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Sample records for unirradiated scid recipients

  1. Severe Combined Immunodeficiency (SCID)

    Science.gov (United States)

    ... with facebook share with twitter share with linkedin Severe Combined Immunodeficiency (SCID) SCID is a group of rare disorders ... life-saving treatments. Why Is the Study of Severe Combined Immunodeficiency (SCID) a Priority for NIAID? SCID is a ...

  2. Eliminating SCID row: new approaches to SCID.

    Science.gov (United States)

    Kohn, Donald B

    2014-12-05

    Treatments for patients with SCID by hematopoietic stem cell transplantation (HSCT) have changed this otherwise lethal primary immune deficiency disorder into one with an increasingly good prognosis. SCID has been the paradigm disorder supporting many key advances in the field of HSCT, with first-in-human successes with matched sibling, haploidentical, and matched unrelated donor allogeneic transplantations. Nevertheless, the optimal approaches for HSCT are still being defined, including determining the optimal stem cell sources, the use and types of pretransplantation conditioning, and applications for SCID subtypes associated with radiosensitivity, for patients with active viral infections and for neonates. Alternatively, autologous transplantation after ex vivo gene correction (gene therapy) has been applied successfully to the treatment of adenosine deaminase-deficient SCID and X-linked SCID by vector-mediated gene addition. Gene therapy holds the prospect of avoiding risks of GVHD and would allow each patient to be their own donor. New approaches to gene therapy by gene correction in autologous HSCs using site-specific endonuclease-mediated homology-driven gene repair are under development. With newborn screening becoming more widely adopted to detect SCID patients before they develop complications, the prognosis for SCID is expected to improve further. This chapter reviews recent advances and ongoing controversies in allogeneic and autologous HSCT for SCID.

  3. Genetics of SCID

    Directory of Open Access Journals (Sweden)

    Cossu Fausto

    2010-11-01

    Full Text Available Abstract Human SCID (Severe Combined Immunodeficiency is a prenatal disorder of T lymphocyte development, that depends on the expression of numerous genes. The knowledge of the genetic basis of SCID is essential for diagnosis (e.g., clinical phenotype, lymphocyte profile and treatment (e.g., use and type of pre-hematopoietic stem cell transplant conditioning. Over the last years novel genetic defects causing SCID have been discovered, and the molecular and immunological mechanisms of SCID have been better characterized. Distinct forms of SCID show both common and peculiar (e.g., absence or presence of nonimmunological features aspects, and they are currently classified into six groups according to prevalent pathophysiological mechanisms: impaired cytokine-mediated signaling; pre-T cell receptor defects; increased lymphocyte apoptosis; defects in thymus embryogenesis; impaired calcium flux; other mechanisms. This review is the updated, extended and largely modified translation of the article "Cossu F: Le basi genetiche delle SCID", originally published in Italian language in the journal "Prospettive in Pediatria" 2009, 156:228-238.

  4. Loss tangent measurements on unirradiated alumina

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J.; Goulding, R.H. [Oak Ridge National Lab., TN (United States)

    1996-04-01

    Unirradiated room temperature loss tangent for sapphire and several commercial grades of polycrystalline alumina are complied for frequencies between 10{sup 5} and 4x10{sup 11} Hz. Sapphire exhibits significantly lower values for the loss tangent at frequencies up to 10{sup 11} Hz. The loss tangents of 3 different grades of Wesgo alumina (AL300, AL995, AL998) and 2 different grades of Coors alumina (AD94, AD995) have typical values near {approx}10{sup -4} at a frequency of 10{sup 8} Hz. On the other hand, the loss tangent of Vitox alumina exhibits a large loss peak tan d{approx} 5x10{sup -3} at this frequency.

  5. CD4+ T lymphocytes injected into severe combined immunodeficient (SCID) mice lead to an inflammatory and lethal bowel disease

    DEFF Research Database (Denmark)

    Claesson, Mogens Helweg; Rudolphi, A; Kofoed, S

    1996-01-01

    Transfer of 2 x 10(5) congenic or semiallogenic purified TCR alphabeta+ CD4+ T cells to SCID mice leads to an infiltration of the recipient gut lamina propria and epithelium with a donor-derived CD4+ T cell subset which induces a lethal inflammatory bowel disease (IBD) in the recipients. In contr...

  6. Rescue Effects: Irradiated Cells Helped by Unirradiated Bystander Cells

    Science.gov (United States)

    Lam, R. K. K.; Fung, Y. K.; Han, W.; Yu, K. N.

    2015-01-01

    The rescue effect describes the phenomenon where irradiated cells or organisms derive benefits from the feedback signals sent from the bystander unirradiated cells or organisms. An example of the benefit is the mitigation of radiation-induced DNA damages in the irradiated cells. The rescue effect can compromise the efficacy of radioimmunotherapy (RIT) (and actually all radiotherapy). In this paper, the discovery and subsequent confirmation studies on the rescue effect were reviewed. The mechanisms and the chemical messengers responsible for the rescue effect studied to date were summarized. The rescue effect between irradiated and bystander unirradiated zebrafish embryos in vivo sharing the same medium was also described. In the discussion section, the mechanism proposed for the rescue effect involving activation of the nuclear factor κB (NF-κB) pathway was scrutinized. This mechanism could explain the promotion of cellular survival and correct repair of DNA damage, dependence on cyclic adenosine monophosphate (cAMP) and modulation of intracellular reactive oxygen species (ROS) level in irradiated cells. Exploitation of the NF-κB pathway to improve the effectiveness of RIT was proposed. Finally, the possibility of using zebrafish embryos as the model to study the efficacy of RIT in treating solid tumors was also discussed. PMID:25625514

  7. Fatigue behavior of unirradiated V-5Cr-5Ti

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    Gieseke, B.G.; Stevens, C.O.; Grossbeck, M.L. [Oak Ridge National Lab., TN (United States)

    1995-04-01

    The objective of this research is to determine the low cycle fatigue behavior of V-5Cr-5Ti alloys for a range of temperatures and the extent of environmental effects at ambient temperatures. The results of in-vacuum low cycle fatigue tests are presented for unirradiated V-5Cr-5Ti tested at room temperature, 240, and 400{degree}C. A comparison of the fatigue data generated in rough and high vacuums shows that a pronounced environmental degradation of the fatiuge properties exists in this alloy at room temperature. Fatigue life was reduced by as much as 84%. Cyclic stress range data and SEM observations suggest that this reduction is due to a combination of increases in rates of crack initiation and subsequent growth. The relative contribution of each difference is dependent upon the strain range.

  8. Tumour necrosis factor-alpha (TNF-alpha) transcription and translation in the CD4+ T cell-transplanted scid mouse model of colitis

    DEFF Research Database (Denmark)

    Williams, A M; Whiting, C V; Bonhagen, K

    1999-01-01

    -labelled riboprobes were used. The prominent myeloid cell infiltrate in diseased tissues comprised F4/80+, Mac-l+ macrophages, neutrophils, dendritic cells and activated macrophages. TNF-alpha transcription and translation were associated with activated macrophages in the lamina propria. Activated macrophages...... recipient colon show a Th1 cytokine phenotype. We have examined the relationship between the phenotype of the cellular infiltrate and the transcription and translation of the proinflammatory cytokine TNF-alpha. The techniques of double indirect immunohistology and in situ hybridization using digoxigenin......The adoptive transfer of activated CD4+ alpha/beta T cell blasts from the spleens of immunocompetent C.B-17+/+ or BALB/cdm2 mice into C.B-17scid/scid (scid) mice induces a colitis in the scid recipient within 8 weeks, which progresses to severe disease within 16 weeks. T cells isolated from...

  9. Optimization of Hydride Rim Formation in Unirradiated Zr 4 Cladding

    Energy Technology Data Exchange (ETDEWEB)

    Shimskey, Rick W.; Hanson, Brady D.; MacFarlan, Paul J.

    2013-09-30

    The purpose of this work is to build on the results reported in the M2 milestone M2FT 13PN0805051, document number FCRD-USED-2013-000151 (Hanson, 2013). In that work, it was demonstrated that unirradiated samples of zircaloy-4 cladding could be pre-hydrided at temperatures below 400°C in pure hydrogen gas and that the growth of hydrides on the surface could be controlled by changing the surface condition of the samples and form a desired hydride rim on the outside diameter of the cladding. The work performed at Pacific Northwest National Laboratory since the issuing of the M2 milestone has focused its efforts to optimize the formation of a hydride rim on available zircaloy-4 cladding samples by controlling temperature variation and gas flow control during pre-hydriding treatments. Surface conditioning of the outside surface was also examined as a variable. The results of test indicate that much of the variability in the hydride thickness is due to temperature variation occurring in the furnaces as well as how hydrogen gas flows across the sample surface. Efforts to examine other alloys, gas concentrations, and different surface conditioning plan to be pursed in the next FY as more cladding samples become available

  10. Atypical radiation response of SCID cells

    Science.gov (United States)

    Chawapun, Nisa

    Murine SCID (severe combined immune deficiency) cells are well known for their defect in DNA double-strand break repair and in variable(diversity)joining [V(D)J] recombination due to a mutation in a catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). As a consequence, scid cells are hypersensitive to ionizing radiation. The present study showed that asynchronous populations of scid cells were about two-fold more sensitive than Balb/c with respect to cell killing and the defect in scid cells was corrected by complementation with human chromosome 8. Analysis of the survival of synchronized populations as a function of the cell cycle revealed that while scid cells were hypersensitive in all cell cycle phases compared to wild-type cells, this hypersensitivity is even more pronounced in G1 phase. The hypersensitivity reduced as the cells progressed into S phase suggested that homologous recombination repair plays a role. The results imply that there are at least two pathways for the repair of DSB DNA, consistent with a model previously proposed by others. The scid cells were also more sensitive to UVC light (254 nm) killing as compared to wild type cells by clonogenic survival. Using a host cell reactivation (HCR) assay to study the nucleotide excision repair (NER) which is the major repair pathway for UV-photoproducts, the results showed that NER in scid cells was not as efficient as CB- 17. This suggests that DNA-PK is involved in NER as well as non-homologous end-joining (NHEJ) DSB repair which is responsible for ionizing radiation sensitivity in scid cells. Repair in scid cells was not totally absent as shown by low dose rate sparing of cell killing after exposure to 137Cs γ-rays at dose rate of 0.6 cGy/h, 1.36 cGy/h, 6 cGy/h as compared to high dose rate at 171 cGy/min, although this phenomenon could be explained partly by proliferation. However, for radiation induced transformation, no significant dose rate effect was seen. A plot of transformation

  11. Neonatal Screening for Severe Combined Immunodeficiency (SCID)

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    Puck, Jennifer M.

    2012-01-01

    Purpose of review Population-based newborn screening for severe combined immunodeficiency (SCID) and related disorders has been instituted in five states, with several more planning to add this testing to their newborn screening panels. This review summarizes the rationale, development, and implementation of SCID screening programs to date and highlights current and future challenges. Recent findings Early results of T-cell receptor excision circle (TREC) testing newborns in pilot states indicate that this addition to the newborn screening panel can be successfully integrated into state public health programs. The TREC test has clinical validity and TRECs, as predicted, are an excellent biomarker of poor T-cell lymphocyte production in the thymus or increased lymphocyte loss resulting in T-cell lymphopenia. A variety of cases with typical SCID genotypes and other conditions have been detected in a timely manner and referred for appropriate early treatment. Summary Early detection of primary immunodeficiency is recognized as important for avoiding infectious complications that compromise outcomes. Routine screening of all newborns with the TREC test, implemented as part of an integrated public health program, can achieve pre-symptomatic diagnosis of SCID and other disorders with T-cell lymphopenia, allowing prompt and effective treatment and leading to a better understanding of the spectrum of these disorders and how to manage them. PMID:22001765

  12. a Study of Stress Relaxation Rate in Un-Irradiated and Neutron-Irradiated Stainless Steel

    Science.gov (United States)

    Ghauri, I. M.; Afzal, Naveed; Zyrek, N. A.

    Stress relaxation rate in un-irradiated and neutron-irradiated 303 stainless steel was investigated at room temperature. The specimens were exposed to 100 mC, Ra-Be neutron source of continuous energy 2-12 MeV for a period ranging from 4 to 16 days. The tensile deformation of the specimens was carried out using a Universal Testing Machine at 300 K. During the deformation, straining was frequently interrupted by arresting the cross head to observe stress relaxation at fixed load. Stress relaxation rate, s, was found to be stress dependent i.e. it increased with increasing stress levels σ0 both in un-irradiated and irradiated specimens, however the rate was lower in irradiated specimens than those of un-irradiated ones. A further decrease in s was observed with increase in exposure time. The experiential decrease in the relaxation rate in irradiated specimens is ascribed to strong interaction of glide dislocations with radiation induced defects. The activation energy for the movement of dislocations was found to be higher in irradiated specimens as compared with the un-irradiated ones.

  13. CONSTRUCTION OF HU-PBL/SCID CHIMERAS AND DEVELOPMENT OF EBV-RELATED LYMPHOMAS

    Institute of Scientific and Technical Information of China (English)

    Run-liang Gan; Ke Lan; Zhi-hua Yin; Li-jiang Wang; Ying Song; Kai-tai Yao

    2005-01-01

    Objective To construct hu-PBL/SCID chimeras and to investigate the development of lymphoma and oncogenicity of the Epstein-Barr virus (EBV).Mtehods Human peripheral blood lymphocytes (PBLs) were isolated from healthy adult donors and transplanted intraperitoneally into severe combined immunodeficient (SCID) mice. Mice with hu-PBL engraftment from healthy EBV seronegative donors were injected intraperitoneally with EBV-containing supematant from suspension culture of B95-8 cell line (active infection), whereas mice receiving lymphocytes from healthy EBV seropositive donors were not re-infected with B95-8 derived EBV (latent infection). Pathological examination and molecular analysis were performed on experimental animals and induced neoplasms.Results In the early stage of this experiment, 12 mice died of acute graft-versus-host disease, mortality was 34.3%(12/35 mice) with an average life span of 17.5 days. In 19 survival hu-PBL/SCID chimeric recipients from 12 healthy donors,tumor incidence was 84.2% (16/19 mice). The average survival time of tumor-bearing mice was 65.5 days. EBV-related neoplasms in SCID mice were nodular tumors with aggressive and fatal features. Histological morphology of tumors exhibited diffuse large cell lymphomas. Immunohistochemistry revealed that LCA (CD45) and L26 (CD20) were positive, but both PS1 (CD3) and UCHL-1 (CD45RO) were negative, and EBV products ZEBRA, LMP1, and EBNA2 were expressed in a small number of tumor cells. EB virus particles were seen in the nuclei of some tumor cells by electron microscopy, and EBV DNA could be amplified in the tumor tissues by PCR. In situ hybridization indicated that the nuclei of tumor cells contained human-specific Alu sequence.Conclusions EBV-induced tumors were human B-cell malignant lymphomas. We obtained direct causative evidence dealing with EBV-associated tumor deriving from normal human cells.

  14. High Temperature Tensile Properties of Unirradiated and Neutron Irradiated 20 Cr-35 Ni Austenitic Steel

    Energy Technology Data Exchange (ETDEWEB)

    Roy, R.B.; Solly, B.

    1966-12-15

    The tensile properties of an unirradiated and neutron irradiated (at 40 deg C) 20 % Cr, 35 % Ni austenitic steel have been studied at 650 deg C, 750 deg C and 820 deg C. The tensile elongation and mode of fracture (transgranular) of unirradiated specimens tested at room temperature and 650 deg C are almost identical. At 750 deg C and 820 deg C the elongation decreases considerably and a large part of the total elongation is non-uniform. Furthermore, the mode of fracture at these temperatures is intergranular and microscopic evidence suggests that fracture is caused by formation and linkup of grain boundary cavities. YS and UTS decrease monotonically with temperature. Irradiated specimens show a further decrease in ductility and an increase in the tendency to grain boundary cracking. Irradiation has no significant effect on the YS, but the UTS are reduced. The embrittlement of the irradiated specimens is attributed to the presence of He and Li atoms produced during irradiation and the possible mechanisms are discussed. Prolonged annealing of irradiated and unirradiated specimens at 650 deg C appears to have no significant effect on tensile properties.

  15. Kinetic analysis for non-isothermal decomposition of unirradiated and γ-irradiated indium acetyl acetonate

    Directory of Open Access Journals (Sweden)

    Refaat Mohammed Mahfouz

    2011-03-01

    Full Text Available Kinetic studies for the non-isothermal decomposition of un-irradiated and γ-irradiated indium acetyl acetonate In(acac3 with 10² kGy total γ-ray dose were carried out in static air. The results showed that the decomposition proceeds in one major step in the temperature range of 150-250 °C with the formation of In2O3 as solid residue. The non-isothermal data for un-irradiated and γ-irradiated In(acac3 were analysed using linear Flynn-Wall-Ozawa (FWO and nonlinear Vyazovkin (VYZ iso-conversional methods. The results of application of these free models on the investigated data showed a systematic dependence of Ea on α indicating a simple decomposition process. No significant changes were observed in both decomposition behaviour and (Eα-α dependency between unirradiated and γ-irradiated In(acac3. Calcination of In(acac3 at 400 °C for 5 hours led to the formation of In2O3 monodispersed nanoparticles. X-ray diffraction, FTIR and SEM techniques were employed for characterization of the synthesised nanoparticles. This is the first attempt to prepare In2O3 nanoparticles by solid state thermal decomposition of In(acac3.

  16. Severe Combined Immunodeficiency (SCID) Presenting with Neonatal Aplastic Anemia

    Science.gov (United States)

    Scott, Angela; Glover, Jason; Skoda-Smith, Suzanne; Torgerson, Troy; Xu, Min; Burroughs, Lauri; Woolfrey, Ann; Fleming, Mark; Shimamura, Akiko

    2015-01-01

    Aplastic anemia in the neonate is rare. We report a case of severe combined immunodeficiency (SCID) presenting with neonatal aplastic anemia. This report highlights the importance of considering SCID early in the evaluation of neonatal aplastic anemia prior to the development of infectious complications. PMID:26011426

  17. Severe combined immunodeficiency (SCID) presenting with neonatal aplastic anemia.

    Science.gov (United States)

    Scott, Angela; Glover, Jason; Skoda-Smith, Suzanne; Torgerson, Troy R; Xu, Min; Burroughs, Lauri M; Woolfrey, Ann E; Fleming, Mark D; Shimamura, Akiko

    2015-11-01

    Aplastic anemia in the neonate is rare. We report a case of severe combined immunodeficiency (SCID) presenting with neonatal aplastic anemia. This report highlights the importance of considering SCID early in the evaluation of neonatal aplastic anemia prior to the development of infectious complications. © 2015 Wiley Periodicals, Inc.

  18. Offspring of xenogeneically-reconstituted scid scid mice are capable of a primary xenogeneic immune response to DNP-KLH

    NARCIS (Netherlands)

    Greenwood, JD; Bos, NA; Croy, BA

    1996-01-01

    Human peripheral blood leukocyte (PBL) reconstitution of severe combined immunodeficient (SCID) mice has provided a small animal model system (hu-PBL-SCID) useful for the study of the human immune system and disease pathogenesis. Transfer of xenogeneic PBL from donors other than humans has also been

  19. Offspring of xenogeneically-reconstituted scid scid mice are capable of a primary xenogeneic immune response to DNP-KLH

    NARCIS (Netherlands)

    Greenwood, JD; Bos, NA; Croy, BA

    1996-01-01

    Human peripheral blood leukocyte (PBL) reconstitution of severe combined immunodeficient (SCID) mice has provided a small animal model system (hu-PBL-SCID) useful for the study of the human immune system and disease pathogenesis. Transfer of xenogeneic PBL from donors other than humans has also been

  20. Differential Secondary Reconstitution of In Vivo-Selected Human SCID-Repopulating Cells in NOD/SCID versus NOD/SCID/γ chainnull Mice

    Directory of Open Access Journals (Sweden)

    Shanbao Cai

    2011-01-01

    Full Text Available Humanized bone-marrow xenograft models that can monitor the long-term impact of gene-therapy strategies will help facilitate evaluation of clinical utility. The ability of the murine bone-marrow microenvironment in NOD/SCID versus NOD/SCID/γ chainnull mice to support long-term engraftment of MGMTP140K-transduced human-hematopoietic cells following alkylator-mediated in vivo selection was investigated. Mice were transplanted with MGMTP140K-transduced CD34+ cells and transduced cells selected in vivo. At 4 months after transplantation, levels of human-cell engraftment, and MGMTP140K-transduced cells in the bone marrow of NOD/SCID versus NSG mice varied slightly in vehicle- and drug-treated mice. In secondary transplants, although equal numbers of MGMTP140K-transduced human cells were transplanted, engraftment was significantly higher in NOD/SCID/γ chainnull mice compared to NOD/SCID mice at 2 months after transplantation. These data indicate that reconstitution of NOD/SCID/γ chainnull mice with human-hematopoietic cells represents a more promising model in which to test for genotoxicity and efficacy of strategies that focus on manipulation of long-term repopulating cells of human origin.

  1. Differential Secondary Reconstitution of In Vivo-Selected Human SCID-Repopulating Cells in NOD/SCID versus NOD/SCID/γ chain Mice.

    Science.gov (United States)

    Cai, Shanbao; Wang, Haiyan; Bailey, Barbara; Hartwell, Jennifer R; Silver, Jayne M; Juliar, Beth E; Sinn, Anthony L; Baluyut, Arthur R; Pollok, Karen E

    2011-01-01

    Humanized bone-marrow xenograft models that can monitor the long-term impact of gene-therapy strategies will help facilitate evaluation of clinical utility. The ability of the murine bone-marrow microenvironment in NOD/SCID versus NOD/SCID/γ chain(null) mice to support long-term engraftment of MGMT(P140K)-transduced human-hematopoietic cells following alkylator-mediated in vivo selection was investigated. Mice were transplanted with MGMT(P140K)-transduced CD34(+) cells and transduced cells selected in vivo. At 4 months after transplantation, levels of human-cell engraftment, and MGMT(P140K)-transduced cells in the bone marrow of NOD/SCID versus NSG mice varied slightly in vehicle- and drug-treated mice. In secondary transplants, although equal numbers of MGMT(P140K)-transduced human cells were transplanted, engraftment was significantly higher in NOD/SCID/γ chain(null) mice compared to NOD/SCID mice at 2 months after transplantation. These data indicate that reconstitution of NOD/SCID/γ chain(null) mice with human-hematopoietic cells represents a more promising model in which to test for genotoxicity and efficacy of strategies that focus on manipulation of long-term repopulating cells of human origin.

  2. IMMUNORESPONSES OF HUMANIZED SCID MICE TO HUMAN LUNG CANCER CELLS

    Institute of Scientific and Technical Information of China (English)

    陈力真; 王树蕙; 张云; 王世真

    1996-01-01

    HuPBL-SCID mice were used to explore how they would response to human ttmoor cells of 801/MLC.Living 801/MLC cells appeared to be fetal to the the mice due to the production of human TNF. The huP-BL-SCID rniee did not generate any noticeable amotmt of specific human immunoglobttlin either by single immunization with living 801/MLC cells or by repeated immunization with irradiated 801/MLC cells. Our preliminary experiments with huPBL-SCID mice showed that such chimeras would he a very useful models for tumor immunological researches.

  3. Safety Analysis Report for Packaging: The unirradiated fuel shipping container USA/9853/AF

    Energy Technology Data Exchange (ETDEWEB)

    1991-10-18

    The HFBR Unirradiated Fuel Shipping Container was designed and fabricated at the Oak Ridge National Laboratory in 1978 for the transport of fuel for the High Flux Beam Reactor (HFBR) for Brookhaven National Laboratory. The package has been evaluated analytically, as well as the comparison to tests on similar packages, to demonstrate compliance with the applicable regulations governing packages in which radioactive and fissile materials are transported. The contents of this Safety Analysis Report for Packaging (SARP) are based on Regulatory Guide 7.9 (proposed Revision 2 - May 1986), 10 CFR Part 71, DOE Order 1540.2, DOE Order 5480.3, and 49 CFR Part 173.

  4. Safety Analysis Report for Packaging: The unirradiated fuel shipping container USA/9853/AF

    Energy Technology Data Exchange (ETDEWEB)

    1991-10-18

    The HFBR Unirradiated Fuel Shipping Container was designed and fabricated at the Oak Ridge National Laboratory in 1978 for the transport of fuel for the High Flux Beam Reactor (HFBR) for Brookhaven National Laboratory. The package has been evaluated analytically, as well as the comparison to tests on similar packages, to demonstrate compliance with the applicable regulations governing packages in which radioactive and fissile materials are transported. The contents of this Safety Analysis Report for Packaging (SARP) are based on Regulatory Guide 7.9 (proposed Revision 2 - May 1986), 10 CFR Part 71, DOE Order 1540.2, DOE Order 5480.3, and 49 CFR Part 173.

  5. Correction of SCID-X1 using an enhancerless Vav promoter.

    Science.gov (United States)

    Almarza, E; Zhang, F; Santilli, G; Blundell, M P; Howe, S J; Thornhill, S I; Bueren, J A; Thrasher, A J

    2011-03-01

    The efficacy of gene therapy for the treatment of inherited immunodeficiency has been highlighted in recent clinical trials, although in some cases complicated by insertional mutagenesis and silencing of vector genomes through methylation. To minimize these effects, we have evaluated the use of regulatory elements that confer reliability of gene expression, but also lack potent indiscriminate enhancer activity. The Vav1 proximal promoter is particularly attractive in this regard and may be useful in situations where high-level or complex regulation of gene expression is not necessary. X-linked severe combined immunodeficiency (SCID-X1) is a good candidate for such an approach, particularly as there may be additional disease-related intrinsic risks of leukemogenesis, and where safety is therefore a paramount concern. We have tested whether lentiviral vectors expressing the common cytokine receptor gamma chain under the control of the proximal Vav1 gene promoter are effective for correction of signaling defects and the disease phenotype. Despite low-level gene expression, we observed near-complete restoration of cytokine-mediated STAT5 phosphorylation in a model cell line. Furthermore, at low vector copy number, highly effective T- and B-lymphocyte reconstitution was achieved in vivo in a murine model of SCID-X1, in both primary and secondary graft recipients. This vector configuration deserves further evaluation and consideration for future clinical trials.

  6. B-cell reconstitution for SCID: should a conditioning regimen be used in SCID treatment?

    Science.gov (United States)

    Haddad, Elie; Leroy, Sandrine; Buckley, Rebecca H

    2013-04-01

    Bone marrow transplantation has resulted in life-saving sustained T-cell reconstitution in many infants with severe combined immunodeficiency (SCID), but correction of B-cell function has been more problematic. At the annual meeting of the Primary Immunodeficiency Treatment Consortium held in Boston, Massachusetts, on April 27, 2012, a debate was held regarding the use of pretransplantation conditioning versus no pretransplantation conditioning in an effort to address this problem. Reviews of the literature were made by both debaters, and there was agreement that there was a higher rate of B-cell chimerism and a lower number of patients who required ongoing immunoglobulin replacement therapy in centers that used pretransplantation conditioning. However, there were still patients who required immunoglobulin replacement in those centers, and therefore pretransplantation conditioning did not guarantee development of B-cell function. Dr Rebecca H. Buckley presented data on B-cell function according to the molecular defect of the patient, and showed that patients with IL-7 receptor α, ADA, and CD3 chain gene mutations can have normal B-cell function after transplantation with only host B cells. Dr Elie Haddad presented a statistical analysis of B-cell function in published reports and showed that only a conditioning regimen that contained busulfan was significantly associated with better B-cell function after transplantation. The question is whether the risk of immediate and long-term toxicity with use of busulfan is justified, particularly in patients with SCID with DNA repair defects and in very young newborns with SCID who will be detected by using newborn screening.

  7. [Gene therapy of SCID-X1].

    Science.gov (United States)

    Baum, C; Schambach, A; Modlich, U; Thrasher, A

    2007-12-01

    X-linked severe combined immunodeficiency (SCID-X1) is an inherited disease caused by inactivating mutations in the gene encoding the interleukin 2 receptor common gamma chain (IL2RG), which is located on the X-chromosome. Affected boys fail to develop two major effector cell types of the immune system (T cells and NK cells) and suffer from a functional B cell defect. Although drugs such as antibiotics can offer partial protection, the boys normally die in the first year of life in the absence of a curative therapy. For a third of the children, bone marrow transplantation from a fully matched donor is available and can cure the disease without major side effects. Mismatched bone marrow transplantation, however, is complicated by severe and potentially lethal side effects. Over the past decade, scientists worldwide have developed new treatments by introducing a correct copy of the IL2RG-cDNA. Gene therapy was highly effective when applied in young children. However, in a few patients the IL2RG-gene vector has unfortunately caused leukaemia. Activation of cellular proto-oncogenes by accidental integration of the gene vector has been identified as the underlying mechanism. In future clinical trials, improved vector technology in combination with other protocol modifications may reduce the risk of this side effect.

  8. Studying Herpesvirus Pathogenesis Using SCID Mice Implanted With Human Tissues

    Institute of Scientific and Technical Information of China (English)

    Marvin; Sommer; Shannon; Taylor; Stacey; Leisenfelder; Robert; Morton; Ann; Arvin; Jennifer; Moffat

    2005-01-01

    Human cytomegalovirus(HCMV)and Varicella Zoster virus(VZV)are belongto herpesvirusfamily.HCMVrarelycaus-es symptomatic diseaseinanimmunocompetent host;however,itis a major cause of infectious morbidityand mortalityinimmunocompromised individuals and developingfetuses.VZVinfectioncauses chickenpoxandshingles.Sincethese spe-cies-specific herpesviruses do notinfect other animals,noanimal model is availablefor pathogenesis studies.Severe com-binedimmunodeficient(SCID)mice implanted with humantissues(SCID-hu)pro...

  9. Rescue effects in radiobiology: Unirradiated bystander cells assist irradiated cells through intercellular signal feedback

    Energy Technology Data Exchange (ETDEWEB)

    Chen, S. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Zhao, Y. [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Han, W. [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Chiu, S.K. [Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong); Zhu, L. [Office of Admission and Careers Advisory Service, Shenzhen University, Shenzhen 518060 (China); Wu, L. [Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031 (China); Yu, K.N., E-mail: peter.yu@cityu.edu.hk [Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong (Hong Kong)

    2011-01-10

    Mammalian cells respond to ionization radiation by sending out extracellular signals to affect non-irradiated neighboring cells, which is referred to as radiation induced bystander effect. In the present paper, we described a phenomenon entitled the 'rescue effects', where the bystander cells rescued the irradiated cells through intercellular signal feedback. The effect was observed in both human primary fibroblast (NHLF) and cancer cells (HeLa) using two-cell co-culture systems. After co-culturing irradiated cells with unirradiated bystander cells for 24 h, the numbers of 53BP1 foci, corresponding to the number of DNA double-strand breaks in the irradiated cells were less than those in the irradiated cells that were not co-cultured with the bystander cells (0.78 {+-} 0.04 foci/cell vs. 0.90 {+-} 0.04 foci/cell) at a statistically significant level. Similarly, both micronucleus formation and extent of apoptosis in the irradiated cells were different at statistically significant levels if they were co-cultured with the bystander cells. Furthermore, it was found that unirradiated normal cells would also reduce the micronucleus formation in irradiated cancer cells. These results suggested that the rescue effects could participate in repairing the radiation-induced DNA damages through a media-mediated signaling feedback, thereby mitigating the cytotoxicity and genotoxicity of ionizing radiation.

  10. Severe combined immunodeficiency (SCID): from molecular basis to clinical management.

    Science.gov (United States)

    Sponzilli, Ivonne; Notarangelo, Luigi D

    2011-04-01

    Primary immune deficiency diseases (PID) comprise a genetically heterogeneous group of disorders that affect distinct components of the innate and adaptive immune system, such as neutrophils, macrophages, dendritic cells, complement proteins, natural killer cells, as well as T and B lymphocytes. Severe combined immunodeficiency (SCID) is a group of disorders characterized by increased susceptibility to severe infections and early death. The diagnosis of SCID is supported by the demonstration of low absolute lymphocyte count and T cell lymphopenia (variably associated with numerical defects of B and NK cells). In the last two decades, advances in the characterization of the molecular pathophysiology of SCID, have permitted the development of novel diagnostic assays based on analysis of the expression of the disease-associated proteins and mutation analysis. More recently, pilot newborn screening programs for the identification of infants with SCID have been initiated in the United States. Prompt and aggressive treatment of infections, antimicrobial prophylaxis (in particular against Pneumocystis jiroveci) and regular administration of immunoglobulins are essential to reduce the risk of early death. However, survival ultimately depends on reconstitution of immune function, that is usually achieved by means of hematopoietic cell transplantation (HCT). Gene therapy and enzyme replacement therapy have also been used successfully is selected forms of SCID. Here we review the molecular and cellular pathophysiology and the mainstay of treatment of SCID.

  11. Differential Secondary Reconstitution of In Vivo-Selected Human SCID-Repopulating Cells in NOD/SCID versus NOD/SCID/γ chainnull Mice

    OpenAIRE

    Shanbao Cai; Haiyan Wang; Barbara Bailey; Jennifer R. Hartwell; Silver, Jayne M.; JULIAR, BETH E.; Sinn, Anthony L.; Baluyut, Arthur R.; Pollok, Karen E.

    2011-01-01

    Humanized bone-marrow xenograft models that can monitor the long-term impact of gene-therapy strategies will help facilitate evaluation of clinical utility. The ability of the murine bone-marrow microenvironment in NOD/SCID versus NOD/SCID/γ chainnull mice to support long-term engraftment of MGMTP140K-transduced human-hematopoietic cells following alkylator-mediated in vivo selection was investigated. Mice were transplanted with MGMTP140K-transduced CD34+ cells and transduced cells selected i...

  12. Overview and Critical Assessment of the Tensile Properties of unirradiated and irradiated EUROFER97

    Energy Technology Data Exchange (ETDEWEB)

    Lucon, E.; Vandermeulen, W.

    2007-10-15

    Material research represents a crucial issue for the assessment of fusion as a future viable source of energy. Structural materials, in particular, need to show a superior mechanical and chemical behaviour to guarantee the safe operation of the reactor during its whole lifetime, while retaining low activation characteristics to minimise the environmental impact of the produced waste. In this context, specific efforts have been focused for the last twenty years in Europe, Japan and the US, on developing suitable Reduced Activation Ferritic Martensitic (RAFM) steels as candidate structural materials. EUROFER97 has recently emerged in Europe as the reference material for the DEMO design. In the framework of the Long-Term Programme of EFDA (European Fusion Development Agreement), a coordinated effort has been launched aimed at providing a critical assessment of the mechanical and microstructural properties of EUROFER97 in the unirradiated and irradiated conditions, based on the results accumulated since the late 90ies within numerous EFDA tasks.

  13. Reactor Materials Program electrochemical potential measurements by ORNL with unirradiated and irradiated stainless steel specimens

    Energy Technology Data Exchange (ETDEWEB)

    Baumann, E.W.; Caskey, G.R. Jr.

    1993-07-01

    Effect of irradiation of stainless steel on electrochemical potential (ECP) was investigated by measurements in dilute HNO{sub 3} and H{sub 2}O{sub 2} solutions, conditions simulating reactor moderator. The electrodes were made from unirradiated/irradiated, unsensitized/sensitized specimens from R-reactor piping. Results were inconclusive because of budgetary restrictions. The dose rate may have been too small to produce a significant radiolytic effect. Neither the earlier CERT corrosion susceptibility tests nor the present ECP measurements showed a pronounced effect of irradiation on susceptibility of the stainless steel to IGSCC; this is confirmed by the absence in the stainless steel of the SRS reactor tanks (except for the C Reactor tank knuckle area).

  14. Newborn screening for SCID identifies patients with ataxia telangiectasia.

    Science.gov (United States)

    Mallott, Jacob; Kwan, Antonia; Church, Joseph; Gonzalez-Espinosa, Diana; Lorey, Fred; Tang, Ling Fung; Sunderam, Uma; Rana, Sadhna; Srinivasan, Rajgopal; Brenner, Steven E; Puck, Jennifer

    2013-04-01

    Severe combined immunodeficiency (SCID) is characterized by failure of T lymphocyte development and absent or very low T cell receptor excision circles (TRECs), DNA byproducts of T cell maturation. Newborn screening for TRECs to identify SCID is now performed in several states using PCR of DNA from universally collected dried blood spots (DBS). In addition to infants with typical SCID, TREC screening identifies infants with T lymphocytopenia who appear healthy and in whom a SCID diagnosis cannot be confirmed. Deep sequencing was employed to find causes of T lymphocytopenia in such infants. Whole exome sequencing and analysis were performed in infants and their parents. Upon finding deleterious mutations in the ataxia telangiectasia mutated (ATM) gene, we confirmed the diagnosis of ataxia telangiectasia (AT) in two infants and then tested archival newborn DBS of additional AT patients for TREC copy number. Exome sequencing and analysis led to 2 unsuspected gene diagnoses of AT. Of 13 older AT patients for whom newborn DBS had been stored, 7 samples tested positive for SCID under the criteria of California's newborn screening program. AT children with low neonatal TRECs had low CD4 T cell counts subsequently detected (R = 0.64). T lymphocytopenia in newborns can be a feature of AT, as revealed by TREC screening and exome sequencing. Although there is no current cure for the progressive neurological impairment of AT, early detection permits avoidance of infectious complications, while providing information for families regarding reproductive recurrence risks and increased cancer risks in patients and carriers.

  15. Sperm quantity and size variation in un-irradiated and irradiated males of the malaria mosquito Anopheles arabiensis Patton

    NARCIS (Netherlands)

    Helinski, M.; Knols, B.G.J.

    2009-01-01

    Anopheles mosquitoes are important candidates for genetic control strategies. However, little is known about sperm quality and quantity as determinants of male reproductive success. In this study, sperm quantity and length variation were assessed in testes of un-irradiated and irradiated Anopheles

  16. Sperm quantity and size variation in un-irradiated and irradiated males of the malaria mosquito Anopheles arabiensis Patton

    NARCIS (Netherlands)

    Helinski, M.; Knols, B.G.J.

    2009-01-01

    Anopheles mosquitoes are important candidates for genetic control strategies. However, little is known about sperm quality and quantity as determinants of male reproductive success. In this study, sperm quantity and length variation were assessed in testes of un-irradiated and irradiated Anopheles a

  17. Responses to recipient and donor B cells by genetically donor T cells from human haploidentical chimeras

    Energy Technology Data Exchange (ETDEWEB)

    Schiff, S.; Sampson, H.; Buckley, R.

    1986-03-01

    Following administration of haploidentical stem cells to infants with severe combined immunodeficiency (SCID), mature T cells of donor karyotype appear later in the recipient without causing graft-versus-host disease. To investigate the effect of the host environment on the responsiveness of these genetically donor T cells, blood B and T lymphocytes from 6 SCID recipients, their parental donors and unrelated controls were purified by double SRBC rosetting. T cells were stimulated by irradiated B cells at a 1:1 ratio in 6 day cultures. Engrafted T cells of donor karyotype gave much smaller responses to irradiated genetically recipient B cells than did fresh donor T cells. Moreover, engrafted T cells of donor karyotype from two of the three SCIDs who are longest post-transplantation responded more vigorously (14,685 and 31,623 cpm) than fresh donor T cells (5141 and 22,709 cpm) to donor B cells. These data indicate that T lymphocytes which have matured from donor stem cells in the recipient microenvironment behave differently from those that have matured in the donor.

  18. CD4+ T regulatory cells from the colonic lamina propria of normal mice inhibit proliferation of enterobacteria-reactive, disease-inducing Th1-cells from scid mice with colitis

    DEFF Research Database (Denmark)

    Gad, M; Brimnes, J; Claesson, Mogens Helweg

    2003-01-01

    Adoptive transfer of CD4+ T cells into scid mice leads to a chronic colitis in the recipients. The transferred CD4+ T cells accumulate in the intestinal lamina propria (LP), express an activated Th1 phenotype and proliferate vigorously when exposed ex vivo to enteric bacterial antigens. As LP CD4......+ T cells from normal BALB/c mice do not respond to enteric bacterial antigens, we have investigated whether colonic LP-derived CD4+ T cells from normal mice suppress the antibacterial response of CD4+ T cells from scid mice with colitis. LP-derived CD4+ T cells cocultured with bone marrow......-derived dendritic cells effectively suppress the antibacterial proliferative response of CD4+ T cells from scid mice with colitis. The majority of these LP T-reg cells display a nonactivated phenotype and suppression is independent of antigen exposure, is partly mediated by soluble factor(s) different from IL-10...

  19. Obtention of fracture properties of unirradiated fuel cladding from ring compression tests

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Rengel, M.A. [Departamento de Ciencia de Materiales, UPM, E.T.S.I. Caminos, Canales y Puertos Profesor Aranguren s/n, E-28040 Madrid (Spain); Consejo de Seguridad Nuclear (CSN), Justo Dorado 11, E-28040 Madrid (Spain); Gomez, F.J.; Ruiz-Hervias, J.; Caballero, L.; Valiente, A. [Departamento de Ciencia de Materiales, UPM, E.T.S.I. Caminos, Canales y Puertos Profesor Aranguren s/n, E-28040 Madrid (Spain)

    2009-06-15

    Zirconium alloy cladding is used as the first structural barrier to contain the nuclear fuel and the fission products. In addition to its neutron transparency, this material has a good corrosion resistance and remarkable mechanical properties at operational temperatures. Consequently, it is or paramount importance to precisely characterize the mechanical behaviour and fracture properties of irradiated cladding to ensure a safe operation. It is known that the mechanical behaviour of unirradiated zirconium alloy cladding is anisotropic. The elastoplastic response depends on the direction, namely radial, hoop or longitudinal. For this reason, different fracture properties should be expected in each direction. From the various tests employed to characterize the mechanical behaviour along the hoop direction in nuclear fuel cladding, the ring compression test is particularly useful to study material fracture. With this test it is possible to determine the moment when a real crack is formed, due to a sudden decrease in the applied load at a given displacement value. The aim of this research is to determine as precisely as possible the value of the fracture energy from the ring compression test load vs. displacement curves. To this end, a finite element calculation incorporating the cohesive zone model was performed. In this case, the cohesive zone theory is applied in its simplest form. It is considered that the cohesive crack transfers a constant stress until the displacement of this cohesive crack reaches a critical value. At this precise moment a real crack is generated. The properties of the softening curve of the cohesive zone model can be obtained by directly comparing the experimental load vs. displacement records with the finite element calculations. The area under the softening curve is the fracture energy, which is directly related with the material fracture toughness. The experimental data used in this work have been obtained on unirradiated Zirlo cladding

  20. Cord blood transplants for SCID: better B-cell engraftment?

    Science.gov (United States)

    Chan, Wan-Yin; Roberts, Robert Lloyd; Moore, Theodore B; Stiehm, E Richard

    2013-01-01

    Hematopoietic stem-cell transplantation is the treatment of choice for severe combined immunodeficiency (SCID). Despite successful T-cell engraftment in transplanted patients, B-cell function is not always achieved; up to 58% of patients require immunoglobulin therapy after receiving haploidentical transplants. We report 2 half-sibling males with X-linked γ-chain SCID treated with different sources of stem cells. Sibling 1 was transplanted with T-cell-depleted haploidentical maternal bone marrow and sibling 2 was transplanted with 7/8 human leukocyte antigen-matched unrelated umbilical cord blood. Both patients received pretransplant conditioning and posttransplant graft-versus-host-disease prophylaxis. B-cell engraftment and function was achieved in sibling 1 but not in sibling 2. This disparate result is consistent with a review of 19 other SCID children who received cord blood transplants. B-cell function, as indicated by no need for immunoglobulin therapy, was restored in 42% of patients given haploidentical transplants and in 68% of patients given matched unrelated donor transplants compared with 80% of patients given cord blood transplants. Cord blood is an alternative source of stem cells for transplantation in children with SCID and has a higher likelihood of B-cell reconstitution.

  1. Selective reconstitution of T lymphocyte subsets in scid mice

    DEFF Research Database (Denmark)

    Reimann, J; Rudolphi, A; Claesson, Mogens Helweg

    1991-01-01

    The 'empty' splenic T-cell compartment of young scid mice was partially and selectively reconstituted by low numbers of adoptively transferred congenic (C.B-17, BALB/c) or semi-allogeneic (dm2), but not completely allogeneic (C57BL/6) CD4+ T cells from adult donor mice. Under the same experimental...

  2. High resolution X-ray diffraction studies on unirradiated and irradiated strontium hexaferrite crystals

    Indian Academy of Sciences (India)

    Balwinder Kaur; Monita Bhat; F Licci; Ravi Kumar; K K Bamzai; P N Kotru

    2012-04-01

    High-resolution X-ray diffraction technique, employing a three-crystal monochromator–collimator combination is used to study the irradiation induced defects in flux grown Sr-hexaferrite crystals irradiated with 50 MeV Li3+ ion beams at room temperature with a fluence value of 1 × 1014 ions/cm2. The diffraction curves of the irradiated crystals suggest the possibility of creation of low angle grain boundaries and other point/clusters of defects causing amorphization in the irradiated crystals. The perfection of the irradiated and unirradiated (0001) cleaved surfaces of the crystals is studied using the bulk method of X-ray topography. The topographs supplement the findings suggestive of modifications in the crystalline quality of SrFe12O19 on irradiation with SHI of Li3+. Etching of the (0001) cleaved surfaces in H3PO4 at 120°C suggests that the dissolution characteristics of the surfaces get affected on irradiation with SHI of Li3+, besides supporting the findings of HRXRD and X-ray topography regarding modifications in the perfection of SrFe12O19 on irradiation.

  3. Properties of unirradiated and irradiated Ti-6Al-4V alloy for ITER flexible connectors

    Energy Technology Data Exchange (ETDEWEB)

    Rodchenkov, B.S., E-mail: rodchen@nikiet.ru [Research and Development Institute of Power Engineering (RDIPE), P.O. Box 788, Moscow 101000 (Russian Federation); Evseev, M.V. [Institute of Reactor Materials, Zarechnyi, Sverdlovsk Region 624051 (Russian Federation); Strebkov, Yu.S. [Research and Development Institute of Power Engineering (RDIPE), P.O. Box 788, Moscow 101000 (Russian Federation); Sinelnikov, L.P.; Shushlebin, V.V. [Institute of Reactor Materials, Zarechnyi, Sverdlovsk Region 624051 (Russian Federation)

    2011-10-01

    The high strength ({alpha} + {beta}) Ti-6Al-4V alloy was selected as the material for flexible attachments of the shield blanket modules in the ITER reactor. The different technologies used for manufacturing this alloy are: forging, stamping or pressing. The microstructures resulting from these processing methods can vary significantly and as a consequence the properties, including irradiation behavior, also vary. There are limited data available on the irradiation behavior of these materials. Specimens cut in the longitudinal and transversal directions of forged and stamped material were studied, with some of the specimens hydrogen charged to {approx}400 ppm H{sub 2}. In the unirradiated condition the forged alloy had slightly more ductility than the stamped alloy. The strength properties of both were practically the same. Neutron irradiation of these materials in the IVV-2M reactor reached doses of {approx}0.2 and 0.3 dpa at temperatures 240-260 deg. C. Irradiation resulted in substantial hardening and significant decrease of the fracture toughness of specimens from both materials.

  4. Hyperbilirubinemia and rapid fatal hepatic failure in severe combined immunodeficiency caused by adenosine deaminase deficiency (ADA-SCID).

    Science.gov (United States)

    Kühl, J S; Schwarz, K; Münch, A; Schmugge, M; Pekrun, A; Meisel, C; Wahn, V; Ebell, W; von Bernuth, H

    2011-03-01

    Adenosin deaminase (ADA) deficiency is the cause for Severe Combined Immunodeficiency (SCID) in about 15% of patients with SCID, often presenting as T (-)B (-)NK (-)SCID. Treatment options for ADA-SCID are enzyme replacement, bone marrow transplantation or gene therapy. We here describe the first patient with ADA-SCID and fatal hepatic failure despite bone marrow transplantation from a 10/10 HLA identical related donor. As patients with ADA-SCID may be at yet underestimated increased risk for rapid hepatic failure we speculate whether hepatitis in ADA-SCID should lead to the immediate treatment with enzyme replacement by pegylated ADA.

  5. The Long Quest for Neonatal Screening for SCID

    Science.gov (United States)

    Buckley, Rebecca H.

    2012-01-01

    Early recognition of SCID is a pediatric emergency, because a diagnosis before live vaccines or non-irradiated blood products are given and before development of infections permits lifesaving unfractionated HLA-identical or T-cell-depleted haploidentical hematopoietic stem cell transplantation, enzyme replacement therapy or gene therapy. The need for newborn screening for this condition has been recognized for the past 15 years. However, implementation of screening required development of an assay for T cell lymphopenia that could be performed on dried blood spots routinely collected from newborn infants for the past 48 years. This was accomplished 6 years ago and there have already been 7 successful pilot studies. A recommendation to add SCID to the routine newborn screening panel was approved by the Secretary’s AdvisoryCommittee on Heritable Disorders of Newborns and Children in 2010 and was soon after approved by the Secretary of Health and Human Services. It is important for allergists, immunologists and other health care providers to take an active role in promoting newborn screening for SCID and other T lymphocyte abnormalities in their states. Even more important will be their roles in establishing accurate diagnoses for screen positive infants and in ensuring that they are given the best possible treatment. PMID:22277203

  6. Subtask 12D6: Fatigue behavior of unirradiated V-5Cr-5Ti

    Energy Technology Data Exchange (ETDEWEB)

    Gieseke, B.G.; Stevens, C.O.; Grossbeck, M.L. [Oak Ridge National Lab., TN (United States)

    1995-03-01

    The objective of this research is to determine the low cycle fatigue behavior of V-5Cr-5Ti alloys for a range of temperatures and the extent of environmental effects at ambient temperatures. The results of in-vacuum low cycle fatigue tests are presented for unirradiated V-5Cr-5Ti tested at room temperature (25, 250, and 400{degrees}C). A comparison of the fatigue data generated in rough and high vacuums shows that a pronounced environmental degradation of the fatigue properties exists in the alloy at room temperature. Fatigue life was reduced by as much as 84%. Cyclic stress range data and SEM observations suggest that this reduction is due to a combination of increases in rates of crack initiation and subsequent growth. The relative contribution of each difference is dependent upon the strain range. In high vacuum, the fatigue results also show a trend of increasing cyclic life with increasing temperature between 25 and 400{degrees}C. From the limited data available, life at 25{degrees}C averages 1.7 times that at 25{degrees}C, and at 400{degrees}C, life averages 3.2 times that at room temperature. Like the environmental effects at 25{degrees}C, the effect of temperature seems to be a function of strain range at each temperature. The total strain range and cycles to failure were correlated using a power law relationship and compared to 20% cold-worked 316 stainless steel and several vanadium-base alloys. The results suggest that V-SCr-5Ti has better resistance to fatigue than 316-SS in the temperature range of 25 to 400{degrees}C. At 400{degrees}C, the data also show that V-5Cr-5Ti out performs Vanstar alloys 7 and 8 over the entire range of strains investigated. Furthermore, the fatigue properties of the V-5Cr-5Ti alloy compare favorably to V-15Cr-57i (at 25{degrees}C) and Vanstar 9 (at 400{degrees}C) at strains greater than 1%. At lower strains, the lower fatigue resistance of V-5Cr-5Ti is attributed to the higher strengths of the V-15Cr-5Ti and Vanstar 9 alloys.

  7. Comparison of ring compression testing to three point bend testing for unirradiated ZIRLO cladding

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2015-04-01

    Safe shipment and storage of nuclear reactor discharged fuel requires an understanding of how the fuel may perform under the various conditions that can be encountered. One specific focus of concern is performance during a shipment drop accident. Tests at Savannah River National Laboratory (SRNL) are being performed to characterize the properties of fuel clad relative to a mechanical accident condition such as a container drop. Unirradiated ZIRLO tubing samples have been charged with a range of hydride levels to simulate actual fuel rod levels. Samples of the hydrogen charged tubes were exposed to a radial hydride growth treatment (RHGT) consisting of heating to 400°C, applying initial hoop stresses of 90 to 170 MPa with controlled cooling and producing hydride precipitates. Initial samples have been tested using both a) ring compression test (RCT) which is shown to be sensitive to radial hydride and b) three-point bend tests which are less sensitive to radial hydride effects. Hydrides are generated in Zirconium based fuel cladding as a result of coolant (water) oxidation of the clad, hydrogen release, and a portion of the released (nascent) hydrogen absorbed into the clad and eventually exceeding the hydrogen solubility limit. The orientation of the hydrides relative to the subsequent normal and accident strains has a significant impact on the failure susceptability. In this study the impacts of stress, temperature and hydrogen levels are evaluated in reference to the propensity for hydride reorientation from the circumferential to the radial orientation. In addition the effects of radial hydrides on the Quasi Ductile Brittle Transition Temperature (DBTT) were measured. The results suggest that a) the severity of the radial hydride impact is related to the hydrogen level-peak temperature combination (for example at a peak drying temperature of 400°C; 800 PPM hydrogen has less of an impact/ less radial hydride fraction than 200 PPM hydrogen for the same thermal

  8. SCID patients with ARTEMIS vs RAG deficiencies following HCT: increased risk of late toxicity in ARTEMIS-deficient SCID.

    Science.gov (United States)

    Schuetz, Catharina; Neven, Benedicte; Dvorak, Christopher C; Leroy, Sandrine; Ege, Markus J; Pannicke, Ulrich; Schwarz, Klaus; Schulz, Ansgar S; Hoenig, Manfred; Sparber-Sauer, Monika; Gatz, Susanne A; Denzer, Christian; Blanche, Stephane; Moshous, Despina; Picard, Capucine; Horn, Biljana N; de Villartay, Jean-Pierre; Cavazzana, Marina; Debatin, Klaus-Michael; Friedrich, Wilhelm; Fischer, Alain; Cowan, Morton J

    2014-01-09

    A subgroup of severe combined immunodeficiencies (SCID) is characterized by lack of T and B cells and is caused by defects in genes required for T- and B-cell receptor gene rearrangement. Several of these genes are also involved in nonhomologous end joining of DNA double-strand break repair, the largest subgroup consisting of patients with T(-)B(-)NK(+)SCID due to DCLRE1C/ARTEMIS defects. We postulated that in patients with ARTEMIS deficiency, early and late complications following hematopoietic cell transplantation might be more prominent compared with patients with T(-)B(-)NK(+)SCID caused by recombination activating gene 1/2 (RAG1/2) deficiencies. We analyzed 69 patients with ARTEMIS and 76 patients with RAG1/2 deficiencies who received transplants from either HLA-identical donors without conditioning or from HLA-nonidentical donors without or with conditioning. There was no difference in survival or in the incidence or severity of acute graft-versus-host disease regardless of exposure to alkylating agents. Secondary malignancies were not observed. Immune reconstitution was comparable in both groups, however, ARTEMIS-deficient patients had a significantly higher occurrence of infections in long-term follow-up. There is a highly significant association between poor growth in ARTEMIS deficiency and use of alkylating agents. Furthermore, abnormalities in dental development and endocrine late effects were associated with alkylation therapy in ARTEMIS deficiency.

  9. Generation of Pediatric Leukemia Xenograft Models in NSG-B2m Mice: Comparison with NOD/SCID Mice.

    Science.gov (United States)

    Gopalakrishnapillai, Anilkumar; Kolb, E Anders; Dhanan, Priyanka; Bojja, Aruna Sri; Mason, Robert W; Corao, Diana; Barwe, Sonali P

    2016-01-01

    Generation of orthotopic xenograft mouse models of leukemia is important to understand the mechanisms of leukemogenesis, cancer progression, its cross talk with the bone marrow microenvironment, and for preclinical evaluation of drugs. In these models, following intravenous injection, leukemic cells home to the bone marrow and proliferate there before infiltrating other organs, such as spleen, liver, and the central nervous system. Moreover, such models have been shown to accurately recapitulate the human disease and correlate with patient response to therapy and prognosis. Thus, various immune-deficient mice strains have been used with or without recipient preconditioning to increase engraftment efficiency. Mice homozygous for the severe combined immune deficiency (SCID) mutation and with non-obese diabetic background (NOD/SCID) have been used in the majority of leukemia xenograft studies. Later, NOD/SCID mice deficient for interleukin 2 receptor gamma chain (IL2Rγ) gene called NSG mice became the model of choice for leukemia xenografts. However, engraftment of leukemia cells without irradiation preconditioning still remained a challenge. In this study, we used NSG mice with null alleles for major histocompatibility complex class I beta2-microglobulin (β2m) called NSG-B2m. This is a first report describing the 100% engraftment efficiency of pediatric leukemia cell lines and primary samples in NSG-B2m mice in the absence of host preconditioning by sublethal irradiation. We also show direct comparison of the engraftment efficiency and growth rate of pediatric acute leukemia cells in NSG-B2m and NOD/SCID mice, which showed 80-90% engraftment efficiency. Secondary and tertiary xenografts in NSG-B2m mice generated by injection of cells isolated from the spleens of leukemia-bearing mice also behaved similar to the primary patient sample. We have successfully engrafted 25 acute lymphoblastic leukemia (ALL) and 5 acute myeloid leukemia (AML) patient samples with

  10. Clinical translation of TALENS: Treating SCID-X1 by gene editing in iPSCs.

    Science.gov (United States)

    Biffi, Alessandra

    2015-04-02

    Mutations causing X-linked severe combined immunodeficiency (SCID-X1) reduce immune cell populations and function and may be amenable to targeted gene correction strategies. Now in Cell Stem Cell, Menon et al. (2015) correct SCID-X1-related blood differentiation defects by TALEN-mediated genome editing in patient-derived iPSCs, suggesting a possible strategy for autologous cell therapy of SCID-X1.

  11. Mechanical properties of type 316L stainless steel welded joint for ITER vacuum vessel (1). Experiment of unirradiated welded joint

    Energy Technology Data Exchange (ETDEWEB)

    Saito, Shigeru; Fukaya, Kiyoshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Ishiyama, Shintaro [Japan Atomic Energy Research Inst., Oarai, Ibaraki (Japan). Oarai Research Establishment; Takahashi, Hiroyuki; Koizumi, Kouichi [Japan Atomic Energy Research Inst., Naka, Ibaraki (Japan). Naka Fusion Research Establishment

    2001-01-01

    In design activity of ITER, the vacuum vessel (VV) is ranked as one of the most important components in core reactor from the view point of first barrier to tritium release from the reactor. The VV of ITER is designed as double walled structure so that some parts of them are not qualified in the conventional design standards. So it is necessary to prepare the new design standards to be applied them. JAERI has executed the preparation activity of the new design standards and the technical data to support them. In this study, the results of metallographic observation and mechanical properties of unirradiated type 316L stainless steel welded joint were reported. (author)

  12. Properties of unirradiated fuel element graphites H-451 and SO818. [Bulk density, tensile properties, thermal expansion, thermal conductivity

    Energy Technology Data Exchange (ETDEWEB)

    Engle, G.B.; Johnson, W.R.

    1976-10-08

    Nuclear graphites H-451, lot 440 (Great Lakes Carbon Corporation (GLCC)), and SO818 (Airco Speer Division, Air Reduction Corporation (AS)) are described, and physical, mechanical, and chemical property data are presented for the graphites in the unirradiated state. A summary of the mean values of the property data and of data on TS-1240 and H-451, lot 426, is tabulated. A direct comparison of H-451, lot 426, chosen for Fort St. Vrain (FSV) fuel reload production, TS-1240, and SO818 may be made from the table. (auth)

  13. The case for mandatory newborn screening for severe combined immunodeficiency (SCID).

    Science.gov (United States)

    Gaspar, H B; Hammarström, L; Mahlaoui, N; Borte, M; Borte, S

    2014-05-01

    Severe combined immunodeficiency (SCID) is the most severe form of inherited primary immunodeficiency and is a paediatric emergency. Delay in recognising and detecting SCID can have fatal consequences and also reduces the chances of a successful haematopoietic stem cell transplant (HSCT). Screening for SCID at birth would prevent children from dying before HSCT can be attempted and would increase the success of HSCT. There is strong evidence to show that SCID fulfills the internationally-established criteria for a condition to be screened for at birth. There is also a test (the T-cell receptor excision circle (TREC) assay) that is now being successfully used in an increasing number of US states to screen for SCID in routine newborn Guthrie samples. Concerted lobbying efforts have highlighted the need for newborn screening (NBS) for SCID, and its implementation is being discussed in Europe both at EU and individual country level, but as yet there is no global mandate to screen for this rare and frequently lethal condition. This paper summarizes the current evidence for, and the success of SCID NBS, together with a review of the practical aspects of SCID testing and the arguments in favour of adding SCID to the conditions screened for at birth.

  14. Dissolution of unirradiated UO{sub 2} fuel in synthetic groundwater. Final report (1996-1998)

    Energy Technology Data Exchange (ETDEWEB)

    Ollila, K. [VTT Chemical Technology, Espoo (Finland)

    1999-05-01

    This study was a part of the EU R and D programme 1994-1998: Nuclear Fission Safety, entitled `Source term for performance assessment of spent fuel as a waste form`. The research carried out at VTT Chemical Technology was focused on the effects of granitic groundwater composition and redox conditions on UO{sub 2} solubility and dissolution mechanisms. The synthetic groundwater compositions simulated deep granitic fresh and saline groundwaters, and the effects of the near-field material, bentonite, on very saline groundwater. Additionally, the Spanish granite/bentonite water was used. The redox conditions (Eh), which are obviously the most important factors that influence on UO{sub 2} solubility under the disposal conditions of spent fuel, varied from strongly oxidising (air-saturated), anaerobic (N{sub 2}, O{sub 2} < l ppm) to reducing (N{sub 2}, low Eh). The objective of the air-saturated dissolution experiments was to yield the maximum solution concentrations of U, and information on the formation of secondary phases that control the concentrations, with different groundwater compositions. The static batch solubility experiments of long duration (up to 1-2 years) were performed using unirradiated UO{sub 2} pellets and powder. Under anaerobic and reducing conditions, the solubilities were also approached from oversaturation. The results of the oxic, air-saturated dissolution experiments with UO{sub 2} powder showed that the increase in the salinity (< 1.7 M) had a minor effect on the measured steady-state concentrations of U. The concentrations, (1.2 ...2.5) x 10{sup -5} M, were at the level of the theoretical solubility of schoepite or another uranyl oxide hydrate, e.g. becquerelite (possibly Na-polyuranate). The higher alkalinity of the fresh (Allard) composition increased the aqueous U concentration. Only some kind of oxidised U-phase (U{sub 3}O{sub 8}-UO{sub 3}) was identified with XRD when studying possible secondary phases after the contact time of one year

  15. New method to calculate the mechanical properties of unirradiated fuel cladding from ring tensile tests

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Rengel, M.A. [Departamento de Ciencia de Materiales, UPM, E.T.S.I. Caminos, Canales y Puertos, Profesor Aranguren s/n, E-28040 Madrid (Spain); Consejo de Seguridad Nuclear (CSN), Justo Dorado 11, E-28040 Madrid (Spain); Gomez, F.J.; Ruiz-Hervias, J.; Caballero, L.; Valiente, A. [Departamento de Ciencia de Materiales, UPM, E.T.S.I. Caminos, Canales y Puertos, Profesor Aranguren s/n, E-28040 Madrid (Spain)

    2009-06-15

    displacement of the loading piece and another one between the equivalent stress in the same point and the nominal applied stress. In the first iteration a calculation is performed with an approximate plastic stress-strain law, and the two above-mentioned relationships are used to determine a new law from the experimental results. In the second iteration the calculation takes into account the new plastic stress-strain law and determines two new relationships. After a few iterations an excellent fit is obtained. This method is an improvement of the original method by Arsene and Bai [3] and allows obtaining the plastic stress-strain curve in the hoop direction in a consistent way. The experimental data used in this work to check the validity of the procedure have been obtained on unirradiated Zirlo cladding, with the standard alloy composition and geometry (outer diameter of the cladding 9.5 mm and a wall thickness of 0.56 mm). References: [1]. Arsene, S.; Bai, J.B. A new approach to measuring transverse properties of structural tubing by a ring test, Journal of Testing and Evaluation, 24: 386-391 (1996) [2]. Arsene, S.; Bai, J. 'A new approach to measuring transverse properties of structural tubing by a ring test-experimental investigation', Journal of Testing and Evaluation, 26: 26-30 (1998) [3]. Arsene, S.; Bai, J.B.; 'Hydride embrittlement and irradiation effects on the hoop mechanical properties of pressurized water reactor (PWR) and boiling-water reactor (BWR) zircaloy cladding tubes: Part I. Hydride embrittlement in stress-relieved, annealed, and recrystallized zircaloys at 20 deg. C and 300 deg. C', Metallurgical and materials and transactions A, 34A: 553-566 (2003) [4]. Chang-Sun Seok, Bong-Kook, K.Linga, 'The properties of the ring and burst creep of zirlo claddings', Engineering Failure Analysis, 13: 389-397 (2006). (authors)

  16. Rabies in Transplant Recipients

    Centers for Disease Control (CDC) Podcasts

    2016-09-19

    Dr. Richard Franka, a CDC scientist, discusses rabies in organ transplant recipients.  Created: 9/19/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 9/19/2016.

  17. Gene therapy outpaces haplo for SCID-X1.

    Science.gov (United States)

    Kohn, Donald B

    2015-06-04

    In this issue of Blood, Touzot et al report that autologous gene therapy/hematopoietic stem cell transplantation (HSCT) for infants with X-linked severe combined immune deficiency (SCID-X1) lacking a matched sibling donor may have better outcomes than haploidentical (haplo) HSCT. Because gene therapy represents an autologous transplant, it obviates immune suppression before and after transplant, eliminates risks of graft versus host disease (GVHD), and, as the authors report, led to faster immunological reconstitution after transplant than did haplo transplant.

  18. Impaired Lymphocytes Development and Xenotransplantation of Gastrointestinal Tumor Cells in Prkdc-Null SCID Zebrafish Model

    Directory of Open Access Journals (Sweden)

    In Hye Jung

    2016-08-01

    Full Text Available Severe combined immunodeficiency (SCID mice have widely been used as hosts for human tumor cell xenograft study. This animal model, however, is labor intensive. As zebrafish is largely emerging as a promising model system for studying human diseases including cancer, developing efficient immunocompromised strains for tumor xenograft study are also demanded in zebrafish. Here, we have created the Prkdc-null SCID zebrafish model which provides the stable immune-deficient background required for xenotransplantation of tumor cell. In this study, the two transcription activator-like effector nucleases that specifically target the exon3 of the zebrafish Prkdc gene were used to induce a frame shift mutation, causing a complete knockout of the gene function. The SCID zebrafish showed susceptibility to spontaneous infection, a well-known phenotype found in the SCID mutation. Further characterization revealed that the SCID zebrafish contained no functional T and B lymphocytes which reflected the phenotypes identified in the mice SCID model. Intraperitoneal injection of human cancer cells into the adult SCID zebrafish clearly showed tumor cell growth forming into a solid mass. Our present data show the suitability of using the SCID zebrafish strain for xenotransplantation experiments, and in vivo monitoring of the tumor cell growth in the zebrafish demonstrates use of the animal model as a new platform of tumor xenograft study.

  19. Special Analysis for the Disposal of the INL Waste Associated with the Unirradiated Light Water Breeder Reactor (LWBR) Waste Stream at the Area 5 Radioactive Waste Management Site

    Energy Technology Data Exchange (ETDEWEB)

    Shott, Gregory [National Security Technologies, LLC, Las Vegas, NV (United States)

    2017-03-21

    This special analysis (SA) evaluates whether the Idaho National Laboratory (INL) Waste Associated with the Unirradiated Light Water Breeder Reactor (LWBR) waste stream (INEL167203QR1, Revision 0) is suitable for shallow land burial (SLB) at the Area 5 Radioactive Waste Management Site (RWMS) on the Nevada National Security Site (NNSS). Disposal of the INL Waste Associated with the Unirradiated LWBR waste meets all U.S. Department of Energy (DOE) Manual DOE M 435.1-1, “Radioactive Waste Management Manual,” Chapter IV, Section P performance objectives (DOE 1999). The INL Waste Associated with the Unirradiated LWBR waste stream is recommended for acceptance with the condition that the total uranium-233 (233U) inventory be limited to 2.7E13 Bq (7.2E2 Ci).

  20. NOD/SCID repopulating cells contribute only to short-term repopulation in the baboon.

    Science.gov (United States)

    Mezquita, P; Beard, B C; Kiem, H-P

    2008-11-01

    We have previously compared the repopulation ability of gene-modified baboon CD34+ cells in an autologous transplantation versus a xenotransplant model in irradiated nonobese diabetic/severe combined immune deficiency (NOD/SCID) mice. Baboon CD34-selected marrow cells were transduced with a gammaretrovirus vector and infused into irradiated baboons and NOD/SCID mice. A limited integration-site analysis could only detect two common retrovirus integration sites in the NOD/SCID and monkey. Here, we performed locus-specific PCR on 30 clones recovered from NOD/SCID beta2-microglobulin mice reconstituted with transduced baboon CD34+ cells. We identified five common integrants in the baboon early after transplant (2-6 weeks) but none during the long-term follow-up (6 and 12 months). These results confirm that repopulating cells in the NOD/SCID mouse contribute only to short-term repopulation in a clinically relevant large animal model.

  1. Lift-based up-ender and methods using same to manipulate a shipping container containing unirradiated nuclear fuel

    Energy Technology Data Exchange (ETDEWEB)

    Nilles, Michael J.

    2017-08-01

    A shipping container containing an unirradiated nuclear fuel assembly is lifted off the ground by operating a crane to raise a lifting tool comprising a winch. The lifting tool is connected with the shipping container by a rigging line connecting with the shipping container at a lifting point located on the shipping container between the top and bottom of the shipping container, and by winch cabling connecting with the shipping container at the top of the shipping container. The shipping container is reoriented by operating the winch to adjust the length of the winch cabling so as to rotate the shipping container about the lifting point. Shortening the winch cabling rotates the shipping container about the lifting point from a horizontal orientation to a vertical orientation, while lengthening the winch cabling rotates the shipping container about the lifting point from the vertical orientation to the horizontal orientation.

  2. NK cells are intrinsically functional in pigs with Severe Combined Immunodeficiency (SCID) caused by spontaneous mutations in the Artemis gene

    Science.gov (United States)

    We have identified Severe Combined Immunodeficiency (SCID) in a line of Yorkshire pigs at Iowa State University. These SCID pigs lack B-cells and T-cells, but possess Natural Killer (NK) cells. This SCID phenotype is caused by recessive mutations in the Artemis gene. Interestingly, two human tumor c...

  3. Differential post-surgical metastasis and survival in SCID, NOD-SCID and NOD-SCID-IL-2Rγ(null mice with parental and subline variants of human breast cancer: implications for host defense mechanisms regulating metastasis.

    Directory of Open Access Journals (Sweden)

    Chloe C Milsom

    Full Text Available We compare for the first time, the metastatic aggressiveness of the parental MDA-MB-231 breast cancer cell line and two luciferase-tagged in vivo-derived and selected pro-metastatic variants (LM2-4/luc⁺ and 164/8-1B/luc⁺ in SCID, NOD-SCID and NOD-SCID-IL-2Rγ(null (NSG mice following orthotopic implantation and primary tumour resection. The variants are known to be more aggressively metastatic in SCID mice, compared to the parental line which has limited spontaneous metastatic competence in these mice. When 2×10⁶ cells were injected into the mammary fat pad, the growth of the resultant primary tumours was identical for the various cell lines in the three strains of mice. However, metastatic spread of all three cell lines, including the MDA-MB-231 parental cell line, was strikingly more aggressive in the highly immunocompromised NSG mice compared to both NOD-SCID and SCID mice, resulting in extensive multi-organ metastases and a significant reduction in overall survival. While these studies were facilitated by monitoring post-surgical spontaneous metastases using whole body bioluminescence imaging, we observed that the luciferase-tagged parental line showed altered growth and diminished metastatic properties compared to its untagged counterpart. Our results are the first to show that host immunity can have a profound impact on the spread of spontaneous visceral metastases and survival following resection of a primary tumour in circumstances where the growth of primary tumours is not similarly affected; as such they highlight the importance of immunity in the metastatic process, and by extension, suggest certain therapeutic strategies that may have a significant impact on reducing metastasis.

  4. Radiation quality-dependence of bystander effect in unirradiated fibroblasts is associated with TGF-β1-Smad2 pathway and miR-21 in irradiated keratinocytes

    Science.gov (United States)

    Yin, Xiaoming; Tian, Wenqian; Wang, Longxiao; Wang, Jingdong; Zhang, Shuyu; Cao, Jianping; Yang, Hongying

    2015-01-01

    Traditional radiation biology states that radiation causes damage only in cells traversed by ionizing radiation. But radiation-induced bystander effect (RIBE), which refers to the biological responses in unirradiated cells when the neighboring cells are exposed to radiation, challenged this old dogma and has become a new paradigm of this field. By nature, RIBEs are the consequences of intercellular communication between irradiated and unirradiated cells. However, there are still some important questions remain unanswered such as whether RIBE is dependent on radiation quality, what are the determining factors if so, etc. Using a transwell co-culture system, we found that HaCaT keratinocytes irradiated with α-particles but not X-rays could induce bystander micronucleus formation in unirradiated WS1 fibroblasts after co-culture. More importantly, the activation of TGF-β1-Smad2 pathway and the consistent decrease of miR-21 level in α-irradiated HaCaT cells were essential to the micronucleus induction in bystander WS1 cells. On the other hand, X-irradiation did not induce bystander effect in unirradiated WS1 cells, accompanied by lack of Smad2 activation and consistent decrease of miR-21 in X-irradiated HaCaT cells. Taken together, these results suggest that the radiation quality-dependence of bystander effect may be associated with the TGF-β1-Smad2 pathway and miR-21 in irradiated cells. PMID:26080011

  5. Radiation quality-dependence of bystander effect in unirradiated fibroblasts is associated with TGF-β1-Smad2 pathway and miR-21 in irradiated keratinocytes.

