersen, Eefke; Passweg, Jakob; Greinix, Hildegard; Duarte, Rafael F; Kröger, Nicolaus; Dreger, Peter; Mohty, Mohamad; Nagler, Arnon; Cesaro, Simone

2016-07-01

We investigated the effect of Epstein-Barr virus (EBV) serostatus on the overall outcome of allogeneic hematopoietic stem-cell transplantation (allo-HSCT). The study included 11,364 patients who underwent allogeneic peripheral-blood or bone marrow transplantation for acute leukemia between 1997 and 2012. We analyzed the impact of donor and recipient EBV serologic status on overall survival, relapse-free survival, relapse incidence, nonrelapse mortality, and incidence of graft-versus-host disease (GVHD) after allo-HSCT. Patients receiving grafts from EBV-seropositive donors had the same overall survival as patients who received grafts from EBV-seronegative donors (hazard ratio [HR], 1.05; 95% CI, 0.97 to 1.12; P = .23). Seropositive donors also had no influence on relapse-free survival (HR, 1.04; 95% CI, 0.97 to 1.11; P = 0.31), relapse incidence (HR, 1.03; 95% CI, 0.94 to 1.12; P = .58), and nonrelapse mortality (HR, 1.05; 95% CI, 0.94 to 1.17; P = .37). However, in univariate analysis, recipients receiving grafts from seropositive donors had a higher risk of chronic GVHD than those with seronegative donors (40.8% v 31.0%, respectively; P donors, the HR for chronic GVHD was 1.30 (95% CI, 1.06 to 1.59; P = .039). In seropositive patients with seropositive donors, the HR was 1.24 (95% CI, 1.07 to 1.45; P = .016) for acute GVHD and 1.43 (95% CI, 1.23 to 1.67; P donors did not have an increased risk of GVHD. Our data suggest that donor EBV status significantly influences development of acute and chronic GVHD after allo-HSCT. © 2016 by American Society of Clinical Oncology.

Graft rejection by cytolytic T cells. Specificity of the effector mechanism in the rejection of allogeneic marrow

International Nuclear Information System (INIS)

Nakamura, H.; Gress, R.E.

1990-01-01

Cellular effector mechanisms of allograft rejection remain incompletely described. Characterizing the rejection of foreign-marrow allografts rather than solid-organ grafts has the advantage that the cellular composition of the marrow graft, as a single cell suspension, can be altered to include cellular components with differing antigen expression. Rejection of marrow grafts is sensitive to lethal doses of radiation in the mouse but resistant to sublethal levels of radiation. In an effort to identify cells mediating host resistance, lymphocytes were isolated and cloned from spleens of mice 7 days after sublethal TBI (650 cGy) and inoculation with allogeneic marrow. All clones isolated were cytolytic with specificity for MHC encoded gene products of the allogeneic marrow donor. When cloned cells were transferred in vivo into lethally irradiated (1025 cGy) recipients unable to reject allogeneic marrow, results utilizing splenic 125IUdR uptake indicated that these MHC-specific cytotoxic clones could suppress marrow proliferation. In order to characterize the effector mechanism and the ability of the clones to affect final engraftment, double donor chimeras were constructed so that 2 target cell populations differing at the MHC from each other and from the host were present in the same marrow allograft. Results directly demonstrated an ability of CTL of host MHC type to mediate graft rejection and characterized the effector mechanism as one with specificity for MHC gene products

Hydrophilic/hydrophobic character of grafted cellulose

Energy Technology Data Exchange (ETDEWEB)

Takacs, E., E-mail: takacs@iki.kfki.h [Institute of Isotopes, Hungarian Academy of Sciences, Budapest (Hungary); Wojnarovits, L. [Institute of Isotopes, Hungarian Academy of Sciences, Budapest (Hungary); Borsa, J. [Budapest University of Technology and Economics (Hungary); Racz, I. [Bay Zoltan Institute for Materials Science and Technology, Budapest (Hungary)

2010-04-15

Vinyl monomers with long paraffin chains were grafted onto two kinds of cellulose (cotton and cotton linter) by direct irradiation grafting technique. The effect of dose, monomer structure and concentration, as well as homopolymer suppressor (styrene) concentration on the grafting yield was studied and the optimal grafting conditions were established. Grafting decreased the swelling of the samples in water and increased their polymer compatibility in polypropylene matrix.

Growth in children following irradiation for bone marrow transplantation

International Nuclear Information System (INIS)

Bushhouse, S.; Ramsay, N.K.; Pescovitz, O.H.; Kim, T.; Robison, L.L.

1989-01-01

Longitudinal height data from 46 pediatric bone marrow transplant (BMT) patients, including 18 with aplastic anemia (AA), 19 with acute nonlymphoblastic leukemia (ANLL), and 9 with acute lymphoblastic leukemia (ALL), were analyzed to assess growth posttransplantation. Patients were prepared for BMT with high-dose cyclophosphamide followed by 7.5 Gy single-dose irradiation; AA patients received total lymphoid irradiation (TLI), and leukemia patients received total body irradiation (TBI). AA patients demonstrated reduced height posttransplant as reflected in a negative mean standard deviation score. The observed reduction was statistically significant only at 3 years following transplant. In contrast, leukemia patients showed a significant loss in relative height that was first visible at 1 year post-BMT and continued until at least 4 years post-BMT. Mean growth velocities in the leukemia patients were significantly below median for the 3 years following transplant. With a median follow-up of 4 years, antithymocyte globulin plus steroids in combination with methotrexate as graft vs. host prophylaxis was associated with less severe growth suppression than methotrexate alone, while there were no significant associations between growth during the first 2 years following transplant and prepubertal status at transplant (as defined by age), graft vs. host disease, thyroid or gonadal function, or previous therapies received by the leukemia patients. Children undergoing marrow transplantation, particularly those receiving TBI, are at significant risk of subsequent growth suppression

