Nanoparticle delivery of donor antigens for transplant tolerance in allogeneic islet transplantation.

Science.gov (United States)

Bryant, Jane; Hlavaty, Kelan A; Zhang, Xiaomin; Yap, Woon-Teck; Zhang, Lei; Shea, Lonnie D; Luo, Xunrong

2014-10-01

Human islet cell transplantation is a promising treatment for type 1 diabetes; however, long-term donor-specific tolerance to islet allografts remains a clinically unmet goal. We have previously shown that recipient infusions of apoptotic donor splenocytes chemically treated with 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (donor ECDI-SP) can mediate long-term acceptance of full major histocompatibility complex (MHC)-mismatched murine islet allografts without the use of immunosuppression. In this report, we investigated the use of poly(lactide-co-glycolide) (PLG) particles in lieu of donor ECDI-SP as a synthetic, cell-free carrier for delivery of donor antigens for the induction of transplant tolerance in full MHC-mismatched murine allogeneic islet transplantation. Infusions of donor antigen-coupled PLG particles (PLG-dAg) mediated tolerance in ∼20% of recipient mice, and the distribution of cellular uptake of PLG-dAg within the spleen was similar to that of donor ECDI-SP. PLG-dAg mediated the contraction of indirectly activated T cells but did not modulate the direct pathway of allorecognition. Combination of PLG-dAg with a short course of low dose immunosuppressant rapamycin at the time of transplant significantly improved the tolerance efficacy to ∼60%. Furthermore, altering the timing of PLG-dAg administration to a schedule that is more feasible for clinical transplantation resulted in equal tolerance efficacy. Thus, the combination therapy of PLG-dAg infusions with peritransplant rapamycin represents a clinically attractive, biomaterials-based and cell-free method for inducing long-term donor-specific tolerance for allogeneic cell transplantation, such as for allogeneic islet transplantation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Using the cost-effectiveness of allogeneic islet transplantation to inform induced pluripotent stem cell-derived β-cell therapy reimbursement.

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Archibald, Peter R T; Williams, David J

2015-11-01

In the present study a cost-effectiveness analysis of allogeneic islet transplantation was performed and the financial feasibility of a human induced pluripotent stem cell-derived β-cell therapy was explored. Previously published cost and health benefit data for islet transplantation were utilized to perform the cost-effectiveness and sensitivity analyses. It was determined that, over a 9-year time horizon, islet transplantation would become cost saving and 'dominate' the comparator. Over a 20-year time horizon, islet transplantation would incur significant cost savings over the comparator (GB£59,000). Finally, assuming a similar cost of goods to islet transplantation and a lack of requirement for immunosuppression, a human induced pluripotent stem cell-derived β-cell therapy would dominate the comparator over an 8-year time horizon.

Basiliximab induced non-cardiogenic pulmonary edema in two pediatric renal transplant recipients.

LENUS (Irish Health Repository)

Dolan, Niamh

2009-11-01

We report two cases of non-cardiogenic pulmonary edema as a complication of basiliximab induction therapy in young pediatric renal transplant patients identified following a retrospective review of all pediatric renal transplant cases performed in the National Paediatric Transplant Centre, Childrens University Hospital, Temple Street, Dublin, Ireland. Twenty-eight renal transplantations, of which five were living-related (LRD) and 23 were from deceased donors (DD), were performed in 28 children between 2003 and 2006. In six cases, transplantations were pre-emptive. Immunosuppression was induced pre-operatively using a combination of basiliximab, tacrolimus and methylprednisolone in all patients. Basiliximab induction was initiated 2 h prior to surgery in all cases and, in 26 patients, basiliximab was re-administered on post-operative day 4. Two patients, one LRD and one DD, aged 6 and 11 years, respectively, developed acute non-cardiogenic pulmonary edema within 36 h of surgery. Renal dysplasia was identified as the primary etiological factor for renal failure in both cases. Both children required assisted ventilation for between 4 and 6 days. While both grafts had primary function, the DD transplant patient subsequently developed acute tubular necrosis and was eventually lost within 3 weeks due to thrombotic microangiopathy and severe acute antibody-mediated rejection despite adequate immunosuppression. Non-cardiogenic pulmonary edema is a potentially devastating post-operative complication of basiliximab induction therapy in young pediatric patients following renal transplantation. Early recognition and appropriate supportive therapy is vital for patient and, where possible, graft survival.

Genetic modification to induce CXCR2 overexpression in mesenchymal stem cells enhances treatment benefits in radiation-induced oral mucositis.

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Shen, Zongshan; Wang, Jiancheng; Huang, Qiting; Shi, Yue; Wei, Zhewei; Zhang, Xiaoran; Qiu, Yuan; Zhang, Min; Wang, Yi; Qin, Wei; Huang, Shuheng; Huang, Yinong; Liu, Xin; Xia, Kai; Zhang, Xinchun; Lin, Zhengmei

2018-02-14

Radiation-induced oral mucositis affects patient quality of life and reduces tolerance to cancer therapy. Unfortunately, traditional treatments are insufficient for the treatment of mucositis and might elicit severe side effects. Due to their immunomodulatory and anti-inflammatory properties, the transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic strategy for mucositis. However, systemically infused MSCs rarely reach inflamed sites, impacting their clinical efficacy. Previous studies have demonstrated that chemokine axes play an important role in MSC targeting. By systematically evaluating the expression patterns of chemokines in radiation/chemical-induced oral mucositis, we found that CXCL2 was highly expressed, whereas cultured MSCs negligibly express the CXCL2 receptor CXCR2. Thus, we explored the potential therapeutic benefits of the transplantation of CXCR 2 -overexpressing MSCs (MSCs CXCR2 ) for mucositis treatment. Indeed, MSCs CXCR2 exhibited enhanced targeting ability to the inflamed mucosa in radiation/chemical-induced oral mucositis mouse models. Furthermore, we found that MSC CXCR2 transplantation accelerated ulcer healing by suppressing the production of pro-inflammatory chemokines and radiogenic reactive oxygen species (ROS). Altogether, these findings indicate that CXCR2 overexpression in MSCs accelerates ulcer healing, providing new insights into cell-based therapy for radiation/chemical-induced oral mucositis.

Caudal Ganglionic Eminence Precursor Transplants Disperse and Integrate as Lineage-Specific Interneurons but Do Not Induce Cortical Plasticity

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Phillip Larimer

2016-08-01

Full Text Available The maturation of inhibitory GABAergic cortical circuits regulates experience-dependent plasticity. We recently showed that the heterochronic transplantation of parvalbumin (PV or somatostatin (SST interneurons from the medial ganglionic eminence (MGE reactivates ocular dominance plasticity (ODP in the postnatal mouse visual cortex. Might other types of interneurons similarly induce cortical plasticity? Here, we establish that caudal ganglionic eminence (CGE-derived interneurons, when transplanted into the visual cortex of neonatal mice, migrate extensively in the host brain and acquire laminar distribution, marker expression, electrophysiological properties, and visual response properties like those of host CGE interneurons. Although transplants from the anatomical CGE do induce ODP, we found that this plasticity reactivation is mediated by a small fraction of MGE-derived cells contained in the transplant. These findings demonstrate that transplanted CGE cells can successfully engraft into the postnatal mouse brain and confirm the unique role of MGE lineage neurons in the induction of ODP.

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

Immune response to uv-induced tumors: transplantation immunity and lymphocyte populations exhibiting anti-tumor activity

International Nuclear Information System (INIS)

Streeter, P.R.

1985-01-01

Ultraviolet light-induced murine skin tumors were analyzed for their ability to induce tumor-specific and cross-protective transplantation immunity in immunocompetent syngeneic mice. These studies revealed that progressor UV-tumors, like regressor UV-tumors, possess tumor-specific transplantation antigens. Cross-protective transplantation immunity to UV-tumors, however, was associated with sensitization to the serum used to culture the tumor lines rather than to cross-reactive or common determinants on UV-tumors. An analysis of the cytolytic activity of lymphocytes from the spleens of mice immunized with either regressor or progressor UV-tumors revealed a striking difference between the two immune splenocyte populations. From regressor tumor-immune animals, cytolytic T (Tc) lymphocytes with specificity for the immunizing tumor were found. However, the analysis of splenic lymphocytes from progressor tumor immune animals revealed no such effector cells. To more effectively examine those lymphocytes exhibiting cytolytic activity in vitro, T lymphocyte cloning technology was used as a means of isolating homogeneous lymphocyte populations with the effector activities described above. The mechanisms where NK cells and other nonspecific effector cells could be induced in tumor-immune animals are discussed in the context of class II restricted immune responses

Very late coronary spasm inducing acute myocardial infarction in a heart transplant recipient.

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Santoro, Francesco; Lopizzo, Agostino; Centola, Antonio; Cuculo, Andrea; Ruggiero, Antonio; Di Biase, Matteo; Brunetti, Natale Daniele

2016-12-01

: We report coronary angio findings of very late (10-year) coronary spasm inducing acute myocardial infarction with typical chest pain in a heart transplant recipient. Coronary spasm was promptly relieved by intra-coronary infusion of nitrates.

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Chemically Induced Reprogramming of Somatic Cells to Pluripotent Stem Cells and Neural Cells.

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Biswas, Dhruba; Jiang, Peng

2016-02-06

The ability to generate transplantable neural cells in a large quantity in the laboratory is a critical step in the field of developing stem cell regenerative medicine for neural repair. During the last few years, groundbreaking studies have shown that cell fate of adult somatic cells can be reprogrammed through lineage specific expression of transcription factors (TFs)-and defined culture conditions. This key concept has been used to identify a number of potent small molecules that could enhance the efficiency of reprogramming with TFs. Recently, a growing number of studies have shown that small molecules targeting specific epigenetic and signaling pathways can replace all of the reprogramming TFs. Here, we provide a detailed review of the studies reporting the generation of chemically induced pluripotent stem cells (ciPSCs), neural stem cells (ciNSCs), and neurons (ciN). We also discuss the main mechanisms of actions and the pathways that the small molecules regulate during chemical reprogramming.

Manipulating transplant morphology to advance post-transplant growth and yield in strawberry

NARCIS (Netherlands)

Reekie, J.Y.

2005-01-01

Two methods were developed to enhance transplant success and minimize water use of strawberry transplants harvested in Canadian nurseries for use in the annual strawberry production system in the Southern United States: mechanical leaf removal by mowing, and chemical control of growth and

Pancreatic Islet Cell Transplantation

Science.gov (United States)

Warnock, Garth L.; Rajotte, Ray V.

1992-01-01

Transplantation of insulin-producing tissue offers a physiologic approach to restoration of glycemic control. Whereas transplantation of vascularized pancreatic grafts has recently achieved encouraging results, pancreatic islet cell transplantation holds the promise of low morbidity and reduced requirements for agressive immunosuppression for recipients. Islet cell transplantation was recently demonstrated to induce euglycemia with insulin independence. Imagesp1656-a PMID:21221366

Immunological tolerance induced by galectin-1 in rat allogeneic renal transplantation.

Science.gov (United States)

Xu, Gaosi; Tu, Weiping; Xu, Chengyun

2010-06-01

The existed literatures indicated that galectin-1 has anti-inflammatory effects and plays a pivotal role in autoimmune diseases. Present study was to identify the roles of galectin-1 in acute animal renal allograft rejection. Rat acute rejection models were erected by allogeneic renal transplantation. Galectin-1 injection was performed in different concentrations in renal recipients post-transplantation. Recipient survivals, CD8+ T cell proliferation, production of IFN-gamma, levels of serum CD30, enzyme-linked immunoabsorbent spot assay (ELISPOT) and immunohistochemistry were observed or tested 7days after renal transplantation. Galectin-1 injection can prolong the recipient animal survival, reduce the serum levels of IFN-gamma, soluble CD30, percentage of CD8+ T cell subset, CD8+ T cell-mediated cytotoxicity, and IFN-gamma ELISPOT frequency for allograft recipients. The therapeutic effects of galectin-1 injection on recipient rats were dose-dependent. Galectin-1 plays an important role in CD8+ T cell-mediated renal rejection by inducing immunological tolerance. Copyright 2010 Elsevier B.V. All rights reserved.

Polymorphisms in CTLA4 influence incidence of drug-induced liver injury after renal transplantation in Chinese recipients.

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Yifeng Guo

Full Text Available Genetic polymorphisms in cytotoxic T lymphocyte-associated antigen 4 (CTLA4 play an influential role in graft rejection and the long-term clinical outcome of organ transplantation. We investigated the association of 5 CTLA4 single-nucleotide polymorphisms (SNPs (rs733618 C/T, rs4553808 A/G, rs5742909 C/T, rs231775 A/G, and rs3087243 G/A with drug-induced liver injury (DILI in Chinese renal transplantation (RT recipients. Each recipient underwent a 24-month follow-up observation for drug-induced liver damage. The CTLA4 SNPs were genotyped in 864 renal transplantation recipients. A significant association was found between the rs231775 genotype and an early onset of DILI in the recipients. Multivariate analyses revealed that a risk factor, recipient rs231775 genotype (p = 0.040, was associated with DILI. Five haplotypes were estimated for 4 SNPs (excluding rs733618; the frequency of haplotype ACGG was significantly higher in the DILI group (68.9% than in the non-DILI group (61.1% (p = 0.041. In conclusion, CTLA4 haplotype ACGG was partially associated with the development of DILI in Chinese kidney transplant recipients. The rs231775 GG genotype may be a risk factor for immunosuppressive drug-induced liver damage.

Direct and Indirect Effects of Cytomegalovirus-induced gamma-delta T Cells after Kidney Transplantation

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Lionel eCouzi

2015-01-01

Full Text Available Despite effective anti-viral therapies, cytomegalovirus (CMV is still associated with direct (CMV disease and indirect effects (rejection and poor graft survival in kidney transplant recipients. Recently, an unconventional T cell population (collectively designated as Vδ2neg γδ T cells has been characterized during the anti-CMV immune response in all solid-organ and bone-marrow transplant recipients, neonates, and healthy people. These CMV-induced γδ T cells undergo a dramatic and stable expansion after CMV infection, in a conventional ‘adaptive’ manner. Similarly as CMV-specific CD8+ αβ T cells, they exhibit an effector/memory TEMRA phenotype and cytotoxic effector functions. Activation of Vd2neg gd T cells by CMV-infected cells involves the TCR and still ill-defined co-stimulatory molecules such LFA-1. A multiple of Vd2neg gd TCR ligands are apparently recognized on CMV-infected cells, the first one identified being the MHC-related molecule endothelial protein C receptor (EPCR. A singularity of CMV-induced Vd2neg gd T cells is to acquire CD16 expression and to exert an antibody-dependent cell-mediated inhibition on CMV replication, which is controlled by a specific cytokine microenvironment. Beyond the well-demonstrated direct anti-CMV effect of Vδ2neg γδ T cells, unexpected indirect effects of these cells have been also observed in the context of kidney transplantation. CMV-induced Vδ2neg γδ T cells have been involved in surveillance of malignancy subsequent to long term immunosuppression. Moreover, CMV-induced CD16+ γδ T cells are cell effectors of antibody-mediated rejection of kidney transplants, and represent a new physiopathological contribution to the well-known association between CMV infection and poor graft survival. All these basic and clinical studies paved the road to the development of a future γδ T cell-based immunotherapy. In the meantime, γδ T cell monitoring should prove a valuable immunological

Progression of nephropathy after islet of langerhans transplantation in alloxan-induced diabetic rats

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César Tadeu Spadella

1997-03-01

Full Text Available We studied the effects of islet of Langerhans transplantation (IT on the kidney lesions of rats with alloxan-induced diabetes. Forty-five inbred male Lewis rats were randomly assigned to 3 experimental groups: group Gl included 15 non-diabetic control rats (NC, group GIT included 15 alloxan-induced diabetic rats (DC, and group III included 15 alloxan-induced diabetic rats that received pancreatic islet transplantation prepared by nonenzymatic method from normal donor Lewis rats and injected into the portal vein (IT. Each group was further divided into 3 subgroups of 5 rats which were sacrificed at 1, 3, and 6 months of follow-up, respectively. Clinical and laboratorial parameters were recorded in the mentioned periods in the 3 experimental groups. For histology, the kidneys of all rats of each subgroup were studied and 50 glomeruli and 50 tubules of each kidney were analyzed using light microscopy by two different investigators in a double blind study. The results showed progressive glomerular basement membrane thickening (GBMT, mesangial enlargement (ME, and Bowman's capsule thickening (BCT in the 3 experimental groups throughout the follow-up. These alterations were significantly more severe in DC rats at 6 months when compared to NC rats (p < 0.01. However, the degree of GBMT, ME, and BCT observed in DC rats was not statistically different from IT rats at 1, 3, and 6 months. In addition, Armanni-Ebstein lesions of the tubules (AE and tubular lumen protein (PRO observed in DC rats were also observed in IT rats all over the study. These lesions were never present in NC rats. We conclude that IT did not prevent progression of kidney lesions in alloxan-induced diabetic rats within 6 months after transplantation.

Chemical Detection Based on Adsorption-Induced and Photo-Induced Stresses in MEMS Devices

Energy Technology Data Exchange (ETDEWEB)

Datskos, P.G.

1999-04-05

Recently there has been an increasing demand to perform real-time in-situ chemical detection of hazardous materials, contraband chemicals, and explosive chemicals. Currently, real-time chemical detection requires rather large analytical instrumentation that are expensive and complicated to use. The advent of inexpensive mass produced MEMS (micro-electromechanical systems) devices opened-up new possibilities for chemical detection. For example, microcantilevers were found to respond to chemical stimuli by undergoing changes in their bending and resonance frequency even when a small number of molecules adsorb on their surface. In our present studies, we extended this concept by studying changes in both the adsorption-induced stress and photo-induced stress as target chemicals adsorb on the surface of microcantilevers. For example, microcantilevers that have adsorbed molecules will undergo photo-induced bending that depends on the number of absorbed molecules on the surface. However, microcantilevers that have undergone photo-induced bending will adsorb molecules on their surfaces in a distinctly different way. Depending on the photon wavelength and microcantilever material, the microcantilever can be made to bend by expanding or contracting the irradiated surface. This is important in cases where the photo-induced stresses can be used to counter any adsorption-induced stresses and increase the dynamic range. Coating the surface of the microstructure with a different material can provide chemical specificity for the target chemicals. However, by selecting appropriate photon wavelengths we can change the chemical selectivity due to the introduction of new surface states in the MEMS device. We will present and discuss our results on the use of adsorption-induced and photo-induced bending of microcantilevers for chemical detection.

Ephedra-Treated Donor-Derived Gut Microbiota Transplantation Ameliorates High Fat Diet-Induced Obesity in Rats.

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Wang, Jing-Hua; Kim, Bong-Soo; Han, Kyungsun; Kim, Hojun

2017-05-23

Changes in gut microbiota (GM) are closely associated with metabolic syndrome, obesity, type 2 diabetes and so on. Several medicinal herbs, including Ephedra sinica (Es), have anti-obesity effects that ameliorate metabolic disorders. Therefore, in this study we evaluated whether Es maintains its anti-obesity effect through Es-altered gut microbiota (EsM) transplantation. GM was isolated from cecal contents of Es treated and untreated rats following repeated transplants into obese rats via oral gavage over three weeks. High-fat-diet (HFD)-induced obese rats transplanted with EsM lost significant body weight, epididymal fat, and perirenal fat weight, but no remarkable changes were observed in abdominal fat, liver, cecum weight and food efficiency ratio. In addition, treatment with EsM also significantly lowered the fasting blood glucose, serum insulin level, and insulin resistance index. Meanwhile, EsM transplantation significantly reduced gene expression of proinflammatory cytokines interleukin-1 and monocyte chemotactic protein-1. Rats treated with EsM also showed changed GM composition, especially blautia, roseburia and clostridium, significantly reduced the level of endotoxin and markedly increased the acetic acid in feces. Overall, our results demonstrated that EsM ameliorates HFD-induced obesity and related metabolic disorders, like hyperglycemia and insulin resistance, and is strongly associated with modulating the distribution of GM, enterogenous endotoxin and enteral acetic acid.

Pim2 cooperates with PML-RARalpha to induce acute myeloid leukemia in a bone marrow transplantation model

DEFF Research Database (Denmark)

Agrawal-Singh, Shuchi; Koschmieder, Steffen; Gelsing, Sandra

2010-01-01

Although the potential role of Pim2 as a cooperative oncogene has been well described in lymphoma, its role in leukemia has remained largely unexplored. Here we show that high expression of Pim2 is observed in patients with acute promyelocytic leukemia (APL). To further characterize the cooperative...... role of Pim2 with promyelocytic leukemia/retinoic acid receptor alpha (PML/RARalpha), we used a well-established PML-RARalpha (PRalpha) mouse model. Pim2 coexpression in PRalpha-positive hematopoietic progenitor cells (HPCs) induces leukemia in recipient mice after a short latency. Pim2-PRalpha cells...... were able to repopulate mice in serial transplantations and to induce disease in all recipients. Neither Pim2 nor PRalpha alone was sufficient to induce leukemia upon transplantation in this model. The disease induced by Pim2 overexpression in PRalpha cells contained a slightly higher fraction...

ES-cell derived hematopoietic cells induce transplantation tolerance.

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Sabrina Bonde

Full Text Available BACKGROUND: Bone marrow cells induce stable mixed chimerism under appropriate conditioning of the host, mediating the induction of transplantation tolerance. However, their strong immunogenicity precludes routine use in clinical transplantation due to the need for harsh preconditioning and the requirement for toxic immunosuppression to prevent rejection and graft-versus-host disease. Alternatively, embryonic stem (ES cells have emerged as a potential source of less immunogenic hematopoietic progenitor cells (HPCs. Up till now, however, it has been difficult to generate stable hematopoietic cells from ES cells. METHODOLOGY/PRINCIPAL FINDINGS: Here, we derived CD45(+ HPCs from HOXB4-transduced ES cells and showed that they poorly express MHC antigens. This property allowed their long-term engraftment in sublethally irradiated recipients across MHC barriers without the need for immunosuppressive agents. Although donor cells declined in peripheral blood over 2 months, low level chimerism was maintained in the bone marrow of these mice over 100 days. More importantly, chimeric animals were protected from rejection of donor-type cardiac allografts. CONCLUSIONS: Our data show, for the first time, the efficacy of ES-derived CD45(+ HPCs to engraft in allogenic recipients without the use of immunosuppressive agents, there by protecting cardiac allografts from rejection.

The Spleen Is an Ideal Site for Inducing Transplanted Islet Graft Expansion in Mice.

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Takeshi Itoh

Full Text Available Alternative islet transplantation sites have the potential to reduce the marginal number of islets required to ameliorate hyperglycemia in recipients with diabetes. Previously, we reported that T cell leukemia homeobox 1 (Tlx1+ stem cells in the spleen effectively regenerated into insulin-producing cells in the pancreas of non-obese diabetic mice with end-stage disease. Thus, we investigated the spleen as a potential alternative islet transplantation site. Streptozotocin-induced diabetic C57BL/6 mice received syngeneic islets into the portal vein (PV, beneath the kidney capsule (KC, or into the spleen (SP. The marginal number of islets by PV, KC, or SP was 200, 100, and 50, respectively. Some plasma inflammatory cytokine levels in the SP group were significantly lower than those of the PV group after receiving a marginal number of islets, indicating reduced inflammation in the SP group. Insulin contents were increased 280 days after islet transplantation compared with those immediately following transplantation (p<0.05. Additionally, Tlx1-related genes, including Rrm2b and Pla2g2d, were up-regulated, which indicates that islet grafts expanded in the spleen. The spleen is an ideal candidate for an alternative islet transplantation site because of the resulting reduced inflammation and expansion of the islet graft.

Antithymocyte antibody-induced coagulopathy in renal transplant recipients.

Science.gov (United States)

Siparsky, N F; Klein, R; Kushnir, L F; Gallichio, M H; Conti, D J

2013-05-01

Antithymocyte antibody (ATA) remains the most commonly used induction immunosuppressive agent in renal transplantation (RT). To date, few case reports of ATA-induced coagulopathy exist. We performed a single-center, retrospective analysis of renal transplant recipients (RTRs) who underwent RT followed by ATA therapy between 2007 and 2011. The protocol used for deceased donor and unrelated living donor recipient immunosuppression was Thymoglobulin (TMG), methylprednisolone, Cellcept, Prograf, and Rapamune. In related living donor recipients, Simulect (SIM) was substituted for TMG. The international normalized ratio (INR) was routinely checked on days 0 and 2, and thereafter at the discretion of the surgeon. RTRs were transfused packed red blood cells (PRBCs) or fresh frozen plasma (FFP) at the discretion of the surgeon. During the study period, 257 RTs were performed at our institution. The following 18 RTR were excluded: simultaneous kidney and pancreas transplant recipients (4), RTRs on warfarin at the time of admission (2), RTRs who received OKT3 (2), and RTRs with INR ≥ 1.2 at the time of admission (10). Of the remaining 239 RTR, 208 (87%) underwent TMG induction therapy; 31 RTR (13%) underwent SIM induction therapy. The mean INR peaked in both groups on day 4 but was higher in TMG recipients (TMG 1.35, SIM 1.20). FFP was transfused in 65 TMG (31%) and 3 SIM (10%) recipients (P = .01); PRBCs were transfused in 88 TMG (44%) and 6 SIM (19%) recipients (P = .02). No patients returned to the operating room for bleeding complications within 7 days of RT. Patient age, gender, ethnicity, and diabetes status were not statistically significant factors in the development of coagulopathy. TMG administration is associated with coagulopathy. Using an INR screening protocol and an aggressive transfusion protocol, bleeding complications associated with coagulopathy can be avoided in this higher-risk group. Copyright © 2013 Elsevier Inc. All rights reserved.

Treatment of Radiation Induced Biological Changes by Bone Marrow Transplantation

International Nuclear Information System (INIS)

El-Missiry, M.A.; Shehata, G.; Roushdy, H.M; Fayed, Th.A.

1999-01-01

Preventing the propagation of radiation induced oxidative damage has been a subject of considerable investigations. The ultimate goal of the present study is to use bone marrow cells to ameliorate or to treat the radiation sickness. Transplantation of bone marrow cell has shown promising results in the present experimental radiation treatment. In this report, suspension of bone marrow cells was injected into rats 12 h. after exposure to 4.5 Gy whole body gamma irradiation. Significant results were recorded on the successful control of the radiation induced disorders in a number of biochemical parameters including certain enzymatic and nonenzymatic antioxidants (superoxide dismutase and glutathione) and certain parameters related to kidney function including creatinine, urea as well as Atpase Activity in blood serum, urine and kidney tissue

Mixed chimerism to induce tolerance for solid organ transplantation

International Nuclear Information System (INIS)

Wren, S.M.; Nalesnik, M.; Hronakes, M.L.; Oh, E.; Ildstad, S.T.

1991-01-01

Chimerism, or the coexistence of tissue elements from more than one genetically different strain or species in an organism, is the only experimental state that results in the induction of donor-specific transplantation tolerance. Transplantation of a mixture of T-cell-depleted syngeneic (host-type) plus T-cell-depleted allogeneic (donor) bone marrow into a normal adult recipient mouse (A + B----A) results in mixed allogeneic chimerism. Recipient mice exhibit donor-specific transplantation tolerance, yet have full immunocompetence to recognize and respond to third-party transplantation antigens. After complete hematolymphopoietic repopulation at 28 days, animals accept a donor-specific skin graft but reject major histocompatibility complex (MHC) locus-disparate third-party grafts. We now report that permanent graft acceptance can also be achieved when the graft is placed at the time of bone marrow transplantation. Histologically, grafts were viable and had only minimal inflammatory changes. This model may have potential future clinical application for the induction of donor-specific transplantation tolerance

Freshly isolated hepatocyte transplantation in acetaminophen-induced hepatotoxicity model in rats Transplante de hepatócitos recém-isolados em um modelo de hepatotoxicidade induzida por acetaminofeno em ratos

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Daniela Rodrigues

2012-12-01

Full Text Available CONTEXT: Hepatocyte transplantation is an attractive therapeutic modality for liver disease as an alternative for orthotopic liver transplantation. OBJECTIVE: The aim of the current study was to investigate the feasibility of freshly isolated rat hepatocyte transplantation in acetaminophen-induced hepatotoxicity model. METHODS: Hepatocytes were isolated from male Wistar rats and transplanted 24 hours after acetaminophen administration in female recipients. Female rats received either 1x10(7 hepatocytes or phosphate buffered saline through the portal vein or into the spleen and were sacrificed after 48 hours. RESULTS: Alanine aminotransferase levels measured within the experiment did not differ between groups at any time point. Molecular analysis and histology showed presence of hepatocytes in liver of transplanted animals injected either through portal vein or spleen. CONCLUSION: These data demonstrate the feasibility and efficacy of hepatocyte transplantation in the liver or spleen in a mild acetaminophen-induced hepatotoxicity model.CONTEXTO: O transplante de hepatócitos é uma modalidade terapêutica atrativa para doenças hepáticas como alternativa ao transplante hepático ortotópico. OBJETIVO: Investigar a factibilidade do uso de hepatócitos frescos isolados de ratos em um modelo de hepatotoxicidade induzida por paracetamol. MÉTODOS: Hepatócitos foram isolados de ratos Wistar machos e transplantados 24 horas após a administração de paracetamol em receptores fêmeas. As ratas receberam 1x10(7 hepatócitos ou tampão salina fosfato pela veia porta ou no baço e foram sacrificadas após 48 horas. RESULTADOS: Os níveis de alanina aminotransferase medidos durante o experimento não diferiram entre os grupos em nenhum momento. Análises moleculares e histológicas demonstraram a presença de hepatócitos no fígado dos animais transplantados pelo baço ou pela veia porta. CONCLUSÃO: Os dados indicam a factibilidade e eficácia do

Tacrolimus-induced thrombotic microangiopathy in orthotopic liver transplant patients: case series of four patients.

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Nwaba, A; MacQuillan, G; Adams, L A; Garas, G; Delriviere, L; Augustson, B; DeBoer, B; Moody, H; Jeffrey, G P

2013-03-01

Thrombotic microangiopathy (TMA) is a potentially fatal complication in solid organ and bone marrow transplant patients, with reported incidence of 0.5-3% and mortality of about 75%. To emphasise the importance of early diagnosis and prompt commencement of therapy results in improved clinical outcomes. A retrospective study of all patients who underwent orthotopic liver transplantation (OLTX) at the Western Australian Liver Transplantation Service from May 1994 to December 2010 was conducted to identify patients who developed tacrolimus-induced TMA. We identified four patients with tacrolimus-induced TMA post-OLTX, derived from a cohort of 104 patients treated with tacrolimus in our institution. The mean age at diagnosis was 40 years, and the mean time of onset was 63 ± 7.5 weeks after OLTX. The indications for OLTX in the four patients were fulminant hepatic failure in three (Wilson disease, paracetamol overdose and post-partum thrombotic thrombocytopenic purpura) and hepatitis C virus-related cirrhosis. All patients had tacrolimus post-OLTX. At diagnosis, tacrolimus was discontinued in all patients, and three of the four patients underwent plasma exchange and all patients improved clinically. Mean duration of follow up was 15 ± 7.5 months. There was no mortality 6 months post-TMA. Early diagnosis with immediate discontinuation or conversion of calcineurin inhibitors and plasma exchange should be offered to OLTX patients with TMA as it results in good outcomes. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

Transplantation of co-aggregates of Sertoli cells and islet cells into liver without immunosuppression.

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Takemoto, Naohiro; Liu, Xibao; Takii, Kento; Teramura, Yuji; Iwata, Hiroo

2014-02-15

Transplantation of islets of Langerhans (islets) was used to treat insulin-dependent diabetes mellitus. However, islet grafts must be maintained by administration of immunosuppressive drugs, which can lead to complications in the long term. An approach that avoids immunosuppressive drug use is desirable. Co-aggregates of Sertoli cells and islet cells from BALB/c mice that were prepared by the hanging drop method were transplanted into C57BL/6 mouse liver through the portal vein as in human clinical islet transplantation. The core part of the aggregates contained mainly Sertoli cells, and these cells were surrounded by islet cells. The co-aggregates retained the functions of both Sertoli and islet cells. When 800 co-aggregates were transplanted into seven C57BL/6 mice via the portal vein, six of seven recipient mice demonstrated quasi-normoglycemia for more than 100 days. The hanging drop method is suitable for preparing aggregates of Sertoli and islet cells for transplantation. Notably, transplantation of these allogeneic co-aggregates into mice with chemically induced diabetes via the portal vein resulted in long-term graft survival without systemic immunosuppression.

Electron microscopic study of spontaneous and experimentally induced leukemia in IRC mice

International Nuclear Information System (INIS)

Hiraki, S.; Ranadive, K.J.; Dmochowski, L.

1974-01-01

Spontaneous, serially transplanted, and experimentally induced leukemias of ICRC mice were studied by electron microscopy in an attempt to detect the presence of virus particles, if any, and to observe the influence of chemical and hormonal treatment on the presence of these virus particles. The first series of experiments included spontaneous, serially transplanted, and radiation-induced leukemia. The paucity of type C virus particles was quite conspicuous in spontaneous leukemia. Serially transplanted and radiation-accelerated leukemic lesions showed the presence of some type C and intracisternal type A particles. Found in two of these leukemic lesions (thymus and lymphosarcoma), in addition to type C virus particles, were budding and some mature type B virus particles, and numerous intracytoplasmic type A particles. ''Viropexis'' of type B virus particles has been observed in the lymphosarcoma and in a leukemic thymus gland. The second series of experiments included leukemia induced in ovariectomized ICRC mice with 20-methylcholanthrene (MCA), pituitary transplants, and ovarian hormones (estradiol and estradiol-progesterone). In ovariectomized ICRC mice, leukemic lesions induced by MCA or pituitary transplants, or by MCA and pituitary transplants, showed type C virus particles and, in most cases, intracisternal type A particles. In leukemia induced in ovariectomized ICRC mice by MCA and estradiol, numerous intracytoplasmic type A particles were observed but no type C virus particles

Long-term experience of steroid-free pediatric renal transplantation

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Wittenhagen, Per; Thiesson, Helle C; Baudier, François

2014-01-01

Increased focus on the potential negative side effects of steroid usage in pediatric transplantation has led to steroid minimization or steroid-free transplantation. In this study, we report results after complete steroid avoidance in renal transplantation in the period 1994-2009. We evaluate...... in the youngest (renal transplantation is safe and protects against steroid-induced obesity and short stature....... the effects of complete steroid avoidance on allograft function, BMI, and linear growth. The majority of transplanted children were induced with antithymocyte globulin and immunosuppressed with a calcineurin inhibitor and mycophenolate mofetil. Steroids were given only when rejection occurred or due...

Effect of transplantation of olfactory ensheathing cell conditioned medium induced bone marrow stromal cells on rats with spinal cord injury

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Feng, Linjie; Gan, Hongquan; Zhao, Wenguo; Liu, Yingjie

2017-01-01

Spinal cord injury is a serious threat to human health and various techniques have been deployed to ameliorate or cure its effects. Stem cells transplantation is one of the promising methods. The primary aim of the present study was to investigate the effect of the transplantation of olfactory ensheathing cell (OEC) conditioned medium-induced bone marrow stromal cells (BMSCs) on spinal cord injury. Rat spinal cord compression injury animal models were generated, and the rats divided into the following three groups: Group A, (control) Dulbecco's modified Eagle's medium-treated group; group B, normal BMSC-treated group; group C, OEC conditioned medium-induced BMSC-treated group. The animals were sacrificed at 2, 4 and 8 weeks following transplantation for hematoxylin and eosin staining, and fluorescence staining of neurofilament protein, growth associated protein-43 and neuron-specific nuclear protein. The cavity area of the spinal cord injury was significantly reduced at 2 and 4 weeks following transplantation in group C, and a significant difference between the Basso, Beattie and Bresnahan score in group C and groups A and B was observed. Regenerated nerve fibers were observed in groups B and C; however, a greater number of regenerated nerve fibers were observed in group C. BMSCs induced by OEC conditioned medium survived in vivo, significantly reduced the cavity area of spinal cord injury, promoted nerve fiber regeneration following spinal cord injury and facilitated recovery of motor function. The present study demonstrated a novel method to repair spinal cord injury by using induced BMSCs, with satisfactory results. PMID:28656221

Chemical compound-based direct reprogramming for future clinical applications

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Takeda, Yukimasa; Harada, Yoshinori; Yoshikawa, Toshikazu; Dai, Ping

2018-01-01

Recent studies have revealed that a combination of chemical compounds enables direct reprogramming from one somatic cell type into another without the use of transgenes by regulating cellular signaling pathways and epigenetic modifications. The generation of induced pluripotent stem (iPS) cells generally requires virus vector-mediated expression of multiple transcription factors, which might disrupt genomic integrity and proper cell functions. The direct reprogramming is a promising alternative to rapidly prepare different cell types by bypassing the pluripotent state. Because the strategy also depends on forced expression of exogenous lineage-specific transcription factors, the direct reprogramming in a chemical compound-based manner is an ideal approach to further reduce the risk for tumorigenesis. So far, a number of reported research efforts have revealed that combinations of chemical compounds and cell-type specific medium transdifferentiate somatic cells into desired cell types including neuronal cells, glial cells, neural stem cells, brown adipocytes, cardiomyocytes, somatic progenitor cells, and pluripotent stem cells. These desired cells rapidly converted from patient-derived autologous fibroblasts can be applied for their own transplantation therapy to avoid immune rejection. However, complete chemical compound-induced conversions remain challenging particularly in adult human-derived fibroblasts compared with mouse embryonic fibroblasts (MEFs). This review summarizes up-to-date progress in each specific cell type and discusses prospects for future clinical application toward cell transplantation therapy. PMID:29739872

A case of tacrolimus-induced encephalopathy after kidney transplantation

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Myoung Uk Kim

2011-01-01

Full Text Available We present a case of tacrolimus-induced encephalopathy after successful kidney transplantation. An 11-year-old girl presented with sudden onset of neurologic symptoms, hypertension, and psychiatric symptoms, with normal kidney function, after kidney transplantation. The symptoms improved after cessation of tacrolimus. Magnetic resonance imaging (MRI showed acute infarction of the middle cerebral artery (MCA territory in the right frontal lobe. Three days later, she had normal mental function and maintained normal blood pressure with left hemiparesis. Follow-up MRI was performed on D19, showing new infarct lesions at both cerebral hemispheres. Ten days later, MRI showed further improvement, but brain single photon emission computed tomography (SPECT showed mild reduction of uptake in both the anterior cingulate gyrus and the left thalamus. One month after onset of symptoms, angiography showed complete resolution of stenosis. However, presenting as a mild fine motor disability of both hands and mild dysarthria, what had been atrophy at both centrum semiovale at 4 months now showed progression to encephalomalacia. There are two points of interest in this case. First, encephalopathy occurred after administration of tacrolimus and improved after discontinuation of the drug. Second, the development of right-side hemiplegia could not be explained by conventional MRI; but through diffusion tensor imaging (DTI and diffusion tensor tractography (DTT of white matter tract, visualization was possible.

Chemical Basis for Qualitative and Quantitative Differences Between ABO Blood Groups and Subgroups: Implications for Organ Transplantation.

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Jeyakanthan, M; Tao, K; Zou, L; Meloncelli, P J; Lowary, T L; Suzuki, K; Boland, D; Larsen, I; Burch, M; Shaw, N; Beddows, K; Addonizio, L; Zuckerman, W; Afzali, B; Kim, D H; Mengel, M; Shapiro, A M J; West, L J

2015-10-01

Blood group ABH(O) carbohydrate antigens are carried by precursor structures denoted type I-IV chains, creating unique antigen epitopes that may differ in expression between circulating erythrocytes and vascular endothelial cells. Characterization of such differences is invaluable in many clinical settings including transplantation. Monoclonal antibodies were generated and epitope specificities were characterized against chemically synthesized type I-IV ABH and related glycans. Antigen expression was detected on endomyocardial biopsies (n = 50) and spleen (n = 11) by immunohistochemical staining and on erythrocytes by flow cytometry. On vascular endothelial cells of heart and spleen, only type II-based ABH antigens were expressed; type III/IV structures were not detected. Type II-based ABH were expressed on erythrocytes of all blood groups. Group A1 and A2 erythrocytes additionally expressed type III/IV precursors, whereas group B and O erythrocytes did not. Intensity of A/B antigen expression differed among group A1 , A2 , A1 B, A2 B and B erythrocytes. On group A2 erythrocytes, type III H structures were largely un-glycosylated with the terminal "A" sugar α-GalNAc. Together, these studies define qualitative and quantitative differences in ABH antigen expression between erythrocytes and vascular tissues. These expression profiles have important implications that must be considered in clinical settings of ABO-incompatible transplantation when interpreting anti-ABO antibodies measured by hemagglutination assays with reagent erythrocytes. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Hepatic Sinusoidal-obstruction Syndrome and Busulfan-induced Lung Injury in a Post-autologous Stem Cell Transplant Recipient.

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Jain, Richa; Gupta, Kirti; Bhatia, Anmol; Bansal, Arun; Bansal, Deepak

2017-09-15

Veno-occlusive disease of the liver is mostly encountered as a complication of hematopoietic stem cell transplantation with myeloablative regimens with an incidence estimated to be 13.7%. It is clinically characterized by tender hepatomegaly, jaundice, weight gain and ascites. Strong clinical suspicion and an early recognition of clinical signs are essential to establish the diagnosis and institute effective regimen. Another complication of cytotoxic drugs given for cancers, is development of busulfan-induced lung injury. A strong index of suspicion is needed for its diagnosis, especially in setting where opportunistic fungal and viral infections manifest similarly. We illustrate the clinical and autopsy finings in a 2½-year-old boy who received autologous stem-cell transplantation following resection of stage IV neuroblastoma. He subsequently developed both hepatic veno-occlusive disease and busulfan-induced lung injury. The autopsy findings are remarkable for their rarity.

Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

International Nuclear Information System (INIS)

Kamiya, Kenji; Nitta, Yumiko; Gould, M.N.

2000-01-01

The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of 60 Co gamma rays at a dose rate of 26.58±1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

Energy Technology Data Exchange (ETDEWEB)

Kamiya, Kenji; Nitta, Yumiko [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine; Gould, M.N.

2000-07-01

The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of {sup 60} Co gamma rays at a dose rate of 26.58{+-}1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

Insulin-producing Cells from Adult Human Bone Marrow Mesenchymal Stromal Cells Could Control Chemically Induced Diabetes in Dogs: A Preliminary Study.

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Gabr, Mahmoud M; Zakaria, Mahmoud M; Refaie, Ayman F; Ismail, Amani M; Khater, Sherry M; Ashamallah, Sylvia A; Azzam, Maha M; Ghoneim, Mohamed A

2018-01-01

Ten mongrel dogs were used in this study. Diabetes was chemically induced in 7 dogs, and 3 dogs served as normal controls. For each diabetic dog, 5 million human bone marrow-derived mesenchymal stem cells/kg were differentiated to form insulin-producing cells using a trichostatin-based protocol. Cells were then loaded in 2 TheraCyte capsules which were transplanted under the rectus sheath. One dog died 4 d postoperatively from pneumonia. Six dogs were followed up with for 6 to 18 mo. Euglycemia was achieved in 4 dogs. Their glucose tolerance curves exhibited a normal pattern demonstrating that the encapsulated cells were glucose sensitive and insulin responsive. In the remaining 2 dogs, the fasting blood sugar levels were reduced but did not reach normal values. The sera of all transplanted dogs contained human insulin and C-peptide with a negligible amount of canine insulin. Removal of the transplanted capsules was followed by prompt return of diabetes. Intracytoplasmic insulin granules were seen by immunofluorescence in cells from the harvested capsules. Furthermore, all pancreatic endocrine genes were expressed. This study demonstrated that the TheraCyte capsule or a similar device can provide adequate immunoisolation, an important issue when stem cells are considered for the treatment of type 1 diabetes mellitus.

Tetanus after allogeneic bone-marrow transplantation

International Nuclear Information System (INIS)

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

1982-01-01

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

Experimentally induced tumors used for angiographic estimation of embolisation and cytostatic treatment

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Strecker, E P; Kraus, W; Fiebig, H H; Kauffmann, G; Hauenstein, K H

1982-02-01

In 12 rats tumors have been induced chemically by intraperitoneal application of dimethylnitrosamine. This method is simple and reliable and the effect of tumor embolization can be followed easily. Thymus aplastic nude mice with transplanted human tumors deserve strict care. Tumor microangiograms of 48 animals demonstrate a close similarity with angiograms of corresponding human tumors. The vascular pattern does not alterate after several transplantations, after cytostatic therapy a slight hypervascularisation developes.

Mechanism of immune tolerance induced by donor derived immature dendritic cells in rat high-risk corneal transplantation

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Xu-Dong Zhao

2013-06-01

Full Text Available AIM: To study the role of immature dendritic cells (imDCs on immune tolerance in rat penetrating keratoplasty (PKP in high-risk eyes and to investigate the mechanism of immune hyporesponsiveness induced by donor-derived imDCs. METHODS: Seventy-five SD rats (recipient and 39 Wistar rats (donor were randomly divided into 3 groups: control, imDC and mature dendritic cell (mDC group respectively. Using a model of orthotopic corneal transplantation in which allografts were placed in neovascularized high-risk eyes of recipient rat. Corneal neovascularization was induced by alkaline burn in the central cornea of recipient rat. Recipients in imDC group or mDC group were injected donor bone marrow-derived imDCs or mDCs of 1×106 respectively 1 week before corneal transplantation via tail vein. Control rat received the same volume of PBS. In each group, 16 recipients were kept for determination of survival time and other 9 recipients were executed on day 3, 7 and 14 after transplantation. Cornea was harvested for hematoxylin-eosin staining and acute rejection evaluation, Western blot was used to detect the expression level of Foxp3. RESULTS: The mean survival time of imDC group was significantly longer than that of control and mDC groups (all P<0.05. The expression level of Foxp3 on CD4+CD25+T cells of imDC group (2.24±0.18 was significantly higher than that in the control (1.68±0.09 and mDC groups (1.46±0.13 (all P<0.05. CONCLUSION: Donor-derived imDC is an effective treatment in inducing immune hyporesponsiveness in rat PKP. The mechanism of immune tolerance induced by imDC might be inhibit T lymphocytes responsiveness by regulatory T cells.

Stem-cell-activated organ following ultrasound exposure: better transplant option for organ transplantation.

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Wang, Sen; Li, Yu; Ji, Ying-Chang; Lin, Chang-Min; Man, Cheng; Zheng, Xiao-Xuan

2010-01-01

Although doctors try their best to protect transplants during surgery, there remain great challenges for the higher survival rate and less rejection of transplants after organ transplantation. Growing evidence indicates that the stem cells could function after injury rather than aging, implying that suitable injury may activate the stem cells of damaged organs. Furthermore, it has been revealed that stem cells can be used to induce tolerance in transplantation and the ultrasound has great biological effects on organs. Basing on these facts, we hypothesize that the stem cells within the transplants can be activated by ultrasound with high-frequency and medium-intensity. Therefore, the stem-cell-activated organs (SCAO) can be derived, and the SCAO will be better transplant option for organ transplantation. We postulate the ultrasound can change the molecular activity and/or quantity of the stem cells, the membrane permeability, the cell-cell junctions, and their surrounding microenvironments. As a result, the stem cells are activated, and the SCAO will acquire more regenerative capacity and less rejection. In the paper, we also discuss the process, methods and models for verifying the theory, and the consequences. We believe the theory may provide a practical method for the clinical application of the ultrasound and stem cells in organ transplantation.

Effect of long-term calcitonin administration on steroid-induced osteoporosis after cardiac transplantation.

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Kapetanakis, Emmanouil I; Antonopoulos, Athanassios S; Antoniou, Theofani A; Theodoraki, Kassiani A; Zarkalis, Dimitrios A; Sfirakis, Peter D; Chilidou, Despina A; Alivizatos, Peter A

2005-05-01

Early, rapid bone loss and fractures after cardiac transplantation are well-documented complications of steroid administration; therefore, we undertook this study on the effects of long-term calcitonin on steroid-induced osteoporosis. Twenty-three heart transplant recipients on maintenance immunosuppression with cyclosporine, mycophenolate mofetil and prednisone were retrospectively studied. All patients received long-term prophylactic treatment with elemental calcium and vitamin D. Twelve (52.2%) patients also received long-term intranasal salmon calcitonin, whereas 11 (47.8%) received none. Bone mineral density and vertebral fractures were assessed at yearly intervals. Statistical comparisons between each group's bone loss during the first year and in the early (1 to 3 years), intermediate (4 to 6 years) and late (7+ years) post-transplantation periods were done. Lumbar spine bone loss was significant during the early follow-up period in the group not receiving calcitonin (0.744 +/- 0.114 g/cm(2) vs 0.978 +/- 0.094 g/cm(2) [p = 0.002]). The calcitonin group showed bone mineral density (BMD) levels within normal average values throughout the study period. BMD increased in the no-calcitonin group during the intermediate (4 to 6 years) and late (7+ years) follow-up periods, with values approaching normal average and no significant difference between the 2 groups (0.988 +/- 0.184 g/cm(2) vs 0.982 +/- 0.088 g/cm(2) [p = 0.944] and 0.89 +/- 0.09 g/cm(2) vs 1.048 +/- 0.239 g/cm(2) [p = 0.474], respectively). Prophylactic treatment with intranasal salmon calcitonin prevents rapid bone loss associated with high-dose steroids early after cardiac transplantation. Long-term administration does not seem warranted in re-establishing BMD.

Limited transplantation of antigen-expressing hematopoietic stem cells induces long-lasting cytotoxic T cell responses.

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Warren L Denning

2011-02-01

Full Text Available Harnessing the ability of cytotoxic T lymphocytes (CTLs to recognize and eradicate tumor or pathogen-infected cells is a critical goal of modern immune-based therapies. Although multiple immunization strategies efficiently induce high levels of antigen-specific CTLs, the initial increase is typically followed by a rapid contraction phase resulting in a sharp decline in the frequency of functional CTLs. We describe a novel approach to immunotherapy based on a transplantation of low numbers of antigen-expressing hematopoietic stem cells (HSCs following nonmyeloablative or partially myeloablative conditioning. Continuous antigen presentation by a limited number of differentiated transgenic hematopoietic cells results in an induction and prolonged maintenance of fully functional effector T cell responses in a mouse model. Recipient animals display high levels of antigen-specific CTLs four months following transplantation in contrast to dendritic cell-immunized animals in which the response typically declines at 4-6 weeks post-immunization. Majority of HSC-induced antigen-specific CD8+ T cells display central memory phenotype, efficiently kill target cells in vivo, and protect recipients against tumor growth in a preventive setting. Furthermore, we confirm previously published observation that high level engraftment of antigen-expressing HSCs following myeloablative conditioning results in tolerance and an absence of specific cytotoxic activity in vivo. In conclusion, the data presented here supports potential application of immunization by limited transplantation of antigen-expressing HSCs for the prevention and treatment of cancer and therapeutic immunization of chronic infectious diseases such as HIV-1/AIDS.

Genetic disassociation of autoimmunity and resistance to costimulation blockade-induced transplantation tolerance in nonobese diabetic mice.

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Pearson, Todd; Markees, Thomas G; Serreze, David V; Pierce, Melissa A; Marron, Michele P; Wicker, Linda S; Peterson, Laurence B; Shultz, Leonard D; Mordes, John P; Rossini, Aldo A; Greiner, Dale L

2003-07-01

Curing type 1 diabetes by islet transplantation requires overcoming both allorejection and recurrent autoimmunity. This has been achieved with systemic immunosuppression, but tolerance induction would be preferable. Most islet allotransplant tolerance induction protocols have been tested in nonobese diabetic (NOD) mice, and most have failed. Failure has been attributed to the underlying autoimmunity, assuming that autoimmunity and resistance to transplantation tolerance have a common basis. Out of concern that NOD biology could be misleading in this regard, we tested the hypothesis that autoimmunity and resistance to transplantation tolerance in NOD mice are distinct phenotypes. Unexpectedly, we observed that (NOD x C57BL/6)F(1) mice, which have no diabetes, nonetheless resist prolongation of skin allografts by costimulation blockade. Further analyses revealed that the F(1) mice shared the dendritic cell maturation defects and abnormal CD4(+) T cell responses of the NOD but had lost its defects in macrophage maturation and NK cell activity. We conclude that resistance to allograft tolerance induction in the NOD mouse is not a direct consequence of overt autoimmunity and that autoimmunity and resistance to costimulation blockade-induced transplantation tolerance phenotypes in NOD mice can be dissociated genetically. The outcomes of tolerance induction protocols tested in NOD mice may not accurately predict outcomes in human subjects.

Female qualities in males: vitellogenin synthesis induced by ovary transplants into the male silkworm, Bombyx mori.

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Yang, Congwen; Lin, Ying; Shen, Guanwang; Chen, Enxiang; Wang, Yanxia; Luo, Juan; Zhang, Haiyan; Xing, Runmiao; Xia, Qingyou

2014-10-10

Female qualities in males are common in vertebrates but have not been extensively reported in insects. Vitellogenin (Vg) is highly expressed in the female fat body and is generally required for the formation of yolk proteins in the insect egg. Vg upregulation is generally regarded as a female quality in female oviparous animals. In this study, we found that Bombyx mori Vg (BmVg) is especially highly expressed in the female pupa. Downregulation of the BmVg gene in the female pupa by RNA interference (RNAi) interfered with egg formation and embryonic development, showing the importance of BmVg in these processes. So, we used BmVg as a biomarker for female qualities in the silkworm. Hematoxylin-eosin staining and immunofluorescence histochemistry showed that ovary transplants induced BmVg synthesis in the male pupa fat body. Ovaries transplanted into male silkworms produced only a few eggs with deformed yolk granules. These results suggested that the amount of BmVg in the male silkworm was insufficient for eggs to undergo complete embryonic development. After 17-beta-estradiol was used to treat male pupae and male pupal fat bodies, BmVg was upregulated in vivo and in vitro. These findings indicated that the male silkworm has innate female qualities that were induced by a transplanted ovary and 17β-estradiol. However, in silkworms, female qualities in males are not as complete as in females. Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical-induced allergy and autoimmunity

NARCIS (Netherlands)

Wulferink, Marty Bernardus Franciscus

2001-01-01

This thesis aims towards a better understanding of the mechanisms that lead to chemical-induced adverse immune effects. We focussed thereby on the initial induction stage of the immune reaction that consists of three major steps: (i) formation of neoantigen, (ii) processing and presentation of the

Surface chemical reactions induced by molecules electronically-excited in the gas

DEFF Research Database (Denmark)

Petrunin, Victor V.

2011-01-01

and alignment are taking place, guiding all the molecules towards the intersections with the ground state PES, where transitions to the ground state PES will occur with minimum energy dissipation. The accumulated kinetic energy may be used to overcome the chemical reaction barrier. While recombination chemical...... be readily produced. Products of chemical adsorption and/or chemical reactions induced within adsorbates are aggregated on the surface and observed by light scattering. We will demonstrate how pressure and spectral dependencies of the chemical outcomes, polarization of the light and interference of two laser...... beams inducing the reaction can be used to distinguish the new process we try to investigate from chemical reactions induced by photoexcitation within adsorbed molecules and/or gas phase photolysis....

Expression of hypoxia-inducible factor-1α and hepatocyte growth factor in development of fibrosis in the transplanted kidney

DEFF Research Database (Denmark)

Kellenberger, Terese; Marcussen, Niels; Nyengaard, Jens Randel

2014-01-01

Late renal graft loss is associated with interstitial fibrosis. Hypoxia-inducible factor-1α (HIF-1α) is thought to facilitate fibrosis through interaction with TGF-β1, while hepatocyte growth factor (HGF) may act antifibrotic in the kidney allograft. The aim of this study was to investigate...... transplantation, but an inverse significant correlation between the HGF expression and the fibrosis score 1 year after transplantation was shown. Even when adjusting for human leucocyte antigen mismatches, there was a significant relationship between fibrosis and HGF expression. Graft survival...... was not significantly correlated to HIF-1α or HGF at 1 year, although the trend was towards better graft survival with high HGF. HGF may have antifibrotic effects in human renal transplants. (Central.Denmark.Region.Committee number: 1-10-72-318-13)....

Acute pancreatitis induced by mycophenolate mofetil in a kidney transplant patient

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Einollahi Behzad

2015-04-01

Full Text Available Acute pancreatitis is a rare life-threatening complication in patients after kidney transplantation. Here we described a 56-year-old man who had received a living related kidney transplant for an end-stage renal disease. In his regular follow-up, his serum creatinine was gradually increased and he underwent an allograft biopsy, which revealed an interstitial nephritis/tubular atrophy grade II. Mycophenolate mofetil (MMF was prescribed to control chronic allograft nephropathy. He presented with complaints of severe abdominal pain, vomiting, loss of appetite and fever requiring hospital admission twelve days later. Acute pancreatitis was diagnosed on the basis of laboratory data and imaging findings during hospital admission. There was no history of alcohol consumption in our patient. Unfortunately he died one week later and autopsy findings demonstrated acute necrotizing pancreatitis. The bladder drainage of this patients was normal. Laboratory findings in this patient did not endorse infections and other possibilities regarding the etiology of acute pancreatitis in this patient. Therefore, we concluded that acute pancreatitis in near the patient was induced by drugs and basis on our evidence, MMF is the most important suspect. This study suggests that acute pancreatitis can be considered as a side effect of MMF.

Disparate roles of zinc in chemical hypoxia-induced neuronal death

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Sujeong eKim

2015-01-01

Full Text Available Accumulating evidence has provided a causative role of zinc (Zn2+ in neuronal death following ischemic brain injury. Using a hypoxia model of primary cultured cortical neurons with hypoxia-inducing chemicals, cobalt chloride (1 mM CoCl2, deferoxamine (3 mM DFX, and sodium azide (2 mM NaN3, we evaluated whether Zn2+ is involved in hypoxic neuronal death. The hypoxic chemicals rapidly elicited intracellular Zn2+ release/accumulation in viable neurons. The immediate addition of the Zn2+ chelator, CaEDTA or N,N,N’N’-tetrakis-(2-pyridylmethyl ethylenediamine (TPEN, prevented the intracellular Zn2+ load and CoCl2-induced neuronal death, but neither 3-hour-later Zn2+ chelation nor a non-Zn2+ chelator ZnEDTA (1 mM demonstrated any effects. However, neither CaEDTA nor TPEN rescued neurons from cell death following DFX- or NaN3-induced hypoxia, whereas ZnEDTA rendered them resistant to the hypoxic injury. Instead, the immediate supplementation of Zn2+ rescued DFX- and NaN3-induced neuronal death. The iron supplementation also afforded neuroprotection against DFX-induced hypoxic injury. Thus, although intracellular Zn2+ release/accumulation is common during chemical hypoxia, Zn2+ might differently influence the subsequent fate of neurons; it appears to play a neurotoxic or neuroprotective role depending on the hypoxic chemical used. These results also suggest that different hypoxic chemicals may induce neuronal death via distinct mechanisms.

Disparate roles of zinc in chemical hypoxia-induced neuronal death.