    Science.gov (United States)

    Yin, Xiaoming; Tian, Wenqian; Wang, Longxiao; Wang, Jingdong; Zhang, Shuyu; Cao, Jianping; Yang, Hongying

    2015-06-16

    Traditional radiation biology states that radiation causes damage only in cells traversed by ionizing radiation. But radiation-induced bystander effect (RIBE), which refers to the biological responses in unirradiated cells when the neighboring cells are exposed to radiation, challenged this old dogma and has become a new paradigm of this field. By nature, RIBEs are the consequences of intercellular communication between irradiated and unirradiated cells. However, there are still some important questions remain unanswered such as whether RIBE is dependent on radiation quality, what are the determining factors if so, etc. Using a transwell co-culture system, we found that HaCaT keratinocytes irradiated with α-particles but not X-rays could induce bystander micronucleus formation in unirradiated WS1 fibroblasts after co-culture. More importantly, the activation of TGF-β1-Smad2 pathway and the consistent decrease of miR-21 level in α-irradiated HaCaT cells were essential to the micronucleus induction in bystander WS1 cells. On the other hand, X-irradiation did not induce bystander effect in unirradiated WS1 cells, accompanied by lack of Smad2 activation and consistent decrease of miR-21 in X-irradiated HaCaT cells. Taken together, these results suggest that the radiation quality-dependence of bystander effect may be associated with the TGF-β1-Smad2 pathway and miR-21 in irradiated cells.

  6. The use of SCID mice in biotechnology and as a model for human disease

    Energy Technology Data Exchange (ETDEWEB)

    Sandhu, J.S. [Univ. of Toronto, Ontario (Canada). Dept. of Surgery]|[Mount Sinai Hospital, Toronto, Ontario (Canada). Samuel Lunenfeld Research Inst.; Boynton, E.; Gorczynski, R. [Univ. of Toronto, Ontario (Canada). Dept. of Surgery; Hozumi, N. [Mount Sinai Hospital, Toronto, Ontario (Canada). Samuel Lunenfeld Research Inst.

    1996-05-01

    The use of SCID (severe combined immunodeficient) mice in medical research and biotechnology has increased tremendously in recent years. This review outlines the major characteristics of these animals and the impediments that they poise to the engraftment of human cells and tissues. The development of the SCID mice pretreatment protocol (anti-asialo GM 1 antisera and radiation) is described, and the results of xenotransplantation studies of human cells and tissues in these pretreated animals are outlined. Wherever possible, data from transplantation studies (of human tissues and cells) in pretreated and nonpretreated animals are compared. The potential of the pretreated SCID mice for medical research and biotechnology is discussed.

  7. Human CD34+ CD133+ hematopoietic stem cells cultured with growth factors including Angptl5 efficiently engraft adult NOD-SCID Il2rγ-/- (NSG mice.

    Directory of Open Access Journals (Sweden)

    Adam C Drake

    Full Text Available Increasing demand for human hematopoietic stem cells (HSCs in clinical and research applications necessitates expansion of HSCs in vitro. Before these cells can be used they must be carefully evaluated to assess their stem cell activity. Here, we expanded cord blood CD34(+ CD133(+ cells in a defined medium containing angiopoietin like 5 and insulin-like growth factor binding protein 2 and evaluated the cells for stem cell activity in NOD-SCID Il2rg(-/- (NSG mice by multi-lineage engraftment, long term reconstitution, limiting dilution and serial reconstitution. The phenotype of expanded cells was characterized by flow cytometry during the course of expansion and following engraftment in mice. We show that the SCID repopulating activity resides in the CD34(+ CD133(+ fraction of expanded cells and that CD34(+ CD133(+ cell number correlates with SCID repopulating activity before and after culture. The expanded cells mediate long-term hematopoiesis and serial reconstitution in NSG mice. Furthermore, they efficiently reconstitute not only neonate but also adult NSG recipients, generating human blood cell populations similar to those reported in mice reconstituted with uncultured human HSCs. These findings suggest an expansion of long term HSCs in our culture and show that expression of CD34 and CD133 serves as a marker for HSC activity in human cord blood cell cultures. The ability to expand human HSCs in vitro should facilitate clinical use of HSCs and large-scale construction of humanized mice from the same donor for research applications.

  8. Recipient block TMA technique.

    Science.gov (United States)

    Mirlacher, Martina; Simon, Ronald

    2010-01-01

    New high-throughput screening technologies have led to the identification of hundreds of genes with a potential role in cancer or other diseases. One way to prioritize the leads obtained in such studies is to analyze a large number of tissues for candidate gene expression. The TMA methodology is now an established and frequently used tool for high-throughput tissue analysis. The recipient block technology is the "classical" method of TMA making. In this method, minute cylindrical tissue punches typically measuring 0.6 mm in diameter are removed from donor tissue blocks and are transferred into empty "recipient" paraffin blocks. Up to 1,000 different tissues can be analyzed in one TMA block. The equipment is affordable and easy to use in places where basic skills in histology are available.

  9. Guidelines for Screening, Early Diagnosis and Management of Severe Combined Immunodeficiency (SCID) in India.

    Science.gov (United States)

    Madkaikar, Manisha; Aluri, Jahnavi; Gupta, Sudhir

    2016-05-01

    Severe combined immunodeficiency (SCID) is one of the most severe and fatal forms of inherited primary immunodeficiency. Early diagnosis of SCID improves the outcome of life before and after hematopoietic stem cell transplant (HSCT). SCID fulfills the internationally-established criteria for a condition to be screened for at birth. T cell receptor excision circle (TREC) assay is commonly used in western countries as part of newborn blood spot screening (NBS) program as the assay has high sensitivity and specificity to identify SCID infants, allowing early intervention and curative bone marrow (BM) transplantation. In India, the blood spot based screening programs are yet to mature into a full-fledged national program. Moreover, TREC assay, a PCR based test, is not widely available and may cost USD 5-7 per test; thus limiting its applicability for screening newborns in Indian scenario. Most of the SCID patients have lymphopenia at birth and routine evaluation for absolute lymphocyte count (ALC) on cord blood samples can help in pre-symptomatic detection and early intervention for neonates with SCID. Although ALC count lacks the sensitivity and specificity of TREC assay; its lower cost and widespread availability makes it an attractive option for identifying newborns with lymphopenia during the post-partum hospital stay. BCG vaccine and other live attenuated vaccines (e.g., oral polio vaccine) should be withheld in lymphopenic infants until SCID is excluded by clinical and/or immunological work-up. A diagnosis of SCID warrants immediate care to prevent and treat infections and wherever feasible, early stem cell transplantation for disease free survival.

  10. How We Manage Adenosine Deaminase-Deficient Severe Combined Immune Deficiency (ADA SCID).

    Science.gov (United States)

    Kohn, Donald B; Gaspar, H Bobby

    2017-02-14

    Adenosine deaminase-deficient severe combined immune deficiency (ADA SCID) accounts for 10-15% of cases of human SCID. From what was once a uniformly fatal disease, the prognosis for infants with ADA SCID has improved greatly based on the development of multiple therapeutic options, coupled with more frequent early diagnosis due to implementation of newborn screening for SCID. We review the various treatment approaches for ADA SCID including allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched sibling or family member or from a matched unrelated donor or a haplo-identical donor, autologous HSCT with gene correction of the hematopoietic stem cells (gene therapy-GT), and enzyme replacement therapy (ERT) with polyethylene glycol-conjugated adenosine deaminase. Based on growing evidence of safety and efficacy from GT, we propose a treatment algorithm for patients with ADA SCID that recommends HSCT from a matched family donor, when available, as a first choice, followed by GT as the next option, with allogeneic HSCT from an unrelated or haplo-identical donor or long-term ERT as other options.

  11. Tensile and electrical properties of unirradiated and irradiated Hycon 3HP{trademark} CuNiBe

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J.; Eatherly, W.S. [Oak Ridge National Lab., TN (United States)

    1996-10-01

    The unirradiated tensile properties of two different heats of Hycon 3HP{trademark} CuNiBe (HT Temper) have been measured over the temperature range of 20-500{degrees}C for longitudinal and long transverse orientations. The room temperature electrical conductivity has also been measured for both heats. Both heats exhibited a very good combination of strength and conductivity at room temperature. The strength remained relatively high at all test temperatures, with a yield strength of 420-520 MPa at 500{degrees}C. However, low levels of ductility (<5% uniform elongation) were observed at test temperatures above 200-250{degrees}C, due to flow localization adjacent to grain boundaries. Fission neutron irradiation to a dose of {approximately}0.7 dpa at temperatures between 100 and 240{degrees}C produced a slight increase in strength and a significant decrease in ductility. The measured tensile elongation increased with increasing irradiation temperature, with a uniform elongation of {approximately}3.3% observed at 240{degrees}C. The electrical conductivity decreased slightly following irradiation, due to the presence of defect clusters and Ni, Zn, Co transmutation products. The data indicate that CuNiBe alloys have irradiated tensile and electrical properties comparable or superior to CuCrZr and oxide dispersion strengthened copper at temperatures <250{degrees}C, and may be suitable for certain fusion energy structural applications.

  12. The Analysis of the General Performance and Mechanical Behavior of Unirradiated FeCrAl Alloys Before and After Welding

    Energy Technology Data Exchange (ETDEWEB)

    Gussev, Maxim N. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Field, Kevin G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Yamamoto, Yukinori [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2016-06-03

    The present report summarizes and discusses the preliminary results for the in-depth characterization of the modern, nuclear-grade FeCrAl alloys currently under development. The alloys were designed for enhanced radiation tolerance and weldability, and the research is currently being pursued by the Department of Energy (DOE) Nuclear Energy Enabling Technologies (NEET) program. Last year, seven candidate FeCrAl alloys with well-controlled chemistry and microstructures were designed and produced; welding was performed under well-controlled conditions. The structure and general performance of unirradiated alloys were assessed using standardized and advanced microstructural characterization techniques and mechanical testing. The primary objective is to identify the best candidate alloy, or at a minimum to identify the contributing factors that increase the weldability and radiation tolerance of FeCrAl alloys, therefore enabling future generations of FeCrAl alloys to deliver better performance parameters. This report is structured so as to describe these critical assessments of the weldability; radiation tolerance will be reported on in later reports from this program.

  13. Disposition of Unirradiated Sodium Bonded EBR-II Driver Fuel Elements and HEU Scrap: Work Performed for FY 2007

    Energy Technology Data Exchange (ETDEWEB)

    Karen A Moore

    2007-04-01

    Specific surplus high enriched uranium (HEU) materials at the Idaho National Laboratory (INL) Materials and Fuels Complex (MFC) will be transferred to a designated off-site receiving facility. The DOE High Enriched Uranium Disposition Program Office (HDPO) will determine which materials, if any, will be prepared and transferred to an off-site facility for processing and eventual fabrication of fuel for nuclear reactors. These surplus HEU materials include approximately 7200 kg unirradiated sodium-bonded EBR-II driver fuel elements, and nearly 800 kg of HEU casting scrap from the process which formed various sodium-bonded fuels (including the EBR-II driver elements). Before the driver fuel can be packaged for shipment, the fuel elements will require removal of the sodium bond. The HEU scrap will also require repackaging in preparation for off-site transport. Preliminary work on this task was authorized by BWXT Y-12 on Nov 6, 2006 and performed in three areas: • Facility Modifications • Safety Documentation • Project Management

  14. Impact of Stromal Sensitivity on Radiation Response of Tumors Implanted in SCID Hosts Revisited

    Science.gov (United States)

    García-Barros, Mónica; Thin, Tin Htwe; Maj, Jerzy; Cordon-Cardo, Carlos; Haimovitz-Friedman, Adriana; Fuks, Zvi; Kolesnick, Richard

    2010-01-01

    Severe combined immunodeficient (SCID) mice carry a germ-line mutation in DNA-PK, associated with deficiency in recognition and repair DNA double strand breaks. Thus, SCID cells and tissues display increased sensitivity to radiation-induced post-mitotic (clonogenic) cell death. Nonetheless, the single radiation doses required for 50% permanent local control (TCD50) of tumors implanted in SCID mice are not significantly different from the TCD50 values of the same tumors in wild-type hosts. Whereas the tumor stroma is derived from the host, the observation that tumors implanted in SCID mice do not exhibit hypersensitivity to radiation might imply that stromal endothelial elements do not contribute substantially to tumor cure by ionizing radiation. Here we challenge this notion, testing the hypothesis that acid sphingomyelinase (ASMase)-mediated endothelial apoptosis, which results from plasma membrane alterations, not DNA damage, is a crucial element in the cure of tumors in SCID mice by single dose radiotherapy (SDRT). We show that endothelium in MCA/129 fibrosarcomas and B16 melanomas exhibit a wild-type apoptotic phenotype in SCID hosts, abrogated in tumors in SCIDasmase−/− littermates, which also acquire resistance to SDRT. Conversion into a radioresistant tumor phenotype when implanted in SCIDasmase−/− hosts provides compelling evidence that cell membrane ASMase-mediated microvascular dysfunction, rather than DNA damage-mediated endothelial clonogenic lethality, plays a mandatory role in the complex pathophysiologic mechanism of tumor cure by SDRT, and provides an explanation for the wild-type SDRT responses reported in tumors implanted in SCID mice. PMID:20924105

  15. A Markov Model to Analyze Cost-Effectiveness of Screening for Severe Combined Immunodeficiency (SCID)

    Science.gov (United States)

    Chan, Kee; APRN, Joie Davis; Pai, Sung-Yun; Bonilla, Francisco A.; Puck, Jennifer M; Apkon, Michael

    2011-01-01

    Objective To evaluate the cost-effectiveness of universal neonatal screening for T cell lymphocytopenia in enhancing quality of life and life expectancy for children with severe combined immunodeficiency (SCID). Methods Decision trees were created and analyzed to estimate the cost, life years, and quality adjusted life years (QALYs) across a population when universal screening for lack of T cells is used to detect SCID, as implemented in five states, compared to detection based on recognizing symptoms and signs of disease. Terminal values of each tree limb were derived through Markov models simulating the natural history of three cohorts: unaffected subjects; those-diagnosed with SCID as neonates (early diagnosis); and those diagnosed after becoming symptomatic and arousing clinical suspicion (late diagnosis). Models considered the costs of screening and of care including hematopoietic cell transplantation for affected individuals. Key decision variables were derived from the literature and from a survey of families with children affected by SCID, which was used to describe the clinical history and healthcare utilization for affected subjects. Sensitivity analyses were conducted to explore the influence of these decision variables. Results Over a 70 year time horizon, the average cost per infant was $8.89 without screening and $14.33 with universal screening. The model predicted that universal screening in the U.S. would cost approximately $22.4 million/year with a gain of 880 life years and 802 QALYs. Sensitivity analyses showed that screening test specificity and disease incidence were critical driving forces affecting the incremental cost-effectiveness ratio (ICER). Assuming a SCID incidence of 1/75,000 births and test specificity and sensitivity each at 0.99, screening remained cost-effective up to a maximum cost of $15 per infant screened. Conclusion At our current estimated screening cost of $4.22/infant, universal screening for SCID would be a cost effective

  16. The influence of late-stage pupal irradiation and increased irradiated: un-irradiated male ratio on mating competitiveness of the malaria mosquito Anopheles arabiensis Patton.

    Science.gov (United States)

    Helinski, M E H; Knols, B G J

    2009-06-01

    Competitiveness of released males in genetic control programmes is of critical importance. In this paper, we explored two scenarios to compensate for the loss of mating competitiveness after pupal stage irradiation in males of the malaria mosquito Anopheles arabiensis. First, competition experiments with a higher ratio of irradiated versus un-irradiated males were performed. Second, pupae were irradiated just prior to emergence and male mating competitiveness was determined. Males were irradiated in the pupal stage with a partially or fully-sterilizing dose of 70 or 120 Gy, respectively. Pupae were irradiated aged 20-26 h (young) as routinely performed, or the pupal stage was artificially prolonged by cooling and pupae were irradiated aged 42-48 h (old). Irradiated males competed at a ratio of 3:1:1 to un-irradiated males for mates in a large cage design. At the 3:1 ratio, the number of females inseminated by males irradiated with 70 Gy as young pupae was similar to the number inseminated by un-irradiated males for the majority of the replicates. At 120 Gy, significantly fewer females were inseminated by irradiated than by un-irradiated males. The irradiation of older pupae did not result in a significantly improved male mating competitiveness compared to the irradiation of young pupae. Our findings indicate that the loss of competitiveness after pupal stage irradiation can be compensated for by a threefold increase of irradiated males, but only for the partially-sterilizing dose. In addition, cooling might be a useful tool to facilitate handling processes of large numbers of mosquitoes in genetic control programmes.

  17. Cell cycle tracking for irradiated and unirradiated bystander cells in a single colony with exposure to a soft X-ray microbeam.

    Science.gov (United States)

    Kaminaga, Kiichi; Noguchi, Miho; Narita, Ayumi; Hattori, Yuya; Usami, Noriko; Yokoya, Akinari

    2016-11-01

    To establish a new experimental technique to explore the photoelectric and subsequent Auger effects on the cell cycles of soft X-ray microbeam-irradiated cells and unirradiated bystander cells in a single colony. Several cells located in the center of a microcolony of HeLa-Fucci cells consisting of 20-80 cells were irradiated with soft X-ray (5.35 keV) microbeam using synchrotron radiation as a light source. All cells in the colony were tracked for 72 h by time-lapse microscopy imaging. Cell cycle progression, division, and death of each cell in the movies obtained were analyzed by pedigree assay. The number of cell divisions in the microcolony was also determined. The fates of these cells were clarified by tracking both irradiated and unirradiated bystander cells. Irradiated cells showed significant cell cycle retardation, explosive cell death, or cell fusion after a few divisions. These serious effects were also observed in 15 and 26% of the bystander cells for 10 and 20 Gy irradiation, respectively, and frequently appeared in at least two daughter or granddaughter cells from a single-parent cell. We successfully tracked the fates of microbeam-irradiated cells and unirradiated bystander cells with live cell recordings, which have revealed the dynamics of soft X-ray irradiated and unirradiated bystander cells for the first time. Notably, cell deaths or cell cycle arrests frequently arose in closely related cells. These details would not have been revealed by a conventional immunostaining imaging method. Our approach promises to reveal the dynamic cellular effects of soft X-ray microbeam irradiation and subsequent Auger processes from various endpoints in future studies.

  18. Revised ANL-reported tensile data for unirradiated and irradiated (FFTF, HFIR) V-Ti and V-Cr-Ti alloys

    Energy Technology Data Exchange (ETDEWEB)

    Billone, M.C. [Argonne National Lab., IL (United States)

    1998-03-01

    The tensile data for all unirradiated and irradiated vanadium alloys samples tested at Argonne National Laboratory (ANL) have been critically reviewed and, when necessary, revised. The review and revision are based on reanalyzing the original load-displacement strip chart recordings by a methodology consistent with current ASTM standards. For unirradiated alloys (162 samples), the revised values differ from the previous values as follows: {minus}11{+-}19 MPa ({minus}4{+-}6%) for yield strength (YS), {minus}3{+-}15 MPa ({minus}1{+-}3%) for ultimate tensile strength (UTS), {minus}5{+-}2% strain for uniform elongation (UE), and {minus}4{+-}2% strain for total elongation (TE). Of these changes, the decrease in {minus}1{+-}6 MPa (0{+-}1%) for UTS, {minus}5{+-}2% for UE, and {minus}4{+-}2% for TE. Of these changes, the decrease in UE values for alloys irradiated and tested at 400--435 C is the most significant. This decrease results from the proper subtraction of nongauge-length deformation from measured crosshead deformation. In previous analysis of the tensile curves, the nongauge-length deformation was not correctly determined and subtracted from the crosshead displacement. The previously reported and revised tensile values for unirradiated alloys (20--700 C) are tabulated in Appendix A. The revised tensile values for the FFTF-irradiated (400--600 C) and HFIR-irradiated (400 C) alloys are tabulated in Appendix B, along with the neutron damage and helium levels. Appendix C compares the revised values to the previously reported values for irradiated alloys. Appendix D contains previous and revised values for the tensile properties of unirradiated V-5Cr-5Ti (BL-63) alloy exposed to oxygen.

  19. Oxidative dissolution of unirradiated Mimas MOX fuel (U/Pu oxides) in carbonated water under oxic and anoxic conditions

    Science.gov (United States)

    Odorowski, Mélina; Jégou, Christophe; De Windt, Laurent; Broudic, Véronique; Peuget, Sylvain; Magnin, Magali; Tribet, Magaly; Martin, Christelle

    2016-01-01

    Few studies exist concerning the alteration of Mimas Mixed-OXide (MOX) fuel, a mixed plutonium and uranium oxide, and data is needed to better understand its behavior under leaching, especially for radioactive waste disposal. In this study, two leaching experiments were conducted on unirradiated MOX fuel with a strong alpha activity (1.3 × 109 Bq.gMOX-1 reproducing the alpha activity of spent MOX fuel with a burnup of 47 GWd·tHM-1 after 60 years of decay), one under air (oxic conditions) for 5 months and the other under argon (anoxic conditions with [O2] MOX pellets under both oxic and anoxic conditions were similar, demonstrating the predominant effect of alpha radiolysis on the oxidative dissolution of the pellets. The uranium released was found to be mostly in solution as carbonate species according to modeling, whereas the Am and Pu released were significantly sorbed or precipitated onto the TiO2 reactor. An intermediate fraction of Am (12%) was also present as colloids. SEM and EPMA results indicated a preferential dissolution of the UO2 matrix compared to the Pu-enriched agglomerates, and Raman spectroscopy showed the Pu-enriched agglomerates were slightly oxidized during leaching. Unlike Pu-enriched zones, the UO2 grains were much more sensitive to oxidative dissolution, but the presence of carbonates did not enable observation of an oxidized layer by Raman spectroscopy with the exception of a few areas revealing the presence of U4O9. This data shows the heterogeneous nature of the alteration and the need to combine information from different techniques to determine the origin of releases.

  20. Cystic metacestodes of a rat-adapted Taenia taeniaeformis established in the peritoneal cavity of scid and nude mice.

    Science.gov (United States)

    Ito, A; Ma, L; Sato, Y

    1997-08-01

    In vitro-hatched (but not activated) oncospheres of a rat-adapted strain of Taenia taeniaeformis intraperitoneally inoculated into severe combined immunodeficiency (scid), congenitally athymic (nude) and immunocompetent (normal) female BALB/c mice developed into cystic metacestodes in the peritoneal cavity (but not in the liver) of scid and nude mice exclusively. This suggests that cystic metacestodes of this parasite, usually harboured in the liver only, can establish in scid and nude mice provided that the oncospheres are inoculated into the peritoneal cavity. Immunodeficient mice, especially scid mice, may be a good experimental animal model for the intermediate host of any taeniid species, of human, domestic- or wild-animal origin.

  1. Human Prolactin Improves Engraftment and Reconstitution of Human Peripheral Blood Lymphocytes in SCID Mice

    Institute of Scientific and Technical Information of China (English)

    Rui Sun; Jian Zhang; Cai Zhang; Jianhua Zhang; Shujuan Liang; Anyuan Sun; Junfu Wang; Zhigang Tian

    2004-01-01

    Recombinant human prolactin (rhPRL) was administered to huPBL-SCID mice to determine its effects on human immunologic reconsfitution and function. The huPBL-SCID mice were given 10 μg I.p. Injection of rhPRL every other day for a total of 10 injections after huPBL were transferred. The results demonstrated that rhPRL improved the engraftment of lymphocytes into thymus, lymph nodes and spleens, showing that the cellularities of these organs increased although the cellularities tended to vary depending on the donor. The amounts of human T cells (HLA-ABC+/CD3+) increased greatly in thymus (14.2 folds), spleen (4.16 folds) and lymph nodes (40.18 folds) after rhPRL injections. The amounts of human B cells (HLA-ABC+/CD19+) also increased greatly in lymph nodes (42.5 folds) and spleen (5.78 folds). The lymph node cells from the rhPRL-treated huPBL-SCID mice were more sensitive to PHA stimulation ([3H] thymidine incorporation). The supernatant of PHA-stimulated PBL from rhPRL-treated huPBL/SCID chimerism contained more cytokines (IFN-γ and IL-2). The natural cytotoxicity against human sensitive target cells, K562 cells, from spleen and bone marrow of hPBL/SCID chimerism was significantly enhanced by rhPRL administration. The lymph node cells were stimulated with LPS in vitro for 3 days and the lymphocytes from the rhPRL-treated huPBL-SCID mice were more sensitive to mitogen stimulation. Both serum total IgG level and IgM level of rhPRL-treated huPBL/SCID chimerism were increased, and even without DT-rechallenge the base line of DT-specific IgG was elevated after rhPRL treatment in huPBL-SCID mice. Thus, rhPRL stimulation promotes reconstitution of human immune system in huPBL-SCID mice.

  2. Human Prolactin Improves Engraftment and Reconstitution of Human Peripheral Blood Lymphocytes in SCID Mice

    Institute of Scientific and Technical Information of China (English)

    RuiSun; JianZhang; CaiZhang; JianhuaZhang; ShujuanLiang; AnyuanSun; JunfuWang; ZhigangTian

    2004-01-01

    Recombinant human prolactin (rhPRL) was administered to huPBL-SCID mice to determine its effects on human immunologic reconstitution and function. The huPBL-SCID mice were given 10 μg i.p. injection of rhPRL every other day for a total of 10 injections after huPBL were transfered. The results demonstrated that rhPRL improved the engraftment of lymphocytes into thymus, lymph nodes and spleens, showing that the cellularities of these organs increased although the cellularities tended to vary depending on the donor. The amounts of human T cells (HLA-ABC+/CD3+) increased greatly in thymus (14.2 folds), spleen (4.16 folds) and lymph nodes (40.18 folds) after rhPRL injections. The amounts of human B cells (HLA-ABC+/CD19+) also increased greatly in lymph nodes (42.5 folds) and spleen (5.78 folds). The lymph node cells from the rhPRL-treated huPBL-SCID mice were more sensitive to PHA stimulation (〔3H〕thymidine incorporation). The supernatant of PHA-stimulated PBL from rhPRL-treated huPBL/SCID chimerism contained more cytokines (IFN-γ and IL-2). The natural cytotoxicity against human sensitive target cells, K562 cells, from spleen and bone marrow of hPBL/SCID chimerism was significantly enhanced by rhPRL administration. The lymph node cells were stimulated with LPS in vitro for 3 days and the lymphocytes from the rhPRL-treated huPBL-SCID mice were more sensitive to mitogen stimulation. Both serum total IgG level and IgM level of rhPRL-treated huPBL/SCID chimerism were increased, and even without DT-rechallenge the base line of DT-specific IgG was elevated after rhPRL treatment in huPBL-SCID mice. Thus, rhPRL stimulation promotes reconstitution of human immune system in huPBL-SCID mice. Cellular & Molecular Immunology. 2004;1(2):129-136.

  3. ESTABLISHMENT OF INTRAPERITONEAL TRANSPLANTATION MODEL OF CISPLATIN-RESISTANT OVARIAN CARCINOMA CELL IN SCID MICE

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hui; ZHAO Qun; ZUO Lian-fu; WANG Xiao-ling; WANG Yong-jun; JIA Jin-hua; KANG Shan

    2006-01-01

    Objective: to develop an intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP cell in severe combined immunodeficiency (SCID) mouse and to study its biologic characteristics. Methods: Sixteen qualified C.B17/SCID mouse were divided into two groups randomly. Human ovarian carcinoma SKOV3 or SKOV3/CDDP cells were injected intraperitoneally into the SCID mouse at the amount of 1×107 cells (0.5 mL) per mouse. The behaviors of mice,tumor growth and morphology were analyzed. The expression of cancer antigen 125 (CA125), GST-π and Topo-Ⅱ were examined by immunohistochemical method. Results: In this experimental study, transplanted tumors are formed in 100%SCID mice in the two groups. The morphology, growth pattern and CA125 secretion of SKOV3/CDDP group were as same as those of SKOV3 group. It shows that the tumors of the two groups kept the characteristics of ovaries serosity papillary adenocarcinoma. Compared with SKOV3 group, the expression of GST-π and Topo-Ⅱ gene in SKOV3/CDDP group were significantly higher (P<0.05). Conclusion: An intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP in SCID mice has been developed successfully. It may be an ideal animal model for biotherapy research of ovarian carcinoma as it can simulate the biological behavior of peritoneal metastasis of human ovarian carcinoma and the drug tolerance is maintained.

  4. New insights and unresolved issues regarding insertional mutagenesis in X-linked SCID gene therapy.

    Science.gov (United States)

    Pike-Overzet, Karin; van der Burg, Mirjam; Wagemaker, Gerard; van Dongen, Jacques J M; Staal, Frank J T

    2007-11-01

    The oncogenic potential of retrovirus-mediated gene therapy has been re-emphasized because four patients developed T-cell acute lymphoblastic leukemia (T-ALL)-like disease from an otherwise successful gene therapy trial for X-linked severe combined immunodeficiency (X-linked SCID). X-linked SCID, a disease caused by inactivating mutations in the IL2Rgamma gene, is part of a heterogeneous group of SCIDs characterized by the lack of T cells in conjunction with the absence of B and/or natural killer (NK) cells. Gene therapy approaches are being developed for this group of diseases. In this review we discuss the various forms of SCID in relation to normal T-cell development. In addition, we consider the possible role of LMO2 and other T-ALL oncogenes in the development of adverse effects as seen in the X-linked SCID gene therapy trial. Furthermore, we debate whether the integration near the LMO2 locus is sufficient to result in T-ALL-like proliferations or whether the gamma-retroviral viral expression of the therapeutic IL2RG gene contributes to leukemogenesis. Finally, we review some newly developed murine models that may have added value for gene therapy safety studies.

  5. Establishment of Retinoblastoma Model in NOD-SCID Mice and Study of Metastasis

    Institute of Scientific and Technical Information of China (English)

    Bo Zhang; Yongping Li; Xiufeng Zhong; Wenge Huang; Li Nie; Wenxin Zhang

    2005-01-01

    Purpose: To establish model of retinoblastoma subcutaneously in NOD-SCID mice and study rules of formation and distribution of retinoblastoma metastasis.Methods: Retinoblastoma cells SO-RB50 were inoculated subcutaneously in NOD-SCID mice. Animal acts and tumor formation, growth and metastasis in NOD-SCID mice were observed. Primary and metastatic tumors were studied pathohistologically by HE and immunohistochemical staining.Results: The latent periods of tumor growth were 12~19 days and the taken rate of tumor was 100%. 32 days later, 5 NOD-SCID mice were found with tumors that had metastasized to areas mainly located in the abdominal cavity and the side of the kidney; the metastatic time of tumors in the mice also differed. The tumor cells of the primary nodules and the metastasis were similar with human retinoblastoma cells and positive in immunohistochemical staining of NSE.Conclusion: The subcutaneous model of retinoblastoma in NOD-SCID mice showed a high taken rate and a short latent period of tumor, which had a high metastatic rate and was the best model in research of behaviors of retinoblastoma at present.

  6. Special Analysis for the Disposal of the Idaho National Laboratory Unirradiated Light Water Breeder Reactor Rods and Pellets Waste Stream at the Area 5 Radioactive Waste Management Site, Nevada National Security Site, Nye County, Nevada

    Energy Technology Data Exchange (ETDEWEB)

    Shott, Gregory [NSTec

    2014-08-31

    The purpose of this special analysis (SA) is to determine if the Idaho National Laboratory (INL) Unirradiated Light Water Breeder Reactor (LWBR) Rods and Pellets waste stream (INEL103597TR2, Revision 2) is suitable for disposal by shallow land burial (SLB) at the Area 5 Radioactive Waste Management Site (RWMS). The INL Unirradiated LWBR Rods and Pellets waste stream consists of 24 containers with unirradiated fabricated rods and pellets composed of uranium oxide (UO2) and thorium oxide (ThO2) fuel in zirconium cladding. The INL Unirradiated LWBR Rods and Pellets waste stream requires an SA because the 229Th, 230Th, 232U, 233U, and 234U activity concentrations exceed the Nevada National Security Site (NNSS) Waste Acceptance Criteria (WAC) Action Levels.

  7. Pathological features of Cryptosporidium andersoni-induced lesions in SCID mice.

    Science.gov (United States)

    Masuno, Koichi; Yanai, Tokuma; Sakai, Hiroki; Satoh, Masaaki; Kai, Chieko; Nakai, Yutaka

    2013-07-01

    To assess the infectivity and the istopathological features of Cryptosporidium andersoni (C. andersoni) in laboratory animals, SCID mice were orally inoculated with oocysts of C. andersoni. Starting one week after inoculation, the SCID mice began shedding oocysts, and this continued for ten weeks. Histopathologically, myriads of C. andersoni were observed on the apical surface of the epithelium in the gastric pit of the glandular stomach. There were few lesions in the gastric epithelium except C. andersoni adhesion. In the lamina propria of the affected mucosa, minimum infiltration of inflammatory cells was observed. Immunohistochemically, C. andersoni demonstrated a positive reaction to a number of primary antibodies of Cryptosporidium parvum. In the experiment described here, few increases were seen in apoptotic epithelial cells in the affected mucosas of the SCID mice, and the nuclear augmentation was not enhanced. It was hypothesized that the absence of apoptosis and cell division were due to a lack of inflammatory cell reaction in the lamina propria.

  8. The SCID-hu mouse as a tool in immunotoxicological risk assessment: Effects of 2-acetyl-4(5)-tetrahydroxybutyl-imidazole (THI) and di-n-butyltin dichloride (DBTC) on the human thymus in SCID-hu mice

    NARCIS (Netherlands)

    Heer, C. de; Schuurman, H.J.; Houben, G.F.; Pieters, R.H.H.; Penninks, A.H.; Loveren, H. van

    1995-01-01

    SCID mice engrafted with human fetal thymus and liver tissue fragments (SCID-hu mice) are currently considered as a new tool in human immunotoxicological risk assessment. Testing of various immunotoxicants exerting thymotoxicity via different intrathymic target cell types is necessary for validation

  9. About the mechanisms governing the hydrogen effect on visco plasticity of unirradiated fully annealed zircaloy-4 sheet

    Energy Technology Data Exchange (ETDEWEB)

    Rupa, N [Electricite de France (EDF), Nuclear Power Div., Lab. Group, 93 - Saint-Denis (France); Clavel, M. [Universite de Technologie de Compiegne, Centre de Recherches de Royalliu, 60 (France); Bouffioux, P.; Domain, C. [Electricite de France, Research engineer, RD Div., Material Study Branch, 77 - Moret sur Loing (France); Legris, A. [Lille-1 Univ., UMR 8517, 59 - Villeneuve-d' Ascq (France)

    2002-07-01

    It has been observed that hydrogen either in solid solution or precipitated under the form of hydrides has an impact on the visco-plasticity of CWSR Zircaloy-4 cladding tubes, increasing significantly the creep resistance. The use of TEM on the structurally complex CWSR material being unlikely to identify the deformation mechanisms, it has been decided to complete this R and D program on recrystallized material. A study has been carried out on fully annealed unirradiated Zircaloy-4 sheet used for the manufacturing of the fuel subassembly grids. Mechanical tests were performed for large ranges of temperatures (300 to 400 deg C), stresses (120 to 250 MPa), and strain rates (2 x 10{sup -7} to 2 x 10{sup -3} s{sup -1}) on as-received and hydrided specimen. The results emphasize: - Hydrogen in solid solution induces a softening of the material. The TEM observations have revealed identical structure of dislocations for both as-received and hydrided specimens. The softening has been particularly observed when dynamic strain aging is activated. It is assumed that atomic hydrogen decreases the dislocation pinning caused by interstitial and/or enhances the intrinsic mobility of the dislocations. With respect to ab initio calculation, atomic hydrogen might be trapped easily by the core of the dislocation, this phenomenon contributing to decrease the lattice friction and to enhance planar glide. - Precipitated hydrides induce a hardening of the material as observed for CWSR Zircaloy 4. The magnitude of the phenomenon depends upon temperature and stress. An analysis of the unload sequences for tension tests and of the secondary strain rates for creep tests leads to the conclusion that hydrides change the kinematics hardening by increasing the internal stress with respect to the as-received material. TEM observation combined with this visco-plasticity approach has revealed that: first, as long as the internal stress is increasing versus plastic strain, hydride are obstacles to

  10. IL7R and RAG1/2 genes mutations/polymorphisms in patients with SCID.

    Science.gov (United States)

    Safaei, Sepideh; Pourpak, Zahra; Moin, Mostafa; Houshmand, Massoud

    2011-06-01

    SCID disorder is major failure of the immune system, usually genetic. The aim of this study was on mutations detection of RAG1, RAG2, and IL7RG genes in SCID cases. Mutation detection was performed by PCR sequencing. Our results indicated that 13 mutations were found through cases which include 4 mutations in IL7R gene (T661I, I138V, T56A, C57W), 7 mutations in RAG1 (W896X, W204R, M324V, T731I, M1006V, K820R, and R249H), and 2 mutations in RAG2 gene (R229W, ΔT251).

  11. Colitic scid mice fed Lactobacillus spp. show an ameliorated gut histopathology and an altered cytokine profile by local T cells

    DEFF Research Database (Denmark)

    Møller, Peter Lange; Pærregaard, Anders; Gad, Monika;

    2005-01-01

    Scid mice transplanted with CD4 T blast cells develop colitis. We investigated if the disease was influenced in colitic mice treated with antibiotic and fed Lactobacillus spp.......Scid mice transplanted with CD4 T blast cells develop colitis. We investigated if the disease was influenced in colitic mice treated with antibiotic and fed Lactobacillus spp....

  12. Den danske udgave af Structured Clinical Interview for DSM-5 Personality Disorders (SCID-5-PD): Rationale, oversigt og oversættelse

    DEFF Research Database (Denmark)

    Kongerslev, Mickey T; Bach, Bo; Olsen, Cecilie Westergaard

    2017-01-01

    The chapter outlines the rationale for using structured clinical interviews to diagnose personality disorder, provides an overview of the changes from SCID-II to SCID-5-PD, and describes the translation procedures used for the Danish version......The chapter outlines the rationale for using structured clinical interviews to diagnose personality disorder, provides an overview of the changes from SCID-II to SCID-5-PD, and describes the translation procedures used for the Danish version...

  13. Genome-wide Gene Expression Profiling of SCID Mice with T-cell-mediated Colitis

    DEFF Research Database (Denmark)

    Brudzewsky, D.; Pedersen, A. E.; Claesson, M. H.

    2009-01-01

    disease. Here, we have investigated severe combined immunodeficient (SCID) mice, which upon adoptive transfer with concanavalin A-activated CD4(+) T cells develop inflammation of the colon with predominance in rectum. Mice with increasing level of inflammation was studied. RNA from rectum of transplanted...

  14. Pertussis toxin B-oligomer inhibits HIV infection and replication in hu-PBL-SCID mice.

    Science.gov (United States)

    Lapenta, Caterina; Spada, Massimo; Santini, Stefano M; Racca, Sara; Dorigatti, Fernanda; Poli, Guido; Belardelli, Filippo; Alfano, Massimo

    2005-04-01

    Bordetella pertussis toxin B-oligomer (PTX-B) has been shown to inhibit HIV infection and replication in vitro. The potential anti-viral effect of PTX-B was tested here in an in vivo surrogate model of HIV infection, i.e. SCID mice reconstituted with human peripheral blood leukocytes (PBL) (hu-PBL-SCID) and infected with a CCR5-dependent (R5) HIV-1 strain. SCID mice inoculated intra-peritoneal (i.p.) with PTX-B and then infected with the R5 strain SF-162 were sacrificed 7 days later and analyzed for human PBL (hu-PBL) lymphoid tissue reconstitution, infection of hu-PBL, plasma viremia and viral rescue from ex vivo-cultivated i.p. hu-PBL. Unlike mice treated with 500 ng per animal of PTX-B showing no evidence of viral inhibition, daily administration of PTX-B (50 ng per mouse) strongly inhibited virus infection and replication, as determined by undetectable viremia, absence of infected hu-PBL and lack of rescue of infectious HIV in most animals. Furthermore, PTX-B injection 2 h before and twice after infection prevented HIV-1 infection and replication in all (10/10) tested animals. Thus, PTX-B potently inhibited virus infection and replication in hu-PBL-SCID mice, supporting the hypothesis that it may represent a new pharmacological agent against HIV-1 infection.

  15. The inclusion of ADA-SCID in expanded newborn screening by tandem mass spectrometry.

    Science.gov (United States)

    la Marca, Giancarlo; Giocaliere, Elisa; Malvagia, Sabrina; Funghini, Silvia; Ombrone, Daniela; Della Bona, Maria Luisa; Canessa, Clementina; Lippi, Francesca; Romano, Francesca; Guerrini, Renzo; Resti, Massimo; Azzari, Chiara

    2014-01-01

    Severe combined immunodeficiency due to adenosine-deaminase defect (ADA-SCID) is usually deadly in childhood because of severe recurrent infections. When clinical diagnosis is done, permanent damages due to infections or metabolite accumulation are often present. Gene therapy, bone marrow transplantation or enzyme replacement therapy may be effective if started early. The aim of this study was to set-up a robust method suitable for screening with a minimized preparation process and with inexpensive running costs, for diagnosing ADA-SCID by tandem mass spectrometry. ADA-SCID satisfies all the criteria for inclusion in a newborn screening program. We describe a protocol revised to incorporate adenosine and 2-deoxyadenosine testing into an expanded newborn screening program. We assessed the effectiveness of this approach testing dried blood spots from 4 genetically confirmed early-onset and 5 delayed-onset ADA-SCID patients. Reference values were established on 50,000 healthy newborns (deoxyadenosine <0.09μmol/L, adenosine <1.61μmol/L). We also developed a second tier test to distinguish true positives from false positives and improve the positive predictive value of an initial abnormal result. In the first 18 months, the pilot project has identified a newborn with a genetically confirmed defect in adenosine deaminase (ADA) gene. The results show that the method having great simplicity, low cost and low process preparations can be fully applicable to a mass screening program.

  16. A novel SCID mouse model for studying spontaneous metastasis of human lung cancer to human tissue.

    Science.gov (United States)

    Teraoka, S; Kyoizumi, S; Seyama, T; Yamakido, M; Akiyama, M

    1995-05-01

    We established a novel severe combined immunodeficient (SCID) mouse model for the study of human lung cancer metastasis to human lung. Implantation of both human fetal and adult lung tissue into mammary fat pads of SCID mice showed a 100% rate of engraftment, but only fetal lung implants revealed normal morphology of human lung tissue. Using these chimeric mice, we analyzed human lung cancer metastasis to both mouse and human lungs by subcutaneous inoculation of human squamous cell carcinoma and adenocarcinoma cell lines into the mice. In 60 to 70% of SCID mice injected with human-lung squamous-cell carcinoma, RERF-LC-AI, cancer cells were found to have metastasized to both mouse lungs and human fetal lung implants but not to human adult lung implants 80 days after cancer inoculation. Furthermore, human-lung adenocarcinoma cells, RERF-LC-KJ, metastasized to the human lung implants within 90 days in about 40% of SCID mice, whereas there were no metastases to the lungs of the mice. These results demonstrate the potential of this model for the in vivo study of human lung cancer metastasis.

  17. Immunoglobulin leakiness in scid mice with CD4(+) T-cell-induced chronic colitis

    DEFF Research Database (Denmark)

    Brimnes, J; Reimann, J; Claesson, Mogens Helweg

    2000-01-01

    Inflammatory bowel disease in scid mice is initiated by transplantation of CD4(+) T-cells from immunocompetent syngenic donor mice. As the disease progresses, immunoglobulin (Ig)-containing cells appear in the gut lamina propria, suggesting that locally accumulating Ig may play a role in disease ...

  18. Development and Safety Assessment of Lentiviral Vector Gene Therapy for SCID-X1

    NARCIS (Netherlands)

    M.W. Huston (Marshall W.)

    2013-01-01

    markdownabstract__Abstract__ This thesis work focuses on exploring ways to improve hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency disease (SCID-X1) using lentiviral vectors and a mouse model of the disease. This involved 3-part approach: modifying some components

  19. Novel metastasis model of human lung cancer in SCID mice depleted of NK cells.

    Science.gov (United States)

    Yano, S; Nishioka, Y; Izumi, K; Tsuruo, T; Tanaka, T; Miyasaka, M; Sone, S

    1996-07-17

    Metastasis is a critical problem in the treatment of human lung cancer. Thus, a suitable animal model of metastasis of human lung cancer is required for in vivo biological and preclinical studies. In this study, we tried to establish a suitable model for this, using SCID mice. Neither human SCLC H69/VP cells (5 x 10(6)) nor squamous-cell carcinoma RERF-LC-AI cells (1 x 10(6)), injected through a tail vein, formed metastases in untreated SCID mice. Pre-treatment of SCID mice with anti-asialo GM1 serum resulted in only a few metastases of H69/VP cells, but pre-treatment with anti-mouse IL-2 receptor beta chain Ab (TM-beta 1) resulted in numerous lymph-node metastases 56 days after tumor inoculation. H69/VP-M cells, an in vivo-selected variant line, formed significant numbers of lymph-node metastases even in SCID mice pre-treated with anti-asialo GM1 serum. SCID mice depleted of NK cells by treatment with TM-beta 1 showed different patterns of metastasis when inoculated intravenously with the 2 different human lung cancer cell lines (H69/VP and RERF-LC-AI cells): H69/VP cells formed metastases mainly in systemic lymph nodes and the liver, whereas RERF-LC-AI cells formed metastases mainly in the liver and kidneys, with only a few in lymph nodes. A histopathological study showed that the metastatic colonies consisted of cancer cells. The numbers of metastatic colonies formed by the 2 cell lines increased with the number of cells inoculated. TM-beta 1 treatment of SCID mice efficiently removed NK cells from peripheral blood for at least 6 weeks, whereas, after treatment of the mice with anti-asialo GM1 serum, NK cells were recovered within 9 days. These findings suggest that NK-cell-depleted SCID mice may be useful as a model in biological and pre-clinical studies on metastasis of human lung cancer.

  20. Generation of Novel Chimeric Mice with Humanized Livers by Using Hemizygous cDNA-uPA/SCID Mice.

    Directory of Open Access Journals (Sweden)

    Chise Tateno

    Full Text Available We have used homozygous albumin enhancer/promoter-driven urokinase-type plasminogen activator/severe combined immunodeficient (uPA/SCID mice as hosts for chimeric mice with humanized livers. However, uPA/SCID mice show four disadvantages: the human hepatocytes (h-heps replacement index in mouse liver is decreased due to deletion of uPA transgene by homologous recombination, kidney disorders are likely to develop, body size is small, and hemizygotes cannot be used as hosts as more frequent homologous recombination than homozygotes. To solve these disadvantages, we have established a novel host strain that has a transgene containing albumin promoter/enhancer and urokinase-type plasminogen activator cDNA and has a SCID background (cDNA-uPA/SCID. We applied the embryonic stem cell technique to simultaneously generate a number of transgenic lines, and found the line with the most appropriate levels of uPA expression-not detrimental but with a sufficiently damaged liver. We transplanted h-heps into homozygous and hemizygous cDNA-uPA/SCID mice via the spleen, and monitored their human albumin (h-alb levels and body weight. Blood h-alb levels and body weight gradually increased in the hemizygous cDNA-uPA/SCID mice and were maintained until they were approximately 30 weeks old. By contrast, blood h-alb levels and body weight in uPA/SCID chimeric mice decreased from 16 weeks of age onwards. A similar decrease in body weight was observed in the homozygous cDNA-uPA/SCID genotype, but h-alb levels were maintained until they were approximately 30 weeks old. Microarray analyses revealed identical h-heps gene expression profiles in homozygous and hemizygous cDNA-uPA/SCID mice were identical to that observed in the uPA/SCID mice. Furthermore, like uPA/SCID chimeric mice, homozygous and hemizygous cDNA-uPA/SCID chimeric mice were successfully infected with hepatitis B virus and C virus. These results indicate that hemizygous cDNA-uPA/SCID mice may be novel and

  1. Radiation-induced apoptosis in SCID Mousespleen after a low-dose irration

    Science.gov (United States)

    Ohnishi, T.; Takahashi, A.; Ohnishi, K.

    Purpose: To estimate the effects of space radiation on health of space crews, we aimed to clarify whether pre-irradiation at a low-dose interferes in a p53-centered signal transduction pathway induced by radiation. By using a severe combined immunodeficiency (Scid) mouse defective DNA-PK activity, we examined the role of DNA-PK activity in radioadaptation induced by low-dose irradiation. Methodology: Specific pathogen free 5-week-old fe male mice of Scid and the parental mice (CB-17 Icr+/+) were irradiated with X-rays at 3.0 Gy 1, 2, 3 or 4 weeks after conditioning irradiation at 0.15, 0.30, 0.45 or 0.60 Gy. The mice spleens were fixed for immunohistochemistry 12 h after irradiation. Bax on formalin-fixed paraffin-embedded sections were stained by the avidin-biotin peroxidase complex method using HISTOFINE SAB-PO(R) kit (Nichirei Co., Tokyo, Japan). Apoptosis incidence in the sections was measured by staining with HE staining. Results: The frequency of Bax- and apoptosis -positive cells increased up to 12 h after irradiation at 3.0 Gy in the spleen of CB-17 Icr+/+ and Scid mice. However, they were not observed by irradiation with low dose at 0.15-0.60 Gy. When pre-irradiation at 0.45 Gy 2 weeks before challenging acute irradiation at 3.0 Gy was performed, Bax accumulation and apoptosis induced by irradiation at 3.0 Gy was depressed in the spleen of CB-17 Icr+/+ mice, but not Scid mice. Conclusions: These data suggest that DNA-PKcs (expressed in CB-17 Icr+/+, not Scid mice) might play a major role on radioadaptation induced by pre-irradiation at low dose in mice spleen. We expect that the present findings will provide useful information for the care of space crews' health.

  2. Responses to larval Taenia taeniaeformis in mice with severe combined immunodeficiency (scid).

    Science.gov (United States)

    Ishiwata, K; Oku, Y; Ito, M; Kamiya, M

    1992-04-01

    Responses to Taenia taeniaeformis infection were studied in mice with severe combined immunodeficiency (scid), which lack functional T and B lymphocytes. In the early phase of infection, accumulation of polymorphonuclear leucocytes (PML) occurred around the larvae in the liver of scid mice and their immunocompetent counterparts, C.B-17, (a BALB/c strain, genetically resistant to this parasite). PML accumulation continued until encapsulation of developing larvae by fibroblasts (14 days p.i.), and subsequent fibrosis resulted in granuloma formation. No infiltration of eosinophils or macrophages around larvae was observed in scid mice prior to granuloma formation, while in C.B-17 mice infiltration was observed as early as 5 days p.i., when specific antibodies could not be detected in the circulation. Most larvae were destroyed by 14 days p.i. in C.B-17 mice. In scid mice the larvae survived but the host capsules (cysts) were thin and most contained blood at 42 days p.i. In these cysts, inflammatory cells were observed on the larval surface and in invaded parasite tissue. Hepatocyte coagulation necrosis adjacent to larvae was commonly found in C.B-17 mice by 5 days p.i., while it did not occur in scid mice throughout these experiments. These results suggest that in host responses to larval T. taeniaeformis, PML accumulation and encapsulation by fibrosis are T and B cell independent, while eosinophil and macrophage infiltration, as well as resistance to infection, are T and/or B cell dependent. Additionally, there may be an association between host cell necrosis around larvae and T and/or B cell responses.

  3. 人急性B淋巴细胞白血病-NOD/SCID/IL2rγnull新生小鼠异种移植模型的建立%Establishment of Human Acute B-Lymphoblastic Leukemia NOD/SCID/ IL2 Receptor γChainnull neonatal Mouse Xenotransplant Model

    Institute of Scientific and Technical Information of China (English)

    孔圆; 刘艳荣; 刘开彦; 黄晓军; Fumihiko Ishikawa; Mine Harada

    2012-01-01

    In order to study human acute B-lymphoblastic leukemia (B-ALL) in vivo, a novel xenotransplant model was established by using neonaial NOD/SCID/IL2 receptor γ chainmall mouse. The CD34+CD19+ bone marrow ( BM) cells were sorted from the CD3- CD4- CD8- fraction of B-ALL patients by fluorescence-activated cell sorting( FACS), and injected into 100 cGy irradiated neonatal NOD/SCID/IL2γmall mice through facial vein. The engraftment and proliferation of human B-ALL cells were monitored by the presence of human CD45+ CD19+ cells in peripheral blood (PB). Human hematopoietic chimerism in PB, BM and spleen of the recipients was examined by multi parameter flow cytometry. Morphological analyses of FACS-sorted murine marrow cells were performed by using May-Grunwald-Giemsa staining. Furthermore, leukemia cell infiltration in the organs was evaluated by hematoxylin-eosin staining. The results indicated that the sorted CD34+ CD19+ cells were able to initiate human B-ALL in vivo. The percentages of humanCms+CD19+ cells in PB, BM and spleen of the recipient mice were (83. 36 ± 10.05)% , (93.88 ±5.05)% and (88.31 ±5.01)% , respectively. Furthermore, the phenotype and morphology of the engrafted human cells were resemble to the original B-ALL cells from the patients. Similar to the clinical features, transplanted leukemic cells infiltrated into the organs, such as liver, lung, kidney and brain in the recipients. It is concluded that neonatal NOD/ SCID/IL2rγnull mice can support efficient engraftment of the sorted CD34+ CD19+ cells from human B-ALL for a long-term period. Human-mouse xenotransplant model using neonatal NOD/SCID/IL2rγnull mouse may provide an important system to study the biology of human B-ALL in vivo.%本研究旨在应用NOD/SCID/Ⅱ2rγnull新生小鼠建立人急性B淋巴细胞白血病(B-ALL)的异种移植模型.NOD/SCID/Ⅱ2rγnull新生期(出生48h之内)小鼠经亚致死剂量(100 cGy) 137Cs全身照射后,由面静脉输注FACSAria流式细胞

  4. Irradiation programme MANITU: Results of pre-examinations and Charpy tests with unirradiated materials; Bestrahlungsprogramm MANITU. Ergebnisse der Voruntersuchungen und der Kerbschlagbiegeversuche mit den unbestrahlten Werkstoffen

    Energy Technology Data Exchange (ETDEWEB)

    Rieth, M.; Dafferner, B.; Ries, H.; Romer, O.

    1995-04-01

    The irradiation project MANITU was planned in the frame of the European Long-term Fusion Materials Development Programme. The results of MANITU will have a lasting influence on the future actions within the materials development programme. The problem of the irradiation induced embrittlement of possible martensitic alloy candidates is still unsolved. But after the evaluation of sub-size Charpy tests with the unirradiated refrence specimens of MANITU a first tendency is recognizable. The Charpy properties of the newly developed low activation 7-10% Cr-WVTa alloys are clearly better compared with the modified commerical 10-11% Cr-NiMoVNb steels. In the present report the pre-examinations are documented and the Charpy test results with unirradiated reference specimens are analysed and assessed. (orig.) [Deutsch] Das Bestrahlungsprojekt MANITU wurde im Rahmen des europaeischen Langzeitprogramms fuer Materialentwicklung fuer die Kernfusion geplant. Die daraus gewonnenen Ergebnisse werden das weitere Vorgehen bei der Materialentwicklung entscheidend beeinflussen. Das Problem der bestrahlungsinduzierten Versproedung bei den in Frage kommenden martensitischen Werkstoffen ist nach wie vor ungeloest. Eine erste Tendenz zeichnet sich nach der Auswertung der Kerbschlagbiegeversuche an den unbestrahlten miniaturisierten Referenzproben des MANITU-Programms ab. Die neu entwickelten niedrig aktivierbaren 7-10% Cr-WVTa-Legierungen weisen gegenueber den modifizierten kommerziellen 10-11% Cr-NiMoVNb-Staehlen deutlich bessere Kerbschlageigenschaften auf. Im vorliegenden Bericht werden die Voruntersuchungen dokumentiert und die Ergebnisse aus den Kerbschlagbiegeversuchen der unbestrahlten Referenzproben analysiert und bewertet. (orig.)

  5. Hemopoietic stem-cell compartment of the SCID mouse: Double-exponential survival curve after [gamma] irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Satoshi (Yokohama City Univ. School of Medicine (Japan) Niigata Univ. (Japan)); Hirabayashi, Yoko; Inoue, Tohru; Kanisawa, Masayoshi; Sasaki, Hideki (Yokohama City Univ. School of Medicine (Japan)); Komatsu, Kenshi (Nagasaki Univ (Japan)); Mori, K.J. (Niigata Univ. (Japan))

    1993-05-15

    It has been reported that SCID (severe combined immunodeficiency, scid/scid) mice are more radiosensitive than normal mice. In the present studies, graded doses of radiation were given to bone marrow cells from SCID mice, and double-exponential survival curves were observed for day-9 and day-12 colony-forming units in the spleen (CFU-S). Single-exponential curves were found for SCID CFU in in vitro assays for granulocyte/macrophage-CFUs and erythroid burst-forming units, as reported elsewhere. Since the size of this more resistant fraction seems to decrease with stem-cell maturation, the finding implies that this fraction is a primitive subpopulation of the stem-cell compartment. The mean lethal dose (D[sub 0]), however, of this less sensitive SCID CFU-S is much less than the D[sub 0] of regular CFU-S in normal littermates. Spleen colonies produced by SCID bone marrow were relatively small and abortive. The size of these colonies decreased nearly exponentially with increasing doses of radiation. These colonies produced by the sensitive fraction have disappeared, being killed by a relatively low dose of radiation. This observation might account for the high lymphomagenesis arising from primitive hemopoietic stem cells in SCID mice, because the smallness of the colonies suggests that there is unrepaired or misrepaired damage. Furthermore, this less sensitive fraction might be a source of the [open quotes]leaky[close quotes] change of T and B cells, possibly due to the induction of an equivocal repair system which appears in the later stages of life in the SCID mice. 34 refs., 5 figs., 3 tabs.

  6. HIV-1 Pathogenesis and Therapeutic Intervention in the SCID-hu Thy/Liv Mouse: A Model for Primary HIV-1 Infection in the Human Thymus

    OpenAIRE

    Su, Lishan

    1997-01-01

    The SCID-hu Thy/Liv mouse is a model for the analysis of human thymopoiesis. It has been constructed by engrafting fragments of human fetal liver and thymus into the immunodeficient C.B-17 scid/scid (SCID) mouse. The resulting ‘Thy/Liv’ organ promotes long-term differentiation of human T cells. Given the apparently normal physiology of the SCID-hu Thy/Liv organ, it has been used to explore the pathophysiologic mechanisms of HIV-1 infection in vivo, and to test therapeutic modalities such as a...

  7. Gene for the catalytic subunit of mouse DNA-dependent protein kinase maps to the scid locus.

    Science.gov (United States)

    Miller, R D; Hogg, J; Ozaki, J H; Gell, D; Jackson, S P; Riblet, R

    1995-01-01

    The gene encoding the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) has been proposed recently as a candidate gene for the mouse severe combined immune deficiency (scid) locus. We have used a partial cDNA clone for human DNA-PKcs to map the mouse homologue using a large interspecific backcross panel. We found that the mouse gene for DNA-PKcs does not recombine with scid, consistent with the hypothesis that scid is a mutation in the mouse gene for DNA-PKcs. Images Fig. 3 PMID:7479885

  8. Pathogenicity of Helicobacter rodentium in A/JCr and SCID mice.

    Science.gov (United States)

    Myles, Matthew H; Livingston, Robert S; Franklin, Craig L

    2004-10-01

    Helicobacter rodentium was first recognized as a potential pathogen when it was isolated, along with Helicobacter bilis, from a colony of scid/Trp53 knockout mice with diarrhea. Clinical disease in these mice was more severe than that previously reported in mice infected with H. bilis alone, thus suggesting that H. rodentium contributed to the pathogenesis of enteritis. The purpose of the study reported here was to address two questions: is H. rodentium pathogenic in mice, and when co-infection with a pathogenic helicobacter occurs, does H. rodentium augment disease? To this end, A/JCr and C.B-17/IcrCrl-scidBr mice were inoculated with H. rodentium and/or H. hepaticus. Twelve weeks after inoculation, mice were euthanized. The cecum and liver were evaluated microscopically for evidence of disease. Cecal interferon-inducible protein 10 (IP-10), macrophage inflammatory protein 1alpha (MIP-1alpha), interleukin 10 (IL-10), and interferon gamma (IFN-gamma) mRNA values were measured as an indicator of mucosal immune response. Hepatic lesions were not identified in mice mono-infected with H. rodentium; likewise, cecal lesion scores were not significantly different from those of uninfected controls. With the exception of an increased IL-10 mRNA value in SCID mice, mean immune-related gene expression in H. rodentium mono-infected and uninfected control mice was not significantly different. In contrast, all mice infected with H. hepaticus developed moderate to severe hepatitis, significant increase in cecal lesion scores, and increased immune-related gene expression. The C.B-17/IcrCrl-scidBr mice co-infected with H. hepaticus and H. rodentium had liquid cecal contents and low terminal body weight. Further, compared with mice infected with H. hepaticus alone, co-infection was associated with significant increases of IL-10, MIP-1alpha, and IP-10 mRNA values in C.B-17/IcrCrl-scidBr and IFN-gamma and MIP-1alpha mRNA values in A/JCr mice. These results suggested that H. rodentium

  9. Application of HSVtk suicide gene to X-SCID gene therapy: ganciclovir treatment offsets gene corrected X-SCID B cells.

    Science.gov (United States)

    Uchiyama, Toru; Kumaki, Satoru; Ishikawa, Yoshinori; Onodera, Masafumi; Sato, Miki; Du, Wei; Sasahara, Yoji; Tanaka, Nobuyuki; Sugamura, Kazuo; Tsuchiya, Shigeru

    2006-03-10

    Recently, a serious adverse effect of uncontrolled clonal T cell proliferation due to insertional mutagenesis of retroviral vector was reported in X-SCID gene therapy clinical trial. To offset the side effect, we have incorporated a suicide gene into therapeutic retroviral vector for selective elimination of transduced cells. In this study, B-cell lines from two X-SCID patients were transduced with bicistronic retroviral vector carrying human gamma c chain cDNA and Herpes simplex virus thymidine kinase gene. After confirmation of functional reconstitution of the gamma c chain, the cells were treated with ganciclovir (GCV). The gamma c chain positive cells were eliminated under low concentration without cytotoxicity on untransduced cells and have not reappeared at least for 5 months. Furthermore, the gamma c chain transduced cells were still sensitive to GCV after five months. These results demonstrated the efficacy of the suicide gene therapy although further in vivo studies are required to assess feasibility of this approach in clinical trial.

  10. IL7R and RAG1/2 Genes Mutations/Polymorphisms in Patients SCID

    Directory of Open Access Journals (Sweden)

    Sepideh Safaei

    2011-06-01

    Full Text Available SCID disorder is major failure of the immune system, usually genetic. The aim of this study was on mutations detection of RAG1, RAG2, and IL7RG genes in SCID cases. Mutation detection was performed by PCR sequencing.Our results  indicated  that 13  mutations  were found  through  cases which  include 4 mutations in IL7R gene (T661I, I138V, T56A, C57W, 7 mutations in RAG1 (W896X, W204R, M324V, T731I, M1006V, K820R, and R249H, and 2 mutations in RAG2 gene (R229W, ΔT251.

  11. Hematopoietic stem cell gene therapy for adenosine deaminase deficient-SCID.

    Science.gov (United States)

    Aiuti, Alessandro; Brigida, Immacolata; Ferrua, Francesca; Cappelli, Barbara; Chiesa, Robert; Marktel, Sarah; Roncarolo, Maria-Grazia

    2009-01-01

    Gene therapy is a highly attractive strategy for many types of inherited disorders of the immune system. Adenosine deaminase (ADA) deficient-severe combined immunodeficiency (SCID) has been the target of several clinical trials based on the use of hematopoietic stem/progenitor cells engineered with retroviral vectors. The introduction of a low intensity conditioning regimen has been a crucial factor in achieving stable engrafment of hematopoietic stem cells and therapeutic levels of ADA-expressing cells. Recent studies have demonstrated that gene therapy for ADA-SCID has favorable safety profile and is effective in restoring normal purine metabolism and immune functions. Stem cell gene therapy combined with appropriate conditioning regimens might be extended to other genetic disorders of the hematopoietic system.

  12. Microenvironment-dependent phenotypic changes in a SCID mouse model for malignant mesothelioma

    OpenAIRE

    Eva eDarai-Ramqvist; Gustav eNilsonne; Carmen eFlores-Staino; Anders eHjerpe; Katalin eDobra

    2013-01-01

    Background and Aims: Malignant mesothelioma is an aggressive, therapy-resistant tumor. Mesothelioma cells may assume an epithelioid or a sarcomatoid phenotype, and presence of sarcomatoid cells predicts poor prognosis. In this study, we investigated differentiation of mesothelioma cells in a xenograft model, where mesothelioma cells of both phenotypes were induced to form tumors in SCID mice. Methods: Xenografts were established and thoroughly characterized using a comprehensive immunohistoch...

  13. Murine adenovirus infection of SCID mice induces hepatic lesions that resemble human Reye syndrome.

    OpenAIRE

    Pirofski, L.; Horwitz, M S; Scharff, M. D.; Factor, S. M.

    1991-01-01

    Murine adenovirus type 1 (MAV-1) infection of CB-17 SCID mice (which are homozygous for the severe combined immunodeficiency mutation) induces hepatic histopathologic and ultrastructural features that are strikingly similar to human Reye syndrome. Gross pathologic examination of MAV-1-infected mice revealed only pale yellow liver tissue. Histopathologic studies of tissue from MAV-1-infected mice revealed diffuse hepatic injury manifested by microvesicular fatty degenerative changes of hepatoc...

  14. Family dynamics and psychosocial functioning in children with SCI/D from Colombia, South America

    Science.gov (United States)

    Nicolais, Christina J.; Perrin, Paul B.; Panyavin, Ivan; Nicholls, Elizabeth G.; Olivera Plaza, Silvia Leonor; Quintero, Lorena Medina; Arango-Lasprilla, Juan Carlos

    2016-01-01

    Objective The purpose of this study was to examine the connections between family dynamics and the psychosocial functioning of children with spinal cord injuries and disorders (SCI/D). Design Cross-sectional. Setting Participants were recruited from communities in Neiva, Colombia. Participants Thirty children with SCI/D and their primary caregiver participated. Children were between 8 and 17 years of age, and had sustained their injury at least six months prior to data collection. Interventions NA. Outcome measures Participating children completed measures assessing their own psychosocial functioning (Children's Depression Inventory, Revised Children's Manifest Anxiety Scale-2, Pediatric Quality of Life Inventory), and their primary caregiver completed measures of family dynamics (Family Adaptability and Cohesion Evaluation Scale- Fourth Edition, Family Communication Scale, Family Assessment Device- General Functioning, Family Satisfaction Scale, Relationship-Focused Coping Scale). Results A correlation matrix showed a number of significant bivariate correlations between child and family variables, and three multiple regressions showed that family satisfaction, empathy, and flexibility significantly explained 27% of the variance in child worry; family satisfaction and communication explained 18% of the variance in child social anxiety; and family cohesion and communication explained 23% of the variance in child emotional functioning. Conclusions These findings highlight the importance of rehabilitation professionals considering the association between family dynamics and the psychosocial functioning of children with SCI/D when working with this population. PMID:25582185

  15. Intravenous injection of a foamy virus vector to correct canine SCID-X1.

    Science.gov (United States)

    Burtner, Christopher R; Beard, Brian C; Kennedy, Douglas R; Wohlfahrt, Martin E; Adair, Jennifer E; Trobridge, Grant D; Scharenberg, Andrew M; Torgerson, Troy R; Rawlings, David J; Felsburg, Peter J; Kiem, Hans-Peter

    2014-06-05

    Current approaches to hematopoietic stem cell (HSC) gene therapy involve the collection and ex vivo manipulation of HSCs, a process associated with loss of stem cell multipotency and engraftment potential. An alternative approach for correcting blood-related diseases is the direct intravenous administration of viral vectors, so-called in vivo gene therapy. In this study, we evaluated the safety and efficacy of in vivo gene therapy using a foamy virus vector for the correction of canine X-linked severe combined immunodeficiency (SCID-X1). In newborn SCID-X1 dogs, injection of a foamy virus vector expressing the human IL2RG gene resulted in an expansion of lymphocytes expressing the common γ chain and the development of CD3(+) T lymphocytes. CD3(+) cells expressed CD4 and CD8 coreceptors, underwent antigen receptor gene rearrangement, and demonstrated functional maturity in response to T-cell mitogens. Retroviral integration site analysis in 4 animals revealed a polyclonal pattern of integration in all dogs with evidence for dominant clones. These results demonstrate that a foamy virus vector can be administered with therapeutic benefit in the SCID-X1 dog, a clinically relevant preclinical model for in vivo gene therapy.

  16. Growth suppressive efficacy of human lak cells against human lung-cancer implanted into scid mice.

    Science.gov (United States)

    Teraoka, S; Kyoizumi, S; Suzuki, T; Yamakido, M; Akiyama, M

    1995-06-01

    The purpose of our study was to determine the efficacy of immunotherapy using human lymphokine activated killer (LAK) cells against a human-lung squamous-cell carcinoma cell line (RERF-LC-AI) implanted into severe combined immunodeficient (SCID) mice. A statistically significant growth suppressive effect on RERF-LC-AI implanted into SCID mice was observed when human LAK cells were administered into the caudal vein of the mice treated with a continuous supply (initiated prior to LAK cells injection) of rIL-2. The human LAK cells stained with PKH 2, a fluorescent dye, for later detection using flow cytometry were administered into the caudal vein of RERF-LC-AI bearing SCID mice; the cells persisted for 7 days in the implanted lung cancer tissue and in the mouse peripheral blood, but for 5 days in the mouse spleen. The number of infiltrated human LAK cells in each tissue increased dose-dependently with the number of injected cells. The results indicate that the antitumor effect most likely occurred during the early implantation period of the human LAK cells. These results demonstrate the applicability of this model to the in vivo study of human lung cancer therapy.

  17. Using ICR and SCID mice as animal models for smallpox to assess antiviral drug efficacy.

    Science.gov (United States)

    Titova, Ksenya A; Sergeev, Alexander A; Zamedyanskaya, Alena S; Galahova, Darya O; Kabanov, Alexey S; Morozova, Anastasia A; Bulychev, Leonid E; Sergeev, Artemiy A; Glotova, Tanyana I; Shishkina, Larisa N; Taranov, Oleg S; Omigov, Vladimir V; Zavjalov, Evgenii L; Agafonov, Alexander P; Sergeev, Alexander N

    2015-09-01

    The possibility of using immunocompetent ICR mice and immunodeficient SCID mice as model animals for smallpox to assess antiviral drug efficacy was investigated. Clinical signs of the disease did not appear following intranasal (i.n.) challenge of mice with strain Ind-3a of variola virus (VARV), even when using the highest possible dose of the virus (5.2 log10 p.f.u.). The 50 % infective doses (ID50) of VARV, estimated by the virus presence or absence in the lungs 3 and 4 days post-infection, were 2.7 ± 0.4 log10 p.f.u. for ICR mice and 3.5 ± 0.7 log10 p.f.u. for SCID mice. After i.n. challenge of ICR and SCID mice with VARV 30 and 50 ID50, respectively, steady reproduction of the virus occurred only in the respiratory tract (lungs and nose). Pathological inflammatory destructive changes were revealed in the respiratory tract and the primary target cells for VARV (macrophages and epithelial cells) in mice, similar to those in humans and cynomolgus macaques. The use of mice to assess antiviral efficacies of NIOCH-14 and ST-246 demonstrated the compliance of results with those described in scientific literature, which opens up the prospect of their use as an animal model for smallpox to develop anti-smallpox drugs intended for humans.

  18. Dynamic Tracking Human Mesenchymal Stem Cells Tropism following Smoke Inhalation Injury in NOD/SCID Mice

    Directory of Open Access Journals (Sweden)

    MeiJuan Song

    2016-01-01

    Full Text Available Multiple preclinical evidences have supported the potential value of mesenchymal stem cells (MSCs for treatment of acute lung injury (ALI. However, few studies focus on the dynamic tropism of MSCs in animals with acute lung injury. In this study, we track systemically transplanted human bone marrow-derived mesenchymal stem cells (hBMSCs in NOD/SCID mice with smoke inhalation injury (SII through bioluminescence imaging (BLI. The results showed that hBMSCs systemically delivered into healthy NOD/SCID mouse initially reside in the lungs and then partially translocate to the abdomen after 24 h. Compared with the uninjured control group treated with hBMSCs, higher numbers of hBMSCs were found in the lungs of the SII NOD/SCID mice. In both the uninjured and SII mice, the BLI signals in the lungs steadily decreased over time and disappeared by 5 days after treatment. hBMSCs significantly attenuated lung injury, elevated the levels of KGF, decreased the levels of TNF-α in BALF, and inhibited inflammatory cell infiltration in the mice with SII. In conclusion, our findings demonstrated that more systemically infused hBMSCs localized to the lungs in mice with SII. hBMSC xenografts repaired smoke inhalation-induced lung injury in mice. This repair was maybe due to the effect of anti-inflammatory and secreting KGF of hMSCs but not associated with the differentiation of the hBMSCs into alveolar epithelial cells.