Skin graft influence in human tissue radiated in nude mice regeneration

International Nuclear Information System (INIS)

Miranda, Jurandir Tomaz de

2016-01-01

Over the last few years it has increased the interest in the human skin grafts radio sterilized for application mainly in extensive and deep burns. Because these grafts quickly grip and present antigenic lower potential, compared with other treatments used. The purpose of this study was to evaluate the histoarchitecture of human skin grafts irradiated with doses 25 kGy, 50 kGy and non-irradiated during the repair tissue process in nude mice submitted by skin grafting in the dorsal region. Three groups of animals received irradiated human skin grafts (25 kGy and 50 kGy) and non-irradiated and were euthanized on the 3 rd , 7 th and 21 th day after the surgery. Indeed, routine histologic procedures, tissue samples were stained with hematoxylin and eosin (HE) for quantification of keratinocytes, fibroblasts, immune cells and blood vessels and immunofluorescence (IF) was performed to determine the expression human collagen type I and collagen type I and III mouse. Therefore, quantification of both the cells and the collagen types was performed by image analysis using Image-Pro Plus 6.0 software. Histologic results demonstrated at a dose of 25 kGy that human skin irradiation when grafted influences the increase in the number of cells in wound site over time and it provides better dispersion of these cells. In addition, on the 21 st day, three groups of animals with human skin graft were embedded part of the graft in the healing process. On the other hand, the group not irradiated showed greater incorporation of the graft (43 %), but less production of collagen type III mouse (22 %). Since the groups irradiated skin graft showed lower graft incorporation (6 and 15%), but with greater production of collagen type III mice (35 % and 28 % to 25 kGy and 50 kGy, respectively). In conclusion, this study presented that the group irradiated to 25 kGy and it has a higher cell proliferation and vessel formation, and better remodeling of the healing area. (author)

Potential for Monitoring Gut Microbiota for Diagnosing Infections and Graft-versus-Host Disease in Cancer and Stem Cell Transplant Patients.

Science.gov (United States)

Koh, Andrew Y

2017-11-01

Gut microbiota, the collective community of microorganisms inhabiting the intestine, have been shown to provide many beneficial functions for the host. Recent advances in next-generation sequencing and advanced molecular biology approaches have allowed researchers to identify gut microbiota signatures associated with disease processes and, in some cases, establish causality and elucidate underlying mechanisms. This report reviews 3 commonly used methods for studying the gut microbiota and microbiome (the collective genomes of the gut microorganisms): 16S rRNA gene sequencing, bacterial group or species-specific quantitative polymerase chain reaction (qPCR), and metagenomic shotgun sequencing (MSS). The technical approaches and resources needed for each approach are outlined, and advantages and disadvantages for each approach are summarized. The findings regarding the role of the gut microbiota in the health of patients with cancer and stem cell transplant (SCT) patients (specifically in modulating the development of gut-derived bacterial infections and a posttransplant immune-mediated complication known as graft-vs-host-disease) are reviewed. Finally, there is discussion of the potential viability of these approaches in the actual clinical treatment of cancer and SCT patients. Advances in next-generation sequencing have revolutionized our understanding of the importance of the gut microbiome to human health. Both 16S rRNA gene sequencing and MSS are currently too labor-intensive or computationally burdensome to incorporate into real-time clinical monitoring of gut microbiomes. Yet, the lessons learned from these technologies could be adapted to currently used methods (e.g., qPCR) that could then be rigorously tested in the clinical care of these patients. © 2017 American Association for Clinical Chemistry.

Pilot study of lithium to restore intestinal barrier function in severe graft-versus-host disease.

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Gideon Steinbach

Full Text Available Severe intestinal graft-vs-host disease (GVHD after allogeneic hematopoietic cell transplantation (HCT causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3, would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregulated inflammatory response to mucosal injury. We conducted an observational pilot study to provide data for the potential design of a randomized study of lithium. Twenty patients with steroid refractory intestinal GVHD meeting enrollment criteria were given oral lithium carbonate. GVHD was otherwise treated per current practice, including 2 mg/kg per day of prednisone equivalent. Seventeen patients had extensive mucosal denudation (extreme endoscopic grade 3 in the duodenum or colon. We observed that 8 of 12 patients (67% had a complete remission (CR of GVHD and survived more than 1 year (median 5 years when lithium administration was started promptly within 3 days of endoscopic diagnosis of denuded mucosa. When lithium was started promptly and less than 7 days from salvage therapy for refractory GVHD, 8 of 10 patients (80% had a CR and survived more than 1 year. In perspective, a review of 1447 consecutive adult HCT patients in the preceding 6 years at our cancer center showed 0% one-year survival in 27 patients with stage 3-4 intestinal GVHD and grade 3 endoscopic appearance in the duodenum or colon. Toxicities included fatigue, somnolence, confusion or blunted affect in 50% of the patients. The favorable outcomes in patients who received prompt lithium therapy appear to support the future conduct of a randomized study of lithium for management of severe GVHD with