Science.gov (United States)

Kim, Sujeong; Seo, Jung-Woo; Oh, Shin Bi; Kim, So Hee; Kim, Inki; Suh, Nayoung; Lee, Joo-Yong

2015-01-01

Accumulating evidence has provided a causative role of zinc (Zn(2+)) in neuronal death following ischemic brain injury. Using a hypoxia model of primary cultured cortical neurons with hypoxia-inducing chemicals, cobalt chloride (1 mM CoCl2), deferoxamine (3 mM DFX), and sodium azide (2 mM NaN3), we evaluated whether Zn(2+) is involved in hypoxic neuronal death. The hypoxic chemicals rapidly elicited intracellular Zn(2+) release/accumulation in viable neurons. The immediate addition of the Zn(2+) chelator, CaEDTA or N,N,N'N'-tetrakis-(2-pyridylmethyl) ethylenediamine (TPEN), prevented the intracellular Zn(2+) load and CoCl2-induced neuronal death, but neither 3 hour later Zn(2+) chelation nor a non-Zn(2+) chelator ZnEDTA (1 mM) demonstrated any effects. However, neither CaEDTA nor TPEN rescued neurons from cell death following DFX- or NaN3-induced hypoxia, whereas ZnEDTA rendered them resistant to the hypoxic injury. Instead, the immediate supplementation of Zn(2+) rescued DFX- and NaN3-induced neuronal death. The iron supplementation also afforded neuroprotection against DFX-induced hypoxic injury. Thus, although intracellular Zn(2+) release/accumulation is common during chemical hypoxia, Zn(2+) might differently influence the subsequent fate of neurons; it appears to play a neurotoxic or neuroprotective role depending on the hypoxic chemical used. These results also suggest that different hypoxic chemicals may induce neuronal death via distinct mechanisms.

In Utero Hepatocellular Transplantation in Rats

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Emma Muñoz-Sáez

2013-01-01

Full Text Available This work represents a step forward in the experimental design of an in utero hepatocellular transplantation model in rats. We focused on the enrichment optimization of isolated fetal hepatocytes suspension, arranging the surgery methodology of in utero transplantation, monitoring the biodistribution of the transplanted hepatocytes, and assessing the success of the transplants. Rat fetuses have been transplanted at the 17th embryonic day (ED17 with fetal hepatocytes isolated from rats at the end of pregnancy (ED21. We assessed possible differences between lymphocyte population, CD4 positive, CD8 positive, double-positive T-cells, and anti-inflammatory cytokines interleukins 4 and 10 (IL4 and IL10 as well. Cellular viability reached the rates of 90–95%. Transplanted groups had a limited success. Transplanted hepatocytes were not able to pass through the hematoplacental barrier. The hepatocytes injected were primarily located in the liver. There was an upward trend in the whole amount of T CD4 and T CD8 cells. There was an increased IL4 in the transplanted groups observed in the pregnant rats. The possibility to induce tolerance in fetuses with a hepatocyte transplant in utero could be a key point to avoid the immunosuppression treatments which must be undergone by transplanted patients.

Mixed chemical-induced oxidative stress in occupational exposure ...

African Journals Online (AJOL)

Mixed chemical-induced oxidative stress in occupational exposure in Nigerians. JI Anetor, SA Yaqub, GO Anetor, AC Nsonwu, FAA Adeniyi, S Fukushima. Abstract. Exposure to single chemicals and associated disorders in occupational environments has received significant attention. Understanding these events holds ...

Nutritional Therapy in Liver Transplantation

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Ahmed Hammad

2017-10-01

Full Text Available Protein-energy malnourishment is commonly encountered in patients with end-stage liver disease who undergo liver transplantation. Malnutrition may further increase morbidity, mortality and costs in the post-transplantation setting. The importance of carefully assessing the nutritional status during the work-up of patients who are candidates for liver replacement is widely recognized. The metabolic abnormalities induced by liver failure render the conventional assessment of nutritional status to be challenging. Preoperative loss of skeletal muscle mass, namely, sarcopenia, has a significant detrimental impact on post-transplant outcomes. It is essential to provide sufficient nutritional support during all phases of liver transplantation. Oral nutrition is preferred, but tube enteral nutrition may be required to provide the needed energy intake. Herein, the latest currently employed perioperative nutritional interventions in liver transplant recipients are thoroughly illustrated including synbiotics, micronutrients, branched-chain amino acid supplementation, immunonutrition formulas, fluid and electrolyte balance, the offering of nocturnal meals, dietary counselling, exercise and rehabilitation.

Confusion and Agitation after a Recent Kidney Transplantation

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Hussein Magdi

2008-01-01

Full Text Available A 51-year-old man, who received a living related transplant from his wife and anti-thymocyte globulin (ATG as induction therapy, developed delayed graft function after transplantation. One day after he received an i.v. dose of ganciclovir, the patient developed hallucinations, confusion and agitation, which worsened the following day. CT-scan of the brain and cerebrospinal fluid were unremarkable. Ganciclovir-induced encepha-lopathy was considered the most likely reason for the patient′s neurological condition, since he recovered completely a few days after discontinuation of this drug. Since anti-CMV prophylactic treatment is now widely used after transplantation, a high index of suspicion is required to diagnose ganciclovir (or acyclovir induced neurotoxicity.

Liver transplantation at Red Cross War Memorial Children's Hospital ...

African Journals Online (AJOL)

The liver transplant programme for infants and children at Red Cross War Memorial ... Four combined liver/kidney transplants have been performed. ... was complicated by chronic rejection (1) and TB-drug-induced subfulminant liver failure (1).

Directly auto-transplanted mesenchymal stem cells induce bone formation in a ceramic bone substitute in an ectopic sheep model.

Science.gov (United States)

Boos, Anja M; Loew, Johanna S; Deschler, Gloria; Arkudas, Andreas; Bleiziffer, Oliver; Gulle, Heinz; Dragu, Adrian; Kneser, Ulrich; Horch, Raymund E; Beier, Justus P

2011-06-01

Bone tissue engineering approaches increasingly focus on the use of mesenchymal stem cells (MSC). In most animal transplantation models MSC are isolated and expanded before auto cell transplantation which might be critical for clinical application in the future. Hence this study compares the potential of directly auto-transplanted versus in vitro expanded MSC with or without bone morphogenetic protein-2 (BMP-2) to induce bone formation in a large volume ceramic bone substitute in the sheep model. MSC were isolated from bone marrow aspirates and directly auto-transplanted or expanded in vitro and characterized using fluorescence activated cell sorting (FACS) and RT-PCR analysis before subcutaneous implantation in combination with BMP-2 and β-tricalcium phosphate/hydroxyapatite (β-TCP/HA) granules. Constructs were explanted after 1 to 12 weeks followed by histological and RT-PCR evaluation. Sheep MSC were CD29(+), CD44(+) and CD166(+) after selection by Ficoll gradient centrifugation, while directly auto-transplanted MSC-populations expressed CD29 and CD166 at lower levels. Both, directly auto-transplanted and expanded MSC, were constantly proliferating and had a decreasing apoptosis over time in vivo. Directly auto-transplanted MSC led to de novo bone formation in a heterotopic sheep model using a β-TCP/HA matrix comparable to the application of 60 μg/ml BMP-2 only or implantation of expanded MSC. Bone matrix proteins were up-regulated in constructs following direct auto-transplantation and in expanded MSC as well as in BMP-2 constructs. Up-regulation was detected using immunohistology methods and RT-PCR. Dense vascularization was demonstrated by CD31 immunohistology staining in all three groups. Ectopic bone could be generated using directly auto-transplanted or expanded MSC with β-TCP/HA granules alone. Hence BMP-2 stimulation might become dispensable in the future, thus providing an attractive, clinically feasible approach to bone tissue engineering. © 2011

[Transplantation-associated infections].

Science.gov (United States)

Würzner, R

2004-01-01

Transplantation-associated infections are caused by an infected transplanted organ or the endogenic or exogenic environment of the recipient in a state of induced immunodeficiency. The best therapy would be to reconstitute the immunodeficiency, but this is usually impossible as it endangers the transplanted organ. Thus, a specific, standardised anti-infectious therapy is needed even in the absence of clearly identified micro-organisms [bacteria (in two thirds gram-positive rods), parasites (in central Europe predominantly Toxoplasma), fungi (especially Candida spp. or Aspergillus spp.) or viruses (such as Parvovirus B19 and Cytomegalovirus)]. Origins of infection (e.g., hygiene), types of infection (e.g., reactivation), typical localisations, diagnostic tools (e.g., blood cultures, antigenic tests, PCR, CT, advantages and disadvantages of antibody assays) and possible therapies are briefly discussed. The take home messages are to avoid economy measures in microbial diagnostics and to use CMV-seronegative donors whenever possible.

Imaging findings in a child with calcineurin inhibitor-induced pain syndrome after bone marrow transplant for beta thalassemia major

Energy Technology Data Exchange (ETDEWEB)

Ayyala, Rama S.; Arnold, Staci D.; Bhatia, Monica; Dastgir, Jahannaz [Columbia University Medical Center, Morgan Stanley Children' s Hospital, Department of Radiology, New York, NY (United States)

2016-10-15

Calcineurin inhibitor-induced pain syndrome is an entity recognized in patients on immunosuppressive therapy after transplantation. Diagnosis is characterized by onset of pain beginning in the setting of an elevated calcineurin-inhibitor trough level. Reducing the medication dose relieves symptoms. Imaging findings can be nonspecific, including bone marrow edema and periosteal reaction. We present the unique case of calcineurin inhibitor-induced pain syndrome in a child and review the imaging findings. (orig.)

Imaging findings in a child with calcineurin inhibitor-induced pain syndrome after bone marrow transplant for beta thalassemia major

International Nuclear Information System (INIS)

Ayyala, Rama S.; Arnold, Staci D.; Bhatia, Monica; Dastgir, Jahannaz

2016-01-01

Calcineurin inhibitor-induced pain syndrome is an entity recognized in patients on immunosuppressive therapy after transplantation. Diagnosis is characterized by onset of pain beginning in the setting of an elevated calcineurin-inhibitor trough level. Reducing the medication dose relieves symptoms. Imaging findings can be nonspecific, including bone marrow edema and periosteal reaction. We present the unique case of calcineurin inhibitor-induced pain syndrome in a child and review the imaging findings. (orig.)

Autologous fat transplantation for depressed linear scleroderma-induced facial atrophic scars.

Science.gov (United States)

Roh, Mi Ryung; Jung, Jin Young; Chung, Kee Yang

2008-12-01

Facial linear scleroderma results in depressed atrophic scars. Autologous fat transplantation has been widely used, and fat appears to be an ideal material for filling depressed atrophic scars and contour deformities, but long-term results for autologous fat transplantation are controversial. To review the short- and long-term results of 20 patients who underwent multiple autologous fat transplantations for depressed atrophic scar correction. Twenty patients with clinically inactive facial linear scleroderma were included. They received at least two transplantations and had a 12-month follow-up evaluation. On the forehead, 51% to 75% improvement (average grading scale: 2.4) was achieved when observed at least 12 months after the last treatment. For the chin, correction was poor (average grading scale: 0.7) with less than 25% improvement. The infraorbital area showed fair correction, but the nose showed poor correction. Two of three patients with scalp reduction surgery showed excellent results, showing only slight scar widening. Autologous fat transplantation is an effective method for long-term correction of depressed atrophic scars left by linear scleroderma on the forehead but is less effective for corrections on the nose, infraorbital area, and chin.

Preclinical Studies of Induced Pluripotent Stem Cell-Derived Astrocyte Transplantation in ALS

Science.gov (United States)

2012-10-01

Pluripotent Stem Cell -Derived Astrocyte Transplantation in ALS PRINCIPAL INVESTIGATOR: Nicholas J. Maragakis, M.D...Pluripotent Stem Cell -Derived Astrocyte Transplantation in ALS 5b. GRANT NUMBER W81XWH-10-1-0520 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...into astrocytes following transplantation. 15. SUBJECT TERMS Stem Cells , iPS cells, astrocytes, familial ALS 16. SECURITY CLASSIFICATION OF

Association Between GLCCI1 Promoter Polymorphism (Rs37972 and Post-Transplant Hypertension in Renal Transplant Recipients

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Aki Mafune Hamada

2017-12-01

Full Text Available Background/Aims: Post-transplant hypertension is highly prevalent in renal transplant recipients and is a risk factor for graft loss, cardiovascular disease and death. Glucocorticoid is used to prevent rejection, but simultaneously increases the risk of post-transplant hypertension. The glucocorticoid-induced transcript 1 (GLCCI1 promoter polymorphism (rs37972 has been reported to be associated with response to glucocorticoid therapy in asthma. We therefore examined the association between GLCCI1 promoter polymorphism and post-transplant hypertension in renal transplant recipients. Methods: We conducted a retrospective cohort study of renal transplantation at a single university hospital from October 2003 to January 2014. Fifty consecutive adult recipients were analyzed, with clinical data retrieved from a prospectively collected database. Genotyping was carried out using genomic DNA derived from recipient’s blood. GLCCI1 immunoreactivity in vascular endothelial cells was quantitatively analyzed by immunohistochemical staining of recipients’ native kidney biopsy-specimens. The primary outcome measure was post-transplant hypertension. Results: Post-transplant hypertension was observed in 14/17 (82% of recipients with CC, 18/20 (90% with CT, and 2/13 (15% with TT genotype. CC/CT genotype was significantly associated with post-transplant hypertension, even after adjustment for covariates (odds ratio, 10.6; 95% confidence intervals, 1.32 to 85.8; P = 0.026. In addition, we observed that GLCCI1 immunoreactivity in arteriolar endothelial cells was higher in kidney specimens obtained from recipients with a CC/CT genotype than a TT genotype (P = 0.021. Conclusion: GLCCI1 promoter polymorphism rs37972 may be associated with post-transplant hypertension.

Etanercept blocks inflammatory responses orchestrated by TNF-α to promote transplanted cell engraftment and proliferation in rat liver

Science.gov (United States)

Viswanathan, Preeti; Kapoor, Sorabh; Kumaran, Vinay; Joseph, Brigid; Gupta, Sanjeev

2014-01-01

Engraftment of transplanted cells is critical for liver-directed cell therapy but most transplanted cells are rapidly cleared from liver sinusoids by proinflammatory cytokines/chemokines/receptors after activation of neutrophils or Kupffer cells. To define whether TNF-α served roles in cell-transplantation-induced hepatic inflammation, we used TNF-α antagonist, etanercept, for studies in syngeneic rat hepatocyte transplantation systems. After cell transplantation, multiple cytokines/chemokines/receptors were overexpressed, whereas etanercept prior to cell transplantation essentially normalized these responses. Moreover, ETN downregulated cell transplantation-induced intrahepatic release of secretory cytokines, such as high mobility group box 1. These effects of etanercept decreased cell transplantation-induced activation of neutrophils but not of Kupffer cells. Transplanted cell engraftment improved by several-fold in etanercept-treated animals. These gains in cell engraftment were repeatedly realized after pretreatment of animals with etanercept before multiple cell transplantation sessions. Transplanted cell numbers did not change over time indicating absence of cell proliferation after etanercept alone. By contrast, in animals preconditioned with retrorsine and partial hepatectomy, cell transplantation after etanercept pretreatment significantly accelerated liver repopulation compared with control rats. We concluded that TNF-α played a major role in orchestrating cell transplantation-induced inflammation through regulation of multiple cytokines/chemokines/receptor expression. As TNF-α antagonism by etanercept decreased transplanted cell clearance, improved cell engraftment and accelerated liver repopulation, this pharmacological approach to control hepatic inflammation will help optimize clinical strategies for liver cell therapy. PMID:24844924

A survey of chemicals inducing lipid peroxidation in biological systems.

Science.gov (United States)

Kappus, H

1987-01-01

A great number of drugs and chemicals are reviewed which have been shown to stimulate lipid peroxidation in any biological system. The underlying mechanisms, as far as known, are also dealt with. Lipid peroxidation induced by iron ions, organic hydroperoxides, halogenated hydrocarbons, redox cycling drugs, glutathione depleting chemicals, ethanol, heavy metals, ozone, nitrogen dioxide and a number of miscellaneous compounds, e.g. hydrazines, pesticides, antibiotics, are mentioned. It is shown that lipid peroxidation is stimulated by many of these compounds. However, quantitative estimates cannot be given yet and it is still impossible to judge the biological relevance of chemical-induced lipid peroxidation.

Long-Term GABA Administration Induces Alpha Cell-Mediated Beta-like Cell Neogenesis

DEFF Research Database (Denmark)

Ben-Othman, Nouha; Vieira, Andhira; Courtney, Monica

2017-01-01

, these neo-generated β-like cells are functional and can repeatedly reverse chemically induced diabetes in vivo. Similarly, the treatment of transplanted human islets with GABA results in a loss of α cells and a concomitant increase in β-like cell counts, suggestive of α-to-β-like cell conversion processes...

Alloreactive regulatory T cells allow the generation of mixed chimerism and transplant tolerance

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Paulina eRuiz

2015-11-01

Full Text Available The induction of donor-specific transplant tolerance is one of the main goals of modern immunology. Establishment of a mixed chimerism state in the transplant recipient has proven to be a suitable strategy for the induction of long-term allograft tolerance; however, current experimental recipient preconditioning protocols have many side effects, and are not feasible for use in future therapies. In order to improve the current mixed chimerism induction protocols, we developed a non-myeloablative bone-marrow transplant protocol using retinoic acid induced alloantigen-specific Tregs, clinically available immunosuppressive drugs and lower doses of irradiation. We demonstrate that retinoic acid induced alloantigen-specific Tregs in addition to a non-myeloablative bone-marrow transplant protocol generates stable mixed chimerism and induce tolerance to allogeneic secondary skin allografts in mice. Therefore, the establishment of mixed chimerism through the use of donor-specific Tregs rather than non-specific immunosuppression could have a potential use in organ transplantation.

Time-resolved resonance fluorescence spectroscopy for study of chemical reactions in laser-induced plasmas.

Science.gov (United States)

Liu, Lei; Deng, Leimin; Fan, Lisha; Huang, Xi; Lu, Yao; Shen, Xiaokang; Jiang, Lan; Silvain, Jean-François; Lu, Yongfeng

2017-10-30

Identification of chemical intermediates and study of chemical reaction pathways and mechanisms in laser-induced plasmas are important for laser-ablated applications. Laser-induced breakdown spectroscopy (LIBS), as a promising spectroscopic technique, is efficient for elemental analyses but can only provide limited information about chemical products in laser-induced plasmas. In this work, time-resolved resonance fluorescence spectroscopy was studied as a promising tool for the study of chemical reactions in laser-induced plasmas. Resonance fluorescence excitation of diatomic aluminum monoxide (AlO) and triatomic dialuminum monoxide (Al 2 O) was used to identify these chemical intermediates. Time-resolved fluorescence spectra of AlO and Al 2 O were used to observe the temporal evolution in laser-induced Al plasmas and to study their formation in the Al-O 2 chemistry in air.

Transplantation of bone marrow-derived mesenchymal stem cells rescues partially rachitic phenotypes induced by 1,25-Dihydroxyvitamin D deficiency in mice

OpenAIRE

Zhang, Zengli; Yin, Shaomeng; Xue, Xian; Ji, Ji; Tong, Jian; Goltzman, David; Miao, Dengshun

2016-01-01

To determine whether the transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) can improve the 1,25(OH)2D deficiency-induced rachitic phenotype, 2×106 BM-MSCs from wild-type mice or vehicle were transplanted by tail vein injection into mice deficient in 1,25(OH)2D due to targeted deletion of 1α(OH)ase (1α(OH)ase-/-). Our results show that 1α(OH)ase mRNA was expressed in the BM-MSCs derived from wild-type mice, and was detected in long bone, kidney and intestine from BM-MSC-t...

Using OCT to predict post-transplant renal function

Science.gov (United States)

Andrews, Peter M.; Chen, Yu; Wierwille, Jeremiah; Joh, Daniel; Alexandrov, Peter; Rogalsky, Derek; Moody, Patrick; Chen, Allen; Cooper, Matthew; Verbesey, Jennifer E.; Gong, Wei; Wang, Hsing-Wen

2013-03-01

The treatment of choice for patients with end-stage renal disease is kidney transplantation. However, acute tubular necrosis (ATN) induced by an ischemic insult (e.g., from prolonged ex vivo storage times, or non-heart beating cadavers) is a major factor limiting the availability of donor kidneys. In addition, ischemic induced ATN is a significant risk factor for eventual graft survival and can be difficult to discern from rejection. Currently, there are no rapid and reliable tests to determine ATN suffered by donor kidneys and whether or not donor kidneys might exhibit delayed graft function. OCT (optical coherence tomography) is a rapidly emerging imaging modality that can function as a type of "optical biopsy", providing cross-sectional images of tissue morphology in situ and in real-time. In a series of recent clinical trials, we evaluated the ability of OCT to image those features of the renal microstructure that are predictive of ATN. Specifically, we found that OCT could effectively image through the intact human renal capsule and determine the extent of acute tubular necrosis. We also found that Doppler based OCT (i.e., DOCT) revealed renal blood flow dynamics that is also reported to be a determiner of post-transplant renal function. This kind of information will allow transplant surgeons to make the most efficient use of available donor kidneys, eliminate the possible use of bad donor kidneys, provide a measure of expected post-transplant renal function, and allow better distinction between post-transplant immunological rejection and ischemic-induced acute renal failure.

High cut-off haemodialysis induces remission of recurrent idiopathic focal segmental glomerulosclerosis after renal transplantation but is no alternative to plasmapheresis

NARCIS (Netherlands)

I. Noorlander (Iris); D.A. Hesselink (Dennis); M. Wabbijn (Marike); M.G.H. Betjes (Michiel)

2011-01-01

textabstractA 26-year-old male experienced a recurrence of idiopathic focal segmental glomerulosclerosis (iFSGS) after his second renal transplant. Reduction of proteinuria was rapidly induced by plasmapheresis (PP) and the patient has remained in remission with a once-weekly PP regimen, which has

Terapia nutricional no transplante hepático Nutritional therapy in liver transplantation

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Mônica Beatriz PAROLIN

2002-04-01

Full Text Available Racional - Deficiências nutricionais, por vezes graves, são comuns em pacientes com insuficiência hepática, candidatos a transplante de fígado. A terapia nutricional pode corrigir total ou parcialmente tais deficiências, melhorando as condições clínicas e o prognóstico desses indivíduos, frente ao grande desafio do transplante hepático. Objetivos - Breve revisão do papel do fígado no metabolismo dos diversos nutrientes. Descrição dos métodos de avaliação do estado nutricional, traçando-se as bases da terapia nutricional segundo condições hepáticas diversas, no pré e pós-transplante, em relação às necessidades calóricas e dos diversos nutrientes. Apresentação de intervenções nutricionais, no controle das complicações metabólicas resultantes do uso de drogas imunossupressoras. Conclusão - A terapia nutricional é valiosa aliada no tratamento clínico de pacientes candidatos ou já submetidos ao transplante hepático, contribuindo para um prognóstico favorável e para a melhora da qualidade de vida desses indivíduos.Background - Malnutrition, sometimes severe is common in patients with chronic hepatic diseases who are candidates for liver transplantation. Nutritional therapy can induce partial or total correction of such deficiencies, improving clinical conditions and prognosis of patients who face the great defiance of liver transplantation. Aims - Brief revision of hepatic role in the metabolism of several nutrients. Description of available methods of dietary therapy and its application both under different abnormal hepatic conditions and pre and post-transplant periods. The role of nutritional intervention in metabolic side effects due to immunosuppressive drugs. Conclusion - Nutritional therapy is a valuable adjuvant resource to the clinical treatment of candidates and submitted patients to hepatic transplantation providing better prognosis and improved life quality.

Derivation of transplantable 7,12-dimethylbenz[a]anthracene-induced chicken fibrosarcoma lines: differences in metastasizing properties and organ specificity

International Nuclear Information System (INIS)

Galton, J.E.; Xue, B.; Hochwald, G.M.; Thorbecke, G.J.

1982-01-01

Transplantable 7,12-dimethylbenz[a]anthracene-induced SC chicken fibrosarcoma (CHCT-NYU) lines were studied for their ability to grow in internal organs after iv injection (artificial metastases) into 1- to 3-week-old chickens. Some tumor lines were recently derived, whereas others were studied after many serial subcutaneous transplantations. Artificial metastases were seen in the stomach, pancreas, lungs, heart, and muscle, and occasionally in the kidneys and liver. Agammaglobulinemic recipients showed more extensive organ involvement than normal recipients of the same age. Whole-body ν-irradiation enhanced the incidence of artificial metastases, particularly in lungs. Antibody from the serum of a primary tumor-bearing host reduced the growth of the corresponding tumor in many organs. The metastatic pattern of line CHCT-NYU4 was a relatively stable property. However, intravenous transplantation of tumor cells from line CHCT-NYU4 taken from the liver, lungs, and pancreas of a single recipient established sublines with changes in organ specificity. After a few such serial transplants of liver-derived tumor, a line was derived that grew virtually in the liver alone. A subline with preference for growth in lungs was also obtained, but its ability to grow in the pancreas persisted. A pancreas-derived tumor line also grew in the liver and lungs. Subcutaneous transplants of tissue fragments of the lung-derived tumor line caused the appearance of spontaneous metastases in lungs. The incidence of spontaneous metastases with the lung-derived line was much greater than that with the liver-derived line or with the original CHCT-NYU4 line

Follicular Viability and Histological Alterations after nAuto-transplantation of Dog Ovaries by Experimentally Inducing Blood Sinus on Stomach

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Hazhir Khoram

2011-01-01

Full Text Available Background:Currently, chemotherapy and radiotherapy are considered most effective methods forcancer treatment, however these strategies often result in fertility problems. A favorable alternativeto prevent fertility loss in cancer patients is the cryopreservation and transplantation of sexualtissues (ovaries and/or testes. There is a low rate of fertilization following cryopreservation ofovaries prior to implantation. Therefore, in our opinion, this low rate is caused by instable bloodflow during organ transplantation. Thus, this study researches a canine ovarian model that focuses ondirect exposure of ovaries with blood in an experimentally induced sinus-like cavity. We implantedthis tissue on the muscular layer of the stomach, which is its most vascularized region.Materials and Methods: Ovarian transplantation was conducted on T1 animals (n=5, bilateralovariectomy was performed on T2 animals (n=5, unilateral ovariectomy was conducted on T3 casesand animals in the control-sham group (n=5 did not undergo ovariectomy or transplantation.Results: All isotransplanted ovaries survived. Ovaries resumed follicular growth andrevascularization. Transplanted ovaries contained 75%-76% of survived small follicles (pre antralafter 60 days. The ovarian granulosa cells showed considerable resistance against ischemia. Afterday 30 no statistically significant differences in the level of estradiol and progesterone were observedbetween T1 animals and the T3 group. T1 animals showed considerably high levels of progesteroneand estradiol in comparison to T2 cases.Conclusion: This study showed that using blood sinus method for ovarian isotransplantation helpsovarian tissue to survive from post implantation ischemia which confirms with normal folliclespresentation and intact endocrine function of the implanted ovaries.

Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

Energy Technology Data Exchange (ETDEWEB)

Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsuneyama, Koichi [Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Sugitani, Toyama 930‐0194 (Japan); Endo, Shinya [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Tsukui, Tohru [Research Center for Genomic Medicine, Saitama Medical University, Yamane, Hidaka 350‐1241 (Japan); Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan); Yokoi, Tsuyoshi, E-mail: tyokoi@p.kanazawa-u.ac.jp [Drug Metabolism and Toxicology, Faculty of Pharmaceutical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920‐1192 (Japan)

2012-10-01

Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

International Nuclear Information System (INIS)

Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori; Tsuneyama, Koichi; Endo, Shinya; Tsukui, Tohru; Toyoda, Yasuyuki; Fukami, Tatsuki; Nakajima, Miki; Yokoi, Tsuyoshi

2012-01-01

Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxic compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression

Intratracheal transplantation of endothelial progenitor cells attenuates smoking-induced COPD in mice

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Shi Z

2017-03-01

Full Text Available Zhihui Shi,1 Yan Chen,1 Jun Cao,2 Huihui Zeng,1 Yue Yang,1 Ping Chen,1 Hong Luo,1 Hong Peng,1 Shan Cai,1 Chaxiang Guan3 1Department of Internal Medicine, Division of Respiratory Disease, The Second Xiangya Hospital, Central-South University, 2Department of Internal Medicine, Division of Respiratory Disease, The People’s Hospital of Hunan Province, 3Department of Physiology, Xiangya Medical School, Central-South University, Changsha, Hunan, People’s Republic of China Background: Endothelial progenitor cells (EPCs might play a protective role in COPD. The aim of this study was to investigate whether intratracheal allogeneic transplantation of bone-marrow-derived EPCs would attenuate the development of smoking-induced COPD in mice.Methods: Isolated mononuclear cells from the bone marrow of C57BL/6J mice were cultured in endothelial cell growth medium-2 for 10 days, yielding EPCs. A murine model of COPD was established by passive 90-day exposure of cigarette smoke. On day 30, EPCs or phosphate-buffered saline alone was administered into the trachea. On day 90, EPCs or 30 µL phosphate-buffered saline alone was administered into the trachea, and on day 120, inflammatory cells, antioxidant activity, apoptosis, matrix metalloproteinase (MMP-2, and MMP-9 were measured.Results: After EPC treatment, the lung function of the mice had improved compared with the untreated mice. Mean linear intercept and destructive index were reduced in the EPCs-treated group compared with the untreated group. In addition, the EPCs-treated mice exhibited less antioxidant activity in bronchoalveolar lavage fluid compared with the untreated mice. Moreover, decreased activities of MMP-2, MMP-9, and TUNEL-positive cells in lung tissues were detected in EPCs-treated mice.Conclusion: Intratracheal transplantation of EPCs attenuated the development of pulmonary emphysema and lung function disorder probably by alleviating inflammatory infiltration, decelerating apoptosis

Rapamycin combined with anti-CD45RB mAb and IL-10 or with G-CSF induces tolerance in a stringent mouse model of islet transplantation.

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Nicola Gagliani

Full Text Available BACKGROUND: A large pool of preexisting alloreactive effector T cells can cause allogeneic graft rejection following transplantation. However, it is possible to induce transplant tolerance by altering the balance between effector and regulatory T (Treg cells. Among the various Treg-cell types, Foxp3(+Treg and IL-10-producing T regulatory type 1 (Tr1 cells have frequently been associated with tolerance following transplantation in both mice and humans. Previously, we demonstrated that rapamycin+IL-10 promotes Tr1-cell-associated tolerance in Balb/c mice transplanted with C57BL/6 pancreatic islets. However, this same treatment was unsuccessful in C57BL/6 mice transplanted with Balb/c islets (classified as a stringent transplant model. We accordingly designed a protocol that would be effective in the latter transplant model by simultaneously depleting effector T cells and fostering production of Treg cells. We additionally developed and tested a clinically translatable protocol that used no depleting agent. METHODOLOGY/PRINCIPAL FINDINGS: Diabetic C57BL/6 mice were transplanted with Balb/c pancreatic islets. Recipient mice transiently treated with anti-CD45RB mAb+rapamycin+IL-10 developed antigen-specific tolerance. During treatment, Foxp3(+Treg cells were momentarily enriched in the blood, followed by accumulation in the graft and draining lymph node, whereas CD4(+IL-10(+IL-4(- T (i.e., Tr1 cells localized in the spleen. In long-term tolerant mice, only CD4(+IL-10(+IL-4(- T cells remained enriched in the spleen and IL-10 was key in the maintenance of tolerance. Alternatively, recipient mice were treated with two compounds routinely used in the clinic (namely, rapamycin and G-CSF; this drug combination promoted tolerance associated with CD4(+IL-10(+IL-4(- T cells. CONCLUSIONS/SIGNIFICANCE: The anti-CD45RB mAb+rapamycin+IL-10 combined protocol promotes a state of tolerance that is IL-10 dependent. Moreover, the combination of rapamycin+G-CSF induces

Optical Coherence Tomography in Kidney Transplantation

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Andrews, Peter M.; Wierwille, Jeremiah; Chen, Yu

End-stage renal disease (ESRD) is associated with both high mortality rates and an enormous economic burden [1]. The preferred treatment option for ESRD that can extend patients' lives and improve their quality of life is kidney transplantation. However, organ shortages continue to pose a major problem in kidney transplantation. Most kidneys for transplantation come from heart-beating cadavers. Although non-heart-beating cadavers represent a potentially large pool of donor kidneys, these kidneys are not often used due to the unknown extent of damage to the renal tubules (i.e., acute tubular necrosis or "ATN") induced by ischemia (i.e., lack of blood flow). Also, ischemic insult suffered by kidneys awaiting transplantation frequently causes ATN that leads to varying degrees of delayed graft function (DGF) after transplantation. Finally, ATN represents a significant risk for eventual graft and patient survival [2, 3] and can be difficult to discern from rejection. In present clinical practice, there is no reliable real-time test to determine the viability of donor kidneys and whether or not donor kidneys might exhibit ATN. Therefore, there is a critical need for an objective and reliable real-time test to predict ATN to use these organs safely and utilize the donor pool optimally. In this review, we provided preliminary data indicating that OCT can be used to predict the post-transplant function of kidneys used in transplantation.

MAPC transplantation confers a more durable benefit than AC133+ cell transplantation in severe hind limb ischemia.

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Aranguren, Xabier L; Pelacho, Beatriz; Peñuelas, Ivan; Abizanda, Gloria; Uriz, Maialen; Ecay, Margarita; Collantaes, María; Araña, Miriam; Beerens, Manu; Coppiello, Giulia; Prieto, Inés; Perez-Ilzarbe, Maitane; Andreu, Enrique J; Luttun, Aernout; Prósper, Felipe

2011-01-01

There is a need for comparative studies to determine which cell types are better candidates to remedy ischemia. Here, we compared human AC133(+) cells and multipotent adult progenitor cells (hMAPC) in a mouse model reminiscent of critical limb ischemia. hMAPC or hAC133(+) cell transplantation induced a significant improvement in tissue perfusion (measured by microPET) 15 days posttransplantation compared to controls. This improvement persisted for 30 days in hMAPC-treated but not in hAC133(+)-injected animals. While transplantation of hAC133(+) cells promoted capillary growth, hMAPC transplantation also induced collateral expansion, decreased muscle necrosis/fibrosis, and improved muscle regeneration. Incorporation of differentiated hAC133(+) or hMAPC progeny into new vessels was limited; however, a paracrine angio/arteriogenic effect was demonstrated in animals treated with hMAPC. Accordingly, hMAPC-conditioned, but not hAC133(+)-conditioned, media stimulated vascular cell proliferation and prevented myoblast, endothelial, and smooth muscle cell apoptosis in vitro. Our study suggests that although hAC133(+) cell and hMAPC transplantation both contribute to vascular regeneration in ischemic limbs, hMAPC exert a more robust effect through trophic mechanisms, which translated into collateral and muscle fiber regeneration. This, in turn, conferred tissue protection and regeneration with longer term functional improvement. © 2011 Cognizant Comm. Corp.

Systematic trends in photonic reagent induced reactions in a homologous chemical family.

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Tibbetts, Katharine Moore; Xing, Xi; Rabitz, Herschel

2013-08-29

The growing use of ultrafast laser pulses to induce chemical reactions prompts consideration of these pulses as "photonic reagents" in analogy to chemical reagents. This work explores the prospect that photonic reagents may affect systematic trends in dissociative ionization reactions of a homologous family of halomethanes, much as systematic outcomes are often observed for reactions between homologous families of chemical reagents and chemical substrates. The experiments in this work with photonic reagents of varying pulse energy and linear spectral chirp reveal systematic correlations between observable ion yields and the following set of natural variables describing the substrate molecules: the ionization energy of the parent molecule, the appearance energy of each fragment ion, and the relative strength of carbon-halogen bonds in molecules containing two different halogens. The results suggest that reactions induced by photonic reagents exhibit systematic behavior analogous to that observed in reactions driven by chemical reagents, which provides a basis to consider empirical "rules" for predicting the outcomes of photonic reagent induced reactions.

Idiopathic pulmonary fibrosis with complication of severe respiratory failure, right heart failure, and steroid induced diabetes – qualification for lung transplantation as a matter of urgency

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Beata P. Kraśnicka-Sokół

2016-09-01

Full Text Available A 62-year-old woman 146 cm tall and weighing 50 kg, due to idiopathic pulmonary fibrosis, was firstly approved for lung transplantation according to the planned mode. Due to the low height of the patient there were difficulties in the selection of the donor and prolonged waiting time for the surgery. Rapid progression of pulmonary hypertension and steroid-induced diabetes forced us to change the mode of the procedure to urgent. The description of the case shows the difficulties in therapy and choosing the appropriate time for lung transplantation. In this case, the collaboration of specialists from various fields in the decision on transplant is noteworthy.

Characterization of Chemically-Induced Bacterial Ghosts (BGs Using Sodium Hydroxide-Induced Vibrio parahaemolyticus Ghosts (VPGs

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Hyun Jung Park

2016-11-01

Full Text Available Acellular bacterial ghosts (BGs are empty non-living bacterial cell envelopes, commonly generated by controlled expression of the cloned lysis gene E of bacteriophage PhiX174. In this study, Vibrio parahaemolyticus ghosts (VPGs were generated by chemically-induced lysis and the method is based on minimum inhibitory concentration (MIC of sodium hydroxide (NaOH, acetic acid, boric acid, citric acid, maleic acid, hydrochloric acid, and sulfuric acid. The MIC values of the respective chemicals were 3.125, 6.25, <50.0, 25.0, 6.25, 1.56, and 0.781 mg/mL. Except for boric acid, the lysis efficiency reached more than 99.99% at 5 min after treatment of all chemicals. Among those chemicals, NaOH-induced VPGs appeared completely DNA-free, which was confirmed by quantitative real-time PCR. Besides, lipopolysaccharides (LPS extracted from the NaOH-induced VPGs showed no distinctive band on SDS-PAGE gel after silver staining. On the other hand, LPS extracted from wild-type bacterial cells, as well as the organic acids-induced VPGs showed triple major bands and LPS extracted from the inorganic acids-induced VPGs showed double bands. It suggests that some surface structures in LPS of the NaOH-induced VPGs may be lost, weakened, or modified by the MIC of NaOH. Nevertheless, Limulus amoebocyte lysate assay revealed that there is no significant difference in endotoxic activity between the NaOH-induced VPGs and wild-type bacterial cells. Macrophages exposed to the NaOH-induced VPGs at 0.5 × 106 CFU/mL showed cell viability of 97.9%, however, the MIC of NaOH did not reduce the cytotoxic effect of wild-type bacterial cells. Like Escherichia coli LPS, the NaOH-induced VPGs are an excellent activator of pro-inflammatory cytokines (IL-1β and iNOS, anti-inflammatory cytokine (IL-10, and dual activities (IL-6 in the stimulated macrophage cells. On the other hand, the induction of TNF-α mRNA was remarkable in the macrophages exposed with wild-type cells. Scanning

Insulin-Like growth factor-II (IGF-II) prevents proinflammatory cytokine-induced apoptosis and significantly improves islet survival after transplantation.

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Hughes, Amy; Mohanasundaram, Daisy; Kireta, Svjetlana; Jessup, Claire F; Drogemuller, Chris J; Coates, P Toby H

2013-03-15

The early loss of functional islet mass (50-70%) due to apoptosis after clinical transplantation contributes to islet allograft failure. Insulin-like growth factor (IGF)-II is an antiapoptotic protein that is highly expressed in β-cells during development but rapidly decreases in postnatal life. We used an adenoviral (Ad) vector to overexpress IGF-II in isolated rat islets and investigated its antiapoptotic action against exogenous cytokines interleukin-1β- and interferon-γ-induced islet cell death in vitro. Using an immunocompromised marginal mass islet transplant model, the ability of Ad-IGF-II-transduced rat islets to restore euglycemia in nonobese diabetic/severe combined immunodeficient diabetic recipients was assessed. Ad-IGF-II transduction did not affect islet viability or function. Ad-IGF-II cytokine-treated islets exhibited decreased cell death (40% ± 2.8%) versus Ad-GFP and untransduced control islets (63.2% ± 2.5% and 53.6% ± 2.3%, respectively). Ad-IGF-II overexpression during cytokine treatment resulted in a marked reduction in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive apoptotic cells (8.3% ± 1.4%) versus Ad-GFP control (41% ± 4.2%) and untransduced control islets (46.5% ± 6.2%). Western blot analysis confirmed that IGF-II inhibits apoptosis via activation of the phosphatidylinositol 3-kinase/Akt signaling pathway. Transplantation of IGF-II overexpressing islets under the kidney capsule of diabetic mice restored euglycemia in 77.8% of recipients compared with 18.2% and 47.5% of Ad-GFP and untransduced control islet recipients, respectively (Pislet transplant outcomes in vivo. Antiapoptotic gene transfer is a potentially powerful tool to improve islet survival after transplantation.

Heterogenic transplantation of bone marrow-derived rhesus macaque mesenchymal stem cells ameliorates liver fibrosis induced by carbon tetrachloride in mouse

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Xufeng Fu

2018-02-01

Full Text Available Liver fibrosis is a disease that causes high morbidity and has become a major health problem. Liver fibrosis can lead to the end stage of liver diseases (livercirrhosisand hepatocellularcarcinoma. Currently, liver transplantation is the only effective treatment for end-stage liver disease. However, the shortage of organ donors, high cost of medical surgery, immunological rejection and transplantation complications severely hamper liver transplantation therapy. Mesenchymal stem cells (MSCs have been regarded as promising cells for clinical applications in stem cell therapy in the treatment of liver diseases due to their unique multipotent differentiation capacity, immunoregulation and paracrine effects. Although liver fibrosis improvements by MSC transplantation in preclinical experiments as well as clinical trials have been reported, the in vivo fate of MSCs after transportation and their therapeutic mechanisms remain unclear. In this present study, we isolated MSCs from the bone marrow of rhesus macaques. The cells exhibited typical MSC markers and could differentiate into chondrocytes, osteocytes, and adipocytes, which were not affected by labeling with enhanced green fluorescent protein (EGFP. The harvested MSCs respond to interferon-γ stimulation and have the ability to inhibit lymphocyte proliferation in vitro. EGFP-labeled MSCs (1 × 106 cells were transplanted into mice with carbon tetrachloride-induced liver fibrosis via tail vein injection. The ability of the heterogenic MSC infusion to ameliorate liver fibrosis in mice was evaluated by a blood plasma chemistry index, pathological examination and liver fibrosis-associated gene expression. Additionally, a small number of MSCs that homed and engrafted in the mouse liver tissues were evaluated by immunofluorescence analysis. Our results showed that the transplantation of heterogenic MSCs derived from monkey bone marrow can be used to treat liver fibrosis in the mouse model and that the

Lung-Derived Microscaffolds Facilitate Diabetes Reversal after Mouse and Human Intraperitoneal Islet Transplantation.

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Abualhassan, Nasser; Sapozhnikov, Lena; Pawlick, Rena L; Kahana, Meygal; Pepper, Andrew R; Bruni, Antonio; Gala-Lopez, Boris; Kin, Tatsuya; Mitrani, Eduardo; Shapiro, A M James

2016-01-01

There is a need to develop three-dimensional structures that mimic the natural islet tissue microenvironment. Endocrine micro-pancreata (EMPs) made up of acellular organ-derived micro-scaffolds seeded with human islets have been shown to express high levels of key beta-cell specific genes and secrete quantities of insulin per cell similar to freshly isolated human islets in a glucose-regulated manner for more than three months in vitro. The aim of this study was to investigate the capacity of EMPs to restore euglycemia in vivo after transplantation of mouse or human islets in chemically diabetic mice. We proposed that the organ-derived EMPs would restore the extracellular components of the islet microenvironment, generating favorable conditions for islet function and survival. EMPs seeded with 500 mouse islets were implanted intraperitoneally into streptozotocin-induced diabetic mice and reverted diabetes in 67% of mice compared to 13% of controls (p = 0.018, n = 9 per group). Histological analysis of the explanted grafts 60 days post-transplantation stained positive for insulin and exhibited increased vascular density in a collagen-rich background. EMPs were also seeded with human islets and transplanted into the peritoneal cavity of immune-deficient diabetic mice at 250 islet equivalents (IEQ), 500 IEQ and 1000 IEQ. Escalating islet dose increased rates of normoglycemia (50% of the 500 IEQ group and 75% of the 1000 IEQ group, n = 3 per group). Human c-peptide levels were detected 90 days post-transplantation in a dose-response relationship. Herein, we report reversal of diabetes in mice by intraperitoneal transplantation of human islet seeded on EMPs with a human islet dose as low as 500 IEQ.

Treating gout in kidney transplant recipients.

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Baroletti, Steven; Bencivenga, Gina Ann; Gabardi, Steven

2004-06-01

To review the etiology, treatment, and preventive strategies of hyperuricemia and gout in kidney transplant recipients. Primary literature was obtained via Medline (1966-June 2003). Studies evaluating treatment and prevention of hyperuricemia and gout in kidney transplantation were considered for evaluation. English-language studies were selected for inclusion. Approximately 14,000 kidney transplantations were performed in the United States in 2003, and of those transplant recipients, nearly 13% will experience a new onset of gout. The prevalence of hyperuricemia is even greater. There are several mechanisms by which hyperuricemia and gout develop in kidney transplant recipients. Medication-induced hyperuricemia and renal dysfunction are 2 of the more common mechanisms. Prophylactic and treatment options include allopurinol, colchicine, corticosteroids, and, if absolutely necessary, nonsteroidal antiinflammatory drugs. It is generally recommended to decide whether the risks of prophylactic therapy and treatment outweigh the benefits. Often, the risk of adverse events associated with agents to treat these ailments tends to outweigh the benefits; therefore, treatment is usually reserved for symptomatic episodes of acute gout. Practitioners must also decide if changes in immunosuppressive regimens may be of benefit on a patient-by-patient basis.

CMV induces HERV-K and HERV-W expression in kidney transplant recipients.

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Bergallo, Massimiliano; Galliano, Ilaria; Montanari, Paola; Gambarino, Stefano; Mareschi, Katia; Ferro, Francesca; Fagioli, Franca; Tovo, Pier-Angelo; Ravanini, Paolo

2015-07-01

Human endogenous retrovirus (HERVs) constitute approximately 8% of the human genome. Induction of HERV transcription is possible under certain circumstances, and may have a possible role in some pathological conditions. The aim of this study was to evaluate HERV-K and -W pol gene expression in kidney transplant recipients and to investigate the possible relationship between HERVs gene expression and CMV infection in these patients. Thirty-three samples of kidney transplant patients and twenty healthy blood donors were used to analyze, HERV-K and -W pol gene RNA expression by relative quantitative relative Real-Time PCR. We demonstrated that HERVs pol gene expression levels were higher in kidney transplant recipients than in healthy subjects. Moreover, HERV-K and -W pol gene expression was significantly higher in the group of kidney transplant recipients with high CMV viral load than in the groups with no or moderate CMV viral load. Our data suggest that CMV may facilitate in vivo HERV activation. Published by Elsevier B.V.

Coarse grain model for coupled thermo-mechano-chemical processes and its application to pressure-induced endothermic chemical reactions

International Nuclear Information System (INIS)

Antillon, Edwin; Banlusan, Kiettipong; Strachan, Alejandro

2014-01-01

We extend a thermally accurate model for coarse grain dynamics (Strachan and Holian 2005 Phys. Rev. Lett. 94 014301) to enable the description of stress-induced chemical reactions in the degrees of freedom internal to the mesoparticles. Similar to the breathing sphere model, we introduce an additional variable that describes the internal state of the particles and whose dynamics is governed both by an internal potential energy function and by interparticle forces. The equations of motion of these new variables are derived from a Hamiltonian and the model exhibits two desired features: total energy conservation and Galilean invariance. We use a simple model material with pairwise interactions between particles and study pressure-induced chemical reactions induced by hydrostatic and uniaxial compression. These examples demonstrate the ability of the model to capture non-trivial processes including the interplay between mechanical, thermal and chemical processes of interest in many applications. (paper)

Transplantation of mesenchymal stem cells cultured on biomatrix support induces repairing of digestive tract defects, in animal model.

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Sîrbu-Boeţi, Mirela-Patricia; Chivu, Mihaela; Pâslaru, Liliana Livia; Efrimescu, C; Herlea, V; Pecheanu, C; Moldovan, Lucia; Dragomir, Laura; Bleotu, Coralia; Ciucur, Elena; Vidulescu, Cristina; Vasilescu, Mihaela; Boicea, Anişoara; Mănoiu, S; Ionescu, M I; Popescu, I

2009-01-01

Transplanted mesenchymal stem cells (MSCs) appear to play a significant role in adult tissue repair. The aim of this research was to obtain MSCs enriched, three dimensional (3D) patches for transplant, and to test their ability to induce repair of iatrogenic digestive tract defects in rats. MSCs were obtained from human and rat bone marrow, cultured in vitro, and seeded in a collagen-agarose scaffold, where they showed enhanced viability and proliferation. The phenotype of the cultured cells was representative for MSCs (CD105+, CD90+, and CD34-, CD45-, CD3-, CD14-). The 3D patch was obtained by laying the MSCs enriched collagen-agarose scaffold on a human or swine aortic fragment. After excision of small portions of the rat digestive tract, the 3D patches were sutured at the edge of the defect using micro-surgical techniques. The rats were sacrificed at time-points and the regeneration of the digestive wall was investigated by immunofluorescence, light and electron microscopy. The MSCs enriched 3D patches were biocompatible, biodegradable, and prompted the regeneration of the four layers of the stomach and intestine wall in rats. Human cells were identified in the rat regenerated digestive wall as a hallmark of the transplanted MSCs. For the first time we constructed 3D patches made of cultured bone marrow MSCs, embedded into a collagen-rich biomatrix, on vascular bio-material support, and transplanted them in order to repair iatrogenic digestive tract defects. The result was a complete repair with preservation of the four layered structure of the digestive wall.

Involvement of MAPK proteins in bystander effects induced by chemicals and ionizing radiation

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Asur, Rajalakshmi; Balasubramaniam, Mamtha; Marples, Brian; Thomas, Robert A.; Tucker, James D.

2010-01-01

Many studies have examined bystander effects induced by ionizing radiation, however few have evaluated the ability of chemicals to induce similar effects. We previously reported the ability of two chemicals, mitomycin C (MMC) and phleomycin (PHL) to induce bystander effects in normal human lymphoblastoid cell lines. The focus of the current study was to determine the involvement of the MAPK proteins in bystander effects induced by physical and chemical DNA damaging agents and to evaluate the effects of MAPK inhibition on bystander-induced caspase 3/7 activation. The phosphorylation levels of the MAPK proteins ERK1/2, JNK, and p38, were measured from 1 to 24 h following direct or bystander exposure to MMC, PHL or radiation. We observed transient phosphorylation, at early time points, of all 3 proteins in bystander cells. We also evaluated the effect of MAPK inhibition on bystander-induced caspase 3/7 activity to determine the role of MAPK proteins in bystander-induced apoptosis. We observed bystander-induced activation of caspase 3/7 in bystander cells. Inhibition of MAPK proteins resulted in a decrease in caspase 3/7 activity at the early time points, and the caspase activity increased (in the case of ERK inhibition) or returned to basal levels (in the case of JNK or p38 inhibition) between 12 and 24 h. PHL is considered to be a radiomimetic agent, however in the present study PHL behaved more like a chemical and not like radiation in terms of MAPK phosphorylation. These results point to the involvement of MAPK proteins in the bystander effect induced by radiation and chemicals and provide additional evidence that this response is not limited to radiation but is a generalized stress response in cells.

Impact of islet size on pancreatic islet transplantation and potential interventions to improve outcome.

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Zorzi, Daria; Phan, Tammy; Sequi, Marco; Lin, Yong; Freeman, Daniel H; Cicalese, Luca; Rastellini, Cristiana

2015-01-01

Better results have been recently reported in clinical pancreatic islet transplantation (ITX) due mostly to improved isolation techniques and immunosuppression; however, some limitations still exist. It is known that following transplantation, 30% to 60% of the islets are lost. In our study, we have investigated 1) the role of size as a factor affecting islet engraftment and 2) potential procedural manipulations to increase the number of smaller functional islets that can be transplanted. C57/BL10 mice were used as donors and recipients in a syngeneic islet transplant model. Isolated islets were divided by size (large, >300 μm; medium 150-300 μm; small, <150 μm). Each size was transplanted in chemically induced diabetic mice as full (600 IEQ), suboptimal (400 IEQ), and marginal mass (200 IEQ). Control animals received all size islets. Engraftment was defined as reversal of diabetes by day 7 posttransplantation. When the superiority of smaller islets was observed, strategies of overdigestion and fragmentation were adopted during islet isolation in the attempt to reduce islet size and improve engraftment. Smaller islets were significantly superior in engraftment compared to medium, large, and control (all sizes) groups. This was more evident when marginal mass data were compared. In all masses, success decreased as islet size increased. Once islets were engrafted, functionality was not affected by size. When larger islets were fragmented, a significant decrease in islet functionality was observed. On the contrary, if pancreata were slightly overdigested, although not as successful as small naive islets, an increase in engraftment was observed when compared to the control group. In conclusion, smaller islets are superior in engraftment following islet transplantation. Fragmentation has a deleterious effect on islet engraftment. Islet isolations can be performed by reducing islet size with slight overdigestion, and it can be safely adopted to improve clinical

Liver transplantation for HCV cirrhosis at Karolinska University Hospital Huddinge, Stockholm.

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Gjertsen, H; Weiland, O; Oksanen, A; Söderdahl, G; Broomé, U; Ericzon, B-G

2006-10-01

Hepatitis C virus (HCV)-induced cirrhosis is the major indication for liver transplantation globally, and an increasing indication for liver transplantation in Sweden. We have retrospectively examined the 120 patients transplanted for HCV cirrhosis from 1987 through 2005, including 11 who received more than one graft. The 1-, 3-, and 5-year postoperative survivals for all patients transplanted for HCV with or without hepatocellular cancer (HCC) were 77%, 66%, and 53%, respectively. HCV patients without HCC had a 1-, 3-, and 5-year survivals of 78%, 73%, and 61%, compared with 84%, 79% and 74%, respectively, for patients transplanted with chronic liver diseases without cancer or HCV. The number of patients with HCV cirrhosis transplanted in our center is increasing. Compared with patients transplanted for other chronic liver diseases, we experienced inferior results among patients with HCV cirrhosis.

Transplante de intestino delgado Small intestine transplantation

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Flávio Henrique Ferreira Galvão

2003-06-01

Full Text Available RACIONAL: Avanços da biotecnologia e o desenvolvimento de novas drogas imunossupressoras melhoraram os resultados do transplante de intestino delgado. Esse transplante é atualmente indicado para casos especiais da falência intestinal. OBJETIVO: A presente revisão realça os recentes desenvolvimentos na área do transplante de intestino delgado. MATERIAL E MÉTODO: Mais de 600 publicações de transplante de intestino delgado foram revisadas. O desenvolvimento da pesquisa, novas estratégias de imunossupressão, monitorização do enxerto e do receptor, e avanços na técnica cirúrgica são discutidos. RESULTADOS: Realizaram-se cerca de 700 transplante de intestino delgado em 55 centros: 44% intestino-fígado, 41% enxerto intestinal isolado e 15% transplante multivisceral. Rejeição e infecção são as principais limitações desse transplante. Sobrevida de 5 anos na experiência internacional é de 46% para o transplante de intestino isolado, 43% para o intestino-fígado e de cerca de 30% para o transplante multivisceral. Sobrevidas prolongadas são mais freqüentes nos centros com maior experiência. Em série de 165 transplantes intestinais na Universidade de Pittsburgh, PA, EUA, foi relatada sobrevida do paciente maior do que 75% no primeiro ano, 54% em 5 anos e 42% em 10 anos. Mais de 90% desses pacientes assumem dieta oral irrestrita. CONCLUSÃO: O transplante de intestino delgado evoluiu de estratégia experimental para uma alternativa viável no tratamento da falência intestinal permanente. Promover o refinamento da terapia imunossupressora, do manejo e prevenção de infecções, da técnica cirúrgica e da indicação e seleção adequada dos pacientes é crucial para melhorar a sobrevida desse transplante.BACKGROUND: Significant progress has been made in clinical small bowel transplantation over the last decade mainly due advances in biotechnology and new immunosuppressive regiments. This transplantation has now been indicated

Retinal stem cells and potential cell transplantation treatments

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Tai-Chi Lin

2014-11-01

Full Text Available The retina, histologically composed of ten delicate layers, is responsible for light perception and relaying electrochemical signals to the secondary neurons and visual cortex. Retinal disease is one of the leading clinical causes of severe vision loss, including age-related macular degeneration, Stargardt's disease, and retinitis pigmentosa. As a result of the discovery of various somatic stem cells, advances in exploring the identities of embryonic stem cells, and the development of induced pluripotent stem cells, cell transplantation treatment for retinal diseases is currently attracting much attention. The sources of stem cells for retinal regeneration include endogenous retinal stem cells (e.g., neuronal stem cells, Müller cells, and retinal stem cells from the ciliary marginal zone and exogenous stem cells (e.g., bone mesenchymal stem cells, adipose-derived stem cells, embryonic stem cells, and induced pluripotent stem cells. The success of cell transplantation treatment depends mainly on the cell source, the timing of cell harvesting, the protocol of cell induction/transplantation, and the microenvironment of the recipient's retina. This review summarizes the different sources of stem cells for regeneration treatment in retinal diseases and surveys the more recent achievements in animal studies and clinical trials. Future directions and challenges in stem cell transplantation are also discussed.

Liver transplant

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Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

Hair Transplants

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... Search Skin Experts Skin Treatments Hair Transplants Share » HAIR TRANSPLANTS Before (left) and after (right) - front of ... transplant. Photo courtesy of N. Sadick What are hair transplants? In punch transplanting, a plug containing hair ...

Bortezomib in Kidney Transplantation

Science.gov (United States)

Raghavan, Rajeev; Jeroudi, Abdallah; Achkar, Katafan; Gaber, A. Osama; Patel, Samir J.; Abdellatif, Abdul

2010-01-01

Although current therapies for pretransplant desensitization and treatment of antibody-mediated rejection (AMR) have had some success, they do not specifically deplete plasma cells that produce antihuman leukocyte antigen (HLA) antibodies. Bortezomib, a proteasome inhibitor approved for the treatment of multiple myeloma (a plasma cell neoplasm), induces plasma cell apoptosis. In this paper we review the current body of literature regarding the use of this biological agent in the field of transplantation. Although limited experience with bortezomib may seem to show promise in the realm of transplant recipients desensitization and treatment of AMR, there is also experience that may suggest otherwise. Bortezomib's role in desensitization protocols and treatment of AMR will be defined better as more clinical data and trials become available. PMID:20953363

Role of gastroesophageal reflux disease in lung transplantation

Science.gov (United States)

Hathorn, Kelly E; Chan, Walter W; Lo, Wai-Kit

2017-01-01

Lung transplantation is one of the highest risk solid organ transplant modalities. Recent studies have demonstrated a relationship between gastroesophageal reflux disease (GERD) and lung transplant outcomes, including acute and chronic rejection. The aim of this review is to discuss the pathophysiology, evaluation, and management of GERD in lung transplantation, as informed by the most recent publications in the field. The pathophysiology of reflux-induced lung injury includes the effects of aspiration and local immunomodulation in the development of pulmonary decline and histologic rejection, as reflective of allograft injury. Modalities of reflux and esophageal assessment, including ambulatory pH testing, impedance, and esophageal manometry, are discussed, as well as timing of these evaluations relative to transplantation. Finally, antireflux treatments are reviewed, including medical acid suppression and surgical fundoplication, as well as the safety, efficacy, and timing of such treatments relative to transplantation. Our review of the data supports an association between GERD and allograft injury, encouraging a strategy of early diagnosis and aggressive reflux management in lung transplant recipients to improve transplant outcomes. Further studies are needed to explore additional objective measures of reflux and aspiration, better compare medical and surgical antireflux treatment options, extend follow-up times to capture longer-term clinical outcomes, and investigate newer interventions including minimally invasive surgery and advanced endoscopic techniques. PMID:28507913

Effect of adipose-derived mesenchymal stem cell transplantation on vascular calcification in rats with adenine-induced kidney disease

OpenAIRE

Yokote, Shinya; Katsuoka, Yuichi; Yamada, Akifumi; Ohkido, Ichiro; Yokoo, Takashi

2017-01-01

Previous studies have investigated the use of mesenchymal stem cells (MSCs) to treat damaged kidneys. However, the effect of adipose-derived MSCs (ASCs) on vascular calcification in chronic kidney disease (CKD) is still poorly understood. In the present study, we explored the potential of ASCs for the treatment of CKD and vascular calcification. CKD was induced in male Sprague-Dawley rats by feeding them a diet containing 0.75% adenine for 4 weeks. ASCs transplantation significantly reduced s...