  19. Dynamic Tracking Human Mesenchymal Stem Cells Tropism following Smoke Inhalation Injury in NOD/SCID Mice

    Science.gov (United States)

    Song, MeiJuan; Zhang, XiuWei; Sun, ShuLi; Xiao, PeiXin; Hou, ShiKe; Ding, Hui; Liu, ZiQuan; Dong, WenLong; Wang, JinQiang; Wang, Xue; Sun, ZhiGuang

    2016-01-01

    Multiple preclinical evidences have supported the potential value of mesenchymal stem cells (MSCs) for treatment of acute lung injury (ALI). However, few studies focus on the dynamic tropism of MSCs in animals with acute lung injury. In this study, we track systemically transplanted human bone marrow-derived mesenchymal stem cells (hBMSCs) in NOD/SCID mice with smoke inhalation injury (SII) through bioluminescence imaging (BLI). The results showed that hBMSCs systemically delivered into healthy NOD/SCID mouse initially reside in the lungs and then partially translocate to the abdomen after 24 h. Compared with the uninjured control group treated with hBMSCs, higher numbers of hBMSCs were found in the lungs of the SII NOD/SCID mice. In both the uninjured and SII mice, the BLI signals in the lungs steadily decreased over time and disappeared by 5 days after treatment. hBMSCs significantly attenuated lung injury, elevated the levels of KGF, decreased the levels of TNF-α in BALF, and inhibited inflammatory cell infiltration in the mice with SII. In conclusion, our findings demonstrated that more systemically infused hBMSCs localized to the lungs in mice with SII. hBMSC xenografts repaired smoke inhalation-induced lung injury in mice. This repair was maybe due to the effect of anti-inflammatory and secreting KGF of hMSCs but not associated with the differentiation of the hBMSCs into alveolar epithelial cells. PMID:27725837

  20. The SCID-hu mouse as a model for HIV-1 infection.

    Science.gov (United States)

    Aldrovandi, G M; Feuer, G; Gao, L; Jamieson, B; Kristeva, M; Chen, I S; Zack, J A

    1993-06-24

    During normal fetal ontogeny, one of the first organs to harbour CD4-positive cells is the thymus. This organ could therefore be one of the earliest targets infected by human immunodeficiency virus type 1 (HIV-1) in utero. HIV-1-infected cells and pathological abnormalities of the thymus have been seen in HIV-1-infected adults and children, and in some fetuses aborted from infected women. Studies of HIV-1 pathogenesis have been hampered by lack of a suitable animal model system. Here we use the SCID-hu mouse as a model to investigate the effect of virus infection on human tissue. The mouse is homozygous for the severe combined immunodeficiency (SCID) defect. The model is constructed by implanting human fetal liver and thymus under the mouse kidney capsule. A conjoint human organ develops, which allows normal maturation of human thymocytes. After direct inoculation of HIV-1 into these implants, we observed severe depletion of human CD4-bearing cells within a few weeks of infection. This correlated with increasing virus load in the implants. Thus the SCID-hu mouse may be a useful in vivo system for the study of HIV-1-induced pathology.

  1. BK Virus Nephropathy in Heart Transplant Recipients.

    Science.gov (United States)

    Joseph, Alin; Pilichowska, Monika; Boucher, Helen; Kiernan, Michael; DeNofrio, David; Inker, Lesley A

    2015-06-01

    Polyomavirus-associated nephropathy (PVAN) has become an important cause of kidney failure in kidney transplant recipients. PVAN is reported to affect 1% to 7% of kidney transplant recipients, leading to premature transplant loss in approximately 30% to 50% of diagnosed cases. PVAN occurring in the native kidneys of solid-organ transplant recipients other than kidney only recently has been noted. We report 2 cases of PVAN in heart transplant recipients, which brings the total of reported cases to 7. We briefly review the literature on the hypothesized causes of PVAN in kidney transplant recipients and comment on whether these same mechanisms also may cause PVAN in other solid-organ transplant recipients. PVAN should be considered in the differential diagnosis when evaluating worsening kidney function. BK viremia surveillance studies of nonkidney solid-organ recipients should be conducted to provide data to assist the transplantation community in deciding whether regular monitoring of nonkidney transplant recipients for BK viremia is indicated.

  2. AMS/DOE Fellowship Recipients

    Energy Technology Data Exchange (ETDEWEB)

    Armstrong, Stephanie [American Meteorological Society, Boston, MA (United States)

    2016-11-21

    The AMS/DOE graduate fellowships were awarded to three students entering their first year of graduate study. The funds allowed each student to take a full course load during their first of year of graduate study which helps each of them to enter the professional, scientific community at an earlier date. Each recipient is academically outstanding, received glowing references of support and demonstrated their strong desire to perform scientific research. As part of the fellowship, each of the students was invited to attend the AMS Annual Meeting where they got to participate in the AMS student conference, attend scientific sessions and visit the exhibition hall. In addition, a student awards luncheon was held where each of the recipients got to meet their sponsor and receive a certificate.

  3. Hypertension in Renal Allograft Recipients

    Directory of Open Access Journals (Sweden)

    Waiser Johannes

    1999-01-01

    Full Text Available Hypertension is a frequent complication after renal transplantation. It contributes to the considerable cardiovascular morbidity and mortality in renal allograft recipients. Additionally, it has a major impact on long-term allograft survival. The pathogenesis of post transplant hypertension is multifactorial. Besides common risk factors, renal allograft recipients accumulate specific risk factors related to the original renal disease, renal transplantation per se and the immunosuppressive regimen. Chronic allograft dysfunction is the main cause of post transplant hypertension. The introduction of calcineurin inhibitors, such as cyclosporine, has increased the prevalence of hypertension. At present, the growing manual of diagnostic and therapeutic tools enables us to adapt better antihypertensive therapy. Tight monitoring, individualization of the immunosuppressive protocol, inclusion of non-pharmacological measures and aggressive antihypertensive treatment should help to minimize the negative implications of post transplant hypertension. Probably, this goal can only be reached by "normalization" of systolic and diastolic blood pressure to below 135/85 mmHg.

  4. Recipient government control under pressure

    DEFF Research Database (Denmark)

    Jansson, Johanna

    -scale infrastructure refurbishment, a key feature of the government‟s agenda at the time. During the 2008-2009 renegotiation phase, the Congolese government‟s ability to exercise control was gradually weakened due to pressure from the traditional donors to rearrange priorities and move macroeconomic concerns, notably...... agenda to secure both Chinese funding and HIPC debt relief. The paper thus concludes that recipient government control was retained, although it was under heavy pressure....

  5. Demodicosis in Renal Transplant Recipients.

    Science.gov (United States)

    Chovatiya, R J; Colegio, O R

    2016-02-01

    Solid organ transplant recipients have an increased incidence of skin infections resulting from immunosuppression. Common pathogens include herpes simplex virus, varicella zoster virus, Gram-positive bacteria and dermatophytes; however, the contribution of multicellular parasitic organisms to dermatologic disease in this population remains less studied. Demodex folliculorum and brevis are commensal mites that reside on human skin. Proliferation of Demodex mites, or demodicosis, is associated with rosacea and rosacea-like disorders, particularly in immunocompromised populations, although their ability to cause disease is still the subject of debate. We present a case series of four renal transplant recipients with the singular chief complaint of acne rosacea who we diagnosed with demodicosis. Although one of the four patients showed complete resolution following initial antiparasitic therapy, the other three required subsequent antibacterial treatment to fully resolve their lesions. We suggest that demodicosis may be more prevalent than once thought in solid organ transplant recipients and showed that Demodex-associated acne rosacea can be effectively treated in this population.

  6. Occupations of SSI recipients who work.

    Science.gov (United States)

    Hemmeter, Jeffrey

    2009-01-01

    This article uses the 2007 American Community Survey to estimate the occupational distribution of Supplemental Security Income (SSI) disability recipients aged 18-61 who work, and it compares their occupational distribution with that of working nonrecipients with and without disabilities. Based on models of occupational choice for working SSI recipients and nonrecipients, predicted occupational distributions are also estimated to understand what occupations are available to SSI recipients. Unlike the nonrecipient populations that are largely composed of sales- and office-based occupations (25 percent), the most common occupations of SSI recipients who work are in services (34 percent) and production, transportation, and material moving (30 percent), although sales- and office-based occupations are also common for SSI recipients (22 percent). The occupational distribution of working SSI recipients is also more concentrated than that of nonrecipient populations. Dissimilarity indices are used to compare the predicted and actual occupational distributions of the SSI recipient population and nonrecipient populations. More than one-half of the difference between the occupations of working SSI recipients and nonrecipients can be explained by demographic characteristics, human capital, and disability type. Additionally, nonemployed SSI recipients have similar predicted occupational distributions as currently employed SSI recipients. Given the estimated occupational distributions and the average earnings of individuals in the most common occupations of SSI recipients, the results suggest that more targeted vocational training may provide expanded opportunities for employment.

  7. Establishment of Orthotopic Xuanwei Lung Cancer SCID Mouse Model 
and Analysis of Biological Properties

    Directory of Open Access Journals (Sweden)

    Yongchun ZHOU

    2012-08-01

    Full Text Available Background and objective The incidence of Xuanwei lung cancer ranks first in China, and its pathogenesis requires in-depth investigation. This study aims to establish an orthotopic Xuanwei lung cancer severe combined immunodeficiency (SCID mouse model and to provide a basic experimental platform for further study. Methods The Xuanwei lung cancer cell line XWLC-05 was inoculated into the lung tissue of SCID mice in high and low doses. The tumor formation rates, tumor characteristics, spontaneous metastases, and survival times of the mice were observed, taking a subcutaneously transplanted tumor as control. Results The tumor formation rates of the orthotopic transplantation of lung cancer cells in high and low doses were 81% and 83%, respectively, among which mice in the high-dose group appeared cachectic on day 13. Extensive invasion and adhesion were observed in the contralateral lung and thoracic cavity, but no distant metastasis was exhibited. Mice with low-dose cells in the orthotopic transplantation group appeared cachectic and distant metastasis occurred on day 25. The tumor formation rates in the subcutaneous inoculation group by the high and low doses of cells were 100% and 94.5%, respectively, and no distant metastasis was observed. The rate of metastasis within the orthotopic transplantation group and between the orthotopic and subcutaneous inoculation groups showed a significant difference (P<0.05. A significant difference was indicated by the survival rate within and between the groups (P<0.001. Conclusion We successfully established an orthotopic XWLC SCID mouse model, which lays the foundation for a more in-depth study.

  8. Tuberculosis in renal transplant recipients.

    Science.gov (United States)

    Lattes, R; Radisic, M; Rial, M; Argento, J; Casadei, D

    1999-06-01

    Tuberculosis (TB) has been described in kidney transplant recipients as an infection with predominantly pulmonary involvement. We report the impact of TB in kidney transplantation. Clinical records of adult kidney recipients, transplanted between 1 January 1986 and 31 December 1995 were analyzed for sex, age, graft origin, immunosuppressive therapy, TB sites, diagnostic methods and concomitant infections. Annual incidence, mean time of onset, relation to rejection treatment, tuberculin skin test (PPD) and outcome were analyzed. Patients with a history of TB or graft loss in the first month were excluded. TB was diagnosed in 14 of 384 (3.64%). Mean age at transplantation was 35 years. Twelve of these received the graft from a living donor. All had triple immunosuppression with cyclosporine. Ten had pulmonary TB, three extrapulmonary infection and one disseminated disease. In 13 cases an invasive diagnostic procedure was performed. Mycobacterium tuberculosis cultures were positive in all cases; microscopy revealed acid-fast bacilli (AFB) in 6, and adenosine deaminase was elevated in CSF and pleural effusion in 2. Annual incidence varied from 0% to 3.1%. At the time of TB presentation 8 patients had other concomitant infections (cytomegalovirus, nocardia, Pneumocystis carinii, disseminated herpes simplex virus). Median time of onset was 13 months. Diagnostic results became available post-mortem in 2 cases, and one had TB in a failing allograft. TB was treated with 4 drugs including rifampin in 10 patients. Cyclosporine was discontinued in one, lowered in one and increased in 8. During treatment 5 patients had rejection episodes. At 1 year, graft survival was 72.7% and patient survival 90.9%. TB was more prevalent when recipient and donor were both PPD positive. In summary: although TB is a growing threat in the transplant setting, early and aggressive diagnosis with meticulous monitoring of immunosuppression allows a successful outcome for both patient and graft

  9. Characterizing T Cells in SCID Patients Presenting with Reactive or Residual T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Atar Lev

    2012-01-01

    Full Text Available Introduction. Patients with severe combined immunodeficiency (SCID may present with residual circulating T cells. While all cells are functionally deficient, resulting in high susceptibility to infections, only some of these cells are causing autoimmune symptoms. Methods. Here we compared T-cell functions including the number of circulating CD3+ T cells, in vitro responses to mitogens, T-cell receptor (TCR repertoire, TCR excision circles (TREC levels, and regulatory T cells (Tregs enumeration in several immunodeficinecy subtypes, clinically presenting with nonreactive residual cells (MHC-II deficiency or reactive cells. The latter includes patients with autoreactive clonal expanded T cell and patients with alloreactive transplacentally maternal T cells. Results. MHC-II deficient patients had slightly reduced T-cell function, normal TRECs, TCR repertoires, and normal Tregs enumeration. In contrast, patients with reactive T cells exhibited poor T-cell differentiation and activity. While the autoreactive cells displayed significantly reduced Tregs numbers, the alloreactive transplacentally acquired maternal lymphocytes had high functional Tregs. Conclusion. SCID patients presenting with circulating T cells show different patterns of T-cell activity and regulatory T cells enumeration that dictates the immunodeficient and autoimmune manifestations. We suggest that a high-tolerance capacity of the alloreactive transplacentally acquired maternal lymphocytes represents a toleration advantage, yet still associated with severe immunodeficiency.

  10. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1.

    Science.gov (United States)

    Hacein-Bey-Abina, Salima; Garrigue, Alexandrine; Wang, Gary P; Soulier, Jean; Lim, Annick; Morillon, Estelle; Clappier, Emmanuelle; Caccavelli, Laure; Delabesse, Eric; Beldjord, Kheira; Asnafi, Vahid; MacIntyre, Elizabeth; Dal Cortivo, Liliane; Radford, Isabelle; Brousse, Nicole; Sigaux, François; Moshous, Despina; Hauer, Julia; Borkhardt, Arndt; Belohradsky, Bernd H; Wintergerst, Uwe; Velez, Maria C; Leiva, Lily; Sorensen, Ricardo; Wulffraat, Nicolas; Blanche, Stéphane; Bushman, Frederic D; Fischer, Alain; Cavazzana-Calvo, Marina

    2008-09-01

    Previously, several individuals with X-linked SCID (SCID-X1) were treated by gene therapy to restore the missing IL-2 receptor gamma (IL2RG) gene to CD34+ BM precursor cells using gammaretroviral vectors. While 9 of 10 patients were successfully treated, 4 of the 9 developed T cell leukemia 31-68 months after gene therapy. In 2 of these cases, blast cells contained activating vector insertions near the LIM domain-only 2 (LMO2) proto-oncogene. Here, we report data on the 2 most recent adverse events, which occurred in patients 7 and 10. In patient 10, blast cells contained an integrated vector near LMO2 and a second integrated vector near the proto-oncogene BMI1. In patient 7, blast cells contained an integrated vector near a third proto-oncogene,CCND2. Additional genetic abnormalities in the patients' blast cells included chromosomal translocations, gain-of-function mutations activating NOTCH1, and copy number changes, including deletion of tumor suppressor gene CDKN2A, 6q interstitial losses, and SIL-TAL1 rearrangement. These findings functionally specify a genetic network that controls growth in T cell progenitors. Chemotherapy led to sustained remission in 3 of the 4 cases of T cell leukemia, but failed in the fourth. Successful chemotherapy was associated with restoration of polyclonal transduced T cell populations. As a result, the treated patients continued to benefit from therapeutic gene transfer.

  11. Lymphoid regeneration from gene-corrected SCID-X1 subject-derived iPSCs.

    Science.gov (United States)

    Menon, Tushar; Firth, Amy L; Scripture-Adams, Deirdre D; Galic, Zoran; Qualls, Susan J; Gilmore, William B; Ke, Eugene; Singer, Oded; Anderson, Leif S; Bornzin, Alexander R; Alexander, Ian E; Zack, Jerome A; Verma, Inder M

    2015-04-02

    X-linked Severe Combined Immunodeficiency (SCID-X1) is a genetic disease that leaves newborns at high risk of serious infection and a predicted life span of less than 1 year in the absence of a matched bone marrow donor. The disease pathogenesis is due to mutations in the gene encoding the Interleukin-2 receptor gamma chain (IL-2Rγ), leading to a lack of functional lymphocytes. With the leukemogenic concerns of viral gene therapy there is a need to explore alternative therapeutic options. We have utilized induced pluripotent stem cell (iPSC) technology and genome editing mediated by TALENs to generate isogenic subject-specific mutant and gene-corrected iPSC lines. While the subject-derived mutant iPSCs have the capacity to generate hematopoietic precursors and myeloid cells, only wild-type and gene-corrected iPSCs can additionally generate mature NK cells and T cell precursors expressing the correctly spliced IL-2Rγ. This study highlights the potential for the development of autologous cell therapy for SCID-X1 subjects.

  12. Effect of clarythromycin on the distant metastases of human lung cancer cells in SCID mice.

    Science.gov (United States)

    Parajuli, P; Yano, S; Hanibuchi, M; Nokihara, H; Shinohara, T; Sone, S

    1998-02-01

    Recently, the use of macrolides is suggested to be therapeutically effective in prolonging the survival of patients with inoperable non-small cell lung cancer. The purpose of this study was to examine therapeutic effects of a macrolide, clarythromycin (CAM) on the metastastic developments of two different human non-small cell lung cancers (squamous cell lung carcinoma RERF-LC-AI, and adenocarcinoma PC-14) in severe combined immunodeficient (SCID) mice depleted or undepleted of natural killer (NK) cells, respectively. CAM, injected subcutaneously at doses of 5 and 10 mg/kg body weight/day from day 7 to 41 after i.v. inoculation of human lung cancer cells, was not effective in inhibiting their distant organ metastases in SCID mice. CAM at concentrations of less than 10 micrograms/ml did not have a direct influence on the proliferation of these tumor cells in vitro. Although CAM alone was not effective in augmenting NK activity, it augmented the IL-2-induced killer (LAK) activity against Daudi cells in vitro. These results suggest that CAM alone may not be enough to control the spread of non-small cell lung cancer in the patient with T cell dysfunction.

  13. Characterizing T cells in SCID patients presenting with reactive or residual T lymphocytes.

    Science.gov (United States)

    Lev, Atar; Simon, Amos J; Trakhtenbrot, Luba; Goldstein, Itamar; Nagar, Meital; Stepensky, Polina; Rechavi, Gideon; Amariglio, Ninette; Somech, Raz

    2012-01-01

    Patients with severe combined immunodeficiency (SCID) may present with residual circulating T cells. While all cells are functionally deficient, resulting in high susceptibility to infections, only some of these cells are causing autoimmune symptoms. Here we compared T-cell functions including the number of circulating CD3(+) T cells, in vitro responses to mitogens, T-cell receptor (TCR) repertoire, TCR excision circles (TREC) levels, and regulatory T cells (Tregs) enumeration in several immunodeficinecy subtypes, clinically presenting with nonreactive residual cells (MHC-II deficiency) or reactive cells. The latter includes patients with autoreactive clonal expanded T cell and patients with alloreactive transplacentally maternal T cells. MHC-II deficient patients had slightly reduced T-cell function, normal TRECs, TCR repertoires, and normal Tregs enumeration. In contrast, patients with reactive T cells exhibited poor T-cell differentiation and activity. While the autoreactive cells displayed significantly reduced Tregs numbers, the alloreactive transplacentally acquired maternal lymphocytes had high functional Tregs. SCID patients presenting with circulating T cells show different patterns of T-cell activity and regulatory T cells enumeration that dictates the immunodeficient and autoimmune manifestations. We suggest that a high-tolerance capacity of the alloreactive transplacentally acquired maternal lymphocytes represents a toleration advantage, yet still associated with severe immunodeficiency.

  14. Model Free Approach for Non-Isothermal Decomposition of Un-Irradiated and g-Irradiated Silver Acetate: New Route for Synthesis of Ag2O Nanoparticles

    Directory of Open Access Journals (Sweden)

    Naser M. Abd El-Salam

    2010-09-01

    Full Text Available Kinetic studies for the non-isothermal decomposition of unirradiated and γ‑irradiated silver acetate with 103 kGy total γ-ray doses were carried out in air. The results showed that the decomposition proceeds in one major step in the temperature range of (180–270 °C with the formation of Ag2O as solid residue. The non-isothermal data for un‑irradiated and γ-irradiated silver acetate were analyzed using Flynn-Wall-Ozawa (FWO and nonlinear Vyazovkin (VYZ iso-conversional methods. These free models on the investigated data showed a systematic dependence of Ea on a indicating a simple decomposition process. No significant changes in the thermal decomposition behavior of silver acetate were recorded as a result of γ-irradiation. Calcinations of γ-irradiated silver acetate (CH3COOAg at 200 °C for 2 hours only led to the formation of pure Ag2O mono-dispersed nanoparticles. X-ray diffraction, FTIR and SEM techniques were employed for characterization of the synthesized nanoparticles.

  15. Clinical characteristics and genetic profiles of 44 patients with severe combined immunodeficiency (SCID): report from Shanghai, China (2004-2011).

    Science.gov (United States)

    Yao, Chun-Mei; Han, Xiao-Hua; Zhang, Yi-Dan; Zhang, Hui; Jin, Ying-Ying; Cao, Rui-Ming; Wang, Xi; Liu, Quan-Hua; Zhao, Wei; Chen, Tong-Xin

    2013-04-01

    Severe combined immunodeficiency (SCID), a rare type of genetic associated immune disorder, is poorly characterized in mainland China. We retrospectively reviewed 44 patients with SCID who received treatment from 2004 to 2011 in Shanghai, China, and herein summarize their clinical manifestations and immunological and preliminary genetic features. The male-to-female ratio was 10:1. Twenty five patients presented with X-SCID symptoms. Only one patient was diagnosed before the onset of symptoms due to positive family history. The mean time of delay in the diagnosis of X-SCID was 2.69 months (range, 0.5-8.67). Thirty-seven of the 44 patients died by the end of 2011 with the mean age of death being 7.87 months (range, 1.33-31). Six patients received hematopoietic stem cell transplantation (HSCT); only one of them survived, who was transplanted twice. The time between onset and death was shorter in the HSCT-treated group compared with the untreated group (2.87 ± 1.28 and 3.34 ± 0.59 months, respectively), probably due to active infections during transplantation. Bacillus Calmette-Guérin (BCG) complications occurred in 14 of the 34 patients who received BCG vaccination. Transfusion-induced graft-versus-host disease occurred in 5 patients. Total 20 mutations in interleukin-2 receptor subunit gamma (IL2RG) were identified in 22 patients, including 11 novel mutations. Most patients were misdiagnosed before referred to our SCID Center. Therefore, establishing more diagnostic centers dedicated to the care of PID and accessible by primary immunodeficiency patients will facilitate early, correct diagnosis and better care of SCID in China.

  16. The Research of DSM - IV SCID in Psychological Autopsy.%DSM - IV临床定式访谈(SCID)在心理解剖诊断中的应用

    Institute of Scientific and Technical Information of China (English)

    许俊亭; 姜潮; 高岩; 刘启贵; 贾树华; 周莉

    2011-01-01

    目的 本研究主要评估SCID在心理解剖中进行精神疾病诊断时的可靠性、灵敏度和特异度问题.方法 对精神疾病住院患者进行SCID访谈(为患者SCID诊断),对患者亲属进行SCID访谈(为心理解剖SCID诊断).计算两种SCID诊断的重测信度,评分者信度以及心理解剖SCID诊断的灵敏度和特异度.结果 患者SCID诊断,除焦虑障碍外,临床常见精神障碍的重测信度及评分者信度都高于0.75;心理解剖SCID诊断的酒精相关障碍、精神病性障碍、双相障碍、抑郁障碍及焦虑障碍的重测信度及评分者信度都大于0.75;在所有轴Ⅰ的疾病中,除酒精滥用和恶劣心境外,心理解剖SCID诊断与患者SCID诊断一致性系数均大于0.6.心理解剖SCID诊断的特异度都大于88%,但敏感度都低于特异度.结论 研究表明SCID诊断具有较高的重测信度和评分者信度.心理解剖SCID诊断具有较好的灵敏度和特异度,与患者SCID诊断的一致性良好.%Objective The reliability, sensitivity, specificity and adoption of the Structured Clinical Interview for DSM - IV Axis I (SCID) in psychological autopsy were investigated. Method All subjects were the psychiatric patients in the No. 7 people * s hospital of Dalian. Diagnosis was made by patients SCID interview and by psychological autopsy SCID interview. Inter - rater reliability and test - retest reliability were assessed in 30 and 35 patients SCID diagnosis and psychological autopsy SCID diagnosis, respectively. Chi - square and kappa analysis were used to determine agreement of diagnoses. Results Kappa coefficients were above 0. 75 for alcohol - related disorders, psychiatric disorders, bipolar disorders and depression disorders for inter - rater and test -retest reliability in patients SCID diagnosis. Kappa coefficients were above 0. 75 for alcohol - related disorders, psychiatric disorders, bipolar disorders, depression disorders and anxiety disorders for inter

  17. A DNA-PKcs mutation in a radiosensitive T-B- SCID patient inhibits Artemis activation and nonhomologous end-joining

    NARCIS (Netherlands)

    M. van der Burg (Mirjam); H. IJspeert (Hanna); N.S. Verkaik (Nicole); T. Turul (Tuba); W.W. Wiegant (Wouter); K. Morotomi-Yano (Keiko); P.O. Mari (Pierre-Olivier); I. Tezcan (Ilhan); D.J. Chen (David); M.Z. Zdzienicka (Malgorzata); J.J.M. van Dongen (Jacques); D.C. van Gent (Dik)

    2009-01-01

    textabstractRadiosensitive T-B- severe combined immunodeficiency (RS-SCID) is caused by defects in the nonhomologous end-joining (NHEJ) DNA repair pathway, which results in failure of functional V(D)J recombination. Here we have identified the first human RS-SCID patient to our knowledge with a

  18. The Structured Clinical Interview for DSM-IV Childhood Diagnoses (Kid-SCID): first psychometric evaluation in a Dutch sample of clinically referred youths

    NARCIS (Netherlands)

    Roelofs, J.; Muris, P.; Braet, C.; Arntz, A.; Beelen, I.

    2015-01-01

    The Structured Clinical Interview for DSM-IV Childhood Disorders (Kid-SCID) is a semi-structured interview for the classification of psychiatric disorders in children and adolescents. This study presents a first evaluation of the psychometric properties of the Kid-SCID in a Dutch sample of children

  19. A DNA-PKcs mutation in a radiosensitive T-B- SCID patient inhibits Artemis activation and nonhomologous end-joining

    NARCIS (Netherlands)

    M. van der Burg (Mirjam); H. IJspeert (Hanna); N.S. Verkaik (Nicole); T. Turul (Tuba); W.W. Wiegant (Wouter); K. Morotomi-Yano (Keiko); P.O. Mari (Pierre-Olivier); I. Tezcan (Ilhan); D.J. Chen (David); M.Z. Zdzienicka (Malgorzata); J.J.M. van Dongen (Jacques); D.C. van Gent (Dik)

    2009-01-01

    textabstractRadiosensitive T-B- severe combined immunodeficiency (RS-SCID) is caused by defects in the nonhomologous end-joining (NHEJ) DNA repair pathway, which results in failure of functional V(D)J recombination. Here we have identified the first human RS-SCID patient to our knowledge with a DNA-

  20. Splenic T helper cell type 1 cytokine profile and extramedullary haematopoiesis in severe combined immunodeficient (scid) mice with inflammatory bowel disease (IBD)

    DEFF Research Database (Denmark)

    Bregenholt, S; Claesson, Mogens Helweg

    1998-01-01

    -transplanted scid mice with IBD. Increased fractions of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and IL-2-positive CD4+ T cells were found in the spleens of diseased mice compared with control mice. Moreover, a small but significant population of CD4+ T cells which stained positive...... for granulocyte-macrophage colony-stimulating factor (GM-CSF) was found in scid mice with IBD but was virtually absent in congenic non-scid control mice. Cloning of granulocyte/ macrophage colony-forming cells (G/M-CFC) revealed that both non-transplanted scid mice and scid mice with IBD had an 8-14-fold increase...

  1. Virus and autoantigen-specific CD4+ T cells are key effectors in a SCID mouse model of EBV-associated post-transplant lymphoproliferative disorders.

    Science.gov (United States)

    Linnerbauer, Stefanie; Behrends, Uta; Adhikary, Dinesh; Witter, Klaus; Bornkamm, Georg W; Mautner, Josef

    2014-05-01

    Polyclonal Epstein-Barr virus (EBV)-infected B cell line (lymphoblastoid cell lines; LCL)-stimulated T-cell preparations have been successfully used to treat EBV-positive post-transplant lymphoproliferative disorders (PTLD) in transplant recipients, but function and specificity of the CD4+ component are still poorly defined. Here, we assessed the tumor-protective potential of different CD4+ T-cell specificities in a PTLD-SCID mouse model. Injection of different virus-specific CD4+ T-cell clones showed that single specificities were capable of prolonging mouse survival and that the degree of tumor protection directly correlated with recognition of target cells in vitro. Surprisingly, some CD4+ T-cell clones promoted tumor development, suggesting that besides antigen recognition, still elusive functional differences exist among virus-specific T cells. Of several EBV-specific CD4+ T-cell clones tested, those directed against virion antigens proved most tumor-protective. However, enriching these specificities in LCL-stimulated preparations conferred no additional survival benefit. Instead, CD4+ T cells specific for unknown, probably self-antigens were identified as principal antitumoral effectors in LCL-stimulated T-cell lines. These results indicate that virion and still unidentified cellular antigens are crucial targets of the CD4+ T-cell response in this preclinical PTLD-model and that enriching the corresponding T-cell specificities in therapeutic preparations may enhance their clinical efficacy. Moreover, the expression in several EBV-negative B-cell lymphoma cell lines implies that these putative autoantigen(s) might also qualify as targets for T-cell-based immunotherapy of virus-negative B cell malignancies.

  2. Accumulation of xenotransplanted canine bone marrow cells in NOD/SCID/γc(null) mice with acute hepatitis induced by CCl4.

    Science.gov (United States)

    Kato, Takashi; Hisasue, Masaharu; Segawa, Kazuhito; Fujimoto, Ayumi; Makiishi, Eri; Neo, Sakurako; Yasuno, Kyohei; Kobayashi, Ryosuke; Tsuchiya, Ryo

    2013-07-31

    Bone marrow cell infusion (BMI) has recently been suggested as an effective therapy for refractory liver disease; however, the efficiency of BMI using canine bone marrow cells (cBMCs) has not been reported. We evaluated the accumulation potential of cBMCs in a mouse model of acute liver failure. Acute hepatitis was induced by carbon tetrachloride (CCl4) treatment in NOD/SCID/γc(null)(NOG) mice and wild-type (WT) C57BL mice, and the characteristics of liver dysfunction and the degree of hepatic injury and regeneration were compared between the two mouse models. Next, female CCl4-treated NOG mice were xenotransplanted with male PKH26-labeled cBMCs, and the potential of cBMCs to accumulate in injured liver tissue compartments was examined. Fluorescence microscopy was performed to histologically detect the infused cBMCs, and DNA polymerase chain reaction was performed for detection of the male Y chromosome (SRY gene) in the recipient female NOG mice. The number of PKH26-positive cBMCs transplanted in the liver tissue gradually increased in the NOG mice. The infused cBMCs were located in the necrotic area of the liver at an early stage after transplantation, and most had accumulated a week after transplantation. However, the therapeutic efficacy of the xenotransplantation remained unclear, because no significant differences were observed concerning the extent liver injury and regeneration between the cBMC-transplanted and saline control mice. These results suggest that cBMCs will specifically accumulate in injured liver tissue and that BMC transplantation may have the potential to repair liver deficiency.

  3. Chronic Myelogenous Leukemia Cells Contribute to the Stromal Myofibroblasts in Leukemic NOD/SCID Mouse In Vivo

    Directory of Open Access Journals (Sweden)

    Ryosuke Shirasaki

    2012-01-01

    Full Text Available We recently reported that chronic myelogenous leukemia (CML cells converted into myofibroblasts to create a microenvironment for proliferation of CML cells in vitro. To analyze a biological contribution of CML-derived myofibroblasts in vivo, we observed the characters of leukemic nonobese diabetes/severe combined immunodeficiency (NOD/SCID mouse. Bone marrow nonadherent mononuclear cells as well as human CD45-positive cells obtained from CML patients were injected to the irradiated NOD/SCID mice. When the chimeric BCR-ABL transcript was demonstrated in blood, human CML cells were detected in NOD/SCID murine bone marrow. And CML-derived myofibroblasts composed with the bone marrow-stroma, which produced significant amounts of human vascular endothelial growth factor A. When the parental CML cells were cultured with myofibroblasts separated from CML cell-engrafted NOD/SCID murine bone marrow, CML cells proliferated significantly. These observations indicate that CML cells make an adequate microenvironment for their own proliferation in vivo.

  4. Cytotoxic reactivity of gut lamina propria CD4+ alpha beta T cells in SCID mice with colitis

    DEFF Research Database (Denmark)

    Bonhagen, K; Thoma, S; Bland, P

    1996-01-01

    Polyclonal, mucosa-seeking memory/effector CD4+ T cells containing a large fraction of blasts activated in situ accumulate in the gut lamina propria of severe-combined immunodeficient (SCID) mice developing colitis after CD4+ T cell transplantation. CD4+ T cells isolated from different repopulated...

  5. Faster T-cell development following gene therapy compared with haploidentical HSCT in the treatment of SCID-X1.

    Science.gov (United States)

    Touzot, Fabien; Moshous, Despina; Creidy, Rita; Neven, Bénédicte; Frange, Pierre; Cros, Guilhem; Caccavelli, Laure; Blondeau, Johanna; Magnani, Alessandra; Luby, Jean-Marc; Ternaux, Brigitte; Picard, Capucine; Blanche, Stéphane; Fischer, Alain; Hacein-Bey-Abina, Salima; Cavazzana, Marina

    2015-06-04

    During the last decade, gene therapy via ex vivo gene transfer into autologous hematopoietic stem cells has emerged as a convincing therapy for severe combined immunodeficiency caused by ILR2G mutation (SCID-X1) despite the occurrence of genotoxicity caused by the integration of first-generation retroviral vectors. However, the place of gene therapy among the therapeutic armamentarium remains to be defined. We retrospectively analyze and compare clinical outcomes and immune reconstitution in 13 consecutive SCID-X1 patients having undergone haploidentical hematopoietic stem cell transplantation (HSCT) and 14 SCID-X1 patients treated with gene therapy over the same period at a single center level: the Necker Children's Hospital (Paris, France). Our results show a clear advantage in terms of T-cell development of gene therapy over HSCT with a mismatched donor. Patients treated with gene therapy display a faster T-cell reconstitution and a better long-term thymic output. Interestingly, this advantage of gene therapy vs haploidentical HSCT seems to be independent of the existence of clinical graft-versus-host disease in the latter condition. If data of safety are confirmed over the long term, gene therapy for SCID-X1 appears to be an equal, if not superior, alternative to haploidentical HSCT.

  6. Modulation of tumor response to photodynamic therapy in severe combined immunodeficient (SCID) mice by adoptively transferred lymphoid cells

    Science.gov (United States)

    Korbelik, Mladen; Krosl, Gorazd; Krosl, Jana; Dougherty, Graeme J.

    1996-04-01

    Photodynamic treatment, consisting of intravenous injection of PhotofrinR (10 mg/kg) followed by exposure to 110 J/cm2 of 630 plus or minus 10 nm light 24 hours later, cured 100% of EMT6 tumors (murine mammary sarcoma) growing in syngeneic immunocompetent BALB/C mice. In contrast, the same treatment produced no cures of EMT6 tumors growing in either nude or SCID mice (immunodeficient strains). EMT6 tumors growing in BALB/C and SCID mice showed no difference in either the level of PhotofrinR accumulated per gram of tumor tissue, or the extent of tumor cell killing during the first 24 hours post photodynamic therapy (PDT). In an attempt to improve the sensitivity to PDT of EMT6 tumors growing in SCID mice, these hosts were given either splenic T lymphocytes or whole bone marrow from BALB/C mice. The adoptive transfer of lymphocytes 9 days before PDT was successful in delaying tumor recurrence but produced no cures. A better improvement in PDT response was obtained with tumors growing in SCID mice reconstituted with BALB/C bone marrow (tumor cure rate of 63%). The results of this study demonstrate that, at least with the EMT6 tumor model, antitumor immune activity mediated by lymphoid cell populations makes an important contribution to the curative effect of PDT.

  7. Higher susceptibility of NOD/LtSz-scid Il2rg-/- NSG mice to xenotransplanted lung cancer cell lines

    Directory of Open Access Journals (Sweden)

    Kanaji N

    2014-10-01

    Full Text Available Nobuhiro Kanaji,1 Akira Tadokoro,1 Kentaro Susaki,1 Saki Yokokura,1 Kiyomi Ohmichi,2 Reiji Haba,2 Naoki Watanabe,1 Shuji Bandoh,1 Tomoya Ishii,1 Hiroaki Dobashi,1 Takuya Matsunaga11Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan; 2Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, JapanPurpose: No lung cancer xenograft model using non-obese diabetic (NOD-scid Il2rg-/- mice has been reported. The purpose of this study is to select a suitable mouse strain as a xenogenic host for testing tumorigenicity of lung cancer.Materials and methods: We directly compared the susceptibility of four immunodeficient mouse strains, c-nu, C.B-17 scid, NOD-scid, and NOD/LtSz-scid Il2rg-/- (NSG mice, for tumor formation from xenotransplanted lung cancer cell lines. Various numbers (101–105 cells/head of two lung cancer cell lines, A549 and EBC1, were subcutaneously inoculated and tumor sizes were measured every week up to 12 weeks.Results: When 104 EBC1 cells were inoculated, no tumor formation was observed in BALB/c-nu or C.B-17 scid mice. Tumors developed in two of the five NOD-scid mice (40% and in all the five NSG mice (100%. When 103 EBC1 cells were injected, no tumors developed in any strain other than NSG mice, while tumorigenesis was achieved in all the five NSG mice (100%, P=0.0079 within 9 weeks. NSG mice similarly showed higher susceptibility to xenotransplantation of A549 cells. Tumor formation was observed only in NSG mice after inoculation of 103 or fewer A549 cells (40% vs 0% in 15 NSG mice compared with others, respectively, P=0.0169. We confirmed that the engrafted tumors originated from inoculated human lung cancer cells by immunohistochemical staining with human cytokeratin and vimentin.Conclusion: NSG mice may be the most suitable strain for testing tumorigenicity of lung cancer, especially if only a few cells

  8. Establishment and evaluation of AML-SCID mice model%AML-SCID 小鼠模型的建立及鉴定*

    Institute of Scientific and Technical Information of China (English)

    贾秀红; 张艳君

    2013-01-01

    目的:筛选出高表达HOXA9、HOXA10基因的急性髓系白血病( Acute myeloid leukemia ,AML)细胞株,并建立AML模型,为研究HOXA9、HOXA10与AML的关系奠定基础。方法经RT-PCR检测HOXA9、HOXA10在U937、HL-60、NB4、Jur-kat中的表达情况,筛选出高表达的细胞株;外周血瑞氏染色、骨髓流式细胞仪、脏器HE染色鉴定移植性U937人白血病重度联合免疫缺陷( Severe combined immunodeficiency ,SCID)小鼠模型。结果 HOXA9、HOXA10在U937中均高表达,在HL-60、Jurkat中不表达(或表达水平较低),NB4高表达HOXA10;U937细胞在濒死小鼠骨髓细胞所占的比例为(20.62±9.66%)%,与对照组比较差异有统计学意义( P <0.05);病理检查发现 U937细胞可浸润肝、脾、肺、肾器官。结论 U937高表达HOXA9、HOXA10,是研究HOXA9、HOXA10基因与白血病关系的合适细胞株,并成功建立U937-SCID人M5型急性髓性白血病模型。%Objective To filter out the AML cell line with the HOXA9,HOXA10 gene high expression and establish the AML mod-el,so to lay the foundation for the study of the relationship between HOXA 9,HOXA10,and AML.Methods The expression of HOXA9 and HOXA10 mRNA in U937,HL-60,NB4,Jurkat were detected by reverse transcription PCR .A human leukemia model with severe combined immunodeficiency ( SCID) was intravenously inoculated with U 937 cells.Peripheral blood cells were stained by Wright stain , flow cytometry instrument analyze the ration of CD 45 positive cells in Bone marrow;organs were made into paraffin sections and then stained by Hematoxylin-eosin.Results HOXA9,HOXA10 mRNA level is high in U937 cells,whereas they cannot be detected in HL-60 or Jurkat cells.HOXA10 mRNA level was high in NB4 cells.The proportion of human CD45+cells reached(20.62 ±9.66%)% of bone marrow cells just prior to death of mice ,which was different from the control group obviously ( P﹤0.05 ) .Pathological examina

  9. Intestinal parasitic infections in renal transplant recipients

    Directory of Open Access Journals (Sweden)

    Mehdi Azami

    2010-02-01

    Full Text Available The impact of intestinal parasitic infection in renal transplant recipients requires careful consideration in the developing world. However, there have been very few studies addressing this issue in Iran. This study was conducted to determine the prevalence of intestinal parasitic infections in renal transplant recipients in Iran. Stool specimens from renal transplant recipients and control groups were obtained between June 2006 and January 2007. The samples screened for intestinal parasitic infections using direct smear, formalin-ether sedimentation, Sheather's flotation and modified Ziehl-Neelsen staining methods. Out of 150 renal transplant recipients, 33.3% (50, and out of 225 control group, 20% (45 were infected with one or more type of intestinal parasites. The parasites detected among patients included Entamoeba coli (10.6%, Endolimax nana (8.7%, Giardia lamblia (7.4%, Blastocystis spp. (4.7%, Iodamoeba butschlii (0.7%, Chilomastix mesnili (0.7% and Ascaris lumbricoides (0.7%. Multiple infections were more common among renal transplant recipients group (p < 0.05. This study highlights the importance of testing for intestinal parasites among Iranian renal transplant recipients. Routine examinations of stool samples for parasites would significantly benefit the renal transplant recipients by contributing to reduce severe infections.

  10. Intestinal parasitic infections in renal transplant recipients

    Directory of Open Access Journals (Sweden)

    Mehdi Azami

    Full Text Available The impact of intestinal parasitic infection in renal transplant recipients requires careful consideration in the developing world. However, there have been very few studies addressing this issue in Iran. This study was conducted to determine the prevalence of intestinal parasitic infections in renal transplant recipients in Iran. Stool specimens from renal transplant recipients and control groups were obtained between June 2006 and January 2007. The samples screened for intestinal parasitic infections using direct smear, formalin-ether sedimentation, Sheather's flotation and modified Ziehl-Neelsen staining methods. Out of 150 renal transplant recipients, 33.3% (50, and out of 225 control group, 20% (45 were infected with one or more type of intestinal parasites. The parasites detected among patients included Entamoeba coli (10.6%, Endolimax nana (8.7%, Giardia lamblia (7.4%, Blastocystis spp. (4.7%, Iodamoeba butschlii (0.7%, Chilomastix mesnili (0.7% and Ascaris lumbricoides (0.7%. Multiple infections were more common among renal transplant recipients group (p < 0.05. This study highlights the importance of testing for intestinal parasites among Iranian renal transplant recipients. Routine examinations of stool samples for parasites would significantly benefit the renal transplant recipients by contributing to reduce severe infections.

  11. HYPERTENSION IN RENAL ALLOGRAFT RECIPIENTS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To further evaluate the effect of hypertension on renal graft function, and the relationship between hypertension, hyperlipoidemia and ischemic heart disease. Methods 102 renal transplant recipients with a functioning renal graft for more than 1 year were enrolled in this study. Renal function was followed for the further 24 months. Results The overall prevalence of hypertension was 89.2%(91/102) and 36.2%(33/91) hypertensive patients had uncontrolled blood pressure. After 24 months those with high blood pressure had significantly higher Scr levels than normotensive patients (P<0.05). The number of different antihypertensive classes required was related to Scr (P<0.05). Plasma cholesterol levels in hypertension patients especially in blood pressure uncontrolled group were significantly elevated (P<0.01). Ischemic heart disease was more common in hypertensive patients (P<0.05). Cyclosporine A was associated with hypertension more frequently than azathioprine and FK506, whereas low-dose prednisolone did not appear to influence blood pressure. Conclusion The data further confirmed that hypertension was associated with hyperlipidemia and ischemic heart disease, and emerged as a predictor of renal graft dysfunction. Whether cyclosporine A should be converted to new immunosuppressive agents and which class of antihypertensive medication is more effective in this population remain open questions.

  12. Recipient Determinants Affecting Conjugational Promiscuity in Enterobacteriaceae

    DEFF Research Database (Denmark)

    Roer, Louise

    -værktøj der kan undersøge DNA sekvenser for kendte RM systemer (RM-Finder). Her viste det sig dog at bakteriernes indhold af RM systemer ikke kunne afspejles i udviklingen af Salmonella enterica, og andre faktorer må derfor spille ind. Ved at bestemme recipient potentialet for en kollektion af Salmonella...... enterica var det igen muligt at benytte hel-genom sekventering og bioinformatik til at undersøge gen-forskelle hos bakterierne der kunne forklare deres recipient potentiale. Indtil nu har det dog ikke været muligt at identificere enkelte recipient gener hos Salmonella enterica der har betydning for god...

  13. Urinary tract infection in kidney transplant recipients.

    Science.gov (United States)

    Chacón-Mora, Natalia; Pachón Díaz, Jerónimo; Cordero Matía, Elisa

    2016-04-21

    Infectious complications remain a major cause of morbidity and mortality among transplant recipients. Urinary tract infection (UTI) is the most common infectious complication in kidney transplant recipients with a reported incidence from 25% to 75%, varies widely likely due to differences in definition, diagnostic criteria, study design, and length of observation. We sought reviews the incidence and importance of urinary tract infection on graft survival, the microbiology with special emphasis on multidrug resistant microorganisms, the therapeutic management of UTI and the prophylaxis of recurrent UTI among solid organ transplant recipients, highlighting the need for prospective clinical trials to unify the clinical management in this population.

  14. IL-3 or IL-7 increases ex vivo gene transfer efficiency in ADA-SCID BM CD34+ cells while maintaining in vivo lymphoid potential.

    Science.gov (United States)

    Ficara, Francesca; Superchi, Daniela B; Hernández, Raisa Jofra; Mocchetti, Cristina; Carballido-Perrig, Nicole; Andolfi, Grazia; Deola, Sara; Colombo, Augusto; Bordignon, Claudio; Carballido, José M; Roncarolo, Maria Grazia; Aiuti, Alessandro

    2004-12-01

    To improve maintenance and gene transfer of human lymphoid progenitors for clinical use in gene therapy of adenosine deaminase (ADA)-deficient SCID we investigated several gene transfer protocols using various stem cell-enriched sources. The lymphoid differentiation potential was measured by an in vitro clonal assay for B/NK cells and in the in vivo SCID-hu mouse model. Ex vivo culture with the cytokines TPO, FLT3-ligand, and SCF (T/F/S) plus IL-3 or IL-7 substantially increased the yield of transduced bone marrow (BM) CD34(+) cells purified from ADA-SCID patients or healthy donors, compared to T/F/S alone. Moreover, the use of IL-3 or IL-7 significantly improved the maintenance of in vitro B cell progenitors from ADA-SCID BM cells and allowed the efficient transduction of B and NK cell progenitors. Under these optimized conditions transduced CD34(+) cells were efficiently engrafted into SCID-hu mice and gave rise to B and T cell progeny, demonstrating the maintenance of in vivo lymphoid reconstitution capacity. The protocol based on the T/F/S + IL-3 combination was included in a gene therapy clinical trial for ADA-SCID, resulting in long-term engraftment of stem/progenitor cells. Remarkably, gene-corrected BM CD34(+) cells obtained from one patient 4 and 11 months after gene therapy were capable of repopulating the lymphoid compartment of SCID-hu hosts.

  15. Cancer incidence in blood transfusion recipients

    DEFF Research Database (Denmark)

    Hjalgrim, Henrik; Edgren, Gustaf; Rostgaard, Klaus

    2007-01-01

    BACKGROUND: Blood transfusions may influence the recipients' cancer risks both through transmission of biologic agents and by modulation of the immune system. However, cancer occurrence in transfusion recipients remains poorly characterized. METHODS: We used computerized files from Scandinavian...... blood banks to identify a cohort of 888,843 cancer-free recipients transfused after 1968. The recipients were followed from first registered transfusion until the date of death, emigration, cancer diagnosis, or December 31, 2002, whichever came first. Relative risks were expressed as ratios...... of the observed to the expected numbers of cancers, that is, standardized incidence ratios (SIRs), using incidence rates for the general Danish and Swedish populations as a reference. All statistical tests were two-sided. RESULTS: During 5,652,918 person-years of follow-up, 80,990 cancers occurred...

  16. Types of Cancer Associated with Transplant Recipients

    Science.gov (United States)

    ... an option. Switching immunosuppression from a calcineurin inhibitor ( Cyclosporine , Tacrolimus ) to a Target-of-Rapamycin (TOR) inhibitor ( ... Douglas W. Post-Transplant De Novo Malignancies in Renal Transplant Recipients: The ... International 2006. Transplantation 70:1747-51, 2000. First ...

  17. Interview with Abel Prize Recipient Lennart Carleson

    DEFF Research Database (Denmark)

    Raussen, Martin; Skau, Christian

    2008-01-01

    Lennart Carleson was the recipient of the 2006 Abel Prize. On May 22, 2006, prior to the Abel Prize celebration in Oslo, Carleson was interviewed. The interview was later shown on Norwegian television.......Lennart Carleson was the recipient of the 2006 Abel Prize. On May 22, 2006, prior to the Abel Prize celebration in Oslo, Carleson was interviewed. The interview was later shown on Norwegian television....

  18. Antibody induction therapy for lung transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Møller, Christian H; Penninga, Ida Elisabeth Irene

    2013-01-01

    Lung transplantation has become a valuable and well-accepted treatment option for most end-stage lung diseases. Lung transplant recipients are at risk of transplanted organ rejection, and life-long immunosuppression is necessary. Clear evidence is essential to identify an optimal, safe...... and effective immunosuppressive treatment strategy for lung transplant recipients. Consensus has not yet been achieved concerning use of immunosuppressive antibodies against T-cells for induction following lung transplantation....

  19. Cytomegalovirus infection in transplant recipients

    Directory of Open Access Journals (Sweden)

    Luiz Sergio Azevedo

    2015-07-01

    Full Text Available Cytomegalovirus infection is a frequent complication after transplantation. This infection occurs due to transmission from the transplanted organ, due to reactivation of latent infection, or after a primary infection in seronegative patients and can be defined as follows: latent infection, active infection, viral syndrome or invasive disease. This condition occurs mainly between 30 and 90 days after transplantation. In hematopoietic stem cell transplantation in particular, infection usually occurs within the first 30 days after transplantation and in the presence of graft-versus-host disease. The major risk factors are when the recipient is cytomegalovirus seronegative and the donor is seropositive as well as when lymphocyte-depleting antibodies are used. There are two methods for the diagnosis of cytomegalovirus infection: the pp65 antigenemia assay and polymerase chain reaction. Serology has no value for the diagnosis of active disease, whereas histology of the affected tissue and bronchoalveolar lavage analysis are useful in the diagnosis of invasive disease. Cytomegalovirus disease can be prevented by prophylaxis (the administration of antiviral drugs to all or to a subgroup of patients who are at higher risk of viral replication or by preemptive therapy (the early diagnosis of viral replication before development of the disease and prescription of antiviral treatment to prevent the appearance of clinical disease. The drug used is intravenous or oral ganciclovir; oral valganciclovir; or, less frequently, valacyclovir. Prophylaxis should continue for 90 to 180 days. Treatment is always indicated in cytomegalovirus disease, and the gold-standard drug is intravenous ganciclovir. Treatment should be given for 2 to 3 weeks and should be continued for an additional 7 days after the first negative result for viremia.

  20. 40 CFR 35.9055 - Evaluation of recipient performance.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Evaluation of recipient performance. 35... Evaluation of recipient performance. The Regional Administrator will oversee each recipient's performance... schedule for evaluation in the assistance agreement and will evaluate recipient performance and...

  1. Towards a rAAV-based gene therapy for ADA-SCID: from ADA deficiency to current and future treatment strategies.

    Science.gov (United States)

    Silver, Jared N; Flotte, Terence R

    2008-07-01

    Adenosine deaminase deficiency fosters a rare, devastating pediatric immune deficiency with concomitant opportunistic infections, metabolic anomalies and multiple organ system pathology. The standard of care for adenosine deaminase deficient severe combined immune deficiency (ADA-SCID) includes enzyme replacement therapy or bone marrow transplantation. Gene therapies for ADA-SCID over nearly two decades have exclusively involved retroviral vectors targeted to lymphocytes and hematopoetic progenitors. These groundbreaking gene therapies represent a revolution in clinical medicine, but come with several challenges, including the risk of insertional mutagenesis. An alternative gene therapy for ADA-SCID may utilize recombinant adeno-associated virus vectors in vivo, with numerous target tissues, to foster ectopic expression and secretion of adenosine deaminase. This review endeavors to describe ADA-SCID, the traditional treatments, previous retroviral gene therapies, and primarily, alternative recombinant adeno-associated virus-based strategies to remedy this potentially fatal genetic disease.

  2. Appearance of Human Plasma Cells Following Differentiation of Human B Cells in NOD/SCID Mouse Spleen

    OpenAIRE

    2003-01-01

    Relatively little is known for the differentiation and maturation process of human B cells to plasma cells. This is particularly important in reconstitution work involving transfer of autoantibodies. To address this issue, we transplanted human peripheral blood mononuclear cells (PBMC) directly into the spleen of irradiated NOD/SCID mice depleted of natural killer cell activity. Within 6 weeks, naïve B cells differentiated into memory B cells and, importantly, the numbers of human CD138+ plas...

  3. Efficient targeting of a SCID gene by an engineered single-chain homing endonuclease.

    Science.gov (United States)

    Grizot, Sylvestre; Smith, Julianne; Daboussi, Fayza; Prieto, Jesús; Redondo, Pilar; Merino, Nekane; Villate, Maider; Thomas, Séverine; Lemaire, Laetitia; Montoya, Guillermo; Blanco, Francisco J; Pâques, Frédéric; Duchateau, Philippe

    2009-09-01

    Sequence-specific endonucleases recognizing long target sequences are emerging as powerful tools for genome engineering. These endonucleases could be used to correct deleterious mutations or to inactivate viruses, in a new approach to molecular medicine. However, such applications are highly demanding in terms of safety. Mutations in the human RAG1 gene cause severe combined immunodeficiency (SCID). Using the I-CreI dimeric LAGLIDADG meganuclease as a scaffold, we describe here the engineering of a series of endonucleases cleaving the human RAG1 gene, including obligate heterodimers and single-chain molecules. We show that a novel single-chain design, in which two different monomers are linked to form a single molecule, can induce high levels of recombination while safeguarding more effectively against potential genotoxicity. We provide here the first demonstration that an engineered meganuclease can induce targeted recombination at an endogenous locus in up to 6% of transfected human cells. These properties rank this new generation of endonucleases among the best molecular scissors available for genome surgery strategies, potentially avoiding the deleterious effects of previous gene therapy approaches.

  4. Microenvironment-dependent phenotypic changes in a SCID mouse model for malignant mesothelioma

    Directory of Open Access Journals (Sweden)

    Eva eDarai-Ramqvist

    2013-08-01

    Full Text Available Background and Aims: Malignant mesothelioma is an aggressive, therapy-resistant tumor. Mesothelioma cells may assume an epithelioid or a sarcomatoid phenotype, and presence of sarcomatoid cells predicts poor prognosis. In this study, we investigated differentiation of mesothelioma cells in a xenograft model, where mesothelioma cells of both phenotypes were induced to form tumors in SCID mice. Methods: Xenografts were established and thoroughly characterized using a comprehensive immunohistochemical panel, array comparative genomic hybridization of chromosome 3, fluorescent in situ hybridization and electron microscopy.Results: Epithelioid and sarcomatoid cells gave rise to xenografts of similar epithelioid morphology. While sarcomatoid-derived xenografts had higher growth rates, the morphology and expression of differentiation-related markers was similar between xenografts derived from both phenotypes. Array comparative genomic hybridization showed a convergent genotype for both xenografts, resembling the original aggressive sarcomatoid cell sub-line.Conclusions: Human mesothelioma xenografts from sarcomatoid and epithelioid phenotypes converged to a similar differentiation state, and genetic analyses suggested that clonal selection in the mouse microenvironment was a major contributing factor. This thoroughly characterized animal model can be used for further studies of molecular events underlying tumor cell differentiation.

  5. Taenia taeniaeformis larval product induces gastric mucosal hyperplasia in SCID mice.

    Science.gov (United States)

    Lagapa, Jose Trinipil G; Oku, Yuzaburo; Nonaka, Nariaki; Kamiya, Masao

    2002-02-01

    The effects of intraperitoneal implantation of Taenia taeniaeformis larvae and inoculation of in vitro larval products on gastric mucosa of SCID mice were investigated in this study. Mice surgically implanted with T. taeniaeformis larvae developed slight and moderate gastric hyperplasia. When in vitro cultured T. taeniaeformis larval excretory-secretory (TtLES) products containing 1 mg of protein were injected daily into mice, they caused gastropathy after 5-7 days. Mice injected daily with 0.5 mg of TtLES products also showed slight gastric hyperplasia after day 14 and 28. The gastropathy was characterized by reduction of both parietal and zymogenic cell number and increased number of alcian blue-periodic acid Schiff (AB-PAS)-positive cells and by two-fold extension of proliferative zone of gastric units. Larval implantation demonstrated a more potent effect in inducing gastropathy than did in vitro larval culture products. Significant decrease in number of parietal cells with concomitant increase of proliferative zone and AB-PAS-positive cell number indicated their important roles in inducing the hyperplastic lesion. Similarities with other gastropathies indicated that there is a common fundamental regulatory mechanism involved, and that the host response may not be specific to parasites. Present study validated the induction of gastric mucosal hyperplasia by larval ES products of T. taeniaeformis. This proved the hypothesis of previous studies suggesting the role of larvae-derived products in inducing gastric mucosal hyperplasia in T. taeniaeformis-infected rats.

  6. Proliferation and apoptosis of lamina propria CD4+ T cells from scid mice with inflammatory bowel disease

    DEFF Research Database (Denmark)

    Bregenholt, S; Reimann, J; Claesson, Mogens Helweg

    1998-01-01

    Scid mice transplanted with low numbers of syngeneic CD4+ T cells, develop a chronic and lethal inflammatory bowel disease (IBD) within 4-6 months. We have used in vivo 5-bromo2-deoxy-uridine (BrdU) labeling to assess the proliferation of lamina propria-derived CD4+ T cells in diseased scid mice....... The hourly rate of renewal of colonic lamina propria CD4+ T cells in diseased mice was 7% compared with 1.5% in normal BALB/c control mice. Transplantation of scid mice with in vitro activated CD4+ T cells accelerated the disease onset and development in a cell dose-dependent fashion when compared with non......-activated CD4+ T cells. In pulse-chase experiments it was shown that BrdU-labeled cells disappeared rapidly from the lamina propria of diseased mice. DNA analysis revealed that this was due to the presence of nearly four times as many apoptotic CD4+ T cells in diseased than in control mice. Further analyses...

  7. Vector integration is nonrandom and clustered and influences the fate of lymphopoiesis in SCID-X1 gene therapy.

    Science.gov (United States)

    Deichmann, Annette; Hacein-Bey-Abina, Salima; Schmidt, Manfred; Garrigue, Alexandrine; Brugman, Martijn H; Hu, Jingqiong; Glimm, Hanno; Gyapay, Gabor; Prum, Bernard; Fraser, Christopher C; Fischer, Nicolas; Schwarzwaelder, Kerstin; Siegler, Maria-Luise; de Ridder, Dick; Pike-Overzet, Karin; Howe, Steven J; Thrasher, Adrian J; Wagemaker, Gerard; Abel, Ulrich; Staal, Frank J T; Delabesse, Eric; Villeval, Jean-Luc; Aronow, Bruce; Hue, Christophe; Prinz, Claudia; Wissler, Manuela; Klanke, Chuck; Weissenbach, Jean; Alexander, Ian; Fischer, Alain; von Kalle, Christof; Cavazzana-Calvo, Marina

    2007-08-01

    Recent reports have challenged the notion that retroviruses and retroviral vectors integrate randomly into the host genome. These reports pointed to a strong bias toward integration in and near gene coding regions and, for gammaretroviral vectors, around transcription start sites. Here, we report the results obtained from a large-scale mapping of 572 retroviral integration sites (RISs) isolated from cells of 9 patients with X-linked SCID (SCID-X1) treated with a retrovirus-based gene therapy protocol. Our data showed that two-thirds of insertions occurred in or very near to genes, of which more than half were highly expressed in CD34(+) progenitor cells. Strikingly, one-fourth of all integrations were clustered as common integration sites (CISs). The highly significant incidence of CISs in circulating T cells and the nature of their locations indicate that insertion in many gene loci has an influence on cell engraftment, survival, and proliferation. Beyond the observed cases of insertional mutagenesis in 3 patients, these data help to elucidate the relationship between vector insertion and long-term in vivo selection of transduced cells in human patients with SCID-X1.

  8. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients.

    Science.gov (United States)

    Howe, Steven J; Mansour, Marc R; Schwarzwaelder, Kerstin; Bartholomae, Cynthia; Hubank, Michael; Kempski, Helena; Brugman, Martijn H; Pike-Overzet, Karin; Chatters, Stephen J; de Ridder, Dick; Gilmour, Kimberly C; Adams, Stuart; Thornhill, Susannah I; Parsley, Kathryn L; Staal, Frank J T; Gale, Rosemary E; Linch, David C; Bayford, Jinhua; Brown, Lucie; Quaye, Michelle; Kinnon, Christine; Ancliff, Philip; Webb, David K; Schmidt, Manfred; von Kalle, Christof; Gaspar, H Bobby; Thrasher, Adrian J

    2008-09-01

    X-linked SCID (SCID-X1) is amenable to correction by gene therapy using conventional gammaretroviral vectors. Here, we describe the occurrence of clonal T cell acute lymphoblastic leukemia (T-ALL) promoted by insertional mutagenesis in a completed gene therapy trial of 10 SCID-X1 patients. Integration of the vector in an antisense orientation 35 kb upstream of the protooncogene LIM domain only 2 (LMO2) caused overexpression of LMO2 in the leukemic clone. However, leukemogenesis was likely precipitated by the acquisition of other genetic abnormalities unrelated to vector insertion, including a gain-of-function mutation in NOTCH1, deletion of the tumor suppressor gene locus cyclin-dependent kinase 2A (CDKN2A), and translocation of the TCR-beta region to the STIL-TAL1 locus. These findings highlight a general toxicity of endogenous gammaretroviral enhancer elements and also identify a combinatorial process during leukemic evolution that will be important for risk stratification and for future protocol design.

  9. Effect of route of infection on outcome of Toxoplasma gondii infection in hu-PBL SCID mice.

    Science.gov (United States)

    Meyer, Desiree J; Allan, Jane E; Beaman, Miles H

    2013-03-01

    Toxoplasma gondii (T. gondii) causes serious infection, especially in immunocompromised hosts. The relevance of animal models of toxoplasmosis to human disease is unclear, but have indicated that the route of Toxoplasma infection may affect the outcome. A humanized model of toxoplasmosis of immunocompromised mice (i.e. hu-PBL SCID), using the intraperitoneal (IP) route demonstrated long-term engraftment of human cells and worsening of inflammation compared to controls. In this study, we examined the effect of route of infection on this hu-PBL SCID model using a Toxoplasma strain (i.e. DAG) isolated from an immunocompromised human. Oral infection led to an asymptomatic infection, whereas animals infected by the IP route succumbed more quickly to infection. Human cells, detected through species-specific β-actin mRNA, were not as prominent in IP-infected animals as compared to orally infected and uninfected animals. There was evidence of control of toxoplasmosis in some orally infected animals, and this was associated with the presence of human cells in multiple tissues. Thus, the route of infection dramatically affects the outcome of infection, either by affecting parasite replication or expansion of human immune cells. Further studies of oral Toxoplasma infection using hu-PBL SCID mice may help in developing chemotherapies and immunotherapeutic strategies for toxoplasmosis.

  10. Recovery and Biodistribution of Ex Vivo Expanded Human Erythroblasts Injected into NOD/SCID/IL2Rγnull mice

    Directory of Open Access Journals (Sweden)

    Barbara Ghinassi

    2011-01-01

    Full Text Available Ex vivo expanded erythroblasts (EBs may serve as advanced transfusion products provided that lodgment occurs in the macrophage-niche of the marrow permitting maturation. EBs expanded from adult and cord blood expressed the receptors (CXCR4, VLA-4, and P-selectin ligand 1 necessary for interaction with macrophages. However, 4-days following transfusion to intact NOD/SCID/IL2Rγnull mice, CD235apos EBs were observed inside CD235aneg splenic cells suggesting that they underwent phagocytosis. When splenectomized and intact NOD/SCID/IL2Rγnull mice were transfused using retrovirally labeled human EBs, human cells were visualized by bioluminescence imaging only in splenectomized animals. Four days after injection, human CD235apos cells were detected in marrow and liver of splenectomized mice but only in spleen of controls. Human CD235apos erythrocytes in blood remained low in all cases. These studies establish splenectomized NOD/SCID/IL2Rγnull mice as a suitable model for tracking and quantification of human EBs in vivo.

  11. Pegademase bovine (PEG-ADA for the treatment of infants and children with severe combined immunodeficiency (SCID

    Directory of Open Access Journals (Sweden)

    Claire Booth

    2009-06-01

    Full Text Available Claire Booth1,2, H Bobby Gaspar1,21Centre for Immunodeficiency, Molecular Immunology Unit, UCL Institute of Child Health, London, UK; 2Dept of Clinical Immunology, Great Ormond Street Hospital NHS Trust, London, UKAbstract: Adenosine deaminase deficiency (ADA is a rare, inherited disorder of purine metabolism characterized by immunodeficiency, failure to thrive and metabolic abnormalities. A lack of the enzyme ADA allows accumulation of toxic metabolites causing defects of both cell mediated and humoral immunity leading to ADA severe combined immune deficiency (SCID, a condition that can be fatal in early infancy if left untreated. Hematopoietic stem cell transplant is curative but is dependent on a good donor match. Other therapeutic options include enzyme replacement therapy (ERT with pegademase bovine (PEG-ADA and more recently gene therapy. PEG-ADA has been used in over 150 patients worldwide and has allowed stabilization of patients awaiting more definitive treatment with hematopoietic stem cell transplant. It affords both metabolic detoxification and protective immune function with patients remaining clinically well, but immune reconstitution is often suboptimal and may not be long lived. We discuss the pharmacokinetics, immune reconstitution, effects on systemic disease and side effects of treatment with PEG-ADA. We also review the long-term outcome of patients receiving ERT and discuss the role of PEG-ADA in the management of infants and children with ADA-SCID, alongside other therapeutic options.Keywords: adenosine deaminase deficiency, PEG-ADA, enzyme replacement therapy, severe combined immune deficiency (SCID

  12. Identification of a nonsense mutation in the carboxyl-terminal region of DNA-dependent protein kinase catalytic subunit in the scid mouse.

    Science.gov (United States)

    Blunt, T; Gell, D; Fox, M; Taccioli, G E; Lehmann, A R; Jackson, S P; Jeggo, P A

    1996-01-01

    DNA-dependent protein kinase (DNA-PK) consists of a heterodimeric protein (Ku) and a large catalytic subunit (DNA-PKcs). The Ku protein has double-stranded DNA end-binding activity that serves to recruit the complex to DNA ends. Despite having serine/threonine protein kinase activity, DNA-PKcs falls into the phosphatidylinositol 3-kinase superfamily. DNA-PK functions in DNA double-strand break repair and V(D)J recombination, and recent evidence has shown that mouse scid cells are defective in DNA-PKcs. In this study we have cloned the cDNA for the carboxyl-terminal region of DNA-PKcs in rodent cells and identified the existence of two differently spliced products in human cells. We show that DNA-PKcs maps to the same chromosomal region as the mouse scid gene. scid cells contain approximately wild-type levels of DNA-PKcs transcripts, whereas the V-3 cell line, which is also defective in DNA-PKcs, contains very reduced transcript levels. Sequence comparison of the carboxyl-terminal region of scid and wild-type mouse cells enabled us to identify a nonsense mutation within a highly conserved region of the gene in mouse scid cells. This represents a strong candidate for the inactivating mutation in DNA-PKcs in the scid mouse. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8816792

  13. Human immune system development and survival of non-obese diabetic (NOD)-scid IL2rγ(null) (NSG) mice engrafted with human thymus and autologous haematopoietic stem cells.

    Science.gov (United States)

    Covassin, L; Jangalwe, S; Jouvet, N; Laning, J; Burzenski, L; Shultz, L D; Brehm, M A

    2013-12-01

    Immunodeficient mice bearing targeted mutations in the IL2rg gene and engrafted with human immune systems are effective tools for the study of human haematopoiesis, immunity, infectious disease and transplantation biology. The most robust human immune model is generated by implantation of human fetal thymic and liver tissues in irradiated recipients followed by intravenous injection of autologous fetal liver haematopoietic stem cells [often referred to as the BLT (bone marrow, liver, thymus) model]. To evaluate the non-obese diabetic (NOD)-scid IL2rγ(null) (NSG)-BLT model, we have assessed various engraftment parameters and how these parameters influence the longevity of NSG-BLT mice. We observed that irradiation and subrenal capsule implantation of thymus/liver fragments was optimal for generating human immune systems. However, after 4 months, a high number of NSG-BLT mice develop a fatal graft-versus-host disease (GVHD)-like syndrome, which correlates with the activation of human T cells and increased levels of human immunoglobulin (Ig). Onset of GVHD was not delayed in NSG mice lacking murine major histocompatibility complex (MHC) classes I or II and was not associated with a loss of human regulatory T cells or absence of intrathymic cells of mouse origin (mouse CD45(+) ). Our findings demonstrate that NSG-BLT mice develop robust human immune systems, but that the experimental window for these mice may be limited by the development of GVHD-like pathological changes.

  14. Opportunistic infections in a renal transplant recipient

    Directory of Open Access Journals (Sweden)

    Vijaya V. Mysorekar

    2012-01-01

    Full Text Available With the present progress in transplantation procedures, there is an improvement in patient and allograft survival. However, the immunosuppression necessary to sustain the allograft predisposes these transplant recipients to infection, which is now a significant cause of morbidity and mortality. We describe a case of a 30-year-old renal transplant recipient with two opportunistic infections, namely, primary cutaneous aspergillosis and intestinal tuberculosis, with terminal enterococcal pleuritis and peritonitis. Control of the degree of immunosuppression, and prompt recognition and treatment of infection are vital for successful organ transplantation.

  15. NOD/scid IL-2Rgnull mice: a preclinical model system to evaluate human dendritic cell-based vaccine strategies in vivo

    Directory of Open Access Journals (Sweden)

    Spranger Stefani

    2012-02-01

    Full Text Available Abstract Background To date very few systems have been described for preclinical investigations of human cellular therapeutics in vivo. However, the ability to carry out comparisons of new cellular vaccines in vivo would be of substantial interest for design of clinical studies. Here we describe a humanized mouse model to assess the efficacy of various human dendritic cell (DC preparations. Two reconstitution regimes of NOD/scid IL2Rgnull (NSG mice with adult human peripheral blood mononuclear cells (PBMC were evaluated for engraftment using 4-week and 9-week schedules. This led to selection of a simple and rapid protocol for engraftment and vaccine evaluation that encompassed 4 weeks. Methods NSG recipients of human PBMC were engrafted over 14 days and then vaccinated twice with autologous DC via intravenous injection. Three DC vaccine formulations were compared that varied generation time in vitro (3 days versus 7 days and signals for maturation (with or without Toll-like receptor (TLR3 and TLR7/8 agonists using MART-1 as a surrogate antigen, by electroporating mature DC with in vitro transcribed RNA encoding full length protein. After two weekly vaccinations, the splenocyte populations containing human lymphocytes were recovered 7 days later and assessed for MART-1-specific immune responses using MHC-multimer-binding assays and functional assessment of specific killing of melanoma tumor cell lines. Results Human monocyte-derived DC generated in vitro in 3 days induced better MART-1-specific immune responses in the autologous donor T cells present in the humanized NSG mice. Moreover, consistent with our in vitro observations, vaccination using mature DC activated with TLR3 and TLR7/8 agonists resulted in enhanced immune responses in vivo. These findings led to a ranking of the DC vaccine effects in vivo that reflected the hierarchy previously found for these mature DC variations in vitro. Conclusions This humanized mouse model system enables

  16. Bone metastasis model with multiorgan dissemination of human small-cell lung cancer (SBC-5) cells in natural killer cell-depleted SCID mice.