Implication of thymoglobulin in kidney transplant patients: review article

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Sudabeh Alatab

2015-11-01

Full Text Available Thymoglobulin is a purified polyclonal immunoglobulin that has been used widely over the last decades in the prevention and treatment of rejection following renal transplantation. This immunoglobulin works against human thymocytes. Since thymoglobulin does not contain the nephrotoxic properties therefore it can be used in induction therapy especially in patients with higher risk of graft rejection such as patients who receive graft from cadavers. Recent research showed also its beneficial role in cross-match-positive transplantation, a role that is mediated through conjunction with inhibitors of terminal complement activation. This immunoglobulin has also been used for treatment of rejection following renal transplantation. Thymoglobulin can have various effects on various Immune system cells including T cells, B cells and also plasma cells. Thymoglobulin also affects the Tcell surface antigens, natural killer-cell antigens, B cell antigens, plasma cell antigens, adhesion molecules and chemokine receptors. Diverse effects of thymoglobulin on the immune system includes: T cell depletion, induce apoptosis in B cell lineage and interference with dendritic cell functional properties. Thymoglobulin can cause acute complications, delayed complications as well as infectious complications. Acute reaction events includes: anaphylaxis, fever, chills, dyspnea, nausea, vomiting and diarrhea. Thymoglobulin also induces cytokine release syndrome manifested by high grade fevers and chills and treated by steroid therapy. Delayed reactions events usually present as serum sickness and infections. Infectious complications are more important and include cytomegalovirus (CMV infection, sepsis, candidiasis, herpes simplex and urinary infections. Thymoglobulin can also induce cytokine release syndrome. It has been thought that thymoglobulin increases the risk of post-transplant lymphoproliferative disorder (PTLD, however, debate still exists whether such an

Combination of exogenous cell transplantation and 5-HT4 receptor agonism induce endogenous enteric neural crest-derived cells in a rat hypoganglionosis model

International Nuclear Information System (INIS)

Yu, Hui; Zheng, Bai-Jun; Pan, Wei-Kang; Wang, Huai-Jie; Xie, Chong; Zhao, Yu-Ying; Chen, Xin-Lin; Liu, Yong; Gao, Ya

2017-01-01

Enteric neural crest-derived cells (ENCCs) can migrate into endogenous ganglia and differentiate into progeny cells, and have even partially rescued bowel function; however, poor reliability and limited functional recovery after ENCC transplantation have yet to be addressed. Here, we investigated the induction of endogenous ENCCs by combining exogenous ENCC transplantation with a 5-HT 4 receptor agonist mosapride in a rat model of hypoganglionosis, established by benzalkonium chloride treatment. ENCCs, isolated from the gut of newborn rats, were labeled with a lentiviral eGFP reporter. ENCCs and rats were treated with the 5-HT 4 receptor agonist/antagonist. The labeled ENCCs were then transplanted into the muscular layer of benzalkonium chloride-treated colons. At given days post-intervention, colonic tissue samples were removed for histological analysis. ENCCs and neurons were detected by eGFP expression and immunoreactivity to p75 NTR and peripherin, respectively. eGFP-positive ENCCs and neurons could survive and maintain levels of fluorescence after transplantation. With longer times post-intervention, the number of peripherin-positive cells gradually increased in all groups. Significantly more peripherin-positive cells were found following ENCCs plus mosapride treatment, compared with the other groups. These results show that exogenous ENCCs combined with the 5-HT 4 receptor agonist effectively induced endogenous ENCCs proliferation and differentiation in a rat hypoganglionosis model. - Highlights: • Survival and differentiation of exogenous ENCCs in treated colons. • With longer times post-intervention, the number of ENCCs and their progeny cells gradually increased. • Exogenous ENCCs combined with the 5-HT4 receptor agonist ffectively induced ENCCs proliferation and differentiation.

Bypass during Liver Transplantation: Anachronism or Revival? Liver Transplantation Using a Combined Venovenous/Portal Venous Bypass—Experiences with 163 Liver Transplants in a Newly Established Liver Transplantation Program

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Anne Mossdorf

2015-01-01

Full Text Available Introduction. The venovenous/portal venous (VVP bypass technique has generally become obsolete in liver transplantation (LT today. We evaluated our experience with 163 consecutive LTs that used a VVP bypass. Patients and Methods. The liver transplant program was started in our center in 2010. LTs were performed using an extracorporal bypass device. Results. Mean operative time was 269 minutes and warm ischemic time 43 minutes. The median number of transfusion of packed cells and plasma was 7 and 14. There was no intraoperative death, and the 30-day mortality was 3%. Severe bypass-induced complications did not occur. Discussion. The introduction of a new LT program requires maximum safety measures for all of the parties involved. Both surgical and anaesthesiological management (reperfusion can be controlled very reliably using a VVP bypass device. Particularly when using marginal grafts, this approach helps to minimise both surgical and anaesthesiological complications in terms of less volume overload, less use of vasopressive drugs, less myocardial injury, and better peripheral blood circulation. Conclusion. Based on our experiences while establishing a new liver transplantation program, we advocate the reappraisal of the extracorporeal VVP bypass.

Immediate re-transplantation following early kidney transplant thrombosis.

LENUS (Irish Health Repository)

Phelan, Paul J

2012-02-01

Allograft thrombosis is a devastating early complication of renal transplantation that ultimately leads to allograft loss. We report here on our experience of nine cases of immediate re-transplantation following early kidney transplant thrombosis at a single centre between January 1990 and June 2009. The mean age was 42.9 years at time of transplant. For seven patients, the allograft thrombosis was their first kidney transplant and seven of the nine cases had a deceased donor transplant. The initial transplants functioned for a mean of 1.67 days and the patients received a second allograft at a mean of 3.1 days after graft failure. All of the re-transplants worked immediately. Four allografts failed after a mean of 52.5 months (2-155 months). Two of these died with a functioning allograft, one failed owing to chronic allograft nephropathy and one owing to persistent acute cellular rejection. The remaining five patients still have a functioning allograft after a mean of 101.8 months (7-187 months). One year allograft and patient survival after re-transplantation were 87.5% and 100% respectively (after 5 years, both were 57%). Immediate re-transplantation following early kidney transplant thrombosis can be a success. It may be considered in selected cases after allograft thrombosis.

Tuberculosis post-liver transplantation: a rare but complicated disease.

Science.gov (United States)

Lu, W; Wai, C T; Da Costa, M; Tambyah, P A; Prabhakaran, K; Lee, K H

2005-03-01

Tuberculosis is a rare but serious complication after transplantation. We report a case and discuss its presentation and management. A 60-year-old Indonesian male presented initially with fever, acute confusion and rapidly progressive right upper lobe pneumonia 3.5 months post-liver transplant, and was diagnosed with pulmonary tuberculosis by positive sputum smear for acid-fast bacilli and tuberculosis culture. Standard anti-tuberculosis therapy was administered but was complicated by interaction with cyclosporine and drug-induced cholestasis. A high level of suspicion, prompt antituberculosis treatment and close follow-up are essential in management of post-transplant tuberculosis.

Effects of radiation and other influences on chemical lymphomagenesis

Energy Technology Data Exchange (ETDEWEB)

Seidel, H.J.

1987-06-01

Methylnitrosourea (MNU) or butylnitrosourea (BNU) was used to induce T cell lymphomas (thymomas) in BDF/sub 1/ mice. In addition to the chemical, X-rays in various dose schedules were applied. An effect of the irradiation (shortening of the latency period) was seen with 12 x 0.25 Gy in protocols with a prolonged median induction time in the controls as a result of a dose reduction of the chemical (median induction time 27-36 weeks instead of 16-18 weeks under optimal conditions using 50 mg kg/sup -1/ of MNU). Preirradiation 2-5 weeks before 40 mg kg/sup -1/ of MNU resulted in enhanced leukaemogenesis. Also, mice with regenerating lympho-haemopoiesis after lethal irradiation and bone marrow transplantation were more sensitive to the effect of both chemicals than were the controls. Treatment with anti-thy 1.2 and with corynebacterium parvum during the latency period had no influence.

Pancreas preservation for pancreas and islet transplantation

Science.gov (United States)

Iwanaga, Yasuhiro; Sutherland, David E.R.; Harmon, James V.; Papas, Klearchos K.

2010-01-01

Purpose of review To summarize advances and limitations in pancreas procurement and preservation for pancreas and islet transplantation, and review advances in islet protection and preservation. Recent findings Pancreases procured after cardiac death, with in-situ regional organ cooling, have been successfully used for islet transplantation. Colloid-free Celsior and histidine-tryptophan-ketoglutarate preservation solutions are comparable to University of Wisconsin solution when used for cold storage before pancreas transplantation. Colloid-free preservation solutions are inferior to University of Wisconsin solution for pancreas preservation prior to islet isolation and transplantation. Clinical reports on pancreas and islet transplants suggest that the two-layer method may not offer significant benefits over cold storage with the University of Wisconsin solution: improved oxygenation may depend on the graft size; benefits in experimental models may not translate to human organs. Improvements in islet yield and quality occurred from pancreases treated with inhibitors of stress-induced apoptosis during procurement, storage, isolation or culture. Pancreas perfusion may be desirable before islet isolation and transplantation and may improve islet yields and quality. Methods for real-time, noninvasive assessment of pancreas quality during preservation have been implemented and objective islet potency assays have been developed and validated. These innovations should contribute to objective evaluation and establishment of improved pancreas preservation and islet isolation strategies. Summary Cold storage may be adequate for preservation before pancreas transplants, but insufficient when pancreases are processed for islets or when expanded donors are used. Supplementation of cold storage solutions with cytoprotective agents and perfusion may improve pancreas and islet transplant outcomes. PMID:18685343

A model for chemically-induced mechanical loading on MEMS

DEFF Research Database (Denmark)

Amiot, Fabien

2007-01-01

The development of full displacement field measurements as an alternative to the optical lever technique to measure the mechanical response for microelectro-mechanical systems components in their environment calls for a modeling of chemically-induced mechanical fields (stress, strain, and displac......The development of full displacement field measurements as an alternative to the optical lever technique to measure the mechanical response for microelectro-mechanical systems components in their environment calls for a modeling of chemically-induced mechanical fields (stress, strain...... of the system free energy and its dependence on the surface amount. It is solved in the cantilever case thanks to an asymptotic analysis, and an approached closed-form solution is obtained for the interfacial stress field. Finally, some conclusions regarding the transducer efficiency of cantilevers are drawn...

Immediate re-transplantation following early kidney transplant thrombosis.

LENUS (Irish Health Repository)

Phelan, Paul J

2011-08-01

Allograft thrombosis is a devastating early complication of renal transplantation that ultimately leads to allograft loss. We report here on our experience of nine cases of immediate re-transplantation following early kidney transplant thrombosis at a single centre between January 1990 and June 2009. The mean age was 42.9 years at time of transplant. For seven patients, the allograft thrombosis was their first kidney transplant and seven of the nine cases had a deceased donor transplant. The initial transplants functioned for a mean of 1.67 days and the patients received a second allograft at a mean of 3.1 days after graft failure. All of the re-transplants worked immediately. Four allografts failed after a mean of 52.5 months (2-155 months). Two of these died with a functioning allograft, one failed owing to chronic allograft nephropathy and one owing to persistent acute cellular rejection. The remaining five patients still have a functioning allograft after a mean of 101.8 months (7-187 months). One year allograft and patient survival after re-transplantation were 87.5% and 100% respectively (after 5 years, both were 57%). Immediate re-transplantation following early kidney transplant thrombosis can be a success. It may be considered in selected cases after allograft thrombosis.

Resistance of transplantation tolerance to X-irradiation

Energy Technology Data Exchange (ETDEWEB)

Holan, V; Hasek, M; Chutna, J [Czechoslovak Academy of Sciences, Prague. Institute of Molecular Genetics

1979-04-01

With regard to the previous finding that suppressor cells participating in the state of transplantation tolerance were radiosensitive, the possibility was investigated whether tolerance can be abolished by irradiation. In the rat model used (AVN recipients, Lewis donors), both neonatally induced tolerance and tolerance induced in the adult life by the transfer of suppressor cells were found to be radioresistant.

Chemical determination of free radical-induced damage to DNA.

Science.gov (United States)

Dizdaroglu, M

1991-01-01

Free radical-induced damage to DNA in vivo can result in deleterious biological consequences such as the initiation and promotion of cancer. Chemical characterization and quantitation of such DNA damage is essential for an understanding of its biological consequences and cellular repair. Methodologies incorporating the technique of gas chromatography/mass spectrometry (GC/MS) have been developed in recent years for measurement of free radical-induced DNA damage. The use of GC/MS with selected-ion monitoring (SIM) facilitates unequivocal identification and quantitation of a large number of products of all four DNA bases produced in DNA by reactions with hydroxyl radical, hydrated electron, and H atom. Hydroxyl radical-induced DNA-protein cross-links in mammalian chromatin, and products of the sugar moiety in DNA are also unequivocally identified and quantitated. The sensitivity and selectivity of the GC/MS-SIM technique enables the measurement of DNA base products even in isolated mammalian chromatin without the necessity of first isolating DNA, and despite the presence of histones. Recent results reviewed in this article demonstrate the usefulness of the GC/MS technique for chemical determination of free radical-induced DNA damage in DNA as well as in mammalian chromatin under a vast variety of conditions of free radical production.

Extensive chimerism in liver transplants: vascular endothelium, bile duct epithelium, and hepatocytes.

NARCIS (Netherlands)

Hove, W.R.; Hoek, B. van; Bajema, I.M.; Ringers, J.; Krieken, J.H.J.M. van; Lagaaij, E.L.

2003-01-01

The transplanted liver has been shown to be particularly capable of inducing tolerance. An explanation may be the presence of chimerism. Cells of donor origin have been found in recipient tissues after transplantation of any solid organ. Evidence for the presence of cells of recipient origin within

Pulmão e transplante renal Lung and renal transplantation

Directory of Open Access Journals (Sweden)

Patrícia Caetano Mota

2009-11-01

diagnostic and therapeutic challenge. Aim: To evaluate patients admitted to the Renal Transplant Unit (RTU of Hospital de S. João with respiratory disease. Subject and methods: We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months. Results: Thirty-six patients were included. Mean age 55.2 (±13.4 years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9% or tacrolimus (22.2% or rapamycin (13.9%. Thirty-one patients (86.1% presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2% pneumonias, 5 (16.1% opportunistic infections, 2 (6.5% tracheobronchitis, and 1 case (3.2% of lung abscesses. Microbiological agent was identified in 7 cases (22.6%. Five patients (13.9% presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%, diagnostic in 10 cases (66.7%. Mean hospital stay was 17.1 (±18.5 days and no related death was observed. Conclusion: Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy.

Pre-liver transplant psychosocial evaluation predicts post-transplantation outcomes.

Science.gov (United States)

Benson, Ariel A; Rowe, Mina; Eid, Ahmad; Bluth, Keren; Merhav, Hadar; Khalaileh, Abed; Safadi, Rifaat

2018-08-01

Psychosocial factors greatly impact the course of patients throughout the liver transplantation process. A retrospective chart review was performed of patients who underwent liver transplantation at Hadassah-Hebrew University Medical Center between 2002 and 2012. A composite psychosocial score was computed based on the patient's pre-transplant evaluation. Patients were divided into two groups based on compliance, support and insight: Optimal psychosocial score and Non-optimal psychosocial score. Post-liver transplantation survival and complication rates were evaluated. Out of 100 patients who underwent liver transplantation at the Hadassah-Hebrew University Medical Center between 2002 and 2012, 93% had a complete pre-liver transplant psychosocial evaluation in the medical record performed by professional psychologists and social workers. Post-liver transplantation survival was significantly higher in the Optimal group (85%) as compared to the Non-optimal group (56%, p = .002). Post-liver transplantation rate of renal failure was significantly lower in the Optimal group. No significant differences were observed between the groups in other post-transplant complications. A patient's psychosocial status may impact outcomes following transplantation as inferior psychosocial grades were associated with lower overall survival and increased rates of complications. Pre-liver transplant psychosocial evaluations are an important tool to help predict survival following transplantation.

Comparative evaluation of hmopolesis and serum proteins from dogs with transmissible venereal tumor by natural ocorrence and induced by alogenic transplant

International Nuclear Information System (INIS)

Aptekmann, K.P.; Costa, M.T.; Fabeni, R. de C.; Santana, A.E.

2005-01-01

The objective of this study was to evaluate the haemopoiesis and total serum proteins of dogs with canine Transmissible Venereal Tumour (TVT) (naturally occurring or induced by allogenic transplant). Complete haemogram, bone marrow evaluation, total serum protein, albumin determination and electrophoretic fractionation of serum proteins were performed. Results revealed normocytic normochromic anaemia and thrombocytopenia in dogs with naturally occurring TVT

Three-year post-transplant medicare payments in kidney transplant recipients: Associations with pre-transplant comorbidities

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Gerardo Machnicki

2011-01-01

Full Text Available Little is known about the influence of pre-transplant comorbidities on post-transplant expenditures. We estimated the associations between pre-transplant comorbidities and post-transplant Medicare costs, using several comorbidity classification systems. We included recipients of first-kidney deceased donor transplants from 1995 through 2002 for whom Medicare was the primary payer for at least one year pre-transplant (N = 25,175. We examined pre-transplant comorbidities as classified by International Classification of Diseases (ICD-9-CM codes from Medicare claims with the Clinical Cla-ssifications Software (CCS and Charlson and Elixhauser algorithms. Post-transplant costs were calcu-lated from payments on Medicare claims. We developed models considering Organ Procurement and Transplantation Network (OPTN variables plus: 1 CCS categories, 2 Charlson, 3 Elixhauser, 4 num-ber of Charlson and 5 number of Elixhauser comorbidities, independently. We applied a novel regression methodology to account for censoring. Costs were estimated at individual and population levels. The comorbidities with the largest impact on mean Medicare payments included cardiovascular disease, ma-lignancies, cerebrovascular disease, mental conditions and functional limitations. Skin ulcers and infec-tions, rheumatic and other connective tissue disease and liver disease also contributed to payments and have not been considered or described previously. A positive graded relationship was found between costs and the number of pre-transplant comorbidities. In conclusion, we showed that expansion beyond the usually considered pre-transplant comorbidities with inclusion of CCS and Charlson or Elixhauser comorbidities increased the knowledge about comorbidities related to augmented Medicare payments. Our expanded methodology can be used by others to assess more accurately the financial implications of renal transplantation to Medicare and individual transplant centers.

Hazard classification of chemicals inducing haemolytic anaemia: An EU regulatory perspective.

NARCIS (Netherlands)

Muller, Andre; Jacobsen, Helene; Healy, Edel; McMickan, Sinead; Istace, Fréderique; Blaude, Marie-Noëlle; Howden, Peter; Fleig, Helmut; Schulte, Agnes

2006-01-01

Haemolytic anaemia is often induced following prolonged exposure to chemical substances. Currently, under EU Council Directive 67/548/EEC, substances which induce such effects are classified as dangerous and assigned the risk phrase R48 'Danger of serious damage to health by prolonged exposure.'

Fruticose lichen transplant technique for air pollution experiments

Energy Technology Data Exchange (ETDEWEB)

Kauppi, M

1976-01-01

Cladonia stellaris (Opiz) Pouz. and Vezta lichens were transplanted into small plastic containers and placed in the area surrounding a chemical factory and in built-up areas in Oulu, Northern Finland. The changes occasioned in the lichens by the effects of air pollution were determined under the microscope, by photography, by measuring their net assimilation rate (URAS-2), chlorophyll content, pH and electrical conductivity, and by various chemical analyses. The results obtained from two autumn series of experiments are presented here. The lichens reacted fairly sharply to pollutants in the air, in a manner reflecting the qualitative differences between the town environment and the fertilizer factory as sources of pollution. The technique described here is compared with transplants of corticolous lichens. It seems that fruticose lichens may be successfully used as pollution indicators provided that the exposure period is short; only a few months.

Combination of exogenous cell transplantation and 5-HT{sub 4} receptor agonism induce endogenous enteric neural crest-derived cells in a rat hypoganglionosis model

Energy Technology Data Exchange (ETDEWEB)

Yu, Hui [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China); Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi’an Jiaotong University, No 96, Yan Ta Xi Road, Xi’an 710061, Shaanxi (China); Zheng, Bai-Jun; Pan, Wei-Kang; Wang, Huai-Jie; Xie, Chong; Zhao, Yu-Ying [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China); Chen, Xin-Lin; Liu, Yong [Institute of Neurobiology, Environment and Genes Related to Diseases Key Laboratory of Chinese Ministry of Education, Xi’an Jiaotong University, No 96, Yan Ta Xi Road, Xi’an 710061, Shaanxi (China); Gao, Ya, E-mail: ygao@mail.xjtu.edu.cn [Department of Pediatric Surgery, the Second Affiliated Hospital, Xi’an Jiaotong University, No 157, Xi Wu Road, Xi’an 710004, Shaanxi (China)

2017-02-01

Enteric neural crest-derived cells (ENCCs) can migrate into endogenous ganglia and differentiate into progeny cells, and have even partially rescued bowel function; however, poor reliability and limited functional recovery after ENCC transplantation have yet to be addressed. Here, we investigated the induction of endogenous ENCCs by combining exogenous ENCC transplantation with a 5-HT{sub 4} receptor agonist mosapride in a rat model of hypoganglionosis, established by benzalkonium chloride treatment. ENCCs, isolated from the gut of newborn rats, were labeled with a lentiviral eGFP reporter. ENCCs and rats were treated with the 5-HT{sub 4} receptor agonist/antagonist. The labeled ENCCs were then transplanted into the muscular layer of benzalkonium chloride-treated colons. At given days post-intervention, colonic tissue samples were removed for histological analysis. ENCCs and neurons were detected by eGFP expression and immunoreactivity to p75{sup NTR} and peripherin, respectively. eGFP-positive ENCCs and neurons could survive and maintain levels of fluorescence after transplantation. With longer times post-intervention, the number of peripherin-positive cells gradually increased in all groups. Significantly more peripherin-positive cells were found following ENCCs plus mosapride treatment, compared with the other groups. These results show that exogenous ENCCs combined with the 5-HT{sub 4} receptor agonist effectively induced endogenous ENCCs proliferation and differentiation in a rat hypoganglionosis model. - Highlights: • Survival and differentiation of exogenous ENCCs in treated colons. • With longer times post-intervention, the number of ENCCs and their progeny cells gradually increased. • Exogenous ENCCs combined with the 5-HT4 receptor agonist ffectively induced ENCCs proliferation and differentiation.

Adipose derived mesenchymal stem cells transplantation via portal vein improves microcirculation and ameliorates liver fibrosis induced by CCl4 in rats

Directory of Open Access Journals (Sweden)

Wang Yu

2012-06-01

Full Text Available Abstract Introduction Adipose derived mesenchymal stem cells (ADMSCs, carrying the similar characteristics to bone marrow mesenchymal stem cells, only much more abundant and easier to obtain, may be a promising treatment for liver fibrosis. We aim to investigate the therapeutic potential of ADMSCs transplantation in liver fibrosis caused by carbon tetrachloride (CCl4 in rats as well as its underlying mechanism, and to further explore the appropriate infusion pathway. Methods ADMSCs were isolated, cultured and identified. Placebo and ADMSCs were transplanted via portal vein and tail vein respectively into carbon tetrachloride (CCl4-induced liver fibrosis rats. Computed tomography (CT perfusion scan and microvessel counts were performed to measure the alteration of liver microcirculation after therapy. Liver function tests and histological findings were estimated. Results CT perfusion scan shown significant decrease of hepatic arterial perfusion index, significant increased portal vein perfusion, total liver perfusion in rats receiving ADMSCs from portal vein, and Factor VIII (FVIII immunohistochemical staining shown significant decrease of microvessels in rats receiving ADMSCs from portal vein, indicating microcirculation improvement in portal vein group. Vascular endothelial growth Factor (VEGF was significantly up-regulated in fibrosis models, and decreased after ADMSCs intraportal transplantation. A significant improvement of liver functional test and histological findings in portal vein group were observed. No significance was found in rats receiving ADMSCs from tail vein. Conclusions ADMSCs have a therapeutic effect against CCl4-mediated liver fibrosis. ADMSCs may benefit the fibrotic liver through alteration of microcirculation, evidenced by CT perfusion scan and down-regulation of VEGF. Intraportal transplantation is a better pathway than tail vein transplantation.

A survey on the effects of Azithromycin in the treatment of gingival overgrowth induced by Cyclosporin in renal transplant patients

Directory of Open Access Journals (Sweden)

Kadkhoda Z.

2004-07-01

Full Text Available Statement of Problem: Gingival overgrowth is a side effect commonly induced by Cyclosporin treatment. The effects of Azithromycin, a macrolidic antibiotic, has been focused on gingival enlargement treatment induced by cyclosporine in numerous articles. Purpose: The goal of the present study was to survey the effects of systemic Azithromycin in the treatment of gingival overgrowth induced by cyclosporine among renal transplant patients. Materials and Methods: In this clinical trial study, 18 renal transplant patients (6 females and 12 males with gingival overgrowth were studied. Samples were randomly divided into two groups: case group were treated by systemic Azithromycin and controls were treated by systemic placebo. Periodontal parameters including bleeding on probing (BOP, clinical crown length (CL, periodontal pocket depth (PPD, gingival overgrowth (GOI and stent-IDP (vertical distant between a stent or plate with teeth occlusal planes at least from three of the most anterior contact points to mesial papillae before treatment, two and six weeks after treatment were measured. To analyze the data, Wilcoxon and Mann-Whitney tests were used. Results: Most of the measured indices, among case and control groups, were significantly improved, after two weeks (P<0.05. No statistically significant differences were found between two groups except for BOP index (P<0.05. In other words, more BOP improvement was observed in the case group after six weeks comparing to the control group. Conclusion: Considering the findings of this study, one can assume that the reported effects of Azithromycine on gingival overgrowth, induced by cyclosporine is somehow exaggerated and the effects attributed this medicine is probably inflammation reduction.

Post-transplant lymphoproliferative disorder following kidney transplantation

DEFF Research Database (Denmark)

Maksten, Eva Futtrup; Vase, Maja Ølholm; Kampmann, Jan

2016-01-01

after long-term post-transplantation follow-up. A retrospective population-based cohort study including all kidney transplant recipients at two Danish centres (1990-2011; population covered 3.1 million; 2175 transplantations in 1906 patients). Pathology reports were reviewed for all patient biopsies...

A novel subcutaneous site of islet transplantation superior to the liver.

Science.gov (United States)

Yasunami, Yohichi; Nakafusa, Yuki; Nitta, Naoyoshi; Nakamura, Masafumi; Goto, Masafumi; Ono, Junko; Taniguchi, Masaru

2018-03-08

Islet transplantation is an attractive treatment for patients with insulin-dependent diabetes mellitus, and currently the liver is the favored transplantation site. However, an alternative site is desirable because of the low efficiency of hepatic transplantation, requiring 2-3 donors for a single recipient, and because the transplanted islets cannot be accessed or retrieved. We developed a novel procedure of islet transplantation to the inguinal subcutaneous white adipose tissue (ISWAT) of mice and described functional and morphological characteristics of transplanted syngeneic islets. Also, it was determined whether islet allograft rejection in the ISWAT can be prevented by immunosuppressive agents. Furthermore, it was examined whether human islets function when grafted in this particular site of immune-deficient mice. In this site, transplanted islets are engrafted as clusters and function to reverse STZ-induced diabetes in mice. Importantly, transplanted islets can be visualized by CT and are easily retrievable, and allograft rejection is preventable by blockade of co-stimulatory signals. Of much importance, the efficiency of islet transplantation in this site is superior to the liver, in which hyperglycemia of diabetic recipient mice is ameliorated after transplantation of 200 syngeneic islets (the islet number yielded from 1 mouse pancreas) to the ISWAT but not to the liver. Furthermore, human islets transplanted in this particular site function to reverse diabetes in immune-deficient mice. Thus, the ISWAT is superior to the liver as the site of islet transplantation, which may lead to improved outcome of clinical islet transplantation.

A glow of HLA typing in organ transplantation

Science.gov (United States)

2013-01-01

The transplant of organs and tissues is one of the greatest curative achievements of this century. In organ transplantation, the adaptive immunity is considered the main response exerted to the transplanted tissue, since the main goal of the immune response is the MHC (major histocompatibility complex) molecules expressed on the surface of donor cells. Cell surface molecules that induce an antigenic stimulus cause the rejection immune response to grafted tissue or organ. A wide variety of transplantation antigens have been described, including the major histocompatibility molecules, minor histocompatibility antigens, ABO blood group antigens and endothelial cell antigens. The sensitization to MHC antigens may be caused by transfusions, pregnancy, or failed previous grafts leading to development of anti-human leukocyte antigen (HLA) antibodies that are important factor responsible for graft rejection in solid organ transplantation and play a role in post-transfusion complication Anti-HLA Abs may be present in healthy individuals. Methods for HLA typing are described, including serological methods, molecular techniques of sequence-specific priming (SSP), sequence-specific oligonucleotide probing (SSOP), Sequence based typing (SBT) and reference strand-based conformation analysis (RSCA) method. Problems with organ transplantation are reservoir of organs and immune suppressive treatments that used to decrease rate of rejection with less side effect and complications. PMID:23432791

Photoacoustic imaging of angiogenesis in subdermal islet transplant sites

Science.gov (United States)

Shi, Wei; Pawlick, Rena; Bruni, Antonio; Rafiei, Yasmin; Pepper, Andrew R.; Gala-Lopez, Boris; Choi, Min; Malcolm, Andrew; Zemp, Roger J.; Shapiro, A. M. James

2016-03-01

Exogenous insulin administration is the mainstay treatment therapy for patients with Type-1 diabetes mellitus (T1DM). However, for select patients, clinical islet transplantation is an alternative therapeutic treatment. In this procedure, islets are transplanted into the hepatic portal vein, and despite improved success within the last decade, obstacles are still associated with this approach. It has been discovered that the subcutaneous space may be an effective alternative site for islet transplantation, and may provide advantages of easy access and potential for simple monitoring. The ability to monitor islet viability and the transplant microenvironment may be key to future success in islet transplantation. A subcutaneous device-less technique has been developed to facilitate angiogenesis in the islet transplant site, however, a method for monitoring the potential engraftment site have yet to be explored fully. Here we demonstrate the ability to track angiogenesis in mice with 1, 2, 3 and 4 weeks post-catheter implant on both sides of the abdomen using a FujiFilm VisualSonics Vevo-LAZR system. Quantitative analysis on vessel densities exhibited gradual vessel growth successfully induced by catheter implantation. Our study demonstrates the ability of employing photoacoustic and micro-ultrasound imaging to track angiogenesis around the catheter site prior to islet transplantation.

Intestinal transplantation: The anesthesia perspective.

Science.gov (United States)

Dalal, Aparna

2016-04-01

Intestinal transplantation is a complex and challenging surgery. It is very effective for treating intestinal failure, especially for those patients who cannot tolerate parenteral nutrition nor have extensive abdominal disease. Chronic parental nutrition can induce intestinal failure associated liver disease (IFALD). According to United Network for Organ Sharing (UNOS) data, children with intestinal failure affected by liver disease secondary to parenteral nutrition have the highest mortality on a waiting list when compared with all candidates for solid organ transplantation. Intestinal transplant grafts can be isolated or combined with the liver/duodenum/pancreas. Organ Procurement and Transplantation Network (OPTN) has defined intestinal donor criteria. Living donor intestinal transplant (LDIT) has the advantages of optimal timing, short ischemia time and good human leukocyte antigen matching contributing to lower postoperative complications in the recipient. Thoracic epidurals provide excellent analgesia for the donors, as well as recipients. Recipient management can be challenging. Thrombosis and obstruction of venous access maybe common due to prolonged parenteral nutrition and/or hypercoaguability. Thromboelastography (TEG) is helpful for managing intraoperative product therapy or thrombosis. Large fluid shifts and electrolyte disturbances may occur due to massive blood loss, dehydration, third spacing etc. Intestinal grafts are susceptible to warm and cold ischemia and ischemia-reperfusion injury (IRI). Post-reperfusion syndrome is common. Cardiac or pulmonary clots can be monitored with transesophageal echocardiography (TEE) and treated with recombinant tissue plasminogen activator. Vasopressors maybe used to ensure stable hemodynamics. Post-intestinal transplant patients may need anesthesia for procedures such as biopsies for surveillance of rejection, bronchoscopy, endoscopy, postoperative hemorrhage, anastomotic leaks, thrombosis of grafts etc. Asepsis

MRI and MRA of kidney transplants - evaluation of vessels and perfusion

International Nuclear Information System (INIS)

Wiesner, W.; Pfammatter, T.; Krestin, G.P.; Debatin, J.F.

1998-01-01

Purpose: To document the value of fast contrast enhanced-sequences in the assessment of the vascular supply and parenchymal perfusion in renal transplants. Patients: 18 recipients of a renal transplant were examined with a 1.5-Tesla-MR-system. The protocol included fast contrast enhanced 3D MR angiography and coronal 2D GRE sequences. The transplant artery and vein were assessed as well as regional parenchymal perfusion. Results: 3D MRA detected three transplant artery stenoses and one occlusion. In addition, two renal vein thromboses and one compression were identified. Perfusion deficits were documented in 8 renal transplants: Renal infarction (n=4), cortical necrosis (n=2), acute tubular necrosis (n=1) and venous ischemia (n=1). Fluid collections were documented as well as dilatation of the collecting system and abnormalities of the surrounding tissues. Conclusion: Contrast enhanced MRI and MRA permit a comprehensive assessment of renal transplants without inducing nephrotoxicity. (orig.) [de

Multiple carcinomas in the hemodialysis access induced ischemic hand of a renal transplant patient.

NARCIS (Netherlands)

Hoek, F. van; Tits, H.W.H.J.; Lijnschoten, I. Van; Haas, B.D. De; Scheltinga, M.R.M.

2010-01-01

Long term immunosuppression following organ transplantation promotes the onset of skin cancers. A renal transplant patient developed multiple hyperkeratotic nodi in the left hand and digital pain following prolonged immunosuppression. Several skin abnormalities were observed in an ischemic and

Seronegative Herpes simplex Associated Esophagogastric Ulcer after Liver Transplantation

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Edouard Matevossian

2008-03-01

Full Text Available Herpes simplex infection is characterized by acute or subacute infection, often followed by a chronic carrier state. Consecutive recurrences may flare up if immunocompromise occurs. Herpes simplex associated esophagitis or duodenal ulcer have been reported in immunocompromised patients due to neoplasm, HIV/AIDS or therapeutically induced immune deficiency. Here we report the case of an HSV-DNA seronegative patient who developed grade III dysphagia 13 days after allogeneic liver transplantation. Endoscopy revealed an esophageal-gastric ulcer, and biopsy histopathology showed a distinct fibroplastic and capillary ulcer pattern highly suspicious for viral infection. Immunohistochemistry staining revealed a distinct nuclear positive anti-HSV reaction. Antiviral therapy with acyclovir and high-dose PPI led to a complete revision of clinical symptoms within 48 h. Repeat control endoscopy after 7 days showed complete healing of the former ulcer site at the gastroesophageal junction. Although the incidence of post-transplantation Herpes simplex induced gastroesophageal disease is low, the viral HSV ulcer may be included into a differential diagnosis if dysphagia occurs after transplantation even if HSV-DNA PCR is negative.

Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation

OpenAIRE

Thomson, Angus W.; Zahorchak, Alan F.; Ezzelarab, Mohamed B.; Butterfield, Lisa H.; Lakkis, Fadi G.; Metes, Diana M.

2016-01-01

Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering...

Effect of genes controlling radiation sensitivity on chemically induced mutations in Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Prakash, L.

1976-01-01

The effect of 16 different genes (rad) conferring radiation sensitivity on chemically induced reversion in the yeast Saccharomyces cerevisiae was determined. The site of reversion used was a well-defined chain initiation mutant mapping in the structural gene coding for iso-1-cytochrome c. High doses of EMS and HNO 2 resulted in decreased reversion of cyc1-131 in rad6, rad9 and rad15 strains compared to the normal RAD + strains. In addition, rad52 greatly decreased EMS reversion of cyc1-131 but had no effect on HNO 2 -induced reversion; rad18, on the other hand, increased HNO 2 -induced reversion but did not alter EMS-induced reversion. When NQO was used as the mutagen, every rad gene tested, except for rad18, had an effect on reversion; rad6, rad9, rad15, rad17, rad18, rad22, rev1, rev2, and rev3 lowered NQO reversion while rad1, rad2, rad3, rad4, rad10, rad12, and rad16 increased it compared to the RAD + strain. The effect of rad genes on chemical mutagenesis is discussed in terms of their effect on uv mutagenesis. It is concluded that although the nature of the repair pathways may differ for uv- and chemically-induced mutations in yeast, a functional repair system is required for the induction of mutation by the chemical agents NQO, EMS, and HNO 2

Strain-induced structural changes and chemical reactions. 1: Thermomechanical and kinetic models

International Nuclear Information System (INIS)

Levitas, V.I.; Nesterenko, V.F.; Meyers, M.A.

1998-01-01

Strain-induced chemical reactions were observed recently (Nesterenko et al) in experiments in the shear band in both Ti-Si and Nb-Si mixtures. Reactions can start in the solid state or after melting of at least one component. One of the aims is to find theoretically whether there are possible macroscopic mechanisms of mechanical intensification of the above and other chemical reactions due to plastic shear in the solid state. Continuum thermodynamical theory of structural changes with an athermal kinetics, which includes martensitic phase transformations, plastic strain-induced chemical reactions and polymorphic transformations, is developed at finite strains. The theory includes kinematics, criterion of structural change and extremum principle for determination of all unknown variable parameters for the case with neglected elastic strains. Thermodynamically consistent kinetic theory of thermally activated structural changes is suggested. The concept of the effective temperature is introduced which takes into account that temperature can vary significantly (on 1,000 K) during the chemical reactions under consideration. The theory will be applied in Part 2 of the paper for the description of chemical reactions in the shear band

Immunosuppressive effect of compound K on islet transplantation in an STZ-induced diabetic mouse model.

Science.gov (United States)

Ma, Peng-Fei; Jiang, Jie; Gao, Chang; Cheng, Pan-Pan; Li, Jia-Li; Huang, Xin; Lin, Ying-Ying; Li, Qing; Peng, Yuan-Zheng; Cai, Mei-Chun; Shao, Wei; Zhu, Qi; Han, Sai; Qin, Qing; Xia, Jun-Jie; Qi, Zhong-Quan

2014-10-01

Islet transplantation is a therapeutic option for type 1 diabetes, but its long-term success is limited by islet allograft survival. Many factors imperil islet survival, especially the adverse effects and toxicity due to clinical immunosuppressants. Compound (Cpd) K is a synthesized analog of highly unsaturated fatty acids from Isatis tinctoria L. (Cruciferae). Here we investigated the therapeutic effect of Cpd K in diabetic mice and found that it significantly prolonged islet allograft survival with minimal adverse effects after 10 days. Furthermore, it reduced the proportion of CD4(+) and CD8(+) T cells in spleen and lymph nodes, inhibited inflammatory cell infiltration in allografts, suppressed serum interleukin-2 and interferon-γ secretion, and increased transforming growth factor-β and Foxp3 mRNA expression. Surprisingly, Cpd K and rapamycin had a synergistic effect. Cpd K suppressed proliferation of naïve T cells by inducing T-cell anergy and promoting the generation of regulatory T cells. In addition, nuclear factor-κB signaling was also blocked. Taken together, these findings indicate that Cpd K may have a potential immunosuppressant effect on islet transplantation. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Isolation of Human Induced Pluripotent Stem Cell-Derived Dopaminergic Progenitors by Cell Sorting for Successful Transplantation

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Daisuke Doi

2014-03-01

Full Text Available Human induced pluripotent stem cells (iPSCs can provide a promising source of midbrain dopaminergic (DA neurons for cell replacement therapy for Parkinson’s disease. However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. Here, we show that human iPSC-derived DA progenitor cells can be efficiently isolated by cell sorting using a floor plate marker, CORIN. We induced DA neurons using scalable culture conditions on human laminin fragment, and the sorted CORIN+ cells expressed the midbrain DA progenitor markers, FOXA2 and LMX1A. When transplanted into 6-OHDA-lesioned rats, the CORIN+ cells survived and differentiated into midbrain DA neurons in vivo, resulting in significant improvement of the motor behavior, without tumor formation. In particular, the CORIN+ cells in a NURR1+ cell-dominant stage exhibited the best survival and function as DA neurons. Our method is a favorable strategy in terms of scalability, safety, and efficiency and may be advantageous for clinical application.

GINGIVAL OVERGROWTH INDUCED BY IMMUNOSUPPRESSIVE TREATMENT WITH CYCLOSPORINE A AND MYCOPHENOLATE MOFETIL IN A PATIENT WITH KIDNEY TRANSPLANT – A CASE REPORT AND LITERATURE REVIEW

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Daniela Trandafir

2013-07-01

Full Text Available Cyclosporine A, a drug that inhibits the immuneresponse, has been widely used for over 30 years in immunosuppressivetherapy protocols for patient‑recipients ofthe transplanted organs. One of the commonly reportedside effects of Cyclosporine A is gingival overgrowth, withvarying degrees of severity, which may interfere with theaesthetics and normal functions of the oral cavity. Combinationwith other drugs that can recognize the gum tissueas a secondary target organ increases the risk ofdrug‑induced gingival overgrowth. In cases where a lowerdose of Cyclosporine A or conversion to another immunosuppressiveagent (a drug not assigned to such a sideeffect are not possible, the management of severe gingivalovergrowth focuses on surgical excision of the excessivelyproliferated gingival tissue. We report the case of a youngadult with moderate drug‑induced gingival overgrowth,the beneficiary of a functional transplanted kidney about9 years ago, treated with two immunosuppressives, whohas undergone gingivectomy with electrocautery, as a necessaryintervention to improve the oral hygiene and toavoid worsening of malfunctions in the oral cavity.

Early Conversion from Tacrolimus to Belatacept in a Highly Sensitized Renal Allograft Recipient with Calcineurin Inhibitor-Induced de novo Post-Transplant Hemolytic Uremic Syndrome

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Vasishta S. Tatapudi

2018-01-01

Full Text Available Background: Kidney transplantation is the first-line therapy for patients with end-stage renal disease since it offers greater long-term survival and improved quality of life when compared to dialysis. The advent of calcineurin inhibitor (CNI-based maintenance immunosuppression has led to a clinically significant decline in the rate of acute rejection and better short-term graft survival rates. However, these gains have not translated into improvement in long-term graft survival. CNI-related nephrotoxicity and metabolic side effects are thought to be partly responsible for this. Case Presentation: Here, we report the conversion of a highly sensitized renal transplant recipient with pretransplant donor-specific antibodies from tacrolimus to belatacept within 1 week of transplantation. This substitution was necessitated by the diagnosis of CNI-induced de novo post-transplant hemolytic uremic syndrome. Conclusion: Belatacept is a novel costimulation blocker that is devoid of the nephrotoxic properties of CNIs and has been shown to positively impact long-term graft survival and preserve renal allograft function in low-immunologic-risk kidney transplant recipients. Data regarding its use in patients who are broadly sensitized to human leukocyte antigens are scarce, and the increased risk of rejection associated with belatacept has been a deterrent to more widespread use of this immunosuppressive agent. This case serves as an example of a highly sensitized patient that has been successfully converted to a belatacept-based CNI-free regimen.

Kidney transplant

Science.gov (United States)

... always take your medicine as directed. Alternative Names Renal transplant; Transplant - kidney Patient Instructions Kidney removal - discharge Images Kidney anatomy Kidney - blood and urine flow Kidneys Kidney transplant - ...

Lung and renal transplantation

Directory of Open Access Journals (Sweden)

Patrícia Caetano Mota

2009-11-01

Full Text Available Renal transplantation is the most common type of solid organ transplantation and kidney transplant recipients are susceptible to pulmonary complications of immunosuppressive therapy, which are a diagnostic and therapeutic challenge. Aim: To evaluate patients admitted to the Renal Transplant Unit (RTU of Hospital de S. João with respiratory disease. Subject and methods: We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months. Results: Thirty-six patients were included. Mean age 55.2 ( ± 13.4 years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9% or tacrolimus (22.2% or rapamycin (13.9%. Thirty-one patients (86.1% presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2% pneumonias, 5 (16.1% opportunistic infections, 2 (6.5% tracheobronchitis, and 1 case (3.2% of lung abscesses. Microbiological agent was identified in 7 cases (22.6%. Five patients (13.9% presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%, diagnostic in 10 cases (66.7%. Mean hospital stay was 17.1 ( ± 18.5 days and no related death was observed. Conclusion: Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy. Resumo: O transplante renal é o transplante de órgãos sólidos mais frequente, sendo os transplantados renais alvo de complicações pulmonares inerentes à própria terapêutica imunossupressora, as quais constituem, por vezes, um desafio diagnóstico e terapêutico. Objectivo: Avaliar os doentes admitidos na Unidade de Transplante Renal (UTR do Hospital de S. João com o diagnóstico de patologia respirat

Post-Renal Transplant Diabetes Mellitus in Korean Subjects: Superimposition of Transplant-Related Immunosuppressant Factors on Genetic and Type 2 Diabetic Risk Factors

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Hyun Chul Lee

2012-06-01

Full Text Available Postrenal transplantation diabetes mellitus (PTDM, or new-onset diabetes after organ transplantation, is an important chronic transplant-associated complication. Similar to type 2 diabetes, decreased insulin secretion and increased insulin resistance are important to the pathophysiologic mechanism behind the development of PTDM. However, β-cell dysfunction rather than insulin resistance seems to be a greater contributing factor in the development of PTDM. Increased age, family history of diabetes, ethnicity, genetic variation, obesity, and hepatitis C are partially accountable for an increased underlying risk of PTDM in renal allograft recipients. In addition, the use of and kinds of immunosuppressive agents are key transplant-associated risk factors. Recently, a number of genetic variants or polymorphisms susceptible to immunosuppressants have been reported to be associated with calcineurin inhibition-induced β-cell dysfunction. The identification of high risk factors of PTDM would help prevent PTDM and improve long-term patient outcomes by allowing for personalized immunosuppressant regimens and by managing cardiovascular risk factors.

Animal Models of Diabetes Mellitus for Islet Transplantation

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Naoaki Sakata

2012-01-01

Full Text Available Due to current improvements in techniques for islet isolation and transplantation and protocols for immunosuppressants, islet transplantation has become an effective treatment for severe diabetes patients. Many diabetic animal models have contributed to such improvements. In this paper, we focus on 3 types of models with different mechanisms for inducing diabetes mellitus (DM: models induced by drugs including streptozotocin (STZ, pancreatomized models, and spontaneous models due to autoimmunity. STZ-induced diabetes is one of the most commonly used experimental diabetic models and is employed using many specimens including rodents, pigs or monkeys. The management of STZ models is well established for islet studies. Pancreatomized models reveal different aspects compared to STZ-induced models in terms of loss of function in the increase and decrease of blood glucose and therefore are useful for evaluating the condition in total pancreatomized patients. Spontaneous models are useful for preclinical studies including the assessment of immunosuppressants because such models involve the same mechanisms as type 1 DM in the clinical setting. In conclusion, islet researchers should select suitable diabetic animal models according to the aim of the study.

Is the repair of articular cartilage lesion by costal chondrocyte transplantation donor age-dependent? An experimental study in rabbits.

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Janusz Popko

2006-09-01

Full Text Available The repair of chondral injuries is a very important problem and a subject of many experimental and clinical studies. Different techniques to induce articular cartilage repair are under investigation. In the present study, we have investigated whether the repair of articular cartilage folowing costal chondrocyte transplantation is donor age-dependent. Transplantation of costal chondrocytes from 4- and 24-week old donors, with artificially induced femoral cartilage lesion, was performed on fourteen 20-week-old New Zealand White male rabbits. In the control group, the lesion was left without chondrocyte transplantation. The evaluation of the cartilage repair was performed after 12 weeks of transplantation. We analyzed the macroscopic and histological appearance of the newly formed tissue. Immunohistochemistry was also performed using monoclonal antibodies against rabbit collagen type II. The newly formed tissue had a hyaline-like appearance in most of the lesions after chondrocyte transplantation. Positive immunohistochemical reaction for collagen II was also observed in both groups with transplanted chondrocytes. Cartilage from adult donors required longer isolation time and induced slightly poorer repair. However, hyaline-like cartilage was observed in most specimens from this group, in contrast to the control group, where fibrous connective tissue filled the lesions. Rabbit costal chondrocytes seem to be a potentially useful material for inducing articular cartilage repair and, even more important, they can also be derived from adult, sexually mature animals.

Combination of exogenous cell transplantation and 5-HT4 receptor agonism induce endogenous enteric neural crest-derived cells in a rat hypoganglionosis model.

Science.gov (United States)

Yu, Hui; Zheng, Bai-Jun; Pan, Wei-Kang; Wang, Huai-Jie; Xie, Chong; Zhao, Yu-Ying; Chen, Xin-Lin; Liu, Yong; Gao, Ya

2017-02-01

Enteric neural crest-derived cells (ENCCs) can migrate into endogenous ganglia and differentiate into progeny cells, and have even partially rescued bowel function; however, poor reliability and limited functional recovery after ENCC transplantation have yet to be addressed. Here, we investigated the induction of endogenous ENCCs by combining exogenous ENCC transplantation with a 5-HT 4 receptor agonist mosapride in a rat model of hypoganglionosis, established by benzalkonium chloride treatment. ENCCs, isolated from the gut of newborn rats, were labeled with a lentiviral eGFP reporter. ENCCs and rats were treated with the 5-HT 4 receptor agonist/antagonist. The labeled ENCCs were then transplanted into the muscular layer of benzalkonium chloride-treated colons. At given days post-intervention, colonic tissue samples were removed for histological analysis. ENCCs and neurons were detected by eGFP expression and immunoreactivity to p75 NTR and peripherin, respectively. eGFP-positive ENCCs and neurons could survive and maintain levels of fluorescence after transplantation. With longer times post-intervention, the number of peripherin-positive cells gradually increased in all groups. Significantly more peripherin-positive cells were found following ENCCs plus mosapride treatment, compared with the other groups. These results show that exogenous ENCCs combined with the 5-HT 4 receptor agonist effectively induced endogenous ENCCs proliferation and differentiation in a rat hypoganglionosis model. Copyright © 2016 Elsevier Inc. All rights reserved.

DNA damage, acetylcholinesterase activity and lysosomal stability in native and transplanted mussels (Mytilus edulis) in areas close to coastal chemical dumping sites in Denmark

DEFF Research Database (Denmark)

Rank, Jette; Lehtonen, Kari K.; Strand, Jakob

2007-01-01

Biomarkers of genotoxicity (DNA damage, measured as tail moment in the Comet assay), neurotoxicity (acetylcholinesterase inhibition, AChE) and general stress (lysosomal membrane stability, LMS) were studied in native and transplanted blue mussels (Mytilus edulis) in coastal areas of western Denmark...... of chemical pollution complex, as seen especially in the variability in results on DNA damage, and also in regard to AChE activity. These investigations further stress the importance of understanding the effects of natural factors (salinity, temperature, water levels, rain and storm events) in correct...

Lack of chemically induced mutation in repair-deficient mutants of yeast

International Nuclear Information System (INIS)

Prakash, L.

1974-01-01

Two genes, rad6 and rad9, that confer radiation sensitivity in the yeast Saccharomyces cerevisiae also greatly reduce the frequency of chemically-induced reversions of a tester mutant cyc1-131, which is a chain initiation mutant in the structural gene determining iso-1-cytochrome c. Mutations induced by ethyl methanesulfonate (EMS), diethyl sulfate (DES), methyl methanesulfonate (MMS), dimethyl sulfate (DMS), nitroquinoline oxide (NQO), nitrosoguanidine (NTG), nitrogen mustard (HN2), β-propiolactone, and tritiated uridine, as well as mutations induced by ultraviolet light (UV) and ionizing radiation were greatly diminished in strains homozygous for either the rad6 or rad9 gene. Nitrous acid and nitrosoimidazolidone (NIL), on the other hand, were highly mutagenic in these repair-deficient mutants, and at low doses, these mutagens acted with about the same efficiency as in the normal RAD strain. At high doses of either nitrous acid or NIL, however, reversion frequencies were significantly reduced in the two rad mutants compared to normal strains. Although both rad mutants are immutable to about the same extent, the rad9 strains tend to be less sensitive to the lethal effect of chemical mutagens than rad6 strains. It is concluded that yeast requires a functional repair system for mutation induction by chemical agents. (auth)

Lack of chemically induced mutation in repair-deficient mutants of yeast.

Science.gov (United States)

Prakash, L

1974-12-01

Two genes, rad6 and rad9, that confer radiation sensitivity in the yeast Saccharomyces cerevisiae also greatly reduce the frequency of chemically-induced reversions of a tester mutant cyc1-131, which is a chain initiation mutant in the structural gene determining iso-1-cytochrome c. Mutations induced by ethyl methanesulfonate (EMS), diethyl sulfate (DES), methyl methanesulfonate (MMS), dimethyl sulfate (DMS), nitroquinoline oxide (NQO), nitrosoguanidine (NTG), nitrogen mustard (HN2), beta-propiolactone, and tritiated uridine, as well as mutations induced by ultraviolet light (UV) and ionizing radiation were greatly diminished in strains homozygous for either the rad6 or rad9 gene. Nitrous acid and nitrosoimidazolidone (NIL), on the other hand, were highly mutagenic in these repair-deficient mutants, and at low doses, these mutagens acted with about the same efficiency as in the normal RAD strain. At high doses of either nitrous acid or NIL, however, reversion frequencies were significantly reduced in the two rad mutants compared to normal strains. Although both rad mutants are immutable to about the same extent, the rad9 strains tend to be less sensitive to the lethal effect of chemical mutagens than rad6 strains. It is concluded that yeast requires a functional repair system for mutation induction by chemical agents.

On the Chemical Mixing Induced by Internal Gravity Waves

Energy Technology Data Exchange (ETDEWEB)

Rogers, T. M. [School of Mathematics, Statistics and Physics, Newcastle University, Newcastle upon Tyne (United Kingdom); McElwaine, J. N. [Planetary Science Institute, Tucson, AZ 85721 (United States)

2017-10-10

Detailed modeling of stellar evolution requires a better understanding of the (magneto)hydrodynamic processes that mix chemical elements and transport angular momentum. Understanding these processes is crucial if we are to accurately interpret observations of chemical abundance anomalies, surface rotation measurements, and asteroseismic data. Here, we use two-dimensional hydrodynamic simulations of the generation and propagation of internal gravity waves in an intermediate-mass star to measure the chemical mixing induced by these waves. We show that such mixing can generally be treated as a diffusive process. We then show that the local diffusion coefficient does not depend on the local fluid velocity, but rather on the wave amplitude. We then use these findings to provide a simple parameterization for this diffusion, which can be incorporated into stellar evolution codes and tested against observations.

Near-field photochemical and radiation-induced chemical fabrication of nanopatterns of a self-assembled silane monolayer

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Ulrich C. Fischer

2014-09-01

Full Text Available A general concept for parallel near-field photochemical and radiation-induced chemical processes for the fabrication of nanopatterns of a self-assembled monolayer (SAM of (3-aminopropyltriethoxysilane (APTES is explored with three different processes: 1 a near-field photochemical process by photochemical bleaching of a monomolecular layer of dye molecules chemically bound to an APTES SAM, 2 a chemical process induced by oxygen plasma etching as well as 3 a combined near-field UV-photochemical and ozone-induced chemical process, which is applied directly to an APTES SAM. All approaches employ a sandwich configuration of the surface-supported SAM, and a lithographic mask in form of gold nanostructures fabricated through colloidal sphere lithography (CL, which is either exposed to visible light, oxygen plasma or an UV–ozone atmosphere. The gold mask has the function to inhibit the photochemical reactions by highly localized near-field interactions between metal mask and SAM and to inhibit the radiation-induced chemical reactions by casting a highly localized shadow. The removal of the gold mask reveals the SAM nanopattern.

Roles of Toll-like receptors in allogeneic islet transplantation.

Science.gov (United States)

Ro, Han; Hong, Juho; Kim, Beom Seok; Lee, Eun Won; Kim, Myung-Gyu; Han, Kyu Hyun; Yeom, Hye-Jung; Lee, Eun Mi; Jeong, Jong Cheol; Oh, Kook-Hwan; Ahn, Curie; Yang, Jaeseok

2012-11-27

Toll-like receptors (TLRs) are involved in the rejection of solid organ allografts. However, the roles of TLRs in islets are still controversial. We investigated the roles of TLRs in donor islets together with those in recipients in allogeneic islet transplantation. To assess the roles of TLRs in either donor islets or recipients, allogeneic islet transplantation was performed using myeloid differentiation factor 88 (MyD88)-knockout (KO), TLR4-KO, or Toll/interleukin-1 receptor domain-containing adaptor-inducing interferon-β (TRIF)-KO mice. Both polyriboinosinic polyribocytidylic acid and lipopolysaccharide (LPS) stimulation induced the mRNA expression of regulated and normal T cell expressed and secreted, interferon-γ-inducible protein-10, monocyte chemotactic protein-1, interleukin-8, and inducible nitric oxide synthase in murine islets, whereas the induction was attenuated in TRIF-KO, interferon-β promoter stimulator-1-KO, and TLR4-KO mice. When islets from MyD88-KO, TLR4-KO, or TRIF-KO C57BL/6 mice were transplanted to BALB/c recipients, graft survival was not better than that of wild-type (WT) islets. However, the survival of the MyD88-KO islet allograft was significantly prolonged when combined with anti-CD40L. In parallel, LPS stimulation in donor islets interfered with anti-CD40L blockade-mediated long-term survival of islet allografts in TLR4-KO recipients. LPS stimulation increased the perigraft infiltration of both T cells and macrophages. Then again, when islets from WT BALB/c mice were transplanted to MyD88-KO, TRIF-KO, or WT C57BL/6 mice, there was no difference in graft survival, although some of the MyD88-KO recipients obtained long-term graft survival. However, anti-CD40L prolonged graft survival significantly in MyD88-KO recipients. The absence of MyD88 in either donors or recipients decreased the perigraft infiltration of inflammatory cells when combined with anti-CD40L. TLRs in both donor islets and recipients are involved in islet allograft

Intestine Transplant

Science.gov (United States)

... After the transplant Preventing rejection Post-transplant medications Types of immunosuppressants Switching immunosuppressants Side effects Other medications Generic and brand name drugs Post-transplant tests Infections and immunity Lifestyle changes Health concerns Back to work or ...

Enhance Therapeutic Effect Compared with Single Transplantation in Systemic Lupus Erythematosus

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Dandan Wang

2012-01-01

Full Text Available The clinical trial of allogenic mesenchymal stem cells (MSCs transplantation for refractory SLE patients has shown significant safety and efficacy profiles. However, the optimum frequency of the MSCs transplantation (MSCT is unknown. This study was undertaken to observe whether double transplantations of MSCs is superior to single transplantation. Fifty-eight refractory SLE patients were enrolled in this study, in which 30 were randomly given single MSCT, and the other 28 were given double MSCT. Patients were followed up for rates of survival, disease remission, and relapse, as well as transplantation-related adverse events. SLE disease activity index (SLEDAI and serologic features were evaluated. Our results showed that no remarkable differences between single and double allogenic MSCT were found in terms of disease remission and relapse, amelioration of disease activity, and serum indexes in an SLE clinical trial with more than one year followup. This study demonstrated that single MSCs transplantation at the dose of one million MSCs per kilogram of body weight was sufficient to induce disease remission for refractory SLE patients.

In Utero Hematopoietic Cell Transplantation for Hemoglobinopathies

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Tippi C. Mackenzie

2015-01-01

Full Text Available In utero hematopoietic cell transplantation (IUHCTx is a promising strategy to circumvent the challenges of postnatal hematopoietic stem cell (HSC transplantation. The goal of IUHCTx is to introduce donor cells into a naïve host prior to immune maturation, thereby inducing donor–specific tolerance. Thus, this technique has the potential of avoiding host myeloablative conditioning with cytotoxic agents. Over the past two decades, several attempts at IUHCTx have been made to cure numerous underlying congenital anomalies with limited success. In this review, we will briefly review the history of IUHCTx and give a perspective on alpha thalassemia major, one target disease for its clinical application.

Aspirin resistance as cardiovascular risk after kidney transplantation

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Sandor, Barbara; Varga, Adam; Rabai, Miklos; Toth, Andras; Papp, Judit; Toth, Kalman; Szakaly, Peter

2014-05-01

International surveys have shown that the leading cause of death after kidney transplantation has cardiovascular origin with a prevalence of 35-40%. As a preventive strategy these patients receive aspirin (ASA) therapy, even though their rate of aspirin resistance is still unknown. In our study, platelet aggregation measurements were performed between 2009 and 2012 investigating the laboratory effect of low-dose aspirin (100 mg) treatment using a CARAT TX4 optical aggregometer. ASA therapy was considered clinically effective in case of low ( i.e., below 40%) epinephrine-induced (10 μM) platelet aggregation index. Rate of aspirin resistance, morbidity and mortality data of kidney transplanted patients (n = 255, mean age: 49 ± 12 years) were compared to a patient population with cardio- and cerebrovascular diseases (n = 346, mean age: 52.6 ± 11 years). Rate of aspirin resistance was significantly higher in the renal transplantation group (RT) compared to the positive control group (PC) (35.9% vs. 25.6%, p aspirin resistance contributes to the high cardiovascular mortality after kidney transplantation.

Hepatocyte transplantation improves early survival after partial hepatic resection and irradiation

International Nuclear Information System (INIS)

Guha, C.; Sharma, A.; Alfieri, A.; Guha, U.; Sokhi, R.; Gagandeep, S.; Gupta, S.; Vikram, B.; RoyChowdhury, J.

1997-01-01

Purpose: Radiation therapy (RT) is limited in its role as an adjuvant therapy of intrahepatic malignancies because of lower tolerance of human liver to irradiation (TD (5(5)) -TD (50(5)) ∼ 30-40 Gy). Although, surgical resection of primary or metastatic hepatic tumors has been shown to prolong survival, it is often limited by the presence of residual disease. RT could potentially improve survival of patients with positive surgical margins. However, radiation damage to the liver may be enhanced by hepatocellular proliferation induced by partial hepatic (PH) resection. We hypothesize that hepatocyte transplantation would be able to provide metabolic support and modulate the development of radiation-induced liver disease post-resection. The present study was designed to test the potential of hepatocyte transplantation in modifying the outcome of hepatocellular damage induced by PH and RT. Methods: Adult male Fischer 344 rats (Charles River) received hepatic irradiation of 50 Gy in a single fraction, after surgical exposure and shielding of the stomach and intestine, using a 320 MGC Philips orthovoltage unit. Immediately following irradiation, a two-third partial hepatectomy was performed. Four days post-radiation, the treatment group was injected with 5 x 10 6 syngeneic hepatocytes into the splenic pulp after a left subcostal incision, which allows homogeneous liver engraftment of the transplanted hepatocytes. Hematoxylin and eosin stains of liver biopsies, performed at various time points (3 days, 1, 2, 3 weeks or, anytime when animals died) were used for histologic evaluation. Time-adjusted survival was calculated from the date of irradiation by the product-limit Kaplan-Meier method, adjusting the denominator at every time point for the number of rats at risk. Results: Eight weeks after RT, 30% (n = 11) of the control animals (PH + 50 Gy) were alive compared to 100% (n = 9) of the transplant recipients (p <0.05). The median survival of the control group was 15

Generation of induced pluripotent stem cells as a potential source of hematopoietic stem cells for transplant in PNH patients.

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Phondeechareon, Tanapol; Wattanapanitch, Methichit; U-Pratya, Yaowalak; Damkham, Chanapa; Klincumhom, Nuttha; Lorthongpanich, Chanchao; Kheolamai, Pakpoom; Laowtammathron, Chuti; Issaragrisil, Surapol

2016-10-01

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia caused by lack of CD55 and CD59 on blood cell membrane leading to increased sensitivity of blood cells to complement. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for PNH, however, lack of HLA-matched donors and post-transplant complications are major concerns. Induced pluripotent stem cells (iPSCs) derived from patients are an attractive source for generating autologous HSCs to avoid adverse effects resulting from allogeneic HSCT. The disease involves only HSCs and their progeny; therefore, other tissues are not affected by the mutation and may be used to produce disease-free autologous HSCs. This study aimed to derive PNH patient-specific iPSCs from human dermal fibroblasts (HDFs), characterize and differentiate to hematopoietic cells using a feeder-free protocol. Analysis of CD55 and CD59 expression was performed before and after reprogramming, and hematopoietic differentiation. Patients' dermal fibroblasts expressed CD55 and CD59 at normal levels and the normal expression remained after reprogramming. The iPSCs derived from PNH patients had typical pluripotent properties and differentiation capacities with normal karyotype. After hematopoietic differentiation, the differentiated cells expressed early hematopoietic markers (CD34 and CD43) with normal CD59 expression. The iPSCs derived from HDFs of PNH patients have normal levels of CD55 and CD59 expression and hold promise as a potential source of HSCs for autologous transplantation to cure PNH patients.

Neuroradiology of the normal and pathological anatomy of the rat brain. Pt. 2. Microangiographic investigations of the vascularisation of transplanted malignant brain tumors

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Schumacher, M; Weisser, G; Voigt, K; Mennel, H D

1980-11-01

70 BD-IX rats, in which chemically induced mixed gliomas have been transplanted intracerebrally, were investigated by microangiography. The pattern and the degree of tumor vascularisation of all animals was correlated with the histological findings. Dependent on the type of the tumor different localisations of tumor growth could be found: G XII-gliomas preferred the juxta-ventricular region and subarachnoid space whereas GL 2.2-gliomas mainly grew as solid intracerebral space occupying lesions. Microangiograms of all tumor stages from the 14th to 42nd day after transplantation revealed a typical vascular pattern consisting of lacunar glomerulose and netlike vessels. Further, necrosis, bleedings into the tumor, and irregularities of the capillary network could be demonstrated. The volume, age and vascularisation of the tumors are correlated and the results are discussed with regard to the principles of tumor growth and malignancy.

Acute rejection after kidney transplantation promotes graft fibrosis with elevated adenosine level in rat.

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Mingliang Li

Full Text Available Chronic allograft nephropathy is a worldwide issue with the major feature of progressive allograft fibrosis, eventually ending with graft loss. Adenosine has been demonstrated to play an important role in process of fibrosis. Our study aimed to investigate the relationship between adenosine and fibrosis in renal allograft acute rejection in rat.Wistar rats and SD rats were selected as experimental animals. Our study designed two groups. In the allograft transplantation group, kidneys of Wistar rats were orthotopically transplanted into SD rat recipients, the same species but not genetically identical, to induce acute rejection. Kidney transplantations of SD rats to SD rats which were genetically identical were served as the control. We established rat models and detected a series of indicators. All data were analyzed statistically. P<0.05 was considered statistically significant.Compared with the control group, levels of adenosine increased significantly in the allograft transplantation group, in which acute rejection was induced (P<0.05. Progressive allograft fibrosis as well as collagen deposition were observed.These findings suggested that level of adenosine was upregulated in acute rejection after kidney allograft transplantation in rat. Acute rejection may promote renal allograft fibrosis via the adenosine signaling pathways.

T Cell-Replete Peripheral Blood Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide Results in Outcomes Similar to Transplantation from Traditionally Matched Donors in Active Disease Acute Myeloid Leukemia.

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How, Joan; Slade, Michael; Vu, Khoan; DiPersio, John F; Westervelt, Peter; Uy, Geoffrey L; Abboud, Camille N; Vij, Ravi; Schroeder, Mark A; Fehniger, Todd A; Romee, Rizwan

2017-04-01

Outcomes for patients with acute myeloid leukemia (AML) who fail to achieve complete remission remain poor. Hematopoietic cell transplantation (HCT) has been shown to induce long-term survival in AML patients with active disease. HCT is largely performed with HLA-matched unrelated or HLA-matched related donors. Recently, HCT with HLA-haploidentical related donors has been identified as a feasible option when HLA-matched donors are not immediately available. However, there are little data comparing outcomes for AML patients with active disease who receive haploidentical versus traditionally matched HCT. We retrospectively analyzed data from 99 AML patients with active disease undergoing allogeneic HCT at a single institution. Forty-three patients received unrelated donor HCT, 32 patients received matched related donor HCT, and 24 patients received peripheral blood haploidentical HCT with post-transplantation cyclophosphamide. We found no significant differences between treatment groups in terms of overall survival (OS), event-free survival, transplantation-related mortality, cumulative incidence of relapse, and cumulative incidence of acute and chronic graft-versus-host disease (GVHD). We performed univariate regression analysis of variables that modified OS in all patients and found only younger age at transplantation and development of chronic GVHD significantly improved outcome. Although limited by our relatively small sample size, these results indicate that haploidentical HCT in active AML patients have comparable outcomes to HCT with traditionally matched donors. Haploidentical HCT can be considered in this population of high-risk patients when matched donors are unavailable or when wait times for transplantation are unacceptably long. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Evaluating the impact of pre-transplant desensitization utilizing a plasmapheresis and low-dose intravenous immunoglobulin protocol on BK viremia in renal transplant recipients.

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Gabardi, S; Townsend, K; Martin, S T; Chandraker, A

2013-08-01

A correlation exists between polyomavirus BK (BKV) viremia in renal transplant recipients (RTR) and the degree of immunosuppression. However, the impact of pre-transplant desensitization on the incidence of BKV viremia is unknown. This retrospective study evaluated living-donor RTR between January 2004 and December 2008 receiving routine BKV viral load monitoring. Patients were divided into those who underwent pre-transplant desensitization (n = 20) and those who did not (n = 71). The primary endpoint was the incidence of BKV viremia at 1 year post transplant. All demographic data were similar, except for more female patients (65% vs. 36.6%; P = 0.0392) in the desensitized group. More desensitized patients had a previous transplant (75% vs. 12.7%; P < 0.0001) and were more likely to be induced with basiliximab (75% vs. 35.2%; P = 0.0021). Following transplantation, antibody-mediated rejection (AMR) rates were highest in the desensitized group (55% vs. 1.4%; P < 0.0001). The incidence of BKV viremia at 1 year post transplant was significantly higher in desensitized patients (45% vs. 19.7%; P = 0.0385). Desensitization was also associated with a higher prevalence of BKV viremia at any time post transplant (50% vs. 22.5%; P = 0.0245), polyomavirus-associated nephropathy (20% vs. 2.8%; P = 0.0198) and BKV-related allograft loss (10% vs. 0%; P = 0.0464). Also of note, in a subgroup analysis of only our desensitized patients, it did not appear that development of AMR significantly impacted the incidence of BKV viremia in these individuals. This analysis reveals that pre-transplant desensitization significantly increases the risk for BKV viremia and nephropathy. © 2013 John Wiley & Sons A/S.

Prospective clinical testing of regulatory dendritic cells (DCreg) in organ transplantation

OpenAIRE

ANGUS W THOMSON; ALAN F ZAHORCHAK; Mohamed B. Ezzelarab; Lisa H. Butterfield; Fadi G. Lakkis; Diana M Metes

2016-01-01

Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering...

Generation, purification and transplantation of photoreceptors derived from human induced pluripotent stem cells.

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Deepak A Lamba

2010-01-01

Full Text Available Inherited and acquired retinal degenerations are frequent causes of visual impairment and photoreceptor cell replacement therapy may restore visual function to these individuals. To provide a source of new retinal neurons for cell based therapies, we developed methods to derive retinal progenitors from human ES cells.In this report we have used a similar method to direct induced pluripotent stem cells (iPS from human fibroblasts to a retinal progenitor fate, competent to generate photoreceptors. We also found we could purify the photoreceptors derived from the iPS cells using fluorescence activated cell sorting (FACS after labeling photoreceptors with a lentivirus driving GFP from the IRBP cis-regulatory sequences. Moreover, we found that when we transplanted the FACS purified iPSC derived photoreceptors, they were able to integrate into a normal mouse retina and express photoreceptor markers.This report provides evidence that enriched populations of human photoreceptors can be derived from iPS cells.

Renal transplantation in Mapuche people.

Science.gov (United States)

Ardiles, R; Beltrán, R; Jerez, V; Droguett, M A; Mezzano, S; Ardiles, L

2008-04-01

Previous studies have demonstrated higher concentrations of some histocompatibility antigens in Mapuche people compared with non-Mapuche Chileans in the renal transplantation program. With the aim of evaluating whether those antigenic differences might induce differences in the outcomes of renal transplantation among patients belonging to that ethnic group, we reviewed HLA studies and at least 6 months follow-up of all patients with a first kidney transplant between 1980 and 2006. The 248 patients had a mean age of 37.6 years, 40% were females, and 48% had living related donors. The mean kidney follow-up was 90 months and patient follow-up was 106 months. Thirty-nine patients (16%) were classified as Mapuche, according to their surnames, including 16 women with overall mean age of 34.5 years, and 14 had been transplanted from a living related donor. Mapuche patients received organs with better HLA matching expressed as number of identities (3.4 +/- 0.1 versus 2.8 +/- 0.1 among non-Mapuche; P or = 3 compatibilities was significantly higher (Mapuche 38% versus non-Mapuche 22%; P Mapuche; and 83% and 65%, respectively, for non-Mapuche. Patient survival rates were 97% at 5 years and 86% at 10 years in the Mapuche group versus 91% and 79%, respectively, in the non-Mapuche group; both results were not significantly different. Our results showed similar outcomes of kidney and patient survivals among Mapuche people even when they received organs with better HLA matches.

[Cooling shell in renal transplantation. Thermometric evaluation of a prototype].

Science.gov (United States)

Desgrandchamps, F; Eugene, M; Tuchschmid, Y; Muller, F; Teillac, P; Idatte, J M; Le Duc, A

1996-02-01

We have developed a cooling system for renal transplants designed to eliminate the second period of warm ischaemia corresponding to the vascular anastomosis phase of renal transplantation. This is an autonomous and independent system which forms a shell around the transplant. Following application of the system, cooling is achieved by refrigeration of a Multitherm sponge contained in the wall of the shell. The thermometric characteristics of a prototype were evaluated in vitro and in vivo in pigs. This system allows the kidney to be preserved at a temperature of less than 10 degrees C for 1 hour without inducing any risk of lesions of the renal surface. Human applications should be developed in the near future.

Islet alloautotransplantation: Allogeneic pancreas transplantation followed by transplant pancreatectomy and islet transplantation.

Science.gov (United States)

Nijhoff, M F; Dubbeld, J; van Erkel, A R; van der Boog, P J M; Rabelink, T J; Engelse, M A; de Koning, E J P

2018-04-01

Simultaneous pancreas-kidney (SPK) transplantation is an important treatment option for patients with type 1 diabetes (T1D) and end-stage renal disease (ESRD). Due to complications, in up to 10% of patients, allograft pancreatectomy is necessary shortly after transplantation. Usually the donor pancreas is discarded. Here, we report on a novel procedure to rescue endocrine tissue after allograft pancreatectomy. A 39-year-old woman with T1D and ESRD who had undergone SPK transplantation required emergency allograft pancreatectomy due to bleeding at the vascular anastomosis. Islets were isolated from the removed pancreas allograft, and almost 480 000 islet equivalents were infused into the portal vein. The patient recovered fully. After 3 months, near-normal mixed meal test (fasting glucose 7.0 mmol/L, 2-hour glucose 7.5 mmol/L, maximal stimulated C-peptide 3.25 nmol/L, without insulin use in the preceding 36 hours) was achieved. Glycated hemoglobin while taking a low dose of long-acting insulin was 32.7 mmol/mol hemoglobin (5.3%). When a donor pancreas is lost after transplantation, rescue β cell therapy by islet alloautotransplantation enables optimal use of scarce donor pancreata to optimize glycemic control without additional HLA alloantigen exposure. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Systemic transplantation of human adipose tissue-derived mesenchymal stem cells for the regeneration of irradiation-induced salivary gland damage.

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Jae-Yol Lim

Full Text Available OBJECTIVES: Cell-based therapy has been reported to repair or restore damaged salivary gland (SG tissue after irradiation. This study was aimed at determining whether systemic administration of human adipose-derived mesenchymal stem cells (hAdMSCs can ameliorate radiation-induced SG damage. METHODS: hAdMSCs (1 × 10(6 were administered through a tail vein of C3H mice immediately after local irradiation, and then this infusion was repeated once a week for 3 consecutive weeks. At 12 weeks after irradiation, functional evaluations were conducted by measuring salivary flow rates (SFRs and salivation lag times, and histopathologic and immunofluorescence histochemistry studies were performed to assay microstructural changes, apoptosis, and proliferation indices. The engraftment and in vivo differentiation of infused hAdMSCs were also investigated, and the transdifferentiation of hAdMSCs into amylase-producing SG epithelial cells (SGCs was observed in vitro using a co-culture system. RESULTS: The systemic administration of hAdMSCs exhibited improved SFRs at 12 weeks after irradiation. hAdMSC-transplanted SGs showed fewer damaged and atrophied acinar cells and higher mucin and amylase production levels than untreated irradiated SGs. Immunofluorescence TUNEL assays revealed fewer apoptotic cells in the hAdMSC group than in the untreated group. Infused hAdMSCs were detected in transplanted SGs at 4 weeks after irradiation and some cells were found to have differentiated into SGCs. In vitro, a low number of co-cultured hAdMSCs (13%-18% were observed to transdifferentiate into SGCs. CONCLUSION: The findings of this study indicate that hAdMSCs have the potential to protect against irradiation-induced cell loss and to transdifferentiate into SGCs, and suggest that hAdMSC administration should be viewed as a candidate therapy for the treatment of radiation-induced SG damage.

Transplant tourism among kidney transplant patients in Eastern Nigeria.

Science.gov (United States)

Okafor, U H

2017-07-05

Transplant tourism entails movement of recipient, donor or both to a transplant centre outside their country of residence. This has been reported in many countries; and has variously been associated with organ trade. The objective of this study is to determine the frequency and pattern of transplant tourism among transplant patients in Eastern Nigeria. This is a non randomized cross sectional study. All kidney transplant patients who presented at Enugu State University Teaching Hospital Parklane Enugu and Hilton Clinics Port Harcourt in Nigeria were recruited. The clinical parameters including the transplant details of all the patients were documented. The data obtained was analysed using SPSS package. A total of one hundred and twenty six patients were studied, 76.2% were males with M:F ratio of 3.2:1 and mean age of 46.9 ± 13.3 years. Fifty four and 58.7% of the patients were managed in a tertiary hospital and by a nephrologist respectively before referral for kidney transplant. Only 15.8% of the patients had their kidney transplant without delay: finance, lack of donor, logistics including delay in obtaining travelling documents were the common causes of the delay. Ninety percent of the patients had their transplant in India with majority of them using commercial donors. India was also the country with cheapest cost ($18,000.00). 69.8% were unrelated donors, 68.2% were commercial donors and 1.6% of the donors were spouse. All the commercial donors received financial incentives and each commercial donor received mean of 7580 ± 1280 dollars. Also 30.2% of the related donors demanded financial incentive. Transplant tourism is prevalent in eastern Nigeria.

Survival of human mesenchymal stromal cells from bone marrow and adipose tissue after xenogenic transplantation in immunocompetent mice

DEFF Research Database (Denmark)

Niemeyer, P; Vohrer, J; Schmal, H

2008-01-01

of the current paper was to evaluate the survival of undifferentiated and osteogenically induced human MSC from different origins after transplantation in immunocompetent mice. METHODS: Human MSC were isolated from bone marrow (BMSC) and adipose tissue (ASC). After cultivation on mineralized collagen, MSC were......INTRODUCTION: Mesenchymal stromal cells (MSC) represent an attractive cell population for tissue engineering purposes. As MSC are described as immunoprivileged, non-autologous applications seem possible. A basic requirement is the survival of MSC after transplantation in the host. The purpose...... transplanted subcutaneously into immunocompetent mice (n=12). Undifferentiated MSC (group A) were compared with osteogenic-induced MSC (group B). Human-specific in situ hybridization and anti-vimentin staining was used to follow MSC after transplantation. Quantitative evaluation of lymphocytes and macrophages...

Photodynamic therapy for actinic keratosis in organ transplant patients

DEFF Research Database (Denmark)

Basset-Seguin, N; Baumann Conzett, K; Gerritsen, M J P

2013-01-01

Background The incidence of actinic keratoses (AK) and non-melanoma skin cancer (NMSC) in organ transplant recipients (OTRs) is significantly higher than in immunocompetent patients. Rates of progression and recurrence following treatment are higher too, in part due to the effects of the immunosu......Background The incidence of actinic keratoses (AK) and non-melanoma skin cancer (NMSC) in organ transplant recipients (OTRs) is significantly higher than in immunocompetent patients. Rates of progression and recurrence following treatment are higher too, in part due to the effects...... investigate induced immunosuppression with PDT in healthy volunteers....

Hyperosmolar nonketotic hyperglycemic coma induced by methylprednisolone pulse therapy for acute rejection after liver transplantation: a case report and review of the literature

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Zhou J

2014-12-01

Full Text Available Jian Zhou,* Weiqiang Ju,* Xiaopeng Yuan, Xiaofeng Zhu, Dongping Wang, Xiaoshun HeOrgan Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China *These authors contributed equally to this work Abstract: Hyperosmolar nonketotic hyperglycemic coma (HNKHC is a serious, rare complication induced by methylprednisolone (MP pulse therapy for acute rejection after orthotopic liver transplantation (OLT. Herein, we report an unusual case of a 58-year-old woman who experienced acute rejection at 30 months after OLT, only one case in which HNKHC resulted in MP pulse therapy for acute rejection in all 913 recipients in our center. The general morbidity of HNKHC was 1.09‰ in this study. HNKHC is characterized by rapid onset, rapid progression, and a lack of specific clinical manifestations. High-dose MP management was a clear risk factor. The principle of treatment included rapid rehydration, low-dose insulin infusion, and correcting disorders of electrolytes and acidosis. In conclusion, clinicians considering MP pulse therapy after OLT should be alert to the occurrence of HNKHC. Keywords: liver transplantation, complications, hyperosmolar nonketotic hyperglycemic coma, methylprednisolone pulse therapy, principle of treatment

Selective drug-induced reduction of blood flow in tumor transplants

International Nuclear Information System (INIS)

Knapp, W.H.; Debatin, J.; Layer, K.; Helus, F.; Altmann, A.; Sinn, H.J.; Ostertag, H.

1985-01-01

The effect of a calcium antagonist and a physiological amine on tumor and muscle perfusion was investigated with the aim of improving the preconditions for external hyperthermia treatment of cancer. Nisoldipine and 5-hydroxy tryptamine (5-HT) were administered ip in Sprague-Dawley rats bearing Walker 256 carcinoma, Yoshida sarcoma, or a homologous tumor transplant derived from a spontaneous leiomyosarcoma of the uterus. At the maximum dosage used, nisoldipine injection caused a decrease of the regional washout rate of Xenon-133 in the Walker carcinoma and an increase in the muscle of the hind leg. 5-HT caused a drop in the Walker carcinoma and only a slight fall of the washout rate in muscle. Tumor-to-muscle uptake ratios of 11 C-butanol fell. Both drugs representing two different rationales of vasomotor action were able to reduce blood flow specifically in transplanted tumors; nisoldipine increased muscle blood flow and decreased arterial blood pressure, whereas 5-HT acted without substantial systemic effects

Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells

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Lee, Eun Sang; Lee, Hae-June; Lee, Yoon-Jin [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Jeong, Jae-Hoon [Division of Radiotherapy, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Kang, Seongman [Division of Life Sciences, Korea University, Seoul 136-701 (Korea, Republic of); Lim, Young-Bin, E-mail: yblim@kirams.re.kr [Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

2014-07-25

Highlights: • UPR activation precedes caspase activation in irradiated IEC-6 cells. • Chemical ER stress inducers radiosensitize IEC-6 cells. • siRNAs that targeted ER stress responses ameliorate IR-induced cell death. • Chemical chaperons prevent cell death in irradiated IEC-6 cells. - Abstract: Radiotherapy, which is one of the most effective approaches to the treatment of various cancers, plays an important role in malignant cell eradication in the pelvic area and abdomen. However, it also generates some degree of intestinal injury. Apoptosis in the intestinal epithelium is the primary pathological factor that initiates radiation-induced intestinal injury, but the mechanism by which ionizing radiation (IR) induces apoptosis in the intestinal epithelium is not clearly understood. Recently, IR has been shown to induce endoplasmic reticulum (ER) stress, thereby activating the unfolded protein response (UPR) signaling pathway in intestinal epithelial cells. However, the consequences of the IR-induced activation of the UPR signaling pathway on radiosensitivity in intestinal epithelial cells remain to be determined. In this study, we investigated the role of ER stress responses in IR-induced intestinal epithelial cell death. We show that chemical ER stress inducers, such as tunicamycin or thapsigargin, enhanced IR-induced caspase 3 activation and DNA fragmentation in intestinal epithelial cells. Knockdown of Xbp1 or Atf6 with small interfering RNA inhibited IR-induced caspase 3 activation. Treatment with chemical chaperones prevented ER stress and subsequent apoptosis in IR-exposed intestinal epithelial cells. Our results suggest a pro-apoptotic role of ER stress in IR-exposed intestinal epithelial cells. Furthermore, inhibiting ER stress may be an effective strategy to prevent IR-induced intestinal injury.

Anisotropic chemical strain in cubic ceria due to oxygen-vacancy-induced elastic dipoles.

Science.gov (United States)

Das, Tridip; Nicholas, Jason D; Sheldon, Brian W; Qi, Yue

2018-06-06

Accurate characterization of chemical strain is required to study a broad range of chemical-mechanical coupling phenomena. One of the most studied mechano-chemically active oxides, nonstoichiometric ceria (CeO2-δ), has only been described by a scalar chemical strain assuming isotropic deformation. However, combined density functional theory (DFT) calculations and elastic dipole tensor theory reveal that both the short-range bond distortions surrounding an oxygen-vacancy and the long-range chemical strain are anisotropic in cubic CeO2-δ. The origin of this anisotropy is the charge disproportionation between the four cerium atoms around each oxygen-vacancy (two become Ce3+ and two become Ce4+) when a neutral oxygen-vacancy is formed. Around the oxygen-vacancy, six of the Ce3+-O bonds elongate, one of the Ce3+-O bond shorten, and all seven of the Ce4+-O bonds shorten. Further, the average and maximum chemical strain values obtained through tensor analysis successfully bound the various experimental data. Lastly, the anisotropic, oxygen-vacancy-elastic-dipole induced chemical strain is polarizable, which provides a physical model for the giant electrostriction recently discovered in doped and non-doped CeO2-δ. Together, this work highlights the need to consider anisotropic tensors when calculating the chemical strain induced by dilute point defects in all materials, regardless of their symmetry.

Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

International Nuclear Information System (INIS)

Camats, Nuria; Garcia, Francisca; Parrilla, Juan Jose; Calaf, Joaquim; Martin, Miguel; Caldes, Montserrat Garcia

2008-01-01

Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p ≤ 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p ≤ 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal cells

Trans-generational radiation-induced chromosomal instability in the female enhances the action of chemical mutagens

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Camats, Nuria [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, Francisca [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, Juan Jose [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, Joaquim [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin, Miguel [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, Montserrat Garcia [Institut de Biotecnologia i Biomedicina (IBB), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)], E-mail: Montserrat.Garcia.Caldes@uab.es

2008-04-02

Genomic instability can be produced by ionising radiation, so-called radiation-induced genomic instability, and chemical mutagens. Radiation-induced genomic instability occurs in both germinal and somatic cells and also in the offspring of irradiated individuals, and it is characterised by genetic changes including chromosomal rearrangements. The majority of studies of trans-generational, radiation-induced genomic instability have been described in the male germ line, whereas the authors who have chosen the female as a model are scarce. The aim of this work is to find out the radiation-induced effects in the foetal offspring of X-ray-treated female rats and, at the same time, the possible impact of this radiation-induced genomic instability on the action of a chemical mutagen. In order to achieve both goals, the quantity and quality of chromosomal damage were analysed. In order to detect trans-generational genomic instability, a total of 4806 metaphases from foetal tissues from the foetal offspring of X-irradiated female rats (5 Gy, acute dose) were analysed. The study's results showed that there is radiation-induced genomic instability: the number of aberrant metaphases and the breaks per total metaphases studied increased and were found to be statistically significant (p {<=} 0.05), with regard to the control group. In order to identify how this trans-generational, radiation-induced chromosomal instability could influence the chromosomal behaviour of the offspring of irradiated rat females in front of a chemical agent (aphidicolin), a total of 2481 metaphases were studied. The observed results showed that there is an enhancement of the action of the chemical agent: chromosomal breaks per aberrant metaphases show significant differences (p {<=} 0.05) in the X-ray- and aphidicolin-treated group as regards the aphidicolin-treated group. In conclusion, our findings indicate that there is trans-generational, radiation-induced chromosomal instability in the foetal

Measuring and monitoring equity in access to deceased donor kidney transplantation.

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Stewart, D E; Wilk, A R; Toll, A E; Harper, A M; Lehman, R R; Robinson, A M; Noreen, S A; Edwards, E B; Klassen, D K

2018-05-07

The Organ Procurement and Transplantation Network monitors progress toward strategic goals such as increasing the number of transplants and improving waitlisted patient, living donor, and transplant recipient outcomes. However, a methodology for assessing system performance in providing equity in access to transplants was lacking. We present a novel approach for quantifying the degree of disparity in access to deceased donor kidney transplants among waitlisted patients and determine which factors are most associated with disparities. A Poisson rate regression model was built for each of 29 quarterly, period-prevalent cohorts (January 1, 2010-March 31, 2017; 5 years pre-kidney allocation system [KAS], 2 years post-KAS) of active kidney waiting list registrations. Inequity was quantified as the outlier-robust standard deviation (SD w ) of predicted transplant rates (log scale) among registrations, after "discounting" for intentional, policy-induced disparities (eg, pediatric priority) by holding such factors constant. The overall SD w declined by 40% after KAS implementation, suggesting substantially increased equity. Risk-adjusted, factor-specific disparities were measured with the SD w after holding all other factors constant. Disparities associated with calculated panel-reactive antibodies decreased sharply. Donor service area was the factor most associated with access disparities post-KAS. This methodology will help the transplant community evaluate tradeoffs between equity and utility-centric goals when considering new policies and help monitor equity in access as policies change. © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.

Post-transplant lymphoproliferative disease in liver transplant recipients

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Mercedes Rubio-Manzanares-Dorado

Full Text Available Introduction: Post-transplant lymphoproliferative syndrome (PTLD is a rare and potentially life-threatening complication after liver transplantation. The aim of this study was to analyze the clinicopathologic features related to PTLD in a single institution after liver transplantation. Methods: Observational study where we have retrospectively analyzed 851 cases who underwent liver transplantation. Ten cases have developed PTLD. Their clinical-pathological characteristics and the treatment received have been analyzed. Results: PTLD incidence was 1.2% (10/851. The mean time from liver transplantation to PTLD diagnosis was 36 months (range 1.2 to 144 months. PTLD localization was extranodal in all cases, the most frequent location being intestinal. Seven cases showed a monomorphic lymphoma which in all cases was differentiated B cell lymphomas. Fifty per cent of the series were seropositive for Epstein-Barr virus. Five patients were alive at the time of the review. Among these patients, we observed three cases of complete remission and two cases of disease stabilization. The death rate was higher in the first year after diagnosis of PTLD. Conclusion: PTLD is a rare complication after liver transplantation, but it may pose a threat to the life of a liver transplant recipient. It is essential to identify patients at risk, to establish an early diagnosis and treatment that can change the outcome of the disease.

Transplantation of human umbilical cord blood-derived mononuclear cells induces recovery of motor dysfunction in a rat model of Parkinson's disease

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Chen C

2016-04-01

Full Text Available Chao Chen,1,* Jing Duan,1,* Aifang Shen,2,* Wei Wang,1 Hao Song,1 Yanming Liu,1 Xianjie Lu,1 Xiaobing Wang,2 Zhiqing You,1 Zhongchao Han,3,4 Fabin Han1 1Center for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital, Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of China; 2Department of Gynecology and Obstetrics, The Liaocheng People's Hospital, Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of China; 3The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences, Peking Union of Medical College, Tianjin, People's Republic of China; 4National Engineering Research Center of Cell Products, AmCellGene Co. Ltd., TEDA, Tianjin, People's Republic of China*These authors contributed equally to this workAbstract: Human umbilical cord blood-derived mononuclear cells (hUCB-MNCs were reported to have neurorestorative capacity for neurological disorders such as stroke and traumatic brain injury. This study was performed to explore if hUCB-MNC transplantation plays any therapeutic effects for Parkinson's disease (PD in a 6-OHDA-lesioned rat model of PD. hUCB-MNCs were isolated from umbilical cord blood and administered to the striatum of the 6-OHDA-lesioned rats. The apomorphine-induced locomotive turning-overs were measured to evaluate the improvement of motor dysfunctions of the rats after administration of hUCB-MNCs. We observed that transplanted hUCB-MNCs significantly improve the motor deficits of the PD rats and that grafted hUCB-MNCs integrated to the host brains and differentiated to neurons and dopamine neurons in vivo after 16 weeks of transplantation. Our study provided evidence that transplanted hUCB-MNCs play therapeutic effects in a rat PD model by differentiating to neurons and dopamine neurons. Keywords: hUCB-MNCs, Parkinson's disease, transplantation

Pre-transplant history of mental health concerns, non-adherence, and post-transplant outcomes in kidney transplant recipients.

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Gumabay, Franz Marie; Novak, Marta; Bansal, Aarushi; Mitchell, Margot; Famure, Olusegun; Kim, S Joseph; Mucsi, Istvan

2018-02-01

The association between pre-transplant mental health concerns and non-adherence and post-transplant outcomes after kidney transplantation is not fully established. We examined the relationship between a pre-transplant history of mental health concerns and non-adherence and post-transplant outcomes among kidney transplant recipients. In this retrospective single center cohort study of adult kidney transplant recipients (n=955) the associations between the history of mental health concerns or non-adherence and the time from kidney transplant to biopsy proven acute rejection; death-censored graft failure and total graft failure were examined using Cox proportional hazards models. Mean (SD) age was 51 (13) years, 61% were male and 27% had a history of diabetes. Twenty-two and 11% of patients had mental health concerns and non-adherence, respectively. Fifteen percent of the patients had acute rejection, 5.6% had death-censored graft failure and 13.0% had total graft failure. The history of mental health concerns was not associated with acute rejection, death-censored graft failure or total graft failure. Patients with versus without a history of non-adherence tended to have higher cumulative incidence of acute rejection (23.3% [95% CI: 16.1, 33.2] vs. 13.6% [95% CI: 11.4, 16.2]) and death-censored graft failure (15.0% [95% CI: 6.9, 30.8] vs. 6.4% [95% CI: 4.7, 8.7]) (log rank p=0.052 and p=0.086, respectively). These trends were not significant after multivariable adjustment. In summary, a history of pre-transplant mental health concerns or non-adherence is not associated with adverse outcomes in patients who completed transplant workup and received a kidney transplant. Copyright © 2018 Elsevier Inc. All rights reserved.

Organ donation and transplantation in Mexico. A transplantation health professionals’ perspective

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Luis Eduardo Hernández-Ibarra

2017-01-01

Full Text Available Objective. We aimed to explore organ donation and transplantation in Mexico from the point of view of transplantation health professionals. Materials and methods. A qualitative study was carried out. Twenty six organ transplantation health professionals from seven states of Mexico participated. Semi-structured face-to-face interviews were conducted mainly in hospital settings. Critical discourse analysis was performed. Results. According to participants, living organ transplantation offers benefits for recipients as well as for donors. Several factors influence the field of transplantation negatively, among them the scarcity of resources that impedes the incorporation of new health personnel, as well as conflicts between transplantation teams with diverse health professionals and authorities. Conclusion. Besides increasing economic resources, transplantation health personnel should be sensitized to find solutions in order to avoid conflicts with different health professionals. Studies on organ donation and transplants also should include other social actors’ viewpoint.

Role of the Slug Transcription Factor in Chemically-Induced Skin Cancer

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Kristine von Maltzan

2016-02-01

Full Text Available The Slug transcription factor plays an important role in ultraviolet radiation (UVR-induced skin carcinogenesis, particularly in the epithelial-mesenchymal transition (EMT occurring during tumor progression. In the present studies, we investigated the role of Slug in two-stage chemical skin carcinogenesis. Slug and the related transcription factor Snail were expressed at high levels in skin tumors induced by 7,12-dimethylbenz[α]anthracene application followed by 12-O-tetradecanoylphorbol-13-acetate (TPA treatment. TPA-induced transient elevation of Slug and Snail proteins in normal mouse epidermis and studies in Slug transgenic mice indicated that Slug modulates TPA-induced epidermal hyperplasia and cutaneous inflammation. Although Snail family factors have been linked to inflammation via interactions with the cyclooxygenase-2 (COX-2 pathway, a pathway that also plays an important role in skin carcinogenesis, transient TPA induction of Slug and Snail appeared unrelated to COX-2 expression. In cultured human keratinocytes, TPA induced Snail mRNA expression while suppressing Slug expression, and this differential regulation was due specifically to activation of the TPA receptor. These studies show that Slug and Snail exhibit similar patterns of expression during both UVR and chemical skin carcinogenesis, that Slug and Snail can be differentially regulated under some conditions and that in vitro findings may not recapitulate in vivo results.

Transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into rat spinal cord injuries does not cause harm.

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Cloutier, Frank; Siegenthaler, Monica M; Nistor, Gabriel; Keirstead, Hans S

2006-07-01

Demyelination contributes to loss of function following spinal cord injury. We have shown previously that transplantation of human embryonic stem cell-derived oligodendrocyte progenitors into adult rat 200 kD contusive spinal cord injury sites enhances remyelination and promotes recovery of motor function. Previous studies using oligodendrocyte lineage cells have noted a correlation between the presence of demyelinating pathology and the survival and migration rate of the transplanted cells. The present study compared the survival and migration of human embryonic stem cell-derived oligodendrocyte progenitors injected 7 days after a 200 or 50 kD contusive spinal cord injury, as well as the locomotor outcome of transplantation. Our findings indicate that a 200 kD spinal cord injury induces extensive demyelination, whereas a 50 kD spinal cord injury induces no detectable demyelination. Cells transplanted into the 200 kD injury group survived, migrated, and resulted in robust remyelination, replicating our previous studies. In contrast, cells transplanted into the 50 kD injury group survived, exhibited limited migration, and failed to induce remyelination as demyelination in this injury group was absent. Animals that received a 50 kD injury displayed only a transient decline in locomotor function as a result of the injury. Importantly, human embryonic stem cell-derived oligodendrocyte progenitor transplants into the 50 kD injury group did not cause a further decline in locomotion. Our studies highlight the importance of a demyelinating pathology as a prerequisite for the function of transplanted myelinogenic cells. In addition, our results indicate that transplantation of human embryonic stem cell-derived oligodendrocyte progenitor cells into the injured spinal cord is not associated with a decline in locomotor function.

Adoptive transfer of transplantation tolerance in the H-2 compatible mouse system CBA/C3H

International Nuclear Information System (INIS)

Siegl, E.; Brock, J.; Schulze, H.A.

1985-01-01

Transfer of neonatally induced tolerance in the H-2 compatible CBA/C3H strain combination is possible with different efficiency by injection of adherent and non-adherent spleen cells, unseparated spleen cells and lymph node cells from C3H-tolerant CBA mice into sublethal irradiated CBA mice. The most efficient cell populations are adherent spleen cells and lymph node cells. Successfull transfer of transplantation tolerance is not possible to non-irradiated mice. The adherent fraction of spleen cells and lymph node cells contains a suppressor cell population responsible for transplantation tolerance against non-H-2 antigens. The induced transplantation tolerance is not due to a chimeric state of C3H-tolerant CBA mice. (author)

Radiation and chemical effects on viral transformation and tumor antigen expression. Annual progress report, August 1, 1978--May 1, 1979

International Nuclear Information System (INIS)

Coggin, J.H. Jr.

1979-01-01

Studies aimed at the biological, biochemical, and immunologic characterization of fetal antigens (EA) in hamsters and mice and locating and determining the distribution of fetal antigens in tumor tissues and in developing fetuses have been underway for several months. Progress has been made in isolating embryonic or fetal antigens from fetuses and from tumor cells. We have developed and reported a reliable lymphocyte transformation assay (LTA) which meets our needs in routinely assaying cell free tumor associated antigen (TAA) preparations from fetal and tumor cells. The assay correlated with transplantation resistance assays and has appropriate specificity. We have also developed the staph-A protein binding assay utilizing anti-serum derived against embryonic antigens present on SV40 tumor cells. In other studies, we have reported increases and perturbations in thymocytes during viral and chemical oncogenesis in hamsters, have developed a simple technique for preserving functional lymphocytes sensitized against TAA by freezing for use in our model system work, have reported the cross-reactivity of tranplantation resistance antigen on a spectrum of chemically induced tumors previously believed to only contain individually specific TSTAs and have recently reported the cross-reactivity of papovavirus induced transplantation resistance antigen in sarcoma cells induced by different viruses. We have concluded our studies of glycosyltransferases in the membranes of developing fetuses and noted no differences in their levels with advancing days of gestation using whold embryo cell populations

Survival of Free and Encapsulated Human and Rat Islet Xenografts Transplanted into the Mouse Bone Marrow

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Meier, Raphael P. H.; Seebach, Jörg D.; Morel, Philippe; Mahou, Redouan; Borot, Sophie; Giovannoni, Laurianne; Parnaud, Geraldine; Montanari, Elisa; Bosco, Domenico; Wandrey, Christine; Berney, Thierry; Bühler, Leo H.; Muller, Yannick D.

2014-01-01

Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow) and 10 days (kidney capsule). Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation. PMID:24625569

Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

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Raphael P H Meier

Full Text Available Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow and 10 days (kidney capsule. Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation.

Thoracic organ transplantation.

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Pierson, Richard N; Barr, Mark L; McCullough, Keith P; Egan, Thomas; Garrity, Edward; Jessup, Mariell; Murray, Susan

2004-01-01

This article presents an overview of factors associated with thoracic transplantation outcomes over the past decade and provides valuable information regarding the heart, lung, and heart-lung waiting lists and thoracic organ transplant recipients. Waiting list and post-transplant information is used to assess the importance of patient demographics, risk factors, and primary cardiopulmonary disease on outcomes. The time that the typical listed patient has been waiting for a heart, lung, or heart-lung transplant has markedly increased over the past decade, while the number of transplants performed has declined slightly and survival after transplant has plateaued. Waiting list mortality, however, appears to be declining for each organ and for most diseases and high-severity subgroups, perhaps in response to recent changes in organ allocation algorithms. Based on perceived inequity in organ access and in response to a mandate from Health Resources and Services Administration, the lung transplant community is developing a lung allocation system designed to minimize deaths on the waiting list while maximizing the benefit of transplant by incorporating post-transplant survival and quality of life into the algorithm. Areas where improved data collection could inform evolving organ allocation and candidate selection policies are emphasized.

Dialysis Facility Transplant Philosophy and Access to Kidney Transplantation in the Southeast.

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Gander, Jennifer; Browne, Teri; Plantinga, Laura; Pastan, Stephen O; Sauls, Leighann; Krisher, Jenna; Patzer, Rachel E

2015-01-01

Little is known about the impact of dialysis facility treatment philosophy on access to transplant. The aim of our study was to determine the relationship between the dialysis facility transplant philosophy and facility-level access to kidney transplant waitlisting. A 25-item questionnaire administered to Southeastern dialysis facilities (n = 509) in 2012 captured the facility transplant philosophy (categorized as 'transplant is our first choice', 'transplant is a great option for some', and 'transplant is a good option, if the patient is interested'). Facility-level waitlisting and facility characteristics were obtained from the 2008-2011 Dialysis Facility Report. Multivariable logistic regression was used to examine the association between the dialysis facility transplant philosophy and facility waitlisting performance (dichotomized using the national median), where low performance was defined as fewer than 21.7% of dialysis patients waitlisted within a facility. Fewer than 25% (n = 124) of dialysis facilities reported 'transplant is our first option'. A total of 131 (31.4%) dialysis facilities in the Southeast were high-performing facilities with respect to waitlisting. Adjusted analysis showed that facilities who reported 'transplant is our first option' were twice (OR 2.0; 95% CI 1.0-3.9) as likely to have high waitlisting performance compared to facilities who reported that 'transplant is a good option, if the patient is interested'. Facilities with staff who had a more positive transplant philosophy were more likely to have better facility waitlisting performance. Future prospective studies are needed to further investigate if improving the kidney transplant philosophy in dialysis facilities improves access to transplantation.

Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury

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Zhijian Cheng

2016-08-01

Full Text Available Neural stem cell (NSC transplantation has been proposed to promote functional recovery after spinal cord injury. However, a detailed understanding of the mechanisms of how NSCs exert their therapeutic plasticity is lacking. We transplanted mouse NSCs into the injured spinal cord seven days after SCI, and the Basso Mouse Scale (BMS score was performed to assess locomotor function. The anti-inflammatory effects of NSC transplantation was analyzed by immunofluorescence staining of neutrophil and macrophages and the detection of mRNA levels of tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β, interleukin-6 (IL-6 and interleukin-12 (IL-12. Furthermore, bone marrow-derived macrophages (BMDMs were co-cultured with NSCs and followed by analyzing the mRNA levels of inducible nitric oxide synthase (iNOS, TNF-α, IL-1β, IL-6 and IL-10 with quantitative real-time PCR. The production of TNF-α and IL-1β by BMDMs was examined using the enzyme-linked immunosorbent assay (ELISA. Transplanted NSCs had significantly increased BMS scores (p < 0.05. Histological results showed that the grafted NSCs migrated from the injection site toward the injured area. NSCs transplantation significantly reduced the number of neutrophils and iNOS+/Mac-2+ cells at the epicenter of the injured area (p < 0.05. Meanwhile, mRNA levels of TNF-α, IL-1β, IL-6 and IL-12 in the NSCs transplantation group were significantly decreased compared to the control group. Furthermore, NSCs inhibited the iNOS expression of BMDMs and the release of inflammatory factors by macrophages in vitro (p < 0.05. These results suggest that NSC transplantation could modulate SCI-induced inflammatory responses and enhance neurological function after SCI via reducing M1 macrophage activation and infiltrating neutrophils. Thus, this study provides a new insight into the mechanisms responsible for the anti-inflammatory effect of NSC transplantation after SCI.

Carinal transplantation.

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Ueda, H; Shirakusa, T

1992-01-01

BACKGROUND: Current techniques of management of carinal lesions are not always satisfactory. Carinal transplantation, if feasible, would be valuable in certain circumstances. METHODS AND RESULTS: Carinal transplantation experiments were performed in dogs. In early cross transplant experiments there were problems in controlling ventilation and in obtaining satisfactory anastomoses, and the animals failed to live for even a few days. In seven subsequent experiments the carinal graft was removed from one dog and transplanted into a second dog. Two dogs lived for over four months with immunosuppression. CONCLUSION: The results suggest that carinal transplantation can succeed if (1) the calibre of the graft is matched with that of the recipient; (2) there is an abundant blood supply to the graft; (3) appropriate immunosuppression is provided; (4) ventilation is adequate during surgery. Images PMID:1465758

An analysis of hereditary increase in frequency of cell mortality induced by external factors (Experiments on nuclear transplantation in amoebae)

International Nuclear Information System (INIS)

Bychkovskaya, I.B.; Ochinskaya, G.K.; Yudin, A.L.; AN SSSR, Leningrad. Inst. Tsitologii)

1980-01-01

By using nuclear transplantations in Amoeba proteus a study was made of a peculiar heritable effect, a stable increase in the frequency of cell mortality incuced by comparatively low doses of x radiation (50 Gy) or slight heating (29 0 C during 6 to 7 h). This effect differs qualitatively from the known radiation effects (reproductive death, lethal sectoring) by its being non-specific for radiation. In addition, the effect is saltatory appearing in 100% of the treated cells and the extent of its expression is not dependent on the dose of an inducing factor (at supra-threshold doses) and the period of time after treatment. It was found that (1) the hereditary changes in amoebae, unlike those resulting in reproductive death, are transmitted during intercellular transplantations both by the nucleus and cytoplasm of an altered cell; (2) the transfer of the character under test is accomplished by means of a certiin factor capable of shuttling between the nucleus and cytoplasm, (3) the effect is not necessarily a consequence of primary injury of nuclear structures and it may be induced by treatment of the cytoplasm of an enucleated cell renucleated then by the nucleus of a normal amoeba. In this respect, the effect under test differs also from the known types of hereditary post-radiation lethal effects which are commonly suggested to involve primary injury of the nucleus. Possible mechanisms of genetic control over the character tested are discussed. (author)

Assessing bone status in patients awaiting liver transplantation.

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Wibaux, Cécile; Legroux-Gerot, Isabelle; Dharancy, Sébastien; Boleslawski, Emmanuel; Declerck, Nicole; Canva, Valérie; Mathurin, Philippe; Pruvot, François-René; Cortet, Bernard

2011-07-01

Osteoporosis is common in liver transplant recipients as a result of both iatrogenic factors and preexisting hepatic osteodystrophy. To assess the prevalences of osteoporosis and fractures and to identify risk factors for these two abnormalities in patients awaiting liver transplantation for end-stage liver disease. Between January 2006 and December 2007, patients on a liver transplant waiting list underwent a routine evaluation comprising the identification of risk factors for osteoporosis, radiographs of the spine, bone mineral density measurements (BMD), and laboratory tests (phosphate and calcium levels, hormone assays, liver function tests, and bone turnover markers). We studied 99 patients (70 males and 20 females; mean age, 55 ± 8 years) including 75% with alcohol-induced cirrhosis with or without hepatocarcinoma. Among them, 36% had radiographic vertebral fractures, 38% had osteoporosis, 35% had osteopenia, and 88% had vitamin D insufficiency or deficiency (25(OH)vitamin D3bone resorption markers correlated negatively with BMD at the spine and hip. The Model for End-Stage Liver Disease score correlated negatively with hip BMD. Our findings suggest high prevalences of low BMD values and vertebral fractures among patients awaiting liver transplantation. Bone status should be evaluated routinely in candidates to liver transplantation. Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Optimization of microwave-induced chemical etching for rapid development of neutron-induced recoil tracks in CR-39 detectors

International Nuclear Information System (INIS)

Sahoo, G.S.; Tripathy, S.P.; Bandyopadhyay, T.

2014-01-01

A systematic investigation is carried out to optimize the recently established microwave-induced chemical etching (MICE) parameters for rapid development of neutron-induced recoil tracks in CR-39 detectors. Several combinations of all available microwave powers with different etching durations were analysed to determine the most suitable etching condition. The etching duration was found to reduce with increasing microwave power and the tracks were observed at about 18, 15, 12, and 6 min for 300, 450, 600 and 900 W of microwave powers respectively compared to a few hours in chemical etching (CE) method. However, for complete development of tracks the etching duration of 30, 40, 50 and 60 min were found to be suitable for the microwave powers of 900, 600, 450 and 300 W, respectively. Temperature profiles of the etchant for all the available microwave powers at different etching durations were generated to regulate the etching process in a controlled manner. The bulk etch rates at different microwave powers were determined by 2 methods, viz., gravimetric and removed thickness methods. A logarithmic expression was used to fit the variation of bulk etch rate with microwave power. Neutron detection efficiencies were obtained for all the cases and the results on track parameters obtained with MICE technique were compared with those obtained from another detector processed with chemical etching. - Highlights: • Microwave-induced chemical etching method is optimized for rapid development of recoil tracks due to neutrons in CR-39 detector. • Several combinations of microwave powers and etching durations are investigated to standardize the suitable etching condition. • Bulk-etch rates are determined for all microwave powers by two different methods, viz. gravimetric and removed thickness method. • The method is found to be simple, effective and much faster compared to conventional chemical etching

Viral Infection: A Potent Barrier to Transplantation Tolerance

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David M. Miller

2008-01-01

Full Text Available Transplantation of allogeneic organs has proven to be an effective therapeutic for a large variety of disease states, but the chronic immunosuppression that is required for organ allograft survival increases the risk for infection and neoplasia and has direct organ toxicity. The establishment of transplantation tolerance, which obviates the need for chronic immunosuppression, is the ultimate goal in the field of transplantation. Many experimental approaches have been developed in animal models that permit long-term allograft survival in the absence of chronic immunosuppression. These approaches function by inducing peripheral or central tolerance to the allograft. Emerging as some of the most promising approaches for the induction of tolerance are protocols based on costimulation blockade. However, as these protocols move into the clinic, there is recognition that little is known as to their safety and efficacy when confronted with environmental perturbants such as virus infection. In animal models, it has been reported that virus infection can prevent the induction of tolerance by costimulation blockade and, in at least one experimental protocol, can lead to significant morbidity and mortality. In this review, we discuss how viruses modulate the induction and maintenance of transplantation tolerance.

Rosiglitazone attenuates transplant arteriosclerosis after allogeneic aorta transplantation in rats

NARCIS (Netherlands)

Onuta, Geanina; Rienstra, Heleen; de Boer, Jan Freark; Boer, Mark Walther; Roks, Anton J. M.; Klatter, Flip A.; Uges, Donald R. A.; Navis, Gerjan; Rozing, Jan; Hillebrands, Jan-Luuk

2007-01-01

Background. Transplant arteriosclerosis is a leading cause of chronic transplant dysfunction and is characterized by occlusive neointima formation in intragraft arteries. Development of transplant arteriosclerosis is refractory to conventional immunosuppressive drugs and adequate therapy is not

Immunogenicity of guinea pig cells transformed in culture by chemical carcinogens.

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Ohanian, S H; McCabe, R P; Evans, C H

1981-12-01

The immunogenicity of inbred strain 2/N guinea pig fibroblasts transformed to the malignant state in vitro by chemical carcinogens was evaluated with the use of a variety of in vivo and in vitro methods including delayed-type hypersensitivity skin and tumor transplantation tests and analysis of antibody production by immunofluorescence, complement fixation, and staphylococcal protein A binding tests. Neoplastic transformation was induced by direct treatment of cells in culture with benzo[a]pyrene, 3-methylcholanthrene, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or by the host-mediated method by which fetuses were exposed to diethylnitrosamine or MNNG in vivo prior to cell culture. Rabbits and syngeneic guinea pigs were inoculated with unirradiated and X-irradiated clonally derived cells. Delayed hypersensitivity skin reactions to immunizing or other cells were equivalent in immunized or control guinea pigs, and no protection to tumor outgrowth from a challenge inoculum of immunizing cells was observed. Antibody activity induced in the sera of immunized guinea pigs was cross-reactive and removed by absorption with nontumorigenic cells. Rabbit antisera after absorption with fetal guinea pig cells were nonreactive with the specific immunizing or other culture cells. Chemical carcinogen-induced neoplastic transformation of guinea pig cells can, therefore, occur without formation of detectable, individually distinct cell surface tumor-specific neoantigens.

Immunogenicity of guinea pig cells transformed in culture by chemical carcinogens

International Nuclear Information System (INIS)

Ohanian, S.H.; McCabe, R.P.; Evans, C.H.

1981-01-01

The immunogenicity of inbred strain 2/N guinea pig fibroblasts transformed to the malignant state in vitro by chemical carcinogens was evaluated with the use of a variety of in vivo and in vitro methods including delayed-type hypersensitivity skin and tumor transplantation tests and analysis of antibody production by immunofluorescence, complement fixation, and staphylococcal protein A binding tests. Neoplastic transformation was induced by direct treatment of cells in culture with benzo[a]pyrene, 3-methylcholanthrene, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or by the host-mediated method by which fetuses were exposed to diethylnitrosamine or MNNG in vivo prior to cell culture. Rabbits and syngeneic guinea pigs were inoculated with unirradiated and X-irradiated clonally derived cells. Delayed hypersensitivity skin reactions to immunizing or other cells were equivalent in immunized or control guinea pigs, and no protection to tumor outgrowth from a challenge inoculum of immunizing cells was observed. Antibody activity induced in the sera of immunized guinea pigs was cross-reactive and removed by absorption with nontumorigenic cells. Rabbit anitsera after absorption with fetal guinea pig cells were nonreactive with the specific immunizing or other cultured cells. Chemical carcinogen-induced neoplastic transformation of guinea pig cells can, therefore, occur without formation of detectable, individually distinct cell surface tumor-specific neoantigens

Transplante de bexiga: estudo piloto Bladder transplant: pilot study

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Frederico Teixeira Brandt

2004-08-01

Full Text Available OBJETIVO: Desenvolver um modelo biológico que seja viável para o estudo sistemático do transplante de bexiga. MÉTODOS: Cães mestiços vivos são usados como doadores e receptores do segmento supra-trigonal da bexiga. RESULTADOS: Os pacientes tansplantados só fizeram uso de imunossupressão por 15 dias, estão vivos e sadios com 18 meses de transplante. Desde o primeiro mês de transplante os cães apresentam controle funcional da micção, inclusive sem urina residual importante. CONCLUSÃO: Transplante de bexiga em cães é um modelo viável, fisiológico e simples.PURPOSE: Our aim was to study the feasible of bladder transplants. METHODS: Alive mongrel dogs are being used as trigone bladder segment donators and receptors RESULTS: The transplanted patients had 15 days of immunosuppression and so far an 18-months satisfactory post-operative outcome. Since a month after surgery, the dogs have been presenting full functional control of micturition and the evaluations have been showing normal bladder storage and contraction capacities. CONCLUSION: bladder transplants in dogs its a possible, physiological and simple model.

Long-term Persistence of Innate Lymphoid Cells in the Gut After Intestinal Transplantation.

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Weiner, Joshua; Zuber, Julien; Shonts, Brittany; Yang, Suxiao; Fu, Jianing; Martinez, Mercedes; Farber, Donna L; Kato, Tomoaki; Sykes, Megan

2017-10-01

Little is known about innate lymphoid cell (ILC) populations in the human gut, and the turnover of these cells and their subsets after transplantation has not been described. Intestinal samples were taken from 4 isolated intestine and 3 multivisceral transplant recipients at the time of any operative resection, such as stoma closure or revision. ILCs were isolated and analyzed by flow cytometry. The target population was defined as being negative for lineage markers and double-positive for CD45/CD127. Cells were further stained to define ILC subsets and a donor-specific or recipient-specific HLA marker to analyze chimerism. Donor-derived ILCs were found to persist greater than 8 years after transplantation. Additionally, the percentage of cells thought to be lymphoid tissue inducer cells among donor ILCs was far higher than that among recipient ILCs. Our findings demonstrate that donor-derived ILCs persist long-term after transplantation and support the notion that human lymphoid tissue inducer cells may form in the fetus and persist throughout life, as hypothesized in rodents. Correlation between chimerism and rejection, graft failure, and patient survival requires further study.

Chemical memory reactions induced bursting dynamics in gene expression.