    Science.gov (United States)

    Miki, T; Yano, S; Hanibuchi, M; Sone, S

    2000-01-01

    Lung cancer is commonly associated with multiorgan metastasis, and bone is a frequent metastatic site for lung cancer. Nevertheless, no bone metastasis model of lung cancer with multiorgan dissemination is available, which could provide opportunity to study the molecular pathogenesis. We examined the abilities of eight human lung cancer cell lines injected intravenously into natural killer (NK) cell-depleted SCID mice to generate metastatic nodules in bone and multiple organs, and explored the correlation of the parathyroid hormone-related protein (PTHrP) with the bone metastasis. Although all the small-cell carcinoma cell lines (SBC-5, SBC-3, SBC-3/ADM, H69, H69/VP) formed metastatic nodules in multiple organs (liver, kidney, and lymph nodes), only SBC-5 cells reproducibly developed bone metastases. Squamous cell carcinoma (RERF-LC-AI) cells metastasized mainly into the liver and kidneys, whereas adenocarcinoma (PC-14, A549) mainly produced colonies in the lungs. As assessed by X-ray photography, the osteolytic bone metastases produced by SBC-5 cells were detected as early as on day 28, and all recipient mice developed bone metastasis by day 35. The expression of PTHrP in eight cell lines was directly correlated with the formation of bone metastasis. No correlation was observed between the formation of bone metastasis and the expression of other metastasis-related cytokines (IL-1, IL-6, IL-8, IL-10, IL-11, TNF-alpha, VEGF, M-CSF). Consistent with the formation of bone metastasis by SBC-5 cells, the levels of PTHrP and calcium in the mouse serum were increased in a time-dependent manner, suggesting that PTHrP produced by human lung cancer may play a crucial role in the formation of bone metastasis and hypercalcemia. These findings indicate that a bone metastasis model of SBC-5 cells may be useful for clarifying the molecular aspects of the metastatic processes in different organ microenvironments and the development of therapeutic modalities for lung cancer

  17. Radiation induced synthesis of In{sub 2}O{sub 3} nanoparticles - Part II: Synthesis of In{sub 2}O{sub 3} nanoparticles by thermal decomposition of un-irradiated and γ-irradiated indium acetylacetonate

    Energy Technology Data Exchange (ETDEWEB)

    Al-Resheedi, Ajayb Saud; Alhokbany, Norah Saad [Department of Chemistry, College of Science, King Saud University, KSU, (Saudi Arabia); Mahfouz, Refaat Mohammed, E-mail: rmhfouz@science.au.edu.eg [Chemistry Department, Faculty of Science, Assiut University, AUN, (Egypt)

    2015-09-15

    Pure cubic phase, In{sub 2}O{sub 3} nanoparticles with porous structure were synthesized by solid state thermal oxidation of un-irradiated and γ-irradiated indium acetyl acetonate in presence and absence of sodium dodecyl sulphate as surfactant. The as- synthesized In{sub 2}O{sub 3} nanoparticles were characterized by X-ray diffraction (XRD), fourier transformation infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transition electron microscopy (TEM) and thermogravimetry (TG). The shapes and morphologies of as- synthesized In{sub 2}O{sub 3} nanoparticles were highly affected by γ-irradiation of indium acetyl acetonate precursor and by addition of sodium dodecyl sulphate as surfactant. Calcination of un-irradiated indium acetyl acetonate precursor to 4 hours of 600 °C leads to the formation of spherical- shaped accumulative and merged In{sub 2}O{sub 3} nanoparticles with porous structure, whereas irregular porous architectures composed of pure In{sub 2}O{sub 3} nanoparticles were obtained by using γ-irradiated indium acetylacetonate precursor. The as- prepared In{sub 2}O{sub 3} nano products exhibit photoluminescence emission (PL) property and display thermal stability in a wide range of temperature (25-800 °C) which suggest possible applications in nanoscale optoelectronic devices. (author)

  18. SLAM family predicting the initiation potential of human acute lymphoblastic leukemia in NOD/SCID mice

    Institute of Scientific and Technical Information of China (English)

    WANG Na; ZHOU Jian-feng; HUANG Liang; XIAO Fei; LIU Jin-ping; WANG Di; GENG Zhe; WANG Jin; MA Shu-yan; SHU Li-li; CHEN Tai-ping

    2011-01-01

    Background The SLAM family recently has been reported to show an important biological role in lymphocyte development and immunological function, and it is efficient to highly purify hematopoietic stem cells using a simple combination of SLAM family members. To elucidate the presence of this family on acute lymphoblastic leukemia (ALL),as well as its relationship with the leukemia-initiating potential, we analyzed the expression pattern of this family members on human ALL progenitor cells, combined with serial xenotransplantation assay.Methods Expression analysis was carried out by flow cytometry. We combined the expression pattern of human CD150,CD244 and CD48 with serial xenotransplantation of B-ALL progenitor cells to indicate their relationship.Results CD48 and CD244 were expressed on most B-ALL progenitor cells, the percentage being (93.08±6.46)% and (63.37±29.31)%, respectively. Interestingly, the proportion of CD150+ cells declined obviously in engrafted cases ((24.94±7.32)%) compared with non-engrafted cases ((77.54±5.93)%, P <0.01), which indicated that only blast cells with low percentage of CD150+ population were able to reconstitute leukemia into primary, secondary and tertiary NOD/SCID mice.Conclusions SLAM family members are present on B-ALL progenitor cells and the leukemia-initiating potential of leukemic blasts is correlated negatively with the proportion of CD150+ cells, the percentage of which can serve as a useful predictor for engraftment success of B-ALL to immune deficient mice.

  19. Human-derived IgG level as an indicator for EBV-associated lymphoma model in Hu-PBL/SCID chimeras.

    Science.gov (United States)

    Tang, Yunlian; He, Rongfang; Zhang, Yang; Liu, Fang; Cheng, Ailan; Wu, Yimou; Gan, Runliang

    2011-05-09

    Epstein-Barr virus (EBV) has a close association with various types of human lymphomas. Animal models are essential to elucidate the pathogenesis of human EBV-associated lymphomas. The aim of the present study is to evaluate the association between human IgG concentration and EBV-associated lymphoma development in huPBL/SCID mice. Human peripheral blood lymphocytes (hu-PBL) from EBV-seropositive donors were inoculated intraperitoneally into SCID mouse. Immunohistochemical staining was used to examine differentiated antigens of tumor cells. EBV infection of the induced tumors was detected by in situ hybridization. IgG concentrations in the serums of 12 SCID mice were measured by unidirectional immunodiffusion assay. 21 out of 29 mice developed tumors in their body. Immunohistochemical staining showed that all induced tumors were LCA (leukocyte common antigen) positive, B-cell markers (CD20, CD79a) positive, and T-cell markers (both CD3 and CD45RO) negative. The tumors can be diagnosed as human B-cell lymphomas by these morphological and immunohistochemical features. In situ hybridization exhibited resultant tumor cells had EBV encoded small RNA-1 (EBER-1). Human-derived IgG could be found in the serum from SCID mice on the 15th day following hu-PBL transplantation, and IgG levels increased with the tumor development in 6 hu-PBL/SCID chimeras. Intraperitoneal transfer of hu-PBLs from EBV+ donors to SCID mice leads to high human IgG levels in mouse serum and B cell lymphomas. Our findings suggest that increasing levels of human-derived IgG in peripheral blood from hu-PBL/SCID mice could be used to monitor EBV-related human B-cell lymphoma development in experimental animals.

  20. Interview with Abel Prize Recipient Lennart Carleson

    DEFF Research Database (Denmark)

    Raussen, Martin; Skau, Christian

    2007-01-01

    Lennart Carleson is the recipient of the 2006 Abel Prize of the Norwegian Academy of Science and Letters. On May 22, 2006, prior to the Abel Prize celebration i Oslo, Carleson was interviewed by Martin Raussen of Aalborg University and Christian Skau of the Norwegian University of Science...

  1. 45 CFR 2543.41 - Recipient responsibilities.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient responsibilities. 2543.41 Section 2543.41 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON...

  2. Intestinal Parasitic Infections in Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    EB Kia

    2007-07-01

    Full Text Available Background: Organ transplant recipients can experience serious diseases from infections due to emerging and reemerging parasitic infections. This study was carried out to evaluate the prevalence of intestinal parasites among renal transplant re-cipients of Iran. "nMethods: This cross-sectional study was conducted from June 2003 to August 2004 on renal transplant recipients in Iran. A total of 706 fecal samples obtained from randomly selected population originated from all over Iran. Patient's information was recorded in a questionnaire before sampling. A sample of stool was taken from each person. Direct wet smear exami-nation, formalin-ether concentration, Ziehl-neelsen staining, and agar plate culture were done for each sample. "nResults: Totally 32 patients (4.5% were positive for parasitic infections. In searching for emerging parasitic infections, the most prevalent parasites were found to be Blastocystis hominis, Giardia lamblia and Entamoeba coli, respectively. The merely ova which were seen were related to Hymenolepis nana. With investigation of healthy control, no significant differ-ence was found between transplanted and normal population. "nConclusion: The population showed controlled rate of intestinal infections probably due to regular awareness concerning risks of opportunistic infections; albeit regular surveillance through routine examination of stool samples for parasites seems considerably advantages the transplant recipient patients.

  3. Hyperthyroidism in a renal transplant recipient.

    Science.gov (United States)

    Peces, R; Navascués, R A; Baltar, J; Laurés, A S; Ortega, F; Alvarez-Grande, J

    1998-01-01

    We report a case of toxic multinodular goiter with severe symptomatic hyperthyroidism in a female diagnosed 5 months after successful renal transplantation. To our knowledge, this is the first well-documented case of hyperthyroidism in a renal transplant recipient that responded well to methimazole. Special attention should be made to the use of methimazole and the possible interaction with immunosuppressive drugs.

  4. Recipient twin limb ischemia with postnatal onset.

    Science.gov (United States)

    Broadbent, Roland Spencer

    2007-02-01

    After the occurrence of 3 local cases of limb ischemia in newborn twins, we reviewed the literature to investigate this combination systematically. This review reveals a distinct condition: postnatal onset limb ischemia affecting recipient twins in twin-twin transfusion syndrome.

  5. The kinetics of early T and B cell immune recovery after bone marrow transplantation in RAG-2-deficient SCID patients.

    Directory of Open Access Journals (Sweden)

    Atar Lev

    Full Text Available The kinetics of T and B cell immune recovery after bone marrow transplantation (BMT is affected by many pre- and post-transplant factors. Because of the profoundly depleted baseline T and B cell immunity in recombination activating gene 2 (RAG-2-deficient severe combined immunodeficiency (SCID patients, some of these factors are eliminated, and the immune recovery after BMT can then be clearly assessed. This process was followed in ten SCID patients in parallel to their associated transplant-related complications. Early peripheral presence of T and B cells was observed in 8 and 4 patients, respectively. The latter correlated with pre-transplant conditioning therapy. Cells from these patients carried mainly signal joint DNA episomes, indicative of newly derived B and T cells. They were present before the normalization of the T cell receptor (TCR and the B cell receptor (BCR repertoire. Early presentation of the ordered TCR gene rearrangements after BMT occurred simultaneously, but this pattern was heterogeneous over time, suggesting different and individual thymic recovery processes. Our findings early after transplant could suggest the long-term patients' clinical outcome. Early peripheral presence of newly produced B and T lymphocytes from their production and maturation sites after BMT suggests donor stem cell origin rather than peripheral expansion, and is indicative of successful outcome. Peripheral detection of TCR excision circles and kappa-deleting recombination excision circles in RAG-2-deficient SCID post-BMT are early markers of T and B cell reconstitution, and can be used to monitor outcome and tailor specific therapy for patients undergoing BMT.

  6. Clinical-scale expansion of CD34(+) cord blood cells amplifies committed progenitors and rapid scid repopulation cells.

    Science.gov (United States)

    Casamayor-Genescà, Alba; Pla, Arnau; Oliver-Vila, Irene; Pujals-Fonts, Noèlia; Marín-Gallén, Sílvia; Caminal, Marta; Pujol-Autonell, Irma; Carrascal, Jorge; Vives-Pi, Marta; Garcia, Joan; Vives, Joaquim

    2017-03-25

    Umbilical cord blood (UCB) transplantation is associated with long periods of aplastic anaemia. This undesirable situation is due to the low cell dose available per unit of UCB and the immaturity of its progenitors. To overcome this, we present a cell culture strategy aimed at the expansion of the CD34(+) population and the generation of granulocyte lineage-committed progenitors. Two culture products were produced after either 6 or 14days of in vitro expansion, and their characteristics compared to non-expanded UCB CD34(+) controls in terms of phenotype, colony-forming activity and multilineage repopulation potential in NOD-scid IL2Rγ(null) mice. Both expanded cell products maintained rapid SCID repopulation activity similar to the non-expanded control, but 14-day cultured cells showed impaired long term SCID repopulation activity. The process was successfully scaled up to clinically relevant doses of 89×10(6) CD34(+) cells committed to the granulocytic lineage and 3.9×10(9) neutrophil precursors in different maturation stages. Cell yields and biological properties presented by the cell product obtained after 14days in culture were superior and therefore this is proposed as the preferred production setup in a new type of dual transplant strategy to reduce aplastic periods, producing a transient repopulation before the definitive engraftment of the non-cultured UCB unit. Importantly, human telomerase reverse transcriptase activity was undetectable, c-myc expression levels were low and no genetic abnormalities were found, as determined by G-banding karyotype, further confirming the safety of the expanded product.

  7. Dexamethasone/1alpha-25-dihydroxyvitamin D3-treated dendritic cells suppress colitis in the SCID T-cell transfer model

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Schmidt, Esben Gjerløff Wedebye; Gad, Monika

    2008-01-01

    severe combined immunodeficient (SCID) mice adoptively transferred with CD4(+) CD25(-) T cells from the development of wasting disease and colitis. We therefore established an in vitro test that could predict the in vivo function of DCs and improve strategies for the preparation of immunomodulatory DCs...... in this model. Based on these in vitro findings, we here evaluate three methods for DC generation including short-term and long-term IL-10 exposure or DC exposure to dexamethasone in combination with vitamin D3 (Dex/D3). All DCs resulted in lower CD4(+) CD25(-) T-cell enteroantigen-specific responses in vitro...

  8. Experimental Support for the Ecoimmunity Theory: Distinct Phenotypes of Nonlymphocytic Cells in SCID and Wild-Type Mice.

    Science.gov (United States)

    Ochayon, David E; Baranovski, Boris M; Malkin, Peter; Schuster, Ronen; Kalay, Noa; Ben-Hamo, Rotem; Sloma, Ido; Levinson, Justin; Brazg, Jared; Efroni, Sol; Lewis, Eli C; Nevo, Uri

    2016-01-01

    Immune tolerance toward "self" is critical in multiple immune disorders. While there are several mechanisms to describe the involvement of immune cells in the process, the role of peripheral tissue cells in that context is not yet clear. The theory of ecoimmunity postulates that interactions between immune and tissue cells represent a predator-prey relationship. A lifelong interaction, shaped mainly during early ontogeny, leads to selection of nonimmune cell phenotypes. Normally, therefore, nonimmune cells that evolve alongside an intact immune system would be phenotypically capable of evading immune responses, and cells whose phenotype falls short of satisfying this steady state would expire under hostile immune responses. This view was supported until recently by experimental evidence showing an inferior endurance of severe combined immunodeficiency (SCID)-derived pancreatic islets when engrafted into syngeneic immune-intact wild-type (WT) mice, relative to islets from WT. Here we extend the experimental exploration of ecoimmunity by searching for the presence of the phenotypic changes suggested by the theory. Immune-related phenotypes of islets, spleen, and bone marrow immune cells were determined, as well as SCID and WT nonlymphocytic cells. Islet submass grafting was performed to depict syngeneic graft functionality. Islet cultures were examined under both resting and inflamed conditions for expression of CD40 and major histocompatibility complex (MHC) class I/II and release of interleukin-1α (IL-1α), IL-1β, IL-6, tumor necrosis factor-α (TNF-α), IL-10, and insulin. Results depict multiple pathways that appear to be related to the sculpting of nonimmune cells by immune cells; 59 SCID islet genes displayed relative expression changes compared with WT islets. SCID cells expressed lower tolerability to inflammation and higher levels of immune-related molecules, including MHC class I. Accordingly, islets exhibited a marked increase in insulin release upon

  9. Sustaining expression of B domain-deleted human factor VIII mediated by using lentiviral vectors in NOD/SCID mouse.

    Science.gov (United States)

    Li, Yan-Jie; Chen, Chong; Zeng, Ling-Yu; Cao, Jiang; Xu, Kai-Lin

    2012-06-01

    Recently, gene therapy has been become a promising approach to cure hemophilia A, a most common recessive bleeding disease. The aim of this study was to determine the perspective of lentiviral vector in hemophilia A gene therapy in vitro and in NOD/SCID mice. Lentivirus transfer vector pXZ9/BDDFVIII containing human B-domain-deleted Factor VIII-IRES-eGFP coding sequence and mock control pXZ9 were constructed. Lentivirus was prepared by co-transfecting 3 plasmids into 293FT cells. 293FT, HLF, human bone marrow mesenchymal stem cells and Chang-liver cells were transfected with the prepared virus. Coagulant activity of human FVIII, human FVIII antigen, human FVIII mRNA transcription and genomic integration were assayed by ELISA, one-step method, RT-PCR and PCR after infection. Lentiviral particles were concentrated by ultracentrifugation and NOD/SCID mice were transfected via portal vein injection. Human FVIII antigen in mouse blood plasma was analyzed by ELISA. eGFP expression was observed by fluorescent microscopy and human FVIII transcription in mouse liver was analyzed by RT-PCR at one month after transduction. The results showed that the high titer of recombinant virus was prepared and used to efficiently transduce the target cells in vitro. At 72 h after transfection, high levels of FVIII activity and FVIII antigen were detected. Human FVIII gene transcription could be detected in the liver of NOD/SCID mice received lentiviral particles carrying FVIII gene. Mouse hepatocytes were transfected with recombinant lentivirus efficiently in vivo. Human FVIII level in mouse blood plasma reached to (49 ± 6) mU, (54 ± 8) mU and (23 ± 4) mU at 72 h, one week and one month after transfection respectively. It is concluded that the lentiviral particles carrying BDDhFVIII gene can high efficiently transfect the target cells both in vitro and in vivo, and the transfected target cells can secrete hFVIII efficiently. The sustained expression of human FVIII in NOD/SCID mice is

  10. Suicide gene therapy of human breast cancer in SCID mice model by the regulation, of Tet-On

    Institute of Scientific and Technical Information of China (English)

    胡维新; 曾赵军; 罗赛群; 陈迁

    2004-01-01

    Background RevTet-On gene expression system was used to deliver the suicide gene tk to human breast cancer cell line MCF-7 and control the tk gene expression level. The animal model of human breast cancer on severe combined immune deficiency (SCID) mice was set up to explore the suicide gene therapy by the regulation of Tet-On.Methods Herpes simplex virus-thymidine kinase (HSVtk) gene was inserted into the plasmid pRevTRE and the recombinant retroviral vector pRevTRE/HSVtk was constructed. Using modified calcium phosphate co-precipitation method, two transfections, pRevTRE/HSVtk and pRevTet-On were performed for MCF-7 cell line and selected by hygromycin B and G418. MCF-7 cell line that stably expressed Tet-regulated tk gene was established. HSVtk gene expression in the MCF/TRE/tk/Tet-On cell line was under the control of Doxycycline (Dox). Cell viability was also determined by MTT assay, whereas HSVtk gene expression was analyzed by reverse transcription-PCR (RT-PCR).Results MCF/TRE/tk/Tet-On cell survival rate was decreased from 100% to less than 20% when ganciclovir (GCV) concentration was increased from 0 to 1000 μg/ml at 1 μg/ml of Dox after 72 hours of GCV administration. At 1 μg/ml of GCV concentration, the cell numbers decreased from 7104 cells/ml to 2×104 cells/ml when Dox concentration was increased from 0 to 1500 ng/ml after 72 hours culture. In addition, bystander effects were generated in vitro when 10%-25% of transduced MCF-7 cells were mixed in untransduced MCF-7 cells. On the other hand, the human breast cancer models in SCID mice were set up. The tk gene was expressed with the regulated character after MCF/TRE/tk/Tet-On cells were implanted into the female SCID mice 7 days after Dox induction followed by intraperitoneally administration of GCV for 23 days. Subcutaneous tumors in SCID mice that were implanted with MCF/TRE/tk/Tet-On cells shrank remarkably after Dox and GCV administration as compared with the control.Conclusion The human breast

  11. 10 CFR 603.215 - Recipient's commitment and cost sharing.

    Science.gov (United States)

    2010-01-01

    ... cost sharing. The purpose of cost sharing is to ensure that the recipient incurs real risk that gives... 10 Energy 4 2010-01-01 2010-01-01 false Recipient's commitment and cost sharing. 603.215 Section... AGREEMENTS Appropriate Use of Technology Investment Agreements § 603.215 Recipient's commitment and cost...

  12. 34 CFR 110.15 - Affirmative action by recipients.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Affirmative action by recipients. 110.15 Section 110.15... ASSISTANCE Standards for Determining Age Discrimination § 110.15 Affirmative action by recipients. Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome...

  13. 43 CFR 17.315 - Affirmative action by recipients.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Affirmative action by recipients. 17.315... Standards for Determining Age Discrimination § 17.315 Affirmative action by recipients. Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome the effects...

  14. 45 CFR 91.16 - Affirmative action by recipient.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Affirmative action by recipient. 91.16 Section 91... for Determining Age Discrimination § 91.16 Affirmative action by recipient. Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome the effects of...

  15. Intrahepatic transplantation of CD34+ cord blood stem cells into newborn and adult NOD/SCID mice induce differential organ engraftment.

    Science.gov (United States)

    Wulf-Goldenberg, Annika; Keil, Marlen; Fichtner, Iduna; Eckert, Klaus

    2012-04-01

    In vivo studies concerning the function of human hematopoietic stem cells (HSC) are limited by relatively low levels of engraftment and the failure of the engrafted HSC preparations to differentiate into functional immune cells after systemic application. In the present paper we describe the effect of intrahepatically transplanted CD34(+) cells from cord blood into the liver of newborn or adult NOD/SCID mice on organ engraftment and differentiation. Analyzing the short and long term time dependency of human cell recruitment into mouse organs after cell transplantation in the liver of newborn and adult NOD/SCID mice by RT-PCR and FACS analysis, a significantly high engraftment was found after transplantation into liver of newborn NOD/SCID mice compared to adult mice, with the highest level of 35% human cells in bone marrow and 4.9% human cells in spleen at day 70. These human cells showed CD19 B-cell, CD34 and CD38 hematopoietic and CD33 myeloid cell differentiation, but lacked any T-cell differentiation. HSC transplantation into liver of adult NOD/SCID mice resulted in minor recruitment of human cells from mouse liver to other mouse organs. The results indicate the usefulness of the intrahepatic application route into the liver of newborn NOD/SCID mice for the investigation of hematopoietic differentiation potential of CD34(+) cord blood stem cell preparations.

  16. Immunosuppression in the elderly renal allograft recipient

    DEFF Research Database (Denmark)

    Montero, Nuria; Pérez-Sáez, María José; Pascual, Julio

    2016-01-01

    avoidance using mycophenolate mofetil (MMF). Observational cohort studies looked at different antibody induction strategies, calcineurin-inhibitors based maintenance immunosuppression, calcineurin-inhibitor-free sirolimus-based therapy and use of MMF versus azathioprine. Treatment with interleukin-2...... receptor antibody induction, calcineurin-inhibitor minimization with MMF and steroid minimization is advisable in the low immunologic risk elderly recipient, considering the increased risk of toxicities, infection and malignancies. In the high immunologic risk elderly recipient, taking into account...... the morbid consequences of acute rejection in the elderly, observational studies support antibody induction with depletive antibodies, calcineurin-inhibitor, MMF and steroids; calcineurin-inhibitor-minimization is not recommended. CONCLUSIONS: There is very limited evidence for the benefits and harms...

  17. Strongyloides stercoralis infection in kidney transplant recipients.

    Science.gov (United States)

    Abdalhamid, Baha A; Al Abadi, Abdul Naser M; Al Saghier, Mohammed I; Joudeh, Amani A; Shorman, Mahmoud A; Amr, Samir S

    2015-01-01

    Strongyloides stercoralis is an uncommon infection in Saudi Arabia. It can establish latency and cause an autoinfection in humans that lasts for years. The infection can get reactivated during immunosuppression and can result in a life-threatening Strongyloides hyperinfection syndrome. We present three cases of renal transplant recipients who developed Strongyloides infection following transplantation. A bronchoalveolar lavage specimen, a duodenal biopsy and/or a stool specimen from these patients revealed evidence of S. stercoralis larvae. The first two patients received kidneys from the same deceased donor, a native of Bangladesh, an area that is highly endemic for S. stercoralis. The data suggest that the first two cases might be donor derived. High-risk donors and recipients should be screened for Strongyloides infection to initiate treatment before transplantation thus reducing morbidity and mortality.

  18. Cardiovascular disease in renal transplant recipients.

    Science.gov (United States)

    McQuarrie, Emily P; Fellström, Bengt C; Holdaas, Hallvard; Jardine, Alan G

    2010-05-01

    Renal transplant recipients have a markedly increased risk of premature cardiovascular disease (CVD) compared with the general population, although considerably lower than that of patients receiving maintenance haemodialysis. CVD in transplant recipients is poorly characterised and differs from the nonrenal population, with a much higher proportion of fatal to nonfatal cardiac events. In addition to traditional ischaemic heart disease risk factors such as age, gender, diabetes and smoking, there are additional factors to consider in this population such as the importance of hypertension, left ventricular hypertrophy and uraemic cardiomyopathy. There are factors specific to transplantation such immunosuppressive therapies and graft dysfunction which contribute to this altered risk profile. However, understanding and treatment is limited by the absence of large randomised intervention trials addressing risk factor modification, with the exception of the ALERT study. The approach to managing these patients should begin early and be multifactorial in nature.

  19. Whooping cough in a renal transplant recipient.

    Science.gov (United States)

    Garbiras, M; Shabaka, A; Calvo, N; Martin, L; Moreno, M A; Lopez de la Manzanara, V; Sanchez-Fructuoso, A I

    2016-04-01

    Whooping cough is a respiratory infection with a severity that varies with age, immune status, and probably with other factors such as the degree of exposure and the virulence of the organism. The most frequent microorganism responsible for whooping cough is Bordetella pertussis. We present the case of a 62-year-old renal transplant recipient presenting with typical and severe manifestations of whooping cough caused by B. pertussis.

  20. E2f1-deficient NOD/SCID mice have dry mouth due to a change of acinar/duct structure and the down-regulation of AQP5 in the salivary gland.

    Science.gov (United States)

    Satoh, Keitaro; Narita, Takanori; Matsuki-Fukushima, Miwako; Okabayashi, Ken; Ito, Tatsuro; Senpuku, Hidenobu; Sugiya, Hiroshi

    2013-02-01

    Non-obese diabetic (NOD) mice have been used as a model for dry mouth. NOD mice lacking the gene encoding E2f1, a transcription factor, develop hyposalivation more rapidly progressively than control NOD mice. However, the model mice are associated with an underlying disease such as diabetes. We have now established E2f1-deficient NOD/severe combined immunodeficiency disease (NOD/SCID.E2f1(-/-)) mice to avoid the development of diabetes (Matsui-Inohara et al., Exp Biol Med (Maywood) 234(12):1525-1536, 2009). In this study, we investigated the pathophysiological features of dry mouth using NOD/SCID.E2f1(-/-) mice. In NOD/SCID.E2f1(-/-) mice, the volume of secreted saliva stimulated with pilocarpine is about one third that of control NOD/SCID mice. In behavioral analysis, NOD/SCID.E2f1(-/-) mice drank plenty of water when they ate dry food, and the frequency and time of water intake were almost double compared with control NOD/SCID mice. Histological analysis of submandibular glands with hematoxylin-eosin stain revealed that NOD/SCID.E2f1(-/-) mice have more ducts than NOD/SCID mice. In western blot analysis, the expression of aquaporin 5 (AQP5), a marker of acinar cells, in parotid and in submandibular glands of NOD/SCID.E2f1(-/-) mice was lower than in NOD/SCID mice. Immunohistochemical analysis of parotid and submandibular acini revealed that the localization of AQP5 in NOD/SCID.E2f1(-/-) mice differs from that in NOD/SCID mice; AQP5 was leaky and diffusively localized from the apical membrane to the cytosol in NOD/SCID.E2f1(-/-) mice. The ubiquitination of AQP5 was detected in submandibular glands of NOD/SCID.E2f1(-/-) mice. These findings suggest that the change of acinar/duct structure and the down-regulation of AQP5 in the salivary gland cause the pathogenesis of hyposalivation in NOD/SCID.E2f1(-/-) mice.

  1. Toxoplasmosis in cord blood transplantation recipients.

    Science.gov (United States)

    Bautista, G; Ramos, A; Forés, R; Regidor, C; Ruiz, E; de Laiglesia, A; Navarro, B; Bravo, J; Portero, F; Sanjuan, I; Fernández, M N; Cabrera, R

    2012-10-01

    Toxoplasmosis is a devastating opportunistic infection that can affect immunocompromised patients such as cord blood transplantation (CBT) recipients. The clinical characteristics of 4 toxoplasmosis CBT patients treated at our institution are reviewed, together with 5 cases collected from the literature. The rate of toxoplasmosis in our hospital was 6% in CBT recipients and 0.2% in other types of allogeneic hematopoietic stem cell transplantation (P < 0.001). Five patients (56%) presented disseminated toxoplasmosis and 4 patients (44%) had localized infection in the central nervous system. In 5 of the 9 patients considered (56%), cytomegalovirus viral replication had been detected before the clinical onset of toxoplasmosis. Seven patients (78%) had previously developed graft-versus-host disease. All patients who exhibited disseminated disease died due to Toxoplasma infection. Pre-transplant serology was positive in 1 patient, negative in 3 patients, and not performed in another. Only 1 of these 5 patients with disseminated disease had received Toxoplasma prophylaxis with cotrimoxazole. It could be concluded that mortality in CBT patients with disseminated toxoplasmosis is unacceptably high. The negative results of serology in the majority of these cases, and its unspecific clinical presentation, makes diagnosis exceedingly difficult. Better diagnostic tests and prophylaxis strategy are needed in CBT recipients.

  2. Systemic correction of storage disease in MPS I NOD/SCID mice using the sleeping beauty transposon system.

    Science.gov (United States)

    Aronovich, Elena L; Bell, Jason B; Khan, Shaukat A; Belur, Lalitha R; Gunther, Roland; Koniar, Brenda; Schachern, Patricia A; Parker, Josh B; Carlson, Cathy S; Whitley, Chester B; McIvor, R Scott; Gupta, Pankaj; Hackett, Perry B

    2009-07-01

    The Sleeping Beauty (SB) transposon system is a nonviral vector that directs transgene integration into vertebrate genomes. We hydrodynamically delivered SB transposon plasmids encoding human alpha-L-iduronidase (hIDUA) at two DNA doses, with and without an SB transposase gene, to NOD.129(B6)-Prkdc(scid) IDUA(tm1Clk)/J mice. In transposon-treated, nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice with mucopolysaccharidosis type I (MPS I), plasma IDUA persisted for 18 weeks at levels up to several hundred-fold wild-type (WT) activity, depending on DNA dose and gender. IDUA activity was present in all examined somatic organs, as well as in the brain, and correlated with both glycosaminoglycan (GAG) reduction in these organs and level of expression in the liver, the target of transposon delivery. IDUA activity was higher in the treated males than in females. In females, omission of transposase source resulted in significantly lower IDUA levels and incomplete GAG reduction in some organs, confirming the positive effect of transposition on long-term IDUA expression and correction of the disease. The SB transposon system proved efficacious in correcting several clinical manifestations of MPS I in mice, including thickening of the zygomatic arch, hepatomegaly, and accumulation of foamy macrophages in bone marrow and synovium, implying potential effectiveness of this approach in treatment of human MPS I.

  3. Suppression subtractive hybridization method for the identification of a new strain of murine hepatitis virus from xenografted SCID mice.

    Science.gov (United States)

    Islam, Mohammed M; Toohey, Brendan; Purcell, Damian F J; Kannourakis, George

    2015-12-01

    During attempts to clone retroviral determinants associated with a mouse model of Langerhans cell histiocytosis (LCH), suppression subtractive hybridization (SSH) was used to identify unique viruses in the liver of severe combined immunodeficiency (SCID) mice transplanted with LCH tissues. A partial genomic sequence of a murine coronavirus was identified, and the whole genome (31428 bp) of the coronavirus was subsequently sequenced using PCR cloning techniques. Nucleotide sequence comparisons revealed that the genome sequence of the new virus was 91-93% identical to those of known murine hepatitis viruses (MHVs). The predicted open reading frame from the nucleotide sequence encoded all known proteins of MHVs. Analysis at the protein level showed that the virus was closely related to the highly virulent MHV-JHM strain. The virus strain was named MHV-MI. No type D retroviruses were found. Degenerate PCR targeting of type D retrovirus and 5'-RACE targeting of other types of retroviruses confirmed the absence of any retroviral association with the LCH xenografted SCID mice.

  4. In Vivo Vascularization of Endothelial Cells Derived from Bone Marrow Mesenchymal Stem Cells in SCID Mouse Model

    Directory of Open Access Journals (Sweden)

    Allameh Abdolamir

    2016-07-01

    Full Text Available Objective In vivo and in vitro stem cell differentiation into endothelial cells is a promising area of research for tissue engineering and cell therapy. Materials and Methods We induced human mesenchymal stem cells (MSCs to differentiate to endothelial cells that had the ability to form capillaries on an extracellular matrix (ECM gel. Thereafter, the differentiated endothelial cells at early stage were characterized by expression of specific markers such as von Willebrand factor (vWF, vascular endothelial growth factor (VEGF receptor 2, and CD31. In this experimental model, the endothelial cells were transplanted into the groins of severe combined immunodeficiency (SCID mice. After 30 days, we obtained tissue biopsies from the transplantation sites. Biopsies were processed for histopathological and double immunohistochemistry (DIHC staining. Results Endothelial cells at the early stage of differentiation expressed endothelial markers. Hematoxylin and eosin (H&E staining, in addition to DIHC demonstrated homing of the endothelial cells that underwent vascularization in the injected site. Conclusion The data clearly showed that endothelial cells at the early stage of differentiation underwent neovascularization in vivo in SCID mice. Endothelial cells at their early stage of differentiation have been proven to be efficient for treatment of diseases with impaired vasculogenesis.

  5. Generation of knockout rats with X-linked severe combined immunodeficiency (X-SCID using zinc-finger nucleases.

    Directory of Open Access Journals (Sweden)

    Tomoji Mashimo

    Full Text Available BACKGROUND: Although the rat is extensively used as a laboratory model, the inability to utilize germ line-competent rat embryonic stem (ES cells has been a major drawback for studies that aim to elucidate gene functions. Recently, zinc-finger nucleases (ZFNs were successfully used to create genome-specific double-stranded breaks and thereby induce targeted gene mutations in a wide variety of organisms including plants, drosophila, zebrafish, etc. METHODOLOGY/PRINCIPAL FINDINGS: We report here on ZFN-induced gene targeting of the rat interleukin 2 receptor gamma (Il2rg locus, where orthologous human and mouse mutations cause X-linked severe combined immune deficiency (X-SCID. Co-injection of mRNAs encoding custom-designed ZFNs into the pronucleus of fertilized oocytes yielded genetically modified offspring at rates greater than 20%, which possessed a wide variety of deletion/insertion mutations. ZFN-modified founders faithfully transmitted their genetic changes to the next generation along with the severe combined immune deficiency phenotype. CONCLUSIONS AND SIGNIFICANCE: The efficient and rapid generation of gene knockout rats shows that using ZFN technology is a new strategy for creating gene-targeted rat models of human diseases. In addition, the X-SCID rats that were established in this study will be valuable in vivo tools for evaluating drug treatment or gene therapy as well as model systems for examining the treatment of xenotransplanted malignancies.

  6. Multilineage hematopoietic reconstitution without clonal selection in ADA-SCID patients treated with stem cell gene therapy.

    Science.gov (United States)

    Aiuti, Alessandro; Cassani, Barbara; Andolfi, Grazia; Mirolo, Massimiliano; Biasco, Luca; Recchia, Alessandra; Urbinati, Fabrizia; Valacca, Cristina; Scaramuzza, Samantha; Aker, Memet; Slavin, Shimon; Cazzola, Matteo; Sartori, Daniela; Ambrosi, Alessandro; Di Serio, Clelia; Roncarolo, Maria Grazia; Mavilio, Fulvio; Bordignon, Claudio

    2007-08-01

    Gene transfer into HSCs is an effective treatment for SCID, although potentially limited by the risk of insertional mutagenesis. We performed a genome-wide analysis of retroviral vector integrations in genetically corrected HSCs and their multilineage progeny before and up to 47 months after transplantation into 5 patients with adenosine deaminase-deficient SCID. Gene-dense regions, promoters, and transcriptionally active genes were preferred retroviral integrations sites (RISs) both in preinfusion transduced CD34(+) cells and in vivo after gene therapy. The occurrence of insertion sites proximal to protooncogenes or genes controlling cell growth and self renewal, including LMO2, was not associated with clonal selection or expansion in vivo. Clonal analysis of long-term repopulating cell progeny in vivo revealed highly polyclonal T cell populations and shared RISs among multiple lineages, demonstrating the engraftment of multipotent HSCs. These data have important implications for the biology of retroviral vectors, the dynamics of genetically modified HSCs, and the safety of gene therapy.

  7. Histopathological and expression profiling studies of early tumor responses to near-infrared PDT treatment in SCID mice

    Science.gov (United States)

    Starkey, Jean R.; Rebane, Aleksander; Drobizhev, Mikhail A.; Meng, Fanqin; Gong, Aijun; Elliott, Aleisha; McInnerney, Kate; Pascucci, Elizabeth; Spangler, Charles W.

    2008-02-01

    A novel class of porphyrin-based near-infrared photodynamic therapy (PDT) sensitizers is studied. We achieve regressions of human small cell lung cancer (NCI-H69), non-small cell lung cancer (A 459) and breast cancer (MDAMB- 231) xenografts in SCID mice at significant tissue depth by irradiation with an amplified femtosecond pulsed laser at 800 nm wavelength. Significant tumor regressions were observed during the first 10-14 days post treatment. Tumor histopathology was consistent with known PDT effects, while no significant changes were noted in irradiated normal tissues. In vivo imaging studies using intravenous injections of fluorescent dextran demonstrated an early loss of tumor blood flow. RNA was isolated from NCI-H69 PDT treated SCID mouse xenografts and paired untreated xenografts at 4 hours post laser irradiation. Similarly RNA was isolated from PDT treated and untreated Lewis lung carcinomas growing in C57/Bl6 mice. Expression profiling was carried out using Affymetrix TM human and mouse GeneChips®. Cluster analysis of microarray expression profiling results demonstrated reproducible increases in transcripts associated with apoptosis, stress, oxygen transport and gene regulation in the PDT treated NCI-H69 samples. In addition, PDT treated Lewis lung carcinomas showed reproducible increases in transcripts associated with immune response and lipid biosynthesis. PDT treated C57/Bl6 mice developed cytotoxic T cell activity towards this tumor, while untreated tumor bearing mice failed to do so.

  8. Appearance of Human Plasma Cells Following Differentiation of Human B Cells in NOD/SCID Mouse Spleen

    Directory of Open Access Journals (Sweden)

    Kentaro Kikuchi

    2003-01-01

    Full Text Available Relatively little is known for the differentiation and maturation process of human B cells to plasma cells. This is particularly important in reconstitution work involving transfer of autoantibodies. To address this issue, we transplanted human peripheral blood mononuclear cells (PBMC directly into the spleen of irradiated NOD/SCID mice depleted of natural killer cell activity. Within 6 weeks, naïve B cells differentiated into memory B cells and, importantly, the numbers of human CD138+ plasma cells in spleen increased by 100 fold after transplantation. Plasma cell numbers correlated with the detection of human IgM and IgG in serum, indicating that human B cells had differentiated into mature plasma cells in the murine spleen. In addition to CD19+ plasma cells, a distinct CD19- plasma cell population was detected, suggesting that downregulation of CD19 associated with maturation of plasma cells occurred. When purified human B cells were transplanted, those findings were not observed. Our results indicate that differentiation and maturation of human B cells and plasma cells can be investigated by transplantation of human PBMC into the spleen of NOD/SCID mice. The model will be useful for studying the differentiation of human B cells and generation of plasma cells.

  9. Multilineage hematopoietic reconstitution without clonal selection in ADA-SCID patients treated with stem cell gene therapy

    Science.gov (United States)

    Aiuti, Alessandro; Cassani, Barbara; Andolfi, Grazia; Mirolo, Massimiliano; Biasco, Luca; Recchia, Alessandra; Urbinati, Fabrizia; Valacca, Cristina; Scaramuzza, Samantha; Aker, Memet; Slavin, Shimon; Cazzola, Matteo; Sartori, Daniela; Ambrosi, Alessandro; Di Serio, Clelia; Roncarolo, Maria Grazia; Mavilio, Fulvio; Bordignon, Claudio

    2007-01-01

    Gene transfer into HSCs is an effective treatment for SCID, although potentially limited by the risk of insertional mutagenesis. We performed a genome-wide analysis of retroviral vector integrations in genetically corrected HSCs and their multilineage progeny before and up to 47 months after transplantation into 5 patients with adenosine deaminase–deficient SCID. Gene-dense regions, promoters, and transcriptionally active genes were preferred retroviral integrations sites (RISs) both in preinfusion transduced CD34+ cells and in vivo after gene therapy. The occurrence of insertion sites proximal to protooncogenes or genes controlling cell growth and self renewal, including LMO2, was not associated with clonal selection or expansion in vivo. Clonal analysis of long-term repopulating cell progeny in vivo revealed highly polyclonal T cell populations and shared RISs among multiple lineages, demonstrating the engraftment of multipotent HSCs. These data have important implications for the biology of retroviral vectors, the dynamics of genetically modified HSCs, and the safety of gene therapy. PMID:17671653

  10. Generation of Knockout Rats with X-Linked Severe Combined Immunodeficiency (X-SCID) Using Zinc-Finger Nucleases

    Science.gov (United States)

    Mashimo, Tomoji; Takizawa, Akiko; Voigt, Birger; Yoshimi, Kazuto; Hiai, Hiroshi; Kuramoto, Takashi; Serikawa, Tadao

    2010-01-01

    Background Although the rat is extensively used as a laboratory model, the inability to utilize germ line-competent rat embryonic stem (ES) cells has been a major drawback for studies that aim to elucidate gene functions. Recently, zinc-finger nucleases (ZFNs) were successfully used to create genome-specific double-stranded breaks and thereby induce targeted gene mutations in a wide variety of organisms including plants, drosophila, zebrafish, etc. Methodology/Principal Findings We report here on ZFN-induced gene targeting of the rat interleukin 2 receptor gamma (Il2rg) locus, where orthologous human and mouse mutations cause X-linked severe combined immune deficiency (X-SCID). Co-injection of mRNAs encoding custom-designed ZFNs into the pronucleus of fertilized oocytes yielded genetically modified offspring at rates greater than 20%, which possessed a wide variety of deletion/insertion mutations. ZFN-modified founders faithfully transmitted their genetic changes to the next generation along with the severe combined immune deficiency phenotype. Conclusions and Significance The efficient and rapid generation of gene knockout rats shows that using ZFN technology is a new strategy for creating gene-targeted rat models of human diseases. In addition, the X-SCID rats that were established in this study will be valuable in vivo tools for evaluating drug treatment or gene therapy as well as model systems for examining the treatment of xenotransplanted malignancies. PMID:20111598

  11. Pegademase bovine (PEG-ADA) for the treatment of infants and children with severe combined immunodeficiency (SCID)

    Science.gov (United States)

    Booth, Claire; Gaspar, H Bobby

    2009-01-01

    Adenosine deaminase deficiency (ADA) is a rare, inherited disorder of purine metabolism characterized by immunodeficiency, failure to thrive and metabolic abnormalities. A lack of the enzyme ADA allows accumulation of toxic metabolites causing defects of both cell mediated and humoral immunity leading to ADA severe combined immune deficiency (SCID), a condition that can be fatal in early infancy if left untreated. Hematopoietic stem cell transplant is curative but is dependent on a good donor match. Other therapeutic options include enzyme replacement therapy (ERT) with pegademase bovine (PEG-ADA) and more recently gene therapy. PEG-ADA has been used in over 150 patients worldwide and has allowed stabilization of patients awaiting more definitive treatment with hematopoietic stem cell transplant. It affords both metabolic detoxification and protective immune function with patients remaining clinically well, but immune reconstitution is often suboptimal and may not be long lived. We discuss the pharmacokinetics, immune reconstitution, effects on systemic disease and side effects of treatment with PEG-ADA. We also review the long-term outcome of patients receiving ERT and discuss the role of PEG-ADA in the management of infants and children with ADA-SCID, alongside other therapeutic options. PMID:19707420

  12. Positive Family History, Infection, Low Absolute Lymphocyte Count (ALC) and Absent Thymic Shadow: Diagnostic Clues for all Molecular Forms of Severe Combined Immunodeficiency (SCID)

    Science.gov (United States)

    McWilliams, Laurie M; Railey, Mary Dell; Buckley, Rebecca H

    2015-01-01

    Background Severe Combined Immunodeficiency (SCID) is a syndrome uniformly fatal during infancy unless recognized and treated successfully by bone marrow transplantation or gene therapy. Because SCID infants have no abnormal physical appearance, diagnosis is usually delayed unless newborn screening is performed. Objective In this study, we sought to evaluate the presenting features of all 172 SCID patients transplanted at this institution over the past 31 years. Methods We reviewed original charts from 172 consecutive classic SCID patients who received either T cell-depleted HLA-haploidentical (N=154) or HLA-identical (N=18) non-ablative related marrow transplants at Duke University Medical Center from 1982–2013. Results The mean age at presentation was 4.87 months. When there was a family history of early infant death or known SCID (63/172 or 37%), the mean presentation age was much earlier, 2.0 months compared to 6.6 months. Failure to thrive was common, with 84 patients (50%) having a weight less than the 5th percentile. The leading infections included oral moniliasis (43%), viral infections (61/172 35.5%) and Pneumocystis jiroveci (26%) pneumonia. The group mean ALC was 1454/cmm; 88% of the infants had an ALC less than 3000/cmm. Absent thymic shadow was seen in 92% of infants with electronic radiographic data available. An absence of T cell function was found in all patients. Conclusions SCID infants appear normal at birth but later present with failure to thrive and/or recurrent fungal, viral and bacterial infections. Low ALCs and absent thymic shadow on chest x-ray are key diagnostic clues. The absence of T cell function confirms the diagnosis. PMID:25824440

  13. Inhibition of Acute in vivo Human Immunodeficiency Virus Infection by Human Interleukin 10 Treatment of SCID Mice Implanted with Human Fetal Thymus and Liver

    Science.gov (United States)

    Kollmann, Tobias R.; Pettoello-Mantovani, Massimo; Katopodis, Nikos F.; Hachamovitch, Moshe; Rubinstein, Arye; Kim, Ana; Goldstein, Harris

    1996-04-01

    To improve the usefulness of in vivo models for the investigation of the pathophysiology of human immunodeficiency virus (HIV) infection, we modified the construction of SCID mice implanted with human fetal thymus and liver (thy/liv-SCID-hu mice) so that the peripheral blood of the mice contained significant numbers of human monocytes and T cells. After inoculation with HIV-159, a primary patient isolate capable of infecting monocytes and T cells, the modified thy/liv-SCID-hu mice developed disseminated HIV infection that was associated with plasma viremia. The development of plasma viremia and HIV infection in thy/liv-SCID-hu mice inoculated with HIV-159 was inhibited by acute treatment with human interleukin (IL) 10 but not with human IL-12. The human peripheral blood mononuclear cells in these modified thy/liv-SCID-hu mice were responsive in vivo to treatment with exogenous cytokines. Human interferon γ expression in the circulating human peripheral blood mononuclear cells was induced by treatment with IL-12 and inhibited by treatment with IL-10. Thus, these modified thy/liv-SCID-hu mice should prove to be a valuable in vivo model for examining the role of immunomodulatory therapy in modifying HIV infection. Furthermore, our demonstration of the in vivo inhibitory effect of IL-10 on acute HIV infection suggests that further studies may be warranted to evaluate whether there is a role for IL-10 therapy in preventing HIV infection in individuals soon after exposure to HIV such as for children born to HIV-infected mothers.

  14. Diagnostic Efficiency among Psychiatric Outpatients of a Self-Report Version of a Subset of Screen Items of the Structured Clinical Interview for DSM-IV-TR Personality Disorders (SCID-II)

    Science.gov (United States)

    Germans, Sara; Van Heck, Guus L.; Masthoff, Erik D.; Trompenaars, Fons J. W. M.; Hodiamont, Paul P. G.

    2010-01-01

    This article describes the identification of a 10-item set of the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) items, which proved to be effective as a self-report assessment instrument in screening personality disorders. The item selection was based on the retrospective analyses of 495 SCID-II interviews. The…

  15. Diagnostic Efficiency among Psychiatric Outpatients of a Self-Report Version of a Subset of Screen Items of the Structured Clinical Interview for DSM-IV-TR Personality Disorders (SCID-II)

    Science.gov (United States)

    Germans, Sara; Van Heck, Guus L.; Masthoff, Erik D.; Trompenaars, Fons J. W. M.; Hodiamont, Paul P. G.

    2010-01-01

    This article describes the identification of a 10-item set of the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) items, which proved to be effective as a self-report assessment instrument in screening personality disorders. The item selection was based on the retrospective analyses of 495 SCID-II interviews. The…

  16. Improving engagement in mental health treatment for home meal recipients with depression

    Directory of Open Access Journals (Sweden)

    Sirey JA

    2013-09-01

    Full Text Available Jo Anne Sirey, Alexandra Greenfield, Alyssa DePasquale, Nathalie Weiss, Patricia Marino, George S Alexopoulos, Martha L Bruce Department of Psychiatry, Weill Cornell Medical College, White Plains, NY, USA Background: Staff who provide support services to older adults are in a unique position to detect depression and offer a referral for mental health treatment. Yet integrating mental health screening and recommendations into aging services requires staff learn new skills to integrate mental health and overcome client barriers to accepting mental health referrals. This paper describes client rates of depression and a novel engagement intervention (Open Door for homebound older adults who are eligible for home delivered meals and screened for depression by in-home aging service programs. Methods: Homebound older adults receiving meal service who endorsed depressive symptoms were interviewed to assess depression severity and rates of suicidal ideation. Open Door is a brief psychosocial intervention to improve engagement in mental health treatment by collaboratively addressing the individual level barriers to care. The intervention targets stigma, misconceptions about depression, and fears about treatment, and is designed to fit within the roles and responsibilities of aging service staff. Results: Among 137 meal recipients who had symptoms when screened for depression as part of routine home meal service assessments, half (51% had Major Depressive Disorder and 13% met criteria for minor depression on the SCID. Suicidal ideation was reported by 29% of the sample, with the highest rates of suicidal ideation (47% among the subgroup of individuals with Major Depressive Disorder. Conclusion: Individuals who endorse depressive symptoms during screening are likely to have clinically significant depression and need mental health treatment. The Open Door intervention offers a strategy to overcome barriers to mental health treatment engagement and to improve

  17. 联合免疫缺陷小鼠的发展及其人免疫重建的研究%Development of SCID mice and the human immune reconstitution in SCID mice

    Institute of Scientific and Technical Information of China (English)

    谭玉波; 林晨; 李扬秋

    2005-01-01

    多年来研究者致力于在联合免疫缺陷小鼠(severe combined immunodeficiency mice,SCID mice)体内重建有功能的人免疫系统,期以解决动物模型难以确切反映人体免疫系统的特点和研究人体免疫应答受限于体外实验的难题1988年Mosier等将人外周血淋巴细胞移植入C.B—17 SCID小鼠首次建立了人源化的SCID鼠模型。人类造血干/祖细胞移植给联合免疫缺陷鼠后可在其体内多系分化、增殖。

  18. Tuberculosis in Hematopoietic Stem Cell Transplant Recipients

    OpenAIRE

    Ramos, Jéssica Fernandes; Batista, Marjorie Vieira; Costa, Silvia Figueiredo

    2013-01-01

    Literature on tuberculosis (TB) occurring in recipients of Hematopoietic Stem Cell Transplant (HSCT) is scanty even in countries where TB is common. Most reports of TB in HSCT patients were from ASIA, in fact the TB incidence ranging from 0.0014 (USA) to 16% (Pakistan). There are few reports of TB diagnosis during the first two weeks after HSCT; most of cases described in the literature occurred after 90 days of HSCT, and the lung was the organ most involved. The mortality ranged from 0 to 50...

  19. Cutaneous malignancies in immunosuppressed organ transplant recipients.

    Science.gov (United States)

    Seda, Ivette M Sosa; Zubair, Adeel; Brewer, Jerry D

    2014-01-01

    During the past century, organ transplantation has delivered the miracle of life to more than 500,000 patients in need. Secondary malignancies have developed as an unforeseen consequence of intense immunosuppressive regimens. Cutaneous malignancies have been recognized as the most frequent cancer that arises post-transplantation. Among organ transplant recipients (OTRs), skin cancer is a substantial cause of morbidity and potential mortality. The authors discuss epidemiology and clinical presentation of cutaneous malignancies; associated risk factors; recommendation for the care of immunosuppressed OTRs, and emerging therapies on the horizon.

  20. OCULAR SYPHILIS IN A KIDNEY TRANSPLANT RECIPIENT

    Science.gov (United States)

    ROMAO, Elen A.; BOLELLA, Valdes R.; NARDIN, Maria Estela P.; HABIB-SIMAO, Maria Lucia; FURTADO, João Marcelo; MOYSES-NETO, Miguel

    2016-01-01

    We present a case of ocular syphilis after a renal transplantation involving progressive vision loss without clinically identifiable ocular disease. Electroretinography showed signs of ischemia, especially in the internal retina. A serological test was positive for syphilis. Lumbar puncture revealed lymphocytic meningitis and a positive serologic test for syphilis in the cerebrospinal fluid. The patient was treated with penicillin, and had a quick vision improvement. In the case of transplant recipients, clinicians should always consider the diagnosis of ocular syphilis in cases with unexplained visual acuity decrement, as this condition may cause serious complications if not treated. PMID:27253748

  1. BK Virus in Recipients of Kidney Transplants.

    Science.gov (United States)

    Hendrix, Kelly M

    2014-01-01

    Since its discovery in 1971, the BK virus, a human polyomavirus, has emerged as a significant cause of renal dysfunction and transplant graft loss in kidney transplant recipients. Improved screening methods have been effective in assisting in the early identification of the virus, and thus, prompt intervention to prevent the progression of the disease. Treatment options for the virus are limited; therefore, lowering immunosuppressive medications should be considered the first line of treatment. Current adjunctive therapies are not guaranteed to control the viral activity and may have limited therapeutic value.

  2. Infections in intestinal and multivisceral transplant recipients.

    Science.gov (United States)

    Timpone, Joseph G; Girlanda, Raffaele; Rudolph, Lauren; Fishbein, Thomas M

    2013-06-01

    Intestinal and multivisceral transplantation has become an effective treatment option for patients with intestinal failure. More potent immunosuppressive therapy has resulted in a decreased incidence of acute rejection and has improved patient survival. However, infectious complications can cause significant morbidity both before and after transplantation. In comparison with other solid organ transplant recipients, these patients experience higher rates of acute allograft rejection, thus requiring higher levels of immunosuppression and escalating the risk of infection. This article reviews the most common infectious disease complications encountered, and proposes a potential temporal association for types of infections in this patient population.

  3. Cutaneous histoplasmosis in renal transplant recipients.

    Science.gov (United States)

    Sun, N Z; Augustine, J J; Gerstenblith, M R

    2014-10-01

    Cutaneous histoplasmosis is a rare entity, although it can be seen in a substantial portion of renal transplant recipients with disseminated disease. The prognosis of disseminated disease is worse than isolated cutaneous involvement, and significant delays in diagnosis are reported. We reviewed reports of cutaneous histoplasmosis with and without dissemination in the setting of renal transplantation to examine incidence, timing of diagnosis, clinical features, and prognosis. Remarkable morphologic variability and the non-specific appearance of skin findings suggest that tissue culture is required for definitive diagnosis. Cutaneous lesions represent an easily accessible source for early diagnosis.

  4. A novel model of SCID-X1 reconstitution reveals predisposition to retrovirus-induced lymphoma but no evidence of gammaC gene oncogenicity.

    Science.gov (United States)

    Scobie, Linda; Hector, Ralph D; Grant, Louise; Bell, Margaret; Nielsen, Anne A; Meikle, Sharon; Philbey, Adrian; Philbey, Adrain; Thrasher, Adrian J; Thrasher, Adrain J; Cameron, Ewan R; Blyth, Karen; Neil, James C

    2009-06-01

    The emergence of leukemia following gene transfer to restore common cytokine receptor gamma chain (gammaC) function in X-linked severe combined immunodeficiency (SCID-X1) has raised important questions with respect to gene therapy safety. To explore the risk factors involved, we tested the oncogenic potential of human gammaC in new strains of transgenic mice expressing the gene under the control of the CD2 promoter and locus control region (LCR). These mice demonstrated mildly perturbed T-cell development, with an increased proportion of thymic CD8 cells, but showed no predisposition to tumor development even on highly tumor prone backgrounds or after gamma-retrovirus infection. The human CD2-gammaC transgene rescued T and B-cell development in gammaC(-/-) mice but with an age-related delay, mimicking postnatal reconstitution in SCID-X1 gene therapy subjects. However, we noted that gammaC(-/-) mice are acutely susceptible to murine leukemia virus (MLV) leukemogenesis, and that this trait was not corrected by the gammaC transgene. We conclude that the SCID-X1 phenotype can be corrected safely by stable ectopic expression of gammaC and that the transgene is not significantly oncogenic when expressed in this context. However, an underlying predisposition conferred by the SCID-X1 background appears to collaborate with insertional mutagenesis to increase the risk of tumor development.

  5. A Novel Model of SCID-X1 Reconstitution Reveals Predisposition to Retrovirus-induced Lymphoma but No Evidence of γC Gene Oncogenicity

    Science.gov (United States)

    Scobie, Linda; Hector, Ralph D; Grant, Louise; Bell, Margaret; Nielsen, Anne A; Meikle, Sharon; Philbey, Adrain; Thrasher, Adrain J; Cameron, Ewan R; Blyth, Karen; Neil, James C

    2009-01-01

    The emergence of leukemia following gene transfer to restore common cytokine receptor γ chain (γC) function in X-linked severe combined immunodeficiency (SCID-X1) has raised important questions with respect to gene therapy safety. To explore the risk factors involved, we tested the oncogenic potential of human γC in new strains of transgenic mice expressing the gene under the control of the CD2 promoter and locus control region (LCR). These mice demonstrated mildly perturbed T-cell development, with an increased proportion of thymic CD8 cells, but showed no predisposition to tumor development even on highly tumor prone backgrounds or after γ-retrovirus infection. The human CD2-γC transgene rescued T and B-cell development in γC−/− mice but with an age-related delay, mimicking postnatal reconstitution in SCID-X1 gene therapy subjects. However, we noted that γC−/− mice are acutely susceptible to murine leukemia virus (MLV) leukemogenesis, and that this trait was not corrected by the γC transgene. We conclude that the SCID-X1 phenotype can be corrected safely by stable ectopic expression of γC and that the transgene is not significantly oncogenic when expressed in this context. However, an underlying predisposition conferred by the SCID-X1 background appears to collaborate with insertional mutagenesis to increase the risk of tumor development. PMID:19337236

  6. Reliability and validity of the Turkish version of the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D): a preliminary study.

    Science.gov (United States)

    Kundakçi, Turgut; Sar, Vedat; Kiziltan, Emre; Yargiç, Ilhan L; Tutkun, Hamdi

    2014-01-01

    A total of 34 consecutive patients with dissociative identity disorder or dissociative disorder not otherwise specified were evaluated using the Turkish version of the Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D). They were compared with a matched control group composed of 34 patients who had a nondissociative psychiatric disorder. Interrater reliability was evaluated by 3 clinicians who assessed videotaped interviews conducted with 5 dissociative and 5 nondissociative patients. All subjects who were previously diagnosed by clinicians as having a dissociative disorder were identified as positive, and all subjects who were previously diagnosed as not having a dissociative disorder were identified as negative. The scores of the main symptom clusters and the total score of the SCID-D differentiated dissociative patients from the nondissociative group. There were strong correlations between the SCID-D and the Dissociative Experiences Scale total and subscale scores. These results are promising for the validity and reliability of the Turkish version of the SCID-D. However, as the present study was conducted on a predominantly female sample with very severe dissociation, these findings should not be generalized to male patients, to dissociative disorders other than dissociative identity disorder, or to broader clinical or nonclinical populations.

  7. Pretransplant mobilization with granulocyte colony-stimulating factor improves b-cell reconstitution by lentiviral vector gene therapy in SCID-X1 mice

    NARCIS (Netherlands)

    M.W. Huston (Marshall W.); A.R.A. Riegman (Adriaan R.A.); R. Yadak (Rana); Y.M. van Helsdingen (Yvette); H. De Boer (Helen); N.P. van Til (Niek); G. Wagemaker (Gerard)

    2014-01-01

    textabstractHematopoietic stem cell (HSC) gene therapy is a demonstrated effective treatment for X-linked severe combined immunodeficiency (SCID-X1), but B-cell reconstitution and function has been deficient in many of the gene therapy treated patients. Cytoreductive preconditioning is known to impr

  8. Restoration of human B-cell differentiation into NOD-SCID mice engrafted with gene-corrected CD34+ cells isolated from Artemis or RAG1-deficient patients.

    Science.gov (United States)

    Lagresle-Peyrou, Chantal; Benjelloun, Fatine; Hue, Christophe; Andre-Schmutz, Isabelle; Bonhomme, Delphine; Forveille, Monique; Beldjord, Kheira; Hacein-Bey-Abina, Salima; De Villartay, Jean-Pierre; Charneau, Pierre; Durandy, Anne; Fischer, Alain; Cavazzana-Calvo, Marina

    2008-02-01

    Severe combined immunodeficiency (SCID) caused by mutation of the recombination-activating gene 1 (RAG1) or Artemis gene lead to the absence of B- and T-cell differentiation. The only curative treatment is allogeneic bone marrow (BM) transplantation, which displays a high survival rate when an HLA compatible donor is available but has a poorer prognosis when the donor is partially compatible. Consequently, gene therapy may be a promising alternative strategy for these diseases. Here, we report that lentiviral gene-corrected BM CD34(+) cells (isolated from Artemis- or RAG1-deficient patients) sustain human B-cell differentiation following injection into non-obese diabetic/SCID (NOD-SCID) mice previously infused with anti-interleukin-2 receptor beta chain monoclonal antibody. In most of the mice BM, engrafted with Artemis-transduced cells, human B-cell differentiation occurred until the mature stage. The B cells were functional as human immunoglobulin M (IgM) was present in the serum. Following injection with RAG1-transduced cells, human engraftment occurred in vivo but B-cell differentiation until the mature stage was less frequent. However, when it occurred, it was always associated with human IgM production. This overall approach represents a useful tool for evaluating gene transfer efficiency in human SCID forms affecting B-cell development (such as Artemis deficiency) and for testing new vectors for improving in vivo RAG1 complementation.

  9. Establishment of xenotransplantation model of human CN-AML with FLT3-ITD (mut) /NPM1 (-) in NOD/SCID mice.

    Science.gov (United States)

    Shang, Zhen; Wang, Jue; Wang, Di; Xiao, Min; Li, Tong-juan; Wang, Na; Huang, Liang; Zhou, Jian-feng

    2013-06-01

    Patients with FLT3-ITD (mut) /NPM1 (-) cytogenetically normal acute myeloid leukemia (CN-AML), as high-risk molecular group in CN-AML, are associated with a worse prognosis than other CN-AML patients. It is beneficial to generate xenotransplantation model of FLT3-ITD (mut) /NPM1 (-) CN-AML to better understand the pathogenesis and therapeutic strategies of such AML subtype. The purpose of present study was to establish the xenotransplantation model in NOD/SCID mice with FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells. The FLT3-ITD (mut) /NPM1 (-) CN-AML primary cells from 3 of 7 cases were successfully transplanted into NOD/SCID mice, and human CD45 positive cells were detected in the peripheral blood, spleen and bone marrow of mice by using flow cytometry. Infiltration of human leukemia cells in various organs of mice was observed by using immunohistochemistry. Gene analysis confirmed sustained FLT3/ITD mutation without NPM1 mutation in mice. By performing serial transplantation, it was found that characteristics of the leukemia cells in secondary and tertiary generation models remained unchanged. Moreover, in vivo cytarabine administration could extend survival of NOD/SCID mice, which was consistent with clinical observation. In conclusion, we successfully established xenotransplantation model of human FLT3-ITD (mut) /NPM1 (-) CN-AML in NOD/SCID mice. The model was able to present primary disease and suitable to evaluate the curative effects of new drugs or therapy strategies.

  10. A Novel Model of SCID-X1 Reconstitution Reveals Predisposition to Retrovirus-induced Lymphoma but No Evidence of γC Gene Oncogenicity.

    Science.gov (United States)

    Scobie, Linda; Hector, Ralph D; Grant, Louise; Bell, Margaret; Nielsen, Anne A; Meikle, Sharon; Philbey, Adrain; Thrasher, Adrain J; Cameron, Ewan R; Blyth, Karen; Neil, James C

    2009-06-01

    The emergence of leukemia following gene transfer to restore common cytokine receptor γ chain (γC) function in X-linked severe combined immunodeficiency (SCID-X1) has raised important questions with respect to gene therapy safety. To explore the risk factors involved, we tested the oncogenic potential of human γC in new strains of transgenic mice expressing the gene under the control of the CD2 promoter and locus control region (LCR). These mice demonstrated mildly perturbed T-cell development, with an increased proportion of thymic CD8 cells, but showed no predisposition to tumor development even on highly tumor prone backgrounds or after γ-retrovirus infection. The human CD2-γC transgene rescued T and B-cell development in γC(-/-) mice but with an age-related delay, mimicking postnatal reconstitution in SCID-X1 gene therapy subjects. However, we noted that γC(-/-) mice are acutely susceptible to murine leukemia virus (MLV) leukemogenesis, and that this trait was not corrected by the γC transgene. We conclude that the SCID-X1 phenotype can be corrected safely by stable ectopic expression of γC and that the transgene is not significantly oncogenic when expressed in this context. However, an underlying predisposition conferred by the SCID-X1 background appears to collaborate with insertional mutagenesis to increase the risk of tumor development.

  11. Correction of murine SCID-X1 by lentiviral gene therapy using a codon-optimized IL2RG gene and minimal pretransplant conditioning

    NARCIS (Netherlands)

    M.W. Huston (Marshall W.); N.P. van Til (Niek); T.P. Visser (Trudi); S.H. Arshad (Syed); M.H. Brugman (Martijn); C. Cattoglio (Claudia); A. Nowrouzi (Ali); Y.J. Li (Yi); A. Schambach (Axel); M.K. Schmidt (Marjanka); J.A.C. Baum (Joel); C. von Kalle (Christof); F. Mavilio (Fulvio); F. Zhang (Fang); M.P. Blundell (Mike P.); A.J. Thrasher (A. J.); M.M.A. Verstegen (Monique); G. Wagemaker (Gerard)

    2011-01-01

    textabstractClinical trials have demonstrated the potential of ex vivo hematopoietic stem cell gene therapy to treat X-linked severe combined immunodeficiency (SCID-X1) using γ-retroviral vectors, leading to immune system functionality in the majority of treated patients without pretransplant condit

  12. Angiopoietin-like 5 and IGFBP2 stimulate ex vivo expansion of human cord blood hematopoietic stem cells as assayed by NOD/SCID transplantation.

    Science.gov (United States)

    Zhang, Cheng Cheng; Kaba, Megan; Iizuka, Satoru; Huynh, HoangDinh; Lodish, Harvey F

    2008-04-01

    Hematopoietic stem cells (HSCs) are the basis of bone marrow transplantation and are attractive target cells for hematopoietic gene therapy, but these important clinical applications have been severely hampered by difficulties in ex vivo expansion of HSCs. In particular, the use of cord blood for adult transplantation is greatly limited by the number of HSCs. Previously we identified angiopoietin-like proteins and IGF-binding protein 2 (IGFBP2) as new hormones that, together with other factors, can expand mouse bone marrow HSCs in culture. Here, we measure the activity of multipotent human severe combined immunodeficient (SCID)-repopulating cells (SRCs) by transplantation into the nonobese diabetic SCID (NOD/SCID) mice; secondary transplantation was performed to evaluate the self-renewal potential of SRCs. A serum-free medium containing SCF, TPO, and FGF-1 or Flt3-L cannot significantly support expansion of the SRCs present in human cord blood CD133+ cells. Addition of either angiopoietin-like 5 or IGF-binding protein 2 to the cultures led to a sizable expansion of HSC numbers, as assayed by NOD/SCID transplantation. A serum-free culture containing SCF, TPO, FGF-1, angiopoietin-like 5, and IGFBP2 supports an approximately 20-fold net expansion of repopulating human cord blood HSCs, a number potentially applicable to several clinical processes including HSC transplantation.

  13. Reconstitution of Scid mice with CD4+CD25- T cells leads to rapid colitis: an improved model for pharmacologic testing

    DEFF Research Database (Denmark)

    Kjellev, Stine; Lundsgaard, Dorthe; Poulsen, Steen Seier

    2006-01-01

    Improved experimental colitis models are needed for evaluation of treatment strategies for IBD. Most current models either lack resemblance to IBD, are complicated to establish, or the colitis occurs slowly and inconsistently. Our aim was to characterize the course of colitis in C.B-17 Scid mice...

  14. Inheritance of Welfare Recipiency: An Intergenerational Study of Social Assistance Recipiency in Postwar Sweden.

    Science.gov (United States)

    Stenberg, Sten-Ake

    2000-01-01

    Study utilizes a longitudinal data set from Sweden to test hypotheses on the inheritance of welfare benefit recipiency as indicated by reliance on means-tested social assistance. A clear intergenerational effect was observed. Effect reflects a combination of social assistance in the family of origin, children's school adjustment, and parental…

  15. Foamy viral vector integration sites in SCID-repopulating cells after MGMTP140K-mediated in vivo selection.

    Science.gov (United States)

    Olszko, M E; Adair, J E; Linde, I; Rae, D T; Trobridge, P; Hocum, J D; Rawlings, D J; Kiem, H-P; Trobridge, G D

    2015-07-01

    Foamy virus (FV) vectors are promising for hematopoietic stem cell (HSC) gene therapy but preclinical data on the clonal composition of FV vector-transduced human repopulating cells is needed. Human CD34(+) human cord blood cells were transduced with an FV vector encoding a methylguanine methyltransferase (MGMT)P140K transgene, transplanted into immunodeficient NOD/SCID IL2Rγ(null) mice, and selected in vivo for gene-modified cells. The retroviral insertion site profile of repopulating clones was examined using modified genomic sequencing PCR. We observed polyclonal repopulation with no evidence of clonal dominance even with the use of a strong internal spleen focus forming virus promoter known to be genotoxic. Our data supports the use of FV vectors with MGMTP140K for HSC gene therapy but also suggests additional safety features should be developed and evaluated.

  16. Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

    Directory of Open Access Journals (Sweden)

    Cheryl A Stoddart

    Full Text Available BACKGROUND: The SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals. METHODOLOGY/PRINCIPAL FINDINGS: Endpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3 as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions. CONCLUSION: Given the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans.

  17. Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

    Science.gov (United States)

    Stoddart, Cheryl A; Bales, Cheryl A; Bare, Jennifer C; Chkhenkeli, George; Galkina, Sofiya A; Kinkade, April N; Moreno, Mary E; Rivera, José M; Ronquillo, Rollie E; Sloan, Barbara; Black, Paul L

    2007-08-01

    The SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals. Endpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions. Given the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans.

  18. Brucellosis in a renal transplant recipient.

    Science.gov (United States)

    Ting, I W; Ho, M W; Sung, Y J; Tien, N; Chi, C Y; Ho, H C; Huang, C C

    2013-10-01

    Brucellosis is one of the most common systemic zoonotic diseases transmitted by consumption of unpasteurized dairy products or by occupational contact with infected animals. Brucellosis is rare in renal transplant recipients. Only 3 cases have been reported in the literature. We report a case of brucellosis with hematologic and hepatobiliary complications in a patient 3 years after renal transplantation. The mean time from transplantation to the diagnosis of brucellosis in these 4 reported patients was 5.1 years (range 17 months to 13 years). All patients had fever and constitutional symptoms, and all attained clinical cure after combination antibiotic therapy. Given the small number of patients, further study is needed to identify the characteristics of brucellosis in renal transplant recipients. Drug interactions and acute renal failure developed in our patient during antibiotic treatment. Therefore, we should monitor the levels of immunosuppressive agents frequently. Several studies have shown in vitro susceptibilities of Brucella melitensis to tigecycline. In our patient, fever finally subsided after tigecycline administration. The minimum inhibitory concentration of tigecycline using Etest was 0.094 μg/mL. Tigecycline may be a potential option for treatment of brucellosis in the setting of transplantation.

  19. Proteinuria in Egyptian renal transplant recipients

    Directory of Open Access Journals (Sweden)

    Essam Khedr

    2015-01-01

    Full Text Available To evaluate the prevalence, risk factors, possible etiology, prognosis and management of proteinuria in renal transplant recipients, we studied 435 adult renal transplant recipient patients randomly selected from our center; 394 patients were reviewed retrospectively and 41 patients were followed-up prospectively for a period of one year. The patients were classified into three groups according to the results of urinalysis and spot urinary albumin creatinine ratio: Group A patients with normoalbuminuria; Group B patients with microalbuminuria; and Group C patients with macroalbuminuria. Persistent post-transplantation proteinuria was detected in 125 (28.8% patients. The etiology of post-transplantation proteinuria included chronic allograft dysfunction in 44 (35.2% patients, acute rejection in 40 (32% patients, transplant glomerulopathy in eight (6.4% patients, glomerular disease in 16 (12.8% patients and other etiology in 17 (13.6% patients. Proteinuric patients demonstrated significantly lower graft survival rates than did those without proteinuria (48.3% versus 51.7%, respectively; P = 0.017; Risk Ratio = 0.403; 95% confidence interval 0.188-0.862. We conclude that proteinuria is prevalent after kidney transplant in our population, and that it is most commonly associated with chronic allograft nephropathy, transplant glomerulopathy, glomerulonephritis and acute rejection. Post-transplant proteinuria is associated with decreased allograft survival.

  20. Lung Cancer in Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Jozicic Mirela

    2016-06-01

    Full Text Available Introduction. Although the incidence of malignancy has increased after solid organ transplantation, data on lung cancer in this group of patients is scarce. The aim of this study was to determine clinical characteristics and outcome of patients who developed lung cancer after renal transplantation. Methods. Among a cohort of 1658 patients who received a transplant at our institution and were followedup between 1973 and 2014, five patients developed lung cancer. We analyzed risk factors, transplantation characteristics, treatment options and survival. Results. Lung cancer was diagnosed in 5 patients (0.3%. Time to diagnosis after the transplant procedure ranged from 26 to 156 months (mean 115 months. All of them had a smoking history. Tumors were classified as IIB (20%, IIIA (40%, and IV (40%. Histological types included adenocarcinoma (80% and there was one case of sarcomatoid carcinoma (20%. One patient had concomitant thyroid papillary carcinoma. Radiotherapy was applied in 2 patients, 2 underwent chemotherapy (erlotinib and combination of carboplatinum and etopozide in one patient each, and 2 died within one month after the diagnosis from disseminated malignant disease. Patients with stage IIIA survived 14 and 24 months after the diagnosis. The patient with sarcomatoid cancer underwent thoracotomy with a complete resection, lost his graft function and died 7 months after the diagnosis. Conclusion. Lung cancer is relatively rare malignancy in renal transplant recipients, but associated with high mortality. Smoking is a significant risk factor, thus smoking cessation should be promoted among renal transplant recipients, as well as regular screening for lung cancer.