Science.gov (United States)

Tian, Tianhai

2013-01-01

Memory is a ubiquitous phenomenon in biological systems in which the present system state is not entirely determined by the current conditions but also depends on the time evolutionary path of the system. Specifically, many memorial phenomena are characterized by chemical memory reactions that may fire under particular system conditions. These conditional chemical reactions contradict to the extant stochastic approaches for modeling chemical kinetics and have increasingly posed significant challenges to mathematical modeling and computer simulation. To tackle the challenge, I proposed a novel theory consisting of the memory chemical master equations and memory stochastic simulation algorithm. A stochastic model for single-gene expression was proposed to illustrate the key function of memory reactions in inducing bursting dynamics of gene expression that has been observed in experiments recently. The importance of memory reactions has been further validated by the stochastic model of the p53-MDM2 core module. Simulations showed that memory reactions is a major mechanism for realizing both sustained oscillations of p53 protein numbers in single cells and damped oscillations over a population of cells. These successful applications of the memory modeling framework suggested that this innovative theory is an effective and powerful tool to study memory process and conditional chemical reactions in a wide range of complex biological systems.

Ectopic Liver Tissue Formation in Rats with Induced Liver Fibrosis

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Bauyrzhan Umbayev

2014-12-01

Full Text Available Introduction: The possible alternative approach to whole-organ transplantation is a cell-based therapy, which can also be used as a "bridge" to liver transplantation.  However, morphological and functional changes in the liver of patients suffering from chronic liver fibrosis and cirrhosis restrict the effectiveness of direct cell transplantation. Therefore, extra hepatic sites for cell transplantation, including the spleen, pancreas, peritoneal cavity, and subrenal capsule, could be a useful therapeutic approach for compensation of liver functions. However, a method of transplantation of hepatocytes into ectopic sites is needed to improve hepatocyte engraftment. Previously published data has demonstrated that mouse lymph nodes can support the engraftment and proliferation of hepatocytes as ES and rescue Fah mice from lethal liver failure. Thus, the aim of the study was to evaluate the engraftment of i.p. injected allogeneic hepatocytes into extra hepatic sites in albino rats with chemically induced liver fibrosis (LF. Materials and methods: Albino rats were randomly divided into 4 groups: (1 intact group (n = 18; (2 rats with induced LF (n = 18; (3 rats with induced LF and transplanted with hepatocytes (n = 18; (4 as a control, rats were treated with cyclosporine A only (n = 18. In order to prevent an immune response, groups 2 and 3 were subjected to immunosuppression by cyclosporine A (25 mg/kg per day. LF was induced using N-nitrosodimethylamine (NDMA, i.p., 10 mg/kg, three times a week for 4 weeks and confirmed by histological analysis of the liver samples. Hepatocytes transplantation (HT was performed two days after NDMA exposure cessation by i.p. injection of 5×106 freshly isolated allogeneic hepatocytes. Liver function was assessed by quantifying blood biochemical parameters (ALT, AST, GGT, total protein, bilirubin, and albumin at 1 week, 1 month, and 2 months after hepatocytes transplantation (HT. To confirm a hepatocytes�

Therapeutic effectiveness of pediatric renal transplantation in 63 cases

Institute of Scientific and Technical Information of China (English)

Han Shu; Wang Mu; Zhu Youhua; Zeng Li; Zhou Meisheng; Zhang Lei; Fu Shangxi; Wang Liming

2008-01-01

Objective: To explore the characteristic of operation, intra-operation treatment and the application of immunosuppressant in pediatric renal transplantation in order to improve therapeutic effectiveness. Methods: From March 1986 to October 2006, the clinical data of 63 children who underwent renal transplantation in our hospital were retrospectively analyzed. Results: The 1-, 3-, 5-, 10-year graft survival rates were 98.4%, 90.5%, 88.9% and 68.3%,respectively. And the corresponding patient survival rates were 100%, 95.2%, 92.1%, 71.4%. The body weight increased 4 to 12 kg and the body height grew up 2 to 6 cm during the first year post-transplantation. The main complications in the first year post-transplantation were hypertension (26/63, 41.3%), crinosity (14/63, 22.2%),drug-induced hepatic injury(11/63, 17.5%), gingival hyperplasia (10/63, 15.8%), pulmonary infection(9/63, 14.3%),bone marrow suppression(5/63, 7.9%), herpes (4/63, 6.3%) and diabetes (3/63, 4.8%). Conclusion: Renal transplantation is a preferred method for the treatment of children in end-stage renal disease (ESRD). Good tissue matching, proper operative time and pattern, peri-operactive care were essential to success, as well as appropriate immuno-suppressant strategy and good compliance.

Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells.

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Burkhardt, Ute E; Hainz, Ursula; Stevenson, Kristen; Goldstein, Natalie R; Pasek, Mildred; Naito, Masayasu; Wu, Di; Ho, Vincent T; Alonso, Anselmo; Hammond, Naa Norkor; Wong, Jessica; Sievers, Quinlan L; Brusic, Ana; McDonough, Sean M; Zeng, Wanyong; Perrin, Ann; Brown, Jennifer R; Canning, Christine M; Koreth, John; Cutler, Corey; Armand, Philippe; Neuberg, Donna; Lee, Jeng-Shin; Antin, Joseph H; Mulligan, Richard C; Sasada, Tetsuro; Ritz, Jerome; Soiffer, Robert J; Dranoff, Glenn; Alyea, Edwin P; Wu, Catherine J

2013-09-01

Patients with advanced hematologic malignancies remain at risk for relapse following reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We conducted a prospective clinical trial to test whether vaccination with whole leukemia cells early after transplantation facilitates the expansion of leukemia-reactive T cells and thereby enhances antitumor immunity. We enrolled 22 patients with advanced chronic lymphocytic leukemia (CLL), 18 of whom received up to 6 vaccines initiated between days 30 and 45 after transplantation. Each vaccine consisted of irradiated autologous tumor cells admixed with GM-CSF-secreting bystander cells. Serial patient PBMC samples following transplantation were collected, and the impact of vaccination on T cell activity was evaluated. At a median follow-up of 2.9 (range, 1-4) years, the estimated 2-year progression-free and overall survival rates of vaccinated subjects were 82% (95% CI, 54%-94%) and 88% (95% CI, 59%-97%), respectively. Although vaccination only had a modest impact on recovering T cell numbers, CD8+ T cells from vaccinated patients consistently reacted against autologous tumor, but not alloantigen-bearing recipient cells with increased secretion of the effector cytokine IFN-γ, unlike T cells from nonvaccinated CLL patients undergoing allo-HSCT. Further analysis confirmed that 17% (range, 13%-33%) of CD8+ T cell clones isolated from 4 vaccinated patients by limiting dilution of bulk tumor-reactive T cells solely reacted against CLL-associated antigens. Our studies suggest that autologous tumor cell vaccination is an effective strategy to advance long-term leukemia control following allo-HSCT. Clinicaltrials.gov NCT00442130. NCI (5R21CA115043-2), NHLBI (5R01HL103532-03), and Leukemia and Lymphoma Society Translational Research Program.

Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation.

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Thomson, Angus W; Zahorchak, Alan F; Ezzelarab, Mohamed B; Butterfield, Lisa H; Lakkis, Fadi G; Metes, Diana M

2016-01-01

Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients' dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP)-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail.

Current Status of Immunomodulatory and Cellular Therapies in Preclinical and Clinical Islet Transplantation

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Preeti Chhabra

2011-01-01

Full Text Available Clinical islet transplantation is a -cell replacement strategy that represents a possible definitive intervention for patients with type 1 diabetes, offering substantial benefits in terms of lowering daily insulin requirements and reducing incidences of debilitating hypoglycemic episodes and unawareness. Despite impressive advances in this field, a limiting supply of islets, inadequate means for preventing islet rejection, and the deleterious diabetogenic and nephrotoxic side effects associated with chronic immunosuppressive therapy preclude its wide-spread applicability. Islet transplantation however allows a window of opportunity for attempting various therapeutic manipulations of islets prior to transplantation aimed at achieving superior transplant outcomes. In this paper, we will focus on the current status of various immunosuppressive and cellular therapies that promote graft function and survival in preclinical and clinical islet transplantation with special emphasis on the tolerance-inducing capacity of regulatory T cells as well as the -cells regenerative capacity of stem cells.

Effects of edaravone, a radical scavenger, on hepatocyte transplantation.

Science.gov (United States)

Hayashi, Chihiro; Ito, Masahiro; Ito, Ryoutaro; Murakumo, Akiko; Yamamoto, Naoki; Hiramatsu, Noriko; Fox, Ira J; Horiguchi, Akihiko

2014-12-01

Hepatocyte transplantation (HTx) has yielded significant improvements in liver function and survival in experimentally induced acute liver failure and liver-based metabolic disease. However, transplantation is inefficient, and it is thought that transplanted hepatocytes have a shortened lifespan because of inflammation involving excess nitric oxide (NO). The present study aimed to clarify whether edaravone, a free radical scavenger used to treat ischemic stroke, could reduce ischemic changes in hepatocyte-transplanted livers. Edaravone (3 mg/kg) was administered intravenously 24 h before HTx to Nagase analbuminemic rats (NARs). Hepatocytes were isolated, and 30 × 10(6) cells were injected in a 1.0-ml volume directly into the spleens of NARs. All experimental groups studied received FK506 to control rejection. Animals in Group A received medium-only; Group B received HTx only; and Group C received HTx and edaravone. Forty-eight hours after transplantation, the hepatocytes from animals were isolated and analyzed for staining with propidium iodide- and annexin-V using flow cytometry. Liver sections were also studied by immunostaining for albumin, and TUNEL. Peripheral blood serum albumin levels were measured on post-transplant days 0, 3, 5, 7, 10 and 14 using ELISA. The edaravone-treated animals demonstrated an increased number of engrafted donor hepatocytes in the liver. The edaravone-treated liver sections also contained fewer TUNEL-positive cells and animals that received edaravone had higher serum albumin levels post-transplantation. Hepatocytes were also found to have increased in numbers 2 weeks following treatment with edaravone. Edaravone administration during HTx can suppress apoptosis near the transplanted cells, increasing engraftment. These studies indicate its potential usefulness for future clinical application. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Evaluation of mechano-chemical degradation induced stresses of polyolefin pipes

Energy Technology Data Exchange (ETDEWEB)

Choi, Byoung Ho [Korea Univ., Seoul (Korea, Republic of); Chudnovsky, Alexander [The University of Illinois, Chicago (United States)

2008-07-01

The fracture phenomena in engineering thermoplastics resulting from chemical degradation is usually observed in the form of a microcrack network within a surface layer of degraded polymer exposed to a combined action of mechanical stresses and chemically aggressive environment. Degradation of polymers is usually manifested in a reduction of molecular weight, increase of crystallinity in semi crystalline polymers, increase of material density, a subtle increase in yield strength, and a dramatic reduction in toughness. The critical level of degradation for fracture initiation depends on the rates of toughness deterioration and build-up of the degradation related stresses as well as on the manufacturing and service stresses. In this paper, the evaluation of mechano-chemical degradation induced stress is attempted, and the application of the evaluated stress to the fracture initiation of polymer pipes is presented.

Evaluation of mechano-chemical degradation induced stresses of polyolefin pipes

International Nuclear Information System (INIS)

Choi, Byoung Ho; Chudnovsky, Alexander

2008-01-01

The fracture phenomena in engineering thermoplastics resulting from chemical degradation is usually observed in the form of a microcrack network within a surface layer of degraded polymer exposed to a combined action of mechanical stresses and chemically aggressive environment. Degradation of polymers is usually manifested in a reduction of molecular weight, increase of crystallinity in semi crystalline polymers, increase of material density, a subtle increase in yield strength, and a dramatic reduction in toughness. The critical level of degradation for fracture initiation depends on the rates of toughness deterioration and build-up of the degradation related stresses as well as on the manufacturing and service stresses. In this paper, the evaluation of mechano-chemical degradation induced stress is attempted, and the application of the evaluated stress to the fracture initiation of polymer pipes is presented

Cytomegalovirus-associated Immune Thrombocytopenic Purpura After Liver Transplantation

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Shu-Hao Wei

2007-01-01

Full Text Available Immune thrombocytopenic purpura (ITP is a rare complication after liver transplantation. Infection with cytomegalovirus (CMV is a frequent complication of organ transplantation and may induce autoimmune diseases, such as ITP. We report a case of ITP after primary CMV infection in a 3-year-old boy recipient of living-related orthotopic liver transplantation (OLT. The ITP developed 2 years after OLT in this patient who had received tacrolimus as an immunosuppressive agent, with nadir platelet counts of 5000/mm3 in 2 weeks. The patient was treated with two courses of intravenous gamma globulin (1 g/kg/day for 2 days and subsequent oral prednisolone (1.3 mg/kg/day for 2 weeks. He recovered from thrombocytopenia 4 weeks later. An inadequate immunosuppression, as evident by the low serum tacrolimus level (5.8 ng/mL before the episode of ITP in this patient, may allow the development of ITP after CMV infection. [J Formos Med Assoc 2007;106(4:327-329

Evolution of the role of the transplant pharmacist on the multidisciplinary transplant team.

Science.gov (United States)

Alloway, R R; Dupuis, R; Gabardi, S; Kaiser, T E; Taber, D J; Tichy, E M; Weimert-Pilch, N A

2011-08-01

Transplant pharmacists have been recognized as an essential part of the transplant team by their colleagues along with several governing and professional organizations. The specific education, training and responsibilities of the transplant pharmacist have not been clearly delineated in the literature. Various pharmacists across the country have been called upon to serve on the transplant team necessitating standardization of their fundamental and desirable activities. Therefore, the purpose of this manuscript is to describe the training and role of a transplant pharmacist on the patient care team and provide a roadmap to implementation of novel transplant pharmacy services. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

Pancreatic islet transplantation

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Corrêa-Giannella Maria

2009-09-01

Full Text Available Abstract Background No formulation of exogenous insulin available to date has yet been able to mimic the physiological nictemeral rhythms of this hormone, and despite all engineering advancements, the theoretical proposal of developing a mechanical replacement for pancreatic β cell still has not been reached. Thus, the replacement of β cells through pancreas and pancreatic islet transplantation are the only concrete alternatives for re-establishing the endogenous insulin secretion in type 1 diabetic patients. Since only 1 to 1.5% of the pancreatic mass corresponds to endocrine tissue, pancreatic islets transplantation arises as a natural alternative. Data from the International Islet Transplant Registry (ITR from 1983 to December 2000 document a total of 493 transplants performed around the world, with progressively worse rates of post-transplant insulin independence. In 2000, the "Edmonton Protocol" introduced several modifications to the transplantation procedure, such as the use of a steroid-free immunosuppression regimen and transplantation of a mean islet mass of 11,000 islet equivalents per kilogram, which significantly improved 1-year outcomes. Although the results of a 5-year follow-up in 65 patients demonstrated improvement in glycemic instability in a significant portion of them, only 7.5% of the patients have reached insulin independence, indicating the need of further advances in the preservation of the function of transplanted islet. In addition to the scarcity of organs available for transplantation, islets transplantation still faces major challenges, specially those related to cell loss during the process of islet isolation and the losses related to the graft site, apoptosis, allorejection, autoimmunity, and immunosuppression. The main strategies to optimize islet transplantation aim at improving all these aspects. Conclusion Human islet transplantation should be regarded as an intervention that can decrease the frequency of

Interneuron progenitor transplantation to treat CNS dysfunction

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Muhammad O Chohan

2016-08-01

Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.

Assessment of immunotoxicity induced by chemicals in human precision-cut lung slices (PCLS).

Science.gov (United States)

Lauenstein, L; Switalla, S; Prenzler, F; Seehase, S; Pfennig, O; Förster, C; Fieguth, H; Braun, A; Sewald, K

2014-06-01

Occupational asthma can be induced by a number of chemicals at the workplace. Risk assessment of potential sensitizers is mostly performed in animal experiments. With increasing public demand for alternative methods, human precision-cut lung slices (PCLS) have been developed as an ex vivo model. Human PCLS were exposed to increasing concentrations of 20 industrial chemicals including 4 respiratory allergens, 11 contact allergens, and 5 non-sensitizing irritants. Local respiratory irritation was characterized and expressed as 75% (EC25) and 50% (EC50) cell viability with respect to controls. Dose-response curves of all chemicals except for phenol were generated. Local respiratory inflammation was quantified by measuring the production of cytokines and chemokines. TNF-α and IL-1α were increased significantly in human PCLS after exposure to the respiratory sensitizers trimellitic anhydride (TMA) and ammonium hexachloroplatinate (HClPt) at subtoxic concentrations, while contact sensitizers and non-sensitizing irritants failed to induce the release of these cytokines to the same extent. Interestingly, significant increases in T(H)1/T(H)2 cytokines could be detected only after exposure to HClPt at a subtoxic concentration. In conclusion, allergen-induced cytokines were observed but not considered as biomarkers for the differentiation between respiratory and contact sensitizers. Our preliminary results show an ex vivo model which might be used for prediction of chemical-induced toxicity, but is due to its complex three-dimensional structure not applicable for a simple screening of functional and behavior changes of certain cell populations such as dendritic cells and T-cells in response to allergens. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Reactivation of Cutaneous Leishmaniasis after Renal Transplantation: A Case Report

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Hossein Mortazavi

2014-01-01

Full Text Available A 45-year-old man with reactivation of previously existing and subsiding cutaneous leishmaniasis on his wrist and lower leg (shin after renal transplantation was admitted to our dermatology service on March 2008. He presented to us with two huge tumoral and cauliflower-like lesions. Skin smear and histopathology of skin showed leishman bodies and confirmed the diagnosis. After renal transplantation, he received cyclosporine plus prednisolone to induce immunosuppression and reduce the probability of transplant rejection. After immunosuppressive therapy, reactivation of cutaneous leishmaniasis with the above presentation took place. The patient responded to 800 mg/day intravenous sodium stibogluconate for 3 weeks plus local cryotherapy. Systemic plus local therapy along with reducing the doses of immunosuppressive drugs led to improvement of lesions. Reactivation of leishmaniasis after immunosuppression has been rarely reported.

Soft X-ray induced chemical modification of polysaccharides in vascular plant cell walls

International Nuclear Information System (INIS)

Cody, George D.; Brandes, Jay; Jacobsen, Chris; Wirick, Susan

2009-01-01

Scanning transmission X-ray microscopy and micro carbon X-ray Absorption Near Edge Spectroscopy (C-XANES) can provide quantitative information regarding the distribution of the biopolymers cellulose, hemicellulose, and lignin in vascular plant cell walls. In the case of angiosperms, flowering plants, C-XANES may also be able to distinguish variations in lignin monomer distributions throughout the cell wall. Polysaccharides are susceptible to soft X-ray irradiation induced chemical transformations that may complicate spectral analysis. The stability of a model polysaccharide, cellulose acetate, to variable doses of soft X-rays under conditions optimized for high quality C-XANES spectroscopy was investigated. The primary chemical effect of soft X-ray irradiation on cellulose acetate involves mass loss coincident with de-acetylation. A lesser amount of vinyl ketone formation also occurs. Reduction in irradiation dose via defocusing does enable high quality pristine spectra to be obtained. Radiation induced chemical modification studies of oak cell wall reveals that cellulose and hemicellulose are less labile to chemical modification than cellulose acetate. Strategies for obtaining pristine C-XANES spectra of polysaccharides are presented.

Cerebral Post-Transplant Lymphoproliferative Disorder Occurring after Renal Transplantation: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Suh, Jang Ho; Byun, Woo Mok; Kim, Hong Chul; Hwang, Min Su [Dept. of Radiology, Yeungnam University College of Medicine, Daegu (Korea, Republic of)

2012-04-15

Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation and immunosuppression. A 36-year-old woman with a history of renal transplantation visited the hospital complaining of headache and on pathology was diagnosed with cerebral PTLD manifesting as multiple rim enhanced masses in both hemispheres. We report here a case of post-transplant lymphoproliferative disorder involving the cerebrum occurring after renal transplantation, and describe the MRI findings for this patient

Cerebral Post-Transplant Lymphoproliferative Disorder Occurring after Renal Transplantation: A Case Report

International Nuclear Information System (INIS)

Suh, Jang Ho; Byun, Woo Mok; Kim, Hong Chul; Hwang, Min Su

2012-01-01

Post-transplant lymphoproliferative disorder (PTLD) is a complication of organ transplantation and immunosuppression. A 36-year-old woman with a history of renal transplantation visited the hospital complaining of headache and on pathology was diagnosed with cerebral PTLD manifesting as multiple rim enhanced masses in both hemispheres. We report here a case of post-transplant lymphoproliferative disorder involving the cerebrum occurring after renal transplantation, and describe the MRI findings for this patient

SERS-Based Prognosis of Kidney Transplant Outcome

Science.gov (United States)

Chi, Jingmao

Kidney transplant is the predominant procedure of all organ transplants around the world. The number of patients on the waiting list for a kidney is growing rapidly, yet the number of donations does not keep up with the fast-growing need. This thesis focuses on the surface-enhanced Raman scattering (SERS) analysis of urine samples for prognosis of kidney transplant outcome, which can potentially let patients have a more timely treatment as well as expand the organ pool for transplant. We have observed unique SERS spectral features from urine samples of kidney transplant recipients that have strong associations with the kidney acute rejection (AR) based on the analysis of urine one day after the transplant. Our ability to provide an early prognosis of transplant outcome is a significant advance over the current gold standard of clinical diagnosis, which occurs weeks or months after the surgical procedure. The SERS analysis has also been applied to urine samples from deceased kidney donors. Excellent classification ability was achieved when the enhanced PCA-LDA analysis was used to classify and identify urine samples from different cases. The sensitivity of the acute tubular necrosis (ATN) class is more than 90%, which can indicate the usable kidneys in the high failure risk category. This analysis can help clinicians identify usable kidneys which would be discarded using conventional clinic methods as high failure risk. To investigate the biomarkers that cause the unique SERS features, an HPLC-SERS-MS approach was established. The high-performance liquid chromatography (HPLC) was used to separate the urinary components to reduce the sample complexity. The mass spectrometry (MS) was used to determine the formulas and the structures of the biomarkers. The presence of 1-methyl-2-pyrrolidone (NMP) and adenine in urine samples were confirmed by both MS and SERS analysis. Succinylmonocholine, a metabolite of suxamethonium, has a potential to be the biomarker that causes

DNA damage, acetylcholinesterase activity and lysosomal stability in native and transplanted mussels (Mytilus edulis) in areas close to coastal chemical dumping sites in Denmark

DEFF Research Database (Denmark)

Rank, J.; Lehtonen, K. K.; Strand, J.

2007-01-01

of chemical pollution complex, as seen especially in the variability in results on DNA damage, and also in regard to AChE activity. These investigations further stress the importance of understanding the effects of natural factors (salinity, temperature, water levels, rain and storm events) in correct......Biomarkers of genotoxicity (DNA damage, measured as tail moment in the Comet assay), neurotoxicity (acetylcholinesterase inhibition, AChE) and general stress (lysosomal membrane stability, LMS) were studied in native and transplanted blue mussels (Mytilus edulis) in coastal areas of western Denmark...... potentially affected by anthropogenic pollution originating from chemical dumping sites. The results indicate responses to pollution in all the biomarkers applied at the suspected areas, but the results were not consistent. Seasonal fluctuations in exposure situations at the study sites make interpretation...

After the Transplant

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... After the transplant Preventing rejection Post-transplant medications Types of immunosuppressants Switching immunosuppressants Side effects Other medications Generic and brand name drugs Post-transplant tests Infections and immunity Lifestyle changes Health concerns Back to work or ...

Stem Cell Transplant

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... Graft-versus-host disease: A potential risk when stem cells come from donors If you receive a transplant ... medications and blood products into your body. Collecting stem cells for transplant If a transplant using your own ...

Cardiac transplantation in South Carolina: 300 transplants.

Science.gov (United States)

Crumbley, A J; Odom, Sylvia; Van Bakel, Adrian B; Pereira, Naveen; Ikonomidis, John S; Bradley, Scott; Kratz, John M; Sade, Robert M; Uber, Walt; Stroud, Martha R; Crawford, Fred A

2006-02-01

For nearly 20 years, the Medical University's Heart Transplant Program has been providing the citizens of South Carolina with excellent results with a minimum of delay. We present here the results of our first 300 heart transplants, spanning the first 18 years of the Cardiac Transplant Program at the Medical University. Overall survival has been very good, with one, five and ten year survival rates in the adults being 92 +/- 2%, 78 +/- 3%, and 58 +/- 4%. The children's group showed survival rates of 94 +/- 5%, 79 +/- 11%, and 79 +/- 11% over the same lengths of time. Most recently, the federally sponsored Scientific Registry of Transplant Recipients (www.ustransplant.org, July 2005) reports for MUSC a one-year survival of 97.67% and three-year survival of 90.74%; both leading the Southeast. We attribute this success to the dedicated work of health care workers at all levels who believe in attention to detail and that the patient always comes first. It is our hope that we will be able to continue to provide expert, state-of-the-art, cardiac transplant services long into the future, while continuing to expand our heart failure management program as dictated by further developments in this rapidly evolving specialty.

Acquisition and Cure of Autoimmune Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

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Hsin-An Hou

2007-09-01

Full Text Available Hematopoietic stem cell transplantation (HSCT can either cause or eliminate autoimmune disease. Here, we report two cases. One was a 33-year-old woman with myelodysplastic syndrome (refractory anemia who received bone marrow transplantation from her human leukocyte antigen (HLA-identical sister who had a history of Graves' disease. Antithyroid antibodies, including antimicrosomal antibody and antithy-roglobulin antibody, appeared 4 months after transplantation. Clinical hyperthyroidism appeared 7 months after transplantation, and a hypothyroid state was noted 2 months later. The other case was a 50-year-old woman with Sjögren's syndrome and hypothyroidism who was diagnosed with peripheral T cell non-Hodgkin's lymphoma. She received allogeneic peripheral blood stem cell transplantation (PBSCT from her histocompatible sister owing to only partial response to traditional chemotherapy. Cure of lymphoma and remission of Sjögren's syndrome was noted 4 years after PBSCT. These two illustrative cases, one of acquisition of hyperthyroidism and the other of remission of Sjögren's syndrome after transplantation, highlights that HSCT can induce adoptive autoimmune disease or cure coincidental autoimmune disease. Donor selection and attentive monitoring is required in such circumstances.

Transcriptome Sequencing of Chemically Induced Aquilaria sinensis to Identify Genes Related to Agarwood Formation.

Science.gov (United States)

Ye, Wei; Wu, Hongqing; He, Xin; Wang, Lei; Zhang, Weimin; Li, Haohua; Fan, Yunfei; Tan, Guohui; Liu, Taomei; Gao, Xiaoxia

2016-01-01

Agarwood is a traditional Chinese medicine used as a clinical sedative, carminative, and antiemetic drug. Agarwood is formed in Aquilaria sinensis when A. sinensis trees are threatened by external physical, chemical injury or endophytic fungal irritation. However, the mechanism of agarwood formation via chemical induction remains unclear. In this study, we characterized the transcriptome of different parts of a chemically induced A. sinensis trunk sample with agarwood. The Illumina sequencing platform was used to identify the genes involved in agarwood formation. A five-year-old Aquilaria sinensis treated by formic acid was selected. The white wood part (B1 sample), the transition part between agarwood and white wood (W2 sample), the agarwood part (J3 sample), and the rotten wood part (F5 sample) were collected for transcriptome sequencing. Accordingly, 54,685,634 clean reads, which were assembled into 83,467 unigenes, were obtained with a Q20 value of 97.5%. A total of 50,565 unigenes were annotated using the Nr, Nt, SWISS-PROT, KEGG, COG, and GO databases. In particular, 171,331,352 unigenes were annotated by various pathways, including the sesquiterpenoid (ko00909) and plant-pathogen interaction (ko03040) pathways. These pathways were related to sesquiterpenoid biosynthesis and defensive responses to chemical stimulation. The transcriptome data of the different parts of the chemically induced A. sinensis trunk provide a rich source of materials for discovering and identifying the genes involved in sesquiterpenoid production and in defensive responses to chemical stimulation. This study is the first to use de novo sequencing and transcriptome assembly for different parts of chemically induced A. sinensis. Results demonstrate that the sesquiterpenoid biosynthesis pathway and WRKY transcription factor play important roles in agarwood formation via chemical induction. The comparative analysis of the transcriptome data of agarwood and A. sinensis lays the foundation

Cooperative unfolding of apolipoprotein A-1 induced by chemical denaturation.

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Eckhardt, D; Li-Blatter, X; Schönfeld, H-J; Heerklotz, H; Seelig, J

2018-05-25

Apolipoprotein A-1 (Apo A-1) plays an important role in lipid transfer and obesity. Chemical unfolding of α-helical Apo A-1 is induced with guanidineHCl and monitored with differential scanning calorimetry (DSC) and CD spectroscopy. The unfolding enthalpy and the midpoint temperature of unfolding decrease linearly with increasing guanidineHCl concentration, caused by the weak binding of denaturant. At room temperature, binding of 50-60 molecules guanidineHCl leads to a complete Apo A-1 unfolding. The entropy of unfolding decreases to a lesser extent than the unfolding enthalpy. Apo A-1 chemical unfolding is a dynamic multi-state equilibrium that is analysed with the Zimm-Bragg theory modified for chemical unfolding. The chemical Zimm-Bragg theory predicts the denaturant binding constant K D and the protein cooperativity σ. Chemical unfolding of Apo A-1 is two orders of magnitude less cooperative than thermal unfolding. The free energy of thermal unfolding is ~0.2 kcal/mol per amino acid residue and ~1.0 kcal/mol for chemical unfolding at room temperature. The Zimm-Bragg theory calculates conformational probabilities and the chemical Zimm-Bragg theory predicts stretches of α-helical segments in dynamic equilibrium, unfolding and refolding independently and fast. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Organ Transplants in Kazakhstan.

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Baigenzhin, Abay; Doskaliyev, Zhaksylyk; Tuganbekova, Saltanat; Zharikov, Serik; Altynova, Sholpan; Gaipov, Abduzhappar

2015-11-01

The Republic of Kazakhstan is one of the fastest developing countries in the world and has a health care system that is unique in Central Asia. Its organ transplant services are also developing rapidly. We aimed to analyze and briefly report on the current status of organ transplant in the Republic of Kazakhstan. We analyzed organ transplant activities in that country for the period 2012 to 2014. All data were collected from the official database of the National Transplant Coordinating Center of the Republic of Kazakhstan. At the end of 2014, the number of transplant centers had increased to 10, three of which could perform multiorgan transplants; during the same period, the number of deceased-donor organ-donating hospitals increased up to 37. By 2013, the transplant activity rate for all centers had reached 9.22 per million population. During the previous 3 years (2012-2014), there was a 3-fold increase in the number of living donors and an 18-fold increase in the number of kidney transplants. Between 2012 and 2014, the number of living-donor liver transplants increased from 17 to 25, and the number of deceased-donor transplants increased from 3 to 7. During the last 3 years (2012-2014), the number of heart transplants increased to 7 cases. During the last 3 years (2012-2014), Kazakhstan achieved a significant improvement in the organization of its transplant services, and a noticeable upward trend in the system continues.

Carinal transplantation.

OpenAIRE

Ueda, H; Shirakusa, T

1992-01-01

BACKGROUND: Current techniques of management of carinal lesions are not always satisfactory. Carinal transplantation, if feasible, would be valuable in certain circumstances. METHODS AND RESULTS: Carinal transplantation experiments were performed in dogs. In early cross transplant experiments there were problems in controlling ventilation and in obtaining satisfactory anastomoses, and the animals failed to live for even a few days. In seven subsequent experiments the carinal graft was removed...

Radiation-induced mammary carcinogenesis in rodent models. What's different from chemical carcinogenesis?

International Nuclear Information System (INIS)

Imaoka, Tatsuhiko; Nishimura, Mayumi; Iizuka, Daisuke; Daino, Kazuhiro; Takabatake, Takashi; Okamoto, Mieko; Kakinuma, Shizuko; Shimada, Yoshiya

2009-01-01

Ionizing radiation is one of a few well-characterized etiologic factors of human breast cancer. Laboratory rodents serve as useful experimental models for investigating dose responses and mechanisms of cancer development. Using these models, a lot of information has been accumulated about mammary gland cancer, which can be induced by both chemical carcinogens and radiation. In this review, we first list some experimental rodent models of breast cancer induction. We then focus on several topics that are important in understanding the mechanisms and risk modification of breast cancer development, and compare radiation and chemical carcinogenesis models. We will focus on the pathology and natural history of cancer development in these models, genetic changes observed in induced cancers, indirect effects of carcinogens, and finally risk modification by reproductive factors and age at exposure to the carcinogens. In addition, we summarize the knowledge available on mammary stem/progenitor cells as a potential target of carcinogens. Comparison of chemical and radiation carcinogenesis models on these topics indicates certain similarities, but it also indicates clear differences in several important aspects, such as genetic alterations of induced cancers and modification of susceptibility by age and reproductive factors. Identification of the target cell type and relevant translational research for human risk management may be among the important issues that are addressed by radiation carcinogenesis models. (author)

Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a Single Transcription Factor

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Ren Guo

2017-08-01

Full Text Available Liver or hepatocytes transplantation is limited by the availability of donor organs. Functional hepatocytes independent of the donor sources may have wide applications in regenerative medicine and the drug industry. Recent studies have demonstrated that chemical cocktails may induce reprogramming of fibroblasts into a range of functional somatic cells. Here, we show that mouse fibroblasts can be transdifferentiated into the hepatocyte-like cells (iHeps using only one transcription factor (TF (Foxa1, Foxa2, or Foxa3 plus a chemical cocktail. These iHeps show typical epithelial morphology, express multiple hepatocyte-specific genes, and acquire hepatocyte functions. Genetic lineage tracing confirms the fibroblast origin of these iHeps. More interestingly, these iHeps are expandable in vitro and can reconstitute the damaged hepatic tissues of the fumarylacetoacetate hydrolase-deficient (Fah−/− mice. Our study provides a strategy to generate functional hepatocyte-like cells by using a single TF plus a chemical cocktail and is one step closer to generate the full-chemical iHeps.

Bioanalytical evidence that chemicals in tattoo ink can induce adaptive stress responses.

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Neale, Peta A; Stalter, Daniel; Tang, Janet Y M; Escher, Beate I

2015-10-15

Tattooing is becoming increasingly popular, particularly amongst young people. However, tattoo inks contain a complex mixture of chemical impurities that may pose a long-term risk for human health. As a first step towards the risk assessment of these complex mixtures we propose to assess the toxicological hazard potential of tattoo ink chemicals with cell-based bioassays. Targeted modes of toxic action and cellular endpoints included cytotoxicity, genotoxicity and adaptive stress response pathways. The studied tattoo inks, which were extracted with hexane as a proxy for the bioavailable fraction, caused effects in all bioassays, with the red and yellow tattoo inks having the greatest response, particularly inducing genotoxicity and oxidative stress response endpoints. Chemical analysis revealed the presence of polycyclic aromatic hydrocarbons in the tested black tattoo ink at concentrations twice the recommended level. The detected polycyclic aromatic hydrocarbons only explained 0.06% of the oxidative stress response of the black tattoo ink, thus the majority of the effect was caused by unidentified components. The study indicates that currently available tattoo inks contain components that induce adaptive stress response pathways, but to evaluate the risk to human health further work is required to understand the toxicokinetics of tattoo ink chemicals in the body. Copyright © 2015 Elsevier B.V. All rights reserved.

Kinetics of electrically and chemically induced swelling in polyelectrolyte gels

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Grimshaw, P. E.; Nussbaum, J. H.; Grodzinsky, A. J.; Yarmush, M. L.

1990-09-01

Controlled swelling and shrinking of polyelectrolyte gels is useful for regulating the transport of solutes into, out of, and through these materials. A macroscopic continuum model is presented to predict the kinetics of swelling in polyelectrolyte gel membranes induced by augmentation of electrostatic swelling forces arising from membrane fixed charge groups. The model accounts for ionic transport within the membrane, electrodiffusion phenomena, dissociation of membrane charge groups, intramembrane fluid flow, and mechanical deformation of the membrane matrix. Model predictions are compared with measurements of chemically and electrically induced swelling and shrinking in crosslinked polymethacrylic acid (PMAA) membranes. Large, reversible changes in PMAA membrane hydration were observed after changing the bath pH or by applying an electric field to modify the intramembrane ionic environment and fixed charge density. A relatively slow swelling process and more rapid shrinking for both chemical and electrical modulation of the intramembrane pH are observed. The model indicates that retardation of membrane swelling is dominated by diffusion-limited reaction of H+ ions with membrane charge groups, and that the more rapid shrinking is limited primarily by mechanical processes.

Three-dimensional laser-induced fluorescence measurements of turbulent chemical plumes

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True, Aaron; Crimaldi, John

2017-11-01

In order to find prey, mates, and suitable habitat, many organisms must navigate through complex chemical plume structures in turbulent flow environments. In this context, we investigate the spatial and temporal structure of chemical plumes released isokinetically into fractal-grid-generated turbulence in an open channel flow. We first utilized particle image velocimetry (PIV) to characterize flow conditions (mean free stream velocities, turbulence intensities, turbulent kinetic energy dissipation rates, Taylor Reynolds numbers). We then implemented a newly developed high-resolution, high-speed, volumetric scanning laser-induced fluorescence (LIF) system for near time-resolved measurements of three-dimensional chemical plume structures. We investigated cases with and without a cylinder wake, and compare statistical (mean, variance, intermittency, probability density functions) and spectral (power spectrum of concentration fluctuations) characteristics of the chemical plume structure. Stretching and folding of complex three-dimensional filament structures during chaotic turbulent mixing is greatly enhanced in the cylinder wake case. In future experiments, we will implement simultaneous PIV and LIF, enabling computation of the covariance of the velocity and chemical concentration fluctuations and thus estimation of turbulent eddy diffusivities. NSF PHY 1555862.

Current Status of Immunomodulatory and Cellular Therapies in Preclinical and Clinical Islet Transplantation

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Chhabra, Preeti; Brayman, Kenneth L.

2011-01-01

Clinical islet transplantation is a β-cell replacement strategy that represents a possible definitive intervention for patients with type 1 diabetes, offering substantial benefits in terms of lowering daily insulin requirements and reducing incidences of debilitating hypoglycemic episodes and unawareness. Despite impressive advances in this field, a limiting supply of islets, inadequate means for preventing islet rejection, and the deleterious diabetogenic and nephrotoxic side effects associated with chronic immunosuppressive therapy preclude its wide-spread applicability. Islet transplantation however allows a window of opportunity for attempting various therapeutic manipulations of islets prior to transplantation aimed at achieving superior transplant outcomes. In this paper, we will focus on the current status of various immunosuppressive and cellular therapies that promote graft function and survival in preclinical and clinical islet transplantation with special emphasis on the tolerance-inducing capacity of regulatory T cells as well as the β-cells regenerative capacity of stem cells. PMID:22046502

[Transplant Surgeon Meets Nephrologist: Important Nephrological Aspects Before and After Kidney or Liver Transplantation].

Science.gov (United States)

Vondran, F W R; Wintterle, S; Bräsen, J H; Haller, H; Klempnauer, J; Richter, N; Lehner, F; Schiffer, M

2017-04-01

In cases of chronic renal insufficiency, successful kidney transplantation is the method of choice to restore patients' health, well-being and physical fitness. The interdisciplinary collaboration of nephrologists and transplant surgeons has always been a prerequisite for the successful pre-, peri- and post-transplant care of renal transplant patients. The same holds true for liver transplant patients. Here the nephrologist is often involved in cases requiring pre- or post-transplant dialysis as well as in decision making for combined liver-kidney transplantation. This review focuses on nephrological aspects in patient care before and after kidney and liver transplantation. Georg Thieme Verlag KG Stuttgart · New York.

Too poor for transplant: finance and insurance issues in transplant ethics.

Science.gov (United States)

Laurentine, Kyle Alexander; Bramstedt, Katrina A

2010-06-01

Donor organs are a scarce gift. Additionally, transplantation is very expensive and the United States lacks universal health insurance for all citizens. These facts combine to make personal finance and insurance some of the criteria for wait listing at US transplant centers. Previous research has shown that the poor and the uninsured (as well as women and nonwhites) are less likely to receive a transplant. Living donor candidates are also limited by the US insurance system. To determine the effect of finance and insurance variables on access to transplant and living donation. A qualitative descriptive study of ethics consultation data contained in a research registry approved by the institutional review board at California Pacific Medical Center. This study analyzes research registry data from a large community hospital in Northern California that serves patients from California, Oregon, and Nevada. The registry data are derived from transplant ethics consultations occurring between January 1, 2007, and June 30, 2009. This study explores the restriction of access to transplantation and of participation in living donation. More than a quarter of all transplant ethics consultation reports described the restriction of transplant-related treatment for reasons rooted in finance or insurance. Individuals on the recipient side and on the donor side were hindered with regard to access. Insurance status and personal ability to pay significantly affect access to transplantation in the United States, and this theme is a frequent feature of ethics consultations at California Pacific Medical Center.

History of Lung Transplantation.

Science.gov (United States)

Dabak, Gül; Şenbaklavacı, Ömer

2016-04-01

History of lung transplantation in the world can be traced back to the early years of the 20 th century when experimental vascular anastomotic techniques were developed by Carrel and Guthrie, followed by transplantation of thoracic organs on animal models by Demikhov and finally it was James Hardy who did the first lung transplantation attempt on human. But it was not until the discovery of cyclosporine and development of better surgical techniques that success could be achieved in that field by the Toronto Lung Transplant Group led by Joel Cooper. Up to the present day, over 51.000 lung transplants were performed in the world at different centers. The start of lung transplantation in Turkey has been delayed for various reasons. From 1998 on, there were several attempts but the first successful lung transplant was performed at Sureyyapasa Hospital in 2009. Today there are four lung transplant centers in Turkey; two in Istanbul, one in Ankara and another one in Izmir. Three lung transplant centers from Istanbul which belong to private sector have newly applied for licence from the Ministry of Health.

Feeder cells support the culture of induced pluripotent stem cells even after chemical fixation.

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Xiao-Shan Yue

Full Text Available Chemically fixed mouse embryonic fibroblasts (MEFs, instead of live feeder cells, were applied to the maintenance of mouse induced pluripotent stem (miPS cells. Formaldehyde and glutaraldehyde were used for chemical fixation. The chemically fixed MEF feeders maintained the pluripotency of miPS cells, as well as their undifferentiated state. Furthermore, the chemically fixed MEF feeders were reused several times without affecting their functions. These results indicate that chemical fixation can be applied to modify biological feeders chemically, without losing their original functions. Chemically fixed MEF feeders will be applicable to other stem cell cultures as a reusable extracellular matrix candidate that can be preserved on a long-term basis.

Perspectives of Older Kidney Transplant Recipients on Kidney Transplantation.

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Pinter, Jule; Hanson, Camilla S; Chapman, Jeremy R; Wong, Germaine; Craig, Jonathan C; Schell, Jane O; Tong, Allison

2017-03-07

Older kidney transplant recipients are susceptible to cognitive impairment, frailty, comorbidities, immunosuppression-related complications, and chronic graft failure, however, there has been limited focus on their concerns and expectations related to transplantation. This study aims to describe the perspectives of older kidney transplant recipients about their experience of kidney transplantation, self-management, and treatment goals to inform strategies and interventions that address their specific needs. Face-to-face semistructured interviews were conducted with 30 kidney transplant recipients aged 65-80 years from five renal units in Australia. Transcripts were analyzed thematically. Six themes were identified: restoring vitality of youth (with subthemes of revived mindset for resilience, embracing enjoyment in life, drive for self-actualization); persisting through prolonged recovery (yielding to aging, accepting functional limitations, pushing the limit, enduring treatment responsibilities); imposing sicknesses (combatting devastating comorbidities, painful restrictions, emerging disillusionment, anxieties about accumulating side effects, consuming treatment burden); prioritizing graft survival (privileged with a miracle, negotiating risks for longevity, enacting a moral duty, preserving the last opportunity); confronting health deterioration (vulnerability and helplessness, narrowing focus to immediate concerns, uncertainty of survival); and value of existence (purpose through autonomy, refusing the burden of futile treatment, staying alive by all means). Older kidney transplant recipients felt able to enjoy life and strived to live at their newly re-established potential and capability, which motivated them to protect their graft. However, some felt constrained by slow recuperation and overwhelmed by unexpected comorbidities, medication-related side effects, and health decline. Our findings suggest the need to prepare and support older recipients for self

Chemical inducible promotor used to obtain transgenic plants with a silent marker

Science.gov (United States)

Chua, Nam-Hai; Aoyama, Takashi

2000-01-01

A chemically inducible promoter is described which may be used to transform plants with genes which are easily regulatable by adding plants or plant cells to a medium containing an inducer of the promoter or by removing the plants or plant cells from such medium. The promoter described is one which is inducible by a glucocorticoid which is not endogenous to plants. Such promoters may be used with a variety of genes such as ipt or knotted1 to induce shoot formation in the presence of a glucocorticoid. The promoter may also be used with antibiotic or herbicide resistance genes which are then regulatable by the presence or absence of inducer rather than being constitutive. Other examples of genes which may be placed under the control of the inducible promoter are also presented.

Radiation Exposure from Diagnostic Imaging in a Cohort of Pediatric Transplant Recipients.

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Alexandra Seal

Full Text Available Recipients of solid organ transplants (SOT have extensive diagnostic imaging (DI. The purpose of this study was to quantify this exposure. Children from northern Alberta with SOTs at Stollery Children's Hospital, Edmonton, Alberta January 1, 2006, to July 31, 2012, were included. Effective doses of radiation were estimated using published norms for DI performed post-transplant up to October 16, 2014. The 54 eligible children had 6215 DI studies (5628 plain films, 293 computerized tomography (CT scans, 149 positron emission topography (PET -CT scans, 47 nuclear medicine scans and 98 cardiac catheterizations. Children less than 5 years of age underwent more DI studies than did older children (median (IQR 140 (66-210 vs 49 (19-105, p = 0.010. Children with post-transplant lymphoproliferative disorder (N = 8 had more CT scans (median (IQR 13 (5.5-36 vs 1 (0-5, p100 mSv. In conclusion, a significant proportion of pediatric transplant recipients have sufficient radiation exposure post-transplant for DI to be at potential risk for radiation-induced malignancies.

transplanted organs

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Rafal Szadujkis-Szadurski

2014-08-01

Full Text Available Rho-kinase and GTP-ase Rho are important regulators of vascular tone and blood pressure. The aim of this study was to investigate the role of Rho-kinase in artery reactions induced by angiotensin II (ANG II and the effects of ischemia-reperfusion injury as well as the function of intra- and extracellular calcium in these reactions. Experiments were performed on mesenteric superior arteries procured from cadaveric organ donors and conserved under the same conditions as transplanted kidneys. The vascular contraction in reaction to ANG II was measured in the presence of Rho-kinase inhibitor Y-27632, after ischemia and reperfusion, in Ca2+ and Ca2+-free solution. The maximal response to ANG II was reduced after ischemia, while an increase was observed after reperfusion. Vascular contraction induced by ANG II was decreased by Y-27632. Y-27632 reduced vascular contraction after reperfusion, both in Ca2+ and Ca2+-free solution. Reperfusion augments vascular contraction in reaction to ANG II. The Rho-kinase inhibitor Y-27632 reduces the hypersensitivity to ANG II after reperfusion mediated by both intra- and extracellular calcium. These results confirm the role of Rho-kinase in receptor-independent function of ANG II and in reperfusion-induced hypersensitivity.

Chemical changes induced on a TiO2 surface by electron bombardment

International Nuclear Information System (INIS)

Vergara, L.I.; Passeggi, M.C.G.; Ferron, J.

2007-01-01

We study the TiO 2 (Ti 4+ ) chemical reduction induced by electron bombardment using Auger electron spectroscopy and factor analysis. We show that the electron irradiation of a TiO 2 sample is characterized by the appearance of a lower Ti oxidation state, Ti 2 O 3 (Ti 3+ ), followed by a further deposition of carbon, which is present inevitably in the environment even under ultra-high vacuum conditions. The appearance of C over the surface is found to be a complex mechanism which affects the reduction process through passivation of the electron-induced oxygen desorption and formation of titanium carbide. For very high irradiation doses, we also found that the chemical changes on the surface are stopped due to the deposition of carbon in a graphitic form

Fluorescence spectroscopy for assessment of liver transplantation grafts concerning graft viability and patient survival

Science.gov (United States)

Vollet Filho, José D.; da Silveira, Marina R.; Castro-e-Silva, Orlando; Bagnato, Vanderlei S.; Kurachi, Cristina

2015-06-01

Evaluating transplantation grafts at harvest is essential for its success. Laser-induced fluorescence spectroscopy (LIFS) can help monitoring changes in metabolic/structural conditions of tissue during transplantation. The aim of the present study is to correlate LIFSobtained spectra of human hepatic grafts during liver transplantation with post-operative patients' mortality rate and biochemical parameters, establishing a method to exclude nonviable grafts before implantation. Orthotopic liver transplantation, piggyback technique was performed in 15 patients. LIFS was performed under 408nm excitation. Collection was performed immediately after opening donor's abdominal cavity, after cold perfusion, end of back-table period, and 5 min and 1 h after warm perfusion at recipient. Fluorescence information was compared to lactate, creatinine, bilirubin and INR levels and to survival status. LIFS was sensitive to liver changes during transplantation stages. Study-in-progress; initial results indicate correlation between fluorescence and life/death status of patients.

Hypothermia broadens the therapeutic time window of mesenchymal stem cell transplantation for severe neonatal hypoxic ischemic encephalopathy.

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Ahn, So Yoon; Chang, Yun Sil; Sung, Dong Kyung; Sung, Se In; Park, Won Soon

2018-05-16

Recently, we have demonstrated that concurrent hypothermia and mesenchymal stem cells (MSCs) transplantation synergistically improved severe neonatal hypoxic ischemic encephalopathy (HIE). The current study was designed to determine whether hypothermia could extend the therapeutic time window of MSC transplantation for severe neonatal HIE. To induce HIE, newborn rat pups were exposed to 8% oxygen for 2 h following unilateral carotid artery ligation on postnatal day (P) 7. After approving severe HIE involving >50% of the ipsilateral hemisphere volume, hypothermia (32 °C) for 2 days was started. MSCs were transplanted 2 days after HIE modeling. Follow-up brain MRI, sensorimotor function tests, assessment of inflammatory cytokines in the cerebrospinal fluid (CSF), and histological evaluation of peri-infarction area were performed. HIE induced progressively increasing brain infarction area over time, increased cell death, reactive gliosis and brain inflammation, and impaired sensorimotor function. All these damages observed in severe HIE showed better, robust improvement with a combination treatment of hypothermia and delayed MSC transplantation than with either stand-alone therapy. Hypothermia itself did not significantly reduce brain injury, but broadened the therapeutic time window of MSC transplantation for severe newborn HIE.

Prospective clinical testing of regulatory dendritic cells (DCreg in organ transplantation

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ANGUS W THOMSON

2016-01-01

Full Text Available Dendritic cells (DC are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients’ dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail.

The chemical cue tetrabromopyrrole from a biofilm bacterium induces settlement of multiple Caribbean corals.

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Sneed, Jennifer M; Sharp, Koty H; Ritchie, Kimberly B; Paul, Valerie J

2014-07-07

Microbial biofilms induce larval settlement for some invertebrates, including corals; however, the chemical cues involved have rarely been identified. Here, we demonstrate the role of microbial biofilms in inducing larval settlement with the Caribbean coral Porites astreoides and report the first instance of a chemical cue isolated from a marine biofilm bacterium that induces complete settlement (attachment and metamorphosis) of Caribbean coral larvae. Larvae settled in response to natural biofilms, and the response was eliminated when biofilms were treated with antibiotics. A similar settlement response was elicited by monospecific biofilms of a single bacterial strain, Pseudoalteromonas sp. PS5, isolated from the surface biofilm of a crustose coralline alga. The activity of Pseudoalteromonas sp. PS5 was attributed to the production of a single compound, tetrabromopyrrole (TBP), which has been shown previously to induce metamorphosis without attachment in Pacific acroporid corals. In addition to inducing settlement of brooded larvae (P. astreoides), TBP also induced larval settlement for two broadcast-spawning species, Orbicella (formerly Montastraea) franksi and Acropora palmata, indicating that this compound may have widespread importance among Caribbean coral species. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Transplantation of Neural Precursor Cells Attenuates Chronic Immune Environment in Cervical Spinal Cord Injury

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Lennart Riemann

2018-06-01

Full Text Available Inflammation after traumatic spinal cord injury (SCI is non-resolving and thus still present in chronic injury stages. It plays a key role in the pathophysiology of SCI and has been associated with further neurodegeneration and development of neuropathic pain. Neural precursor cells (NPCs have been shown to reduce the acute and sub-acute inflammatory response after SCI. In the present study, we examined effects of NPC transplantation on the immune environment in chronic stages of SCI. SCI was induced in rats by clip-compression of the cervical spinal cord at the level C6-C7. NPCs were transplanted 10 days post-injury. The functional outcome was assessed weekly for 8 weeks using the Basso, Beattie, and Bresnahan scale, the CatWalk system, and the grid walk test. Afterwards, the rats were sacrificed, and spinal cord sections were examined for M1/M2 macrophages, T lymphocytes, astrogliosis, and apoptosis using immunofluorescence staining. Rats treated with NPCs had compared to the control group significantly fewer pro-inflammatory M1 macrophages and reduced immunodensity for inducible nitric oxide synthase (iNOS, their marker enzyme. Anti-inflammatory M2 macrophages were rarely present 8 weeks after the SCI. In this model, the sub-acute transplantation of NPCs did not support survival and proliferation of M2 macrophages. Post-traumatic apoptosis, however, was significantly reduced in the NPC group, which might be explained by the altered microenvironment following NPC transplantation. Corresponding to these findings, reactive astrogliosis was significantly reduced in NPC-transplanted animals. Furthermore, we could observe a trend toward smaller cavity sizes and functional improvement following NPC transplantation. Our data suggest that transplantation of NPCs following SCI might attenuate inflammation even in chronic injury stages. This might prevent further neurodegeneration and could also set a stage for improved neuroregeneration after SCI.

Effective Prolonged Therapy with Voriconazole in a Lung Transplant Recipient with Spondylodiscitis Induced by Scedosporium apiospermum

OpenAIRE

Luijk, B.; Ekkelenkamp, M. B.; De Jong, P. A.; Kwakkel-van Erp, J. M.; Grutters, J. C.; van Kessel, D. A.; van de Graaf, E. A.

2011-01-01

Scedosporium/Pseudallescheria species are frequently seen in cystic fibrosis patients. However, disseminated forms after lung transplantation in these patients are rarely seen, but often with poor outcome. In this case report we describe a lung transplant recipient with cystic fibrosis who developed a spondylodiscitis that was caused by Scedosporium apiospermu...

Blood and Bone Marrow Transplant?

Science.gov (United States)

... Topics / Blood and Bone Marrow Transplant Blood and Bone Marrow Transplant Also known as Hematopoietic Stem Cell Transplant , Hematopoietic ... person, called a donor, it is an allogeneic transplant. Blood or bone marrow transplants most commonly are used to treat ...

Pulmão e transplante renal

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Patrícia Caetano Mota

2009-11-01

complications of immunosuppressive therapy, which are a diagnostic and therapeutic challenge.Aim: To evaluate patients admitted to the Renal Transplant Unit (RTU of Hospital de S. João with respiratory disease.Subject and methods: We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months.Results: Thirty-six patients were included. Mean age 55.2 (±13.4 years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9% or tacrolimus (22.2% or rapamycin (13.9%. Thirty-one patients (86.1% presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2% pneumonias, 5 (16.1% opportunistic infections, 2 (6.5% tracheobronchitis, and 1 case (3.2% of lung abscesses. Microbiological agent was identified in 7 cases (22.6%. Five patients (13.9% presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%, diagnostic in 10 cases (66.7%. Mean hospital stay was 17.1 (±18.5 days and no related death was observed.Conclusion: Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy.Rev Port Pneumol 2009; XV (6: 1073-1099 Palavras-chave: Pulmão, transplante renal, imunossupressão, Key-words: Lung, renal transplantation, immunosuppression

Behavioral Evaluation of hMSC-GFP+ Transplantation in an Hemiparkinson Experimental Model in Wistar Rat

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Jéssica Paola Alcázar Arzuza

2017-05-01

Full Text Available The effect of hMSCs-GFP+ transplantation was evaluated in an experimental model of Parkinson's disease (PD in 27 Wistar rats, or in three experimental groups: control (CON  n=7, injured (LES n=10 and transplanted (LES+T n=10. In order to evaluate the influence of the transplantation on the motor behavior, one month after the injury, rotation behavior induced by apomorphine, neurological test, transversal bar and SNpc cells positive to TH were developed. Using the Anova test, there was a decrease in the number of turns in transplanted animals (p=0.005 as well as in the neurological test (p=0.0004 and in the transverse bar that lead to this group in an intermediate position regarding LES and CON groups. There is a possible recovery of the transplantation-mediated nigroestriatal pathway of hMSC-GFP +.

Kaposi's sarcoma in organ transplant recipients. The Collaborative Transplantation Research Group of Ile de France.

Science.gov (United States)

Farge, D

1993-01-01

Kaposi's Sarcoma (KS) is a tumour of multicentric origin with increased frequency after organ transplantation. To date, only North American data from the Cincinnati Transplant Tumor Registry have given some information about this disease in organ transplant recipients, but its true prevalence still has to be determined. In order to analyze Kaposi's sarcoma after kidney, liver and heart transplantation, we performed a retrospective study using the oldest registry of organ transplant recipients in Europe. Among all 7923 organ transplant recipients recorded in the Groupe Collaboratif de Recherche en Transplantation de l'Ile de France (GCIF) registry from 1968 to 1990, we analyzed the prevalence and the clinical characteristics of Kaposi's sarcoma in 6229 kidney, 727 liver and 967 heart transplant recipients. In the subgroup of kidney transplant recipients, we assessed the role of cyclosporine on disease evolution. Overall prevalence of Kaposi's sarcoma after organ transplantation was 0.52%, but it was significantly higher among liver (1.24%) than among kidney (0.45%) and heart (0.41%) transplant recipients. Chronic hepatitis B surface antigen carriers were more frequent in liver than in kidney transplant recipients who developed Kaposi's sarcoma (66% vs 21%, p < 0.03). Following kidney transplantation, Kaposi's sarcoma was more severe in patients receiving cyclosporine (n = 16) when compared with those under conventional immunosuppression (n = 12). True prevalence of Kaposi's sarcoma among European transplant recipients is high (0.52%) and appeared significantly higher in liver compared with other organ transplant recipients. Cyclosporine seems to increase severity of the disease among kidney transplant recipient.

Chemically induced and light-independent cryptochrome photoreceptor activation.

Science.gov (United States)

Rosenfeldt, Gesa; Viana, Rafael Muñoz; Mootz, Henning D; von Arnim, Albrecht G; Batschauer, Alfred

2008-01-01

The cryptochrome photoreceptors of higher plants are dimeric proteins. Their N-terminal photosensory domain mediates dimerization, and the unique C-terminal extension (CCT) mediates signaling. We made use of the human FK506-binding protein (FKBP) that binds with high affinity to rapamycin or rapamycin analogs (rapalogs). The FKBP-rapamycin complex is recognized by another protein, FRB, thus allowing rapamycin-induced dimerization of two target proteins. Here we demonstrate by bioluminescence resonance energy transfer (BRET) assays the applicability of this regulated dimerization system to plants. Furthermore, we show that fusion proteins consisting of the C-terminal domain of Arabidopsis cryptochrome 2 fused to FKBP and FRB and coexpressed in Arabidopsis cells specifically induce the expression of cryptochrome-controlled reporter and endogenous genes in darkness upon incubation with the rapalog. These results demonstrate that the activation of cryptochrome signal transduction can be chemically induced in a dose-dependent fashion and uncoupled from the light signal, and provide the groundwork for gain-of-function experiments to study specifically the role of photoreceptors in darkness or in signaling cross-talk even under light conditions that activate members of all photoreceptor families.

High physiological prolactin induced by pituitary transplantation decreases BMD and BMC in the femoral metaphysis, but not in the diaphysis of adult female rats.

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Thongchote, Kanogwun; Charoenphandhu, Narattaphol; Krishnamra, Nateetip

2008-02-01

High physiological prolactin (PRL) stimulated intestinal calcium absorption and renal calcium uptake in mammals. Previous histomorphometric study revealed a significant increase in bone turnover in the trabecular part of the PRL-exposed long (cortical) bone; however, whole-bone densitometric analysis was unable to demonstrate such effect. We therefore studied differential changes in bone mineral density (BMD) and contents (BMC) of the femoral diaphysis and metaphysis in adult female rats exposed to high PRL induced by anterior pituitary (AP) transplantation. The estrogen-dependent effects of PRL on the femur were also investigated. We found that chronic exposure to PRL had no effect on BMD or BMC of the femoral diaphysis, which represented the cortical part of the long bone. It is interesting that 7 weeks after an AP transplantation, BMD and BMC of the femoral metaphysis were significantly decreased by 8% and 14%, respectively. Ovariectomy (Ovx) for 2, 5, and 7 weeks also decreased BMD and BMC in the femoral metaphysis, but not in the diaphysis. However, the AP transplantation plus Ovx (AP+Ovx) produced no additive effects. Nevertheless, 2.5 microg/kg 17beta-estradiol (E2) supplementation abolished the osteopenic effects of both Ovx and AP+Ovx on the femur. As for the L5-6 vertebrae, BMD and BMC were not affected by PRL exposure, but were significantly decreased by Ovx and AP+Ovx, and such decreases were completely prevented by E2 supplementation. It could be concluded that high physiological PRL induced a significant osteopenia in the trabecular part, i.e., the metaphysis, of the femora of adult female rats in an estrogen-dependent manner. Since PRL had no detectable effect on the vertebrae, the effects of PRL on bone appeared to be site-specific.

Opportunities to deter transplant tourism exist before referral for transplantation and during the workup and management of transplant candidates.

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Gill, Jagbir; Diec, Olivier; Landsberg, David N; Rose, Caren; Johnston, Olwyn; Keown, Paul A; Gill, John S

2011-05-01

Transplant tourism is a global issue, and physicians in the developed world may be in a position to actively deter this practice. To examine such opportunities, we identified 93 residents of British Columbia, Canada who had a kidney graft through tourism and determined their previous interactions with our transplant programs. These patients were mainly ethnic minorities (90%) who traveled to their country of origin for transplantation. Many tourists were transplanted early in their disease course, with 27 having a preemptive transplant. Among the 65 tourists referred for transplant, 33 failed to complete the evaluation. All tourists who completed an evaluation were placed on a waiting list in British Columbia and, after waiting a median of 2 years, pursued tourism. Most of these patients (62%) had a potential living donor, but none had an approved donor, with 13 donors found medically unsuitable, 8 ABO incompatible, and 12 who did not complete their evaluation. Thus, strategies to deter tourism should start before the development of end-stage renal disease and should be part of pretransplant workup and wait-list management, focusing on patients not progressing through their evaluation, those with a declined living donor, and those facing longer wait times, as these groups appear to be at higher risks for transplant tourism. Further studies are needed to identify individuals at risk for transplant tourism and to define effective strategies to deter these individuals.

Transplant tourism: Outcomes of United States residents who undergo kidney transplantation overseas.

Science.gov (United States)

Canales, Muna T; Kasiske, Bertram L; Rosenberg, Mark E

2006-12-27

Although international commerce in kidney transplantation is a reality, little is known about U.S. residents who travel abroad for kidney transplantation. We retrospectively reviewed the clinical outcomes of patients who were evaluated at the University of Minnesota Medical Center or Hennepin County Medical Center, but then surreptitiously underwent kidney transplantation overseas. We identified 10 patients who underwent kidney transplantation outside the United States between September 16, 2002 and June 30, 2006 and then returned for care in our programs. Eight were transplanted in Pakistan (all Somali), one was transplanted in China (Chinese), and one was transplanted in Iran (Iranian). All but one had a living donor. Mean age was 36.8+/-12.5 years with median follow-up of 2.0 years (range 0.4-3.7). Three patients communicated their intent to travel abroad before transplantation. Induction immunosuppressive therapy (if any) was available in 3/10, and initial maintenance immunosuppression was known in 5/10. Complications were primarily infectious, with six potentially life-threatening infections in four patients. At last follow-up, mean serum creatinine was 1.13+/-0.34 mg/dL, acute rejection occurred in 2/10, 1/10 grafts failed due to acute rejection, and 9/10 patients were alive. Kidney function and graft survival were generally good after surreptitious overseas kidney transplantation. Major problems included incomplete perioperative information communicated to the posttransplant care facility and a high incidence of posttransplant infections. Longer follow-up and detailed cost analysis are needed to better understand the implications of the growing phenomenon of transplant tourism.

Evaluation of contributing factors of post transplant erythrocytosis in renal transplant patients

International Nuclear Information System (INIS)

Ahmed, S.; Ahmed, E.; Naqvi, R.; Qureshi, S.

2012-01-01

Objective: To evaluate the prevalence and contributing factors causing post transplant erythrocytosis in renal transplant patients. Methods: This retrospective study was conducted on live related renal transplant patients at SIUT. The records of all transplant recipients transplanted between April 2008 and December 2008 and who had at least 24 months follow up were studied. Patients in whom haematocrit exceeded 51% and those who received treatment for it were classified into post transplant erythrocytosis group. Results: Out of 200 renal transplant patients who had functioning graft at the time of analysis, 40 (20%) developed post transplant erythrocytosis (HCT >51%) after a mean interval of 9.5+- 2.5 months. Patients with erythrocytosis were mostly males (95% in PTE group vs 73.75% in non PTE group) ,had a shorter period on dialysis before undergoing renal transplantation (9.28 months in PTE group vs 14.56 months in non PTE group) and had relatively better graft function at the onset of erythrocytosis as judged by serum creatinine (S. Creatinine of 1.06+-0.29 mg/dl in PTE group vs 1.37 +- 0.51 mg/dl in non PTE group). No thrombotic complications were observed. All patients with erythrocytosis were treated with enalapril (ACE inhibitors) and 28 out of 40 required phlebotomy in addition to ACE inhibitors. The mean HCT at the time of last follow up in treated patients was 48.61+-1.85%. Conclusion: Post transplant erythrocytosis generally occurs in male patients with good graft function, thrombotic complications are of rare occurrence and response to ACE inhibitors is good. (author)

Syngeneic transplantation in aplastic anemia

DEFF Research Database (Denmark)

Gerull, Sabine; Stern, Martin; Apperley, Jane

2013-01-01

Aplastic anemia is usually treated with immunosuppression or allogeneic transplant, depending on patient and disease characteristics. Syngeneic transplant offers a rare treatment opportunity with minimal transplant-related mortality, and offers an insight into disease mechanisms. We present here...... a retrospective analysis of all syngeneic transplants for aplastic anemia reported to the European Group for Blood and Marrow Transplantation. Between 1976 and 2009, 88 patients received 113 transplants. Most transplants (n=85) were preceded by a conditioning regimen, 22 of these including anti-thymocyte globulin...

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

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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.

Chemical inducible promoter used to obtain transgenic plants with a silent marker

Science.gov (United States)

Aoyama, Takashi; Zuo, Jianru; Chua, Nam-Hai

2004-08-31

A chemically inducible promoter is described that may be used to transform plants, including tobacco and lettuce, with genes which are easily regulatable by adding the plants or plant cells to a medium containing an inducer of the promoter or by removing the plants or plant cells from such medium. The promoter described is one that is inducible by a glucocorticoid which is not endogenous to plants. Such promoters may be used with a variety of genes such as ipt or knotted1 to induce shoot formation in the presence of a glucocorticoid. The promoter may also be used with antibiotic or herbicide resistance genes which are then regulatable by the presence or absence of inducer rather than being constitutive. Other examples of genes which may be placed under the control of the inducible promoter are also presented.

Therapeutic efficacy of human hepatocyte transplantation in a SCID/uPA mouse model with inducible liver disease.

Directory of Open Access Journals (Sweden)

Donna N Douglas

2010-02-01

Full Text Available Severe Combined Immune Deficient (SCID/Urokinase-type Plasminogen Activator (uPA mice undergo liver failure and are useful hosts for the propagation of transplanted human hepatocytes (HH which must compete with recipient-derived hepatocytes for replacement of the diseased liver parenchyma. While partial replacement by HH has proven useful for studies with Hepatitis C virus, complete replacement of SCID/uPA mouse liver by HH has never been achieved and limits the broader application of these mice for other areas of biomedical research. The herpes simplex virus type-1 thymidine kinase (HSVtk/ganciclovir (GCV system is a powerful tool for cell-specific ablation in transgenic animals. The aim of this study was to selectively eliminate murine-derived parenchymal liver cells from humanized SCID/uPA mouse liver in order to achieve mice with completely humanized liver parenchyma. Thus, we reproduced the HSVtk (vTK/GCV system of hepatic failure in SCID/uPA mice.In vitro experiments demonstrated efficient killing of vTK expressing hepatoma cells after GCV treatment. For in vivo experiments, expression of vTK was targeted to the livers of FVB/N and SCID/uPA mice. Hepatic sensitivity to GCV was first established in FVB/N mice since these mice do not undergo liver failure inherent to SCID/uPA mice. Hepatic vTK expression was found to be an integral component of GCV-induced pathologic and biochemical alterations and caused death due to liver dysfunction in vTK transgenic FVB/N and non-transplanted SCID/uPA mice. In SCID/uPA mice with humanized liver, vTK/GCV caused death despite extensive replacement of the mouse liver parenchyma with HH (ranging from 32-87%. Surprisingly, vTK/GCV-dependent apoptosis and mitochondrial aberrations were also localized to bystander vTK-negative HH.Extensive replacement of mouse liver parenchyma by HH does not provide a secure therapeutic advantage against vTK/GCV-induced cytotoxicity targeted to residual mouse hepatocytes

3-bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth.

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Wang, Ting-An; Zhang, Xiao-Dong; Guo, Xing-Yu; Xian, Shu-Lin; Lu, Yun-Fei

2016-03-01

Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT.

What can happen after lung transplantation and the importance of the time since transplantation: radiological review of post-transplantation complications.

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Daimiel Naranjo, I; Alonso Charterina, S

2016-01-01

Lung transplantation is the best treatment option in the final stages of diseases such as cystic fibrosis, pulmonary hypertension, chronic obstructive pulmonary disease, or idiopathic pulmonary fibrosis. Better surgical techniques and advances in immunosuppressor treatments have increased survival in lung transplant recipients, making longer follow-up necessary because complications can occur at any time after transplantation. For practical purposes, complications can be classified as early (those that normally occur within two months after transplantation), late (those that normally occur more than two months after transplantation), or time-independent (those that can occur at any time after transplantation). Many complications have nonspecific clinical and radiological manifestations, so the time factor is key to narrow the differential diagnosis. Imaging can guide interventional procedures and can detect complications early. This article aims to describe and illustrate the complications that can occur after lung transplantation from the clinical and radiological viewpoints so that they can be detected as early as possible. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

A plant-based chemical genomics screen for the identification of flowering inducers.

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Fiers, Martijn; Hoogenboom, Jorin; Brunazzi, Alice; Wennekes, Tom; Angenent, Gerco C; Immink, Richard G H

2017-01-01

Floral timing is a carefully regulated process, in which the plant determines the optimal moment to switch from the vegetative to reproductive phase. While there are numerous genes known that control flowering time, little information is available on chemical compounds that are able to influence this process. We aimed to discover novel compounds that are able to induce flowering in the model plant Arabidopsis. For this purpose we developed a plant-based screening platform that can be used in a chemical genomics study. Here we describe the set-up of the screening platform and various issues and pitfalls that need to be addressed in order to perform a chemical genomics screening on Arabidopsis plantlets. We describe the choice for a molecular marker, in combination with a sensitive reporter that's active in plants and is sufficiently sensitive for detection. In this particular screen, the firefly Luciferase marker was used, fused to the regulatory sequences of the floral meristem identity gene APETALA1 (AP1) , which is an early marker for flowering. Using this screening platform almost 9000 compounds were screened, in triplicate, in 96-well plates at a concentration of 25 µM. One of the identified potential flowering inducing compounds was studied in more detail and named Flowering1 (F1). F1 turned out to be an analogue of the plant hormone Salicylic acid (SA) and appeared to be more potent than SA in the induction of flowering. The effect could be confirmed by watering Arabidopsis plants with SA or F1, in which F1 gave a significant reduction in time to flowering in comparison to SA treatment or the control. In this study a chemical genomics screening platform was developed to discover compounds that can induce flowering in Arabidopsis. This platform was used successfully, to identify a compound that can speed-up flowering in Arabidopsis.

Transplantation of premolars as an approach for replacing avulsed teeth

DEFF Research Database (Denmark)

Andreasen, Jens Ove; Schwartz, Ole; Kofoed, Thomas

2009-01-01

Autotransplantation of premolars to the anterior region subsequent to tooth loss represent a unique treatment method that has a number of advantages in comparison with other tooth substitution methods. A tooth transplant has a bone inducing capacity implying that lost labial bone is regenerated. ...

Graft Growth and Podocyte Dedifferentiation in Donor-Recipient Size Mismatch Kidney Transplants.

Science.gov (United States)

Müller-Deile, Janina; Bräsen, Jan Hinrich; Pollheimer, Marion; Ratschek, Manfred; Haller, Hermann; Pape, Lars; Schiffer, Mario

2017-10-01

Kidney transplantation is the treatment choice for patients with end-stage renal diseases. Because of good long-term outcome, pediatric kidney grafts are also accepted for transplantation in adult recipients despite a significant mismatch in body size and age between donor and recipient. These grafts show a remarkable ability of adaptation to the recipient body and increase in size in a very short period, presumably as an adaptation to hyperfiltration. We investigated renal graft growth as well as glomerular proliferation and differentiation markers Kiel-67, paired box gene 2 and Wilms tumor protein (WT1) expression in control biopsies from different transplant constellations: infant donor for infant recipient, infant donor for child recipient, infant donor for adult recipient, child donor for child recipient, child donor for adult recipient, and adult donor for an adult recipient. We detected a significant increase in kidney graft size after transplantation in all conditions with a body size mismatch, which was most prominent when an infant donated for a child. Podocyte WT1 expression was comparable in different transplant conditions, whereas a significant increase in WT1 expression could be detected in parietal epithelial cells, when a kidney graft from a child was transplanted into an adult. In kidney grafts that were relatively small for the recipients, we could detect reexpression of podocyte paired box gene 2. Moreover, the proliferation marker Kiel-67 was expressed in glomerular cells in grafts that increased in size after transplantation. Kidney grafts rapidly adapt to the recipient size after transplantation if they are transplanted in a body size mismatch constellation. The increase in transplant size is accompanied by an upregulation of proliferation and dedifferentiation markers in podocytes. The different examined conditions exclude hormonal factors as the key trigger for this growth so that most likely hyperfiltration is the key trigger inducing the

Rain-Induced Wash-Off of Chemical Warfare Agent (VX) from Foliar Surfaces of Living Plants Maintained in a Surety Hood

Science.gov (United States)

2016-09-01

RAIN-INDUCED WASH-OFF OF CHEMICAL WARFARE AGENT (VX) FROM FOLIAR SURFACES OF LIVING PLANTS MAINTAINED IN A...Final 3. DATES COVERED (From - To) May 2014 – Sep 2015 4. TITLE AND SUBTITLE Rain-Induced Wash-Off of Chemical Warfare Agent (VX) from Foliar...galli Foliage Chemical warfare agent (CWA) O-ethyl-S-(2

Bioethics of organ transplantation.

Science.gov (United States)

Caplan, Arthur

2014-03-01

As the ability to transplant organs and tissues has grown, the demand for these procedures has increased as well--to the point at which it far exceeds the available supply creating the core ethical challenge for transplantation--rationing. The gap between supply and demand, although large, is worse than it appears to be. There are two key steps to gaining access to a transplant. First, one must gain access to a transplant center. Then, those waiting need to be selected for a transplant. Many potential recipients do not get admitted to a program. They are deemed too old, not of the right nationality, not appropriate for transplant as a result of severe mental impairment, criminal history, drug abuse, or simply because they do not have access to a competent primary care physician who can refer them to a transplant program. There are also financial obstacles to access to transplant waiting lists in the United States and other nations. In many poor nations, those needing transplants simply die because there is no capacity or a very limited capacity to perform transplants. Although the demand for organs now exceeds the supply, resulting in rationing, the size of waiting lists would quickly expand were there to suddenly be an equally large expansion in the number of organs available for transplantation. Still, even with the reality of unavoidable rationing, saving more lives by increasing organ supply is a moral good. Current public policies for obtaining organs from cadavers are not adequate in that they do not produce the number of organs that public polls of persons in the United States indicate people are willing to donate.

Effectiveness of Multimedia for Transplant Preparation for Kidney Transplant Waiting List Patients.

Science.gov (United States)

Charoenthanakit, C; Junchotikul, P; Sittiudomsuk, R; Saiyud, A; Pratumphai, P

2016-04-01

A multimedia program could effectively advise patients about preparing for transplantation while on the waiting list for a kidney transplant. This study aimed to compare knowledge about transplant preparation for patients on a kidney transplant waiting list before and after participating in a multimedia program, and to evaluate patient satisfaction with the multimedia program. Research design was quasiexperimental with the use of 1 group. Subjects were 186 patients on the kidney transplant waiting list after HLA matching in Ramathibodi Hospital. The questionnaires were developed by the researchers. The statistical tools used were basic statistics, percentage, average, standard deviation, and the difference of score between before and after participation in the multimedia program (t test). The evaluation knowledge for transplant preparation for kidney transplant waiting list patients after participating in the multimedia program averaged 85.40%, and there was an increased improvement of score by an average 3.27 out of a possible full score of 20 (P multimedia program had good average, 4.58. Copyright © 2016 Elsevier Inc. All rights reserved.

Key issues in transplant tourism.

Science.gov (United States)

Akoh, Jacob A

2012-02-24

Access to organ transplantation depends on national circumstances, and is partly determined by the cost of health care, availability of transplant services, the level of technical capacity and the availability of organs. Commercial transplantation is estimated to account for 5%-10% (3500-7000) of kidney transplants performed annually throughout the world. This review is to determine the state and outcome of renal transplantation associated with transplant tourism (TT) and the key challenges with such transplantation. The stakeholders of commercial transplantation include: patients on the waiting lists in developed countries or not on any list in developing countries; dialysis funding bodies; middlemen, hosting transplant centres; organ-exporting countries; and organ vendors. TT and commercial kidney transplants are associated with a high incidence of surgical complications, acute rejection and invasive infection which cause major morbidity and mortality. There are ethical and medical concerns regarding the management of recipients of organs from vendors. The growing demand for transplantation, the perceived failure of altruistic donation in providing enough organs has led to calls for a legalised market in organ procurement or regulated trial in incentives for donation. Developing transplant services worldwide has many benefits - improving results of transplantation as they would be performed legally, increasing the donor pool and making TT unnecessary. Meanwhile there is a need to re-examine intrinsic attitudes to TT bearing in mind the cultural and economic realities of globalisation. Perhaps the World Health Organization in conjunction with The Transplantation Society would set up a working party of stakeholders to study this matter in greater detail and make recommendations.

Gene expression changes in the injured spinal cord following transplantation of mesenchymal stem cells or olfactory ensheathing cells.

Directory of Open Access Journals (Sweden)

Abel Torres-Espín

Full Text Available Transplantation of bone marrow derived mesenchymal stromal cells (MSC or olfactory ensheathing cells (OEC have demonstrated beneficial effects after spinal cord injury (SCI, providing tissue protection and improving the functional recovery. However, the changes induced by these cells after their transplantation into the injured spinal cord remain largely unknown. We analyzed the changes in the spinal cord transcriptome after a contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting. The gene profiles were analyzed by clustering and functional enrichment analysis based on the Gene Ontology database. We found that both MSC and OEC transplanted acutely after injury induce an early up-regulation of genes related to tissue protection and regeneration. In contrast, cells transplanted at 7 days after injury down-regulate genes related to tissue regeneration. The most important change after MSC or OEC transplant was a marked increase in expression of genes associated with foreign body response and adaptive immune response. These data suggest a regulatory effect of MSC and OEC transplantation after SCI regarding tissue repair processes, but a fast rejection response to the grafted cells. Our results provide an initial step to determine the mechanisms of action and to optimize cell therapy for SCI.

Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients 2014 Data Report: Intestine.

Science.gov (United States)

Cai, Junchao; Wu, Guosheng; Qing, Annie; Everly, Matthew; Cheng, Elaine; Terasaki, Paul

2014-01-01

As of September 19, 2014, 2441 cases of intestinal transplantation have been performed in 46 centers (2400 deceased, 41 living). Eight centers did more than 100 transplants. Annual case numbers peaked in 2007 (N = 198) and steadily decreased to 109 cases in 2013. Short gut syndrome (68%) and functional bowel problems (15%) are two major indications for intestinal transplantation. The 3 major types of transplants involving the intestine include: isolated intestine transplant (I); simultaneous intestine, liver, and pancreas transplant (I+L+P); and, combined intestine and liver (I+L) transplant. Graft survival has significantly improved in recent years, mainly due to improved first year graft survival. The 1-, 5-, and 10-year graft survivals were: 74%, 42%,and 26%, respectively (I); 70%, 50%, and 40%, respectively (I+L+P); and 61%, 46%, and 40%, respectively (I+L). The longest graft survivals for I, l+L+P, and l+L were 19 years, 16 years, and 23 years, respectively. Steroids, Thymoglobulin, and rituximab are 3 major induction agents used in recent years. Prograf, steroids, and Cellcept are 3 major maintenance agents. Induction recipients (68% of all patients) had a significantly lower acute rejection rate than nonrecipients before discharge (60% versus 75%, p compatible transplants. ABO identical transplant recipients had a significantly higher 5-year graft survival rate than ABO compatible recipients (39% versus 21%, p compatible (N = 188, 11%) than in the early decade (p compatible transplants were lower than those of ABO identical transplants. However, the difference did not reach statistical significance (46% versus 49%, p = 0.07). The effect of ABO compatibility on graft outcome was further confirmed by Cox Analysis. ABO incompatible transplants are still rarely performed (N = 4) in intestine. In conclusion, annual case numbers of intestinal transplants have been decreasing, regardless of improved graft survival. ABO compatible intestinal transplants previously

[Liver transplantation].

Science.gov (United States)

Pompili, Maurizio; Mirante, Vincenzo Giorgio; Rapaccini, Gian Ludovico; Gasbarrini, Giovanni

2004-01-01

Liver transplantation represents the first choice treatment for patients with fulminant acute hepatitis and for patients with chronic liver disease and advanced functional failure. Patients in the waiting list for liver transplantation are classified according to the severity of their clinical conditions (evaluated using staging systems mostly based on hematochemical parameters related to liver function). This classification, together with the blood group and the body size compatibility, remains the main criterion for organ allocation. The main indications for liver transplantation are cirrhosis (mainly HCV-, HBV- and alcohol-related) and hepatocellular carcinoma emerging in cirrhosis in adult patients, biliary atresia and some inborn errors of metabolism in pediatric patients. In adults the overall 5-year survival ranges between 60 and 70%, in both American and European series. Even better results have been reported for pediatric patients: in fact, the 5-year survival rate for children ranges between 70 and 80% in the main published series. In this study we evaluated the main medical problems correlated with liver transplantation such as immunosuppressive treatment, acute and chronic rejection, infectious complications, the recurrence of the liver disease leading to transplantation, and cardiovascular and metabolic complications.

Suppressive effects of coffee on the SOS responses induced by UV and chemical mutagens

International Nuclear Information System (INIS)

Obana, Hirotaka; Nakamura, Sei-ichi; Tanaka, Ryou-ichi

1986-01-01

SOS-inducing activity of UV or chemical mutagens was strongly suppressed by instant coffee in Salmonella typhimurium TA1535/pSK1002. As decaffeinated instant coffee showed a similarly strong suppressive effect, it would seem that caffeine, a known inhibitor of SOS responses, is not responsible for the effect observed. The suppression was also shown by freshly brewed coffee extracts. However, the suppression was absent in green coffee-bean extracts. These results suggest that coffee contains some substance(s) which, apart from caffeine, suppresses SOS-inducing activity of UV or chemical mutagens and that the suppressive substance(s) are produced by roasting coffee beans. (Auth.)

Bone metabolism dynamics in the early post-transplant period following kidney and liver transplantation.

Science.gov (United States)

Schreiber, Peter W; Bischoff-Ferrari, Heike A; Boggian, Katia; Bonani, Marco; van Delden, Christian; Enriquez, Natalia; Fehr, Thomas; Garzoni, Christian; Hirsch, Hans H; Hirzel, Cédric; Manuel, Oriol; Meylan, Pascal; Saleh, Lanja; Weisser, Maja; Mueller, Nicolas J

2018-01-01

Bone disease contributes to relevant morbidity after solid organ transplantation. Vitamin D has a crucial role for bone metabolism. Activation of vitamin D depends on the endocrine function of both, liver and kidney. Our study assessed key markers of bone metabolism at time of transplantation and 6 months after transplantation among 70 kidney and 70 liver recipients. In 70 kidney recipients 25-OH vitamin D levels did not differ significantly between peri-transplant (median 32.5nmol/l) and 6 months post-transplant (median 41.9nmol/l; P = 0.272). Six months post-transplant median 1, 25-(OH)2 vitamin D levels increased by >300% (from 9.1 to 36.5ng/l; Ptransplantation and of intact parathyroid hormone 6 months post-transplant. Among 70 liver recipients, 25-OH vitamin D, 1, 25-(OH)2 vitamin D and intact parathyroid hormone levels were not significantly altered between peri-transplant and 6 months post-transplant. Contrary to kidney recipients, median CTx increased by 60.0% (from 0.45 to 0.72 ng/ml; P = 0.002) and P1NP by 49.3% (from 84.0 to 125.4ng/ml; P = 0.001) in the longitudinal course. Assessed biomarkers didn't differ between liver recipients with and without fractures. To conclude, the assessed panel of biomarkers proved highly dynamic after liver as well as kidney transplantation in the early post-transplant period. After kidney transplantation a significant gain in 1, 25-(OH)2 vitamin D combined with a decline in iPTH, CTx and P1NP, whereas after liver transplantation an increase in CTx and P1NP were characteristic.

Aging impairs recipient T cell intrinsic and extrinsic factors in response to transplantation.

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Hua Shen

Full Text Available As increasing numbers of older people are listed for solid organ transplantation, there is an urgent need to better understand how aging modifies alloimmune responses. Here, we investigated whether aging impairs the ability of donor dendritic cells or recipient immunity to prime alloimmune responses to organ transplantation.Using murine experimental models, we found that aging impaired the host environment to expand and activate antigen specific CD8(+ T cells. Additionally, aging impaired the ability of polyclonal T cells to induce acute allograft rejection. However, the alloimmune priming capability of donor dendritic cells was preserved with aging.Aging impairs recipient responses, both T cell intrinsic and extrinsic, in response to organ transplantation.

The Additional Detrimental Effects of Cold Preservation on Transplantation-Associated Injury in Kidneys from Living and Brain-Dead Donor Rats

NARCIS (Netherlands)

Hoeger, Simone; Petrov, Kiril; Reisenbuechler, Anke; Fontana, Johann; Selhorst, Jochen; Hanusch, Christine; Beck, Grietje; Seelen, Marc A.; van Son, Willem J.; Waldherr, Ruediger; Schnuelle, Peter; Yard, Benito A.

2009-01-01

Background. Brain death and cold preservation are major alloantigen-independent risk factors for transplantation Outcome. The present study was conducted to assess the influence of these factors on transplantation-associated injury independently or in combination. Methods. Brain death was induced in

Changing Patterns of Foreigner Transplants in Korea and Overseas Organ Transplants Among Koreans.

Science.gov (United States)

Ahn, Hyung Joon; Kim, Hwi Won; Han, Miyeun; Jeon, Hee Jung; Kwon, Oh Jung; Ahn, Curie

2018-02-01

This study aimed to estimate the numbers of foreign patients seeking organ transplantation (OT) in Korea and to examine the relationship between the trend of deceased donors in Korea and number of Korean patients seeking OT overseas since 2000. Data on foreigners who received a transplant in Korea were obtained from the Korean Network for Organ Sharing. Data on overseas transplants were obtained from 42 transplant centers surveyed through transplant coordinators. A total of 336 foreigners underwent OT (kidney transplantation [KT], 174; liver transplantation [LT], 162) in Korea between 2006 and 2016. The Mongolians were the most common foreigners who undergo KTs (32%), followed by the Chinese (18%), Americans (9%), and Emiratis (7%). Among foreigners undergoing LTs, the most common country of origin was Mongolia (39%), followed by United Arab Emirates (23%), China (13%), and the United States (6%). A total of 2206 Korean patients underwent overseas OT (KT, 977; LT, 1229) between 2000 and 2016. In 97% of overseas KT cases (n = 942) and 98% (n = 1205) of overseas LT cases, the transplantations were performed in China. The relationship between the number of deceased donors in Korea and the number of overseas transplants after 2006 indicates a highly negative correlation. (ρ = -0.988, P tourism.

Heart transplantation from older donors

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V. N. Poptsov

2017-01-01

Full Text Available In the current situation of the shortage of suitable donor organs, heart transplantation from older donors is one of the ways to increase the performance of more heart transplants, particularly, in patients with urgent need of transplantation. While planning a heart transplantation from older donor one should consider increased risk of early cardiac allograft dysfunction, preexisting coronary artery disease, accelerated transplant vasculopathy which may adversely affect early and long-term survival of recipients. Subject to careful selection of donor–recipient pairs, effective prevention and treatment of early cardiac allograft dysfunction, pre-existing atherosclerosis and transplant vasculopathy the early and long-term survival of heart transplant recipients from older donors is comparable to heart transplantation from young donors.

Redox Active Transition Metal ions Make Melanin Susceptible to Chemical Degradation Induced by Organic Peroxide.

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Zadlo, Andrzej; Pilat, Anna; Sarna, Michal; Pawlak, Anna; Sarna, Tadeusz

2017-12-01

With aging, retinal pigment epithelium melanosomes, by fusion with the age pigment lipofuscin, form complex granules called melanolipofuscin. Lipofuscin granules may contain oxidized proteins and lipid hydroperoxides, which in melanolipofuscin could chemically modify melanin polymer, while transition metal ions present in melanin can accelerate such oxidative modifications. The aim of this research was to examine the effect of selected transition metal ions on melanin susceptibility to chemical modification induced by the water-soluble tert-butyl hydroperoxide used as an oxidizing agent. Synthetic melanin obtained by DOPA autooxidation and melanosomes isolated from bovine retinal pigment epithelium were analyzed. To monitor tert-butyl hydroperoxide-induced oxidative changes of DMa and BMs, electron paramagnetic resonance spectroscopy, UV-vis absorption spectroscopy, dynamic light scattering, atomic force microscopy and electron paramagnetic resonance oximetry were employed. These measurements revealed that both copper and iron ions accelerated chemical degradation induced by tert-butyl hydroperoxide, while zinc ions had no effect. Strong prooxidant action was detected only in the case of melanosomes and melanin degraded in the presence of iron. It can be postulated that similar chemical processes, if they occur in situ in melanolipofuscin granules of the human retinal pigment epithelium, would modify antioxidant properties of melanin and its reactivity.

Relapsed Diffuse Large B-Cell Lymphoma Treated by Reduced-Intensity Allogeneic Stem Cell Transplantation with Donor Lymphocyte Infusion

International Nuclear Information System (INIS)

Chudhry, Q.N.; Ahmed, P.; Ullah, K.; Satti, T.M.; Raza, S.; Mehmood, S.K.; Akram, M.; Ahmed, S.

2010-01-01

A 42 years old male with relapsed diffuse large B-cell lymphoma was given second-line chemotherapy followed by reduced intensity allogeneic stem cell transplantation from HLA matched brother. Twelve weeks post transplant, his disease relapsed evidenced by the appearance of lymphoma cells in the peripheral blood and declining donor chimerism. Donor lymphocyte infusion was given that induced complete lymphoma remission. The patient is well 3 years post transplant with his disease in complete remission. (author)

Chemical reactions induced and probed by positive muons

International Nuclear Information System (INIS)

Ito, Yasuo

1990-01-01

The application of μ + science, collectively called μSR, but encompassing a variety of methods including muon spin rotation, muon spin relaxation, muon spin repolarization, muon spin resonance and level-crossing resonance, to chemistry is introduced emphasizing the special aspects of processes which are 'induced and probed' by the μ + itself. After giving a general introduction to the nature and methods of muon science and a short history of muon chemistry, selected topics are given. One concerns the usefulness of muonium as hydrogen-like probes of chemical reactions taking polymerization of vinyl monomers and reaction with thiosulphate as examples. Probing solitons in polyacetylene induced and probed by μ + is also an important example which shows the unique nature of muonium. Another important topic is 'lost polarization'. Although this term is particular to muonium. Another important topic is 'lost polarization'. Although this term is particular to muon chemistry, the chemistry underlining the phenomenon of lost polarization has an importance to both radiation and hot atom chemistries. (orig.)

Indications for Corneal Transplantation at a Tertiary Referral Center in Tehran

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Mohammad Zare

2010-01-01

Full Text Available Purpose: To report the indications and techniques of corneal transplantation at a tertiary referral center in Tehran over a 3-year period. Methods: Records of patients who had undergone any kind of corneal transplantation at Labbafinejad Medical Center, Tehran, Iran from March 2004 to March 2007 were reviewed to determine the indications and types of corneal transplantation. Results: During this period, 776 eyes of 756 patients (including 504 male subjects with mean age of 41.3±21.3 years underwent corneal transplantation. The most common indication was keratoconus (n=317, 40.8% followed by bullous keratopathy (n=90, 11.6%, non-herpetic corneal scars (n=62, 8.0%, infectious corneal ulcers (n=61, 7.9%, previously failed grafts (n=61, 7.9%, endothelial and stromal corneal dystrophies (n=28, 3.6%, and trachoma keratopathy (n=26, 3.3%. Other indications including Terrien′s marginal degeneration, post-LASIK keratectasia, trauma, chemical burns, and peripheral ulcerative keratitis constituted the rest of cases. Techniques of corneal transplantation included penetrating keratoplasty (n=607, 78.2%, deep anterior lamellar keratoplasty (n=108, 13.9%, conventional lamellar keratoplasty (n=44, 5.7%, automated lamellar therapeutic keratoplasty (n=8, 1.0%, and Descemet stripping endothelial keratoplasty (n=6, 0.8% in descending order. The remaining cases were endothelial keratoplasty and sclerokeratoplasty. Conclusion: In this study, keratoconus was the most common indication for penetrating keratoplasty which was the most prevalent technique of corneal transplantation. However, deep anterior lamellar keratoplasty is emerging as a growing alternative for corneal pathologies not involving the endothelium.

Advances in transplantation immunology.

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Morris, P J

1987-09-01

Although there have been dramatic advances in clinical organ transplantation over the past 20 years, rejection, both acute and chronic, and the complications of immunosuppression remain major problems. Nevertheless as our understanding of the immune response to a vascularized organ allograft develops, so too will our ability to develop more specific immunosuppression. In any strategy for more specific immunosuppression compatibility for the major histocompatibility complex of antigens (HLA in man) is likely to be important. Monoclonal antibodies to T cell subpopulations, or even to T cells specifically activated by the graft, provide methods of suppressing the immune response at a more specific level. The recognition that stable grafts are maintained, at least in experimental rodent models, by T suppressor cells may allow development of precise methods of inducing the generation of such cells in clinical practice. The induction of tolerance in the adult animal can be achieved in a number of ways, the most promising of which for clinical application, is antigen pretreatment. If tolerance could be achieved in clinical practice within the not too distant future, then this would represent the attainment of the ultimate goal of transplantation.

Sensitivity of neuroprogenitor cells to chemical-induced apoptosis using a multiplexed assay suitable for high-throughput screening

International Nuclear Information System (INIS)

Druwe, Ingrid; Freudenrich, Theresa M.; Wallace, Kathleen; Shafer, Timothy J.; Mundy, William R.

2015-01-01

High-throughput methods are useful for rapidly screening large numbers of chemicals for biological activity, including the perturbation of pathways that may lead to adverse cellular effects. In vitro assays for the key events of neurodevelopment, including apoptosis, may be used in a battery of tests for detecting chemicals that could result in developmental neurotoxicity. Apoptosis contributes to nervous system development by regulating the size of the neuroprogenitor cell pool, and the balance between cellular proliferation and apoptosis during neuroprogenitor cell proliferation helps to determine the size and shape of the nervous system. Therefore, chemicals that affect apoptosis during neuronal development can have deleterious effects on the developing brain. The present study examined the utility of a high-throughput assay to detect chemical-induced apoptosis in mouse or human neuroprogenitor cells, as well as differentiated human neurons derived from induced pluripotent stem cells. Apoptosis was assessed using an assay that measures enzymatic activity of caspase-3/7 in a rapid and cost efficient manner. The results show that all three commercially available models generated a robust source of proliferating neuroprogenitor cells, and that the assay was sensitive and reproducible when used in a multi-well plate format. There were differences in the response of rodent and human neuroprogenitor cells to a set of chemicals previously shown to induce apoptosis in vitro. Neuroprogenitor cells were more sensitive to chemical-induced apoptosis than differentiated neurons, suggesting that neuroprogenitor cells are one of the cell models that should be considered for use in a developmental neurotoxicity screening battery

Everolimus: a review of its pharmacologic properties and use in solid organ transplantation

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Paul Huiras

2011-10-01

Full Text Available The aim of this review article is to review the pharmacology, pharmacokinetics, efficacy and safety of everolimus. Primary literature was obtained via MEDLINE. Studies and abstracts evaluating everolimus in solid organ transplantation were considered for evaluation. English-language studies and abstracts only were selected for inclusion. Everolimus, a proliferation signal inhibitor that prevents growth factor-induced cell proliferation, is effective in reducing the incidence of acute rejection in solid organ transplantation. This agent is also useful in reducing cyclosporine-related nephrotoxicity. Everolimus directly inhibits vascular remodelling and intimal thickening, which are often associated with chronic rejection. Clinical trials have shown that everolimus is generally safe. The most commonly reported adverse events were haematologic effects and hyperlipidaemia. Everolimus is the second proliferation signal inhibitor to be proven effective in preventing acute rejection in solid organ transplant recipients. However, its exact role in the transplant immunosuppressive armamentarium is still unknown.

The impact of repeated mismatches in kidney transplantations performed after nonrenal solid organ transplantation.

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Côté, J M; Zhang, X; Dahhou, M; Sapir-Pichhadze, R; Foster, B; Cardinal, H

2018-01-01

The aim of this study was to determine whether kidney transplantations performed after previous nonrenal solid organ transplants are associated with worse graft survival when there are repeated HLA mismatches (RMM) with the previous donor(s). We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients. Our cohort comprised 6624 kidney transplantations performed between January 1, 1990 and January 1, 2015. All patients had previously received 1 or more nonrenal solid organ transplants. RMM were observed in 35.3% of kidney transplantations and 3012 grafts were lost over a median follow-up of 5.4 years. In multivariate Cox regression analyses, we found no association between overall graft survival and either RMM in class 1 (hazard ratio [HR]: 0.97, 95% confidence interval [CI] 0.89-1.07) or class 2 (HR: 0.95, 95% CI 0.85-1.06). Results were similar for the associations between RMM, death-censored graft survival, and patient survival. Our results suggest that the presence of RMM with previous donor(s) does not have an important impact on allograft survival in kidney transplant recipients who have previously received a nonrenal solid organ transplant. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Nutrient Induced Type 2 and Chemical Induced Type 1 Experimental Diabetes Differently Modulate Gastric GLP-1 Receptor Expression

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Olga Bloch

2015-01-01

Full Text Available T2DM patients demonstrate reduced GLP-1 receptor (GLP-1R expression in their gastric glands. Whether induced T2DM and T1DM differently affect the gastric GLP-1R expression is not known. This study assessed extrapancreatic GLP-1R system in glandular stomach of rodents with different types of experimental diabetes. T2DM and T1DM were induced in Psammomys obesus (PO by high-energy (HE diet and by streptozotocin (STZ in Sprague Dawly (SD rats, respectively. GLP-1R expression was determined in glandular stomach by RT PCR and immunohistomorphological analysis. The mRNA expression and cellular association of the GLP-1R in principal glands were similar in control PO and SD rats. However, nutrient and chemical induced diabetes resulted in opposite alterations of glandular GLP-1R expression. Diabetic PO demonstrated increased GLP-1R mRNA expression, intensity of cellular GLP-1R immunostaining, and frequency of GLP-1R positive cells in the neck area of principal glands compared with controls. In contrast, SD diabetic rats demonstrated decreased GLP-1 mRNA, cellular GLP-1R immunoreactivity, and frequency of GLP-1R immunoreactive cells in the neck area compared with controls. In conclusion, nutrient and chemical induced experimental diabetes result in distinct opposite alterations of GLP-1R expression in glandular stomach. These results suggest that induced T1DM and T2DM may differently modulate GLP-1R system in enteropancreatic axis.

Acute myeloid leukemia after kidney transplantation: a case report and literature review

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Francesca Cardarelli

Full Text Available Abstract The incidence of malignancy is greater in kidney transplant recipients compared to the general population, though the higher risk is not equally distributed to all types of cancers. In face of the increased longevity of renal transplant recipients, certain cancers, such as acute leukemias, are becoming more prevalent. Acute myeloid leukemia (AML typically presents with cytopenias and infections, both common findings after kidney transplantation. Therefore, the diagnosis of AML may be initially overlooked in these patients. We report the case of a 33-year-old man who presented with fever, pancytopenia and acute worsening of his renal allograft function 9 years after a living unrelated kidney transplant. After initial negative infectious work-up, a kidney biopsy revealed C4d-positive antibody-mediated rejection in combination with scattered atypical inflammatory cells. A subsequent bone marrow biopsy confirmed AML. He underwent successful induction chemotherapy with daunorubucin and cytarabine and ultimately achieved a complete remission. However, he developed a Page kidney with worsening renal function and abdominal pain three weeks after biopsy in the setting of chemotherapy-induced thrombocytopenia. Herein, we discuss the prevalence, risk factors, presentation and management of leukemia after kidney transplantation.

Cyclophosphamide/x-ray: combined mode preparation for transplantation therapy

International Nuclear Information System (INIS)

Meredith, R.; Okunewick, J.; Shadduck, R.; Raikow, R.; Brozovich, B.; Seeman, P.

1979-01-01

Use of total body irradiation (TBI) and/or chemotherapy as a preparation for marrow transplantation in the treatment of leukemia has been only moderately successful in the clinic. Although cyclophosphamide (CY) has shown promise as a marrow ablative agent, leukemia relapses are often found, and optimal therapeutic protocols have not been established. Our transplantation therapy studies of murine leukemia with parental recipients and hybrid donors provide an excellent model for research aimed at improved survival of human transplant patients. Utilizing a murine leukemia induced by a virus, various doses of CY in combination with sub-lethal irradiation were compared to determine the optimal pretreatment for transplantation therapy. Both normal and leukemic mice were engrafted with virus resistant, histocompatible marrow following these preparations, then monitored for survival and long term effects. Leukemic mice were also evaluated for pluripotent as well as myeloid committed stem cells as a measure of the effectiveness of the treatment in elimination of leukemic cells. Leukemic groups were also compared for the percentage and time of leukemia relapse. All CY/X-ray combinations were more effective in elimination of stem cell populations than supralethal TBI alone. However, the best survival was obtained with lethal TBI alone or low dose CY in combination with 550 R

Late-onset acute rejection after living donor liver transplantation

Institute of Scientific and Technical Information of China (English)

Nobuhisa Akamatsu; Yasuhiko Sugawara; Sumihito Tamura; Junichi Keneko; Yuichi Matsui; Kiyoshi Hasegawa; Masatoshi Makuuchi

2006-01-01

AIM: To investigate the incidence and risk factors of late-onset acute rejection (LAR) and to clarify the effectiveness of our immunosuppressive regime consisting of life-long administration of tacrolimus and steroids.METHODS: Adult living donor liver transplantation recipients (n = 204) who survived more than 6 mo after living donor liver transplantation were enrolled.Immunosuppression was achieved using tacrolimus and methylprednisolone. When adverse effects of tacrolimus were detected, the patient was switched to cyclosporine. Six months after transplantation,tacrolimus or cyclosporine was carefully maintained at a therapeutic level. The methylprednisolone dosage was maintained at 0.05 mg/kg per day by oral administration.Acute rejections that occurred more than 6 mo after the operation were defined as late-onset. The median followup period was 34 mo.RESULTS: LAR was observed in 15 cases (7%) and no chronic rejection was observed. The incidence of hyperlipidemia, chronic renal failure, new-onset posttransplantation diabetes, and deep fungal infection were 13%, 2%, 24%, and 17%, respectively. Conversion from tacrolimus to cyclosporine was required in 38 patients (19%). Multivariate analysis revealed that a cyclosporinebased regimen was significantly associated with LAR.CONCLUSION: Both LAR and drug-induced adverse events happen at a low incidence, supporting the safety and efficacy of the present immunosuppression regimen for living donor liver transplantation.

Imaging in pancreatic transplants

International Nuclear Information System (INIS)

Heller, Matthew T; Bhargava, Puneet

2014-01-01

Pancreatic transplantation, performed alone or in conjunction with kidney transplantation, is an effective treatment for advanced type I diabetes mellitus and select patients with type II diabetes mellitus. Following advancements in surgical technique, postoperative management, and immunosuppression, pancreatic transplantation has significantly improved the length and quality of life for patients suffering from pancreatic dysfunction. While computed tomography (CT) and magnetic resonance imaging (MRI) have more limited utility, ultrasound is the preferred initial imaging modality to evaluate the transplanted pancreas; gray-scale assesses the parenchyma and fluid collections, while Doppler interrogation assesses vascular flow and viability. Ultrasound is also useful to guide percutaneous interventions for the transplanted pancreas. With knowledge of the surgical anatomy and common complications, the abdominal radiologist plays a central role in the perioperative and postoperative evaluation of the transplanted pancreas

Study on the identification method of chemical warfare agents with spectroscopy of neutron induced γ rays

International Nuclear Information System (INIS)

Liu Boxue; Li Yun; Li Xiangbao

1996-01-01

The paper briefly describes some non-destructive verification technologies of chemical warfare agents in-site, and some application of neutron induced gamma ray analysis, such as multi-elements analysis of coal, hidden explosive detection and identification of chemical agents. It also describes some problems in developing the portable isotopic neutron spectroscopy for non-destructive evaluation of chemical warfare agents

Chemical reactions induced by fast neutron irradiation

International Nuclear Information System (INIS)

Katsumura, Y.

1989-01-01

Here, several studies on fast neutron irradiation effects carried out at the reactor 'YAYOI' are presented. Some indicate a significant difference in the effect from those by γ-ray irradiation but others do not, and the difference changes from subject to subject which we observed. In general, chemical reactions induced by fast neutron irradiation expand in space and time, and there are many aspects. In the time region just after the deposition of neutron energy in the system, intermediates are formed densely and locally reflecting high LET of fast neutrons and, with time, successive reactions proceed parallel to dissipation of localized energy and to diffusion of the intermediates. Finally the reactions are completed in longer time region. If we pick up the effects which reserve the locality of the initial processes, a significant different effect between in fast neutron radiolysis and in γ-ray radiolysis would be derived. If we observe the products generated after dissipation and diffusion in longer time region, a clear difference would not be observed. Therefore, in order to understand the fast neutron irradiation effects, it is necessary to know the fundamental processes of the reactions induced by radiations. (author)

Design of transplanting mechanism for system of rice intensification (SRI) transplanter in Kedah, Malaysia

Science.gov (United States)

Imran, M. S.; Manan, M. S. Abdul; Khalil, A. N. M.; MdNaim, M. K.; Ahmad, R. N.

2017-08-01

There is a demand to develop transplanter specifically for system of rice intensification (SRI) cultivation in Malaysia. This SRI transplanter is different from conventional transplanter as it is required special requirements for transplanting. The work focused on transplanting mechanism design which can be later attached to SRI transplanter. The mechanical design was established using linkage mechanism, having a wheel that act as timing wheel that will control the distance between transplanted seedlings. The linkage mechanism also control the opening of the flapper that allow the seedling together with its nursery soil to be dropped, and control the stopper to prevent next seedling from sliding down the tray. The use of simple mechanism will have low cost for fabrication. The design was analysed using motion analysis software. Results show the design is perfectly good and can be fabricated without any problem. The animation successfully shows the perfect movement of the mechanism and transplanting process.

Breast Reconstruction After Solid Organ Transplant.

Science.gov (United States)

Koonce, Stephanie L; Giles, Brian; McLaughlin, Sarah A; Perdikis, Galen; Waldorf, James; Lemaine, Valerie; TerKonda, Sarvam

2015-09-01

Solid organ transplant patients frequently develop posttransplant malignancies including breast cancer. They may desire breast reconstruction after mastectomy, which could potentially be complicated by their transplant status, immunosuppressive regimen, and previous operations. We review our experience with patients who have undergone solid organ transplant and subsequent breast reconstruction after mastectomy After institutional review board approval, we queried our prospective breast reconstruction and solid organ transplant databases for corresponding patients. Inclusion criteria comprised breast reconstruction after solid organ transplant. A chart review was conducted of identified patients. Seventeen patients were identified: 1 pulmonary transplant, 4 cardiac transplants, 2 liver transplants, 1 pancreas transplant, 2 combined kidney/pancreas transplants, and 7 kidney transplants. Indications for mastectomy included posttransplant malignancy and prophylaxis. Median time from transplant to completion of reconstruction was 186 months (range, 11-336 months). Median age at transplant was 34.5 years (range, 21-65 years) with the median age of the patients at reconstructive surgery 51.5 years (range, 34-71 years). Median body mass index was 25.3 (range, 21.3-46.5). No significant complications were noted after reconstructive surgery. All patients were on full immunosuppression at time of reconstruction. Breast reconstruction is a viable option for transplant patients after mastectomy and should not be refused based on their transplant status. Close coordination with the transplant team and careful preoperative planning is essential for optimal outcomes.

Choosing a Transplant Center

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... however you can Daughter's dying wish became mother's motivation Be The Match Blog Stories Anna, transplant recipient ... for transplant costs. Location – You might have to travel to receive a transplant. Consider how far the ...

Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome.

Science.gov (United States)

King, Aileen J F; Griffiths, Lisa A; Persaud, Shanta J; Jones, Peter M; Howell, Simon L; Welsh, Nils

2016-05-01

Introduction Improving islet transplantation outcome could not only bring benefits to individual patients but also widen the patient pool to which this life-changing treatment is available. Imatinib has previously been shown to protect beta cells from apoptosis in a variety of in vitro and in vivo models. The aim of this study was to investigate whether imatinib could be used to improve islet transplantation outcome. Methods Islets were isolated from C57Bl/6 mice and pre-cultured with imatinib prior to exposure to streptozotocin and cytokines in vitro. Cell viability and glucose-induced insulin secretion were measured. For transplantation experiments, islets were pre-cultured with imatinib for either 72 h or 24 h prior to transplantation into streptozotocin-diabetic C57Bl/6 mice. In one experimental series mice were also administered imatinib after islet transplantation. Results Imatinib partially protected islets from beta cell death in vitro. However, pre-culturing islets in imatinib or administering the drug to the mice in the days following islet transplantation did not improve blood glucose concentrations more than control-cultured islets. Conclusion Although imatinib protected against beta cell death from cytokines and streptozotocin in vitro, it did not significantly improve syngeneic islet transplantation outcome.

Appraisal of transplant-related stressors, coping strategies, and psychosocial adjustment following kidney transplantation.

Science.gov (United States)

Pisanti, Renato; Lombardo, Caterina; Luszczynska, Aleksandra; Poli, Luca; Bennardi, Linda; Giordanengo, Luca; Berloco, Pasquale Bartolomeo; Violani, Cristiano

2017-10-01

This study examined the relations between appraisal of transplant-related stressors, coping, and adjustment dimensions following kidney transplantation (KT). Two models were tested: (1) the main effects model proposing that stress appraisal and coping strategies are directly associated with adjustment dimensions; and (2) the moderating model of stress proposing that each coping strategy interacts with stress appraisal. Importantly, there is a lack of research examining the two models simultaneously among recipients of solid organ transplantation. A total of 174 KT recipients completed the questionnaires. Predictors of post-transplant adjustment included appraisal of transplant-related stressors and coping strategies (task-, emotion-, and avoidance-focused). Adjustment dimensions were psychological distress, worries about the transplant, feelings of guilt, fear of disclosure of transplant, adherence, and responsibility for the functioning of the new organ. The main and moderating effects were tested with regression analyses. Appraisal of transplant-related stressors and emotion-oriented coping were related to all adjustment dimensions, except of adherence and responsibility. Task-oriented coping was positively related to responsibility. Avoidance-oriented coping was negatively correlated with adherence. Only 1 out of 18 hypothesized interactive terms was significant, yielding a synergistic interaction between appraisal of transplant-related stressors and emotion-oriented coping on the sense of guilt. The findings have the potential to inform interventions promoting psychosocial adjustment among KT recipients. Copyright © 2016 John Wiley & Sons, Ltd.

Chemically-induced solid-state dewetting of thin Au films

International Nuclear Information System (INIS)

Gazit, Nimrod; Klinger, Leonid; Rabkin, Eugen

2017-01-01

We employed the solid state dewetting technique to produce nanoparticles of silver-gold alloy on a sapphire substrate. We deposited a thin gold layer on the substrate with alloy nanoparticles, and studied its thermal stability at low homological temperatures. We demonstrated that a large number of densely spaced holes form at the initial stages of dewetting of the gold layer with nanoparticles. A similar homogeneous gold film deposited on a bare sapphire substrate remained stable under identical annealing conditions, exhibiting the onset of dewetting at higher temperatures, and with a lower number of holes. We attributed the decreased thermal stability of the gold film deposited on the substrate with the silver-gold nanoparticles to accelerated grooving at the grain boundaries and triple junctions in the film. The grooving process is accelerated by the diffusion fluxes of Au atoms driven from the film towards the nanoparticles by the gradient of chemical potential. We developed a quantitative model of this chemically-induced dewetting process, and discussed its applicability for the design of better catalytic systems. Our work demonstrates that the chemical driving forces have to be reckoned with in the analysis of thermal stability of multicomponent thin films.

Split-liver transplantation : An underused resource in liver transplantation

NARCIS (Netherlands)

Rogiers, Xavier; Sieders, Egbert

2008-01-01

Split-liver transplantation is an efficient tool to increase the number of liver grafts available for transplantation. More than 15 years after its introduction only the classical splitting technique has reached broad application. Consequently children are benefiting most from this possibility.

Analysis of hemodialysis patients’ thoughts about kidney transplantation and the national organ transplant system in terms of organ transplantation services management

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Yasin Uzuntarla

2017-03-01

Results: It was determined that the hemodialysis patients responding to the survey were in the 20-95 age group with an average age of 58,64±15,64 years. 87,9% of the patients reported that they had been briefed about kidney transplants, 32,2% of those had been briefed said that the information had been delivered by the dialysis physician, 77,7% stated that they wanted a kidney transplant from a cadaver, 49,5% did not want a kidney transplant from a live donor and 35,5% indicated that the national organ transplant system operated adequately. Furthermore, it was noted that 50,9% of the responders were registered on the waiting lists of kidney transplant centers. Conclusions: It was concluded that it is necessary to provide sufficient information to hemodialysis patients about kidney transplants and the national organ transplant system to steer them to transplant centers. It is anticipated that the results of this study will assist officers of the Ministry of Health, politicians involved in health issues, decision makers and health professionals. [Arch Clin Exp Surg 2017; 6(1.000: 33-37

The lived experience of autologous stem cell-transplanted patients: Post-transplantation and before discharge.

Science.gov (United States)

Alnasser, Qasem; Abu Kharmah, Salahel Deen; Attia, Manal; Aljafari, Akram; Agyekum, Felicia; Ahmed, Falak Aftab

2018-04-01

To explore the lived experience of the patients post-haematopoietic stem cell transplantation and specifically after engraftment and before discharge. Patients post-stem cell transplantation experience significant changes in all life aspects. Previous studies carried out by other researchers focused mainly on the postdischarge experience, where patients reported their perceptions that have always been affected by the life post-transplantation and influenced by their surroundings. The lived experience of patients, specifically after engraftment and prior to discharge (the "transition" phase), has not been adequately explored in the literature. Doing so might provide greater insight into the cause of change post-haematopoietic stem cell transplantation. This study is a phenomenological description of the participants' perception about their lived experience post-haematopoietic stem cell transplantation. The study used Giorgi's method of analysis. Through purposive sampling, 15 post-haematopoietic stem cell transplantation patients were recruited. Data were collected by individual interviews. Data were then analysed based on Giorgi's method of analysis to reveal the meaning of a phenomenon as experienced through the identification of essential themes. The analysis process revealed 12 core themes covered by four categories that detailed patients lived experience post-haematopoietic stem cell transplantation. The four categories were general transplant experience, effects of transplantation, factors of stress alleviation and finally life post-transplantation. This study showed how the haematopoietic stem cell transplantation affected the patients' physical, psychological and spiritual well-being. Transplantation also impacted on the patients' way of thinking and perception of life. Attending to patients' needs during transplantation might help to alleviate the severity of the effects and therefore improve experience. Comprehensive information about transplantation needs

Chemical leucoderma induced by ear-ring stoppers made of polyvinyl chloride

Directory of Open Access Journals (Sweden)

Reena Sharma

2012-01-01

Full Text Available We report a case of chemical leucoderma (CL in a 15-year-old girl, who developed patterned depigmentation at the back of both ear lobules after contact with plastic ear-ring stoppers made of polyvinyl chloride (PVC after continuous use for 6-7 months. Patch test with Indian standard series and cosmetic series was negative after 48 h, but she refused patch testing for extended duration as the possibility of induced depigmentation at the test site was unacceptable to her. To the best of our knowledge, this is the first report of plastic ear-ring stopper induced CL.

A crowdsourcing workflow for extracting chemical-induced disease relations from free text.

Science.gov (United States)

Li, Tong Shu; Bravo, Àlex; Furlong, Laura I; Good, Benjamin M; Su, Andrew I

2016-01-01

Relations between chemicals and diseases are one of the most queried biomedical interactions. Although expert manual curation is the standard method for extracting these relations from the literature, it is expensive and impractical to apply to large numbers of documents, and therefore alternative methods are required. We describe here a crowdsourcing workflow for extracting chemical-induced disease relations from free text as part of the BioCreative V Chemical Disease Relation challenge. Five non-expert workers on the CrowdFlower platform were shown each potential chemical-induced disease relation highlighted in the original source text and asked to make binary judgments about whether the text supported the relation. Worker responses were aggregated through voting, and relations receiving four or more votes were predicted as true. On the official evaluation dataset of 500 PubMed abstracts, the crowd attained a 0.505F-score (0.475 precision, 0.540 recall), with a maximum theoretical recall of 0.751 due to errors with named entity recognition. The total crowdsourcing cost was $1290.67 ($2.58 per abstract) and took a total of 7 h. A qualitative error analysis revealed that 46.66% of sampled errors were due to task limitations and gold standard errors, indicating that performance can still be improved. All code and results are publicly available athttps://github.com/SuLab/crowd_cid_relexDatabase URL:https://github.com/SuLab/crowd_cid_relex. © The Author(s) 2016. Published by Oxford University Press.