  1. Gastrointestinal complications in renal transplant recipients.

    Science.gov (United States)

    Ponticelli, Claudio; Passerini, Patrizia

    2005-06-01

    Gastrointestinal complications are frequent in renal transplant recipients and can include oral lesions, esophagitis, peptic ulcer, diarrhea, colon disorders and malignancy. Oral lesions may be caused by drugs such as cyclosporine and sirolimus, by virus or fungal infections. Leukoplakia may develop in patients with Epstein-Barr virus (EBV) infection. The commonest esophageal disorder is represented by fungal esophagitis usually caused by candida. A number of patients may suffer from nausea, vomiting and gastric discomfort. These disorders are more frequent in patients treated with mycophenolate mofetil (MMF). Peptic ulcer is more rare than in the past. Patients with a history of peptic ulcer are particularly prone to this complication. Other gastroduodenal disorders are caused by cytomegalovirus (CMV) and herpes simplex infection. Diarrhea is a frequent disorder which may be caused by pathogen microorganisms or by immunosuppressive agents. The differential diagnosis may be difficult. Colon disorders mainly consist of hemorrhage, usually sustained by CMV infection, or perforation which may be caused by diverticulitis or intestinal ischemia. Colon cancer, anal carcinoma, and EBV-associated lymphoproliferative disorders are particularly frequent in transplant recipients. A particular gastric lymphoma called mucosa-associated lymphoid tissue (MALT) lymphoma may develop in renal transplant patients. It usually responds to the eradication of Helicobacter pylori.

  2. 24 CFR 585.401 - Recordkeeping by recipients.

    Science.gov (United States)

    2010-04-01

    ..., architectural and engineering fees, construction, rehabilitation, operating costs or replacement reserves for... any books, documents, papers, and records of the recipient that are pertinent to assistance...

  3. Skin Cancer Risk in Hematopoietic Stem-Cell Transplant Recipients Compared With Background Population and Renal Transplant Recipients

    DEFF Research Database (Denmark)

    Omland, Silje Haukali; Gniadecki, Robert; Hædersdal, Merete

    2016-01-01

    IMPORTANCE: While a high risk of nonmelanoma skin cancer is well recognized in solid-organ transplant recipients, the risk of skin cancer in hematopoietic stem-cell transplant (HSCT) recipients has not been extensively studied. OBJECTIVE: To determine the risk of cutaneous cancer in HSCT recipients...... and compare it with the risk in renal transplant recipients (RTRs) and individuals who have not received any transplant. DESIGN, SETTING, AND PARTICIPANTS: A nationwide population-based cohort study from the Danish National Hospital Register including 3302 patients who underwent HSCT (1007 allogeneic, 2295...... cancer between transplant recipients and background population, we used a stratified proportional hazard regression model for hazard ratio (HR) estimations. By use of the cumulative incidence, we estimated 5- and 10-year risks of skin cancers. All RTR and HSCT recipients were treated and followed up...

  4. Recipients affect prosocial and altruistic choices in jackdaws, Corvus monedula.

    Directory of Open Access Journals (Sweden)

    Christine Schwab

    Full Text Available Other-regarding preferences are a critical feature of human cooperation but to what extent non-human animals exhibit these preferences is a matter of intense discussion. We tested whether jackdaws show prosocial behaviour (providing benefits to others at no cost to themselves and altruism (providing benefits to others while incurring costs with both sibling and non-sibling recipients. In the prosocial condition, a box was baited on both the actor's and the recipient's side (1/1 option, whereas another box provided food only for the actor (1/0 option. In the altruistic condition, the boxes contained food for either the actor (1/0 option or the recipient (0/1 option. The proportion of selfish (1/0 option and cooperative (1/1 and 0/1 option, respectively actors' choices was significantly affected by the recipients' behaviour. If recipients approached the boxes first and positioned themselves next to the box baited on their side, trying to access the food reward (recipient-first trials, actors were significantly more cooperative than when the actors approached the boxes first and made their choice prior to the recipients' arrival (actor-first trials. Further, in recipient-first trials actors were more cooperative towards recipients of the opposite sex, an effect that was even more pronounced in the altruistic condition. Hence, at no cost to the actors, all recipients could significantly influence the actors' behaviour, whereas at high costs this could be achieved even more so by recipients of different sex. Local/stimulus enhancement is discussed as the most likely cognitive mechanism to account for these effects.

  5. Establishment of a retinoic acid-resistant human acute promyelocytic leukaemia (APL) model in human granulocyte-macrophage colony-stimulating factor (hGM-CSF) transgenic severe combined immunodeficiency (SCID) mice.

    Science.gov (United States)

    Fukuchi, Y; Kizaki, M; Kinjo, K; Awaya, N; Muto, A; Ito, M; Kawai, Y; Umezawa, A; Hata, J; Ueyama, Y; Ikeda, Y

    1998-10-01

    To understand the mechanisms and identify novel approaches to overcoming retinoic acid (RA) resistance in acute promyelocytic leukaemia (APL), we established the first human RA-resistant APL model in severe combined immunodeficiency (SCID) mice. UF-1 cells, an RA-resistant APL cell line established in our laboratory, were transplanted into human granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing SCID (hGMTg SCID) mice and inoculated cells formed subcutaneous tumours in all hGMTg SCID mice, but not in the non-transgenic control SCID mice. Single-cell suspensions (UF-1/GMTg SCID cells) were similar in morphological, immunological, cytogenetic and molecular genetic features to parental UF-1 cells. All-trans RA did not change the morphological features of cells or their expression of CD11b. RA did not alter the growth curve of cells as determined by MTT assay, suggesting that UF-1/GMTg SCID cells are resistant to RA. These results demonstrate that this is the first RA-resistant APL animal model that may be useful for investigating the biology of this myeloid leukaemia in vivo, as well as for evaluating novel therapeutic approaches including patients with RA-resistant APL.

  6. Diagnostic efficiency among psychiatric outpatients of a self-report version of a subset of screen items of the Structured Clinical Interview for DSM-IV-TR Personality Disorders (SCID-II).

    Science.gov (United States)

    Germans, Sara; Van Heck, Guus L; Masthoff, Erik D; Trompenaars, Fons J W M; Hodiamont, Paul P G

    2010-12-01

    This article describes the identification of a 10-item set of the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) items, which proved to be effective as a self-report assessment instrument in screening personality disorders. The item selection was based on the retrospective analyses of 495 SCID-II interviews. The psychometric properties were studied in a prospective validation study in a random sample of Dutch adult psychiatric outpatients, using the SCID-II interview as the gold standard. First, all patients completed the short questionnaire. One week later, they were interviewed with the full SCID-II. After another week, the short questionnaire was readministered. According to the scores obtained with the full SCID-II, 97 patients (50%) had a personality disorder. The set of 10 SCID-II items correctly classified 78% of all participants. The sensitivity, specificity, and positive and negative power were 0.78, 0.78, 0.78, and 0.78, respectively. The results based on the retrospectively obtained data were rather similar to those obtained in the prospective validation study. Therefore, it is concluded that the set of 10 SCID-II items can be useful as a quick self-report personality disorder screen in a population of psychiatric outpatients.

  7. Resistant bacteria in stem cell transplant recipients

    Directory of Open Access Journals (Sweden)

    Nucci Marcio

    2002-01-01

    Full Text Available Bacterial infections account for most infections in hematopoietic stem cell transplant recipients. While early mortality reduced dramatically with the introduction of the concept of empirical antibiotic therapy in neutropenic patients, no effect of prophylaxis on the mortality was observed in many studies. On the other hand, antibiotic prophylaxis has resulted in the emergence of resistance among bacteria. In addition, the choice of the antibiotic regimen for empirical therapy and the practices of antibiotic therapy during neutropenia may result in a significant shift in the pattern of bacterial infections. The use of quinolones and vancomycin as prophylaxis, and of carbapenems and vancomycin in the empirical antibiotic therapy, are associated with the appearance of resistant Gram-positive and Gram-negative bacteria. Therefore, hematologists must be aware of the impact of these practices on the emergence of infections due to multi-resistant pathogens, since these infections may be associated with increased mortality.

  8. Immunologic monitoring in kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Natavudh Townamchai

    2013-06-01

    Full Text Available Transplant biopsy has always been the gold standard for assessing the immune response to a kidney allograft (Chandraker A: Diagnostic techniques in the work-up of renal allograft dysfunction—an update. Curr Opin Nephrol Hypertens 8:723–728, 1999. A biopsy is not without risk and is unable to predict rejection and is only diagnostic once rejection has already occurred. However, in the past two decades, we have seen an expansion in assays that can potentially put an end to the “drug level” era, which until now has been one of the few tools available to clinicians for monitoring the immune response. A better understanding of the mechanisms of rejection and tolerance, and technological advances has led to the development of new noninvasive methods to monitor the immune response. In this article, we discuss these new methods and their potential uses in renal transplant recipients.

  9. Colonic Malakoplakia in a Liver Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Peter TW Kim

    2007-01-01

    Full Text Available Malakoplakia is a rare inflammatory condition seen in transplant patients. There are two previously reported cases of malakoplakia involving the gastrointestinal tract in liver transplant patients. The present paper reports a case of colonic malakoplakia in a 58-year-old woman, a liver transplant recipient who was receiving immunosuppressive drugs. She presented with chronic diarrhea while on tacrolimus. There was no history of antecedent infection. Colonoscopy showed patchy mucosal edema, but no discrete yellow plaques or nodules. The diagnosis was made by colon biopsies, which showed chronic inflammation with many histiocytes containing Michaelis-Gutmann bodies. Although rare, malakoplakia is one of many potential causes of diarrhea in a transplant patient. The present case indicates that malakoplakia may be associated with chronic diarrhea, even if there are no macroscopic lesions seen during colonoscopy.

  10. Pulmonary Infection In Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Rassulineiad M

    2003-11-01

    Full Text Available Renal transplantation is ideal treatment of chronic renal failure. Pulmonary infection is a common and serious post transplant infection requiring hospitalization and is associated with high mortality. Increased susceptibility to infection is due to a decrease in the patients' immunological response caused by immunosuppression through drug administration, and by other influences."nMaterials and Methods: This study was case series and prospective, from July 2001 to July 2002 in Imam Khomeini hospital of Tehran."nResults: 164 renal transplant recipients were studied, 14 patients (8.5% had pulmonary infection, 11 of them (78.6% were female and 3 (21.4% were male. The mean age of them was 42.6 years. The patients were followed up for 9 to 12 months. All patients were on triple immunosuppressive regimens. The interval between transplantation and the appearance of pneumonia was 2 months to 10 years. The time of beginning infection in 3 cases (21.4% was between 1 to 6 months post transplantation, 11 cases (78.6% were occurred beyond 6 months after transplantation. In 7 cases (50%, pulmonary infection was occurred during first year after transplantation. None of the 14 patients developed pulmonary infection in first month after transplantation. BAL were used in 6 cases (42.8% of pulmonary infection, and organism were detected in 5 of them (83.3%. The most common clinical feature was fever. Six cases were due to mycobacterium tuberculosis (42.9%, this organism was the most common ethiology of pneumonia. In this study tuberculosis was seen in 3.6% of renal transplant recipients. One patient had pulmonary mucormycosis. All patients with pulmonary TB were cured, and other cases with unknown case, were cured with empirical treatment."nConclusion: Our finding indicate the invasive diagnostic procedures are required in order to earlier and reliable diagnosis and then better outcome of transplantation."n"n"n"n"n"n"n 

  11. Microenterprise Development: An Employment Option for Welfare Recipients.

    Science.gov (United States)

    Friedman, Pamela

    2001-01-01

    This document examines microenterprise development as an employment option for Temporary Assistance for Needy Families (TANF) recipients. The document begins with a brief discussion of the feasibility of self-employment as an option for TANF recipients, particularly in a slow economy. The next section answers policy questions pertaining to the…

  12. Profiles of blood and blood component transfusion recipients in Zimbabwe

    NARCIS (Netherlands)

    Mafirakureva, Nyashadzaishe; Khoza, Star; Hassall, Oliver; Faragher, Brian E.; Kajja, Isaac; Mvere, David A.; Emmanuel, Jean C.; Postma, Maarten J.; van Hulst, Marinus

    2015-01-01

    Background. There are limited published data on the characteristics of blood transfusion recipients in sub-Saharan Africa. This study describes the demographic characteristics of blood transfusion recipients and patterns of blood and blood component use in Zimbabwe. Materials and methods. Data on th

  13. Increased rejection of murine allogeneic bone marrow in presensitized recipients

    NARCIS (Netherlands)

    vanOs, R; deWitte, T; Dillingh, JH; Mauch, PM; Down, JD

    1997-01-01

    The role of presensitizing murine recipients with donor spleen cells prior to T cell-depleted or -repleted H-2 compatible allogeneic bone marrow transplantation (BMT) was investigated at two different doses of total body irradiation (TBI). Recipients that were presensitized with 2 x 10(7) irradiated

  14. Recipient Recommendation in Enterprises Using Communication Graphs and Email Content

    NARCIS (Netherlands)

    Graus, D.; van Dijk, D.; Tsagkias, M.; Weerkamp, W.; de Rijke, M.

    2014-01-01

    We address the task of recipient recommendation for emailing in enterprises. We propose an intuitive and elegant way of modeling the task of recipient recommendation, which uses both the communication graph (i.e., who are most closely connected to the sender) and the content of the email.

  15. Constrictive pericarditis in a renal transplant recipient with tuberculosis.

    Science.gov (United States)

    Sreejith, P; Kuthe, S; Jha, V; Kohli, H S; Rathi, M; Gupta, K L; Sakhuja, V

    2010-07-01

    Tuberculosis is a common cause of pericarditis in the developing countries and constrictive pericarditis is a serious sequel. There are only three cases of constrictive pericarditis in kidney transplant recipients previously reported in literature. Here, we report a case of constrictive pericarditis developing in a renal transplant recipient while on antituberculous therapy for tuberculous pleural effusion.

  16. 38 CFR 18.516 - Affirmative action by recipients.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Affirmative action by... Determining Age Discrimination § 18.516 Affirmative action by recipients. Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome the effects of conditions that resulted...

  17. 44 CFR 7.924 - Affirmative action by recipient.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Affirmative action by... Standards for Determining Age Discrimination § 7.924 Affirmative action by recipient. Even in the absence of a finding of discrimination, a recipient may take affirmative action to overcome the effects...

  18. Profiles of blood and blood component transfusion recipients in Zimbabwe

    NARCIS (Netherlands)

    Mafirakureva, Nyashadzaishe; Khoza, Star; Hassall, Oliver; Faragher, Brian E.; Kajja, Isaac; Mvere, David A.; Emmanuel, Jean C.; Postma, Maarten J.; van Hulst, Marinus

    2015-01-01

    Background. There are limited published data on the characteristics of blood transfusion recipients in sub-Saharan Africa. This study describes the demographic characteristics of blood transfusion recipients and patterns of blood and blood component use in Zimbabwe. Materials and methods. Data on

  19. 75 FR 42786 - Accounting Guide for LSC Recipients (2010 Edition)

    Science.gov (United States)

    2010-07-22

    ... Accounting Guide for LSC Recipients (2010 Edition) AGENCY: Legal Services Corporation. ACTION: Notice. SUMMARY: The Legal Services Corporation (LSC) is revising the Accounting Guide for LSC Recipients to reflect changes that have occurred since the last publication of the Accounting Guide (the ``Guide'') in...

  20. 42 CFR 121.7 - Identification of organ recipient.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Identification of organ recipient. 121.7 Section... DEVELOPMENT ORGAN PROCUREMENT AND TRANSPLANTATION NETWORK § 121.7 Identification of organ recipient. (a) List....8. (3) When a donor or donor organ does not meet a transplant program's donor acceptance...

  1. 45 CFR 1643.5 - Recipient policies and recordkeeping.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Recipient policies and recordkeeping. 1643.5 Section 1643.5 Public Welfare Regulations Relating to Public Welfare (Continued) LEGAL SERVICES CORPORATION RESTRICTION ON ASSISTED SUICIDE, EUTHANASIA, AND MERCY KILLING § 1643.5 Recipient policies and...

  2. Transmission of donor melanoma to multiple organ transplant recipients.

    Science.gov (United States)

    Morris-Stiff, G; Steel, A; Savage, P; Devlin, J; Griffiths, D; Portman, B; Mason, M; Jurewicz, W A

    2004-03-01

    Malignant melanoma represents the most common tumour responsible for donor-derived post transplantation malignancies. We report the varied presentation and outcome of three graft recipients (two kidney and hepatic) who developed metastatic melanoma following cadaveric organ transplantation from a single multiorgan donor. Two of the recipients presented with symptomatic metastatic lesions and the third patient, despite being carefully monitored, developed evidence of metastatic cutaneous melanoma. Two of the patients died as a direct result of their melanomas. The recipients of corneal and cardiac grafts remain disease-free. We conclude that despite careful screening, donor-derived tumours remain a not uncommon clinical entity. The identification of a lesion in one recipient should prompt immediate examination and investigation of the remaining recipients of multiorgan donations.

  3. A case of IL-7R deficiency caused by a novel synonymous mutation and implications for mutation screening in SCID diagnosis.

    Directory of Open Access Journals (Sweden)

    FERNANDO GALLEGO-BUSTOS

    2016-10-01

    Full Text Available Reported synonymous substitutions are generally non-pathogenic and rare pathogenic synonymous variants may be disregarded unless there is a high index of suspicion. In a case of IL7 receptor deficiency SCID, the relevance of a non-reported synonymous variant was only suspected through the use of additional in silico computational tools which focused on the impact of mutations on gene splicing. The pathogenic nature of the variant was confirmed using experimental validation of the effect on mRNA splicing and IL7 pathway function. This case reinforces the need to use additional experimental methods to establish the functional impact of specific mutations, in particular for cases such as SCID where prompt diagnosis can greatly impact on diagnosis, treatment and survival.

  4. Cancer risk among lung transplant recipients with cystic fibrosis.

    Science.gov (United States)

    Fink, Aliza K; Yanik, Elizabeth L; Marshall, Bruce C; Wilschanski, Michael; Lynch, Charles F; Austin, April A; Copeland, Glenn; Safaeian, Mahboobeh; Engels, Eric A

    2017-01-01

    Previous studies demonstrated increased digestive tract cancers among individuals with cystic fibrosis (CF), particularly among lung transplant recipients. We describe cancer incidence among CF and non-CF lung recipients. We used data from the US transplant registry and 16 cancer registries. Standardized incidence ratios (SIRs) compared cancer incidence to the general population, and competing risk methods were used for the cumulative incidence of colorectal cancer. We evaluated 10,179 lung recipients (1681 with CF). Risk was more strongly increased in CF recipients than non-CF recipients for overall cancer (SIR 9.9 vs. 2.7) and multiple cancers including colorectal cancer (24.2 vs. 1.7), esophageal cancer (56.3 vs. 1.3), and non-Hodgkin lymphoma (61.8 vs. 9.4). At five years post-transplant, colorectal cancer was diagnosed in 0.3% of CF recipients aged <50 at transplant and 6.4% aged ≥50. CF recipients have increased risk for colorectal cancer, suggesting a need for enhanced screening. Copyright © 2016 European Cystic Fibrosis Society. All rights reserved.

  5. Effects of dendritic cells from cord blood CD34+ cells on human hepatocarcinoma cell line BEL-7402 in vitro and in SCID mice

    Institute of Scientific and Technical Information of China (English)

    Zhong-Jing Su; Hai-Bin Chen; Jin-Kun Zhang; Lan Xu

    2005-01-01

    AIM: To develop a cancer vaccine of dendritic cells derived from human cord blood CD34+ cells and to investigate its cytotoxicity on human hepatocarcinoma cells in vitro and in sever combined immunodeficiency (SCTD) mice.METHODS: Lymphocytes from cord blood or peripheral blood were primed by DCs, which were derived from cord blood and pulsed with whole tumor cell lysates. Nonradiative neutral red uptake assay was adopted to detect the cytotoxicity of primed lymphocytes on human hepatocarcinoma cell line BEL-7402 in vitro. The anti-tumor effect of primed lymphocytes in vivo was detected in SCID mice, including therapeutic effect and vaccination effect.RESULTS: The cytotoxicity of DC vaccine primed lymphocytes from cord blood or peripheral blood on human hepatocarcinoma cell line BEL-7402 was significantly higher than that of unprimed lymphocytes in vitro (44.09% vs 14.69%,47.92% vs 19.44%, P<0.01). There was no significant difference between the cytotoxicity of primed lymphocytes from cord blood and peripheral blood (P>0.05). The tumor growth rate and tumor size were smaller in SCID mice treated or vaccinated with primed lymphocytes than those with unprimed lymphocytes. SCID mice vaccinated with primed lymphocytes had a lower tumor incidence (80%vs 100%, P<0.05) and delayed tumor latent period compared with mice vaccinated with unprimed lymphocytes (11 d vs 7 d, P<0.01).CONCLUSION: Vaccine of cord blood derived-DCs has an inhibitory activity on growth of human hepatocarcinoma cells in vitro and in SCID mice. The results also implicate the potential role of cord blood derived-DC vaccine in clinical tumor immunotherapy.

  6. Selection of a rare neutralization-resistant variant following passive transfer of convalescent immune plasma in equine infectious anemia virus-challenged SCID horses.

    Science.gov (United States)

    Taylor, Sandra D; Leib, Steven R; Carpenter, Susan; Mealey, Robert H

    2010-07-01

    Vaccines preventing HIV-1 infection will likely elicit antibodies that neutralize diverse strains. However, the capacity for lentiviruses to escape broadly neutralizing antibodies (NAbs) is not completely understood, nor is it known whether NAbs alone can control heterologous infection. Here, we determined that convalescent immune plasma from a horse persistently infected with equine infectious anemia virus (EIAV) neutralized homologous virus and several envelope variants containing heterologous principal neutralizing domains (PND). Plasma was infused into young horses (foals) affected with severe combined immunodeficiency (SCID), followed by challenge with a homologous EIAV stock. Treated SCID foals were protected against clinical disease, with complete prevention of infection occurring in one foal. In three SCID foals, a novel neutralization-resistant variant arose that was found to preexist at a low frequency in the challenge inoculum. In contrast, SCID foals infused with nonimmune plasma developed acute disease associated with high levels of the predominant challenge virus. Following transfer to an immunocompetent horse, the neutralization-resistant variant induced a single febrile episode and was subsequently controlled in the absence of type-specific NAb. Long-term control was associated with the presence of cytotoxic T lymphocytes (CTL). Our results demonstrate that immune plasma with neutralizing activity against heterologous PND variants can prevent lentivirus infection and clinical disease in the complete absence of T cells. Importantly, however, rare neutralization-resistant envelope variants can replicate in vivo under relatively broad selection pressure, highlighting the need for protective lentivirus vaccines to elicit NAb responses with increased breadth and potency and/or CTL that target conserved epitopes.

  7. 急性淋巴细胞白血病CD34+CD38-细胞在NOD/SCID小鼠体内的自我更新与增值能力%Self-renewal and proliferation capability of CD34 + CD38 - cells from acute lymphoblastic leukemia patients transplanted in NOD/SCID mice

    Institute of Scientific and Technical Information of China (English)

    周晓燕; 龙娟; 谭俊杰; 邹琳

    2012-01-01

    Objective To explore the feasibility of establishing mouse model of leukemia by transplantion of human acute lymphoblastic leukemia (ALL) CD34+ CD38- cells into immunodeficient (NOD/SCID) mice, and to study the capability of self-renewal and proliferation in the mice. Methods The CD34+ CD38- cells were isolated from ALL patients and then identified, and the CD34- CD38+ cells were used as control. These cells were transplanted into sublethally irradiated NOD/SCID mice by tail-vein injection of 10 cells per recipient. The changes of peripheral blood were monitored continuously , and histopathological examination of the bone marrow, spleen and liver was performed in each death or dying mouse. Results The number of leukocytes in mouse peripheral blood was increased after inoculation of CD34+ CD38- or CD34- CD38+ cells at 4 weeks, peaked at 8 weeks up to 15 × 109~20 × 109/L, and also increased the number of original and blast lymphocytes. There were mainly increased the number of the original and blast lymphocytes (40% ) in the bone marrow, as well as the leukemic cells infiltrating in the spleen and liver of CD34 ' CD38 ~ mice, which was more obvious than that of the control CD34- CD38+ mice. Conclusions CD34+ CD38- cells from ALL patients can be successfully transplanted into NOD/SCID mice to induce leukemia, indicating that the CD34+ CD38- cells have the capability of self-renewal and proliferation. This model can be used as an important and useful tool for studies on leukemia-initiating cells.%目的 探索急性淋巴细胞白血病(ALL)患者CD34+ CD38-细胞移植到NOD/SCID小鼠体内建立白血病的可行性、自我更新与增殖潜能.方法 分选并鉴定ALL患者骨髓CD34+ CD38-细胞及对照CD34- CD38+细胞后,经尾静脉分别注射104个细胞于亚致死剂量射线照射的NOD/SCID小鼠体内,连续监测小鼠状态以及外周血血象改变,对濒死或死亡小鼠进行骨髓检查、肝脾病理学检查.结果

  8. Completely anonymous multi-recipient signcryption scheme with public verification.

    Science.gov (United States)

    Pang, Liaojun; Li, Huixian; Gao, Lu; Wang, Yumin

    2013-01-01

    Most of the existing multi-recipient signcryption schemes do not take the anonymity of recipients into consideration because the list of the identities of all recipients must be included in the ciphertext as a necessary element for decryption. Although the signer's anonymity has been taken into account in several alternative schemes, these schemes often suffer from the cross-comparison attack and joint conspiracy attack. That is to say, there are few schemes that can achieve complete anonymity for both the signer and the recipient. However, in many practical applications, such as network conference, both the signer's and the recipient's anonymity should be considered carefully. Motivated by these concerns, we propose a novel multi-recipient signcryption scheme with complete anonymity. The new scheme can achieve both the signer's and the recipient's anonymity at the same time. Each recipient can easily judge whether the received ciphertext is from an authorized source, but cannot determine the real identity of the sender, and at the same time, each participant can easily check decryption permission, but cannot determine the identity of any other recipient. The scheme also provides a public verification method which enables anyone to publicly verify the validity of the ciphertext. Analyses show that the proposed scheme is more efficient in terms of computation complexity and ciphertext length and possesses more advantages than existing schemes, which makes it suitable for practical applications. The proposed scheme could be used for network conferences, paid-TV or DVD broadcasting applications to solve the secure communication problem without violating the privacy of each participant.

  9. Completely anonymous multi-recipient signcryption scheme with public verification.

    Directory of Open Access Journals (Sweden)

    Liaojun Pang

    Full Text Available Most of the existing multi-recipient signcryption schemes do not take the anonymity of recipients into consideration because the list of the identities of all recipients must be included in the ciphertext as a necessary element for decryption. Although the signer's anonymity has been taken into account in several alternative schemes, these schemes often suffer from the cross-comparison attack and joint conspiracy attack. That is to say, there are few schemes that can achieve complete anonymity for both the signer and the recipient. However, in many practical applications, such as network conference, both the signer's and the recipient's anonymity should be considered carefully. Motivated by these concerns, we propose a novel multi-recipient signcryption scheme with complete anonymity. The new scheme can achieve both the signer's and the recipient's anonymity at the same time. Each recipient can easily judge whether the received ciphertext is from an authorized source, but cannot determine the real identity of the sender, and at the same time, each participant can easily check decryption permission, but cannot determine the identity of any other recipient. The scheme also provides a public verification method which enables anyone to publicly verify the validity of the ciphertext. Analyses show that the proposed scheme is more efficient in terms of computation complexity and ciphertext length and possesses more advantages than existing schemes, which makes it suitable for practical applications. The proposed scheme could be used for network conferences, paid-TV or DVD broadcasting applications to solve the secure communication problem without violating the privacy of each participant.

  10. In vivo assay of human NK-dependent ADCC using NOD/SCID/gammac(null) (NOG) mice.

    Science.gov (United States)

    Shiokawa, Miho; Takahashi, Takeshi; Murakami, Akihiro; Kita, Shoichi; Ito, Mamoru; Sugamura, Kazuo; Ishii, Naoto

    2010-09-03

    Monoclonal antibodies are essential to the success of molecularly targeted therapies. Recently, numerous therapeutic antibodies have been developed for various diseases, including cancer and autoimmune diseases. Experimental systems to effectively evaluate these candidate antibodies are urgently needed. One of the mechanisms used by antibodies to kill tumor cells is antibody-dependent cellular cytotoxicity (ADCC), in which natural killer cells (NK) are the main mediator. The capacity to induce ADCC has conventionally been assessed in the human-mouse xeno-graft model, in which human peripheral blood mononuclear cells (PBMC), containing NK cells along with antibodies, are administered to tumor-bearing immunodeficient mice. However, contamination from other cellular populations often affects tumor growth, making it difficult to evaluate the antibody's effect. In this study, we established a new NK-dependent ADCC assay model using a supra-immunodeficient strain of mice, NOD/SCID/gammac(null) (NOG). Our model system simply consisted of three elements: isolated human NK cells, a Burkitt's lymphoma cell line (Daudi), and an anti-CD20 antibody (Rituximab). In this experimental setting, human NK cells from healthy donors retained their killing activity and suppressed the growth of Daudi cells in NOG mice when they were administered along with Rituximab. This system, therefore, is useful for evaluating the in vivo function of human NK cells.

  11. Newborn Screening for Primary Immunodeficiencies: Focus on Severe Combined Immunodeficiency (SCID and Other Severe T-Cell Lymphopenias

    Directory of Open Access Journals (Sweden)

    Stephan Borte

    2015-12-01

    Full Text Available Primary immunodeficiencies (PID are congenital disorders of immune competence, which are mainly characterized by a pathological susceptibility to infection. More than 240 PID disease entities have been defined so far, accounting for a broad spectrum of clinical symptoms and severity. Severe PID are increasingly becoming appreciated as a relevant health problem, and diagnostic procedures and screening profiles to allow earliest possible diagnosis on a population scale have already been developed in the USA and few European countries. The most severe PID are characterized by significant mortality in the first years of life, as well as serious morbidity with irreversible organ damage. This applies in particular to PID that are defined by the absence or functional anergy of T-lymphocytes (severe combined immunodeficiency; SCID or B-lymphocytes (e.g., X-linked agammaglobulinemia; XLA. A strategy to improve the outcome of severe PID by prompt diagnosis and immediate adequate treatment is screening newborns for the presence of T and B cells.

  12. Pharmacokinetics and tissue distribution of inositol hexaphosphate in C.B17 SCID mice bearing human breast cancer xenografts.

    Science.gov (United States)

    Eiseman, Julie; Lan, Jing; Guo, Jianxia; Joseph, Erin; Vucenik, Ivana

    2011-10-01

    Inositol hexaphosphate (IP(6)) is effective in preclinical cancer prevention and chemotherapy. In addition to cancer, IP(6) has many other beneficial effects for human health, such as reduction in risk of developing cardiovascular disease and diabetes and inhibition of kidney stone formation. Studies presented here describe the pharmacokinetics, tissue distribution, and metabolism of IP(6) following intravenous (IV) or per os (PO) administration to mice. SCID mice bearing MDA-MB-231 xenografts were treated with 20 mg/kg IP(6) (3 μCi per mouse [(14)C]-uniformly ring-labeled IP(6)) and euthanized at various times after IP(6) treatment. Plasma and tissues were analyzed for [(14)C]-IP(6) and metabolites by high-performance liquid chromatography with radioactivity detection. Following IV administration of IP(6), plasma IP(6) concentrations peaked at 5 minutes and were detectable until 45 minutes. Liver IP(6) concentrations were more than 10-fold higher than plasma concentrations, whereas other normal tissue concentrations were similar to plasma. Only inositol was detected in xenografts. After PO administration, IP(6) was detected in liver; but only inositol was detectable in other tissues. After both IV and PO administration, exogenous IP(6) was rapidly dephosphorylated to inositol; however, alterations in endogenous IPs were not examined.

  13. Pharmacological Evaluation of the SCID T Cell Transfer Model of Colitis: As a Model of Crohn's Disease

    Directory of Open Access Journals (Sweden)

    Thomas Lindebo Holm

    2012-01-01

    Full Text Available Animal models are important tools in the development of new drug candidates against the inflammatory bowel diseases (IBDs Crohn's disease and ulcerative colitis. In order to increase the translational value of these models, it is important to increase knowledge relating to standard drugs. Using the SCID adoptive transfer colitis model, we have evaluated the effect of currently used IBD drugs and IBD drug candidates, that is, anti-TNF-α, TNFR-Fc, anti-IL-12p40, anti-IL-6, CTLA4-Ig, anti-α4β7 integrin, enrofloxacin/metronidazole, and cyclosporine. We found that anti-TNF-α, antibiotics, anti-IL-12p40, anti-α4β7 integrin, CTLA4-Ig, and anti-IL-6 effectively prevented onset of colitis, whereas TNFR-Fc and cyclosporine did not. In intervention studies, antibiotics, anti-IL-12p40, and CTLA4-Ig induced remission, whereas the other compounds did not. The data suggest that the adoptive transfer model and the inflammatory bowel diseases have some main inflammatory pathways in common. The finding that some well-established IBD therapeutics do not have any effect in the model highlights important differences between the experimental model and the human disease.

  14. Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and trisomy 8 mosaicism: a case report.

    Science.gov (United States)

    Engel, Barbara C; Podsakoff, Greg M; Ireland, Joanna L; Smogorzewska, E Monika; Carbonaro, Denise A; Wilson, Kathy; Shah, Ami; Kapoor, Neena; Sweeney, Mirna; Borchert, Mark; Crooks, Gay M; Weinberg, Kenneth I; Parkman, Robertson; Rosenblatt, Howard M; Wu, Shi-Qi; Hershfield, Michael S; Candotti, Fabio; Kohn, Donald B

    2007-01-15

    A patient with adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) was enrolled in a study of retroviral-mediated ADA gene transfer to bone marrow hematopoietic stem cells. After the discontinuation of ADA enzyme replacement, busulfan (75 mg/m2) was administered for bone marrow cytoreduction, followed by infusion of autologous, gene-modified CD34+ cells. The expected myelosuppression developed after busulfan but then persisted, necessitating the administration of untransduced autologous bone marrow back-up at day 40. Because of sustained pancytopenia and negligible gene marking, diagnostic bone marrow biopsy and aspirate were performed at day 88. Analyses revealed hypocellular marrow and, unexpectedly, evidence of trisomy 8 in 21.6% of cells. Trisomy 8 mosaicism (T8M) was subsequently diagnosed by retrospective analysis of a pretreatment marrow sample that might have caused the lack of hematopoietic reconstitution. The confounding effects of this preexisting marrow cytogenetic abnormality on the response to gene transfer highlights another challenge of gene therapy with the use of autologous hematopoietic stem cells.

  15. Establishment of NOD/SCID mouse models of human hepatocellular carcinoma via subcutaneous transplantation of histologically intact tumor tissue

    Institute of Scientific and Technical Information of China (English)

    Mingxia Yan; Hong Li; Fangyu Zhao; Lixing Zhang; Chao Ge; Ming Yao; Jinjun Li

    2013-01-01

    Hepatocellular carcinoma (HCC) is one of the most deadly human cancers,but it is very difficult to establish an animal model by using surgical specimens.In the present experiment,histologically intact fresh surgical specimens of HCC were subcutaneously transplanted in non-obese diabetic/severe combined immunodeficienccy (NOD/SCID) mice.The biological characteristics of the original and the corresponding transplanted tumors and cell lines were investigated.The results showed that 5 new animal models and 2 primary cell lines were successfully established from surgical specimens.Hematoxylin-eosin staining showed that xenografts retained major histological features of the original surgical specimens.The two new cell lines had been cultivated for 3 years and successively passaged for more than 100 passages in vitro.The morphological characteristics and biologic features of the two cell lines were genetically similar to the original tumor.The subcutaneous transplant animal models with histologically intact tumor tissue and primary cell lines could be useful for in vivo and in vitro testing of anti-cancer drugs and be ideal models to study various biologic features of HCC.

  16. IgE basement membrane zone antibodies induce eosinophil infiltration and histological blisters in engrafted human skin on SCID mice.

    Science.gov (United States)

    Zone, John J; Taylor, Ted; Hull, Christopher; Schmidt, Linda; Meyer, Laurence

    2007-05-01

    Bullous pemphigoid (BP) is characterized by the deposition of IgG in the basement membrane zone, infiltration of eosinophils, and blister formation. The purpose of this study was to evaluate a potential role of IgE basement membrane antibodies in the histological findings of BP. LABD97 is a component of the shed ectodomain of bullous pemphigoid antigen 2. We have developed an IgE hybridoma to LABD97 antigen. This hybridoma was injected subcutaneously in SCID mice with engrafted human skin. A subcutaneous hybridoma secreting IgE antibodies developed. An IgE mouse hybridoma to trinitrophenyl was used as a control. Human grafts and mouse skin were examined grossly over 21 days, histologically, and immunopathologically at day 21 after injection of the hybridoma. A visible subcutaneous tumor developed in 10-14 days. Erythema and intense scratching developed 2-3 days before the tumor in test mice, but not in controls. At day 21, 16/16 test mice developed intense eosinophil infiltration and degranulation of the human mast cells within the grafts and 13/16 developed histological, but not clinically visible, basement membrane blisters. Human skin grafts of control mice and normal mouse skin on the test mice and control mice did not develop any histological abnormalities. IgE antibodies to LABD97 recapitulate the histological inflammatory process seen in BP.

  17. A New IL-2RG Gene Mutation in an X-linked SCID Identified through TREC/KREC Screening: a Case Report

    Directory of Open Access Journals (Sweden)

    Maryam Nourizadeh

    2015-10-01

    Full Text Available Severe combined immunodeficiency (SCID represents a rare group of primary immunodeficiency disorders (PIDs, with known or unknown genetic alterations. Here, we report a new interleukin 2 receptor, gamma chain (IL-2RG mutation in an Iranian SCID newborn.The patient was a 6-day old boy with a family history of PID. The child was screened using a molecular-based analysis for the assessment of T cell receptor excision circles (TRECs and kappa-deleting recombination excision circles (KRECs. Moreover, a complete immunological evaluation and gene sequencing was performed.Results showed undetectable TREC but a high level of KREC copy numbers. Flowcytometric data indicated low numbers of T and NK cells, but elevated number of B cells. A novel substitution in IL2RG: c.675 C>A, leading to p.225 Ser>Arg was found. Based on the functional analysis, the mutation is predicted to be damaging. The patient was diagnosed as a T B+ NK X-linked SCID.

  18. Pretransplant mobilization with granulocyte colony-stimulating factor improves B-cell reconstitution by lentiviral vector gene therapy in SCID-X1 mice.

    Science.gov (United States)

    Huston, Marshall W; Riegman, Adriaan R A; Yadak, Rana; van Helsdingen, Yvette; de Boer, Helen; van Til, Niek P; Wagemaker, Gerard

    2014-10-01

    Hematopoietic stem cell (HSC) gene therapy is a demonstrated effective treatment for X-linked severe combined immunodeficiency (SCID-X1), but B-cell reconstitution and function has been deficient in many of the gene therapy treated patients. Cytoreductive preconditioning is known to improve HSC engraftment, but in general it is not considered for SCID-X1 since the poor health of most of these patients at diagnosis and the risk of toxicity preclude the conditioning used in standard bone marrow stem cell transplantation. We hypothesized that mobilization of HSC by granulocyte colony-stimulating factor (G-CSF) should create temporary space in bone marrow niches to improve engraftment and thereby B-cell reconstitution. In the present pilot study supplementing our earlier preclinical evaluation (Huston et al., 2011), Il2rg(-/-) mice pretreated with G-CSF were transplanted with wild-type lineage negative (Lin(-)) cells or Il2rg(-/-) Lin(-) cells transduced with therapeutic IL2RG lentiviral vectors. Mice were monitored for reconstitution of lymphocyte populations, level of donor cell chimerism, and antibody responses as compared to 2 Gy total body irradiation (TBI), previously found effective in promoting B-cell reconstitution. The results demonstrate that G-CSF promotes B-cell reconstitution similar to low-dose TBI and provides proof of principle for an alternative approach to improve efficacy of gene therapy in SCID patients without adverse effects associated with cytoreductive conditioning.

  19. Successful reconstitution of immunity in ADA-SCID by stem cell gene therapy following cessation of PEG-ADA and use of mild preconditioning.

    Science.gov (United States)

    Gaspar, H Bobby; Bjorkegren, Emma; Parsley, Kate; Gilmour, Kimberly C; King, Doug; Sinclair, Joanna; Zhang, Fang; Giannakopoulos, Aris; Adams, Stuart; Fairbanks, Lynette D; Gaspar, Jane; Henderson, Lesley; Xu-Bayford, Jin Hua; Davies, E Graham; Veys, Paul A; Kinnon, Christine; Thrasher, Adrian J

    2006-10-01

    Gene therapy is a promising treatment option for monogenic diseases, but success has been seen in only a handful of studies thus far. We now document successful reconstitution of immune function in a child with the adenosine deaminase (ADA)-deficient form of severe combined immunodeficiency (SCID) following hematopoietic stem cell (HSC) gene therapy. An ADA-SCID child who showed a poor response to PEG-ADA enzyme replacement was enrolled into the clinical study. Following cessation of enzyme replacement therapy, autologous CD34(+) HSCs were transduced with an ADA-expressing gammaretroviral vector. Gene-modified cells were reinfused following one dose of preconditioning chemotherapy. Two years after the procedure, immunological and biochemical correction has been maintained with progressive increase in lymphocyte numbers, reinitiation of thymopoiesis, and systemic detoxification of ADA metabolites. Sustained vector marking with detection of polyclonal vector integration sites in multiple cell lineages and detection of ADA activity in red blood cells suggests transduction of early hematopoietic progenitors. No serious side effects were seen either as a result of the conditioning procedure or due to retroviral insertion. Gene therapy is an effective treatment option for the treatment of ADA-SCID.

  20. Monocyte-derived dendritic cells induce a house dust mite-specific Th2 allergic inflammation in the lung of humanized SCID mice: involvement of CCR7.

    Science.gov (United States)

    Hammad, Hamida; Lambrecht, Bart N; Pochard, Pierre; Gosset, Philippe; Marquillies, Philippe; Tonnel, André-Bernard; Pestel, Joël

    2002-08-01

    In rodents, airway dendritic cells (DCs) capture inhaled Ag, undergo maturation, and migrate to the draining mediastinal lymph nodes (MLN) to initiate the Ag-specific T cell response. However, the role of human DCs in the pathogenesis of the Th2 cell-mediated disease asthma remains to be clarified. Here, by using SCID mice engrafted with T cells from either house dust mite (HDM)-allergic patients or healthy donors, we show that DCs pulsed with Der p 1, one of the major allergens of HDM, and injected intratracheally into naive animals migrated into the MLN. In the MLN, Der p 1-pulsed DCs from allergic patients induced the proliferation of IL-4-producing CD4(+) T cells, whereas those from healthy donors induced IFN-gamma-secreting cells. In reconstituted human PBMC-reconstituted SCID mice primed with pulsed DCs from allergic patients, repeated exposure to aerosols of HDM induced 1) a strong pulmonary inflammatory reaction rich in T cells and eosinophils, 2) an increase in IL-4 and IL-5 production in the lung lavage fluid, and 3) increased IgE production compared with that in mice primed with unpulsed DCs. All these effects were reduced following in vivo neutralization of the CCR7 ligand secondary lymphoid tissue chemokine. These data in human PBMC-reconstituted SCID mice show that monocyte-derived DCs might play a key role in the pathogenesis of the pulmonary allergic response by inducing Th2 effector function following migration to the MLN.

  1. Development of Cryptosporidium parvum-Induced Gastrointestinal Neoplasia in Severe Combined Immunodeficiency (SCID) Mice: Severity of Lesions Is Correlated with Infection Intensity

    Science.gov (United States)

    Certad, Gabriela; Creusy, Colette; Ngouanesavanh, Tramy; Guyot, Karine; Gantois, Nausicaa; Mouray, Anthony; Chassat, Thierry; Flament, Nicolas; Fleurisse, Laurence; Pinon, Anthony; Delhaes, Laurence; Dei-Cas, Eduardo

    2010-01-01

    We reported previously that Cryptosporidium parvum was able to induce intestinal tumors in severe combined immunodeficiency (SCID) mice treated with corticoids. To further characterize this Cryptosporidium-induced cell transformation, SCID mice treated with dexamethasone were challenged with C. parvum oocysts, and euthanatized sequentially after infection for histologic examination. Ki-67 was used as a marker of cellular proliferation. Our previous results were confirmed, and it was also found that mice receiving higher inocula (106–107) experienced more severe neoplastic development. Additionally, neoplastic changes were observed not only in the caecum but also in the stomach and duodenum of some animals. Interestingly, SCID mice (6/6) inoculated with 105–107 oocysts showed high grade intraepithelial neoplasia or adenomas with high grade dysplasia in the caecum after Day 46 post-infection (PI). Immunohistochemistry for Ki-67 staining indicated the neoplastic process associated to cryptosporidiosis, and evidenced the first immunohistochemical alterations at early stages of the process, even at 3 weeks PI. PMID:20134002

  2. ACUTE APENDICITIS IN LIVER TRANSPLANT RECIPIENTS.

    Science.gov (United States)

    Fonseca-Neto, Olival Cirilo Lucena da; Lima, Heloise Caroline de Souza; Melo, Paulo Sérgio Vieira de; Lemos, Roberto; Leitão, Laércio; Amorim, Américo Gusmão; Lacerda, Cláudio Moura

    2016-03-01

    Appendicitis is a common cause of emergency surgery that in the population undergoing organ transplantation presents a rare incidence due to late diagnosis and treatment. To report the occurrence of acute appendicitis in a cohort of liver transplant recipients. Retrospective analysis in a period of 12 years among 925 liver transplants, in witch five cases of acute appendicitis were encountered. Appendicitis occurred between three and 46 months after liver transplantation. The age ranged between 15 and 58 years. There were three men and two women. The clinical presentations varied, but not discordant from those found in non-transplanted patients. Pain was a symptom found in all patients, in two cases well located in the right iliac fossa (40%). Two patients had symptoms characteristic of peritoneal irritation (40%) and one patient had abdominal distention (20%). All patients were submitted to laparotomies. In 20% there were no complications. In 80% was performed appendectomy complicated by suppuration (40%) or perforation (40%). Superficial infection of the surgical site occurred in two patients, requiring clinical management. The hospital stay ranged from 48 h to 45 days. Acute appendicitis after liver transplantation is a rare event being associated with a high rate of drilling, due to delays in diagnosis and therapy, and an increase in hospital stay.

  3. Criteria for selecting organ donors and recipients.

    Science.gov (United States)

    Michielsen, P

    1990-11-01

    As there is a world-wide shortage of organs for transplantation, the selection of the patients is more defined by the availability of transplantable organs than by the medical condition of the potential recipient. This shortage of cadaveric organs is mainly responsible for the use of living donors. With HLA identical sibling donors the results are better than with cadaveric organs, but the ethical problems are usually underestimated. For the parent-to-child donation, the HLA compatibility is less than what could be achieved with well-matched cadaveric donors. The use of genetically unrelated donors is unacceptable from the ethical as well as from the medical point of view. The short- and long-term risk of donation has been insufficiently documented. The experience with the introduction of an opting-out legislation in Belgium in 1987 demonstrates that the shortage of cadaveric organs can be overcome. Harmonization of the legislation is, however, necessary so as to achieve comparable organ retrieval rates between countries participating in organ-exchange organisations.

  4. Pregnancy outcome in renal transplant recipients.

    Science.gov (United States)

    Kuvacić, I; Sprem, M; Skrablin, S; Kalafatić, D; Bubić-Filipi, L; Milici D

    2000-09-01

    To correlate pregnancy outcome with complications in pregnancy and transplantation-to-pregnancy interval in renal transplant recipients in Croatia. Data on 23 pregnancies after prepregnancy stabilization of blood pressure and normalization of graft function were retrospectively analyzed. The mean interval between transplantation and conception was 3.1 years. Primary renal disease was chronic glomerulonephritis in 7, chronic pyelonephritis in 7 and agenesis of right kidney and stenosis of left renal artery in 1 patient. There were 10 term and 5 preterm deliveries, 6 induced and 2 spontaneous abortions. The mean gestational age was 38.1 weeks and the mean newborn birthweight was 3015 g. The prematurity rate was 21.7%. Patients with arterial hypertension in pregnancy, elevated serum creatinine level and bacteriuria, as well as those with conception occurring less than 2 years after transplantation, had a higher rate of therapeutic and spontaneous abortions, preterm deliveries and low birth weight infants. The interval between transplantation and conception, as well as allograft function during pregnancy, seem to be of great importance for successful obstetric outcome in renal transplant patients.

  5. Nonmelanoma Skin Cancer in Nonwhite Organ Transplant Recipients.

    Science.gov (United States)

    Pritchett, Ellen N; Doyle, Alden; Shaver, Christine M; Miller, Brett; Abdelmalek, Mark; Cusack, Carrie Ann; Malat, Gregory E; Chung, Christina Lee

    2016-12-01

    Organ transplant recipients have a higher incidence of skin cancer. This risk is magnified over time and with continued exposure to immunosuppression. Skin cancer in nonwhite patients is associated with greater morbidity and mortality owing to diagnosis at a more advanced stage, which suggests that nonwhite organ transplant recipients are at even higher risk. To describe demographic and clinical factors and the incidence of skin cancer in nonwhite organ transplant recipients. We performed a retrospective medical record review of patients who were organ transplant recipients (154 were white and 259 nonwhite [black, Asian, Hispanic, Pacific Islander]) seen from November 1, 2011, to April 18, 2016 at an academic referral center. Variables were analyzed and compared between racial groups, including sex, age, race/ethnicity, Fitzpatrick type, type and location of skin cancer, type of organ transplanted, time to diagnosis of skin cancer after transplantation, and history of condyloma acuminata and/or verruca vulgaris. Most of the 413 patients (62.7%) evaluated were nonwhite organ transplant recipients; 264 were men, and 149 were women. Their mean (SD) age was 60.09 (13.59) years. Nineteen skin cancers were identified in 15 patients (5.8%) representing 3 racial/ethnic groups: black (6 patients), Asian (5), and Hispanic (4). All squamous cell carcinomas in blacks were diagnosed in the in situ stage, located on sun-protected sites, and occurred in patients whose lesions tested positive for human papilloma virus (HPV) and/or who endorsed a history of condyloma acuminata or verruca vulgaris. Most skin cancers in Asians were located on sun-exposed areas and occurred in individuals who emigrated from equatorial locations. Nonwhite organ transplant recipients are at risk for developing skin cancer posttransplantation. Follow-up in a specialized transplant dermatology center and baseline total-body skin examination should be part of posttransplantation care in all organ

  6. Strongyloides stercoralis infection in an intestinal transplant recipient.

    Science.gov (United States)

    Hsu, C N; Tseng, S H; Chang, S W; Chen, Y

    2013-08-01

    Strongyloides stercoralis is a helminth in tropical and subtropical areas. It may cause latent infection and progress to Strongyloides hyperinfection syndrome, which is associated with a high mortality rate. Transplant recipients under the treatment of immunosuppressant agents are at risk of severe S. stercoralis infection. According to related literature, most cases of S. stercoralis infection after solid organ transplantation are caused by reactivation of latent infections in the recipients, whereas only a few are acquired from the donors. We report on an intestinal transplant recipient who had S. stercoralis infection diagnosed by a larva of this parasite found in the stool from the ileostomy stoma 1 month after transplantation. The donor was considered the source of the infection because the donor was from an endemic area and had marked eosinophilia, and the recipient had no contact history or clinical manifestations related to the S. stercoralis infection before transplantation. The patient was treated with ivermectin and exhibited no evidence of infection after 7 months.

  7. Head and neck malignancies in Croatian renal transplant recipients

    National Research Council Canada - National Science Library

    Basić-Jukić, Nikolina; Bubić-Filipi, Ljubica; Prgomet, Drago; Djanić Hadzibegović, Ana; Bilić, Mario; Kovac, Lana; Kastelan, Zeljko; Pasini, Josip; Mokos, Ivica; Basić-Koretić, Martina; Kes, Petar

    2010-01-01

    Renal transplantation is associated with increased incidence of cancer. We reviewed a large series of renal transplant recipients to determine the incidence and outcome of patients with malignant changes located at the head and neck...

  8. Dietary Acid Load and Metabolic Acidosis in Renal Transplant Recipients

    NARCIS (Netherlands)

    Berg, van den Else; Engberink, M.F.; Brink, E.J.; Baak, van M.A.; Joosten, M.M.; Gans, R.O.B.; Navis, G.; Bakker, S.J.L.

    2012-01-01

    Background and objectives Acidosis is prevalent among renal transplant recipients (RTRs) and adversely affects cardiometabolic processes. Factors contributing to acidosis are graft dysfunction and immunosuppressive drugs. Little is known about the potential influence of diet on acidosis in RTRs. Thi

  9. Cadaver renal transplant outcome in recipients with autolymphocytotoxic antibodies.

    Science.gov (United States)

    Ettenger, R B; Jordan, S C; Fine, R N

    1983-05-01

    The major impact of autolymphocytotoxic antibodies (ALCA) on renal transplantation has been in the interpretation of the pretransplant crossmatch as a cause of false-positive results. Less attention has been paid to the direct affects of ALCA on renal allografts. We have examined the sera of 38 recipients of 41 cadaver renal allografts for the presence of ALCA. There were 9 patients with ALCA who received 10 allografts. In these allografts with ALCA, actuarial graft survival was significantly improved (P less than 0.05) over that of 31 transplants without ALCA. In recipients with ALCA, graft survival was 90% at six months and 60% at one and two years; in recipients without ALCA, graft survival was 48% at six months, 35% at one year and 24% at two years. ALCA may be exerting graft-enhancing properties by means of an autoregulatory effect upon the recipient's immunologic system.

  10. Dietary Acid Load and Metabolic Acidosis in Renal Transplant Recipients

    NARCIS (Netherlands)

    Berg, van den Else; Engberink, M.F.; Brink, E.J.; Baak, van M.A.; Joosten, M.M.; Gans, R.O.B.; Navis, G.; Bakker, S.J.L.

    2012-01-01

    Background and objectives Acidosis is prevalent among renal transplant recipients (RTRs) and adversely affects cardiometabolic processes. Factors contributing to acidosis are graft dysfunction and immunosuppressive drugs. Little is known about the potential influence of diet on acidosis in RTRs.

  11. Active Labour Market Programme Participation for Unemployment Insurance Recipients

    DEFF Research Database (Denmark)

    Filges, Trine; Smedslund, Geir; Jørgensen, Anne-Marie Klint

    2016-01-01

    Objective: This review evaluates the effectiveness of Active Labour Market Programme (ALMP) participation on employment status for unemployment insurance recipients. Methods and Analysis: We followed Campbell Collaboration guidelines to conduct a systematic review. Results: A total of 73 studies...

  12. Multifocal bacterial osteomyelitis in a renal allograft recipient following urosepsis.

    Science.gov (United States)

    Valson, A T; David, V G; Balaji, V; John, G T

    2014-05-01

    Non-tubercular bacterial osteomyelitis is a rare infection. We report on a renal allograft recipient with osteomyelitis complicating urosepsis, manifesting as a multifocal infection poorly responsive to appropriate antibiotics and surgical intervention and culminating in graft loss.

  13. Lactobacillus rhamnosus bacteremia in a kidney transplant recipient.

    Science.gov (United States)

    Falci, D R; Rigatto, M H; Cantarelli, V V; Zavascki, A P

    2015-08-01

    Lactobacillus rhamnosus is a rare clinical pathogen. A case of bacteremia caused by L. rhamnosus in a kidney transplant recipient is described. Once considered only as a contaminant or a low-virulence organism, L. rhamnosus might be an opportunistic pathogen in immunocompromised patients. To our knowledge, this is the first report of primary bloodstream infection caused by L. rhamnosus in a kidney transplant recipient. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Cryptococcal meningitis presenting as sinusitis in a renal transplant recipient.

    Science.gov (United States)

    Iyer, S P; Movva, K; Wiebel, M; Chandrasekar, P; Alangaden, G; Carron, M; Tranchida, P; Revankar, S G

    2013-10-01

    Cryptococcal meningitis is a relatively common invasive fungal infection in immunocompromised patients, especially in solid organ transplant recipients. Clinical presentation typically includes fever, headache, photophobia, neck stiffness, and/or altered mental status. Unusual presentations may delay diagnosis. Therapy is challenging in renal transplant patients because of the nephrotoxicity associated with amphotericin B, the recommended treatment. We present a case of cryptococcal meningitis in a renal transplant recipient presenting as acute sinusitis with successful treatment using fluconazole as primary therapy.

  15. Imaging in Lung Transplantation: Surgical Considerations of Donor and Recipient.

    Science.gov (United States)

    Backhus, Leah M; Mulligan, Michael S; Ha, Richard; Shriki, Jabi E; Mohammed, Tan-Lucien H

    2016-03-01

    Modifications in recipient and donor criteria and innovations in donor management hold promise for increasing rates of lung transplantation, yet availability of donors remains a limiting resource. Imaging is critical in the work-up of donor and recipient including identification of conditions that may portend to poor posttransplant outcomes or necessitate modifications in surgical technique. This article describes the radiologic principles that guide selection of patients and surgical procedures in lung transplantation.

  16. Dream anxiety in renal transplant recipients.

    Science.gov (United States)

    Yazla, Ece; Ozkurt, Sultan; Musmul, Ahmet

    2015-06-01

    Although low quality of sleep has been reported in kidney transplant patients with functioning allografts, there are no previous studies investigating the dreams of these patients. We aimed to investigate the differences in dream anxiety level between renal transplant patients and healthy control subjects. We also planned to compare depression and anxiety symptoms, sleep quality and sleepiness level between these two groups. Twenty-two living-donor renal transplant recipients followed at an outpatient nephrology clinic and 22 healthy controls were enrolled in this observational cross-sectional study. Sociodemographic Data Collection Form, and the Van Dream Anxiety Scale (VDAS), the Pittsburg Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), Beck Depression and Anxiety Inventories were used for the assessment of the necessary features. Hemoglobin (Hb), blood urea nitrogen (BUN), creatinine (Cr) and glucose levels were measured. There were no significant differences between the groups in terms of dream anxiety (p = 0.45), depression (p = 0.76), sleep quality (p = 0.8), insomnia severity (p = 0.08) and Hb (p = 0.11) and glucose levels (p = 0.14). Although, BUN (p = 0.00) and creatinine (p = 0.00) levels differed significantly between the two groups, both parameters were found to be within their normal range. In our study, chronic renal failure patients with a successful kidney transplant were found to be able to completely return to normal in terms of metabolic parameters, sleep quality and mood. Similar levels of dream anxiety are also consistent with these findings.

  17. Epidemiology of infections in kidney transplant recipients - data miner's approach.

    Science.gov (United States)

    Wojciuk, Bartosz; Myślak, Marek; Pabisiak, Krzysztof; Ciechanowski, Kazimierz; Giedrys-Kalemba, Stefania

    2015-06-01

    Infections remain a frequent complication following organ transplantation. Agents present within the general population remain common in recurrent infections among renal transplant recipients. Data mining methodology has become a promising source of information about patterns in the organ transplant recipient population. The aim of the study was to use data mining to describe the factors influencing single and recurrent infections in kidney transplant recipients. A group of 159 recipients who underwent kidney transplantation between 2005 and 2008 was analysed. RapidMiner and Statistica softwares were used to create decision tree models based on CART Quinlan and C&RT algorithms. There were 171 microbiologically confirmed episodes among 67 recipients (41%), and 191 separate species isolations were performed. Over 50% of the infected patients underwent two or more infectious episodes. Two classification decision tree models were created. The following features were enabled to differentiate the groups with single or recurrent infections: the duration of cold ischaemia, the post-transplant hospitalization period, the cause of chronic kidney disease and pathogens. The post-transplant hospitalization period and the length of cold ischaemia appear to be the principal parameters differentiating the subpopulations analysed. These coexisting factors, connected with recurrent infections in kidney transplant recipients, resemble a network which requires an advanced analysis to support the traditional statistics.

  18. Recipient design in human communication: simple heuristics or perspective taking?

    Science.gov (United States)

    Blokpoel, Mark; van Kesteren, Marlieke; Stolk, Arjen; Haselager, Pim; Toni, Ivan; van Rooij, Iris

    2012-01-01

    Humans have a remarkable capacity for tuning their communicative behaviors to different addressees, a phenomenon also known as recipient design. It remains unclear how this tuning of communicative behavior is implemented during live human interactions. Classical theories of communication postulate that recipient design involves perspective taking, i.e., the communicator selects her behavior based on her hypotheses about beliefs and knowledge of the recipient. More recently, researchers have argued that perspective taking is computationally too costly to be a plausible mechanism in everyday human communication. These researchers propose that computationally simple mechanisms, or heuristics, are exploited to perform recipient design. Such heuristics may be able to adapt communicative behavior to an addressee with no consideration for the addressee's beliefs and knowledge. To test whether the simpler of the two mechanisms is sufficient for explaining the "how" of recipient design we studied communicators' behaviors in the context of a non-verbal communicative task (the Tacit Communication Game, TCG). We found that the specificity of the observed trial-by-trial adjustments made by communicators is parsimoniously explained by perspective taking, but not by simple heuristics. This finding is important as it suggests that humans do have a computationally efficient way of taking beliefs and knowledge of a recipient into account.

  19. Recipient design in human communication: Simple heuristics or perspective taking?

    Directory of Open Access Journals (Sweden)

    Mark eBlokpoel

    2012-09-01

    Full Text Available Humans have a remarkable capacity for tuning their communicative behaviors to different addressees, a phenomenon also known as recipient design. It remains unclear how this tuning of communicative behavior is implemented during live human interactions. Classical theories of communication postulate that recipient design involves perspective taking, i.e., the communicator selects her behavior based on her hypotheses about beliefs and knowledge of the recipient. More recently, researchers have argued that perspective taking is computationally too costly to be a plausible mechanism in everyday human communication. These researchers propose that computationally simple mechanisms, or heuristics, are exploited to perform recipient design. Such heuristics may be able to adapt communicative behavior to an addressee with no consideration for the addressee's beliefs and knowledge. To test whether the simpler of the two mechanisms is sufficient for explaining the `how' of recipient design we studied communicators' behaviors in the context of a non-verbal communicative task (the Tacit Communication Game, TCG. We found that the specificity of the observed trial-by-trial adjustments made by communicators is parsimoniously explained by perspective taking, but not by simple heuristics. This finding is important as it suggests that humans do have a computationally efficient way of taking beliefs and knowledge of a recipient into account.

  20. Postoperative acute kidney injury in living donor liver transplantation recipients.

    Science.gov (United States)

    Atalan, Hakan K; Gucyetmez, Bulent; Aslan, Serdar; Yazar, Serafettin; Polat, Kamil Y

    2017-09-05

    There are many risk factors for postoperative acute kidney injury in liver transplantation. The aim of this study is to investigate the risk factors for postoperative acute kidney injury in living donor liver transplantation recipients. 220 living donor liver transplantation recipients were retrospectively evaluated in the study. According to the Kidney Disease Improving Global Outcomes Guidelines, acute kidney injury in postoperative day 7 was investigated for all patients. The patient's demographic data, preoperative and intraoperative parameters, and outcomes were recorded. Acute kidney injury was found in 27 (12.3%) recipients. In recipients with acute kidney injury, female population, model for end-stage liver disease score, norepinephrine requirement, duration of mean arterial pressure less than 60 mmHg, the usage of gelatin and erythrocyte suspension and blood loss were significantly higher than recipients with nonacute kidney injury (for all p5 mL kg-1 and duration of MAP less than 60 mmHg ≥5.5 minutes respectively (for all p<0.05). In living donor liver transplantation recipients, serum tacrolimus levels, intraoperative blood loss, hypotension period and the usage of gelatin may be risk factors for acute kidney injury in the early postoperative period.

  1. 10 CFR 4.338 - Remedial and affirmative action by recipients.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Remedial and affirmative action by recipients. 4.338... and affirmative action by recipients. (a) Where NRC finds a recipient has discriminated on the basis... discrimination, a recipient may take affirmative action to overcome the effects of conditions that resulted...

  2. Serving underserved transplant recipients: experience of the Medication Access Program

    Directory of Open Access Journals (Sweden)

    Spivey CA

    2014-05-01

    Full Text Available Christina A Spivey,1 Marie A Chisholm-Burns,1 Charlene Garrett,2 Kenneth M Duke21University of Tennessee College of Pharmacy, Memphis, TN, USA; 2University of Georgia College of Pharmacy, Athens, GA, USAObjective: Programs have been established to help underserved, solid-organ transplant recipients and other patient populations address the burden of medication regimen costs. The purpose of this study was to describe one such program, the Medication Access Program (MAP, and the population of solid-organ transplant recipients it serves. An additional objective was to compare characteristics of recipients whose MAP enrollment was continued versus those who were discontinued during the annual re-enrollment period.Methods: Enrollment into MAP is based on referral from a pharmacist or another health care professional/transplant team member. To enroll, a recipient must complete an application which includes information about demographics, health care coverage, income, and medication regimen. To maintain enrollment, patients must complete a renewal application on an annual basis. Data were collected from renewal applications for 2012 and 2011 (for those who did not return the 2012 renewal applications. Chi-square analyses and Student’s t-test for independent samples were conducted to compare the characteristics of those who renewed their MAP enrollment in 2012 and those who were discontinued because they did not return the renewal application. Multivariate stepwise logistic regression was conducted to determine variables predictive of MAP continuation status.Results: In total, 246 recipients were included. The majority qualified for Medicare (67.9%, did not qualify for Medicaid (69.9%, and did not have private health care coverage (63.8%. Significantly more continued recipients qualified for Medicare compared to discontinued recipients (P=0.002. Discontinued recipients had a greater number of past discontinuations than continued recipients

  3. Recipient Capacity of Tvaeren, a Baltic Bay

    Energy Technology Data Exchange (ETDEWEB)

    Agnedal, P.O.; Bergstroem, S.O.W.

    1966-07-15

    The research station at Studsvik is situated on the Baltic coast and includes several reactors and laboratories, a waste disposal plant serving both the station and waste producers outside Studsvik. A storage plant for irradiated fuel from power reactors has also been built. A total of 850 people are employed. The waste disposal plant was designed for a personnel of 900 using foreign information to correlate waste amounts to personnel. After a delay production has increased at a rate very close to the one expected. The composition of the waste is varied and difficult to predict. Minor amounts of fission products, active corrosion products, and fissile materials have been detected. Most of the waste activity is released to a strait leading into the Bay. Large volumes of water with very low specific activity are released immediately off the coast. Hydrological and dispersion data for the bay are quoted from a paper presented at the symposium mentioned below. The Baltic has brackish water. Both the chemistry and the biology are quite different from those of marine or fresh water recipients. A short description is given of the fauna and flora and important food webs are discussed. The different ways in which man is exposed to radioactivity in waste releases are dependent upon biological accumulation in living organisms and adsorption to dead materials. Fish consumption is the type of exposure which is likely to be the most critical, though it is possible that the exposure from sunbathing and fishing-gear handling could reach similar significance if conservative calculations are used. Accumulation factors from water to fish are given for iron, cobalt,and zinc . Permissible releases have been calculated using relevant accumulation factors. Fission products and corrosion products seem to be of similar significance with regard to possible human exposure. Permission to release liquid waste is granted by water courts in Sweden and operations inspected by special authorities

  4. Cutaneous Manifestations in Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Fatma Elif Demirgüneş

    2008-05-01

    Full Text Available Background and Design: This study is designed to determine the prevalence and the clinical spectrum of skin diseases in renal transplant recipients (RTRs.Material and Method: In this study RTRs who were referred to our department between 2005 and 2007 for dermatologic examination were evaluated. Dermatologic investigation included direct clinical observation and culture or histolopathological investigation when indicated. Patients were divided into three groups: group A, post-transplantation periods £1 year; group B, post-transplantation periods of 1-5 years; and group C, post-transplantation periods >5 years. Results: In this study 88 (M=50, F=38 RTRs were evaluated. The mean age was 37 ± 12 years and the median interval since transplantation was 38.5 months (range=1 month-27 years. Over a 2-year period 298 cutaneous manifestations were identified. Ninety-five immunosuppressive (IS drug-related manifestations were observed in 58 (%65.9 patients and the most common one was acneiform eruption (n=23. Forty (45.5% patients developed cutaneous viral infections, consisting of verruca vulgaris (n=29, herpes zoster (n=9, herpes simplex (n=5, molluscum (n=2 and varicella (n=1 infections. Superficial fungal infections were observed in 35(39.2% patients, most common lesions were dermatophytosis (n = 23 and pityriasis versicolor (n=17. Bacterial infections were observed in 14 (%16 patients, folliculitis was present in 12 of them. Premalignant and malignant lesions were identified in 12 (%13.6 patients, consisting of actinic keratoses (n=9, basal cell carcinoma (n=2, squamous cell carcinoma (n=1 and Kaposi's sarcoma (n=1. There were more premalignant and malignant lesions in patients receiving azathioprine (p=0.002. Cutaneous viral infections were more common in group C (p=0.023 and IS drug-related manifestations were more common in group A (p=0.003. Conclusion: Most common cutaneous manifestation among RTRs was IS drug-related and seen in early post

  5. Profiles of blood and blood component transfusion recipients in Zimbabwe

    Science.gov (United States)

    Mafirakureva, Nyashadzaishe; Khoza, Star; Hassall, Oliver; Faragher, Brian E.; Kajja, Isaac; Mvere, David A.; Emmanuel, Jean C.; Postma, Maarten J.; van Hulst, Marinus

    2015-01-01

    Background There are limited published data on the characteristics of blood transfusion recipients in sub-Saharan Africa. This study describes the demographic characteristics of blood transfusion recipients and patterns of blood and blood component use in Zimbabwe. Materials and methods Data on the characteristics of the blood transfusion recipients (age, sex, blood group), blood components received (type, quantity), discharge diagnoses and outcomes following transfusion (discharge status, duration of stay in hospital), were retrospectively collected from four major hospitals for the period from January 1, 2012 to December 31, 2012. Diagnoses were grouped into broad categories according to the disease headings of the International Classification of Diseases (ICD-10). Surgical procedures were grouped into broad categories according to organ system using ICD-9. Results Most of the 1,793 transfusion recipients studied were female (63.2%) and in the reproductive age group, i.e. 15–49 years (65.3%). The median age of the recipients was 33 years (range, 0–93). The majority of these recipients (n=1,642; 91.6%) received a red blood cell transfusion. The majority of the patients were diagnosed with conditions related to pregnancy and childbirth (22.3%), and diseases of blood and blood-forming organs (17.7%). The median time spent in hospital was 8 days (range, 0–214) and in-hospital mortality was 15.4%. Discussion Our sample of blood transfusion recipients were fairly young and most of them received red blood cell transfusions. The majority of patients in the reproductive age group received blood transfusions for pregnancy and childbirth-related diagnoses. PMID:26192782

  6. DIETARY MANAGEMENT FOR DYSLIPIDEMIA IN LIVER TRANSPLANT RECIPIENTS

    Science.gov (United States)

    PINTO, Andressa S.; CHEDID, Marcio F.; GUERRA, Léa T.; CABELEIRA, Daiane D.; KRUEL, Cleber D. P.

    2016-01-01

    ABSTRACT Background: Dyslipidemia occurs in approximately 70% of all liver transplant (LT) recipients, and no prior control studies have demonstrated any dietary intervention to change it. Aim: To analyze the effects of a dietary intervention on the lipid profile of dyslipidemic LT recipients. Methods: All LT recipients with dyslipidemia on clinical follow-up were enrolled. Anthropometric evaluation, food history, body composition (bioimpedance) and assessment of basal metabolism through indirect calorimetry were performed. Patients met with a dietitian and an individualized diet based on estimate of basal metabolism and consisting of 25% of the total energy value in total fat and measures were measured at baseline and six months after intervention. Results: Fifty-thee out of 56 patients concluded follow-up; age was 59±10 years; 29 were men (51.8%). The analysis pre- and post-intervention were, respectively: TC 238.9±30 and 165.1±35, pmeasures were not modified. Conclusions: Dietary counseling with prescription of individualized diet based on estimate of basal metabolism through indirect calorimetry was able to manage dyslipidemia in most LT recipients; so, all dyslipidemic LT recipients must be enrolled on a dietary program. PMID:28076479

  7. Management of viral hepatitis in liver transplant recipients

    Directory of Open Access Journals (Sweden)

    Soung Won Jeong

    2014-12-01

    Full Text Available Recurrence of viral hepatitis after liver transplantation (LT can progress to graft failure and lead to a decrease in long-term survival. Recently, there have been remarkable improvement in the treatment of chronic hepatitis B (CHB using potent antiviral agents. Combination of hepatitis B immunoglobulin and potent antiviral therapy has brought marked advances in the management of CHB for liver transplant recipients. Post-transplant antiviral therapy for hepatitis C virus infection is generally reserved for patients showing progressive disease. Acheiving a sustained virological response in patients with LT greatly ameliorates graft and overall survival, however this only occurs in 30% of transplant recipient using pegylated interferon and ribavirin (RBV. Direct acting antivirals such as protease inhibitors, polymerase or other non-structural proteins inhibitors are anticipated to establish the new standard of care for transplant recipients. In liver transplant recipients, hepatitis E virus infection is an uncommon disease. However, it can lead to chronic hepatitis and cirrhosis and may require retransplantation. Recently, 3-month course of RBV monotherapy has been reported as an effective treatment. This review focuses on the recent management and therapeutic approaches of viral hepatitis in liver transplant recipient.

  8. Tuberculosis in a renal allograft recipient presenting with intussusception.

    Science.gov (United States)

    Mohapatra, A; Basu, G; Sen, I; Asirvatham, R; Michael, J S; Pulimood, A B; John, G T

    2012-01-01

    Extra-pulmonary tuberculosis (TB) is more common in renal allograft recipients and may present with dissemination or an atypical features. We report a renal allograft recipient with intestinal TB presenting 3 years after transplantation with persistent fever, weight loss, diarrhea, abdominal pain and mass in the abdomen with intestinal obstruction. He was diagnosed to be having an ileocolic intussusception which on resection showed a granulomatous inflammation with presence of acid-fast bacilli (AFB) typical of Mycobacterium tuberculosis. In addition, AFB was detected in the tracheal aspirate, indicating dissemination. He received anti-TB therapy (ATT) from the fourth postoperative day. However, he developed a probable immune reconstitution inflammatory syndrome (IRIS) with multiorgan failure and died on 11(th) postoperative day. This is the first report of intestinal TB presenting as intussusception in a renal allograft recipient. The development of IRIS after starting ATT is rare in renal allograft recipients. This report highlights the need for a high index of suspicion for diagnosing TB early among renal transplant recipients and the therapeutic dilemma with overwhelming infection and development of IRIS upon reduction of immunosuppression and starting ATT.

  9. The Effects of Absorptive Capacity and Recipient Collaborativeness as Technology Recipient Characteristics on Degree of Inter-Firm Technology Transfer

    Directory of Open Access Journals (Sweden)

    A. W. Sazali

    2009-01-01

    Full Text Available Problem statement: As an efficient means to increase global competitiveness, technological capabilities and potential for local innovation, organizations in the developing countries are working hard to collaborate, learn and internalize their foreign partner’s technological knowledge by forming strategic alliances or International Joint Ventures (IJVs. Technology recipient characteristics, as one of the important actors/facilitators of inter-firm technology transfer, have increasingly become crucial factors in determining the success or failure of inter-firm technology transfer within IJVs. Since the current issue on inter-firm Technology Transfer (TT in the developing countries is centered on the efficiency and effectiveness of the transfer process by the Multinationals (MNCs therefore the success is often associated with or measured by degree of technology transferred to local partners. Based on the underlying knowledge-based view and organizational learning perspective, this study aims to empirically examine the effects of two critical elements of technology recipient characteristics: Absorptive Capacity (ACAP and Recipient Collaborativeness (RCOL on degree of technology transfer: Degree of tacit and explicit knowledge in IJVs. Approach: Using the quantitative analytical approach, the theoretical model and hypotheses in this study were tested based on empirical data gathered from 128 joint venture companies registered with the Registrar of Companies Of Malaysia (ROC. Data obtained from the survey questionnaires were analyzed using the correlation coefficients and multiple linear regression analyses. Results: The results revealed that recipient collaborativeness as the critical element of technology recipient characteristics has strong significant effects on both degrees of tacit and explicit knowledge. Although absorptive capacity has been strongly emphasized of its significance effect, however, the results are not statistically significant

  10. Expression of the chemokine receptor CXCR7 in CXCR4-expressing human 143B osteosarcoma cells enhances lung metastasis of intratibial xenografts in SCID mice.

    Science.gov (United States)

    Brennecke, Patrick; Arlt, Matthias J E; Muff, Roman; Campanile, Carmen; Gvozdenovic, Ana; Husmann, Knut; Holzwarth, Nathalie; Cameroni, Elisabetta; Ehrensperger, Felix; Thelen, Marcus; Born, Walter; Fuchs, Bruno

    2013-01-01

    More effective treatment of metastasizing osteosarcoma with a current mean 5-year survival rate of less than 20% requires more detailed knowledge on mechanisms and key regulatory molecules of the complex metastatic process. CXCR4, the receptor of the chemokine CXCL12, has been reported to promote tumor progression and metastasis in osteosarcoma. CXCR7 is a recently deorphanized CXCL12-scavenging receptor with so far not well-defined functions in tumor biology. The present study focused on a potential malignancy enhancing function of CXCR7 in interaction with CXCR4 in osteosarcoma, which was investigated in an intratibial osteosarcoma model in SCID mice, making use of the human 143B osteosarcoma cell line that spontaneously metastasizes to the lung and expresses endogenous CXCR4. 143B osteosarcoma cells stably expressing LacZ (143B-LacZ cells) were retrovirally transduced with a gene encoding HA-tagged CXCR7 (143B-LacZ-X7-HA cells). 143B-LacZ-X7-HA cells co-expressing CXCR7 and CXCR4 exhibited CXCL12 scavenging and enhanced adhesion to IL-1β-activated HUVEC cells compared to 143B-LacZ cells expressing CXCR4 alone. SCID mice intratibially injected with 143B-LacZ-X7-HA cells had significantly (plung metastases than mice injected with 143B-LacZ cells. Unexpectedly, 143B-LacZ-X7-HA cells, unlike 143B-LacZ cells, also metastasized with high incidence to the auriculum cordis. In conclusion, expression of the CXCL12 scavenging receptor CXCR7 in the CXCR4-expressing human 143B osteosarcoma cell line enhances its metastatic activity in intratibial primary tumors in SCID mice that predominantly metastasize to the lung and thereby closely mimic the human disease. These findings point to CXCR7 as a target, complementary to previously proposed CXCR4, for more effective metastasis-suppressive treatment in osteosarcoma.

  11. A self-inactivating lentiviral vector for SCID-X1 gene therapy that does not activate LMO2 expression in human T cells.

    Science.gov (United States)

    Zhou, Sheng; Mody, Disha; DeRavin, Suk See; Hauer, Julia; Lu, Taihe; Ma, Zhijun; Hacein-Bey Abina, Salima; Gray, John T; Greene, Michael R; Cavazzana-Calvo, Marina; Malech, Harry L; Sorrentino, Brian P

    2010-08-12

    To develop safer and more effective vectors for gene therapy of X-linked severe combined immunodeficiency (SCID-X1), we have evaluated new self-inactivating lentiviral vectors based on the HIV virus. The CL20i4-hgamma(c)-Revgen vector contains the entire human common gamma chain (gamma(c)) genomic sequence driven by the gamma(c) promoter. The CL20i4-EF1alpha-hgamma(c)OPT vector uses a promoter fragment from the eukaryotic elongation factor alpha (EF1alpha) gene to express a codon-optimized human gamma(c) cDNA. Both vectors contain a 400-bp insulator fragment from the chicken beta-globin locus within the self-inactivating long-terminal repeat. Transduction of bone marrow cells using either of these vectors restored T, B, and natural killer lymphocyte development and function in a mouse SCID-X1 transplantation model. Transduction of human CD34(+) bone marrow cells from SCID-X1 patients with either vector restored T-cell development in an in vitro assay. In safety studies using a Jurkat LMO2 activation assay, only the CL20i4-EF1alpha-hgamma(c)OPT vector lacked the ability to transactivate LMO2 protein expression, whereas the CL20i4-hgamma(c)-Revgen vector significantly activated LMO2 protein expression. In addition, the CL20i4-EF1alpha-hgamma(c)OPT vector has not caused any tumors in transplanted mice. We conclude that the CL20i4-EF1alpha-hgamma(c)OPT vector may be suitable for testing in a clinical trial based on these preclinical demonstrations of efficacy and safety.

  12. Macrophage colony-stimulating factor gene transduction into human lung cancer cells differentially regulates metastasis formations in various organ microenvironments of natural killer cell-depleted SCID mice.

    Science.gov (United States)

    Yano, S; Nishioka, Y; Nokihara, H; Sone, S

    1997-02-15

    We investigated whether local production of macrophage colony-stimulating factor (M-CSF), responsible for migration and activation of monocytes/macrophages at a tumor growth site, affected the metastatic pattern of lung cancer. For this, highly metastatic human squamous (RERF-LC-AI) or small (H69/VP) cell lung carcinoma cells were transduced with the human M-CSF gene inserted into pRc/CMV-MCSF to establish M-CSF-producing clones (MCSF-AI-9-18, MCSF-AI-9-24, and MCSF-VP-5). M-CSF gene transduction had no effect on the expression of surface antigen or on in vitro proliferation. After s.c. injection into SCID mice, the growth rates of M-CSF-producing cells were slower than those of parent or mock-transduced cells. In the metastatic model in SCID mice depleted of natural killer cells, RERF-LC-AI cells formed metastases mainly in the liver and kidneys, whereas H69/VP cells metastasized mainly to the liver and systemic lymph nodes. The numbers of metastatic colonies of MCSF-AI-9-18 and MCSF-AI-9-24 cells in the liver but not the kidneys were significantly reduced. The development of lymph node metastases of MCSF-VP-5 cells was also less than that of parent or mock-transduced cells. Treatment of SCID mice with anti-human M-CSF antibody resulted in a significant increase in liver metastases of their M-CSF gene transfectants. No significant differences were observed in the distributions in mice or in the in vitro invasive potentials of MCSF-AI-9-18 cells and Neo-AI-3 cells. These findings indicate that the antimetastatic effect of M-CSF may be specific to particular organs, suggesting the influence of heterogeneity of organ microenvironments on the metastasis of lung cancer.

  13. NOD/SCID-GAMMA mice are an ideal strain to assess the efficacy of therapeutic agents used in the treatment of myeloma bone disease.

    Science.gov (United States)

    Lawson, Michelle A; Paton-Hough, Julia M; Evans, Holly R; Walker, Rebecca E; Harris, William; Ratnabalan, Dharshi; Snowden, John A; Chantry, Andrew D

    2015-01-01

    Animal models of multiple myeloma vary in terms of consistency of onset, degree of tumour burden and degree of myeloma bone disease. Here we describe five pre-clinical models of myeloma in NOD/SCID-GAMMA mice to specifically study the effects of therapeutic agents on myeloma bone disease. Groups of 7-8 week old female irradiated NOD/SCID-GAMMA mice were injected intravenously via the tail vein with either 1x106 JJN3, U266, XG-1 or OPM-2 human myeloma cell lines or patient-derived myeloma cells. At the first signs of morbidity in each tumour group all animals were sacrificed. Tumour load was measured by histological analysis, and bone disease was assessed by micro-CT and standard histomorphometric methods. Mice injected with JJN3, U266 or OPM-2 cells showed high tumour bone marrow infiltration of the long bones with low variability, resulting in osteolytic lesions. In contrast, mice injected with XG-1 or patient-derived myeloma cells showed lower tumour bone marrow infiltration and less bone disease with high variability. Injection of JJN3 cells into NOD/SCID-GAMMA mice resulted in an aggressive, short-term model of myeloma with mice exhibiting signs of morbidity 3 weeks later. Treating these mice with zoledronic acid at the time of tumour cell injection or once tumour was established prevented JJN3-induced bone disease but did not reduce tumour burden, whereas, carfilzomib treatment given once tumour was established significantly reduced tumour burden. Injection of U266, XG-1, OPM-2 and patient-derived myeloma cells resulted in less aggressive longer-term models of myeloma with mice exhibiting signs of morbidity 8 weeks later. Treating U266-induced disease with zoledronic acid prevented the formation of osteolytic lesions and trabecular bone loss as well as reducing tumour burden whereas, carfilzomib treatment only reduced tumour burden. In summary, JJN3, U266 or OPM-2 cells injected into NOD/SCID-GAMMA mice provide robust models to study anti-myeloma therapies

  14. NOD/SCID-GAMMA mice are an ideal strain to assess the efficacy of therapeutic agents used in the treatment of myeloma bone disease.

    Directory of Open Access Journals (Sweden)

    Michelle A Lawson

    Full Text Available Animal models of multiple myeloma vary in terms of consistency of onset, degree of tumour burden and degree of myeloma bone disease. Here we describe five pre-clinical models of myeloma in NOD/SCID-GAMMA mice to specifically study the effects of therapeutic agents on myeloma bone disease. Groups of 7-8 week old female irradiated NOD/SCID-GAMMA mice were injected intravenously via the tail vein with either 1x106 JJN3, U266, XG-1 or OPM-2 human myeloma cell lines or patient-derived myeloma cells. At the first signs of morbidity in each tumour group all animals were sacrificed. Tumour load was measured by histological analysis, and bone disease was assessed by micro-CT and standard histomorphometric methods. Mice injected with JJN3, U266 or OPM-2 cells showed high tumour bone marrow infiltration of the long bones with low variability, resulting in osteolytic lesions. In contrast, mice injected with XG-1 or patient-derived myeloma cells showed lower tumour bone marrow infiltration and less bone disease with high variability. Injection of JJN3 cells into NOD/SCID-GAMMA mice resulted in an aggressive, short-term model of myeloma with mice exhibiting signs of morbidity 3 weeks later. Treating these mice with zoledronic acid at the time of tumour cell injection or once tumour was established prevented JJN3-induced bone disease but did not reduce tumour burden, whereas, carfilzomib treatment given once tumour was established significantly reduced tumour burden. Injection of U266, XG-1, OPM-2 and patient-derived myeloma cells resulted in less aggressive longer-term models of myeloma with mice exhibiting signs of morbidity 8 weeks later. Treating U266-induced disease with zoledronic acid prevented the formation of osteolytic lesions and trabecular bone loss as well as reducing tumour burden whereas, carfilzomib treatment only reduced tumour burden. In summary, JJN3, U266 or OPM-2 cells injected into NOD/SCID-GAMMA mice provide robust models to study anti

  15. Homozygosity for a novel adenosine deaminase (ADA) nonsense mutation (Q3>X) in a child with severe combined immunodeficiency (SCID)

    Energy Technology Data Exchange (ETDEWEB)

    Santisteban, I.; Arrendondo-Vega, F.X.; Kelly, S. [Duke Univ. Medical Center, Durham, NC (United States)]|[Hospital for Sick Children, Ontario (Canada)] [and others

    1994-09-01

    A Somali girl was diagnosed with ADA-deficient SCID at 7 mo; she responded well to PEG-ADA replacement and is now 3.3 yr old. ADA mRNA was undetectable (Northern) in her cultured T cells, but was present in T cells of her parents and two sibs. All PCR-amplified exon 1 genomic clones from the patient had a C>T transition at bp 7 relative to the start of translation, replacing Gln at codon 3 (AGA) with a termination codon (TGA, Q3>X). Patient cDNA (prepared by RT-PCR with a 5{prime} primer that covered codons 1-7) had a previously described polymorphism, K80>R, but was otherwise normal, indicating that no other coding mutations were present. A predicted new genomic BfaI restriction site was used to establish her homozygosity for Q3>X and to analyze genotypes of family members. We also analyzed the segregation of a variable Alu polyA-associated TAAA repeat (AluVpA) situated 5{prime} of the ADA gene. Three different AluVpA alleles were found, one of which was only present in the father and was not associated with his Q3>X allele. Because the father`s RBCs had only {approximately}15% of normal ADA activity, we analyzed his ADA cDNA. We found a G>A transition at bp 425 that substitutes Gln for Arg142, a solvent-accessible residue, and eliminates a BsmAI site in exon 5. ADA activity of the R142>Q in vitro translation product was 20-25% of wild type ADA translation product, suggesting that R142>Q is a new {open_quote}partial{close_quote} ADA deficiency mutation. As expected, Q3>X mRNA did not yield a detectable in vitro translation product. We conclude that the patient`s father is a compound heterozygote carrying the ADA Q3>X/R142>Q genotype. {open_quote}Partial{close_quote} ADA deficiency unassociated with immunodeficiency is relatively common in individuals of African descent. The present findings and previous observations suggest that {open_quote}partial{close_quote} ADA deficiency may have had an evolutionary advantage.

  16. Cervical Carcinoma in a Renal Transplant Recipient: A Case Report.

    Science.gov (United States)

    Tuncer, Hasan Aykut; Kirnap, Mahir; Dursun, Polat; Ayhan, Ali; Moray, Gokhan; Haberal, Mehmet

    2016-02-01

    A range of cancer types, at increased rates, is described in renal transplant recipients receiving immunosuppression. Aside from immunodeficiency, heightened medical surveillance for cancer, lifestyle, and other risk factors all play a role. Although the relation between cancer risk and degree of immunodeficiency might not be linear, and might be different for a wide range of cancer subtypes, human papillomavirus-related cancers in long-term transplant recipients may suggest the role of even modest immunosuppression, when present long enough. High-risk human papillomavirus types are recognized as the cause of cancer of the cervix. We report a 49-year-old female renal transplant recipient diagnosed with cervical squamous cell carcinoma, 5 years after the transplant. Based on this patient, we highlight difficulties in surgical approach and the importance of close clinical follow-up including regular gynecologic screening for cervical premalignant and malignant lesions.

  17. Prognosis of HTLV-1 positive renal transplant recipients in Iran

    Directory of Open Access Journals (Sweden)

    Orode Naghibi

    2011-01-01

    Full Text Available The human T lymphocyte virus-1 (HTLV-1 is the responsible pathogen for diseases such as HTLV-1 associated myelopathy (HAM and adult T-cell leukemia (ATL. Mashhad, in northeast Iran, with high instances of this infection, has a noticeable number of infected renal failure patients. Since immunosuppressive drugs might decrease the latency period of HTLV-1 or increase its complications, the question arises whether HTLV-1 positive renal failure patients are suitable candidates for kidney transplants. To answer this, HTLV-1 positive recipients were evaluated in our study. Patients were divided into two groups. First group consisted of patients at the Imam Reza Hospital dialysis center. Second group had 20 kidney transplantation recipients consisting of ten infected and ten uninfected recipients as control from Imam Reza. Medical history of these patients was recorded and evaluated. The follow-up periods were between one and six years. Among them, 3.8% of patients undergoing dialysis were infected. The most important fact resulting from this study is that none of the infected recipients suffered from HAM or ATL during the follow-up period. In addition, it did not show any significant difference in the incidence of post-transplant complications between the infected and non-infected groups. Our study indicates that HTLV-1 positive patients may undergo kidney transplant without fear of increased incidence of side effects than those found in uninfected recipients. Because of short-term follow-up, probable long latency period of the virus, and the limited number of infected recipients, further work on this issue would be prudent.

  18. Recipient aging accelerates acquired transthyretin amyloidosis after domino liver transplantation.

    Science.gov (United States)

    Misumi, Yohei; Narita, Yasuko; Oshima, Toshinori; Ueda, Mitsuharu; Yamashita, Taro; Tasaki, Masayoshi; Obayashi, Konen; Isono, Kaori; Inomata, Yukihiro; Ando, Yukio

    2016-05-01

    Domino liver transplantation (DLT) with liver grafts from patients with hereditary transthyretin (TTR) amyloidosis has been performed throughout the world because of a severe liver graft shortage. Reports of acquired systemic TTR amyloidosis in domino liver recipients have been increasing; however, the precise pathogenesis and clinical course of acquired TTR amyloidosis remains unclear. We analyzed the relationship between the occurrence of acquired amyloidosis and clinical features in 22 consecutive domino liver donors with hereditary TTR amyloidosis (10 males and 12 females; mean age at DLT: 37.2 years; TTR mutations: V30M [n = 19], Y114C [n = 1], L55P [n = 1], and S50I [n = 1]) and 22 liver recipients (16 males and 6 females; mean age at DLT, 46.2 years). The mean times from DLT to amyloid first appearance and transplant recipient symptom onset were 8.2 years and 9.9 years, respectively. Kaplan-Meier analysis and quantification of the amyloid deposition revealed aging of recipients correlated with early de novo amyloid deposition. The sex of donors and recipients and the age, disease duration, and disease severity of donors had no significant effect on the latency of de novo amyloid deposition. In conclusion, our results demonstrate that recipient aging is associated with the early onset de novo amyloidosis. Because acquired amyloidosis will likely increase, careful follow-up for early amyloidosis detection and new treatments, including TTR stabilizers and gene-silencing therapies, are required. Liver Transplantation 22 656-664 2016 AASLD. © 2015 American Association for the Study of Liver Diseases.

  19. Trends in disability benefit recipient rates in post industrialised countries

    DEFF Research Database (Denmark)

    Rasmussen, Martin

    This working paper is part of a study organized by International Social Security Association (ISSA). The study is called Trends in disability benefit recipient rates in post-industrial societies. The other countries participating in the study are Sweden, United States, United Kingdom, The Netherl......This working paper is part of a study organized by International Social Security Association (ISSA). The study is called Trends in disability benefit recipient rates in post-industrial societies. The other countries participating in the study are Sweden, United States, United Kingdom...

  20. Immunosuppressive T-cell antibody induction for heart transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Møller, Christian H; Gustafsson, Finn

    2013-01-01

    Heart transplantation has become a valuable and well-accepted treatment option for end-stage heart failure. Rejection of the transplanted heart by the recipient's body is a risk to the success of the procedure, and life-long immunosuppression is necessary to avoid this. Clear evidence is required...... to identify the best, safest and most effective immunosuppressive treatment strategy for heart transplant recipients. To date, there is no consensus on the use of immunosuppressive antibodies against T-cells for induction after heart transplantation....

  1. Toxoplasmic encephalitis associated with meningitis in a heart transplant recipient.

    Science.gov (United States)

    Baliu, C; Sanclemente, G; Cardona, M; Castel, M A; Perez-Villa, F; Moreno, A; Cervera, C

    2014-08-01

    Toxoplasma gondii is an opportunistic pathogen that causes neurologic and extraneurologic manifestations in immunosuppressed patients. Encephalitis and intracranial mass lesions are easily recognized as typical manifestations of toxoplasmosis. However, meningitis caused by T. gondii is a rare condition with very few cases described in the literature. We present the case of a heart transplant recipient who developed toxoplasmic encephalitis associated with meningitis. After an extensive review of the medical literature, we found only 1 case of meningitis in solid organ transplant recipients and meningitis in immunocompromised individuals.

  2. Donor and recipient sex in allogeneic stem cell transplantation: what really matters

    Science.gov (United States)

    Kim, Haesook T.; Zhang, Mei-Jie; Woolfrey, Ann E.; St. Martin, Andrew; Chen, Junfang; Saber, Wael; Perales, Miguel-Angel; Armand, Philippe; Eapen, Mary

    2016-01-01

    We investigated whether and how recipient-donor sex affects transplantation outcomes of 11,797 patients transplanted between 2008 and 2010. Thirty-seven percent were male recipients with male donors, 21% male recipients with female donors, 25% female recipients with male donors, and 17% female recipients with female donors. In multivariable analyses, male recipients had inferior overall survival and progression-free survival compared to females regardless of donor sex, with an 11% relative increase in the hazard of death (P<0.0001) and a 10% relative increase in the hazard of death or relapse (P<0.0001). The detrimental effect of male recipients varied by donor sex. For male recipients with male donors, there was a 12% relative increase in the subdistribution hazard of relapse compared with female recipients with male donors (P=0.0036) and male recipients with female donors (P=0.0037). For male recipients with female donors, there was a 19% relative increase in the subdistribution hazard of non-relapse mortality compared with male recipients with male donors (P<0.0001) and a 22% relative increase compared with female recipients with male donors (P=0.0003). In addition, male recipients with female donors showed a 21% relative increase in the subdistribution hazard of chronic graft-versus-host disease (P<0.0001) compared with female recipients with male donors. Donor sex had no effect on outcomes for female recipients. Transplantation of grafts from male and female donors was associated with inferior overall survival and progression-free survival in male recipients with differing patterns of failure. Recipient sex is an important prognostic factor independent of donor sex. PMID:27354023

  3. Hereditary multiple intestinal atresia (HMIA) with severe combined immunodeficiency (SCID): a case report of two siblings and review of the literature on MIA, HMIA and HMIA with immunodeficiency over the last 50 years

    Science.gov (United States)

    Ali, Yasser Ali Hussein; Rahman, Sajjad; Bhat, Venkatraman; Thani, Sheikha Al; Ismail, Adel; Bassiouny, Ibrahim

    2011-01-01

    Hereditary multiple intestinal atresia (HMIA), a presumed autosomal recessive disorder, is an unusual and rare form of recurrent intestinal atresia which can be associated with severe combined immunodeficiency (SCID). The combination of HMIA and SCID is invariably lethal. The authors describe this fatal association in two siblings. The parents are consanguineous and have three other normal healthy children. Both index cases had abnormal antenatal ultrasounds and were symptomatic after birth. The final diagnosis of HMIA with SCID was confirmed in both siblings. They were never able to receive enteral feeds, remained totally dependent on parenteral nutrition, had repeated episodes of sepsis and died after a very difficult neonatal intensive care course. In this article we have reviewed the clinical course and outcome of both cases. The existing literature on multiple intestinal atresia, HMIA and HMIA with immunodeficiency is also reviewed. PMID:22715199

  4. The majority of lamina propria CD4(+) T-cells from scid mice with colitis undergo Fas-mediated apoptosis in vivo

    DEFF Research Database (Denmark)

    Bregenholt, S; Petersen, T R; Claesson, Mogens Helweg

    2001-01-01

    We have previously shown that adoptively transferred CD4(+) T-cells mediate an chronic colitis in severe combined immune deficient (scid) mice. Colitis is accompanied by activation and apoptosis of Fas ligand and TNF-alpha expressing CD4(+) T-cells in the diseased colonic lamina propria (Eur. J....... Immunol. 28:3655 (1998)). Here we investigate the apoptosis-inducing mechanism in these lamina propria infiltrating CD4(+) T-cells. We observe that freshly isolated lamina propria CD4(+) T-cells can kill Fas transfected P815 mastocytoma cells in a TCR/CD3 redirected chromium-release assay, but do...... not express TNF-alpha mediated cytotoxicity. Pre-incubation of the isolated lamina propria CD4(+) T-cells with an anti-FasL antiserum partially blocked killing of the Fas transfected target cells, indicating a role for the Fas-FasL system in the killing process. Treatment of scid mice with colitis with anti...

  5. Murine leukemias with retroviral insertions at Lmo2 are predictive of the leukemias induced in SCID-X1 patients following retroviral gene therapy.

    Directory of Open Access Journals (Sweden)

    Utpal P Davé

    2009-05-01

    Full Text Available Five X-linked severe combined immunodeficiency patients (SCID-X1 successfully treated with autologous bone marrow stem cells infected ex vivo with an IL2RG-containing retrovirus subsequently developed T-cell leukemia and four contained insertional mutations at LMO2. Genetic evidence also suggests a role for IL2RG in tumor formation, although this remains controversial. Here, we show that the genes and signaling pathways deregulated in murine leukemias with retroviral insertions at Lmo2 are similar to those deregulated in human leukemias with high LMO2 expression and are highly predictive of the leukemias induced in SCID-X1 patients. We also provide additional evidence supporting the notion that IL2RG and LMO2 cooperate in leukemia induction but are not sufficient and require additional cooperating mutations. The highly concordant nature of the genetic events giving rise to mouse and human leukemias with mutations at Lmo2 are an encouraging sign to those wanting to use mice to model human cancer and may help in designing safer methods for retroviral gene therapy.

  6. Murine leukemias with retroviral insertions at Lmo2 are predictive of the leukemias induced in SCID-X1 patients following retroviral gene therapy.

    Science.gov (United States)

    Davé, Utpal P; Akagi, Keiko; Tripathi, Rati; Cleveland, Susan M; Thompson, Mary A; Yi, Ming; Stephens, Robert; Downing, James R; Jenkins, Nancy A; Copeland, Neal G

    2009-05-01

    Five X-linked severe combined immunodeficiency patients (SCID-X1) successfully treated with autologous bone marrow stem cells infected ex vivo with an IL2RG-containing retrovirus subsequently developed T-cell leukemia and four contained insertional mutations at LMO2. Genetic evidence also suggests a role for IL2RG in tumor formation, although this remains controversial. Here, we show that the genes and signaling pathways deregulated in murine leukemias with retroviral insertions at Lmo2 are similar to those deregulated in human leukemias with high LMO2 expression and are highly predictive of the leukemias induced in SCID-X1 patients. We also provide additional evidence supporting the notion that IL2RG and LMO2 cooperate in leukemia induction but are not sufficient and require additional cooperating mutations. The highly concordant nature of the genetic events giving rise to mouse and human leukemias with mutations at Lmo2 are an encouraging sign to those wanting to use mice to model human cancer and may help in designing safer methods for retroviral gene therapy.

  7. Correction of murine SCID-X1 by lentiviral gene therapy using a codon-optimized IL2RG gene and minimal pretransplant conditioning.

    Science.gov (United States)

    Huston, Marshall W; van Til, Niek P; Visser, Trudi P; Arshad, Shazia; Brugman, Martijn H; Cattoglio, Claudia; Nowrouzi, Ali; Li, Yuedan; Schambach, Axel; Schmidt, Manfred; Baum, Christopher; von Kalle, Christof; Mavilio, Fulvio; Zhang, Fang; Blundell, Mike P; Thrasher, Adrian J; Verstegen, Monique M A; Wagemaker, Gerard

    2011-10-01

    Clinical trials have demonstrated the potential of ex vivo hematopoietic stem cell gene therapy to treat X-linked severe combined immunodeficiency (SCID-X1) using γ-retroviral vectors, leading to immune system functionality in the majority of treated patients without pretransplant conditioning. The success was tempered by insertional oncogenesis in a proportion of the patients. To reduce the genotoxicity risk, a self-inactivating (SIN) lentiviral vector (LV) with improved expression of a codon optimized human interleukin-2 receptor γ gene (IL2RG) cDNA (coγc), regulated by its 1.1 kb promoter region (γcPr), was compared in efficacy to the viral spleen focus forming virus (SF) and the cellular phosphoglycerate kinase (PGK) promoters. Pretransplant conditioning of Il2rg(-/-) mice resulted in long-term reconstitution of T and B lymphocytes, normalized natural antibody titers, humoral immune responses, ConA/IL-2 stimulated spleen cell proliferation, and polyclonal T-cell receptor gene rearrangements with a clear integration preference of the SF vector for proto-oncogenes, contrary to the PGK and γcPr vectors. We conclude that SIN lentiviral gene therapy using coγc driven by the γcPr or PGK promoter corrects the SCID phenotype, potentially with an improved safety profile, and that low-dose conditioning proved essential for immune competence, allowing for a reduced threshold of cell numbers required.

  8. Comparing the Personality Disorder Interview for DSM-IV (PDI-IV) and SCID-II borderline personality disorder scales: an item-response theory analysis.

    Science.gov (United States)

    Huprich, Steven K; Paggeot, Amy V; Samuel, Douglas B

    2015-01-01

    One-hundred sixty-nine psychiatric outpatients and 171 undergraduate students were assessed with the Personality Disorder Interview-IV (PDI-IV; Widiger, Mangine, Corbitt, Ellis, & Thomas, 1995) and the Structured Clinical Interview for DSM-IV Axis II disorders (SCID-II; First, Gibbon, Spitzer, Williams, & Benjamin, 1997) for borderline personality disorder (BPD). Eighty individuals met PDI-IV BPD criteria, whereas 34 met SCID-II BPD criteria. Dimensional ratings of both measures were highly intercorrelated (rs = .78, .75), and item-level interrater reliability fell in the good to excellent range. An item-response theory analysis was performed to investigate whether properties of the items from each interview could help understand these differences. The limited agreement seemed to be explained by differences in the response options across the two interviews. We found that suicidal behavior was among the most discriminating criteria on both instruments, whereas dissociation and difficulty controlling anger had the 2 lowest alpha parameter values. Finally, those meeting BPD criteria on both interviews had higher levels of anxiety, depression, and more impairments in object relations than those meeting criteria on just the PDI-IV. These findings suggest that the choice of measure has a notable effect on the obtained diagnostic prevalence and the level of BPD severity that is detected.

  9. Long-Term Quantitative Biodistribution and Side Effects of Human Mesenchymal Stem Cells (hMSCs Engraftment in NOD/SCID Mice following Irradiation

    Directory of Open Access Journals (Sweden)

    Sabine François

    2014-01-01

    Full Text Available There is little information on the fate of infused mesenchymal stem cells (MSCs and long-term side effects after irradiation exposure. We addressed these questions using human MSCs (hMSCs intravenously infused to nonobese diabetic/severe combined immunodeficient (NOD/SCID mice submitted to total body irradiation (TBI or local irradiation (abdominal or leg irradiation. The animals were sacrificed 3 to 120 days after irradiation and the quantitative and spatial distribution of hMSCs were studied by polymerase chain reaction (PCR. Following their infusion into nonirradiated animals, hMSCs homed to various tissues. Engraftment depended on the dose of irradiation and the area exposed. Total body irradiation induced an increased hMSC engraftment level compared to nonirradiated mice, while local irradiations increased hMSC engraftment locally in the area of irradiation. Long-term engraftment of systemically administered hMSCs in NOD/SCID mice increased significantly in response to tissue injuries produced by local or total body irradiation until 2 weeks then slowly decreased depending on organs and the configuration of irradiation. In all cases, no tissue abnormality or abnormal hMSCs proliferation was observed at 120 days after irradiation. This work supports the safe and efficient use of MSCs by injection as an alternative approach in the short- and long-term treatment of severe complications after radiotherapy for patients refractory to conventional treatments.

  10. Intratibial injection of human multiple myeloma cells in NOD/SCID IL-2Rγ(null mice mimics human myeloma and serves as a valuable tool for the development of anticancer strategies.

    Directory of Open Access Journals (Sweden)

    Julia Schueler

    Full Text Available BACKGROUND: We systematically analyzed multiple myeloma (MM cell lines and patient bone marrow cells for their engraftment capacity in immunodeficient mice and validated the response of the resulting xenografts to antimyeloma agents. DESIGN AND METHODS: Using flow cytometry and near infrared fluorescence in-vivo-imaging, growth kinetics of MM cell lines L363 and RPMI8226 and patient bone marrow cells were investigated with use of a murine subcutaneous bone implant, intratibial and intravenous approach in NOD/SCID, NOD/SCID treated with CD122 antibody and NOD/SCID IL-2Rγ(null mice (NSG. RESULTS: Myeloma growth was significantly increased in the absence of natural killer cell activity (NSG or αCD122-treated NOD/SCID. Comparison of NSG and αCD122-treated NOD/SCID revealed enhanced growth kinetics in the former, especially with respect to metastatic tumor sites which were exclusively observed therein. In NSG, MM cells were more tumorigenic when injected intratibially than intravenously. In NOD/SCID in contrast, the use of juvenile long bone implants was superior to intratibial or intravenous cancer cell injection. Using the intratibial NSG model, mice developed typical disease symptoms exclusively when implanted with human MM cell lines or patient-derived bone marrow cells, but not with healthy bone marrow cells nor in mock-injected animals. Bortezomib and dexamethasone delayed myeloma progression in L363- as well as patient-derived MM cell bearing NSG. Antitumor activity could be quantified via flow cytometry and in vivo imaging analyses. CONCLUSIONS: Our results suggest that the intratibial NSG MM model mimics the clinical situation of the disseminated disease and serves as a valuable tool in the development of novel anticancer strategies.

  11. Ralstonia mannitolilytica infection in renal transplant recipient: First report

    Directory of Open Access Journals (Sweden)

    Mukhopadhyay C

    2003-01-01

    Full Text Available Ralstonia mannitolilytica is being increasingly identified as an opportunist pathogen in immunocompromised patients. We report the first case of post renal transplant infection by R. mannitolilytica, in a 14-year-old recipient. The graft and the patient were saved with prompt microbiological identification, sensitivity testing and subsequent administration of appropriate antibiotic.

  12. Who are the job seekers? : Explaining unemployment among doctoral recipients

    NARCIS (Netherlands)

    Yerkes, M.; Van de Schoot, R.; Sonneveld, H.

    2012-01-01

    Despite increased attention for doctoral education in recent years, one particular phenomenon has received little attention—the unemployment of doctoral candidates following graduation. While the unemployment of doctoral recipients is relatively low in comparison to the general popula-tion, the

  13. Depicted welfare recipient stereotypes in Norway and Denmark

    DEFF Research Database (Denmark)

    Dencker-Larsen, Sofie; Lundberg, Kjetil G.

    2016-01-01

    stereotypical symbols and images targeting them. In this study we have investigated how welfare recipients in Norway and Denmark, and caseworkers in Denmark, understand and account for images which, through the use of stereotypes, directly or indirectly may question welfare recipients’ work ethic...

  14. Depicted welfare-recipient stereotypes in Norway and Denmark

    DEFF Research Database (Denmark)

    Dencker-Larsen, Sofie; Lundberg, Kjetil G.

    2016-01-01

    stereotypical symbols and images targeting them. In this study we have investigated how welfare recipients in Norway and Denmark, and caseworkers in Denmark, understand and account for images which, through the use of stereotypes, directly or indirectly may question welfare recipients’ work ethic...

  15. Calcification Propensity and Survival among Renal Transplant Recipients

    NARCIS (Netherlands)

    Keyzer, Charlotte A.; de Borst, Martin H.; van den Berg, Else; Jahnen-Dechent, Willi; Arampatzis, Spyridon; Farese, Stefan; Bergmann, Ivo P.; Floege, Juergen; Navis, Gerjan; Bakker, Stephan J. L.; van Goor, Harry; Eisenberger, Ute; Pasch, Andreas

    2016-01-01

    Calciprotein particle maturation time (T-50) in serum is a novel measure of individual blood calcification propensity. To determine the clinical relevance of T-50 in renal transplantation, baseline serum T-50 was measured in a longitudinal cohort of 699 stable renal transplant recipients and the ass

  16. 34 CFR 110.38 - Remedial action by recipients.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Remedial action by recipients. 110.38 Section 110.38 Education Regulations of the Offices of the Department of Education OFFICE FOR CIVIL RIGHTS, DEPARTMENT OF EDUCATION NONDISCRIMINATION ON THE BASIS OF AGE IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL...

  17. Iron Deficiency, Anemia and Mortality in Renal Transplant Recipients

    NARCIS (Netherlands)

    Eisenga, Michele F.; Minovic, Isidor; Berger, Stefan P.; Kootstra-Ros, Jenny E.; van den Berg, Else; Riphagen, Ineke J.; Navis, Gerjan; van der Meer, Peter; Bakker, Stephan J. L.; Gaillard, Carlo A. J. M.

    2016-01-01

    Anemia, iron deficiency anemia (IDA), and iron deficiency (ID) are highly prevalent in renal transplant recipients (RTR). Anemia is associated with poor outcome, but the role of ID is unknown. Therefore, we aimed to investigate the association of ID, irrespective of anemia, with all-cause mortality

  18. 41 CFR 101-8.708 - Affirmative action by recipient.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Affirmative action by... affirmative action to overcome the effects resulting in limited participation in the recipient's program or... FEDERAL FINANCIAL ASSISTANCE 8.7-Discrimination Prohibited on the Basis of Age § 101-8.708...

  19. 7 CFR 252.5 - Recipient agency responsibilities.

    Science.gov (United States)

    2010-01-01

    ... arise from the operation of the distribution program. (c) Refunds. A recipient agency purchasing end... if the total anticipated refund due for all purchases of end product from that processor during the... AGRICULTURE GENERAL REGULATIONS AND POLICIES-FOOD DISTRIBUTION NATIONAL COMMODITY PROCESSING PROGRAM §...

  20. 13 CFR 302.16 - Reports by Recipients.

    Science.gov (United States)

    2010-01-01

    ... effectiveness of the Investment Assistance provided in fulfilling the Project's purpose (including alleviation... under the Government Performance and Results Act of 1993 and to monitor internal, Investment and Project... GENERAL TERMS AND CONDITIONS FOR INVESTMENT ASSISTANCE § 302.16 Reports by Recipients. (a) In...

  1. Sodium intake and blood pressure in renal transplant recipients

    NARCIS (Netherlands)

    van den Berg, Else; Geleijnse, Johanna M.; Brink, Elizabeth J.; van Baak, Marleen A.; van der Heide, Jaap J. Homan; Gans, Rijk O. B.; Navis, Gerjan; Bakker, Stephan J. L.

    2012-01-01

    Hypertension is common among renal transplant recipients (RTR) and a risk factor for graft failure and mortality. Sodium intake is a well-established determinant of blood pressure (BP) in the general population. However, data in RTR are limited. International guidelines recommend a maximum daily sod

  2. Is Giving Scholarship Worth the Effort? Loyalty among Scholarship Recipients

    Science.gov (United States)

    Nurlida, Ismail

    2015-01-01

    To stay ahead of competition, a significant factor has now become of significance; student loyalty towards higher learning institutions. Hence, scholarship recipients have the expectation to demonstrate a certain degree of loyalty towards their education sponsor. In addition, they play an important role as opinion leaders and walking advertisement…

  3. Melanoma in Organ Transplant Recipients: Incidence, Outcomes and Management Considerations

    Directory of Open Access Journals (Sweden)

    Faisal R. Ali

    2012-01-01

    Full Text Available The incidence of melanoma continues to increase year on year. With better surgical techniques and medical management, greater numbers of organ transplants are being performed annually with much longer graft survival. The authors review our current understanding of the incidence of melanoma amongst organ transplant recipients, outcomes compared to the immunocompetent population, and management strategies in this burgeoning group.

  4. 42 CFR 456.411 - Recipient information required for UR.

    Science.gov (United States)

    2010-10-01

    ...) The name of the recipient's physician. (c) The name of the qualified mental retardation professional... mental retardation professional believes continued stay is necessary. (h) Other supporting material that... care required under § 456.372; (f) Initial and subsequent continued stay review dates described under...

  5. Liver allograft pathology in healthy pediatric liver transplant recipients.

    Science.gov (United States)

    Briem-Richter, Andrea; Ganschow, Rainer; Sornsakrin, Marijke; Brinkert, Florian; Schirmer, Jan; Schaefer, Hansjörg; Grabhorn, Enke

    2013-09-01

    Liver transplantation offers excellent results for children with end-stage liver disease, and efforts should be directed toward maintaining long-term graft health. We evaluate graft pathology in healthy pediatric transplant recipients with low-maintenance immunosuppressive medications to assess whether protocol biopsies are helpful for adapting immunosuppression and protecting long-term graft function. Liver biopsies were performed on 60 healthy pediatric liver transplant recipients, and histological findings were correlated with laboratory, serological, and radiological results. Fourteen patients (23%) were diagnosed with acute or early chronic rejection, and immunosuppressive medications were increased in these children. Liver function tests did not correlate with histological findings. The incidence of fibrosis was 36% in transplant recipients five or more years after liver transplantation. We observed an unexpectedly high prevalence of rejection and fibrosis in children with no laboratory abnormalities, which led to changes in their immunosuppressive medications. Scheduled biopsies appear to be useful in pediatric transplant recipients with low immunosuppressive medications for early detection of morphological changes in liver transplants. Further studies are needed to evaluate whether adaption of immunosuppression helps to reduce tissue damage and the incidence of allograft dysfunction in the long term.

  6. Long-term histopathology of allografts in sensitized kidney recipients.

    Science.gov (United States)

    Miura, Masayoshi; Harada, Hiroshi; Fukasawa, Yuichiro; Hotta, Kiyohiko; Itoh, Yosuke; Tamaki, Tohru

    2012-07-01

    Successful desensitization therapy has brought satisfying short-term outcomes in the recipients with anti-donor antibody. We analyzed the long-term pathology of the allografts in the sensitized kidney recipients. Eleven stable recipients after desensitization against positive flow cytometry T-cell crossmatch (FTXM) were included. They were divided into two groups, based on the protocol biopsies findings at three to eight yr (group 1: subclinical glomerulitis and/or peritubular capillaritis, n = 5 and group 2: no rejection, n = 6). Estimated glomerular filtration rate (eGFR), presence of donor-specific antibody (DSA), mean channel shift (MCS) of FTXM, urine protein levels, acute antibody-mediated rejection (AAMR) episodes, and protocol biopsy findings were compared. Chronic transplant glomerulopathy was found in final biopsy of all group 1 cases. DSA was positive in 60% but C4d was positive in 20% case of the group 1. The history of AAMR was only found in the group 1. There was no difference in eGFR decline or proteinuria. The MCS of FTXM was higher in the group 1. The recipients with AAMR history, high MCS in FTXM, and subclinical microvascular inflammation in the early protocol biopsies have risk for developing chronic rejection in long term.

  7. Epidemiogic aspects of skin cancer in organ-transplant recipients

    NARCIS (Netherlands)

    Wisgerhof, Hermina Christina

    2011-01-01

    The risk of (skin) cancer is highly increased in organ-transplant recipients who are kept on immunesuppressive drugs to prevent graft rejection. This thesis dealt with the epidemiologic aspects and risk factors for cancer focused on cutaneous squamous cell carcinoma and basal cell carcinoma.

  8. Sodium intake and blood pressure in renal transplant recipients

    NARCIS (Netherlands)

    Berg, van den E.; Geleijnse, J.M.; Brink, E.J.; Baak, van M.A.; Homan van der Heide, van der J.J.; Gans, R.O.B.; Navis, G.; Bakker, S.J.L.

    2012-01-01

    Background - Hypertension is common among renal transplant recipients (RTR) and a risk factor for graft failure and mortality. Sodium intake is a well-established determinant of blood pressure (BP) in the general population. However, data in RTR are limited. International guidelines recommend a maxi

  9. Efficacy of isoniazid prophylaxis in renal allograft recipients.

    Science.gov (United States)

    Naqvi, R; Akhtar, S; Noor, H; Saeed, T; Bhatti, S; Sheikh, R; Ahmed, E; Akhtar, F; Naqvi, A; Rizvi, A

    2006-09-01

    The efficacy of isoniazid (INH) prophylaxis in renal allograft recipients who are on long-term immunosuppression in a region highly prevalent for tuberculosis (TB) was studied. INH (300 mg/d in patients weighing more than 35 kg and 5 mg/kg/d in patients with Pyridoxine 50 mg/d for 1 year was started in randomly assigned renal allograft recipients. Occurrence of clinical tuberculosis during the initial 2 years posttransplantation was observed in the risk group and patients at no risk. Risks were defined as acute rejection episodes and exposure to antirejection therapy, past history of TB completely or incompletely treated, radiological evidence of past tuberculosis, history of tuberculosis in close contacts. Among 480 patients registered in the study, INH prophylaxis was given to 219 randomly assigned renal allograft recipients. Results were compared among patients developing TB during the initial 2 years posttransplantation in both the groups. Risk factors were analyzed for comparison in both groups. No significant difference was observed in terms of past history of TB, TB in close contacts, episodes of acute rejection during the initial 3 months, and comorbidities such as cytomegalovirus infection, hepatitis C virus infection, and posttransplant diabetes. One patient from the INH group and 10 patients from the non-INH group developed TB during the initial 2 years posttransplantation (P < .0001). None of patients required discontinuation of INH. INH was observed to be safe and effective as a chemoprophylactic agent in renal allograft recipients.

  10. Iron Deficiency, Anemia and Mortality in Renal Transplant Recipients

    NARCIS (Netherlands)

    Eisenga, Michele F.; Minovic, Isidor; Berger, Stefan P.; Kootstra-Ros, Jenny E.; van den Berg, Else; Riphagen, Ineke J.; Navis, Gerjan; van der Meer, Peter; Bakker, Stephan J. L.; Gaillard, Carlo A. J. M.

    2016-01-01

    Anemia, iron deficiency anemia (IDA), and iron deficiency (ID) are highly prevalent in renal transplant recipients (RTR). Anemia is associated with poor outcome, but the role of ID is unknown. Therefore, we aimed to investigate the association of ID, irrespective of anemia, with all-cause mortality

  11. Racial Recipients, Social Distance, and Sharing Behavior in Children

    Science.gov (United States)

    Zinser, Otto; And Others

    1976-01-01

    Preschoolers (N=36) and second graders (N=41) were asked to rank preference of a white child, black and an Indian. Subjects were middle-class white southern students who ranked the sharing of small items and their companions in hypothetical social interaction situations. Influence of race of the recipient on sharing behavior is believed to vary…

  12. Is Giving Scholarship Worth the Effort? Loyalty among Scholarship Recipients

    Science.gov (United States)

    Nurlida, Ismail

    2015-01-01

    To stay ahead of competition, a significant factor has now become of significance; student loyalty towards higher learning institutions. Hence, scholarship recipients have the expectation to demonstrate a certain degree of loyalty towards their education sponsor. In addition, they play an important role as opinion leaders and walking advertisement…

  13. Sodium intake and blood pressure in renal transplant recipients

    NARCIS (Netherlands)

    Berg, E. van den; Geleijnse, J.M.; Brink, E.J.; Baak, M.A. van; Homan van der Heide, J.J.; Gans, R.O.B.; Navis, G.; Bakker, S.J.L.

    2012-01-01

    Background. Hypertension is common among renal transplant recipients (RTR) and a risk factor for graft failure and mortality. Sodium intake is a well-established determinant of blood pressure (BP) in the general population. However, data in RTR are limited. International guidelines recommend a maxim

  14. Tacrolimus versus cyclosporin as primary immunosuppression for lung transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Penninga, Ida Elisabeth Irene; Møller, Christian H

    2013-01-01

    Lung transplantation is a well-accepted treatment for people with most end-stage lung diseases. Although both tacrolimus and cyclosporin are used as primary immunosuppressive agents in lung transplant recipients, it is unclear which of these drugs is better in reducing rejection and death without...

  15. Iron Deficiency, Anemia and Mortality in Renal Transplant Recipients

    NARCIS (Netherlands)

    Eisenga, Michele F; Minovic, Isidor; Berger, Stefan P; Kootstra-Ros, Jenny E; van den Berg, Else; Riphagen, Ineke J; Navis, Gerjan; van der Meer, Peter; Bakker, Stephan J L; Gaillard, Carlo A J M

    2016-01-01

    Anemia, iron deficiency anemia (IDA) and iron deficiency (ID) are highly prevalent in renal transplant recipients (RTR). Anemia is associated with poor outcome, but the role of ID is unknown. Therefore, we aimed to investigate the association of ID, irrespective of anemia, with all-cause mortality i

  16. Predictors and consequences of fatigue in prevalent kidney transplant recipients

    NARCIS (Netherlands)

    W. Chan; J.A. Bosch; D. Jones; O. Kaur; N. Inston; S. Moore; A. McClean; P.G. McTernan; L. Harper; A.C. Phillips; R. Borrows

    2013-01-01

    Background: Fatigue has been underinvestigated in stable kidney transplant recipients (KTRs). The objectives of this study were to investigate the nature, severity, prevalence, and clinical awareness of fatigue in medically stable KTRs, examine the impact of fatigue on quality of life (QoL), and exp

  17. Sodium intake and blood pressure in renal transplant recipients

    NARCIS (Netherlands)

    van den Berg, Else; Geleijnse, Johanna M.; Brink, Elizabeth J.; van Baak, Marleen A.; van der Heide, Jaap J. Homan; Gans, Rijk O. B.; Navis, Gerjan; Bakker, Stephan J. L.

    Hypertension is common among renal transplant recipients (RTR) and a risk factor for graft failure and mortality. Sodium intake is a well-established determinant of blood pressure (BP) in the general population. However, data in RTR are limited. International guidelines recommend a maximum daily

  18. Epidemiogic aspects of skin cancer in organ-transplant recipients

    NARCIS (Netherlands)

    Wisgerhof, Hermina Christina

    2011-01-01

    The risk of (skin) cancer is highly increased in organ-transplant recipients who are kept on immunesuppressive drugs to prevent graft rejection. This thesis dealt with the epidemiologic aspects and risk factors for cancer focused on cutaneous squamous cell carcinoma and basal cell carcinoma.

  19. 14 CFR 1274.205 - Consortia as recipients.

    Science.gov (United States)

    2010-01-01

    ... better share the projects financial costs (e.g., the 50 percent recipient's cost share or other costs of...). (Also see § 1274.940.) The inclusion of non-profit or educational institutions, small businesses, or... should also address to the extent appropriate— (1) Commitments of financial, personnel, facilities...

  20. Sex differences among recipients of benzodiazepines in Dutch general practice.

    NARCIS (Netherlands)

    Waals, F.W. van der; Mohrs, J.; Foets, M.

    1993-01-01

    Objective: To analyse sex differences among recipients of benzodiazepines in Dutch general practice. Design-Study of consultations and associated interventions as recorded in the Dutch national survey of general practice. Setting: Practices of 45 general practitioners monitored during 1 April to 30

  1. 45 CFR 89.3 - Organizational integrity of recipients.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Organizational integrity of recipients. 89.3 Section 89.3 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION ORGANIZATIONAL INTEGRITY OF ENTITIES IMPLEMENTING PROGRAMS AND ACTIVITIES UNDER THE LEADERSHIP ACT § 89.3 Organizational...

  2. Combination treatment of human umbilical cord matrix stem cell-based interferon-beta gene therapy and 5-fluorouracil significantly reduces growth of metastatic human breast cancer in SCID mouse lungs.

    Science.gov (United States)

    Rachakatla, Raja Shekar; Pyle, Marla M; Ayuzawa, Rie; Edwards, Sarah M; Marini, Frank C; Weiss, Mark L; Tamura, Masaaki; Troyer, Deryl

    2008-08-01

    Umbilical cord matrix stem (UCMS) cells that were engineered to express interferon-beta (IFN-beta) were transplanted weekly for three weeks into MDA 231 breast cancer xenografts bearing SCID mice in combination with 5-fluorouracil (5-FU). The UCMS cells were found within lung tumors but not in other tissues. Although both treatments significantly reduced MDA 231 tumor area in the SCID mouse lungs, the combined treatment resulted in a greater reduction in tumor area than by either treatment used alone. These results indicate that a combination treatment of UCMS-IFN-beta cells and 5-FU is a potentially effective therapeutic procedure for breast cancer.

  3. The myelin basic protein-specific T cell repertoire in (transgenic) Lewis rat/SCID mouse chimeras: preferential V beta 8.2 T cell receptor usage depends on an intact Lewis thymic microenvironment.

    Science.gov (United States)

    Kääb, G; Brandl, G; Marx, A; Wekerle, H; Bradl, M

    1996-05-01

    In the Lewis rat, myelin basic protein (MBP)-specific, encephalitogenic T cells preferentially recognize sequence 68-88, and use the V beta 8.2 gene to encode their T cell receptors. To analyze the structural prerequisites for the development of the MBP-specific T cell repertoire, we reconstituted severe-combined immunodeficient (SCID) mice with fetal (embryonic day 15-16) Lewis rat lymphoid tissue, and then isolated MBP-specific T cell lines from the adult chimeras after immunization. Two types of chimera were constructed: SCID mice reconstituted with rat fetal liver cells only, allowing T cell maturation within a chimeric SCID thymus consisting of mouse thymic epithelium and rat interdigitating dendritic cells, and SCID mice reconstituted with rat fetal liver cells and rat fetal thymus grafts, allowing T cell maturation within the chimeric SCID and the intact Lewis rat thymic microenvironment. Without exception, the T cell lines isolated from MBP-immunized SCID chimeras were restricted by MHC class II of the Lewis rat (RT1.B1), and none by I-Ad of the SCID mouse. Most of the T cell lines recognized the immunodominant MBP epitope 68-88. In striking contrast to intact Lewis rats, in SCID mice reconstituted by rat fetal liver only, MBP-specific T cell clones used a seemingly random repertoire of V beta genes without a bias for V beta 8.2. In chimeras containing fetal Lewis liver plus fetal thymus grafted under the kidney capsule, however, dominant utilization of V beta 8.2 was restored. The migration of liver-derived stem cells through rat thymus grafts was documented by combining fetal tissues from wild-type and transgenic Lewis rats. The results confirm that the recognition of the immunodominant epitope 68-88 by MBP-specific encephalitogenic T cells is a genetically determined feature of the Lewis rat T cell repertoire. They further suggest that the formation of the repertoire requires T cell differentiation in a syngeneic thymic microenvironment.

  4. Transplantation of marrow cells from children with standard risk-acute lymphoblastic leukemia at the end of therapy into NOD/SCID mice for detecting residual leukemic cells with in vivo growth potential.

    Science.gov (United States)

    Ramírez, Manuel; Díaz, Miguel A; Madero, Luis; Bueren, Juan A

    2003-12-01

    In the present work, we developed a strategy for detecting residual leukemia in the marrow of children with standard risk-acute lymphoblastic leukemia (sr-ALL) at the end of therapy, based on the capacity of human leukemic cells for growing in the NOD/SCID mice marrow microenvironment. Mononuclear (MN) marrow cells from 62 patients were injected into sublethally irradiated NOD/SCID mice and the engraftment kinetics and composition of the human grafts were determined periodically. The presence of human leukemic cells with immunophenotypes and clonal DNA markers similar to those of the original leukemic clone was studied.

  5. Molecular appraisal of intestinal parasitic infection in transplant recipients

    Science.gov (United States)

    Yadav, Pooja; Khalil, Shehla; Mirdha, Bijay Ranjan

    2016-01-01

    Background & objectives: Diarrhoea is the main clinical manifestation caused by intestinal parasitic infections in patients, with special reference to transplant recipients who require careful consideration to reduce morbidity and mortality. Further, molecular characterization of some important parasites is necessary to delineate the different modes of transmission to consider appropriate management strategies. We undertook this study to investigate the intestinal parasitic infections in transplant recipients with or without diarrhoea, and the genotypes of the isolated parasites were also determined. Methods: Stool samples from 38 transplant recipients comprising 29 post-renal, two liver and seven bone marrow transplant (BMT) recipients presenting with diarrhoea and 50 transplant recipients (42 post-renal transplant, eight BMT) without diarrhoea were examined for the presence of intestinal parasites by light microscopy using wet mount, modified Ziehl–Neelsen staining for intestinal coccidia and modified trichrome staining for microsporidia. Genotypes of Cryptosporidium species were determined by multilocus genotyping using small subunit ribosomal (SSUrRNA), Cryptosporidium oocyst wall protein (COWP) and dihydrofolate reductase (DHFR) as the target genes. Assemblage study for Giardia lamblia was performed using triose phosphate isomerase (TPI) as the target gene. Samples were also screened for bacterial, fungal and viral pathogens. Results: The parasites that were detected included Cryptosporidium species (21%, 8/38), Cystoisospora (Isospora) belli (8%, 3), Cyclospora cayetanensis (5%, 2), G. lamblia (11%, 4), Hymenolepis nana (11%, 4), Strongyloides stercoralis (3%, 1) and Blastocystis hominis (3%, 1). Multilocus genotyping of Cryptosporidium species at SSUrRNA, COWP and DHFR loci could detect four isolates of C. hominis; two of C. parvum, one of mixed genotype and one could not be genotyped. All the C. hominis isolates were detected in adult post

  6. Molecular appraisal of intestinal parasitic infection in transplant recipients

    Directory of Open Access Journals (Sweden)

    Pooja Yadav

    2016-01-01

    Full Text Available Background & objectives: Diarrhoea is the main clinical manifestation caused by intestinal parasitic infections in patients, with special reference to transplant recipients who require careful consideration to reduce morbidity and mortality. Further, molecular characterization of some important parasites is necessary to delineate the different modes of transmission to consider appropriate management strategies. We undertook this study to investigate the intestinal parasitic infections in transplant recipients with or without diarrhoea, and the genotypes of the isolated parasites were also determined. Methods: Stool samples from 38 transplant recipients comprising 29 post-renal, two liver and seven bone marrow transplant (BMT recipients presenting with diarrhoea and 50 transplant recipients (42 post-renal transplant, eight BMT without diarrhoea were examined for the presence of intestinal parasites by light microscopy using wet mount, modified Ziehl-Neelsen staining for intestinal coccidia and modified trichrome staining for microsporidia. Genotypes of Cryptosporidium species were determined by multilocus genotyping using small subunit ribosomal (SSUrRNA, Cryptosporidium oocyst wall protein (COWP and dihydrofolate reductase (DHFR as the target genes. Assemblage study for Giardia lamblia was performed using triose phosphate isomerase (TPI as the target gene. Samples were also screened for bacterial, fungal and viral pathogens. Results: The parasites that were detected included Cryptosporidium species (21%, 8/38, Cystoisospora (Isospora belli (8%, 3, Cyclospora cayetanensis (5%, 2, G. lamblia (11%, 4, Hymenolepis nana (11%, 4, Strongyloides stercoralis (3%, 1 and Blastocystis hominis (3%, 1. Multilocus genotyping of Cryptosporidium species at SSUrRNA, COWP and DHFR loci could detect four isolates of C. hominis; two of C. parvum, one of mixed genotype and one could not be genotyped. All the C. hominis isolates were detected in adult post

  7. Therapeutic regulation of systemic inflammation in xenograft recipients.

    Science.gov (United States)

    Iwase, Hayato; Liu, Hong; Li, Tao; Zhang, Zhongquiang; Gao, Bingsi; Hara, Hidetaka; Wijkstrom, Martin; Long, Cassandra; Saari, Ryan; Ayares, David; Cooper, David K C; Ezzelarab, Mohamed B

    2017-03-01

    Inflammation is known to preclude tolerance after transplantation. We have previously shown that systemic inflammation in xenograft recipients (SIXR) precedes activation of coagulation in the absence of T cell responses. Accordingly, SIXR may amplify innate and adaptive immune responses against xenografts after pig-to-primate xenotransplantation, even with efficient immunosuppressive therapy. We evaluated the impact of anti-inflammatory agents on pro-inflammatory cytokines and chemokines in pig artery patch and heart xenograft recipients. Baboons received an artery patch (Group1, n=8) or heart (Group2, n=4) from genetically engineered pigs. All baboons received lymphodepletion with thymoglobulin (ATG) and costimulation blockade-based immunosuppression (anti-CD40 and/or CTLA4Ig). In Group1, baboons received either (i) no anti-inflammatory agents (n=2), (ii) cobra venom factor (CVF, n=2), (iii) α1-antitrypsin (AAT, n=2), or (iv) interleukin (IL)-6 receptor antagonist (IL-6RA, n=2). In Group2, all baboon received corticosteroids, either without (n=2) or with (n=2) IL-6RA. Serum IFN-γ, TNF-α, IL-1β, IL-17, IL-6, IL-8, MCP-1, and sCD40L levels were measured by Luminex. Fibrinogen, D-dimers, and C-reactive protein (C-RP) were also measured. Recipient baboon T cell proliferation was evaluated by mixed lymphocyte reaction (MLR) before and after transplantation. Pig and baboon tissue factor (TF) mRNA levels in heart xenografts were measured by RT-PCR. In no recipient was a marked increase in T cell response to pig cells observed after transplantation. In Groups 1 and 2, post-transplantation levels of IFN-γ, TNF-α, IL-1β, and IL-17 remained comparable to or lower than pre-transplant levels, except in one heart recipient that succumbed to CMV infection. In Group1, when no anti-inflammatory agent was administered, post-transplant levels of IL-6, IL-8, and MCP-1 were elevated. After CVF, IL-6, IL-8, and MCP-1 remained low. After IL-6RA, IL-6 and MCP-1 were elevated

  8. Employing mated females as recipients for transfer of cloned dog embryos.

    Science.gov (United States)

    Kim, Geon A; Oh, Hyun Ju; Park, Jung Eun; Kim, Min Jung; Park, Eun Jung; Lim, Sang Hyun; Kang, Sung Keun; Jang, Goo; Lee, Byeong Chun

    2013-01-01

    It has been suggested that co-transferring parthenogenetic embryos could improve the pregnancy success rate with cloned embryos in mammals. As an alternative to co-transferring parthenotes, in dogs we employed recipient females that possessed in vivo-fertilised embryos as a result of mating to determine whether mated bitches could be suitable recipients for cloned embryos. The effect of using mated recipients on implantation and pregnancy rates of canine somatic cell nuclear transfer embryos was also determined. Cloned embryos were transferred into the oviducts of naturally synchronous females that had mated with male dogs before ovulation. The pregnancy rate appeared to be similar between mated recipients (50%) and non-mated recipients (28.57%; P>0.05). However, the delivery rate of cloned pups was significantly higher in mated recipients than non-mated recipients (10.53 vs 2.38%; Pdogs can be used as recipients for cloned embryos.

  9. Depressive symptoms and associated factors among renal-transplant recipients in China

    Directory of Open Access Journals (Sweden)

    Xiaohong Lin

    2016-12-01

    Conclusion: Depression is common among RT recipients in China. Employment status, economic burden, inhabitation area, and social support are the main factors affecting depression among RT recipients. Follow-up clinics should prescribe the evaluation of depression as a routine examination for RT patients. Moreover, depressed recipients must be provided with individualized care by collecting information on the depressive symptoms, employment status, economic burden, inhabitation area, and perceived social support of recipients.

  10. 42 CFR 456.604 - Physician team member inspecting care of recipients.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Physician team member inspecting care of recipients... Intermediate Care Facilities and Institutions for Mental Diseases § 456.604 Physician team member inspecting care of recipients. No physician member of a team may inspect the care of a recipient for whom he...

  11. 13 CFR 117.6 - Remedial and affirmative action by recipients.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Remedial and affirmative action by... 1975, AS AMENDED § 117.6 Remedial and affirmative action by recipients. (a) Where a recipient is found...) Even in the absence of a finding of discrimination, a recipient may take affirmative action to...

  12. 45 CFR 90.49 - Remedial and affirmative action by recipients.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Remedial and affirmative action by recipients. 90..., Conciliation and Enforcement Procedures § 90.49 Remedial and affirmative action by recipients. (a) Where a... remedial action. (b) Even in the absence of a finding of discrimination, a recipient may take...

  13. 24 CFR 146.47 - Remedial and affirmative action by recipients.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Remedial and affirmative action by... Remedial and affirmative action by recipients. (a) Where the Secretary finds that a recipient has... action. (b) Even in the absence of a finding of discrimination, a recipient may take affirmative...

  14. Stability and Longevity in the Publication Careers of U.S. Doctorate Recipients

    NARCIS (Netherlands)

    Waaijer, C.J.F.; Macaluso, B.; Sugimoto, C.R.; Larivière, V.

    2016-01-01

    Since the 1950s, the number of doctorate recipients has risen dramatically in the United States. In this paper, we investigate whether the longevity of doctorate recipients' publication careers has changed. This is achieved by matching 1951-2010 doctorate recipients with rare names in astrophysics,

  15. 45 CFR 400.61 - Services to public/private RCA recipients.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Services to public/private RCA recipients. 400.61... Refugee Cash Assistance § 400.61 Services to public/private RCA recipients. (a) Services provided to recipients of refugee cash assistance in the public/private RCA program may be provided by the...

  16. Caregiver Confidence: Does It Predict Changes in Disability among Elderly Home Care Recipients?

    Science.gov (United States)

    Li, Lydia W.; McLaughlin, Sara J.

    2012-01-01

    Purpose of the study: The primary aim of this investigation was to determine whether caregiver confidence in their care recipients' functional capabilities predicts changes in the performance of activities of daily living (ADL) among elderly home care recipients. A secondary aim was to explore how caregiver confidence and care recipient functional…

  17. Stability and Longevity in the Publication Careers of U.S. Doctorate Recipients

    NARCIS (Netherlands)

    Waaijer, C.J.F.; Macaluso, B.; Sugimoto, C.R.; Larivière, V.

    2016-01-01

    Since the 1950s, the number of doctorate recipients has risen dramatically in the United States. In this paper, we investigate whether the longevity of doctorate recipients' publication careers has changed. This is achieved by matching 1951-2010 doctorate recipients with rare names in astrophysics,

  18. Expression of the chemokine receptor CXCR7 in CXCR4-expressing human 143B osteosarcoma cells enhances lung metastasis of intratibial xenografts in SCID mice.

    Directory of Open Access Journals (Sweden)

    Patrick Brennecke

    Full Text Available More effective treatment of metastasizing osteosarcoma with a current mean 5-year survival rate of less than 20% requires more detailed knowledge on mechanisms and key regulatory molecules of the complex metastatic process. CXCR4, the receptor of the chemokine CXCL12, has been reported to promote tumor progression and metastasis in osteosarcoma. CXCR7 is a recently deorphanized CXCL12-scavenging receptor with so far not well-defined functions in tumor biology. The present study focused on a potential malignancy enhancing function of CXCR7 in interaction with CXCR4 in osteosarcoma, which was investigated in an intratibial osteosarcoma model in SCID mice, making use of the human 143B osteosarcoma cell line that spontaneously metastasizes to the lung and expresses endogenous CXCR4. 143B osteosarcoma cells stably expressing LacZ (143B-LacZ cells were retrovirally transduced with a gene encoding HA-tagged CXCR7 (143B-LacZ-X7-HA cells. 143B-LacZ-X7-HA cells co-expressing CXCR7 and CXCR4 exhibited CXCL12 scavenging and enhanced adhesion to IL-1β-activated HUVEC cells compared to 143B-LacZ cells expressing CXCR4 alone. SCID mice intratibially injected with 143B-LacZ-X7-HA cells had significantly (p<0.05 smaller primary tumors, but significantly (p<0.05 higher numbers of lung metastases than mice injected with 143B-LacZ cells. Unexpectedly, 143B-LacZ-X7-HA cells, unlike 143B-LacZ cells, also metastasized with high incidence to the auriculum cordis. In conclusion, expression of the CXCL12 scavenging receptor CXCR7 in the CXCR4-expressing human 143B osteosarcoma cell line enhances its metastatic activity in intratibial primary tumors in SCID mice that predominantly metastasize to the lung and thereby closely mimic the human disease. These findings point to CXCR7 as a target, complementary to previously proposed CXCR4, for more effective metastasis-suppressive treatment in osteosarcoma.

  19. Human intestinal epithelial cells produce proinflammatory cytokines in response to infection in a SCID mouse-human intestinal xenograft model of amebiasis.

    Science.gov (United States)

    Seydel, K B; Li, E; Swanson, P E; Stanley, S L

    1997-01-01

    The protozoan parasite Entamoeba histolytica causes amebic dysentery and amebic liver abscess, diseases associated with significant morbidity and mortality worldwide. E. histolytica infection appears to involve the initial attachment of amebic trophozoites to intestinal epithelial cells, followed by lysis of these cells and subsequent invasion into the submucosa. A recent in vitro study (L. Eckmann, S. L. Reed, J. R. Smith, and M. F. Kagnoff, J. Clin. Invest. 96:1269-1279, 1995) demonstrated that incubation of E. histolytica trophozoites with epithelial cell lines results in epithelial cell production of inflammatory cytokines, including interleukin-1 (IL-1) and IL-8, suggesting that intestinal epithelial cell production of cytokines might play a role in the inflammatory response and tissue damage seen in intestinal amebiasis. To determine whether intestinal epithelial cell production of IL-1 and IL-8 occurs in response to E. histolytica infection in vivo and as an approach to studying the specific interactions between amebic trophozoites and human intestine, we used a SCID mouse-human intestinal xenograft (SCID-HU-INT) model of disease, where human intestinal xenografts were infected with virulent E. histolytica trophozoites. Infection of xenografts with E. histolytica trophozoites resulted in extensive tissue damage, which was associated with the development of an early inflammatory response composed primarily of neutrophils. Using oligonucleotide primers that specifically amplify human IL-1beta and IL-8, we could demonstrate by reverse transcription PCR that mRNA for both IL-1beta and IL-8 is produced by human intestinal xenografts in response to amebic infection. The increase in human intestinal IL-1beta and IL-8 in response to invasive amebiasis was confirmed by enzyme-linked immunosorbent assays specific for human IL-1beta and IL-8. Using immunohistochemistry, we confirmed that human intestinal epithelial cells were the source of IL-8 in infected xenografts

  20. Split liver transplantation benefits the recipient of the 'leftover liver'.

    Science.gov (United States)

    Dunn, S P; Haynes, J H; Nicolette, L A; Falkenstein, K; Pierson, A; Billmire, D F; Vinocur, C D; Weintraub, W

    1997-02-01

    The division of a single hepatic allograft to create two reduced-size grafts has been reported with decreased graft survival (50%) resulting in decreased enthusiasm for this approach. The authors reviewed their experience with 12 recipients of this procedure to evaluate the outcome of the children electively undergoing transplant with the "leftover liver." A retrospective review of six pairs of children receiving part of one hepatic allograft included donor anatomy, recipient operation, and allograft and patient outcomes. Recipient pairs were selected according to blood type compatibility, medical priority, and size restrictions of the larger right lobe and the smaller left lateral segment. Patient and graft survival were compared with elective and urgent patients undergoing whole or reduced-size transplants. Six donors weighed 71.8 +/- 17.4 kg and were 22.6 +/- 11.0 years of age. Recipients of the right lobe were 11.8 +/- 4.2 years of age and weighed 41.9 +/- 14 kg. Recipients of the left lateral segment were 1.81 +/- 1.1 years of age and weighed 9.85 +/- 1.82 kg. Six patients were initially offered the donor allograft because of their hospitalization, critical illness or waiting time. Six additional patients electively underwent transplantation with the leftover liver. Donor organs were screened for normal arterial anatomy. Division of the allograft was performed on the back table in the falciform groove. Generally the left lateral segment graft received the major portion of the hepatic artery and the right lobe the major portion of the portal vein. Five of six (83%) elective patients, two receiving the right lobe and three receiving the left lateral segment had prompt recovery and left the hospital without surgical complication. One recipient of a right lobe transplant died from primary allograft nonfunction. These results are not different from the outcomes of all elective patients who underwent transplantation with whole or reduced-sized transplants in the

  1. Hindi language tool for assessing pediatric cochlear implant recipients.

    Science.gov (United States)

    Mittal, Ruchika; Raj, Anoop; Ramalingam, W V B S

    2015-09-01

    Presently, in India, western material is mainly used for the assessment and planning of habilitation activities for paediatric cochlear implant (CI) recipients. There is no assessment material available in Hindi. Therefore, the present study aimed to develop a parental questionnaire to assess auditory, speech and language skills of paediatric CI recipients in Hindi language for the age range of 3-7 years. Most commonly used assessment material/curricula used in Indian cochlear implant clinics and primary school Hindi language teachers were consulted during the development of the parental questionnaire. The developed questionnaire was then given to the parents of 50 normal hearing, Hindi speaking children in the age range of 3-7 years, five experienced speech and language pathologist working in the field of paediatric CI and to the same primary school Hindi language teachers who were consulted in the beginning to validate the content of the questionnaire. Based on the feedback from parents, personal observations and views from other professionals, the questionnaire was modified to incorporate the suggestions and the questionnaire was finalized. The final questionnaire has three subtests (1, 2 and 3) to assess auditory, language and speech skills of the CI recipients respectively. The final questionnaire was given to the Hindi speaking parents of 50 CI recipients in the age range of 3-7 years who fulfilled the eligibility criteria. Both the parents were asked to fill the final questionnaire together in the clinic at 0 (switch-on), 1, 6 and 12 months post switch-on of the implant. All the cochlear implant recipients could be evaluated by the questionnaire and none of the recipient scored zero on the questionnaire at any time interval. The developed questionnaire had shown high reliability and internal consistency producing alpha values of 0.9201, 0.7425 and 0.9311 for the subtest 1, 2 and the entire questionnaire respectively. The alpha value was not calculated for

  2. Modulation of the allergen-induced human IgE response in Hu-SCID mice: inhibitory effect of human recombinant IFN-gamma and allergen-derived lipopeptide.