A crowdsourcing workflow for extracting chemical-induced disease relations from free text

Science.gov (United States)

Li, Tong Shu; Bravo, Àlex; Furlong, Laura I.; Good, Benjamin M.; Su, Andrew I.

2016-01-01

Relations between chemicals and diseases are one of the most queried biomedical interactions. Although expert manual curation is the standard method for extracting these relations from the literature, it is expensive and impractical to apply to large numbers of documents, and therefore alternative methods are required. We describe here a crowdsourcing workflow for extracting chemical-induced disease relations from free text as part of the BioCreative V Chemical Disease Relation challenge. Five non-expert workers on the CrowdFlower platform were shown each potential chemical-induced disease relation highlighted in the original source text and asked to make binary judgments about whether the text supported the relation. Worker responses were aggregated through voting, and relations receiving four or more votes were predicted as true. On the official evaluation dataset of 500 PubMed abstracts, the crowd attained a 0.505 F-score (0.475 precision, 0.540 recall), with a maximum theoretical recall of 0.751 due to errors with named entity recognition. The total crowdsourcing cost was $1290.67 ($2.58 per abstract) and took a total of 7 h. A qualitative error analysis revealed that 46.66% of sampled errors were due to task limitations and gold standard errors, indicating that performance can still be improved. All code and results are publicly available at https://github.com/SuLab/crowd_cid_relex Database URL: https://github.com/SuLab/crowd_cid_relex PMID:27087308

Donor transplant programme

International Nuclear Information System (INIS)

Abu Bakar Sulaiman

1999-01-01

The transplantation of organs and tissues from one human to another human has become an essential and well established form of therapy for many types of organ and tissue failure. In Malaysia, kidney, cornea and bone marrow transplantation are well established. Recently, liver, bone and heart transplanation have been performed. Unfortunately, because of the lack of cadaveric organ donation, only a limited number of solid organ transplantation have been performed. The cadaveric organ donor rate in Malaysia is low at less than one per million population. The first tissue transplanted in Malaysia was the cornea which was performed in the early 1970s. At that time and even now the majority of corneas came from Sri Lanka. The first kidney transplant was performed in 1975 from a live related donor. The majority of the 629 kidney transplants done at Hospital Kuala Lumpur to date have been from live related donors. Only 35 were from cadaver donors. Similarly, the liver transplantation programme which started in 1995 are from live related donors. A more concerted effort has been made recently to increase the awareness of the public and the health professionals on organ and tissue donation. This national effort to promote organ and tissue donation seems to have gathered momentum in 1997 with the first heart transplant successfully performed at the National Heart Institute. The rate of cadaveric donors has also increased from a previous average of I to 2 per year to 6 per year in the last one year. These developments are most encouraging and may signal the coming of age of our transplantati on programme. The Ministry of Health in conjunction with various institutions, organizations and professional groups, have taken a number of proactive measures to facilitate the development of the cadaveric organ donation programme. Efforts to increase public awareness and to overcome the negative cultural attitude towards organ donation have been intensified. Equally important are efforts

Pulmonary rehabilitation in lung transplant candidates.

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Li, Melinda; Mathur, Sunita; Chowdhury, Noori A; Helm, Denise; Singer, Lianne G

2013-06-01

While awaiting lung transplantation, candidates may participate in pulmonary rehabilitation to improve their fitness for surgery. However, pulmonary rehabilitation outcomes have not been systematically evaluated in lung transplant candidates. This investigation was a retrospective cohort study of 345 pre-transplant pulmonary rehabilitation participants who received a lung transplant between January 2004 and June 2009 and had available pre-transplant exercise data. Data extracted included: 6-minute walk tests at standard intervals; exercise training details; health-related quality-of-life (HRQL) measures; and early post-transplant outcomes. Paired t-tests were used to examine changes in the 6MW distance (6MWD), exercise training volume and HRQL during the pre-transplant period. We evaluated the association between pre-transplant 6MWD and transplant hospitalization outcomes. The final 6MWD prior to transplantation was only 15 m less than the listing 6MWD (n = 200; p = 0.002). Exercise training volumes increased slightly from the start of the pulmonary rehabilitation program until transplant: treadmill, increase 0.69 ml/kg/min (n = 238; p volumes are well preserved among lung transplant candidates participating in pulmonary rehabilitation, even in the setting of severe, progressive lung disease. Participants with greater exercise capacity prior to transplantation have more favorable early post-transplant outcomes. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

PHENOMENON OF DEMIKHOV. "Transplantation of vital organs In experiment" (1960. Transplantation immunity, artifi cial circulation in organ transplantation

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S. P. Glyantsev

2017-01-01

Full Text Available The article (the fourth of five presents the analysis of the 4th and 5th chapters from V.P.Demikhov's monograph "Transplantation of vital organs in experiment" (MedGIz Publisher, Moscow, 1960, where he described his studies of transplantation immunity in originally created models and his use of artificial blood-circulation systems in experimental organ transplantation. It has been shown that V.P.Demikhov changed his views on the tissue biological incompatibility in homoplastic transplants and turned from the Michurin-Pavlov's concepts (1946–1953 to natural-scientific views (1959. Meanwhile, his multiple attempts to study both the morphological and humoral immunological response to transplanted organs did not give conclusive results because of lacking the experience of such studies even in the country's leading scientists and due the imperfection of their techniques. Realizing that the retrieval of a beating heart from a human would have created further problems for its subsequent transplantation, V.P. Demikhov attempted to reanimate human hearts in corpses by means of extracorporeal devices to provide artificial circulation. Methodologically, those devices were based on S.S.Bryukhonenko's research and his "auto-injector" pump modified by V.P.Demikhov. However, by 1960, those studies had not come beyond the experiments.

Encapsulated Islet Transplantation: Where Do We Stand?

Science.gov (United States)

Vaithilingam, Vijayaganapathy; Bal, Sumeet; Tuch, Bernard E

2017-01-01

Transplantation of pancreatic islets encapsulated within immuno-protective microcapsules is a strategy that has the potential to overcome graft rejection without the need for toxic immunosuppressive medication. However, despite promising preclinical studies, clinical trials using encapsulated islets have lacked long-term efficacy, and although generally considered clinically safe, have not been encouraging overall. One of the major factors limiting the long-term function of encapsulated islets is the host's immunological reaction to the transplanted graft which is often manifested as pericapsular fibrotic overgrowth (PFO). PFO forms a barrier on the capsule surface that prevents the ingress of oxygen and nutrients leading to islet cell starvation, hypoxia and death. The mechanism of PFO formation is still not elucidated fully and studies using a pig model have tried to understand the host immune response to empty alginate microcapsules. In this review, the varied strategies to overcome or reduce PFO are discussed, including alginate purification, altering microcapsule geometry, modifying alginate chemical composition, co-encapsulation with immunomodulatory cells, administration of pharmacological agents, and alternative transplantation sites. Nanoencapsulation technologies, such as conformal and layer-by-layer coating technologies, as well as nanofiber, thin-film nanoporous devices, and silicone based NanoGland devices are also addressed. Finally, this review outlines recent progress in imaging technologies to track encapsulated cells, as well as promising perspectives concerning the production of insulin-producing cells from stem cells for encapsulation.

Novel immunological strategies for islet transplantation.

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Tezza, Sara; Ben Nasr, Moufida; Vergani, Andrea; Valderrama Vasquez, Alessandro; Maestroni, Anna; Abdi, Reza; Secchi, Antonio; Fiorina, Paolo

2015-08-01

Islet transplantation has been demonstrated to improve glycometabolic control, to reduce hypoglycemic episodes and to halt the progression of diabetic complications. However, the exhaustion of islet function and the side effects related to chronic immunosuppression limit the spread of this technique. Consequently, new immunoregulatory protocols have been developed, with the aim to avoid the use of a life-time immunosuppression. Several approaches have been tested in preclinical models, and some are now under clinical evaluation. The development of new small molecules and new monoclonal or polyclonal antibodies is continuous and raises the possibility of targeting new costimulatory pathways or depleting particular cell types. The use of stem cells and regulatory T cells is underway to take advantage of their immunological properties and to induce tolerance. Xenograft islet transplantation, although having severe problems in terms of immunological compatibility, could theoretically provide an unlimited source of donors; using pigs carrying human immune antigens has showed indeed promising results. A completely different approach, the use of encapsulated islets, has been developed; synthetic structures are used to hide islet alloantigen from the immune system, thus preserving islet endocrine function. Once one of these strategies is demonstrated safe and effective, it will be possible to establish clinical islet transplantation as a treatment for patients with type 1 diabetes long before the onset of diabetic-related complications. Copyright © 2014 Elsevier Ltd. All rights reserved.

Impact of HLA diversity on donor selection in organ and stem cell transplantation.

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Tiercy, Jean-Marie; Claas, Frans

2013-01-01

The human major histocompatibility complex is a multigene system encoding polymorphic human leucocyte antigens (HLA) that present peptides derived from pathogens to the immune system. The high diversity of HLA alleles and haplotypes in the worldwide populations represents a major barrier to organ and allogeneic hematopoietic stem cell transplantation, because HLA incompatibilities are efficiently recognized by T and B lymphocytes. In organ transplantation, pre-transplant anti-HLA antibodies need to be taken into account for organ allocation. Although HLA-incompatible transplants can be performed thanks to immunosuppressive drugs, the de novo production of anti-HLA antibodies still represents a major cause of graft failure. The HLAMatchmaker computer algorithm determines the immunogenicity of HLA mismatches and allows to define HLA antigens that will not induce an antibody response. Because of the much higher stringency of HLA compatibility criteria in stem cell transplantation, the best donor is a HLA genotypically identical sibling. However, more than 50% of the transplants are now performed with hematopoietic stem cells from volunteer donors selected from the international registry. The development of European national registries covering populations with different HLA haplotype frequencies is essential for optimizing donor search algorithms and providing the best chance for European patients to find a fully compatible donor.

Pre-transplantation glucose testing for predicting new-onset diabetes mellitus after renal transplantation.

Science.gov (United States)

Ramesh Prasad, G V; Huang, M; Bandukwala, F; Nash, M M; Rapi, L; Montada-Atin, T; Meliton, G; Zaltzman, J S

2009-02-01

New-onset diabetes after renal transplantation (NODAT) adversely affects graft and patient survival. However, NODAT risk based on pre-transplant blood glucose (BG) levels has not been defined. Our goal was to identify the best pre-transplant testing method and cut-off values. We performed a case-control analysis of non-diabetic recipients who received a live donor allograft with at least 6 months post-transplant survival. Pre-transplant glucose abnormalities were excluded through 75 g oral glucose tolerance testing (OGTT) and random BG (RBG) measurement. NODAT was defined based on 2003 Canadian Diabetes Association criteria. Multivariate logistic and Cox regression analysis was performed to determine independent predictor variables for NODAT. Receiver-operating-characteristic (ROC) curves were constructed to determine threshold BG values for diabetes risk. 151 recipients met initial entry criteria. 12 had pre-transplant impaired fasting glucose and/or impaired glucose tolerance, among who 7 (58%) developed NODAT. In the remaining 139, 24 (17%) developed NODAT. NODAT risk exceeded 25% for those with pre-transplant RBG > 6.0 mmol/l and 50% if > 7.2 mmol/l. Pre-transplant RBG provided the highest AUC (0.69, p = 0.002) by ROC analysis. Increasing age (p = 0.025), acute rejection (p = 0.011), and RBG > 6.0 mmol/l (p = 0.001) were independent predictors of NODAT. Pre-transplant glucose testing is a specific marker for NODAT. Patients can be counseled of their incremental risk even within the normal BG range if the OGTT is normal.

Hazard classification of chemicals inducing haemolytic anaemia: An EU regulatory perspective

DEFF Research Database (Denmark)

Muller, A.; Jacobsen, Helene; Healy, E.

2006-01-01

Haemolytic anaemia is often induced following prolonged exposure to chemical substances. Currently, under EU Council Directive 67/548/EEC, substances which induce such effects are classified as dangerous and assigned the risk phrase R48 'Danger of serious damage to health by prolonged exposure......! Whilst the general classification criteria for this endpoint are outlined in Annex VI of this Directive, they do not provide specific information to assess haemolytic anaemia. This review produced by the EU Working Group on Haemolytic Anaemia provides a toxicological assessment of haemolytic anaemia...... and proposes criteria that can be used in the assessment for classification of substances which induce such effects. An overview of the primary and secondary effects of haemolytic anaemia which can occur in rodent repeated dose toxicity studies is given. A detailed analysis of the toxicological significance...

Induction of tolerance and prolongation of islet allograft survival by syngeneic hematopoietic stem cell transplantation in mice.

Science.gov (United States)

Yang, Shi-feng; Xue, Wu-jun; Lu, Wan-hong; Xie, Li-yi; Yin, Ai-ping; Zheng, Jin; Sun, Ji-ping; Li, Yang

2015-10-01

Syngeneic or autologous hematopoietic stem cells transplantation (HSCT) has been proposed to treat autoimmune diseases because of its immunosuppressive and immunomodulatory effects, which can also contribute to posttransplant antirejection therapy. In this study, we explored the tolerogenic effect of syngeneic HSCT on prolonging islet allograft survival. C57BL/6 mice received syngeneic HSCT plus preconditioning with sublethal irradiation. Then islets of BALB/c mice were transplanted into the renal subcapsular of C57BL/6 mice after chemically induced into diabetes. HSCT mice exhibited improved islet allograft survival and increased serum insulin compared to control mice. Islet allografts of HSCT mice displayed lower level lymphocyte infiltration and stronger insulin staining than control mice. T cells of HSCT mice proliferated poorly in response to allogeneic splenocytes compared to control mice. Mice appeared reversed interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio to a Th2 immune deviation after syngeneic HSCT. The percentage of CD8(+) T cells was lower, while percentage of CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) was higher in HSCT mice than control mice. HSCT mice showed higher percentage of CTLA-4(+) T cells and expression of CTLA-4 mRNA than control mice. Targeting of CTLA-4 by intraperitoneal injection of anti-CTLA-4 mAb abrogated the effect of syngeneic HSCT on prolonging islet allograft survival, inhibiting activity of T cells in response to alloantigen, promoting Th1 to Th2 immune deviation and up regulating CD4(+)CD25(+)Foxp3(+) Tregs. Syngeneic HSCT plus preconditioning of sublethal irradiation induces tolerance and improves islet allograft survival in fully mismatched mice model. Th1 to Th2 immune deviation, increased CD4(+)CD25(+)Foxp3(+) Tregs and up-regulation of CTLA-4 maybe contribute to the tolerogenic effect induced by syngeneic HSCT. Copyright © 2015 Elsevier B.V. All rights reserved.

[Serum soluble HLA-G, soluble CD30 is correlated to the time after transplantation in renal transplant recipients].

Science.gov (United States)

Jin, Zhankui; Xu, Cuixiang; Duan, Wanli; Yang, Jiangcun; Tian, Puxun

2017-07-01

Objective To investigate the expressions of serum soluble human leukocyte antigen G (sHLA-G) and soluble CD30 (sCD30) in renal transplant recipients at different time after transplantation, and explore the relationship between the expressions of serum sHLA-G, sCD30 and the time after renal transplantation. Methods Eleven kidney transplant recipients and 10 healthy donors were selected, in which the dynamic changes of serum sHLA-G and sCD30 were detected by ELISA before transplantation and 1 year after transplantation; 33 kidney transplant recipients with normal renal graft were selected and divided into three groups: 1-5 years, 5-10 years and 10 years post-transplantation. The expressions of serum sHLA-G and sCD30 in the recipients were tested over one year after transplantation. Results The level of serum sHLA-G before transplantation was not significantly different from that of the control group. There was no significant difference between pre-transplantation, 1 week and 1 month after transplantation. Serum sHLA-G level of renal transplant recipients at 3 months after transplantation was higher than that 1 month after transplantation. There was no significant change in serum sHLA-G level among 3, 6 and 12 months after transplantation. The level of serum sHLA-G in the group of transplant time >10 years was significantly higher than that in the group of transplant time ≤5 years. The serum sHLA-G level was significantly associated with the time after renal transplantation. The level of serum sCD30 before transplantation was higher than that in the control group and decreased in 1 week after transplantation. There were no significant differences in sCD30 level between 1, 3, 6, and 12 months after transplantation, and similarly, there were also no significant differences between the groups of transplant time ≤5 years, 5-10 years and 10 years after transplantation. The level of sCD30 was significantly associated with the time within 1 month after renal

Microsurgical techniques for experimental kidney transplantation and general guidelines to establish studies about transplantation immunology Técnicas microcirúrgicas para transplante renal experimental e condutas para estabelecer experimentos sobre imunologia do transplante

Directory of Open Access Journals (Sweden)

Paulo Ney Aguiar Martins

2003-08-01

Full Text Available Experimental models of organ transplantation played a crucial role to establish the principles of transplantation immunology. The renal transplantation in rodents became the most used model to study the mechanisms of allograft rejection. To perform it, it is necessary to master the microsurgery techniques and the research group should cooperate with other specialists in the field. In this article we review the surgical techniques employed in rats, and we draw guidelines to establish studies about transplantation immunology.Os princípios da imunologia do transplante estabeleceram-se após o surgimento de modelos experimentais. Esses modelos foram fundamentais para descoberta de mecanismos de tolerância imunológica e as bases genéticas da reação de rejeição. Transplante renal em roedores utilizando técnicas de microcirurgia tornou-se o modelo ideal, e abriu um novo horizonte para condução de pesquisas sobre imunologia e fisiologia de transplantes. Neste artigo revisamos as técnicas de transplante renal, e esboçamos diretrizes para elaboração de estudos imunológicos em modelos de rejeição.

Proteomic analysis of tyrosine phosphorylation during human liver transplantation

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Boutros Tarek

2007-01-01

Full Text Available Abstract Background Ischemia-reperfusion (I/R causes a dramatic reprogramming of cell metabolism during liver transplantation and can be linked to an alteration of the phosphorylation level of several cellular proteins. Over the past two decades, it became clear that tyrosine phosphorylation plays a pivotal role in a variety of important signalling pathways and was linked to a wide spectrum of diseases. Functional profiling of the tyrosine phosphoproteome during liver transplantation is therefore of great biological significance and is likely to lead to the identification of novel targets for drug discovery and provide a basis for novel therapeutic strategies. Results Using liver biopsies collected during the early phases of organ procurement and transplantation, we aimed at characterizing the global patterns of tyrosine phosphorylation during hepatic I/R. A proteomic approach, based on the purification of tyrosine phosphorylated proteins followed by their identification using mass spectrometry, allowed us to identify Nck-1, a SH2/SH3 adaptor, as a potential regulator of I/R injury. Using immunoblot, cell fractionation and immunohistochemistry, we demonstrate that Nck-1 phosphorylation, expression and localization were affected in liver tissue upon I/R. In addition, mass spectrometry identification of Nck-1 binding partners during the course of the transplantation also suggested a dynamic interaction between Nck-1 and actin during I/R. Conclusion Taken together, our data suggest that Nck-1 may play a role in I/R-induced actin reorganization, which was previously reported to be detrimental for the hepatocytes of the transplanted graft. Nck-1 could therefore represent a target of choice for the design of new organ preservation strategies, which could consequently help to reduce post-reperfusion liver damages and improve transplantation outcomes.

Plasma EBV microRNAs in paediatric renal transplant recipients.

Science.gov (United States)

Hassan, Jaythoon; Dean, Jonathan; De Gascun, Cillian F; Riordan, Michael; Sweeney, Clodagh; Connell, Jeff; Awan, Atif

2018-06-01

Epstein-Barr virus (EBV) was the first human virus identified to express microRNA (miRNA). To date, 44 mature miRNAs are encoded for within the EBV genome. EBV miRNAs have not been profiled in paediatric renal transplant recipients. In this study, we investigated circulating EBV miRNA profiles as novel biomarkers in paediatric renal transplant patients. Forty-two microRNAs encoded within 2 EBV open reading frames (BART and BHRF) were examined in renal transplant recipients who resolved EBV infection (REI) or maintained chronic high viral loads (CHL), and in non-transplant patients with acute infectious mononucleosis (IM). Plasma EBV-miR-BART2-5p was present in higher numbers of IM (7/8) and CHL (7/10) compared to REI (7/12) patients. A trend was observed between the numbers of plasma EBV miRNAs expressed and EBV viral load (p < 0.07). Several EBV-miRs including BART7-3p, 15, 9-3p, 11-3p, 1-3p and 3-3p were detected in IM and CHL patients only. The lytic EBV-miRs, BHRF1-2-3p and 1-1, indicating active viral replication, were detected in IM patients only. One CHL patient developed post-transplant lymphoproliferative disease (PTLD) after several years and analysis of 10 samples over a 30-month period showed an average 24-fold higher change in plasma EBV-miR-BART2-5p compared to the CHL group and 110-fold higher change compared to the REI group. Our results suggest that EBV-miR-BART2-5p, which targets the stress-induced immune ligand MICB to escape recognition and elimination by NK cells, may have a role in sustaining high EBV viral loads in CHL paediatric kidney transplant recipients.

Anti mutagenesis of chemical modulators against damage induced by reactor thermal neutrons

International Nuclear Information System (INIS)

Zambrano A, F.; Guzman R, J.; Garcia B, A.; Paredes G, L.; Delfin L, A.

1999-01-01

The mutations are changes in the genetic information whether for spontaneous form or induced by the exposure of the genetic material to certain agents, called mutagens: chemical or physical (diverse types of radiations). As well as exist a great variety of mutagens and pro mutagens (these last are agents which transform themselves in mutagens after the metabolic activation). Also several chemical compounds exist which are called antimutagens because they reduce the mutagens effect. The C vitamin or ascorbic acid (A A) presents antimutagenic and anti carcinogenic properties. On the other hand a sodium/copper salt derived from chlorophyll belonging to the porphyrin group (C L) contains a chelated metal ion in the center of molecule. It is also an antioxidant, antimutagenic and anti carcinogenic compound, it is called chlorophyllin. The objective of this work is to establish if the A A or the C L will reduce the damages induced by thermal and fast reactor neutrons. (Author)

Pediatric Liver Transplantation: Our Experiences.

Science.gov (United States)

Basturk, Ahmet; Yılmaz, Aygen; Sayar, Ersin; Dinçhan, Ayhan; Aliosmanoğlu, İbrahim; Erbiş, Halil; Aydınlı, Bülent; Artan, Reha

2016-10-01

The aim of our study was to evaluate our liver transplant pediatric patients and to report our experience in the complications and the long-term follow-up results. Patients between the ages of 0 and 18 years, who had liver transplantation in the organ transplantation center of our university hospital between 1997 and 2016, were included in the study. The age, sex, indications for the liver transplantation, complications after the transplantation, and long-term follow-up findings were retrospectively evaluated. The obtained results were analyzed with statistical methods. In our organ transplantation center, 62 pediatric liver transplantations were carried out since 1997. The mean age of our patients was 7.3 years (6.5 months-17 years). The 4 most common reasons for liver transplantation were: Wilson's disease (n=10; 16.3%), biliary atresia (n=9; 14.5%), progressive familial intrahepatic cholestasis (n=8; 12.9%), and cryptogenic cirrhosis (n=7; 11.3%). The mortality rate after transplantation was 19.6% (12 of the total 62 patients). The observed acute and chronic rejection rates were 34% and 4.9%, respectively. Thrombosis (9.6%) was observed in the hepatic artery (4.8%) and portal vein (4.8%). Bile leakage and biliary stricture rates were 31% and 11%, respectively. 1-year and 5-year survival rates of our patients were 87% and 84%, respectively. The morbidity and mortality rates in our organ transplantation center, regarding pediatric liver transplantations, are consistent with the literature.

[Risk factors for skin cancer development in patients after organ transplantation].

Science.gov (United States)

Imko-Walczuk, Beata; Piesiaków, Maria Luiza; Okuniewska, Aleksandra; Jaśkiewicz, Janusz; Lizakowski, Sławomir; Dębska-Ślizień, Alicja; Rutkowski, Bolesław

2012-11-13

Cancer has become the second most common cause of death in patients after organ transplantation. Among all cancers arising de novo after transplantation skin cancers are the most common, accounting for 95% of all skin neoplasms. Due to the significantly higher morbidity, aggressive, rapid progression of cancer and unfavorable prognosis, the population requires a specific oncological approach. Therefore, special attention should be paid to factors predisposing to the development of cancer, including skin cancer, in patients after organ transplantation. Some of these factors are well understood, while the role of others is still ambiguous. Among the etiological factors mentioned are those that are associated with the recipient. These include genetic factors such as male sex, fair skin and inability to be tanned, and compatibility of the HLA system, and non genetic factors such as patient age, chronic skin ulcers and scars, the type of transplanted organ, immunosuppression, and particularly the type and cumulative doses of drugs. In addition, the pathogenesis of cancer is influenced by environmental factors such as exposure to sunlight and therefore latitude, ionizing radiation, chemical carcinogens and viral infections. Knowledge of etiological factors and mechanisms of etiopathogenesis allow for indication and observation of patients with increased risk of cancer as well as faster healing in these patients.  

POSSIBLE NATURE OF THE RADIATION-INDUCED SIGNAL IN NAILS: HIGH-FIELD EPR, CONFIRMING CHEMICAL SYNTHESIS, AND QUANTUM CHEMICAL CALCULATIONS

Science.gov (United States)

Tipikin, Dmitriy S.; Swarts, Steven G.; Sidabras, Jason W.; Trompier, François; Swartz, Harold M.

2016-01-01

Exposure of finger- and toe-nails to ionizing radiation generates an Electron Paramagnetic Resonance (EPR) signal whose intensity is dose dependent and stable at room temperature for several days. The dependency of the radiation-induced signal (RIS) on the received dose may be used as the basis for retrospective dosimetry of an individual's fortuitous exposure to ionizing radiation. Two radiation-induced signals, a quasi-stable (RIS2) and stable signal (RIS5), have been identified in nails irradiated up to a dose of 50 Gy. Using X-band EPR, both RIS signals exhibit a singlet line shape with a line width around 1.0 mT and an apparent g-value of 2.0044. In this work, we seek information on the exact chemical nature of the radiation-induced free radicals underlying the signal. This knowledge may provide insights into the reason for the discrepancy in the stabilities of the two RIS signals and help develop strategies for stabilizing the radicals in nails or devising methods for restoring the radicals after decay. In this work an analysis of high field (94 GHz and 240 GHz) EPR spectra of the RIS using quantum chemical calculations, the oxidation–reduction properties and the pH dependence of the signal intensities are used to show that spectroscopic and chemical properties of the RIS are consistent with a semiquinone-type radical underlying the RIS. It has been suggested that semiquinone radicals formed on trace amounts of melanin in nails are the basis for the RIS signals. However, based on the quantum chemical calculations and chemical properties of the RIS, it is likely that the radicals underlying this signal are generated from the radiolysis of L-3,4-dihydroxyphenylalanine (DOPA) amino acids in the keratin proteins. These DOPA amino acids are likely formed from the exogenous oxidation of tyrosine in keratin by the oxygen from the air prior to irradiation. We show that these DOPA amino acids can work as radical traps, capturing the highly reactive and unstable

Concurrent validity of kidney transplant questionnaire in US renal transplant recipients

Directory of Open Access Journals (Sweden)

Chisholm-Burns MA

2011-10-01

Full Text Available Marie A Chisholm-Burns1,2, Steven R Erickson3, Christina A Spivey1, Rainer WG Gruessner2, Bruce Kaplan4 1Department of Pharmacy Practice and Science, University of Arizona College of Pharmacy, Tucson, AZ; 2Department of Surgery, University of Arizona College of Medicine, Tucson, AZ; 3Department of Clinical Sciences, University of Michigan College of Pharmacy, Ann Arbor, MI; 4Department of Medicine, The University of Arizona College of Medicine Tucson, AZ, USA Background: Valid instrumentation in the assessment of health-related quality of life (HQoL in renal transplant recipients is critical to identifying particular nuances and determinants of HQoL in this population. Therefore, the validity of disease-specific instruments to measure HQoL in renal transplant recipients, such as the Kidney Transplant Questionnaire (KTQ, needs further investigation. The objective of this study was to assess the concurrent validity of the KTQ in adult US renal transplant recipients using the well established SF-12 Health Survey version 2 (SF-12v2 as the comparison instrument. Methods: One hundred and fourteen renal transplant recipients met the following inclusion criteria for this study, ie, were at least 21 years of age, more than two years post-transplant, and receiving immunosuppressant therapy. Subjects were asked to complete a series of HQoL instruments, ie, the KTQ and the SF-12v2 (physical component summary [PCS-12] and mental component summary [MCS-12]. Descriptive statistics were calculated, and correlational analyses were conducted to examine the concurrent validity of the HQoL instruments. Results: Among 100 participants (87.7% response rate, the majority of participants were male (52%, had deceased donor transplants (63%, and received Medicare benefits (84%. PCS-12 was positively correlated with three of five KTQ subscales (P < 0.05, ie, KTQ-physical (r = 0.43, KTQ-fatigue (r = 0.42, and KTQ-uncertainty/fear (r = 0.2. MCS-12 was positively correlated

Chemically induced magnetism in atomically precise gold clusters.

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Krishna, Katla Sai; Tarakeshwar, Pilarisetty; Mujica, Vladimiro; Kumar, Challa S S R

2014-03-12

Comparative theoretical and experimental investigations are reported into chemically induced magnetism in atomically-precise, ligand-stabilized gold clusters Au25 , Au38 and Au55 . The results indicate that [Au25 (PPh3 )10 (SC12 H25 )5 Cl2 ](2+) and Au38 (SC12 H25 )24 are diamagnetic, Au25 (SC2 H4 Ph)18 is paramagnetic, and Au55 (PPh3 )12 Cl6 , is ferromagnetic at room temperature. Understanding the magnetic properties resulting from quantum size effects in such atomically precise gold clusters could lead to new fundamental discoveries and applications. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Induction of transplantation tolerance to fully mismatched cardiac allografts by T cell mediated delivery of alloantigen

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Tian, Chaorui; Yuan, Xueli; Jindra, Peter T.; Bagley, Jessamyn; Sayegh, Mohamed H.; Iacomini, John

2010-01-01

Induction of transplantation tolerance has the potential to allow for allograft acceptance without the need for life-long immunosuppression. Here we describe a novel approach that uses delivery of alloantigen by mature T cells to induce tolerance to fully allogeneic cardiac grafts. Adoptive transfer of mature alloantigen-expressing T cells into myeloablatively conditioned mice results in long-term acceptance of fully allogeneic heart transplants without evidence of chronic rejection. Since myeloablative conditioning is clinically undesirable we further demonstrated that adoptive transfer of mature alloantigen-expressing T cells alone into mice receiving non-myeloablative conditioning resulted in long-term acceptance of fully allogeneic heart allografts with minimal evidence of chronic rejection. Mechanistically, tolerance induction involved both deletion of donor-reactive host T cells and the development of regulatory T cells. Thus, delivery of alloantigen by mature T cells induces tolerance to fully allogeneic organ allografts in non-myeloablatively conditioned recipients, representing a novel approach for tolerance induction in transplantation. PMID:20452826

Immune System and Kidney Transplantation.

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Shrestha, Badri Man

2017-01-01

The immune system recognises a transplanted kidney as foreign body and mounts immune response through cellular and humoral mechanisms leading to acute or chronic rejection, which ultimately results in graft loss. Over the last five decades, there have been significant advances in the understanding of the immune responses to transplanted organs in both experimental and clinical transplant settings. Modulation of the immune response by using immunosuppressive agents has led to successful outcomes after kidney transplantation. The paper provides an overview of the general organisation and function of human immune system, immune response to kidney transplantation, and the current practice of immunosuppressive therapy in kidney transplantation in the United Kingdom.

Mixed allogeneic reconstitution (A+B----A) to induce donor-specific transplantation tolerance. Permanent acceptance of a simultaneous donor skin graft

International Nuclear Information System (INIS)

Ildstad, S.T.; Wren, S.M.; Oh, E.; Hronakes, M.L.

1991-01-01

Mixed allogeneic reconstitution, in which a mixture of T-cell-depleted bone marrow of syngeneic host and allogeneic donor type is transplanted into a lethally irradiated recipient (A+B----A), results in mixed lymphopoietic chimerism with engraftment of a mixture of both host and donor bone marrow elements. Recipients are specifically tolerant to donor both in vitro and in vivo. Donor-specific skin grafts survive indefinitely when they are placed after full bone marrow repopulation at 28 days, while third-party grafts are rapidly rejected. To determine whether a delay of a month or more for full bone marrow repopulation is required before a donor-specific graft can be placed, we have now examined whether tolerance induction can be achieved if a graft is placed at the time of bone marrow transplantation. Permanent acceptance of donor-specific B10.BR skin grafts occurred when mixed allogeneic chimerism (B10+B10.BR----B10) was induced and a simultaneous allogeneic donor graft placed. In vitro, mixed reconstituted recipients were specifically tolerant to the B10.BR donor lymphoid cells but fully reactive to MHC-disparate third-party (BALB/c; H-2dd) when assessed by mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays. These data therefore indicate that a donor-specific graft placed at the time of mixed allogeneic reconstitution is permanently accepted without rejection. To determine whether an allogeneic skin graft alone without allogeneic bone marrow would be sufficient to induce tolerance, syngeneic reconstitution (B10----B10) was carried out, and a simultaneous B10.BR allogeneic skin graft placed. Although skin grafts were prolonged in all recipients, all grafts rejected when full lymphopoietic repopulation occurred at 28 days

Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels.

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Uzunalli, Gozde; Tumtas, Yasin; Delibasi, Tuncay; Yasa, Oncay; Mercan, Sercan; Guler, Mustafa O; Tekinay, Ayse B

2015-08-01

Pancreatic islet transplantation is a promising treatment for type 1 diabetes. However, viability and functionality of the islets after transplantation are limited due to loss of integrity and destruction of blood vessel networks. Thus, it is important to provide a proper mechanically and biologically supportive environment for enhancing both in vitro islet culture and transplantation efficiency. Here, we demonstrate that heparin mimetic peptide amphiphile (HM-PA) nanofibrous network is a promising platform for these purposes. The islets cultured with peptide nanofiber gel containing growth factors exhibited a similar glucose stimulation index as that of the freshly isolated islets even after 7 days. After transplantation of islets to STZ-induced diabetic rats, 28 day-long monitoring displayed that islets that were transplanted in HM-PA nanofiber gels maintained better blood glucose levels at normal levels compared to the only islet transplantation group. In addition, intraperitoneal glucose tolerance test revealed that animals that were transplanted with islets within peptide gels showed a similar pattern with the healthy control group. Histological assessment showed that islets transplanted within peptide nanofiber gels demonstrated better islet integrity due to increased blood vessel density. This work demonstrates that using the HM-PA nanofiber gel platform enhances the islets function and islet transplantation efficiency both in vitro and in vivo. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Clinical pancreatic islet transplantation.

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Shapiro, A M James; Pokrywczynska, Marta; Ricordi, Camillo

2017-05-01

Clinical pancreatic islet transplantation can be considered one of the safest and least invasive transplant procedures. Remarkable progress has occurred in both the technical aspects of islet cell processing and the outcomes of clinical islet transplantation. With >1,500 patients treated since 2000, this therapeutic strategy has moved from a curiosity to a realistic treatment option for selected patients with type 1 diabetes mellitus (that is, those with hypoglycaemia unawareness, severe hypoglycaemic episodes and glycaemic lability). This Review outlines the techniques required for human islet isolation, in vitro culture before the transplant and clinical islet transplantation, and discusses indications, optimization of recipient immunosuppression and management of adjunctive immunomodulatory and anti-inflammatory strategies. The potential risks, long-term outcomes and advances in treatment after the transplant are also discussed to further move this treatment towards becoming a more widely available option for patients with type 1 diabetes mellitus and eventually a potential cure.

Ex Vivo Normothermic Perfusion Induces Donor-Derived Leukocyte Mobilization and Removal Prior to Renal Transplantation

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John P. Stone

2016-11-01

Discussion: We demonstrate that ex vivo normothermic perfusion initiates an inflammatory cytokine storm and release of mitochondrial and genomic DNA. This is likely to be responsible for immune cell activation and mobilization into the circuit prior to transplantation. Interestingly this did not have an impact on renal function. These data therefore suggest that normothermic perfusion can be used to immunodeplete and to saturate the pro-inflammatory capacity of donor kidneys prior to transplantation.

Graft Growth and Podocyte Dedifferentiation in Donor-Recipient Size Mismatch Kidney Transplants

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Janina Müller-Deile, MD

2017-10-01

Full Text Available Background. Kidney transplantation is the treatment choice for patients with end-stage renal diseases. Because of good long-term outcome, pediatric kidney grafts are also accepted for transplantation in adult recipients despite a significant mismatch in body size and age between donor and recipient. These grafts show a remarkable ability of adaptation to the recipient body and increase in size in a very short period, presumably as an adaptation to hyperfiltration. Methods. We investigated renal graft growth as well as glomerular proliferation and differentiation markers Kiel-67, paired box gene 2 and Wilms tumor protein (WT1 expression in control biopsies from different transplant constellations: infant donor for infant recipient, infant donor for child recipient, infant donor for adult recipient, child donor for child recipient, child donor for adult recipient, and adult donor for an adult recipient. Results. We detected a significant increase in kidney graft size after transplantation in all conditions with a body size mismatch, which was most prominent when an infant donated for a child. Podocyte WT1 expression was comparable in different transplant conditions, whereas a significant increase in WT1 expression could be detected in parietal epithelial cells, when a kidney graft from a child was transplanted into an adult. In kidney grafts that were relatively small for the recipients, we could detect reexpression of podocyte paired box gene 2. Moreover, the proliferation marker Kiel-67 was expressed in glomerular cells in grafts that increased in size after transplantation. Conclusions. Kidney grafts rapidly adapt to the recipient size after transplantation if they are transplanted in a body size mismatch constellation. The increase in transplant size is accompanied by an upregulation of proliferation and dedifferentiation markers in podocytes. The different examined conditions exclude hormonal factors as the key trigger for this growth so that

Evaluation of Chemical Changes in Some Soybean Mutants Induced by Gamma Irradiation

International Nuclear Information System (INIS)

Abd-Elkalik, K.; Mekkawy, S.H.; El-Demerdash, H.M.

2010-01-01

The Egyptian soybean cultivar Giza-22 was used to induce genetic variability by using gamma rays at dose levels of 100, 150 and 200 Gy. Sixteen mutants (including parental cultivar) were evaluated in M3 generation for their agronomic traits and chemical analysis was done in seeds of M3 generation. Four mutants A21 (150 Gy), A22, A23 and A24 (200 Gy) showed superiority in their agronomic traits compared with parental cultivar. The results of chemical analysis of seeds of M3 generation showed that, oil and energy contents were unaffected by irradiation treatments while protein contents were significantly increased at doses 150 and 200 Gy. Phenolic and tannin contents in seeds of M3 generation showed no significant changes in their percentages due to irradiation treatments. Gamma irradiation significantly increased in linoleic acid content in most of the mutants compared with the control (Giza-22), whereas, there were decreases in linolenic acid content. Investigation of amino acid composition of mutants of M3 generation revealed significant increases in the essential amino acids in most mutants induced by gamma irradiation at 150 and 200 Gy. It could be suggested that the use of gamma irradiation can induce an improvement of the oil and protein composition in soybean

ABO-incompatible kidney transplantation

DEFF Research Database (Denmark)

Schousboe, Karoline; Titlestad, Kjell; Baudier, Francois

2010-01-01

INTRODUCTION: Kidney transplantation is the optimal treatment for many patients with end-stage renal disease (ESRD). Due to shortage of donor kidneys in Denmark, there is a need to expand the possibilities for donation. At the Odense University Hospital (OUH), we have introduced ABO......-incompatible kidney transplantation. We used antigenspecific immunoadsorptions to remove blood group antibodies and anti-CD20 antibody (rituximab) to inhibit the antibody production. The aim of introducing the ABO-incompatible kidney transplantation at the OUH was to increase the rate of living donor kidney...... transplantation without increasing rejection or mortality rates. MATERIAL AND METHODS: Retrospective evaluation. Eleven patients received ABO-incompatible kidney transplantation. The patients were followed for 3-26 months. RESULTS: One patient had an antibody-mediated rejection, one patient suffered T...

What's hot, what's new in basic science: report from the American Transplant Congress 2015.

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Heeger, P S

2015-11-01

Research reports presented at the American Transplant Congress 2015 provided an array of basic science findings of relevance to the transplant community. Among key themes is the concept that ischemia-reperfusion injury and early posttransplantation inflammation is linked to adaptive alloimmunity and transplant injury. Molecular and cellular mechanisms contributing to these interactions were highlighted. The relevance of understanding how blocking costimulation, including CD40/CD154 interactions, affects various aspects of the alloimmune response was enhanced by the description of preclinical studies demonstrating efficacy of a unique, blocking anti-CD40 monoclonal antibody that could potentially be used in humans. The identification of mechanisms underlying interactions among T cell subsets and B cells, including follicular helper T cells, regulatory T cells, effector B cells, and regulatory B cells, provides multiple previously unrecognized targets for future therapeutic interventions. Additional reports of interest include novel insights into effects of the gut microbiome on graft survival and the ability to differentiate insulin-secreting, islet-like cells from induced pluripotent stem cells. Overall, the reported basic science findings from American Transplant Congress 2015 add to the fundamental understanding of innate and adaptive alloimmunity and provide novel and testable hypotheses that have the potential to be translated into improved clinical care of transplant patients. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Central pontine myelinolysis (CPM) associated with tacrolimus (FK506) after liver transplantation.

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Fukazawa, Kyota; Nishida, Seigo; Aguina, Luz; Pretto, Ernesto

2011-01-01

Central pontine myelinolysis (CPM) is the most detrimental neurologic complication after liver transplantation. The incidence of CPM after liver transplantation ascends to 17%. Although the precise etiology and pathogenesis of CPM is largely unknown, a growing literature implicates a possible role of immunosuppressive agents, such as Cyclosporine (incidence 30%) on its development. Other immunosuppressive agents also can cause CPM but the frequency of these cases is less compared to Cyclosporine. There is only one case report for Tacrolimus (FK506)-associated speech disorder, which might be an atypical presentation of CPM, and no case reports for Rapamycin. We present a case of Tacrolimus induced CPM. A 62-year-old woman who underwent liver transplantation developed clinical symptoms with radiologic evidence consistent with CPM 7 days after liver transplant. Since the electrolytes in this patient remained normal from her admission, the hypothesis of inmunossupressor neurotoxicity was established and the therapy was switched, resulting in an evident clinical and radiological improvement of her condition in the following days. Five months later, the patient's only neurological deficit was slight dysarthria and a follow-up MRI showed no abnormalities. This case provides evidence of Tacrolimus-associated CPM after transplantation, which presented with a classic "lock-in syndrome" with radiographic confirmation.

Nonprescription analgesics and their use in solid-organ transplantation: a review.

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Gabardi, Steven; Luu, Linh

2004-09-01

To review the pharmacology, adverse events, drug interactions, and use of the nonprescription analgesics in solid-organ transplant recipients. Studies evaluating nonprescription analgesics in solid-organ transplantation were considered for evaluation. English-language studies were selected for inclusion. Nonprescription analgesics (aspirin, choline salicylate, magnesium salicylate, sodium salicylate, ibuprofen, ketoprofen, naproxen sodium, and acetaminophen) are the most commonly purchased over-the-counter agents in the United States. These agents, although generally considered safe, have been associated with a number of toxicities. The salicylates and nonsteroidal anti-inflammatory drugs have been associated with gastrointestinal damage, hematologic changes, liver and kidney dysfunction, and breathing difficulties. Acetaminophen has been shown to induce hematologic changes and liver and renal dysfunction. A closer look at the nonprescription analgesics reveals their potential for harm when used by solid-organ transplant recipients. In this patient population, the salicylates and nonsteroidal anti-inflammatory drugs should generally be avoided if possible, because of their potential toxicities, especially renal dysfunction. Low-dose aspirin, for the prevention of cardiovascular and cardiocerebral events, appears to be safe, but patients must still be followed closely. Acetaminophen is generally considered the nonprescription analgesic and antipyretic of choice in transplant recipients because of its favorable toxicity profile. However, it is imperative that patients and transplant practitioners are aware that this agent is not without toxicities and proper monitoring is advised.

Hematopoietic chimerism and transplantation tolerance: a role for regulatory T cells

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Lise ePasquet

2011-12-01

Full Text Available The major obstacle in transplantation medicine is rejection of donor tissues by the host’s immune system. Immunosuppressive drugs can delay but not prevent loss of transplants, and their efficiency is strongly impacted by inter-individual pharmacokinetic differences. Moreover, due to the global immunosuppression induced and to the broad distribution of their targets amongst human tissues, these drugs have severe side effects. Induction of donor-specific non-responsiveness (i.e. immunological tolerance to transplants would solve these problems and would substantially ameliorate patients’ quality of life. It is widely believed that bone marrow or hematopoietic stem cell transplantation, and resulting (mixed hematopoietic chimerism, invariably leads to immunological tolerance to organs of the same donor. A careful analysis of the literature, reviewed here, indeed shows that chimerism consistently prolongs allograft survival. However, in absence of additional conditioning leading to the development of active regulatory mechanisms, it does not prevent chronic rejection. A central role for active tolerance in transplantation-tolerance is also supported by recent data showing that genuine immunological tolerance to organ allografts can be achieved by combining induction of hematopoietic chimerism with infusion of regulatory T lymphocytes. Therefore, conditioning regimens that lead to the establishment of hematopoietic chimerism plus active regulatory mechanisms appear required for induction of genuine tolerance to allogeneic grafts.

Pre-transplant reversible pulmonary hypertension predicts higher risk for mortality after cardiac transplantation.

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Butler, Javed; Stankewicz, Mark A; Wu, Jack; Chomsky, Don B; Howser, Renee L; Khadim, Ghazanfar; Davis, Stacy F; Pierson, Richard N; Wilson, John R

2005-02-01

Pre-transplant fixed pulmonary hypertension is associated with higher post-transplant mortality. In this study, we assessed the significance of pre-transplant reversible pulmonary hypertension in patients undergoing cardiac transplantation. Overall, we studied 182 patients with baseline normal pulmonary pressures or reversible pulmonary hypertension, defined as a decrease in pulmonary vascular resistance (PVR) to 50 mm Hg had a higher risk of death (odds ratio [OR] 5.96, 95% confidence interval [CI] 1.46 to 19.84 as compared with PAS 4.0 WU, but patients with TPG > or =16 had a higher risk of mortality (OR 4.93, 95% CI 1.84 to 13.17). PAS pressure was an independent predictor of mortality (OR 1.04, 95% CI 1.02 to 1.06). Recipient body mass index, history of sternotomy; and donor ischemic time were the other independent predictors of mortality. Pre-transplant pulmonary hypertension, even when reversible to a PVR of < or =2.5 WU, is associated with a higher mortality post-transplant.

Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma.

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Burra, Patrizia; Zanetto, Alberto; Germani, Giacomo

2018-02-09

Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

Fecal microbiota transplant

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... page: //medlineplus.gov/ency/article/007703.htm Fecal microbiota transplant To use the sharing features on this page, please enable JavaScript. Fecal microbiota transplantation (FMT) helps to replace some of the " ...

Differential expression of proteoglycans in tissue remodeling and lymphangiogenesis after experimental renal transplantation in rats.

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Heleen Rienstra

Full Text Available BACKGROUND: Chronic transplant dysfunction explains the majority of late renal allograft loss and is accompanied by extensive tissue remodeling leading to transplant vasculopathy, glomerulosclerosis and interstitial fibrosis. Matrix proteoglycans mediate cell-cell and cell-matrix interactions and play key roles in tissue remodeling. The aim of this study was to characterize differential heparan sulfate proteoglycan and chondroitin sulfate proteoglycan expression in transplant vasculopathy, glomerulosclerosis and interstitial fibrosis in renal allografts with chronic transplant dysfunction. METHODS: Renal allografts were transplanted in the Dark Agouti-to-Wistar Furth rat strain combination. Dark Agouti-to-Dark Agouti isografts and non-transplanted Dark Agouti kidneys served as controls. Allograft and isograft recipients were sacrificed 66 and 81 days (mean after transplantation, respectively. Heparan sulfate proteoglycan (collXVIII, perlecan and agrin and chondroitin sulfate proteoglycan (versican expression, as well as CD31 and LYVE-1 (vascular and lymphatic endothelium, respectively expression were (semi- quantitatively analyzed using immunofluorescence. FINDINGS: Arteries with transplant vasculopathy and sclerotic glomeruli in allografts displayed pronounced neo-expression of collXVIII and perlecan. In contrast, in interstitial fibrosis expression of the chondroitin sulfate proteoglycan versican dominated. In the cortical tubular basement membranes in both iso- and allografts, induction of collXVIII was detected. Allografts presented extensive lymphangiogenesis (p<0.01 compared to isografts and non-transplanted controls, which was associated with induced perlecan expression underneath the lymphatic endothelium (p<0.05 and p<0.01 compared to isografts and non-transplanted controls, respectively. Both the magnitude of lymphangiogenesis and perlecan expression correlated with severity of interstitial fibrosis and impaired graft function

Renal transplantation at the Johns Hopkins Comprehensive Transplant Center.

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Montgomery, Robert A; Cooper, Matthew; Kraus, Edward; Rabb, Hamid; Samaniego, Milagros; Simpkins, Christopher E; Sonnenday, Christopher J; Ugarte, Richard M; Warren, Daniel S; Zachary, Andrea A

2003-01-01

A stagnant supply of transplantable organs in the face of a relentless burgeoning of transplant waiting lists has created a crisis. Necessity continues to be the mother of invention and as the crisis has deepened it has served as a crucible for the development of new ways to think about perennial problems. Our program has taken a 2-pronged approach to increasing the organ supply for our patients. First, through innovations like the laparoscopic donor nephrectomy, ABO-incompatible and positive-crossmatch transplantation protocols, unconventional paired kidney exchanges, and the use of altruistic donors we have more than doubled our utilization of live donor organs. At the same time, we have developed algorithms and interrogative techniques to enhance the intelligent use of kidneys from expanded criteria donors for patients who do not have an available live donor. The laparoscopic nephrectomy has proven to be a safe and effective way of removing a significant barrier to live donation. Our results from 100 ABOi, (+)XM, and PKE transplants are similar to national statistics for compatible live donor transplants, suggesting that existing paradigms of compatibility can be safely expanded. These encouraging early outcomes and the savings they transmit to the health care system have allowed us to obtain insurance coverage for the InKTP programs, setting the stage for further expansion of these opportunities to broaden the options for patients with end-stage renal disease.

[Kidney transplantation epidemiology in France].

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Hiesse, Christian

2013-11-01

Kidney transplantation activity in France is among the most important worldwide: in 2011, 2976 transplants have been performed (47.5 per million population), and the number of patients living with a functional graft is estimated around 30,000, representing 44.7% of all patients (n = 67,270) treated for end-stage renal failure. However, the rate of preemptive kidney transplants remains very low, only 3.3% of incident patients starting renal replacement therapy. The analysis of demand showed a progressive increase in recent years, as demonstrated by the registration rate on the kidney transplantation waiting list, increasing by 5% yearly between 2006 and 2010, but with huge differences according to age categories and regional registration areas, reflecting discrepant appreciations in indications for kidney transplantation. The median waiting time between registration and transplantation increased progressively in recent years, reaching 22.3 months with considerable variations according to regional areas and transplantation teams. Kidney transplantation activity, while increasing continuously, is far to cover the rising demand, and inexorably patients accumulate on the waiting list (around 9000 patients were registered by January 2012). This situation is the consequence of insufficient organ procurement activity. The deceased organ procurement rate remained high: 1572 harvested donors in 2011 (24.1 per million population), but the proportion of older donors rose in recent years, to reach the rate of 26% of donors older than 65 years in 2011. The procurement activity of donors after cardiac arrest was reintroduced in 2006, but increased slowly: 65 transplants were performed in 2011 using kidney procured in non heart-beating donors. The living donor kidney transplantation activity has markedly increased recently: 302 living donor transplantations were performed in 2011, representing 10.1% of the kidney transplantations. Facing the predictable increase in the number of

Liver transplantation in the Nordic countries - An intention to treat and post-transplant analysis from The Nordic Liver Transplant Registry 1982-2013

DEFF Research Database (Denmark)

Fosby, Bjarte; Melum, Espen; Bjøro, Kristian

2015-01-01

AIM AND BACKGROUND: The Nordic Liver Transplant Registry (NLTR) accounts for all liver transplants performed in the Nordic countries since the start of the transplant program in 1982. Due to short waiting times, donor liver allocation has been made without considerations of the model of end-stage...

Biomarkers of DNA and cytogenetic damages induced by environmental chemicals or radiation

International Nuclear Information System (INIS)

1999-01-01

This paper presents and discusses results from the studies on various biomarkers of the DNA and cytogenetic damages induced by environmental chemicals or radiation. Results of the biomonitoring studies have shown that particularly in the condition of Poland, health hazard from radiation exposure is overestimated in contradistinction to the environmental hazard

Illness intrusiveness among survivors of autologous blood and marrow transplantation.

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Schimmer, A D; Elliott, M E; Abbey, S E; Raiz, L; Keating, A; Beanlands, H J; McCay, E; Messner, H A; Lipton, J H; Devins, G M

2001-12-15

Illness-induced disruptions to lifestyles, activities, and interests (i.e., illness intrusiveness) compromise subjective well-being. The authors measured illness intrusiveness in autologous blood and bone marrow transplantation (ABMT) survivors and compared the results with survivors of solid organ transplants. Forty-four of 64 consecutive ABMT survivors referred to the University of Toronto ABMT long-term follow-up clinic completed the Illness Intrusiveness Ratings Scale (IIRS), the Affect Balance Scale (ABS), the Atkinson Life Happiness Rating (ATKLH), the Beck Hopelessness Scale (BHS), and the Center for Epidemiologic Studies Depression (CES-D) Scale. Mean time from ABMT to evaluation was 4.6 +/- 2.8 years. All patients were in remission or had stable disease at the time of evaluation. Autologous blood and bone marrow transplantation patients' IIRS scores were compared with scores reported by recipients of kidney (n = 357), liver (n = 150), lung (n = 77), and heart (n = 60) transplants. Mean IIRS score for the 44 ABMT patients was 37.2 +/- 17 (maximum possible score, 91; minimum possible score, 13). Higher IIRS scores correlated with lower scores on the ABS (r = -0.54; P work, financial situation, and active recreation. Despite achieving a remission after ABMT, patients continue to experience illness intrusiveness compromising subjective well-being. Copyright 2001 American Cancer Society.

Chemical Exacerbation of Light-induced Retinal Degeneration in F344/N Rats in National Toxicology Program Rodent Bioassays

OpenAIRE

Yamashita, Haruhiro; Hoenerhoff, Mark J.; Peddada, Shyamal D.; Sills, Robert C.; Pandiri, Arun R.

2016-01-01

Retinal degeneration due to chronic ambient light exposure is a common spontaneous age-related finding in albino rats, but it can also be related to exposures associated with environmental chemicals and drugs. Typically, light induced retinal degeneration has a central/hemispherical localization where as chemical induced retinal degeneration has a diffuse localization. This study was conducted to identify National Toxicology Program (NTP) rodent bioassays with treatment-related retinal degene...

Development of PET Imaging to Visualize Activated Macrophages Accumulated in the Transplanted iPSc-Derived Cardiac Myocytes of Allogeneic Origin for Detecting the Immune Rejection of Allogeneic Cell Transplants in Mice.

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Noriyuki Kashiyama

Full Text Available Allogeneic transplantation (Tx of induced pluripotent stem cells (iPSCs is a promising tissue regeneration therapy. However, this inevitably induces macrophage-mediated immune response against the graft, limiting its therapeutic efficacy. Monitoring the magnitude of the immune response using imaging tools would be useful for prolonging graft survival and increasing the therapy longevity. Minimally invasive quantitative detection of activated macrophages by medical imaging technologies such as positron emission tomography (PET imaging targets translocator protein (TSPO, which is highly expressed on mitochondrial membrane, especially in activated macrophage. N,N-diethyl-2-[4-(2-fluoroethoxy phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide (DPA-714 is known as a TSPO ligand used in clinical settings. We herein hypothesized that immune rejection of the transplanted iPSC-derived cardiomyocytes (iPSC-CMs of allogeneic origin may be quantitated using 18F-DPA-714-PET imaging study. iPSC-CM cell-sheets of C57BL/6 mice origin were transplanted on the surface of the left ventricle (LV of C57BL/6 mice as a syngeneic cell-transplant model (syngeneic Tx group, or Balb/c mice as an allogeneic model (allogeneic Tx group. 18F-DPA-714-PET was used to determine the uptake ratio, calculated as the maximum standardized uptake value in the anterior and septal wall of the LV. The uptake ratio was significantly higher in the allogeneic Tx group than in the syngeneic group or the sham group at days 7 and day 10 after the cell transplantation. In addition, the immunochemistry showed significant presence of CD68 and CD3-positive cells at day 7 and 10 in the transplanted graft of the allogeneic Tx group. The expression of TSPO, CD68, IL-1 beta, and MCP-1 was significantly higher in the allogeneic Tx group than in the syngeneic Tx and the sham groups at day 7. The 18F-DPA-714-PET imaging study enabled quantitative visualization of the macrophages-mediated immune

Long term beneficial effect of neurotrophic factors-secreting mesenchymal stem cells transplantation in the BTBR mouse model of autism.

Science.gov (United States)

Perets, Nisim; Segal-Gavish, Hadar; Gothelf, Yael; Barzilay, Ran; Barhum, Yael; Abramov, Natalie; Hertz, Stav; Morozov, Darya; London, Michael; Offen, Daniel

2017-07-28

Autism spectrum disorders (ASD) are neurodevelopmental disabilities characterized by severe impairment in social communication skills and restricted, repetitive behaviors. We have previously shown that a single transplantation of mesenchymal stem cells (MSC) into the cerebral lateral ventricles of BTBR autistic-like mice resulted in an improvement across all diagnostic criteria of ASD. We suggested that brain-derived neurotrophic factor (BDNF), a protein which supports the survival and regeneration of neurons secreted by MSC, largely contributed to the beneficial behavioral effect. In this study, we investigated the behavioral effects of transplanted MSC induced to secrete higher amounts of neurotrophic factors (NurOwn ® ), on various ASD-related behavioral domains using the BTBR mouse model of ASD. We demonstrate that NurOwn ® transplantation had significant advantages over MSC transplantation in terms of improving communication skills, one and six months following treatment, as compared to sham-treated BTBR mice. Furthermore, NurOwn ® transplantation resulted in reduced stereotypic behavior for as long as six months post treatment, compared to the one month improvement observed in the MSC treated mice. Notably, NurOwn ® treatment resulted in improved cognitive flexibility, an improvement that was not observed by MSC treatment. Both MSC and NurOwn ® transplantation induced an improvement in social behavior that lasted for six months. In conclusion, the present study demonstrates that a single transplantation of MSC or NurOwn ® have long-lasting benefits, while NurOwn ® may be superior to MSC treatment. Copyright © 2017. Published by Elsevier B.V.

Transplant tourism: a growing phenomenon.

Science.gov (United States)

Cohen, David J

2009-03-01

Medical tourism is increasing owing to high costs of care, lack of availability or long waits for procedures, and improvements in technology and standards of care in many countries. Transplant tourism is one example of medical tourism that has been attracting increasing attention because of concerns over poor treatment and outcomes of both donors and recipients. Most such cases involve vended kidneys obtained from vulnerable populations, and both donors and recipients receive inferior care by US standards. This commentary discusses a paper by Gill et al. that compared outcomes of 33 transplant tourists with those of patients transplanted at a US center. Fewer complications and better outcomes were seen in patients transplanted in the US center than among transplant tourists. Large transplant centers with long waiting times are increasingly likely to see patients return newly transplanted from overseas; such patients require urgent attention, with particular consideration to infectious complications.