    Science.gov (United States)

    Duez, C; Gras-Masse, H; Hammad, H; Akoum, H; Didierlaurent, A; André, C; Tonnel, A B; Pestel, J

    2001-01-01

    We have previously established a model to study the in vivo human IgE response using humanized SCID mice. Allergic SCID mice were obtained following intraperitoneal injection with mononuclear cells from Dermatophagoides pteronyssinus (Dpt)-sensitive patients, and sensitization by Dpt allergen intraperitoneal injection (immunization) or Dpt aerosol (inhalation). Human serum IgE was measured in allergic SCID mice after administration of human recombinant IFN-gamma or the lipopeptide LP 52-71 (derived from peptide p52-71 from Der p 1, Dpt major allergen, coupled to a lipophilic moiety), during the immunization or the inhalation phase. IFN-gamma inhibited human IgE production when given at the time of immunization, but not during inhalation. This effect was long-lasting as Dpt aerosol, given one month after immunization and IFN-gamma administration, failed to increase IgE levels. Unlike Dpt or p52-71, LP 52-71 failed to induce human IgE production at day 14 and 21 after its injection, but did inhibit the development of the IgE response after a secondary Dpt-challenge. Moreover, LP 52-71 administration 14 days after Dpt inhalation decreased IgE levels, in contrast to peptide 52-71, which increased IgE levels. Thus, taken together these results indicate that the development of the human IgE response in allergic SCID mice can be modulated by modified allergen and a Th1 cytokine.

  3. Diagnostic efficiency among psychiatric outpatients of a self-report version of a subset of screen items of the Structured Clinical Interview for DSM-IV-TR Personality Disorders (SCID-II).

    NARCIS (Netherlands)

    Germans, S.; Heck, G.L. van; Masthoff, E.D.M.; Trompenaars, F.J.; Hodiamont, P.P.G.

    2010-01-01

    This article describes the identification of a 10-item set of the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) items, which proved to be effective as a self-report assessment instrument in screening personality disorders. The item selection was based on the retrospective

  4. Absence of lactobacilli containing glycolipids with the α-galactose epitope and the enhanced fucosylation of a receptor glycolipid GA1 in the digestive tracts of immune-deficient scid mice.

    Science.gov (United States)

    Iwamori, Masao; Tanaka, Kyoko; Adachi, Shigeki; Aoki, Daisuke; Nomura, Taisei

    2015-07-01

    The Lactobacillus species in the digestive tracts of immune-deficient scid mice was distinct from that in control mice, i.e. Lactobacillus murinus in scid and L. johnsonii in control mice, according to their 16S-rRNA, indicating that a symbiotic relationship between lactobacilli and a host is established under pressure from the immune system. The caecal and colonal contents rich in L. murinus of scid mice were loose with a strong sour smell, resulting in diarrhoea, and those with L. johnsonii in control mice included abundant solid materials. Lactobacillus glycolipids were revealed to be recognized by the immune system, and by TLC-immunostaining, LacTetH-DG (Galα1-6Galα1-6Galα1-2Glcα1-3'DG) of L. johnsonii was detected in the stomach, caecum and colon of control mice, but not in those of scid ones, in which fucosylation of a receptor GA1 for L. johnsonii was enhanced more than 4-fold compared with in the control mice. Thus, structural modification of receptor glycolipids was revealed to occur in the process of establishment of a symbiotic relationship between lactobacilli and a host. LacTetH-DG was also immunogenic to human, because of the presence of natural antibodies against it, and the antibody binding to it was comparable to that of blood group- and species-related glycosphingolipids.

  5. Accumulation of immunoglobulin-containing cells in the gut mucosa and presence of faecal immunoglobulin in severe combined immunodeficient (scid) mice with T cell-induced inflammatory bowel disease (IBD)

    DEFF Research Database (Denmark)

    Bregenholt, S; Brimnes, J; Reimann, J

    1998-01-01

    and IgG2b were found to accumulate in colon segments displaying the most severe histopathology, including inflammatory cellular infiltration, epithelial hyperplasia and ulcerative lesions. Compared with colon segments of normal C.B-17 mice, the lesional scid colon shows increased levels of cells positive...

  6. Lack of nonfunctional B-cell receptor rearrangements in a patient with normal B cell numbers despite partial RAG1 deficiency and atypical SCID/Omenn syndrome

    DEFF Research Database (Denmark)

    Ohm-Laursen, Line; Nielsen, Christian; Fisker, Niels

    2008-01-01

    and the patient had eosinophilia. These presentations are consistent with atypical severe combined immunodeficiency (SCID)/Omenn Syndrome and the diagnosis was confirmed by demonstration of homozygosity for the R841W mutation in the catalytic core of RAG1. Comparison of the patient's immunoglobulin heavy chain...... chromosome 14. CONCLUSION: We hypothesize that the R841W mutation causes a malfunction of RAG1 that has differential outcome on V(D)J recombination in B and T cells, as the patient had normal B cell numbers but suffered severe alpha-beta T-cell immunodeficiency.......INTRODUCTION: A 2.5-month old boy presented with recurrent wheezing, protracted diarrhea, erythrodermia, and failure to thrive. METHODS AND RESULTS: Laboratory analysis showed lymphocytopenia with severely reduced T-cell numbers but normal numbers of B and NK cells. Serum IgE was increased...

  7. 人免疫重建NOD/SCID小鼠模型的建立%Establishment of Human Immune Reconstitute NOD/SCID Mice Model

    Institute of Scientific and Technical Information of China (English)

    颜汝平; 李翀; 周海滨; 王剑松; 袁国红; 赵献

    2011-01-01

    Objective To study the establishment method of human immune reconstitute animal model in NOD/SCID mice and the characteristics of immunologic reconstitution. Methods 16 NOD/SCID mice were randomly divided into experimental group (n = 8) and control group (n = 8). The peripheral blood mononuclear cells (PBMCs) were isolated from fresh peripheral blood of healthy people using Ficoll lymphocyte separating medium, and then were transplanted into experimental mice by intraperitoneal injection. Mice in control group was injected PBS buffer. In the 4th, 8th and 12th weeks, human CD3 T and CD19 B lymphocytes in the blood of mice were detected by flow cytometry, human IgG protein content in the blood of mice was measured by ELISA method and the infiltration of human CD3 T and CD19 B lymphocytes in mice spleen and liver were detected by immunohistochemical staining. Results After 4 weeks, human CD3 T and CD19 B lymphocytes in peripheral blood of experimental mice were respectively 85.6% and 76.7% of the total monocytes, and were also detected in mice spleen. The amount of human IgG in serum of experimental mice after 4,8 and 12 weeks of transplantation were respectively(863 ± 12.5) μg/mL, (1217 ± 16.7) μg/mL and(958 ± 13.1) μg/mL. Conclusions Human immune reconstitute NOD/SCID mice model can be successfully established by intraperitoneal injection of human PBMC. The method is simple and reliable.%目的 探讨NOD/SCID(nonobese diabetic/severe combined immunodeficient)小鼠人免疫重建模型的建立方法和免疫特性.方法 16只NOD/SCID小鼠随机分成实验组和对照组,每组8只.Ficoll密度梯度离心法分离人外周血单个核细胞(peripheral blood mononuclear cell,PBMC),通过腹腔注射移植给实验组小鼠,空白对照组小鼠每只腹腔注射无菌PBS,第4、8和12周时,流式细胞术检测小鼠外周血中人的CD3T、CD19B淋巴细胞,ELISA法测定小鼠血清中人IgG含量,免疫组织化学染色检测

  8. Long-term maintenance of skin immune system in a NOD-Scid IL2rγ(null) mouse model transplanted with human skin.

    Science.gov (United States)

    Soria, Angèle; Boccara, David; Chonco, Louis; Yahia, Nora; Dufossée, Mélody; Cardinaud, Sylvain; Moris, Arnaud; Liard, Christelle; Joulin-Giet, Alix; Julithe, Marion; Mimoun, Maurice; Combadière, Béhazine; Perrin, Hélène

    2014-11-01

    We developed a NOD-Scid IL2rγ(null) mouse model transplanted with human skin that brings fundamental insight on in vivo cellular mechanisms of intradermal immunization and antigen presentation by dermal dendritic and epidermal Langerhans cells for skin T-cell immunity. Indeed, T-cell immunity is a crucial checkpoint for the induction of in vivo rapid control of skin infection. With the long-term preservation of a complete human skin immune system, this model offers the unique opportunity not only to better understand mechanisms of skin immune response but also to test new compounds and devices for cutaneous routes of vaccination, as well as new therapeutics approach for skin diseases, allergies or infections.

  9. Kidney recipients experiences before during and after kidney transplantation

    DEFF Research Database (Denmark)

    Nielsen, Charlotte

    Background Kidney transplantation is considered to be the best treatment for terminal renal insufficiency. Kidney transplant patients report higher quality of life because they avoid regular dialysis treatment that causes side effects, complications, restrictions and limitations in their daily...... and after the kidney transplant, through outpatient visits and during possible hospitalization, which can occur due to complications or disease progression. Objective To explore the coherence of the kidney transplant process in order to explain the lived experiences of kidney recipients before, during...... and after kidney transplantation. Method Participant observation and semi-structured individual interviews was conducted with kidney recipients before, during and after kidney transplantation. Data analysis is inspired by Ricoeur's interpretation theory on three levels: Naive reading; structural analysis...

  10. PSYCHOLOGICAL ADAPTATION AND REHABILITATION OF RECIPIENTS OF DONOR ORGANS

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    S. V. Gautier

    2016-01-01

    Full Text Available The paper analyzes the nature of psychological adaptation and rehabilitation of patients, recipients of solid organs. The results of the clinical and psychological work with patients, recipients of donor organs, carried out in theSverdlovskRegionalClinicalHospital№ 1 are shown. Special attention has been paid to the study of motivation as the main psychological factor in the process of adaptation and rehabilitation. We have also shown the infl uence of body image and self-evaluation on the emotional state of patients after the operation. Special stress is laid on the significance of psychological factors which improve the quality of the patient’s life. The main principles and the system of psychological rehabilitation are presented. 

  11. Renal transplantation between HIV-positive donors and recipients justified.

    Science.gov (United States)

    Muller, Elmi; Barday, Zunaid; Mendelson, Marc; Kahn, Delawir

    2012-03-02

    HIV infection was previously an absolute contraindication to renal transplantation. However, with the advent of highly active antiretroviral therapy (HAART), renal transplantation using HIV-negative donor kidneys has successfully been employed for HIV-infected patients with end-stage renal failure. In resource-limited countries, places on dialysis programmes are severely restricted; HIV-infected patients, like many others with co-morbidity, are often denied treatment. Kidneys (and other organs) from HIV-infected deceased donors are discarded. The transplantation of HIV-positive donor kidneys to HIV-infected recipients is now a viable alternative to chronic dialysis or transplantation of HIV-negative donor kidneys. This significantly increases the pool of donor kidneys to the advantage of HIV-positive and -negative patients. Arguments are presented that led to our initiation of renal transplantation from HIV-positive deceased donors to HIV-positive recipients at Groote Schuur Hospital, Cape Town.

  12. Central nervous system syndromes in solid organ transplant recipients.

    Science.gov (United States)

    Wright, Alissa J; Fishman, Jay A

    2014-10-01

    Solid organ transplant recipients have a high incidence of central nervous system (CNS) complications, including both focal and diffuse neurologic deficits. In the immunocompromised host, the initial clinical evaluation must focus on both life-threatening CNS infections and vascular or anatomic lesions. The clinical signs and symptoms of CNS processes are modified by the immunosuppression required to prevent graft rejection. In this population, these etiologies often coexist with drug toxicities and metabolic abnormalities that complicate the development of a specific approach to clinical management. This review assesses the multiple risk factors for CNS processes in solid organ transplant recipients and establishes a timeline to assist in the evaluation and management of these complex patients.

  13. Prevalence of hepatitis G virus infection in kidney transplant recipients.

    Science.gov (United States)

    Dussol, B; Charrel, R; De Lamballerie, X; Berthezene, P; Brunet, P; De Micco, P; Raoult, D; Berland, Y

    1997-08-15

    We investigated the prevalence, risk factors, and consequences of hepatitis G virus (HGV) infection in 87 kidney transplant recipients. Infection was diagnosed with reverse transcriptase polymerase chain reaction using primers in the NS3 region of the viral genoma. Twenty-four patients (27.5%) were HGV RNA positive (HGV+ group) and 63 patients (72.5%) were HGV RNA negative (HGV- group). No statistically significant differences were found between the two groups for age, sex, transplantation and hemodialysis duration, number of kidney transplantations, serum creatinine, history of transfusions, hepatitis B and C virus infections, and percentage of patients having suffered from acute rejection. Acute and chronic hepatitis were not more prevalent in the HGV+ group than in the HGV- group. HGV infection is highly prevalent in kidney transplant recipients but does not alter liver or kidney functions. HGV contamination may be linked to nosocomial transmission during long-term hemodialysis.

  14. Urinary tract infections and asymptomatic bacteriuria in renal transplant recipients

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    Rabi Yacoub

    2011-01-01

    Full Text Available Asymptomatic bacteriuria and urinary tract infection are common complications after kidney transplantation. In this population, if urinary tract infection occurred in the first six months post procedure, it carries a grave impact on both graft and patient survival. Renal transplant recipients with urinary tract infection are often clinically asymptomatic as a consequence of immunosuppression. Urinary tract infection, however, may progress to acute pyelonephritis, bacteremia and the full blown picture of urosepsis. PubMed and Cochrane databases were searched. The purpose of this review is to discuss the screening and treatment of urinary tract infection and asymptomatic bacteriuria in renal transplant recipients and to evaluate the guidelines on the basis of a review of published evidence.

  15. Disseminated Mycobacterium haemophilum infection in a renal transplant recipient.

    Science.gov (United States)

    Brix, Silke R; Iking-Konert, Christof; Stahl, Rolf A K; Wenzel, Ulrich

    2016-10-31

    Opportunistic infections are a major concern in renal and transplant medicine. We present the case of a renal transplant recipient with a generalised Mycobacterium haemophilum infection after an increase in immunosuppressive therapy and treatment with a tumour necrosis factor-α (TNF-α) inhibitor. Infection involved skin and soft tissue, joints and bones, as well as the renal transplant with an interstitial nephritis. Rapid diagnosis using PCR and DNA sequencing allowed early appropriate treatment. Triple antibiotic therapy and reduction in immunosuppression resulted in a slow but sustained recovery. Immunosuppression causes severe opportunistic infections. TNF-α inhibitors are very effective and well tolerated but have an increased susceptibility to infections with mycobacteria. Mycobacterial infections represent a significant clinical risk to transplant recipients because of their aggressive clinical course and the need for complex toxic antibiotic treatments. In these patients, M. haemophilum is a cause of skin infections.

  16. Poliomyelitis in MuLV-infected ICR-SCID mice after injection of basement membrane matrix contaminated with lactate dehydrogenase-elevating virus.

    Science.gov (United States)

    Carlson Scholz, Jodi A; Garg, Rohit; Compton, Susan R; Allore, Heather G; Zeiss, Caroline J; Uchio, Edward M

    2011-10-01

    The arterivirus lactate dehydrogenase-elevating virus (LDV) causes life-long viremia in mice. Although LDV infection generally does not cause disease, infected mice that are homozygous for the Fv1(n) allele are prone to develop poliomyelitis when immunosuppressed, a condition known as age-dependent poliomyelitis. The development of age-dependent poliomyelitis requires coinfection with endogenous murine leukemia virus. Even though LDV is a common contaminant of transplantable tumors, clinical signs of poliomyelitis after inadvertent exposure to LDV have not been described in recent literature. In addition, LDV-induced poliomyelitis has not been reported in SCID or ICR mice. Here we describe the occurrence of poliomyelitis in ICR-SCID mice resulting from injection of LDV-contaminated basement membrane matrix. After exposure to LDV, a subset of mice presented with clinical signs including paresis, which was associated with atrophy of the hindlimb musculature, and tachypnea; in addition, some mice died suddenly with or without premonitory signs. Mice presenting within the first 6 mo after infection had regions of spongiosis, neuronal necrosis and astrocytosis of the ventral spinal cord, and less commonly, brainstem. Axonal degeneration of ventral roots prevailed in more chronically infected mice. LDV was identified by RT-PCR in 12 of 15 mice with typical neuropathology; positive antiLDV immunolabeling was identified in all PCR-positive animals (n = 7) tested. Three of 8 mice with neuropathology but no clinical signs were LDV negative by RT-PCR. RT-PCR yielded murine leukemia virus in spinal cords of all mice tested, regardless of clinical presentation or neuropathology.

  17. Integration of retroviral vectors induces minor changes in the transcriptional activity of T cells from ADA-SCID patients treated with gene therapy.

    Science.gov (United States)

    Cassani, Barbara; Montini, Eugenio; Maruggi, Giulietta; Ambrosi, Alessandro; Mirolo, Massimiliano; Selleri, Silvia; Biral, Erika; Frugnoli, Ilaria; Hernandez-Trujillo, Vivian; Di Serio, Clelia; Roncarolo, Maria Grazia; Naldini, Luigi; Mavilio, Fulvio; Aiuti, Alessandro

    2009-10-22

    Gene transfer into hematopoietic stem cells by gamma-retroviral vectors (RVs) is an effective treatment for inherited blood disorders, although potentially limited by the risk of insertional mutagenesis. We evaluated the genomic impact of RV integration in T lymphocytes from adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) patients 10 to 30 months after infusion of autologous, genetically corrected CD34(+) cells. Expression profiling on ex vivo T-cell bulk population revealed no difference with respect to healthy controls. To assess the effect of vector integration on gene expression at the single-cell level, primary T-cell clones were isolated from 2 patients. T-cell clones harbored either 1 (89.8%) or 2 (10.2%) vector copies per cell and displayed partial to full correction of ADA expression, purine metabolism, and T-cell receptor-driven functions. Analysis of RV integration sites indicated a high diversity in T-cell origin, consistently with the polyclonal T-cell receptor-Vbeta repertoire. Quantitative transcript analysis of 120 genes within a 200-kb window around RV integration sites showed modest (2.8- to 5.2-fold) dysregulation of 5.8% genes in 18.6% of the T-cell clones compared with controls. Nonetheless, affected clones maintained a stable phenotype and normal in vitro functions. These results confirm that RV-mediated gene transfer for ADA-SCID is safe, and provide crucial information for the development of future gene therapy protocols. The trials described herein have been registered at http://www.clinicaltrials.gov as #NCT00598481 and #NCT00599781.

  18. Validity of a self-reported diagnosis of depression among participants in a cohort study using the Structured Clinical Interview for DSM-IV (SCID-I

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    Pla Jorge

    2008-06-01

    Full Text Available Abstract Background Depression assessment in population studies is usually based on depressive symptoms scales. However, the use of scales could lead to the choice of an arbitrary cut-off point depending on the sample characteristics and on the patient diagnosis. Thus, the use of a medical diagnosis of depression could be a more appropriate approach. Objective To validate a self-reported physician diagnosis of depression using the Structured Clinical Interview for DSM-IV (SCID-I as Gold Standard and to assess the factors associated to a valid self-reported diagnosis. Methods The SUN Project is a cohort study based on university graduates followed-up through postal questionnaires. The response to the question included in the questionnaire: Have you ever been diagnosed of depression by a physician? was compared to that obtained through the SCID-I applied by a psychiatrist or a clinical psychologist. The percentages of confirmed depression and non-depression were assessed for the overall sample and according to several characteristics. Logistic regression models were fitted to ascertain the association between different factors and a correct classification regarding depression status. Results The percentage of confirmed depression was 74.2%; 95% confidence interval (95% CI = 63.3–85.1. Out of 42 participants who did not report a depression diagnosis in the questionnaire, 34 were free of the disease (%confirmed non-depression = 81.1%; 95% CI = 69.1–92.9. The probability of being a true positive was higher among ex-smokers and non-smokers and among those overweight or obese but the differences were not statistically significant. Conclusion The validity of a self-reported diagnosis of depression in the SUN cohort is adequate. Thus, this question about depression diagnosis could be used in further investigations regarding this disease in this graduate cohort study.

  19. Multifunctional interleukin-1beta promotes metastasis of human lung cancer cells in SCID mice via enhanced expression of adhesion-, invasion- and angiogenesis-related molecules.

    Science.gov (United States)

    Yano, Seiji; Nokihara, Hiroshi; Yamamoto, Akihiko; Goto, Hisatsugu; Ogawa, Hirohisa; Kanematsu, Takanori; Miki, Toyokazu; Uehara, Hisanori; Saijo, Yasuo; Nukiwa, Toshihiro; Sone, Saburo

    2003-03-01

    We examined whether interleukin-1 (IL-1), a multifunctional proinflammatory cytokine, progresses or regresses metastasis of lung cancer. Exogenous IL-1beta enhanced expression of various cytokines (IL-6, IL-8, and vascular endothelial growth factor (VEGF)) and intracellular adhesion molecule-1 (ICAM-1) by A549, PC14, RERF-LC-AI, and SBC-3 cells expressing IL-1 receptors. A549 cells transduced with human IL-1beta-gene with the growth-hormone signaling-peptide sequence (A549/IL-1beta) secreted a large amount of IL-1beta protein. Overexpression of IL-1beta resulted in augmentation of expression of the cytokines, ICAM-1, and matrix metalloproteinase-2 (MMP-2). A549/IL-1beta cells intravenously inoculated into severe combined immunodeficiency (SCID) mice distributed to the lung more efficiently and developed lung metastasis much more rapidly than did control A549 cells. Treatment of SCID mice with anti-IL-1beta antibody inhibited formation of lung metastasis by A549/IL-1beta cells. Moreover, A549/IL-1beta cells inoculated in the subcutis grew more rapidly, without necrosis, than did control A549 cells, which produced smaller tumors with central necrosis, suggesting involvement of angiogenesis in addition to enhanced binding in the high metastatic potential of A549/IL-1beta cells. Histological analyses showed that more host-cell infiltration, fewer apoptotic cells, more vascularization, and higher MMP activity were observed in tumors derived from A549/IL-1beta cells, compared with tumors derived from control A549 cells. These findings suggest that IL-1beta facilitates metastasis of lung cancer via promoting multiple events, including adhesion, invasion and angiogenesis.

  20. Human bone marrow mesenchymal stem cells display anti-cancer activity in SCID mice bearing disseminated non-Hodgkin's lymphoma xenografts.

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    Paola Secchiero

    Full Text Available BACKGROUND: Although multimodality treatment can induce high rate of remission in many subtypes of non-Hodgkin's lymphoma (NHL, significant proportions of patients relapse with incurable disease. The effect of human bone marrow (BM mesenchymal stem cells (MSC on tumor cell growth is controversial, and no specific information is available on the effect of BM-MSC on NHL. METHODOLOGY/PRINCIPAL FINDINGS: The effect of BM-MSC was analyzed in two in vivo models of disseminated non-Hodgkin's lymphomas with an indolent (EBV(- Burkitt-type BJAB, median survival = 46 days and an aggressive (EBV(+ B lymphoblastoid SKW6.4, median survival = 27 days behavior in nude-SCID mice. Intra-peritoneal (i.p. injection of MSC (4 days after i.p. injection of lymphoma cells significantly increased the overall survival at an optimal MSC:lymphoma ratio of 1:10 in both xenograft models (BJAB+MSC, median survival = 58.5 days; SKW6.4+MSC, median survival = 40 days. Upon MSC injection, i.p. tumor masses developed more slowly and, at the histopathological observation, exhibited a massive stromal infiltration coupled to extensive intra-tumor necrosis. In in vitro experiments, we found that: i MSC/lymphoma co-cultures modestly affected lymphoma cell survival and were characterized by increased release of pro-angiogenic cytokines with respect to the MSC, or lymphoma, cultures; ii MSC induce the migration of endothelial cells in transwell assays, but promoted endothelial cell apoptosis in direct MSC/endothelial cell co-cultures. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate that BM-MSC exhibit anti-lymphoma activity in two distinct xenograft SCID mouse models of disseminated NHL.

  1. Late Acute Rejection Occuring in Liver Allograft Recipients

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    Eric M Yoshida

    1996-01-01

    Full Text Available To study the effect of immunosuppressive reduction on the incidence and consequence of late acute rejection (LAR in liver allograft recipients, mean daily prednisone dose, mean cyclosporine A (CsA trough and nadir levels were retrospectively reviewed for the nearest 12-week period preceding six episodes of LAR in five liver allograft recipients (group 1. Results were compared with those from a cohort of 12 liver allograft recipients who did not develop LAR (group 2. LAR was defined as acute rejection occurring more than 365 days post-transplantation. Median follow-up for both groups was similar (504 days, range 367 to 1050, versus 511 days, range 365 to 666, not significant. Mean trough CsA levels were lower in patients with LAR compared with those without (224±66 ng/mL versus 233±49 ng/mL but the difference was not statistically significant. In contrast, mean daily prednisone dose (2.5±1.6 mg/ day versus 6.5±2.9 mg/day, P=0.007 and CsA nadir values (129±60 ng/mL versus 186±40 ng/mL, P=0.03 were significantly lower in patients who developed LAR compared with those who did not. Five of six episodes (83% of LAR occurred in patients receiving less than 5 mg/day of prednisone, versus a single LAR episode in only one of 12 patients (8% receiving prednisone 5 mg/day or more (P=0.004. In all but one instance, LAR responded to pulse methylprednisolone without discernible affect on long term graft function. The authors conclude that liver allograft recipients remain vulnerable to acute rejection beyond the first post-transplant year; and reduction of immunosuppressive therapy, particularly prednisone, below a critical, albeit low dose, threshold increases the risk of LAR.

  2. Twin pregnancy in a liver transplant recipient with HIV infection.

    Science.gov (United States)

    Van Schalkwyk, McI; Westbrook, R H; O'Beirne, J; Wright, A; Gonzalez, A; Johnson, M A; Kinloch-de Loës, S

    2016-10-05

    We are not aware of a report detailing the complex obstetrical and medical management of twin pregnancy in the context of HIV infection and early post-liver transplantation period. Here we describe the successful outcome of a twin pregnancy in a 28-year-old HIV-positive female receiving antiretroviral therapy and immunosuppressive therapy who was the recipient of a liver transplant for previous drug-induced liver failure.

  3. Lymphocyte Activation Markers in Pediatric Kidney Transplant Recipients

    OpenAIRE

    Fatina I Fadel; Elghoroury, Eman A.; Elshamaa, Manal F.; Bazaraa, Hafez M; Salah, Doaa M.; Kassem, Neemat M. A.; Ibrahim, Mona H.; El-Saaid, Gamila S.; Nasr, Soha A.; Koura, Hala M.

    2015-01-01

    Background and objectives: The role of CD4+CD25+ T regulatory cells (Tregs) in immune tolerance in experimental transplantation is very important but the clinical significance of circulating Tregs in the peripheral blood is undetermined. We evaluated the association between the frequency of T cell activation markers CD25 and CD71 and clinical parameters that may affect the level of these T cell markers. Methods: In 47peditric kidney transplant (KT) recipients and 20 healthy controls, the freq...

  4. Strategies to reduce clinical inertia in hypertensive kidney transplant recipients

    OpenAIRE

    Panek Romauld; Kiberd James; Kiberd Bryce

    2007-01-01

    Abstract Background Many kidney transplant recipients have hypertension. Elevated systolic blood pressures are associated with lower patient and kidney allograft survival. Methods This retrospective analysis examined the prevalence of clinical inertia (failure to initiate or increase therapy) in the treatment of hypertension before and after the introduction of an automated device (BpTRU) in the kidney transplant clinic. Results Historically only 36% (49/134) of patients were prescribed a cha...

  5. Basosquamous Cell Carcinoma Developing from a Renal Transplantation Recipient

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    Akira Tsukada

    2012-10-01

    Full Text Available We describe a case of basosquamous cell carcinoma arising from a 52-year-old Japanese renal transplantation recipient (RTR. In the present case, we investigated the immunohistochemical profiles of tumor-infiltrating lymphocytes, focusing on cytotoxic granules, granulysin-bearing cells and immunosuppressive cells, such as regulatory T cells and tumor-associated macrophages. Our present study suggests some of the possible mechanisms for the carcinogenesis of cutaneous malignancy in RTRs.

  6. Alcohol and substance abuse in solid-organ transplant recipients.

    Science.gov (United States)

    Parker, Richard; Armstrong, Matthew J; Corbett, Chris; Day, Edward J; Neuberger, James M

    2013-12-27

    This review focuses on alcohol and substance abuse in the context of solid-organ transplantation. Alcohol and substance abuse are common and may lead to a need for solid-organ transplantation and may also contribute to significant physical and psychologic problems that impact upon the recipient. Damaging levels of alcohol intake can occur in the absence of dependence. Alcohol or substance abuse after transplantation is associated with poor medication compliance and this may increase risk of graft loss. Intravenous drug use is associated with increased risk of infections (especially secondary to opportunistic organisms-bacterial, viral, protozoal, and others-and such infections may be more severe in the immunosuppressed), but there is only anecdotal evidence that such behavior has a worse outcome in transplant recipients. Whereas previous alcohol excess and drug use in kidney recipients are both associated with a small but statistically significantly increased risk of adverse outcomes (hazard ratio, 1.16-1.56), alcohol use within recommended guidelines after transplantation appears safe and possibly beneficial. Robust data are lacking for other organs, but those available suggest that heart transplantation is safe in individuals with a history of alcohol or substance abuse. Health specialists in drug or alcohol addiction should carefully screen all potential transplant candidates for these conditions, and where there is evidence of dependency or abuse, effective psychologic and physical treatment should be offered. Studies have shown that interventions such as psychologic intervention have improved alcohol behavior in the context of liver transplantation. Although there are no comparable studies with other solid-organ recipients, it is reasonable to expect transferable outcomes.

  7. RECIPIENT PRETRANSPLANT INOSINE MONOPHOSPHATE DEHYDROGENASE ACTIVITY IN NONMYELOABLATIVE HCT

    Science.gov (United States)

    Bemer, Meagan J.; Risler, Linda J.; Phillips, Brian R.; Wang, Joanne; Storer, Barry E.; Sandmaier, Brenda M.; Duan, Haichuan; Raccor, Brianne S.; Boeckh, Michael J.; McCune, Jeannine S.

    2014-01-01

    Mycophenolic acid, the active metabolite of mycophenolate mofetil (MMF), inhibits inosine monophosphate dehydrogenase (IMPDH) activity. IMPDH is the rate-limiting enzyme involved in de novo synthesis of guanosine nucleotides and catalyzes the oxidation of inosine 5’- monophosphate (IMP) to xanthosine 5’-monophosphate (XMP). We developed a highly sensitive liquid chromatography–mass spectrometry method to quantitate XMP concentrations in peripheral blood mononuclear cells (PMNC) isolated from the recipient pretransplant and used this method to determine IMPDH activity in 86 nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) patients. The incubation procedure and analytical method yielded acceptable within-sample and within-individual variability. Considerable between-individual variability was observed (12.2-fold). Low recipient pretransplant IMPDH activity was associated with increased day +28 donor T-cell chimerism, more acute graft-versus-host disease (GVHD), lower neutrophil nadirs, and more cytomegalovirus reactivation, but not with chronic GVHD, relapse, non-relapse mortality, or overall mortality. We conclude that quantitation of the recipient’s pretransplant IMPDH activity in PMNC lysate could provide a useful biomarker to evaluate a recipient’s sensitivity to MMF, but confirmatory studies are needed. Further trials should be conducted to confirm our findings and to optimize postgrafting immunosuppression in nonmyeloablative HCT recipients. PMID:24923537

  8. Somatic cell bovine cloning: Effect of donor cell and recipients

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Adult somatic cell nuclear transfer was conducted by using cultured ear fibroblast cells obtained from a Holstein female cow (GN) and a Galoway herd bull (GLV). The percentages of reconstructed eggs developed into blastocysts were similar in GN (23.98%, 123 of 513) and in GLV groups (29.55%, 138 of 467). However, the rate of reconstructed female (GN) embryos developed into term was higher than that of male (GLV) (8.02% and 1.82%, respectively). Three kinds of cows, Luxi Yellow cows, Holstein heifers and Holstein cows with normal reproductive records were used as recipients. When the reconstructed embryos from GN were transferred, there was no difference in the pregnancy rate among three kinds of recipients, but the abortion rate of Luxi Yellow cows was significantly higher (85.71%) than in the other two groups (14.29% and 0%, respectively; P < 0.05). And the percentages of newborn calves in transferred embryos were significantly different between Luxi Yellow cows and Holstein breed (1.54%, 10.39% and 20.0%, respectively, P < 0.05). However, when reconstructed embryos from GLV were transferred, there was no difference among three kinds of recipients in the pregnancy rate, the abortion rate and the delivery rate.

  9. A Survey of Bacterial Infections in Bone Marrow Transplant Recipients

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    MH Shirazi

    2007-09-01

    Full Text Available "nBackground: Bone marrow transplant (BMT recipients are prone to bacterial, viral and fungal infections. Bacterial infec­tion is considered as one of the common and serious complications in bone marrow transplant recipients. The aim of this study was to determine the rate of bacterial infections in bone marrow transplant recipients."nMethods: Fifty-two blood and 25 catheter samples were obtained from 23 patients who were hospitalized in bone marrow trans­plantation unit in Shariati Hospital in Tehran. Bacterial strains were isolated and identified by the standard conven­tional bacteriological methods. Antimicrobial susceptibility was performed according to the guidelines from NCCLS using 18 different antibiotics."nResults:  The strains of Staphylococci, Streptococcus viridans, Pseudomonas aeruginosa and Escherichia coli were isolated from 8(66.7%, 1(8.3%, 2 (16.7% and the 1(8.3% cases, respectively."nConclusion: Current study indicated that the bacterial infections particularly those caused by the Gram-positive cocci were still as important problem in bone marrow transplant.

  10. Urinary Tract Infection among Renal Transplant Recipients in Yemen.

    Science.gov (United States)

    Gondos, Adnan S; Al-Moyed, Khaled A; Al-Robasi, Abdul Baki A; Al-Shamahy, Hassan A; Alyousefi, Naelah A

    2015-01-01

    Urinary tract infection (UTI) is the most common complication following kidney transplantation (KT), which could result in losing the graft. This study aims to identify the prevalence of bacterial UTI among KT recipients in Yemen and to determine the predisposing factors associated with post renal transplantation UTI. A cross sectional study included of 150 patients, who underwent KT was conducted between June 2010 and January 2011. A Morning mid-stream urine specimen was collected for culture and antibiotic susceptibility test from each recipient. Bacterial UTI was found in 50 patients (33.3%). The prevalence among females 40.3% was higher than males 29%. The UTI was higher in the age group between 41-50 years with a percentage of 28% and this result was statistically significant. Predisposing factors as diabetes mellitus, vesicoureteral reflux, neurogenic bladder and polycystic kidney showed significant association. High relative risks were found for polycystic kidney = 13.5 and neurogenic bladder = 13.5. The most prevalent bacteria to cause UTI was Escherichia coli represent 44%, followed by Staphylococcus saprophyticus 34%. Amikacin was the most effective antibiotic against gram-negative isolates while Ciprofloxacin was the most effective antibiotic against Staphylococcus saprophyticus. In conclusion, there is high prevalence of bacterial UTI among KT recipients in Yemen. Diabetes mellitus, vesicoureteral reflux, neurogenic bladder, polycystic kidney and calculi were the main predisposing factors.

  11. Donor/Recipient Enhancement of Memory in Rat Hippocampus

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    Sam A Deadwyler

    2013-12-01

    Full Text Available The critical role of the mammalian hippocampus in the formation, translation and retrieval of memory has been documented over many decades. There are many theories of how the hippocampus operates to encode events and a precise mechanism was recently identified in rats performing a short-term memory task which demonstrated that successful information encoding was promoted via specific patterns of activity generated within ensembles of hippocampal neurons. In the study presented here these ‘representations’ were extracted via a customized nonlinear multi-input multi-output (MIMO mathematical model which allowed prediction of successful performance on specific trials within the testing session. A unique feature of this characterization was demonstrated when successful information encoding patterns were derived online from well-trained donor animals during difficult long-delay trials and delivered via online electrical stimulation to synchronously tested naïve recipient animals never before exposed to the delay feature of the task. By transferring such model-derived trained (donor animal hippocampal firing patterns via stimulation to coupled naïve recipient animals, their task performance was facilitated in a direct donor-recipient manner. This provides the basis for utilizing extracted appropriate neural information from one brain to induce, recover, or enhance memory related processing in the brain of another subject.

  12. Urinary Tract Infection among Renal Transplant Recipients in Yemen.

    Directory of Open Access Journals (Sweden)

    Adnan S Gondos

    Full Text Available Urinary tract infection (UTI is the most common complication following kidney transplantation (KT, which could result in losing the graft. This study aims to identify the prevalence of bacterial UTI among KT recipients in Yemen and to determine the predisposing factors associated with post renal transplantation UTI. A cross sectional study included of 150 patients, who underwent KT was conducted between June 2010 and January 2011. A Morning mid-stream urine specimen was collected for culture and antibiotic susceptibility test from each recipient. Bacterial UTI was found in 50 patients (33.3%. The prevalence among females 40.3% was higher than males 29%. The UTI was higher in the age group between 41-50 years with a percentage of 28% and this result was statistically significant. Predisposing factors as diabetes mellitus, vesicoureteral reflux, neurogenic bladder and polycystic kidney showed significant association. High relative risks were found for polycystic kidney = 13.5 and neurogenic bladder = 13.5. The most prevalent bacteria to cause UTI was Escherichia coli represent 44%, followed by Staphylococcus saprophyticus 34%. Amikacin was the most effective antibiotic against gram-negative isolates while Ciprofloxacin was the most effective antibiotic against Staphylococcus saprophyticus. In conclusion, there is high prevalence of bacterial UTI among KT recipients in Yemen. Diabetes mellitus, vesicoureteral reflux, neurogenic bladder, polycystic kidney and calculi were the main predisposing factors.

  13. Risk and outcome of pyelonephritis among renal transplant recipients.

    Science.gov (United States)

    Graversen, Mette Elneff; Dalgaard, Lars Skov; Jensen-Fangel, Søren; Jespersen, Bente; Østergaard, Lars; Søgaard, Ole Schmeltz

    2016-06-10

    Urinary tract infection is the most common infectious disease requiring hospitalisation following renal transplantation. However, the risk and outcome of post-transplant pyelonephritis remains unclear. This population-based cohort study was conducted from 1 January 1990 to 31 December 2009. Each member of a Danish population-based, nationwide cohort of first-time renal transplant recipients was matched by age and gender with up to 19 population controls. Information on hospital discharge diagnosis, emigration, and mortality was obtained from nationwide administrative databases. Individuals were observed from the date of first renal transplantation and until graft loss, emigration, or death. Risk factors were assessed by Poisson regression. The incidence rate (IR) of first-time hospitalisation for pyelonephritis was 18.5 (95 % confidence interval [CI]: 16.4-20.9) per 1,000 person-years of follow-up (PYFU) among renal transplant recipients (N = 2,656) and 0.26 (CI: 0.21-0.31) per 1,000 PYFU among population controls (N = 49,226) yielding an incidence rate-ratio (IRR) of 72.0 (95 % CI: 57.8-89.7). Among renal transplant recipients, the risk of pyelonephritis decreased during the entire study period and was lowest in 2005-09 (IRR = 0.46, CI: 0.31-0.68). The highest risk of pyelonephritis was observed within the first six months post-transplantation (IR = 69.9 per 1,000 PYFU; CI: 56.4-86.7). Other risk factors for post-transplant pyelonephritis included female gender, high Charlson comorbidity index score, HLA-DR mismatch, cause of renal failure, and calendar period. Interestingly, we found that the combined risk of graft loss and death was 45 %, (CI: 19-77 %) higher in renal transplant recipients following post-transplant pyelonephritis compared to those who had no admission due to pyelonephritis. The risk of first-time hospitalisation for pyelonephritis among renal transplant recipients is high. Further, post-transplant pyelonephritis was

  14. 34 CFR 611.47 - What are a scholarship recipient's reporting responsibilities upon the close of the LEA's...

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What are a scholarship recipient's reporting... EDUCATION TEACHER QUALITY ENHANCEMENT GRANTS PROGRAM Scholarships § 611.47 What are a scholarship recipient...'s academic year, a scholarship recipient whose LEA reports under § 611.46(a) that he or she...

  15. Gastrointestinal complications in liver transplant recipients: MITOS study.

    Science.gov (United States)

    Herrero, J I; Benlloch, S; Bernardos, A; Bilbao, I; Castells, L; Castroagudin, J F; González, L; Irastorza, I; Navasa, M; Otero, A; Pons, J A; Rimola, A; Suárez, F; Casanovas, T; Otero, E; Rodríguez, M; Serrano, T; Otero, S; López, I; Miras, M; Prieto, M

    2007-09-01

    Liver transplant recipients frequently suffer gastrointestinal (GI) complications but their prevalence and their influence on quality of life remain unknown. The objective of this study was to asses the prevalence, impact on quality of life, and management of GI complications in liver transplant recipients. This was an epidemiologic, cross-sectional, multicenter study. Four hundred seventeen liver recipients were recruited in 14 centers. A questionnaire was filled for every patient. The median age of the patients was 55 years. The median time since transplantation was 4.1 +/- 4 years. Whereas 19.2% presented some GI disease before transplantation, 49.4% showed this type of complication after transplantation. Diarrhea was the most prevalent GI complication, and anorexia was the GI disorder that affected patients daily activities the most frequently. GI complications were more frequent among female patients, subjects with pretransplantation hiatal hernia, and those readmitted after transplantation. Of the patients with GI complications, 70.9% received pharmacological treatment (89.7% with gastric protectors). Immunosuppressive therapy was also modified because of GI complications. Immunosuppressive drug dose was reduced in 18.1%, transiently stopped in 3.4%, and definitively stopped in 3.4% of cases. The drug most frequently changed was mycophenolate mofetil: dose reduction, 23.6%; transient withdrawal, 5.7%; and definitive withdrawal, 6.6%. The prevalence of GI complications in the liver transplant population was approximately 50%. GI complications showed a significant impact on the quality of life of the patients. They were related to female gender, to pretransplantation GI pathology, and posttransplantation hospital admission. These complications were frequently managed with pharmacological therapy or with changes in immunosuppressive therapy.

  16. Orangutans modify facial displays depending on recipient attention

    Directory of Open Access Journals (Sweden)

    Bridget M. Waller

    2015-03-01

    Full Text Available Primate facial expressions are widely accepted as underpinned by reflexive emotional processes and not under voluntary control. In contrast, other modes of primate communication, especially gestures, are widely accepted as underpinned by intentional, goal-driven cognitive processes. One reason for this distinction is that production of primate gestures is often sensitive to the attentional state of the recipient, a phenomenon used as one of the key behavioural criteria for identifying intentionality in signal production. The reasoning is that modifying/producing a signal when a potential recipient is looking could demonstrate that the sender intends to communicate with them. Here, we show that the production of a primate facial expression can also be sensitive to the attention of the play partner. Using the orangutan (Pongo pygmaeus Facial Action Coding System (OrangFACS, we demonstrate that facial movements are more intense and more complex when recipient attention is directed towards the sender. Therefore, production of the playface is not an automated response to play (or simply a play behaviour itself and is instead produced flexibly depending on the context. If sensitivity to attentional stance is a good indicator of intentionality, we must also conclude that the orangutan playface is intentionally produced. However, a number of alternative, lower level interpretations for flexible production of signals in response to the attention of another are discussed. As intentionality is a key feature of human language, claims of intentional communication in related primate species are powerful drivers in language evolution debates, and thus caution in identifying intentionality is important.

  17. Recipients of major scientific awards: A descriptive and predictive analysis

    Science.gov (United States)

    Barbee, Andrew Calvin

    Recent trends demonstrate an increase of women in leadership roles, STEM fields, and participating in higher education including graduate and doctoral programs, which is a result of Title IX. This quantitative study considered major scientific awards awarded to females and examines demographic characteristics of awardees from the Nobel, National Academy of Sciences (NAS), and National Science Foundation (NSF). More specifically, the following awards were examined the Nobel Prize in Chemistry, the NAS Public Welfare Medal, and the NSF National Medal of Science within the discipline of Physical Science. Also, this study focused on equality to determine if a fair playing field and equal opportunity for women in academics has improved since Title IX. A limited amount of research has explored female award recipients. Specifically, existing research, has not examined the pinnacle of academic performance in the form of national and international awards. In the present study, I posed research questions relating to demographic characteristics of award recipients from the Nobel, NAS, and NSF between 1975 and 2015. Additionally, I examined if sex and age of the awardees could predict early career award obtainment. Through the frame of Social cognitive theory (Bandura, 1986, 1997, and 2005) I considered how perceptions of gender roles are a product of influence by society and the possible connection to performance. Results indicated a limited number of females have received these scientific awards and the awardees age could predict receiving an award early in their career. Additionally, the study provided insight into the progression of Title IX within the context of athletics and academics. It addressed the incremental and systematic increase in academics for women at high school, college, career, and scientific awards. Perhaps most importantly, it identified an observed pattern for female science award recipients reaching a critical mass and a tipping point.

  18. Outcome of Renal Transplant in Recipients With Vasculitis.

    Science.gov (United States)

    Barbouch, Samia; Hajji, Meriam; Aoudia, Raja; Ounissi, Monther; Zammouri, Asma; Goucha, Rym; Ben Hamida, Fathi; Bacha, Mohammed Mongi; Abderrahim, Ezzedine; Ben Abdallah, Taieb

    2017-02-01

    End-stage renal disease develops in a high percentage of patients with vasculitis, in whom kidney transplant has become a therapeutic option. However, limited data are available on the prognosis and outcomes after kidney transplant in these patients. We aimed to compare the long-term graft survival and graft function in 8 renal transplant recipients with vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis, Goodpasture syndrome, and Henoch-Schonlein purpura) with the other kidney recipients at a single center. We conducted a retrospective study of patients followed for chronic renal failure associated with vasculitis before renal transplant. We excluded patients with no biopsy-proven nephropathy. There was no difference in the occurrence of metabolic and cardiovascular complications in our case group compared with the other graft recipients. Infections were frequent and included cytomegalovirus and urinary tract infection. The rates of bacterial and viral infection were equivalent in our population. The incidence of allograft loss was estimated at 1.8%, less than that seen in our entire transplant population. The presence of vasculitis was not significantly related to renal failure (P = .07). Extrarenal relapse occurred in 1 patient with microscopic polyangiitis. Antineutrophil cytoplasmic antibody levels in patients with granulomatosis with polyangiitis and microscopic polyangiitis did not seem to influence the renal outcome (P = .08). Circulating antineutrophil cytoplasmic antibodies were associated with the development of vascular lesions in the graft but were not significantly correlated with graft survival (P = .07). This study supports the theory that renal transplant is an effective treatment option for patients with end-stage renal disease secondary to vasculitis. These patients fare similarly to, if not better than, other patients.

  19. Anti-inflammatory profile of paricalcitol in kidney transplant recipients.

    Science.gov (United States)

    Donate-Correa, Javier; Henríquez-Palop, Fernando; Martín-Núñez, Ernesto; Hernández-Carballo, Carolina; Ferri, Carla; Pérez-Delgado, Nayra; Muros-de-Fuentes, Mercedes; Mora-Fernández, Carmen; Navarro-González, Juan F

    2017-06-13

    Paricalcitol, a selective vitamin D receptor activator, is used to treat secondary hyperparathyroidism in kidney transplant patients. Experimental and clinical studies in non-transplant kidney disease patients have found this molecule to have anti-inflammatory properties. In this exploratory study, we evaluated the anti-inflammatory profile of paricalcitol in kidney-transplant recipients. Thirty one kidney transplant recipients with secondary hyperparathyroidism completed 3 months of treatment with oral paricalcitol (1μg/day). Serum concentrations and gene expression levels of inflammatory cytokines in peripheral blood mononuclear cells were analysed at the beginning and end of the study. Paricalcitol significantly decreased parathyroid hormone levels with no changes in calcium and phosphorous. It also reduced serum concentrations of interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) by 29% (P<0.05) and 9.5% (P<0.05) compared to baseline, respectively. Furthermore, gene expression levels of IL-6 and TNF-α in peripheral blood mononuclear cells decreased by 14.1% (P<0.001) and 34.1% (P<0.001), respectively. The ratios between pro-inflammatory cytokines (TNF-α and IL-6) and anti-inflammatory cytokines (IL-10), both regarding serum concentrations and gene expression, also experienced a significant reduction. Paricalcitol administration to kidney transplant recipients has been found to have beneficial effects on inflammation, which may be associated with potential clinical benefits. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  20. Roma ethnicity and clinical outcomes in kidney transplant recipients.

    Science.gov (United States)

    Molnar, Miklos Z; Langer, Robert M; Remport, Adam; Czira, Maria E; Rajczy, Katalin; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P; Novak, Marta; Mucsi, Istvan; Rosivall, Laszlo

    2012-06-01

    Racial and ethnic disparities among North American patients with chronic kidney disease have received significant attention. In contrast, little is known about health-related outcomes of patients with end-stage renal disease among the Roma minority, also known as gypsies, compared to Caucasian individuals. We prospectively assessed the association between Roma ethnicity and long-term clinical outcomes in kidney transplant recipients. In a prevalent cohort of renal transplant recipients, followed up over a median of 94 months, we prospectively collected socio-demographic, medical (and transplant related) characteristics and laboratory data at baseline from 60 Roma and 1,003 Caucasian patients (mean age 45 (SD = 11) and 49 (SD = 13) years, 33 and 41% women, 18 and 17% with diabetes mellitus, respectively). Survival analyses examined the associations between Roma ethnicity and all-cause mortality and death-censored graft loss or death with functioning renal allograft. During the follow-up period, 341 patients (32%) died. Two-hundred eighty (26%) patients died with a functioning graft and 201 patients (19%) returned to dialysis. After multivariable adjustments, Roma ethnicity was associated with 77% higher risk of all-cause mortality (Hazard Ratio (HR): 1.77; 95% confidence interval (CI): 1.02, 3.07), two times higher risk of mortality with functioning graft (2.04 [1.17-3.55]) and 77% higher risk of graft loss (1.77 [1.01-3.13]), respectively. Roma ethnicity is independently associated with increased mortality risk and worse graft outcome in kidney transplant recipients. Further studies should identify the factors contributing to worse outcomes among Roma patients.

  1. Intractable urinary tract infection in a renal transplant recipient

    Directory of Open Access Journals (Sweden)

    Satish Renuka

    2009-01-01

    Full Text Available Urinary tract infections (UTI are the most common bacterial infections after renal transplantation and are associated with significant morbidity and mortality. Recurrent or relapsing infections are not uncommon in the early post-transplant period and superadded fungal UTI can occur in these patients, posing a difficult therapeutic problem. Literature on recurrent UTI after transplant as well as the ideal approach to such patients is scanty. We present the case of a renal al-lograft recipient who presented with relapsing bacterial UTI complicated by systemic fungemia; also, a brief review of fungal UTI is attempted.

  2. PERFORMANCE EVALUATION OF ENDOVASCULAR MYOCARDIUM REVASCULARIZATION IN RENAL TRANSPLANT RECIPIENTS

    Directory of Open Access Journals (Sweden)

    I. G. Ryadovoy

    2012-01-01

    Full Text Available Coronary artery stenting was performed at 75 renal transplant recipients. Diffuse multiple and expressed calcified coronary artery disease took place that created many difficulties during the procedures. In result of endovascular treatments positive dynamics of clinical condition in the nearest postoperative period was marked, tolerance to physical exercise was increased and according to this the functional class of angina was reduced. Cardiac and general mortality after treatment in comparison to the data of foreign authors was lower and comparable with demographic death rate of the population for persons of the same sex and age. 

  3. Active Labour Market Programme Participation for Unemployment Insurance Recipients

    DEFF Research Database (Denmark)

    Filges, Trine; Smedslund, Geir; Jørgensen, Anne-Marie Klint

    2016-01-01

    Objective: This review evaluates the effectiveness of Active Labour Market Programme (ALMP) participation on employment status for unemployment insurance recipients. Methods and Analysis: We followed Campbell Collaboration guidelines to conduct a systematic review. Results: A total of 73 studies...... met the inclusion criteria and were critically appraised by the review authors. The available evidence suggests that there is a general effect of participating in ALMP. The findings are mixed, however, depending on the approach used to investigate the effect, with no effect found of being assigned...

  4. What distinguishes passive recipients from active decliners of sales flyers

    DEFF Research Database (Denmark)

    Jensen, Birger Boutrup; Orquin, Jacob Lund; Bech-Larsen, Tino

    2014-01-01

    While sales flyer ad spending in Denmark has increased over the last decade ,the proportion of consumers declining to receive such flyers has been ever-increasing. To address this paradox, attitudinal and behavioural factors distinguishing passive recipients from active decliners of sales flyers...... on the Internet.To reach the decliners, retailers could focus on the possibilities of the Internet, but to stop the trend of escalating numbers of decliners, retailers will have to address the perceived inconvenience and uselessness of sales flyers....

  5. Identification of donor melanoma in a renal transplant recipient.

    Science.gov (United States)

    Wilson, L J; Horvat, R T; Tilzer, L; Meis, A M; Montag, L; Huntrakoon, M

    1992-12-01

    A patient with chronic renal failure received a closely matched cadaveric kidney. Approximately 3 months after transplantation, the patient developed a metastatic malignant melanoma. A large retroperitoneal mass consisting of large pleomorphic polygonal neoplastic cells was found close to the donated kidney. This tumor was diagnosed as a malignant melanoma. DNA analysis of this tumor, the donated kidney, and the recipient indicated that the melanoma originated from the donor. Although this is not the first report of a donated melanoma, it is the first report of definitive DNA analysis of the origin of the malignant cells.

  6. Disseminated mucormycosis with myocardial involvement in a renal transplant recipient.

    Science.gov (United States)

    Nam, Y; Jung, J; Park, S S; Kim, S J; Shin, S J; Choi, J H; Kim, M; Yoon, H E

    2015-12-01

    We report the case of a renal transplant recipient with pulmonary and splenic mucormycosis whose demise was accelerated by a myocardial abscess. Once pulmonary and splenic mucormycosis was diagnosed, liposomal amphotericin B was started and immunosuppressant treatments were discontinued. The pulmonary cavities regressed during treatment, but new myocardial and peri-allograft abscesses developed. The myocardial abscess diffusely infiltrated the left ventricular wall and was associated with akinesia, which led to sudden cardiac arrest. This case demonstrates a rare manifestation of mucormycosis and highlights the fatality and invasiveness of this infection.

  7. Acute appendicitis mistaken as acute rejection in renal transplant recipients.

    Directory of Open Access Journals (Sweden)

    Talwalkar N

    1994-01-01

    Full Text Available Case histories of 2 renal transplant recipients are reported who had presenting features of fever, leukocytosis and pain/tenderness over right iliac fossa and were diagnosed to be due to acute appendicitis rather than more commonly suspected acute rejection episode which has very similar features. Diagnosis of acute appendicitis was suspected on the basis of rectal examination and later confirmed by laparotomy. The purpose of this communication is to emphasize the need for proper diagnosis in patient with such presentation; otherwise wrong treatment may be received.

  8. Type 4 renal tubular acidosis in a kidney transplant recipient

    Directory of Open Access Journals (Sweden)

    Manjunath Kulkarni

    2016-02-01

    Full Text Available We report a case of a 66-year-old diabetic patient who presented with muscle weakness 2 weeks after kidney transplantation. Her immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. She was found to have hyperkalemia and normal anion gap metabolic acidosis. Tacrolimus levels were in therapeutic range. All other drugs such as beta blockers and trimethoprim – sulfamethoxazole were stopped. She did not respond to routine antikalemic measures. Further evaluation revealed type 4 renal tubular acidosis. Serum potassium levels returned to normal after starting sodium bicarbonate and fludrocortisone therapy. Though hyperkalemia is common in kidney transplant recipients, determining exact cause can guide specific treatment.

  9. Type 4 renal tubular acidosis in a kidney transplant recipient.

    Science.gov (United States)

    Kulkarni, Manjunath

    2016-02-01

    We report a case of a 66-year-old diabetic patient who presented with muscle weakness 2 weeks after kidney transplantation. Her immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. She was found to have hyperkalemia and normal anion gap metabolic acidosis. Tacrolimus levels were in therapeutic range. All other drugs such as beta blockers and trimethoprim - sulfamethoxazole were stopped. She did not respond to routine antikalemic measures. Further evaluation revealed type 4 renal tubular acidosis. Serum potassium levels returned to normal after starting sodium bicarbonate and fludrocortisone therapy. Though hyperkalemia is common in kidney transplant recipients, determining exact cause can guide specific treatment.

  10. THE PURE RED BLOOD CELL APLASIA IN RENAL TRANSPLANT RECIPIENT

    Directory of Open Access Journals (Sweden)

    B. T. Dzumabaeva

    2011-01-01

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

  11. Residual amoebic liver abscess in a prospective renal transplant recipient

    Directory of Open Access Journals (Sweden)

    Ashish V Choudhrie

    2012-01-01

    Full Text Available Amoebic liver abscess (ALA is by far the most common extraintestinal manifestation of invasive amoebiasis. The vast majority of these resolve with treatment; however, a small percentage of the treated ALAs are known to persist asymptomatically. Herein, we present a prospective renal allograft recipient with a residual liver abscess who had a successful renal transplant after treatment. In our opinion, persistence of a radiological finding of residual abscess in the absence of clinical disease does not appear to be a contraindication to renal transplantation.

  12. Acute serum amyloid A induces migration, angiogenesis, and inflammation in synovial cells in vitro and in a human rheumatoid arthritis/SCID mouse chimera model.

    LENUS (Irish Health Repository)

    Connolly, Mary

    2010-06-01

    Serum amyloid A (A-SAA), an acute-phase protein with cytokine-like properties, is expressed at sites of inflammation. This study investigated the effects of A-SAA on chemokine-regulated migration and angiogenesis using rheumatoid arthritis (RA) cells and whole-tissue explants in vitro, ex vivo, and in vivo. A-SAA levels were measured by real-time PCR and ELISA. IL-8 and MCP-1 expression was examined in RA synovial fibroblasts, human microvascular endothelial cells, and RA synovial explants by ELISA. Neutrophil transendothelial cell migration, cell adhesion, invasion, and migration were examined using transwell leukocyte\\/monocyte migration assays, invasion assays, and adhesion assays with or without anti-MCP-1\\/anti-IL-8. NF-kappaB was examined using a specific inhibitor and Western blotting. An RA synovial\\/SCID mouse chimera model was used to examine the effects of A-SAA on cell migration, proliferation, and angiogenesis in vivo. High expression of A-SAA was demonstrated in RA patients (p < 0.05). A-SAA induced chemokine expression in a time- and dose-dependent manner (p < 0.05). Blockade with anti-scavenger receptor class B member 1 and lipoxin A4 (A-SAA receptors) significantly reduced chemokine expression in RA synovial tissue explants (p < 0.05). A-SAA induced cell invasion, neutrophil-transendothelial cell migration, monocyte migration, and adhesion (all p < 0.05), effects that were blocked by anti-IL-8 or anti-MCP-1. A-SAA-induced chemokine expression was mediated through NF-kappaB in RA explants (p < 0.05). Finally, in the RA synovial\\/SCID mouse chimera model, we demonstrated for the first time in vivo that A-SAA directly induces monocyte migration from the murine circulation into RA synovial grafts, synovial cell proliferation, and angiogenesis (p < 0.05). A-SAA promotes cell migrational mechanisms and angiogenesis critical to RA pathogenesis.

  13. Epidemiological profile of nonmelanoma skin cancer in renal transplant recipients: experience of a referral center

    OpenAIRE

    Ferreira, Flávia Regina; Ogawa, Marilia Marufuji; Nascimento, Luiz Fernando Costa; Tomimori, Jane

    2014-01-01

    BACKGROUND: Nonmelanoma skin cancer is the most common form of cancer in humans and also the malignant disease that is increasingly common among kidney transplant recipients. OBJECTIVE: To determine the epidemiological characteristics of renal transplant recipients with nonmelanoma skin cancer seen at a referral transplantation center. METHODS: Cross-sectional descriptive study with renal transplant recipients presenting nonmelanoma skin cancer, treated at a transplantation referral cente...

  14. Interrelation between donor and recipient heart rates during exercise after heterotopic cardiac transplantation.

    OpenAIRE

    Yusuf, S; Mitchell, A; Yacoub, M H

    1985-01-01

    The interrelation between the rates of the innervated recipient heart and the denervated donor heart at rest, on standing, and during the different phases of maximal exercise was studied in nine patients 1-6 months after heterotopic cardiac transplantation. The resting heart rate was significantly higher in the donor heart compared with the recipient heart. Eight of the nine recipient hearts and none of the donor hearts showed an increase in heart rate on standing up. All patients were exerci...

  15. Electrolytes Disturbance and Cyclosporine Blood Levels among Kidney Transplant Recipients

    Science.gov (United States)

    Einollahi, B.; Nemati, E.; Rostami, Z.; Teimoori, M.; Ghadian, A. R.

    2012-01-01

    Background: Kidney transplantation is associated with various biochemical abnormalities such as changes in serum blood level of sodium (Na), potassium (K), calcium (Ca), and phosphorous (P). Although cyclosporine (CsA) is used commonly, the prevalence of its side effects, including electrolytes disturbance, is not well understood. Objective: To find the prevalence of electrolytes disturbance and its relation to CsA blood levels. Methods: In a retrospective study, 3308 kidney transplant recipients transplanted between 2008 and 2011 were studied. We evaluated the relation between serum Ca, P, Na, K and CsA trough (C0) and 2-hour post-dose (C2) levels. Results: The mean±SD age of recipients was 37±15 years; 63% of patients were male. Overall, C2 levels had correlation with Ca blood level (p=0.018; OR: 1.13, 95%CI: 1.02–1.25), C0 levels had also correlation with blood levels of P and Cr (p<0.001; OR: 1.83, 95% CI: 1.59–2.11). Conclusion: Electrolyte disturbances are prevalent. Higher serum levels of CsA can worsen the allograft function by disturbing the serum P and Ca levels. PMID:25013642

  16. Forgotten ureteric stents in renal transplant recipients: three case reports.

    Science.gov (United States)

    Bardapure, Mallikarjun; Sharma, Ajay; Hammad, Abdul

    2014-01-01

    Ureteric stents are widely used in renal transplantation to minimize the early urological complications. Ureteric stents are removed between two and 12 weeks following trans-plantation, once the vesico-ureteric anastomosis is healed. Ureteric stents are associated with considerable morbidity due to complications such as infection, hematuria, encrustations and migration. Despite the patient having a regular follow-up in the renal transplant clinic, ureteric stents may be overlooked and forgotten. The retained or forgotten ureteric stents may adversely affect renal allograft function and could be potentially life-threatening in immunocompromised transplant recipients with a single transplant kidney. Retrieving these retained ureteric stents could be challenging and may necessitate multimodal urological treatments. We report three cases of forgotten stents in renal transplant recipients for more than four years. These cases emphasize the importance of patient education about the indwelling ureteric stent and possibly providing with a stent card to the patient. Maintaining a stent register, with a possible computer tracking system, is highly recommended to prevent such complications.

  17. Usefulness and limitations of transthoracic echocardiography in heart transplantation recipients

    Directory of Open Access Journals (Sweden)

    Galderisi Maurizio

    2008-01-01

    Full Text Available Abstract Transthoracic echocardiography is a primary non-invasive modality for investigation of heart transplant recipients. It is a versatile tool which provides comprehensive information about cardiac structure and function. Echocardiographic examinations can be easily performed at the bedside and serially repeated without any patient's discomfort. This review highlights the usefulness of Doppler echocardiography in the assessment of left ventricular and right ventricular systolic and diastolic function, of left ventricular mass, valvular heart disease, pulmonary arterial hypertension and pericardial effusion in heart transplant recipients. The main experiences performed by either standard Doppler echocardiography and new high-tech ultrasound technologies are summarised, pointing out advantages and limitations of the described techniques in diagnosing acute allograft rejection and cardiac graft vasculopathy. Despite the sustained efforts of echocardiographic technique in predicting the biopsy state, endocardial myocardial biopsies are still regarded as the gold standard for detection of acute allograft rejection. Conversely, stress echocardiography is able to identify accurately cardiac graft vasculopathy and has a recognised prognostic in this clinical setting. A normal stress-echo justifies postponement of invasive studies. Another use of transthoracic echocardiography is the monitorisation and the visualisation of the catheter during the performance of endomyocardial biopsy. Bedside stress echocardiography is even useful to select appropriately heart donors with brain death. The ultrasound monitoring is simple and effective for monitoring a safe performance of biopsy procedures.

  18. Considerations in the medical management of pregnancy in transplant recipients.

    Science.gov (United States)

    Josephson, Michelle A; McKay, Dianne B

    2007-04-01

    Pregnancy, although rare in the patient with end-stage renal disease, is not uncommon in the transplant recipient. Physicians taking care of transplant recipients must be able to inform patients about the potential risks of pregnancy in this setting. The patient and her partner must know that the risks associated with pregnancy increase with worsening kidney function and hypertension. Current consensus opinion is that pregnancy can be relatively safely undertaken by 1 year after transplant if the patient has had no rejections during the year, allograft function is adequate, there are no infections that could affect the fetus, the patient is not taking teratogenic medications, and immunosuppressive medication dosing is stable. Consideration must be given to immunosuppression during pregnancy both with respect to the specific agents as well as the level of dosing. None of the medications are FDA category A; all are B or higher. Part of planning for pregnancy should include an evaluation of immunosuppression medication and a plan to modify the regimen prior to conception if its use may be risky for the developing fetus. Rejection can occur during a kidney transplant, so maintaining adequate immunosuppression is important. Other issues that need to be managed when caring for a pregnant transplant patient include: potential for infection (urinary tract infections are very common), hypertension, and anemia. The type of delivery, posttransplant contraception, and breast-feeding also need to be addressed.

  19. Iatrogenic Pulmonary Nodule in a Heart Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Atul C. Mehta

    2014-01-01

    Full Text Available A 58-year-old female with a history of non-Hodgkin lymphoma and end-stage nonischemic cardiomyopathy from Adriamycin toxicity underwent orthotic heart transplantation during June 2013. She developed shortness of breath in September 2013 and was suspected to have invasive pulmonary aspergillosis. A flexible bronchoscopy (FB with a transbronchial biopsy (TBBx was performed. She was found to have a focal lung nodule in the same location at the site of the TBBx on day 13 after the FB. Spontaneous resolution of the nodule was confirmed on the computed tomography (CT scan of chest performed at 3 months. We believe that this nodule was as a consequence of the TBBx. Formation of a peripheral pulmonary nodule (PPN following a TBBx is occasionally encountered among the recipients of the lung transplantation. To our knowledge, this is the first case of TBBx producing a pulmonary nodule in a heart transplant recipient. Physicians caring for the patients with heart transplantation should be cognizant of the iatrogenic nature of such nodule to avoid unnecessary diagnostic work-up.

  20. Reproductive health in Irish female renal transplant recipients.

    LENUS (Irish Health Repository)

    Kennedy, C

    2012-02-01

    OBJECTIVE: To report the pregnancy outcomes in Irish female renal transplant recipients on modern maintenance immunosuppression. METHODS: The Republic of Ireland transplant database was accessed to identify the patient cohort in question. All female renal transplant recipients whose transplantation was in Ireland before or during their reproductive years were included. A questionnaire was sent to the identified women. A chart review was performed for those women who reported a pregnancy following renal transplantation. RESULTS: Two hundred and ten women met the inclusion criteria. There was a response rate of 70% (n = 148). Eighteen women reported 29 pregnancies. The live birth rate was 76%. The mean gestation of the live births was 36.2 weeks with a mean birth weight of 3.0 kg. There were six cases of pre-eclampsia. Twin pregnancies and those entering pregnancy with a creatinine greater than 135 micromol\\/l had particularly complicated clinical courses. Four women had not conceived post transplant despite actively trying for over 1 year. Two women utilised assisted fertility methods (in vitro fertilisation), one of whom became pregnant. CONCLUSIONS: A significant proportion of women who attempt to conceive following renal transplantation are successful, without the use of assisted fertility. Pregnancy in this setting warrants meticulous multidisciplinary care.

  1. Severe Necrotizing Adenovirus Tubulointerstitial Nephritis in a Kidney Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Ravi Parasuraman

    2013-01-01

    Full Text Available Adenoviruses (AdV are emerging pathogens with a prevalence of 11% viruria and 6.5% viremia in kidney transplant recipients. Although AdV infection is common, interstitial nephritis (ADVIN is rare with only 13 biopsy proven cases reported in the literature. We report a case of severe ADVIN with characteristic histological features that includes severe necrotizing granulomatous lesion with widespread tubular basement membrane rupture and hyperchromatic smudgy intranuclear inclusions in the tubular epithelial cells. The patient was asymptomatic at presentation, and the high AdV viral load (quantitative PCR>2,000,000 copies/mL in the urine and 646,642 copies/mL in the serum confirmed the diagnosis. The patient showed excellent response to a combination of immunosuppression reduction, intravenous cidofovir, and immunoglobulin therapy resulting in complete resolution of infection and recovery of allograft function. Awareness of characteristic biopsy findings may help to clinch the diagnosis early which is essential since the disseminated infection is associated with high mortality of 18% in kidney transplant recipients. Cidofovir is considered the agent of choice for AdV infection in immunocompromised despite lack of randomized trials, and the addition of intravenous immunoglobulin may aid in resolution of infection while help prevention of rejection.

  2. Endothelial Dysfunction and Vitamin D Levels in Kidney Allograft Recipients

    Directory of Open Access Journals (Sweden)

    Mehmet ALTAN

    2012-01-01

    Full Text Available There have been several studies demonstrating a relationship between vitamin D and cardiovascular disease. Vitamin D Deficiency/Insufficiency (D/I is a common problem in chronic renal disease and also renal transplant recipients, however, there is a variation between the summer and winter periods.We investigated whether there is a relationship between vitamin D D/I and endothelial dysfunction in renal transplant recipients (RTR. We also evaluated vitamin D levels in summer and winter. Flowmediated dilatation (FMD, soluble endothelial protein receptor C (sEPRC and soluble thrombomodulin (sTM were chosen for markers of endothelial function.Firty-five patients were recruited to the study. Winter measurements were performed on March, summer measurements were performed in September.In the winter, methe an vitamin D level was 18.8±7.5, compared with 34.3±13.0 ng/ml in the summer period (p<0.0001. There were 38 (84% and 20 (44% patients in the winter and summer periods with vitamin D D/I, respectively. We did not find any significant association between vitamin D D/I and FMD, sTM or sEPCR in either period.While vitamin D D/I is a common finding during winter in RTR, it recovers in the summer. Moreover, vitamin D D/I seems not to be associated with endothelial dysfunction.

  3. Oral manifestations of allograft recipients before and after renal transplantation

    Directory of Open Access Journals (Sweden)

    Gita Rezvani

    2014-01-01

    Full Text Available Renal transplantation is considered the best treatment option for patients with end-stage renal disease. In this study, the prevalence of oral lesions was studied in a cohort of renal transplant recipients before and after transplantation. Fifty-nine kidney transplant recipients were examined one week before and four months after transplantation. The information gathered included age, sex, smoking history, duration on dialysis, drugs and their doses. There were 41 males (69.5% and 18 females (30.5% with a mean age of 37 years. Before surgery, two patients had non-specific lesions and two other patients had leukoedema. Following transplantation, 24 patients (40.7% did not have any specific lesion. In six patients, we observed non-specific erythematous lesions (10.2%. Other recorded observations are as follows: Gingival hyperplasia in five patients (8.5%, oral candidiasis of the erythematous type in five patients (8.5%, hairy leukoplakia in four patients (6.8% and leukoedema in seven patients (11.9%. In our study patients, the prevalence of oral lesions increased after transplantation, although it was lower than that reported in other studies. This could be due to the differences in sample size, differences between Iranian race and other races and different pharmaceutical formulation of the drug produced in Iran.

  4. Asymptomatic bacteriuria and urinary tract infections among renal allograft recipients.

    Science.gov (United States)

    Singh, Ramandeep; Geerlings, Suzanne E; Bemelman, Frederike J

    2015-02-01

    Bacteriuria is common among renal allograft recipients. It can be categorized into asymptomatic bacteriuria (ASB) and urinary tract infection (UTI). However, in medical literature, the classifications of bacteriuria are often not clear or ASB is also classified as a UTI. This contributes to difficulties in interpretation of the incidence and risk factors of these two entities. In this review, we describe the epidemiology, risk factors, management and the impact on renal allograft function of these two entities separately according to the recent literature. Risk factors for ASB are not completely comparable to the risk factors of UTIs. Persistent ASB has been associated with development of acute rejection and allograft pyelonephritis. The available data suggest that treatment of ASB is not very effective. Prophylaxis with trimethoprim-sulfamethoxazole does not prevent UTIs such as allograft pyelonephritis. Blood stream infections and emphysematous allograft pyelonephritis are associated with renal allograft loss. ASB is the most common manifestation of bacteriuria after renal transplantation. More effective interventions are needed to prevent bacteriuria. Renal allograft recipients with persistent ASB should be closely monitored since they could be at risk for developing not only UTIs, such as allograft pyelonephritis, but also acute rejection.