Methylene Blue for Vasoplegia When on Cardiopulmonary Bypass During Double-Lung Transplantation.

Science.gov (United States)

Carley, Michelle; Schaff, Jacob; Lai, Terrance; Poppers, Jeremy

2015-10-15

Vasoplegia syndrome, characterized by hypotension refractory to fluid resuscitation or high-dose vasopressors, low systemic vascular resistance, and normal-to-increased cardiac index, is associated with increased morbidity and mortality after cardiothoracic surgery. Methylene blue inhibits inducible nitric oxide synthase and guanylyl cyclase, and has been used to treat vasoplegia during cardiopulmonary bypass. However, because methylene blue is associated with increased pulmonary vascular resistance, its use in patients undergoing lung transplantion has been limited. Herein, we report the use of methylene blue to treat refractory vasoplegia during cardiopulmonary bypass in a patient undergoing double-lung transplantation.

Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model

OpenAIRE

Takagi, Ryoji; Ishimaru, Junko; Sugawara, Ayaka; Toyoshima, Koh-ei; Ishida, Kentaro; Ogawa, Miho; Sakakibara, Kei; Asakawa, Kyosuke; Kashiwakura, Akitoshi; Oshima, Masamitsu; Minamide, Ryohei; Sato, Akio; Yoshitake, Toshihiro; Takeda, Akira; Egusa, Hiroshi

2016-01-01

The integumentary organ system is a complex system that plays important roles in waterproofing, cushioning, protecting deeper tissues, excreting waste, and thermoregulation. We developed a novel in vivo transplantation model designated as a clustering-dependent embryoid body transplantation method and generated a bioengineered three-dimensional (3D) integumentary organ system, including appendage organs such as hair follicles and sebaceous glands, from induced pluripotent stem cells. This bio...

Risk factors for Epstein-Barr virus-related post-transplant lymphoproliferative disease after allogeneic hematopoietic stem cell transplantation.

Science.gov (United States)

Uhlin, Michael; Wikell, Helena; Sundin, Mikael; Blennow, Ola; Maeurer, Markus; Ringden, Olle; Winiarski, Jacek; Ljungman, Per; Remberger, Mats; Mattsson, Jonas

2014-02-01

Allogeneic hematopoietic stem cell transplantation is a successful treatment for hematologic malignancies and a variety of genetic and metabolic disorders. In the period following stem cell transplantation, the immune-compromised milieu allows opportunistic pathogens to thrive. Epstein-Barr virus-associated post-transplant lymphoproliferative disease can be a life-threatening complication for transplanted patients because of suppressed T-cell-mediated immunity. We analyzed possible risk factors associated with post-transplant lymphoproliferative disease in a cohort of over 1,000 patients. The incidence of post-transplant lymphoproliferative disease was 4%. Significant risk factors identified by multivariate analysis were: human leukocyte antigen-mismatch (PEpstein-Barr virus mismatch recipient-/donor+ (Pdisease grade II to IV (P=0.006), pre-transplant splenectomy (P=0.008) and infusion of mesenchymal stromal cells (P=0.015). The risk of post-transplant lymphoproliferative disease has increased in more recent years, from less than 2% before 1998 to more than 6% after 2011. Additionally, we show that long-term survival of patients with post-transplant lymphoproliferative disease is poor despite initial successful treatment. The 3-year survival rate among the 40 patients with post-transplant lymphoproliferative disease was 20% as opposed to 62% among patients without post-transplant lymphoproliferative disease (Pdisease after transplantation in need of pre-emptive measures.

Force-induced chemical reactions on the metal centre in a single metalloprotein molecule

Science.gov (United States)

Zheng, Peng; Arantes, Guilherme M.; Field, Martin J.; Li, Hongbin

2015-01-01

Metalloproteins play indispensable roles in biology owing to the versatile chemical reactivity of metal centres. However, studying their reactivity in many metalloproteins is challenging, as protein three-dimensional structure encloses labile metal centres, thus limiting their access to reactants and impeding direct measurements. Here we demonstrate the use of single-molecule atomic force microscopy to induce partial unfolding to expose metal centres in metalloproteins to aqueous solution, thus allowing for studying their chemical reactivity in aqueous solution for the first time. As a proof-of-principle, we demonstrate two chemical reactions for the FeS4 centre in rubredoxin: electrophilic protonation and nucleophilic ligand substitution. Our results show that protonation and ligand substitution result in mechanical destabilization of the FeS4 centre. Quantum chemical calculations corroborated experimental results and revealed detailed reaction mechanisms. We anticipate that this novel approach will provide insights into chemical reactivity of metal centres in metalloproteins under biologically more relevant conditions. PMID:26108369

The incidence of post-transplant cancer among kidney transplant recipients is associated with the level of tacrolimus exposure during the first year after transplantation.

Science.gov (United States)

Lichtenberg, Shelly; Rahamimov, Ruth; Green, Hefziba; Fox, Benjamin D; Mor, Eytan; Gafter, Uzi; Chagnac, Avry; Rozen-Zvi, Benaya

2017-07-01

Immunosuppressive therapy plays a major role in the development of post-transplant cancer. In this nested case-control study of kidney transplant recipients (KTRs), we investigated whether the incidence of post-transplant cancer is associated with the level of tacrolimus exposure over time. We screened the Rabin Medical Center database for adults who received kidney transplants between 2001 and 2014 and developed post-transplant cancer (excluding basal and squamous cell skin cancers). They were matched against KTRs without cancer. All patients received a maintenance immunosuppressive treatment with tacrolimus, mycophenolate mofetil and corticosteroids. The degree of exposure to tacrolimus was estimated as the time-weighted average (tTWA) value of tacrolimus blood levels. The tTWA was calculated as the area under the curve divided by time at 1, 6, and 12 months after transplantation and at time of cancer diagnosis. Thirty-two cases were matched against 64 controls. tTWA values above 11 ng/mL at 6 and 12 months after transplantation were associated with odds ratio (OR) of 3.1 (95% CI 1.1-9) and 11.7 (95% CI = 1.3-106), respectively, for post-transplant cancer; and with OR of 5.2 (95% CI 1.3-20.5) and 14.1 (95% CI = 1.5-134.3), respectively, for cancer diagnosed more than 3 years after transplantation. Exposure to a tacrolimus time-weighted average level above 11 ng/mL at 6 or 12 months after kidney transplantation is associated with an increased risk of developing cancer.

What's hot, what's new in clinical organ transplantation: report from the American Transplant Congress 2015.

Science.gov (United States)

Sung, R S

2015-11-01

Innovative and exciting advances in the clinical sciences in organ transplantation were presented at the American Transplant Congress 2015. The full spectrum of transplantation was covered, with important developments in many topics. Key areas covered by presentations included living donor outcomes, optimal utilization and allocation of deceased donors, new immunosuppression regimens, antibody-mediated rejection and tolerance induction. This review highlights some of the most interesting and noteworthy clinical presentations from the meeting. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Transplant experiments uncover Baltic Sea basin-specific responses in bacterioplankton community composition and metabolic activities.

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Lindh, Markus V; Figueroa, Daniela; Sjöstedt, Johanna; Baltar, Federico; Lundin, Daniel; Andersson, Agneta; Legrand, Catherine; Pinhassi, Jarone

2015-01-01

Anthropogenically induced changes in precipitation are projected to generate increased river runoff to semi-enclosed seas, increasing loads of terrestrial dissolved organic matter and decreasing salinity. To determine how bacterial community structure and functioning adjust to such changes, we designed microcosm transplant experiments with Baltic Proper (salinity 7.2) and Bothnian Sea (salinity 3.6) water. Baltic Proper bacteria generally reached higher abundances than Bothnian Sea bacteria in both Baltic Proper and Bothnian Sea water, indicating higher adaptability. Moreover, Baltic Proper bacteria growing in Bothnian Sea water consistently showed highest bacterial production and beta-glucosidase activity. These metabolic responses were accompanied by basin-specific changes in bacterial community structure. For example, Baltic Proper Pseudomonas and Limnobacter populations increased markedly in relative abundance in Bothnian Sea water, indicating a replacement effect. In contrast, Roseobacter and Rheinheimera populations were stable or increased in abundance when challenged by either of the waters, indicating an adjustment effect. Transplants to Bothnian Sea water triggered the initial emergence of particular Burkholderiaceae populations, and transplants to Baltic Proper water triggered Alteromonadaceae populations. Notably, in the subsequent re-transplant experiment, a priming effect resulted in further increases to dominance of these populations. Correlated changes in community composition and metabolic activity were observed only in the transplant experiment and only at relatively high phylogenetic resolution. This suggested an importance of successional progression for interpreting relationships between bacterial community composition and functioning. We infer that priming effects on bacterial community structure by natural episodic events or climate change induced forcing could translate into long-term changes in bacterial ecosystem process rates.

Exchange donor transplantation: ethical option for living renal transplantation.

Science.gov (United States)

Gürkan, A; Kaçar, S; Varılsuha, C; Tilif, S; Turunç, V; Doǧan, M; Dheir, H; Sahin, S

2011-04-01

Taking in consideration the opinion of our team, which necessitates obligation of a relative relation between donors and recipients (genetic or matrimonial), we performed donor exchanges as an ethical alternative in living donor transplantations. We reviewed the outcomes of our exchange series. Between July 2003 and August 2010 we performed 110 exchange donor transplantations in four hospitals: one four-way, two three-way, and 100 two-way cases. Donors were mostly spouses (n = 71) or mothers (n = 15). The mean age of the donors was 48.8 (range = 23-69) and the recipients 41.4 years (range = 5-66). Two were transplanted preemptively and the others had a mean dialysis duration of 43 months (range = 1-120). Among 110 patients, three compatible pairs joined the group voluntarily; 71, due to ABO incompatibility and 36, due to crossmatch positivity. Induction therapy was used in 92 patients. HLA mismatches (MM) were: one MM in three; two MM in three; three MM in 18, four MM in 36; five MM in 34; and six MM in 18. Among 90 patients tested for panel-reactive antibodies PRA, five showed class I and 10, class II positivity. In 11 patients, B-cell positivity was detected by flow cytometry. Delayed graft function (n = 2), acute rejection (n = 11), BK virus infection (n = 1), and cytomegalovirus infection (n = 3) were seen postoperatively. Three (2.7%) patients died due to sepsis. Five patients returned to dialysis program due to interstitial fibrosis tubular atrophy (IFTA) (n = 2), renal vein thrombosis (n = 1), de novo glomerulopathy (n = 1), or primary nonfunction (n = 1). The 1- and 5-year patient and graft survival rates were 96% and 96%, 95% and 89%, respectively. We believe that exchange donor transplantation is as successful as direct transplants; it is a good, ethical alternative to unrelated living transplantations. Copyright © 2011 Elsevier Inc. All rights reserved.

Identifying Barriers to Preemptive Kidney Transplantation in a Living Donor Transplant Cohort

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Ryan A. Helmick, MD

2018-04-01

Conclusions. Even among a patient population that is primarily white, educated, and has a spouse or first-degree relative donor, PreKTx rates remain concerningly low. Increased time between diagnosis or education and transplant are predictors of PreKTx. Greater emphasis on transplant education earlier in the stages of chronic kidney disease and community outreach from transplant centers may help to increase the rate of PreKTx.

Carcinoma of the tongue in a renal transplant recipient: A rare post-transplant malignancy

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Jai Prakash

2015-01-01

Full Text Available Current immunosuppression improved long-term outcome of transplant patients, but it also increased the incidence of de novo malignancy. Organ transplant recipients have a threeto four-fold increased risk of developing carcinoma in comparison with the general population. Common malignancies encountered after transplantation include cancer of the skin, lips, post-transplant lymphoproliferative disease, ano-genital carcinoma and Kaposi sarcoma. Squamous cell carcinoma of the tongue is very rare. We report here a case of squamous cell carcinoma of the tongue in an adult male patient who developed it 11 years post-transplant. He underwent right hemiglossectomy and his graft function remained stable.

Induction of transplantation tolerance by combining non-myeloablative conditioning with delivery of alloantigen by T cells

Science.gov (United States)

Tian, Chaorui; Yuan, Xueli; Bagley, Jessamyn; Blazar, Bruce R.; Sayegh, Mohamed H.; Iacomini, John

2008-01-01

The observation that bone marrow derived hematopoietic cells are potent inducers of tolerance has generated interest in trying to establish transplantation tolerance by inducing a state of hematopoietic chimerism through allogeneic bone marrow transplantation. However, this approach is associated with serious complications that limit its utility for tolerance induction. Here we describe the development of a novel approach that allows for tolerance induction without the need for an allogeneic bone marrow transplant by combining non-myeloablative host conditioning with delivery of donor alloantigen by adoptively transferred T cells. CBA/Ca mice were administered 2.5Gy whole body irradiation (WBI). The following day the mice received Kb disparate T cells from MHC class I transgenic CBK donor mice, as well as rapamycin on days 0–13 and anti-CD40L monoclonal antibody on days 0–5, 8,11 and 14 relative to T cell transfer. Mice treated using this approach were rendered specifically tolerant to CBK skin allografts through a mechanism involving central and peripheral deletion of alloreactive T cells. These data suggest robust tolerance can be established without the need for bone marrow transplantation using clinically relevant non-myeloablative conditioning combined with antigen delivery by T cells. PMID:18280792

Association between pre-transplant dialysis modality and patient and graft survival after kidney transplantation

DEFF Research Database (Denmark)

Kramer, Anneke; Jager, Kitty J; Fogarty, Damian G

2012-01-01

Previous studies have found inconsistent associations between pre-transplant dialysis modality and subsequent post-transplant survival. We aimed to examine this relationship using the instrumental variable method and to compare the results with standard Cox regression.......Previous studies have found inconsistent associations between pre-transplant dialysis modality and subsequent post-transplant survival. We aimed to examine this relationship using the instrumental variable method and to compare the results with standard Cox regression....

The Ocular Surface Chemical Burns

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Medi Eslani

2014-01-01

Full Text Available Ocular chemical burns are common and serious ocular emergencies that require immediate and intensive evaluation and care. The victims of such incidents are usually young, and therefore loss of vision and disfigurement could dramatically affect their lives. The clinical course can be divided into immediate, acute, early, and late reparative phases. The degree of limbal, corneal, and conjunctival involvement at the time of injury is critically associated with prognosis. The treatment starts with simple but vision saving steps and is continued with complicated surgical procedures later in the course of the disease. The goal of treatment is to restore the normal ocular surface anatomy and function. Limbal stem cell transplantation, amniotic membrane transplantation, and ultimately keratoprosthesis may be indicated depending on the patients’ needs.

Employment 12 months after kidney transplantation: An in-depth bio-psycho-social analysis of the Swiss Transplant Cohort.

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Brigitta Danuser

Full Text Available Return to work with or after a chronic disease is a dynamic process influenced by a variety of interactions between personal, work, societal and medical resources or constraints. The aim of this study was to identify predictors for employment 12 months after transplantation in kidney patients, applying a bio-psycho-social model.All kidney patients followed in the Swiss Transplant Cohort between May 2008 and December 2012, aged 18 to 65 were assessed before, 6 and 12 months after transplantation.Of the 689 included patients, 56.2% worked 12 months post- transplantation compared to 58.9% pre-transplantation. Age, education, self-perceived health (6 months post- transplantation, pre- transplantation employment and receiving an organ from a living donor are significant predictors of employment post- transplantation. Moreover, while self-perceived health increased post- transplantation, depression score decreased only among those employed 12 months post- transplantation. Pre- transplantation employment status was the main predictor for post- transplantation employment (OR = 18.6 and was associated with sex, age, education, depression and duration of dialysis. An organ from a living donor (42.1% was more frequent in younger patients, with higher education, no diabetes and shorter waiting time to surgery.Transplantation did not increase employment in end-stage kidney disease patients but helped maintaining employment. Pre-transplantation employment has been confirmed to be the most important predictor of post-transplantation employment. Furthermore, socio-demographic and individual factors predicted directly and indirectly the post-transplantation employment status. With living donor, an additional predictor linked to social factors and the medical procedure has been identified.

Development of the National Transplant Program Has Significantly Decreased but Not Ended Transplant Tourism in Montenegro.

Science.gov (United States)

Ratkovic, M; Basic Jukic, N; Kastelan, Z; Radunovic, D; Kavaric, P; Brezak, J; Topalovic Grkovic, M; Hudolin, T; Prelevic, V

2018-06-01

Organ transplantation has prolonged and improved the lives of many patients around the world. However, a widespread shortage of donors remains the main factor that has led to organ trafficking and transplant tourism. To stop transplant tourism and to provide optimal treatment for its citizens with end-stage renal disease, Montenegro started performing renal transplantations in September 2012. Thirty-five transplantations have been performed since that time, 34 from living donors and only 1 from a deceased donor. This practice has significantly decreased but not ended transplant tourism in Montenegro. Copyright © 2018 Elsevier Inc. All rights reserved.

Thoracic organ transplantation: laboratory methods.

Science.gov (United States)

Patel, Jignesh K; Kobashigawa, Jon A

2013-01-01

Although great progress has been achieved in thoracic organ transplantation through the development of effective immunosuppression, there is still significant risk of rejection during the early post-transplant period, creating a need for routine monitoring for both acute antibody and cellular mediated rejection. The currently available multiplexed, microbead assays utilizing solubilized HLA antigens afford the capability of sensitive detection and identification of HLA and non-HLA specific antibodies. These assays are being used to assess the relative strength of donor specific antibodies; to permit performance of virtual crossmatches which can reduce the waiting time to transplantation; to monitor antibody levels during desensitization; and for heart transplants to monitor antibodies post-transplant. For cell mediated immune responses, the recent development of gene expression profiling has allowed noninvasive monitoring of heart transplant recipients yielding predictive values for acute cellular rejection. T cell immune monitoring in heart and lung transplant recipients has allowed individual tailoring of immunosuppression, particularly to minimize risk of infection. While the current antibody and cellular laboratory techniques have enhanced the ability to manage thoracic organ transplant recipients, future developments from improved understanding of microchimerism and graft tolerance may allow more refined allograft monitoring techniques.

Lung transplantation in children. Specific aspects.

Science.gov (United States)

Moreno Galdó, Antonio; Solé Montserrat, Juan; Roman Broto, Antonio

2013-12-01

Lung transplantation has become in recent years a therapeutic option for infantswith terminal lung disease with similar results to transplantation in adults.In Spain, since 1996 114 children lung transplants have been performed; this corresponds to3.9% of the total transplant number.The most common indication in children is cystic fibrosis, which represents between 70-80% of the transplants performed in adolescents. In infants common indications areinterstitial lung disease and pulmonary hypertension.In most children a sequential double lung transplant is performed, generally with the help ofextracorporeal circulation. Lung transplantation in children presents special challenges in monitoring and follow-up, especially in infants, given the difficulty in assessing lung function and performing transbronchial biopsies.There are some more specific complications in children like postransplant lymphoproliferative syndrome or a greater severity of respiratory virus infections .After lung transplantation children usually experiment a very important improvement in their quality of life. Eighty eight per cent of children have no limitations in their activity after 3 years of transplantation.According to the registry of the International Society for Heart & Lung Transplantation (ISHLT) survival at 5 years of transplantation is 54% and at 10 years is around 35%. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Chemical modifications of polymer films induced by high energy heavy ions

International Nuclear Information System (INIS)

Zhu Zhiyong; Sun Youmei; Liu Changlong; Liu Jie; Jin Yunfan

2002-01-01

Polymer films including polyethylene terephthalate (PET), polystyrene (PS) and polycarbonate (PC) were irradiated at room temperature with ions of 35 MeV/u 40 Ar, 25 MeV/u 84 Kr, 15.1 MeV/u 136 Xe and 11.4 MeV/u 238 U to fluences ranging from 9x10 9 to 5.5x10 12 ions/cm 2 . The radiation-induced chemical changes of the materials were investigated by Fourier-transform infrared (FTIR) and ultraviolet/visible spectroscopies. It is found that the absorbance in the ultraviolet and visible range induced by all irradiations follows a linear relationship with fluence. The radiation-induced absorbance normalized to one particle increases slowly with increasing of electronic energy loss below about 8 keV/nm followed by a sharp increase up to about 15 keV/nm above which saturation is reached. FTIR measurements reveal that the materials suffer serious degradation through bond breaking. The absorbance of the typical infrared bands decays exponentially with increase of ion fluence and the bond-disruption cross-section shows a sigmoid variation with electronic energy loss. In PET loss of crystallinity is attributed to the configuration transformation of the ethylene glycol residue from trans into the gauche. Alkyne end groups are induced in all the materials above certain electronic energy loss threshold, which is found to be about 0.8 keV/nm for PS and 0.4 keV/nm for PC. The production cross-section of alkyne end group increases with increasing of electronic energy loss and shows saturation at high electronic energy loss values. It is concluded that not only the physical processes but also the chemical processes of the energy deposition determine the modification of polymer

The management of perioperative nutrition in patients with end stage liver disease undergoing liver transplantation.

Science.gov (United States)

Zhang, Qi-Kun; Wang, Meng-Long

2015-10-01

Malnutrition is found in almost 100% of patients with end stage liver disease (ESLD) awaiting transplantation and malnutrition before transplantation leads to higher rates of post-transplant complications and worse graft survival outcomes. Reasons for protein energy malnutrition include several metabolic alterations such as inadequate intake, malabsorption, and overloaded expenditure. And also, stress from surgery, gastrointestinal reperfusion injury, immunosuppressive therapy and corticosteriods use lead to delayed bowl function recovery and disorder of nutrients absorption. In the pretransplant phase, nutritional goals include optimization of nutritional status and treatment of nutrition-related symptoms induced by hepatic decompensation. During the acute post-transplant phase, adequate nutrition is required to help support metabolic demands, replenish lost stores, prevent infection, arrive at a new immunologic balance, and promote overall recovery. In a word, it is extremely important to identify and correct nutritional deficiencies in this population and provide an adequate nutritional support during all phases of liver transplantation (LT). This study review focuses on prevalence, nutrition support, evaluation, and management of perioperative nutrition disorder in patients with ESLD undergoing LT.

Transplantation of endothelial progenitor cells ameliorates vascular dysfunction and portal hypertension in carbon tetrachloride-induced rat liver cirrhotic model.

Science.gov (United States)

Sakamoto, Masaharu; Nakamura, Toru; Torimura, Takuji; Iwamoto, Hideki; Masuda, Hiroshi; Koga, Hironori; Abe, Mitsuhiko; Hashimoto, Osamu; Ueno, Takato; Sata, Michio

2013-01-01

In cirrhosis, sinusoidal endothelial cell injury results in increased endothelin-1 (ET-1) and decreased nitric oxide synthase (NOS) activity, leading to portal hypertension. However, the effects of transplanted endothelial progenitor cells (EPCs) on the cirrhotic liver have not yet been clarified. We investigated whether EPC transplantation reduces portal hypertension. Cirrhotic rats were created by the administration of carbon tetrachloride (CCl(4) ) twice weekly for 10 weeks. From week 7, rat bone marrow-derived EPCs were injected via the tail vein in this model once a week for 4 weeks. Endothelial NOS (eNOS), vascular endothelial growth factor (VEGF) and caveolin expressions were examined by Western blots. Hepatic tissue ET-1 was measured by a radioimmunoassay (RIA). Portal venous pressure, mean aortic pressure, and hepatic blood flow were measured. Endothelial progenitor cell transplantation reduced liver fibrosis, α-smooth muscle actin-positive cells, caveolin expression, ET-1 concentration and portal venous pressure. EPC transplantation increased hepatic blood flow, protein levels of eNOS and VEGF. Immunohistochemical analyses of eNOS and isolectin B4 demonstrated that the livers of EPC-transplanted animals had markedly increased vascular density, suggesting reconstitution of sinusoidal blood vessels with endothelium. Transplantation of EPCs ameliorates vascular dysfunction and portal hypertension, suggesting this treatment may provide a new approach in the therapy of portal hypertension with liver cirrhosis. © 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Cell transplantation for Parkinson's disease

Institute of Scientific and Technical Information of China (English)

Jia Liu; Hongyun Huang

2006-01-01

OBJECTIVE: The motor symptoms of Parkinson's disease (PD) can be improved by cell transplantation,which has caught general attention from the field of the therapy for PD recently. In this paper, we summarize the cell-based therapy for PD.DATA SOURCES: A search for English literature related to the cellular transplantation of PD from January 1979to July 2006 was conducted in Medline with the key words of "Parkinson's disease, cell transplantation,embryonic stem cells, neural stem cells".STUDY SELECTTON: Data were checked in the first trial, and literatures about PD and cell transplantation were selected. Inclusive criteria: ① PD; ② Cell transplantation. Exclusive criteria: repetitive researches.DATA EXTRACTTON: A total of 100 papers related to cellular transplant and PD were collected and 41literatures were in accordance with the inclusive criteria.DATA SYNTHESIS: PD is a neural degeneration disease that threatens the health of the aged people, and most traditional therapeusis cannot delay its pathological proceeding. Cell transplantation is becoming popular as a new therapeutic tool, and the cells used to transplant mainly included dopamine-secreting cells, fetal ventral mesencephalic cells, embryonic stem cells and neural stem cells up to now. Animal experiment and clinical test demonstrate that cell transplantation can relieve the motor symptoms of Parkinson's disease obviously, but there are some problems need to be solved.CONCLUSTON: Cell transplantation has visible therapeutic efficacy on PD. Following the improvement of technique, and we have enough cause to credit that cell therapy may cure PD in the future.

Intellectual and Academic Outcomes After Pediatric Liver Transplantation: Relationship with Transplant-Related Factors.

Science.gov (United States)

Afshar, Soheil; Porter, Melanie; Barton, Belinda; Stormon, Michael

2018-05-09

As survival rates for pediatric liver transplantation continue to increase, research attention is turning towards long-term functional consequences, with particular interest in whether medical and transplant-related factors are implicated in neurocognitive outcomes. The relative importance of different factors is unclear, due to a lack of methodological uniformity, inclusion of differing primary diagnoses, variable transplant policies, and organ availability in different jurisdictions. This cross-sectional, single-site study sought to address various methodological limitations in the literature and the paucity of studies conducted outside of North America and Western Europe by examining the intellectual and academic outcomes of Australian pediatric liver transplant recipients (N = 40). Participants displayed significantly poorer intellectual and mathematical abilities compared to the normative population. Greater time on the transplant waitlist was a significant predictor of poorer verbal intelligence, working memory, mathematical abilities and reading, but only when considering the subgroup of children with biliary atresia. These findings support reducing the time children wait for a transplant as a priority. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Lentivirus-Induced Dendritic Cells (iDC for Immune-Regenerative Therapies in Cancer and Stem Cell Transplantation

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Renata Stripecke

2014-08-01

Full Text Available Conventional dendritic cells (cDC are ex vivo differentiated professional antigen presenting cells capable of potently stimulating naïve T cells and with vast potential for immunotherapeutic applications. The manufacture of clinical-grade cDC is relatively complex and requires several days for completion. Clinical trials showed poor trafficking of cDC from subcutaneous injection sites to lymph nodes (LN, where DC can optimally stimulate naïve lymphocytes for long-lasting memory responses. We demonstrated in mouse and human systems that a single overnight ex vivo lentiviral (LV gene transfer into DC precursors for production of combination of cytokines and antigens was capable to induce autonomous self-differentiation of antigen-loaded DC in vitro and in vivo. These highly viable induced DC (iDC effectively migrated from the injected skin to LN, where they effectively activated de novo antigen-specific effector memory T cells. Two iDC modalities were validated in relevant animal models and are now in clinical development: Self-differentiated Myeloid-derived Antigen-presenting-cells Reactive against Tumors co-expressing GM-CSF/IL-4/TRP2 for melanoma immunotherapy in the autologous setting (SmartDCtrp2, and Self-differentiated Myeloid-derived Lentivirus-induced against human cytomegalovirus as an allogeneic matched adoptive cell after stem cell transplantation (SmyleDCpp65. The lentiviral vector design and packaging methodology has “evolved” continuously in order to simplify and optimize function and biosafety of in vitro and in vivo genetic reprogramming of iDC. Here, we address the challenges seeking for new creations of genetically programmed iDC and integrase-defective LV vaccines for immune regeneration.

Customizing Fair Use Transplants

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Peter K. Yu

2018-02-01

Full Text Available In the past decade, policymakers and commentators across the world have called for the introduction of copyright reform based on the fair use model in the United States. Thus far, Israel, Liberia, Malaysia, the Philippines, Singapore, South Korea, Sri Lanka and Taiwan have adopted the fair use regime or its close variants. Other jurisdictions such as Australia, Hong Kong and Ireland have also advanced proposals to facilitate such adoption. This article examines the increasing efforts to transplant fair use into the copyright system based on the U.S. model. It begins by briefly recapturing the strengths and weaknesses of legal transplants. The article then scrutinizes the ongoing effort to transplant fair use from the United States. Specifically, it identifies eight modalities of transplantation. This article concludes with five lessons that can be drawn from studying the ongoing transplant efforts.

Anticonvulsant activity of B2, an adenosine analog, on chemical convulsant-induced seizures.

Directory of Open Access Journals (Sweden)

Min Li

Full Text Available Epilepsy is a chronic neurological disorder characterized by recurrent seizures. However, approximately one-third of epilepsy patients still suffer from uncontrolled seizures. Effective treatments for epilepsy are yet to be developed. N (6-(3-methoxyl-4-hydroxybenzyl adenine riboside (B2 is a N(6-substitued adenosine analog. Here we describe an investigation of the effects and mechanisms of B2 on chemical convulsant-induced seizures. Seizures were induced in mice by administration of 4-aminopyridine (4-AP, pentylenetetrazol (PTZ, picrotoxin, kainite acid (KA, or strychnine. B2 has a dose-related anticonvulsant effect in these chemical-induced seizure models. The protective effects of B2 include increased latency of seizure onset, decreased seizure occurrence, shorter seizure duration and reduced mortality rate. Radioligand binding and cAMP accumulation assays indicated that B2 might be a functional ligand for both adenosine A1 and A2A receptors. Furthermore, DPCPX, a selective A1 receptor antagonist, but not SCH58261, a selective A2A receptor antagonist, blocked the anticonvulsant effect of B2 on PTZ-induced seizure. c-Fos is a cellular marker for neuronal activity. Immunohistochemical and western blot analyses indicated that B2 significantly reversed PTZ-induced c-Fos expression in the hippocampus. Together, these results indicate that B2 has significant anticonvulsant effects. The anticonvulsant effects of B2 may be attributed to adenosine A1 receptor activation and reduced neuronal excitability in the hippocampus. These observations also support that the use of adenosine receptor agonist may be a promising approach for the treatment of epilepsy.

POSSIBLE NATURE OF THE RADIATION-INDUCED SIGNAL IN NAILS: HIGH-FIELD EPR, CONFIRMING CHEMICAL SYNTHESIS, AND QUANTUM CHEMICAL CALCULATIONS.

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Tipikin, Dmitriy S; Swarts, Steven G; Sidabras, Jason W; Trompier, François; Swartz, Harold M

2016-12-01

Exposure of finger- and toe-nails to ionizing radiation generates an Electron Paramagnetic Resonance (EPR) signal whose intensity is dose dependent and stable at room temperature for several days. The dependency of the radiation-induced signal (RIS) on the received dose may be used as the basis for retrospective dosimetry of an individual's fortuitous exposure to ionizing radiation. Two radiation-induced signals, a quasi-stable (RIS2) and stable signal (RIS5), have been identified in nails irradiated up to a dose of 50 Gy. Using X-band EPR, both RIS signals exhibit a singlet line shape with a line width around 1.0 mT and an apparent g-value of 2.0044. In this work, we seek information on the exact chemical nature of the radiation-induced free radicals underlying the signal. This knowledge may provide insights into the reason for the discrepancy in the stabilities of the two RIS signals and help develop strategies for stabilizing the radicals in nails or devising methods for restoring the radicals after decay. In this work an analysis of high field (94 GHz and 240 GHz) EPR spectra of the RIS using quantum chemical calculations, the oxidation-reduction properties and the pH dependence of the signal intensities are used to show that spectroscopic and chemical properties of the RIS are consistent with a semiquinone-type radical underlying the RIS. It has been suggested that semiquinone radicals formed on trace amounts of melanin in nails are the basis for the RIS signals. However, based on the quantum chemical calculations and chemical properties of the RIS, it is likely that the radicals underlying this signal are generated from the radiolysis of L-3,4-dihydroxyphenylalanine (DOPA) amino acids in the keratin proteins. These DOPA amino acids are likely formed from the exogenous oxidation of tyrosine in keratin by the oxygen from the air prior to irradiation. We show that these DOPA amino acids can work as radical traps, capturing the highly reactive and unstable sulfur

Islet transplantation using donors after cardiac death: report of the Japan Islet Transplantation Registry.

Science.gov (United States)

Saito, Takuro; Gotoh, Mitsukazu; Satomi, Susumu; Uemoto, Shinji; Kenmochi, Takashi; Itoh, Toshinori; Kuroda, Yoshikazu; Yasunami, Youichi; Matsumoto, Shnichi; Teraoka, Satoshi

2010-10-15

This report summarizes outcomes of islet transplantation employing donors after cardiac death (DCD) between 2004 and 2007 as reported to the Japan Islet Transplantation Registry. Sixty-five islet isolations were performed for 34 transplantations in 18 patients with insulin-dependent diabetes mellitus, including two patients who had prior kidney transplantation. All but one donor (64/65) was DCD at the time of harvesting. Factors influencing criteria for islet release included duration of low blood pressure of the donor, cold ischemic time, and usage of Kyoto solution for preservation. Multivariate analysis selected usage of Kyoto solution as most important. Of the 18 recipients, 8, 4, and 6 recipients received 1, 2, and 3 islet infusions, respectively. Overall graft survival defined as C-peptide level more than or equal to 0.3 ng/mL was 76.5%, 47.1%, and 33.6% at 1, 2, and 3 years, respectively, whereas corresponding graft survival after multiple transplantations was 100%, 80.0%, and 57.1%, respectively. All recipients remained free of severe hypoglycemia while three achieved insulin independence for 14, 79, and 215 days. HbA1c levels and requirement of exogenous insulin were significantly improved in all patients. Islet transplantation employing DCD can ameliorate severe hypoglycemic episodes, significantly improve HbA1c levels, sustain significant levels of C-peptide, and achieve insulin independence after multiple transplantations. Thus, DCD can be an important resource for islet transplantation if used under strict releasing criteria and in multiple transplantations, particularly in countries where heart-beating donors are not readily available.

Pattern of leukemia induction in BC3F1 mice transplanted with irradiated lymphohemopoietic tissues

International Nuclear Information System (INIS)

Covelli, V.; Di Majo, V.; Bassani, B.; Metalli, P.; Silini, G.

1982-01-01

(C57BL/Cne X C3H/Cne)F 1 male mice spontaneously develop reticulum cell sarcoma (RCS) with an average final incidence of 56%; neither myeloid leukemia (ML) nor thymic lymphoma (TL) has been observed in intact animals. X rays (4Gy, 250 kV) induce a few cases of ML but no TL. In increasing the dose to 6 Gy, we observed a few cases of TL, no ML, and a drastic reduction (8%) of RCS. The same dose of 6 Gy fractionated into four weekly doses of 1.5 Gy induced 24% of TL. By transplanting cells into appropriately preirradiated (4 Gy) syngeneic recipients we found evidence that four weekly doses of 1.5 Gy to donor animals caused an excess of ML and drastic changes of both TL and RCS incidences and rates in recipients as a function of time postirradiation at which the lymphohemopoietic tissues are transplanted. Furthermore, the same transplanted animals showed an evident acceleration of time of appearance of RCS and an enhanced incidence of NL; the latter effect is significant 10 days after the last X-ray fraction, but not thereafter. These data are in line with the hypothesis that committed cells for these two types of systemic tumors may be present among the irradiated transplanted tissues

Chemically induced aneuploidy in mammalian cells: mechanisms and biological significance in cancer

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Oshimura, M.; Barrett, J.C.

1986-01-01

A literature review with over 200 references examines the growing body of evidence from human and animal cancer cytogenetics that aneuploidy is an important chromosome change in carcinogenesis. Evidence from in vitro cell transformation studies supports the idea that aneuploidy has a direct effect on the conversion of a normal cell to a preneoplastic or malignant cell. Induction of an aneuploid state in a preneoplastic or neoplastic cell could have any of the following four biological effects: a change in gene dosage, a change in gene balance, expression of a recessive mutation, or a change in genetic instability (which could secondarily lead to neoplasia). There are a number of possible mechanisms by which chemicals might induce aneuploidy, including effects on microtubules, damage to essential elements for chromosome function reduction in chromosome condensation or pairing, induction of chromosome interchanges, unresolved recombination structures, increased chromosome stickiness, damage to centrioles, impairment of chromosome alignment ionic alterations during mitosis, damage to the nuclear membrane, and a physical disruption of chromosome segregation. Therefore, a number of different targets exist for chemically induced aneuploidy.

Validation of the Dutch version of the transplant effects questionnaire in liver transplant recipients

NARCIS (Netherlands)

Annema, Coby; Roodbol, Petrie F.; Stewart, Roy E.; Ranchor, Adelita V.

Little is known about the extent to which transplant recipients face emotional problems with the receipt of a transplanted organ. The Transplant Effects Questionnaire (TxEQ) enables the quantification of these problems. This study evaluates the psychometric properties of the Dutch translation of the

Noninvasive imaging of transplanted living functional cells transfected with a reporter estrogen receptor gene

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Takamatsu, Shinji [Biomedical Imaging Research Center, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Yoshida, Fukui 910-1193 (Japan)]. E-mail: shinjit@fmsrsa.fukui-med.ac.jp; Furukawa, Takako [Biomedical Imaging Research Center, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Yoshida, Fukui 910-1193 (Japan); Mori, Tetsuya [Biomedical Imaging Research Center, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Yoshida, Fukui 910-1193 (Japan); Yonekura, Yoshiharu [Biomedical Imaging Research Center, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Yoshida, Fukui 910-1193 (Japan); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, 23-3 Shimoaizuki, Matsuoka, Yoshida, Fukui 910-1193 (Japan)

2005-11-01

The transplantation of functional cells such as dopaminergic cells into damaged tissue is now clinically ongoing, but at present the population of surviving cells at the transplantation site mostly cannot be noninvasively examined. To visualize surviving transplanted functional cells using a noninvasive method, we chose the estrogen receptor ligand binding domain (ERL) as a reporter molecule and 16{alpha}-[{sup 18}F]-fluoro-17{beta}-estradiol (FES) for its ligand. We used a mouse embryonic stem (ES) cell line for recipient cells as a model. To obtain ES cells that constitutively or inducibly express ERL, we transfected two types of expression vectors into EB5 parental ES cell line using the lipofection method and obtained about 30 clones for each of the two types of transfectants. Then, to examine the expression level of ERL, we performed Western blotting analysis. Ligand uptake experiments were carried out using [{sup 3}H]-estradiol with or without excessive unlabeled estradiol for control cells and ERL transfectants. Each selected clone was also used for in vivo positron emission tomography (PET) imaging studies involving FES in nude mice transplanted with control cells and ERL transfectants. In some of the clones transfected with the inducible-type ERL gene, protein was expressed much higher than in the controls. However, constitutive-type ERL gene-transfected ES cells showed no protein production in spite of their gene expression activity being considerably high. All clones also expressed equal levels of the Oct-3/4 gene, a marker of pluripotency, in comparison with the parental cells. Also, the specific uptake of [{sup 3}H]-estradiol was over 30 times higher in inducer-treated ERL-expressing ES cells compared to untreated control cells. Finally, by performing dynamic PET imaging, we successfully visualized ERL-expressing teratomas using FES.

Noninvasive imaging of transplanted living functional cells transfected with a reporter estrogen receptor gene

International Nuclear Information System (INIS)

Takamatsu, Shinji; Furukawa, Takako; Mori, Tetsuya; Yonekura, Yoshiharu; Fujibayashi, Yasuhisa

2005-01-01

The transplantation of functional cells such as dopaminergic cells into damaged tissue is now clinically ongoing, but at present the population of surviving cells at the transplantation site mostly cannot be noninvasively examined. To visualize surviving transplanted functional cells using a noninvasive method, we chose the estrogen receptor ligand binding domain (ERL) as a reporter molecule and 16α-[ 18 F]-fluoro-17β-estradiol (FES) for its ligand. We used a mouse embryonic stem (ES) cell line for recipient cells as a model. To obtain ES cells that constitutively or inducibly express ERL, we transfected two types of expression vectors into EB5 parental ES cell line using the lipofection method and obtained about 30 clones for each of the two types of transfectants. Then, to examine the expression level of ERL, we performed Western blotting analysis. Ligand uptake experiments were carried out using [ 3 H]-estradiol with or without excessive unlabeled estradiol for control cells and ERL transfectants. Each selected clone was also used for in vivo positron emission tomography (PET) imaging studies involving FES in nude mice transplanted with control cells and ERL transfectants. In some of the clones transfected with the inducible-type ERL gene, protein was expressed much higher than in the controls. However, constitutive-type ERL gene-transfected ES cells showed no protein production in spite of their gene expression activity being considerably high. All clones also expressed equal levels of the Oct-3/4 gene, a marker of pluripotency, in comparison with the parental cells. Also, the specific uptake of [ 3 H]-estradiol was over 30 times higher in inducer-treated ERL-expressing ES cells compared to untreated control cells. Finally, by performing dynamic PET imaging, we successfully visualized ERL-expressing teratomas using FES

About the Operation: Heart Transplant

Science.gov (United States)

... After the transplant Preventing rejection Post-transplant medications Types of immunosuppressants Switching immunosuppressants Side effects Other medications Generic and brand name drugs Post-transplant tests Infections and immunity Lifestyle changes Health concerns Back to work or ...

Organ Transplantation: Frequently Asked Questions

Science.gov (United States)

... After the transplant Preventing rejection Post-transplant medications Types of immunosuppressants Switching immunosuppressants Side effects Other medications Generic and brand name drugs Post-transplant tests Infections and immunity Lifestyle changes Health concerns Back to work or ...

Radionuclide evaluation of renal transplants

International Nuclear Information System (INIS)

Yang Hong; Zhao Deshan

2000-01-01

Radionuclide renal imaging and plasma clearance methods can quickly quantitate renal blood flow and function in renal transplants. They can diagnose acute tubular necrosis and rejection, renal scar, surgical complications such as urine leaks, obstruction and renal artery stenosis after renal transplants. At the same time they can assess the therapy effect of renal transplant complications and can also predict renal transplant survival from early post-operative function studies

Allogeneic and Autologous Bone-Marrow Transplantation

OpenAIRE

Deeg, H. Joachim

1988-01-01

The author of this paper presents an overview of the current status of bone marrow transplantation, including indications, pre-transplant considerations, the transplant procedure, acute and delayed transplant-related problems, results currently attainable, and a short discussion of possible future developments.

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

Microfluidic generated EGF-gradients induce chemokinesis of transplantable retinal progenitor cells via the JAK/STAT and PI3kinase signaling pathways.

Directory of Open Access Journals (Sweden)

Uchenna J Unachukwu

Full Text Available A growing number of studies are evaluating retinal progenitor cell (RPC transplantation as an approach to repair retinal degeneration and restore visual function. To advance cell-replacement strategies for a practical retinal therapy, it is important to define the molecular and biochemical mechanisms guiding RPC motility. We have analyzed RPC expression of the epidermal growth factor receptor (EGFR and evaluated whether exposure to epidermal growth factor (EGF can coordinate motogenic activity in vitro. Using Boyden chamber analysis as an initial high-throughput screen, we determined that RPC motility was optimally stimulated by EGF concentrations in the range of 20-400 ng/ml, with decreased stimulation at higher concentrations, suggesting concentration-dependence of EGF-induced motility. Using bioinformatics analysis of the EGF ligand in a retina-specific gene network pathway, we predicted a chemotactic function for EGF involving the MAPK and JAK-STAT intracellular signaling pathways. Based on targeted inhibition studies, we show that ligand binding, phosphorylation of EGFR and activation of the intracellular STAT3 and PI3kinase signaling pathways are necessary to drive RPC motility. Using engineered microfluidic devices to generate quantifiable steady-state gradients of EGF coupled with live-cell tracking, we analyzed the dynamics of individual RPC motility. Microfluidic analysis, including center of mass and maximum accumulated distance, revealed that EGF induced motility is chemokinetic with optimal activity observed in response to low concentration gradients. Our combined results show that EGFR expressing RPCs exhibit enhanced chemokinetic motility in the presence of low nanomole levels of EGF. These findings may serve to inform further studies evaluating the extent to which EGFR activity, in response to endogenous ligand, drives motility and migration of RPCs in retinal transplantation paradigms.

Socioeconomic aspects of heart transplantation.

Science.gov (United States)

Evans, R W

1995-03-01

Heart transplantation is an established treatment modality for end-stage cardiac disease. Unfortunately, relative to other health care priorities, heart transplantation has fallen into disrepute. Efforts to reform the health care system have focused on three fundamental issues--cost, quality, and access. On each count, heart transplantation is vulnerable to criticism. Managed care is an incremental approach to health care reform that imposes fiscal constraint on providers. This constraint is expressed in the form of capitation which, in turn, requires providers to assume risk and accept economic responsibility for clinical decisions. While the need for transplantation is considerable, there are both clinical and economic factors limiting the overall level of activity. In 1993, over 2200 heart transplants were performed in the United States on people who were dying of end-stage cardiac disease. The total demand for heart transplantation was estimated to be about 5900 persons, which was not met due to an insufficient supply of donor hearts. Absent donors, the fiscal consequences of heart transplantation are minimized. In 1993, actuaries estimated that the total charge per heart transplant was $209,100. By designating centers based on price and quality considerations, managed care plans have reduced this per procedure expense to less than $100,000. While the benefits of transplantation are noteworthy, there are still concerns. Sixty percent of patients report that they are able to work, but only 30% do so. Employers hope to improve upon this record by expanding the designated center approach. In conclusion, the future of heart transplantation is unclear. Opportunities for innovation are limited, although the management of heart failure is an area of increased interest.

Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches

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Sudin eBhattacharya

2012-12-01

Full Text Available We provide an overview of computational systems biology approaches as applied to the study of chemical- and drug-induced toxicity. The concept of ‘toxicity pathways’ is described in the context of the 2007 US National Academies of Science report, Toxicity testing in the 21st Century: A Vision and A Strategy. Pathway mapping and modeling based on network biology concepts are a key component of the vision laid out in this report for a more biologically-based analysis of dose-response behavior and the safety of chemicals and drugs. We focus on toxicity of the liver (hepatotoxicity – a complex phenotypic response with contributions from a number of different cell types and biological processes. We describe three case studies of complementary multi-scale computational modeling approaches to understand perturbation of toxicity pathways in the human liver as a result of exposure to environmental contaminants and specific drugs. One approach involves development of a spatial, multicellular virtual tissue model of the liver lobule that combines molecular circuits in individual hepatocytes with cell-cell interactions and blood-mediated transport of toxicants through hepatic sinusoids, to enable quantitative, mechanistic prediction of hepatic dose-response for activation of the AhR toxicity pathway. Simultaneously, methods are being developing to extract quantitative maps of intracellular signaling and transcriptional regulatory networks perturbed by environmental contaminants, using a combination of gene expression and genome-wide protein-DNA interaction data. A predictive physiological model (DILIsymTM to understand drug-induced liver injury (DILI, the most common adverse event leading to termination of clinical development programs and regulatory actions on drugs, is also described. The model initially focuses on reactive metabolite-induced DILI in response to administration of acetaminophen, and spans multiple biological scales.

Pretreatment with a γ-Secretase Inhibitor Prevents Tumor-like Overgrowth in Human iPSC-Derived Transplants for Spinal Cord Injury

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Toshiki Okubo

2016-10-01

Full Text Available Neural stem/progenitor cells (NS/PCs derived from human induced pluripotent stem cells (hiPSCs are considered to be a promising cell source for cell-based interventions that target CNS disorders. We previously reported that transplanting certain hiPSC-NS/PCs in the spinal cord results in tumor-like overgrowth of hiPSC-NS/PCs and subsequent deterioration of motor function. Remnant immature cells should be removed or induced into more mature cell types to avoid adverse effects of hiPSC-NS/PC transplantation. Because Notch signaling plays a role in maintaining NS/PCs, we evaluated the effects of γ-secretase inhibitor (GSI and found that pretreating hiPSC-NS/PCs with GSI promoted neuronal differentiation and maturation in vitro, and GSI pretreatment also reduced the overgrowth of transplanted hiPSC-NS/PCs and inhibited the deterioration of motor function in vivo. These results indicate that pretreatment with hiPSC-NS/PCs decreases the proliferative capacity of transplanted hiPSC-NS/PCs, triggers neuronal commitment, and improves the safety of hiPSC-based approaches in regenerative medicine.

Bone-marrow transplant - series (image)

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Bone-marrow transplants are performed for: deficiencies in red blood cells (aplastic anemia) and white blood cells (leukemia or ... Bone-marrow transplants prolong the life of patients who might otherwise die. As with all major organ transplants, however, ...

Moisture-induced solid state instabilities in α-chymotrypsin and their reduction through chemical glycosylation

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Solá Ricardo J

2010-08-01

Full Text Available Abstract Background Protein instability remains the main factor limiting the development of protein therapeutics. The fragile nature (structurally and chemically of proteins makes them susceptible to detrimental events during processing, storage, and delivery. To overcome this, proteins are often formulated in the solid-state which combines superior stability properties with reduced operational costs. Nevertheless, solid protein pharmaceuticals can also suffer from instability problems due to moisture sorption. Chemical protein glycosylation has evolved into an important tool to overcome several instability issues associated with proteins. Herein, we employed chemical glycosylation to stabilize a solid-state protein formulation against moisture-induced deterioration in the lyophilized state. Results First, we investigated the consequences of moisture sorption on the stability and structural conformation of the model enzyme α-chymotrypsin (α-CT under controlled humidity conditions. Results showed that α-CT aggregates and inactivates as a function of increased relative humidity (RH. Furthermore, α-CT loses its native secondary and tertiary structure rapidly at increasing RH. In addition, H/D exchange studies revealed that α-CT structural dynamics increased at increasing RH. The magnitude of the structural changes in tendency parallels the solid-state instability data (i.e., formation of buffer-insoluble aggregates, inactivation, and loss of native conformation upon reconstitution. To determine if these moisture-induced instability issues could be ameliorated by chemical glycosylation we proceeded to modify our model protein with chemically activated glycans of differing lengths (lactose and dextran (10 kDa. The various glycoconjugates showed a marked decrease in aggregation and an increase in residual activity after incubation. These stabilization effects were found to be independent of the glycan size. Conclusion Water sorption leads to

Sporotrichosis in Renal Transplant Patients

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Paulo Gewehr

2013-01-01

Full Text Available The current report describes two renal transplant recipients who presented with sporotrichosis. In addition, the authors review the general aspects of sporotrichosis in renal transplant recipients reported in the literature. Sporotrichosis is a rare fungal infection in transplant patients and has been reported primarily in renal transplant recipients not treated with antifungal prophylaxis. Extracutaneous forms of sporotrichosis without skin manifestations and no previous history of traumatic injuries have been described in such patients and are difficult to diagnose. Renal transplant recipients with sporotrichosis described in the present report were successfully treated with antifungal therapy including amphotericin B deoxycholate, lipid amphotericin B formulations, fluconazole and itraconazole.

Chemically induced transition phenomena in polyurethanes as seen from generalized mode Grueneisen parameters

Energy Technology Data Exchange (ETDEWEB)

Mueller, U; Philipp, M; Bactavatchalou, R; Sanctuary, R; Baller, J; Zielinski, B; Krueger, J K [Laboratoire de Physique des Materiaux, Universite du Luxembourg, 162A, Avenue de la Faiencerie, L-1115 (Luxembourg); Possart, W; Alnot, P [Laboratoire Europeen de Recherche, Universitaire Saarland-Lorraine (Luxembourg)], E-mail: ulrich.mueller@uni.lu

2008-05-21

Many phenomenological properties of reactive polymers like polyurethanes increase or decrease continuously in the course of the curing process before saturating at the end of the chemical reaction. This holds true for instance for the mass density, the refractive index, the chemical turnover and the hypersonic properties. The reason for this monotone behaviour is that the chemical reaction behaves like a continuous succession of irreversible phase transitions. These transitions are superposed by the sol-gel transition and possibly by the chemically induced glass transition, with the drawback that the latter two highlighted transitions are often hidden by the underlying curing process. In this work we propose generalized mode Grueneisen parameters as an alternative probe for elucidating the polymerization process itself and the closely related transition phenomena. As a model system we use polyurethane composed of a diisocyanate and varying ratios of difunctional and trifunctional alcohols.

Imaging in transplantation

International Nuclear Information System (INIS)

Bankier, A.A.

2008-01-01

This book covers all topics related to the imaging of organ transplantation. An introductory section addresses such issues as organ procurement, patient selection, immune responses, and ethical and economic considerations. The main part of the book then offers in-depth coverage of heart, renal, liver, lung, bone marrow and pancreatic and intestinal transplantation. Each of these topics is discussed firstly in a clinical chapter and then in a radiological chapter. The clinical chapters detail the epidemiology, clinical background, and surgical procedures, as well as any clinically relevant issues of which the radiologist should be aware. The radiological chapters describe and depict the imaging manifestations of specific organ transplantations, document the normal radiological appearance of transplanted organs and consider both early and late complications. This is a unique, superbly illustrated volume that will be of great assistance to all who work in this field. (orig.)

Multimodality postoperative imaging of liver transplantation

International Nuclear Information System (INIS)

Zamboni, Giulia A.; Pedrosa, Ivan; Kruskal, Jonathan B.; Raptopoulos, Vassilios

2008-01-01

Liver transplantation is the only effective and definitive treatment for patients with end-stage liver disease. The shortage of cadaveric livers has lead to the increasing use of split-liver transplantation and living-donor liver transplantation, but the expansion of the donor pool has increased the risk for postoperative vascular and biliary complications. Early recognition of the imaging appearances of the various postoperative complications of liver transplantation is crucial for both graft and patient survival. This review describes the imaging findings of normal and abnormal transplanted liver parenchyma and of vascular and biliary post-transplantation complications. (orig.)

How Should Social Media Be Used in Transplantation? A Survey of The American Society of Transplant Surgeons.

Science.gov (United States)

Henderson, Macey L; Adler, Joel T; Van Pilsum Rasmussen, Sarah E; Thomas, Alvin G; Herron, Patrick D; Waldram, Madeleine M; Ruck, Jessica M; Purnell, Tanjala S; DiBrito, Sandra R; Holscher, Courtenay M; Haugen, Christine E; Alimi, Yewande; Konel, Jonathan M; Eno, Ann K; Garonzik Wang, Jacqueline M; Gordon, Elisa J; Lentine, Krista L; Schaffer, Randolph L; Cameron, Andrew M; Segev, Dorry L

2018-04-21

Social media platforms are increasingly used in surgery and have shown promise as effective tools to promote deceased donation and expand living donor transplantation. There is growing need to understand how social media-driven communication is perceived by providers in the field of transplantation. We surveyed 299 members of the American Society of Transplant Surgeons (ASTS) about their use of, attitudes toward, and perceptions of social media and analyzed relationships between responses and participant characteristics. Respondents used social media to communicate with: family and friends (76%), surgeons (59%), transplant professionals (57%), transplant recipients (21%), living donors (16%), and waitlisted candidates (15%). Most respondents (83%) reported using social media for at least one purpose. While most (61%) supported sharing information with transplant recipients via social media, 42% believed it should not be used to facilitate living donor-recipient matching. Younger age (p=0.02) and fewer years of experience in the field of transplantation (p=0.03) were associated with stronger belief that social media can be influential in living organ donation. Respondents at transplant centers with higher reported use of social media had more favorable views about sharing information with transplant recipients (psocial media. Transplant center involvement and support for social media may influence clinician perceptions and practices. Increasing use of social media among transplant professionals may provide an opportunity to deliver high quality information to patients.

Motion Transplantation Techniques: A Survey

NARCIS (Netherlands)

van Basten, Ben; Egges, Arjan

2012-01-01

During the past decade, researchers have developed several techniques for transplanting motions. These techniques transplant a partial auxiliary motion, possibly defined for a small set of degrees of freedom, on a base motion. Motion transplantation improves motion databases' expressiveness and

Pregnancy after kidney transplantation: high rates of maternal complications

Directory of Open Access Journals (Sweden)

Cristina Candido

Full Text Available Abstract Introduction: Women regain fertility a few time after renal transplantation. However, viability of pregnancy and maternal complications are still unclear. Objective: To describe the outcomes of pregnancies in kidney transplanted patients, focusing on maternal complications. Methods: Retrospective study of pregnancies in kidney transplanted patients between 2004 and 2014, followed up 12 months after delivery. Each pregnancy was considered an event. Results: There were 53 pregnancies in 36 patients. Mean age was 28 ± 5years. Pregnancy occurred 4.4 ± 3.0 years post-transplant. Immunosuppression before conception was tacrolimus, azathioprine, and prednisone in 74% of the cases. There were 15% miscarriages in the 1st trimester and 8% in 2nd trimester. In 41% of the cases, it was necessary to induce labor. From all births, 22% were premature and 17% very premature. There were 5% stillbirths and 5% of neonatal deaths. De novo proteinuria occurred in 60%, urinary tract infection in 23%, preeclampsia in 11%, acute rejection in 6%, and graft loss in 2% of the cases. It was observed a significant increase in creatinine at preconception comparing to 3rd trimester and follow-up (1.17 vs. 1.46 vs. 1.59 mg/dL, p < 0.001. Conclusion: Although the sample is limited, the number of miscarriages was higher than in the general population, with high rates of maternal complications. Sustained increase of creatinine suggests increased risk of graft loss in long-term.

Psychological rejection of the transplanted organ and graft dysfunction in kidney transplant patients

Directory of Open Access Journals (Sweden)

Látos M

2016-06-01

Full Text Available Melinda Látos,1 György Lázár,1 Zoltán Horváth,1 Victoria Wittmann,1 Edit Szederkényi,1 Zoltán Hódi,1 Pál Szenohradszky,1 Márta Csabai2 1Department of Surgery, Faculty of Medicine, 2Psychology Institute, University of Szeged, Szeged, Hungary Abstract: Interdisciplinary studies suggest that the mental representations of the transplanted organ may have a significant effect on the healing process. The objective of this study was to examine the representations of the transplanted organ and their relationship with emotional and mood factors, illness perceptions, and the functioning of the transplanted organ. One hundred and sixty-four kidney transplant patients were assessed using the Spielberger Anxiety Inventory, the Beck’s Depression Scale, the Posttraumatic Growth Inventory, the Brief Illness Perception Questionnaire, and the Transplanted Organ Questionnaire. Medical parameters were collected from the routine clinical blood tests (serum creatinine and estimated glomerular filtration rate levels and biopsy results. Our most outstanding results suggest that kidney-transplanted patients’ illness representations are associated with health outcomes. The Transplanted Organ Questionnaire “psychological rejection” subscale was connected with higher serum creatinine and estimated glomerular filtration rate levels. Logistic regression analysis showed that psychological rejection subscale, Brief Illness Perception Questionnaire, and Posttraumatic Growth Questionnaire total scores were associated with graft rejection. These results may serve as a basis for the development of complex treatment interventions, which could help patients to cope with the bio-psycho-social challenges of integrating the new organ as part of their body and self. Keywords: anxiety, depression, illness representations, posttraumatic growth, psychological rejection, renal transplantation