  5. Donor-Recipient Size Mismatch in Paediatric Renal Transplantation

    Directory of Open Access Journals (Sweden)

    J. Donati-Bourne

    2014-01-01

    Full Text Available Introduction. End stage renal failure in children is a rare but devastating condition, and kidney transplantation remains the only permanent treatment option. The aim of this review was to elucidate the broad surgical issues surrounding the mismatch in size of adult kidney donors to their paediatric recipients. Methods. A comprehensive literature search was undertaken on PubMed, MEDLINE, and Google Scholar for all relevant scientific articles published to date in English language. Manual search of the bibliographies was also performed to supplement the original search. Results. Size-matching kidneys for transplantation into children is not feasible due to limited organ availability from paediatric donors, resulting in prolonged waiting list times. Transplanting a comparatively large adult kidney into a child may lead to potential challenges related to the surgical incision and approach, vessel anastomoses, wound closure, postoperative cardiovascular stability, and age-correlated maturation of the graft. Conclusion. The transplantation of an adult kidney into a size mismatched paediatric recipient significantly reduces waiting times for surgery; however, it presents further challenges in terms of both the surgical procedure and the post-operative management of the patient’s physiological parameters.

  6. Risk factors for invasive fungal infections in liver transplant recipients

    Institute of Scientific and Technical Information of China (English)

    LIAO Yong; Thomas Hartmann; AO Jun-hong; YANG Rong-ya

    2012-01-01

    To the editor:Invasive fungal infections (IFIs) are significant complications in liver transplant recipients, which are associated with high morbidity/mortality and higher healthcare costs.The incidence of IFIs is mainly influenced by the patients'clinical condition,the level of immune suppression,surgical factors,and the technical complexity of the surgery.We read with great interest the research article by Shi et al.1 Although they have reached a high curative ratio with their "experiential" therapy based on their previous clinical experience,they did not provide us with detailed,definite criteria for identifying suspected patients and allowing for their early "experiential" treatment.Updated,standardized guidelines from the Invasive Fungal Infections Cooperative Group in Europe and the Mycoses Study Group in the United States provide definitions of patients,who are eligible for enrollment in clinical trials.The "Probable" and "Possible" IFIs were defined based on specific host factors,clinical manifestations of fungal infection and mycological findings.The current diagnostic methods for fungal infections lack sensitivity and specificity,so understanding the risk factors associated with fungal infections in liver transplant recipients may improve identification of high-risk patients and guide appropriate initiation of early antifungal treatment.

  7. Abdominal complications in pediatric bone marrow transplant recipients.

    Science.gov (United States)

    Day, D L; Carpenter, B L

    1993-09-01

    Abdominal problems and catastrophes often complicate the clinical course after bone marrow transplantation (BMT) in children. These complications can be grouped into categories of infection, chemotherapy and radiation toxicity, graft-versus-host disease (GVHD), recurrent or de novo malignancy, and miscellaneous complications and can involve the hepatobiliary system, pancreas, spleen, gastrointestinal tract, and urinary tract. Infection is common after BMT: the causative organism depends on the changing immunologic state of the recipient and even on environmental factors such as recent construction, humidity, and antibiotic use. Chemotherapy and radiation therapy can cause hepatic veno-occlusive disease, pancreatitis, nephritis, and hemorrhagic cystitis. GVHD is a process in which donor lymphoid cells produce damage to recipient target organs, especially skin, liver, and intestinal mucosa. Recurrent or de novo disease or malignancies, particularly B-cell lymphomas, may develop in chronically immunocompromised children. Other problems include stone disease, splenic and renal infarction, and complications of hyperalimentation therapy. Abdominal imaging, including plain radiography, contrast material-enhanced studies of the bowel, real-time and duplex sonography, and computed tomography, is essential in diagnosing these problems and evaluating response to therapy.

  8. Management of Hepatitis B Virus Infection in Liver Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Joy Varghese

    2013-12-01

    Full Text Available Hepatitis B virus (HBV-related liver disease is a common indication for liver transplantation (LT in Asian countries.1 When left untreated, the overall five-year survival rate in HBV-related cirrhosis is 71%, which in cases of decompensated cirrhosis decreases to 14%.2 In the 1980s, hepatitis B-related acute liver failure and chronic liver disease (CLD were considered contraindications for LT because of almost universal graft reinfection and high rates of graft and recipient failure (>50%.3-4 These patients had severe and rapidly progressive liver disease with a two-year graft and patient survival of 50% compared to 80% in those transplanted for non-HBV-related CLD.5 As a result, there were fewer LT for HBV liver disease for several years.6 However, with the introduction of nucleoside and nucleotide analogues and the use of intra and post- operative hepatitis B immunoglobulin (HBIG, there was renewed interest in the application of LT in these patients. There was a significant decrease in post-operative HBV recurrence rates.7-9 The current overall survival of patients transplanted for HBV-related cirrhosis has improved to 85% at one year, and 75% at five years.7,10-12 The present review highlights issues pertaining to HBV reinfection and de novo infection in LT recipients with recommendations for its management.

  9. Clostridium difficile infection in solid organ transplant recipients.

    Science.gov (United States)

    Nanayakkara, Deepa; Nanda, Neha

    2017-08-01

    Clostridium difficile infection (CDI) is a major healthcare-associated infection that causes significant morbidity and an economic impact in the United States. In this review, we provide an overview of Clostridium difficile infection in solid organ transplant recipients with an emphasis on recent literature. C. difficile in solid organ transplant population has unique risk factors. Fecal microbiota transplantation has shown favorable results in treatment of recurrent C. difficile in this population. Preliminary data from animal studies suggests excellent efficacy with immunization against C. difficile toxins. Over the last decade, number of individuals receiving solid organ transplants has increased exponentially making peri-transplant complications a common occurrence.C. difficile is a frequent cause of morbidity in solid organ transplant recipients. Early and accurate diagnosis of C. difficile requires a stepwise approach. Differentiating between asymptomatic carriage and infection is a diagnostic challenge. Microbial diversity is inversely proportional to risk of C. difficile infection. Antimicrobial stewardship programs help to retain microbial diversity in individuals susceptible to CDI. Recurrent or relapsing C. difficile infection require fecal microbiota transplantation for definitive cure.

  10. The Critically Ill Kidney Transplant Recipient: A Narrative Review.

    Science.gov (United States)

    Canet, Emmanuel; Zafrani, Lara; Azoulay, Élie

    2016-06-01

    Kidney transplantation is the most common solid organ transplantation performed worldwide. Up to 6% of kidney transplant recipients experience a life-threatening complication that requires ICU admission, chiefly in the late posttransplantation period (≥ 6 months). Acute respiratory failure and septic shock are the main reasons for ICU admission. Cardiac pulmonary edema, bacterial pneumonia, acute graft pyelonephritis, and bloodstream infections account for the vast majority of diagnoses in the ICU. Pneumocystis jirovecii pneumonia is the most common opportunistic infection, and one-half of the patients so infected require mechanical ventilation. The incidence of cytomegalovirus visceral infections in the era of preemptive therapy has dramatically decreased. Drug-related neutropenia, sirolimus-related pneumonitis, and posterior reversible encephalopathy syndrome are among the most common immunosuppression-associated toxic effects. Importantly, the impact of critical illness on graft function is worrisome. Throughout the ICU stay, acute kidney injury is common, and about 40% of the recipients require renal replacement therapy. One-half of the patients are discharged alive and free from dialysis. Hospital mortality can reach 30% and correlates with acute illness severity and reason for ICU admission. Transplant characteristics are not predictors of short-term survival. Graft survival depends on pre-ICU graft function, disease severity, and renal toxicity of ICU investigations and treatments.

  11. Forgotten ureteric stents in renal transplant recipients: Three case reports

    Directory of Open Access Journals (Sweden)

    Mallikarjun Bardapure

    2014-01-01

    Full Text Available Ureteric stents are widely used in renal transplantation to minimize the early urological complications. Ureteric stents are removed between two and 12 weeks following trans-plantation, once the vesico-ureteric anastomosis is healed. Ureteric stents are associated with considerable morbidity due to complications such as infection, hematuria, encrustations and migration. Despite the patient having a regular follow-up in the renal transplant clinic, ureteric stents may be overlooked and forgotten. The retained or forgotten ureteric stents may adversely affect renal allograft function and could be potentially life-threatening in immunocompromised transplant recipients with a single transplant kidney. Retrieving these retained ureteric stents could be challenging and may necessitate multimodal urological treatments. We report three cases of forgotten stents in renal transplant recipients for more than four years. These cases emphasize the importance of patient education about the indwelling ureteric stent and possibly providing with a stent card to the patient. Maintaining a stent register, with a possible computer tracking system, is highly recommended to prevent such complications.

  12. Clinical Outcomes and Quality of Life in Recipients of Livers Donated after Cardiac Death

    Directory of Open Access Journals (Sweden)

    Neehar D. Parikh

    2015-01-01

    Full Text Available Donation after cardiac death (DCD has expanded in the last decade in the US; however, DCD liver utilization has flattened in recent years due to poor outcomes. We examined clinical and quality of life (QOL outcomes of DCD recipients by conducting a retrospective and cross-sectional review of patients from 2003 to 2010. We compared clinical outcomes of DCD recipients (n=60 to those of donation after brain death (DBD liver recipients (n=669 during the same time period. DCD recipients had significantly lower rates of 5-year graft survival (P<0.001 and a trend toward lower rates of 5-year patient survival (P=0.064 when compared to the DBD cohort. In order to examine QOL outcomes in our cohorts, we administered the Short Form Liver Disease Quality of Life questionnaire to 30 DCD and 60 DBD recipients. The DCD recipients reported lower generic and liver-specific QOL. We further stratified the DCD cohort by the presence of ischemic cholangiopathy (IC. Patients with IC reported lower QOL when compared to DBD recipients and those DCD recipients without IC (P<0.05. While the results are consistent with clinical experience, this is the first report of QOL in DCD recipients using standardized measures. These data can be used to guide future comparative effectiveness studies.

  13. Nontuberculous mycobacterial infection in hematopoietic stem cell and solid organ transplant recipients.

    Science.gov (United States)

    Doucette, Karen; Fishman, Jay A

    2004-05-15

    Nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms. In immunocompetent hosts, they are a rare cause of disease. In immunocompromised hosts, disease due to NTM is well documented. Reports of NTM disease have increased in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. This increase may reflect increased numbers of transplants, intensification of immune suppressive regimens, prolonged survival of transplant recipients, and/or improved diagnostic techniques. The difficulty of diagnosis and the impact associated with infections due to NTM in HSCT and SOT recipients necessitates that, to ensure prompt diagnosis and early initiation of therapy, a high level of suspicion for NTM disease be maintained. The most common manifestations of NTM infection in SOT recipients include cutaneous and pleuropulmonary disease, and, in HSCT recipients, catheter-related infection. Skin and pulmonary lesions should be biopsied for histologic examination, special staining, and microbiologic cultures, including cultures for bacteria, Nocardia species, fungi, and mycobacteria. Mycobacterial infections associated with catheters may be documented by tunnel or blood (isolator) cultures. Susceptibility testing of mycobacterial isolates is an essential component of optimal care. The frequent isolation of NTM other than Mycobacterium avium complex (MAC) from transplant recipients limits the extrapolation of therapeutic data from human immunodeficiency virus-infected individuals to the population of transplant recipients. Issues involved in the management of NTM disease in transplant recipients are characterized by a case of disseminated infection due to Mycobacterium avium complex in a lung transplant recipient, with a review of the relevant literature.

  14. 42 CFR 436.1003 - Recipients overcoming certain conditions of eligibility.

    Science.gov (United States)

    2010-10-01

    ... THE VIRGIN ISLANDS Federal Financial Participation (FFP) Ffp for Expenditures for Determining Eligibility and Providing Services § 436.1003 Recipients overcoming certain conditions of eligibility. FFP...

  15. Rituximab induction therapy in highly sensitized kidney transplant recipients

    Institute of Scientific and Technical Information of China (English)

    YIN Hang; WAN Hao; HU Xiao-peng; LI Xiao-bei; WANG Wei; LIU Hang; REN Liang; ZHANG Xiao-dong

    2011-01-01

    Background The number of highly sensitized patients is rising, and sensitization can lead to renal transplant failure.The present study aimed to investigate the safety and efficacy of renal transplantation following induction therapy with rituximab in highly sensitized kidney transplant recipients.Methods Seven highly sensitized kidney transplant recipients who underwent rituximab therapy from December 2008 to December 2009 were retrospectively analyzed. There were 3 men and 4 women, with a mean age of 38.5 years (range, 21-47 years). The duration of hemodialysis was 3-12 months, with a mean duration of 11 months. For 4 patients,this was the second transplant; the previous graft survival time was 2-11 years, with a mean survival time of 5.8 years. All the female recipients had history of multiple pregnancies, and all patients had previously received blood transfusions. All donors were men, with a mean age of 32.5 years (range, 25-37 years). In 2 of the 7 patients, both class I and class II of panel reactive antibody were high; the remaining 5 patients showed either high in class I or in class II of panel reactive antibody. The mean panel reactive antibody value was 31% for class I and 51% for class II respectively. The donors and the recipients had the same blood type, with low lymphocyte cytotoxicity ranging from 2% to 5%. The human leukocyte antigen (HLA) mismatch numbers were from 2 to 4. All patients received tacrolimus (0.1 mg·kg-1·d-1) and mycophenolate mofetil (750 mg twice per day) orally 3 days prior to surgery. All patients received a single dose of 600 mg rituximab (375 mg/m2) infusion on the day before surgery and polyclonal antibody (antithymocyte globulin) on the day of surgery.Postoperative creatinine, creatinine clearance rate, and occurrence of rejection by pathological biopsy confirmation were monitored.Results No patient had delayed graft function after surgery. Two patients had acute rejection, one on day 7 and the other on day 13 post

  16. Characterization of human CD8+TCR- facilitating cells in vitro and in vivo in a NOD/SCID/IL2rγnull mouse model

    Science.gov (United States)

    Huang, Y.; Elliott, M. J.; Yolcu, E. S.; Miller, T. O.; Ratajczak, J.; Bozulic, L. D.; Wen, Y.; Xu, H.; Ratajczak, M. Z.; Ildstad, S. T.

    2017-01-01

    CD8+/TCR- facilitating cells (FC) in mouse BM significantly enhance engraftment of hematopoietic stem/progenitor cells (HSPC). Human FC phenotype and mechanism of action remain to be defined. We report for the first time the phenotypic characterization of human FC and correlation of phenotype with function. Approximately half of human FC are CD56neg; the remainder CD56bright. The CD56neg FC subpopulation significantly promotes homing of HSPC to BM in NSG mouse recipients and enhances hematopoietic colony formation in vitro. The CD56neg FC subpopulation promotes rapid reconstitution of donor HSPC without GVHD. However, recipients of CD56bright FC plus HSPC exhibit low donor chimerism early after transplantation but the level of chimerism significantly increases with time. Recipients of HSPC plus CD56neg or CD56bright FC showed durable donor chimerism at significantly higher levels in BM. The majority of both FC subpopulations express CXCR4. Co-culture of CD56bright FC with HSPC up-regulates cathelicidin and beta defensin-2, factors that prime responsiveness of HSPC to SDF-1. Both FC subpopulations significantly up-regulated mRNA expression of the HSPC growth factors and Flt3-Ligand. These results indicate that human FC exert a direct effect on HSPC to enhance engraftment. Human FC offer a potential regulatory cell-based therapy for enhancement of engraftment and prevention of GVHD. PMID:26550777

  17. Histopathological characteristics of human non-tumor thyroid tissues in a long-term model of adenomatous goiter xenografts in the NOD/Shi-scid, IL-2Rγ(null) mouse.

    Science.gov (United States)

    Fujii, Etsuko; Kato, Atsuhiko; Chen, Yu Jau; Matsubara, Koichi; Ohnishi, Yasuyuki; Suzuki, Masami

    2014-07-01

    There is a growing need for modeling the human thyroid to link data obtained from animals to humans because of its sensitivity to radiation exposure and endocrine disruption chemicals. In a scid mouse model produced by transplanting human thyroid tissues, leakiness and thymic lymphoma that occurs spontaneously in the scid mouse can complicate the interpretation of experimental results. Considering that the NOD.Cg-Prkdc(scid)Il2rg(tm1Sug)/Jic mouse (NOD/Shi-scid, IL-2Rγ(null) or NOG mouse) may be a better host because this strain has low incidence of leakiness and thymic lymphoma, we have evaluated the potential of a model that allows long-term observation of non-tumor human thyroid tissues in this mouse. We transplanted tissues of human adenomatous goiter into NOG mice and examined the tissues histopathologically. The morphology of human adenomatous goiter tissues was maintained from 24 to 44 weeks after transplantation in NOG mice with no noted differences between donor-matched tissues or the weeks after transplantation. The tissues expressed thyroglobulin protein and mRNA as well as thyroperoxidase. Endothelial cells originating from human were found in the transplanted tissues and were thought to be a characteristic of this model. The intactness of the tissues before transplantation was found to affect the rate of tissue engraftment. From the present results we have concluded that transplanted thyroid tissues in NOG mice maintain the histopathological characteristics of their origin for long terms. Therefore this model was thought feasible for toxicity evaluation. Copyright © 2014 Elsevier GmbH. All rights reserved.

  18. Carrier frequency of a nonsense mutation in the adenosine deaminase (ADA) gene implies a high incidence of ADA-deficient severe combined immunodeficiency (SCID) in Somalia and a single, common haplotype indicates common ancestry

    DEFF Research Database (Denmark)

    Sanchez Sanchez, Juan Jose; Monaghan, Gemma; Børsting, Claus

    2007-01-01

    , with severe ADA-SCID, were registered in the Greater London area. Patients and their parents were investigated for the nonsense mutation Q3X (ADA c7C>T), two missense mutations K80R (ADA c239A>G) and R142Q (ADA c425G>A), and a TAAA repeat located at the 3' end of an Alu element (AluVpA) positioned 1.1 kb...

  19. Selective Regulation of Human Immunodeficiency Virus-Infected CD4+ Lymphocytes by a Synthetic Immunomodulator Leads to Potent Virus Suppression In Vitro and in hu-PBL-SCID Mice

    OpenAIRE

    Bahr, George M.; Darcissac, Edith C. A.; Castéran, Nathalie; Amiel, Corinne; Cocude, Cécile; Truong, Marie-José; Dewulf, Joëlle; Capron, André; Mouton, Yves

    2001-01-01

    We have previously observed that the synthetic immunomodulator Murabutide inhibits human immunodeficiency virus type 1 (HIV-1) replication at multiple levels in macrophages and dendritic cells. The present study was designed to profile the activity of Murabutide on CD8-depleted phytohemagglutinin-activated lymphocytes from HIV-1-infected subjects and on the outcome of HIV-1 infection in severe combined immunodeficiency mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mic...

  20. New Onset Diabetes Mellitus in Living Donor versus Deceased Donor Liver Transplant Recipients: Analysis of the UNOS/OPTN Database

    Directory of Open Access Journals (Sweden)

    Anitha D. Yadav

    2013-01-01

    Full Text Available New onset diabetes after transplantation (NODAT occurs less frequently in living donor liver transplant (LDLT recipients than in deceased donor liver transplant (DDLT recipients. The aim of this study was to compare the incidence and predictive factors for NODAT in LDLT versus DDLT recipients. The Organ Procurement and Transplant Network/United Network for Organ Sharing database was reviewed from 2004 to 2010, and 902 LDLT and 19,582 DDLT nondiabetic recipients were included. The overall incidence of NODAT was 12.2% at 1 year after liver transplantation. At 1, 3, and 5 years after transplant, the incidence of NODAT in LDLT recipients was 7.4, 2.1, and 2.6%, respectively, compared to 12.5, 3.4, and 1.9%, respectively, in DDLT recipients. LDLT recipients have a lower risk of NODAT compared to DDLT recipients (hazard ratio = 0.63 (0.52–0.75, P<0.001. Predictors for NODAT in LDLT recipients were hepatitis C (HCV and treated acute cellular rejection (ACR. Risk factors in DDLT recipients were recipient male gender, recipient age, body mass index, donor age, donor diabetes, HCV, and treated ACR. LDLT recipients have a lower incidence and fewer risk factors for NODAT compared to DDLT recipients. Early identification of risk factors will assist timely clinical interventions to prevent NODAT complications.

  1. Generation and Disease Model Relevance of a Manganese Enhanced Magnetic Resonance Imaging-Based NOD/scid-IL-2Rγc(null) Mouse Brain Atlas.

    Science.gov (United States)

    Sajja, Balasrinivasa R; Bade, Aditya N; Zhou, Biyun; Uberti, Mariano G; Gorantla, Santhi; Gendelman, Howard E; Boska, Michael D; Liu, Yutong

    2016-03-01

    Strain specific mouse brain magnetic resonance imaging (MRI) atlases provide coordinate space linked anatomical registration. This allows longitudinal quantitative analyses of neuroanatomical volumes and imaging metrics for assessing the role played by aging and disease to the central nervous system. As NOD/scid-IL-2Rγ(c)(null) (NSG) mice allow human cell transplantation to study human disease, these animals are used to assess brain morphology. Manganese enhanced MRI (MEMRI) improves contrasts amongst brain components and as such can greatly help identifying a broad number of structures on MRI. To this end, NSG adult mouse brains were imaged in vivo on a 7.0 Tesla MR scanner at an isotropic resolution of 100 μm. A population averaged brain of 19 mice was generated using an iterative alignment algorithm. MEMRI provided sufficient contrast permitting 41 brain structures to be manually labeled. Volumes of 7 humanized mice brain structures were measured by atlas-based segmentation and compared against non-humanized controls. The humanized NSG mice brain volumes were smaller than controls (p < 0.001). Many brain structures of humanized mice were significantly smaller than controls. We posit that the irradiation and cell grafting involved in the creation of humanized mice were responsible for the morphological differences. Six NSG mice without MnCl2 administration were scanned with high resolution T2-weighted MRI and segmented to test broad utility of the atlas.

  2. Establishment of human patient-derived endometrial cancer xenografts in NOD scid gamma mice for the study of invasion and metastasis.

    Directory of Open Access Journals (Sweden)

    Kenji Unno

    Full Text Available Most endometrial cancers are detected early and have a good prognosis, while some endometrial cancers are highly invasive, metastasize early, and respond suboptimally to therapy. Currently, appropriate model systems to study the aggressive nature of these tumors are lacking. The objective of this study was to establish a mouse xenograft model of endometrial tumors derived from patients in order to study the biological aggressive characteristics that underlie invasion and metastasis.Endometrial tumor tissue fragments (1.5 mm × 1.5 mm from patients undergoing surgery, were transplanted under the renal capsule of NOD scid gamma mice. After 6-8 weeks, tumors were excised and serially transplanted into additional mice for propagation. Immunohistochemical analysis of the tumors was done for various tumor markers.Four cases of different subtypes of endometrial cancer were grown and propagated in mice. Three of the four tumor cases invaded into the kidneys and to adjacent organs. While all tumors exhibited minimal to no staining for estrogen receptor α, progesterone receptor staining was observed for tumor grafts. In addition, levels and localization of E-cadherin, cytokeratin and vimentin varied depending on subtype. Finally, all tumor xenografts stained positively for urokinase plasminogen activator while 3 tumor xenografts, which showed invasive characteristics, stained positively for urokinase plasminogen activator receptor.Endometrial tumors transplanted under the renal capsule exhibit growth, invasion and local spread. These tumors can be propagated and used to study aggressive endometrial cancer.

  3. Genetic correction of β-thalassemia patient-specific iPS cells and its use in improving hemoglobin production in irradiated SCID mice.

    Science.gov (United States)

    Wang, Yixuan; Zheng, Chen-Guang; Jiang, Yonghua; Zhang, Jiqin; Chen, Jiayu; Yao, Chao; Zhao, Qingguo; Liu, Sheng; Chen, Ke; Du, Juan; Yang, Ze; Gao, Shaorong

    2012-04-01

    The generation of induced pluripotent stem cells (iPSCs) from differentiated somatic cells by over-expression of several transcription factors has the potential to cure many genetic and degenerative diseases currently recalcitrant to traditional clinical approaches. One such genetic disease is β-thalassemia major (Cooley's anemia). This disease is caused by either a point mutation or the deletion of several nucleotides in the β-globin gene, and it threatens the lives of millions of people in China. In the present study, we successfully generated iPSCs from fibroblasts collected from a 2-year-old patient who was diagnosed with a homozygous 41/42 deletion in his β-globin gene. More importantly, we successfully corrected this genetic mutation in the β-thalassemia iPSCs by homologous recombination. Furthermore, transplantation of the genetically corrected iPSCs-derived hematopoietic progenitors into sub-lethally irradiated immune deficient SCID mice showed improved hemoglobin production compared with the uncorrected iPSCs. Moreover, the generation of human β-globin could be detected in the mice transplanted with corrected iPSCs-derived hematopietic progenitors. Our study provides strong evidence that iPSCs generated from a patient with a genetic disease can be corrected by homologous recombination and that the corrected iPSCs have potential clinical uses.

  4. Dynamics of gene-modified progenitor cells analyzed by tracking retroviral integration sites in a human SCID-X1 gene therapy trial.

    Science.gov (United States)

    Wang, Gary P; Berry, Charles C; Malani, Nirav; Leboulch, Philippe; Fischer, Alain; Hacein-Bey-Abina, Salima; Cavazzana-Calvo, Marina; Bushman, Frederic D

    2010-06-03

    X-linked severe-combined immunodeficiency (SCID-X1) has been treated by therapeutic gene transfer using gammaretroviral vectors, but insertional activation of proto-oncogenes contributed to leukemia in some patients. Here we report a longitudinal study of gene-corrected progenitor cell populations from 8 patients using 454 pyrosequencing to map vector integration sites, and extensive resampling to allow quantification of clonal abundance. The number of transduced cells infused into patients initially predicted the subsequent diversity of circulating cells. A capture-recapture analysis was used to estimate the size of the gene-corrected cell pool, revealing that less than 1/100th of the infused cells had long-term repopulating activity. Integration sites were clustered even at early time points, often near genes involved in growth control, and several patients harbored expanded cell clones with vectors integrated near the cancer-implicated genes CCND2 and HMGA2, but remain healthy. Integration site tracking also documented that chemotherapy for adverse events resulted in successful control. The longitudinal analysis emphasizes that key features of transduced cell populations--including diversity, integration site clustering, and expansion of some clones--were established early after transplantation. The approaches to sequencing and bioinformatics analysis reported here should be widely useful in assessing the outcome of gene therapy trials.

  5. T-cell receptor gene therapy targeting melanoma-associated antigen-A4 inhibits human tumor growth in non-obese diabetic/SCID/γcnull mice.

    Science.gov (United States)

    Shirakura, Yoshitaka; Mizuno, Yukari; Wang, Linan; Imai, Naoko; Amaike, Chisaki; Sato, Eiichi; Ito, Mamoru; Nukaya, Ikuei; Mineno, Junichi; Takesako, Kazutoh; Ikeda, Hiroaki; Shiku, Hiroshi

    2012-01-01

    Adoptive cell therapy with lymphocytes that have been genetically engineered to express tumor-reactive T-cell receptors (TCR) is a promising approach for cancer immunotherapy. We have been exploring the development of TCR gene therapy targeting cancer/testis antigens, including melanoma-associated antigen (MAGE) family antigens, that are ideal targets for adoptive T-cell therapy. The efficacy of TCR gene therapy targeting MAGE family antigens, however, has not yet been evaluated in vivo. Here, we demonstrate the in vivo antitumor activity in immunodeficient non-obese diabetic/SCID/γc(null) (NOG) mice of human lymphocytes genetically engineered to express TCR specific for the MAGE-A4 antigen. Polyclonal T cells derived from human peripheral blood mononuclear cells were transduced with the αβ TCR genes specific for MAGE-A4, then adoptively transferred into NOG mice inoculated with MAGE-A4 expressing human tumor cell lines. The transferred T cells maintained their effector function in vivo, infiltrated into tumors, and inhibited tumor growth in an antigen-specific manner. The combination of adoptive cell therapy with antigen peptide vaccination enhanced antitumor activity, with improved multifunctionality of the transferred cells. These data suggest that TCR gene therapy with MAGE-A4-specific TCR is a promising strategy to treat patients with MAGE-A4-expressing tumors; in addition, the acquisition of multifunctionality in vivo is an important factor to predict the quality of the T-cell response during adoptive therapy with human lymphocytes.

  6. Genetic correction of β-thalassemia patient-specific iPS cells and its use in improving hemoglobin production in irradiated SCID mice

    Institute of Scientific and Technical Information of China (English)

    Yixuan Wang; Juan Du; Ze Yang; Shaorong Gao; Chen-Guang Zheng; Yonghua Jiang; Jiqin Zhang; Jiayu Chen; Chao Yao; Qingguo Zhao; Sheng Liu; Ke Chen

    2012-01-01

    The generation of induced pluripotent stem cells (iPSCs) from differentiated somatic cells by over-expression of several transcription factors has the potential to cure many genetic and degenerative diseases currently recalcitrant to traditional clinical approaches.One such genetic disease is β-thalassemia major (Cooley's anemia).This disease is caused by either a point mutation or the deletion of several nucleotides in the β-globin gene,and it threatens the lives of millions of people in China.In the present study,we successfully generated iPSCs from fibroblasts collected from a 2-year-old patient who was diagnosed with a homozygous 41/42 deletion in his β-globin gene.More importantly,we successfully corrected this genetic mutation in the β-thalassemia iPSCs by homologous recombination.Furthermore,transplantation of the genetically corrected iPSCs-derived hematopoietic progenitors into sub-lethally irradiated immune deficient SCID mice showed improved hemoglobin production compared with the uncorrected iPSCs.Moreover,the generation of human β-globin could be detected in the mice transplanted with corrected iPSCs-derived hematopietic progenitors.Our study provides strong evidence that iPSCs generated from a patient with a genetic disease can be corrected by homologous recombination and that the corrected iPSCs have potential clinical uses.

  7. Efficient construction of producer cell lines for a SIN lentiviral vector for SCID-X1 gene therapy by concatemeric array transfection.

    Science.gov (United States)

    Throm, Robert E; Ouma, Annastasia A; Zhou, Sheng; Chandrasekaran, Anantharaman; Lockey, Timothy; Greene, Michael; De Ravin, Suk See; Moayeri, Morvarid; Malech, Harry L; Sorrentino, Brian P; Gray, John T

    2009-05-21

    Retroviral vectors containing internal promoters, chromatin insulators, and self-inactivating (SIN) long terminal repeats (LTRs) may have significantly reduced genotoxicity relative to the conventional retroviral vectors used in recent, otherwise successful clinical trials. Large-scale production of such vectors is problematic, however, as the introduction of SIN vectors into packaging cells cannot be accomplished with the traditional method of viral transduction. We have derived a set of packaging cell lines for HIV-based lentiviral vectors and developed a novel concatemeric array transfection technique for the introduction of SIN vector genomes devoid of enhancer and promoter sequences in the LTR. We used this method to derive a producer cell clone for a SIN lentiviral vector expressing green fluorescent protein, which when grown in a bioreactor generated more than 20 L of supernatant with titers above 10(7) transducing units (TU) per milliliter. Further refinement of our technique enabled the rapid generation of whole populations of stably transformed cells that produced similar titers. Finally, we describe the construction of an insulated, SIN lentiviral vector encoding the human interleukin 2 receptor common gamma chain (IL2RG) gene and the efficient derivation of cloned producer cells that generate supernatants with titers greater than 5 x 10(7) TU/mL and that are suitable for use in a clinical trial for X-linked severe combined immunodeficiency (SCID-X1).

  8. Transplantation of human spleen into immunodeficient NOD/SCID IL2Rγ(null) mice generates humanized mice that improve functional B cell development.

    Science.gov (United States)

    Chung, Yun Shin; Son, Jin Kyung; Choi, Bongkum; Park, Jae Berm; Chang, Jun; Kim, Sung Joo

    2015-12-01

    We previously generated humanized TB34N mice that received human fetal thymus (T), bone tissue (B) and fetal liver-derived (FL)-CD34(+) cells (34) in immunodeficient, NOD/SCID IL2Rγ(null) (N) mice. Although humanized TB34N mice had excellent hematopoiesis, here, we sought to further improve this model by additional transplantation of human spleen tissue (S) as a secondary hematopoietic tissue (TBS34N). The human spleen grafts were enlarged and differentiated into a similar morphology of adult humans, including follicular lymphoid structures with T- and B-cells. The TBS34N mice mimicked mature human immune system (HIS): mature T- and B-cells and follicular dendritic cells; activated germinal center B-cells expressing CD71, BR3(+) cells, memory B-cells and activation-induced cytidine deaminase(+) B-cells; CD138(+) plasma cells were enriched in the mouse spleen. HBsAg-specific hIgG antibodies were secreted into the sera of all TBS34N mice upon immunization with HBsAg. Taken together, the humanized TBS34N mice improved mature HIS and achieved adaptive antibody responses.

  9. Measures of kidney function by minimally invasive techniques correlate with histological glomerular damage in SCID mice with adriamycin-induced nephropathy.

    Science.gov (United States)

    Scarfe, Lauren; Rak-Raszewska, Aleksandra; Geraci, Stefania; Darssan, Darsy; Sharkey, Jack; Huang, Jiaguo; Burton, Neal C; Mason, David; Ranjzad, Parisa; Kenny, Simon; Gretz, Norbert; Lévy, Raphaël; Kevin Park, B; García-Fiñana, Marta; Woolf, Adrian S; Murray, Patricia; Wilm, Bettina

    2015-09-02

    Maximising the use of preclinical murine models of progressive kidney disease as test beds for therapies ideally requires kidney function to be measured repeatedly in a safe, minimally invasive manner. To date, most studies of murine nephropathy depend on unreliable markers of renal physiological function, exemplified by measuring blood levels of creatinine and urea, and on various end points necessitating sacrifice of experimental animals to assess histological damage, thus counteracting the principles of Replacement, Refinement and Reduction. Here, we applied two novel minimally invasive techniques to measure kidney function in SCID mice with adriamycin-induced nephropathy. We employed i) a transcutaneous device that measures the half-life of intravenously administered FITC-sinistrin, a molecule cleared by glomerular filtration; and ii) multispectral optoacoustic tomography, a photoacoustic imaging device that directly visualises the clearance of the near infrared dye, IRDye 800CW carboxylate. Measurements with either technique showed a significant impairment of renal function in experimental animals versus controls, with significant correlations with the proportion of scarred glomeruli five weeks after induction of injury. These technologies provide clinically relevant functional data and should be widely adopted for testing the efficacies of novel therapies. Moreover, their use will also lead to a reduction in experimental animal numbers.

  10. Host-specific response to HCV infection in the chimeric SCID-beige/Alb-uPA mouse model: role of the innate antiviral immune response.

    Directory of Open Access Journals (Sweden)

    Kathie-Anne Walters

    2006-06-01

    Full Text Available The severe combined immunodeficiency disorder (SCID-beige/albumin (Alb-urokinase plasminogen activator (uPA mouse containing a human-mouse chimeric liver is currently the only small animal model capable of supporting hepatitis C virus (HCV infection. This model was utilized to characterize the host transcriptional response to HCV infection. The purpose of these studies was to investigate the genetic component of the host response to HCV infection and also to distinguish virus-induced gene expression changes from adaptive HCV-specific immune-mediated effects. Gene expression profiles from HCV-infected mice were also compared to those from HCV-infected patients. Analyses of the gene expression data demonstrate that host factors regulate the response to HCV infection, including the nature of the innate antiviral immune response. They also indicate that HCV mediates gene expression changes, including regulation of lipid metabolism genes, which have the potential to be directly cytopathic, indicating that liver pathology may not be exclusively mediated by HCV-specific adaptive immune responses. This effect appears to be inversely related to the activation of the innate antiviral immune response. In summary, the nature of the initial interferon response to HCV infection may determine the extent of viral-mediated effects on host gene expression.

  11. Peripheral-type benzodiazepine receptor levels correlate with the ability of human breast cancer MDA-MB-231 cell line to grow in SCID mice.

    Science.gov (United States)

    Hardwick, M; Rone, J; Han, Z; Haddad, B; Papadopoulos, V

    2001-11-01

    MDA-MB-231 (MDA-231) human breast cancer cells have a high proliferation rate, lack the estrogen receptor, express the intermediate filament vimentin, the hyaluronan receptor CD44, and are able to form tumors in nude mice. The MDA-231 cell line has been used in our laboratory to examine the role of the peripheral-type benzodiazepine receptor (PBR) in the progression of cancer. During these studies 2 populations of MDA-231 cells were subcloned based on the levels of PBR. The subclones proliferated at approximately the same rate, lacked the estrogen receptor, expressed vimentin and CD44, and had the same in vitro chemoinvasive and chemotactic potential. Both restriction fragment length polymorphism and comparative genomic hybridization analyses of genomic DNA from these cells indicated that both subclones are of the same genetic lineage. Only the subclone with high PBR levels, however, was able to form tumors when injected in SCID mice. These data suggest that the ability of MDA-231 cells to form tumors in vivo may depend on the amount of PBR present in the cells.

  12. Recipient and donor thrombophilia and the risk of portal venous thrombosis and hepatic artery thrombosis in liver recipients

    Directory of Open Access Journals (Sweden)

    Ayala Rosa

    2011-11-01

    Full Text Available Abstract Background Vascular complications, such as HAT, are an important cause of graft loss and recipient mortality. We aimed to characterize post-transplant thrombotic events in a cohort of liver transplant recipients, and identify independent risk factors for these complications. Methods We conducted a thrombophilic study of 293 orthotopic liver transplants performed in the Digestive Surgery Department of the 12 de Octubre Hospital (Madrid, Spain between January 2001 and December 2006. Results The most frequent post-transplant thrombotic events were HAT (9% and PVT (1.7%. The one variable associated with post-transplant thrombotic event was a high fibrinogen level in the global cohort of liver transplantation. But toxicity as event post-OLT has been associated with post-transplant thrombotic event in the retrospective group and high fibrinogen level and low protein C levels were associated post-transplant thrombotic event in the prospective group. Liver disease relapse (HR 6.609, p In conclusion, high fibrinogen and decreased protein C levels were associated with allograft thrombosis. Further studies are required in order to assess the clinical relevance of these parameters in prospective studies and to study the effect of anticoagulation prophylaxis in this group of risk.

  13. [Sensitivity and specificity between the Composite International Diagnostic Interview Version 3.0 (World Mental Health, CIDI) and the Standardised Clinical Evaluation version I (SCID-I) in a mental health survey of the city of Medellin, 2012].

    Science.gov (United States)

    Montoya Gonzalez, Laura Elisa; Restrepo Bernal, Diana Patricia; Mejía-Montoya, Roberto; Bareño-Silva, José; Sierra-Hincapié, Gloria; Torres de Galvis, Yolanda; Marulanda-Restrepo, Daniel; Gómez-Sierra, Natalia; Gaviria-Arbeláez, Silvia

    2016-01-01

    In order to address the mental health problems of the Colombian population it is necessary to have diagnostic tools (local and international) that are valid, easy to apply, and comparable. To compare the sensitivity and specificity between the CIDI 3.0 and the SCID-I for major depressive disorder, bipolar I and II disorder, and substance dependence disorder. Cross-sectional study comparing the life prevalence of three mental disorders in 100 subjects using the CIDI 3.0 and the SCID-I. The study was approved by the Institutional Ethics Committee. The two diagnostic interviews were performed that measured by sensitivity, specificity, positive predictive value and negative predictive value with confidence intervals of 95%. The SPSS version 21.0 software was used for data analysis. The median age was 43.5 years, with an interquartile interval of 30 years. The highest sensitivity (Se) and specificity (Sp) was observed for drug dependence diagnosis - with 80%, (95%CI, 34.94-100), and 98.46 (95%CI, 94.7-100), respectively. SCID-I and CIDI 3.0 showed different levels of sensitivity and specificity for the three disorders studied with: high for substance dependence disorder, moderate for bipolar disorder I and II, and low for major depressive disorder. Copyright © 2015 Asociación Colombiana de Psiquiatría. All rights reserved.

  14. PP146. Psychological assessment of renal transplant recipients during pregnancy.

    Science.gov (United States)

    Neto, V L L Belardi; de Oliveira, L G; Sass, N

    2012-07-01

    Although many centers have reported their experience on maternal and perinatal outcomes in renal transplant recipients. Very few information can be found about the psychological aspects that may rise for these patients during pregnancy. Considering the importance of the psychological concerns for this kind of patients, we have developed a protocol to better assist renal transplant recipients during pregnancy and here we show what we have learnt. To understand how the maternal concerns are seen from renal transplant recipients in terms of psychological aspects. Fifteen pregnant kidney transplanted women with an average age of 27.5years were included in the study. All patients have been investigated beyond the 20th week of pregnancy to delivery. The study is cross-sectional, qualitative, and participation is based on developed phenomenological method. Final data analysis will be done through thematic analysis and hermeneutics of meaning. The only exclusion criteria were the current presence of psychiatric disorders or use of drugs that could influence cognitive and emotional aspects during the psychological evaluation. During the last two years we have observed in these women that all of them are aware of the risks of pregnancy after transplantation. Qualitative aspects were: Pregnant with kidney transplantation show: in relation to pregnancy, the desire to be mothers, to give a son to her husband, to become a healthy person again; they believe that conception is God's will, they have fear of pregnancy, ambivalence of feelings (fear and happiness). In relation to the graft, they reported fear of baby malformations, fear and anguish of graft loss, still consider it worth the risk of having the baby, and some women name the graft, if it were another infant. In relation to delivery, state anxiety and anguish at the proximity of labor (fear of labor pain, anesthesia, cesarean section, vaginal delivery and the "psychic pain"). Pending the final results of this study, we

  15. Alemtuzumab induction therapy in highly sensitized kidney transplant recipients

    Institute of Scientific and Technical Information of China (English)

    L(U) Tie-ming; YANG Shun-liang; WU Wei-zhen; TAN Jian-ming

    2011-01-01

    Background Immunosuppression for immunologically high-risk kidney transplant patients usually involves antithymocyte globulin induction with triple drug maintenance therapy. Alemtuzumab, a humanized anti-CD52 antibody,was expected to be a promising induction therapy agent for kidney transplantation. However, currently no consensus is available about its efficacy and safety. This study aimed to evaluate the efficacy and safety of alemtuzumab as immune induction therapy in highly sensitized kidney transplant recipients.Methods In this prospective, open-label, randomized, controlled trial, we enrolled 23 highly immunological risk patients (panel reactive antibody >20%). They were divided into two groups: alemtuzumab group (trial group) and anti-thymocyte globulin (ATG) group (control group). Patients in the alemtuzumab group received intravenous alemtuzumab (15 mg) as a single dose before reperfusion. At the 24th hour post-operation, another dosage of alemtuzumab (15 mg) was given.The control group received a bolus of rabbit ATG (9 mg/kg), which was given 2 hours before kidney transplantation and lasted until the removal of vascular clamps when the anastomoses were completed. Maintenance immunosuppression in both groups comprised standard triple therapy consisting of tacrolimus, prednisone, and mycophenolate mofetil (MMF).Acute rejection (AR) and infection episodes were recorded, and kidney function was monitored during a 2-year follow-up.χ2 test, t test and Kaplan-Meier analysis were performed with SPSS17.0 software.Results Median follow-up was 338 days. In both the alemtuzumab group and ATG group, creatinine and blood urea nitrogen values in surviving recipients were similar (P >0.05). White blood cell counts were significantly reduced in the alemtuzumab group for the most time points up to 6 months (P <0.05). One patient receiving alemtuzumab died for acute myocardial infarction at the 65th day post-operation. Two ATG patients died for severe pulmonary

  16. Cystatin C enhances GFR estimating Equations in Kidney Transplant Recipients

    Science.gov (United States)

    Kukla, Aleksandra; Issa, Naim; Jackson, Scott; Spong, Richard; Foster, Meredith C.; Matas, Arthur J.; Mauer, Michael S.; Eckfeldt, John H.; Ibrahim, Hassan N.

    2014-01-01

    Background The glomerular filtration rate (GFR) estimating equation incorporating both cystatin C and creatinine perform better than those using creatinine or cystatin C alone in patients with reduced GFR. Whether this equation performs well in kidney transplant recipients cross-sectionally, and more importantly, over time has not been addressed. Methods We analyzed four GFR estimating equations in participants of the Angiotensin II Blockade for Chronic Allograft Nephropathy Trial (NCT 00067990): Chronic Kidney Disease Epidemiology Collaboration equations based on serum cystatin C and creatinine (eGFR (CKD-EPI-Creat+CysC)), cystatin C alone (eGFR (CKD-EPI-CysC)), creatinine alone (eGFR (CKD-EPI-Creat)) and the Modification of Diet in Renal Disease study equation (eGFR(MDRD)). Iothalamate GFR served as a standard (mGFR). Results mGFR, serum creatinine, and cystatin C shortly after transplant were 56.1 ± 17.0 mL/min/1.73 m2, 1.2 ± 0.4 mg/dL, and 1.2 ± 0.3 mg/L respectively. eGFR (CKD-EPI-Creat+CysC) was most precise (R2=0.50) but slightly more biased than eGFR (MDRD); 9.0 ± 12.7 ml/min/1.73m2 vs. 6.4 ± 15.8 ml/min/1.73m2, respectively. This improved precision was most evident in recipients with mGFR >60 ml/min/1.73m2. For relative accuracy, eGFR (MDRD) and eGFR (CKD-EPI-Creat+CysC) had the highest percentage of estimates falling within 30% of mGFR; 75.8% and 68.9%, respectively. Longitudinally, equations incorporating cystatin C most closely paralleled the change in mGFR. Conclusion eGFR (CKD-EPI-Creat+CysC) is more precise and reflects GFR change over time reasonably well. eGFR (MDRD) had superior performance in recipients with mGFR between 30–60 ml/min/1.73m2. PMID:24457184

  17. Trends in disability benefit recipient rates in post industrialised countries

    DEFF Research Database (Denmark)

    Rasmussen, Martin

    This working paper is part of a study organized by International Social Security Association (ISSA). The study is called Trends in disability benefit recipient rates in post-industrial societies. The other countries participating in the study are Sweden, United States, United Kingdom......, The Netherlands, and Israel. The study is organized in two phases. In phase one, country reports are prepared, and in phase two, comparative studies are carried out. This paper is related to the first phase. Previous versions of the paper have been discussed with Steen Bengtsson, Ole Gregersen, Jan Høgelund......, and Jørgen Søndergaard. I am thankful for their suggestions and help. The participating countries have financed the study....

  18. GU Evaluation and Management of Renal Transplant Candidates and Recipients

    Directory of Open Access Journals (Sweden)

    Peter N. Bretan

    2004-01-01

    Full Text Available There are more than 200,000 end stage renal disease (ESRD patients who are potential transplant candidates and more than 100,000 previously transplanted renal recipients with functioning allografts in the United States 1. Fifty-seven percent of these patients are male and forty percent are greater than 50 years of age 2, 3. Diabetes is the most common cause of kidney failure. It is evident that many patients are at high risk for development of urologic problems and thus it is estimated that the average urologist will care for up to ten of these patients yearly4. Thus a review of the genitourinary (GU evaluation and management of these patients is timely.

  19. Antibody induction versus corticosteroid induction for liver transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Wettergren, André; Wilson, Colin H

    2014-01-01

    BACKGROUND: Liver transplantation is an established treatment option for end-stage liver failure. To date, no consensus has been reached on the use of immunosuppressive T-cell specific antibody induction compared with corticosteroid induction of immunosuppression after liver transplantation....... OBJECTIVES: To assess the benefits and harms of T-cell specific antibody induction versus corticosteroid induction for prevention of acute rejection in liver transplant recipients. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register...... of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 30 September 2013 together with reference checking, citation searching, contact with trial authors and pharmaceutical companies...

  20. Microsporidia Infection in a Mexican Kidney Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Oscar Xavier Hernández-Rodríguez

    2012-01-01

    Full Text Available Microorganisms of the microsporidia group are obligated intracellular protozoa that belong to the phylum Microspora; currently they are considered to be related or belong to the fungi reign. It is considered an opportunistic infection in humans, and 14 species belonging to 8 different genera have been described. Immunocompromized patients such as those infected with human immunodeficiency virus (HIV, also HIV serum-negative asymptomatic patients, with poor hygienic conditions, and recipients of bone marrow or solid organ transplantation are susceptible to develop deinfection. Sixty transplanted patients with renal microsporidia infection have been reported worldwide. The aim of this paper is to inform about the 2nd case of kidney transplant and microsporidia infection documented in Mexico.

  1. Periostitis secondary to prolonged voriconazole therapy in lung transplant recipients.

    Science.gov (United States)

    Wang, T F; Wang, T; Altman, R; Eshaghian, P; Lynch, J P; Ross, D J; Belperio, J A; Weigt, S S; Saggar, R; Gregson, A; Kubak, B; Saggar, R

    2009-12-01

    We report five cases of possible drug-induced periostitis associated with long-term use of voriconazole therapy after lung transplantation (LT). The diagnosis of periostitis was made by the documentation of bone pain, elevation of serum alkaline phosphatase and characteristic findings on radionuclide bone imaging in the absence of any identifiable rheumatologic disease. This periostitis appears similar to hypertrophic osteoarthopathy (HOA) but does not meet all criteria for HOA. In all patients, the symptoms resolved rapidly after discontinuation of voriconazole therapy. Awareness of this potential syndrome, which manifests as bone pain, elevated serum alkaline phosphatase and a bone scan suggestive of periostitis, is necessary in LT recipients on long-term voriconazole.

  2. Personalized persuasion: tailoring persuasive appeals to recipients' personality traits.

    Science.gov (United States)

    Hirsh, Jacob B; Kang, Sonia K; Bodenhausen, Galen V

    2012-06-01

    Persuasive messages are more effective when they are custom-tailored to reflect the interests and concerns of the intended audience. Much of the message-framing literature has focused on the advantages of using either gain or loss frames, depending on the motivational orientation of the target group. In the current study, we extended this research to examine whether a persuasive appeal's effectiveness can be increased by aligning the message framing with the recipient's personality profile. For a single product, we constructed five advertisements, each designed to target one of the five major trait domains of human personality. In a sample of 324 survey respondents, advertisements were evaluated more positively the more they cohered with participants' dispositional motives. These results suggest that adapting persuasive messages to the personality traits of the target audience can be an effective way of increasing the messages' impact, and highlight the potential value of personality-based communication strategies.

  3. Recipients of 2013 EPS High Energy & Particle Physics Prize

    CERN Multimedia

    ATLAS, Experiment

    2014-01-01

    (From left) Joe Incandela, Peter Higgs, Francois Englert, Tejinder Virdee, Dave Charlton, and Peter Jenni. Higgs and Englert gave the prizes to the recipients of the 2013 European Physical Society's High Energy and Particle Physics Prize, for an outstanding contribution to high energy physics. "For the discovery of a Higgs boson, as predicted by the Brout-Englert-Higgs mechanism," the prize was awarded to the ATLAS and CMS collaborations. Spokesperson for CMS, Incandela, and Spokesperson for ATLAS, Charlton, accepted the awards on their collaborations' behalf. "For their pioneering and outstanding leadership roles in the making of the ATLAS and CMS experiments," the prize was awarded to Jenni, Virdee, and Michel Della Negra (not present). Image: ATLAS

  4. Pityriasis Versicolor on Penile Shaft in a Renal Transplant Recipient

    Science.gov (United States)

    Ryu, Han-Won; Cho, Jae-We

    2012-01-01

    Pityriasis versicolor is a superficial infection of the stratum corneum, which is caused by the Malassezia species. Tge Malassezia species consist of 12 subspecies, including M. furfur, M. pachydermatis, M. symphodialis and M. globasa. The Malassezia species are classified as a normal flora, particularly in the sebum rich areas of the skin, and they convert from saprophytic yeast to parasitic mycelial morpholgic form to cause clinical disease. But majorities of their distributions are in the upper back, the neck, the thighs, and the forearm, and not in the penis. It is well known that the renal transplant patients, who take immunosuppressive agents, have impairment in the protective cell mediated immunity. Thus, they are more susceptible to infectious diseases, such as a fungal infection. Therefore, clinical manifestations show higher incidence of disease, but they mostly occur in an expected distribution. We here report a case of pityriasis versicolor in a renal transplant recipient on penile shaft, which is an unusual area. PMID:22879720

  5. Unusual complication of percutaneous nephrostomy in a renal transplant recipient

    Directory of Open Access Journals (Sweden)

    Martina Paetzel

    2010-11-01

    Full Text Available Context: Ureteral obstruction, resulting in impaired graft function, is a well-known problem following renal transplantation. Management of ureteral complications includes percutaneous nephrostomy, which is considered to be a safe and effective measure. Case Report: Here, we demonstrate a case of a 35-year old renal allograft recipient with primary graft function but stagnating serum creatinine following extraction of the double-J catheter. Ureteral stenosis was suspected by ultrasound imaging and magnetic resonance tomography, and urinary flow was preserved with a percutaneous nephrostomy. However, early displacement of the percutaneous nephrostomy catheter resulted in distinct clinical discomfort. CT imaging suggested an intra-abdominal position of the catheter’s tip, requiring immediate surgical action. Conclusion: The present case demonstrates that performing PCN following renal transplantation may have unexpected risks.

  6. BK virus in solid organ transplant recipients: an emerging syndrome.

    Science.gov (United States)

    Mylonakis, E; Goes, N; Rubin, R H; Cosimi, A B; Colvin, R B; Fishman, J A

    2001-11-27

    BK virus is a human polyomavirus associated with a range of clinical presentations from asymptomatic viruria with pyuria to ureteral ulceration with ureteral stenosis in renal transplant patients or hemorrhagic cystitis in bone marrow transplant recipients. Infection of renal allografts has been associated with diminished graft function in some individuals. Fortunately, however, the majority of patients with BK virus infections are asymptomatic. The type, duration, and intensity of immunosuppression are major contributors to susceptibility to the activation of BK virus infection. Histopathology is required for the demonstration of renal parenchymal involvement; urine cytology and viral polymerase chain reaction methods are useful adjunctive diagnostic tools. Current, treatment of immunosuppressed patients with polyomavirus viruria is largely supportive and directed toward minimizing immunosuppression. Improved diagnostic tools and antiviral therapies are needed for polyomavirus infections.

  7. Pityriasis versicolor on penile shaft in a renal transplant recipient.

    Science.gov (United States)

    Ryu, Han-Won; Cho, Jae-We; Lee, Kyu-Suk

    2012-08-01

    Pityriasis versicolor is a superficial infection of the stratum corneum, which is caused by the Malassezia species. Tge Malassezia species consist of 12 subspecies, including M. furfur, M. pachydermatis, M. symphodialis and M. globasa. The Malassezia species are classified as a normal flora, particularly in the sebum rich areas of the skin, and they convert from saprophytic yeast to parasitic mycelial morpholgic form to cause clinical disease. But majorities of their distributions are in the upper back, the neck, the thighs, and the forearm, and not in the penis. It is well known that the renal transplant patients, who take immunosuppressive agents, have impairment in the protective cell mediated immunity. Thus, they are more susceptible to infectious diseases, such as a fungal infection. Therefore, clinical manifestations show higher incidence of disease, but they mostly occur in an expected distribution. We here report a case of pityriasis versicolor in a renal transplant recipient on penile shaft, which is an unusual area.

  8. Mandarin melody recognition by pediatric cochlear implant recipients.

    Science.gov (United States)

    Hsiao, Feilin

    2008-01-01

    This study investigated the ability of children with implants who speak Mandarin Chinese, a tonal language, to recognize familiar melodies. It further examined the relative contributions of pitch, rhythm, and lyrics to melody recognition. Two groups of participants (ages 7-15; n = 20 for each group), those with cochlear implants and those with typical hearing, listened to 2 sets (traditional Mandarin children's songs and children's songs from Western cultures translated into Mandarin) of three melodies. These melodies were presented in 3 conditions: (a) melodic contour only (pitches in equal durations); (b) melodic contour with rhythmic patterns; and (c) melodic contour with rhythmic patterns and lyrics. The results indicated that pediatric cochlear implant recipients performed with greater accuracy in melody recognition when lyrics were available. Their scores were significantly lower when melodies containing only pitch features. Providing the rhythmic patterns aided participants' identification of the target melodies, but less so than the lyrics. Applications of findings to aural rehabilitation are discussed.

  9. Cerebral Nocardiosis in a Renal Transplant Recipient: A Case Report

    Directory of Open Access Journals (Sweden)

    Srinivas K

    2000-01-01

    Full Text Available A 53-year-old renal allograft recipient developed nocardial cerebral abscess. It manifested clinically with encephalitis, polycythemia, convulsions, syndrome of inappropriate secretion of antidiuretic hormone (SIADH and a space-occupying lesion presenting as multiple ring shadows in the left fronto-parietal lobe on computerized tomography (CT scan of the brain. The initial clinical presentation included an afebrile patient with headache, convulsions and altered sensorium with no lateralising neurological deficit. He deteriorated later and developed coma with right hemiplegia. Purulent material was drained through left frontal craniotomy, and the culture confirmed the presence of nocardial infection. Despite aggressive therapy, the patient died a few days later. We conclude that high degree of early suspicion, diagnosis and prompt treatment should be stressed.

  10. Cystic duct remnant mucocele in a liver transplant recipient

    Energy Technology Data Exchange (ETDEWEB)

    Ahlawat, Sushil K. [Georgetown University Hospital, Department of Medicine, Division of Gastroenterology, Washington, DC (United States); University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ (United States); Fishbien, Thomas M. [Georgetown University Hospital, Department of Medicine, Division of Gastroenterology, Washington, DC (United States); Haddad, Nadim G. [Georgetown University Hospital, Department of Surgery, Division of Transplant Surgery, Washington, DC (United States)

    2008-08-15

    Cystic duct remnant mucocele is an extremely rare complication of liver transplantation in children. Surgical correction is usually required for cystic duct remnant mucocele when it causes biliary obstruction. We describe a 14-month-old liver transplant recipient who presented with biliary obstruction 1 month after orthotopic liver transplantation with an end-to-end choledochocholedocal biliary anastomosis for hepatoblastoma. US, CT and cholangiography findings were consistent with mucocele of the allograft cystic duct remnant. Surgery was not needed in our patient because the mucocele and biliary obstruction had resolved on repeat imaging most likely due to guidewire manipulation during cholangiography, resulting in opening of the cystic duct remnant orifice and drainage into the common duct. (orig.)

  11. Management of venous stenosis in living donor liver transplant recipients

    Institute of Scientific and Technical Information of China (English)

    Jie Yang; Ming-Qing Xu; Lu-Nan Yan; Wu-Sheng Lu; Xiao Li; Zheng-Rong Shi; Bo Li; Tian-Fu Wen; Wen-Tao Wang; Jia-Ying Yang

    2009-01-01

    AIM: To retrospectively evaluate the management and outcome of venous obstruction after living donor liver transplantation (LDLT).METHODS: From February 1999 to May 2009, 1 intraoperative hepatic vein (HV) tension induced HV obstruction and 5 postoperative HV anastomotic stenosis occurred in 6 adult male LDLT recipients. Postoperative portal vein (PV) anastomotic stenosis occurred in 1 pediatric left lobe LDLT. Patients ranged in age from 9 to 56 years (median, 44 years). An air balloon was used to correct the intraoperative HV tension. Emergent surgical reoperation, transjugular HV balloon dilatation with stent placement and transfemoral venous HV balloon dilatation was performed for HV stenosis on days 3, 15, 50, 55, and 270 after LDLT, respectively. Balloon dilatation followed with stent placement via superior mesenteric vein was performed for the pediatric PV stenosis 168 d after LDLT.RESULTS: The intraoperative HV tension was corrected with an air balloon. The recipient who underwent emergent reoperation for hepatic stenosis died of hemorrhagic shock and renal failure 2 d later. HV balloon dilatation via the transjugular and transfemoral venous approach was technically successful in all patients. The patient with early-onset HV stenosis receiving transjugular balloon dilatation and stent placement on the 15th postoperative day left hospital 1 wk later and disappeared, while the patient receiving the same interventional procedures on the 50th postoperative day died of graft failure and renal failure 2 wk later. Two patients with late-onset HV stenosis receiving balloon dilatation have survived for 8 and 4 mo without recurrent stenosis and ascites, respectively. Balloon dilatation and stent placement via the superior mesenteric venous approach was technically successful in the pediatric left lobe LDLT, and this patient has survived for 9 mo without recurrent PV stenosis and ascites.CONCLUSION: Intraoperative balloon placement, emergent reoperation, proper

  12. CINACALCET IN TREATMENT OF HYPERPARATHYROIDISM IN RECIPIENTS OF RENAL GRAFT

    Directory of Open Access Journals (Sweden)

    O. N. Vetchinnikova

    2014-01-01

    Full Text Available Aim. Evaluate the efficacy and safety of cinacalcet in the treatment of hyperparathyroidism (HPT in renal transplant recipients. Materials and methods. During the year, three patients with satisfactory functioning kid- ney transplant (glomerular filtration rate − GFR 44–80 ml/min and HPT (parathyroid hormone − PTH 320– 348 pg/ml, resistant to treatment with active forms of vitamin D and hypercalcemia (2,6–3,1 mmol/l were treated with cinacalcet (initial dose of 30 mg/day, supporting − 60–15 mg/day with the added in 2–3 months alfacalcidol (0,25–0,75 μg/day. Investigated the serum concentrations and renal excretion of calcium and phos- phorus, PTH, renal transplant function (blood creatinine, GFR, plasma concentrations of tacrolimus, bone mine- ral density (BMD in different parts of the skeleton (dual energy X-ray absorptiometry. Results. A month later, the level of calcium in the blood to normal, PTH levels decreased by 1,2–3,2 times. A year later, in two patients, blood levels of PTH was back to normal, one − up − 142 pg/ml. Renal excretion of calcium varied differently − in two patients increased gradually, without exceeding the physiological norm, and in one − remained stable. Gene- ral pattern in the dynamics of serum concentration and urinary excretion of phosphorus was not observed. Renal graft function remained stable − GFR 46–76 ml/min. BMD of the distal forearm, femoral neck and lumbar spine in two patients remained the same, in one − increased by 14, 6 and 7%. Adverse events were absent. Conclusion. Application of cinacalcet is promising for the correction of HPT in renal transplant recipients

  13. Physical activity and metabolic syndrome in liver transplant recipients.

    Science.gov (United States)

    Kallwitz, Eric R; Loy, Veronica; Mettu, Praveen; Von Roenn, Natasha; Berkes, Jamie; Cotler, Scott J

    2013-10-01

    There is a high prevalence of metabolic syndrome in liver transplant recipients, a population that tends to be physically inactive. The aim of this study was to characterize physical activity and evaluate the relationship between physical activity and metabolic syndrome after liver transplantation. A cross-sectional analysis was performed in patients more than 3 months after transplantation. Metabolic syndrome was classified according to National Cholesterol Education Panel Adult Treatment Panel III guidelines. Physical activity, including duration, frequency, and metabolic equivalents of task (METs), was assessed. The study population consisted of 204 subjects, with 156 more than 1 year after transplantation. The median time after transplantation was 53.5 months (range = 3-299 months). The mean duration of exercise was 90 ± 142 minutes, and the mean MET score was 3.6 ± 1.5. Metabolic syndrome was observed in 58.8% of all subjects and in 63.5% of the subjects more than 1 year after transplantation. In a multivariate analysis involving all subjects, metabolic syndrome was associated with a time after transplantation greater than 1 year [odds ratio (OR) = 2.909, 95% confidence interval (CI) = 1.389-6.092] and older age (OR = 1.036, 95% CI = 1.001-1.072). A second analysis was performed for only patients more than 1 year after transplantation. In a multivariate analysis, metabolic syndrome was associated with lower exercise intensity (OR = 0.690, 95% CI = 0.536-0.887), older age (OR = 1.056, 95% CI = 1.014-1.101), and pretransplant diabetes (OR = 4.246, 95% CI = 1.300-13.864). In conclusion, metabolic syndrome is common after liver transplantation, and the rate is significantly higher in patients more than 1 year after transplantation. The observation that exercise intensity is inversely related to metabolic syndrome after transplantation is novel and suggests that physical activity might provide a means for reducing metabolic syndrome complications in liver

  14. Echinocandin Resistance in Candida Species Isolates from Liver Transplant Recipients.

    Science.gov (United States)

    Prigent, Gwénolé; Aït-Ammar, Nawel; Levesque, Eric; Fekkar, Arnaud; Costa, Jean-Marc; El Anbassi, Sarra; Foulet, Françoise; Duvoux, Christophe; Merle, Jean-Claude; Dannaoui, Eric; Botterel, Françoise

    2017-02-01

    Liver transplant recipients are at risk of invasive fungal infections, especially candidiasis. Echinocandin is recommended as prophylactic treatment but is increasingly associated with resistance. Our aim was to assess echinocandin drug resistance in Candida spp. isolated from liver transplant recipients treated with this antifungal class. For this, all liver-transplanted patients in a University Hospital (Créteil, France) between January and June of 2013 and 2015 were included. Susceptibilities of Candida isolates to echinocandins were tested by Etest and the EUCAST reference method. Isolates were analyzed by FKS sequencing and genotyped based on microsatellites or multilocus sequence typing (MLST) profiles. Ninety-four patients were included, and 39 patients were colonized or infected and treated with echinocandin. Echinocandin resistance appeared in 3 (8%) of the treated patients within 1 month of treatment. One patient was colonized by resistant Candida glabrata, one by resistant Candida dubliniensis, and one by resistant Candida albicans Molecular analysis found three mutations in FKS2 HS1 (F659S, S663A, and D666E) for C. glabrata and one mutation in FKS1 HS1 (S645P) for C. dubliniensis and C. albicans Susceptible and resistant isolates belonged to the same genotype. To our knowledge, this is the first study on echinocandin resistance in Candida spp. in a liver transplant population. Most resistant isolates were found around/in digestive sites, perhaps due to lower diffusion of echinocandin in these sites. This work documents the risk of emergence of resistance to echinocandin, even after short-term treatment. Copyright © 2017 Prigent et al.

  15. Prostate carcinoma in liver transplant recipients: Think about it!

    Science.gov (United States)

    Tillou, Xavier; Chiche, Laurence; Guleryuz, Kerem; Hervé, Sophie; Bensadoun, Henri; Doerfler, Arnaud

    2015-06-01

    To analyze retrospectively our series of prostate cancer (PC) in liver transplant recipients (LTRs) given an increase in frequency in an aging recipient population when no studies were reported in literature. We conducted a retrospective analysis of LTRs in a single institution. After liver transplantation, all patients were followed up in our institution with an annual digital rectal examination by a urologist and prostate-specific antigen measurement after the age of 50 years. Between 1995 and 2013, among 361 male LTRs, 12 (3.3%) had PC. The mean age at diagnosis was 62.8 years, and the time lapse between liver transplantation and diagnosis was 55.7 months. The median initial prostate-specific antigen level was 7.4ng/ml. In total, 9 patients underwent radical prostatectomy. Histological findings showed 5 pT2 and 4 pT3 cancers. A patient showed invasion in the lymph nodes and was treated with hormonotherapy. Another patient had a biochemical recurrence at 10 months and underwent salvage radiotherapy. After 32.9 months of follow-up, no other patients showed any recurrence. Moreover, 1 patient was treated by radiohormonotherapy for high-risk PC with no recurrence at 65 months, and 1 patient was treated with high-intensity focal ultrasound. There was 1 patient with metastatic disease who received hormonotherapy and died 5 months after diagnosis. Our incidence of intermediate- and high-risk PCs in LTRs was slightly higher than in the general population. In the absence of any recommendations, individual screening should be proposed to LTRs. The treatment of choice remains surgery or radiotherapy to ensure a good carcinologic control. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Dyslipidaemia among renal transplant recipients: cyclosporine versus tacrolimus.

    Science.gov (United States)

    Fazal, Muhammad Asim; Idrees, Muhammad Khalid; Akhtar, Syed Fazal

    2014-05-01

    To compare new onset dyslipidaemia in live-related renal transplant recipients taking cyclosporine versus tacrolimus after 3 months of therapy. The randomised controlled trial was conducted at the Sindh Institute of Urology and Transplantation (SIUT) Karachi, from September 2010 to April 2011, and included 182 End Stage Renal Disease patients on maintenance haemodialysis with pre-transplant normal lipid profile. The patients, who had live-related renal transplant, were randomly allocated to two equal groups using lottery. Group A received cyclosporine (3 mg/kg) and group B was treated with tacrolimus (0.1 mg/kg). All patients had pre-transplant fasting lipid profile checked when they were on maintenance haemodialysis and 3 months after renal transplantation. Serum fasting lipid profile was collected by taking 5 ml blood by venipuncture after an overnight fast of 9-12 hours. SPSS 10 was used for statistical analyses. Of the 182 patients, 144 (79.1%) were males and 38 (20.9%) were females. The overall mean age was 30.18 +/- 9.57 years, and the mean weight was 54.41 +/- 11.144 kg. Significant difference was not observed between the two groups regarding age and weight of the patients. Dyslipidaemia was found in 115(63.2%) subjects; 61(67%) in group A and 54 (59.3%) in group B. There was no statistical difference (p=0.28) when comparison was done after 3 months of therapy. The occurrence of new onset hyperlipidaemia is similar in renal transplant recipients receiving either cyclosporine or tacrolimus in first 3 months post-transplant, but there is room for more research in this field as dyslipidaemia following successful renal transplantation is a frequent and persistent complication.

  17. Cardiac surgery is successful in heart transplant recipients.

    Science.gov (United States)

    Holmes, Timothy R; Jansz, Paul C; Spratt, Phillip; Macdonald, Peter S; Dhital, Kumud; Hayward, Christopher; Arndt, Grace T; Keogh, Anne; Hatzistergos, Joanna; Granger, Emily

    2014-08-01

    Improved survival of heart transplant (HTx) recipients and increased acceptance of higher risk donors allows development of late pathology. However, there are few data to guide surgical options. We evaluated short-term outcomes and mortality to guide pre-operative assessment, planning, and post-operative care. Single centre, retrospective review of 912 patients who underwent HTx from February 1984 - June 2012, identified 22 patients who underwent subsequent cardiac surgery. Data are presented as median (IQR). Indications for surgery were coronary allograft vasculopathy (CAV) (n=10), valvular disease (n=6), infection (n=3), ascending aortic aneurysm (n=1), and constrictive pericarditis (n=2). There was one intraoperative death (myocardial infarction). Hospital stay was 10 (8-21) days. Four patients (18%) returned to theatre for complications. After cardiac surgery, survival at one, five and 10 years was 91±6%, 79±10% and 59±15% with a follow-up of 4.6 (1.7-10.2) years. High pre-operative creatinine was a univariate risk factor for mortality, HR=1.028, (95%CI 1.00-1.056; p=0.05). A time dependent Cox proportional hazards model of the risk of cardiac surgery post-HTx showed no significant hazard; HR=0.87 (95%CI 0.37-2.00; p=0.74). Our experience shows cardiac surgery post-HTx is associated with low mortality, and confirms that cardiac surgery is appropriate for selected HTx recipients. Copyright © 2014 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  18. Cyclosporine-induced renal dysfunction in human renal allograft recipients.

    Science.gov (United States)

    Kiberd, B A

    1989-12-01

    Cyclosporine-treated renal allograft recipients frequently suffer CsA-related nephrotoxicity and hypertension. This study demonstrates that glomerular filtration rate is reduced acutely by 13% (P less than 0.02) and renal vascular resistance increased by 30% (P less than 0.05), immediately after patients take their CsA dose. The reduction in GFR is directly related to their trough CsA level (r = 0.82; P less than 0.01). The lower the trough CsA level the greater the fall in GFR after the CsA dose. Plasma renin activity does not increase after the CsA dose (pre-CsA 0.6 +/- 0.2 ng/L/sec vs. post-CsA 0.4 +/- 0.1 ng/L/sec; P = NS), and therefore cannot be responsible for the reduction in renal function. Short-term nifedipine treatment is effective in preventing the acute reduction in GFR (P less than 0.05). This occurred despite no apparent effect of nifedipine in altering trough or post-dose CsA levels. Furthermore nifedipine was effective in lowering both the mean arterial blood pressure (109 mmHg to 94 mmHg; P less than 0.01) and the elevated renal vascular resistance (25% reduction; P less than 0.02) observed in these patients. These results suggest that nifedipine may be a suitable agent for limiting acute CsA nephrotoxicity and for treating CsA-associated hypertension in renal allograft recipients.

  19. The meaning of care dependency as shared by care givers and care recipients : a concept analysis

    NARCIS (Netherlands)

    Boggatz, Thomas; Dijkstra, Ate; Lohrmann, Christa; Dassen, Theo

    2007-01-01

    Aim. This paper is a report of a concept analysis to identify a meaning of care dependency that can be shared by both care givers and care recipients. Background. Care dependency can be perceived from the care recipient's and the care giver's perspective. To allow for comparisons, both sides should

  20. Cancer Incidence among Heart, Kidney, and Liver Transplant Recipients in Taiwan.

    Directory of Open Access Journals (Sweden)

    Kwai-Fong Lee

    Full Text Available Population-based evidence of the relative risk of cancer among heart, kidney, and liver transplant recipients from Asia is lacking. The Taiwan National Health Insurance Research Database was used to conduct a population-based cohort study of transplant recipients (n = 5396, comprising 801 heart, 2847 kidney, and 1748 liver transplant recipients between 2001 and 2012. Standardized incidence ratios and Cox regression models were used. Compared with the general population, the risk of cancer increased 3.8-fold after heart transplantation, 4.1-fold after kidney transplantation and 4.6-fold after liver transplantation. Cancer occurrence showed considerable variation according to transplanted organs. The most common cancers in all transplant patients were cancers of the head and neck, liver, bladder, and kidney and non-Hodgkin lymphoma. Male recipients had an increased risk of cancers of the head and neck and liver, and female kidney recipients had a significant risk of bladder and kidney cancer. The adjusted hazard ratio for any cancer in all recipients was higher in liver transplant recipients compared with that in heart transplant recipients (hazard ratio = 1.5, P = .04. Cancer occurrence varied considerably and posttransplant cancer screening should be performed routinely according to transplanted organ and sex.